Carotid artery-cavernous sinus fistula.
Carotid artery-cavernous sinus fistula is a lesion most often associated with massive head trauma. The maxillofacial surgeon must be able to diagnose this major complication of head trauma, use proper diagnostic techniques, and initiate appropriate therapeutic regimens. The symptoms of pulsatile headache, bruit, and visual change accompany the physical findings of bruit, conjunctival engorgement, chemosis, proptosis, and ophthalmoplegia. A number of procedures have been devised to correct this difficult lesion, ranging from cervical ligation to balloon occlusion. Two cases of carotid artery-cavernous sinus fistula are reported in detail, documenting clinical findings, treatment, and long-term sequelae. Although surgical treatment is not within the scope of this specialty, the otolaryngologist must understand the vascular dynamics and surgical procedures related to this traumatic lesion.


Examining the Temporal and Spatial Models of China's Circular Economy Based upon Detailed Data of E-Plastic Recycling.
Examining the circular economy model is crucial to enable the scaling up of industry and anthropogenic circularity practice. Electrical and electronic waste plastic (e-plastic) has become the focus of urban mining and circular economy due to its rapid growth, valuable resource and potential risks. This article focuses on the recycling companies' experience in China from 2012 to 2017. The average recycling rate was 33.3% and the recycling amount in 2017 was 558 kt. A two-dimensional coupling model of economic development and renewable resources is firstly constructed. Eventually, four typical resource-based regional models are summarized, namely for demonstration regional model, commissioned regional model, traditional model and potential regional model. It also puts forward differentiated suggestions in terms of maintaining demonstration, strengthening policies, promoting transformation, and tapping potential. At the same time, it is recommended to explore the construction of large-region resource-based recycling centers and big data centers in resource-based demonstration areas.


Short-Form Ron Promotes Spontaneous Breast Cancer Metastasis through Interaction with Phosphoinositide 3-Kinase.
Receptor tyrosine kinases (RTKs) have been the subject of intense investigation due to their widespread deregulation in cancer and the prospect of developing targeted therapeutics against these proteins. The Ron RTK has been implicated in tumor aggressiveness and is a developing target for therapy, but its function in tumor progression and metastasis is not fully understood. We examined Ron activity in human breast cancers and found striking predominance of an activated Ron isoform known as short-form Ron (sfRon), whose function in breast tumors has not been explored. We found that sfRon plays a significant role in aggressiveness of breast cancer in vitro and in vivo. sfRon expression was sufficient to convert slow-growing, nonmetastatic tumors into rapidly growing tumors that spontaneously metastasized to liver and bones. Mechanistic studies revealed that sfRon promotes epithelial-mesenchymal transition, invasion, tumor growth, and metastasis through interaction with p85, the regulatory subunit of phosphoinositide 3-kinase (PI3K). Inhibition of PI3K activity, or introduction of a single mutation in the p85 docking site on sfRon, completely eliminated the ability of sfRon to promote tumor growth, invasion, and metastasis. These findings reveal sfRon as an important new player in breast cancer and validate Ron and PI3K as therapeutic targets in this disease.


Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi, Sn): High Chemical Flexibility Resulting in Good Nonlinear-Optical Properties.
Seven acentric sulfides Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi, Sn) were grown by a high-temperature salt flux method. The crystal structures of the Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi, Sn) compounds were determined by single-crystal X-ray diffraction with the aid of solid-state NMR spectroscopy. The Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi) compounds are isostructural and crystallize in the Ba6Ag4Sn4S16 structure type. The Sn-containing compound exhibits high structural similarity to Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi) with the presence of an interstitial atomic position partially occupied by Sn atoms. The chemical bonding characteristics of Ba6(Cu2.9Sn0.4)Sn4S16 were understood with electron localization function calculations coupled with crystal orbital Hamilton population calculations. The Ba-S and Cu-S interactions are dominantly ionic, but the Sn-S interactions consist of strong covalent bonding characteristics in Ba6(Cu2.9Sn0.4)Sn4S16. The monovalent Cu atoms, mixed with certain metals with various oxidation states, significantly shift the optical properties of the Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi) compounds. This results in a good balance between the second-harmonic-generation (SHG) response and laser damage threshold (LDT). Ba6(Cu1.9Zn1.1)Sn4S16 possesses a high SHG response and a high LDT of 2.8 × AGS and 3 × AGS, respectively. A density functional theory calculation revealed that CuS4 and SnS4 tetrahedra significantly contribute to the SHG response in Ba6(Cu2Mg)Sn4S16, which also confirmed that CuS4 tetrahedra are crucial for the stability and optical properties of the Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi, Sn) compounds revealed by electronic structure analysis.


Co-transport of biochar colloids with organic contaminants in soil column.
Co-transport of biochar (BC) colloids with coexisting organic contaminants (OCs) in soil involves complex interactions among BC colloids, OCs, and soil particles, which is significant for the environmental application and risk assessment of BC and yet has not been well addressed. This study explored co-transports of three typical OCs (i.e., phenanthrene (PHN), atrazine (ATZ), and oxytetracycline (OTC)) and BC colloids obtained from bulk BCs with different charring temperatures (200-700 °C) and particle sizes (250 nm, 500 nm, and 1 μm) in a soil column of 9 cm in height. Considerable transport of BC colloids alone was observed and the maximum breakthrough concentration (C/Co) increased from 0.08 to 0.77 as the charring temperature decreased from 700 to 200 °C. The mobilities of PHN, OTC, and ATZ alone were very low but were greatly increased by co-transports with BC colloids, and their maximum C/Co values were within 0.05-0.33, 0.03-0.44, and 0.05-0.62, respectively, in the absence and presence of various BC colloids. The enhancement effect of BC colloids on the OC transport decreased with increasing charring temperature or particle size of BC colloids. BC colloids mainly acted as a vehicle to facilitate the transport of OCs, and dissolved organic carbon from BC colloids also contributed to the increased mobility of OCs in dissolved form. These findings provide new insights into co-transport of BC colloids and contaminants in soil.


An Analysis of Growth Regulator Interactions and Gene Expression during Auxin-Induced Cell Elongation Using Cloned Complementary DNAs to Auxin-Responsive Messenger RNAs.
We have examined the effects of cytokinin, fusicoccin, and ethylene on auxin-induced changes in gene expression during auxin-promoted cell elongation in soybean (Glycine max L. Merr. cv Wayne) using cloned cDNAs to two auxin-responsive mRNAs (Walker, Key 1982 Proc Natl Acad Sci USA 79: 7185-7989). RNA blot analyses demonstrate that under conditions of cytokinin inhibition of auxin-promoted cell elongation the levels of these two auxin-responsive mRNAs is unaltered. Fusicoccin-promoted elongation is not associated with an enhanced expression of these two mRNAs, suggesting that the increased levels of these mRNAs observed during auxin-promoted cell elongation are not simply due to enhanced rates of cell elongation. We have also determined that ethylene plays no apparent role in the regulation of expression of these mRNAs. However, the auxins indole-3-acetic acid, 2,4-dichlorophenoxyacetic acid, and alpha-naphthalene acetic acid all enhance an accumulation of these mRNAs. We conclude that the regulation of these mRNAs is directly dependent on auxin. That auxin-promoted cell elongation is dependent upon the increased accumulation of these mRNAs remains to be determined.


Modulation of glial activation by astrocyte-derived protein S100B: differential responses of astrocyte and microglial cultures.
The astrocyte-derived protein S100B stimulates production of inducible nitric oxide synthase and nitric oxide (NO) in astrocytes [Hu et al., 1996, J. Biol. Chem. 271:2543], but its effect on microglia is not known. In addition, S100B's ability to modulate the activity of other glial activating agents has not been defined. In this study, we compared the ability of S100B to stimulate NO in cultures of rat primary astrocytes and the BV-2 murine microglial cell line, and investigated the effect of the combined action of S100B and other stimuli known to activate glial cells. S100B itself stimulated the production of NO in astrocytes, and did not modify or potentiated only weakly the NO production induced by interleukin-1 beta, tumor necrosis factor alpha, dibutyryl cyclic AMP, zymosan A or lipid A. In contrast, S100B alone did not induce NO in BV-2 cells but strongly potentiated NO production in the presence of lipid A but not zymosan A. The deletion of eight C-terminal amino acid residues in S100B leads to a loss of the effect of S100B on microglia but not on astrocytes. These results demonstrate that responses of glial cells to extracellular S100B can vary depending on the cell type, and suggest that different structural features of S100B are important for the protein's effects on microglia and astrocytes.


Comparative Analysis of Spatial Distribution of Cholera by Temporal Fragments from 2000 to 2018.
Cholera is caused by V.cholerae (serogroups O1 and O139) and has a close relationship with socio-environmental conditions, especially basic sanitation. Analytical methodologies for collecting quantitative data on health indicators are widely used to support epidemiological surveillance actions in human health. This work aims to verify the fluctuation of the spatial distribution of cholera in the world, by temporal fragments, between 2000 and 2018. During the analyzed period, approximately 5.3 billion cases with 75.6 thousand deaths occurred, with emphasis on the regions of Africa, South Asia, and the Caribbean, showing that the disease is still a serious public health problem, especially in populations in precarious situations. Although the methodology employed in this study presents practical obstacles of underreporting and integration between the different collection platforms, it is an important tool in the construction of health surveillance measures for infectious diseases.


Mechanisms for virus-induced liver disease: tumor necrosis factor-mediated pathology independent of natural killer and T cells during murine cytomegalovirus infection.
The contribution of endogenous NK cells and cytokines to virus-induced liver pathology was evaluated during murine cytomegalovirus infections of mice. In immunocompetent C57BL/6 mice, the virus induced a self-limited liver disease characterized by hepatitis, with focal inflammation, and large grossly visible subcapsular necrotic foci. The inflammatory foci were most numerous and contained the greatest number of cells 3 days after infection; they colocalized with areas of viral antigen expression. The largest number of necrotic foci was found 2 days after infection. Overall hepatic damage, assessed as increased expression of liver enzymes in serum, accompanied the development of inflammatory and necrotic foci. Experiments with neutralizing antibodies demonstrated that although virus-induced tumor necrosis factor (TNF) can have antiviral effects, it also mediated significant liver pathology. TNF was required for development of hepatic necrotic foci and increased levels of liver enzymes in serum but not for increased numbers of inflammatory foci. The necrotic foci and liver enzyme indications of pathology occurred independently of NK and T cells, because mice rendered NK-cell deficient by treatment with antibodies, T- and B-cell-deficient Rag-/- mice, and NK- and T-cell-deficient E26 mice all manifested both parameters of disease. Development of necrotic foci and maximally increased levels of liver enzymes in serum also were TNF dependent in NK-cell-deficient mice. Moreover, in the immunodeficient E26 mice, virus-induced liver disease was progressive, with eventual death of the host, and neutralization of TNF significantly increased longevity. These results establish conditions separating hepatitis from significant liver damage and demonstrate a cytokine-mediated component to viral pathogenesis.


Outcome after acute incomplete sirolimus-eluting stent apposition as assessed by serial intravascular ultrasound.
We investigated the fate of postprocedural incomplete stent apposition (ISA) after sirolimus-eluting stent (SES) implantation by evaluating long-term intravascular ultrasound findings in 168 consecutive patients (182 de novo lesions). Postprocedural ISA was defined as > or = 1 stent strut that was clearly separated from the vessel wall with evidence of blood speckle behind the strut without overlapping a side branch. After SES implantation, there were 61 ISA sites in 46 stents in 31 patients (23 at the proximal edge, 7 at the distal edge, and 31 within the stent body). There were no clinical, procedural, or intravascular ultrasound measurement differences between patients and lesions with versus without ISA. At follow-up, 15 acute ISA sites (25%) in 11 patients completely resolved and 40 sites (75%) in 20 patients persisted, although 32 of 46 persisting ISA sites (70%) decreased. There was a greater decrease in effective lumen area and a greater increase in peristent plaque area in the complete-resolution group than in the persistent-ISA group. No lesion developed stent thrombosis or in-stent restenosis (angiographic diameter stenosis > 50%). Six acute ISA sites were also associated with new, late acquired ISA, only 1 of which resulted in aneurysm formation. Although most ISAs after SES implantation do not resolve completely, the incidence of restenosis or thrombosis is not affected.


Substituted pyrroles via olefin cross-metathesis.
Olefin cross-metathesis (CM) provides a short and convenient entry to diverse trans-γ-aminoenones. When exposed to either acid or Heck arylation conditions, these intermediates are converted to mono-, di-, or trisubstituted pyrroles. The value of this chemistry is demonstrated by its application to the tetrasubstituted pyrrole subunit of Atorvastatin.


Mesenchymal Stem Cells Derived Extracellular Vesicles Alleviate Traumatic Hemorrhagic Shock Induced Hepatic Injury via IL-10/PTPN22-Mediated M2 Kupffer Cell Polarization.
Traumatic hemorrhagic shock (THS) is a major cause of mortality and morbidity worldwide in severely injured patients. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and tissue repair potential mainly through a paracrine pathway mediated by MSC-derived extracellular vesicles (MSC-EVs). Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine that plays a crucial role during the inflammatory response, with a broad range of effects on innate and adaptive immunity, preventing damage to the host and maintaining normal tissue homeostasis. However, the function and mechanism of IL-10 in MSC-mediated protective effect in THS remain obscure. Here, we show that MSCs significantly attenuate hepatic injury and inflammation from THS in mice. Notably, these beneficial effects of MSCs disappeared when IL-10 was knocked out in EVs or when recombinant IL-10 was administered to mice. Mechanistically, MSC-EVs function to carry and deliver IL-10 as cargo. WT MSC-EVs restored the function of IL-10 KO MSCs during THS injury. We further demonstrated that EVs containing IL-10 mainly accumulated in the liver during THS, where they were captured by Kupffer cells and induced the expression of PTPN22. These effects subsequently shifted Kupffer cells to an anti-inflammatory phenotype and mitigated liver inflammation and injury. Therefore, our study indicates that MSC-EVs containing IL-10 alleviate THS-induced hepatic injury and may serve as a cell-free therapeutic approach for THS.


Middle ear adenoma. A cytologically uniform neoplasm displaying a variety of architectural patterns.
Seven patients with middle ear adenomas (MEA) are presented. MEA are cytologically stereotyped neoplasms with a spectrum of architectural patterns. All tumors were composed of uniform, round, or ovoid cells that resembled normal middle ear epithelium. The histologic patterns varied from tumor to tumor and within a single lesion. Broad sheets of tightly packed cells were commonly present, but glandular and cribriform areas were also frequent. Complex, interdigitating trabeculae, rows of individual cells, and dissociated cells were sometimes seen. Grimelius argyrophil stains were focally positive in three of five stained tumors, but Churukian-Schenk argyrophil preparations demonstrated only rare positive cells in two of these cases. Lysozyme was demonstrable immunohistochemically in each tumor. Lysozyme is present in normal middle ear epithelium and may be a useful marker for MEA, since the tumor is apparently derived from these cells. The clinical features of the seven cases that we report are combined with 44 MEA from the literature. MEA seldom recurs after excision and very rarely invades bone. No patient died of disease. The clinical and histologic distinction of these tumors from plasmacytoma, paraganglioma, ceruminoma, carcinoid tumor, and papillary carcinoma is discussed.


[REM sleep modulation by non-GABAergic neurons of the hypothalamus and basal forebrain].
The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal connections with structures that control other states of the sleep-wakefulness cycle, many situated in the basal forebrain and the diencephalon. The aim of the present revision is to map, using the results described in previous publications of our group, the local origin of the basal forebrain and hypothalamus non-GABAergic projections to the vRPO, and specially the contribution of the hypothalamic neurons positive to hypocretin/orexin (H/O) peptides. I summarize non-GABAergic projections to the vRPO from the: ipsilateral central amygdaline nucleus and the stria terminalis bed nuclei, bilateral projections, but most abundant in the ipsilateral side, from the median preoptic nucleus, medial and lateral preoptic areas, abundant from the zona incerta and dorsal, lateral, posterior and perifornical hypothalamic areas. Very abundant bilateral projections of H/O neurons to the vRPO are described, expressive of the important modulation exerted by these neurons on the vRPO nucleus. I discuss the functional significance of the above results and the corresponding mechanisms, supported by physiological and ultrastructural results of our group. Based on the connections and action mechanisms of H/O neurons on the vRPO, which produce the decreased activity of neurons in this nucleus and, therefore, inhibition of REM sleep, I reflect briefly on narcolepsy pathophysiology.


Liquid chromatographic determination of fumonisins B1, B2, and B3 in corn silage.
Corn silage was dried, ground, and then extracted with 0.1 M ethylenediaminetetraacetic acid. The filtrate was applied to a FumoniTest immunoaffinity column. Fumonisins were derivatized with naphthalene-2,3-dicarboxaldehyde, separated on a C(18) liquid chromatographic column, and detected by fluorescence. The detection limits for fumonisin B(1), fumonisin B(2), and fumonisin B(3) were 50, 25, and 25 ng/g of dried silage, respectively. Recoveries of fumonisin B(1), fumonisin B(2), and fumonisin B(3) from wet and dried corn silage spiked over the range of 100-5000 ng/g averaged 91-106%. The method was applied to corn silage samples collected from the midwestern area of the United States during 2001-2002. Of 89 corn silage samples, fumonisin B(1), fumonisin B(2), and fumonisin B(3) were found in 86 (97%), 64 (72%), and 51 (57%) of the samples. The mean positive levels of fumonisin B(1), fumonisin B(2), and fumonisin B(3) were 615, 93, and 51 ng/g, respectively, in dried silage. This suggests that fumonisins may be frequent low level contaminants in corn silage.


An old friend who has overstayed their welcome: the ALSFRS-R total score as primary endpoint for ALS clinical trials.
Objective: The ALSFRS-R is limited by multidimensionality, which originates from the summation of various subscales. This prevents a direct comparison between patients with identical total scores. We aim to evaluate how multidimensionality affects the performance of the ALSFRS-R in clinical trials. Methods: We simulated clinical trial data with different treatment effects for the ALSFRS-R total score and its subscales (i.e. bulbar, fine motor, gross motor and respiratory). We considered scenarios where treatment reduced the rate of ALSFRS-R subscale decline either uniformly (i.e. all subscales respond identically to treatment) or non-uniformly (i.e. subscales respond differently to treatment). Two main analytical strategies were compared: (1) analyzing only the total score or (2) utilizing a subscale-based test (i.e. alternative strategy). For each analytical strategy, we calculated the empirical power and required sample size. Results: Both strategies are valid when there is no treatment benefit and provide adequate control of type 1 error. If all subscales respond identically to treatment, using the total score is the most powerful approach. As the differences in treatment responses between subscales increase, the more the total score becomes affected. For example, to detect a 40% reduction in the bulbar rate of decline with 80% power, the total score requires 1380 patients, whereas this is 336 when using the alternative strategy. Conclusions: Ignoring the multidimensional structure of the ALSFRS-R total score could have negative consequences for ALS clinical trials. We propose determining treatment benefit on a subscale level, prior to stating whether a treatment is generally effective.


Examining the Change of Human Mobility Adherent to Social Restriction Policies and Its Effect on COVID-19 Cases in Australia.
The policy induced decline of human mobility has been recognised as effective in controlling the spread of COVID-19, especially in the initial stage of the outbreak, although the relationship among mobility, policy implementation, and virus spread remains contentious. Coupling the data of confirmed COVID-19 cases with the Google mobility data in Australia, we present a state-level empirical study to: (1) inspect the temporal variation of the COVID-19 spread and the change of human mobility adherent to social restriction policies; (2) examine the extent to which different types of mobility are associated with the COVID-19 spread in eight Australian states/territories; and (3) analyse the time lag effect of mobility restriction on the COVID-19 spread. We find that social restriction policies implemented in the early stage of the pandemic controlled the COVID-19 spread effectively; the restriction of human mobility has a time lag effect on the growth rates of COVID-19, and the strength of the mobility-spread correlation increases up to seven days after policy implementation but decreases afterwards. The association between human mobility and COVID-19 spread varies across space and time and is subject to the types of mobility. Thus, it is important for government to consider the degree to which lockdown conditions can be eased by accounting for this dynamic mobility-spread relationship.


Energy minimization in medical image analysis: Methodologies and applications.
Energy minimization is of particular interest in medical image analysis. In the past two decades, a variety of optimization schemes have been developed. In this paper, we present a comprehensive survey of the state-of-the-art optimization approaches. These algorithms are mainly classified into two categories: continuous method and discrete method. The former includes Newton-Raphson method, gradient descent method, conjugate gradient method, proximal gradient method, coordinate descent method, and genetic algorithm-based method, while the latter covers graph cuts method, belief propagation method, tree-reweighted message passing method, linear programming method, maximum margin learning method, simulated annealing method, and iterated conditional modes method. We also discuss the minimal surface method, primal-dual method, and the multi-objective optimization method. In addition, we review several comparative studies that evaluate the performance of different minimization techniques in terms of accuracy, efficiency, or complexity. These optimization techniques are widely used in many medical applications, for example, image segmentation, registration, reconstruction, motion tracking, and compressed sensing. We thus give an overview on those applications as well.


CD4+ T cells regulate surgical and postinfectious adhesion formation.
The development of adhesions in the peritoneal and pelvic cavities, which commonly form after surgery or infection, cause significant morbidity and mortality. However, the pathogenesis of adhesion formation is still poorly understood. Because T cells are important in orchestrating fibrinogenic tissue disorders, we hypothesized that they play a critical role in the pathogenesis of peritoneal adhesion formation. Using a cecal abrasion surgical model in rodents, T cell depletion and adoptive transfer experiments demonstrated that this host response is dependent on CD4+ alphabeta T cells. These cells were also critical to adhesion formation associated with experimental intraabdominal sepsis. T cell transfer studies with mice deficient in signal transducer and activator of transcription (Stat)4 and Stat6 revealed that adhesion formation was dependent on a T helper 1 response. Activated T cells homed to the peritoneal cavity 6 hours after cecal abrasion surgery and predominated at this site during adhesiogenesis. Increased levels of the T cell-derived proinflammatory cytokine interleukin (IL)-17 and of neutrophil chemoattractant CXC chemokines macrophage inflammatory protein-2/CXCL8 and cytokine-induced neutrophil chemoattractant/CXCL1 were associated with adhesion formation. The production of these chemokines was dependent on T cells. Furthermore, the administration of neutralizing antibodies specific for IL-17 or the receptor that binds these CXC chemokines, CXC chemokine receptor 2, significantly reduced the degree of adhesion formation. These results demonstrate for the first time that the immunopathogenesis of adhesion formation is under the control of T cells and that T cell-derived cytokines and chemokines play important roles in the development of this deleterious host response.


Charge transport characteristics of a high-mobility diketopyrrolopyrrole-based polymer.
In this study, we attempt to unveil the charge-transport abnormality of the widely studied diketopyrrolopyrrole (DPP)-based polymers with exceptionally high charge carrier mobility [>5 cm(2) V(-1) s(-1)]. Based on the electric field and temperature dependence of the charge-transport characteristics of the field effect transistor (FET) geometry of one of the highly conductive DPP derivatives, namely, (poly[2,5-bis(7-decylnonadecyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione-(E)-(1,2-bis(5-(thiophen-2-yl)selenophen-2-yl)ethene) (PDPPDTSE), we show that the high gate-source bias drew the carriers closer to the interface of the semiconductor/dielectric layers where the density of state (DOS) of the charge carrier is significantly broader than the bulk. We argue that the intrinsically narrow DOS in the PDPPDTSE bulk resulted in significantly different charge-transport behavior between the semiconductor bulk and the semiconductor/dielectric interface, which was not visible in the other low-mobility organic semiconductors that contain intrinsically high density of trap states in their bulk. To avoid these charge transport abnormalities, we try to operate the FETs under low gate bias without compromising the accumulated charge carrier density. By carefully employing a thin metal oxide covered with a self-assembled monolayer (SAM) as a dielectric layer, we can demonstrate low-voltage PDPPDTSE FETs with near-ideal performance both in terms of hysteresis-free operation and operating reliability while maintaining a high charge carrier mobility of ~2.8 cm(2) V(-1) s(-1).


Modulation of RNA function by aminoglycoside antibiotics.
One of the most important families of antibiotics are the aminoglycosides, including drugs such as neomycin B, paromomycin, gentamicin and streptomycin. With the discovery of the catalytic potential of RNA, these antibiotics became very popular due to their RNA-binding capacity. They serve for the analysis of RNA function as well as for the study of RNA as a potential therapeutic target. Improvements in RNA structure determination recently provided first insights into the decoding site of the ribosome at high resolution and how aminoglycosides might induce misreading of the genetic code. In addition to inhibiting prokaryotic translation, aminoglycosides inhibit several catalytic RNAs such as self-splicing group I introns, RNase P and small ribozymes in vitro. Furthermore, these antibiotics interfere with human immunodeficiency virus (HIV) replication by disrupting essential RNA-protein contacts. Most exciting is the potential of many RNA-binding antibiotics to stimulate RNA activities, conceiving small-molecule partners for the hypothesis of an ancient RNA world. SELEX (systematic evolution of ligands by exponential enrichment) has been used in this evolutionary game leading to small synthetic RNAs, whose NMR structures gave valuable information on how aminoglycosides interact with RNA, which could possibly be used in applied science.


Behavioural and new pharmacological treatments for constipation: getting the balance right.
Chronic constipation affects almost one in six adults and is even more frequent in the elderly. In the vast majority of patients, there is no obstructive mucosal or structural cause for constipation and, after excluding relatively rare systemic diseases (commonest of which is hypothyroidism), the differential diagnosis is quickly narrowed down to three processes: evacuation disorder of the spastic (pelvic floor dyssynergia, anismus) or flaccid (descending perineum syndrome) varieties, and normal or slow transit constipation. Treatment of chronic constipation based on identifying the underlying pathophysiology is generally successful with targeted therapy. The aims of this review are to discuss targeted therapy for chronic constipation: behavioural treatment for outlet dysfunction and pharmacological treatment for constipation not associated with outlet dysfunction. In particular, we shall review the evidence that behavioural treatment works for evacuation disorders, describe the new treatment options for constipation not associated with evacuation disorder, and demonstrate how 'targeting therapy' to the underlying diagnosis results in a balanced approach to patients with these common disorders.


Imaging in Endovascular Stroke Trials.
Ischemic stroke remains a leading cause of death and disability worldwide. Various endovascular trials have addressed clinical outcomes without elucidating the impact of imaging studies in patient selection. The success of recent endovascular trials was bolstered by the use of advanced imaging techniques for optimal selection of reperfusion candidates. This seminal juncture in the history of stroke trials warrants further consideration on the use of imaging to guide future refinements in the treatment of acute stroke. In this article, we systematically review the imaging methodology and key facets used in all published endovascular stroke trials to date, discuss the success of recent trials using latest advanced imaging techniques and focus on the importance of imaging studies for future patient selection.


Behavioral evidence for attention selection as entrained synchronization without awareness.
Animal physiological and human neuroimaging studies have established a link between attention and γ-band (30-90 Hz) oscillations and synchronizations. However, a behavioral link between entrained γ-band oscillations and attention has been fraught with technical challenges. In particular, while entrainment at mid-γ band (40-70 Hz) has been claimed to be privileged in evoking attentional modulations without awareness, the effect may be attributed to display artifacts. Here, by exploiting isoluminant chromatic flicker without luminance modulation and not subject to these artifacts, we tested attentional attraction by chromatic flicker too fast to perceive. Awareness of flicker was subjectively and objectively tested with a high-powered design and evaluated with traditional and Bayesian statistics. Across 2 experiments in human participants, we observed-and also replicated-that 30-Hz chromatic flicker outside mid-γ band attracted attention, resulting in a facilitation effect at a 50 ms interstimulus interval (ISI) and an inhibition effect at a 500 ms ISI. The attention test was confirmed to be more sensitive to the cue than the direct cue-localization task was. We further showed that these attention effects were absent for 50-Hz chromatic flicker. These results provide strong direct evidence against a privileged role of mid-γ band in unconscious attention, but are consistent with known cortical responses to chromatic flicker in early visual cortex. Taken together, our findings provide behavioral evidence that entrained synchronization may serve as a mechanism for bottom-up attention selection and that chromatic flicker may offer a fruitful avenue for investigating unconscious processing. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Homers regulate drug-induced neuroplasticity: implications for addiction.
Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.


Segmental muscle vibration improves reaching movement in patients with chronic stroke. A randomized controlled trial.
Segmental muscle vibration (SMV) has been used to improve gait and to reduce spasticity in stroke patients. No data exist about the possibility to improve upper limb motor function by using SMV. Forty-four patients with hemiparesis following chronic stroke were randomized to an experimental (n = 24) and a control group (n = 20). Patients in the experimental group received two weeks of general physical therapy and SMV over the biceps brachii and flexor carpi ulnaris muscles of the paretic side, while those in the control group received two weeks of general physical therapy. Kinematic analysis of reaching movement was performed at baseline and two weeks after treatment ended. Normalized jerk, indicating the smoothness of movement, significantly improved in the experimental group, with significant difference emerging between groups at the post-treatment evaluation. Patients in the experimental group also displayed a significant improvement for mean linear velocity, mean angular velocity at shoulder, distance to target at the end of movement and movement duration. No differences emerged between baseline and post-treatment evaluations in the control group. when added to general physical therapy, SMV is effective in improving, in a short-term period, upper limb motor performances of reaching movement in chronic stroke patients.


A P element-homologous sequence in the house fly, Musca domestica.
Sequences homologous to the P transposable element have been identified in Musca domestica. Sequence analysis of a genomic clone (Md-P1) indicates that, although the house fly P element has lost its coding capacity, the basic general structure of drosophilid P elements is present. The house fly P element sequence shares a number of structural features with that from the blow fly, Lucilia cuprina, including a large intron separating exons 1 and 2, two additional introns interrupting exon 2 and the apparent absence of inverted repeat termini. Within a relatively well-conserved central region, the house fly sequence shows 59% similarity to the D. melanogaster P element, but distal regions are more diverged. Southern blot analysis of several strains indicated the presence of at least four P element copies.


Recombinant GroES in combination with CpG oligodeoxynucleotides protects mice against Mycobacterium avium infection.
The groES gene of Mycobacterium avium strain 485 was cloned and expressed in Escherichia coli and the recombinant GroES protein was purified by affinity chromatography. The GroES preparation showed high purity by electrophoresis and immunoblotting. Immuno-electron microscopy showed that GroES was located both in the cytoplasm and on the surface of the mycobacterial cells and thus is readily available to interact with the host immune system. BALB/c mice were immunised intranasally with recombinant GroES, alone or in combination with a synthetic oligodeoxynucleotide containing unmethylated CpG motifs, and tested for protection against infection with M. avium. Neither GroES nor CpG alone provided any protection against subsequent challenge with M. avium, whereas a combination of the two significantly protected the lungs and spleen against colonisation by M. avium after intranasal challenge with a low dose of the organism. This indicates that intranasal administration of GroES and CpG oligodeoxynucleotides increases the resistance of BALB/c mice to M. avium infection.


Autophagy Improves ARA-Rich TAG Accumulation in Mortierella alpina by Regulating Resource Allocation.
The present study was designed to explore the possibility of improving lipid production in oleaginous filamentous fungus Mortierella alpina based on an autophagy regulation strategy. According to multiomics information, vacuolate-centered macroautophagy was identified as the main type of autophagy in M. alpina under nitrogen-limited conditions. Mutation of autophagy-related gene MAatg8 led to impaired fatty acid synthesis, while overexpression of both MAatg8 and phosphatidylserine decarboxylases (MApsd2) showed promoting effects on fatty acid synthesis. MAatg8 overexpression strain with external supply of ethanolamine significantly increased arachidonic acid (ARA)-rich triacylglycerol (TAG) and biomass synthesis in M. alpina, and the final fatty acid content increased by approximately 110% compared with that in the wild-type strain. Metabolomics and lipidomics analyses revealed that cell autophagy enhanced the recycling of preformed carbon, nitrogen, and lipid in mycelium, and the released carbon skeleton and energy were contributed to the accumulation of TAG in M. alpina. This study suggests that regulation of autophagy-related MAatg8-phosphatidylethanolamine (MAatg8-PE) conjugation system could be a promising strategy for attaining higher lipid production and biomass growth. The mechanism of autophagy in regulating nitrogen limitation-induced lipid accumulation elucidated in this study provides a reference for development of autophagy-based strategies for improving nutrient use efficiency and high value-added lipid production by oleaginous microorganism. IMPORTANCE Studies have indicated that functional oil accumulation occurs in oleaginous microorganisms under nitrogen limitation. However, until now, large-scale application of nitrogen-deficiency strategies was limited by low biomass. Therefore, the identification of the critical nodes of nitrogen deficiency-induced lipid accumulation is urgently needed to further guide functional oil production. The significance of our research is in uncovering the function of cell autophagy in the ARA-rich TAG accumulation of oleaginous fungus M. alpina and demonstrating the feasibility of improving lipid production based on an autophagy regulation strategy at the molecular and omics levels. Our study proves that regulation of cell autophagy through the MAatg8-PE conjugation system-related gene overexpression or exogenous supply of ethanolamine would be an efficient strategy to increase and maintain biomass productivity when high TAG content is obtained under nitrogen deficiency, which could be useful for the development of new strategies that will achieve more biomass and maximal lipid productivity.


Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study.
Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β=4.6, 95% CI 0.5, 8.7) and BDE-153 (β=4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.


Validation of a mass spectrometry method to quantify oak ellagitannins in wine samples.
Detection and individual quantification of oak wood ellagitannins in oak barrel aged red wine samples are difficult mainly due to their low levels and the similarity between their structures. In this work, a quantification method using mass spectrometry has been developed and validated to quantify wine ellagitannins after sample fractionation with a previously reported method. The use of an internal standard is a requirement to correct mass signal variability. (-)-Gallocatechin, among the different tested compounds, was the only one that proved to be a suitable internal standard making possible the accurate and individual quantification of the main oak wood ellagitannins. The developed methodology has been used to detect and quantify these ellagitannins in different Spanish commercial wines, proving its usefulness.


[Thrombophilias associated with cerebral venous thrombosis].
Many coagulation disorders have been associated with cerebral venous thrombosis. These disorders may be primary like protein C and S deficiency, antithrombine III deficiency and activated protein C resistance. Antiphospholipid antibodies represent an acquired disorders of coagulation. A prothrombotic state induced by more common factor including oral contraceptive, pregnancy and puerperium increases the venous thrombosis risk.


Light- and Manganese-Initiated Borylation of Aryl Diazonium Salts: Mechanistic Insight on the Ultrafast Time-Scale Revealed by Time-Resolved Spectroscopic Analysis.
Manganese-mediated borylation of aryl/heteroaryl diazonium salts emerges as a general and versatile synthetic methodology for the synthesis of the corresponding boronate esters. The reaction proved an ideal testing ground for delineating the Mn species responsible for the photochemical reaction processes, that is, involving either Mn radical or Mn cationic species, which is dependent on the presence of a suitably strong oxidant. Our findings are important for a plethora of processes employing Mn-containing carbonyl species as initiators and/or catalysts, which have considerable potential in synthetic applications.


Effects of exposure to environmental tobacco smoke on reproductive health.
The scientific evidence on the effects of preconceptional and prenatal exposure to environmental tobacco smoke on reproductive health is reviewed in this article. The evidence is the most convincing for the adverse effects of environmental tobacco smoke on birthweight. In meta-analyses, exposure to environmental tobacco smoke has been estimated to reduce mean birthweight by about 25-40 grams. The majority of the studies on low birthweight also show a moderately or slightly increased risk among infants of exposed women. There is also some support for an association between high exposure to environmental tobacco smoke and preterm birth. The evidence on the effects of environmental tobacco smoke on spontaneous abortion and birth defects is weak and inconsistent. Very little is known about the impact of exposure on fertility, menstrual function, reproductive health of men, and childhood cancer. Further studies, paying attention to study design and careful exposure assessment, are therefore needed on these associations.


Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen metabolites and endothelial function in Japanese patients: The GREAT clinical study.
Patients with growth hormone deficiency (GHD) have an increased risk of atherosclerosis and vascular mortality. Evidence suggests that endothelial dysfunction is involved in all stages of atherogenesis. This study examined the effect of growth hormone (GH) replacement therapy on diacron-reactive oxygen metabolites (d-ROMs) and endothelial function in Japanese patients with GHD, using peripheral arterial tonometry. This was an open-label, prospective, case-control study. Nine patients with GHD who had not previously received any GH replacement therapy were enrolled. The following parameters were evaluated at baseline (before treatment), and after 24 weeks of GH replacement therapy: endothelial function using the reactive hyperemia index (RHI; EndoPAT® system), d-ROMs, blood pressure, and fasting lipid levels. Plasma GH and insulin-like growth factor-1 (IGF-1) levels were measured at baseline and after 24 weeks of GH replacement therapy. We also enrolled eight controls with pituitary disease but no GH deficiency. Over 24 weeks of GH replacement therapy, the serum IGF-1 levels normalized with significant improvement in the RHI (from 1.65 ± 0.33 to 1.92 ± 0.26, p < 0.05) and decreased d-ROM levels (from 356.8 ± 64.1 to 303.1 ± 43.3 U.CARR, p < 0.05). There were no significant improvements in the RHI or d-ROM levels in controls. GH replacement therapy in Japanese patients with GHD may be mediated by the reduced oxidative stress and the d-ROMs associated with the treatment.


Serotonergic modulation of dopamine neurotransmission: a mechanism for enhancing therapeutics in schizophrenia.
Although the principal mechanism by which all antipsychotic drugs act is the blockade of dopamine D-2 receptors, typical antipsychotics given in doses within the clinically effective range induce extrapyramidal symptoms (EPS). Serotonin Hydroxytryptamine, 5-HT can modulate the activity of dopaminergic neurons, while the activity of atypical antipsychotic agent towards serotonin receptors is involved in the ability of these agents to produce fewer EPS. In order to extend therapeutics in schizophrenia, it is important to examine the serotonergic modulation of neuroleptic activity. This review analyzes differences in neurochemical, behavioral and pharmacological profiles of typical and atypical antipsychotics and the role of serotonin receptors in the attenuation of EPS-induced by the typical neuroleptics. In addition to blocking dopamine receptors, the atypical antipsychotics also have affinities for serotonin receptors. Serotonergic modulation of motor activity appears primarily of inhibitory type. Stimulation of somatodendritic 5-HT-1A receptors decreases the availability of 5-HT at inhibitory 5-HT-2C receptors located on dopaminergic neurons to attenuate acute parkinsonian-like effects of typical antipsychotics. An increase in the effectiveness of pre and postsynaptic 5-HT-1A receptors following long-term administration of haloperidol raises the possibility that 5-HT agonists may also prove useful for the alleviation of late appearing tardive dyskinesias. Clinicians can now apply the knowledge of serotonergic modulation of neuroleptic action to the treatment of schizophrenic patients by using selected serotonergic anxiolytics and antidepressants as adjuvants in the treatment of schizophrenia.


Equilibrium, kinetic and solvent effect studies on the reactions of [RuIII(Hedta)(H2O)] with thiols.
The interaction of [Ru(III)(edta)(H(2)O)](-) with a series of selected thiols having extra functional groups was investigated potentiometrically and kinetically. The pK(a) values of the uncoordinated carboxylic acid group and coordinated water molecule are 3.12 and 7.41, respectively, in aqueous solution at 25 degrees C and 0.1 M ionic strength. The formation constants of the complexes were determined in the pH range 3-9, and the concentration distribution of the various complex species was evaluated as a function of pH. The effect of dioxane on the pK(a) values of [Ru(III)(Hedta)(H(2)O)] and the formation constants of the corresponding thiol complexes is presented. The study also provides mechanistic information on the reaction of [Ru(III)(edta)(H(2)O)](-) with the thiols. The low values of DeltaH(not equal) and negative values of DeltaS(not equal) and DeltaV(not equal) for the substitution reactions of [Ru(III)(edta)(H(2)O)](-) clearly support the associative character of the substitution process.


Mutagenesis and phenotyping resources in zebrafish for studying development and human disease.
The zebrafish (Danio rerio) is an important model organism for studying development and human disease. The zebrafish has an excellent reference genome and the functions of hundreds of genes have been tested using both forward and reverse genetic approaches. Recent years have seen an increasing number of large-scale mutagenesis projects and the number of mutants or gene knockouts in zebrafish has increased rapidly, including for the first time conditional knockout technologies. In addition, targeted mutagenesis techniques such as zinc finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short sequences (CRISPR) or CRISPR-associated (Cas), have all been shown to effectively target zebrafish genes as well as the first reported germline homologous recombination, further expanding the utility and power of zebrafish genetics. Given this explosion of mutagenesis resources, it is now possible to perform systematic, high-throughput phenotype analysis of all zebrafish gene knockouts.


[Dose distribution during irradiation of the retrobulbar space--results of measurements on a phantom].
The transverse dose distribution in case of X-ray and cobalt irradiation of the retrobulbar space was measured in a water phantom. As expected, the crystalline lens receives a smaller dose by cobalt irradiation with lead shielding in front of the eye than by X-irradiation. In case of cobalt irradiation, the dorsal portions lying within the hypophyseal region can only be sufficiently protected by a special block cast by us in a divergent form and surrounding the irradiation field. If X-ray irradiation is performed with a field size of 2 X 4 cm2, the 50% isodose encloses just the complete retrobulbar space. Taking into consideration a second contralateral field, the crystalline lens is exposed to less than 10% of the maximum dose. Thus the doses applied usually in radiotherapy of endocrine ophthalmopathy, i.e. 15 to 20 Gy, lead to an unproblematic crystalline lens exposure of 150 to 200 rad.


Healthcare worker choice and low back force between self-chosen and highest bed height when boosting a patient up in bed.
Healthcare workers have a high rate of low back injury due to patient handling tasks. These workers receive training in patient handling methods such as adjusting bed height, but often ignore them. In this study, 35 healthcare workers completed patient boosts at a self-chosen bed height and again with the bed in a higher standardised position. Motion capture and force data were collected for analysis. Given the choice, less than half of participants adjusted the bed at all and none of them moved the bed to the highest position (99.1 cm). The self-chosen bed position yielded significantly higher low back force than the higher position at L4-L5 and L5-S1 (p = 0.02, p = 0.01 respectively). Low back forces can be reduced by raising the bed prior to engaging in patient handling tasks, which is a simple step that can reduce forces placed on healthcare workers' low backs. Practitioner summary: Healthcare workers experience high rates of low back pain secondary to patient handling tasks. In this cross-sectional crossover study, healthcare workers consistently chose a low bed height when boosting a patient, which resulted in higher low back loads compared to the highest bed height.


Dietary intakes of children with Crohn's disease.
Approximately 25 % of individuals with Crohn's disease (CD), a life-long relapsing-remitting disease, are diagnosed during childhood and adolescence. Symptoms of CD, including abdominal pain, nausea and diarrhoea, can lead to reduced food intake, which may negatively have an impact on nutritional status during this critical period of growth and development. The aims of the present study were to assess the growth and adequacy of dietary intakes of children with CD at Sydney Children's Hospital, Randwick, and compare with healthy controls. Sixty-three subjects aged 10-16 years were recruited, including: children with active CD (n 18), children with CD in remission (n 23) and healthy controls (n 22). Dietary intake was assessed using a FFQ and compared with current Australian recommended dietary intakes (RDI). Growth and dietary intakes were compared between groups. Subjects with active CD had lower weight and BMI Z scores than children in remission and controls. The energy intakes of children with active CD and those in remission were significantly lower than estimated energy requirements (P = 0.001 and P = 0.03 respectively). Children with active CD did not meet the RDI for Fe and their Ca intake was lower than the RDI (P = 0.04). In conclusion, the dietary intake of children with active CD was impaired, with inadequate intakes of energy, Ca and Fe. Reduced energy intakes during active disease may contribute to poor weight gain and impaired growth. Quantifying nutrient intake and ascertaining requirements for nutritional supplementation are essential components of successful management in paediatric CD.


The Limitation of Randomized Control Trials on the Influence of Acupuncture and In Vitro Fertilization: A Literature Review.
Objective: Acupuncture has gained popularity among patients undergoing in vitro fertilization (IVF). However, the beneficial effect of acupuncture for improving IVF success is controversial and debatable. Given that different meta-analyses have come to different conclusions, it is crucial to explore the clinical trials in more detail. This literature review examined the limitation of randomized controlled trials (RCTs) on the influence of acupuncture in IVF. Methods: This review began with 844 studies. The inclusion criteria were studies that had acupuncture treatments in conjunction with IVF. After exclusion criteria were applied, the final number of peer-reviewed studies was 10. Results: There were substantial variations in the results of the 10 RCTs. This seemed to suggest that acupuncture was not effective in conjunction with IVF treatment. However, limitations emerged that might explain these variations in results. Such limitations include timing of acupuncture and point selections; acupuncture not performed by experienced licensed acupuncturists; lack of Traditional Chinese Medicine diagnoses and fixed protocols causing biases; acupuncture dosages; and using sham acupuncture as a control. Conclusions: There is an urgent need for further research into the effectiveness of acupuncture for improving IVF outcomes. This review provides insight into this complex and controversial topic, revealing limitations of the clinical trials that led to different conclusions. If future research can examine acupuncture treatment carefully to resemble real-world clinical practice-having appropriate controls and individualized acupuncture treatments-increasingly positive effects from acupuncture in IVF may be expected.


Isolation and Antibiotic Resistant Research of Tetragenococcus halophilus from Xuanwei Ham, A China High-Salt-Fermented Meat Products.
We assessed the prevalence of antibiotic resistant and antibiotic resistance genes for 49 Tetragenococcus halophilus (T. halophilus) strains isolated from Xuawei ham in China. The antibiotic resistance phenotype was detected by the Bauer-Kirby (K-B) method and the results showed that 49 isolates can be considered completely susceptible to penicillin, ampicillin, amoxicillin, cefradine, cefotaxime, tetracyclines, minocycline, doxycycline, and vancomycin, but resistant to gentamicin, streptomycin, neomycin, polymyxinB, cotrimoxazole. This resistance was sufficiently high to consider the potential for acquisition of transmissible determinants. A total of 32 isolates were resistant to ofloxacin, 4 isolates were resistant to ciprofloxacin and chloramphenicol, and 2 isolates were resistant to ceftazidime and ticarcillin. The antibiotic resistance genes were detected by routine polymerase chain reaction (PCR). Among the 26 antibiotic resistance genes, 5 varieties of antibiotic resistance genes, including acrB, blaTEM, AAda1, SulII, and GyrB were detected and the detection rates were 89.79%, 47.7%, 16.33%, 77.55%, and 75.51%, respectively. The potential acquisition of transmissible determinants for antibiotic resistance and antibiotic resistance genes identified in this study necessitate the need for a thorough antibiotic resistance safety assessment of T. halophilus before it can be considered for use in food fermentation processes.


Arabidopsis GOLD36/MVP1/ERMO3 Is Required for Powdery Mildew Penetration Resistance and Proper Targeting of the PEN3 Transporter.
The Arabidopsis PENETRATION 3 (PEN3) ATP binding cassette (ABC) transporter contributes to penetration resistance against nonadapted powdery mildew fungi and is targeted to papillae deposited at sites of interaction with the fungus. Timely recruitment of PEN3 and other components of penetration resistance to the host-pathogen interface is important for successful defense against this biotrophic pathogen. A forward genetic screen was previously carried out to identify Arabidopsis mutants that mistarget the PEN3 transporter or fail to accumulate PEN3 at sites of attempted powdery mildew penetration. This study focuses on PEN3 mistargeting in the aberrant localization of PEN3 4 (alp4) mutant and identification of the causal gene. In the alp4 mutant, PEN3 accumulates within the endomembrane system in an apparently abnormal endoplasmic reticulum and is not exported into papillae at powdery mildew penetration sites. This targeting defect compromises defenses at the host-pathogen interface, resulting in increased penetration success by a nonadapted powdery mildew. Genetic mapping identified alp4 as an allele of GOLGI DEFECTS 36 (GOLD36), a gene encoding a GDSL-lipase/esterase family protein that is involved in maintaining normal morphology and organization of multiple endomembrane compartments. Genetic complementation confirmed that mutation in GOLD36 is responsible for the PEN3 targeting and powdery mildew penetration resistance defects in alp4. These results reinforce the importance of endomembrane trafficking in resistance to haustorium-forming phytopathogens such as powdery mildew fungi.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Implant Supported Fixed Dental Prostheses Using a New Monotype Zirconia Implant-A Case Report.
Currently, titanium or specific titanium alloys are the most often used materials for the fabrication of dental implants. Many studies have confirmed the osseointegrative capacity and clinical long-term performance of moderately rough titanium implants. However, disadvantages have also been reported with regard to peri-implant infections and the titanium metal properties. Tooth colored ceramic implants have attracted the interest of clinicians since the end of the 1960s. Initially, alumina was used for the fabrication of ceramic implants; however, due to the poor biomechanical properties, alumina implants are not commercially available any more. Since end of the 1990s, zirconia has been established in dentistry due to its superior biomechanical properties compared to other oxide ceramics such as alumina. Currently, zirconia is the material of choice for the fabrication of ceramic implants. Zirconia implants show superior biocompatibility compared to titanium and other metals. Additionally, it has been reported that zirconia implants with a micro-rough surface topography show at least a comparable osseointegrative capacity and similar clinical survival rates to moderately rough titanium implants. The present case reports a fixed implant-supported reconstruction of a large edentulous space with compromised local bone conditions using new monotype zirconia dental implants with a micro-rough surface topography.


The role of cell-mediated immunity against influenza and its implications for vaccine evaluation.
Influenza vaccines remain the most effective tools to prevent flu and its complications. Trivalent or quadrivalent inactivated influenza vaccines primarily elicit antibodies towards haemagglutinin and neuraminidase. These vaccines fail to induce high protective efficacy, in particular in older adults and immunocompromised individuals and require annual updates to keep up with evolving influenza strains (antigenic drift). Vaccine efficacy declines when there is a mismatch between its content and circulating strains. Current correlates of protection are merely based on serological parameters determined by haemagglutination inhibition or single radial haemolysis assays. However, there is ample evidence showing that these serological correlates of protection can both over- or underestimate the protective efficacy of influenza vaccines. Next-generation universal influenza vaccines that induce cross-reactive cellular immune responses (CD4+ and/or CD8+ T-cell responses) against conserved epitopes may overcome some of the shortcomings of the current inactivated vaccines by eliciting broader protection that lasts for several influenza seasons and potentially enhances pandemic preparedness. Assessment of cellular immune responses in clinical trials that evaluate the immunogenicity of these new generation vaccines is thus of utmost importance. Moreover, studies are needed to examine whether these cross-reactive cellular immune responses can be considered as new or complementary correlates of protection in the evaluation of traditional and next-generation influenza vaccines. An overview of the assays that can be applied to measure cell-mediated immune responses to influenza with their strengths and weaknesses is provided here.


FireStem2D--a two-dimensional heat transfer model for simulating tree stem injury in fires.
FireStem2D, a software tool for predicting tree stem heating and injury in forest fires, is a physically-based, two-dimensional model of stem thermodynamics that results from heating at the bark surface. It builds on an earlier one-dimensional model (FireStem) and provides improved capabilities for predicting fire-induced mortality and injury before a fire occurs by resolving stem moisture loss, temperatures through the stem, degree of bark charring, and necrotic depth around the stem. We present the results of numerical parameterization and model evaluation experiments for FireStem2D that simulate laboratory stem-heating experiments of 52 tree sections from 25 trees. We also conducted a set of virtual sensitivity analysis experiments to test the effects of unevenness of heating around the stem and with aboveground height using data from two studies: a low-intensity surface fire and a more intense crown fire. The model allows for improved understanding and prediction of the effects of wildland fire on injury and mortality of trees of different species and sizes.


A new technique for rigid gas permeable contact lens fitting following penetrating keratoplasty.
To evaluate a new, rigid gas permeable contact lens fitting technique following penetrating keratoplasty. For the correction of postoperative anisometropia or astigmatism, a rigid gas permeable, tetra-curve contact lens with an overall diameter of 12.0 mm and a back optic zone diameter of 8.5 mm was fitted in 36 eyes of 33 patients, 7 months after penetrating keratoplasty. The contact lens back optic zone radius was selected using the videokeratography values over the elevated edges of the transplant wound (with the sutures in place). Graft clarity, visual outcome, and corneal topography were evaluated up to 3 years after surgery at intervals of 6 months. Throughout the follow-up period (range 6-36, mean 19.3+/-sd 11.8 months), all grafts remained clear. Mean contact lens daily wearing time averaged 13.6 (+/- sd 4.7) hours. Mean best-corrected visual acuity improved from +0.36 (+/- sd 0.18) LogMAR with spectacles to +0.11 (+/- sd 0.11) LogMAR with contact lenses (p < 0.0001). One patient was excluded from the study due to a lack of motivation and one had an adverse reaction to the stitches. To improve the visual performance following penetrating keratoplasty, the described fitting technique, guided by videokeratography, eased selection of the back optic zone radius of the initial trial lens. The large diameter contact lenses with a tetra-curve design were well tolerated in all patients for more than 13 hours daily.


Fibronectin Adherent Cell Populations Derived From Avascular and Vascular Regions of the Meniscus Have Enhanced Clonogenicity and Differentiation Potential Under Physioxia.
The meniscus is composed of an avascular inner region and vascular outer region. The vascular region has been shown to contain a progenitor population with multilineage differentiation capacity. Strategies facilitating the isolation and propagation of these progenitors can be used to develop cell-based meniscal therapies. Differential adhesion to fibronectin has been used to isolate progenitor populations from cartilage, while low oxygen or physioxia (2% oxygen) enhances the meniscal phenotype. This study aimed to isolate progenitor populations from the avascular and vascular meniscus using differential fibronectin adherence and examine their clonogenicity and differentiation potential under hyperoxia (20% oxygen) and physioxia (2% oxygen). Human vascular and avascular meniscus cells were seeded onto fibronectin-coated dishes for a short period and monitored for colony formation under either hyperoxia or physioxia. Non-fibronectin adherent meniscus cells were also expanded under both oxygen tension. Individual fibronectin adherent colonies were isolated and further expanded, until approximately ten population doublings (passage 3), whereby they underwent chondrogenic, osteogenic, and adipogenic differentiation. Physioxia enhances clonogenicity of vascular and avascular meniscus cells on plastic or fibronectin-coated plates. Combined differential fibronectin adhesion and physioxia isolated a progenitor population from both meniscus regions with trilineage differentiation potential compared to equivalent hyperoxia progenitors. Physioxia isolated progenitors had a significantly enhanced meniscus matrix content without the presence of collagen X. These results demonstrate that combined physioxia and fibronectin adherence can isolate and propagate a meniscus progenitor population that can potentially be used to treat meniscal tears or defects.


Experimental autoimmune glomerulonephritis in rats by soluble isologous or homologous antigens from glomerular and tubular basement membranes.
Experimental autoimmune glomerulonephritis was induced in inbred WKY/NCrj rats and Wistar (closed colony) rats by a single injection of isologous or homologous soluble antigens from glomerular and tubular basement membranes. Glomerular and tubular basement membranes were trypsin digested and applied to an affinity column to which rabbit antibodies to bovine nephritogenic antigen had been coupled. The adsorbed fraction was nephritogenic when it was injected into rat footpads with Freund's complete adjuvant. Glomerulonephritis with long-lasting proteinuria and haematuria developed 2 to 3 weeks after the injection, and it was characterized histologically by endocapillary hypercellularity of mononuclear cells, capsular adhesion, sclerosis of capillary tufts, and crescent formation. Immunofluorescence study revealed the linear deposition of rat IgG along the glomerular basement membrane. Some rats with the nephritis had pulmonary hemorrhage. These results suggest that this experimental model is similar to the experimental glomerulonephritis induced in rats by bovine nephritogenic antigen, and to human anti-glomerular basement membrane antibody-induced glomerulonephritis including Goodpasture's syndrome.


Tactile signage leads the way.
As implementation of Part III of the 1995 Disability Discrimination Act draws closer, service providers are looking to their obligations and how they can fulfil them in a cost-effective way. Most sighted people assume that blind or visually impaired people read Braille and therefore Braille signage is a perfectly adequate measure. In fact this is a misconception.


Transforming Nursing Students' Attitudes Toward End-of-Life Care.
End-of-life care is an important nursing competency and must be incorporated into the baccalaureate nursing curriculum. The purpose of this research was to examine the outcomes of an actual hospice compared with a simulated hospice clinical experience. This pretest and posttest nonequivalent 2-group design consisted of a sample of 65 undergraduate nursing students enrolled in a community health course. All students enrolled in the community health course have 1 day for hospice experience and a 2-hour orientation from the nurse educator at a local hospice agency. Students enrolled in the first 7 weeks were paired with a hospice nurse and conducted home visits. Students enrolled in the second 7-week session participated in 2 simulated hospice clinical experiences on campus. Thirty-two students were in the simulated hospice group and 33 were in the home hospice group. Attitudes toward end-of-life care were measured before and after the intervention with the Frommelt Attitudes Toward Care of the Dying. The findings indicated positive attitude changes toward end-of-life care. After the hospice clinical experience, both groups seemed to show increases in their mean Frommelt Attitudes Toward Care of the Dying scores, possibly indicating a greater comfort with caring for dying patients.


Serum enzymes in diseases of the thyroid gland.
Serum enzyme assays have been carried out in 66 patients suffering from diseases of the thyroid gland. Sixty per cent. of the hypothyroid patients had increased levels of aldolase and glutamic oxaloacetic transaminase, and 90% had high activities of creatine kinase. The significance of these findings, especially with regard to creatine kinase, is discussed.


How can we maximize the use of our operating lists? An analysis of factors influencing theatre efficiency in oculoplastic day surgery.
Operating theatre utilization has become the principal measure of NHS operating theatre service performance. We analysed data from oculoplastic theatres in a tertiary centre to identify factors influencing theatre efficiency. We conducted three audits on operating theatre utilization in 2011, 2014 and 2015. Data was collected from real time information entered into the hospital database, including time of arrival, induction, first cut and close of operation. The primary outcome measure was the operating list utilization rate, a combined value of anaesthetic and surgical time as a proportion of the total planned session time. The initial 2011 audit recorded an operating list utilization rate of 81.2%. However, this dropped to 64.5% in 2014 following new management and a move to a new theatre suite. Analysis of the factors contributing to poor theatre efficiency led to changes that streamlined the patient pathway, including standardized case scheduling and reducing staggered patient arrival. A 2015 reaudit analyzing the effects of these changes demonstrated an increase in the operating list utilization rate to 78%. It was significantly higher (p < 0.01) for whole-day lists (85%) compared to half-day lists (75%), suggesting that whole-day lists were more efficient. Operating theatres are a valuable resource and the factors affecting theatre efficiency within our unit are common and will be relevant to units elsewhere. Correcting them can lead to significant improvements in patient care. Data from this study may provide a benchmark for other units in the United Kingdom.


Antiproliferative and erythroid differentiation of piperazine and triphenyl derivatives against k-562 human chronic myelogenous leukemia.
Five piperazine derivatives (S)-4-benzyl-1-(4-bromo-3-methylphenyl)-2 methylpiperazine (A), (S)-1-benzyl-3-isobutylpiperazine-2,5-dione (B), (S)-1-benzyl-3 methylpiperazine-2,5-dione (C), (S)-1,3-dibenzylpiperazine-2,5-dione (D), (E)-1-(3-methyl 4-((E)-3-(2-methylpropylidene) piperazin-1-yl) phenyl)-2-(2 methylpropylidene) piperazine (E) and triphenyl derivative ammonium 2-((2,3',3''-trimethyl-[1,1':4',1''-terphenyl]-4 yl)oxy)acetate (F) were tested for inhibition of K-562 cell proliferation and for induction of erythroid differentiation. Among them, two piperazine and one triphenyl derivatives, compounds A, E, and F inhibited the proliferation of the K562 cell lines exhibiting inhibition concentration 50 (IC50) (IC50) of values 30.10±1.6, 4.60±0.4 and 25.70±1.10 μg ml(-1), respectively. If compound A and F were added to suboptimal concentrations of the established anticancer drugs cytosine arabinoside or mithramycin, pronounced synergic effects were observed.


Silicon-Based All-Dielectric Metasurface on an Iron Garnet Film for Efficient Magneto-Optical Light Modulation in Near IR Range.
All-dielectric nanostructures provide a unique low-loss platform for efficiently increasing light-matter interaction via excitation of the localized or propagating optical modes. Here, we report on the transverse magneto-optical Kerr effect enhancement in an all-dielectric metasurface based on a two-dimensional array of Si nanodisks on a cerium substituted dysprosium iron garnet thin film. We observed up to 15% light intensity modulation under TM modes excitation. The observed magneto-optical effect is nearly independent of the rotation of the light incidence plane with respect to the metasurface. Being compatible with conventional semiconductor technology, our structure holds promise for device applications, such as light modulators, magnetic and chemical sensors.


The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle.
We have determined the complete mRNA sequence of FHL3 (formerly SLIM2). We have confirmed that it is a member of the family of LIM proteins that share a similar secondary protein structure, renamed as Four-and-a-Half-LIM domain (or FHL) proteins in accordance with this structure. The "half-LIM" domain is a single zinc finger domain that may represent a subfamily of LIM domains and defines this particular family of LIM proteins. The distribution of FHL mRNA expression within a variety of murine tissues is complex. Both FHL1 and FHL3 were expressed in a number of skeletal muscles while FHL2 was expressed at high levels in cardiac muscle. Localisation of FHL3 to human chromosome 1 placed this gene in the proximity of, but not overlapping with, alleles associated with muscle diseases. FHL1 and FHL3 mRNAs were reciprocally expressed in the murine C2C12 skeletal muscle cell line and this suggested that the pattern of expression was linked to key events in myogenesis.


Method for umbilical cord blood-derived basophils by FCM.
We have devised a method for the purification of human basophils from umbilical cord blood by FCM. Umbilical cord blood was collected from six healthy, full-term deliveries. After separation of red blood cells, mononuclear cells were isolated by Ficoll-Hypaque. Six samples followed by positive selection using flowcytometry (FCM) for CD203c(+)CD45(int+) cells. Purity and recovery of cells were measured. Purity and recovery of basophils by FCM with CD203c(+)CD45(int+) markers were 95.02 +/- 2.94% and 61.42 +/- 5.95%. Cell sorting for CD203c(+)CD45(int+) cells by FCM is an improved method for obtaining pure umbilical cord blood-derived basophils. We established cord blood-derived basophil purification technique as a source from which active basophils can be isolated for immunochemical characterization.


Synthesis and biological evaluation of 2,5-bis(alkylamino)-1,4-benzoquinones.
A series of twelve 2,5-bis(alkylamino)-1,4-benzoquinones were prepared in yields ranging from 9-58% via the reaction between p-benzoquinone and various amines. The structures of the synthesized compounds were confirmed by IR, 1H- and 13C-NMR and MS analyses. The phytotoxicity of the 2,5-bis(alkylamino)-1,4-benzoquinones was evaluated against two crop species, Cucumis sativus and Sorgum bicolor, at 1.0 x 10(-3) mol/L. In general, the quinones displayed inhibitory effects on the dicotyledonous species C. sativus (7-74%). On the other hand stimulatory effects were observed on S. bicolor (monocotyledonous). Similar results were observed in the biological assays carried out with the weed species Ipomoea grandifolia (dicotyledonous) and Brachiaria decumbens (monocotyledonous). In addition, the cytotoxicity of the 2,5-bis(alkylamino)-1,4-benzoquinones was assayed against HL-60 (leukemia), MDA-MB-435 (melanoma), SF-295 (brain) and HCT-8 (colon) human cancer cell lines and human peripheral blood mononuclear cells (PBMC), as representatives of healthy cells, using a MTT and an Alamar Blue assay. Compound 12 was the most active, displaying cytotoxicity against all cancer cell lines tested.


Seasonal changes in spermatogenesis of the Japanese lesser horseshoe bat, Rhinolophus cornutus from a morphological viewpoint.
Seasonal changes in spermatogenesis of Japanese lesser horseshoe bats, Rhinolophus cornutus, captured in Aomori Prefecture (Japan) were examined by light microscopy. In March, the seminiferous tubules revealed almost no lumen. The seminiferous epithelium consisted of Sertoli cells and spermatogonia. The interstitium occupied a relatively large area. In June, the seminiferous tubules gradually increased in diameter. Lumen was clearly seen at the center of seminiferous tubules. Mitotic figures of spermatogonia and spermatocytes were occasionally recognized. Interstitium occupation was still abundant. In August, the diameter of seminiferous tubules maximized. The interstitium occupied only a small area. Active spermatogenesis was obvious at this time. Released spermatozoa were frequently observed within the expanded lumen. In October, although spermatogenesis was still active, the diameter of seminiferous tubules tended to decrease in size. In December, active spermatogenesis completely disappeared. The diameter of tubules greatly decreased. In most cases, the seminiferous epithelium contained only Sertoli cells and spermatogonia. Thus, spermatogenesis in Japanese lesser horseshoe bats occurs from the middle or late summer to the middle autumn in Aomori Prefecture. In epididymal tracts, aggregated spermatozoa were recognized throughout the year. The cytoplasm of all Leydig cells in the interstitium was positive for 3beta-hydroxysteroid dehydrogenase throughout the year.


Diversity-oriented synthesis as a tool for chemical genetics.
Chemical genetics is an approach for identifying small molecules with the ability to induce a biological phenotype or to interact with a particular gene product, and it is an emerging tool for lead generation in drug discovery. Accordingly, there is a need for efficient and versatile synthetic processes capable of generating complex and diverse molecular libraries, and Diversity-Oriented Synthesis (DOS) of small molecules is the concept of choice to give access to new chemotypes with high chemical diversity. In this review, the combination of chemical genetics and diversity-oriented synthesis to identify new chemotypes as hit compounds in chemical biology and drug discovery is reported, giving an overview of basic concepts and selected case studies.


Dim light at night interacts with intermittent hypoxia to alter cognitive and affective responses.
Obstructive sleep apnea (OSA) and dim light at night (dLAN) have both been independently associated with alterations in mood and cognition. We aimed to determine whether dLAN would interact with intermittent hypoxia (IH), a condition characteristic of OSA, to alter the behavioral, cognitive, and affective responses. Adult male mice were housed in either standard lighting conditions (14:10-h light-dark cycle; 150 lux:0 lux) or dLAN (150 lux:5 lux). Mice were then exposed to IH (15 cycles/h, 8 h/day, FiO2 nadir of 5%) for 3 wk, then tested in assays of affective and cognitive responses; brains were collected for dendritic morphology and PCR analysis. Exposure to dLAN and IH increased anxiety-like behaviors, as assessed in the open field, elevated plus maze, and the light/dark box. dLAN and IH increased depressive-like behaviors in the forced swim test. IH impaired learning and memory performance in the passive avoidance task; however, no differences were observed in spatial working memory, as assessed by y-maze or object recognition. IH combined with dLAN decreased cell body area in the CA1 and CA3 regions of the hippocampus. Overall, IH decreased apical spine density in the CA3, whereas dLAN decreased spine density in the CA1 of the hippocampus. TNF-α gene expression was not altered by IH or lighting condition, whereas VEGF expression was increased by dLAN. The combination of IH and dLAN provokes negative effects on hippocampal dendritic morphology, affect, and cognition, suggesting that limiting nighttime exposure to light in combination with other established treatments may be of benefit to patients with OSA.


Effect of cement type, relining procedure, and length of cementation on pull-out bond strength of fiber posts.
As opposed to the cementation metal posts, the cementation of fiber posts has several details that can significantly influence the success of post retention. This study evaluated the effect of the relining procedure, the cement type, and the luted length of the post on fiber posts retention. One hundred eighty bovine incisors were selected to assess post retention; after endodontic treatment, the canals were flared with diamonds burs. Post holes were prepared in lengths of 5, 7.5, and 10 mm; the fiber posts were relined with composite resin and luted with RelyX ARC, RelyX Unicem, or RelyX Luting 2. All cements are manufactured by 3M ESPE (St. Paul, MN). Samples were subjected to a pull-out bond strength test in a universal testing machine; the results (N) were submitted to a three-way analysis of variance and the Tukey post hoc test (alpha = 0.05). The improvement of post retention occurred with the increase of the post length luted into the root canal; the relining procedure improved the pull-out bond strength. RelyX Unicem and RelyX ARC showed similar values of retention, both showing higher values than RelyX Luting 2. Post length, the relining procedure, and the cement type are all important factors for improving the retention of fiber posts.


Post-transcriptional regulation of 2-acetyl-1-pyrroline (2-AP) biosynthesis pathway, silicon, and heavy metal transporters in response to Zn in fragrant rice.
Fragrant rice (Oryza sativa L.) has a high economic and nutritional value, and the application of micronutrients regulates 2-acetyl-1-pyrroline (2-AP) production, which is responsible for aroma in fragrant rice. Alternative splicing (AS) is an important post-transcriptional regulatory mechanism to generate transcript variability and proteome diversity in plants. However, no systematic investigation of AS events in response to micronutrients (Zn) has been performed in fragrant rice. Furthermore, the post-transcriptional regulation of genes involved in 2-AP biosynthesis is also not known. In this study, a comprehensive analysis of AS events under two gradients of Zn treatment in two different fragrant rice cultivars (Meixiangzhan-2 and Xiangyaxiangzhan) was performed based on RNA-seq analysis. A total of 386 and 598 significant AS events were found in Meixiangzhan-2 treated with low and high doses of Zn, respectively. In Xiangyaxiangzhan, a total of 449 and 598 significant AS events were found in low and high doses of Zn, respectively. Go analysis indicated that these genes were highly enriched in physiological processes, metabolism, and cellular processes in both cultivars. However, genotype and dose-dependent AS events were also detected in both cultivars. By comparing differential AS (DAS) events with differentially expressed genes (DEGs), we found a weak overlap among DAS and DEGs in both fragrant rice cultivars indicating that only a few genes are post-transcriptionally regulated in response to Zn treatment. We further report that Zn differentially regulates the expression of 2-AP biosynthesis-related genes in both cultivars and Zn treatment altered the editing frequency of single nucleotide polymorphism (SNPs) in the genes involved in 2-AP biosynthesis. Finally, we showed that epigenetic modifications associated with active gene transcription are generally enriched over 2-AP biosynthesis-related genes. Similar to the 2-AP pathway, we found that heavy metal transporters (genes related to silicon, iron, Zn and other metal transport) are also regulated at transcriptional and post-transcriptional levels in response to Zn in fragrant rice. Taken together, our results provide evidence of the post-transcriptional gene regulation in fragrant rice in response to Zn treatment and highlight that the 2-AP biosynthesis pathway and heavy metal transporters may also be regulated through epigenetic modifications. These findings will serve as a cornerstone for further investigation to understand the molecular mechanisms of 2-AP biosynthesis and regulation of heavy metal transporters in fragrant rice.


Clinical data retrieval: 25 years of temporal query management at the University of Vienna Medical School.
Today, many clinical information systems include analysis components which allow clinicians to apply a selection of predefined statistical functions that satisfy typical cases. They are mostly to inflexible to handle complex, non-standard problems, however. The focus of this paper, therefore, is to present an approach that enables clinicians to autonomously create ad hoc queries including temporal relations in an interactive environment. We developed the query language AMAS, which was specifically customized for users from the medical domain to flexibly retrieve and interpret temporal, clinical data. AMAS provides for a significant temporal expressiveness in data retrieval using time-stamped clinical databases and relies on an operator-operand concept for the specification of a query. Within the last 25 years, four different clinical retrieval systems have been implemented at the Department of Medical Computer Sciences, based on the AMAS query language. Currently, these systems allow access to the medical records of more than 2 million patients. Physicians of 46 different departments at the University of Vienna and Graz Medical Schools have made extensive use of these systems in the course of clinical research and patient care, executing more than 10,000 queries per year. We discuss a list of 20 issues that represent the most essential lessons we have learned in the development of the four systems mentioned above. Amongst others, our experiences indicate that the operator-operand concept allows on intuitive specification of complex, temporal queries. Further, customization to different user classes, based on their statistical background, is essential.


[Children and adolescents with mental disorders as orphans of managed care?].
Failure of incentive to investigation in infantile pharmaceutical trials has lead to insufficient supply with drugs within pediatrics and child- and adolescent psychiatry in Germany. In practice, drugs that are approved for adults are used to treat minors as a remedy. In many areas such "off label use" has become the medical standard and is therefore owed by the doctor under medical malpractice law. The principle of economy, that rules the law of public health insurance, forbids the prescription of drugs, that are not tested. However, as minors have the right to equal protection, the principle of economy can not prohibit off label use to the determent of minors. By virtue of the European orphan drug direction we can expect an improvement of drug supply in the field of pediatrics and child- and adolescent psychiatry in the long run. But meanwhile it would be unethical and unlawful to deny minors through restrictions on drug prescription a standard treatment, where the medical standard demands off label use of a pharmaceutical product.


Conservative therapy for adnexal torsion. A case report.
Adnexal torsion has traditionally been treated with oophorectomy because of the fear that untwisting the ovarian pedicle may result in a thrombotic embolus. Such a patient had bilateral adnexal torsion secondary to dermoid cysts. Since standard therapy, oophorectomy, was performed, the patient was surgically castrated. A review of the literature revealed no reported cases of a thrombotic embolus arising from the untwisting of twisted adnexa and supported conservation of the adnexa rather than routine extirpation, except when necrotic.


Simultaneous laparoscopic nephroureterectomy and robot-assisted radical cystectomy: Lessons learned from our initial experience.
In patients with high-risk bladder cancer and concomitant upper urinary tract malignancies, simultaneous cystectomy and nephroureterectomy is the principle oncological procedure of choice. Nevertheless, there are still not many reports of simultaneous robot-assisted radical cystectomy (RARC) and nephroureterectomy. Therefore, the aim of this study was to evaluate outcomes and complications of simultaneous RARC and laparoscopic nephroureterectomy in our institution. This case series evaluated our initial clinical results of 3 patients who underwent simultaneous laparoscopic unilateral nephroureterectomy and RARC with the da Vinci Xi system between 2019 and 2020 at our hospital. Demographic data, preoperative parameters, and postoperative parameters were retrospectively analyzed. All 3 patients were men whose median age was 75 years (range 73-89 years). The median total operative time was 435 minutes (range 429-484 minutes), median estimated blood loss was 377 mL (range 125-410 mL), and median hospital stay was 26 days (range 21-36 days). In all 3 cases, each trocar was used in 7 ports. The postoperative complications were stratified according to the Clavien-Dindo Classification system, and a grade 3B complication developed in 1 patient: trocar site herniation of the small bowel. We reported our initial experience of simultaneous laparoscopic nephroureterectomy and RARC. A large-scale prospective, randomized, controlled trial will be required to prove the feasibility and safety of simultaneous laparoscopic nephroureterectomy and RARC.


Cortical activity elicited by changes in auditory stimuli: different sources for the magnetic N100m and mismatch responses.
Magnetic responses to frequent and infrequent auditory stimuli, all presented in the same stimulus block in randomized order, were recorded. The standard stimuli, comprising 90% of all the stimuli, were 100-ms, 1000 Hz, 90dB sinusoidal tone bursts. There were three deviant tones, each presented at a probability of 3.3%, which differed from the standard tone on one dimension only: frequency deviant (1500 Hz), intensity deviant (67dB SPL), or duration deviant (50 ms). All mismatch fields, i.e., responses elicited by different deviants, as well as N100m to the standards and deviants, could be explained by neural activity in the supratemporal auditory cortex. The source of N100m to standards and deviants was significantly posterior to the sources for the three different mismatch fields. The mean locations of the equivalent dipoles for the different mismatch fields did not differ significantly from each other, but some differences were found for individual subjects.


The relationship between repressive and defensive coping styles and monocyte, eosinophile, and serum glucose levels: support for the opioid peptide hypothesis of repression.
The opioid peptide hypothesis of repression (1) predicts that repressive coping is associated with increased functional endorphin levels in the brain, which can result in decreased immunocompetence and hyperglycemia. In a random sample of 312 patients seen at a Yale Medical School outpatient clinic, significant main effects of coping style were found for monocyte and eosinophile counts, serum glucose levels, and self-reports of medication allergies. Specifically, repressive and defensive high-anxious patients demonstrated significantly decreased monocyte counts. In addition, repressive coping was associated with elevated eosinophile counts, serum glucose levels, and self-reported reactions to medications. This behavioral, immunologic, and endocrine profile is consistent with the opioid peptide hypothesis, which provides an integrative framework for relating the attenuated emotional experience of pain and distress characteristic of repressive coping with reduced resistance to infectious and neoplastic disease.


Monoclonal antibody against Toll-like receptor 4 attenuates ventilator-induced lung injury in rats by inhibiting MyD88- and NF-κB-dependent signaling.
The mechanisms through which mechanical ventilation causes non-infectious inflammatory diseases and lung injury are poorly understood. Animals models of this type of injury suggest that it involves signaling mediated by Toll‑like receptor (TLR)4 and 9. In this study, in order to gain further insight into the involvement of TLR4 in this type of injury, we performed in vivo and in vitro experiments to determine the mechanisms through which TLR4 triggers inflammation. We also examined whether the use of TLR4 monoclonal antibody (mAb) can alleviate this type of injury. For this purpose, rats were tracheotomized and administered intratracheal injections of anti‑TLR4 mAb or saline, and then ventilated for 4 h at a high tidal volume (HTV) of 40 ml/ kg or allowed to breathe spontaneously for the same period of time (controls). Alveolar macrophages (AMs) were isolated from the bronchoalveolar lavage fluid (BALF) of the rats and stimulated for 16 h with tumor necrosis factor (TNF)‑α in the presence or absence of anti‑TLR4 mAb. Lung injury was assessed by examining lung histopathology, lung wet/dry weight ratio, BALF total protein and cytokine levels in BALF and plasma. The mRNA and protein expression levels of TLR4, TLR9, myeloid differentiation factor 88 (Myd88) and nuclear factor (NF)‑κB were measured in cultured macrophages. Compared to the controls (spontaneous breathing), the ventilated rats exhibited greater pulmonary permeability, more severe inflammatory cell infiltration/lung edema, and higher levels of interleukin (IL)‑1β, IL‑6 and TNF‑α in BALF and plasma. The AMs from the ventilated rats expressed higher mRNA and protein levels of TLR4, TLR9, Myd88 and NF‑κB compared with the macrophages from the spontaneously breathing rats. The ventilated rats pre‑treated with anti‑TLR4 mAb exhibited markedly attenuated signs of ventilation‑induced injury, such as less lung inflammation and pulmonary edema, fewer cells in BALF, and lower levels of ILs and TNF‑α in BALF and plasma. Similarly, the TNF‑α‑dependent increases in the mRNA and protein expression of TLR4, Myd88 and NF‑κB in AMs were attenuated when TNF‑α was co‑administered with anti‑TLR4 mAb than when TNF-α was administered alone. Co‑administering anti-TLR4 mAb also reduced the TNF‑α‑dependent secretion of ILs. On the whole, our data demonstrate that TLR4 contributes significantly to ventilation‑induced lung injury by activating the Myd88/NF‑κB pathway, and pre‑treating rats with anti‑TLR4 mAb partially protects them against this type of injury by inhibiting Myd88/NF-κB signaling.