Supplementation with dietary linseed oil during peri-puberty stimulates steroidogenesis and testis development in rams.
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), such as α-linolenic acid (ALA), eicosapentaenoic acid, and docosahexaenoic acid, are involved in male reproductive function. In this study, we investigated the effects of linseed oil (LO) as a source of ALA on the steroidogenesis and changes of testicular histology in rams. Sixteen 3-month old rams during peri-puberty were randomly assigned into two groups. Eight rams were assigned as the control group, and the other received LO (4% dry matter of total diet) as the LO treatment group. After an 81-day feeding trial, the rams were slaughtered and investigated. Results revealed that compared with control group, diet containing LO did not affect body weight (36.87 ± 0.53 kg vs. 37.65 ± 0.64 kg, respectively; P = 0.361), average daily gain (227.47 ± 5.82 g vs. 237.95 ± 9.22 g, respectively; P = 0.353) and epididymis weight (40.77 ± 4.41 g vs. 45.53 ± 4.01 g, respectively; P = 0.398), however, it up-regulated PUFAs metabolism and steroidogenesis-related genes mRNA expression (P < 0.05), and increased plasma estradiol concentration (14.88 ± 0.67 pg/mL vs. 19.50 ± 1.27 pg/mL, respectively; P < 0.05). Therefore, LO stimulated seminiferous tubule development and increased the number of Sertoli cells (19.17 ± 2.14 vs. 27.2 ± 2.39, respectively; P < 0.01), germ-cell layers, as well as testis weight (148.65 ± 22.66 g vs. 249.96 ± 30.63 g, respectively; P < 0.05). All these results suggested that LO can improve testis development during peri-puberty by regulating steroidogenesis in rams' testes.


Biocompatible microemulsions and their prospective uses in drug delivery.
Efficacy of lipophilic drugs is often hindered due to their poor aqueous solubility leading to low absorption after in vivo administration. A part of the administered dose is absorbed and reaches the pharmacological site of action and the remainder causes toxicity and undesirable side effects due to unwanted biodistribution. Enhancement in drug efficacy and lowering of drug toxicity could be achieved through encapsulation and delivery of the lipophilic drugs in aqueous based delivery systems. Microemulsions are macroscopically homogeneous pseudoternary and ternary colloidal assemblies having polar and nonpolar micro domains. Their dispersed phases in nanodimension have good shelf-life (due to thermodynamic stability), large surface area, low viscosity (in some compositions), and ultraslow surface tension. These properties qualify them to be prospective drug delivery systems provided they are composed of biocompatible excipients. Due to the existence of polar, nonpolar, and interfacial microdomains, encapsulation of different kinds of drugs is possible. The review entails reports on development and characterization of biocompatible microemulsion systems and their evaluation as probable vehicles for encapsulation, stabilization, and delivery of bioactive natural products and prescription drugs.


Mutable influences on intimate partner abuse screening in health care settings: a synthesis of the literature.
For more than a decade, professional medical and nursing associations have recommended universal screening for intimate partner abuse (IPA). This review of 44 studies examines IPA screening during this period. The purposes of the review are to (a) identify mutable influences on IPA screening, (b) summarize what is known about altering these influences, and (c) outline an agenda for improving IPA screening. Evidence to date indicates that screening is not universal. Promising approaches to improvement start with provider training and relatively simple environmental adjustments. Unanswered empirical questions include "What are the essential components of effective training? Which health care providers are best positioned to screen under which circumstances? Which of the untested mutable influences will further improve IPA screening practice?" The review leads to the following practice recommendations: (a) Interventions should focus on clinicians in training (e.g., medical residents), and (b) screening approaches must be tailored to various practice settings.


Protist homologs of the meiotic Spo11 gene and topoisomerase VI reveal an evolutionary history of gene duplication and lineage-specific loss.
Spo11 is a meiotic protein of fundamental importance as it is a conserved meiosis-specific transesterase required for meiotic recombination initiation in fungi, animals, and plants. Spo11 is homologous to the archaebacterial topoisomerase VIA (Top6A) gene, and its homologs are broadly distributed among eukaryotes, with some eukaryotes having more than one homolog. However, the evolutionary relationships among these genes are unclear, with some debate as to whether eukaryotic homologs originated by lateral gene transfer. We have identified and characterized protist Spo11 homologs by degenerate polymerase chain reaction (PCR) and sequencing and by analyses of sequences from public databases. Our phylogenetic analyses show that Spo11 homologs evolved by two ancient eukaryotic gene duplication events prior to the last common ancestor of extant eukaryotes, resulting in three eukaryotic paralogs: Spo11-1, Spo11-2, and Spo11-3. Spo11-1 orthologs encode meiosis-specific proteins and are distributed broadly among eukaryotic lineages, though Spo11-1 is absent from some protists. This absence coincides with the presence of Spo11-2 orthologs, which are meiosis-specific in Arabidopsis and are found in plants, red algae, and some protists but absent in animals and fungi. Spo11-3 encodes a Top6A subunit that interacts with topoisomerase VIB (Top6B) subunits, which together play a role in vegetative growth in Arabidopsis. We identified Spo11-3 (Top6A) and Top6B homologs in plants, red algae, and a few protists, establishing a broader distribution of these genes among eukaryotes, indicating their likely vertical descent followed by lineage-specific loss.


Exploratory studies to investigate a linked prebiotic origin of RNA and coded peptides.
An introduction to the premise that RNA and genetically coded proteins should not be viewed as etiologically discrete entities in the origin of life is presented. This premise follows from the mutual interdependence of RNA and coded proteins in biology and the lack of prebiotically plausible constitutional self-assembly processes leading to either polymeric species. The RNA:coded peptides subsystem and its informational core, the genetic code, are then analysed retrosynthetically to suggest a (replicative) synthesis involving the intermediacy of aminoacyl-RNA trimers (cf. Scheme 5). A number of potential candidate aminoacyl-RNA trimers are identified (23-26; Scheme 6) and a chemical strategy to assess their validity is outlined. Experimental investigation of potential aminoacylation chemistry, nucleobase assembly and phosphate activation rules out three of the trimers but suggests that 26 is worthy of further investigation.


Chicken Intestinal Mycobiome: Initial Characterization and Its Response to Bacitracin Methylene Disalicylate.
The gastrointestinal (GI) tract harbors a diverse population of microorganisms. While much work has been focused on the characterization of the bacterial community, very little is known about the fungal community, or mycobiota, in different animal species and chickens in particular. Here, we characterized the biogeography of the mycobiota along the GI tract of day 28 broiler chicks and further examined its possible shift in response to bacitracin methylene disalicylate (BMD), a commonly used in-feed antibiotic, through Illumina sequencing of the internal transcribed spacer 2 (ITS2) region of fungal rRNA genes. Out of 124 samples sequenced, we identified a total of 468 unique fungal features that belong to four phyla and 125 genera in the GI tract. Ascomycota and Basidiomycota represented 90% to 99% of the intestinal mycobiota, with three genera, i.e., Microascus, Trichosporon, and Aspergillus, accounting for over 80% of the total fungal population in most GI segments. Furthermore, these fungal genera were dominated by Scopulariopsis brevicaulis (Scopulariopsis is the anamorph form of Microascus), Trichosporon asahii, and two Aspergillus species. We also revealed that the mycobiota are more diverse in the upper than lower GI tract. The cecal mycobiota transitioned from being S. brevicaulis dominant on day 14 to T. asahii dominant on day 28. Furthermore, 2-week feeding of 55 mg/kg BMD tended to reduce the cecal mycobiota α-diversity. Taken together, we provided a comprehensive biogeographic view and succession pattern of the chicken intestinal mycobiota and its influence by BMD. A better understanding of intestinal mycobiota may lead to the development of novel strategies to improve animal health and productivity.IMPORTANCE The intestinal microbiota is critical to host physiology, metabolism, and health. However, the fungal community has been often overlooked. Recent studies in humans have highlighted the importance of the mycobiota in obesity and disease, making it imperative that we increase our understanding of the fungal community. The significance of this study is that we revealed the spatial and temporal changes of the mycobiota in the GI tract of the chicken, a nonmammalian species. To our surprise, the chicken intestinal mycobiota is dominated by a limited number of fungal species, in contrast to the presence of hundreds of bacterial taxa in the bacteriome. Additionally, the chicken intestinal fungal community is more diverse in the upper than the lower GI tract, while the bacterial community shows an opposite pattern. Collectively, this study lays an important foundation for future work on the chicken intestinal mycobiome and its possible manipulation to enhance animal performance and disease resistance.


Photodynamic treatment of the dermatophyte Trichophyton rubrum and its microconidia with porphyrin photosensitizers.
The application of photosensitizers for the treatment of fungal infections is a new and promising development within the field of photodynamic treatment (PDT). Dermatophytes, fungi that can cause infections of the skin, hair and nails, are able to feed on keratin. Superficial mycoses are probably the most prevalent of infectious diseases in all parts of the world. One of the most important restrictions of the current therapeutic options is the return of the infection and the duration of the treatment. This is especially true in the case of infections of the nail (tinea unguium) caused by Trichophyton rubrum, an anthropophilic dermatophyte with a worldwide distribution. Recently, we demonstrated that 5,10,15-tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and deuteroporphyrin monomethylester were excellent photosensitizers toward T. rubrum when using broadband white light. This study demonstrates the photodynamic activity of these photosensitizers with red light toward both a suspension culture of T. rubrum and its isolated microconidia. The higher penetration depth of red light is important for the PDT of nail infections. In addition, we tested the photodynamic activity of a newly synthesized porphyrin, quinolino-[4,5,6,7-efg]-7-demethyl-8-deethylmesoporphyrin dimethylester, displaying a distinct peak in the red part of the spectrum. However, its photodynamic activity with red light toward a suspension culture of T. rubrum appeared to be only fungistatic. Sylsens B was the best photosensitizer toward both T. rubrum and its microconidia. A complete inactivation of the fungal spores and destruction of the fungal hyphae was found. In studies into the photostability, Sylsens B appeared to be photostable under the conditions used for fungal PDT. A promising result of this study is the demonstration of the complete degradation of the fungal hyphae in the time after the PDT and the inactivation of fungal spores, both with red light. These results offer the ingredients for a future treatment of fungal infections, including those of the nail.


Metals in cyanobacteria: analysis of the copper, nickel, cobalt and arsenic homeostasis mechanisms.
Traces of metal are required for fundamental biochemical processes, such as photosynthesis and respiration. Cyanobacteria metal homeostasis acquires an important role because the photosynthetic machinery imposes a high demand for metals, making them a limiting factor for cyanobacteria, especially in the open oceans. On the other hand, in the last two centuries, the metal concentrations in marine environments and lake sediments have increased as a result of several industrial activities. In all cases, cells have to tightly regulate uptake to maintain their intracellular concentrations below toxic levels. Mechanisms to obtain metal under limiting conditions and to protect cells from an excess of metals are present in cyanobacteria. Understanding metal homeostasis in cyanobacteria and the proteins involved will help to evaluate the use of these microorganisms in metal bioremediation. Furthermore, it will also help to understand how metal availability impacts primary production in the oceans. In this review, we will focus on copper, nickel, cobalt and arsenic (a toxic metalloid) metabolism, which has been mainly analyzed in model cyanobacterium Synechocystis sp. PCC 6803.


Air-induced anti-Markovnikov addition of secondary phosphine oxides and H-phosphinates to alkenes.
[reaction: see text] Air (oxygen) induces the addition of secondary phosphine oxides and H-phosphinates to alkenes to selectively produce the corresponding anti-Markovnikov adducts in good to high yields. Mechanistic studies show that the addition probably proceeds via a radical chain mechanism.


The effectiveness of school dental screening: a cluster-randomized control trial.
Dental screening of children in schools is undertaken in many countries. There is no evidence that this activity is effective. The objective of our study was to determine if school dental screening of children reduces untreated disease or improves attendance at the population level. A four-arm cluster-randomized controlled trial was undertaken in the northwest of England. In total, 16,864 children aged 6-9 years in 168 schools were randomly allocated to 3 test groups, which received screening according to different models, and a control, which received no intervention. There were no significant differences in caries increment in the primary and secondary dentitions or in the proportions of children attending a dentist after screening between the control group and the 3 intervention arms. School dental screening delivered according to 3 different models was not effective at reducing levels of active caries and increasing attendance in the population under study.


The peculiarities of winter wheat eyespot management under Lithuanian conditions.
Research evidence suggests that in Lithuania eyespot incidence in winter wheat crops was from 33 to 60% annually. Climatic conditions are the most important factor influencing the infection of winter wheat by eyespot. The variation of the climatic conditions (rainfall and number of rainy days) in the autumn and spring, the incidence and disease severity index (DSI%) of eyespot in winter wheat were mathematically described by a linear regression. The amount of rainfall during the autumn and spring periods until winter wheat second node stage (15 May) and eyespot incidence at soft dough stage showed a strong statistically significant liner correlation R = 0.789 (P < or = 0.01). During the summer period the amount of rainfall showed a moderate statistically significant liner correlation with disease severity index (DSI%) R = 0.550 (P < or = 0.05). To ascertain the necessity of fungicide use for eyespot control in winter wheat crops under Lithuanian conditions, field experiments were conducted over the 2008-2011 period. A significant reduction in the disease incidence and severity resulting from fungicide application was established only in 2010, when eyespot infection level was the highest. This was determined by one third higher precipitation in the autumn and spring of that year and significantly higher number of rainy days compared with other years.


Effect of a rapeseed oil substituting diet on serum lipids and lipoproteins in children and adolescents with familial hypercholesterolemia.
Familial hypercholesterolemia (FH) is a predominantly inherited disorder, which contributes to a defect of the LDL-cholesterol receptor. For adults with familial hypercholesterolemia (FH), it is known that a supplementary diet of monounsaturated fatty acids reduces elevated levels of total cholesterol and LDL-cholesterol and may further increase HDL-cholesterol. In particular the reduced intake of dietary fat reduces total serum cholesterol and LDL-cholesterol in the range of 10% to 15% and inhibits LDL-oxidation. Once the diagnosis of familial hypercholesterolemia is made in early childhood a supplementary diet with rapeseed oil should be started as early as possible to prevent development of atherosclerosis and subsequent complications. So far there are no reports of a lipid lowering diet enriched with rapeseed oil in children and adolescents. Seventeen children and young adolescents (male = 6, female = 11, ages 4 to 19 years) diagnosed with FH were enrolled in this study. They received dietary training and a classical low fat/low cholesterol diet enriched with rapeseed oil over five months. In the first two months they received orally mean 15 g/day (8-23 g/day), for the remaining three months mean 22 g/day (15-30 g/day) rapeseed oil. The calculation of the three-days dietary protocols showed the following characteristics: 29.5% calories from fat, 14.3% calories from protein and 54.6% calories from carbohydrates. The subjects had six sessions of dietary counseling, and serum lipids levels and lipoprotein(a) were estimated; each month's diet adherence was controlled by a dietitian and discussed with the patients and their families during this five-month study. During five months of rapeseed oil diet serum triglycerides decreased by 29% (119.2+/-62.8 mg/dL vs. 84.9 mean +/- 39.7 mg/dL), VLDL-cholesterol by 27% (23+/-12 mg/dL vs. 17+/-8 mg/dL), total cholesterol by 10% (233+/-35 mg/dL vs. 213+/-36 mg/dL), LDL-cholesterol by 7% (151+/-31 mg/dL vs. 142+/-31 mg/dL). HDL-cholesterol (59+/-15 mg/dL vs. 57+/-11 mg/dL) and Lp(a) (29.8+/-36.3 mg/dL vs. 32.6+/-40.7 mg/dL) were not changed significantly. The diet was well accepted; in most families a sustained change was reported. Our results indicate that in children and adolescents with FH a lipid-lowering diet with rapeseed oil has a similar effect on total serum cholesterol and LDL-cholesterol compared to classical cholesterol reduction diets (step I). However, an additional pronounced effect on lowering of triglycerides and VLDL-cholesterol can be observed.


Cas12a-Based Diagnostics for Potato Purple Top Disease Complex Associated with Infection by 'Candidatus Phytoplasma trifolii'-Related Strains.
'Candidatus Phytoplasma trifolii' is a cell wall-less phytopathogenic bacterium that infects many agriculturally important plant species such as alfalfa, clover, eggplant, pepper, potato, and tomato. The phytoplasma is responsible for repeated outbreaks of potato purple top (PPT) and potato witches' broom (PWB) that occurred along the Pacific Coast of the United States since 2002, inflicting significant economic losses. To effectively manage these phytoplasmal diseases, it is important to develop diagnostic tools for specific, sensitive, and rapid detection of the pathogens. Here we report the development of a DNA endonuclease targeted CRISPR trans reporter (DETECTR) assay that couples isothermal amplification and Cas12a transcleavage of fluorescent oligonucleotide reporter for highly sensitive and specific detection of 'Candidatus Phytoplasma trifolii'-related strains responsible for PPT and PWB. The DETECTR assay was capable of specifically detecting the 16S-23S ribosomal DNA intergenic transcribed spacer sequences from PPT- and PWB-diseased samples at the attomolar sensitivity level. Furthermore, the DETECTR strategy allows flexibility to capture assay outputs with fluorescent microplate readers or lateral flow assays for potentially high-throughput and/or field-deployable disease diagnostics.


[Effect of Wenyang Huazhuo Tongluo Recipe on Peripheral Blood Thl7/Treg Cell Balance in Systemic Sclerosis Patients].
To observe the effect of Wenyang Huazhuo Tongluo Recipe (WYHZTLR) on the proportion of T helper 17 cells (Thl7)/regulatory T cells (Treg), and serum levels of IL-17 and IL-10 in peripheral blood of systemic sclerosis (SSc) patients with yang qi insufficiency and turbidity induced collaterals blockage syndrome (YQITICBS). Totally 82 SSc patients were randomly assigned to the Western medicine group (as the control group) and the integrated Chinese and Western medicine group (as the treatment group), 41 cases in each group. All patients took methotrexate (MTX) tablet and prednisone tablet. Patients in the treatment group additionally took WYHZTLR. The treatment course for all was six consecutive months. Besides, another 70 healthy volunteers were recruited as a healthy control group (as the healthy group). Percentages of Th17 and Treg in peripheral blood were detected by flow cytometry. Serum levels of IL-17, IL-10, von Willebrand factor (vWF), aminoterminal propeptide of type l procollagen (PIIINP), and cross-linked carboxyterminal telopeptide of type I collagen ( I CTP) were measured by double antibody sandwich ELISA. The correlations between Th17/Treg and levels of vWF, PIIINP, I CTP, skin score, and disease activity index were observed by Pearson correlation analysis. The percentage of Th17 in peripheral blood, ratios of Th17/Treg, and the serum level of IL-17 were significantly higher, but the percentage of Treg and the serum level of IL-10 were significantly lower in SSc patients, when compared with those of the healthy group (P <0. 05, P <0. 01). Compared with the same group before treatment, the percentage of Thl7, ratios of Thl7/Treg, and levels of IL-17, vWF, and PIIINP all decreased in the two groups after treatment (P <0.05, P <0.01), but the percentage of Treg and the IL-10 level increased (P <0. 05, P <0. 01). Meanwhile,the level of I CTP was higher in the treatment group after treatment (P <0. 05). The improvement of all indices except the percentage of Th17 was more obvious in the treatment group than in the control group (P <0. 05, P <0. 01). The ratio of Th17/Treg was positively correlated with levels of vWF, PIIINP, skin score, and disease activity index before and after treatment respectively (P <0. 01), but with no obvious correlation with the level of I CTP (P >0. 05). WYHZTLR could achieve its therapeutic effect on SSc patients by regulating Th17/Treg imbalance, lowering levels of vWF and PIIINP, and elevating the level of I CTP.


Heat-related cardiorespiratory mortality: Effect modification by air pollution across 482 cities from 24 countries.
Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations. We investigated the effects of heat on cardiovascular and respiratory mortality and its modification by air pollution during summer months (six consecutive hottest months) in 482 locations across 24 countries. Location-specific daily death counts and exposure data (e.g., particulate matter with diameters ≤ 2.5 µm [PM2.5]) were obtained from 2000 to 2018. We used location-specific confounder-adjusted Quasi-Poisson regression with a tensor product between air temperature and the air pollutant. We extracted heat effects at low, medium, and high levels of pollutants, defined as the 5th, 50th, and 95th percentile of the location-specific pollutant concentrations. Country-specific and overall estimates were derived using a random-effects multilevel meta-analytical model. Heat was associated with increased cardiorespiratory mortality. Moreover, the heat effects were modified by elevated levels of all air pollutants in most locations, with stronger effects for respiratory than cardiovascular mortality. For example, the percent increase in respiratory mortality per increase in the 2-day average summer temperature from the 75th to the 99th percentile was 7.7% (95% Confidence Interval [CI] 7.6-7.7), 11.3% (95%CI 11.2-11.3), and 14.3% (95% CI 14.1-14.5) at low, medium, and high levels of PM2.5, respectively. Similarly, cardiovascular mortality increased by 1.6 (95%CI 1.5-1.6), 5.1 (95%CI 5.1-5.2), and 8.7 (95%CI 8.7-8.8) at low, medium, and high levels of O3, respectively. We observed considerable modification of the heat effects on cardiovascular and respiratory mortality by elevated levels of air pollutants. Therefore, mitigation measures following the new WHO Air Quality Guidelines are crucial to enhance better health and promote sustainable development.


Zinc Uptake, Photosynthetic Efficiency and Oxidative Stress in the Seagrass Cymodocea nodosa Exposed to ZnO Nanoparticles.
We characterized zinc oxide nanoparticles (ZnO NPs) by dynamic light scattering (DLS) measurements, and transmission electron microscopy (TEM), while we evaluated photosystem II (PSII) responses, Zn uptake kinetics, and hydrogen peroxide (H2O2) accumulation, in C. nodosa exposed to 5 mg L-1 and 10 mg L-1 ZnO NPs for 4 h, 12 h, 24 h, 48 h and 72 h. Four h after exposure to 10 mg L-1 ZnO NPs, we noticed a disturbance of PSII functioning that became more severe after 12 h. However, after a 24 h exposure to 10 mg L-1 ZnO NPs, we observed a hormetic response, with both time and dose as the basal stress levels needed for induction of the adaptive response. This was achieved through the reduced plastoquinone (PQ) pool, at a 12 h exposure, which mediated the generation of chloroplastic H2O2; acting as a fast acclimation signaling molecule. Nevertheless, longer treatment (48 h and 72 h) resulted in decreasing the photoprotective mechanism to dissipate excess energy as heat (NPQ) and increasing the quantum yield of non-regulated energy loss (ΦNO). This increased the formation of singlet oxygen (1O2), and decreased the fraction of open reaction centers, mostly after a 72-h exposure at 10 mg L-1 ZnO NPs due to increased Zn uptake compared to 5 mg L-1.


Genetic dissection of plant cell-wall biosynthesis.
The plant cell wall is a complex structure consisting of a variety of polymers including cellulose, xyloglucan, xylan and polygalacturonan. Biochemical and genetic analysis has made it possible to clone genes encoding cellulose synthases (CesA). A comparison of the predicted protein sequences in the Arabidopsis genome indicates that 30 divergent genes with similarity to CesAs exist. It is possible that these cellulose synthase-like (Csl) proteins do not contribute to cellulose synthesis, but rather to the synthesis of other wall polymers. A major challenge is, therefore, to assign biological function to these genes. In an effort to address this issue we have systematically identified T-DNA or transposon insertions in 17 Arabidopsis Csls. Phenotypic characterization of "knock-out" mutants includes the determination of spectroscopic profile differences in mutant cell walls from wild-type plants by Fourier-transform IR microscopy. A more precise characterization includes cell wall fractionation followed by neutral sugar composition analysis by anionic exchange chromatography.


Evaluation of the Geometric and Dosimetric Accuracy of Synthetic Computed Tomography Images for Magnetic Resonance Imaging-only Stereotactic Radiosurgery.
Introduction Stereotactic radiosurgery (SRS) plans created using synthetic computed tomography (CT) images derived from magnetic resonance imaging (MRI) data may offer the advantage of inhomogeneity correction by convolution algorithms, as is done for CT-based plans. We sought to determine and validate the clinical significance and accuracy of synthetic CT images for inhomogeneity correction in MRI-only stereotactic radiosurgery plans for treatment of brain tumors. Methods In this retrospective study, data from two patients with brain metastases and one with meningioma who underwent imaging with multiple modalities and received frameless SRS treatment were analyzed. The SRS plans were generated using a convolution algorithm to account for brain inhomogeneity using CT and synthetic CT images and compared with the original clinical TMR10 plans created using MRI images. Results Synthetic CT-derived SRS plans are comparable with CT-based plans using convolution algorithm, and for some targets, based on location, they provided better coverage and a lower maximum dose. Conclusions The results suggest similar dose delivery results for CT and synthetic CT-based treatment plans. Synthetic CT plans offered a noticeable improvement in target dose coverage and a more gradual dose fall-off relative to TMR10 MRI-based plans. The major disadvantage is a slightly increased dose (by 0.37%) to nearby healthy tissue (brainstem) for synthetic CT-based plans relative to those created using clinical MRI images, which may be a problem for patients undergoing high-dose treatment.


Clinical outcomes and quality of life in patients with Stanford type B aortic dissection after endovascular repair.
Aortic dissection is a severe and life-threatening disease that is usually linked with numerous possible complications. Stanford type B aortic dissection patients often choose endovascular repair due to its mini-invasiveness and quick recovery. This study concerns with medial-term outcome and quality of life (QoL) in patients with Stanford type B aortic dissection after endovascular repair. From January 2014 until July 2016, 40 patients with Stanford type B aortic dissection received an endovascular repair. Of the total number of patients, 35 were males (87.5%) and 5 females (12.5%), mean aged 80.9±14.1 years. The Medical Outcomes Study-Short Form-36 (MOS SF-36) was used to assess the QoL preoperatively and after endovascular repair. The first follow-up (FU) of SF-36 questionnaire (FU1) was obtained within 3.9±0.3 months after repair, and the second (FU2), 25.6±6.5 months thereafter. None of patient died during the observational period, and one patient lost to FU. SF-36 observation showed the best-scoring domain was 'Role emotion', 'Vitality' and 'Mental health' were also scored well preoperatively. Except for 'Role emotion' and 'Mental health', all remained domains were significantly improved both FU1 and FU2. Endovascular repair in patients with Stanford type B aortic dissection enables excellent clinical outcomes and QoL.


Reverse total shoulder arthroplasty.
Reverse total shoulder arthroplasty was initially approved for use in rotator cuff arthropathy and well as chronic pseudoparalysis without arthritis in patients who were not appropriate for tendon transfer reconstructions. Traditional surgical options for these patients were limited and functional results were sub-optimal and at times catastrophic. The use of reverse shoulder arthroplasty has been found to effectively restore these patients function and relieve symptoms associated with their disease. The procedure can be done through two approaches, the deltopectoral or the superolateral. Complication rates associated with the use of the prosthesis have ranged from 8-60% with more recent reports trending lower as experienced is gained. Salvage options for a failed reverse shoulder prosthesis are limited and often have significant associated disability. Indications for the use of this prosthesis continue to be evaluated including its use for revision arthroplasty, proximal humeral fracture and tumor. Careful patient selection is essential because of the significant risks associated with the procedure.


Electrochemical Flow-ELISA for Rapid and Sensitive Determination of Microcystin-LR Using Automated Sequential Injection System.
An amperometric immunoanalysis system based on monoclonal antibodies immobilized on Sepharose beads and packed into a micro-immunocolumn was developed for the quantification of microcystin-LR. Microcystin-LR (MCLR) was used as a reference microcystin variant. Inside the immunocolumn, free microcystins and microcystin-horseradish peroxidase (tracer) were sequentially captured by the immobilized antibodies, and the detection was performed electrochemically using Super AquaBlue ELISA substrate 2,2'-azinobis(3-ethylbenzothiazoline-sulfonic acid) (ABTS). The ABTS●+ generated by enzymatic oxidation of ABTS was electrochemically determined at a carbon working electrode by applying a reduction potential set at 0.4 V versus Ag/AgCl reference electrode. The peak current intensity was inversely proportional to the amount of analyte bound to the immunocolumn. The amperometric flow-ELISA system, which was automatically controlled through the CapSenzeTM (Lund, Sweden) computer software, enabled determination of MCLR as low as 0.01 µg/L. The assay time was very short (20 min for one assay cycle). In addition, the electrochemical signals were not significantly affected by possible interferences which could be present in the real samples. Along with the simplicity of automation, this makes the developed method a promising tool for use in water quality assessment.


Mixed Infection with Plasmodium falciparum and Plasmodium ovale in a Returned Traveller: the First Case in Korea.
Mixed-species malaria infections are often unrecognized or underestimated. We hereby report the first described case of mixed infection with Plasmodium falciparum and Plasmodium ovale malaria in a returned traveller in Korea. In August 2016, a 25-year-old returned traveller from Cameroon and Democratic Republic of Congo presented with fever. He was diagnosed as P. falciparum malaria and successfully treated with artesunate. And 5 weeks after the completion of treatment, he presented with fever and diagnosed as P. ovale infection. P. ovale infection is a rare cause of malaria and often shows delayed presentation due to its dormant liver stage as hypnozoites. At re-presentation, the immunochromatographic test and microscopic examinations of our patient did not reveal P. ovale, which was only detected via polymerase chain reaction (PCR) assay. This case highlights the importance of considering malaria infection even in persons who have previously received malaria treatment. It also shows the usefulness of PCR testing for diagnosing P. ovale infections, which often present with a low level of parasitaemia.


What's New in Addiction Prevention in Young People: A Literature Review of the Last Years of Research.
Rationale: Addiction prevention is a major public health problem, particularly concerning young people. Despite the consensus that primary prevention is essential, the evaluation of its impact is questioned. Objective: The objective of this paper is to assess the latest knowledge of addiction prevention programs for young people. Method: Review a collection of research articles using a keyword-based search on three databases: Pubmed, Eric, and PsycInfo. The research was carried out using three groups of keywords and the eligibility study was completed using two criteria: articles published between 2010 and 2017, and articles in refereed journals. Results: Of a total of 13,720 articles in the three databases, 32 studies were included in the review and listed in a grid with five themes: authors, type of population, total population, addictive behavior, and results. Four categories were created based on the objective of the studies: the evaluation of prevention strategies, the study of risk factors for consumption, the prevalence study and other subjects studied. The analysis of the corpus was used to establish a list of risk factors to be taken into consideration in future interventions and research. A list of key elements for performing effective interventions and future research is also proposed. Conclusion: The understanding of the prevention strategies implementation process is discussed as a central element for future research, which will combine stakeholders and researchers. The complexity of the situations and the multifactorial aspects of addiction prevention in young people require a multidisciplinary approach involving the various stakeholders and researchers.


Fall panicum (Panicum dichotomiflorum) hepatotoxicosis in horses and sheep.
Fourteen horses at a boarding stable in Virginia were diagnosed with hepatic disease and locally grown hay was implicated as the cause. Panicum dichotomiflorum, the predominant grass species in the hay, is hepatotoxic to horses. Naturally occurring cases were adult horses of various breeds. Two healthy adult horses and 2 healthy adult sheep were used in feeding trials. Blood and liver specimens collected from affected animals during the outbreak were analyzed. Some of the affected animals were treated supportively; the main intervention was hay withdrawal. Feeding trials were not blinded and no treatments were provided. Blood and liver specimens were collected and analyzed throughout the trials. Five affected animals were euthanized, whereas the others recovered. One research horse was euthanized for postmortem examination, and the other research animals recovered after hay withdrawal. All affected animals had evidence of hepatic disease with abnormally high aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP) activity. Evaluation of liver biopsy specimens disclosed mild lymphocytic and histiocytic inflammation, mild vacuolar change (hydropic degeneration), prominently clumped chromatin, and necrosis of individual hepatocytes. Severe hepatotoxicosis developed rapidly after Panicum hay exposure. Patchy hepatocyte necrosis was observed, implicating apoptosis as the mechanism of hepatotoxicosis. Absence of fibrosis in the research animals indicates that immediate withdrawal of Panicum hay should allow all but severely affected animals to recover from acute exposure.


The changing landscape of antiviral treatment of herpes zoster: a 17-year population-based cohort study.
Herpes zoster (HZ) is a common viral disease that produces a painful vesicular rash. Early use of antiviral medications is recommended, as it reduces pain and speeds healing. A population-based observational study was conducted to evaluate the changing burden of HZ in the province of Manitoba (Canada) over a period of 17 years. Administrative health care data including medical and hospital records were examined, and International Classification of Diseases, Ninth Revision, Clinical Modification and International Classification of Diseases, Tenth Revision, Clinical Modification codes were used to identify episodes of HZ between April 1, 1997 and March 31, 2014 in persons aged 20 or over. Annual age-adjusted incidence and hospitalization rates were calculated. Prescription records of HZ-diagnosed persons for acyclovir, valacyclovir, and famciclovir were used to calculate the rates and costs of antiviral treatment. There were 73,893 identified cases of HZ and 1,245 HZ-related hospitalizations between 1997 and 2013. Of these episodes, 42,270 (57.2%) were treated with antiviral medications at a total cost of $4,708,065 (CAD). The age-adjusted incidence of HZ rose from 4.67/1,000 person years in 1997/1998 to 5.67/1,000 person years in 2013/2014, a 21.9% increase. Antiviral treatment rates increased from 41.7% to 66.2% of all diagnosed episodes. Mean treatment costs per episode dropped from $127.29 in 1997/1998 to $56.06 in 2013/2014, primarily due to the introduction of generic antiviral medications. The total cost of antiviral treatment peaked in 2005/2006 at $329,935 and dropped steadily thereafter to $223,973 in 2013/2014. HZ-related hospitalization rates decreased from 3.1% to 0.9%. While both the incidence of HZ and the rates of antiviral treatment have risen substantially, the economic burden from antiviral treatment has been decreasing since a peak in 2005/2006 and was only 3.2% higher in 2013/2014 than in 1997/1998. This drop in cost is attributed to the introduction of generic antiviral drugs.


Prevalence of molecular markers of Plasmodium falciparum drug resistance in Dakar, Senegal.
As a result of the widespread resistance to chloroquine and sulphadoxine-pyrimethamine, artemisinin-based combination therapy (ACT) (including artemether-lumefantrine and artesunate-amodiaquine) has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Intermittent preventive treatments with anti-malarial drugs based on sulphadoxine-pyrimethamine are also given to children or pregnant women once per month during the transmission season. Since 2006, there have been very few reports on the susceptibility of Plasmodium falciparum to anti-malarial drugs. To estimate the prevalence of resistance to several anti-malarial drugs since the introduction of the widespread use of ACT, the presence of molecular markers associated with resistance to chloroquine and sulphadoxine-pyrimethamine was assessed in local isolates at the military hospital of Dakar. The prevalence of genetic polymorphisms in genes associated with anti-malarial drug resistance, i.e., Pfcrt, Pfdhfr, Pfdhps and Pfmdr1, and the copy number of Pfmdr1 were evaluated for a panel of 174 isolates collected from patients recruited at the military hospital of Dakar from 14 October 2009 to 19 January 2010. The Pfcrt 76T mutation was identified in 37.2% of the samples. The Pfmdr1 86Y and 184F mutations were found in 16.6% and 67.6% of the tested samples, respectively. Twenty-eight of the 29 isolates with the 86Y mutation were also mutated at codon 184. Only one isolate (0.6%) had two copies of Pfmdr1. The Pfdhfr 108N/T, 51I and 59R mutations were identified in 82.4%, 83.5% and 74.1% of the samples, respectively. The double mutant (108N and 51I) was detected in 83.5% of the isolates, and the triple mutant (108N, 51I and 59R) was detected in 75.3%. The Pfdhps 437G, 436F/A and 613S mutations were found in 40.2%, 35.1% and 1.8% of the samples, respectively. There was no double mutant (437G and 540E) or no quintuple mutant (Pfdhfr 108N, 51I and 59R and Pfdhps 437G and 540E). The prevalence of the quadruple mutant (Pfdhfr 108N, 51I and 59R and Pfdhps 437G) was 36.5%. Since 2004, the prevalence of chloroquine resistance had decreased. The prevalence of isolates with high-level pyrimethamine resistance is 83.5%. The prevalence of isolates resistant to sulphadoxine is 40.2%. However, no quintuple mutant (Pfdhfr 108N, 51I and 59R and Pfdhps 437G and 540E), which is associated with a high level of sulphadoxine-pyrimethamine resistance, has been identified to date. The resistance to amodiaquine remains moderate.


Effect of levothyroxine on total lipid profiles as assessed by analytical capillary isotachophoresis in a patient with hypothyroidism.
The patient was a 51-year-old Japanese female who had been diagnosed with hyperlipidemia. At the first medical examination, her serum levels of total cholesterol (TC) and triglyceride (TG) were 482 and 205 mg/dl, respectively. Since hyperlipidemia was not improved by pravastatin, atorvastatin or niceritrol, and since the levels of thyroid-stimulating hormone (TSH) and free T4 were 730 IU/ml and 0.3 ng/dl, respectively, the patient was diagnosed as secondary hyperlipidemia with hypothyroidism. A method for the charge isolation of lipoproteins using capillary isotachophoresis (cITP) is proposed as a clinical application because it allows us to quantitatively measure electronegative low-density lipoprotein cholesterol (LDL-C), a potent marker of coronary heart disease. After 5 months of treatment with levothyroxine, Serum TC and LDL-C levels drastically decreased without statin treatment and high-density lipoprotein cholesterol (HDL-C) increased. In the lipoprotein profiles as assessed by cITP after treatment with levothyroxin, all HDL-C subfractions were increased and fast-migrating LDL/electronegative LDL appeared to be greatly reduced after treatment, while the area under the non-modified LDL peak was increased. The cITP analysis was able to obtain more information about coronary risk factors and may be clinically useful for evaluating the effect of treatment with levothyroxine in patients with hypothyroidism and secondary hyperlipidemia.


Masking of electrical by acoustic stimuli: behavioral evidence for tonotopic organization.
When pure-tone acoustic masking stimuli of various frequencies were presented simultaneously with electrical stimuli applied to cochlear nucleus, only those maskers within a limited frequency range interfered with the detection of the electrical stimuli. The form of the masking functions obtained suggest that the electrical stimulus directly activated only a small population of neurons which were functioning in a tonotopic fashion.


Lifestyle and prevalence of dysmenorrhea among Spanish female university students.
The aim of this study was to determine the prevalence of primary dysmenorrhea in a sample of Spanish university students, and to describe their menstrual characteristics, lifestyle habits and associated risk factors. This cross-sectional study was conducted with a total of 258 young female university students recruited from the Ciudad Real Faculty of Nursing, with a mean age of 20.63± 3.32 years. An anonymous self-report questionnaire was used to collect data from students. This included sociodemographic characteristics, lifestyle habits, gynecological personal history and the severity of pain using the visual analogue scale. The statistical analysis of the data included calculation of the mean, percentages, chi-square analysis of the data and logistic regression. The prevalence of dysmenorrhea was of 74.8% (n = 193) with a mean pain severity of 6.88 (±1.71). Our results show that 38.3% of students described their menstrual pain as severe and 58% as moderate. The bivariate analysis showed statistically significant differences between students with and without dysmenorrhea: a higher proportion of women with dysmenorrhea had a greater duration of the menstruation flow (p = .003), a longer duration of the menstrual cycle (p = .046), were not using the oral contraceptive pill (p = .026) and had a family history of dysmenorrhea (p = .001). Backward step-wise binary logistic regression analysis using all the significant bivariate variables including lifestyle variables revealed the following risk factors: drinking cola drinks, duration of the menstrual flow, eating meat and having a first-degree relative affected by dysmenorrhea.


Altered expression of lysosomal associated membrane protein 1 in esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers. LAMP1, major protein components of lysosome, is primarily located on the lysosomal membrane and rarely expressed on the surface of normal cells, playing an important role in the lysosome-mediated physiological processes. Previous studies confirmed that LAMP1 showed high expression in astrocytoma. The purpose of this study was to investigate the expression levels of LAMP1 and to discuss its roles in ESCC. We collected 610 tissue samples of ESCC patients to construct tissue microarrays, which were subsequently stained by immunohistochemistry with LAMP1 antibody. After immunohistochemical staining, a total of 584 patients, including 453 men and 131 women, were analysed. The positive immunostaining was mainly located at the cytoplasm. The LAMP1 expression levels were significantly different between different T status (P<0.001), TNM stages (P<0.01) and degrees of tumor histological differentiation (P<0.001). Besides, LAMP1 expression levels were positively correlated with TNM stages (P<0.05). The higher the TNM stages, the higher the LAMP1 expression levels. Similar results also appeared in degrees of tumor histological differentiation (P<0.01), but not in ages, genders, tumor size, T status, lymphatic metastasis and tumor locations (P>0.05). LAMP1 is involved in the TNM stages and histological differentiation of the ESCC. Targeted therapy for LAMP1 may be a promising novel therapeutic strategy against poorly differentiated ESCC.


[Primary lymphoma of the thyroid gland. Diagnostic and therapeutic discussion. Apropos of 4 cases].
Non Hodgkin lymphomas (NHL) of the thyroid are rather uncommon and account for about 7.7 p.100 of the tumours of the gland. They are remarkable by their usual occurrence in patients with Hashimoto's disease and by controversy about their therapy. The clinical features and the course of four additional cases occurring in four female patients (ages ranged from 61 to 73 years) are reported. The clinical picture was that of a quickly growing diffuse or multinodular goiter, squeezing surrounding neck structures. Antithyroid antibodies were present in 3 cases; microscopical examination showed cytologic features of lymphocytic thyroiditis. Two patients died within a few months, the follow-up is about two years for the others. Two main problems are discussed. First, NHL of the thyroid usually occurs in patients with Hashimoto's disease: how to confidently recognize lymphomas by fine needle biopsy in such cases? Second, which is the best treatment? The authors think that lymphomas of the thyroid have to be considered rather as lymphomas than thyroid tumours. Therefore the cure of the disease may need chemotherapy, in some cases associated with radiotherapy according to careful staging and grading in each case.


Preemptive meloxicam achieves a better effect on postoperative pain control and similar tolerance compared with postoperative meloxicam in patients receiving arthroscopic knee surgery.
This study aimed to compare the efficacy and safety of very early preemptive meloxicam, early preemptive meloxicam, and postoperative meloxicam administration for postoperative pain relief in patients undergoing arthroscopic knee surgery (AKS). Three hundred and six patients about to receive AKS were consecutively enrolled in this randomized, controlled study and randomly allocated into three groups: very early analgesia (VEA) group, early analgesia (EA) group, and postoperative analgesia (PA) group. Pain visual analog scale (VAS) score at rest and at flexion, patient global assessment (PGA) score, consumption of rescue pethidine, and adverse events (AEs) were assessed. Pain VAS score and severity at rest/flexion were all decreased in the VEA group compared with EA group and PA group at 4 h post-operation and were also reduced in the VEA and EA groups compared with the PA group at 8 h and 12 h post-operation. PGA score was lower in the VEA group compared with the EA group and PA group at 4 h post-operation, and was attenuated in the VEA group and the EA group compared with the PA group at 8 h, 12 h, and 24 h post-operation as well. Consumption of rescue pethidine was less in the VEA group than that in the PA group. In addition, no difference in the incidence of AEs was found among the VEA, EA, and PA groups. In conclusion, preemptive meloxicam is more effective in postoperative pain control and equally tolerated compared with postoperative meloxicam in patients receiving AKS.


Pyruvate kinase (PK) deficiency in Jordan.
The clinical and biochemical aspects of two cases of PK deficiency associated with chronic hemolytic anemia in two unrelated patients are reported. The residual erythrocyte PK enzymes in both patients were characterized by the recommended methods of the International Committee for Standardization in Hematology (ICSH). Patient (W.Q.) had 60% residual PK activity and may be considered homozygous on the basis of consanguinity in the family. This patient suffered from moderate hemolytic anemia that improved after splenectomy. The enzymatic properties were: low activity, moderate thermal stability, reduced affinity for phosphoenol-pyruvate (PEP), and normal electrophoretic mobility. Patient (E.O.) had 42% residual PK activity and may be considered compound heterozygous since his parents are not related. He suffered from moderate hemolytic anemia. The enzymatic properties were: low activity, moderate thermal stability, reduced affinity for PEP and minimal retardation in electrophoretic migration. Theses two cases of PK deficiency are the first to be discovered in Jordan and probably the first in any Arab country.


Risk of childhood leukaemia in the vicinity of nuclear installations--findings and recent controversies.
The identification of a local excess of cancer cases, possibly associated with ionizing radiation, always receives substantial media coverage and communication about clusters is difficult. We reviewed studies that examined the risk of leukaemia among young people near nuclear installations. An excess of leukaemia exists near some nuclear installations, at least for the reprocessing plants at Sellafield and Dounreay and the nuclear power plant Krümmel. Nonetheless, the results of multi-site studies invalidate the hypothesis of an increased risk of leukaemia related to nuclear discharge. Up until now, analytic studies have not found an explanation for the leukaemia clusters observed near certain nuclear installations. The hypothesis of an infectious aetiology associated with population mixing has been proposed, but needs to be investigated further. The review illustrates two recent examples in France (La Hague reprocessing plant) and in Germany (Krümmel power plant), where controversies developed after reports of increased leukaemia risks. These examples show the importance of recalling the current epidemiological knowledge and of using systematic recording of cases to replace the alleged excesses in a more general framework. Some elements should also be suggested from the recent French and German experiences to reinforce credibility in the results.


[Venous thrombosis of the arm consistent with a tumor of the first rib].
Enchondroma of the first rib is a rare cause of Thoracic Outlet Syndrome (TOS) manifested by deep venous thrombosis (DVT). Diagnostic difficulties and therapeutic options are discussed. DVT of the upper limb represent 2%-4% of all DVT and are divided into primary and secondary. Venous compression represents 8% of TOS and generally results from a narrowing of the costo-clavicular space. A post-thrombotic syndrome (PTS) is found in 40%-80% despite anticoagulation and rest. However following local infusion of thrombolytic agents only 10% of the subjects develop PTS. Follow-up studies reveal a complete recanalisation of the vein in 45% of the patients treated with thrombolysis, whereas it occurs in only 4% under anticoagulation alone. This favourable result is obtained at the cost of an increased risk of hemorrhagic complications (5%). The solitary enchondroma is a benign cartilaginous tumor preferentially localised in the extremities, hands and feet. A review of the literature reveals that a total of 40 cases of enchondromas have been reported so far, among which 18 were localised in the first rib. The proximity of the neuro-vascular elements and a possible malignant transformation in 2% of the cases justify the ablation of the tumor. Thrombolysis is still highly controversial but gives the best long term prognosis in young patients.


Response to therapy of papillary thyroid cancer of known BRAF status.
A dynamic risk stratification with modified initial estimated risk based on response to therapy and disease course is one of the crucial changes adopted recently by the American Thyroid Association (ATA). This approach focuses on an individualized risk-adapted approach to the management of differentiated thyroid cancer. The BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). However, the prognostic value of this mutation remains unclear. The aim of this study was to examine the relation between the BRAF V600E status in PTC and all ATA response-to-therapy categories, as well as the recurrence and persistence of both biochemical disease and structural disease. Unselected PTC cases with known BRAF status diagnosed from 2000 to 2013 and actively monitored at one institution (n=723) were reviewed retrospectively. The association between the BRAF V600E mutation and clinicopathological characteristics, ATA 2015 response-to-therapy category, recurrence after a period of no evidence of disease (NED) and persistent biochemical or structural disease, was analysed. BRAF V600E was found in 65.7% (475/723) of PTC cases. Although BRAF mutation status correlated significantly with certain clinicopathological prognostic factors, there was no correlation with any of the response-to-therapy categories. Recurrences and persistent biochemical or structural disease were not associated with BRAF status. Our data are consistent with those of other studies reporting a positive relation between BRAF V600E mutation and poor prognostic factors in PTC; however, the BRAF status did not significantly correlate with a response to therapy.


Acute kidney injury with pigment nephropathy following spider bite: a rarely reported entity in India.
Acute kidney injury (AKI) can be seen in tropical regions following bites of various venomous animals and insects. Renal failure is seen most commonly following the bite of spiders of the Loxosceles spp. Dermonecrosis, systemic inflammatory response, hemolysis, rhabdomyolysis, and direct venom-related effects are postulated as causes of AKI. We report a documented case of AKI with pigment nephropathy following the bite of a brown spider from a tropical region which is known to have many venomous animals but has no previous reports of AKI following spider bite. Whether this is due to absence of toxic spider species or underreporting needs to be determined.


Virus-resembling nano-structures for near infrared fluorescence imaging of ovarian cancer HER2 receptors.
Ovarian cancer remains the dominant cause of death due to malignancies of the female reproductive system. The capability to identify and remove all tumors during intraoperative procedures may ultimately reduce cancer recurrence, and lead to increased patient survival. The objective of this study is to investigate the effectiveness of an optical nano-structured system for targeted near infrared (NIR) imaging of ovarian cancer cells that over-express the human epidermal growth factor receptor 2 (HER2), an important biomarker associated with ovarian cancer. The nano-structured system is comprised of genome-depleted plant-infecting brome mosaic virus doped with NIR chromophore, indocyanine green, and functionalized at the surface by covalent attachment of monoclonal antibodies against the HER2 receptor. We use absorption and fluorescence spectroscopy, and dynamic light scattering to characterize the physical properties of the constructs. Using fluorescence imaging and flow cytometry, we demonstrate the effectiveness of these nano-structures for targeted NIR imaging of HER2 receptors in vitro. These functionalized nano-materials may provide a platform for NIR imaging of ovarian cancer.


Brain gamma-aminobutyric acid abnormality in tardive dyskinesia. Reduction in cerebrospinal fluid GABA levels and therapeutic response to GABA agonist treatment.
A double-blind, placebo-controlled trial of gamma-vinyl gamma-aminobutyric acid (GVG) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c) pyridine-3-ol (THIP) was carried out in drug-free schizophrenic patients with tardive dyskinesia. A significant decrease in dyskinetic symptoms occurred with the administration of GVG, associated with a twofold increase in cerebrospinal fluid levels of GABA; THIP produced a more moderate, yet consistent decrease in the involuntary movements. A pathophysiologic role for gamma-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia. A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls. These data compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.


Prognostic Impact of Nucleophosmin 1 (NPM1) Gene Mutations in Egyptian Acute Myeloid Leukemia Patients.
Somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, are the most frequent mutations in patients with acute myeloid leukemia. The aim of the study was to assess the prevalence and prognostic impact of NPM1 gene mutations in adult AML patients. Polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) were used to screen 55 AML patients for mutations of NPM1 gene. NPM1 mutations were found in 12 (21.8%) of 55 patients, significantly associated with higher total leukocytie count, marrow blast percentage (p=0.03 and p=0.02, respectively), and M5 subtype (p<0.001). Patients with NPM1 mutations had significantly higher complete remission rates (p=0.003) and a trend to lower rates of mortality, relapse and refractory disease (p=0.28, p=0.45 and p=0.08, respectively). Survival analysis showed significantly longer disease-free survival (mean 18.635±1.229 versus 11.041±1.250 months, p=0.044) and overall survival (mean 19.810±1.624 versus 12.063±1.244 months, p=0.041) in patients with NPM1 mutations compared with those without. Multivariate analyses confirmed NPM1 mutation as a significant independent predictor for disease-free survival (HR=0.066, p=0.001) and overall survival (HR=0.125, p=0.002). NPM1 mutation is a prognostic factor for a favorable outcome in Egyptian population. This finding is of major clinical importance since it strongly suggests that NPM1 mutations may allow one to divide the heterogeneous patient group of AML into prognostically different subgroups. None declared.


The biological activity of derivatives of 2-[(o-; and p-substituted)aminophenyl]-3H-5-[(o-; and p-substituted)phenyl]-7-chloro-1,4-benzodiazepines and 1-alkyl-3H-5-[(o-; and p- substituted) phenyl]-7-chloro-1,4-benzodiazepin-2-one.
Eight of a series of twelve new 2-[(o-; and p-substituted)aminophenyl]-3H-5-[(o-; and p-substituted)phenyl]-7-chloro-1,4-benzodiazepinines (VI, 1-12; Fig. 1) and two of eleven new 1-alkyl-3H-5-[(o-; and p-substituted)phenyl]-7-chloro-1,4-benzodiazepin-2-one (IV, 1-12; Fig. 2) were tested for their pharmacological and/or biological activity as anxiolytics.


The effect of serum albumin on the radiolysis of DNA studied by constant field electrophoresis and compared to alterations caused by low molecular weight OH. scavengers.
After radiolysis of calf thymus DNA in 10(-2) mol dm-3 phosphate buffer at pH7 under N2, N2O and air the yields of double-strand breaks (dsb) have been determined by constant field electrophoresis. Double-strand (dsb) breaks were formed according to a linear-quadratic relationship with dose showing a lower G-value under aerobic than under anaerobic conditions (G (air) = 1.4 nmolJ-1; G (N2) = 2.1 nmolJ-1; G (N2O) = 4.9 nmolJ-1). To test the reliability of this system the effect of low molecular weight OH. scavengers which were already used in comparable work with plasmid DNA were studied. The results with plasmid DNA and calf thymus DNA obtained by different techniques of electrophoresis agreed quite well. Under N2 more protection was obtained with ethanol than with DMSO or with t-butanol. Under air, double-strand breakage was further decreased and reached the same level with all of these scavengers. Furthermore the constant field electrophoresis gives similar results as the low-angle light scattering technique for radiation induced double strand breakage of calf thymus DNA. When BSA was used at the same scavenger capacity as the low molecular weight scavengers, the protection against double strand breakage was less if radiolysis was carried out in the presence of proteins. Under anaerobic conditions the protection factor was 13 in the presence of BSA, while with DMSO or t-butanol this factor was about 100 and with ethanol 300. In contrast to the low molecular weight OH. scavengers oxygen enhanced radiation-induced double-strand breakage with BSA. It is assumed that protein peroxyl radicals may cause strand breakage.


The association between severe fetal congenital heart defects and placental vascular malperfusion lesions.
Studies have shown an association between infant with congenital heart defects (CHD) and the risk of preeclampsia. We aimed to characterize placental histopathology from pregnancies who underwent termination of pregnancy (TOP) because of severe CHD. This was a case control study. The medical files of all TOPs due to fetal congenital malformations were reviewed. Cases with CHD included hypoplastic left heart, transposition of great arteries, AV canal, tetralogy of Fallot, double outlet RV, and coractation of aorta. The controls included TOPs due to congenital central nervous system defects (CNS group) that were matched in a 1:1 ratio, by gestational age and maternal age. Placental lesions were classified to maternal and fetal vascular malperfusion (MVM and FVM) and inflammatory lesions. Higher rates of any MVM or FVM lesion were observed in placentas from the CHD group (n = 32) as compared with the CNS group (n = 32), 40.6% versus 12.5% respectively, p = .02. As compared with the CNS group, the CHD group had more abnormal coiling of umbilical cord (p = .01). Placental vascular malperfusion lesions are more common in pregnancies complicated with CHD as compared with CNS malformations. These findings support the hypothesis of similar etiopathogenetic factors, contributing to the development of preeclampsia and CHD.


Home-based walking during pregnancy affects mood and birth outcomes among sedentary women: A randomized controlled trial.
We examined the effects of home-based walking on sedentary Japanese women's pregnancy outcomes and mood. A randomized controlled trial was conducted, involving 118 women aged 22-36 years. Participants were randomly assigned to walking intervention (n = 60) or control (n = 58) groups. The walking group was instructed to walk briskly for 30 min, three times weekly from 30 weeks' gestation until delivery. Both groups counted their daily steps using pedometers. Pregnancy and delivery outcomes were assessed, participants completed the Profile of Mood States, and we used the intention-to-treat principle. Groups showed no differences regarding pregnancy or delivery outcomes. The walking group exhibited decreased scores on the depression-dejection and confusion subscales of the Profile of Mood States. Five of the 54 women in the intervention group who remained in the study (9.2%) completed 100% of the prescribed walking program; 32 (59.3%) women completed 80% or more. Unsupervised walking improves sedentary pregnant women's mood, indicating that regular walking during pregnancy should be promoted in this group.


Prediction of beta-turns.
A residue-coupled model is proposed to predict the beta-turns in proteins. The rates of correct prediction for the 455 beta-turn tetrapeptides and 3807 non-beta-turn tetrapeptides in the training database are 94.7 and 81.3%, respectively. The rates of correct prediction for the 110 beta-turn tetrapeptides and 30,229 non-beta-turn tetrapeptides in the testing database are 80.0 and 80.2%, respectively. Compared with the rates of correct prediction based on the residue-independent model reported previously, the quality of prediction is significantly improved by the new model, implying that the residue-coupled effect along a polypeptide chain is important for the formation of reversal turns, such as beta-turns, during the process of protein folding.


First Analysis of Jupiter in Gamma Rays and a New Search for Dark Matter.
We present the first dedicated γ-ray analysis of Jupiter, using 12 years of data from the Fermi Telescope. We find no robust evidence of γ-ray emission, and set upper limits of ∼10^{-9} GeV cm^{-2} s^{-1} on the Jovian γ-ray flux. We point out that Jupiter is an advantageous dark matter (DM) target due to its large surface area (compared with other solar system planets), and cool core temperature (compared with the Sun). These properties allow Jupiter to both capture and retain lighter DM, providing a complementary probe of sub-GeV DM. We therefore identify and perform a new search for DM-sourced γ-rays in Jupiter, where DM annihilates to long-lived particles, which can escape the Jovian surface and decay into γ rays. We consequently constrain DM-proton scattering cross sections as low as about 10^{-40} cm^{2}, showing Jupiter is up to 10 orders of magnitude more sensitive than direct detection. This sensitivity is reached under the assumption that the mediator decay length is sufficient to escape Jupiter, and the equilibrium between DM capture and annihilation; sensitivities can be lower depending on the DM model. Our work motivates follow-up studies with upcoming MeV telescopes such as AMEGO and e-ASTROGAM.


A Road Not Taken: substance abuse programming in the New York City jail system.
Substance abuse represents one of the most common diagnoses in jail settings and features prominently in the path into criminal justice involvement. In addition, substance abuse plays a major role in mortality, morbidity, and recidivism after release from jail. In 2008, a substance abuse treatment program was begun within the New York City jail system, the nation's second largest. This program, A Road Not Taken (ARNT), works collaboratively with courts, security officials within the jail, and community programs to identify inmates who have substance abuse concerns and provide in-jail programming and coordination of treatment after jail. An evaluation of ARNT participants revealed that they experienced a lower rate in incarceration after their program participation than they did before participation.


Recent developments in beta-lactamase research and their implications for the future.
beta-Lactamases, major determinants of bacterial resistance to beta-lactam antibiotics, can be classified into specific molecular classes following identification of active-site amino acid or nucleotide sequences. The use of gene probes for epidemiologic purposes is becoming commoner. A semiempirical classification scheme has been proposed using substrate profiles and inhibition by clavulanic acid and aztreonam as criteria. Class 1 cephalosporinases are potently inhibited by aztreonam but poorly inhibited by clavulanate, whereas class 2 penicillinases and broad-spectrum beta-lactamases have very poor affinities for aztreonam but are inhibited by clavulanic acid. Class 3 beta-lactamases include the metalloenzymes. Resistance to beta-lactam antibiotics can be related to many beta-lactamase-mediated phenomena, including increased frequency of beta-lactamase production in clinical isolates, wider distribution of beta-lactamase-mediating plasmids, production of multiple beta-lactamases, induction of chromosomal class 1 cephalosporinases, selection of depressed mutants for production of class 1 enzymes, leakage of beta-lactamase from gram-negative organisms, functions of penicillin-binding proteins as beta-lactamases, and identification of novel beta-lactamases.


[Research advances in the pathogenesis of non-alcoholic fatty liver disease-associated liver cancer].
Nonalcoholic fatty fiver disease (NAFLD) is one of the most common causes of chronic liver disease in clinical practice. It develops from simple fatty liver, nonalcoholic fatty hepatitis to liver fibrosis which may develop liver cirrhosis and result in hepatocellular carcinoma(HCC) eventually. Although studies show that many cell signaling pathways, genes and cell factors are involved in the progression and development of NAFLD related HCC, the exact mechanism underling the pathogenesis of NAFLD-HCC remains poorly understand. Here in this review, we give a summary of the recent findings at home and abroad that describe the epidemiology and pathogenesis of NAFLD associated HCC.


Inhibition of Notch signaling induces extensive intussusceptive neo-angiogenesis by recruitment of mononuclear cells.
Notch is an intercellular signaling pathway related mainly to sprouting neo-angiogenesis. The objective of our study was to evaluate the angiogenic mechanisms involved in the vascular augmentation (sprouting/intussusception) after Notch inhibition within perfused vascular beds using the chick area vasculosa and MxCreNotch1(lox/lox) mice. In vivo monitoring combined with morphological investigations demonstrated that inhibition of Notch signaling within perfused vascular beds remarkably induced intussusceptive angiogenesis (IA) with resultant dense immature capillary plexuses. The latter were characterized by 40 % increase in vascular density, pericyte detachment, enhanced vessel permeability, as well as recruitment and extravasation of mononuclear cells into the incipient transluminal pillars (quintessence of IA). Combination of Notch inhibition with injection of bone marrow-derived mononuclear cells dramatically enhanced IA with 80 % increase in vascular density and pillar number augmentation by 420 %. Additionally, there was down-regulation of ephrinB2 mRNA levels consequent to Notch inhibition. Inhibition of ephrinB2 or EphB4 signaling induced some pericyte detachment and resulted in up-regulation of VEGFRs but with neither an angiogenic response nor recruitment of mononuclear cells. Notably, Tie-2 receptor was down-regulated, and the chemotactic factors SDF-1/CXCR4 were up-regulated only due to the Notch inhibition. Disruption of Notch signaling at the fronts of developing vessels generally results in massive sprouting. On the contrary, in the already existing vascular beds, down-regulation of Notch signaling triggered rapid augmentation of the vasculature predominantly by IA. Notch inhibition disturbed vessel stability and led to pericyte detachment followed by extravasation of mononuclear cells. The mononuclear cells contributed to formation of transluminal pillars with sustained IA resulting in a dense vascular plexus without concomitant vascular remodeling and maturation.


Qi-fu-yin attenuated cognitive disorders in 5xFAD mice of Alzheimer's disease animal model by regulating immunity.
Cognitive impairment is the main symptom of Alzheimer's disease (AD). Accumulating evidence implicate that immunity plays an important role in AD. Here, we investigated the effect of Qi-fu-yin (QFY) on cognitive impairment and cytokine secretion of 5xFAD mice. We used 2.5-month-old 5xFAD transgenic mice for behavioral tests to observe the changes in cognitive function after QFY treatment. After the behavioral experiment, the whole brain, cortex and plasma of each mouse were collected for soluble Aβ analysis, immunohistochemical experiment and cytokine analysis. Here we found that the treatment of QFY ameliorated the ability of object recognition, passive avoidance responses and the ability of spatial learning and memory in 5xFAD mice. The deposits of β1 - 42 and Aβ1 - 40 were alleviated and the ration of Aβ1 - 42/Aβ1 - 40 was decrease in the plasma and brain of 5xFAD mice administrated with QFY. The administration of QFY promoted the secretion of anti-inflammatory cytokines, IL-5, IL-10 and G-CSF, and reduced the content of proinflammatory cytokines IFN-γ in plasma of 5xFAD mice. Notably, we found that the treatment of QFY decreased the concentration of CCL11 in the brain and plasma of 5xFAD mice. This suggested that QFY improved cognition and reduced Aβ deposits in 5xFAD mice by regulating abnormal immunity in 5xFAD mice. QFY may be as a potential therapeutic agent for AD.


Resources for Bosonic Quantum Computational Advantage.
Quantum computers promise to dramatically outperform their classical counterparts. However, the nonclassical resources enabling such computational advantages are challenging to pinpoint, as it is not a single resource but the subtle interplay of many that can be held responsible for these potential advantages. In this Letter, we show that every bosonic quantum computation can be recast into a continuous-variable sampling computation where all computational resources are contained in the input state. Using this reduction, we derive a general classical algorithm for the strong simulation of bosonic computations, whose complexity scales with the non-Gaussian stellar rank of both the input state and the measurement setup. We further study the conditions for an efficient classical simulation of the associated continuous-variable sampling computations and identify an operational notion of non-Gaussian entanglement based on the lack of passive separability, thus clarifying the interplay of bosonic quantum computational resources such as squeezing, non-Gaussianity, and entanglement.


Presurgical evaluation of the motor hand area with functional MR imaging in patients with tumors and dysplastic lesions.
To test an optimized functional magnetic resonance (MR) imaging procedure to depict the motor hand representation area (HRA) in patients with epilepsy lesions near the central sulcus. Fast low-angle shot MR imaging was performed with an oblique single-section imaging technique in eight control subjects (10 hemispheres) and six patients (12 hemispheres). Three series of five activation images (obtained while subjects performed repetitive finger-to-thumb opposition movements) and five rest images were acquired. Each hemisphere was studied in three adjacent sections. Difference maps (obtained with simple subtraction between activation and rest images) were compared with t-test maps. In control subjects, the HRA was visible in 27 of 30 sections. Qualitatively, activation was seen better on t-test maps in 14 and on difference maps in four of these sections. In all patients, motor activation could be seen in the hemisphere that contained the lesion. This activation was considered normal in four patients. In two patients, the HRA was deformed. Functional MR imaging activation in the motor area was confirmed with Penfield stimulation in five patients. Functional MR imaging findings in the preoperative assessment of dysplastic lesions around the central sulcus are the same as for tumors. t-test maps are superior to difference maps in the treatment of motor functional MR imaging data.


Lithium toxicity in plants: Reasons, mechanisms and remediation possibilities - A review.
Lithium (Li) is a naturally occurring element; however, it is one of the non-essential metals for life. Lithium is becoming a serious matter of discussion for the people who do research on trace metals and environmental toxicity in plants. Due to limited information available regarding its mobility from soil to plants, the adverse effects of Li toxicity to plants are still unclear. This article briefly discusses issues around Li, its role and its essentiality in plants and research directions that may assist in inter-disciplinary studies to evaluate the importance of Li's toxicity. Further, potential remediation approaches will also be highlighted in this review. Briefly, Li influenced the growth of plants in both stimulation and reduction ways, depending on the concentration of Li in growth medium. On the negative side, Li reduces the plant growth by interrupting numerous physiological processes and altering metabolism in plant. The contamination of soil by Li is becoming a serious problem, which might be a threat for crop production in the near future. Additionally, lack of considerable information about the tolerance mechanisms of plants further intensifies the situation. Therefore, future research should emphasize in finding prominent and approachable solutions to minimize the entry of Li from its sources (especially from Li batteries) into the soil and food chain.


Functional K-doping of eumelanin thin films: Density functional theory and soft x-ray spectroscopy experiments in the frame of the macrocyclic protomolecule model [corrected].
We demonstrate the possibility to achieve the doping of eumelanin thin films through K(+) incorporation during the electrodeposition of the film. K-doping changes the optical properties of the eumelanin thin films, reducing the energy gap from 1.0 to 0.6 eV, with possible implications for the photophysical properties. We have identified the doping-related occupied and unoccupied electronic states and their spectral weight using resonant photoemission spectroscopy (ResPES) and x-ray absorption at the C and N K-edges (near edge x-ray absorption fine spectroscopy, NEXAFS). All data are consistently interpreted by ab initio calculations of the electronic structure within the frame of the macrocycle model developed for the eumelanin protomolecule. Our analysis puts in evidence the intercalation of K with one specific oligomer (a tetramer composed of one indolequinone and 3 hydroquinone monomers) in correspondence of the nitrogen macrocycle. The predicted variation of the tetramer spacing is also in agreement with the recent x-ray diffraction experiments. The charge donation from K to N and C atoms gives rise to new electronic states at the top of the valence band and in NEXAFS resonances of the unoccupied orbitals. The saturation of the tetramer macrocycles leaves an excess of K that bind to N and C atoms in alternative configurations, as witnessed by the occurrence of additional spectral features in the carbon-related ResPES measurements.


Binocular enhancement of visual acuity.
Using a computerized test system, we compared binocular and monocular visual optotype acuity, varying both contrast and contrast disparity between the two eyes. When contrast was the same in the two eyes, binocular acuity was better than best monocular acuity by an average of 0.045 log minimum angle of resolution, or 11%. When contrast differed in the two eyes, binocular acuity in most but not all cases was still better than the monocular acuity of the eye that received the higher contrast. This binocular advantage became smaller but remained significant as contrast disparity became larger. These results are most simply explained by threshold contrast summation of high-spatial-frequency letter components.


[Experience with the screening of pregnant women for hepatitis B virus and the vertical transmission of the virus].
The authors started the checking for the hepatitis B virus in pregnant women of the town Ajka and its surroundings 10 years ago and then they extended it over the whole county. They examined 33,433 pregnant women from 1980 to 1990 and found that 0.5% of them were HBV carrier state (that is 169 persons), while in endemic territories they found a higher rate (0.74%). The existence of vertical transmission can be proved by the positive data of 120 infancy born to 72 symptomless HBV carrier mothers. The frequency of transmission is 4%. At the beginning of the check-up they gave passive then active-passive immunisation to the children born to carrier mothers. The results of immunisation were controlled by clinical and laboratory tests. They suggest that their worked-out check-up and care model--which is unique in Hungary in its kind and is also a part of the programme to prevent cancer--should be introduced all over the country.


Clustering gene expression data using a graph-theoretic approach: an application of minimum spanning trees.
Gene expression data clustering provides a powerful tool for studying functional relationships of genes in a biological process. Identifying correlated expression patterns of genes represents the basic challenge in this clustering problem. This paper describes a new framework for representing a set of multi-dimensional gene expression data as a Minimum Spanning Tree (MST), a concept from the graph theory. A key property of this representation is that each cluster of the expression data corresponds to one subtree of the MST, which rigorously converts a multi-dimensional clustering problem to a tree partitioning problem. We have demonstrated that though the inter-data relationship is greatly simplified in the MST representation, no essential information is lost for the purpose of clustering. Two key advantages in representing a set of multi-dimensional data as an MST are: (1) the simple structure of a tree facilitates efficient implementations of rigorous clustering algorithms, which otherwise are highly computationally challenging; and (2) as an MST-based clustering does not depend on detailed geometric shape of a cluster, it can overcome many of the problems faced by classical clustering algorithms. Based on the MST representation, we have developed a number of rigorous and efficient clustering algorithms, including two with guaranteed global optimality. We have implemented these algorithms as a computer software EXpression data Clustering Analysis and VisualizATiOn Resource (EXCAVATOR). To demonstrate its effectiveness, we have tested it on three data sets, i.e. expression data from yeast Saccharomyces cerevisiae, expression data in response of human fibroblasts to serum, and Arabidopsis expression data in response to chitin elicitation. The test results are highly encouraging. EXCAVATOR is available on request from the authors.


Effective Vortioxetine Dose Varies with Extent of Antidepressant Use Across Countries.
One of the possible explanations for the antidepressant resistance is tolerance to the effect of increasing synaptic serotonin. Vortioxetine is thought to work through a combination of two pharmacological modes of action: serotonin reuptake inhibition and modification of serotonin receptor activity, in a dose-dependent manner. This mechanism of action allows for examination of the hypothesis that antidepressant non-response may be due to exposure to persistently elevated synaptic amine levels. We hypothesized that lower doses of vortioxetine, which exclusively inhibit serotonin reuptake, would not be effective in the setting of prolonged exposure to antidepressants, but higher doses, which interact in various ways to multiple post-synaptic serotonin receptors, would be relatively more effective in the setting of prolonged, prestudy antidepressant exposure. We examined the relationship between Defined Daily Dose (DDD), which is a measure of the extent of antidepressant use in each country, and the minimal effective dose of vortioxetine. There is a significant relationship between the DDD and effective vortioxetine dose (P = 0.035). In countries with high antidepressant utilization, higher doses of vortioxetine were required, and obverse was true in countries with lower antidepressant utilization. These data support the hypothesis that tolerance to serotonin reuptake inhibition drives poor antidepressant response.


Explaining the barriers to donor participation in the field of health: a qualitative study.
Iran's health system is facing increasing costs and a lack of resources. Developing the financial participation of donors is one of the ways to strengthen the financial health system. This research was done to explain the barriers to donors' participation in the field of health. This qualitative study was conducted in 2022 using semi-structured interviews with 22 experts, health donors, policymakers, and managers in Iran. The conventional content analysis method was also used for data analysis. The review and classification of the interviews showed that the participation of donors in the health system includes four main issues: the incompleteness of legal processes, the lack of continuous communication with the charity, management, and resources problems, and the insufficient awareness of the donors about the problems and needs of the health system and 18 subtopics. Donors play an important role in financing, developing resources, providing health services, and financially supporting patients in Iran's health system. Therefore, by recognizing and removing obstacles to the participation of donors, policymakers and managers of the health system should target the participation of donors with proper planning, organization, guidance, and supervision, and avoid parallel work and waste of resources.


Tree colonization by the Asian longhorn beetle, Anoplophora glabripennis (Coleoptera: Cerambycidae): effect of habitat and tree suitability.
Tree colonization and feeding activity of the invasive wood-borer Asian longhorn beetle (Anoplophora glabripennis), an Asian pest introduced into North America and Europe, was studied in a newly invaded area in Italy. The hypothesis being tested was that the reproductive success of the insect depend on habitat type and tree suitability. Adult beetles were caged on branches of host and nonhost species, in both urban and forest habitats. Two months later, number and size of feeding patches on plant tissues, eggs laid, and surviving larvae were assessed. Bark concentration of C and N was also measured from the same trees. Results indicated that the mean area of plant tissues consumed by adult feeding was significantly larger on trees growing in forest than in urban habitat, although within the same habitat there were no differences between susceptible and nonsusceptible trees. ALB tree colonization, in terms of number of eggs laid and young larvae survival, was not affected by habitat while it was higher on susceptible trees. Although trees growing in forests had a lower nitrogen concentration, they allowed colonization rates similar to those of trees growing in the urban habitat. Hence, the amount of carbon and nitrogen did not fully explain tree suitability or habitat selection. We suggest compensatory feeding as a potential mechanism that might explain this peculiar situation, as supported by a more intensive feeding activity recorded on trees in the forest. Suitability of different trees may be due to other factors, such as secondary chemical compounds.


Bibliometric analysis of global literature productivity in systemic lupus erythematosus from 2013 to 2022.
Bibliometric analysis is a mature method for quantitative evaluation of academic productivity. In view of the rapid development of research in the field of systemic lupus erythematosus (SLE) in the past decade, we used bibliometric methods to comprehensively analyze the literature in the field of SLE from 2013 to 2022. The relevant literature in the field of SLE from 2013 to 2022 was screened in the Web of Science Core Collection database. After obtaining and sorting out the data, CiteSpace and VOSviewer software were used to visualize the relevant data, and SPSS software was used for scientific statistics. A total of 18,450 publications were included in this study. The number of articles published over the past 10 years has generally shown an upward trend, while Altmetric attention scores have also shown a clear upward trend in general and in most countries. Citation analysis and Altmetric analysis can mutually prove and supplement the influence of papers. The USA, China, Japan, Italy, and the UK are the most productive countries, but China and Japan are significantly inferior to other countries in terms of research influence. Four of the top ten authors are at the center of the collaboration network. LUPUS is the most contributing journal. The theme of systemic lupus erythematosus research mainly focuses on the pathogenesis, treatment, and management of SLE, and the emerging trend is related research on machine learning and immune cells. This study shows the research status of SLE, clarifies the main contributors in this field, discusses and analyzes the research hotspots and trends in this field, and provides reference for further research in this field to promote the development of SLE research. Key Points • Through bibliometric analysis, Altmetric analysis, and visual analysis, we reveal the global productivity characteristics of SLE-related papers in the past 10 years. • The number of global SLE-related studies has shown a significant increase, indicating that SLE is still a hot topic and deserves further study. • Citation analysis and Altmetric analysis can mutually prove and supplement the influence of papers, and the attention of related literature among non-professional researchers is increasing. • The theme of SLE research mainly focuses on the pathogenesis, treatment, and management of SLE. The emerging trend is machine learning and immune cells, which may provide new strategies for the diagnosis and treatment of SLE in the future.


Silencing of ATP4B of ATPase H+/K+ Transporting Beta Subunit by Intragenic Epigenetic Alteration in Human Gastric Cancer Cells.
The ATPase H+/K+ Transporting Beta Subunit (ATP4B) encodes the β subunit of the gastric H+, K+-ATPase, which controls gastric acid secretion and is therefore a target for acid reduction. Downregulation of ATP4B was recently observed in human gastric cancer (GC) without known mechanisms. In the present study, we demonstrated that ATP4B expression was decreased in human GC tissues and cell lines associated with DNA hypermethylation and histone hypoacetylation of histone H3 lysine 9 at its intragenic region close to the transcriptional start site. The expression of ATP4B was restored in GC cell lines by treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-AZA), or histone deacetylase inhibitor, trichostatin A (TSA), with further enhancement by combined treatment with both drugs. In contrast, 5-AZA had no effect on ATP4B expression in human hepatocellular carcinoma (HCC) and pancreatic cancer cell lines, in which ATP4B was silenced and accompanied by intragenic methylation. Chromatin immunoprecipitation (ChIP) showed that, in BGC823 GC cells, histone H3 lysine 9 acetylation (H3K9ac) was enhanced in the intragenic region of ATP4B upon TSA treatment, whereas 5-AZA showed a minimal effect. Additionally, ATP4B expression enhanced the inhibitory effects of chemotherapeutic mediation docetaxel on GC cell growth. Thus, as opposed to HCC and pancreatic cancer cells, the silencing of ATP4B in GC cells is attributable to the interplay between intragenic DNA methylation and histone acetylation of ATP4B, the restoration of which is associated with a favorable anticancer effect of docetaxel. These results have implications for targeting epigenetic alteration at the intragenic region of ATP4B in GC cells to benefit diagnosis and treatment of GC.


Neural and molecular bases of nonassociative and associative learning in Aplysia.
A model that summarizes some of the neural and molecular mechanisms contributing to short- and long-term sensitization is shown in Figure 14. Sensitizing stimuli lead to the release of a modulatory transmitter such as 5-HT. Both serotonin and sensitizing stimuli lead to an increase in the synthesis of cAMP and the modulation of a number of K+ currents through protein phosphorylation. Closure of these K+ channels leads to membrane depolarization and the enhancement of excitability. An additional consequence of the modulation of the K+ currents is a reduction of current during the repolarization of the action potential, which leads to an increase in its duration. As a result, Ca2+ flows into the cell for a correspondingly longer period of time, and additional transmitter is released from the cell. Modulation of the pool of transmitter available for release (mobilization) also appears to occur as a result of sensitizing stimuli. Recent evidence indicates that the mobilization process can be activated by both cAMP-dependent protein kinase and protein kinase C. Thus, release of transmitter is enhanced not only because of the greater influx of Ca2+ but also because more transmitter is made available for release by mobilization. The enhanced release of transmitter leads to enhanced activation of motor neurons and an enhanced behavioral response. Just as the regulation of membrane currents is used as a read out of the memory for short-term sensitization, it also is used as a read out of the memory for long-term sensitization. But long-term sensitization differs from short-term sensitization in that morphological changes are associated with it, and long-term sensitization requires new protein synthesis. The mechanisms that induce and maintain the long-term changes are not yet fully understood (see the dashed lines in Fig. 14) although they are likely to be due to direct interactions with the translation apparatus and perhaps also to events occurring in the cell nucleus. Nevertheless, it appears that the same intracellular messenger, cAMP, that contributes to the expression of the short-term changes, also triggers cellular processes that lead to the long-term changes. One possible mechanism for the action of cAMP is through its regulation of the synthesis of membrane modulatory proteins or key effector proteins (for example, membrane channels). It is also possible that long-term changes in membrane currents could be due in part to enhanced activity of the cAMP-dependent protein kinase so that there is a persistent phosphorylation of target proteins.(ABSTRACT TRUNCATED AT 400 WORDS)


Piribedil (ET 495) in the treatment of Parkinson's disease combined with amantadine or levodopa.
The further therapeutic benefit of piribedil when combined with amantadine or Levodopa was studied by a double-blind, cross-over trial in 15 patients with Parkinson's disease. A significant improvement at the 5 per cent level for akinesia, gait, speech disorder and facial expression occurred when piribedil was added to Levodopa; and a more highly significant improvement at the 1 per cent level for akinesia, facial expression and finger dexterity occurred with piribedil and amantadine. No significant improvement occurred for special timed tests. Improvement was associated with side effects in both groups of patients. Side effects occurred with both placebo and active piribedil. Only nausea during piribedil and Levodopa treatment reached statistical significance when compared with the placebo. Piribedil did not give rise to any haematological or biochemical complications. Our findings suggest that piribedil is of further therapeutic benefit when added to amantadine or Levodopa. It was suggested that the improvement which occurred together with amantadine could be due to the combined action of both drugs on dopamine receptors.