4-IHC classification of breast cancer subtypes in a large cohort of a clinical cancer registry: use in clinical routine for therapeutic decisions and its effect on survival.
The aim of the present study was to evaluate to what extent the combination of standard histopathological parameters determines the biology of breast cancer and the effect on therapy and prognosis. The Clinical Cancer Registry Regensburg (Bavaria, Germany) included n = 4,480 female patients with primary, non-metastatic (M0) invasive breast cancer diagnosed between 2000 and 2012. Immuno-histochemical analyses, i.e., estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 (4-IHC), defined the tumor biological subtypes Luminal A, Luminal B, HER2-like, and Basal-like. Subtype-related differences in therapies and overall survival (OS) were analyzed using multivariable statistical methods. 4344 patients (97.0 %) could be classified into the four common tumor biological subtypes. The two most frequent entities were Luminal A (48.4 %), Luminal B (24.8 %), HER2-like (17.8 %), and Basal-like subtype (9.0 %). A multivariable Cox regression model showed that the best 7-year OS was seen in Luminal A patients and that OS of Luminal B and HER2-like patients was comparable (HR = 1.59, P < 0.001 versus HR = 1.51, P = 0.03). Lowest OS was seen in patients with Basal-like tumors (HR = 2.18, P < 0.001). In conclusion, the classification of tumor biological subtypes by the ER, PR, HER2, and Ki-67 biomarkers is practical in routine clinical work. Providing that quality assurance of these markers is ensured, this classification is useful for making therapy decisions in the routine clinical management of breast cancer patients.


The cholesterol metabolite 27-hydroxycholesterol inhibits SARS-CoV-2 and is markedly decreased in COVID-19 patients.
There is an urgent need to identify antivirals against the coronavirus SARS-CoV-2 in the current COVID-19 pandemic and to contain future similar emergencies early on. Specific side-chain cholesterol oxidation products of the oxysterols family have been shown to inhibit a large variety of both enveloped and non-enveloped human viral pathogens. Here we report on the in vitro inhibitory activity of the redox active oxysterol 27-hydroxycholesterol against SARS-CoV-2 and against one of the common cold agents HCoV-OC43 human coronavirus without significant cytotoxicity. Interestingly, physiological serum levels of 27-hydroxycholesterol in SARS-CoV-2 positive subjects were significantly decreased compared to the matched control group, reaching a marked 50% reduction in severe COVID-19 cases. Moreover, no correlation at all was observed between 24-hydroxycholesterol and 25-hydroxycholesterol serum levels and the severity of the disease. Opposite to that of 27-hydroxycholesterol was the behaviour of two recognized markers of redox imbalance, i.e. 7-ketocholesterol and 7β-hydroxycholesterol, whose serum levels were significantly increased especially in severe COVID-19. The exogenous administration of 27-hydroxycholesterol may represent in the near future a valid antiviral strategy in the worsening of diseases caused by present and emerging coronaviruses.


RNA turnover in cultured hamster embryo cells: identification of modified nucleoside end products.
Fourteen methylated nucleosides (N-2-dimethylGuo, N-2-methylGuo, N-1-methylGuo, N-5-methylUrd, N-3-methylUrd, N-1-methylAdo, N-3-methylCyd, N-5-methylCyd, N-1-methyllno, 2'-Omethyl-Cyd, 2'-O-methylUrd, 2'-0-methylGuo, 2'-0-methyllno, and thymidine) and one methylated base (m7Gua) have been identified as normal excretion products of cultured hamster embryo cells. The methylated nucleosides are excreted in the culture media subsequent to RNA turnover. The excretion pattern of the base-methylated nucleosides was determined by continuous labeling of serum-stimulated quiescent hamster embryo cells with [3H-CH3]methionine and measurement of radioactivity in the excreted nucleosides between 23 and 81 1/2 hours after the label was added. These nucleosides accumulate exponentially until a maximum level is reached after 60 hours. These maximum levels were maintained for at least an additional 20 hours.


Gonadal development and function after immature testicular tissue banking as part of high-risk gonadotoxic treatment.
Experimental fertility preservation programs have been started to safeguard the future fertility of prepubertal and pubertal males requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies evaluating the effects on their gonadal development and function related to the testicular biopsy procedure are rather limited. This two-center follow-up study (between 2002 and 2020) evaluated the gonadal development and function of a cohort of 59 prepubertal and pubertal males who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of the testicular biopsy procedure and the high-risk gonadotoxic treatment. Testicular growth and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin B (INHB) were analyzed after treatment completion, and compared between males accepting TTB and those refusing TTB (control) as well as between HR-C/R and CT-HSCT treatment protocols. Of the 59 prepubertal and pubertal males included, 25 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted for 39 males and refused for 20 males. Most patients were prepubertal at diagnosis (85%), at TTB (79%), and at treatment completion (76%), and pubertal or postpubertal at their last follow-up visit (66%). After 5.0 (1.0-13.0) years post treatment, most patients show normal testicular volumes (83%) and normal LH (89%), FSH (87%), T (87%), and INHB (79%) serum levels. The testicular biopsy procedure did not have an effect on testicular growth, LH, FSH, T, and INHB. Significantly more small postpubertal testicular volumes (p = .0278) and low INHB serum levels (p = .0130) were recorded after CT-HSCT, especially after myeloablative conditioning. The clinical follow-up data demonstrate no effect related to the biopsy procedure, but a substantial risk for impaired gonadal development after high-risk gonadotoxic treatment, in particular myeloablative CT-HSCT. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.


Retroviruses, apoptosis and autogenes.
Autoimmunity and autoimmune disease are not the same. Autoimmunity is a normal consequence of aging, potentially reversible and possibly physiological. Autoimmune disease is dependent on genetic, viral, hormonal and psychoneuroimmunological factors. Aside from the apparently normal regulation of autoimmune responses by immune response genes, little is known about other genetic factors. Here, Norman Talal and John Mountz propose the term autogene to describe non-MHC genes which directly or indirectly interfere with important immunoregulatory actions. When mutated or otherwise genetically altered (e.g. by retrotransposon insertion), these genes predispose to immune dysregulation, lymphoproliferation and autoimmunity.


Numerical study of plasma generation process and internal antenna heat loadings in J-PARC RF negative ion source.
A numerical model of plasma transport and electromagnetic field in the J-PARC (Japan Proton Accelerator Research Complex) radio frequency ion source has been developed to understand the relation between antenna coil heat loadings and plasma production/transport processes. From the calculation, the local plasma density increase is observed in the region close to the antenna coil. Electrons are magnetized by the magnetic field line with absolute magnetic flux density 30-120 Gauss which leads to high local ionization rate. The results suggest that modification of magnetic configuration can be made to reduce plasma heat flux onto the antenna.


Exact interface model for wetting in the planar Ising model.
At the wetting transition in the two-dimensional Ising model the long contour (interface) gets depinned from the substrate. It is found that on sufficiently large length scales the statistics of the long contour are described by a unique probability measure corresponding to a continuous "interface model" with an interface binding "potential" given by a Dirac delta function supported on the substrate. A lattice solid-on-solid model is shown to give similar results.


Diffusion-weighted magnetic resonance imaging of femoral head osteonecrosis in two groups of patients: Legg-Perthes-Calve and Avascular necrosis.
The aim of this prospective study was to evaluate the value of diffusion-weighted magnetic resonance imaging (DW-MRI) in patients with osteonecrosis. Patients were divided into two subgroups as avascular necrosis (AVN) of femoral head for adult group and Legg-Calvé-Perthes (LCP) patients for children. Seventeen patients with femoral head AVN (mean age 42.3 years) and 17 patients with LCP (mean age 8.2 years) were included in this study. Diagnosis confirmed with clinical and other imaging procedures among the patients complaining hip pain. DW images were obtained using the single-shot echo planar sequence and had b values of 0, 500, 1000 s/mm(2). The apparent diffusion coefficient (ADC) values were measured from ADC maps in epiphysis of patients with AVN, both from metaphysis and epiphysis in patients with LCP, respectively. Mann-Whitney U test was used to compare ADC values. The mean ADC value of femoral heads (1.285 ± 0.204 × 10(-3) mm(2)/s) was increased in patients with AVN when compared to normal bone tissue (0.209 ± 0.214 × 10(-3) mm(2)/s) (p < 0.01). The mean ADC values (×10(-3) mm(2)/s) of both metaphysis (0.852 ± 0.293) and epiphysis (0.843 ± 0.332) were also increased in patients with LCP and differences were statistically significant (p < 0.01). As a result, osteonecrosis shows increased ADC values. But it is a controversial concept that DWI offers a valuable data to conventional MRI or not. However, as there are report states, there is a correlation between the stage of the disease with ADC values in the LCP disease. DWI is a fast, without-contrast administration technique and provides quantitative values additional to conventional MR techniques; we believe DWI may play an additional assistance to the diagnosis and treatment for LCP patients. Multicentric larger group studies may provide additional data to this issue.


Tracking celiac disease-triggering peptides and whole wheat flour quality as function of germination kinetics.
Germination is already a well-accepted process by consumers with many products made from sprouted seeds or containing limited amounts of flour form sprouted grains. The present work aimed assessing the usefulness of germination in reducing gluten peptides associated with celiac disease, at the same time evaluating some technological features of the obtained germinated wheat. In the first part of the work, celiac disease (CD)-triggering peptides were tracked as a function of germination kinetics (from day 1 to day 6). Using simulated gastrointestinal digestion and liquid chromatography coupled to mass spectrometry, ten celiac disease triggering peptides were identified: seven peptides presumably involved in the adaptive immune response (TI) and three peptides mainly involved in the innate immune response (TT). All the identified peptides belonged to gliadins. TI track pattern showed three phases: the first two days displayed a significant degradation, a stability phase was observed from day 3 to day 5, and finally a drastic reduction occurred on the 6th day. For TT peptides, important degradation was exclusively observed at the 6th day. In the second part, some techno-functional features of germinated whole wheat flour were assessed to estimate its potential as an alternative to conventional flour. Functionality comparison of the non-germinated versus germinated flours revealed that germination significantly influenced solvents retention capacities as well as swelling and solubility. Thus, with a reduced amount of celiac disease triggering peptides, but also with different technological behavior compared to traditional wheat flour.


Development of the WHO eye care competency framework.
The eye care workforce, particularly in lower resource settings, face challenges of limited integration into the health system, limited workforce capacity, mismatch of workforce to population need and poor quality of care. In recognition of these challenges, coupled with a gap in existing tools, provides a strong rationale for the development of the Eye care competency framework (ECCF). A mixed methods approach was utilised to develop and validate the ECCF. Content was developed by extracting relevant components of existing frameworks used both within and outside of eye care. A diverse technical working group provided feedback and guidance on the structure, design, and content to create a preliminary draft. Competencies and activities were validated using a modified-Delphi study, and the framework was then piloted at four sites to understand how the tool can be implemented in different settings. The final version of the ECCF included eight outcomes, nine guiding principles, and content of each of the key elements, including the six domains, 22 competencies, 21 activities, 193 behaviours and 234 tasks, and the knowledge and skills that underpin them. 95/112 participants from the six WHO regions completed the modified-Delphi study, yielding an average of 96% agreement across the competencies and activities in the ECCF. The pilot showcased the versatility and flexibility of the ECCF, where each of the four sites had a different experience in implementing the ECCF. All sites found that the ECCF enabled them to identify gaps within their current workforce documentation. The ECCF was developed using a collaborative approach, reflecting the opinions of participants and stakeholders from all around the world. The comprehensive competencies and activities developed in the ECCF encompass the diverse roles of eye care workers, and thus encourage multi-disciplinary care and better integration into the health system. It is recommended that eye care workforce planners and developers use the ECCF, and adapt it to their context, to support workforce development and focus on the quality and scope of eye care service provision.


Abundance data of benthic peracarid crustaceans from the South Atlantic and Southern Ocean.
Peracarid data were collected in the Southern Ocean and South Atlantic Ocean. Sampling was performed during nine different expeditions on board of RRS James Clark Ross and RV Polarstern, using epibenthic sledges (EBS) at depth ranging between 160-6348 m at 109 locations. The correlation between environmental variables and peracarid abundance was investigated. Abundance data comprise a total of 128570 peracarids (52366 were amphipods, 28516 were cumaceans, 36142 isopods, 5676 mysidaceans and 5870 were tanaidaceans). The presented data are useful to investigate the composition and abundance patterns of peracarid orders at a wide depth range and spatial scale in the Southern Ocean. They can also be reused to compare their abundance with that of other taxa in broader ecological surveys.


Identification of halosalicylamide derivatives as a novel class of allosteric inhibitors of HCV NS5B polymerase.
Halosalicylamide derivatives were identified from high-throughput screening as potent inhibitors of HCV NS5B polymerase. The subsequent structure and activity relationship revealed the absolute requirement of the salicylamide moiety for optimum activity. Methylation of either the hydroxyl group or the amide group of the salicylamide moiety abolished the activity while the substitutions on both phenyl rings are acceptable. The halosalicylamide derivatives were shown to be non-competitive with respect to elongation nucleotide and demonstrated broad genotype activity against genotype 1-3 HCV NS5B polymerases. Inhibitor competition studies indicated an additive binding mode to the initiation pocket that is occupied by the thiadiazine class of compounds and an additive binding mode to the elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase.


Alterations of oral microbiota in Chinese children with viral encephalitis and/or viral meningitis.
The role of oral microbiota in viral encephalitis and/or viral meningitis (VEVM) remains unclear. In this hospital-based, frequency-matched study, children with clinically diagnosed VEVM (n = 68) and those with other diseases (controls, n = 68) were recruited. Their oral swab samples were collected and the oral microbiota was profiled using 16S rRNA gene sequencing. The oral microbiota of children with VEVM exhibited different beta diversity metrics (unweighted UniFrac distance: P < 0.001, R2 = 0.025, Bray-curtis dissimilarity: P = 0.045, R2 = 0.011, and Jaccard dissimilarity: P < 0.001, R2 = 0.017) and higher relative abundances of taxa identified by Linear discriminant analysis (LDA) with effect size (Enterococcus, Pedobacter, Massilia, Prevotella_9, Psychrobacter, Butyricimonas, Bradyrhizobium, etc., LDA scores > 2.0) when compared with the control group. The higher pathway abundance of steroid hormone biosynthesis predicted by oral microbiota was suggested to be linked to VEVM (q = 0.020). Further, a model based on oral microbial traits showed good predictive performance for VEVM with an area under the receiver operating characteristic curve of 0.920 (95% confidence interval: 0.834-1.000). Similar results were also obtained between children with etiologically diagnosed VEVM (n = 43) and controls (n = 68). Our preliminary study identified VEVM-specific oral microbial traits among children, which can be effective in the diagnosis of VEVM.


Common variants of ACE contribute to variable age-at-onset of Alzheimer's disease.
Studies on the role that genetic variation may play in a complex human disease can be empowered by an assessment of both disease risk in case-control or family models and of quantitative traits that reflect elements of disease etiology. An excellent example of this can be found for the epsilon4 allele of APOE in relation to Alzheimer's disease (AD) for which association with both risk and age-at-onset (AAO) is evident. Following a recent demonstration that variants of the gene encoding angiotensin I converting enzyme ( ACE) contribute to AD risk, we have explored the potential influence of ACE upon AAO in AD. A total of 2861 individuals from three European populations, including six independent AD samples, have been examined in this study. Three single nucleotide polymorphisms (SNPs) previously demonstrated to have maximum effects upon ACE plasma levels and that span the ACE locus were genotyped in these materials. A strong effect upon AAO was observed for marker rs4343 in exon 17 ( P<0.0001), but evidence was also obtained indicating a possible independent effect of marker rs4291 ( P=0.0095) located in the ACE promoter. Effects were consistent with data from previous studies suggesting association with AD in case-control models, whereby alleles demonstrated to confer risk to disease also appear to reduce AAO. Equivalent effects were evident regardless of APOE epsilon4 carrier status and in both males and females. These results provide an important complement to existing AD risk data, confirming that ACE harbors sequence variants that contribute to aspects of AD pathology.


[Pharyngeal complications following ventral fusion operations of the cervical spine].
Dysphagias that are due to cervical spine surgery are increased. A complication that has not yet been described is explained and pointed out by two case reports. Possible life threatening consequences are discussed.


Deep learning model fusion improves lung tumor segmentation accuracy across variable training-to-test dataset ratios.
This study aimed to investigate the robustness of a deep learning (DL) fusion model for low training-to-test ratio (TTR) datasets in the segmentation of gross tumor volumes (GTVs) in three-dimensional planning computed tomography (CT) images for lung cancer stereotactic body radiotherapy (SBRT). A total of 192 patients with lung cancer (solid tumor, 118; part-solid tumor, 53; ground-glass opacity, 21) who underwent SBRT were included in this study. Regions of interest in the GTVs were cropped based on GTV centroids from planning CT images. Three DL models, 3D U-Net, V-Net, and dense V-Net, were trained to segment the GTV regions. Nine fusion models were constructed with logical AND, logical OR, and voting of the two or three outputs of the three DL models. TTR was defined as the ratio of the number of cases in a training dataset to that in a test dataset. The Dice similarity coefficients (DSCs) and Hausdorff distance (HD) of the 12 models were assessed with TTRs of 1.00 (training data: validation data: test data = 40:20:40), 0.791 (35:20:45), 0.531 (31:10:59), 0.291 (20:10:70), and 0.116 (10:5:85). The voting fusion model achieved the highest DSCs of 0.829 to 0.798 for all TTRs among the 12 models, whereas the other models showed DSCs of 0.818 to 0.804 for a TTR of 1.00 and 0.788 to 0.742 for a TTR of 0.116, and an HD of 5.40 ± 3.00 to 6.07 ± 3.26 mm better than any single DL models. The findings suggest that the proposed voting fusion model is a robust approach for low TTR datasets in segmenting GTVs in planning CT images of lung cancer SBRT.


Comparison of the Effects of 0.1% Fluorometholone and 1% Prednisolone on Intraocular Pressure and Schirmer Tear Test in Equine Eye.
This research was performed to compare the effects of prednisolone and fluorometholone on intraocular pressure (IOP) and Schirmer tear test (STT) in the normal equine eye. Sixteen normal mares aged between 6 and 10 years were used for this study. Horses were randomly assigned to two groups. Eight horses in the first group received 0.2 mL of topical 1% prednisolone in one eye and the contralateral eye was used as control (0.2 mL of saline was instilled). The second group received 0.2 mL of 0.1% fluorometholone in a randomly selected eye and the contralateral eye served as control and received 0.2 mL of saline. STT values and IOP were determined using STT strips and rebound, respectively, at the baseline, and 30-, 60-, 90-, and 180-minutes post eyedrop instillation. Mean (SD) IOPs at the baseline in the treated eyes of the first and second groups were 28.5 (5.4) and 27.5 (4.9) mm Hg, respectively. STT values at the baseline in the treated eyes of the first and second groups were 26.0 (1.8) mm/min and 24.0 (4.0) mm/min, respectively. Neither prednisolone nor fluorometholone caused significant changes in the IOP during 3 hours of monitoring (P > .05). There were no significant differences in the mean levels of STT in the control and treatment eyes, either between groups or within each group (P > .05). In conclusion, one dose (0.2 mL) of 1% prednisolone or 0.1% fluorometholone after 3 hours did not alter the IOP and STT in healthy horses. Further research for a longer period on normal horses and horses with uveitis is warranted.


Highly effective remediation of Pb(II) and Hg(II) contaminated wastewater and soil by flower-like magnetic MoS2 nanohybrid.
The efficient enrichment and remediation of heavy metals from realistic wastewater and contaminated soil containing large excess of competitive ions remains a daunting challenge by far. In the present study, flower-like molybdenum disulfide decorated with iron oxide nanoparticles (MoS2/Fe3O4) is designed via a two-step hydrothermal method and mainly applied in the removal of Hg(II) and Pb(II) ions in aqueous environment. Exhaustive morphological, chemical and magnetic characterizations verify the successful formation of magnetic MoS2/Fe3O4. Batch adsorption experiments show that the obtained MoS2/Fe3O4 nanohybrid enables efficient capture of Hg(II) and Pb(II) ions, accompanied by ease-of-separation from solution by simply applying a magnet. In this respect, high adsorption capacities (263.6 mg g-1 for Pb(II) and 428.9 mg g-1 for Hg(II)) can be gained under optimized conditions (pH = 5.0; 298 K; nanohybrid dosage: 0.8 g L-1 and the contact time: 180 min). In addition, the effects of different parameters such as initial Pb(II)/Hg(II) concentration (50-500 mg L-1), temperature (298, 308 and 318 K) and co-existing ions (Zn(II), Cu(II), Cd(II) and Mg(II)) were systematically probed. The favorable adsorption capacity, selectivity and recyclability mainly originates from the strong Hg2+/Pb2+···S2- bonding interactions. Practical application potential of magnetic MoS2/Fe3O4 nanohybrid in realistic lead-acid battery industry wastewater and Pb(II)-contaminated soil is further explored, achieving promising results with high Pb(II) removal efficiency of 99.63% for wastewater and 57.15% for soil. Simple preparation, easy separation and high adsorption capacity would foster thus-designed sulfide-based nanohybrid a promising adsorbent for heavy metal removal from wastewater and contaminated soil.


Fifteen-month follow up of an assertive community treatment program for chronic patients with mental illness.
The aim of this study was to evaluate the effect of an Assertive Community Treatment (ACT) program on psychiatric symptoms, global functioning, life satisfaction, and recovery-promoting relationships among individuals with mental illness. Participants were patients at the Suwon Mental Health Center. Thirty-two patients were part of the ACT program and 32 patients matched for age, sex, and mental illness were in a standard case-management program and served as a control group. Follow-up with patients occurred every 3 months during the 15 months after a baseline interview. Participants completed the Brief Psychiatric Rating Scale (BPRS), Global Assessment of Functioning (GAF) Scale, Life Satisfaction Scale, and Recovery-Promoting Relationship Scale (RPRS). No significant differences were noted in the sociodemographic characteristics of the ACT and the case-management group. According to the BPRS, the ACT group showed a significant reduction in symptom severity, but the ACT program was not significantly more effective at reducing psychiatric symptoms from baseline to the 15-month follow-up compared to the case-management approach. The ACT group showed more significant improvement than the control group in terms of the GAF Scale. Both groups showed no significant differences in the change of life satisfaction and in the change of recovery-promoting relationships. We observed a significant increase in recovery-promoting relationships in the control group, but the degree of change of recovery-promoting relationships through time flow between groups was not significantly different. In this study, we observed that ACT was significantly better at improving the GAF than case management and that participation in ACT was associated with a significant decrease in BPRS scores. However, ACT did not demonstrate an absolute superiority over the standard case-management approach in terms of the BPRS and the measures of life satisfaction and recovery-promoting relationships. ACT may have some advantages over a standard case management approach.


Droperidol inhibits tracheal contraction induced by serotonin, histamine or carbachol in guinea pigs.
Droperidol (D) is effective in the treatment of patients with status asthmaticus. It has been reported that D inhibits the bronchoconstriction induced by serotonin (5-HT) but not that by histamine (H) or acetylcholine. However, haloperidol, another butyrophenone, is known to interact with and inhibit calmodulin, an intracellular Ca(++)-binding protein which is important in the contraction of smooth muscles. The present study was designed to investigate the effects of D on tracheal contractions induced by 5-HT, H or carbachol (C) and to determine the contribution of alpha-adrenoceptors to the relaxant effect of D in vitro. Tracheas of female guinea pigs were cut spirally into strips and mounted in water-jacketed organ baths in Tyrode's solution, aerated with a mixture of 95% O2 and 5% CO2 at 37 degrees C. The changes in isometric tension induced by each spasmogen in the strips were measured with a transducer and a polygraph. We found that D inhibited the tracheal contractions induced by 5-HT, H or C in a concentration-dependent manner. At 1.25 x 10(-6) M D blocked the effect of 10(-4) M 5-HT by 44.1 +/- 4.3% and at 2.5 x 10(-6) M by 63.8 +/- 3.8%. Similarly, at 5.0 x 10(-6) M concentration, D blocked the effect of 10(-5) M H by 27.7 +/- 5.3% and at 10(-5) M by 56.2 +/- 2.6%. Furthermore, 5 x 10(-6) M of D reduced the contractions produced by 10(-7) M C by 37.1 +/- 3.0% and 10(-5) M of D by 76.1 +/- 3.2%. The inhibiting effect of D was strongest on contractions induced by 5-HT. Prazosin (10(-6) M) affected neither 5-HT-induced contractions nor the inhibition by D. Our data indicate that D partially blocks the contractile responses not only to 5-HT, an effect which would be mediated through a blockade of the 5-HT receptors, but also to H or C, probably through inhibition of calmodulin. Our data support previous reports indicating that droperidol may be an important therapeutic agent in the treatment of patients with hyperreactive airways.


Evolution of acute myocarditis in a pediatric population: An MRI based study.
Cardiac Magnetic Resonance (CMR) data regarding myocarditis presentation and disease course is still lacking in pediatric patients. We evaluate baseline CMR and evolution of functional and tissue abnormalities in children with acute myocarditis. CMR was performed in 125 patients with clinical diagnosis of acute myocarditis. Clinical follow-up was performed for a median of 498 (214-923) days. LVEF was depressed (<55%) in 56 cases (45%) upon baseline CMR. LGE was found in 93 patients (77%) of cases. LGE was exclusively subepicardial in 29 patients (23%), while other LGE patterns (midwall/mixed) were present in 64 (51%). CMR was repeated in 92 (74%) patients. 67% presented recover of function at a median of 170 (70-746) days after onset of symptoms. Midwall/mixed LGE pattern had a statistically significant correlation with absent recover of function (OR 0.20 p 0.036). Thirteen patients (16%) had recovery from LV dysfunction but with persistence of LGE. Sub-epicardial pattern of LGE (OR 3.33, 95% CI 1.08-10.2, p = 0.036) and the presence of fever at admission (OR 4.67, 95% CI 1.16-18.7, p = 0.03) were associated with a significantly higher likelihood of complete normalization while midwall/mixed LGE pattern was associated with non-recovery. In pediatric myocarditis, midwall/mixed LGE pattern is associated with absent recover of function. Patients with recover of function may still have persistence of LGE, while a complete recovery from functional and tissue abnormalities is found only in a third of patients. Midwall/mixed pattern of LGE at first MRI was associated to worse outcome.


Prolonged phorbol ester treatment down-regulates protein kinase C isozymes and increases contraction rate in neonatal cardiac myocytes.
We have determined the effects of chronic exposure to the protein kinase C (PKC) activating drug 4-beta phorbol 12-myristate-13-acetate (PMA) on PKC isozymes and the rate of spontaneous contraction in neonatal rat cardiac myocytes in culture. Western blot analyses revealed that a two day exposure to 0.1-1 nM PMA increased the total amount of delta PKC, whereas, 100 nM PMA concentrations caused a complete down-regulation of the alpha PKC and an 80 kDa zeta PKC-like protein. In addition, 100 nM PMA treatment for 2 days did not result in complete down-regulation of the beta, delta, and epsilon PKC isozymes in Western blot and immunocytochemical studies. We also found a PKC-mediated enhancement of the rate of contraction in these cells following prolonged exposure to PMA (1-100nM). Our studies suggest that this enhancement of contraction rate may be mediated by the beta, delta, or epsilon PKC isozymes. A better understanding of the role(s) of PKC isozymes in the modulation of cardiac functions may reveal selective targets for therapies of cardiac disorders.


Depletion of liver regulatory heme in benzene exposed rats.
The effect of a single dose of benzene (0.5 ml/kg body wt i.p.) on the heme saturation of tryptophan pyrrolase activity in liver was examined. There was a significant decrease in the heme saturation of hepatic tryptophan pyrrolase, suggesting depletion of "regulatory heme". After benzene administration there was significant increase in delta-aminolevulinate (ALA) synthetase activity (approx. 2-fold) while delta-aminolevulinate dehydratase activity was significantly decreased, however, ferrochelatase and heme oxygenase activities were unaltered. Administration of tryptophan to benzene pretreated rats showed a reversal of benzene effects on heme synthesizing enzymes: there is an increase in the heme saturation of tryptophan pyrrolase and decrease in delta-aminolevulinate synthetase. However, there was no significant alteration in the activity of delta-aminolevulinate dehydratase.


The natural history of abdominal aortic aneurysm.
The outcome of 65 patients with unoperated abdominal aortic aneurysms (AAA) were reviewed in order to evaluate the natural history and "quality of life". An estimated cumulative life-table was constructed. Of the 65 patients admitted to the department (from 1972 to 1984), 52 were discharged from the hospital and not operated on because of concurrent medical disorders. These patients were divided into two groups: 34 with asymptomatic AAA on admission to the department and 18 with symptoms. During follow-up, 38 patients died, 71% in the asymptomatic and 78% in the symptomatic group. Less than 50% of all the patients died of concurrent disease. Of the patients in the asymptomatic group with a small aneurysm, 38% died of rupture of AAA. As AAA is a disease with a high mortality, the co-existent medical disorders must be very "serious" if the patient is not to be offered an operation. Even small, asymptomatic AAAs may rupture and should be operated on. No factor seemed to predict the natural history for the individual patient. A score system, for example, the "Boston score", is recommended. This would facilitate good objective assessment of the patients entering into future studies and the evaluation of "survival curves" will improve.


Synthesis and bioactivities of Phenazine-1-carboxylic acid derivatives based on the modification of PCA carboxyl group.
Phenazine-1-carboxylic acid (PCA) as a natural product widely exists in microbial metabolites of Pseudomonads and Streptomycetes and has been registered for the fungicide against rice sheath blight in China. To find higher fungicidal activities compounds and study the effects on fungicidal activities after changing the carboxyl group of PCA, we synthesized a series of PCA derivatives by modifying the carboxyl group of PCA and their structures were confirmed by 1H NMR and HRMS. Most compounds exhibited significant fungicidal activities in vitro. In particular, compound 6 exhibited inhibition effect against Rhizoctonia solani with EC50 values of 4.35mg/L and compound 3b exhibited effect against Fusarium graminearum with EC50 values of 8.30mg/L, compared to the positive control PCA with its EC50 values of 7.88mg/L (Rhizoctonia solani) and 127.28mg/L (Fusarium graminearum), respectively. The results indicated that the carboxyl group of PCA could be modified to be amide group, acylhydrazine group, ester group, methyl, hydroxymethyl, chloromethyl and ether group etc. And appropriate modifications on carboxyl group of PCA were useful to extend the fungicidal scope.


Ultrastructural study of lens fiber damages after laser irradiation.
Lens fiber lesions after laser irradiation were studied in the albino rats. Loss of cytoplasmic contrast, pulling apart of intercellular cell junctions and increase of intracellular vesicles were observed.


Canonicity Effect on Sentence Processing of Persian-speaking Broca's Patients.
Fundamental notions of mapping hypothesis and canonicity were scrutinized in Persian-speaking aphasics. To this end, the performance of four age-, education-, and gender matched Persian-speaking Broca's patients and eight matched healthy controls in diverse complex structures were compared via the conduction of two tasks of syntactic comprehension and grammaticality judgment. The tested structures included subject agentive, agentive passive, object experience, subject experience, subject cleft, and object cleft constructions. Our results, while corroborating the predictions of the mapping hypothesis, showed that in structures, in which linguistic elements were substituted and dislocated out of their canonical syntactic positions, namely, agentive passive, subject experiencer, object experiencer, and object cleft constructions, Broca's problems escalated. In contrast, in those structures whose constituent concatenations were aligned with canonical syntactic structures, namely subject agentive, and cleft structures, patients had above the chance performance. Ultimately, the theoretical and clinical implications of the study were discussed. The number of predicates in a sentence, predicate types (psychological and agentive), as well as semantic heuristics and canonicity all by all could be regarded as the major culprits for aphasics' poor performance.


Dual extensor tendon entrapment in Galeazzi fracture-dislocation: a case report.
A rare case of blocked reduction of the distal radio-ulnar joint in a Galeazzi fracture-dislocation is presented. In this case both the extensor carpi ulnaris and extensor digiti minimi tendons were displaced on either side of the ulnar head. After relocation of these tendons the distal radio-ulnar joint could be easily reduced.


Characterization of virus-like particles from a psoriatic patient with respect to the possible presence of particle-associated RNA and RNA-directed DNA polymerase.
Subcellular particles resembling retroviruses with respect to their morphology, density, and protein composition, and which are present in the urine of a psoriatic patient have been analysed for the presence of high-molecular-weight polyadenylated RNA and RNA-directed DNA polymerase activity. Neither RNA-directed DNA polymerase activity nor high-molecular-weight polyadenylated RNA was detected in preparations containing the purified virus-like particles. This was the case even when the amount of particles analysed exceeded by a factor of 50 or more the amount of avian myeloblastosis virus in which both polymerase activity and RNA were detected.


The influence of gender and age on the thickness and echo-density of skin.
The more recent use of ultrasound scanning allows a direct measurement on unmodified skin, and is considered to be a reliable method for in vivo measurement of epidermal and dermal thickness. The objective of this study was to assess the influence of gender and age on the thickness and echo-density of skin measured by high frequency ultrasonography (HFUS). This study was carried out on 30 healthy volunteers (17 female, 13 male) with age range of 24-61 years old. The thickness and echo-density of dermis as well as epidermal entrance echo thickness in five anatomic sites (cheek, neck, palm, dorsal foot, and sole) were measured using two different types of B mode HFUS, 22 and 50 MHz frequencies. The epidermal entrance echo thickness and thickness of dermis in males were higher than females, which was statistically significant on neck and dorsum of foot. The echo-density of dermis was higher in females on all sites, but was only statistically significant on neck. The epidermal entrance echo thickness and thickness of dermis in young age group was statistically higher than old group on sole and dorsal of the foot respectively. Overall, the skin thickness decreased with age. High frequency ultrasonography method provides a simple non-invasive method for evaluating the skin thickness and echo-density. Gender and age have significant effect on these parameters. Differences in study method, population, and body site likely account for different results previously reported.


Association between Estrogen Receptor Alpha Gene Polymorphisms and Susceptibility to Idiopathic Scoliosis in Bulgarian Patients: A Case-Control Study.
The current consensus on idiopathic scoliosis maintains that it has a multifactorial etiology with genetic predisposing factors. Estrogen receptor alpha gene has been considered as candidate gene of idiopathic scoliosis. We conducted a case-control study of Bulgarian population samples (eighty patients with idiopathic scoliosis and one hundred-sixty healthy unrelated gender-matched controls) trying to investigate the association between common genetic polymorphisms of estrogen receptor alpha and the susceptibility to idiopathic scoliosis. Molecular detection of the restriction polymorphisms XbaI and PvuII was performed by polymerase chain reaction following by restriction fragment length polymorphism. The statistical analysis was performed by Pearson's chi-squared test. Our case-control study showed statistically significant association between the PvuII polymorphism and susceptibility to idiopathic scoliosis and curve progression. No genotype or allele of XbaI polymorphism was found to be correlated with the onset or severity of the disease. The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.


Role of Plasmids in Co-Selection of Antimicrobial Resistances Among Escherichia coli Isolated from Pigs.
Co-selection is thought to occur when resistance genes are located on the same mobile genetic element. However, this mechanism is currently poorly understood. In this study, complete circular plasmids from swine-derived Escherichia coli were sequenced with short and long reads to confirm that resistance genes involved in co-resistance were co-transferred by the same plasmid. Conjugative transfer tests were performed, and multiple resistance genes were transmitted. The genes possessed by the donor, transconjugant, and plasmid of the donor were highly similar. In addition, the sequences of the plasmid of the donor and the plasmid of the transconjugant were almost identical. Resistance genes associated with statistically significant combinations of antimicrobial use and resistance were co-transmitted by the same plasmid. These results suggest that resistance genes may be involved in co-selection by their transfer between bacteria on the same plasmid.


Systemic inflammation induces COX-2 mediated prostaglandin D2 biosynthesis in mice spinal cord.
Although prostaglandin (PG)D2 is one of the main metabolites of the cyclooxygenase (COX) pathway of arachidonate metabolism in the brain, relatively little is known about the regulation of PGD2 biosynthesis in the spinal cord during systemic inflammation. Therefore, the present study was aimed at investigating the effect of endotoxin treatment on spinal PGD2 biosynthesis in BALB/c mice. Spinal inflammatory response to systemic endotoxin was verified by determination of spinal TNFalpha and IL-1beta mRNA. COX-1, COX-2, membrane-bound prostaglandin E synthase-1 (mPGES-1), and lipocalin-type prostaglandin D synthase (L-PGDS) mRNA and protein were determined by RT-PCR and western blot, respectively. The concentrations of immunoreactive PGD2 and PGE2 were measured in superfusion media of spinal cord samples in-vitro. Endotoxin treatment (1 mg/kg; 24 h before) enhanced the expression of COX-2, mPGES-1, and L-PGDS mRNA and protein in spinal cord, while there was no significant effect on COX-1 mRNA and protein. In superfusion media of spinal cord samples obtained from endotoxin treated mice, the concentrations of immunoreactive PGE2 and PGD2 were higher than in the control group suggesting enhanced spinal PG biosynthesis after endotoxin treatment. Addition of the selective COX-2 inhibitor lumiracoxib (100 nM) to the superfusion medium did not significantly affect PGE2 or PGD2 release in spinal cord obtained from non-treated mice. In spinal cord of endotoxin-treated mice, lumiracoxib (100 nM) attenuated PGE2 and PGD2 release to values similar to those observed in tissue obtained from non-endotoxin-treated mice. These results show enhanced expression of spinal L-PGDS and increased spinal PGD2 biosynthesis during systemic inflammation whereby enhanced biosynthesis seems to be dependent primarily on COX-2 activity.


Effects of acetamiprid on life cycle development of predatory mite Amblyseius cucumeris (Acari: Phytoseiidae) after contact exposure.
Amblyseius cucumeris (Oudemans) is a beneficial non-target arthropod (NTA) and a key predator of pest mites in integrated pest management (IPM) programs across china. The toxic effects of insecticides have been extensively reported on predatory mites, but few studies devoted to the toxicity of compounds to A. cucumeris. In this study, the effects of a single application of acetamiprid against the A. cucumeris were investigated in a 48-h acute and a 30-d chronic test. In both tests the insecticide acetamiprid was applied once. In the acute test, the "open glass plate method" was used, with a 48-h LC50 value of 223.6 (149.8-336.9) mg a. i. L-1 for adult female. The LC50 was 1.49-fold the Maximum field recommended concentration. In the chronic test, exposure concentrations (1.12, 2.24, 4.47, 8.94, and 22.4 mg a. i. L-1) were designed based on a preliminary 48-h LC50 value for adult female. Above treatment levels of 2.24-4.47 mg a. i. L-1 reduce the total development time, survival rates and food consumption of A. cucumeris in different development stages. In addition, at acetamiprid concentrations higher than 2.24 mg a. i. L-1 serious effect on the capacity of oviposition of female adults were observed. However, even the highest treatment level of 22.4 mg a. i. L-1 did not affect egg hatching rates of exposed eggs. Acetamiprid had significant adverse effects on different development life stages of A. cucumeris. The results provide informative data for implementing biological and chemical control strategies in integrated pest management of spider mites.


Sharing Knowledge to an Entrant for Production Investment Confronting COVID-19: Incentive Alignment and Lose-Lose Dilemma.
Facing the urgent demand of medical devices for COVID-19 treatment, many automakers have recently begun manufacturing ventilators, even though they are inefficient in production and uninformed of demand variability. To help them, some incumbent ventilator manufacturers have chosen to share knowledge, such as production techniques and demand information. Clearly, the incumbent ventilator manufacturers are fulfilling social responsibility, but is their knowledge sharing rewarding, especially when the automakers are entrant rivals? If possible, are win-win situations in the sense of social responsibility and firms' profitability identifiable? In this work, we develop a game-theoretic model in which an incumbent and an entrant ventilator manufacturer engage in two-dimensional competition in production investment and sales volume. We examine the incumbent manufacturer's profitability with and without knowledge sharing by formulating the tradeoffs among supply expansion, intensified competition, and the entrant's production efficiency improvement and demand variance reduction. We identify both "win-win" and "lose-lose" situations for the two competing manufacturers. Specifically, we find that free knowledge could be harmful for the entrant manufacturer, but the incumbent manufacturer benefits from knowledge sharing when market competition is intense, or when market competition is mild but the production investment efficiency varies.


Notes on three braconid wasps (Hymenoptera: Braconidae, Doryctinae) parasitizing oak long-horned beetle, Massicus raddei (Coleoptera: Cerambycidae), a severe pest of Quercus spp. in China, together with the description of a new species.
Three species of Doryctinae (Hymenoptera: Braconidae) parasitize larvae of oak longhorn beetle Massicus raddei Blessig (Coleoptera: Cerambycidae), a serious wood borer pest in North China. Rhoptrocentrus quercusi sp. nov., is described as a new species and Doryctes petiolatus Shestakov, as well as Zombrus bicolor (Enderlein). The three species are idiobiont ectoparasitoids, and may have potential for biological control of oak longhorn beetle.


Heterotopic Ossification after Trauma.
Heterotopic ossification (HO) refers to benign ectopic bone formation in soft tissue and is common following trauma surgery. HO bone can restrict movement and progress into ankylosis that may necessitate surgical intervention. This article discusses the current literature on the pathophysiology, prophylaxis, treatment, and epidemiology of postoperative HO following orthopedic trauma.


[Comparison and evaluation of the Binax EIA and Biotest EIA urinary antigen kits for detection of Legionella pneumophila antigen in urine samples].
The Binax and the Biotest urinary antigen kits for detection of L. pneumophila antigen were compared by testing of selected 67 urine samples obtained from EWGLI as reference samples in External Quality Assessment Scheme. Thirty nine were positive with the Binax kit (100% of sensitivity), and 33 were positive with the Biotest (84.6% of sensitivity). The test specificities were 100% for the both kits. It was concluded that the Binax kit was more suitable for the routine diagnosis of Legionella infections than the Biotest kit.


Direct oral anticoagulants for the treatment of splanchnic vein thrombosis - A systematic review and meta-analysis.
Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism in the splanchnic venous system, with scarce evidence surrounding its management. We assessed the efficacy and safety of direct oral anticoagulant (DOAC) to low-molecular-weight heparins (LMWH), vitamin-k antagonists (VKAs), or no anticoagulation. We conducted a systematic review and meta-analysis with the primary efficacy outcome being complete recanalization of affected vessels and primary safety outcome being major bleeding. Meta-analysis was done using a random-effects model, with dichotomous outcomes being synthesized with odds ratios (ORs) and corresponding 95 % CIs. Seven non-randomized and one randomized study involving 883 participants were included for analysis. DOACs were more effective than VKAs (OR = 4.33; 95 % CI: 2.4, 7.83; n = 1 study) in non-cirrhotic patients and no anticoagulation in cirrhotic patients (OR = 3.86; 95 % CI: 1.49, 10.03; n = 3 studies). DOACs had a statistically significant reduction in major bleeding compared to observation [OR = 0.09; 95 % CI: 0.03, 0.29; n = 3 studies], LMWHs [OR = 0.13; 95 % CI: 0.03, 0.29; n = 1 study] and VKAs [OR = 0.12; 95 % CI: 0.02, 0.69; n = 2 studies] in non-cirrhotic patients. No difference in major bleeding was found between DOACs and observation, LMWH, or VKAs in cirrhotic patients. DOACs appear to be a favorable alternative to VKAs and LMWHs in non-cirrhotic patients. This avenue of research would benefit from larger studies that adjust for SVT etiologies, patient risk factors, and overall bleeding risk.


Quantitative corneal endothelial evaluation in intraocular lens implantation and cataract surgery.
We analyzed pre- and postoperative corneal endothelial photographs of 33 intraocular lens patients and found an average endothelial cell density loss of 14%. Twenty-six cataract patients, similarly examined, showed a 13% mean endothelial cell loss. In 14 of the intraocular lens patients, a second postoperative evaluation of the central endothelium, at a later date, revealed a trend toward continuing cell loss. Our results indicate fewer endothelial cells were lost after intraocular lens implantation than has been previously reported. This may be accounted for by our considering only patients with normal corneas for lens implantation, and by our constant maintenance of the anterior chamber with an air bubble during lens implant surgery.


Efficient synthesis of 3-furanosyl-6'-furanosylphosphinate through a tandem sequential radical process.
The sodium salt of hypophosphorous acid is shown to act as a double radical precursor in a double, sequential radical addition on 3-exo-methylenefuranose derivative 14 and 4-ethylenefuranose 10 to furnish phosphinates 18d in good overall yields. Unambiguous structural assignment establishes the high diastereoselection of the process.


Air quality equity in US climate policy.
The United States government has indicated a desire to advance environmental justice through climate policy. As fossil fuel combustion produces both conventional pollutants and greenhouse gas (GHG) emissions, climate mitigation strategies may provide an opportunity to address historical inequities in air pollution exposure. To test the impact of climate policy implementation choices on air quality equity, we develop a broad range of GHG reduction scenarios that are each consistent with the US Paris Accord target and model the resulting air pollution changes. Using idealized decision criteria, we show that least cost and income-based emission reductions can exacerbate air pollution disparities for communities of color. With a suite of randomized experiments that facilitates exploration of a wider climate policy decision space, we show that disparities largely persist despite declines in average pollution exposure, but that reducing transportation emissions has the most potential to reduce racial inequities.


Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure.
This study sought to assess the impact of the selective aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF) < or =40% and clinical signs of heart failure. In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p = 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF < or =40% and clinical signs of heart failure. We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial. At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p = 0.004) and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone and placebo-treated patients, respectively; p = 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p = 0.003) and the risk of sudden cardiac death by 37% (p = 0.051). Eplerenone 25 mg/day significantly reduced all-cause mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF < or =40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI.


The Net Generation of nursing: keeping empathetic communication alive.
Electronic communication has had a profound impact on generations, in the nursing profession as well as in society as a whole. Nursing educators struggle with facilitating verbal communication skills in didactic and clinical settings, particularly with the Net Generation. Online education is rapidly becoming the norm in degree-completion programs. Nursing educators must assure that empathetic communication with patients will not become a lost art.


Radiological and clinical findings of pulmonary aspergillosis following solid organ transplant.
To evaluate the radiological and clinical findings in patients with pulmonary aspergillosis after solid organ transplantation. This study included 13 consecutive patients (five liver, four kidney, and four heart transplant; 10 male and three female; median age 54 years; range 13-63 years) with histologically confirmed pulmonary aspergillosis after solid organ transplantation at a tertiary referral hospital. Chest radiographs and computed tomography (CT) examinations performed for diagnosis were available in all patients. Radiological findings, such as lesion characteristics, location, and associated findings, were assessed retrospectively by two radiologists. The changes in radiological findings and clinical response after treatment were also assessed. Clinical findings, such as time of onset, initial symptoms, clinical course, and laboratory findings, were reviewed. The most common radiographic and CT findings were pulmonary nodules or masses (n=12). The number of nodules or masses was less than 10 in eight patients. Associated findings were surrounding ground-glass opacity (n=4), central low density (n=8), central air cavity (n=5), and air bronchogram (n=3). Follow-up radiographs and/or CT after treatment showed improvement in eight patients, persistence in two, and deterioration in three. The onset time of pulmonary aspergillosis was a median of 32 days (range 15-165 days). The most common symptom at diagnosis was fever (n=6). Ten of 13 patients did not have leucopaenia. There were two aspergillosis-associated deaths during the follow-up period. The most common radiological finding of pulmonary aspergillosis after solid organ transplantation is multiple nodules or masses, which commonly appear within 1 month following transplantation.


The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells.
In rodents, research has revealed a role of liver X receptors (LXR) in controlling lipid homeostasis and regulating the synthesis of polyunsaturated fatty acids (PUFA). Recent data suggest that LXRB is the predominant LXR subtype in ruminant mammary cells, but its role in lipid metabolism is unknown. It was hypothesized that LXRB plays a role in lipid homeostasis via altering the synthesis of PUFA in the ruminant mammary gland. We used overexpression and knockdown of LXRB in goat primary mammary epithelial cells (GMEC) to evaluate abundance of lipogenic enzymes, fatty acid profiles, content of lipid stores and activity of the stearoyl-CoA desaturase (SCD1) promoter. Overexpression of LXRB markedly upregulated the protein abundance of LXRB while incubation with siRNA targeting LXRB markedly decreased abundance of LXRB protein. Overexpression of LXRB plus T0901317 (T09, a ligand for LXR) dramatically upregulated SCD1 and elongation of very long chain fatty acid-like fatty acid elongases 5-7 (ELOVL 5-7), which are related to PUFA synthesis. Compared with the control, cells overexpressing LXRB and stimulated with T09 had greater concentrations of C16:0, 16:1, 18:1n7,18:1n9 and C18:2 as well as desaturation and elongation indices of C16:0. Furthermore, LXRB-overexpressing cells incubated with T09 had greater levels of triacylglycerol and cholesterol. Knockdown of LXRB in cells incubated with T09 led to downregulation of genes encoding elongases and desaturases. Knockdown of LXRB attenuated the increase in triacylglycerol and cholesterol that was induced by T09. In cells treated with dimethylsulfoxide, knockdown of LXRB increased the concentration of C16:0 at the expense of C18:0, while a significant decrease in C18:2 was observed in cells incubated with both siLXRB and T09. The abundance of sterol regulatory element binding transcription factor 1 precursor (pSREBP1) and its mature fragment (nSREBP1) was upregulated by T09, but not LXRB overexpression. In the cells cultured with T09, knockdown of LXRB downregulated the abundance for pSREBP1 and nSREBP1. Luciferase reporter assays revealed that the activities of wild type SCD1 promoter or fragment with SREBP1 response element (SRE) mutation were decreased markedly when LXRB was knocked down. Activity of the SCD1 promoter that was induced by T09 was blocked when the SRE mutation was introduced. The current study provides evidence of a physiological link between the LXRB and SREBP1 in the ruminant mammary cell. An important role was revealed for the LXRB-SREBP1 network in the synthesis of PUFA via the regulation of genes encoding elongases and desaturases. Thus, targeting this network might elicit broad effects on lipid homeostasis in ruminant mammary gland.


Treatment strategy for patients with colorectal cancer and synchronous irresectable liver metastases.
The aim of this case-matched study was to determine the best treatment strategy for patients with asymptomatic colorectal cancer and irresectable synchronous liver metastases. Between 1997 and 2002, 27 patients with asymptomatic colorectal cancer and irresectable synchronous liver metastases were treated by chemotherapy without initial primary resection (chemotherapy group). These 27 patients were compared with 32 patients matched for age, sex, performance status, primary tumour location, number of liver metastases, nature of irresectable disease and type of chemotherapy, but who were treated initially by resection of primary tumour (resection group). The 2-year actuarial survival rate was 41 per cent in the chemotherapy group and 44 per cent in the resection group (P = 0.753). In the latter group, the mortality and morbidity rates for primary resection were 0 and 19 per cent (six of 32 patients) respectively. In the chemotherapy group, intestinal obstruction related to the primary tumour occurred in four of 27 patients. The mean overall hospital stay was 11 days in the chemotherapy group and 22 days in the resection group (P = 0.003). Systemic chemotherapy without resection of the bowel cancer is the option of choice because, for most patients, it is associated with a shorter hospital stay and avoids surgery without a detrimental effect on survival.


Prevalence, subtypes and risk factors of Blastocystis spp. infection among pre- and perimenopausal women.
Blastocystis spp. are considered pathogenic or commensal organisms, although the majority of researchers suggest that these are neglected pathogens. The main aim of this study was to determine the prevalence and subtype distribution of Blastocystis spp. in pre- and perimenopausal women, with respect to socio-demographic (age and place of residence), and epidemiological factors, as well as drinking tap water, contact with domestic animals, traveling abroad, health status, and presence of gastrointestinal symptoms. Additionally, the objective was to compare hematological and biochemical parameters of Blastocystis spp. infected and uninfected women. The study included 425 women aged 45-60. Their stool samples were examined microscopically and analyzed by a conventional polymerase chain reaction (cPCR). Blastocystis spp. were detected in 6.1% of pre- and perimenopausal women. Molecular analysis of the stool samples identified seven Blastocystis subtypes (ST1-ST4, ST6, ST7, and ST9). Blastocystis subtypes 2 and 3 were the most prevalent. The presence of Blastocystis spp. was not significantly related to socio-demographic and epidemiological factors. There were also no significant associations between Blastocystis spp. and blood parameters, or gastrointestinal symptoms. This study complements the limited available data on the prevalence of Blastocystis spp. in pre- and perimenopausal women. It is also the first report showing the presence of Blastocystis subtype 9 in Poland.


Spectral and structural studies of copper(II) complexes of thiosemicarbazones derived from salicylaldehyde and containing ring incorporated at N(4)-position.
Mononuclear and binuclear copper(II) complexes (1-8) with two ONS donor thiosemicarbazone ligands {salicylaldehyde 3-hexamethyleneiminyl thiosemicarbazone [H2L1] and salicylaldehyde 3-tetramethyleneiminyl thiosemicarbazone [H2L2]} have been prepared and physico-chemically characterized. IR, electronic and EPR spectra of the complexes have been obtained. The thiosemicarbazones bind to metal as dianionic ONS donor ligands in all the complexes except in [Cu(HL1)2] (2) and [Cu(HL2)2] (6). In compounds 2 and 6 the ligands are coordinated as monoanionic HL- ones. The magnetic susceptibility measurements indicate that all the complexes are paramagnetic. In complex [(CuL1)2] (1), the magnetic moment value is lower than the expected spin only value. In all the complexes g(||)>g( perpendicular)>2.0023 and G values within the range 2.5-3.5 are consistent with dx2-y2 ground state. The complexes were given the formula as [(CuL1)2] (1); [Cu(HL1)2] (2); [CuL1bpy] (3); [CuL1phen] (4); [CuL1gamma-pic].2H2O (5); [Cu(HL2)2] (6); [CuL2py].3H2O (7); [CuL2bipy] (8). The structure of the compound 8 have been solved by single crystal X-ray crystallography and was found to be distorted square pyramid around copper(II) ion.


Distribution and speciation of Sb and toxic metal(loid)s near an antimony refinery and their effects on indigenous microorganisms.
Although several studies have investigated the effects of Sb contamination on surrounding environments and indigenous microorganisms, little is known about the effect of co-contamination of Sb and toxic metal(loid)s. In this study, the occurrence of Sb and other toxic metal(loid)s near an operating Sb refinery and near-field landfill site were investigated. Topsoil samples near the refinery had high Sb levels (∼3250 mg kg-1) but relatively low concentrations of other toxic metal(loid)s. However, several soil samples taken at greater depth from the near-field landfill site contained high concentrations of As and Pb, as well as extremely high Sb contents (∼21,400 mg kg-1). X-ray absorption fine structure analysis showed that Sb in the soils from both sites was present as Sb(V) in the form of tripuhyite (FeSbO4), a stable mineral. Three-dimensional principal coordinate analysis showed that microbial community compositions in samples with high toxic metal(loid)s concentrations were significantly different from other samples and had lower microbial populations (∼104 MPN g-1). Sequential extraction results revealed that Sb is present primarily in the stable residual fraction (∼99 %), suggesting low Sb bioavailability. However, microbial redundancy analysis suggested that the more easily extractable Pb might be the major factor controlling microbial community compositions at the site.


An improved processing of radioimmunoassay data by means of a desk-top calculator. (1) Comparison of regression procedures applied to selected kinds of radioimmunoassay.
By means of a programmable desk-top calculator, goodness-of-fit of 3 regression models, four-parameter logistic, quadratic logit-log and linear logit-log models, were evaluated by analysis of variance (F test) for data of 6 kinds of radioimmunoassays (RIA); thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), insulin (IRI), cortisol, triiodothyronine (T3). Scatchard plot analyses were made with the representative data of these RIAs in order to find the best choice of regression model in relation to the characteristics of antigen-antibody reaction. The analysis of goodness-of-fit of the regression models by means of an F test disclosed the relation between the choice of regression models and the kinds of RIA, which could be grouped into 3 types: (1) almost identical degree of fit with any of 3 regression models (FSH and T3), (2) more or less equal degree of satisfactory fit with the logistic and quadratic logit-log models (TSH and cortisol), (3) best degree of fit with the aquadratic logit-log model among 3 (LH and IRI). The analysis of data with Scatchard plot discriminated 3 general types of curves; (1) linear (FSH) and T3), (2) linear with tail (TSH and cortisol) and (3) hyperbola (LH and IRI). From these findings, the following tentative conclusions were reached: RIA with linear pattern on Scatchard plot can be satisfactorily regressed with either of 3 models, RIA with linear with tail pattern regressed with either the logistic or quadratic logit-log model, and RIA with hyperbolic pattern regressed best with the quadratic logit-log model.


Problems in measuring the JTC-bias in patients with psychotic disorders with the fish task: a secondary analysis of a baseline assessment of a randomized controlled trial.
The jumping to conclusions bias (JTC) is considered to be an important causal factor in theoretical models for the formation and maintenance of delusions. However, recent meta-analytic findings show a rather equivocal pattern of results regarding associations between JTC and delusions. Thus, the present study aims to investigate in a large sample whether the JTC-bias is more pronounced in patients with psychotic disorders in comparison to controls and whether the JTC bias is associated with a more severe delusional conviction, persecutory delusions, and positive symptoms in general. Patients with psychotic disorders (n = 300) enrolled in a therapy trial and healthy controls (n = 51) conducted a variant of the beads task (fish task) as a measure for the JTC-bias at the start of the trial. Further, clinical interviews were used to assess patients' delusional severity and delusional conviction. There were no statistically significant differences between patients with psychotic disorders (with 53% displaying the JTC-bias) and controls (41%). Furthermore, there were no statistically significant correlations between JTC measures and persecutory delusions, delusional conviction, and positive symptoms. We found no differences in JTC between patients with psychotic disorders and healthy controls, which is in part in line with meta-analytic findings using a wide range of JTC task variants. Interestingly, patients with psychotic disorders displayed JTC rates commonly found in the literature, while healthy control subjects showed an unexpectedly high level of JTC. The task variant we used in the present study (fish task) is discussed as a potential reason for our results, as it may induce a more deliberative reasoning style in controls as compared to the traditional beads task. Furthermore, possible implications for the measurement of the JTC-bias, in general, are discussed. ISRCTN29242879 ( isrctn.com ), date of registration: April 12th 2006, retrospectively registered.


The effect of combinations of qinghaosu (artemisinin) with standard antimalarial drugs in the suppressive treatment of malaria in mice.
Artemisinin is a novel antimalarial drug isolated in China from the wormwood plant Artemisia annua L. Studies with rodent malaria were carried out to detect antagonism and synergism with a variety of antimalarial drugs. Isobolograms of drug interaction were plotted at the ED90 level. With a normally susceptible strain of Plasmodium berghei, marked potentiative synergism was found with mefloquine, tetracycline and spiramycin. There was some synergism also with primaquine. Combinations of artemisinin with dapsone, sulfadiazine, sulfadoxine, pyrimethamine, pyrimethamine/sulfadoxine and cycloguanil showed antagonism. A high degree of potentiation was shown between artemisinin and primaquine with a primaquine-resistant strain, whilst the combination with mefloquine showed enhanced potentiation with a mefloquine-resistant strain. Combinations of artemisinin with mefloquine, primaquine, tetracycline or clindamycin showed marked potentiation with an artemisinin-resistant strain. The mechanisms underlying the drug interactions observed are discussed.


Removal of third molars in Scottish oral and maxillofacial surgery units: a review of practice in 1995 and 2002.
We audited the practice of removal of third molars in Scottish oral and maxillofacial (OMFS) units in 1995 and in 2002. We collected data from anonymous structured postal questionnaires from 12 Scottish OMFS units about patients referred for removal of third molars in 1995 and 11 units in 2002. The percentage of patients who had no treatment increased from 11% in 1995 (102/928) to 16% in 2002 (66/412). The incidence of prophylactic removal of third molars decreased between the two periods. Removal of third molars under local anaesthesia with or without sedation increased from 35% (325/928) in 1995 to 54% (223/412) in 2002. Removal of third molars under general anaesthesia decreased from 54% in 1995 to 30% in 2002.


[X-ray computed tomographic aspects of medium-sized free peritoneal effusions (supramesocolic level)].
This study was conducted in 10 patients recently treated by peritoneal dialysis, and without a previous history of peritoneal disorders. Its aim was to determine the normal distribution of a two litre liquid effusion in the mesocolic recesses. A detailed description of the anatomy of the supramesocolic peritoneum precedes the study CAT scan results.


Knowledge, Attitude, and Practice Towards Biosimilars and Interchangeable Products: A Prescriptive Insight by the Pharmacists.
Pharmacists being the drug experts need to be well aware of the applied handling of biosimilar medicines (BSMs). They are an integral educator, trailblazer, and advocate of biosimilar integration across all clinical settings. Therefore, the current study was conducted to assess the pharmacists' knowledge, attitude, and practices of integrating BSMs into clinical practice. The cross-sectional study was conducted from August 2019 to November 2019. The community pharmacies, clinical and academic settings in Karachi were approached for gathering the responses of pharmacists towards BSMs and interchangeable products using a 30-item survey form. Pearson correlation and independent sample t-test were used to identify the relationship among independent variables and the responses, considering p values <0.05 as statistically significant. Overall, there were 305 survey forms used with a response rate of 87.14%. More than 80% of the respondents have good knowledge about the definition, characteristics, safety and efficacy, compatibility, cost issues, and utilization of BSMs. Around half of the respondents (48.9%, [95% CI 46.6-51.2]) were confident in using BSMs in clinical practice. However, they were concerned about the BSM's safety profile (45.2%, [95% CI 42.1-48.3]), quality (30.2%, [95% CI 28.3-32.1]), and efficacy issues (32.3%, [95% CI 31.2-37.5]). The findings revealed that pharmacists were well informed about the BSMs. However, some of the responses to the attitude demonstrated a lack of understanding of the application of that knowledge. The respondents persuaded that advanced patterns of diseases, product marketing stipulations, and need for better patient care drives higher demand for developing BSMs and were enthusiastic about gaining more insight to integrate BSMs into routine clinical practice.


Mapping wetlands in the Lower Mekong Basin for wetland resource and conservation management using Landsat ETM images and field survey data.
The Mekong River Basin is considered to be the second most species rich river basin in the world. The 795,000 km(2) catchment encompasses several ecoregions, incorporating biodiverse and productive wetland systems. Eighty percent of the rapidly expanding population of the Lower Mekong Basin (LMB), made up in part by Lao PDR, Thailand, Cambodia and Viet Nam, live in rural areas and are heavily reliant on wetland resources. As the populations of Cambodia and Lao PDR will double in the next 20 years, pressure on natural resources and particularly wetlands can only increase. For development planning, resource and conservation management to incorporate wetland issues, information on the distribution and character of Mekong wetlands is essential. The existing but outdated wetland maps were compiled from secondary landuse-landcover data, have limited coverage, poor thematic accuracy and no meta-data. Therefore the Mekong River Commission (MRC) undertook to produce new wetland coverage for the LMB. As resources, funding and regional capacity are limited, it was determined that the method applied should use existing facilities, be easily adaptable, and replicable locally. For the product to be useful it must be accepted by local governments and decision makers. The results must be of acceptable accuracy (>75%) and the methodology should be relatively understandable to non-experts. In the first stage of this exercise, field survey was conducted at five pilot sites covering a range of typical wetland habitats (MRC wetland classification) to supply data for a supervised classification of Landsat ETM images from the existing MRC archive. Images were analysed using ERDAS IMAGINE and applying Maximum Likelihood Classification. Field data were reserved to apply formal accuracy assessment to the final wetland habitat maps, with resulting accuracy ranging from 77 to 94%. The maps produced are now in use at a Provincial and National level in three countries for resource and conservation planning and management applications, including designation of a Ramsar wetland site of international importance.


Fever in uremia: production of leukocytic pyrogen by chronic dialysis patients.
Uremic patients frequently have low baseline temperatures and a blunted febrile response to infection. We investigated the first step in the generation of a febrile response, the production of leukocytic pyrogen (LP) by blood monocytes, in 12 patients on chronic hemodialysis, five patients on continuous ambulatory peritoneal dialysis (CAPD), and 17 control subjects. No significant differences were found in the amount of LP produced by hemodialysis patients, CAPD patients, and control subjects. Uremic serum did not decrease LP production by monocytes from control subjects. Hemodialysis patients who were consistently hypothermic (mean oral predialysis temperature less than or equal to 35.6 degrees F) produced as much LP as those with more normal oral temperatures (mean oral predialysis temperature greater than or equal to 36.8 degrees F). Decreased production of LP does not explain the blunted febrile response noted in patients with chronic renal failure.


Tissue factor and coronary artery disease.
Plaque disruption with superimposed thrombosis is the main cause of acute coronary events such as acute myocardial infarction and unstable angina. Among other factors, tissue factor seems to play an important role determining plaque thrombogenicity. Tissue factor is a potent initiator of the coagulation cascade situated within the vessel wall and is highly exposed to the blood after plaque rupture. Several mediators involved in the process of atherosclerotic plaque formation are capable of inducing tissue factor expression in cells such as monocytes, macrophages and endothelial cells, which under normal conditions do not express tissue factor or to a limited extent only. The increased expression of tissue factor is not limited to the plaque but is also found in circulating monocytes in patients with acute coronary syndromes. In addition, studies have shown an important contribution of tissue factor in the pathogenesis of thrombosis and restenosis after balloon angioplasty. Recent basic studies focus on the therapeutic inhibition of tissue factor. Specific and non-specific inhibitors of tissue factor or the tissue factor/factor VIIa complex have been developed or identified, and have been tested in experimental studies. Clinical studies are currently being initiated. In this review, we present the current knowledge on the role of tissue factor in atherosclerosis, arterial intervention and potential pharmacological approaches, with focus on acute coronary syndromes.


Unrecognized pulmonary arterial hypertension in hospitalized patients.
Pulmonary hypertension (PH) is an underdiagnosed and potentially fatal condition. The utility of screening for PH in hospitalized patients undergoing echocardiography is unknown. The goal of this study was to determine the prevalence of undiagnosed pulmonary hypertension (PH) and probable pulmonary arterial hypertension (PAH) in hospitalized patients undergoing echocardiography for any indication. All hospitalized patients undergoing echocardiography were identified and echocardiographs reviewed prospectively for the presence of a tricuspid regurgitant (TR) jet. Electronic medical records (EMR) of patients with a TR jet ≥ 3 m/s were reviewed for identifiable causes of pulmonary hypertension. Patients with no identifiable cause were classified as presumptive World Health Organization (WHO) Group 1 PH (also known as PAH). These PAH patients were compared to other PH patients for baseline demographic characteristics and comorbidities as well as 30-day readmission and mortality. The admitting physicians of patients classified as PH were advised to consider further evaluation including right heart catheterization. We reviewed 4417 consecutive echocardiograms and identified 448 with a TR jet ≥ 3 m/s. Of these 448 patients with PH, 47 were identified as "presumptive PAH" and the other 401 as having PH belonging to WHO Groups 2-5. Presumptive PAH represented 1% of screened echocardiograms and 10.5% of those identified to have an elevated TR jet. Of the patients identified as presumptive PAH, 8 underwent further evaluation including a right heart catheterization, where 5 were confirmed to have PAH. Kaplan-Meier analysis revealed 30-day readmission was higher among those classified as PAH. Our data shows that pulmonary hypertension, as defined by TR jet ≥ 3 m/s, is frequently encountered in hospitalized patients undergoing echocardiography for any reason. A careful review of echocardiogram findings and clinical history suggested 10.5% of those with PH (and 1% of all screened patients) may meet the criteria for PAH. Considering PH is a fatal condition which is frequently missed, a hospital screening program seems feasible.


High-fat diet alters gene expression in the liver and colon: links to increased development of aberrant crypt foci.
Obesity is associated with an increased risk of colon cancer. High-fat diets that lead to obesity may be a contributing factor, but the mechanisms are unknown. This study examines susceptibility to azoxymethane (AOM)-induced precancerous lesions in mice in response to consumption of either a low or a high-fat diet and associated molecular changes in the liver and colon. Gene markers of xenobiotic metabolism, leptin-regulated inflammatory cytokines and proliferation were assessed in liver and colon in response to high-fat feeding to determine links with increased sensitivity to AOM. High-fat feeding increased development of AOM-induced precancerous lesions and was associated with increased CYP2E1 gene expression in the liver, but not the colon. Leptin receptors and the colon stem cell marker (Lgr5) were down-regulated in the proximal colon, with a corresponding up-regulation of the inflammatory cytokine (IL6) in response to high-fat feeding. Notably in the distal colon, where aberrant crypt foci develop in response to AOM, the proliferative stem cell marker, Lgr5, was significantly up-regulated with high-fat feeding. The current study provides evidence that high-fat diets can alter regulation of molecular markers of xenobiotic metabolism that may expose the colon to carcinogens, in parallel with activation of β-catenin-regulated targets regulating colon epithelial cells. High-fat diets associated with obesity may alter multiple molecular factors that act synergistically to increase the risk of colon cancer associated with obesity.


Myocardial injury and bypass grafting. Value of serum enzymes in diagnosis.
To clarify the value of serum enzymes in the detection of intraoperative and postoperative myocardial injury associated with coronary artery bypass grafting, we evaluated 70 consecutive patients (151 grafts). We used electrocardiograms and serial determinations of serum levels: serum glutamic oxaloacetic transaminase (SGOT), creatinine phosphokinase (CPK), lactic dehydrogenase (LDH), and LDH isoenzymes on Days zero, 1, 3, 5, 7, and 10. Patency of all grafts 1 week postoperatively was 92 per cent. Fourteen patients (20 per cent) had ECG evidence of acute myocardial infarction (AMI) or ischemia lasting longer than 48 hours. This incidence of AMI was attendant with no deaths or discernible changes in postoperative ventriculography. LDH-1 (cardiac fraction) was elevated in all patients with myocardial injury. Late elevation of LDH-1 occurred in 2 patients at the time of postoperative catheterization, 1 of whom had negative findings on ECG. Diagnostic correlation was not observed with total LDH, CPK, or SGOT. Predisposing factors to AMI included preinfarction angina (4 of 14 patients), occluded grafts (4 of 14), and a bypass time greater than 120 minutes.


Prevalence of Haemoproteus spp. (Apicomplexa: Haemoproteidae) in tortoises in Brazil and its molecular phylogeny.
Captive terrestrial tortoises of the species Chelonoidis carbonaria (n = 17) and Chelonoidis denticulata (n = 37) in the state of Minas Gerais, southeastern Brazil, were examined for hematozoans by using a combination of microscopic and molecular methods. Microscopic examination revealed young intra-erythrocytic forms in blood smears from both species of tortoises. The results of PCR, sequencing, and phylogenetic analysis indicated that these parasites belonged to the Haemoproteus spp., whose observed prevalence was 17.6 % in C. carbonaria and 13.5 % in C. denticulata. Phylogenetic analysis indicated that these sequences formed a clade that was grouped with other sequences of Haemoproteus spp. parasites in birds, separate from the clade formed by Haemoproteus spp. of reptiles. This study expands the information regarding the occurrence and distribution of hemosporidia in turtles and is the first study of blood parasites in C. carbonaria.


Evaluation of the effect of alpha-tocopherol on anxiety and the neuroinflammatory process during alcohol withdrawal in a model of forced and chronic self-administration of liquid diet containing ethanol: Behavioral and neurochemical evidence.
Alcoholism affects about 2 billion people worldwide. Withdrawal causes a neuroinflammatory response that increases anxiety. α-tocopherol is the most important antioxidant that has its in vivo action currently known. Therefore, this study aimed to evaluate the effect of α-tocopherol on the neuroinflammatory process in brain regions involved in anxiety and its anxiolytic potential during alcohol withdrawal. For this, male Wistar rats were divided into four groups and submitted to a procedure of forced and chronic self-administration of liquid diet containing 6% and 8% ethanol for 15 days, followed by abrupt interruption of treatment. Animals in the control group received the liquid diet without ethanol. Twenty-four or 48 h after ethanol discontinuation, and 30 min after the last administration of α-tocopherol or saline, animals were evaluated in the elevated plus maze, light/dark box, and open field tests. At the end of the tests, each experimental group underwent brain tissue collection for analysis of cytokine levels. The results showed that: alcohol induces the neuroinflammatory process and anxiety; the stress generated by withdrawal can induce oxidative stress, which alters the production of inflammatory cytokines in the amygdaloid nuclei (AN) and medial hypothalamic nucleus (mHN); α-tocopherol exhibited anxiolytic and anti-inflammatory activity, attenuating the anxious behavior of abstinent animals and reducing neuroinflammation in AN and mHN; and the intensity of the anxiolytic and anti-inflammatory effect of α-tocopherol is dose-dependent. These results identify α-tocopherol as a potential therapeutic target supporting the fight against relapse during alcohol withdrawal.


Low dose ketamine as an analgesic adjuvant in difficult pain syndromes: a strategy for conversion from parenteral to oral ketamine.
Ketamine is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist with analgesic and dissociative anesthetic properties. Low dose or sub-anesthetic doses of ketamine have been used effectively as either a primary analgesic or analgesic adjuvant in a variety of pain syndromes. In this paper, three patients with difficult to treat, predominantly neuropathic pain syndromes will be described. Their pain syndromes were initially managed successfully with the addition of low dose parenteral ketamine as an analgesic adjuvant. The strategy of concurrently starting ketamine at a low dose, i.e., 40-60 mg over 24 hours, with a benzodiazepine proved effective in preventing psychotomimetic side effects. An unavoidable shortage of ketamine prompted a literature search, which suggested that the equianalgesic dose of oral ketamine could be lower than the parenteral dose. Subsequently the patients were converted to oral ketamine at doses 30 to 40% of the previous parenteral dose. Their pain syndromes remained controlled on the lower dose of oral ketamine with remarkably few side effects. The implications of this warrant further discussion and study.


Estimation of aboveground biomass of vegetation based on landsat 8 OLI images.
Remote sensing estimation of aboveground biomass for desert oasis vegetation in arid area is an important means to monitor land desertification, it is of great significance to accurately evaluate the carbon sink change of desert oasis ecosystem, and maintain the stability of oasis ecosystem. The aboveground biomass information of vegetation, such as vegetation index and band factor in a delta oasis area is obtained by using Landsat 8 OLI image data; Based on the combination with the measured aboveground biomass data of vegetation, the optimal estimation model of aboveground biomass of four vegetation types (arbors, shrubs, herbs and crops) in this area is established, and the above ground biomass of vegetation was retrieved and verified. The results showed that: (1) there was a very significant correlation between the remote sensing factors of aboveground biomass of four vegetation types and the measured aboveground biomass, and the correlation coefficient ranged from 0.711 to 0.756 (P < 0.01); (2) multiple stepwise regression (MSR) model is the optimal estimation model of aboveground biomass of arbors and shrubs, and partial least squares regression (PLSR) model is the optimal estimation model of aboveground biomass of herbs and crops, the estimation results have a good linear fitting relationship with the measured results; (3) the order of aboveground biomass of vegetation in oasis area from low to high is: herbs < shrubs < arbors < crops. Among them, the aboveground biomass of grass is mainly below 280 g m-2, the aboveground biomass of shrub is mainly 280-950 g m-2, and the aboveground biomass of four vegetation is mainly distributed in 280-1450 g m-2. Based on the Landsat 8 OLI image data, the remote sensing estimation model can accurately estimate the aboveground biomass of four oasis vegetation types (arbors, shrubs, herbs and crops), and reveal the spatial distribution characteristics of aboveground biomass of oasis vegetation.


Epigenetic age analysis of brain in major depressive disorder.
A large body of evidence indicates major depressive disorder (MDD) associated with biological aging acceleration. In this study, we aim to assess epigenetic aging in different prefrontal sub-regions and cell types from postmortem tissues in MDD by using two public methylation datasets (subjects are 40 and 58 respectively). Results showed that brain epigenetic age has a strong correlation with chronological age in both datasets. However, there are no significant differences in epigenetic aging acceleration between MDD and controls in all prefrontal sub-regions and cell types. In conclusion, this study provides evidence against epigenetic aging acceleration in the brain in MDD.


Transculturation of Madness: The Double Origin of Lu Xun's "Diary of a Madman".
Over the years scholars have examined the allegorical features of the depiction of madness in Lu Xun's "Diary of a Madman," yet to date little research has taken into consideration the intercultural angle embedded in the narrative's intersection of three cultures, namely Russian, Japanese and Chinese. This paper traces the European-Japanese-Sino route of modern neologisms of madness to explore the introduction of such neologisms into the modern Chinese language and how it corresponds with changing patterns of knowledge and power. I use my study of transculturation on the macro scale to frame a reexamination of the lexicon in "Diary of a Madman." I focus especially on kuangren and pohaikuang, the two key words employed by Lu Xun, to see how they contribute to the ambiguity in his attitude towards the power struggle between the East and the West, the old and the new.


Continuous resin refilling and hydrogen bond synergistically assisted 3D structural color printing.
3D photonic crystals (PCs) have attracted extensive attention due to their unique optical properties. However, fabricating 3D PCs structure by 3D printing colloidal particles is limited by control of assembly under a fast-printing speed. Here, we employ continuous digital light processing (DLP) 3D printing strategy with hydrogen bonds assisted colloidal inks for fabricating well-assembled 3D PCs structures. Stable dispersion of colloidal particles inside UV-curable system induced by hydrogen bonding and suction force induced by continuous curing manner cooperatively realize the simultaneous macroscopic printing and microscopic particle assembly, which endows volumetric color property. Structural color can be well regulated by controlling the particle diameter and printing speed, through which various complex 3D structures with desired structural color distribution and optical light-guide properties are acquired. This 3D color construction approach shows great potential in customized jewelry accessories, decoration and optical device preparation, and will innovate the development of structural color.


The control mechanism of relaxation in molluscan catch-muscle (ABRM).
The relaxing effects of 5-hydroxytryptamine (5-HT) have been tested on glycerol-extracted and chemically treated fibres (EDTA and Triton X-100 at two ionic strengths (0.06 and 0.28) and two pH's (6.5 and 7.0). The resistance to stretch of the two muscle preparations has been studied in the low Ca2+ medium i.e. without contractile activity in presence and in absence of 5-HT. The presence of 5-HT reduces significantly the resistance to stretch of chemically treated fibers in conditions of ionic strength 0.28 and 7.0, but has no effect on glycerol extracted fibres. 2. After the maximal tension has been developed in a high Ca2+ solution (10-6 M) the rate of relaxation of chemically treated fibres, induced by a low Ca2+ solution (10-9 M) at ionic strength 0.28 and pH 7.0 is increased by the addition of 5-HT. No effect is observed in glycerol extreacted fibres. 3. Chemically treated fibres in catch-state induced at ionic strength 0.28 and pH 6.5. 4. Cyclic AMP (c-AMP) induces the same relaxing effects at 5-HT on chemically treated fibres in the same conditions of ionic strength, pH and Ca2+ concentration. 5. The results are in disagreement with the hypothesis that the catch-state in ABRM is due to a lowering of the intracellular strength and pH; they suggest that the intracellular physiological conditions are rather near ionic strength 0.28 and pH 7.0 even in catch-state. We suppose that the relaxing effect of 5-HT, is not be due to a decrease of the intracellular free Ca2+ level but rather to an increase of the rate of Ca2+ release from the contractile proteins, and that it is mediated through c-AMP and intracellular relaxing mediator.


The preparation of cultured rabies virus and the production of antiserum for human use.
In this paper we describe a methodology for the preparation of the Pasteur strain of fixed rabies virus in BHK-21 clone 13 cells and also its use for the production of antisera in horses. The methodology showed here is simple, rapid, facilitates the attainment of high protective titers, and the antisera produced are of high quality.


Full-length 3'-untranslated region reporter construction with recombineering.
Complexity in higher animals derives in part from various modalities of protein-coding gene expression regulation, including microRNA repression by binding to 3'-untranslated regions (UTRs) of specific genes. Reporter constructs containing candidate microRNA target sites are a popular approach of functional studies, and full-length 3'-UTR sequences are preferred because they contain all regulatory elements and preserve higher order structure as much as possible. However, this approach is often handicapped by the extreme length of the 3'-UTR. Here, we present a rapid and accurate cloning procedure to generate full-length 3'-UTR reporter constructs by recombinogenic engineering (recombineering) in vivo cloning. The approach includes making retrieval constructs by sequence- and ligation-independent cloning (SLIC) and retrieving the full-length 3'-UTR in one exon to the retrieval construct from a bacterial artificial chromosome (BAC) by recombineering to generate the final full-length 3'-UTR reporter construct for the gene of interest. This method is successfully implemented with mouse full-length 3'-UTRs of Igf1 (6.5 kb), Igf1r (7.5 kb), and Sp1 (5.5 kb). Expansion of this method is adaptable to retrieve 3'-UTRs encoded in more than one exon by removing the introns from the BAC first with recombineering. This method will advance functional studies of regulation of gene expression at the post-transcriptional level through microRNA suppression.


Immediate Implants.
Immediate implants have become a popular option for replacing teeth. This article describes the surgical and restorative considerations involved in the planning and placement of an immediate implant. Immediate implants require appropriate hard and soft tissue assessment. Virtual planning can help assist in planning of immediate implants. Radiographic and computed tomographic guidance can help in establishing the relationship between the planned implant to the hard tissue and anatomic structures. This article discusses a technique in fabrication of the immediate provisional and final restoration.