Evaluation of genetic risk, its clinical manifestation and disease management based on 18 susceptibility gene markers among West-Slavonic patients with sarcoidosis.
Sarcoidosis is a heterogenous, multisystemic inflammatory disease that primarily affects lungs. In this study, we multiplex genotyped 18 single-nucleotide polymorphisms (SNPs) to replicate the findings from previous genome-wide association studies (GWAS) and candidate gene studies, and extended analyses to different clinical manifestations (Löfgren's syndrome and chest X-ray [CXR] stages) including treatment response among West-Slavonic subjects (564 sarcoidosis patients and 301 healthy controls). We confirm the replication (with Bonferroni's correction) of ANXA11 rs1049550 as protective variant for sarcoidosis (odds ratio [OR] = 0.71, p = 1.33 × 10-3), non-LS (OR = 0.66, p = 2.71 × 10-4) and CXR stages 2-4 (OR = 0.62, p = 7.48 × 10-5) compared to controls in West-Slavonic population. We also validate the association of risk variants C6orf10 rs3129927 (OR = 2.61, p = 2.60 × 10-8), TNFA rs1800629 (OR = 1.56, p = 6.65 × 10-4), ATF6B rs3130288 (OR = 2.75, p = 1.06 × 10-9) and HLA-DQA1 rs2187668 (OR = 1.74, p = 8.83 × 10-4) with sarcoidosis compared to controls. For sub-phenotypes compared to controls, risk variants C6orf10 rs3129927 (OR = 5.35, p = 1.07 × 10-12), TNFA rs1800629 (OR = 2.66, p = 5.94 × 10-7), ATF6B rs3130288 (OR = 5.24, p = 5.21 × 10-13), LRRC16A rs9295661 (OR = 2.97, p = 4.29 × 10-4), HLA-DQA1 rs2187668 (OR = 3.14, p = 1.09 × 10-6) and HLA-DRA rs3135394 (OR = 5.23, p = 8.25 × 10-13) were associated with LS while C6orf10 rs3129927 (OR = 1.96, p = 4.27 × 10-4) and ATF6B rs3130288 (OR = 2.15, p = 3.36 × 10-5) were associated with non-LS. For CXR stages compared to controls, C6orf10 rs3129927 (OR = 3.67, p = 3.63 × 10-11), TNFA rs1800629 (OR = 1.84, p = 1.32 × 10-4), ATF6B rs3129927 (OR = 3.63, p = 1.82 × 10-11), HLA-DQA1 rs2187668 (OR = 2.13, p = 9.59 × 10-5) and HLA-DRA rs3135394 (OR = 3.42, p = 3.45 × 10-10) were risk variants for early CXR stages 0-1 while C6orf10 rs3129927 (OR = 1.99, p = 5.51 × 10-4), ATF6B rs3129927 (OR = 2.23, p = 3.52 × 10-5) and HLA-DRA rs3135394 (OR = 1.85, p = 2.00 × 10-3) were risk variants for advanced CXR stages 2-4. The present findings nominate gene variants as plausible prognostic markers for clinical phenotypes, treatment response and disease resolution/progression and may form the basis for establishing genotype-phenotype relationships in patients with sarcoidosis among West-Slavonic population.


The influence of gender on human innate immunity.
Several experimental, clinical, and epidemiologic studies indicate a better prognosis in women after an infectious challenge. The monocyte/macrophage, as coordinators of the innate immune response to sepsis, secrete plasma inflammatory cytokines. Elevated plasma cytokine levels are inversely correlated with outcome. In addition, single-nucleotide polymorphisms related to these cytokine genes and in genes important for lipopolysaccharide (LPS) detection, particularly toll-like receptor-4, have been associated with variations in clinical outcome. We hypothesize that the gender differences in clinical outcome are due to measurable differences in cytokine responses and intracellular signaling, and these differences are independent of polymorphism carrier status. Venous blood samples from healthy subjects (56 men, 23 women) were incubated with LPS, and supernatant cytokine levels were determined by enzyme-linked immunosorbent assay. In a randomly chosen subgroup, (8 men, 4 women), peripheral blood mononuclear cells were isolated, and LPS-mediated intracellular mitogen-activated protein kinase (MAPK) phosphorylation was assayed via Western blot analysis. Each subject was screened for the following SNPs: tumor necrosis factor alpha (TNF-alpha) -308G/A, interleukin (IL)-6 -174G/C, IL-1beta -31C/T, and toll-like receptor-4 (TLR4) +896A/G. Women produced significantly less LPS-induced TNF-alpha and IL-1beta but not IL-6. When the analysis was adjusted for the presence of each polymorphism, the differences in TNF-alpha and IL-1beta accumulation persisted. Female gender was associated with lower MAPK phosphorylation at each LPS concentration but was not statistically significant. Gender-specific differences in LPS-induced TNF-alpha and IL-1beta were observed, possibly attributed to alterations in MAPK phosphorylation. Furthermore, studies investigating the influence of genomic variation on the innate immune response should address potential gender-related differences.


Quinazolines: combined type 3 and 4 phosphodiesterase inhibitors.
A series of quinazolines has been prepared and evaluated for its ability to inhibit cyclic AMP phosphodiesterase type 3, type 4A, 4B and 4D. The most potent inhibitors showed IC50 values in the nanomolar range for type 3 and type 4 isoforms and bind with high affinity to the [3H]rolipram binding site. These quinazolines represent a new family of potent mixed PDE 3/4 inhibitors and are expected to have a therapeutic potential.


Chemopreventive effects of a serratane-type triterpenoid, 3alpha-methoxyserrat-14-en-21beta-ol (PJ-1), against rat lung carcinogenesis.
Our efforts to search for cancer-chemopreventive agents have been focused on constituents from materials of trees such as leaves and bark as waste in the forestry industry. Cancer-chemopreventive effects of a serratane-type triterpenoid from the bark of Picea jezoensis, 3alpha-methoxyserrat-14-en-21beta-ol (PJ-1), were here examined in a revised rat multi-organ carcinogenesis (DMBDD) model. Male 6-week-old F344 rats received combined treatment with five different carcinogens and starting 1 week thereafter were administered PJ-1 at a dose of 2mg/kg or 6mg/kg body wt i.g. (five times/week) or the vehicle as a control (1ml of 0.5% CMC). At the termination at week 30, significant decrease of adenomas (P<0.01) and total tumors (P<0.01) and a trend for reduction of adenocarcinoma multiplicity in the lung were observed, but without any modulating influence in other major organs. The cell proliferation indices in the lungs tended to be decreased in the PJ-1 administered groups, with apparent induction of CYP2B1/2 mRNA expression to recover the values observed in non-initiated controls. These results indicate that PJ-1 exerts cancer-chemopreventive effects on rat lung carcinogenesis after multi-organ initiation.


Modulation of rat erythrocyte antioxidant defense system by buthionine sulfoximine and its reversal by glutathione monoester therapy.
The protective effects of glutathione monoester (GME) on buthionine sulfoximine (BSO)-induced glutathione (GSH) depletion and its sequel were evaluated in rat erythrocyte/erythrocyte membrane. Animals were divided into three groups (n=6 in each): control, BSO and BSO+GME group. Administration of BSO, at a concentration of 4 mmol/kg bw, to the albino rats resulted in depletion of blood GSH level to about 59%. GSH was elevated several folds in the GME group as compared to the control (P<0.05) and BSO (P<0.001) groups. Decreased concentration of vitamin E was found in the erythrocyte membrane isolated from BSO-administered animals. Antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were also found to be altered due to BSO-induced GSH depletion in blood erythrocytes. The SOD and CAT activities in BSO group were significantly lower (P<0.001) than the other groups. Lipid peroxidation index and malondialdehyde (MDA) levels in erythrocytes and their membranes were increased to about 45% and 40%, respectively. The activities of Ca2+ ATPase, Mg2+ ATPase and Na+K+ ATPase were lower than those of control group (P<0.05), whereas the activities of these enzymes were found to be restored to normal followed by GME therapy (P<0.05). Cholesterol, phospholipid and C/P ratio and some of the phospholipid classes like phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin were significantly (P<0.05) altered in the erythrocyte membranes of BSO-administered rats compared with those of control group. These parameters were restored to control group levels in GME-treated group. Oxidative stress may play a major role in the BSO-mediated gamma glutamyl cysteine synthetase (gamma-GCS) inhibition and hence the depletion of GSH. In conclusion, our findings have shown that antioxidant status decreased and lipid peroxidation increased in BSO-treated rats. GME potentiates the RBC and blood antioxidant defense mechanisms and decreases lipid peroxidation.


Effectiveness comparisons of Chinese patent medicine on treating premature ejaculation: A systematic review and meta-analysis.
Premature ejaculation (PE) is a form of male sexual dysfunction. As people's lifestyle changes and the population ages, the incidence of PE continues to increase. Chinese patent medicines have been widely used in clinical practice as derivatives of traditional Chinese medicine (TCM). Many clinical trials have proven that Chinese patent medicine has a significant effect in the treatment of PE. In this systematic review, we aim to evaluate the effectiveness and safety of Chinese patent medicine for PE. We will search for PubMed, Cochrane Library, AMED, Embase, WorldSciNet, Nature, Science online and China Journal Full-text Database, China Biomedical Literature CD-ROM Database, and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to September 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the RevMan 5.3 and Stata 13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of PE. This systematic review will evaluate the efficacy and safety of TCM for treating PE. Because all of the data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. PROSPERO CRD42017065316.


Distress Tolerance and Psychological Comorbidity in Patients Seeking Bariatric Surgery.
Distress intolerance is characterized by a low threshold for negative emotional experiences and lack of emotion regulation and has been shown to predict various health outcomes. As such, the primary aim of this study was to determine the association between distress tolerance and psychological variables (eating behaviors, mood, substance use, trauma history), completion of bariatric surgery, and post-bariatric surgery weight loss outcomes and follow up with a provider. Two hundred forty-eight patients (75 % female, 89 % Caucasian) underwent a multidisciplinary evaluation for bariatric surgery and were assessed for psychiatric disorders via semi-structured clinical interview and psychometric questionnaires. Low distress tolerance was associated with symptoms of depression (p ≤ 0.001), anxiety (p ≤ 0.001), disordered eating behaviors (p ≤ 0.001), substance abuse (p ≤ 0.001), a history of being the victim of childhood sexual abuse (p ≤ 0.001), and with high BMI (p < .05). Patients endorsing higher levels of distress tolerance were more likely to undergo bariatric surgery (p < .01). Distress tolerance was not related to 2-year post-surgical weight loss outcomes or follow up with a provider. The ability to tolerate negative affect may be a variable that differentiates which patients undergo bariatric surgery rather than early postoperative outcomes.


Surgical correction of external genitalia and lower genitourinary tract of markedly virilized child.
Three children who were seen with marked androgenization, including clitoromegaly, labial fusion, and absent vaginal introitus are presented. In each, the vagina was found to be entering at the level of the posterior urethra. Vaginoplasty was performed in each child utilizing a transperineal "pull through" technique. Reduction clitoroplasty was performed in 1 patient. The advantages and optimal timing of these techniques are discussed.


Physiopathology of ventricular tachyarrhythmias.
Ventricular arrhythmias may be the result of three mechanisms: abnormal automaticity, triggered activity complicating early or late after-depolarizations, and reentry by circular pathway or by reflection. These three fundamental mechanisms have been observed in the intact heart in experimental models of myocardial ischemia and digitalis intoxication. In man, the arguments in favor of a given mechanism are indirect and may be determined by their response to stimulation. It may be possible to state the following conclusions: (1) reentry is at the origin of ventricular fibrillation, certain ventricular tachycardias of bundle branch reentry and probably most chronic sustained ventricular tachycardias that are easily inducible; (2) the mechanism of certain other ventricular arrhythmias sustained remains unknown; (3) even when arrhythmias are associated with reentry, the triggering extrasystole can arise from a focal origin.


Interpreting resting heart rate variability in complex populations: the role of autonomic reflexes and comorbidities.
Resting heart rate variability (HRV) is an important biomarker linking mental health to cardiovascular outcomes. However, resting HRV is also impaired in autonomic neuropathy, a common and underdiagnosed complication of common medical conditions which is detected by testing autonomic reflexes. We sought to describe the relationship between autonomic reflex abnormalities and resting HRV, taking into consideration medical comorbidities and demographic variables. Participants (n = 209) underwent a standardized autonomic reflex screen which was summarized as the Composite Autonomic Severity Score (CASS) and included measures of reflexive HRV, e.g., heart rate with deep breathing (HRDB). Resting HRV measures were: pNN50 (percentage of NN intervals that differ by > 50 ms) and cvRMSSD (adjusted root mean square of successive differences). In univariate analyses, lower resting HRV was associated with: older age, higher CASS, neuropathy on examination, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and psychiatric disease. Adaptive regression spline analysis revealed that HRDB explained 27% of the variability in resting HRV for participants with values of HRDB in the normal range. Outside this range, there was no linear relationship because: (1) when HRDB was low (indicating autonomic neuropathy), resting HRV was also low with low variance; and (2) when HRDB was high, the variance in resting HRV was high. In multivariate models, only HRDB was significantly independently associated with cvRMSSD and pNN50. Subclinical autonomic neuropathy, as evidenced by low HRDB and other autonomic reflexes, should be considered as a potential confounder of resting HRV in research involving medically and demographically diverse populations.


Draft Genome Sequence of Lactobacillus rhamnosus OSU-PECh-69, a Cheese Isolate with Antibacterial Activity.
The novel strain Lactobacillus rhamnosus OSU-PECh-69 was isolated from provolone cheese. It produces antimicrobial agents having a molecular mass of 5 to 10 kDa that are active against Gram-positive and Gram-negative bacteria. The strain has a genome sequence of 3,057,669 bp, a GC content of 46.6%, and up to two gene clusters encoding bacteriocins.


Adult-onset primary open-angle glaucoma caused by mutations in optineurin.
Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.


Interaction between Prion Protein's Copper-Bound Octarepeat Domain and a Charged C-Terminal Pocket Suggests a Mechanism for N-Terminal Regulation.
Copper plays a critical role in prion protein (PrP) physiology. Cu(2+) binds with high affinity to the PrP N-terminal octarepeat (OR) domain, and intracellular copper promotes PrP expression. The molecular details of copper coordination within the OR are now well characterized. Here we examine how Cu(2+) influences the interaction between the PrP N-terminal domain and the C-terminal globular domain. Using nuclear magnetic resonance and copper-nitroxide pulsed double electron-electron resonance, with molecular dynamics refinement, we localize the position of Cu(2+) in its high-affinity OR-bound state. Our results reveal an interdomain cis interaction that is stabilized by a conserved, negatively charged pocket of the globular domain. Interestingly, this interaction surface overlaps an epitope recognized by the POM1 antibody, the binding of which drives rapid cerebellar degeneration mediated by the PrP N terminus. The resulting structure suggests that the globular domain regulates the N-terminal domain by binding the Cu(2+)-occupied OR within a complementary pocket.


Endoscopy Reports for Rectosigmoid Tumors: Frequently Missing Key Information Needed for Surgical Planning.
Endoscopy reports by gastroenterologists describing rectosigmoid tumors often are missing crucial data for surgical planning, leading to high rates of repeat exams before surgical decision-making. We hypothesize that there will be significant deficiencies in the endoscopic reporting of rectosigmoid lesions leading to high rates of repeat endoscopic examination at our institution. Retrospective review from January 2016 to November 2019 included 188 patients with rectosigmoid lesions referred for surgery with an outside endoscopy report. Three criteria were abstracted from these reports or included pictures: (1) distance from the tumor to an anatomical landmark (anal verge, dentate line, sphincter), (2) Tattoo placement (if performed) and location, and (3) tumor relationship to the valves of Houston. Reports were classified exemplary, nearly adequate, or inadequate if 3, 2, and ≤ 1 of these criteria were met, respectively. Distance was reported in 38.8% (n = 73) of reports, with the anal verge being the most commonly reported anatomical landmark (32.4%, n = 61 reports). Tattoo was placed in 34.6% (n = 65), though only 21.8% (n = 41) described the location of the tattoo relative to the tumor. Relationship to the valves of Houston was seen in 29.2% (n = 55) of reports. Only 5.3% (n = 10) of outside endoscopy reports were graded as exemplary, 20.2% (n = 38) nearly adequate, and the remaining 74.5% (n = 140) inadequate. A total of 87.5% (n = 165) of patients required repeat endoscopy with a significantly higher proportion from the inadequate group. Many referring endoscopy reports contain inadequate information for the surgical planning of rectosigmoid tumor resection. Efforts to improve documentation (particularly about distance and location within the rectum) must be undertaken.


In vitro antimycobacterial activity and HPLC-DAD screening of phenolics from Ficus benjamina L. and Ficus luschnathiana (Miq.) Miq. leaves.
The total phenolic content (Folin-Ciocalteu) of the leaves of Ficus benjamina and Ficus luschnathiana was evaluated and screened by HPLC-DAD. Ficus luschnathiana crude extract (CE) presented phenolic content higher than that of F. benjamina (149.92 ± 3.65 versus 122.63 ± 2.79 mg of GAE). Kaempferol (1.63 ± 0.16 mg g(-1) dry weight of CE) and chlorogenic acid (17.77 ± 0.57 mg g(-1) of butanolic fraction) were identified and quantified in F. benjamina, whereas rutin (1.39 ± 0.20 mg g(-1)), caffeic (1.14 ± 0.13 mg g(-1)) and chlorogenic (3.73 ± 0.29 mg g(-1)) acids were quantified in the CE of F. luschnathiana. Additionaly, rutin (15.55 ± 1.92 mg g(-1)) and quercetin (3.53 ± 0.12 mg g(-1)) were quantified in ethyl acetate and butanolic fractions, respectively. Antimycobacterial activity of CEs and fractions was evaluated against Mycobacterium smegmatis by broth microdilution method. Ethyl acetate fraction from F. benjamina and n-butanol fraction from F. luschnathiana displayed the highest inhibitory activity (MIC = 312.50 µg mL(-1) and 156.25 µg mL(-1), respectively). Further studies are required to identify the compounds directly related to antimycobacterial activity.


How we do it: adaptation of music instruction for pediatric cochlear implant recipients.
This paper outlines the skills required for participation in structured music programs and possible adaptations to facilitate successful participation by pediatric cochlear implant recipients. Common curricular components that present the structural features of music and the implications for perceptual and music production skills are discussed. A checklist of practical recommendations for clinicians, educators, and parents is provided to ensure success in integrating cochlear implant recipients into early childhood music programs.


2,5-Diaryloxadiazoles and their precursors as novel inhibitors of cathepsins B, H and L.
High levels of cathepsins indicated in various pathological conditions like arthritis, cancer progressions, and atherosclerosis explains the need to explore potential inhibitors of these proteases which can be of great therapeutic significance. We, in the present work, report the synthesis of some 2,5-diaryloxadiazoles from N-subsitutedbenzylidenebenzohydrazides. The synthesized compounds were screened for their inhibitory potential on cathepsins B, H and L. Structure Activity Relationship studies show that 2,5-diaryloxadiazoles were less inhibitory than their precursors. 1i and 2k have been found to be most inhibitory to cathepsins B and L. Their Ki values have been calculated as 11.38×10(-8)M and 66.4×10(-8)M for cathepsin B and 4.2×10(-9)M and 47.31×10(-9)M for cathepsin L, respectively. However, cathepsin H activity was maximally inhibited by compounds, 1e and 2c with Ki values of 4.4×10(-7)M and 5.6×10(-7)M, respectively. Enzyme kinetic studies suggest that these compounds are competitive inhibitors to the enzymes. The results have been compared with docking results obtained using iGemDock.


Corrigendum to "The impact of digital transformation on innovation performance - The mediating role of innovation factors" [9(3) (March 2023), e13916].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e13916.].


Screening of genes expressed in vivo after infection by Vibrio anguillarum M3.
Genes uniquely expressed in vivo may contribute to the overall pathogenicity of an organism and are likely to serve as potential targets for the development of new vaccine. This study aims to screen the genes expressed in vivo after Vibrio anguillarum infection by in vivo-induced antigen technology (IVIAT). The convalescent-phase sera were obtained from turbot (Scophthalmus maximus) survived after infection by the virulent V. anguillarum M3. The pooled sera were thoroughly adsorbed with M3 cells and Escherichia coli BL21 (DE3) cells. A genomic expression library of M3 was constructed and screened for the identification of immunogenic proteins by colony immunoblot analysis with the adsorbed sera. After three rounds of screening, 19 putative in vivo-induced (ivi) genes were obtained. These ivi genes were catalogued into four functional groups: regulator/signalling, metabolism, biological process and hypothetical proteins. Three ivi genes were insertion-mutated, and the growth and 50% lethal dose (LD(50) ) of these mutants were evaluated. The identification of ivi genes in V. anguillarum M3 sheds light on understanding the bacterial pathogenesis and provides novel targets for the development of new vaccines and diagnostic reagents. To the best of our knowledge, this is the first report describing in vivo-expressed genes of V. anguillarum using IVIAT. The screened ivi genes in this study could be new virulent factors and targets for the development of vaccine, which may have implications for the development of diagnostic regents.


Identification of two forms of molybdate-stabilized, non-transformed glucocorticoid hormone-receptor complex by gel filtration chromatography.
Glucocorticoid-receptor complexes in rat thymus cytosol were characterized by gel-filtration chromatography on Agarose A-1.5 m and Sephacryl S-300. Two forms of non-transformed complex were identified at low ionic strength in the presence of molybdate, with Stokes radii of approx 8 nm and 6 nm. The 8 nm molybdate-stabilized form could be converted to the 6 nm form by chromatography on Sephacryl S-300 or Lipidex 1000 or by incubation with dextran-charcoal or phospholipase C, but not by chromatography on Sephadex G-25; none of the treatments promoted receptor transformation. It is suggested that the change in Stokes radius from 8 to 6 nm results from the removal of a lipid factor responsible for maintaining the complex in the 8 nm form.


Synaptic Rectification Controls Nonlinear Spatial Integration of Natural Visual Inputs.
A central goal in the study of any sensory system is to predict neural responses to complex inputs, especially those encountered during natural stimulation. Nowhere is the transformation from stimulus to response better understood than the vertebrate retina. Nevertheless, descriptions of retinal computation are largely based on stimulation using artificial visual stimuli, and it is unclear how these descriptions map onto the encoding of natural stimuli. We demonstrate that nonlinear spatial integration, a common feature of retinal ganglion cell (RGC) processing, shapes neural responses to natural visual stimuli in primate Off parasol RGCs, whereas On parasol RGCs exhibit surprisingly linear spatial integration. Despite this asymmetry, both cell types show strong nonlinear integration when presented with artificial stimuli. We show that nonlinear integration of natural stimuli is a consequence of rectified excitatory synaptic input and that accounting for nonlinear spatial integration substantially improves models that predict RGC responses to natural images.


The accuracy of a novel pedicle screw insertion technique assisted by a special angular scale in the subaxial cervical spine using lateral mass as a reference marker.
Posterior cervical pedicle screw (CPS) internal fixation has better biomechanical stability than other posterior cervical fixation methods. However, this technique is limited in clinical practice due to the complex anatomical structure and the adjacent relationship of the cervical pedicle, and the high risk of neurovascular injury. The purpose of this study was to describe a novel subaxial CPS insertion technique assisted by a special angular scale using lateral mass as a reference marker and to evaluate the accuracy of CPS placement and the distribution characteristics of CPS misplacement. A total of 36 patients with subaxial cervical spine diseases who underwent posterior CPS fixation were consecutively selected. The optimal entry point on the posterior surface of the lateral mass was identified on the three-dimensional cervical model reconstructed from preoperative computed tomography (CT) images. The pedicle transverse angle (PTA) and pedicle-lateral mass angle (PLMA) were measured on the transverse and sagittal CT images respectively. The pedicle screws were inserted according to the preoperatively planned entry point and angles. We analysed the postoperative CT images for CPS misplacement rates and perforation directions following the Lee classification. Overall, 177 pedicle screws were inserted, of which 119 (67.2%) were classified as grade 0, 43 (24.3%) as grade 1, 12 (6.8%) as grade 2 and 3 (1.7%) as grade 3 by the postoperative CT images. The accuracy rate of CPS placement was 91.5%. Of the 15 misplaced pedicle screws (grades 2 and 3), 11 were lateral pedicle perforations, 3 were superior perforations and 1 was an inferior perforation. There were no neurovascular injuries related to CPS misplacement. With our technique, the optimal entry point and two angles (PTA and PLMA) were identified for CPS insertion. The novel CPS insertion technique assisted by a special angular scale provides high accuracy and few complications.


Two cases of quadricuspid aortic valve.
Quadricuspid aortic valve is a rare congenital malformation of the aortic valve. Most cases are discovered incidentally at autopsy or at aortic valve replacement. Recent advances in echocardiography epecially transesophageal echocardiography led to diagnosis of more cases before surgery. Two cases of quadricuspid aortic valve are presented.


The main issues affecting coasts of the Indian and western Pacific Oceans: a meta-analysis from Seas at the Millennium.
A review of the world oceans in three volumes by 365 scientists, provides scope for several 'meta-analyses' of the main problems affecting over 100 areas in the year 2000. This article summarises the main issues affecting a sub-set of the reviewed areas, covering Asian, African and Arabian countries dealt with in Volume 2, which included over 50 articles. From all issues raised, assessment is made of the nature of the major ones, including evaluation of reasons why so many of them remain important issues after so much attention to them. These include long standing problems, several problems more newly flagged as becoming particularly important, the issue of global warming and no less than three related issues connected with fishing and over exploitation. One or two issues such as industrial pollution and sewage, previously considered of almost universal concern, almost traditional pollution issues even, continue to feature strongly for some countries, but while these were almost always referred to in Seas chapters, by and large these categories appear not to be the most pressing of issues today, except in localized areas (albeit areas where huge numbers of people live). Perhaps other issues have simply taken over. They are excluded from this article.


Solid state characterization of an neuromuscular blocking agent--GW280430A.
GW280430A is an ultrashort-acting neuromuscular blocking agent and is targeted for muscle relaxation as part of the intubation surgical procedure. The objective of this work was to perform solid state characterization on GW280430A and to evaluate the relationship between water content and glass transition temperature (Tg). GW280430A was characterized by differential scanning calorimetry, thermogravimetric analysis, powder X-ray diffraction (PXRD), microscopy and moisture sorption. The effect of water content on the Tg of GW280430A was evaluated by equilibrating the material over saturated salt solutions at a range of relative humidities (6.4-72.6%) and determining the Tg by DSC using hermetically sealed aluminum pans. GW280430A undergoes dehydration at 40 degrees C, glass transition at 130 degrees C and decomposition at 190 degrees C by differential scanning calorimetry. By PXRD and moisture sorption, GW280430A is an amorphous material and deliquesces at about 70% RH at room temperature. Water acts as a potent plasticizer for GW280430A and the Tg decreases significantly as the water content increases. No measurable decomposition of GW280430A was observed after 4 weeks at 40 degrees C/75% RH.


Biophysical properties of tear film lipid layer I. Surface tension and surface rheology.
Tear film lipid layer (TFLL) is the outmost layer of the tear film. It plays a crucial role in stabilizing the tear film by reducing surface tension and retarding evaporation of the aqueous layer. Dysfunction of the TFLL leads to dysfunctional tear syndrome, with dry eye disease (DED) being the most prevalent eye disease, affecting 10%-30% of the world population. To date, except for treatments alleviating dry eye symptoms, effective therapeutic interventions in treating DED are still lacking. Therefore, there is an urgent need to understand the biophysical properties of the TFLL with the long-term goal to develop translational solutions in effectively managing DED. Here, we studied the composition-function correlations of an artificial TFLL, under physiologically relevant conditions, using a novel experimental methodology called constrained drop surfactometry. This artificial TFLL was composed of 40% behenyl oleate and 40% cholesteryl oleate, representing the most abundant wax ester and cholesteryl ester in the natural TFLL, respectively, and 15% phosphatidylcholine and 5% palmitic-acid-9-hydroxy-stearic-acid (PAHSA), which represent the two predominant polar lipid classes in the natural TFLL. Our study suggests that the major biophysical function of phospholipids in the TFLL is to reduce the surface tension, whereas the primary function of PAHSA is to optimize the rheological properties of the TFLL. These findings have novel implications in better understanding the physiological and biophysical functions of the TFLL and may offer new translational insight to the treatment of DED.


Human cortex: reflections of mirror neurons.
Claims to have identified mirror neurons in human cortex have been controversial. A recent study has applied an fMRI adaptation protocol to the problem and come up with novel evidence for the existence of movement-selective mirror neurons in human cortex.


[Video head impulse test or caloric irrigation?. Contemporary diagnostic tests for vestibular schwannoma].
The video head impulse test (vHIT) is a new method for investigating vestibular function that is currently poorly studied in terms of its value for clinical diagnosis in otolaryngology. Both the caloric irrigation and vHIT serve to evaluate the horizontal vestibulo-ocular reflex. In the present study, caloric irrigation and vHIT were compared in 46 patients with vestibular schwannoma. Caloric irrigation exhibits a higher sensitivity than vHIT (72% versus 41%) and both tests show only a moderate correlation. Tumor size and hearing level was significantly correlated with caloric abnormalities but not with vHIT findings. Since caloric irrigation and vHIT measure the hVOR in low and high frequency ranges, respectively, these tests have to be considered complementary and are valuable in both diagnostics and therapeutic decisions.


The maximal activity of phosphate-dependent glutaminase and glutamine metabolism in the colon and the small intestine of streptozotocin-diabetic rats.
The effects of short- and long-term diabetes on the maximal activities of phosphate-dependent glutaminase and glutamine metabolism were studied in the colon and the small intestine of streptozotocin-diabetic rats. The maximal activity of colonic phosphate-dependent glutaminase was decreased [44% in mucosal scrapings (p less than 0.01); 29% in whole colon (p less than 0.001)] or unchanged in short- or long-term diabetes respectively. That of the small intestine was increased in both short- (110%) and long-term (200%-500%) diabetes; insulin treatment corrected this increase. Acute insulin-deficiency (using anti-insulin serum) resulted in the increase (18%, p less than 0.05) of the activity of only intestinal glutaminase. Chemically-induced acidosis and alkalosis decreased (46%, p less than 0.001) and increased (24%, p less than 0.001), respectively, the activity of intestinal glutaminase, but had no effect on the colonic enzyme. Changes in glutaminase of the enlarged colon and small intestine were only detectable when activities were measured in whole organ. Arteriovenous-difference measurements showed diminished metabolism of plasma glutamine by the gut which correlated with the duration of the state of diabetes, and was accompanied by enhanced release by skeletal muscle and increased uptake by both kidney and liver. It is concluded that insulin is directly or indirectly involved in the regulation of glutamine metabolism of the gut.


Effects of Epstein-Barr virus on the development of dendritic cells derived from cord blood monocytes: an essential role for apoptosis.
Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus, which can adapt and evade host immune defense. Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses. This study investigated the effects of EBV on cord blood monocytes derived DCs (CBDC). Monocytes were isolated from cord blood and cultured in medium containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8 supernatant was added in monocytes culture medium for EBV infection at day 0. Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane potential (MMP) were detected by flow cytometry. The morphology was observed by Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3, 8 and 9 activity was measured. Phenotypic characterization of DCs was changed in EBV-treated group. Chromatin condensation and DNA fragmentation were observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and caspase 9 activation were enhanced in the EBV-treated group. This was accompanied by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV-treated group and compared to mock-infected group. These results suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC apoptosis in caspase-dependent manner with involvement of the mitochondrial pathway. This might help EBV to evade host immune responses to establish persistent infection.


The effect of carbamazepine on the post-tetanic twitch tension in the diaphragm of the mouse.
The effects of carbamazepine (0.084-0.25 mM) on the post-tetanic potentiation of the twitch tension, were studied on the isolated phrenic nerve diaphragm preparation of the mouse. Carbamazepine decreased the post-tetanic potentiation of the twitch tension. The maximal depressant effect was found after higher frequencies and longer durations of stimulation. After repetitive stimulation, the amplitude of the endplate potential and the frequency of miniature endplate potentials were potentiated. Carbamazepine decreased the post-tetanic potentiation of the amplitude of endplate potential and the frequency of miniature endplate potentials. The directly-elicited muscle action potential was not affected when post-tetanic potentiation of the twitch tension was decreased. It is concluded that carbamazepine suppressed the post-tetanic potentiation of the indirectly-elicited twitch tension, mainly due to its pre-synaptic inhibitory effect.


Patterns of religiosity and spirituality of psychiatrists in Brazil and the implications for clinical practice: a latent profile analysis.
Although there is consensus, in psychiatry, over the inclusion of religious and spiritual aspects when evaluating and treating the patient, investigation of these dimensions is rare. There is evidence as to the relationship between psychiatrists' religious/spiritual beliefs and their willingness to discuss a patient's religion and spirituality (R/S). Due to the lack of information about how psychiatrists in Brazil deal with R/S in patient care, the aim of the present study is to analyze the religious/spiritual profile of these professionals and to ascertain its influence on attitudes and behavior in clinical practice. Five hundred and ninety-two psychiatrists from Brazil answered a questionnaire about R/S in clinical practice. The latent profile analysis was used to search for differences of religious/spiritual profiles. The ANOVA and Pearson's chi-square tests were employed to identify any correlation between clinical opinion and behaviors according to the different profiles. Two religious/spiritual profiles were identified (entropy value > 0,96): the so called "less religious" group (n = 245), comprised predominantly by men, professionally more experienced, with a higher level of academic education (Master or PhD degrees) and were the ones who least enquired about their patients' R/S; and the "more religious" psychiatrists (n = 347) those who had higher consideration for R/S on health, and who more often addressed R/S with their patients and therefore usually ascribed importance to include R/S in their professional training. The latent profile analysis produced two distinct classes between the Brazilian psychiatrists according to their R/S views: the more religious professionals, who investigate the patient's R/S in a more detailed manner, and the less religious, who tend to disregard this aspect.


Conversion and Self-Transformation in Christian Monasticism: A Cognitive Perspective.
Religious conversion involves changes in the convert's way of thinking and behaving. This paper focuses on the unique form that this transformative process took within the Christian monastic movement in late antiquity. Treating monastic conversion as a gradual process in which the convert is an active participant, it examines the ways in which monastic converts were able to intentionally promote such a change and influence its direction. This study draws on research in cognitive psychology and neuroscience on the cognitive underpinnings of self-transformation in order to reconstruct from the literary sources of Near Eastern monasticism the strategies and training methods that late antique monks employed in order to facilitate and sustain the transformation implicated in conversion.


The H-2KbtsA58 transgenic mouse: a new tool for the rapid generation of novel cell lines.
The ability to generate expanded populations of individual cell types able to undergo normal differentiation in vitro and in vivo is of critical importance in the investigation of the mechanisms that underly differentiation and in studies on the use of cell transplantation to repair damaged tissues. This review discusses the development of a strain of transgenic mice that allows the direct derivation of conditionally immortal cell lines from a variety of tissues, simply by dissociation of the tissue of interest and growth of cells in appropriate conditions. In these mice the tsA58 mutant of SV40 large T antigen is controlled by the interferon-inducible Class I antigen promoter. Cells can be grown for extended periods in vitro simply by growing them at 33 degrees C in the presence of interferon, while still retaining the capacity to undergo normal differentiation in vivo and in vitro. In addition, it appears that cell lines expressing mutant phenotypes can readily be generated by preparing cultures from appropriate offspring of matings between H-2KbtsA58 transgenic mice and mutant mice of interest.


Comment on "Eocene Fagaceae from Patagonia and Gondwanan legacy in Asian rainforests".
Wilf et al (Research Articles, 7 June 2019, eaaw5139) claim that Castanopsis evolved in the Southern Hemisphere from where it spread to its modern distribution in Southeast Asia. However, extensive paleobotanical records of Antarctica and Australia lack evidence of any Fagaceae, and molecular patterns indicate shared biogeographic histories of Castanopsis, Castanea, Lithocarpus, and Quercus subgenus Cerris, making the southern route unlikely.


PDGF-BB-Dependent Neurogenesis Buffers Depressive-Like Behaviors by Inhibition of GABAergic Projection from Medial Septum to Dentate Gyrus.
Hippocampal circuitry stimulation is sufficient to regulate adult hippocampal neurogenesis and ameliorate depressive-like behavior, but its underlying mechanism remains unclear. Here, it is shown that inhibition of medial septum (MS)-dentate gyrus (DG) circuit reverses the chronic social defeat stress (CSDS)-induced depression-like behavior. Further analysis exhibits that inhibition of gamma-aminobutyric acidergic neurons in MS projecting to the DG (MSGABA+ -DG) increases the expression of platelet-derived growth factor-BB (PDGF-BB) in somatostatin (SOM) positive interneurons of DG, which contributes to the antidepressant-like effects. Overexpression of the PDGF-BB or exogenous administration of PDGF-BB in DG rescues the effect of chronic stress on the inhibition of neural stem cells (NSCs) proliferation and dendritic growth of adult-born hippocampal neurons, as well as on depressive-like behaviors. Conversely, knockdown of PDGF-BB facilitates CSDS-induced deficit of hippocampal neurogenesis and promotes the susceptibility to chronic stress in mice. Finally, conditional knockdown platelet-derived growth factor receptor beta (PDGFRβ) in NSCs blocks an increase in NSCs proliferation and the antidepressant effects of PDGF-BB. These results delineate a previously unidentified PDGF-BB/PDGFRβ signaling in regulating depressive-like behaviors and identify a novel mechanism by which the MSGABA+ -DG pathway regulates the expression of PDGF-BB in SOM-positive interneurons.


Three-dimensional arterial spin labeling-guided dose painting radiotherapy for non-enhancing low-grade gliomas.
To investigate the feasibility and dosimetric characteristics of dose painting for non-enhancing low-grade gliomas (NE-LGGs) guided by three-dimensional arterial spin labeling (3D-ASL). Eighteen patients with NE-LGGs were enrolled. 3D-ASL, T2 fluid-attenuated inversion recovery (T2 Flair) and contrast-enhanced T1-weighted magnetic resonance images were obtained. The gross tumor volume (GTV) was delineated on the T2 Flair. The hyper-perfusion region of the GTV (GTV-ASL) was determined by 3D-ASL, and the GTV-SUB was obtained by subtracting the GTV-ASL from the GTV. The clinical target volume (CTV) was created by iso-tropically expanding the GTV by 1 cm. The planning target volume (PTV), PTV-ASL were obtained by expanding the external margins of the CTV, GTV-ASL, respectively. PTV-SUB was generated by subtracting PTV-ASL from PTV. Three plans were generated for each patient: a conventional plan (plan 1) without dose escalation delivering 95-110% of 45-60 Gy in 1.8-2 Gy fractions to the PTV and two dose-painting plans (plan 2 and plan 3) with dose escalating by 10-20% (range, 50-72 Gy) to the PTV-ASL based on plan 1. The plan 3 was obtained from plan 2 without the maximum dose constraint. The dosimetric differences among the three plans were compared. The volume ratio of the PTV-ASL to the PTV was (23.49 ± 11.94)% (Z = - 3.724, P = 0.000). Compared with plan 1, D2%, D98% and Dmean of PTV-ASL increased by 14.67%,16.17% and 14.31% in plan2 and 19.84%,15.52% and 14.27% in plan3, respectively (P < 0.05); the D2% of the PTV and PTV-SUB increased by 11.89% and 8.34% in plan 2, 15.89% and 8.49% in plan 3, respectively (P < 0.05). The PTV coverages were comparable among the three plans (P > 0.05). In plan 2 and plan 3, the conformity indexes decreased by 18.60% and 12.79%; while the homogeneity index increased by 1.43 and 2 times (P < 0.05). Compared with plan 1, the D0.1 cc of brain stem and Dmax of optic chiasma were slightly increased in plan 2 and plan 3, and the absolute doses met the dose constraint. The doses of the other organs at risk (OARs) were similar among the three plans (P > 0.05). The dose delivered to hyper-perfusion volume derived from 3D-ASL can increased by 10-20% while respecting the constraints to the OARs for NE-LGGs, which provides a basis for future individualized and precise radiotherapy, especially if the contrast agent cannot be injected or when contrast enhancement is uncertain.


Identification of a potent and selective σ₁ receptor agonist potentiating NGF-induced neurite outgrowth in PC12 cells.
Herein we report the synthesis, drug-likeness evaluation, and in vitro studies of new sigma (σ) ligands based on arylalkenylaminic scaffold. For the most active olefin the corresponding arylalkylamine was studied. Novel arylalkenylamines generally possess high σ(1) receptor affinity (K(i) values <25 nM) and good σ(1)/σ(2) selectivity (K(i)σ(2) >100). Particularly, the piperidine derivative (E)-17 and its arylalkylamine analog (R,S)-33 were observed to be excellent σ(1) receptor ligands (K(i)=0.70 and 0.86 nM, respectively) and to display significantly high selectivity over σ(2), μ-, and κ-opioid receptors and phencyclidine (PCP) binding site of the N-methyl-d-aspartate (NMDA) receptors. Moreover in PC12 cells (R,S)-33 promoted the nerve growth factor (NGF)-induced neurite outgrowth and elongation. Co-administration of the selective σ(1) receptor antagonist BD-1063 totally counteracted this effect, confirming that σ(1) receptors are involved in the (R,S)-33 modulation of the NGF effect in PC12 cells and suggesting a σ(1) agonist profile. As a part of our work, a threedimensional σ(1) pharmacophore model was also developed employing GALAHAD methodology. Only active compounds were used for deriving this model. The model included two hydrophobes and a positive nitrogen as relevant features and it was able to discriminate between molecules with and without affinity toward σ(1) receptor subtype.


How Do COVID-19 Inpatients in the Denver Metropolitan Area Measure Up?
Inpatient data for COVID-19 (SARS-CoV-2) afflicted inpatients remain sparse. Data are needed to create accurate projections for resource consumption as the pandemic continues. Published reports of inpatient data have come from China, Italy, Singapore, and both the East and West coasts of the United States. The objective is to present our inpatient experience with COVID-19. Design, Setting, and Participants. This is a retrospective study of 681 patients with laboratory-confirmed COVID-19 from six hospitals in the Denver metropolitan area admitted between February 18 and April 30, 2020. Clinical outcomes of patients discharged or expired by April 30, 2020, were analyzed. Main Outcomes. We compiled patient demographics, length of stay, number of patients transferred to or admitted to the ICU, ICU length of stay, mechanical ventilation requirements, and mortality rates. Of the 890 patients with laboratory-confirmed COVID-19, 681 had discharged and were included in this analysis. We observed 100% survival of the 0-18 age group (n = 2), 97% survival of the 19-30 age group, 95% survival of the 31-64 age group, 79% survival of the 65-84 age group, and 75% survival of the 85 and older age group. Our total inpatient mortality was 13% (91 patients), rising to 29% (59 patients) for those requiring ICU care. Compared to similar reports from other metropolitan areas, our analysis of discharged or expired COVID-19 patients from six major hospitals in the Denver metropolitan area revealed a lower mortality. This includes the subset of patients admitted to the ICU regardless of the need for intubation. A lower ICU length of stay was also observed.


Biochemical failure as a determinant of distant metastasis and death in prostate cancer treated with radiotherapy.
Biochemical failure (BF), defined by a rising prostate-specific antigen (PSA) profile, is an early surrogate of treatment failure. However, little evidence is available to show that BF is associated with death for patents with prostate cancer treated with radiotherapy. We examined the relationship between BF and death from prostate cancer. A total of 942 patients were treated between 1987 and 1998 with external beam radiotherapy who had sufficient PSA determinations in follow-up for the analyses described. The median radiation dose was 72 Gy, median PSA was 9.9 ng/mL, and median follow-up was 73 months. The American Society for Therapeutic Radiology and Oncology consensus definition was used to define BF. Kaplan-Meier calculations were from the start of radiotherapy. Cox proportional hazards regression multivariate analyses were used to investigate the association of BF (time-dependent variable) and other factors to distant metastasis (DM), cause-specific death (CSD), and overall death (OD). The year of treatment was included in some of the multivariate analyses to correct for potential unknown factors that may have occurred during the years of the study, such as stage migration. BF was observed in 316 patients (34%), and 66 (7%) experienced DM, 32 (3%) died of prostate cancer, and 230 (24%) died overall during the study period. The Kaplan-Meier 5-year rate estimates from the start of treatment for BF, DM, CSD, and OD were 38%, 6%, 3%, and 13%, respectively. All patients with DM had BF. In multivariate analyses, BF was associated with DM and CSD, but not OD. The inclusion of the year of treatment did not alter these relationships. BF, as a time-dependent covariate, was the strongest determinant of DM and was also very significantly related to CSD. The inclusion of the year of treatment had little effect on these associations. Longer follow-up is needed to determine conclusively the relationship of BF to OD.


Decrease in protein phosphorylation in central and peripheral nervous tissues of methylmercury-treated rat.
The protein phosphorylation in extracts of nervous tissues of rats acutely exposed to methylmercury chloride (seven daily injections of 10 mg methylmercury chloride/kg body weight) was examined. In the brain, the phosphorylating activity was dependent on cAMP and Mg2+. The effect of methylmercury on the phosphorylation of brain proteins, including tubulin and MAP-2, was hardly discernible. In peripheral nervous tissues such as the dorsal and ventral roots, sciatic nerves and dorsal root ganglia, the phosphorylating activity was dependent on Ca2+, and the maximal activity was obtained when the tissues were extracted in the presence of 1% Triton X-100. SDS-Polyacrylamide gel electrophoresis revealed that the major phosphorylated proteins in the peripheral tissues were myelin proteins. The effects of methylmercury were not uniform regarding protein species and tissues. The most marked changes were observed in sciatic nerves, in which phosphorylation of the 33 kDa, 28 kDa, 19 kDa, 18 kDa and 15 kDa proteins was significantly decreased in the symptomatic phase of intoxication.


Consumption advisories for salmon based on risk of cancer and noncancer health effects.
The levels of dioxins/furans, polychlorinated biphenyls (PCBs), and chlorinated pesticides were determined in farmed salmon for eight regions in Europe, North America, and South America, in salmon fillets purchased in 16 cities in Europe and North America, and in five species of wild Pacific salmon. Upon application of US Environmental Protection Agency (USEPA) methods for developing fish consumption advisories for cancer from mixtures of all of these substance for which USEPA has reported a cancer slope factor, the most stringent recommendation, for farmed salmon from northern Europe, was for consumption of at most one meal every 5 months in order to not exceed an elevated risk of cancer of more than 1 in 100,000. Farmed salmon from North and South America triggered advisories of between 0.4 and one meal per month. Retail market samples, in general, reflected levels found in regionally farmed fish, although much of the US salmon comes from Chile, which had somewhat lower contaminant levels than the North American farmed samples. Upon consideration of all of these organochlorine compounds as a mixture, even wild Pacific salmon triggered advisories of between one and less than five meals per month. The advisories are driven by the non-dioxin-like PCBs and pesticides and not by dioxins/furans and coplanar PCBs. For noncancer effects for contaminants where USEPA has provided a reference dose only endrin and PCBs triggered any significant advisory. For both of these in the worst case, farmed salmon from northern Europe, the advice was not more than three meals per month.


Regulation of expression of a wound-inducible tomato inhibitor I gene in transgenic nightshade plants.
A wound-inducible proteinase Inhibitor I gene from tomato containing 725 bp of the 5' region and 2.5 kbp of the 3' region was stably incorporated into the genome of black nightshade plants (Solanum nigrum) using an Agrobacterium Ti plasmid-derived vector. Transgenic nightshade plants were selected that expressed the tomato Inhibitor I protein in leaf tissue. The leaves of the plants contained constitutive levels of the inhibitor protein of up to 60 micrograms/g tissue. These levels increased by a factor of about two in response to severe wounding. Only leaves and petioles exhibited the presence of the inhibitor, indicating that the gene exhibited the same tissue specificity of expression found in situ in wounded tomato leaves. Inhibitor I was extracted from leaves of wounded transformed nightshade plants and was partially purified by affinity chromatography on a chymotrypsin-Sepharose column. The affinity-purified protein was identical to the native tomato Inhibitor I in its immunological reactivity and in its inhibitory activity against chymotrypsin. The protein exhibited the same Mr of 8 kDa as the native tomato Inhibitor I and its N-terminal amino acid sequence was identical to that of the native tomato inhibitor I, indicating that the protein was properly processed in nightshade plants. These experiments are the first report of the expression of a member of the wound-inducible tomato Inhibitor I gene family in transgenic plants. The results demonstrate that the gene contains elements that can be regulated in a wound-inducible, tissue-specific manner in nightshade plants.


Chronic diarrhea of childhood and the misuse of elimination diets.
A prospective study was undertaken of 108 children referred for outpatient evaluation of chronic recurrent diarrhea. The majority of the children did not have a serious underlying disorder. Elimination diets (milk free, egg free, wheat free) were widely prescribed for the treatment of chronic diarrhea and were given for longer intervals than originally recommended. Elimination diets sometimes resulted in inadequate caloric intake and failure to thrive. Wheat (gluten)-free diets were prescribed for over one month in 59% of children without a specific diagnosis being made. These findings indicate that elimination diets are frequently misused, and prolonged adherence to elimination diets may result in nutritional damage. The indiscriminate use of wheat-free diets for the treatment of chronic diarrhea may be masking the diagnosis of celiac disease and may account for the low incidence of this disorder in the United States.


Gender differences in neurodevelopment and epigenetics.
The concept that the brain differs in make-up between males and females is not new. For example, it is well established that anatomists in the nineteenth century found sex differences in human brain weight. The importance of sex differences in the organization of the brain cannot be overstated as they may directly affect cognitive functions, such as verbal skills and visuospatial tasks in a sex-dependent fashion. Moreover, the incidence of neurological and psychiatric diseases is also highly dependent on sex. These clinical observations reiterate the importance that gender must be taken into account as a relevant possible contributing factor in order to understand the pathogenesis of neurological and psychiatric disorders. Gender-dependent differentiation of the brain has been detected at every level of organization--morphological, neurochemical, and functional--and has been shown to be primarily controlled by sex differences in gonadal steroid hormone levels during perinatal development. In this review, we discuss howthe gonadal steroid hormone testosterone and its metabolites affect downstream signaling cascades, including gonadal steroid receptor activation, and epigenetic events in order to differentiate the brain in a gender-dependent fashion.


Assessment of fatigue damage in welded aluminum joints subjected to multiaxial stress state.
The aluminum has mechanical properties enable to a better finishing in welded region. However, it fails eventually when a dynamic load is applied. This study estimated the damage by multiaxial fatigue present in welded joints of bicycle frames, the methodologies of analysis are based on Findley's and Dang Van's Methods. Seven experiments were performed on two pipes with welded joints. These pipes were choosen according to Bike S/A data, numerical simulations in bicycle frame and previous analysis of specialized literature. Therefore, lifespan result of frame, in function the distance, is 3 × 1 0 4 km - 5.5 × 1 0 4 km.


Bitter taste of saccharin related to the genetic ability to taste the bitter substance 6-n-propylthiouracil.
Bitter taste thresholds for 6-n-propylthiouracil are bimodally distributed, dividing subjects into tasters and nontasters. Their taste worlds differ with regard to the sweetness of sucrose and saccharin and to the bitterness of saccharin. These differences suggest that nontasters tend to perceive less bitterness in saccharin at concentrations used in beverages.


Effect of fluoridated paste on the failure rate of precoated brackets bonded with self-etching primer: a prospective split-mouth study.
The aim of this prospective randomized clinical trial was to determine the effect of using fluoridated paste (Dentsply, York, Pa) compared with plain pumice (Ortho Technology, Tampa, Fla) on the clinical bond failure rates of precoated brackets bonded with self-etching primer. A split-mouth technique was used. The teeth in the maxillary right and mandibular left quadrants were prepared with a fluoridated paste only, and the teeth in the maxillary left and mandibular right quadrants were prepared with plain pumice before bonding the precoated brackets. A total of 627 brackets in 34 orthodontic patients (20 female, 14 male) were included in this study; 315 brackets were bonded after pumice treatment, and 312 were bonded after paste treatment. The patients were followed for 6 months to determine the rates of bracket failure. The overall failure rate was 8%. The failure rates for pumice and paste were 4.8% and 11.2%, respectively. The McNemar test showed a statistically significant difference between the 2 groups. Based on tooth type, the failure rate of the maxillary canine and the mandibular central incisor brackets were significantly different for paste and pumice. There was also a difference in the survival rates of the brackets in both groups. Preparation of the enamel surface with fluoridated paste before bonding with self-etching primer is not recommended. However, the use of plain pumice is recommended, even if it is time-consuming.


A borderline form of empty follicle syndrome. Case report.
Empty follicle syndrome is known as the failure of oocyte retrieval despite the adequate response to ovarian stimulation. It is a rare phenomenon in in-vitro fertilization and borderline forms of this syndrome have also been described. Two cycles in the same patient were stimulated with GnRH agonist/hMG and recFSH; the first followed the long and the second followed the short protocol. There was a sudden drop in estradiol levels while the ovaries contained a large number of small and medium sized follicles. hCG was administered and oocyte retrieval was performed 36 hours later. There was no indication of low hCG levels. For the first cycle two oocytes were collected: one degenerated and one of poor quality. The second cycle resulted in total failure of oocyte retrieval. The two cycles were classified as borderline forms of empty follicle syndrome. The possible aetiology is discussed.


[Protective effect of human decay accelerating factor on mouse cells].
To observe the protective effect of human decay accelerating factor (DAF) expressed in mouse myeloma cells against the injury of human serum complement. Mouse myeloma cells were transfected with human DAF cDNA and then put into normal human serum culture to observe if they were injured. The mouse cells containing human DAF cDNA and expressing human DAF survived for more than 48 hours and passed on from generation to generation in the culture medium containing human normal serum. However, the control mouse cells died in 1 - 4 hours. Human DAF protects mouse cells from injuring by human complement.


Resolution of low back symptoms after corrective surgery for dropped-head syndrome: a report of two cases.
Cervical deformity can influence global sagittal balance. We report two cases of severe low back pain and lower extremity radicular pain associated with dropped-head syndrome. Symptoms were relieved by cervical corrective surgery. Two Japanese women with dropped head syndrome complained of severe low back pain and lower extremity radicular pain on walking. Radiographs showed marked cervical spine kyphosis and lumbar spine hyperlordosis. After cervicothoracic posterior corrective fusion was performed, cervical kyphosis was corrected and lumbar lordosis decreased, and low back pain and leg pain were relieved in both patients. Cervical deformity can influence global sagittal balance. Marked cervical kyphosis in patients with dropped-head syndrome can induce compensatory thoracolumbar hyperlordosis. Low back symptoms in patients with dropped-head syndrome are attributable to this compensatory lumbar hyperlordosis. Symptoms of lumbar canal stenosis may result from cervical deformity and can be improved with cervical corrective surgery.


The effects of altitude training are mediated primarily by acclimatization, rather than by hypoxic exercise.
For training at altitude to be effective, it must provide some advantage above and beyond similar training at sea level. This advantage could be provided by: 1) acclimatization to altitude which improves oxygen transport and/or utilization; 2) hypoxic exercise which "intensifies" the training stimulus; or 3) some combination of both. Controlled studies of "typical" altitude training, involving both altitude acclimatization and hypoxic exercise have never been shown to improve sea level performance. This failure has been attributed to reduced training loads at altitude. One approach developed by Levine and Stray-Gundersen, called "living high-training low" has been shown to improve sea level performance over events lasting 8-20 minutes. This strategy combines altitude acclimatization (2,500 m) with low altitude training to get the optimal effect. The opposite strategy, "living low-training high" is proposed by Dr. Hoppeler in this debate. In defense of the primacy of the altitude acclimatization effect, data will be presented to support the following: 1). Living high-training low clearly improves performance in athletes of all abilities; 2). The mechanism of this improvement is primarily an increase in erythropoietin leading to increased red cell mass, VO2max, and running performance; 3). Rather than intensifying the training stimulus, training at altitude leads to the opposite effect--reduced speeds, reduced power output, reduced oxygen flux--and, following the principal of symmorphosis, is not likely to provide any advantage for a well trained athlete; 4). At the moderate altitudes used by most athletes, resting oxygen delivery to skeletal muscle is well preserved, arguing against any detrimental effect on "protein synthesis"; 5). It is possible however, that at significantly higher altitudes, acclimatization leads to appetite suppression, inhibition of protein synthesis, muscle wasting, excessive ventilatory work, and metabolic compensation that is NOT advantageous for a competitive athlete.


Differences in fine arabinoxylan structures govern microbial selection and competition among human gut microbiota.
Dietary fibers are known to modulate microbiome composition, but it is unclear to what extent minor fiber structural differences impact community assembly, microbial division of labor, and organismal metabolic responses. To test the hypothesis that fine linkage variations afford different ecological niches for distinct communities and metabolism, we employed a 7-day in vitro sequential batch fecal fermentation with four fecal inocula and measured responses using an integrated multi-omics approach. Two sorghum arabinoxylans (SAXs) were fermented, with one (RSAX) having slightly more complex branch linkages than the other (WSAX). Although there were minor glycoysl linkage differences, consortia on RSAX retained much higher species diversity (42 members) than on WSAX (18-23 members) with distinct species-level genomes and metabolic outcomes (e.g., higher short chain fatty acid production from RSAX and more lactic acid produced from WSAX). The major SAX-selected members were from genera of Bacteroides and Bifidobacterium and family Lachnospiraceae. Carbohydrate active enzyme (CAZyme) genes in metagenomes revealed broad AX-related hydrolytic potentials among key members; however, CAZyme genes enriched in different consortia displayed various catabolic domain fusions with diverse accessory motifs that differ among the two SAX types. These results suggest that fine polysaccharide structure exerts deterministic selection effect for distinct fermenting consortia.


Statin use may reduce lower extremity peak force via reduced engagement in muscle-strengthening activities.
Stain use is often associated with an increased likelihood of musculoskeletal complications such as injuries and pain. Consequently, it is plausible to suggest that statin use may indirectly influence lower extremity muscular strength via reduced engagement in muscle-strengthening activities (MSA). However, this has yet to be examined. Therefore, the purpose of this study was to examine whether statin use was associated with muscular strength via engagement in MSA. Data from the 1999-2002 NHANES were used, with 2775 adults (50-85 years) constituting the analytic sample. Statin use was assessed from an interviewer, engagement in MSA (e.g. resistance training) was assessed via survey and lower extremity isokinetic knee extension strength (IKES) was assessed objectively using the Kin Com MP dynamometer. Weighted multivariable linear regression analysis showed no direct association between statin use and IKES (βadjusted = 7·0 newton ∆, P = 0·23). Statin use, however, was associated with a 35% reduced odds of engaging in MSA (ORadjusted = 0·65, P = 0·04), and engaging in MSA was positively associated with IKES (βadjusted = 19·9 newton ∆, P = 0·001). The bootstrap Barron and Kenny mediational analysis indeed demonstrated that statin use was indirectly associated with IKES via MSA (indirect effect coefficient: -0·005; 95% CI: -0·01 to -0·001; P<0·05). Statin use was not directly associated with IKES, but was indirectly associated with IKES via MSA. In conclusion, statin use may decrease muscle force by influencing engagement in MSA. We wish to suggest that a decrease in MSA may be related to an increase in muscle pain associated with statin therapy.


Neurotoxicity of FIV and FIV envelope protein in feline cortical cultures.
The neurotoxic effects of the feline immunodeficiency virus (FIV) and FIV envelope proteins were measured in primary cultures of feline cortical neurons. Envelope protein from the FIV-PPR strain promoted neuronal swelling and death, whereas envelope protein from the FIV-34TF10 isolate produced intermediate or negligible toxicity. No effect was observed in control cultures treated with envelope protein from the Epstein-Barr virus. A concentration-effect curve showed that FIV-PPR protein produced maximal toxicity at 200 pM protein and decreased toxicity at higher concentrations, which is consistent with previous reports of the HIV-1 surface glycoprotein, gp120. These effects required the presence of low concentrations of glutamate. Using the natural host cells as targets, the effects of envelope protein and infectious virions were directly compared. All of the toxic activity could be attributed to non-infectious interactions between the viral envelope and target cells. Addition of 1 microM tetrodotoxin failed to block the effects of FIV-PPR in the presence of 20 microM glutamate. Toxicity would appear to involve two steps in which the envelope protein first sensitizes neurons through non-synaptic interactions (TTX insensitive) thereby setting the stage for enhanced synaptic activation via glutamate receptors (TTX sensitive).


Nerve Growth Factor modulates LPS - induced microglial glycolysis and inflammatory responses.
Microglia, the parenchymal immune cells of the central nervous system, orchestrate neuroinflammation in response to infection or damage, and promote tissue repair. However, aberrant microglial responses are integral to neurodegenerative diseases and critically contribute to disease progression. Thus, it is important to elucidate how microglia - mediated neuroinflammation is regulated by endogenous factors. Here, we explored the effect of Nerve Growth Factor (NGF), an abundant neurotrophin, on microglial inflammatory responses. NGF, via its high affinity receptor TrkA, downregulated LPS - induced production of pro-inflammatory cytokines and NO in primary mouse microglia and inhibited TLR4 - mediated activation of the NF-κB and JNK pathways. Furthermore, NGF attenuated the LPS - enhanced glycolytic activity in microglia, as suggested by reduced glucose uptake and decreased expression of the glycolytic enzymes Pfkβ3 and Ldhα. Consistently, 2DG - mediated glycolysis inhibition strongly downregulated LPS - induced cytokine production in microglial cells. Our findings demonstrate that NGF attenuates pro-inflammatory responses in microglia and may thereby contribute to regulation of microglia - mediated neuroinflammation.


Effects of epinephrine on branchial non-electrolyte permeability in rainbow trout.
Using isolated heads perfused at constant pressure, at rates close to those occurring in vivo, the permeability of the gills of the trout Salmo gairdneri to a range of solutes was measured. Under epinephrine-free conditions, butanol and water showed similar high branchial permeability coefficients. Urea, inulin and dextrans (mol. wt 3000 and 20 000) were 7-12 times less permeant, and mannitol 60-70 times less permeant than water or butanol. Epinephrine, at 10(-6) M, greatly increased the permeability of the gills to the small hydrophilic molecules, water and urea, and to the lipophilic substance, butanol, but did not affect the penetration of the large hydrophilic solutes, mannitol, inulin and dextrans. In the presence of 10(-6) M propanolol, a beta-blocker, epinephrine had no effect on the permeation of any of the test substances except that the permeability to urea decreased somewhat. The results suggest that epinephrine increases the permeability of the membranes of the branchial cells but does not affect the permeation of substances that cross the gill walls by paracellular routes or via an intracellular 'bulk-transport' mechanism. Such an action would be expected to increase the branchial transfer of oxygen.


Comparison of Tele-Education and Conventional Cardiopulmonary Resuscitation Training During COVID-19 Pandemic.
Cardiopulmonary resuscitation (CPR) performed by lay rescuers can increase a person's chance of survival. The COVID-19 pandemic enforced prevention policies that encouraged social distancing, which disrupted conventional modes of health care education. Tele-education may benefit CPR training during the pandemic. Our aim was to compare CPR knowledge and skills using tele-education vs. conventional classroom teaching methods. A noninferiority trial was conducted as a Basic Life Support workshop. Participants were randomly assigned to a tele-education or conventional group. Primary outcomes assessed were CPR knowledge and skills and secondary outcomes assessed were individual skills, ventilation, and chest compression characteristics. Pretraining knowledge scores (mean ± standard deviation [SD] 3.50 ± 2.18 vs. 4.35 ± 1.70; p = 0.151) and post-training knowledge scores (7.91 ± 2.14 vs. 8.52 ± 0.90; p = 0.502) of the tele-education and conventional groups, respectively, had no statistically significant difference. Both groups' training resulted in a significant and comparable gain in knowledge scores (p < 0.001). The tele-education and conventional groups skill scores (mean ± SD 78.30 ± 6.77 vs. 79.65 ± 9.93; p = 0.579) had no statistical difference. Skillset scores did not differ statistically except for the compression rate and ventilation ratio; the conventional group performed better (p = 0.042 vs. p = 0.017). The tele-education and conventional groups' number of participants passed the skill test (95.5% and 91.3%, respectively; p = 1.000). Tele-education offers a pragmatic and reasonably effective alternative to conventional CPR training during the COVID-19 pandemic.


Hydraulic fracturing in cells and tissues: fracking meets cell biology.
The animal body is largely made of water. A small fraction of body water is freely flowing in blood and lymph, but most of it is trapped in hydrogels such as the extracellular matrix (ECM), the cytoskeleton, and chromatin. Besides providing a medium for biological molecules to diffuse, water trapped in hydrogels plays a fundamental mechanical role. This role is well captured by the theory of poroelasticity, which explains how any deformation applied to a hydrogel causes pressure gradients and water flows, much like compressing a sponge squeezes water out of it. Here we review recent evidence that poroelastic pressures and flows can fracture essential biological barriers such as the nuclear envelope, the cellular cortex, and epithelial layers. This type of fracture is known in engineering literature as hydraulic fracturing or 'fracking'.


Association between body height and serve speed in elite tennis players.
The purpose of this study was to determine the association between the body height (BH) of elite tennis players and their serve speeds: SF (fastest serve in a match), S1 (average speed of the first serve in a match), and S2 (average speed of the second serve in a match). Data were collected from the world's best tennis players who participated in all four Grand Slam tournaments in 2008 (men, n = 78-84, BH = 1.85 +/- 0.07 m; women, n = 70-78, BH = 1.73 +/- 0.07 m). Statistically significant correlations (r) between BH and serve speed were found in all 24 statistical analyses (p < 0.01). The correlation coefficients were similar in men and women. The correlation coefficients of BH with SF and S1 ranged 0.48-0.64 for men and 0.48-0.59 for women. The correlations between BH and S2 were weaker and more variable (r = 0.20-0.50 for men and 0.24-0.42 for women). The BH of the men explained 27%, 30%, and 14% of the variance of SF, S1, and S2, respectively, with corresponding values for female players of 27%, 27%, and 12%.


On the nature of thumbs.
Asymmetric regulation of Hox gene expression pre-dates the appearance of tetrapod digits, and was co-opted in the development of 'thumbness'. This asymmetric expression correlates with independent morphological evolutionary variation of digit 1.


Management of Helicobacter pylori infection in paediatric patients in Europe: results from the EuroPedHp Registry.
The EuroPedHp-registry aims to monitor guideline-conform management, antibiotic resistance, and eradication success of 2-week triple therapy tailored to antibiotic susceptibility (TTT) in Helicobacter pylori-infected children. From 2017 to 2020, 30 centres from 17 European countries reported anonymized demographic, clinical, antibiotic susceptibility, treatment, and follow-up data. Multivariable logistic regression identified factors associated with treatment failure. Of 1605 patients, 873 had follow-up data (53.2% female, median age 13.0 years, 7.5% with ulcer), thereof 741 (85%) treatment naïve (group A) and 132 (15%) after failed therapy (group B). Resistance to metronidazole was present in 21% (A: 17.7%, B: 40.2%), clarithromycin in 28.8% (A: 25%, B: 51.4%), and both in 7.1% (A: 3.8%, B: 26.5%). The majority received 2-week tailored triple therapy combining proton pump inhibitor (PPI), amoxicillin with clarithromycin (PAC) or metronidazole (PAM). Dosing was lower than recommended for PPI (A: 49%, B: 41%) and amoxicillin (A: 6%, B: 56%). In treatment naïve patients, eradication reached 90% (n = 503, 95% CI 87-93%) and 93% in compliant children (n = 447, 95% CI 90-95%). Tailored triple therapy cured 59% patients after failed therapy (n = 69, 95% CI 48-71%). Treatment failure was associated with PAM in single clarithromycin resistance (OR = 2.47, 95% CI 1.10-5.53), with PAC in single metronidazole resistance (OR = 3.44, 95% CI 1.47-8.08), and with low compliance (OR = 5.89, 95% CI 2.49-13.95). Guideline-conform 2-weeks therapy with PPI, amoxicillin, clarithromycin or metronidazole tailored to antibiotic susceptibility achieves primary eradication of ≥ 90%. Higher failure rates in single-resistant strains despite tailored treatment indicate missed resistance by sampling error.


Intraoperative amylase level of pancreatic juice as a simple predictor of pancreatic fistula after pancreaticoduodenectomy.
A soft remnant texture of the pancreas is commonly accepted as a risk factor for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). However, its assessment is subjective. The aim of this study was to evaluate the significance of intraoperative amylase level of the pancreatic juice as a risk factor of POPF after PD. This study included 75 patients who underwent PD between November 2014 and April 2020 at Jikei University Hospital. We investigated the relationship between pancreatic texture, intraoperative amylase level of pancreatic juice, results of the pathological evaluations, and the incidence of POPF. Twenty-three patients (31%) developed POPF. The significant predictors of POPF were non-ductal adenocarcinoma (p < 0.01), soft pancreatic remnant (p < 0.01), high intraoperative blood loss (p < 0.01), high intraoperative amylase level of pancreatic juice (p < 0.01), and low pancreatic fibrosis (p < 0.01). Multivariate analysis revealed that the significant independent predictors of POPF were high intraoperative blood loss (p < 0.01) and high intraoperative amylase level of pancreatic juice (p = 0.02). Receiver operating characteristic (ROC) analysis showed that the cut-off value for the intraoperative amylase level of pancreatic juice was 2.17 × 105 IU/L (area under the curve = 0.726, sensitivity = 95.7%, and specificity = 50.0%) CONCLUSIONS: The intraoperative amylase level of pancreatic juice is a reliable objective predictor for POPF after PD.


Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report.
The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.


Chemical synthesis of 23 kDa glycoprotein by repetitive segment condensation: a synthesis of MUC2 basal motif carrying multiple O-GalNAc moieties.
Peptide thioester corresponding to a MUC2 tandem repeat unit, which retains seven GalNAc moieties, was prepared by the Fmoc method followed by the low TfOH treatment to remove benzyl groups at the carbohydrate portions. The glycosylated peptide thioester was then consecutively joined by the activation of a thioester group by silver ions to obtain a MUC2 tandem repeat model composed of 141 amino acids with 42 GalNAc moieties.


The use of non-linear regression analysis and the F test for model discrimination with dose-response curves and ligand binding data.
Computer fitting of binding data is discussed and it is concluded that the main problem is the choice of starting estimates and internal scaling parameters, not the optimization software. Solving linear overdetermined systems of equations for starting estimates is investigated. A function, Q, is introduced to study model discrimination with binding isotherms and the behaviour of Q as a function of model parameters is calculated for the case of 2 and 3 sites. The power function of the F test is estimated for models with 2 to 5 binding sites and necessary constraints on parameters for correct model discrimination are given. The sampling distribution of F test statistics is compared to an exact F distribution using the Chi-squared and Kolmogorov-Smirnov tests. For low order modes (n less than 3) the F test statistics are approximately F distributed but for higher order models the test statistics are skewed to the left of the F distribution. The parameter covariance matrix obtained by inverting the Hessian matrix of the objective function is shown to be a good approximation to the estimate obtained by Monte Carlo sampling for low order models (n less than 3). It is concluded that analysis of up to 2 or 3 binding sites presents few problems and linear, normal statistical results are valid. To identify correctly 4 sites is much more difficult, requiring very precise data and extreme parameter values. Discrimination of 5 from 4 sites is an upper limit to the usefulness of the F test.


Decay of heat acclimation during exercise in cold and exposure to cold environment.
Sixteen male students exercised for 14 days (1 h/day) in the heat for heat acclimation (HA). During deacclimation (DA) one group exercised in the cold (EXG, n=8) for 60 min/day (morning) and was exposed to the cold for another hour (afternoon) for 14 days. The other group was exposed to the cold (EPG, n=8) for 1 h each in the morning and afternoon (Ta: 18.0 degrees C, RH: 58%) over the same period. All returned to exercise in the heat for reacclimation (RA) for 10 days. Subjects were tested on days 1, 16, 21, 32, 36 and 44 on a bicycle ergometer for 60 min at 60% of VO(2max) in the heat (Ta: 31.1 degrees C, RH: 70%). Rectal temperature (T (re)) and heart rate (HR) at 40 min of exercise were used to determine the decay/gain of HA, which was calculated using the formula described by Pandolf et al. (Ergonomics, 20:399-408, 1977). After HA (day 16) T (re) and HR decreased significantly. During DA, EXG showed decay in T (re) of 24 and 35% and HR of 29 and 35% on days 21 and 32, respectively. For EPG the corresponding decay was of 2 and 9% for T (re) and 17 and 17% for HR. After 10 days of RA, EXG showed gains of 11% in T (re) and 12% in HR, while EPG showed gains of 47% in T (re) and 38% in HR. In conclusion, EXG had greater decay during DA and lower gains in RA compared to EPG. However, the differences between groups were significant only for T (re) after 4 days of DA.


Repurposing Probenecid for the Treatment of Heart Failure (Re-Prosper-HF): a study protocol for a randomized placebo-controlled clinical trial.
Improving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes-istaroxime and probenecid-improve contractility through an increase in systolic intracellular calcium without activating cAMP production. Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of the transient receptor potential vanilloid 2 channel. Translational studies have shown that it improves calcium cycling and contractility without activating noxious pathways associated with cAMP-dependent calcitropes and can improve cardiac function in patients with HFrEF. The Re-Prosper-HF study (Repurposing Probenecid for the Treatment of Heart Failure with Reduced Ejection Fraction) is a three-site double-blinded randomized-controlled trial that will test the hypothesis that probenecid can improve cardiac function in patients with HFrEF. Up to 120 patients will be randomized in this double-blind, placebo-controlled study that will assess whether oral probenecid administered at 1 g orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function (aim 1), functional status (aim 2), and self-reported health status (aim 3). Findings from this study will provide data informing its use for improving symptomatology in patients with HFrEF as well as exploratory data for outcomes such as hospital admission rates. The Re-Prosper HF Study (Re-Prosper HF) is registered on ClinicalTrials.gov with the identifier as NCT04551222. Registered on 9 September 2020.


Implicit theories of body weight and engagement in healthy lifestyles among young adults: The mediating effect of self-control.
Engaging in a healthy lifestyle could be helpful to decrease lifestyle-related health risks and bring long-term health benefits. This research investigated how implicit theories of body weight influence people's engagement in healthy lifestyle among young adults in China. The results suggested that implicit theories of body weight significantly influence people's engagement in heathy eating behaviors and physical activity. Self-control mediated the effect of implicit (incremental) theories of body weight on people's engagement in healthy eating. Implications of the current research for understanding how to promote engagement in healthy lifestyle and directions for future research are discussed.


Hypofibrinogenaemia and hypocalcaemia in adult trauma patients receiving pre-hospital packed red blood cell transfusions: Potential for supplementary pre-hospital therapeutic interventions.
To report the arrival ionised calcium (iCa) and fibrinogen concentrations in trauma patients treated with packed red blood cells by the road-based high-acuity response units of a metropolitan ambulance service. A retrospective review of trauma patients treated with packed red blood cells by high-acuity response units between January 2012 and December 2016. Patients were identified from databases at southeast Queensland adult trauma centres, Pathology Queensland Central Transfusion Laboratory, Gold Coast University Hospital blood bank and the Queensland Ambulance Service. Patient characteristics, results of laboratory tests within 30 min of ED arrival were analysed. A total of 164 cases were analysed. The median injury severity score was 33.5 (interquartile range 22-41), with blunt trauma the commonest mechanism of injury (n = 128, 78.0%). Fifty-eight of the 117 patients (24.4%) with fibrinogen measured had a fibrinogen concentration ≤1.5 g/L; 79 of the 123 patients (64.2%) with an international normalised ratio (INR) measurement had an INR >1.2; 97 of 148 patients (63.8%) with an iCa measured, had an iCa below the Pathology Queensland reference range of 1.15-1.32 mmol/L. Arrival fibrinogen concentration ≤1.5 g/L and arrival iCa ≤1.00 were associated with in-hospital mortality with odds ratio 11.90 (95% confidence interval 4.50-31.65) and odds ratio 4.97 (95% confidence interval 1.42-17.47), respectively. Hypocalcaemia and hypofibrinogenaemia on ED arrival were common in this cohort. Future work should evaluate whether outcomes improve by correction of these deficits during the pre-hospital phase of trauma care.


Linear and Multi-Photon Fluorescence of Thiophene Based Copolymer with Electron-Accepting Side Chains.
A novel copolymer poly(thiophene-2,5-diyl-2,5-di-n-octyloxycarbonyl-1,4-phenylene), denoted as P33, is introduced as potential material for photovoltaics, polymer light-emitting diodes, and/or organic transistors. P33 dissolved in chloroform is investigated by steady-state absorption, linear/non-linear fluorescence spectroscopies and time-resolved fluorescence spectroscopy. Molar extinction coefficient, fluorescence quantum yield, and singlet fluorescence lifetime of P33 are determined to be 18,315 M-1 cm-1, 0.4, and 810 ps, respectively. The P33 fluorescence fast components of decay times are 1.2 ps, 2.0 ps, and 0.5 ps for increasing wavelengths of 480 nm, 500 nm, and 520 nm, respectively. The fast component is attributed to a transport of nearly instantaneously formed excitons to localized states known as downhill energy transfer. Additionally multi-photon excited fluorescence is observed for pumping with wavelengths of 800 nm and 1200 nm. Two-photon absorption cross-section is determined to be 6.9 GM. These spectroscopic studies provide basic fluorescence characteristics of the novel thiophene copolymer P33.


Detection of melamine in a human renal uric acid stone by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).
The link between melamine-contaminated daily foodstuffs and urolithiasis formation has drawn an international concern. However, detection of melamine levels in urine may not completely represent external melamine exposure. Thus, finding an additional analytical method for the study of environmental melamine exposure and its adverse effect in humans is crucial. Eleven adult patients diagnosed with uric acid urolithiasis were retrospectively analyzed. Melamine levels in their overnight one-spot urine samples were measured by a triple quadrupole liquid chromatography tandem mass spectrometry (LC-MS/MS). The compositions of stone samples were analyzed by the Fourier transform infrared (FTIR) spectrophotometer and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Seven (63.6%) out of 11 patients had detectable melamine levels in their urine specimens (method of detection limit: 0.8 ng/ml). Three patients (27.3%) were highly suspected of having melamine-containing urolithiasis in FTIR spectra. In one of those three cases who still had available stored stone specimens, MALDI-TOF MS further confirmed melamine components in this male patient's stone specimens. In contrast, his urinary melamine level was below the detection limit by LC-MS/MS. Direct analysis of melamine in the composition of urolithiasis by MALDI-TOF MS can be an additional analytical method to evaluate for external melamine exposure.


Enhanced catalytic peroxymonosulfate activation for sulfonamide antibiotics degradation over the supported CoSx-CuSx derived from ZIF-L(Co) immobilized on copper foam.
The CoSx-CuSx was firmly immobilized on copper foam (CF) substrate to fabricate supported CoSx-CuSx/CF using ZIF-L(Co)/CF as a self-sacrificing template, in which CF substrate played an important role in improving the adhesion between CF and target catalyst as well as the interfacial interaction between CoSx and CuSx. The CoSx-CuSx/CF performed well in catalytic peroxymonosulfate (PMS) activation, which can accomplish 97.0% sulfamethoxazole (SMX) degradation within 10 min due to the special structure and Co2+ regeneration promoted by S2- and Cu+. The influences of pH, PMS dosage, catalyst dosage, co-existing anions and natural organic matter (NOM) on SMX removal were studied in detail. CoSx-CuSx/CF presented excellent catalytic activity and reusability, which might be fascinating candidate for real wastewater treatment. The possible pathway of SMX degradation was proposed, and the toxicity of the intermediates during the degradation process were evaluated. It is noteworthy that long-term continuous degradation of sulfonamide antibiotics was achieved using a self-developed continuous-flow fixed-bed reactor. This work demonstrated that CF as a substrate to fabricate supported catalysts derived from MOF had great potential in actual wastewater remediation.


Identification and immune characteristics of molecular subtypes related to protein glycosylation in Alzheimer's disease.
Protein glycosylation has been confirmed to be involved in the pathological mechanisms of Alzheimer's disease (AD); however, there is still a lack of systematic analysis of the immune processes mediated by protein glycosylation-related genes (PGRGs) in AD. Transcriptomic data of AD patients were obtained from the Gene Expression Omnibus database and divided into training and verification datasets. The core PGRGs of the training set were identified by weighted gene co-expression network analysis, and protein glycosylation-related subtypes in AD were identified based on k-means unsupervised clustering. Protein glycosylation scores and neuroinflammatory levels of different subtypes were compared, and functional enrichment analysis and drug prediction were performed based on the differentially expressed genes (DEGs) between the subtypes. A random forest model was used to select important DEGs as diagnostic markers between subtypes, and a line chart model was constructed and verified in other datasets. We evaluated the differences in immune cell infiltration between the subtypes through the single-sample gene set enrichment analysis, analyzed the correlation between core diagnostic markers and immune cells, and explored the expression regulation network of the core diagnostic markers. Eight core PGRGs were differentially expressed between the training set and control samples. AD was divided into two subtypes with significantly different biological processes, such as vesicle-mediated transport in synapses and neuroactive ligand-receptor interactions. The high protein glycosylation subtype had a higher level of neuroinflammation. Riluzole and sulfasalazine were found to have potential clinical value in this subtype. A reliable construction line chart model was constructed based on nine diagnostic markers, and SERPINA3 was identified as the core diagnostic marker. There were significant differences in immune cell infiltration between the two subtypes. SERPINA3 was found to be closely related to immune cells, and the expression of SERPINA3 in AD was found to be regulated by a competing endogenous RNA network that involves eight long non-coding RNAs and seven microRNAs. Protein glycosylation and its corresponding immune process play an important role in the occurrence and development of AD. Understanding the role of PGRGs in AD may provide a new potential therapeutic target for AD.


The nurse's role in promoting breast awareness.
Breast cancer affects up to one in 12 women in the UK. Breast awareness, which is advocated in place of routine breast examination, involves women becoming more familiar with their bodies. Nurses have a vital role to play in encouraging women to become more breast aware. Their health promotion activities in this area can have an important impact on the uptake of breast screening initiatives.