Electromyographic heterogeneity in the human temporalis muscle.
This study examined the possible existence of regional differences in activation of the temporalis muscle. Since the muscle is fan-shaped, its fibers pull in different directions. This suggests regional specialization for different motor tasks. EMG activity was registered by six bipolar fine-wire electrodes inserted anteroposteriorly across the muscle belly. Muscle signals were recorded during different static bite tasks for which both the direction and magnitude of bite force were specified. The results showed that the ratio of activities of the six muscle regions changed with the direction of bite force. This indicates a partitioning of the excitatory command to the muscle's motoneuron pool. Alteration in activity with changing bite-force direction was generally the smallest in the anterior-most region of the muscle, the largest in the posterior-most region, and the intermediate in the interjacent regions. Generally, all muscle regions exhibited the highest EMG activity when the bite force was in an approximately posterolateral direction. The muscle was activated uniformly only for bites in this preferential direction. Activity in the regions appeared to be scaled up or down in a linear way according to the desired bite-force level. The results indicate that the direction of pull of the muscle and the maximal force it can produce are not fixed, but depend on the direction of bite force.


The nuclear receptor Hr46/Hr3 is required in the blood brain barrier of mature males for courtship.
The blood brain barrier (BBB) forms a stringent barrier that protects the brain from components in the circulation that could interfere with neuronal function. At the same time, the BBB enables selective transport of critical nutrients and other chemicals to the brain. Beyond these functions, another recently recognized function is even less characterized, specifically the role of the BBB in modulating behavior by affecting neuronal function in a sex-dependent manner. Notably, signaling in the adult Drosophila BBB is required for normal male courtship behavior. Courtship regulation also relies on male-specific molecules in the BBB. Our previous studies have demonstrated that adult feminization of these cells in males significantly lowered courtship. Here, we conducted microarray analysis of BBB cells isolated from males and females. Findings revealed that these cells contain male- and female-enriched transcripts, respectively. Among these transcripts, nuclear receptor Hr46/Hr3 was identified as a male-enriched BBB transcript. Hr46/Hr3 is best known for its essential roles in the ecdysone response during development and metamorphosis. In this study, we demonstrate that Hr46/Hr3 is specifically required in the BBB cells for courtship behavior in mature males. The protein is localized in the nuclei of sub-perineurial glial cells (SPG), indicating that it might act as a transcriptional regulator. These data provide a catalogue of sexually dimorphic BBB transcripts and demonstrate a physiological adult role for the nuclear receptor Hr46/Hr3 in the regulation of male courtship, a novel function that is independent of its developmental role.


Association between UGT1A1*28*28 genotype and lung cancer in the Japanese population.
Lung cancer is the leading cause of cancer death and is closely linked to tobacco smoking. Genetic polymorphisms in genes that encode enzymes involved in metabolizing tobacco carcinogens could affect an individual's risk for lung cancer. While polymorphism of UDP-glucuronosyltransferase1A1 (UGT1A1) is involved in detoxification of benzo(a)pyrene-7,8-dihydrodiol(-), a major tobacco carcinogen, the association between UGT1A1 genotype and lung cancer has not been examined. We retrieved the clinical data of 5,285 patients who underwent systemic chemotherapy at Kyoto University Hospital. A total of 765 patients (194 lung cancer patients and 671 patients with other malignancies) with UGT1A1 genotyping data were included in this analysis. We used logistic regression with recessive, dominant, and additive models to identify differences in genotype frequencies between lung cancer and other malignancies. In the recessive model, UGT1A1*28*28 genotype was significantly associated with lung cancer compared to other malignancies (odds ratio 5.3, P = 0.0083). Among lung cancer patients with a smoking history, squamous cell carcinoma was significantly predominant in patients with UGT1A1*28*28 compared to those with other UGT1A1 genotypes (P = 0.024). This is the first study to demonstrate a significant association between the homozygous UGT1A1*28 genotype and lung cancer.


[Endoscopic brachytherapy for early stage lung cancer of the hilar type].
Endoscopic brachytherapy (ESBT) is a new technique presently being investigated for the treatment of cancer involving the tracheobronchial tree. This paper reports on the potential application of ESBT to the local treatment of cancer of the respiratory tract. Between September 1992 and December 1998, ESBT was performed in 52 patients with early-stage tracheobronchial cancer at the National Cancer Center Hospital. In all 52 cases tracheobronchial cancer was histologically confirmed by biopsy before treatment. Of the 52 patients who received ESBT, 51 showed a complete response to this therapy. Of the 52 patients, 27 patients are alive 12-80 months after therapy with no apparent recurrence or metastasis, and 25 patients have died. The 5-year survival rate of the 52 patients is 72.6%.


[Comparative pharmacokinetics and renal accumulation of the iodized contrast media: ioxitalamic acid, ioxaglic acid and iohexol in the rabbit].
Male and female rabbits were given a I.V. bolus injection of a single 5 ml/kg dose of either ioxitalamic acid, ioxaglic acid or iohexol. Animals were killed 2 hours, 8 hours and 24 hours after the injection. One group of animals received a continuous I.V. infusion of contrast agent at a constant rate of 2.5 ml/kg/hour of four hours. Animals were killed 30 minutes after the end of the infusion. Plasma and tissue concentrations of contrast agents were assayed using an HPLC method. A pharmacokinetic study was performed after the I.V. bolus injection. This study shows that: 1) Plasma elimination half-lives were identical in males and in females as well as for all three products. This half life is about 45 minutes. The distribution volume was identical in male and females as well as for all three products and was comprised between 20% and 26% of body weight. 2) For all three contrast agents, the renal cortical concentrations are higher than in the medulla or the papilla at all the observation times. The renal cortical accumulation of contrast agents is persistent in comparison to plasma concentrations. 3) Ionic and lipophilic properties of contrast agents seem to play an important role on the renal accumulation pattern.


The effect of polychlorinated biphenyls on the uptake of dopamine and other neurotransmitters into rat brain synaptic vesicles.
Studies have shown that polychlorinated biphenyls may affect cognitive functions both in human and also in experimental animals. One of the neurochemical parameters that is changed after exposure to these compounds is a reduction in the dopamine level in the brain, although the mechanism behind this reduction is not known. We have therefore investigated whether this reduction could be caused by an effect on vesicular uptake. ortho-Chlorinated biphenyls are found to be competitive inhibitors of dopamine transport into synaptic vesicles from rat brain with K(i) concentrations as low as 4 microM. In contrast, several nonortho-chlorinated biphenyls did not inhibit vesicular uptake. The inhibition was specific for dopamine, in that the uptake of glutamate and GABA was inhibited at higher PCB concentrations under identical conditions. The vesicular Mg-ATPase proton pump was also inhibited at higher concentrations of PCBs than the dopamine transport. Uptake of methylamine gave no indication of any disruption of the vesicular proton gradient. The inhibition of dopamine vesicular uptake by PCBs was competitive. Several of the ortho-PCBs also inhibited the binding of tetrabenazine, which is known to bind to a site close to the dopamine binding site, at the vesicular transporter. The results show that inhibition of vesicular uptake may contribute to the decrease of dopamine reported in nervous tissue after exposure to PCBs under different conditions.


Complex formation and catalytic activation by the PII signaling protein of N-acetyl-L-glutamate kinase from Synechococcus elongatus strain PCC 7942.
The signal transduction protein P(II) from the cyanobacterium Synechococcus elongatus strain PCC 7942 forms a complex with the key enzyme of arginine biosynthesis, N-acetyl-l-glutamate kinase (NAGK). Here we report the effect of complex formation on the catalytic properties of NAGK. Although pH and ion dependence are not affected, the catalytic efficiency of NAGK is strongly enhanced by binding of P(II), with K(m) decreasing by a factor of 10 and V(max) increasing 4-fold. In addition, arginine feedback inhibition of NAGK is strongly decreased in the presence of P(II), resulting in a tight control of NAGK activity under physiological conditions by P(II). Analysis of the NAGK-P(II) complex suggests that one P(II) trimer binds to one NAGK hexamer with a K(d) of approximately 3 nm. Complex formation is strongly affected by ATP and ADP. ADP is a strong inhibitor of complex formation, whereas ATP inhibits complex formation only in the absence of divalent cations or in the presence of Mg(2+) ions, together with increased 2-oxoglutarate concentrations. Ca(2+) is able to antagonize the negative effect of ATP and 2-oxoglutarate. ADP and ATP exert their adverse effect on NAGK-P(II) complex formation through binding to the P(II) protein.


Discriminant function analysis of the central portion of the innominate.
Terry Collection innominates of 260 American whites and blacks (65 males and 65 females of each race) were analyzed by discriminant function analysis for sex assessment, race known, and for simultaneous race and sex assessment. Measurements from the preservationally favored central portion of the innominate were chosen for their potential usefulness in forensic casework and to objectify long-recognized "formal" differences between the sexes in the greater sciatic notch. These included acetabular diameter, greater sciatic notch height, and position of greatest notch depth. Accuracy of sex prediction when race is known is roughly 90% in both the base sample of 260 and a test sample of 200 (50 additional individuals for each group). For simultaneous race and sex assessment, accuracy of prediction is roughly 60% for each group in both samples. This represents about a 45% reduction in error over random assignment by race and sex.


Results of the Sensory Profile in children with suspected childhood apraxia of speech.
Speech-sound disorders are common in preschool-age children, and are characterized by difficulty in the planning and production of speech sounds and their combination into words and sentences. The objective of this study was to review and compare the results of the Sensory Profile (Dunn, 1999) in children with a specific type of speech-sound disorder, childhood apraxia of speech (CAS), and to explore the relationship between sensory processing and sound-production deficits. Participants were identified prospectively through an interdisciplinary apraxia clinic at a tertiary care pediatric hospital, and results of the Sensory Profile were compiled and reviewed. Thirty-eight children aged 3 to 10 years with suspected CAS were evaluated from July 2003 to July 2005. The results of the Sensory Profile indicated a difference for these children in several factor clusters when compared to typical peers from the normative population of the Sensory Profile. These findings imply that children with suspected CAS may present with differences in sensory processing in addition to speech impairment. When present, these differences in sensory processing could be addressed with specific therapeutic approaches through occupational therapy or consultation with an occupational therapist.


Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations.
The human aging process is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Despite their potential correlation, the relationship between cancer- and ageing-related transcriptional changes is largely unknown. In this study, we aimed to analyze aging-associated transcriptional patterns in publicly available bulk mRNA-seq and single-cell RNA-seq (scRNA-seq) datasets for chronic myelogenous leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC), and pancreatic ductal adenocarcinoma (PDAC). Indeed, we detected that various aging/senescence-induced genes (ASIGs) were upregulated in malignant diseases compared to healthy control samples. To elucidate the importance of ASIGs during cell development, pseudotime analyses were performed, which revealed a late enrichment of distinct cancer-specific ASIG signatures. Notably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. While only minor correlations were detected between ASIGs and transcriptome-wide changes in PDAC, a high proportion of ASIGs was induced in CML, CRC, HCC, and LC samples. These unique cellular subpopulations could serve as a basis for future studies on the role of aging and senescence in human malignancies.


Lamins are rapamycin targets that impact human longevity: a study in centenarians.
The dynamic organisation of the cell nucleus is profoundly modified during growth, development and senescence as a result of changes in chromatin arrangement and gene transcription. A plethora of data suggests that the nuclear lamina is a key player in chromatin dynamics and argues in favour of a major involvement of prelamin A in fundamental mechanisms regulating cellular senescence and organism ageing. As the best model to analyse the role of prelamin A in normal ageing, we used cells from centenarian subjects. We show that prelamin A is accumulated in fibroblasts from centenarians owing to downregulation of its specific endoprotease ZMPSTE24, whereas other nuclear envelope constituents are mostly unaffected and cells do not enter senescence. Accumulation of prelamin A in nuclei of cells from centenarians elicits loss of heterochromatin, as well as recruitment of the inactive form of 53BP1, associated with rapid response to oxidative stress. These effects, including the prelamin-A-mediated increase of nuclear 53BP1, can be reproduced by rapamycin treatment of cells from younger individuals. These data identify prelamin A and 53BP1 as new targets of rapamycin that are associated with human longevity. We propose that the reported mechanisms safeguard healthy ageing in humans through adaptation of the nuclear environment to stress stimuli.


Personalized antiplatelet therapy: state of the art.
Overwhelming evidence exists that thrombus generation resulting from platelet activation and aggregation is the primary process involved in the occurrence of the myocardial infarction and stent thrombosis. Despite the proven clinical efficacy of dual antiplatelet therapy, wide antiplatelet response variability associated with clopidogrel therapy was demonstrated in pharmacodynamic studies where approximately one in three patients exhibited high on-treatment platelet reactivity (HPR). Generally, physicians do not objectively assess the intensity of the adenosine diphosphate-P2Y12 interaction in their high-risk patients treated with clopidogrel. Instead most clinicians use a non-selective or one-size-fits-all approach. HPR and CYP2C19 LoF carriage are associated with clinical outcomes in high-risk clopidogrel-treated patients who have undergone percutaneous coronary intervention (PCI). Although we do not yet have conclusive evidence from a large-scale randomized trial that personalized antiplatelet therapy improves patient outcomes, a class IIb recommendation has been given in the guidelines to perform genotyping or phenotyping in high-risk PCI patients if a change in antiplatelet therapy will ensue based on the test results. It may be reasonable at this time to assess platelet function and perform genotyping in clopidogrel-treated high-risk patients and treat with more potent P2Y12 receptor therapy selectively.


Insomnia: nonpharmacologic management by private practice physicians.
We report a survey investigation on the perceived value of behavioral assessment and the use of nonpharmacologic treatment of insomnia by 159 physicians in private practice in Davidson County, Tennessee. They generally attributed limited value to behavioral assessment, and reported infrequent use of nonpharmacologic treatment. However, the more patients the physicians saw with insomnia as the chief symptom, the more they tended to value behavioral assessment and other diagnostic procedures. Endorsement of behavioral assessment and all other diagnostic practices was in turn related to the use of behavioral treatment techniques. We suggest that a lack of awareness of the value of alternative assessment and treatment strategies may account for physicians' limited use of nonpharmacologic approaches to this common yet frequently serious medical problem.


A 52 Years Old Male Presented With Acute Kidney Injury with Hepatitis after Taking Fish Gallbladder.
A 52 years old male was admitted at National Institute of Kidney Diseases & Urology, Dhaka, Bangladesh on 16th September 2016 with the history of oliguria, nausea, vomiting & swelling of both legs following consumption of rohu fish gall bladder for the permanent remedy of recurrent abdominal discomfort. He was admitted and received antiemetic, proton pump inhibitor. He had azotemia & underwent urgent haemodialysis (HD). Renal function improved over a period of 5 weeks. Fish gallbladder poisoning is quite frequent in several developing country of Southeast Asia. Rohu fish is commonly consumed in our country but cases of fish bile poisoning are not very common.


Modern multiple myeloma therapy: deep, sustained treatment response and good clinical outcomes.
In the USA at the beginning of this century, the average overall survival in patients with multiple myeloma was about 3 years. Around that time, three drugs (bortezomib, lenalidomide and thalidomide) were introduced for the treatment of multiple myeloma and, in 2012, carfilzomib received accelerated approval by the US Food and Drug Administration (FDA). Driven by access to better drugs, median overall survival in younger patients (aged <50 years) was >10 years by 2014. The FDA approved 14 new drugs for the treatment of cancer in 2015; four of these were approved for the treatment of myeloma (panobinostat, daratumumab, elotuzumab and ixazomib). In 2015 and 2016, expanded label indications were approved by the FDA for lenalidomide and carfilzomib, respectively. The recent increase in approved, highly effective combination therapies for patients with multiple myeloma has led the way to redefining the goals of therapy. Here, we review and provide a clinical perspective on the treatment goals and management of multiple myeloma in the era of modern therapy. Recent meta-analyses show that minimal residual disease (MRD) negativity is associated with longer progression-free and overall survival in patients with multiple myeloma. With the use of modern combination therapy, large proportions (>60-70%) of newly diagnosed multiple myeloma patients achieve complete responses and MRD negativity. Modern combination therapies induce rapid, deep and sustainable responses (including MRD negativity), supporting a treatment paradigm shift away from palliative two-drug combinations towards the use of modern, potent, three- or four-drug combination regimens in early lines of therapy. Data support the use of modern therapy upfront rather than reserving it for later stages of the disease. As survival time increases with modern combination therapies, development of early reliable surrogate end-points for survival, such as MRD negativity, are needed for expedited read-out of future randomized clinical trials.


Multi-wall carbon nanotubes (MWCNTs)-doped polypyrrole DNA biosensor for label-free detection of genetically modified organisms by QCM and EIS.
In this paper, we describe DNA electrochemical detection for genetically modified organism (GMO) based on multi-wall carbon nanotubes (MWCNTs)-doped polypyrrole (PPy). DNA hybridization is studied by quartz crystal microbalance (QCM) and electrochemical impedance spectroscopy (EIS). An increase in DNA complementary target concentration results in a decrease in the faradic charge transfer resistance (R(ct)) and signifying "signal-on" behavior of MWCNTs-PPy-DNA system. QCM and EIS data indicated that the electroanalytical MWCNTs-PPy films were highly sensitive (as low as 4pM of target can be detected with QCM technique). In principle, this system can be suitable not only for DNA but also for protein biosensor construction.


The anti-adipogenic effect of macrophage-conditioned medium requires the IKKβ/NF-κB pathway.
Macrophage-secreted factors inhibit adipogenesis, but the underlying mechanism is not well understood. Our objective was to determine if anti-adipogenic signaling pathways in human preadipocytes are activated by macrophage-conditioned medium (MacCM). Human abdominal subcutaneous stromal preadipocytes were treated with adipogenic inducers in either standard medium or medium conditioned by human THP-1 macrophages. THP-1-MacCM increased inhibitor of κB kinase β (IKKβ) phosphorylation, inhibitor of NF-κB α (IκBα) degradation, and NF-κB activity in human preadipocytes in a time-dependent manner. Concomitant treatment of human abdominal subcutaneous preadipocytes with sc-514, a selective inhibitor of IKKβ, prevented the inhibitory effect of THP-1-MacCM on lipid accumulation and expression of adipogenic markers. Our data indicate that activation of the preadipocyte IKKβ/NF-κB pathway is required for the anti-adipogenic effect of THP-1-MacCM on human adipogenesis.


Co(III)/Alkali-Metal(I) Heterodinuclear Catalysts for the Ring-Opening Copolymerization of CO2 and Propylene Oxide.
The ring-opening copolymerization of carbon dioxide and propene oxide is a useful means to valorize waste into commercially attractive poly(propylene carbonate) (PPC) polyols. The reaction is limited by low catalytic activities, poor tolerance to a large excess of chain transfer agent, and tendency to form byproducts. Here, a series of new catalysts are reported that comprise heterodinuclear Co(III)/M(I) macrocyclic complexes (where M(I) = Group 1 metal). These catalysts show highly efficient production of PPC polyols, outstanding yields (turnover numbers), quantitative carbon dioxide uptake (>99%), and high selectivity for polyol formation (>95%). The most active, a Co(III)/K(I) complex, shows a turnover frequency of 800 h-1 at low catalyst loading (0.025 mol %, 70 °C, 30 bar CO2). The copolymerizations are well controlled and produce hydroxyl telechelic PPC with predictable molar masses and narrow dispersity (Đ < 1.15). The polymerization kinetics show a second order rate law, first order in both propylene oxide and catalyst concentrations, and zeroth order in CO2 pressure. An Eyring analysis, examining the effect of temperature on the propagation rate coefficient (kp), reveals the transition state barrier for polycarbonate formation: ΔG‡ = +92.6 ± 2.5 kJ mol-1. The Co(III)/K(I) catalyst is also highly active and selective in copolymerizations of other epoxides with carbon dioxide.


Purification and characterization of glucose dehydrogenase from a heterotrophically grown blue-green alga.
NADP- and NAD-dependent glucose dehydrogenase was partially purified from a dark-grown blue-green alga (endophytic Nostoc strain MAC). Polyacrylamide gel electrophoresis established that a single protein possessed dual activity for either NADP or NAD. No other electron acceptor substituted for pyridine nucleotides and no evidence for a flavin prosthetic group was found. Although the Km for NADP was 8.8 mum and for NAD 328 mum, the enzyme was equally active with NAD or NADP at saturating levels of substrates. The enzyme was similar to previously described glucose dehydrogenase in that it had a high Km for glucose (18-20 mm at 35 C) and an alkaline pH optimum of 7.6 to 9.4.


IL-7 adjuvant treatment enhances long-term tumor-antigen-specific CD8+ T-cell responses after immunization with recombinant lentivector.
Immunization with recombinant lentivector elicits higher frequencies of tumor antigen-specific memory CD8+ T cells than peptide-based vaccines. This finding correlates with our observation that, upon recombinant lentivector immunization, a higher fraction of antigen-specific effector CD8+ T cells does not down-regulate the expression of the survival/memory marker interleukin-7 receptor alpha chain (IL-7Ralpha). Here we show that, surprisingly, higher expression of IL-7Ralpha on recombinant lentivector-induced effector CD8+ T cells does not result in the up-regulation of survival molecules, such as Bcl-2. We thus hypothesized that physiologic levels of IL-7 might be limiting in vivo for delivering survival signals to the expanding population of effector cells. To test this hypothesis, we administered recombinant IL-7 during the effector phase of the response. We observed an up-regulation of Bcl-2 and a strong expansion of antigen-specific effector CD8+ T cells, and of naive CD8+ T cells. Strikingly, IL-7 treatment elicited also a significant increase in the number of antigen-specific memory CD8+ T cells in recombinant lentivector-immunized mice, but not in peptide-immunized mice. Altogether, these data show that IL-7 adjuvant treatment can enhance long-term antigen-specific CD8+ T-cell responses. However, its efficacy depends on the expression of IL-7Ralpha at the surface of effector CD8+ T cells.


Activity of the retinoblastoma family proteins, pRB, p107, and p130, during cellular proliferation and differentiation.
Genetic evidence from retinoblastoma patients and experiments describing the mechanism of cellular transformation by the DNA tumor viruses have defined a central role for the retinoblastoma protein (pRB) family of tumor suppressors in the normal regulation of the eukaryotic cell cycle. These proteins, pRB, p107, and p130, act in a cell cycle-dependent manner to regulate the activity of a number of important cellular transcription factors, such as the E2F-family, which in turn regulate expression of genes whose products are important for cell cycle progression. In addition, inhibition of E2F activity by the pRB family proteins is required for cell cycle exit after terminal differentiation or nutrient depletion. The loss of functional pRB, due to mutation of both RB1 alleles, results in deregulated E2F activity and a predisposition to specific malignancies. Similarly, inactivation of the pRB family by the transforming proteins of the DNA tumor viruses overcomes cellular quiescence and prevents terminal differentiation by blocking the interaction of pRB, p107, and p130 with the E2F proteins, leading to cell cycle progression and, ultimately, cellular transformation. Together these two lines of evidence implicate the pRB family of negative cell cycle regulators and the E2F family of transcription factors as central components in the cell cycle machinery.


Roles of Akt and glycogen synthase kinase 3beta in the ultraviolet B induction of cyclooxygenase-2 transcription in human keratinocytes.
Ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) expression plays an important role in UVB tumor promotion. We examined whether Akt and glycogen synthase kinase 3beta (GSK-3beta), components of the phosphatidylinositol 3'-kinase pathway, are involved in UVB induction of COX-2 transcription. UVB caused Akt phosphorylation at both Thr-308 and Ser-473 that was inhibited by LY294002, a phosphatidylinositol 3'-kinase inhibitor. LY294002 also decreased the expression of endogenous COX-2 protein and a luciferase construct driven by COX-2 promoter. Similarly, UVB caused phosphorylation of GSK-3beta (Ser-9) and presumably inactivation of GSK-3beta. Inhibition of GSK-3beta by lithium induced endogenous COX-2 protein expression and COX-2 promoter activity. Finally, overexpression of a dominant-negative Akt mutant or wild-type GSK-3beta suppressed UVB-mediated induction of COX-2 promoter. These studies suggest that inactivation of GSK-3beta through activation of Akt plays an important role in the UVB induction of COX-2 transcription.


Even experts cannot agree on the optimal use of platelet-rich plasma in lateral elbow tendinopathy: an international Delphi study.
Platelet-rich plasma (PRP) is widely used in the management of lateral elbow tendinopathy (LET) despite conflicting evidence on its effectiveness. With high levels of user experience, this study aimed to assess consensus amongst experts on its clinical use. A three-round international Delphi study was conducted. Participants were invited through national society mailing lists and contact lists derived from a systematic search of the literature on PRP. In round one, a primary working group developed 40 statements on PRP preparation and clinical application. In rounds two and three, an international group of researchers on PRP and clinical users of the device scored their levels of agreement with the statements on a five-point scale. Consensus was defined as an interquartile range of ≤ 1. Consensus of agreement was only reached for 17/40 (42.5%) statements. For statements on PRP formulation, consensus of agreement was reached in 2/6 statements (33%). Only limited consensus on the contraindications, delivery strategy and delivery technique was achieved. Experts reached very limited consensus on the use of PRP in LET. High levels of user experience have not resulted in a convergence of opinion on the technical components of PRP formulation and delivery, substantiating the need for further studies and improved trial reporting.


Interaction of E. coli outer-membrane protein A with sugars on the receptors of the brain microvascular endothelial cells.
Esherichia coli, the most common gram-negative bacteria, can penetrate the brain microvascular endothelial cells (BMECs) during the neonatal period to cause meningitis with significant morbidity and mortality. Experimental studies have shown that outer-membrane protein A (OmpA) of E. coli plays a key role in the initial steps of the invasion process by binding to specific sugar moieties present on the glycoproteins of BMEC. These experiments also show that polymers of chitobiose (GlcNAcbeta1-4GlcNAc) block the invasion, while epitopes substituted with the L-fucosyl group do not. We used HierDock computational technique that consists of a hierarchy of coarse grain docking method with molecular dynamics (MD) to predict the binding sites and energies of interactions of GlcNAcbeta1-4GlcNAc and other sugars with OmpA. The results suggest two important binding sites for the interaction of carbohydrate epitopes of BMEC glycoproteins to OmpA. We identify one site as the binding pocket for chitobiose (GlcNAcbeta1-4GlcNAc) in OmpA, while the second region (including loops 1 and 2) may be important for recognition of specific sugars. We find that the site involving loops 1 and 2 has relative binding energies that correlate well with experimental observations. This theoretical study elucidates the interaction sites of chitobiose with OmpA and the binding site predictions made in this article are testable either by mutation studies or invasion assays. These results can be further extended in suggesting possible peptide antagonists and drug design for therapeutic strategies.


ACEA Attenuates Oxidative Stress by Promoting Mitophagy via CB1R/Nrf1/PINK1 Pathway after Subarachnoid Hemorrhage in Rats.
Endovascular perforation was performed to establish a SAH model of rats. ACEA was administered intraperitoneally 1 h after SAH. The CB1R antagonist AM251 was injected intraperitoneally 1 h before SAH induction. Adenoassociated virus- (AAV-) Nrf1 shRNA was infused into the lateral ventricle 3 weeks before SAH induction. Neurological tests, immunofluorescence, DHE, TUNEL, Nissl staining, transmission electron microscopy (TEM), and Western blot were performed. The expression of CB1R, Nrf1, PINK1, Parkin, and LC3II increased and peaked at 24 h after SAH. ACEA treatment exhibited the antioxidative stress and antiapoptosis effects after SAH. In addition, ACEA treatment increased the expression of Nrf1, PINK1, Parkin, LC3II, and Bcl-xl but repressed the expression of Romo-1, Bax, and cleaved caspase-3. Moreover, the TEM results demonstrated that ACEA promoted the formation of mitophagosome and maintained the normal mitochondrial morphology of neurons. The protective effect of ACEA was reversed by AM251 and Nrf1 shRNA, respectively. This study demonstrated that ACEA alleviated oxidative stress and neurological dysfunction by promoting mitophagy after SAH, at least in part via the CB1R/Nrf1/PINK1 signaling pathway.


Resting-state posterior alpha power changes with prolonged exposure in a natural environment.
Exposure to environments that contain natural features can benefit mood, cognition, and physiological responses. Previous research proposed exposure to nature restores voluntary attention - attention that is directed towards a task through top down control. Voluntary attention is limited in capacity and depletes with use. Nature provides unique stimuli that do not require voluntary attention; therefore, the neural resources needed for attention to operate efficiently are theorized to restore when spending time in nature. Electroencephalography reflects changes in attention through fluctuations in power within specific frequencies. The current study (N = 29) measured changes in averaged resting state posterior alpha power before, during, and after a multiday nature exposure. Linear mixed-effects models revealed posterior alpha power was significantly lower during the nature exposure compared to pre-trip and post-trip testing, suggesting posterior alpha power may be a potential biomarker for differences related to exposure to natural and urban environments.


[Genetic analysis of a pedigree affected with congenital high myopia caused by a novel splice site variant of COL11A1 gene].
To analyze genetic variant in a pedigree affected with congenital high myopia. Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing. The pedigree was also subjected to co-segregation analysis. WES has identified a novel splice site heterozygous variant (c.2556+1G>A) in the COL11A1 gene in the proband. Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556+1G>A), while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants, the variant was classified as "likely pathogenic" (PVS1+PM2). A novel splice variant (c.2556+1G>A) of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia, which probably underlies the disease.


What is the major driver of China's hospital medical expenditure growth? A decomposing analysis.
This study aimed to quantify increases in the medical expenditures of public hospitals associated with changes in service use and prices, which could inform policy efforts to curb the future growth of hospital medical expenditures. Nationwide and provincial data regarding service volume, service price and intensity of public hospitals' outpatient and inpatient care from 2008 to 2018 were extracted from the China Health Statistical Yearbooks, and population size data were obtained from the 2019 China Statistical Yearbook. A decomposition analysis was performed to measure the relative effects of changes in service use (volume or its subcomponent factors) and service price and intensity on the increase in the inpatient and outpatient total medical expenditures of public hospitals from 2008 to 2018. After adjusting for price inflation, the total medical expenditure of public hospitals increased by approximately threefold from 2008 to 2018. During this period, the increase in service volume was associated with 67.4% of the observed increase in the total medical expenditures in the inpatient sector and 57.2% of the observed increase in the total medical expenditures in the outpatient sector. Most of the service volume effect is due to an increase in the hospital utilisation rate. The growth in the utilisation rate was associated with 73.7% of the observed growth in the total medical expenditures in the inpatient sector and 60.3% of the observed growth in the total medical expenditures in the outpatient sector. Service use, rather than price, appears to be the major driver of increases in medical expenditures in Chinese hospitals. An important policy implication for China and other countries with similar drivers is that the effect of controlling price and intensity growth on containing medical costs could be limited and controlling service utilisation growth could be essential.


[Vecuronium in infants and children: clinical and neuromuscular effects].
The neuromuscular and cardiovascular effects of vecuronium (Norcuron, Organon Teknika) were studied in 58 infants (1 day-10 months) and 65 children (1-6 years) anaesthetized either with halothane or under balanced anaesthesia. After a bolus dose of 70 micrograms/kg vecuronium the time course of neuromuscular blockade was determined using an electromyographic equipment. Onset time (time to maximal effect) was significantly shorter in infants compared with children; 1.4 +/- 0.7 min (min +/- SD) and 2.7 +/- 0.8 min, respectively. In contrast the recovery index (time for 25% to 75% recovery) was longer in infants than in children 18 +/- 6.7 min and 10 +/- 2.3 min, respectively. Repetitive administration of vecuronium, up to five maintenance doses, did not show any cumulative effects in children under balanced anaesthesia. After repetitive administration the recovery index was 12 +/- 1.7 min. Vecuronium (a bolus dose of 80 or 100 micrograms/kg) did not cause any significant change of blood pressure in infants and children anaesthetized either with halothane or by balanced anaesthesia. Infants under balanced anaesthesia showed a significant decrease in heart rate 15 min after administration of vecuronium. In contrast an increase in heart rate could be observed in children under halothane anesthesia, which was not attributed to vecuronium.


Copper ferrite nanoparticles induced cytotoxicity and oxidative stress in Channel catfish ovary cells.
Nanomaterials are the sixth most emerging contaminants that are entering into aquatic habitat posing a risk to the inhabiting organisms. Nanoparticles of copper ferrite have been extensively used in biomedical applications. However, very limited studies are available on the cytotoxicity evaluation of copper ferrite nanoparticles (CuFe2O4NPs) on different cell lines. The current work investigates on the cytotoxicity, oxidative stress and morphological variations triggered by CuFe2O4NPs in Channel catfish ovary (CCO) cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), neutral red uptake (NRU), lipid peroxidation (LPO), catalase (CAT), reduced glutathione (GSH), glutathione sulfotransferase (GST) and glutathione peroxidase (GPX) assays after 24 h of treatment. Dose dependent decline in cell survival was noticed in MTT and NRU assays. A significant increase in LPO, GST and GPX was observed in CCO cells exposed to CuFe2O4NPs after 24 h of treatment. However, the CAT and GSH levels in CCO cells exposed to CuFe2O4NPs decreased significantly after 24 h. The CCO cells exposed to 10 μg/mL concentration of CuFe2O4NPs for 24 h showed remarkable changes in their morphology. Further, the study also describes the detailed mechanism of toxicity of CuFe2O4NPs in other model cell lines to probe the risk of inhabiting organisms.


Use of spinal cord stimulator for treatment of lumbar radiculopathy in a patient with severe kyphoscoliosis.
Spinal cord stimulation (SCS) has been a therapeutic option for chronic pain for over 40 years with a common indication being failed back surgery syndrome (FBSS). This case reports the successful implantation of a spinal cord stimulator in a patient with FBSS and kyphoscoliosis for treatment of radicular pain. Technical considerations and anatomical difficulties that may be encountered during placement with kyphoscoliosis will be discussed. This patient had failed other therapies including oral medications, epidural steroid injections, spinal surgeries, and physical and aquatic therapies. On physical examination the patient had a severely deformed lumbar spine. Careful review of the spine radiographs and CT scan revealed lead placement might be possible at the level of T12-L1 or L1-2. A Medline search did not reveal a case of kyphoscoliosis with radicular pain treated with SCS. After a successful percutaneous trial, a SCS was implanted. Fourteen weeks later, the patient reported being pain free with an increased physical activity level and opioid discontinuation. Technical considerations with kyphoscoliosis may discourage pain physicians from attempting SCS. This case illustrates that with careful selection, some of these patients may be candidates for SCS with good results.


Hedgehog Pathway Inhibitor Therapy for Locally Advanced and Metastatic Basal Cell Carcinoma: A Systematic Review and Pooled Analysis of Interventional Studies.
Hedgehog pathway inhibitors (HPIs) were made available by US Food and Drug Administration approval in 2012 for vismodegib and 2015 for sonidegib. Both target the Smoothened molecule and are indicated for locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC). To evaluate clinical experience with HPIs, including efficacy and adverse effects. We conducted a systematic review in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EMBASE, using search terms "vismodegib," "sonidegib," "Erivedge," "Odomza," "basal cell carcinoma," and "BCC." We included clinical trials, retrospective medical record reviews, and prospective case series that used HPIs for the treatment of laBCC or mBCC in human subjects. Individual case reports and limited, retrospective case series were excluded from our review. Data were extracted independently by 2 reviewers on a predesigned, standardized form. The following data were recorded: number of patients with laBCC or mBCC, dose and frequency of drug administration, median duration of treatment, clearance and recurrence rates, and adverse effects. Eleven vismodegib articles (published between 2009 and 2015) met criteria for inclusion, and 8 articles were able to be pooled for analysis. The 8 pooled articles included 744 total patients with 704 patients clinically evaluable. Sonidegib did not yield enough publications for a formal analysis. Objective response to vismodegib for laBCC had a weighted average of 64.7% (95% CI, 63.7%-65.6%); complete response averaged 31.1% (95% CI, 30.4%-31.8%). Objective response for mBCC was 33.6% (95% CI, 33.1%-34.2%); complete response averaged 3.9% (95% CI, 3.3%-4.4%). Median duration of therapy was 35.8 weeks (95% CI, 35.1-36.5 weeks). In a systematic review of HPIs for laBCC and mBCC, vismodegib, but not sonidegib, had enough studies to warrant a pooled analysis. Vismodegib was identified to have a significant, consistent effect on the median duration of therapy of laBCC and mBCC. While mBCC responses are superior to any traditional approach, the response rate for laBCC might be considered in the context of other standard treatment options including surgery and radiation therapy.


Effect of straining on the lower esophageal sphincter: identification of the "straining-esophageal reflex" and its role in gastroesophageal competence mechanism.
The lower esophagus is intra-abdominal and exposed to intra-abdominal pressure (IAP) variations that may lead to gastroesophageal reflux (GER). We investigated the hypothesis that the lower esophageal sphincter (LES) undergoes phasic contraction on IAP increase, with a resulting inhibition of the stress GER. The study comprised 17 subjects (age 42.3 +/- 8.7 SD yr, 10 men, 7 women) who were scheduled for surgical repair of abdominal hernia. The patients had no swallowing problems. The electromyographic (EMG) activity of the LES and pressure within the LES were recorded at rest and during increased IAP (coughing, straining). The recording was repeated after LES anesthetization or saline infiltration. The LES EMG at rest showed regular slow waves (SWs), superimposed on or followed by random action potentials (APs). Coughing or straining induced increase of the SWs parameters and also of the APs; although the increase with straining was less than with coughing, the difference was insignificant. Coughing or straining increased the LES pressure significantly (p < .05, p < .05, respectively). Ten minutes after LES anesthetization, coughing or straining did not produce significant LES EMG or pressure changes, while saline infiltration of LES caused LES response similar to preinjection. Thus, coughing and straining effected an increase of the LES EMG activity and pressure, an action presumably mediated through a reflex that we call the "straining-esophageal reflex." This reflex seems to be evoked during increased intra-abdominal pressure and to effect LES contraction, thus, sharing with other factors in prevention of gastroesophageal reflux.


Use of noninvasive positive pressure ventilation and spinal anesthesia during hip replacement arthroplasty in a patient with severe chronic obstructive pulmonary disease: case report.
Anesthetic management of patients with severe chronic obstructive pulmonary disease is extensively discussed, due to the high rates of complications in this subtype of patients submitted to medium and high complexity surgical procedures. The objective of this study is to report use of noninvasive positive pressure mechanical ventilation - bilevel positive airway pressure - and spinal anesthesia in a patient with severe chronic obstructive pulmonary disease during total hip arthroplasty. An 81 year old, male patient with severe chronic obstructive pulmonary disease (GOLD 4) was submitted to total hip arthroplasty due to a femoral bone fracture under spinal anestesia and noninvasive positive pressure mechanical ventilation-bilevel positive airway pressure with expiratory pressure of 7 cmH2O, inspiratory pressure of 15 cmH2O and O2 flow of 3 L/min. During the procedure, the patient had one episode of bronchospasm that was promptly reverted pharmacologically with no complications in the postoperative period. The combination of less invasive anesthetic and ventilation techniques is easy to apply and may be useful in the perioperative management of patients with high anesthetic morbidity. Interaction between clinical, surgical and anesthetic teams for these cases is very important to reduce the mortality associated with extensive procedures in severe patients.


MODELLING THE EXPOSURE OF RESIDENTS OF A RADIUM-CONTAMINATED LIVING PLACE.
Within the framework of the Swiss Radium Action Plan 2015-22, which aims to investigate and remediate sites contaminated by the radium used in the Swiss watch industry, a reference level of 1 mSv per y has been defined for the exposure of residents. An additional protection objective has been set for soil contamination, which should not exceed the value of 1000 Bq per kg 226Ra. Based on measurements on the study sites, the doses received by residents were calculated accordingly to the methodology, in both indoor and outdoor areas, taking into account external exposure and ingestion. The site diagnosis approach consists of a screening procedure based on a rapid measurement, followed, if necessary, by additional analysis to estimate doses. Sites where modelling indicates that the reference level or the complementary protection objective for soil contamination have been exceeded are subject to remediation. The application of the methodology based on these radiological criteria to 752 sites diagnosed until December 2020 indicates a rate of sites (buildings and outdoor areas) requiring remediation of ~16%. The annual doses to residents calculated by modelling are between 1 and 20 mSv per y for these sites.


Facile Functionalization of Electrospun Poly(ethylene-co-vinyl alcohol) Nanofibers via the Benzoxaborole-Diol Interaction.
A facile functionalization method of poly(ethylene-co-vinyl alcohol) (EVOH) nanofiber meshes was demonstrated by utilizing the benzoxaborole-diol interaction between EVOH and benzoxaborole-based copolymers (BOP). EVOH and BOP were firstly mixed to prepare the quasi-gel-state solution with enough viscosity for electro-spinning. The fiber morphology was controlled via changing the mixing ratio of EVOH and BOP. The prepared EVOH/BOP nanofiber mesh showed good stability in aqueous solution. Over 97% of the nanofibers remained after the immersion test for 24 h in acid or alkali aqueous solutions without changing their morphology. Temperature and pH-responsive moieties were copolymerized with BOP, and cationic dye was easily immobilized into the nanofiber mesh via an electrostatic interaction. Therefore, the proposed functionalization technique is possible to perform on multi-functionalized molecule-incorporated nanofibers that enable the fibers to show the environmental stimuli-responsive property for the further applications of the EVOH materials.


A Pediatric Case of Transformed Mycosis Fungoides in a BRCA2 Positive Patient.
Cutaneous T-cell lymphomas are very rare in children. Although mycosis fungoides is the most common of these rare cutaneous T-cell lymphomas in children, transformation to an aggressive malignancy remains extremely uncommon, and there are no clear guidelines for clinical management in the pediatric population. In addition, the increased usage of next-generation sequencing for pediatric patients with unusual malignancies may result in the discovery of pathogenic germline mutations, though the association between these mutations and the patient's cancer is not always clear. We present here a unique pediatric case of transformed mycosis fungoides in a patient with BRCA2 mutation.


Pelvic floor rehabilitation in the treatment of fecal incontinence.
Fecal incontinence (FI) is a prevalent problem that can drastically affect quality of life. Pelvic floor rehabilitation is an important first-line treatment for patients with FI, and many published case reports and a small number of randomized controlled trials (RCTs) provide limited evidence for its efficacy. Pelvic floor rehabilitation approaches to the treatment of FI include pelvic floor muscle training, biofeedback, and volumetric training with rectal balloon catheters. Various forms of external electrical stimulation have also been described and may be of added benefit. Behavioral bowel retraining is an important part of a good rehabilitative approach as well. Pelvic floor rehabilitation treatment for FI is thought to be effective and safe, with reported success rates in a majority of studies at 50 to 80%. Many more high-quality RCTs are needed to define optimal treatment protocols.


A new method for approximation of physiological signals.
A new robust method for the approximation of physiological signals is proposed. The noise must satisfy only one condition: that the probabilities for positive and negative values are equal. Our results illustrate that the proposed method provides a more accurate approximation of signals than either the least square error or the least absolute deviation method in cases that include unknown noise density.


Prevalence and Scanning Electron Microscopic Identification of Anoplocephalid Cestodes among Small Ruminants in Senegal.
This study was undertaken to determine the prevalence of anoplocephalid cestodes in sheep and goats in Senegal. Intestines of 462 sheep and 48 goats were examined; 47.4% of sheep and 6.2% of goats were infected. The species identified and their prevalence were, among sheep, Avitellina centripunctata 38.7%, Moniezia expansa 15.4%, Stilesia globipunctata 16.7%, and Thysaniezia ovilla 0.4%. Among goats, they were M. expansa 6.2% and T. ovilla 2.1%. The prevalence of all species was not statistically different between dry and rainy seasons. The infections were single or multiple. Indeed, 56.2% of sheep were infected by a single species, 37.4% by two species, and 6.4% by three species. For goats, 66.7% were infected by M. expansa and 33.3% by both M. expansa and T. ovilla. Scanning electron microscopic (SEM) observations of tapeworms show the general diagnosis characters of these species.


[Higher production of tumor necrosis factor (TNF) elicited by a biological response modifier (BRM) in aging mice].
We investigated age-related changes in the capacity for tumor necrosis factor (TNF) production in young and aged inbred C3H/He mice by injecting them with OK-432, a biological response modifier (BRM). An intravenous injection of 0.4mg of OK-432 was found to induce TNF production and two consecutive injections of 2KE of OK-432 induced much higher TNF production. Both the single and two consecutive injections of OK-432 induced significantly higher TNF production in aged mice than in young ones. Furthermore, the TNF-productive response to the two consecutive injections of OK-432 seemed to increase with aging. Male mice tended to show a marginally higher TNF-productive response than females. The mechanism by which aged mice have a higher capacity for TNF production is not clear. The following possibilities are conceivable. 1) Macrophages which are major TNF producer cells may be activated in aged mice. 2) Specific T cells which are cross-reactive to antigenic determinants in OK-432 may be increased in number in aging mice and activate macrophages effectively to produce TNF when stimulated by OK-432. In general, immunological functions tend to decline with aging. Our present results, however, suggest that by using an appropriate BRM we may be able to induce higher TNF production in the aged. This might lead to effective prevention and therapy for tumors, which increase in incidence with age.


Formation of magnesium-phosphoenzyme and magnesium-calcium-phosphoenzyme in the phosphorylation of adenosine triphosphatase by orthophosphate in sarcoplasmic reticulum. Models of a reaction sequence.
The aim of the present study was to test simple reaction sequences which describe calcium-independent plus calcium-dependent phosphorylation of sarcoplasmic reticulum transport. ATPase by orthophosphate including the function of magnesium in phosphoenzyme formation. The reaction schemes considered were based on the reaction sequence for calcium-independent phosphorylation proposed previously; namely that the transport enzyme (E) forms a ternary complex (Mg . E . Pi), by random binding of free magnesium and free orthophosphate, which is in equilibrium with the magnesium-phosphoenzyme (Mg . E-P). Phosphorylation, performed at pH 7.0 20 degrees C and a constant free orthophosphate concentration using sarcoplasmic reticulum vesicles either unloaded or loaded passively with calcium in the presence of 5 mM or 40 mM CaCl2, resulted in a gradual decrease in the apparent magnesium half-saturation constant and an increase in maximum phosphoprotein formation with increasing calcium loads. When phosphorylation of sarcoplasmic reticulum vesicles preloaded in the presence of 5 mM CaCl2 was performed at a constant free magnesium concentration, a decrease in the apparent orthophosphate half-saturation constant and an increase in maximum phosphoprotein formation was observed as compared with vesicles from which calcium inside has been removed by ionophore X-537A plus EGTA treatment; however, both parameters remained unchanged by increasing free magnesium from 20 mM to 30 mM. When phosphorylation of sarcoplasmic reticulum vesicles passively loaded with calcium in the presence of 40 mM CaCl2, at which the saturation of the low-affinity calcium binding sites of the ATPase is presumably near maximum, was performed at increasing concentrations of free orthophosphate, there was a parallel shift of phosphoprotein formation as a function of free magnesium and vice versa, with no change in the maximum phosphoenzyme formation. Comparison of the experimental data with the pattern of phosphoprotein formation predicted from model equations for various theoretical possible reaction sequences suggests that phosphoenzyme formation from orthophosphate possesses the following features. Firstly, calcium present at the inside of the sarcoplasmic reticulum membrane binds to the free enzyme and in sequential order to E . Mg . Pi or Mg . E-P or to both, but neither to E. Mg nor to E . Pi. Secondly, calcium-independent and calcium-dependent phosphoproteins are magnesium-phosphoenzymes. Calcium-dependent phosphoenzyme is a magnesium-calcium-enzyme phosphate complex with 1 magnesium, 2 calciums and 1 orthophosphate (the last covalently) bound to the enzyme [Mg . E-P . (Cai)2], and not a 'calcium-phosphoprotein' without bound magnesium.


Support for the microgenderome invites enquiry into sex differences.
The microgenderome defines the interaction between microbiota, sex hormones and the immune system. Our recent research inferred support for the microgenderome by showing sex differences in microbiota-symptom associations in a clinical sample of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). This addendum expands upon the sex-specific pattern of associations that were observed. Interpretations are hypothesized in relation to genera versus species-level analyses and D-lactate theory. Evidence of sex-differences invites future research to consider sex comparisons in microbial function even when microbial abundance is statistically similar. Pairing assessment of clinical symptoms with microbial culture, DNA sequencing and metabolomics methods will help advance our current understandings of the role of the microbiome in health and disease.


[Cytology of the corneal endothelium in endothelial dystrophy].
The corneal endothelium of 17 corneal buttons with endothelial dystrophy was investigated by means of vital staining and light microscopy. Each type of dystrophy was characterized by typical morphological changes in the endothelium: in Fuch's endothelial dystrophy (n = 13), subendothelial guttata formation is characteristic; in congenital hereditary endothelial dystrophy (n = 2), a high amount of multinucleated endothelial cells was found; in posterior polymorphous dystrophy (n = 2), a multilayered endothelium was the striking feature. There is a coherent endothelial cell layer in endothelial dystrophy that may indicate a disturbance in the endothelial pump function rather than a barrier defect caused by gaps between the endothelial cells.


Cement coating of osteoarticular allografts in rats to prevent the immune response.
Recently, more attention is being paid to the treatment of the articular surface defect in the young, active individual. Resurfacing or "shell" allografts are being considered as one of the alternatives for treatment. The immune response by the host may be the chief obstacle to the successful use of fresh osteoarticular allografts. Since proteins on the surfaces of allograft bone cells are considered to be the principal antigens eliciting the immune response, we hypothesized that mechanical masking of these cells by a biodegradeable blocking agent might prevent the immune response. Osteoarticular allografts of the distal femur were performed in rats and the cut surfaces of the graft were coated with cement before implantation. In a preliminary experiment, six biodegradeable cement materials were tried (bone wax, zinc polycarboxylate, collodion, fibrin adhesive, zinc oxide, and isobutyl-cyanoacrylate). Of these, the zinc oxide cement and isobutyl-cyanoacrylate were effective in inhibiting the immune response observed in control rat distal femur allografts. A second experiment was performed using nine rats with zinc oxide and nine rats with isobutyl-cyanoacrylate cements. These were compared with 20 control rats that had allografts without cement coating. Eighteen of the control rats (90%) developed an immune response, while only 22% (2/9) of the rats with zinc oxide coating and 33% (3/9) of the rats with isobutylcyanoacrylate developed an immune response. In a third experiment distal femur allografts were performed in 13 rats using only the liquid component of the zinc oxide cement.(ABSTRACT TRUNCATED AT 250 WORDS)


Cost-utility analysis of second-line therapy with rituximab compared to tumour necrosis factor inhibitors in rheumatoid arthritis.
To compare direct costs and treatment utility associated with the second-line therapy with rituximab and tumour necrosis factor inhibitors (TNFis) (adalimumab, etanercept, and infliximab) in patients with Rheumatoid Arthritis (RA) using data from a prospective registry. Health Assessment Questionnaire Disability Index (HAQ-DI) scores and RA-related healthcare resource utilization data (biologic agents and visits to rheumatologists) were extracted from a registry (Quebec, Canada) for patients with RA (n = 129) who had to discontinue a first-line TNFi and were treated with rituximab, adalimumab, etanercept, or infliximab as the second-line therapy between January 2007 and May 2016. A decision analytic model followed patients for 1 and 6 years. Treatment utility was measured as quality-adjusted life-years (QALYs) gained, which were calculated from HAQ-DI scores observed over the follow-up time. Quebec 2020 unit costs (Canadian Dollars, $) were used to value healthcare resource consumption. A probabilistic sensitivity analysis was performed with 10,000 Monte Carlo simulations to assess uncertainty around point-estimates of cost-utility. Over 1-year, rituximab and etanercept resulted in the effectiveness of 0.80 QALYs gained at the cost of $14,291and $18,880, respectively, and were dominant (i.e. associated with lower costs and more QALYs gained) compared to adalimumab (0.79 QALYs, $18,825) and infliximab (0.76 QALYs, $20,158). Over 6-years, rituximab (4.42 QALYs, $82,402) was dominant compared to adalimumab (4.30 QALYs, $101,420), etanercept (4.02 QALYs, $99,191), and infliximab (3.71 QALYs, $100,396). In the probabilistic analysis, rituximab was dominant over adalimumab, etanercept, and infliximab with the probability of 0.51, 0.62, and 0.65, respectively. Real-world data revealed differences between alternative biologic agents used as the second-line therapy in terms of both treatment costs for the healthcare system and utility of treatment for patients. Therefore, new guidelines on the order of selecting and switching biologic agents should be explored.


Corticotropin-releasing factor is cytoprotective in Xenopus tadpole tail: coordination of ligand, receptor, and binding protein in tail muscle cell survival.
Upon metamorphosis, amphibian tadpoles lose their tails through programmed cell death induced by thyroid hormone (T3). Before transformation, the tail functions as an essential locomotory organ. The binding protein for the stress neuropeptide corticotropin-releasing factor (CRF; CRF-BP) is strongly up-regulated in the tail of Xenopus tadpoles during spontaneous or T3-induced metamorphosis. This finding led us to investigate physiological roles for CRF and CRF-BP in tadpole tail. We found CRF, CRF-BP, and functional CRF1 receptor in tail and CRF and functional CRF1 receptors, but not CRF-BP, in the tail muscle-derived cell line XLT-15. CRF, acting via the CRF1 receptor, slowed spontaneous tail regression in explant culture and caused a reduction in caspase 3/7 activity. CRF increased, but stable CRF-BP overexpression decreased, [3H]thymidine incorporation in XLT-15 cells. Overexpression of CRF-BP in vivo accelerated the loss of tail muscle cells during spontaneous metamorphosis. Lastly, exposure of tail explants to hypoxia increased CRF and urocortin 1 but strongly decreased CRF-BP mRNA expression. We show that CRF is expressed in tadpole tail, is up-regulated by environmental stressors, and is cytoprotective. The inhibitory binding protein for CRF is regulated by hormones or by environmental stressors and can modulate CRF bioactivity.


Outbreak of SARS-CoV-2 at a hospice: terminated after the implementation of enhanced aerosol infection control measures.
Outbreaks of COVID-19 in hospices for palliative care patients pose a unique and difficult situation. Staff, relatives and patients may be possible sources and recipients of infection. We present an outbreak of COVID-19 in a hospice setting, during the UK's first pandemic wave. During the outbreak period, 26 patients and 30 staff tested SARS-CoV-2 positive by laboratory-based RT-PCR testing. Most infected staff exhibited some mild, non-specific symptoms so affected staff members may not have voluntarily self-isolated or had themselves tested on this basis. Similarly, for infected patients, most became symptomatic and were then isolated. Additional, enhanced aerosol infection control measures were implemented, including opening of all windows where available; universal masking for all staff, including in non-clinical areas and taking breaks separately; screening for asymptomatic infection among staff and patients, with appropriate isolation (at home for staff) if infected; performing a ventilation survey of the hospice facility. After these measures were instigated, the numbers of COVID-19 cases decreased to zero over the following three weeks. This outbreak study demonstrated that an accurate understanding of the routes of infection for a new pathogen, as well as the nature of symptomatic versus asymptomatic infection and transmission, is crucial for controlling its spread.


Hematopoietic stem cells in Drosophila.
The Drosophila lymph gland, the source of adult hemocytes, is established by mid-embryogenesis. During larval stages, a pool of pluripotent hemocyte precursors differentiate into hemocytes that are released into circulation upon metamorphosis or in response to immune challenge. This process is controlled by the posterior signaling center (PSC), which is reminiscent of the vertebrate hematopoietic stem cell niche. Using lineage analysis, we identified bona fide hematopoietic stem cells (HSCs) in the lymph glands of embryos and young larvae, which give rise to a hematopoietic lineage. These lymph glands also contain pluripotent precursor cells that undergo a limited number of mitotic divisions and differentiate. We further find that the conserved factor Zfrp8/PDCD2 is essential for the maintenance of the HSCs, but dispensable for their daughter cells, the pluripotent precursors. Zfrp8/PDCD2 is likely to have similar functions in hematopoietic stem cell maintenance in vertebrates.


Injuries Associated with Crutch Use: A Narrative Review.
Crutches are commonly prescribed in physiatric settings to help offload the lower extremities. Crutch use, however, results in abnormal and repetitive weight-bearing through the upper extremities that may result in secondary injury. This narrative review investigates injury types and risk factors associated with crutch use in order to guide healthcare providers on injury prevention strategies. Medline, EMBASE, CINAHL, and the Cochrane Library were systematically reviewed for publications between 1950 and 2018 on neurological, musculoskeletal, or vascular complications associated with crutch use. Titles and abstracts (n = 2395) were screened by two authors. Sixty studies were eligible. Articles were reviewed for level of evidence, crutch type, participant characteristics, and injury characteristics. There were 42 axillary crutch studies, 12 forearm crutch studies, and 6 studies that did not specify crutch type. These studies incorporated 622 individuals, and most were case series or case reports (n = 54). Axillary crutch use was most commonly associated with axillobrachial arterial complications due to pressure from the axillary bar (n = 34). Forearm crutch use was most commonly associated with compressive neuropathies due to pressure from the forearm cuff (n = 6). Improper crutch fitting and/or use were identified as contributing factors to injury in 22 cases. Duration of crutch use and medical comorbidities also influenced the types of injuries seen. There are rare but potentially serious complications associated with crutch use. When prescribing crutches, clinicians should ensure they are properly fit, engage in appropriate gait training, be aware of common crutch-related injuries, and consider potential patient-specific injury risk factors in order to minimize injury risk.


Concentrations of endothelin-1 in maternal and umbilical cord blood at various stages of pregnancy.
To examine the role of endothelin (ET) in the maternal and fetal circulation, the levels of endothelin-1-like immunoreactivity (ET-1-LI) in the plasma of maternal vein (MV), umbilical vein (UV), and umbilical artery (UA) were determined by a sensitive radioimmunoassay (RIA). Levels of ET-1-LI in MV did not show any significant change (9.9 +/- 1.5 pg/ml, n = 26) throughout normal pregnancy and were similar to those of normal nonpregnant women (10.7 +/- 2.5 pg/ml, n = 5). Levels of ET-1-LI in UV and UA obtained at normal deliveries at term were about three times higher than those in MV. In the patients with mild and severe pre-eclampsia, the levels of plasma ET-1-LI were significantly higher than those of normal pregnancy (14.3 +/- 2.2 pg/ml, n = 5 and 27.2 +/- 8.6 pg/ml, n = 5, respectively). However, in pregnant women with chronic hypertension, the levels of ET-1-LI did not increase when the hypertension did not worsen during pregnancy (11.4 +/- 1.6 pg/ml, n = 7). Moreover, in two pregnant women with abnormally stimulated coagulation, such as acute or subacute DIC, the levels of ET-1-LI were extremely high and returned gradually to those of normal nonpregnant women after the coagulation was normalized by treatment. These results suggest the possibility that ET-1 plays an important role in the pathophysiology of preeclampsia.


A case of metastatic uterine adenocarcinoma in a southern white rhinoceros (Ceratotherium simum simum).
A 39-yr-old, acyclic, uniparous, female white rhinoceros with a history of recurrent vaginal bleeding was euthanized following a period of respiratory distress and ill-thrift. The rhinoceros' uterus had previously been evaluated by ultrasound and diffuse endometrial hyperplasia and two benign uterine leiomyomas had been diagnosed. At necropsy examination, a large, infiltrative, metastatic uterine adenocarcinoma was found multifocally throughout the uterus, scattered within the peritoneal cavity, on the diaphragm, the splenic capsule, the pleural surface of the lung and mesenteric lymph nodes. A large volume (100 L) of ascites fluid was present in the abdominal and pleural cavities.


High-resolution dose-response screening using droplet-based microfluidics.
A critical early step in drug discovery is the screening of a chemical library. Typically, promising compounds are identified in a primary screen and then more fully characterized in a dose-response analysis with 7-10 data points per compound. Here, we describe a robust microfluidic approach that increases the number of data points to approximately 10,000 per compound. The system exploits Taylor-Aris dispersion to create concentration gradients, which are then segmented into picoliter microreactors by droplet-based microfluidics. The large number of data points results in IC(50) values that are highly precise (± 2.40% at 95% confidence) and highly reproducible (CV = 2.45%, n = 16). In addition, the high resolution of the data reveals complex dose-response relationships unambiguously. We used this system to screen a chemical library of 704 compounds against protein tyrosine phosphatase 1B, a diabetes, obesity, and cancer target. We identified a number of novel inhibitors, the most potent being sodium cefsulodine, which has an IC(50) of 27 ± 0.83 μM.


Effectiveness and safety of expanded perioperative thromboprophylaxis in complex gynecologic surgery.
To determine the effectiveness and safety of an expanded perioperative venous thromboembolism (VTE) prophylaxis strategy in women undergoing complex gynecologic surgery. We performed a cohort study of 527 patients undergoing major surgery at a single institution over a thirty-month interval during which the gynecologic oncology service implemented an expanded approach to VTE prophylaxis. We compared rates of VTE pre- and post-intervention as well as bleeding and infectious complications. Prior to the intervention, there were 23 VTE events in 345 patients (rate of 6.67%): 8 deep vein thromboses (DVTs) and 15 pulmonary emboli (PEs). Post-intervention, there were 5 VTE events in 182 patients (2.7%): 3 DVTs and 2 PEs (RR=0.4, p=0.056). Time-to-event analysis showed a significantly higher incidence of VTE events in the pre-intervention time frame compared to the post-intervention period (p=0.049). There were no significant differences in bleeding or infection complications between groups. Implementation of a perioperative VTE prophylaxis protocol was safe, feasible and resulted in a clinically significant reduction in symptomatic VTE. Preoperative single-dose unfractionated heparin for all patients, combined with two weeks of thromboprophylaxis in gynecologic cancer patients, may decrease VTE events without increasing bleeding or infection.


Effect of a rapid maxillary expansion on snoring and sleep in children: a pilot study.
The aim of this study was to assess the efficacy of the McNamara rapid palatal expansion device for the treatment of sleep disorders in children. The sample enrolled 12 children aged 4-11 years. Children with snoring and bruxism whose parents did not agree to tonsil surgery were included in the study. During the initial evaluation, a questionnaire addressing sleep was administered, and plaster models were made for the construction of the McNamara rapid maxillary expansion device. The expansion period was 7-15 days, and the McNamara device was removed after 6-8 months. The same questionnaire was administered again after 30 days of use of the orthopedic appliance. The data were analyzed using the McNemar test, with the level of significance set to 5% (P<0.05). Significant improvements were found in tiredness upon waking (P=0.002), mood (P=0.008), lip seal (P=0.031), drooling during sleep (P=0.031), snoring (P=0.001), and bruxism (P=0.0062). The use of non-invasive methods, such as rapid maxillary expansion, can be an effective treatment for snoring and other undesirable sleep behaviors in children.


Clinical-dosimetric relationship between lacrimal gland dose and ocular toxicity after intensity-modulated radiotherapy for sinonasal tumours.
To characterise the relationship between lacrimal gland dose and ocular toxicity among patients treated by intensity-modulated radiotherapy (IMRT) for sinonasal tumours. 40 patients with cancers involving the nasal cavity and paranasal sinuses were treated with IMRT to a median dose of 66.0 Gy. Toxicity was scored using the Radiation Therapy Oncology Group morbidity criteria based on conjunctivitis, corneal ulceration and keratitis. The paired lacrimal glands were contoured as organs at risk, and the mean dose, maximum dose, V10, V20 and V30 were determined. Statistical analysis was performed using logistic regression and the Akaike information criterion (AIC). The maximum and mean dose to the ipsilateral lacrimal gland were 19.2 Gy (range, 1.4-75.4 Gy) and 14.5 Gy (range, 11.1-67.8 Gy), respectively. The mean V10, V20 and V30 values were 50%, 25% and 17%, respectively. The incidence of acute and late Grade 3+ toxicities was 23% and 19%, respectively. Based on logistic regression and AIC, the maximum dose to the ipsilateral lacrimal gland was identified as a more significant predictor of acute toxicity (AIC, 53.89) and late toxicity (AIC, 32.94) than the mean dose (AIC, 56.13 and 33.83, respectively). The V20 was identified as the most significant predictor of late toxicity (AIC, 26.81). A dose-response relationship between maximum dose to the lacrimal gland and ocular toxicity was established. Our data suggesting a threshold relationship may be useful in establishing dosimetric guidelines for IMRT planning that may decrease the risk of acute and late lacrimal toxicities in the future. A threshold relationship between radiation dose to the lacrimal gland and ocular toxicity was demonstrated, which may aid in treatment planning and reducing the morbidity of radiotherapy for sinonasal tumours.


Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in carcinoid tumors.
Although all carcinoids are potentially malignant, their biologic behavior is quite variable. Currently there are no reliable morphological criteria to predict metastatic potential. Cell adhesion molecules, such as CD44 and E-cadherin, are considered important in regulating invasion and metastasis of tumors. Also, angiogenesis has been shown to be associated with tumor growth and progression. In this study, we examined 51 carcinoids, including 13 carcinoids with known lymph node and/or visceral metastasis, for expression of CD44s (the standard form of CD44) and E-cadherin by immunohistochemistry. We found that 55% and 37% of carcinoids were negative for CD44s and E-cadherin, respectively. Carcinoids with lymph node and/or visceral metastasis were significantly more frequently negative for CD44s than were those without demonstrated metastasis (P =.030). Ten of 11 tumors with lymph node metastasis lacked CD44s (P =.022), whereas E-cadherin was negative in only 3 (P =.975). Additionally, we analyzed microvessel density to evaluate the role of tumor angiogenesis in the tumor behavior. Carcinoid tumors in general demonstrated high microvessel density (160 +/- 82/five 200x fields), irrespective of location and with and without metastasis. These results suggest that loss of CD44s, but not E-cadherin, may be a useful predictor of metastatic potential of carcinoid tumors.


Design Innovation and Entrepreneurship Organization Based on Psychological Cognitiveness of the Space Narrative.
The high-quality workspace can be used as a physical carrier for design innovation and entrepreneurial organizational culture to continuously change the psychological cognition and behavior of employees in community of practice. The spatial narrative of the culture of design innovation and entrepreneurial organizations means to integrate entrepreneurship and organizational culture into the space through visual presentation. Whether the spatial narrative is successful or not needs to be judged by whether the change of people's psychological cognition achieves the expected effect. The traditional qualitative research methods such as interviews and questionnaires cannot fully and accurately present the psychological cognitive mechanism of design Innovation and entrepreneurship organization members. We use virtual reality technology combined with electrophysiological technology to conduct experiments. We use these technologies to conduct quantitative experiments on psychological cognition in community of practice. This study will select a design innovation and entrepreneurial organization, randomly select 20 participants, and divide them into 2 groups for experimentation. The VR scene is based on their real office space as a prototype. Put the visual elements of corporate culture in one of the VR scenes. The other VR scene as a reference does not incorporate visual elements of organizational culture. Participants participated in the experiment in these two VR scenarios. There are many advanced devices that can accurately test individual psychological changes, but the ErgoLab man-machine environment test platform, can collect and compare these data [physiological data, electroencephalogram (EEG) data, and behavior data] in real-time and comprehensively, which is its advantage. According to the experimental results, judge the changes in the psychological cognitive data of the participants before and after the placement of the spatial narrative in design innovation and entrepreneurial organizations. The experiment combined interviews and questionnaires to ensure the authenticity of the quantitative data. The conclusion of the experiment will produce an accurate quantitative study on the psychological cognition of the spatial narrative of design innovation and entrepreneurial organizational culture. A sense of organizational belonging, collective sense, pride, mission, and work fun can be generated in the workspace.


Functional effects of parasites on food web properties during the spring diatom bloom in Lake Pavin: a linear inverse modeling analysis.
This study is the first assessment of the quantitative impact of parasitic chytrids on a planktonic food web. We used a carbon-based food web model of Lake Pavin (Massif Central, France) to investigate the effects of chytrids during the spring diatom bloom by developing models with and without chytrids. Linear inverse modelling procedures were employed to estimate undetermined flows in the lake. The Monte Carlo Markov chain linear inverse modelling procedure provided estimates of the ranges of model-derived fluxes. Model results support recent theories on the probable impact of parasites on food web function. In the lake, during spring, when 'inedible' algae (unexploited by planktonic herbivores) were the dominant primary producers, the epidemic growth of chytrids significantly reduced the sedimentation loss of algal carbon to the detritus pool through the production of grazer-exploitable zoospores. We also review some theories about the potential influence of parasites on ecological network properties and argue that parasitism contributes to longer carbon path lengths, higher levels of activity and specialization, and lower recycling. Considering the "structural asymmetry" hypothesis as a stabilizing pattern, chytrids should contribute to the stability of aquatic food webs.


Lack of Linkages among Fruiting Depth, Weight, and Maturity in Irrigated Truffle Fungi Marks the Complexity of Relationships among Morphogenetic Stages.
The highly prized black truffle (Tuber melanosporum) has become a model species for ectomycorrhizal fungi biology. However, several questions concerning its reproductive phase remain unanswered. To provide new hypotheses on the fruitbody formation process, we have explored the causal links among development characters of black truffle fruitbodies that are primarily linked to either the mating process, fruitbody growing stage, or maturation. Path analysis was applied to test causal models outlining the relationships among fruitbody development characters such as fruiting depth, weight, shape, and spore maturity. These characters were investigated over a two-season survey and three soil typologies (plus peat-based substrate) under irrigated conditions. We found a clear and generalized relationship between fruitbody weight and shape. Among clusters of fruitbodies we found a positive relationship between the weight of the largest fruitbody and the weight of the remaining fruitbodies. However, no generalized relationships among characters linked to different development stages appeared. Our results were noticeably consistent across soil typologies, both for fruitbodies growing singly and in clusters, indicating that early-developing fruitbody characters did not influence characters linked to subsequent morphogenetic stages. The lack of links among stages opens new perspectives for pre-harvest quality management with stage-specific cultivation practices.


Changes in susceptibility of tissues to lipid peroxidation after ingestion of various levels of docosahexaenoic acid and vitamin E.
To examine the effects of dietary docosahexaenoic acid (DHA) on the potential changes in endogenous lipid peroxidation in the liver and kidney, diets containing a fixed amount of vitamin E (VE; RRR-alpha-tocopherol equivalent; 134 mg/kg diet) and a graded amount of DHA at the levels of 0, 1.0, 3.4 and 8.7% of total dietary energy were fed to rats for 14 d (Expt 1). In Expt 2, diets containing a fixed amount of DHA (8.7% of total dietary energy) and a graded amount of VE at the levels of 54, 134 and 402 mg/kg were fed to rats for 15 d. In Expt 1 it was found that endogenous lipid peroxide contents of the liver and kidney, as measured by thiobarbituric acid value and chemiluminescence intensity, were higher, and their alpha-tocopherol contents lower than those of the controls, with a gradual increase and decrease in values respectively as the dietary DHA level increased (Expt 1). However, the contents of water-soluble antioxidants, i.e. ascorbic acid and non-protein-SH (glutathione), increased with increases in the dietary DHA level, while the Se-dependent glutathione peroxidase (EC 184.108.40.206) activities did not change or tended to be lower. When the graded level of VE was given to rats in Expt 2, lipid peroxide contents in the liver and kidney did not change significantly in response to the increasing levels of dietary VE, although their alpha-tocopherol contents were higher than control values, increasing with increases in the dietary VE levels. The lipid peroxide scavengers other than alpha-tocopherol changed similarly to those in Expt 1. The results obtained in Expts 1 and 2 indicate that DHA enhances the susceptibility of the liver and kidney to lipid peroxidation concomitant with higher levels of DHA in these tissues, as shown by the fatty acid composition. In addition, VE is unable to protect membranes of the liver and kidney rich in DHA from lipid peroxidation, even after ingestion of the highest level of VE. However, the liver lipid peroxide content of the group given the highest level of DHA was not as high as expected, based on the peroxidizability index which was calculated from the fatty acid composition of the liver lipid.


Attitudes toward mental illness among medical students and impact of temperament.
Mental health-related stigma is a serious problem that has undesirable consequences for individuals with mental disorders including physical health disparities, increasing mortality, and social dysfunction. Besides, these individuals frequently report feeling 'devalued, dismissed, and dehumanized' when encountering health professionals who are also perpetrators of stigmatizing attitudes and discriminatory behaviors. The present study concentrates on attitudes, and behavioral responses of medical students and junior doctors toward individuals with a mental illness and explores factors associated with stigma including temperament. A cross-sectional study was conducted among medical students and junior doctors from medical schools of universities in Tunisia. All participants were invited to complete a brief anonymous electronic survey administered on the google forms online platform. Data were collected using self-administered questionnaires, Stigma Measurement, Mental Illness: Clinicians' Attitudes (MICA), Assessment of Affective Temperament, TEMPS-A scale. A total of 1,028 medical students and junior doctors were recruited. The completion of a psychiatry clerkship for medical students didn't improve significantly the level of stigma toward people with a mental illness. Students in the fourth year had significantly the lowest MICA scores comparing to other students. Psychiatrists had significantly lower scores of explicit stigma attitudes than the other groups (Mean score = 0.42). As for other specialties, surgical residents had more stigmatizing attitudes than those who had medical specialties. 70% of participants believed that people with a mental illness are more dangerous than the other patients. Hyperthymic temperament was significantly associated with decreased stigma attitudes toward patients with mental illness. A combination of medical school experiences of psychiatry's theoretical learning and clerkship and wider societal beliefs are important factors that shape students. Awareness of this will enable educators to develop locally relevant anti-stigma teaching resources throughout the psychiatry curriculum to improve students' attitudes toward mental illnesses.


Reactivity of lysyl residues on the (Ca(2+)-Mg2+)-ATPase to 7-amino-4-methylcoumarin-3-acetic acid succinimidyl ester.
The (Ca(2+)-Mg2+)-ATPase of sarcoplasmic reticulum was labeled with the succinimidyl ester of 7-amino-4-methylcoumarin-3-acetic (AMCA). Although a large number of residues were labeled, it was found that Lys-492 was labeled preferentially at pH values between 6 and 8, consistent with an unusual environment for this residue. Labeling was reduced in the presence of ATP, suggesting that Lys-492 is in or near the ATP binding site of the ATPase. Other identified residues labeled by AMCA were Lys-35, Lys-135, Lys-218, Lys-371, and Lys-605. It is suggested that these represent surface-exposed lysyl residues. Lys-515, labeled by fluorescein isothiocyanate (FITC), was not labeled by AMCA. Labeling with AMCA at pH 6.0 has no effect on ATPase activity, suggesting that Lys-492 is not essential for activity. The fluorescence of AMCA-labeled ATPase did not change on addition of either ATP in the presence of Ca2+ or Pi in the absence of Ca2+, suggesting that Lys-492 was not affected by any major conformational changes on the ATPase. The efficiency of fluorescence energy transfer between AMCA and FITC labels on the ATPase was unaffected by binding Ca2+ or vanadate, arguing against any large-scale movement of the cytoplasmic domains of the ATPase.


Frequency doubling perimetry screening mode compared to the full-threshold mode.
The diagnostic performance of the frequency doubling perimetry (FDT) C20-1 screening mode was compared to that of the C20 full-threshold mode. For the number of defects p < 1% in the total deviation plot, both modes appeared to perform similarly in terms of sensitivity, specificity, and area under the receiver-operating characteristic (ROC) curve. Different cut-off points should be applied for both modes to obtain equal sensitivity and specificity values, and - related to that - for most subjects more defects were found in full-threshold mode than in screening mode. For the screening mode, we found a sensitivity of 0.91 and a specificity of 0.88 at a cut-off point of >0 defects, and an area under the ROC curve of 0.93.


[Allergic bronchopulmonary mycosis due to Schizophyllum commune and Aspergillus fumigatus].
A 53-year-old man who had been suffering from asthma presented to our hospital because of abnormal shadows detected on a chest X-ray film during a routine medical examination. A biopsy specimen of a mucus plug obtained by bronchoscopy showed fungal hyphae, eosinophils, and Charcot-Leyden crystals, with evidence of lung tissue eosinophilia. Schizophyllum commune and Aspergillus fumigatus were isolated from his sputum, bronchial washing specimens and the mucus plug. We detected specific immunoglobulin E anti-Aspergillus fumigatus responses and precipitating antibodies against Schizophyllum commune and Aspergillus fumigatus, which led to the diagnosis of allergic bronchopulmonary mycosis caused by both fungi. We gave him fluticasone/salmeterol and itraconazole; thereafter, his symptoms of cough and sputum production and his radiological findings all improved.


Evaluation of linkage efficiency between manufacturing industry and logistics industry considering the output of unexpected pollutants.
Applied a non-radical non-oriented Slack Based Measure (SBM) model of Data Envelopment Analysis (DEA) to measure the linkage efficiency between the two sectors from 2009 to 2016. The paper analyzes the current situation of manufacturing and logistics efficiency, presents a way to improve the linkage efficiency of manufacturing and logistics industry, and using Tobit regression to analyze the environmental factors that affect the linkage efficiency. The results show that: Totality, the two industries in the three northeast provinces show a steady development trend in the period from 2009 to 2016, but the development of the two industries in northeast China is still insufficient. Unexpected pollutant output is the main reason for the decline of manufacturing efficiency in the regions. The redundancy of input factors is the main reason that affects the efficiency decline of the logistics industry. The results of Tobit regression analysis show that the investment of science and technology and opening to the outside world have a positive influence on the efficiency of the two industries, and government consumption has a negative effect on the efficiency of the two industries. This is to correctly understand and grasp the status of two industry linkage development in three northeast provinces. And it provides a certain basis for the development policy of the two-industry linkage development.Implications: Due to the availability of data, reference to the relevant achievements of the research on the linkage between manufacturing industry and logistics industry. The transportation industry, warehousing, and postal and telecommunications industry data are generally used as logistics industry data. Manufacturing data replaced by industrial data. The manufacturing industry is the core industry in the industrial system. Its output value accounts for more than 90% of industrial output value, so it can reflect the development trend of the manufacturing industry in general.


[Evaluation of functional adaptation level in air specialists according to biochemical indexes of saliva secretion].
It was examined a capability of evaluation of functional condition of air staff by indexes of natrium, kalium, cortisol and glucose in saliva. There were realized 5 series of examinations with participations of 71 airplane pilot of the same level in conditions of realizing flies of different difficultness. Saliva sampling was effectuated before and after the flies not later then 10-15 minutes after landing. On pre-flight medical examination and after performance of task of air relay there was registration of systolic, diasystolic blood pressure and cardiac rate. It was posed the correlation of physiological indexes with percentage of examined ingredients in saliva in different flight loads. The results of examinations speak for capability of using of indexes of percentage of natrium, kalium, cortisol and glucose in saliva for evaluation of functional condition of airplane pilots during effectuating the flies and rating of value of flight load with account of individual peculiarities.


Eco-immunology and bioinvasion: revisiting the evolution of increased competitive ability hypotheses.
Immunity is at the core of major theories related to invasion biology. Among them, the evolution of increased competitive ability (EICA) and EICA-refined hypotheses have been used as a reference work. They postulate that the release from pathogens often experienced during invasion should favour a reallocation of resources from (costly) immune defences to beneficial life-history traits associated with invasive potential. We review studies documenting immune changes during animal invasions. We describe the designs and approaches that have been applied and discuss some reasons that prevent drawing generalized conclusions regarding EICA hypotheses. We detail why a better assessment of invasion history and immune costs, including immunopathologies and parasite communities, could improve our understanding of the relationships between immunity and invasion success. Finally, we propose new perspectives to revisit the EICA hypotheses. We first emphasize the neutral and adaptive mechanisms involved in immune changes, as well as timing of the later. Such investigation will help decipher whether immune changes are a consequence of pre-adaptation, or the result of postintroduction adaptations to invasion front conditions. We next bring attention to new avenues of research that remain unexplored, namely age-dependent immunity and gut microbiota, potential key factors underlying adaptation to invasion front environment and modulating invasion success.