Proton translocation by the cytochrome bc1 complexes of phototrophic bacteria: introducing the activated Q-cycle.
The cytochrome bc1 complexes are proton-translocating, dimeric membrane ubiquinol:cytochrome c oxidoreductases that serve as "hubs" in the vast majority of electron transfer chains. After each ubiquinol molecule is oxidized in the catalytic center P at the positively charged membrane side, the two liberated electrons head out, according to the Mitchell's Q-cycle mechanism, to different acceptors. One is taken by the [2Fe-2S] iron-sulfur Rieske protein to be passed further to cytochrome c1. The other electron goes across the membrane, via the low- and high-potential hemes of cytochrome b, to another ubiquinone-binding site N at the opposite membrane side. It has been assumed that two ubiquinol molecules have to be oxidized by center P to yield first a semiquinone in center N and then to reduce this semiquinone to ubiquinol. This review is focused on the operation of cytochrome bc1 complexes in phototrophic purple bacteria. Their membranes provide a unique system where the generation of membrane voltage by light-driven, energy-converting enzymes can be traced via spectral shifts of native carotenoids and correlated with the electron and proton transfer reactions. An "activated Q-cycle" is proposed as a novel mechanism that is consistent with the available experimental data on the electron/proton coupling. Under physiological conditions, the dimeric cytochrome bc1 complex is suggested to be continually primed by prompt oxidation of membrane ubiquinol via center N yielding a bound semiquinone in this center and a reduced, high-potential heme b in the other monomer of the enzyme. Then the oxidation of each ubiquinol molecule in center P is followed by ubiquinol formation in center N, proton translocation and generation of membrane voltage.


Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids.
The growth hormone (GH) gene family represents an erratic and complex evolutionary pattern, involving many evolutionary events, such as multiple gene duplications, positive selection, the birth-and-death process and gene conversions. In the present study, we cloned and sequenced GH-like genes from three species of New World monkeys (NWM). Phylogenetic analysis strongly suggest monophyly for NWM GH-like genes with respect to those of Old World monkeys (OWM) and hominoids, indicating that independent gene duplications have occurred in NWM GH-like genes. There are three main clusters of genes in putatively functional NWM GH-like genes, according to our gene tree. Comparison of the ratios of nonsynonymous and synonymous substitutions revealed that these three clusters of genes evolved under different kinds of selective pressures. Detailed analysis of the evolution of pseudogenes showed that the evolutionary pattern of this gene family in platyrrhines is in agreement with the so-called birth-and-death process.


[Coral and cranio-maxillofacial surgery. Results of an experimental study on sheep].
Goniopora Lobata and Polyphyllia Talpina are tested on ten sheep with a follow up of 12 months. The material of reference is a glassceramic CAP 42. Different implantation sides are used: craniofacial and orthopedic. A macro and microscopic postoperative study is performed at 3, 6, 9 and 12 months. The results show: a perfect biocompatibility; a disappearance without colonisation of Goniopora Lobata associated with a complete bone regeneration at 12 months; a later resorption of Polyphyllia Talpina with a fibrous colonisation without osseous transformation. Perspective of using in cranio-maxillo-facial surgery are exposed.


Systematic review protocol examining the effectiveness of hospital clowns for symptom cluster management in paediatrics.
Clown intervention may playing an important complementary role in paediatric care and recovery. However, data on its utility for symptom cluster management of hospitalised children and adolescents in acute and chronic disorders are yet to be critically evaluated. As clinicians strive to minimise the psychological burden during hospitalisation, it is important that they are aware of the scientific evidences available regarding clown intervention for symptom management. We aim to provide quality evidence for the effectiveness of clown intervention on symptom cluster management in paediatric inpatients, both in acute and chronic conditions. A systematic review of randomised controlled trials (RCTs) and non-randomised controlled trials (NRCTs) will be conducted. MEDLINE, Web of Science, Cochrane Library, Science Direct, PsycINFO, CINAHL, LILACS and SciELO databases will be searched from January 2000 to December 2018. Primary outcomes will include measures related with the effect of clown intervention on symptom cluster of paediatric inpatients (anxiety, depression, pain, fatigue, stress and psychological, emotional responses and perceived well-being). Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the methodological appraisal of the studies will be assessed by the Jadad Scale as well as Cochrane Risk-of-Bias Tool for RCTs, and Risk-of-Bias In Non-Randomized Studies Tool for NRCTs. A narrative synthesis will be conducted for all included studies. Also, if sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges' g score for both fixed and random effect models. I 2 statistics will be used to assess heterogeneity and identify their potential sources. As it will be a systematic review, without human beings involvement, there will be no requirement for ethical approval. Findings will be disseminated widely through peer-reviewed publication and in various media, for example, conferences, congresses or symposia. CRD42018107099.


Transplanting the Untransplantable.
With implementation of the Kidney Allocation System, the growth of kidney paired donation programs, and advances in desensitization and immunosuppression, the outlook for "untransplantable" kidney transplantation candidates has never been more promising. The Kidney Allocation System prioritized compatible matches for candidates with calculated panel-reactive antibody levels of 98%, 99%, or 100% and broadened allocation of non-A1 and non-A1-B subgroup kidneys to blood group type B candidates. Concurrently, the growth of kidney paired donation programs and use of incompatible transplantation as part of kidney paired donation to achieve "more compatible" kidney transplantation has improved options for candidates with an incompatible living donor. Finally, advances in desensitization and immunosuppression have strengthened the ability to manage donor-specific antibodies and antibody-mediated rejection. Although no patient should be labeled "untransplantable" due to blood group type or donor-specific antibody, all candidates should be provided with individualized and realistic counseling regarding their anticipated wait times for deceased donor or kidney paired donation matching, with early referral to expert centers when needed. In this Perspective, we consider blood group type ABO incompatibility, HLA antigen incompatibility, antibody-mediated rejection, kidney paired donation, and recent developments in incompatible transplantation in more depth and recommend an approach to the sensitized candidate.


Factors associated with stress in mothers of children with autism.
The objective of this case-control study was to investigate the determinants of maternal stress in mothers of children with autism. Mothers of 31 children with autism from mental health clinics were matched by child age/gender and mother age to 31 mothers of children without mental health problems, drawn from public schools and a primary care unit. Logistic regression models showed that the presence of stress in mothers was primarily associated with having a child with autism. However, poor expression of affect, little interest in people, being an older mother, and having a younger child also contributed to increased stress levels. Although having a child with autism was the main factor responsible for stress, the presence of the other factors further increased maternal stress. The implication is that a subgroup of mothers of children with autism is more prone to experience stress, thus requiring special attention from mental health professionals.


Characterization of a purified glycoprotein from Schistosoma mansoni eggs: specificity, stability, and the involvement of carbohydrate and peptide moieties in its serologic activity.
A major egg glycoprotein (MEG) was purified from a crude soluble extract of Schistosoma mansoni ova (Egyptian strain) by successive steps of lectin affinity and ion-exchange chromatography. Radioiodinated MEG exhibited a single precipitation band upon immunodiffusion against antiserum from chronically infected mice, and ran as a single band on PAGE (Rf 0.38) and SDS-PAGE (Rf 0.36). Its estimated m.w. was 70,000. The degree of stage and species specificity of MEG and the effect of various treatments on its serologic reactivity were determined by radioimmunoassay (RIA). A low degree of cross-reactivity between MEG and similarly prepared soluble antigens from adult worms and cercariae was demonstrated by RIA inhibition tests, whereas a high degree of cross-reactivity was found between MEG and a crude soluble S. haematobium egg antigen. In similar RIA inhibition tests, the Puerto Rican S. mansoni had a lower degree of cross-reactivity with S. haematobium than the Egyptian strain. MEG was four times more abundant in SEA from a Puerto Rican strain of S. mansoni than in SEA from the Egyptian strain. The serologic reactivity of MEG was stable to heat at 100 degrees C for 60 min, to 0.1 N NaOH or HCl, and to 10% TCA. Treatment of MEG with pronase caused a limited fragmentation of the molecule and some loss of its serologic reactivity. Periodate oxidation resulted in a substantial loss of molecular mass and of serologic reactivity, leaving a low residual activity that is only partially cross-reactive with the bulk of MEG. These results suggest the importance of both carbohydrate and peptide moieties of MEG for its serologic reactivity.


Synthesis of C-4 substituted nicotine derivatives via an N-acylpyridinium salt of (S)-nicotine.
[reaction: see text] A variety of novel nicotine derivatives were prepared from (S)-nicotine via a two-step sequence. Addition of a cuprate reagent to an N-acylpyridinium salt of nicotine, followed by aromatization with elemental sulfur, afforded C-4 substituted nicotines in moderate to high yield. Using this method, 4-(dimethylphenylsilyl)nicotine was prepared and oxidized to afford (S)-4-hydroxynicotine.


Grass consensus STS markers: an efficient approach for detecting polymorphism in Lolium.
For ryegrass and many forage crops, characterization of varieties is often difficult for two reasons: few of discriminant morphological traits and a great within-varieties variation. Futhermore, few molecular markers are publicly accessible. In this paper we describe two approaches for the development of 42 sequence-tagged-site (STS) markers. Firstly, 14 STS markers were developed from Lolium sequences found in data bases. Secondly, 28 STS markers were developed from sequences found in related species of Gramineae. Out of 42 STS markers developed, 85.8% yielded successfull amplification and 62% revealed a high level of polymorphism with an average of five alleles per locus. The analysis of amplicons reveals a high STS marker specificity, a high conservation in gene structure and a strong intron sequence homology between allelic forms. Moreover, the majority of the STS markers can be considered as "universal markers" because 81% of these STS markers amplified successfully across 20 related grass species. These results permit us to consider the use of these markers in synteny studies.


Genotype by Environment Interaction: The Greatest Obstacle in Precise Determination of Rice Sheath Blight Resistance in the Field.
Rice sheath blight (SB) is the most serious rice disease in China. Resistance of rice to SB is a quantitative trait that is easily influenced by the environment; however, the extent of environmental influence on SB field resistance is still poorly understood. To identify rice genotype by environment interactions for SB resistance, 211 rice genotypes originating from 15 countries were planted and evaluated for SB field resistance in six different environments between 2012 and 2016 after inoculation with the SB pathogen isolate ZJ03. In addition, 65 rice genotypes were evaluated for SB field resistance in another four environments between 2013 and 2016 using ZJ03. Variations in SB field resistance were observed in different genotypes in different environments using objective and subjective rating methods. Two-way analysis of variance indicated that the interaction between the genotype and environment had a highly significant effect on SB field resistance. This analysis indicated that the environment had more of an influence than the genotype itself on SB field resistance, and the genotype by environment interaction was the greatest obstacle in obtaining a precise determination of SB field resistance in rice. The most resistant genotype, GD66, is a good candidate for genetic studies and breeding.


RCM-mediated synthesis of trifluoromethyl-containing nitrogen heterocycles.
A ring-closing metathesis mediated pathway to trifluoromethyl-containing piperidines is detailed. This involves the development of a synthetic route to a new (trifluoromethyl)allylating reagent via a Diels-Alder/retro-Diels-Alder strategy, its application in the synthesis of a series of trifluormethyl-substituted diolefin precursors for ring-closing metathesis, and eventually the successful cyclization of these precursor molecules into the corresponding functionalized piperidines.


Chronic treatment with a precursor of cellular phosphatidylcholine ameliorates morphological and behavioral effects of aging in the mouse [correction of rat] hippocampus.
Normal aging is commonly associated with a decline in memory, mainly for that related with newly acquired information. The hippocampal formation (HF) is a brain region that has been implicated in this dysfunction. Within the HF there are several cellular types, such as pyramidal cells, granule neurons of the dentate gyrus, and astrocytes. CDP-choline is a well-known intermediate in the biosynthesis of phosphatidylcholine, a phospholipid essential for neuronal membrane preservation and function; thus, this compound would attenuate the process of neuronal aging. To test this, three groups of male mice were used in this study. An adult 12-month-old group (ACG), a 24-month-old (OCG), and an old experimental group (OEG) were administered orally a solution of CDP-choline (150 mg/kg per day) from 12 up to 24 months. Experimental observations suggest that CDP-choline has a positive effect on memory (reference errors were attenuated), and hippocampal morphology resembled that of younger animals.


Expression and characterization of bioactive recombinant human alpha-lactalbumin in the milk of transgenic cloned cows.
Improvement of the nutritional value of cow milk with transgenic expression of recombinant human alpha-lactalbumin (alpha-LA) has been previously attempted. However, the detailed characterization of the recombinant protein and analysis of the transgenic milk components are not explored yet. Here, we first report production of healthy transgenic cows by somatic cell nuclear transfer, in which expression of up to 1.55 g/L of recombinant human alpha-LA was achieved. The recombinant human alpha-LA was purified from transgenic milk and displayed physicochemical properties similar to its natural counterpart with respect to molecular weight, structure, and regulatory activity for beta-1,4-galactosyltransferase. Additionally, no N-glycosylation was found in the recombinant human alpha-LA, whereas the endogenous bovine alpha-LA was glycosylated at the unusual site (71)Asn-Ile-(73)Cys. Compared with milk from nontransgenic cows, expression of the transgene did not materially alter milk composition, such as fat and protein content. Our research thus provides scientific evidence supporting the feasibility of humanizing cow milk.


Anthocyanin induces apoptosis of DU-145 cells in vitro and inhibits xenograft growth of prostate cancer.
To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2×10⁶) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.


Primary emotional traits in patients with personality disorders.
There is a longstanding tradition that connects temperament pathology and personality disorders. Emotions are the major constituents of temperament. In mammals, seven primary emotions have been identified: SEEKING, FEAR, CARE, RAGE, SADNESS/PANIC, LUST and PLAY. The study aimed at exploring the relationship between primary emotions and personality disorders (PDs). Five hundred forty-six patients with different degrees and qualities of personality pathology, admitted to treatment in specialized PD services, were diagnosed according to Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and their primary emotional profiles were assessed by the Affective Neuroscience Personality Scales. The Affective Neuroscience Personality Scales explained 19% of the variance in borderline and avoidant criteria. The DSM-IV PD categories displayed different patterns of association to the primary emotions, e.g. the borderline PD profile suggested low thresholds for RAGE and SADNESS, but on the positive side a propensity for SEEKING. In contrast, the dependent PD profile suggested a low threshold for SADNESS but a high threshold for RAGE and SEEKING. The results are promising for a more coherent and evolution-based overall theory of PDs, and the correlations found in this study indicate testable causal pathways to PDs. Copyright © 2016 John Wiley & Sons, Ltd.


Interaction of Proteins with Polyelectrolytes: Comparison of Theory to Experiment.
We discuss recent investigations of the interaction of polyelectrolytes with proteins. In particular, we review our recent studies on the interaction of simple proteins such as human serum albumin (HSA) and lysozyme with linear polyelectrolytes, charged dendrimers, charged networks, and polyelectrolyte brushes. In all cases discussed here, we combined experimental work with molecular dynamics (MD) simulations and mean-field theories. In particular, isothermal titration calorimetry (ITC) has been employed to obtain the respective binding constants Kb and the Gibbs free energy of binding. MD simulations with explicit counterions but implicit water demonstrate that counterion release is the main driving force for the binding of proteins to strongly charged polyelectrolytes: patches of positive charges located on the surface of the protein become multivalent counterions of the polyelectrolyte, thereby releasing a number of counterions condensed on the polyelectrolyte. The binding Gibbs free energy due to counterion release is predicted to scale with the logarithm of the salt concentration in the system, which is verified by both simulations and experiment. In several cases, namely, for the interaction of proteins with linear polyelectrolytes and highly charged hydrophilic dendrimers, the binding constant could be calculated from simulations to very good approximation. This finding demonstrated that in these cases explicit hydration effects do not contribute to the Gibbs free energy of binding. The Gibbs free energy can also be used to predict the kinetics of protein uptake by microgels for a given system by applying dynamic density functional theory. The entire discussion demonstrates that the direct comparison of theory with experiments can lead to a full understanding of the interaction of proteins with charged polymers. Possible implications for applications, such as drug design, are discussed.


Case report: Squamous cell carcinoma and spindle cell sarcoma (SCS) arising in a mature cystic teratoma of the ovary.
Malignant transformation of mature ovarian teratoma is a rare phenomenon, mainly occurring in postmenopausal period. Squamous cell carcinoma accounts for 80% of all malignant transformations. Sarcoma transformation is much less common and tends to imply a poorer prognosis and aggressiveness. We report a case of undifferentiated sarcoma with squamous cell carcinoma in a mature cystic teratoma of the ovary in a 36-year-old woman. The tumor shows epithelial and stromal components. This is a unique report of a benign teratoma of the ovary with malignant transformation, showing epithelial and sarcomatous components. This young woman presented with abdominal distension and a rapidly enlarging ovario-derived pelvic mass with a slightly elevated CA199 tumor marker of 115.9 U/ml. The woman underwent transabdominal excision of the left ovarian cyst on October 20, 2020. During the operation, rapid freezing pathological examination did not indicate malignancy. The postoperative paraffin pathology revealed undifferentiated sarcoma with squamous cell carcinoma (from mature cystic teratoma malignancy), and she finally received comprehensive staging surgery. Postoperative paraffin pathology showed no residual cancer in uterus and other tissues, and all lymph nodes were negative. The patient was finally diagnosed with ovarian malignant tumor IC1 stage (high-grade spindle cell sarcoma complicated with squamous cell carcinoma). Chemotherapy was completed three times after surgery, and no signs of recurrence were found after follow-up. The preoperative diagnosis and intraoperative rapid freezing examination of malignant transformation of mature teratoma of ovary are challenging.


The eggs of Anopheles galvaoi and Anopheles evansae, two species of the subgenus Nyssorhynchus.
The ultrastructure of the eggs of Anopheles (Nyssorhynchus) galvaoi Causey, Deane, and Deane and Anopheles (Nyssorhynchus) evansae (Brethes) are described and illustrated with scanning electron micrographs. The eggs of these species are similar to those of Anopheles (Nyssorhynchus) aquasalis Curry, Anopheles (Nyssorhynchus) oswaldoi (Peryassu), and Anopheles (Nyssorhynchus) konderi Galvão and Damasceno in having floats long, widely joined posteriorly on the dorsal surface, the frill encircling the anterior end of the egg, and the crown absent. A few distinctive characters to distinguish An. evansae from An. galvaoi are given.


The art and science of a behavioural approach to care.
Behavioural psychology has much to offer residents, families and staff. Properly developed, a behavioural approach to care is at once humane, scientific and practical. In our experience, the dedication of resources and expertise to implementation of a behavioural approach to care has been truly beneficial for all concerned.


Acetylated HMG1 protein interacts specifically with homologous DNA polymerase alpha in vitro.
The acetylated, deacetylated and nonacetylated forms of HMG1 proteins from Guerin ascites tumour cells and calf thymus were separated and their in vitro interactions with homologous and heterologous DNA polymerases were studied. It has been found that only the acetylated form of HMG1 proteins forms a specific complex with homologous DNA polymerase alpha and stimulates its activity in vitro. The acetylation therefore is necessary for their possible function in DNA replication. This finding represents an evidence for a relationship between the acetylation of HMG1 proteins and their biological role.


Biocompatibility of collagen membranes crosslinked with glutaraldehyde or diphenylphosphoryl azide: an in vitro study.
Crosslinking of collagen biomaterials increases their resistance to degradation in vivo. Glutaraldehyde (GA) is normally used to crosslink collagen biomaterial, but is often cytotoxic. Diphenylphosphoryl azide (DPPA) has recently been proposed as reagent, but little is known about its effects on cell behavior. In this study, we determined which collagen membrane was the most biocompatible: Paroguide which is crosslinked with DPPA and contains chondroitin sulfate; Opocrin which is crosslinked with DPPA; Biomed Extend which is crosslinked with GA; and Bio-Gide which is left untreated. Cell proliferation and extracellular matrix macromolecule deposition were evaluated in human fibroblasts cultured on the membranes. The GA-crosslinked Biomed Extend membrane and the not-crosslinked Bio-Gide membrane reduced cell growth and collagen secretion compared with DPPA-crosslinked biomembranes. When Paroguide and Opocrin were compared, better results were obtained with Paroguide. The greatest amount of transforming growth factor beta1, a growth factor involved in extracellular matrix macromolecule accumulation and in tissue regeneration, was produced by cells cultured on Paroguide, with Opocrin second. Our data suggest that the DPPA method is more biocompatible than the GA for crosslinking collagen biomaterials and that membranes made of collagen plus chondroitin sulfate are better than membranes made of pure collagen.


One-Pot Electrochemical Nickel-Catalyzed Decarboxylative Sp2-Sp3 Cross-Coupling.
A one-pot electrochemical nickel-catalyzed decarboxylative sp2-sp3 cross-coupling reaction has been developed using redox-active esters prepared in situ from alkyl carboxylates and N-hydroxyphthalimide tetramethyluronium hexafluorophosphate (PITU). This undivided cell one-pot method enables C-C bond formation using inexpensive, benchtop-stable reagents with isolated yields up to 95% with good functional group tolerance, which includes nitrile, ketone, ester, alkene and selectivity over other aromatic halogens.


Impact of 30 mg/kg amikacin and 8 mg/kg gentamicin on serum concentrations in critically ill patients with severe sepsis.
Low first-dose peak serum concentrations of amikacin and gentamicin are commonly reported in ICU patients. The present study aimed to assess whether 30 mg/kg amikacin or 8 mg/kg gentamicin achieved target concentrations in ICU patients with severe sepsis. Sixty-three ICU patients (Simplified Acute Physiology Score II = 43 ± 16) with severe sepsis and an indication for intravenous amikacin (n = 47) or gentamicin (n = 16) were included. The first (30 mg/kg amikacin; 8 mg/kg gentamicin) and subsequent doses and corresponding peak concentrations (30 min after the completion of an infusion) were recorded. French guideline target concentrations were ≥60 and ≥30 mg/L for amikacin and gentamicin, respectively. A target pharmacokinetic/pharmacodynamic ratio of 10 × MIC was also measured. Pulmonary, abdominal and urinary tract infections were diagnosed in 56 patients. Infection was confirmed in 37 patients (59%). The targeted first-dose peak concentration was achieved in 37/63 patients (59%) [amikacin 36/47 (77%) and gentamicin 1/16 (6%)], and 59/63 patients (94%) achieved the pharmacokinetic/pharmacodynamic ratio using the MIC data that were available from 21 patients. However, the second dose of aminoglycoside was withheld because of high trough concentrations in nearly half of patients who did not have renal dysfunction. In this study, 30 mg/kg amikacin and 8 mg/kg gentamicin led to target peak serum concentrations in 59% of patients.


Tepoxalin a dual 5-LOX-COX inhibitor and erlotinib an EGFR inhibitor halts progression of gastric cancer in tumor xenograft mice.
GC is associated with over expression of epidermal growth factor receptor (EGRF), Cyclooxygenase-2 (COX-2) and 5-Lipoxygenase (5-LOX). We postulated that targeting these pathways will result in better treatment efficacy than using a single agent with higher dose which may cause toxicity and resistance. We evaluated Tepoxalin (TPX) a dual 5-LOX-COX inhibitor and Erlotinib (ERB) an EGFR inhibitor alone and combination in MGC-803 injected tumor xenografts mice. Female nude mice were selected and injected subcutaneously with MGC-803 GC cells and were grouped after the tumor model was formed. The treatment of TPX, ERB and their combination was given for 21 days. After treatment protocol proliferating index was measured, expression of apoptosis related proteins, 5-LOX, COX-2, EGFR, vascular endothelial growth factor-C (VEGF-C) and density of lymphatic vessel density was evaluated in tumor tissues. TUNEL assay was done for apoptosis. The outcomes of study revealed that TPX and ERB alone inhibited the growth of tumor but their combination showed a synergistic antitumor activity. TPX and ERB alone resulted in apoptosis and antiproliferative effect, whereas their combination showed highly significant results (P<0.01). TPX alone and its combination with ERB suppressed 5-LOX, COX-2, EGFR and VEGF-C and caused inhibition of lymphangiogenesis, however ERB alone was unable to affect expression of VEGF-C and lymphangiogenesis. The results confirmed combination of TPX and ERB produced a synergistic anticancer and antitumor activity, possibly by promoting apoptosis and antiproliferative effect on tumor cells via suppressing expression of COX-2, 5-LOX, EGFR and VEGF-C.


Draft Genome Sequence of Hydrotalea flava Strain CCUG 51397T.
We report the draft genome sequence of Hydrotalea flava CCUG 51397(T), the type strain of the genus Hydrotalea (family Chitinophagaceae), isolated from water samples in southern Sweden.


The concept of "silencing the self" in low-income, aging, HIV-infected African American women: a 10-year community-based participatory program of research with results.
Despite a resilient spirit, the challenges that face low-income, aging Black women living with HIV infection are immense. This article describes a 10-year iterative history of using the Theory of Silencing the Self (TSTS) as an explanatory model that was found to be gender sensitive, culturally relevant, and helpful in guiding a community-based participatory research group of low-income, HIV-infected Black women living in Boston, Massachusetts. The group, called Sistah Powah, used the TSTS to design and implement a structured writing intervention in a women's drop-in center targeting low-income, aging Black women living with HIV infection as a way to give them and others a voice.


[New Japanese GCP--from the standpoint of a sponsor].
The new Japanese GCP enacted on the basis of ICH-GCP adopts more clear concepts of quality assurance for a clinical trial. This article briefly describes its principles. Sponsors are now responsible not only for initiation but also for management of clinical trials. Thus, discussions have been under taken the points to be considered in, among others, imple mentation/maintenance of the Quality Assurance/ Control systems, preparation/amendment of a clinical trial protocol, entrusting to a coordinating investigator/committee, monitoring, audit, and direct access to source documents and all other trial-related records. Further, this addresses the required reorganization which the sponsor should strive for as well as the sponsor's requests to participating medical institutions such as adoption of a "study coordinator". To improve the quality of a clinical trial, it would be necessary to refer not only to GCP but also to other current guidelines such as those harmonized at the ICH.


[Ankle arthritis: joint-preserving surgery and total ankle arthroplasty].
Ankle arthritis affects approximately 1% of the adult population worldwide and represents a serious global disease burden. However, compared with hip arthritis and knee arthritis, the clinical understanding and treatment of ankle arthritis are still in their infancy. For end-stage ankle arthritis, ankle arthrodesis was considered as the "gold standard" in the past. However, ankle arthrodesis will result in loss of joint mobility, altered gait, limited daily activities, and accelerated degeneration of adjacent joints. Therefore, how to preserve the range of motion of the ankle joint while relieving pain is the key to the treatment of ankle arthritis. Currently, the surgical treatment of ankle arthritis includes arthroscopic debridement, periarticular osteotomies, osteochondral transplantation, ankle distraction arthroplasty, ankle arthrodesis, and total ankle arthroplasty. The choice of treatment should be individualized and based on various factors such as the patient's symptoms, signs, imaging performance, complaints, and financial situation. However, there are no guidelines that give clear treatment recommendations. Therefore, it is necessary to conduct extensive and in-depth discussions on the diagnosis and treatment of ankle arthritis.


Bioinformatics-based analysis of the involvement of AC005550.3, RP11-415D17.3, and RP1-140K8.5 in homocysteine-induced vascular endothelial injury.
This study aimed to explore the role of certain genes and long non-coding RNAs (lncRNAs) in homocysteine (HCY)-induced vascular endothelial injury. HUVECs were treated with HCY, then cell cycle and apoptosis were analyzed by flow cytometry. HUVECs were then sequenced and analyzed using bioinformatics, with a focus on differentially expressed genes/lncRNA (DEGs/DEL), protein-protein interaction (PPI), functional enrichment analyses, and lncRNA-target prediction. Although HCY did not affect the cell cycle, it significantly increased the number of apoptotic cells. In total, 382 DEGs and 147 DELs were identified; DEGs such as CD34, FGF2, and SERPINE1 were the hub nodes in the PPI network, in addition to being the targets of AC005550.3, RP11-415D17.3, and RP1-140K8.5, respectively. Functional enrichment analysis showed that the targets of downregulated AC005550.3 and RP11-415D17.3 were significantly enriched in blood vessel development and those of upregulated RP1-140K8.5 were enriched in fibrinolysis. RT-qPCR showed that the mRNA levels of AC005550.3, RP11-415D17.3, and RP1-140K8.5 were consistent with the results predicted by our bioinformatics analysis. In conclusion, downregulated AC005550.3 and RP11-415D17.3 targeting CD34 and FGF2 and upregulated RP1-140K8.5 targeting SERPINE1 may play an important role in HCY-induced vascular endothelial injury by regulating blood vessel development and fibrinolysis, respectively.


Desipramine-induced apoptosis in human PC3 prostate cancer cells: activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation.
The antidepressant desipramine has been shown to induce a rise in cytosolic Ca2+ levels ([Ca2+]i) and cytotoxicity in human PC3 prostate cancer cells, but the mechanisms underlying its cytotoxic effect is unclear. Cell viability was examined by WST-1 assays. Apoptosis was assessed by propidium iodide staining and an increase in caspase-3 activation. Phosphorylation of protein kinases was analyzed by immunoblotting. Desipramine caused cell death via apoptosis in a concentration-dependent manner. Immunoblotting data revealed that desipramine activated the phosphorylation of c-Jun NH2-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SP600125 (a selective JNK inhibitor) partially prevented cells from apoptosis. Pretreatment with BAPTA/AM, a Ca2+ chelator, to prevent desipramine-induced [Ca2+]i rises worsened desipramine-induced cytotoxicity. Immunoblotting data suggest that BAPTA/AM pretreatment enhanced desipramine-evoked JNK phosphorylation and caspase-3 cleavage. The results suggest that in PC3 cells, desipramine caused apoptosis via inducing JNK-associated caspase-3 activation, and [Ca2+]i rises may slow down or alleviate desipramine-induced cytotoxicity.


Acute encephalopathy associated with intravenous immunoglobulin therapy.
Intravenous immunoglobulin therapy is useful against various immune system disorders and viral infections. It is generally safe, and serious adverse reactions are uncommon. We report a rare case of acute encephalopathy following intravenous immunoglobulin therapy for human herpes virus 6 infection in a child. MR imaging findings suggest that the dominant causative mechanism of acute encephalopathy is cytotoxic edema, and the findings indicate 2 primary mechanisms. Reversibility of the restriction of water diffusion (low apparent diffusion coefficient value) on diffusion-weighted MR imaging suggests intramyelinic edema in the myelin sheath, and an increase of glutamate and glutamine complex peak on MR spectroscopy suggests excitotoxic injury to the neurons and astrocytes.


Distal Stressors and Depression among Homeless Men.
Depression is a common problem among homeless men that may interfere with functional tasks, such as securing stable housing, obtaining employment, and accessing health services. Previous research on depression among homeless men has largely focused on current psychosocial resources, substance abuse, and past victimization. Guided by Ensel and Lin's life course stress process model, the authors examined whether distal stressors, including victimization and exposure to parent problems in childhood, contributed to men's depression above and beyond current (or proximal) stressors, such as substance abuse and health problems, and social resources. The sample consisted of 309 homeless men who had entered a federally funded emergency shelter. Using the Burns Depression Checklist, the authors found that one out of three men met the threshold for moderate to severe depression during the past week. The logistic regression showed that past exposure to parent problems was related to depression after accounting for current stressors and social resources (number of close adult relationships and whether their emotional support needs were met). Past victimization was not related to depression. To address men's depression, workers should concurrently provide services that meet men's basic needs (for example, housing) and address their relationship needs, including their need for emotional support.


The ArcB leucine zipper domain is required for proper ArcB signaling.
The Arc two-component system modulates the expression of numerous genes in response to respiratory growth conditions. This system comprises ArcA as the response regulator and ArcB as the sensor kinase. ArcB is a tripartite histidine kinase whose activity is regulated by the oxidation of two cytosol-located redox-active cysteine residues that participate in intermolecular disulfide bond formation. Here, we report that the ArcB protein segment covering residues 70-121, fulfills the molecular characteristics of a leucine zipper containing coiled coil structure. Also, mutational analyses of this segment reveal three different phenotypical effects to be distributed along the coiled coil structure of ArcB, demonstrating that this motif is essential for proper ArcB signaling.


Pollutant loads of surface runoff in Wuhan City Zoo, an urban tourist area.
The pollutant loads of surface runoff in an urban tourist area have been investigated for two years in the Wuhan City Zoo, China. Eight sampling sites, including two woodlands, three animal yards, two roofs and one road, were selected for sampling and study. The results indicate that pollutants ranked in a predictable order of decreasing load (e.g. animal yard > roof > woodland > road), with animal yards acting as the key pollution source in the zoo. Pollutants were transported mainly by particulate form in runoff. Particulate nitrogen and particulate phosphorous accounted on average for 61%, 78% of total pollutant, respectively, over 13 monitored rainfall events. These results indicate the treatment practices should be implemented to improve particulate nutrient removal. Analysis of the M(V) curve indicate that no first flush effect existed in the surface runoff from pervious areas (e.g. woodland, animal ground yard), whereas a first flush effect was evident in runoff from impervious surfaces (e.g. animal cement yard, roof, road).


Effect of moisture content on the invertase activity of freeze-dried S. cerevisiae.
The invertase activity of intact Saccharomyces cerevisiae submitted to freezing-thawing was affected by pH, the chemical nature of the buffer, and the freezing cooling rate (CR), leading in some cases to a complete invertase inactivation (acetate buffer, pH 4.0, CR = 0.5 degree C/min). Once established under adequate freezing conditions the invertase activity remained unchanged after freeze-drying. Nevertheless, in some cases the cell-growing capability after freeze-drying diminished around 70%, mainly if the frozen cell suspension was attained through freezing carried out at CR = 0.5 degree C/min. Water sorption isotherms of freeze-dried samples (freeze-dryer Edwards L-4KR; 30 degrees C and 0.1 mB) were determined at 10 and 25 degrees C. The monolayer moisture content (MMC) at each temperature (12.7 and 3.71 for 10 and 25 degrees C, respectively) was calculated from isotherms by applying BET and GAB models. Freeze-dried yeast with water activity (Aw) between 0 and 0.33 (about the MMC value) maintained at 25 degrees C for 235 days and at 89 degrees C for 15 min retained at least 85% of its original invertase activity (IA), whereas samples with Aw > MMC lost at least 60% of its IA. X ray diffraction showed that the freeze-dried cake before and after storage presented an amorphous structure.


Leveraging built environment interventions to equitably promote health during and after COVID-19 in Toronto, Canada.
A key public health response to the COVID-19 pandemic is the mandate to stay home and practice physical distancing. In Canada, with essential activities such as grocery shopping, outdoor exercise and transportation, people need to be able to safely navigate dense, urban spaces while staying at least two metres or six feet apart. This pandemic has exacerbated the health inequities across neighbourhoods in cities like Toronto, Canada which are often segregated along racial and income lines. These inequities impact who has access to urban infrastructure that promotes health and quality of life. Safety in a time of COVID-19 goes beyond just exposure to the virus, it is complicated by notions of who belongs where, and who has access to what resources. The built environment has a role in maintaining and promoting physical and mental health during this pandemic and beyond it. This paper puts forwards three considerations for built environment interventions to promote health equitably: (i) addressing structural determinants of health and embedding anti-racist intersectional principles, (ii) revisiting tactical urbanism as a health promotion tool and (iii) rethinking community engagement processes through equity-based placemaking. This paper outlines four built environment interventions in Toronto, Canada that seek to address the challenges in navigating urban space safely in the short term, including street design that prioritizes pedestrians, protected cycling infrastructure, access to inclusive green space and safe, affordable housing. Longer-term strategies to create health-promoting urban environments that are equitable are discussed and may be valuable to other cities with similar urban equity concerns.


Comparing the Efficacy of the Total Stabilizing and Posterior Stabilizing Knee Prostheses in Obese and Preobese Females: A Retrospective Cohort Study.
Obesity is associated with increased surgical complications that may lead to suboptimal total knee arthroplasty (TKA) outcomes. Additionally, females exhibit increased rates of severe, clinical osteoarthritis OA, along with increased ligamentous laxity. Therefore, obese females present a particularly challenging case for TKA with increased joint loads coupled with a propensity for instability. This study retrospectively analyzed knee range of motion and stability of one TKA designs with two different degrees of polyethylene conformity in the obese female population. The implants (Stryker Triathlon total stabilizing [TS] and Stryker Triathlon posterior stabilizing [PS]) differ in their level of constraint, with the TS being more constrained. We hypothesized that the TS implants would be associated with improved functional outcomes in the obese female population, secondary to increased coronal stability to offset the ligamentous laxity. Of 482 knees reviewed, 173 met the inclusion criteria of: female, body mass index (BMI) ≥ 25, receiving TS (N = 93), or PS (N = 8). Primary knee outcome measures were: active flexion, passive flexion, active extension, passive extension, and stability at 0° and 30° flexion. These factors were statistically analyzed at preop, 2-week, 6-week, 3-month, and 1-year time points. Preoperatively, the TS cohort was significantly higher in BMI and knee laxity, potentially starting this cohort at a functional disadvantage. Postoperatively, the TS implant was associated with a statistically significant early improvement in active and passive knee extension. There was no longer any significant difference in knee laxity postop. Our data support the hypothesis that obese females may benefit from the increased stability afforded by the TS design.


Identification of desethyl procainamide in patients: a new metabolite of procainamide.
Desethyl procainamide (PADE) was identified in the urine of a patient treated with procainamide (PA) by high-performance liquid chromatography followed by solid-probe mass spectrometry. PADE prevented ventricular fibrillation in chloroform-asphyxiated mice but PA was 1.5 times more potent than PADE with respect to dose and 1.7 times more potent with respect to plasma concentration measured after administration of antiarrhythmic ED50 doses of the two compounds. N-acetylprocainamide was found to be 1.8 times more potent than desethyl N-acetylprocainamide with respect to dose and 2.9 times more potent with respect to plasma concentration. Measurements of PA, PADE, N-acetylprocainamide and desethyl-N-acetylprocainamide concentrations in 10 patients receiving long-term PA therapy suggest that only PA and N-acetylprocainamide concentrations make important contributions to observed therapeutic responses.


Immunoelectron microscopic localization of thyroglobulin in human follicular adenoma.
An electron microscopic immunohistochemical localization of thyroglobulin (TG) using PAP methods has been made in 15 cases of cold follicular adenoma. All cases of follicular adenoma showed organ specific functions such as synthesis, storage, reabsorption, and hydrolysis of thyroglobulin except for an area composed of follicular cells with trabecular arrangement. Immuno-reaction product for TG was precisely demonstrated in follicular lumina, subapical vesicles and reabsorbed colloid droplets. The reaction product observed in the follicular lumen was clearly demarcated from the cytoplasm of the follicular cells by the apical plasma membrane. The subapical vesicles ranging approximately from 50 millimicrons to 300 millimicrons in diameter were rarely observed in follicular adenoma and some of them fused with the reabsorbed colloid droplets. The reabsorbed colloid droplets usually had the intense reaction product and hydrolyzed colloid droplets had a vacuole containing floccular low electron dense materials. There is no reaction product in rough endoplasmic reticulum and Golgi complexes.


Composite fault reconstruction and fault-tolerant control design for cyber-physical systems: An interval type-2 fuzzy approach.
This article scrutinizes the stabilization and fault reconstruction issues for interval type-2 fuzzy-based cyber-physical systems with actuator faults, deception attacks and external disturbances. The primary objective of this research is to formulate the learning observer system with the interval type-2 fuzzy technique that reconstructs the actuator faults as well as the immeasurable states of the addressed fuzzy based model. Further, the information of reconstructed actuator faults is incorporated in the developed controller with the imperfect premise variables for ensuring the stabilization of the system under consideration. At the same time, the H∞ technique is employed to reduce the impact of external disturbances in the considered model. In addition to that, the deception attacks are represented as a stochastic variable that satisfies the Bernoulli distributions. On the ground of this, a set of sufficient criteria is deduced in the context of linear matrix inequalities to affirm the stability of the addressed systems. Furthermore, the requisite gain matrices are computed by resolving the obtained linear matrix inequality based stability criteria. At last, two simulation examples, including the mass-spring-damper system are exhibited to demonstrate the usefulness of analytical findings of the developed strategy.


The effect of in-office bleaching materials with different pH on the surface topography of bovine enamel.
This study evaluated the alterations of surface topography of the bovine enamel caused by different pH of in-office bleaching agents. 23% H2O2 with pH 5.5, 7.0 and 8.5 were applied on the bovine tooth specimens (n=10) and photo-irradiated for 10 min. The bleaching procedure was repeated three times and specimens were subjected to linear surface roughness (Ra) and Vickers microhardness test (VHN) at baseline and after three consecutive applications. The morphological alterations were observed before and after third bleaching application. Data were analyzed by two-way ANOVA followed by Tukey's HSD. The pH of the bleaching agent significantly affects the Ra and VHN (p<0.05). Low pH yielded a significant increase in Ra and decrease in VHN. All the groups showed morphological alterations and profound effect was found in pH 5.5 group. It was concluded that the pH of the bleaching agent can affect Ra, VHN and surface morphology.


The histidine kinase inhibitor Sda binds near the site of autophosphorylation and may sterically hinder autophosphorylation and phosphotransfer to Spo0F.
Histidine kinases are widely used by bacteria, fungi and plants to sense and respond to changing environmental conditions. Signals in addition to those directly sensed by the kinase are often integrated by proteins that fine-tune the biological response by modulating the activity of the kinase or its targets. The Bacillus subtilis histidine kinase KinA promotes the initiation of sporulation when nutrients are limiting, but sporulation can be delayed by two inhibitors of KinA, Sda (when DNA replication is perturbed) or KipI (under unknown conditions). We have identified residues in the dimerization/histidine-phosphotransfer (DHp) domain of KinA that are functionally important for inhibition by Sda and KipI and overlapping surface-exposed residues that lie close to or comprise the Sda binding site. Sda inhibits the intermolecular transfer of phosphate from the catalytic ATP-binding (CA) domain of KinA to the autophosphorylation site in the DHp domain when the domains are split into separate polypeptides, either by steric hindrance or by altering the conformation of the DHp domain. Sda also slows the rate of phosphotransfer from KinA approximately P to its target, Spo0F, consistent with our finding that a KinA residue important for Sda function overlaps with the predicted Spo0F binding site on KinA.


Hybrid adeno-associated virus bearing nonhomologous inverted terminal repeats enhances dual-vector reconstruction of minigenes in vivo.
We have previously demonstrated that hybrid adeno-associated viral (AAV) vectors bearing nonhomologous inverted terminal repeats (ITRs) enhance directional intermolecular recombination and the efficiency of dual-AAV vector trans-splicing in cultured cells. Using hybrid-ITR vectors carrying two exons of a lacZ minigene, we demonstrate that this dual-vector approach also mediates higher levels (3- to 6-fold) of gene reconstitution in mouse skeletal muscle, liver, and heart. Inhibition of the proteasome by systemic administration of Doxil (Food and Drug Administration-approved lipid-formulated doxorubicin) further enhanced dual-vector trans-splicing 6- to 12-fold in two mouse strains. Hence, using hybrid-ITR AAV vectors in combination with proteasome modulation enhanced dual-vector delivery of a transgene approximately 36-fold over the current dual-vector trans-splicing approaches. These data provide in vivo evidence that ITR sequence-dependent homologous recombination, rather than nonhomologous end joining, is the predominant mechanism for AAV genome heterodimerization. Hence, enhanced directional recombination provided by hybrid-ITR vectors may be a useful in vivo strategy for improving dual-vector delivery of transgenes larger than the AAV packaging limit.


Characteristics of the RNA synthesized in vitro by the normal human small lymphocyte and the changes induced by phytohemagglutinin stimulation.
These studies demonstrate that the circulating human small lymphocyte synthesizes ribonucleic acid (RNA) of high molecular weight which is not primarily a ribosomal precursor and which is, in part, complementary to human deoxyribonucleic acid (DNA). The stimulation of these lymphocytes by PHA brings a cell population in which few ribosomes are synthesized to a functional condition in which a large amount of these particles are produced. This increase in the synthesis of ribosomal RNA is one of the earliest and most relevant effects of PHA on the RNA metabolism of small lymphocytes.


Accessing Physical Activity and Health Disparities among Underserved Hispanic Children: The Role of Actual and Perceived Motor Competence.
Promoting physical activity (PA) and eliminating health disparities among underserved minority children is a public health priority. The main purpose of this study was to examine the relationship of actual motor competence (a set of object control skills) and perceived motor competence with PA participation and health-related quality of life (HRQoL) among underserved Hispanic children who were born in the U.S. Guided by Stodden et al.'s conceptual model, we tested the direct and indirect effects (mediational model) of actual motor competence on health-related outcomes (PA and HRQoL) through perceived motor competence. Participants were 215 underserved Hispanic children (Mage = 10.55 years, SD = 0.53 [age range 10-12]; 51.6% boys), recruited from four elementary schools in the southwestern U.S., who completed validated questionnaires assessing their perceived motor competence, PA, and HRQoL. Their actual motor skills were assessed using PE MetricsTM. After examining the associations among the variables, we tested the hypothesized model using structural equation modeling (SEM; AMOS 25). The hypothesized model indicated a good fit (χ²/df = 38.427/24 = 1.60 < 5; non-normed fit index (NFI) = 0.93; comparative fit index (CFI) = 0.968; root mean square error of approximation (RMSEA) = 0.053 [0.016, 0.083]). The effect of actual motor competence on PA and HRQoL was fully mediated by perceived motor competence. The findings demonstrated the mediating role of perceived motor competence between actual motor competence and health-related outcomes (PA and HRQoL) among underserved Hispanic children. The results highlight that actual motor competence significantly predicted underserved Hispanic children' perceived motor competence, which in turn positively predicted their PA and HRQoL. These findings have significant practical implications for future intervention strategies of randomized clinical trials in schools aimed at promoting PA and HRQoL and eliminating health disparities among underserved Hispanic children.


Acyclovir ointment does not affect the dark-field examination in primary syphilis.
In the cases of two patients and in a rabbit with experimental syphilis, treatment of primary syphilis lesions with 5% acyclovir ointment did not affect detection of Treponema pallidum by dark-field microscopy. These results indicate that the dark-field examination need not be delayed in patients whose genital ulcers have been treated with acyclovir ointment.


[Not Available].
The author outlines the activity of Russian sanitary detachments in the Balkan perinsula during 1876. They offered substantial medical aid to the rebels from Herzegovina and Bosna, to the wounded and ill soldiers, making part of the Serbian and Montenegro army during fighting activities, as well as to civil population.


Neuromuscular regulation of T-cell activation.
Recent investigations in our laboratory have shown that murine intestinal smooth muscle cells (ISMCs) can exert an immunomodulatory effect on T-cells. Therefore, we examined the effects of substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) on the ability of ISMCs to modulate T-cell proliferation and lymphokine generation. T-cell proliferation was observed when these cells were co-cultured with IFN-pretreated C57/BL6 ISMCs which expressed major histocompatibility complex II (MHC II), but not during T-cell co-culture with C2D (MHC II -/-) ISMCs pretreated in the same manner. T-cell proliferation during co-culture with C57/BL6 ISMCs was also associated with significantly enhanced T-cell synthesis of IFN. When CGRP (at 10(-9) M), but not substance P or VIP, was added to C57/BL6 ISMCs during the IFN-pretreatment period. T-cell proliferation was significantly increased. However, increased T-cell proliferation was not observed if the concentration of CGRP was increased to 10(-6) M. At the higher concentration, addition of substance P or VIP during the pretreatment period significantly inhibited the subsequent T-cell proliferation. Pretreatment of C57/BL6 ISMCs with any of the three neuropeptides and IFN resulted in the diminished production of IL-4 and IFN by co-cultured T-cells. A similar pattern of cytokine secretion was observed during T-cell co-culture with IFN- and neuropeptide-pretreated C2D ISMCs except when 10(-6) M substance P was added; IFN secretion by co-cultured T-cells was increased 4-fold under these conditions. Taken together, these data show a direct modulatory role for neuropeptides in the interaction between ISMCs and T-cells and suggest that, in general, neuropeptides may dampen immune responses in the neuromuscular layers of the inflamed intestine.


Genetics and Genomic Regions Affecting Response to Newcastle Disease Virus Infection under Heat Stress in Layer Chickens.
Newcastle disease virus (NDV) is a highly contagious avian pathogen that poses a tremendous threat to poultry producers in endemic zones due to its epidemic potential. To investigate host genetic resistance to NDV while under the effects of heat stress, a genome-wide association study (GWAS) was performed on Hy-Line Brown layer chickens that were challenged with NDV while under high ambient temperature to identify regions associated with host viral titer, circulating anti-NDV antibody titer, and body weight change. A single nucleotide polymorphism (SNP) on chromosome 1 was associated with viral titer at two days post-infection (dpi), while 30 SNPs spanning a quantitative trait loci (QTL) on chromosome 24 were associated with viral titer at 6 dpi. Immune related genes, such as CAMK1d and CCDC3 on chromosome 1, associated with viral titer at 2 dpi, and TIRAP, ETS1, and KIRREL3, associated with viral titer at 6 dpi, were located in two QTL regions for viral titer that were identified in this study. This study identified genomic regions and candidate genes that are associated with response to NDV during heat stress in Hy-Line Brown layer chickens. Regions identified for viral titer on chromosome 1 and 24, at 2 and 6 dpi, respectively, included several genes that have key roles in regulating the immune response.


Validation experiment of a numerically processed millimeter-wave interferometer in a laboratory.
We propose a new interferometer system for density profile measurements. This system produces multiple measurement chords by a leaky-wave antenna driven by multiple frequency inputs. The proposed system was validated in laboratory evaluation experiments. We confirmed that the interferometer generates a clear image of a Teflon plate as well as the phase shift corresponding to the plate thickness. In another experiment, we confirmed that quasi-optical mirrors can produce multiple measurement chords; however, the finite spot size of the probe beam degrades the sharpness of the resulting image.


Aortic-right atrial tunnel.
We describe an asymptomatic 1-year-old boy who presented a continuous murmur, and was found to have a tunnel between the right atrium and the aorta. The definitive diagnosis was established by both echocardiography and aortography, and surgical interruption of the tunnel was successful. We emphasise the rarity of this condition, and discuss its major features.


The USA-USSR collaborative cross-cultural comparison of autogenic training and thermal biofeedback in the treatment of mild hypertension.
We have conducted a cross-cultural (USA and USSR) comparison of thermal biofeedback (TBF) and autogenic training (AT) to a self-relaxation control condition in 59 unmedicated males with mild hypertension. Identical assessment and treatment protocols were carried out in both settings (Albany, New York, and Moscow). Treatments were delivered in small groups on an outpatient basis twice per week for 10 weeks. Results showed comparable, significant (p less than .05), short-term decreases (M = 8.5 mm Hg) in diastolic blood pressure (DBP) for both treatments at both sites. However, the Soviet patients, starting with significantly (p less than .01) higher systolic blood pressures (SBPs), showed significant decreases (M = 12.8 mm Hg) in SBP, whereas the American patients did not change appreciably (M = 4.6 mm Hg). During follow-up, the treated Soviet patients showed significantly (p less than .05) better maintenance of treatment effects, from 3 months to 1 year, than did the American patients. At 1 year, 75% of the treated Soviet patients had DBPs less than 90 mm Hg, whereas only 24% of the American patients had comparable DBPs.


Disparities in prevalence of heart failure according to age, multimorbidity level and socioeconomic status in southern Sweden: a cross-sectional study.
The aim of this study was to compare the prevalence of heart failure (HF) in relation to age, multimorbidity and socioeconomic status of primary healthcare centres in southern Sweden. A cross-sectional study. The data were collected concerning diagnoses at each consultation in all primary healthcare centres and secondary healthcare in the southernmost county of Sweden at the end of 2015. The individuals living in southern Sweden in 2015 aged 20 years and older. The study population of 981 383 inhabitants was divided into different categories including HF, multimorbidity, different levels of multimorbidity and into 10 CNI (Care Need Index) groups depending on the socioeconomic status of their listed primary healthcare centre. Prevalence of HF was presented according to age, multimorbidity level and socioeconomic status. Logistic regression was used to further analyse the associations between HF, age, multimorbidity level and socioeconomic status in more complex models. The total prevalence of HF in the study population was 2.06%. The prevalence of HF increased with advancing age and the multimorbidity level. 99.07% of the patients with HF fulfilled the criteria for multimorbidity. The total prevalence of HF among the multimorbid patients was only 5.30%. HF had a strong correlation with the socioeconomic status of the primary healthcare centres with the most significant disparity between 40 and 80 years of age: the prevalence of HF in primary healthcare centres with the most deprived CNI percentile was approximately twice as high as in the most affluent CNI percentile. The patients with HF were strongly associated with having multimorbidity. HF patients was a small group of the multimorbid population associated with socioeconomic deprivation that challenges efficient preventive strategies and health policies.


25-hydroxyvitamin D status is associated with chronic cerebral small vessel disease.
The aim of this study was to determine the association between 25-hydroxyvitamin D (25(OH)D) and neuroimaging correlates of cerebral small vessel disease. We identified 759 consecutive patients with acute ischemic stroke or transient ischemic attack. Lacunes, white matter hyperintensity, and cerebral microbleed (CMB) were assessed using MR images. Deep CMB was defined as the presence of CMB in basal ganglia, thalamus, or brain stem. The association between 25(OH)D and small vessel disease was tested using linear and logistic regression analyses. Mean age was 68 (±13) years. Mean level of 25(OH)D was 34.1±17.8 nmol/L. On bivariate analysis, a 25-nmol/L decrease in 25(OH)D was associated with lacunes (regression coefficient, 0.23; 95% confidence interval [CI], 0.02-0.45), severe white matter hyperintensity (odds ratio, 2.05; 95% CI, 1.41-3.08), and deep CMB (odds ratio, 1.28; 95% CI, 1.01-1.63). Also, 25(OH)D deficiency (≤25 nmol/L) was associated with lacunes (regression coefficient, 0.5; 95% CI, 0.04-0.95), severe white matter hyperintensity (odds ratio, 2.74; 95% CI, 1.31-6.45), and deep CMB (odds ratio, 1.68; 95% CI, 1.03-2.78). The association remained significant even after multivariable adjustment and in the subgroup of previously healthy patients. 25(OH)D is inversely associated with lacunes, white matter hyperintensity, and deep CMB. Our findings suggest that 25(OH)D is linked to small vessel disease, and in future trials it should be tested whether 25(OH)D supplementation can prevent small vessel disease.


A Case of E-cigarette or Vaping Product Use-Associated Lung Injury Mimicking Miliary Tuberculosis.
E-cigarette usage or vaping is becoming more popular as an alternative option to cigarette smoking. Vaping is associated with a wide degree of pulmonary injuries such as asthma, chronic obstructive pulmonary disease or E-cigarette or vaping product use-associated lung injury (EVALI). E-cigarette or vaping product use-associated lung injury is an acute or subacute respiratory illness that can be severe and life-threatening. Miliary tuberculosis, on the other hand, is a rare form of tuberculosis that results from hematogenous dissemination of Mycobacterium tuberculosis, affecting multiple organs and systems. It is characterized by the presence of small, firm white nodules resembling millet seeds. We report a case of a young patient presenting to the hospital with features suggestive of miliary tuberculosis in the CT scan of the chest. Diagnosis of EVALI was reached after extensive diagnostic workup including tuberculosis revealed negative.


The complete chloroplast genome of Ocimum americanum Linnaeus 1755 and phylogenetic analysis among the Lamiaceae family.
Ocimum americanum Linnaeus 1755 (Lemon basil) is an essential medicinal species in the Ocimum genus. Its leaf decoction is traditionally used to treat diabetes, constipation, diarrhea, piles, and dysentery. The essential oils from this species have intense fungicidal activity. The complete chloroplast genome sequence of O. americanum was assembled from Illumina paired-end sequencing data. The O. americanum chloroplast genome was 152,460 bp in length, containing a large single copy (LSC) region of 83,459 bp and a small single copy (SSC) region of 17,607 bp, separated by a pair of inverted repeats (IRs) of 25,697 bp. The genome contained 134 unique genes, including 89 protein-coding, 37 tRNA, and eight rRNA genes. Among them, nine genes had a single intron, and two genes contained two introns. The overall GC content of the chloroplast genome was 38%, while the corresponding values of LSC, SSC, and IR regions were 35.8%, 31.7%, and 43.1%, respectively. In the phylogenetic analysis, all the Ocimum species formed a group closely related to Plectranthus barbatus. O. americanum was more closely related to O. gratissimum and O. basilicum than the other species of Ocimum included in this study.


Teachers' work-related non-literature-known building-related symptoms are also connected to indoor toxicity: A cross-sectional study.
A previous study showed that classical building-related symptoms (BRS) were related to indoor dust and microbial toxicity via boar sperm motility assay, a sensitive method for measuring mitochondrial toxicity. In this cross-sectional study, we analyzed whether teachers' most common work-related non-literature-known BRS (nBRS) were also associated with dust or microbial toxicity. Teachers from 15 schools in Finland completed a questionnaire evaluating 20 nBRS including general, eye, respiratory, hearing, sleep, and mental symptoms. Boar sperm motility assay was used to measure the toxicity of extracts from wiped dust and microbial fallout samples collected from teachers' classrooms. 231 teachers answered a questionnaire and their classroom toxicity data were recorded. A negative binomial mixed model showed that teachers' work-related nBRS were 2.9-fold (95% CI: 1.2-7.3) higher in classrooms with highly toxic dust samples compared to classrooms with non-toxic dust samples (p = 0.024). The RR of work-related nBRS was 1.8 (95% CI: 1.1-2.9) for toxic microbial samples (p = 0.022). Teachers' BRS appeared to be broader than reported in the literature, and the work-related nBRS were associated with toxic dusts and microbes in classrooms.


Coronary heart disease risk reduction in postmenopausal women: the role of statin therapy and hormone replacement therapy.
The incidence of coronary heart disease in women rises sharply in the years following menopause, and prescribing of hormone replacement therapy in the belief that it might compensate for the loss of estrogen-mediated cardioprotection is widespread. However, controlled trials have failed to show a beneficial effect of hormone replacement therapy on the incidence of coronary events, and recent evidence suggests that hormone replacement therapy may even have a deleterious effect on primary coronary heart disease prevention. Statins are recommended as first-line treatment for lowering low-density lipoprotein cholesterol levels in women and are extremely valuable in reducing coronary heart disease risk in this group. An awareness of the benefits of appropriate statin treatment, and evidence showing that they can be safely added to hormone replacement therapy prescribed for the relief of menopausal symptoms and osteoporosis, provides the opportunity to optimize clinical outcomes for coronary heart disease among the large and expanding population of postmenopausal women.


[Study on action mechanism of adjuvant therapeutic effect compound Ejiao slurry in treating cancers based on network pharmacology].
Recently, compound Ejiao slurry (FFEJJ) had been applied to treat cancer patients in clinic, with obvious curative effect. In this study, data and literatures were collected from the TCM chemical component database to establish the chemical component database of FFEJJ. Afterwards, MetaDrug software was used to predict the targets of FFEJJ and obtain the compound-target network. Next, the compound-target network was compared and analyzed to obtain the "compound-target-tumor target" heterogeneous network. Besides, further analysis was made on gene functions and metabolic pathway. The results indicated that FFEJJ could directly resist tumors by regulating cancer cell differentiation, growth, proliferation and apoptosis, and show an adjuvant therapeutic effect by enriching the blood and increasing the immunity.


Computed tomography and magnetic resonance imaging contrast media injectors: technical feature review - what is really needed?
There has been little technical innovation over the last few years for contrast media (CM) injectors that are used for diagnostic imaging (computed tomography [CT], magnetic resonance imaging [MRI], and hybrid imaging systems, such as positron emission tomography-CT or magnetic resonance-positron emission tomography) examinations. The medical need of CM for the enhancement of diagnostic images has been around for a long time, but the application of the CM into the blood stream comes with potential medical complications for the patient and requires a lot of operator experience and training. Most power injector systems that are currently used can do significantly more than what is typically required; this complexity however, adds error potential and cost. This paper focuses on the main features that CM injector systems should have and highlights the technical developments that are useful to have but which add complexity and cost, increase setup time, and require intensive training for safe use. CM injection protocols are very different between CT and MRI, with CT requiring many more variances, has a need for multiphase protocols, and requires a higher timing accuracy. A CM injector used in the MRI suite, on the other-hand, could only need a relatively time insensitive injection with a standard injection flow rate and a volume that is dependent on the patients' weight. This would make easy and lightweight systems possible, which are able to safely and accurately perform the injection task, while allowing full MRI compatibility with relatively low cost investment and consumable costs.


Evaluation of Hi-Tec Implant Restoration in Mandibular First Molar Region- A Prospective Clinical Study.
Missing teeth lead to loss of structural balance, inefficient function, poor aesthetics and psychological effects on human beings, which needs restoration for normal contour, function and aesthetics. Several natural or synthetic substitutes are being used for replacement of missing tooth since centuries. Implants are the latest modality of replacement. So, the study was aimed to assess clinical success rate of Hi-Tec implant; which is economical and new in market. Results of the study will help clinician for appropriate implant selection. The study included 10 patients from 19 to 31 years and needed restoration of missing mandibular first molar. Restoration had done using Hi Tec Single-tooth implants with metal-ceramic single crown prosthesis after three months of osseointegration. The implants were evaluated clinically (bleeding on probing, probing depth, implant mobility- periotest) and radiographically (marginal bone loss and peri-implant radiolucency) for six years. The observers were blinded for the duration of the study to prevent bias. All the patients had uneventful post-surgical healing. No bleeding on probing, Implant mobility, peri-implant radiolucency with minimal marginal bone loss and constant probing depths were observed well within the normal range during follow-up periods. Two stage single-tooth Hi Tec implant restoration can be used as a successful treatment modality for replacing mandibular first molar in an economic way. However, these results were obtained after 6 years of follow up with a smaller sample size, so long term multi center studies with a larger sample size is recommended for the predictability of success rate conclusively.


Circadian pattern of prolactin and growth hormone levels in female rats of two strains.
Plasma growth hormone and prolactin levels were determined by radioimmunoassay at intervals of 2 hr during the light phase of a controlled light-dark cycle in virgin female (COBS F/Crl BR) and [Sch:SPD(SD)BR] rats. Peak prolactin concentrations were observed in the afternoon during proestrus and estrus in both rat stocks. Growth hormone exhibited wide fluctuations in the Sch:SPD rat, attaining peak levels at 1300 hr, but no apparent periodicity was observed in the COBS rats.


Cost Evaluation Analysis of Genetic Testing and Tailored Adjuvant Imatinib in Patients With Resected High-Risk GI Stromal Tumors: The Brazilian Perspective.
Mutations of the KIT gene are the molecular hallmark of most GI stromal tumors (GISTs). Imatinib has revolutionized GIST treatment. Adjuvant imatinib for 3 years is the standard of care for high-risk resected GIST. However, the GIST molecular biologic profile has found different responses to this approach. Despite this, genetic testing at diagnosis is not a routine and empirical adjuvant imatinib remains the rule. Barriers to genetic profiling include concerns about the cost and utility of testing. This analysis aims to determine whether targeted genetic testing reduces costs as an ancillary tool for a limited-resource scenario instead of adjuvant empirical imatinib in patients with resected high-risk GIST. The cost evaluation analysis of molecular testing for GIST was based on the Cost of Preventing an Event (COPE), considering the Number Needed to Treat and the costs of each test compared with the cost of 3-year empirical adjuvant imatinib and real treatment costs (median number of cycles) from the public and private Brazilian Healthcare System's perspective. The analysis compared the costs of the molecular tests (broad next-generation sequencing [NGS], GS Infinity DNA/RNA assay, and targeted NGS: GS Focus GIST and the Fleury GIST Tumor DNA sequencing panel), costs of drug acquisition, considering discounts (imatinib mesylate and Glivec), and the costs of supportive care. In both scenarios, public and private, regardless of the use of imatinib or Glivec, tailoring adjuvant treatment reduced costs, irrespective of the number of cycles. The only exception was the combination of the broad NGS test and imatinib in the Public Healthcare System. The molecularly tailored adjuvant imatinib reduced costs considering the COPE of available NGS tests for both the public and private Brazilian health care systems.


Caffeine delays autonomic recovery following acute exercise.
Impaired autonomic recovery of heart rate (HR) following exercise is associated with an increased risk of sudden death. Caffeine, a potent stimulator of catecholamine release, has been shown to augment blood pressure (BP) and sympathetic nerve activity; however, whether caffeine alters autonomic function after a bout of exercise bout remains unclear. In a randomized, crossover study, 18 healthy individuals (26 ± 1 years; 23.9 ± 0.8 kg·m(-2)) ingested caffeine (400 mg) or placebo pills, followed by a maximal treadmill test to exhaustion. Autonomic function and ventricular depolarization/repolarization were determined using heart rate variability (HRV) and corrected QT interval (QTc), respectively, at baseline, 5, 15, and 30 minutes post-exercise. Maximal HR (HRmax) was greater with caffeine (192 ± 2 vs. 190 ± 2 beat·min(-1), p < 0.05). During recovery, HR, mean arterial pressure (MAP), and diastolic blood pressure (DBP) remained elevated with caffeine (p < 0.05). Natural log transformation of low-to-high frequency ratio (LnLF/LnHF) of HRV was increased compared with baseline at all time points in both trials (p < 0.05), with less of an increase during 5 and 15 minutes post-exercise in the caffeine trial (p < 0.05). QTc increased from baseline at all time points in both trials, with greater increases in the caffeine trial (p < 0.05). Caffeine ingestion disrupts post-exercise autonomic recovery because of increased sympathetic nerve activity. The prolonged sympathetic recovery time could subsequently hinder baroreflex function during recovery and disrupt the stability of autonomic function, potentiating a pro-arrhythmogenic state in young adults.


The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.
The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.


Mental Rotation of Tactical Instruction Displays Affects Information Processing Demand and Execution Accuracy in Basketball.
In sports games, coaches often use tactic boards to present tactical instructions during time-outs (e.g., 20 s to 60 s in basketball). Instructions should be presented in a way that enables fast and errorless information processing for the players. The aim of this study was to test the effect of different orientations of visual tactical displays on observation time and execution performance. High affordances in visual-spatial transformation (e.g., mental rotation processes) might impede information processing and might decrease execution performance with regard to the instructed playing patterns. In a within-subjects design with 1 factor, 10 novice students were instructed with visual tactical instructions of basketball playing patterns with different orientations either showing the playing pattern with low spatial disparity to the players' on-court perspective (basket on top) or upside down (basket on bottom). The self-chosen time for watching the pattern before execution was significantly shorter and spatial accuracy in pattern execution was significantly higher when the instructional perspective and the real perspective on the basketball court had a congruent orientation. The effects might be explained by interfering mental rotation processes that are necessary to transform the instructional perspective into the players' actual perspective while standing on the court or imagining themselves standing on the court. According to these results, coaches should align their tactic boards to their players' on-court viewing perspective.


Predicting Short- and Long-Term Mating Orientations: The Role of Sex and the Dark Tetrad.
Previous literature has extensively considered factors that influence short- and long-term mating orientations, with specific attention given to individual differences (e.g., sex and personality). Although research has established the role "darker" personality traits (i.e., the dark triad) play in mating orientation, this triad has recently been reconceptualized as a tetrad. Due to this reconceptualization, the current study sought to establish the utility of sex and the dark tetrad in predicting individual short- and long-term mating orientations. In addition, as an alternative to previous methodology, the orientations were assessed using a continuous measure. A total of 464 participants, ages 18 to 69, completed an online questionnaire assessing dark tetrad traits and mating orientations. Results showed that sex, trait psychopathy, and trait sadism were significant predictors of a short-term mating orientation. For long-term mating orientations, there was no predictive utility of sex, but there were positive associations for narcissism and negative associations for psychopathy and sadism. These findings add further understanding of the predictors of mating orientation and the utility of the tetrad in predicting mating orientations. In addition, the findings offer future mating orientation studies an alternative measure to the traditional dichotomous format.


A Biochemometric Approach for the Identification of In Vitro Anti-Inflammatory Constituents in Masterwort.
Peucedanum ostruthium (L.) Koch, commonly known as masterwort, has a longstanding history as herbal remedy in the Alpine region of Austria, where the roots and rhizomes are traditionally used to treat disorders of the gastrointestinal and respiratory tract. Based on a significant NF-κB inhibitory activity of a P. ostruthium extract (PO-E), this study aimed to decipher those constituents contributing to the observed activity using a recently developed biochemometric approach named ELINA (Eliciting Nature's Activities). This -omics tool relies on a deconvolution of the multicomponent mixture, which was employed by generating microfractions with quantitative variances of constituents over several consecutive fractions. Using an optimized and single high-performance counter-current chromatographic (HPCCC) fractionation step 31 microfractions of PO-E were obtained. 1H NMR data and bioactivity data from three in vitro cell-based assays, i.e., an NF-ĸB reporter-gene assay and two NF-κB target-gene assays (addressing the endothelial adhesion molecules E-selectin and VCAM-1) were collected for all microfractions. Applying heterocovariance analyses (HetCA) and statistical total correlation spectroscopy (STOCSY), quantitative variances of 1H NMR signals of neighboring fractions and their bioactivities were correlated. This revealed distinct chemical features crucial for the observed activities. Complemented by LC-MS-CAD data this biochemometric approach differentiated between active and inactive constituents of the complex mixture, which was confirmed by NF-κB reporter-gene testing of the isolates. In this way, four furanocoumarins (imperatorin, ostruthol, saxalin, and 2'-O-acetyloxypeucedanin), one coumarin (ostruthin), and one chromone (peucenin) were identified as NF-κB inhibiting constituents of PO-E contributing to the observed NF-ĸB inhibitory activity. Additionally, this approach also enabled the disclose of synergistic effects of the PO-E metabolites imperatorin and peucenin. In sum, prior to any isolation an early identification of even minor active constituents, e.g. peucenin and saxalin, ELINA enables the targeted isolation of bioactive constituents and, thus, to effectively accelerate the NP-based drug discovery process.


Investigation of functional roles of transcription termination factor-1 (TTF-I) in HIV-1 replication.
Transcription termination factor-1 (TTF-I) is an RNA polymerase 1-mediated transcription terminator and consisting of a C-terminal DNA-binding domain, central domain, and N-terminal regulatory domain. This protein binds to a so-called 'Sal box' composed of an 11-base pair motif. The interaction of TTF-I with the 'Sal box' is important for many cellular events, including efficient termination of RNA polymerase-1 activity involved in pre-rRNA synthesis and formation of a chromatin loop. To further understand the role of TTF-I in human immunodeficiency virus (HIV)-I virus production, we generated various TTF-I mutant forms. Through a series of studies of the over-expression of TTF-I and its derivatives along with co-transfection with either proviral DNA or HIV-I long terminal repeat (LTR)-driven reporter vectors, we determined that wild-type TTF-I downregulates HIV-I LTR activity and virus production, while the TTF-I Myb-like domain alone upregulated virus production, suggesting that wild-type TTF-I inhibits virus production and trans-activation of the LTR sequence; the Myb-like domain of TTF-I increased virus production and trans-activated LTR activity. [BMB Reports 2018; 51(7): 338-343].


Comparison of neoadjuvant chemotherapy followed by surgery vs. surgery alone for locally advanced gastric cancer: a meta-analysis.
The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer, but the effects on safety and survival are still controversial. The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery (NACS) and surgery alone (SA) for locally advanced gastric cancer. Databases (PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar) were explored for relative studies from January 2000 to January 2021. The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale, respectively. The Review Manager software (version 5.3) was used to perform this meta-analysis. The overall survival was evaluated as the primary outcome, while perioperative indicators and post-operative complications were evaluated as the secondary outcomes. Twenty studies, including 1420 NACS cases and 1942 SA cases, were enrolled. The results showed that there were no significant differences in overall survival (P = 0.240), harvested lymph nodes (P = 0.200), total complications (P = 0.080), and 30-day post-operative mortality (P = 0.490) between the NACS and SA groups. However, the NACS group was associated with a longer operation time (P < 0.0001), a higher R0 resection rate (P = 0.003), less reoperation (P = 0.030), and less anastomotic leakage (P = 0.007) compared with SA group. Compared with SA, NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage. While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.


Norepinephrine stimulates the epithelial Na+ channel in cortical collecting duct cells via α2-adrenoceptors.
There is good evidence for a causal link between excessive sympathetic drive to the kidney and hypertension. We hypothesized that sympathetic regulation of tubular Na(+) absorption may occur in the aldosterone-sensitive distal nephron, where the fine tuning of renal Na(+) excretion takes place. Here, the appropriate regulation of transepithelial Na(+) transport, mediated by the amiloride-sensitive epithelial Na(+) channel (ENaC), is critical for blood pressure control. To explore a possible effect of the sympathetic transmitter norepinephrine on ENaC-mediated Na(+) transport, we performed short-circuit current (Isc) measurements on confluent mCCDcl1 murine cortical collecting duct cells. Norepinephrine caused a complex Isc response with a sustained increase of amiloride-sensitive Isc by ∼44%. This effect was concentration dependent and mediated via basolateral α2-adrenoceptors. In cells pretreated with aldosterone, the stimulatory effect of norepinephrine was reduced. Finally, we demonstrated that noradrenergic nerve fibers are present in close proximity to ENaC-expressing cells in murine kidney slices. We conclude that the sustained stimulatory effect of locally elevated norepinephrine on ENaC-mediated Na(+) absorption may contribute to the hypertensive effect of increased renal sympathetic activity.


Soil ecotoxicology in Latin America: Current research and perspectives.
Soils from some Latin American countries support the highest biodiversity levels on the planet and simultaneously have some of the most serious environmental impacts attributed to both historical and current agricultural practices and industrial activities. Soil contamination has resulted from intensive use of pesticides, extensive mining and other industrial activities, and uncontrolled management of waste within inappropriate regulatory frameworks. The present study presents an overview of the scientific research on soil ecotoxicology conducted in Latin America, summarizing the recent advances and highlighting the needs for further refinements in this research field. Most of the contributions to the scientific literature have been from Brazil. The most investigated issue is the ecotoxicity of pesticides and earthworms, which were the organisms most frequently used as test species. Needs identified by Latin American researchers include methods and procedures for: 1) identifying and collecting natural soils to be used as reference test-substrates in tests, 2) identifying and discerning the range of sensitivities of native test species to soil contaminants, 3) developing environmental guidelines applicable to tropical/subtropical conditions, and 4) developing methods and procedures for higher tier testing for full development and implementation of environmental risk assessment schemes. The protection of Latin American soils, including provision of goods and services, is currently framed in legislation and other regulations, but implementation requires significant improvement and additional training programs. Environ Toxicol Chem 2017;36:1795-1810. © 2017 SETAC.


Standardization of nasometry for normal Egyptian Arabic speakers.
The aim of this study was to collect the normative values of nasalance for Egyptian Arabic speakers in different age groups, using Arabic speech samples in order to compare patients with disturbed nasality. This study included 300 normal Egyptian volunteers divided into three groups according to their ages: group I = children (n = 92; age 3 years, 3 months to 9 years), group II = teenagers (n = 76; age 9-18 years) and group III = adults (n = 132; age above 18 years). The Nasometer II 6400 was used for the analysis of speech samples. All subjects were asked to perform four speech tasks that were based on the MacKay-Kummer SNAP Test-R and modified to be applicable to the Arabic language, especially to the Egyptian dialect. The normative values for nasometric assessment in the different age groups were studied. The results demonstrated nasalance score variations according to age and gender. Most of the nasalance score norms of the Egyptian children demonstrated statistically significant differences when compared with the norms of children for the MacKay-Kummer Test-R. The Egyptian Arabic SNAP test is an easy, noninvasive and objective procedure that is suitable for all age groups.


Inhibition of C. albicans Dimorphic Switch by Cobalt(II) Complexes with Ligands Derived from Pyrazoles and Dinitrobenzoate: Synthesis, Characterization and Biological Activity.
Seven cobalt(II) complexes of pyrazole derivatives and dinitrobenzoate ligands were synthesized and characterized. The single-crystal X-ray diffraction structure was determined for one of the ligands and one of the complexes. The analysis and spectral data showed that all the cobalt complexes had octahedral geometries, which was supported by DFT calculations. The complexes and their free ligands were evaluated against fungal strains of Candida albicans and emerging non-albicans species and epimastigotes of Trypanosoma cruzi. We obtained antifungal activity with a minimum inhibitory concentration (MIC) ranging from 31.3 to 250 µg mL-1. The complexes were more active against C. krusei, showing MIC values between 31.25 and 62.5 µg mL-1. In addition, some ligands (L1-L6) and complexes (5 and Co(OAc)2 · 4H2O) significantly reduced the yeast to hypha transition of C. albicans at 500 µg mL-1 (inhibition ranging from 30 to 54%). Finally, the complexes and ligands did not present trypanocidal activity and were not toxic to Vero cells. Our results suggest that complexes of cobalt(II) with ligands derived from pyrazoles and dinitrobenzoate may be an attractive alternative for the treatment of diseases caused by fungi, especially because they target one of the most important virulence factors of C. albicans.


Reconstitution of vesicle fusions occurring in endocytosis with a cell-free system.
We have used defined subcellular fractions to reconstitute in a cell-free system vesicle fusions occurring in the endocytic pathway. The endosomal fractions were prepared by immuno-isolation using as antigen an epitope located on a foreign protein, the transmembrane glycoprotein G (G-protein) of vesicular stomatitis virus. The G-protein was first implanted in the cell plasma membrane and subsequently endocytosed for 15 to 30 min at 37 degrees C. The endosomal fractions were immuno-isolated on a solid support using as antigen the cytoplasmic domain of the G-protein in combination with a specific monoclonal antibody. For comparative studies the plasma membrane was immuno-isolated from cells in the absence of G internalization with a monoclonal antibody against the exoplasmic domain of the G-protein. The immuno-isolated endosomal vesicles contained 70% of horseradish peroxidase internalized in the endosome fluid phase, exhibited an acidic luminal pH as shown by acridine orange fluorescence and differed in their protein composition from the immuno-isolated plasma membrane fraction. The fusion of endocytic vesicles originating from different stages of the pathway was studied in a cell-free assay using both a bio-chemical and a morphological detection system. These well defined endosomal vesicles were immuno-isolated with the G-protein on the solid support and provided the recipient compartment of the fusion (acceptor). They were mixed with a post-nuclear supernatant containing endosomes loaded with exogenous lactoperoxidase (donor) at 37 degrees C. Fusion delivered the donor peroxidase to the lumen of acceptor vesicles permitting fusion-specific iodination of the G-protein itself. The fusion of vesicles required ATP and was detected only with an endosomal fraction prepared after internalization of the G-protein for 15 min at 37 degrees C but not with a plasma membrane or with an endosomal fraction prepared after 30 min G-protein internalization.