Abscisic acid induced protection against photoinhibition of PSII correlates with enhanced activity of the xanthophyll cycle.
The exogenous application of abscisic acid (ABA) to barely seedlings resulted in partial protection of the PSII photochemistry against photoinhibition at low temperature, the effect being most pronounced at 10(-5) M ABA. This was accompanied by higher photochemical quenching (qP) in ABA-treated leaves. A considerable increase (122%) in the amount of total carotenoids and xanthophylls (antheraxanthin, violaxanthin and zeaxanthin) was also found in the seedlings subjected to ABA. The activity of the xanthophyll cycle measured by the epoxidation state of xanthophylls under high-light treatment was higher in ABA-treated plants compared with the control. This corresponds to a higher value (0.411) of non-photochemical quenching (qNP) observed in ABA-treated than in control (0.306) leaves.


Central effect of agents which alter sodium transport on water drinking in the rat.
The central effect of ouabain (OUA), ethacrynic acid (EA) and diphenylhydantoin (DPH) on water drinking was studied in rats. OUA and EA inhibit cellular Na efflux, increasing intracellular (IC) Na content, while DPH inhibits cellular Na influx lowering IC sodium content. The animals were injected into the third ventricle (3V), fourth ventricle (4V), lateral ventricle (LV), or lateral hypothalamus (LH). Ouabain (50 pg) and EA (50 ng) when injected into the 3V or LV significantly decreased the water intake induced by 24 hr water deprivation. No effect was observed after injections in other loci, thus supporting the hypothesis that sensors could be located in the circumventricular organs, in an area without the blood brain barrier. DPH (270 ng) injected into the 3V or LV significantly enhanced water intake in rats deprived of water for 14 hr, but it did not increase water intake in water-repleted rats. DPH also enhanced water intake induced by cellular-dehydration (2 M NaCl IP). These results suggest that changes in the Na content of sensor cells located on or near the walls of the 3V could be responsible for the movement of water between the cells and their medium, in agreement with the osmoreceptor hypothesis for thirst.


Staphylococcus aureus-derived peptidoglycan induces Cx43 expression and functional gap junction intercellular communication in microglia.
Gap junctions serve as intercellular conduits that allow the exchange of small molecular weight molecules (up to 1 kDa) including ions, metabolic precursors and second messengers. Microglia are capable of recognizing peptidoglycan (PGN) derived from the outer cell wall of Staphylococcus aureus, a prevalent CNS pathogen, and respond with the robust elaboration of numerous pro-inflammatory mediators. Based on recent reports demonstrating the ability of tumor necrosis factor-alpha and interferon-gamma to induce gap junction coupling in macrophages and microglia, it is possible that pro-inflammatory mediators released from PGN-activated microglia are capable of inducing microglial gap junction communication. In this study, we examined the effects of S. aureus-derived PGN on Cx43, the major connexin in microglial gap junction channels, and functional gap junction communication using single-cell microinjections of Lucifer yellow (LY). Exposure of primary mouse microglia to PGN led to a significant increase in Cx43 mRNA and protein expression. LY microinjection studies revealed that PGN-treated microglia were functionally coupled via gap junctions, the specificity of which was confirmed by the reversal of activation-induced dye coupling by the gap junction blocker 18-alpha-glycyrrhetinic acid. In contrast to PGN-activated microglia, unstimulated cells consistently failed to exhibit LY dye coupling. These results indicate that PGN stimulation can induce the formation of a functional microglial syncytium, suggesting that these cells may be capable of influencing neuro-inflammatory responses in the context of CNS bacterial infections through gap junction intercellular communication.


A continuous homologation of esters: an efficient telescoped reduction-olefination sequence.
A continuous protocol for the two-carbon homologation of esters to α,β-unsaturated esters is described. This multireactor homologation telescopes an ester reduction, phosphonate deprotonation, and Horner-Wadsworth-Emmons olefination, thus converting a three-operation procedure into a single, uninterrupted system that eliminates the need for isolation or purification of the aldehyde intermediates. The homologated products are obtained in high yield and selectivity.


Effects of treatment with a lithium-imipramine combination on components of adenylate cyclase in the cerebral cortex of the rat.
This study was aimed at investigating the effects of treatment with a lithium-imipramine combination on the activity of adenylate cyclase in membranes from the cerebral cortex of the rat. Treatment with (1) lithium for 2 weeks, yielding a level of lithium in serum of 0.54 +/- 0.12 mmol/l, (2) imipramine for 4 weeks (10 mg/kg i.p. twice per day) and (3) a combination of the two drugs reduced isoprenaline-induced stimulation of adenylate cyclase by GTP, with a greater decrement with the combined treatment. None of the treatments exerted any effect on the activity of the enzyme stimulated by GTP alone. Lithium ex vivo inhibited the calcium (Ca2+)- and Gpp(NH)p-stimulated activity of adenylate cyclase, but imipramine ex vivo did not affect the activity of adenylate cyclase, stimulated by these activators. The lithium-imipramine treatment reduced Ca2(+)- and Gpp(NH)p-stimulated activity of adenylate cyclase, but this was not different from that observed in the lithium-treated group. In conclusion, the beta-adrenoceptor-stimulated adenylate cyclase was affected markedly by administration of lithium and imipramine together. In contrast to lithium ex vivo, imipramine ex vivo did not impair the activity of either the guanine nucleotide regulatory protein or the catalytic subunit, since no change in activity was observed in the presence of beta,gamma-imidoguanosine-5' triphosphate (Gpp(NH)p) or Ca2+. Furthermore, lithium ex vivo exerted its post-receptor effects on the adenylate cyclase, independent of imipramine. The decrement in activity of beta-adrenergic adenylate cyclase, induced by administration of the two drugs together may partly be involved in the therapeutic action of the augmentation of antidepressants by lithium in refractory depression.


Comparison of electromagnetic and optical navigation assisted Endo-TLIF in the treatment of lumbar spondylolisthesis.
Uniportal full endoscopic posterolateral transforaminal lumbar interbody fusion (Endo-TLIF) with percutaneous pedicle screw fixation is a promising, minimally invasive method for the treatment of lumbar spondylolisthesis. However, repeated radiation exposure from X-rays and the steep learning curve remain to be improved.


Chromosomal organization and nucleotide sequence of the genes coding for the elongation factors G and Tu of the apple proliferation phytoplasma.
Genes coding for elongation factors G (fus) and Tu (tuf) of the non-culturable apple proliferation (AP) phytoplasma were cloned and sequenced. Arrangement of these genes and identification of the ribosomal protein gene rps7 upstream of the fus gene suggest a transcriptional organization similar to that of the streptomycin operon of Escherichia coli and other bacteria. The fus and tuf genes from other tested phytoplasmas were found to be similarly linked as in the AP agent. Thus, it is likely that they show a similar chromosomal arrangement. This organization would be in contrast to that of the phylogenetically distinctly different culturable mollicutes of the genus Mycoplasma in which the tuf and fus genes are separately transcribed.


A low-energy-gap organic dye for high-performance small-molecule organic solar cells.
A novel donor-acceptor-acceptor (D-A-A) donor molecule, DTDCTB, in which an electron-donating ditolylaminothienyl moiety and an electron-withdrawing dicyanovinylene moiety are bridged by another electron-accepting 2,1,3-benzothiadiazole block, has been synthesized and characterized. A vacuum-deposited organic solar cell employing DTDCTB combined with the electron acceptor C(70) achieved a record-high power conversion efficiency (PCE) of 5.81%. The respectable PCE is attributed to the solar spectral response extending to the near-IR region and the ultracompact absorption dipole stacking of the DTDCTB thin film.


The proto-oncogene/translation factor eIF4E: a survey of its expression in breast carcinomas.
The eukaryotic translation initiation factor eIF-4E binds to the cap structure of mRNAs as one component of the eIF-4 translation initiation complex, which mediates the recruitment of mRNA to the ribosomes. Overexpression of eIF-4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of growth-control gene products which are normally translationally repressed. Whereas the mechanism of eIF-4E-mediated transformation is being actively pursued, clinical investigations into the expression of eIF-4E in prevalent human cancers are lacking. We have recently initiated a screen of breast carcinomas by probing with eIF-4E antiserum. Using Western blots, we have analyzed the level of eIF-4E in 38 carcinomas, 7 normal samples and 3 fibroadenomas. We found that eIF-4E was elevated 3- to 10-fold in virtually all the carcinomas we analyzed, but not in fibroadenomas. This analysis was also confirmed by immunohistological staining in situ, showing that overexpression of eIF-4E can be readily identified at the single-cell level. Our results suggest that an elevation of eIF-4E may be an essential component in the development of breast cancer.


Vertical and horizontal inequality are status and power differences: applications to stereotyping by competence and warmth.
Status (respect, prestige) and power (resource control) arguably form two kinds of inequality. Status differences appear culturally reasonable as vertical inequality-with a common rationale: meritocracy (deservingness). High-status individuals and groups are accorded competence. Status differences divide people by inequality, but so do differences in power (sharing resource control). Power-sharing (or not) can be cooperative, peer interdependence, tending toward equality, or competitive rivalry, negative interdependence, tending toward inequality. This kind of (in)equality-power-sharing (or not)-theoretically differs from vertical status differences. Orientation to power-sharing thus is horizontal (in)equality. One end creates competitive friction among the distrusted and dissimilar. At the other end, horizontal equality creates mutual cooperation of the warm, similar, and familiar. Distinguishing status and power differences broadens inequality's scope.


Tetrandrine slows the radiographic progression of progressive massive fibrosis in pneumoconiosis: a retrospective cohort study.
This study aims to explore the clinical effect of Tetrandrine (Tet) on progressive massive fibrosis (PMF) of pneumoconiosis. This retrospective study collected 344 pneumoconiosis patients with PMF, and 127 were eligible for the final analysis, including 57 patients in the Tet group and 70 patients in the control group. The progress of imaging and lung function were compared between the two groups. After 13 months (median) of treatment, the size of PMF was smaller in the Tet group than that in the control group (1526 vs. 2306, p=0.001), and the size was stable in the Tet group (1568 vs. 1526, p= 0.381), while progressed significantly in the control group (2055 vs. 2306, p=0.000). The small nodule profusion and emphysema were also milder than that in the control group (6.0 vs. 7.5, p=0.046 and 8.0 vs. 12, p=0.016 respectively). Pulmonary ventilation function parameters FVC and FEV1 improved in the Tet group (3222 vs. 3301, p=0.021; 2202 vs. 2259, p=0.025 respectively) and decreased in the control group (3272 vs. 3185, p= 0.00; 2094 vs. 1981, p=0.00 respectively). FEV1/FVC was also significantly higher in the Tet group than that in the control group (68.45vs. 60.74, p=0.001). However, similar result was failed to observed for DLco%, which showed a significant decrease in both groups. Tet has shown great potential in the treatment of PMF by slowing the progression of pulmonary fibrosis and the decline of lung function.


Anti-IgE and Con A-induced histamine release from mast cells of four rat strains: correlation with total serum IgE.
Anti-IgE- and Con A-induced histamine release from serosal mast cells were compared to each other and to total serum levels of IgE in non-immunized, alum-injected, and Silica gel-injected rats of the BN, Fischer, PVG, and SD strains. The results indicate that the degree of anti-IgE- and Con A-induced release is strain-dependent and varies with immunization conditions. Furthermore, there is a gross but not complete correlation between the degree of serosal mast cell histamine release induced by the two secretagogues. However, Con A- or anti-IgE-induced release could significantly be correlated to serum levels of total IgE only in the Fischer strain but not in the BN or the PVG strains. In the SD strain, Con A-induced release correlated to serum IgE levels in Silica gel-injected but not in alum-injected animals.


Induction of oral tolerance in bone marrow transplantation recipients suppresses graft-versus-host disease in a semiallogeneic mouse model.
Graft-versus-host disease (GVHD) is the major obstacle for successful allogeneic stem cell transplantation (SCT). Morbidity and mortality are high, and novel therapeutic strategies are required. Current therapy, which is based mainly on immunosuppression, is associated with a high degree of complications. Immune hyporesponsiveness induced by oral antigen administration has recently been shown to prevent the development of chronic GVHD (cGVHD) in a murine model. The aim of the present study was to evaluate whether it is possible to induce tolerance and to alleviate GVHD in a semiallogeneic transplantation model in mice. GVHD was generated by infusing 2 x 10(7) splenocytes from C57BL/6 donor mice into (C57BL/6 x Balb/c)F1 recipient mice, which received 7 Gy (60)Co total body irradiation (TBI) prior to transplantation. Oral tolerance was induced by feeding recipient F1 mice with five oral doses of proteins, 50 micro g/mouse, extracted from C57BL/6 splenocytes on alternate days following transplantation. In vitro mixed lymphocyte reaction (MLR) from tolerized and nontolerized mice was performed. Recipient mice were followed for chimerism, and for clinical and histological parameters of GVHD. Induction of tolerance was documented by a significant reduction in MLR response of tolerated vs nontolerated splenocytes. A significant alleviation of the clinical and pathological manifestation of GVHD was observed in the liver, small bowel, and skin. Tolerance induction did not jeopardize engraftment. These results may constitute a step towards reducing the frequency of GVHD via manipulation of the immune system.


Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab.
The bispecific T cell engager blinatumomab has shown encouraging clinical activity in B-precursor acute lymphoblastic leukemia (ALL). However, about half of relapsed/refractory patients do not respond to therapy. Here, we present the case of a 32-year-old male patient with refractory B-precursor ALL who was resistant to treatment with blinatumomab. Bone marrow immunohistochemistry revealed T cell infiltrates and an increase in programmed death-ligand 1 (PD-L1)-positive ALL cells as a potential immune escape mechanism. We were able to recapitulate the clinical observation in vitro by showing that blinatumomab was not able to mediate cytotoxicity of CD19-positive ALL cells using autologous T cells. In contrast, the addition of healthy donor T cells led to lysis of ALL cells.These results strongly encourage further systematic evaluation of checkpoint molecules in cases of blinatumomab treatment failure and might highlight a possible mechanism to overcome resistance to this otherwise highly effective treatment.


Antimicrobial activity of amniotic fluid against Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum.
Amniotic fluids obtained by amniocentesis at 16 weeks to term were examined for the presence of Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum. Of 140 fluids tested, none harbored chlamydiae, and only one harbored mycoplasma, M. hominis. A number of amniotic fluids were subsequently tested for their ability to inhibit the growth of these microorganisms. Amniotic fluids and chlamydial suspensions in a 2:1 ratio were incubated 30 to 90 minutes before their inoculation in McCoy cells. Procedures were followed for chlamydial isolation. Genital mycoplasmas were incubated with amniotic fluid samples for 24 or 48 hours at 35 degrees C. Growth in amniotic fluid specimens was compared with growth in pseudoamniotic fluid and broth controls. Fourteen amniotic fluid specimens collected from gestations of 16 to 40 weeks, were found to be inhibitory to the formation of inclusions of C. trachomatis in McCoy cells. Ten amniotic fluid specimens (16 to 39 weeks, gestation) demonstrated various degrees of inhibition against M. hominis, and three fluids were inhibitory to the growth of Ureaplasma. The inhibitor was heat and protease resistant and activity was proportional to concentration. The molecular weight of the inhibitor was probably greater than 10,000 daltons, and pH, although perhaps a contributing factor, was not the cause of the inhibition.


Addressing poor nutrition to promote heart health: moving upstream.
Current dietary recommendations for cardiovascular disease prevention suggest dietary patterns that promote achieving healthy weight, emphasize vegetables, legumes, fruit, whole grains, fish and nuts, substituting mono-unsaturated fats for saturated fats and restricting dietary sodium to less than 2300 mg/day. However, trends in nutrient intake and food consumption patterns suggest that the need for improvement in the dietary patterns of Canadians is clear. Influencing eating behaviour requires more than addressing nutrition knowledge and perceptions of healthy eating - it requires tackling the context within which individuals make choices. A comprehensive approach to improving nutrition includes traditional downstream strategies such as counselling to improve knowledge and skills; midstream strategies such as using the media to change social norms; and upstream strategies such as creating supportive environments through public policy including regulatory measures. While the evidence base for more upstream strategies continues to grow, key examples of comprehensive approaches to population change provide a call to action.


Liver function markers and haematological dynamics during acute and chronic phases of experimental Fasciola hepatica infection in cattle treated with triclabendazole.
Fasciola hepatica, a worldwide-distributed liver fluke, is one of the causative agents of fasciolosis, a zoonotic disease that affects livestock and humans. In livestock, fasciolosis causes huge economic losses worldwide, reducing animal fertility, milk production, weight gain and condemnation of livers. In spite of the availability of drugs, such as triclabendazole (TCZ), for the treatment of fasciolosis, they do not necessarily prevent liver damage or parasite reinfection and can eventually increase parasite resistance. The aim of this research was to relate the hepatic function, haematological parameters, leukocyte counts in circulation and parasite egg shedding during F. hepatica acute and chronic phases of infection in cattle as well as to determine how these parameters change with TCZ-treatment of chronically infected cattle. Our results show that increased levels of serum aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) were detected in early stages of the experimental infection. Moreover, high circulating eosinophil count and plateletcrit levels were correlated with fluke number in livers from infected cattle. On the other hand, although TCZ-treatment in the chronic phase of infection reduced parasite burden and damage in the liver, it was not able to completely avoid them. In conclusion, our work sheds light into the physiopathological mechanisms induced during fluke infection in cattle, revealing the complexity of the host response to the infection, together with the effects of TCZ-treatment in chronically infected animals.


Rab GTPases in vesicular transport.
Specificity and directionality are two features shared by the numerous steps of membrane transport that connect cellular organelles. By shuttling between specific membrane compartments and the cytoplasm, small GTPases of the Rab family appear to regulate membrane traffic in a cyclical manner. The restriction of certain Rab proteins to differentiated cell types supports a role for these GTPases in defining the specificity of membrane trafficking.


Spontaneous Intracranial Hypotension: Pathogenesis, Diagnosis, and Treatment.
Spontaneous intracranial hypotension (SIH) is a clinical syndrome that is increasingly recognized as an important and treatable secondary cause of headaches. Insight into the condition has evolved significantly over the past decade, resulting in a greater understanding of the underlying pathophysiology, development of new diagnostic imaging tools, and a broadening array of targeted treatment options. This article reviews the clinical presentation and pathogenesis of SIH, discusses the important role of imaging in diagnosis, and describes how imaging guides treatment.


Regulation of macrophage migration and activity by high-mobility group box 1 protein released from periodontal ligament cells during orthodontically induced periodontal repair: an in vitro and in vivo experimental study.
Recent studies have shown that periodontal ligament (PDL) cells interact with macrophages from the immune system during orthodontically induced repair of periodontal tissue. Hypothesizing that high-mobility group box 1 (HMGB1) protein is released by mechanically stressed PDL cells into the extracellular space and has a role in mediating the local immune response by acting as an "alarmin", this study was performed to further elucidate these cellular interactions, with a special focus on the impact of proinflammatory mediators secreted by PDL cells on macrophage physiology. The study included an in vivo part in which orthodontic stress was induced in rats and their PDL analyzed for expression of HMGB1 by immunohistochemistry after 5 days of tooth movement. In the in vitro part, human PDL cells were subjected to compressive loading, followed by stimulating human macrophages with conditioned supernatants of these stressed PDL cells and analyzing how mediators that had been released by these cells into the medium would impact macrophage physiology. Assays for macrophage migration and osteoclast differentiation were used in addition to immunohistochemistry, enzyme-linked immunosorbent assays, and western blotting. Induction of mechanical stress was found to upregulate HMGB1 expression both in vivo and in vitro. At the same time, translocation HMGB1 from nuclei into cytoplasm was observed. Culturing macrophages in conditioned PDL cell medium was associated with enhanced chemotactic migration and osteoclast differentiation. Addition of anti-HMGB1 antibodies to inhibit HMGB1 in the conditioned medium was found to significantly attenuate these effects. A less marked increase of migration and osteoclast differentiation by macrophages was observed after isolated addition of HMGB1, at its observed pathological concentration, to nonconditioned medium. This study clearly indicates an immunomodulatory potential of human PDL cells via release of mediators, including HMGB1 protein. Our finding that these mediators modify the migration and differentiation of macrophages as a function of periodontal repair during orthodontic treatment broadens the theoretical basis toward developing interventional strategies to avoid orthodontically induced root resorption.


Chondroitinase ABC promotes functional recovery after spinal cord injury.
The inability of axons to regenerate after a spinal cord injury in the adult mammalian central nervous system (CNS) can lead to permanent paralysis. At sites of CNS injury, a glial scar develops, containing extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to axon growth in vitro, and regenerating axons stop at CSPG-rich regions in vivo. Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity. To test the functional effects of degrading chondroitin sulphate (CS)-GAG after spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned dorsal columns of adult rats. We show that intrathecal treatment with ChABC degraded CS-GAG at the injury site, upregulated a regeneration-associated protein in injured neurons, and promoted regeneration of both ascending sensory projections and descending corticospinal tract axons. ChABC treatment also restored post-synaptic activity below the lesion after electrical stimulation of corticospinal neurons, and promoted functional recovery of locomotor and proprioceptive behaviours. Our results demonstrate that CSPGs are important inhibitory molecules in vivo and suggest that their manipulation will be useful for treatment of human spinal injuries.


Estimation of antibody levels after COVID-19 vaccinations: Preliminary evidence for immune interoception.
To date, 72 % of the world's population has received at least one COVID-19 vaccination. The number of antibodies produced by some individuals is exponentially higher than in others, for various mostly unknown reasons. This variation causes great diversity in the future susceptibility to infection by the original or variants of the SARS-CoV-2 virus. The following study investigated whether individuals were able to estimate the strength of their antibody response after their COVID-19 vaccinations. 166 recently vaccinated participants provided a blood sample for determination of antibody titers. Participants were asked to estimate how many antibodies they thought they had produced, and were further asked how protected they felt from COVID-19 due to vaccination. Both self-rated antibody levels, and feelings of protection against COVID-19 were significantly related to their actual IgG spike antibody titers, after controlling for age, days since vaccination, BMI and cross vaccination. These results suggest that individuals may have a form of "immune interoception" which relates to their response to their COVID-19 vaccination.


Social inequality in premature mortality among Polish urban adults during economic transition.
Rates of premature mortality among adults are important measures of the economic and psychosocial well-being of human populations. In many countries, such rates are, as a rule, inversely related to the level of attained education. We examined changes in educational group-specific mortality rates among urban adults in Poland during the country's rapid transition in the 1990s from a socialist command economy to a free market system. Two census-based analyses of individual death records of urban dwellers aged 35-64 years were compared. We utilized all records of death, which occurred during the 2-year periods 1988-89 and 2001-02. Population denominators were taken from the censuses of 1988 and 2002. The age-specific mortality rates were used to evaluate absolute differences in mortality. To assess relative differences between educational levels, mortality rate ratios (MRRs) with 95% CI (confidence interval) were calculated using Poisson regression. A regular educational gradient in mortality persisted in each 10-year age group throughout the period covered by our data. Moreover, age-specific mortality rates declined steadily in all educational groups, and this decline was most marked in the two oldest age groups (45-54 and 55-64 years). The trend was accompanied by widening of educational differences in mortality as expressed by MRRs. Systemic political transformation in Poland has brought a mixture of beneficial and detrimental effects on the well-being of society. With regard to the changes in rates of premature mortality among adults, the benefits have prevailed, although individuals with the lowest educational level benefited less than those with the highest education.


Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail: a post hoc analysis.
The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants METHODS: We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models. Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82-0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80-0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87-0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82-0.99) p = 0.028]. These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk. https://www.clinicaltrials.gouv . Unique Identifier NCT01394952).


Isolation and characterization of human and mouse WDR19,a novel WD-repeat protein exhibiting androgen-regulated expression in prostate epithelium.
Androgens regulate important processes involved in the normal development and function of the human and rodent prostate glands. Here we report the isolation and characterization of a new androgen-regulated gene, designated WDR19, that encodes repeating sequence motifs found in the WD-repeat family of proteins. The WD repeat is a conserved domain of approximately 40 amino acids that is typically bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. WD-repeat proteins are a large group of structurally related proteins that participate in a wide range of cellular functions, including transmembrane signaling, mRNA modification, vesicle formation, and vesicular trafficking. The WDR19 gene comprises 36 exons and is located on chromosome 4p15-4p11. The predicted protein contains six WD repeats, a clathrin heavy-chain repeat, and three transmembrane domains. Sequence analysis reveals that the WDR19 gene is conserved from Caenorhabditis elegans to human. WDR19 is expressed in normal and neoplastic prostate epithelium as demonstrated by RNA in situ hybridization and is regulated by androgenic hormones. WDR19 transcripts exhibit alternative splicing in which two isoforms appear to be prostate restricted, a property that could be exploited for designing diagnostic or therapeutic strategies for prostate carcinoma.


Oral uracil-tegafur compared with intravenous chemotherapy as adjuvant therapy for resected early-stage non-small cell lung cancer patients.
Studies comparing the effectiveness of either adjuvant oral uracil-tegafur (UFT) or intravenous chemotherapy on early-stage (stage I and II) non-small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited. From January 2011 to December 2017, patients with early-stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse-free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders. A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49-0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61-0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score-matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48-1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72-1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non-drinker (HR: 0.66, 95% CI: 0.34-0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42-0.97, p = 0.0341). This population-based study in the real-world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early-stage NSCLC patients after surgery.


Ecological differences and competitive interaction between Drosophila melanogaster and Drosophila simulans in small laboratory populations.
In interspecific competition studies, some cases of apparent change in competitive ability have been reported. But the change in competitive outcome could equally well be due to character displacement. As a preliminary to studies of the effects of association of D. melanogaster (yellow white mutant strain) and D. simulans (vermilion mutant strain), the nature and extent of ecological differences between them, and the nature of their competitive interaction was studied. Differences between the strains were shown for oviposition site preferences, and for larval and pupal distribution. In pure species cultures, simulans showed a greater preference than melanogaster for oviposition in the center of the medium surface. In mixed populations, simulans had an increased preference for this oviposition site, where melanogaster was at low frequency. D. simulans larvae utilized the lower half of the medium to a significantly greater extent than did melanogaster. At low density (5 pairs of parents) in pure species cultures, 68.7% of simulans pupae were on the medium surface. As parental numbers increased, this proportion decreased. The distribution of melanogaster pupae was quite different, with only 8 to 12% on the medium at all densities. But the remaining pupae tended to occur higher on the cylinder wall as parental numbers increased. The competitive interaction changed during the developmental period. At four and eight days after culture initiation, simulans appeared superior, while for total adult progeny production, melanogaster was slightly superior. These strans of the two species were not ecologically equivalent.


Proteomic analysis of the effect of hemin in breast cancer.
Heme, an iron-containing prosthetic group found in many proteins, carries out diverse biological functions such as electron transfer, oxygen storage and enzymatic reactions. Hemin, the oxidised form of heme, is used to treat porphyria and also to activate heme-oxygenase (HO) which catalyses the rate-limiting step in heme degradation. Our group has previously demonstrated that hemin displays antitumor activity in breast cancer (BC). The aim of this work has been to study the effect of hemin on protein expression modifications in a BC cell line to gain insight into the molecular mechanisms of hemin antitumor activity. For this purpose, we carried out proteome analysis by Mass Spectrometry (MS) which showed that 1309 proteins were significantly increased in hemin-treated cells, including HO-1 and the proteases that regulate HO-1 function, and 921 proteins were significantly decreased. Furthermore, the MS-data analysis showed that hemin regulates the expression of heme- and iron-related proteins, adhesion and cytoskeletal proteins, cancer signal transduction proteins and enzymes involved in lipid metabolism. By biochemical and cellular studies, we further corroborated the most relevant in-silico results. Altogether, these results show the multiple physiological effects that hemin treatment displays in BC and demonstrate its potential as anticancer agent.


Treatment delay and reperfusion management of acute ST-segment elevation myocardial infarction: analysis of the China STEMI Care Project Phase 1.
The China ST-segment elevation myocardial infarction (STEMI) Care Project (CSCAP) was launched in 2011 to address the problems of insufficient reperfusion and long treatment delay in STEMI care in China. To describe the baseline status of STEMI emergency care in Tertiary PCI Hospitals using Phase 1 (CSCAP-1) data. CSCAP-1 is a prospective multi-center STEMI registry. A total of 4191 patients with symptom onset within 12 or 12-36 h requiring primary percutaneous coronary intervention (PCI), were enrolled from 53 tertiary PCI hospitals in 14 provinces, municipalities, and autonomous regions of China in CSCAP-1. Among them, 49.0% were self-transported to the hospital, 26.5% were transferred to the hospital by calling the emergency medical services directly, and 24.5% were transferred from other hospitals. In patients with symptom onset within 12 h, 83.2% received primary PCI, 5.9% received thrombolysis and 10.9% received conservative medications. The median door-to-balloon time was 115 (85-170) min and the median door-to-needle time for in-hospital thrombolysis was 80 (50-135) min. The overall in-hospital all-cause mortality was 2.4%, while it was 5.3% in the non-reperfusion group and 2.1% in the reperfusion group (P < 0.001). Although a long treatment delay and a high proportion of patients transporting themselves to the hospital were observed, trends were positive with greater adoption of primary PCI and lower in-hospital mortality in tertiary hospitals in China. Our results provided important information for further integrated STEMI network construction in China.


Association of COL1A2 (PvuII) gene polymorphism with risk and severity of dental fluorosis - A case control study.
Dental fluorosis is a foremost public health problem in many countries, including India. Very few studies investigated gene polymorphism and risk of dental fluorosis. Genetic polymorphisms in Collagen Type I, alpha 2 (COL1A2) gene, found to be linked with bone pathogenesis, may affect the tooth formation resulting in the vulnerability to dental fluorosis. To assess the association between COL1A2 (PvuII) gene polymorphism and risk as well as severity of dental fluorosis. The present case control study was conducted among participants with (n = 60) and without (n = 60) dental fluorosis. Dental fluorosis was assessed using Modified Dean's fluorosis index (1942). The PvuII polymorphisms (in exon 25) inside the COL1A2 gene were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) procedure. Statistical analysis were carried out with Chi-square test and Odds Ratio (OR) was determined with multivariate logistic regression analysis. The genetic polymorphism in COL1A2 PvuII was found to be associated with the risk of dental fluorosis which was highly significant (p < 0.001). The odds ratio was 31.4 times [OR = 31.9, 95% CI: 3.9-48.7] higher for the homozygous PP genotype group and 4.0 times [OR = 4.0, 95% CI: 1.0-10.7] higher for the heterozygous Pp genotype. Genetic polymorphism of COL1A2 was found to be associated with dental fluorosis. The present study provides an insight for identification of the population who may subsist at risk of developing dental fluorosis in their later life.


The comet assay for the evaluation of gut content genotoxicity: Use in human studies as an early biomarker of colon cancer risk.
This short narrative review describes the use of the comet assay to evaluate the formation of genotoxic compounds in the gut lumen in human studies. The fecal water genotoxicity assay is based on ability of the gut content to induce genotoxicity in a cellular model, employing the aqueous component of the feces (fecal water) as this is supposed to contain most of the reactive species and to convey them to the intestinal epithelium. This non-invasive and low-cost assay has been demonstrated to be associated with colon cancer risk in animal models, and although the final validation against human tumors is lacking, it is widely used as a colo-rectal cancer risk biomarker in human nutritional intervention studies. The contribution given to the field of nutrition and cancer by the FW genotoxicity assay is highlighted, particularly in conjunction with other risk biomarkers, to shed light on the complex relationship among diet, microbiota, individual subject characteristics and the formation of genotoxic compounds in the gut.


Conversion of Lactobacillus pentosus D-lactate dehydrogenase to a D-hydroxyisocaproate dehydrogenase through a single amino acid replacement.
The single amino acid replacement of Tyr52 with Leu drastically increased the activity of Lactobacillus pentosus NAD-dependent D-lactate dehydrogenase toward larger aliphatic or aromatic 2-ketoacid substrates by 3 or 4 orders of magnitude and decreased the activity toward pyruvate by about 30-fold, converting the enzyme into a highly active D-2-hydroxyisocaproate dehydrogenase.


Pharmacokinetics of di-isononyl phthalate in freely moving rats by UPLC-MS/MS.
Di-isononyl phthalate (DINP) is a general-purpose plasticizer for polyvinyl chloride. However, this industrial chemical plasticizer used as a clouding agent has recently contaminated food and beverages that had been inspected by Taiwan Food and Drug Administration. This study develops a sensitive and specific method combining ultra-performance liquid chromatography with electrospray ionization tandem mass spectrometry (UPLC-MS/MS) to investigate the pharmacokinetics of DINP in freely moving rats. Multiple reaction monitoring (MRM) was used to monitor the transition of the protonated molecule m/z of 419 [M+H](+) to the product ion 149 for DINP. The analyte was analyzed by UPLC-MS/MS with C18 column (100×2.1mm, 1.7 μm) which was equilibrated and eluted with an isocratic mixture of acetonitrile-ammonium acetate water solution (90:10, v/v) at a flow rate of 0.3 mL/min. Linear calibration curves were obtained for DINP concentration ranges of 0.05-2.5 μg/mL in plasma and feces. The feces were homogenized mechanically using 50% acetonitrile as the medium. The pharmacokinetic curve demonstrates that the disposition of DINP in rat plasma was fitted well by the two-compartment model after DINP administration (10 mg/kg, i.v.). The elimination half-life of DINP was 364±146 min and 150±58 min for intravenous (10 mg/kg) and oral (100 mg/kg) administration, respectively. The pharmacokinetic data indicate that the oral bioavailability of DINP in freely moving rats was about 1.19%. The total DINP excretion up to 48 h was 13.64±3.99% in feces.


Characterization of phosphatidate phosphohydrolase activity associated with isolated lamellar bodies.
It has been demonstrated that lamellar bodies isolated from porcine lung have L-alpha-phosphatidate phosphohydrolase (EC 18.104.22.168) activity which cannot be accounted for by microsomal or mitochondrial contamination. Phosphatidate phosphohydrolase activity associated with the lamellar bodies is relatively insensitive to Mg2+ and more heat labile than the activity associated with whole lung microsomes. The enzyme was found to be the most active phosphohydrolase present in isolated lamellar bodies and is inhibited by 5 mM Be2+. Lamellar bodies isolated from human and rat lung tissue were also found to have this activity, and the functional role of the enzyme in lamellar bodies is proposed in relation to glycerophospholipid metabolism.


High-performance liquid chromatographic determination of lamivudine in human serum using liquid-liquid extraction; application to pharmacokinetic studies.
A simple, fast, and sensitive high performance liquid chromatographic (HPLC) assay was developed for quantitation of lamivudine in human serum. Lamivudine is polar compound and its extraction from the human serum in previously published HPLC methods involved either protein precipitation or solid phase extraction techniques. However, existence of endogenous peaks which interfere with the drug or appeared as late eluting peaks and lead to long run time of analysis has been reported. Application of either an ion pairing agent in the mobile phase or time consuming column purge has been used in the published methods. Present paper describes liquid - liquid extraction of lamivudine and internal standard (famotidine) using dichloromethane-isopropyl alcohol (1:1, v/v) as an extracting solvent and salting out approach. The mobile phase was a mixture of phosphate buffer (0.05 M) containing triethylamine (1 mL/L, v/v; pH 3.5) and methanol (91:9, v/v) at a flow rate of 2.2 mL/min. The analysis was performed on a column (150 mm x 6 mm i.d.) which was packed with 5 microm particles of ODS packing material. Under these conditions no interference in the assay from any endogenous substance was observed. The limit of quantification was evaluated to be 5 ng/mL. Accuracy and precision of the method were also studied and the technique was shown to be selective and linear into the concentration range of 5-2500 ng/mL. This method has been used in two randomized crossover bioequivalence studies of 100 and 150 mg lamivudine preparations in 12 and 24 healthy volunteers, respectively.


Relationship between penicillin and cephalosporin resistance of Streptococcus pneumoniae strains and its inflammatory activity in the experimental model of meningitis.
Using a rabbit model of meningitis, we sought to compare the inflammatory activity induced by three pneumococcal strains with different susceptibilities to penicillin and cephalosporins, belonging to the serotypes 3, 6B and 23F at different inoculum sizes. These serotypes are prevalent in Western Europe and are believed to produce a moderate-to-severe cerebrospinal fluid (CSF) inflammatory response. Only minor differences were observed in the inflammatory activity evoked by the three strains in the subarachnoid space, and most were probably related to differences in bacterial counts. Infection by serotype 23F caused secondary bacteremia in all challenged animals. Our findings reinforce the concept that resistant pneumococci are not more virulent, a fact that should be taken into account when evaluating the efficacy of different anti-pneumococcal therapies. However, the frequent induction of secondary bacteremia by the resistant serotype 23F requires further study.


Utilization of oil palm biodiesel solid residue as renewable sources for preparation of granular activated carbon by microwave induced KOH activation.
In this work, preparation of granular activated carbon from oil palm biodiesel solid residue, oil palm shell (PSAC) by microwave assisted KOH activation has been attempted. The physical and chemical properties of PSAC were characterized using scanning electron microscopy, volumetric adsorption analyzer and elemental analysis. The adsorption behavior was examined by performing batch adsorption experiments using methylene blue as dye model compound. Equilibrium data were simulated using the Langmuir, Freundlich and Temkin isotherm models. Kinetic modeling was fitted to the pseudo-first-order, pseudo-second-order and Elovich kinetic models, while the adsorption mechanism was determined using the intraparticle diffusion and Boyd equations. The result was satisfactory fitted to the Langmuir isotherm model with a monolayer adsorption capacity of 343.94mg/g at 30°C. The findings support the potential of oil palm shell for preparation of high surface area activated carbon by microwave assisted KOH activation.


Primary hepatocellular carcinoma in Australia: Aetiological considerations.
This is a study of aetiological associations in patients with primary hepatocellular carcinoma (PHC). Thirty new patients with PHC were seen in a five-year period. The most common aetiological association was alcoholic cirrhosis. This was implicated in the development of PHC in 13 patients. However, since the introduction of radioimmunoassay for hepatitis B surface antigen (HBsAg) there have been six patients with HBsAg-associated PHC. Thus, for the first time, an association of hepatitis B virus with PHC is described in this country.


Removal of petroleum sulfonate from aqueous solutions using freshly generated magnesium hydroxide.
Freshly generated magnesium hydroxide (FGMH), produced by adding water-soluble magnesium salts to highly alkaline solutions, was used to remove anionic surfactant petroleum sulfonate (PS) from aqueous solutions. Adsorption experiments were carried out to investigate the effects of pH, adsorbent dosage, contact time, PS concentration, and temperature. The results showed that FGMH displayed excellent treatment efficiency for PS in the pH range 12.0-13.0. The maximum PS removal efficiency was reached within 60 s. The best dosage of magnesium chloride was 2.0 g/L. The adsorption capacity of FGMH for PS decreased as the temperature increased from 303 K to 333 K. The adsorption process was exothermic. The removal mechanism of PS by FGMH may be a coagulation-adsorption process involving a combination of flocculation, adsorption, charge neutralization, and netting catch affection. The results of this study showed that FGMH can be effectively used to treat surfactant wastewaters.


Age and cell density dependent changes of gangliosides in human diploid fibroblasts.
The gangliosides in human diploid fibroblasts--TIG-1, TIG-7, and IMR-90--were analysed at different cell densities at early and late passages to clarify the relationship between age and cell density dependent changes of the gangliosides. In early passages, the ganglioside concentrations increased with increase in cell density. At late passages, however, the concentrations were lower than those at the early passages either in the growing or confluent phase, and slightly increased with increase in cell density. The pattern of ganglioside compositions were apparently different between early and late passage cells either in growing or confluent state. In the early passages, GM3 and GD3 were major constituents, and GM2, GD1a, or the other more complex gangliosides were detected as minor components. With increase in cell density, the content of GM3 decreased, whereas GD3 and the others increased. At the late passages, however, GM3 was the major component, and GD3, GM2, or GD1a were minor, but the others were hardly detectable. The ganglioside pattern did not change with increase in cell density. Thus, the age-dependent changes of gangliosides could be distinguished from the cell density dependent alterations.


VO2max (VO2peak) in elite athletes under high-intensity interval training: A meta-analysis.
Consensus is lacking regarding whether high-intensity interval training (HIIT) effectively improves VO2max (VO2peak) in elite athletes (Athlete must be involved in regular competition at the national level). This meta-analysis compared the effects of HIIT and conventional training methods (continuous training, repeated-sprint training, high volume low-intensity training, high-intensity continuous running, sprint-interval training, moderate-intensity continuous training)on VO2max in elite athletes. Nine studies were included, comprising 176 elite athletes (80 female). Compared to that with conventional training, VO2max was significantly increased after HIIT (overall: 0.58 [0.30, 0.87], I2 = 0.49, P = 0.03; males: 0.41 [0.06, 0.76], I2 = 0%, P = 0.89). VO2max had positive training effects when the HIIT recovery period had an interval time ≥2 min (0.44 [0.03, 0.84], I2 = 0%, P = 0.99) and recovery phase intensity ≤40% (0.38 [0.05, 0.71], I2 = 0%, P = 0.96). Thus, HIIT shows superiority over conventional training methods in improving VO2max, promoting aerobic capacity, in elite athletes.


Individuals Matter: Dilemmas and Solutions in Conservation and Animal Welfare Practices in Zoos.
Compassionate conservation advocates for minimizing individual suffering in conservation practice and adheres to the principle "individuals matter"-intrinsically, in and of themselves. Our objective is to determine the extent to which, and how, zoos recognize the intrinsic value of wild individuals beyond their status as members of species or ecosystems. We analyzed discourses surrounding the Smithsonian National Zoo in the U.S.A., the zoos of the Muséum National d'Histoire Naturelle in France, and the Seoul Grand Park Zoo in South Korea. Using existing literature on zoos, conservation, animal welfare, and rights, we distilled two discourses (justificatory and abolitionist). Through interviews with professionals in the zoo, conservation, welfare, and animal rights communities, we demonstrate how actors frame individual zoo animals as (1) sentient persons, (2) reproductive components, and (3) species ambassadors. Our analysis shows how actors' views shape three zoo practices related to ex situ conservation: (1) captivity, (2) captive breeding, and (3) culling. This analysis revealed two significant findings. First, actors representing the justificatory discourse fail to frame animals as intrinsically valuable individuals. Second, within the constraints of the zoo, the intrinsic value of individual animals is recognized through welfare practices and education focused on fulfilling animal interests.


Green investment, institutional quality, and environmental performance: evidence from G-7 countries using panel NARDL approach.
The foremost purpose of the study is to establish a point that an economy of G-7 countries has an abundance of resources to tackle the environmental changes that occur in the world, but these countries are still behind the line because in this modern era, environmental performance changes their shape, dimension, and nature very frequently and create a huge impact on globalization of world economy. To fill this gap, we use green investment, institutional quality, and economic growth on environmental performance for this, we use four proxies for green investment and three proxies for greenhouse gas, and we also use six proxies of institutional quality to do this using period of 1997 to 2021. Moreover, we have used the panel nonlinear autoregressive distributed lag method to evaluate the long-run and short-run asymmetric effects of green investment, institutional quality, and economic growth on greenhouse gas emissions. The findings of the study affirm that the positive change of green investment has a positive and significant relationship with environmental performance, while the negative change of green investment has a significant and positive influence with environmental performance in the long run. Furthermore, the outcomes demonstrate that the positive shock of institutional quality has a positive and significant relationship with environmental performance, while the negative shock of intuitional quality has a significant and positive association with environmental performance in the long run, whereas positive change in economic growth has a positive and significant with the environmental performance, while the negative change of economic growth has a positive effect with environmental performance in the long run. This study finds future precautions that institutional quality has to perform exceptionally and shows results very rapidly, while green investment with economic growth has also made a deadly combination to control greenhouse gas emission, so the role of G-7 countries is pretty clear and straight. Furthermore, it is suggested that governments and policymakers take a proactive stance to promote resource acquisition and investment across all industries. To reduce gas emissions, public interest might also be complementary to private ones. So, economic policymakers, specifically in G-7 countries, should consider strategies that support sustainable economic growth.


The stimulation of bone growth by ultrasound.
The ultrasonic stimulation of bone growth was investigated in an experimental work in which a set of 45 rabbits were studied according to the following procedure: a) bilateral osteotomy of fibula (23 animals) and bilateral drilled holes on the cortex of femur (22 animals); b) exposure of ultrasound for 15 min per day. c) Radiological and histological evaluations of the progress of the callus; d) photography and measurements of the area of the callus; e) graphical comparisons using the results between controls and stimulated limbs. Pulsed ultrasound, in the form of short bursts, was used at low intensities (below cavitation threshold) so that the temperature variation, at the osteotomy site, was of the order of 0.01 degrees C (constant) a fact that reinforces the assumption that the stimulation mechanism due to the appearance of electric potentials is of non-thermal origin such as that caused by piezoelectricity.


Acetylcholine release in the cat caudate nucleus measured with the choline oxidase method.
A chemiluminescent assay for the estimation of acetylcholine (ACh) was used to measure ACh release in caudate nuclei (CN) of halothane-anaesthetized cats implanted with push-pull cannulae. The validity of the entire experimental approach used was shown by the fact that ACh release was calcium-dependent and was increased by depolarizing agents (potassium ions, veratridine) as well as by atropine. The effects of GABA (10(-5) M, 30 min) unilateral application into the ventralis medialis and ventralis lateralis thalamic nuclei on ACh release in both CN were then examined. This treatment, known to increase DA release bilaterally, decreased ACh release in both CN. These data further reveal the role of thalamic nuclei in the bilateral regulation of the activity of neurons identified within the basal ganglia and are discussed in the light of the well-known inhibitory influence of nigrostriatal DA neurons on striatal cholinergic neurons.


A laboratory study of changes in vertical dimension using a compression molding and a pour resin technique.
A controlled investigation was conducted to compare the increase in vertical dimension of complete dentures after processing with a compression molding technique and with a pour resin technique. The smallest increase in vertical dimension of occlusion was obtained with the compression molding technique.


In vitro binding and internalization of HIV envelope glycoproteins by human epidermal Langerhans cells does not require the CD4-gp120-binding site.
Langerhans cells (LC) are epidermal dendritic cells which express several surface antigens, among them the CD4 antigens. Recent data demonstrated that LC constitute target and storage cells for HIV. To better understand the interactions between HIV and LC, we investigated, in the present work, the fate of HIV envelope glycoproteins (gp120 and gp160) incubated with healthy human trypsinized LC in suspensions. After trypsin treatment, only the epitope for OKT4 appeared to be resistant on LC. In the absence of antigenic sites identified by OKT4A, Leu3a or BL4 (epitopes implicated in HIV binding), LC bound and internalized recombinant HIV gp120 or gp160. This finding supports the hypothesis that there exists at the surface of LC a second molecule which may act as an HIV receptor.


Evidence for in vitro and in vivo expression of the conserved VAR3 (type 3) plasmodium falciparum erythrocyte membrane protein 1.
Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion antigen family are major contributors to the pathogenesis of P. falciparum malaria infections. The PfEMP1-encoding var genes are among the most diverse sequences in nature, but three genes, var1, var2csa and var3 are found conserved in most parasite genomes. The most severe forms of malaria disease are caused by parasites expressing a subset of antigenically conserved PfEMP1 variants. Thus the ubiquitous and conserved VAR3 PfEMP1 is of particular interest to the research field. Evidence of VAR3 expression on the infected erythrocyte surface has never been presented, and var3 genes have been proposed to be transcribed and expressed differently from the rest of the var gene family members. In this study, parasites expressing VAR3 PfEMP1 were generated using anti-VAR3 antibodies and the var transcript and PfEMP1 expression profiles of the generated parasites were investigated. The IgG reactivity by plasma from children living in malaria-endemic Tanzania was tested to parasites and recombinant VAR3 protein. Parasites from hospitalized children were isolated and the transcript level of var3 was investigated. Var3 is transcribed and its protein product expressed on the surface of infected erythrocytes. The VAR3-expressing parasites were better recognized by children´s IgG than a parasite line expressing a Group B var gene. Two in 130 children showed increased recognition of parasites expressing VAR3 and to the recombinant VAR3 protein after a malaria episode and the isolated parasites showed high levels of var3 transcripts. Collectively, the presented data suggest that var3 is transcribed and its protein product expressed on the surface of infected erythrocytes in the same manner as seen for other var genes both in vitro and in vivo. Only very few children exhibit seroconversion to VAR3 following a malaria episode requiring hospitalization, supporting the previous conclusion drawn from var3 transcript analysis of parasites collected from children hospitalized with malaria, that VAR3 is not associated with severe anaemia or cerebral malaria syndromes in children.


A risk prediction model for acute kidney injury in patients with pulmonary tuberculosis during anti-tuberculosis treatment.
Acute kidney injury (AKI) is not a rare complication during anti-tuberculosis treatment in some patients with pulmonary tuberculosis (PTB). We aimed to develop a risk prediction model for early recognition of patients with PTB at high risk for AKI during anti-TB treatment. This retrospective cohort study assessed the clinical baseline, and laboratory test data of 315 inpatients with active PTB who were screened for predictive factors from January 2019 to June 2020. The elements were analyzed by logistic regression analysis. A nomogram was established by the results of the logistic regression analysis. The prediction model discrimination and calibration were evaluated by the concordance index (C-index), ROC curve, and Hosmer-Lemeshow analysis. A total of 315 patients with PTB were enrolled (67 patients with AKI and 248 patients without AKI). Seven factors, including microalbuminuria, hematuria, cystatin-C (CYS-C), albumin (ALB), creatinine-based estimated glomerular filtration rates (eGFRs), body mass index (BMI), and CA-125 were acquired to develop the predictive model. According to the logistic regression, microalbuminuria (OR = 3.038, 95%CI 1.168-7.904), hematuria (OR = 3.656, 95%CI 1.325-10.083), CYS-C (OR = 4.416, 95%CI 2.296-8.491), and CA-125 (OR = 3.93, 95%CI 1.436-10.756) were risk parameter, while ALB (OR = 0.741, 95%CI 0.650-0.844) was protective parameter. The nomogram demonstrated good prediction in estimating AKI (C-index= 0.967, AUC = 0.967, 95%CI (0.941-0.984), sensitivity = 91.04%, specificity = 93.95%, Hosmer-Lemeshow analysis SD = 0.00054, and quantile of absolute error = 0.049). Microalbuminuria, hematuria, ALB reduction, elevated CYS-C, and CA-125 are predictive factors for the development of AKI in patients with PTB during anti-TB treatments. The predictive nomogram based on five predictive factors is achieved good risk prediction for AKI during anti-TB treatments.


A systematic review of stercoral perforation.
Stercoral perforation is a rarely suspected life-threatening condition. Early diagnosis is difficult but essential. A comprehensive systematic review was performed to evaluate its presentation, diagnosis and treatment. A systematic review was carried out of Embase, MEDLINE, PubMed and Cochrane databases for all articles published between 1998 and 2011. Only studies describing stercoral perforation were included. Twenty-four relevant articles were found including 137 patients (median age = 62 years) with stercoral perforation, of whom 81% had chronic constipation. Stercoral perforation was diagnosed by CT scan in 90% of 31 patients, with the commonest findings being a combination of faecal impaction (84%) and subphrenic (90%) or extraluminal air (61%). The commonest site of perforation was the sigmoid colon (50%) followed by the rectosigmoid junction (24%). The overall mortality was 34%. Stercoral perforation should be suspected in elderly and chronically constipated patients with unexplained abdominal pain and investigated appropriately with a CT scan to allow timely and optimal treatment.


Laparoscopic transmesenteric pyeloplasty and isthmusectomy for adult horseshoe kidney with recurrent symptomatic hydronephrosis.
There is no consensus for the horseshoe kidneys with recurrent symptomatic hydronephrosis, so we presented our initial experience with a laparoscopic transmesenteric approach. Five patients with symptomatic ureteropelvic junction obstruction were identified by computed tomography urography. The laparoscopic transmesenteric approach was performed in such a way that the mesentery of the small intestine was incised along with the blood vessels longitudinally, and the isthmus was isolated to avoid injury to the mesenteric blood supply; then we cut the isthmus using an endostapler. The ureteropelvic junction obstruction was removed via the Anderson-Hynes technique. The operation time was 135-204 min, and the estimated blood loss was 50-120 mL. Patients had a 5.7-day stay postoperatively, there were no other injuries or complications, and ultrasound scans or computed tomography urography showed good postoperative effects. Laparoscopic transmesenteric surgery is a feasible and safe procedure for selected cases with horseshoe kidney with recurrent symptomatic hydronephrosis.


Effects of developmental exposure to bisphenol A on brain and behavior in mice.
Bisphenol A (BPA) is a widespread estrogenic chemical used in the production of polycarbonate, and epoxy resins lining food and beverage cans and in dental sealants. During fetal life the intrauterine environment is critical for the normal development, and even small changes in the levels of hormones, such as estradiol or estrogen-mimicking chemicals, can lead to changes in brain function and consequently in behavior. We review here a series of ethological studies on the effects of maternal oral exposure during the last part of gestation (prenatal exposure) or from gestation day 11 to postnatal day 7 (perinatal exposure) to a low, environmentally relevant dose of BPA (10 microg/kg bw/day) on behavioral responses of CD-1 mouse offspring. We examined both male and female offspring and found that maternal exposure to BPA affected: (1) behavioral responses to novelty before puberty and, as adults; (2) exploration and activity in a free-exploratory open field; (3) exploration in the elevated plus maze and (4) sensitivity to amphetamine-induced reward in the conditioned place preference test. A consistent effect of the maternal exposure to BPA is that in all these different experimental settings, while a significant sex difference was observed in the control group, exposure to BPA decreased or eliminated the sex difference in behavior. In addition, exposure of female mice to BPA in both adulthood or during fetal life altered subsequent maternal behavior. These findings, together with those from other laboratories, are evidence of long-term consequences of maternal exposure to low-dose BPA at the level of neurobehavioral development.


RNA interaction and cleavage of poly(C)-binding protein 2 by hepatitis A virus protease.
The poly(rC)-binding protein PCBP2 has multiple functions in post-transcriptional control of host and viral gene expression. Since it interacts with picornaviral RNA structures, it was proposed that PCBP2 regulates viral genome translation and replication. The hepatitis A virus (HAV), an atypical picornavirus, contains an unusual pyrimidine-rich tract (pY1) with unknown functions. Using in vivo and in vitro assays, we provide direct evidence that PCBP2 interacts with pY1 and that binding is mediated by KH domains 1 and 3. Proteolytic cleavage by the viral protease 3C generates a C-terminally truncated polypeptide with highly reduced RNA affinity. The results suggest that during HAV infection PCBP2 cleavage might specifically down-regulate viral protein synthesis, thereby giving way to viral RNA synthesis.


A quartz crystal microbalance biosensor based on polyethylenimine-modified gold electrode to detect hepatitis B biomarker.
Biomarkers-based QCM-biosensors are suitable tools for the label-free detection of infectious diseases. In the current study, a QCM-biosensor was developed for the detection of HBsAg. Briefly, anti-HBsAg antibodies were covalently bound to the primary amines after PEI and thiolated-PEI surface modifications of gold-electrode. After RSM optimization, the statistical analysis revealed no significant difference between the immobilization yields of modified layers. Therefore, the PEI-modified QCM-biosensor was selected for further analysis. The PEI-surface was evaluated by FESEM, AFM, ATR-FTIR, and CA measurement. The surface hydrophilicity and its roughness were increased after PEI-coating. Also, FTIR confirmed the PEI-layering on the gold-surface. RSM optimization increased the antibody immobilization yield up to 80%. The QCM-biosensor showed noteworthy results with a wide dynamic range of 1-1 × 103 ng/mL, LOD of 3.14 ng/mL, LOQ of 9.52 ng/mL, and detection capability in human-sera, which were comparable with the ELISA. The mean accuracy of the QCM-biosensor was obtained at 91% when measured by the spike recovery test using human-sera. The biosensor was completely regenerated using 50 mM NaOH and 1% SDS. The benefits provided by the developed biosensor such as broad dynamic range, sensitivity, selectivity, stability, regenerate ability, and low cost suggest its potential application for the non-invasive and timely monitoring of HBV-biomarker.


Age changes in the human female urethra: a morphometric study.
Aging in the human female urethra can contribute towards urinary problems. To our knowledge the effect of age on urethral tissues has not been quantified previously. Histological sections were prepared from 8 regions along the length of the urethra from 26 women between 19 and 88 years old. Using quantitative morphological techniques the relative volume fractions of various tissue components were determined. As age increased there was a decrease in the relative volume of striated muscle and blood vessels, and an increase in the relative volume of connective tissue. There was no change in the smooth muscle components. These age changes in the human female urethra may lead to impairment of urethral function.


Airborne mycotoxins in dust from grain elevators.
Workers in grain elevators are exposed to grain dust and may therefore have an increased risk of inhalatory contact with mycotoxins. To study the mycotoxin burden of such environments, settled grain dust samples (n=35) were collected from several locations of a total of 13 grain elevators in Germany, and analysed for ochratoxin A (OTA, detection limit 0.01 ng/g), deoxynivalenol (DON, detection limit 15 ng/g), and zearalenone (ZEA, detection limit 6 ng/g), respectively. Cytotoxicity of these samples was assessed by a MTT bioassay with a swine kidney target cell line. Additionally, the airborne dust concentration of these locations was determined. Nearly all settled dust samples contained OTA (96%), DON (100%), and ZEA (100%) with median concentrations of 0.4 ng/g, 416 ng/g, and 126 ng/g, respectively. Cytotoxic effects in varying degrees from weakly to highly toxic were caused by crude extracts of 86% of the dust samples. However, cytotoxicity did not correlate with mycotoxin levels in these samples and thus indicated the presence of cytotoxic compounds of unknown origin. Based on the mycotoxin findings in settled dust samples and the airborne dust concentrations, the average airborne mycotoxin concentrations were estimated to be 0.002 ng/m(3) (OTA), 2 ng/m(3) (DON), and 1 ng/m(3) (ZEA), respectively. The relevance of these findings for occupational health was assessed by comparison with WHO recommendations for the maximum tolerable daily (oral) intake (TDI). Even in a worst case scenario, the calculated inhalatory intake was far below the TDI values. However, considering the uncertainties resulting from different exposure pathways, namely oral ingestion versus inhalation, further research should primarily address the problem of how adequate assessment criteria for airborne exposure to mycotoxins could be established.


SIZ1-Mediated SUMOylation of ROS1 Enhances Its Stability and Positively Regulates Active DNA Demethylation in Arabidopsis.
The 5-methylcytosine DNA glycosylase/lyase REPRESSOR OF SILENCING 1 (ROS1)-mediated active DNA demethylation is critical for shaping the genomic DNA methylation landscape in Arabidopsis. Whether and how the stability of ROS1 may be regulated by post-translational modifications is unknown. Using a methylation-sensitive PCR (CHOP-PCR)-based forward genetic screen for Arabidopsis DNA hyper-methylation mutants, we identified the SUMO E3 ligase SIZ1 as a critical regulator of active DNA demethylation. Dysfunction of SIZ1 leads to hyper-methylation at approximately 1000 genomic regions. SIZ1 physically interacts with ROS1 and mediates the SUMOylation of ROS1. The SUMOylation of ROS1 is reduced in siz1 mutant plants. Compared with that in wild-type plants, the protein level of ROS1 is significantly decreased, whereas there is an increased level of ROS1 transcripts in siz1 mutant plants. Our results suggest that SIZ1-mediated SUMOylation of ROS1 promotes its stability and positively regulates active DNA demethylation.


Precise pathological classification of non-small cell lung adenocarcinoma and squamous carcinoma based on an integrated platform of targeted metabolome and lipidome.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the most common subtypes of NSCLC. Despite genetic differences between LUAD and LUSC have been clarified in depth, the metabolic differences of these two subtypes are still unclear. Totally, 128 plasma samples of NSCLC patients were collected before initial treatments, followed by determination of LC-ESI-Q TRAP-MS/MS. Differentially expressed metabolites were screened based on a strict standard. Based on the integrated platform of targeted metabolome and lipidome, a total of 1141 endogenous metabolites (including 809 lipids) were finally detected in the plasma of NSCLC patients, including 16 increased and 3 decreased endogenous compounds in LUAD group when compared with LUSC group. Thereafter, a logistic regression model integrating four differential metabolites [2-(Methylthio) ethanol, Cortisol, D-Glyceric Acid, and N-Acetylhistamine] was established and could accurately differentiate LUAD and LUSC with an area under the ROC curve of 0.946 (95% CI 0.886-1.000). The cut-off value showed a satisfactory efficacy with 92.0% sensitivity and 92.9% specificity. KEGG functional enrichment analysis showed these differentially expressed metabolites could be further enriched in riboflavin metabolism, steroid hormone biosynthesis, prostate cancer, etc. The endogenous metabolites identified in this study have the potential to be used as novel biomarkers to distinguish LUAD from LUSC. Our research might provide more evidence for exploring the pathogenesis and differentiation of NSCLC. This research could promote a deeper understanding and precise treatment of lung cancer.


The cost-effectiveness of social distancing measures for mitigating the COVID-19 pandemic in a highly-populated country: A case study in Indonesia.
As one of the strategies to mitigate the COVID-19 pandemic, social distancing (SD) measures are recommended to control disease spread and reduce the attack rate. Therefore, this study aims to estimate the costs and effects of SD measures through school closures, workforce, and community contact reductions for mitigating the COVID-19 pandemic in Indonesia. Two mitigation scenarios of SD for 1 month and continuous SD were compared with the baseline (no intervention). A modified Susceptible-Exposed-Infected-Recovered (SEIR) compartmental model accounting for disease spread during the latent period was applied by considering a 1-year time horizon. The costs of healthcare, school closures, and productivity loss due to disease as well as intervention were considered to estimate the total pandemic cost among all scenarios. In a comparison with the baseline, the result showed that total savings in scenarios of SD for 1 month and continuous SD was approximately $415 billion and $699 billion, respectively, while the averted deaths were 4.6 million and 8.5 million, respectively. Sensitivity analysis showed that basic reproduction number, infectious period, daily wage, incubation period, daily ICU admission cost, and case fatality rate were the most influential parameters affecting the savings and the number of averted deaths. SD measures through school closures, workforce, and community contact reductions were concluded to be cost-saving. Increasing the duration of social distancing tends to increase both the savings and the number of averted deaths.


Protective and anti-inflammatory effect of a traditional Chinese medicine, Xia-Bai-San, by modulating lung local cytokine in a murine model of acute lung injury.
We investigated the effects of Xia-Bai-San (XBS) on acute lung inflammation induced by LPS in vivo. Mice were challenged with intratracheal lipopolysaccharide (100 microg) 30 min before administering XBS (1 mg/kg oral administration). Bronchoalveolar lavage fluid (BALF) was obtained after 4 and 24 h to measure proinflammatory cytokine (TNF-alpha, IL-1beta, IL-6), anti-inflammatory cytokines (IL-10), chemokines (KC, MCP-1 and MIP-2), total cell counts, nitric oxide production, and proteins. The results indicated that XBS down-regulated the LPS-induced expression of TNF-alpha, IL-1beta, IL-6, KC, MIP-2, and MCP-1. Furthermore, it also enhanced the production of IL-10, which had increased 24 h after LPS challenge. In addition, total leukocyte counts, nitric oxide production, iNOS expression, and BALF's proteins had significantly decreased 24 h after LPS challenge. XBS was also believes to have reduced the acute inflammation by attenuating the activation of NF-kappaB. In conclusion, XBS seem to suppress lipopolysaccharide-induced lung inflammation by stimulating the production of anti-inflammatory cytokines in lung. These results suggest that XBS could be a useful adjunct in the treatment of acute respiratory distress syndrome.


Synaptic fine structure and the termination of corticospinal fibers in the lateral basal region of the cat spinal cord.
The lateral basal region (LBR) of the spinal cord gray matter (Rexed's laminae IV-VII) by physiologic and anatomic criteria is the major terminal zone for the corticospinal (CS) tract in the cat. The neurons in this area are medium-sized with abundant spines on their dendrites. Axon terminals on the dendrites and somata of these neurons form synapses easily classified as asymmetric with spheroid vesicles and symmetric with flattened vesicles. There are rare exceptions to this. In a systematic count of terminals, 82% have spheroid and 18% flattened vesicles. The majority of all terminals are on dendrites (84.9%) and a minority on somata (14.1%). Less than 1% are axoaxonic. Degeneration of the corticospinal tract was produced by transecting one hemisphere of our experimental cats. Its termination in the lower cervical cord was studied for 17 hours to 7 days after surgery. Vesicle depletion and clumping and dense polymembranous inclusions were the most common forms of degeneration. Filamentous proliferation in the terminals was also prominent; dark degeneration, however, was infrequent. The percent of degenerating CS terminals in the LBR was the following: 17 hours - 2.2%, 36 hours - 4.19%, 2 days - 10.3%, 3 days - 8.4%, 4 days - 6.9%, 7 days - 10.25%; 84.8% of degenerating CS terminals were axodendritic and 15.2% axosomatic.


Oncogenic PTEN functions and models in T-cell malignancies.
PTEN is a protein phosphatase that is crucial to prevent the malignant transformation of T-cells. Although a numerous mechanisms regulate its expression and function, they are often altered in T-cell acute lymphoblastic leukaemias and T-cell lymphomas. As such, PTEN inactivation frequently occurs in these malignancies, where it can be associated with chemotherapy resistance and poor prognosis. Different Pten knockout models recapitulated the development of T-cell leukaemia/lymphoma, demonstrating that PTEN loss is at the center of a complex oncogenic network that sustains and drives tumorigenesis via the activation of multiple signalling pathways. These aspects and their therapeutic implications are discussed in this review.


Dissecting the Conformational Dynamics of the Bile Acid Transporter Homologue ASBTNM.
Apical sodium-dependent bile acid transporter (ASBT) catalyses uphill transport of bile acids using the electrochemical gradient of Na+ as the driving force. The crystal structures of two bacterial homologues ASBTNM and ASBTYf have previously been determined, with the former showing an inward-facing conformation, and the latter adopting an outward-facing conformation accomplished by the substitution of the critical Na+-binding residue glutamate-254 with an alanine residue. While the two crystal structures suggested an elevator-like movement to afford alternating access to the substrate binding site, the mechanistic role of Na+ and substrate in the conformational isomerization remains unclear. In this study, we utilized site-directed alkylation monitored by in-gel fluorescence (SDAF) to probe the solvent accessibility of the residues lining the substrate permeation pathway of ASBTNM under different Na+ and substrate conditions, and interpreted the conformational states inferred from the crystal structures. Unexpectedly, the crosslinking experiments demonstrated that ASBTNM is a monomer protein, unlike the other elevator-type transporters, usually forming a homodimer or a homotrimer. The conformational dynamics observed by the biochemical experiments were further validated using DEER measuring the distance between the spin-labelled pairs. Our results revealed that Na+ ions shift the conformational equilibrium of ASBTNM toward the inward-facing state thereby facilitating cytoplasmic uptake of substrate. The current findings provide a novel perspective on the conformational equilibrium of secondary active transporters.


Factors influencing RNA yield from placenta tissue.
High yield and integrity of placental RNA are crucial for placental transcriptomics studies. We assessed the effects of time to placental collection post-delivery; tissue storage, amount and method used for extraction; mode of delivery; and tissue type on total RNA yield. The optimal protocol for RNA extraction from placental tissue includes cryofreezing of the sample upon collection and RNA extraction from 50 mg of tissue using TRIzol reagent. Decidua yielded highest RNA quantity/mg of tissue, followed by villous tissue and the chorion. Comparisons with murine kidney and HEK293T show lower placental RNA yield, likely due to highly dense and heterogeneous tissue make-up and potential high placental nuclease activity.


Associations between sociodemographic and clinicopathological factors and breast cancer subtypes in a population-based study.
This study examines the factors distinguishing breast cancer (BC) subtypes. We examined subtypes in 629 women with invasive BC, diagnosed from 2006 to 2012, and enrolled in an epidemiological study in New Jersey. Using molecular characteristics from pathology reports, BCs were categorized as luminal A, luminal B, non-luminal HER2-expressing, or triple-negative breast cancer (TNBC) subtypes. Multinomial logistic models (luminal A as referent) were used to describe BC subtype associations. Women with luminal B tumors were more likely to be younger at diagnosis [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.0-3.4] and to have higher-grade (OR 2.6, 95% CI 1.5-4.7), larger (OR 1.9, 95% CI 1.0-3.6), and Ki67-positive tumors (OR 2.1, 95% CI 1.1-4.0). Women with non-luminal HER2-expressing BCs were more likely to have higher-grade tumors (OR 14.5, 95% CI 5.3-39.7). Women with TNBCs were more likely to be African-American (OR 1.9, 95% CI 1.0-3.4) and to have higher-grade (OR 9.7, 95% CI 5.1-18.4), larger (OR 2.2, 95% CI 1.0-4.8), and Ki67-positive (OR 2.9, 95% CI 1.6-5.2) tumors. Notably, compared to the luminal A subtype, luminal B, non-luminal HER2-expressing, and triple-negative subtypes were more frequently self-detected; however, these associations were attenuated in multivariable models. These findings suggest that some BC subtypes were associated with features denoting more aggressive phenotypes, namely higher grade, larger size, and Ki67 positivity, and possibly patient self-detection among some women. These findings highlight a need for enhanced screening, particularly among younger women, racial/ethnic minorities, and lower socioeconomic subgroups.


Effects of the catecholaminergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on adrenal chromaffin cells in culture.
N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is an inhibitor of noradrenaline uptake and a neurotoxin known to deplete noradrenaline levels with little effect on dopamine, serotonin or adrenaline in the central nervous system. The present study tested the effects of DSP-4 on catecholamine uptake, release and content in cultures of isolated bovine adrenal chromaffin cells. DSP-4 selectively inhibited the acute uptake of [3H]noradrenaline with little or no effect on [3H]adrenaline or [3H]dopamine uptake. In cultures preloaded with [3H]catecholamines, DSP-4 stimulated the release of [3H]noradrenaline and, to a small extent, also [3H]adrenaline and [3H]dopamine. However, the drug did not stimulate the release of appreciable amounts of endogenous adrenaline, noradrenaline or dopamine. A high concentration of DSP-4 inhibited the carbachol-stimulated release of adrenaline, noradrenaline and dopamine from the cells. Following a 1-hr exposure to the drug, DSP-4 decreased adrenaline, noradrenaline and dopamine levels in the cells with no gross morphologic changes in the cells. Reductions in adrenaline and noradrenaline levels were almost equal in magnitude, while dopamine was depleted to a somewhat greater extent under some conditions. Longer exposure to DSP-4 resulted in morphological changes in the cells, suggesting that the drug is also toxic to chromaffin cells in culture.


Association of Remdesivir use with bradycardia: A systematic review and meta-analysis.
Remdesivir has been used for coronavirus disease 2019 (COVID-19) pneumonia with oxygen requirements that do not require mechanical intubation, and several studies showed a reduction in disease duration. However, there is a concern about bradycardia as its side effect. We aimed to investigate the association between Remdesivir and bradycardia by integrating findings from prior studies. We queried PubMed and EMBASE in February 2023 and performed a meta-analysis of studies investigating bradycardia in patients who did or did not receive Remdesivir. The outcome of interest was the rate of bradycardia and in-hospital mortality. We identified eight studies involving 8993 patients, of which seven studies investigated bradycardia. Six studies were observational, one was a case-control, and one was a randomized trial. Incidence of bradycardia was 400/3480 patients (22.3%, 95% confidence interval, CI: [6.5-54.4], I2 = 99%) in the Remdesivir group and 294/5005 (9.8%, 95% CI: [2.8-29], I2 = 98.61) in the non-Remdesivir group. The odds ratio of bradycardia was 2.11 (95% CI: [1.65-2.71], I2 = 22%, p < 0.001) for the Remdesivir group. There was no difference in mortality between the two groups. Patients who received Remdesivir for COVID-19 were more likely to develop bradycardia. The effect of confounding factors should be considered to further clarify the possible association.


Fatigue in breast cancer survivors: the impact of a mind-body medicine intervention.
To evaluate a mind-body medicine (MBM) program for its impact on persistent fatigue following breast cancer treatment. Quasiexperimental. An urban community hospital and a health department in a semirural county, both in Maryland. 68 breast cancer survivors who were at least six months postadjuvant chemotherapy and/or radiation therapy and had a baseline fatigue score of 50 or lower per the vitality subscale of the SF-36® Health Survey. A 10-week group-based MBM program for breast cancer survivors with persistent fatigue was evaluated using a pretest/post-test study design. Sustained change in fatigue severity as measured by the Piper Fatigue Scale (PFS), SF-36 vitality subscale, and 10 cm visual analog scale (VAS). Participants were 2.6 years post-treatment, with a mean age of 56.8 years. Overall, fatigue scores improved by 40%. The mean PFS improved from a score of 6 (SD = 1.6) at baseline to 4.2 (SD = 2) at the end of the program (p < 0.001), with additional improvement at two months and sustained at six months (X = 3.6, SD = 2, p < 0.001). Results from the SF-36 and VAS also showed significant improvement in fatigue (p < 0.001). The findings support the use of a holistic MBM intervention to reduce persistent fatigue in breast cancer survivors. Results should be confirmed with a randomized clinical trial. Nurses and other healthcare team members can effectively impact persistent fatigue in breast cancer survivors through the use of a multipronged MBM program.


[The peculiarities of the radiation mutagenesis of Cyclops kolensis and Cyclops insignis (Crustacea, Copepoda)].
The frequency of the chromosomes aberrations (FA) of Cyclops kolensis before chromatin diminution (CD), which were inducted by gamma-irradiation in 50 times exceeds the FA of Cyclops kolensis after CD, during the CD, reducing the genome of C. kolensis in 15 times. During the embryogenesis the FA of Cyclops insignis doesn't change. The obtained results show us a low level of the spontaneous mutagenesis of C. kolensis and C. insignis embrios. The FA of Cyclops kolensis is correlated with the doses 1, 2, 3, 5 Gy gamma-irradiation. The similarity of the CD mechanism and of the mechanism of the chromosome aberrations is supposed.


The C. elegans healthspan and stress-resistance assay toolkit.
A wealth of knowledge on the genetic mechanisms that govern aging has emerged from the study of mutants that exhibit enhanced longevity and exceptional resilience to adverse environmental conditions. In these studies, lifespan has been an excellent proxy for establishing the rate of aging, but it is not always correlated with qualitative measures of healthy aging or 'healthspan'. Although the attributes of healthspan have been challenging to define, they share some universal features that are increasingly being incorporated into aging studies. Here we describe methods used to determine Caenorhabditis elegans healthspan. These include assessments of tissue integrity and functionality and resistance to a variety of biotic and abiotic stressors. We have chosen to include simple, rapid assays in this collection that can be easily undertaken in any C. elegans laboratory, and can be relied on to provide a preliminary but thorough insight into the healthspan of a population.


Protocol for sodium depletion and measurement of sodium appetite in mice.
Sodium appetite is a state that motivates animals to consume normally unappetizing concentrations of sodium. Here we describe a protocol to induce sodium appetite in mice by furosemide-induced diuresis and measure sodium intake using volumetric drinking tubes. This protocol induces sodium appetite rapidly and can be used to assess the effect of various treatments on sodium appetite. This protocol does not require electronic equipment and can be implemented easily. For complete details on the use and execution of this protocol, please refer to Park et al. (2020).


Characteristics of patients referred to psychiatrists for competency evaluations.
Requests for inpatient psychiatric consultations at a general hospital over a three-year period were reviewed. Of 2,423 referrals, 79 (3.3%) were specifically for evaluation of competency, and 78.5% of those cases resulted in a diagnosis of an organic mental disorder. The proportion of referrals with organic mental disorder was significantly greater than it was in a control population of patients referred for consultation for any reason. Patients with organic mental disorder who were referred for competency evaluation had greater cognitive impairment than did control subjects.


First-trimester septic abortion due to Salmonella enteritidis Oranienburg.
Septic abortion caused by transplacental salmonella infection is extremely rare; there are no reported cases of serotype oranienburg as an etiology. We describe a patient with non-typhoidal Salmonella enteritidis serotype oranienburg as a cause of first-trimester pregnancy loss. The rapid progression of this patient's septicemia and adverse outcome is described. The epidemiology and natural history of salmonella infections are also discussed. Non-typhoidal salmonella is still a cause of morbidity in Western countries. This infection can result in rapid-onset fetal demise and septic abortion.


Pharmacologic analysis of 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine-induced increases in cutaneous vascular permeability in the rat.
1-0-Alkyl-2-Acetyl-sn-Glycero-3-Phosphocholine (AGEPC) produced dose-dependent (75-500 ng/site) increases in cutaneous vascular permeability (CVP) in rats as measured by extravasation of Evans blue dye. In contrast, lyso-AGEPC, at 1000 ng/site, was without effect. Pyrilamine, methysergide, and phenoxybenzamine, antagonists of mast-cell derived mediators, did not affect the AGEPC-induced increase in CVP. Likewise, agents capable of inhibiting mast cell mediator release, such as disodium cromoglycate, PRD-92-EA, theophylline, or nifedipine, had no effect. The cyclooxygenase inhibitor indomethacin produced significant inhibition of the response to AGEPC, whereas the lipoxygenase inhibitor nordihydroguiaretic acid (NDGA) and the peptide leukotriene antagonist FPL 55712 were without effect. The response to AGEPC was enhanced by the vasodilator PGE2 and inhibited by the vasoconstrictor phenylephrine. The selective AGEPC antagonist CV-3988 provided marked inhibition of the response. Unaccountably, the combination of indomethacin and CV-3988 provided no greater inhibition of the responses than either agent alone. These observations indicate that the AGEPC-induced increase in CVP in rats is mediated in part by products of the cyclooxygenase pathway and in part by activation of an AGEPC receptor.


The Impact of Topical Corticosteroids Used in Conjunction with Antiamoebic Therapy on the Outcome of Acanthamoeba Keratitis.
To examine the impact of topical corticosteroid use after the start of antiamoebic therapy (AAT) on the outcomes of Acanthamoeba keratitis (AK) therapy. Cohort study. A total of 196 patients diagnosed with AK at Moorfields Eye Hospital, London, between January 1991 and April 2012. In 13 patients with bilateral AK, 1 eye was randomly excluded from analysis. Patient demographics and clinical examination findings were collected both at the start of AAT and subsequently at the time that topical corticosteroid therapy was initiated. Preliminary a priori investigations were used to identify effect modifiers/confounders and extreme associations requiring consideration in multivariate regression modeling. A multivariable logistic model, optimized for assessment of corticosteroid use after the start of AAT, was used to estimate the odds ratios (ORs) of a suboptimal outcome. Suboptimal outcome was defined as final visual acuity ≤20/80, corneal perforation, or the need for keratoplasty. In multivariable analysis, restricted to 129 eyes (1 eye per patient) free of scleritis and hypopyon at the start of AAT, topical corticosteroids were not associated with worse outcomes (OR, 1.08; 95% confidence interval [CI], 0.39-3.03), even when corticosteroids had been used before the start of AAT. Risk factors significantly associated with worse outcomes were topical corticosteroid use before the start of AAT (OR, 3.85; 95% CI, 1.35-11.03), a corneal ring infiltrate (together with at least 1 other feature of AK) present at the start of AAT (OR, 5.89; 95% CI, 1.17-29.67), and age ≥33 years at the start of AAT (OR, 4.02; 95% CI, 1.46-11.06). Many corneal specialists currently are uncertain about the risk benefit associated with the use of topical corticosteroids for the management of inflammatory complications of AK. The evidence from this study gives clinicians and patients reassurance that the potential benefits of topical corticosteroid therapy, for treating pain and discomfort, are not associated with worse outcomes when initiated after starting modern AAT. Other potential benefits, in terms of resolution of inflammatory complications, will not be demonstrated without a carefully designed randomized clinical trial.