Ventilatory chemosensitivity and thermogenesis of the chicken hatchling after embryonic hypercapnia.
Hypoxia during incubation results in hatchlings with a reduced thermogenic capacity and a blunted ventilatory (V (E)) chemosensitivity (Szdzuy, K., Mortola, J.P., 2007b. Ventilatory chemosensitivity of the 1-day-old chicken hatchling after embryonic hypoxia. Am. J. Physiol. (Regul. Integr. Comp. Physiol.) 293, R1640-R1649). We asked if similar effects occurred with embryonic hypercapnia, that is, with a non-hypoxic sustained stimulation of the chemoreceptors. White Leghorn chicken eggs were incubated at 38 degrees C either in air (controls, C) or in 4% CO(2) from embryonic day 5 (4% CO(2)), hatching included. The 4% CO(2) embryos hatched about 12h later than C, with similar body weight. On the day of hatching the thermogenic capacity, assessed from the changes in oxygen consumption (.V(O2)) during 1h at 30 degrees C, increased from the early (about 3h old) to the late hours (about 20 h old), and was similar between 4% CO(2) and C. Ventilatory chemosensitivity was evaluated from the changes in (.V(E)) and in ventilatory equivalent (.V(E)/.V(O2)) during acute hypoxia (15 and 10% O(2), 20 min each) or hypercapnia (2 and 4% CO(2), 20 min each). Both at the early and late hours (.V(E)) chemosensitivity was lower in 4% CO(2) than in C. The .V(E)/.V(O2) responses of 4% CO(2) in hypoxia and hypercapnia averaged, respectively, about 45 and 60% of C. A separate set of eggs incubated in 2% CO(2) gave results qualitatively intermediate between C and 4% CO(2). We conclude that prenatal hypercapnia does not compromise the newborn's thermogenesis, but, like hypoxia, affects the development of respiratory control, resulting in a blunted chemosensitivity.


Protrusion of a peritoneal catheter through the umblicus: an unusual complication of a ventriculoperitoneal shunt.
Protrusion of a ventriculoperitoneal (VP) shunt through the umblicus is one of the rare complications of shunt insertion reported in the medical literature. One such case is presented here in a child in whom a VP shunt had been placed for congenital hydrocephalus.


Protein kinase C-dependent inhibition of the lysosomal degradation of endocytosed proteins in rat hepatocytes.
We studied the role of protein kinase C (PKC) in the lysosomal processing of endocytosed proteins in isolated rat hepatocytes. We used [14C]sucrose-labeled horseradish peroxidase ([14C]S-HRP) to simultaneously evaluate endocytosis and lysosomal proteolysis. The PKC activator phorbol 12-myristate 13-acetate (PMA) inhibited the lysosomal degradation of [14C]S-HRP (1 microM PMA: 40% inhibition, P<.05), without affecting either the endocytic uptake or the delivery to lysosomes. However, PMA was not able to affect the lysosomal processing of the beta-galactosidase substrate dextran galactosyl umbelliferone. The PKC inhibitors, chelerytrine (Che), staurosporine (St) and Gö 6976, prevented PMA inhibitory effect on lysosomal proteolysis. Nevertheless, purified PKC failed to alter proteolysis in [14C]S-HRP-loaded isolated lysosomes, suggesting that intracellular intermediates are required. PMA induced phosphorylation and hepatocyte membrane-to-lysosome redistribution of the myristoylated alanine-rich C kinase substrate (MARCKS) protein, raising the possibility that MARCKS mediates the PKC-induced inhibition of lysosomal proteolysis.


Assessing the inhibitory potency of galectin ligands identified from combinatorial (glyco)peptide libraries using surface plasmon resonance spectroscopy.
Combinatorial (glyco)peptide libraries offer the possibility to define effective inhibitors of protein (lectin)-glycan interactions. If a (glyco)peptide surpasses the inhibitory potency of the free sugar, then the new peptide-lectin contacts underlying the affinity enhancement may guide further rational drug design. Focusing on the adhesion/growth regulatory human galectins 1 and 3, a screening of three combinatorial solid-phase (glyco)peptide libraries, containing Gal(beta1-O)Thr, Gal(beta1-S)Cys/Gal(beta1-N)Asn, and Lac(beta1-O)Thr, with the fluorescently labeled lectins had led to a series of lead compounds. To define the inhibitory potency of a selection of resynthesized (glyco)peptides systematically, a surface plasmon resonance-based inhibition assay with immobilized asialofetuin was set up. (Glyco)Peptides with up to 66-fold potency relative to free lactose as inhibitor were characterized. The presence of lactose in the most effective glycopeptides indicated the presence of affinity-enhancing peptide-lectin contacts. In addition to drug design, they may be helpful for fine-structural analysis of the binding sites.


Demographics and trends in the acute presentation of diverticular disease: a national study.
Diverticular disease (DD) is a major health problem in the Western world. The aim of this study was to describe demographics and trends in acute DD admissions in New Zealand. Information pertaining to acute hospital admissions between January 2000 and June 2012 for a primary diagnosis of large bowel DD was retrieved from a national database. There were 25,167 admissions for acute DD. Mean age of presentation decreased from 65.9 years in 2000 to 64.1 years in 2012 (P < 0.001). Mean age was lower in men than women (61.4 versus 67.4 years, P < 0.001). Although men comprised 45.2% of the cohort they were over-represented in the 18-44 years stratum (68.6 versus 31.4%; P < 0.001). Europeans accounted for 84.8% of admissions and presented at an older age (65.8 years) than Māori (56.2 years), Pacific Islanders (58.4 years) or Asians (58.9 years) (P < 0.001). Acute DD admissions were higher in more deprived populations (P < 0.001). Mean length of hospital stay (LOS) reduced from 5.8 days in 2000 to 4.1 days in 2012 (P < 0.001). LOS increased with age (P < 0.001) and deprivation (P = 0.013), but did not differ between ethnicities (P = 0.088). Computed tomography scanning of acute admissions doubled from 2000 to 2012 (29.7-59.2%; P < 0.001) with a halving in the use of acute in-patient colonoscopy (26.1-13.2%; P < 0.001) and emergent surgery (14.8-7.2%; P < 0.001). Percutaneous drain use increased from 0.6% in 2000 to 1.1% in 2012 (P = 0.003). Acute DD is a source of considerable morbidity in New Zealand and there have been significant changes in its admission demographics and trends over the last decade.


Physical demands in Spanish male and female elite football referees during the competition: a prospective observational study.
The aim of this study was to analyze the physical demands of elite male and female field referees in match play and compare the physical demands between male and female football referees in the competition. Match data were collected from 36 elite football referees (19 males and 17 females) during a total of 409 football matches. Electronic performance and tracking systems based on global positioning systems (GPS) were used in this research. Male referees experienced significantly greater physical demands (p < 0.05) in men league than female referees in women league for total distance, explosive distance, high-intensity breaking distance, total of sprints, sprinting distance, high-speed running distance, high-speed running actions, maximal speed, total of accelerations and decelerations, maximal acceleration and deceleration, acceleration/deceleration. Therefore, strength and conditioning coaches should consider these gender differences in match demands to maximize the fitness-fatigue response of the referees since this may lead to a better performance during the decision-making process in the competition.


Incremental Healthcare Cost Implications of Retreatment Following Ureteroscopy or Percutaneous Nephrolithotomy for Upper Urinary Tract Stones: A Population-Based Study of Commercially-Insured US Adults.
This study describes the incremental healthcare costs associated with retreatment among adults undergoing ureteroscopy (URS) or percutaneous nephrolithotomy (PCNL) for upper urinary tract stones (UUTS). The IBM® MarketScan® Commercial Database was used to identify adults aged 18-64 years with UUTS treated with URS or PCNL between January 2010 and December 2019. Patients had 12 months of continuous insurance coverage before (baseline) and after (follow-up) the first (index) procedure. The primary outcome was total all-cause healthcare costs measured over the 365-day follow-up period, not inclusive of index costs. Generalized linear models were used to estimate the incremental costs associated with retreatment within 90 (early) or 91-365 days post-index (later) relative no retreatment. The models adjusted for demographics, comorbidities, stone(s) location, treatment setting, procedural characteristics (eg, 1-step vs 2-step PCNL) and index year. Approximately 23% (27,402/119,800) of URS patients were retreated (82% had early retreatments). The adjusted mean total cost was $10,478 (95% CI: $10,281-$10,675) for patients with no retreatment, $25,476 (95% CI: $24,947-$26,004) for early retreatment ($14,998 incremental increase, p<0.01), and $32,868 [95% CI: $31,887-$33,850] for later retreatment ($22,391 incremental increase, p<0.01). Approximately 36% (1957/5516) of PCNL patients were retreated (78% had early retreatments). The adjusted mean total cost was $13,446 (95% CI: $12,659-$14,273) for patients with no retreatment, $37,036 [95% CI: $34,926-$39,145]) for early retreatment ($23,570 incremental increase, p<0.01), and $35,359 (95% CI: $32,234-$38,484) for later retreatment ($21,893 incremental increase, p<0.01). Retreatment during the first year following URS or PCNL was needed in 23% and 36% of patients, respectively, and was associated with an economic burden of up to $23,500 per patient. The high rate of retreatment and associated costs demonstrate there is an unmet need to improve mid- to long-term results in URS and PCNL.


Substance P-containing nerve fibres in large peripheral blood vessels of the rat.
Substance P-immunoreactive nerve fibres were localized by the indirect immunohistochemical method in the adventitia and the adventitial-medial border of large peripheral arteries and veins of the rat. Arteries showed a richer substance P-containing innervation than veins. The superior mesenteric artery was densely innervated, whereas no substance P-containing fibres were found around the carotid artery. Substance P produced a vasoconstriction of the veins, but was basically without effect on arteries, although with the carotid artery a dose-dependent relaxation was observed. The absence of a correlation between the degree of innervation of the blood vessels and their responsiveness to exogenous substance P suggests that there nerves do not subserve a vasomotor function. The depletion of substance P immunoreactivity from nerves in arteries and veins by capsaicin suggest that substance P-containing vascular nerves are primarily sensory in nature.


A study of the vaginal contraceptive sponge used with and without the fertility awareness method.
The actual effectiveness rates of natural and barrier methods of family planning are lower than the theoretical ones. If couples accurately defined the limits of the fertile phase and used barriers at that time, then actual effectiveness might increase. A randomized, controlled clinical trial was initiated to determine the effectiveness of the contraceptive sponge used only during the fertile time and to compare this with sponge use at every intercourse. Recruitment problems and discontinuation forced the early termination of this study, but qualitative information about compliance and acceptability was collected. Common sponge problems were reported as were misuses of the sponge, but problems and misuse were not related. Determination of the fertile phase was reportedly easy, but complaints of and discontinuation for inconvenience occurred. For unplanned pregnancies, contraceptive behaviors around the time of conception are presented.


Culture and acculturation influences on Palestinian perceptions of prenatal genetic counseling.
Patient cultural backgrounds strongly influence decision-making processes and outcomes in genetic counseling. The present study investigated influences of culture and acculturation on prenatal decision making processes of native Palestinians and Palestinian Americans. Seventeen native Palestinians and 14 first-generation, Palestinian Americans were interviewed and asked to imagine themselves as patients in hypothetical premarital and prenatal situations. Five major issues were investigated: 1) Influence of family history of an inherited condition on pre-marital decisions; 2) Perceptions of non-directive genetic counselor statements regarding options; 3) Role of gender in prenatal decisions; 4) Gender differences in emotional expression; and 5) Role of family and society in prenatal decisions. Several similarities and differences in native Palestinian and Palestinian American responses were obtained. Similarities appear to be due to common cultural roots, while differences may be due to acculturation. Practice and research recommendations are provided.


Cotranscription of 5S rRNA-tRNA(Arg)(ACG) from Brassica napus chloroplasts and processing of their intergenic spacer.
S1 mapping showed that at least a significant portion of the 5S rRNA and tRNA(Arg)(ACG) is co-transcribed in canola chloroplast, making trnR the last gene transcribed in an operon of which the final sequence is 5'-16S-tRNA(Ile)-tRNA(Ala)-23S-4.5S-5S-tRNA(Arg)-3'. Various RNA termini representing RNA processing sites at several parts of the 5S rRNA-tRNA(Arg) area were detected. This gene spacer is substantially conserved among various species compared here, and a secondary structure model for this chloroplast region in canola applies to other plant sequences. The conservation of this intergenic sequence suggests a functional role, possibly by providing recognition structures for endogenous RNases involved in its maturing process.


Early history of ESPEN.
Since the European Society of Parenteral and Enteral Nutrition (ESPEN) is now well established as a major international scientific organisation, it may be of interest to recall how the Society came to be formed and how it evolved during its first few years. A chronological view will be given of the way ESPEN was organised during the early years, followed by a commentary on the development of its many roles.


The role of long noncoding RNAs in liquid-liquid phase separation.
Long noncoding RNAs (lncRNAs), which are among the most well-characterized noncoding RNAs, have attracted much attention due to their regulatory functions and potential therapeutic options in many types of disease. Liquid-liquid phase separation (LLPS), the formation of droplet condensates, is involved in various cellular processes, but the molecular interactions of lncRNAs in LLPS are unclear. In this review, we describe the research development on LLPS, including descriptions of various methods established to identify LLPS, summarize the physiological and pathological functions of LLPS, identify the molecular interactions of lncRNAs in LLPS, and present the potential applications of leveraging LLPS in the clinic. The aim of this review is to update the knowledge on the association between LLPS and lncRNAs, which might provide a new direction for the treatment of LLPS-mediated disease.


Canadian Physicians' Breach of Duty to Patients and Communities from the Acquisition of Indigenous Skulls in the 19th Century to the Abandonment of People with AIDS in the 20th Century.
The impact of the Vienna Protocol transcends the world of Jewish law and provides important ethical considerations for modern medicine. This article provides a series of examples demonstrating how Canadian medical history intersects with the Vienna Protocol, and why historical insight remains relevant. Investigations into this exploitation include this author's own inquiry and attempt to repatriate Canadian indigenous skulls (a gift from William Osler to Rudolf Virchow), the glaring maltreatment of Aboriginal children in Canadian nutrition experiments, and the maltreatment of Canadian AIDS patients in the 1980s.


Correction: Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.
[This corrects the article DOI: 10.1371/journal.pntd.0009427.].


Atomic insight into Ge₁₋xSnx using atom probe tomography.
Ge(1-x)Sn(x) is receiving a growing interest in the scientific community, as it has important applications in opto-electronic devices, ( as stressor) Source/Drain materials for Ge and SiGe MOSFETS. It is predicted that at 10% Sn concentration or even lower, unstrained Ge(1-x)Sn(x) will exhibit a direct band gap. Moreover, in strained Ge(1-x)Sn(x) the expected concentration of Sn for this cross-over is even lower. As the theoretical Sn incorporation in Ge(1-x)Sn(x) is less than 1%, and Ge(1-x)Sn(x) is prone to relaxation, routes towards the growth of metastable strained films has been extensively explored. Although Ge(1-x)Sn(x) films (with x up to 10%) have been grown using various methods like molecular beam epitaxy, CVD growth etc. there remain issues with tendency of these layers to relax. Detailed studies on the relaxation mechanisms and effects on the Sn-atoms require suitable characterization techniques. Various techniques have been used to study the surface of the film, crystallography or concentration of Sn in the film but none of them provides information at the atomic scale as they average over many layers and atoms. Atom probe tomography (APT) analysis, on the other hand, is one such method that can provide atomic scale resolutions (∼0.3 nm) due to its ability to perform atom by atom analysis. In this paper we explore the use of APT for characterizing Ge(1-x)Sn(x) layers. We comment on the difference of field evaporation values of Ge and Sn in Ge(1-x)Sn(x) layer by taking a closer look at the co-evaporation of the two elements and comment on the accuracy of depth reconstruction of APT for Ge(1-x)Sn(x) layer. Comparing the Sn-distributions and their local surroundings we saw a tendency for the Sn to locally enrich forming Sn clusters. Higher order clusters were observed for the relaxed sample.


Hypothesis for the molecular physiology of the Romano-Ward long QT syndrome.
The aim of this review was to develop a hypothesis for the molecular pathophysiology of the inherited long QT syndrome. The pathophysiology of the long QT syndrome is unknown. An abnormality of the sympathetic nervous system has been suspected because of the slow heart rates observed and the common precipitation of syncope by adrenergic stimulation (exercise or fright). The characteristic QT prolongation and torsade de pointes arrhythmias suggest a potassium ion (K+) abnormality. Recent findings from molecular biology and genetic linkage analysis studies provide a basis for a new hypothesis that unifies these clinical manifestations. Several recent studies regarding ras proteins were evaluated and correlated. Associations between ras proteins, G protein function and the known features of the long QT syndrome were identified. Based on these associations, a hypothesis for the molecular pathophysiology was developed. The Romano-Ward long QT phenotype is linked to the Harvey ras-1 gene on chromosome 11 in many, but not all, families. Ras genes exhibit G protein properties, acting as intermediaries in transmembrane signaling pathways including K+ and beta-adrenergic channels. Mutation of ras p21 protein significantly reduces the G protein function of the ras protein, thereby interfering with signal transduction. These various studies suggest that a mutation of the disease gene (not necessarily H-ras-1) alters the G protein function of the gene and interferes with delayed rectifier K+ and beta-receptor channel signaling. This hypothesis appears to explain and unify the several characteristic features of the long QT syndrome.


Prospects for gene transfer for clinical heart failure.
Congestive heart failure is an inexorable disease associated with unacceptably high morbidity and mortality. Preclinical results indicate that gene transfer using various proteins is a safe and effective approach for increasing function of the failing heart. In the current review, we provide a summary of cardiac gene transfer in general and summarize findings using adenylyl cyclase 6 as therapeutic gene in the failing heart. We also discuss the potential usefulness of a new treatment for congestive heart failure, paracrine-based gene transfer.


Dimethyl and diethyl esters of 5,6-bis-(pyridin-2-yl)pyrazine-2,3-di-carb-oxy-lic acid: a comparison.
In dimethyl 5,6-bis-(pyridin-2-yl)pyrazine-2,3-di-carboxyl-ate, C18H14N4O4, (I), and diethyl 5,6-bis-(pyridin-2-yl)pyrazine-2,3-di-carboxyl-ate, C20H18N4O4, (II), the dimethyl and diethyl esters of 5,6-bis-(pyridin-2-yl)pyrazine-2,3-di-carb-oxy-lic acid, the orientation of the two pyridine rings differ. In (I), pyridine ring B is inclined to pyrazine ring A by 44.8 (2)° and the pyridine and pyrazine N atoms are trans to one another, while pyridine ring C is inclined to the pyrazine ring by 50.3 (2)°, with the pyridine and pyrazine N atoms cis to one another. In compound (II), the diethyl ester, which possesses twofold rotation symmetry, the pyridine ring is inclined to the pyrazine ring by 40.7 (1)°, with the pyridine and pyrazine N atoms trans to one another. In the crystal of (I), mol-ecules are linked by C-H⋯N hydrogen bonds, forming chains along [001]. The chains are linked by C-H⋯π inter-actions, forming a three-dimensional structure. In the crystal of (II), mol-ecules are linked via C-H⋯O hydrogen bonds, forming a three-dimensional framework. There are C-H⋯π inter-actions present within the framework.


An Examination of Modifiable Risk Factors in Stroke Survivors, with a view to recurrent stroke prevention.
Stroke is a major public health problem worldwide, as more people survive their initial stroke event and subsequently live with chronic disability. While extensive research has focused upon preventing primary strokes comparatively little research has examined secondary stroke prevention. We analysed data collected from a survey of 576 participants from the 45 and Up Study who had a clinical diagnosis of stroke. Health status was assessed using a variety of validated instruments. Demographics and modifiable risk factors, including health behaviours and diagnosed conditions, were also measured. Logistic regression model building was used to examine the relationship between each modifiable risk factor and the independent variables of demographics and health status measures. The average time since the most recent stroke for study participants was 10.4 (SD = 8.9) years, with the majority of participants (73.2%) having had only one stroke in total. Regression modelling revealed that health-related hardiness, quality of life, depression and fatigue scores were all statistically significantly associated with heart disease, anxiety, depression and physical activity. For stroke characteristics, years since the most recent stroke was associated with heart disease and the number of strokes was associated with anxiety/nervous disorder, diabetes and alcohol consumption. Among other identified targets for secondary stroke prevention, fatigue and depressive symptoms appear to be common factors affecting several modifiable stroke risk factors. Addressing fatigue and depressive symptoms may therefore have a positive effect on secondary stroke prevention strategies in post stroke adults. All practitioners providing care for post-stroke adults can work towards improving these health factors thereby enhancing and prioritising secondary stroke prevention strategies.


Developmental activation of the H-2K gene is correlated with an increase in DNA methylation.
Embryonal carcinoma cell lines present strong developmental analogies with early embryonic cells. Previous studies have shown that treatment of F9 teratocarcinoma cells with retinoic acid induces the expression of the classical transplantation antigens which are indispensable for effective interactions between cells. In contrast to several genes that were analyzed, all of which were highly and heterogeneously methylated in F9 cells, the H-2K gene was poorly methylated if at all. Activation of the H-2K gene upon differentiation of F9 cells was accompanied by an increase in DNA methylation. While increased methylation of the H-2K gene in one of the two homologous chromosomes was correlated with a low level of expression, increased methylation in both chromosomes was associated with a high level of expression. Treatment of differentiated F9 cells with 5-azacytidine resulted in inhibition of DNA methylation and a concomitant repression of the H-2K gene expression. Thus, in contrast to the many examples of an inverse correlation between the level of gene methylation and its transcriptional activity, expression of the H-2K gene is directly correlated with the extent of methylation. This finding offers an explanation whereby the hypomethylation observed in tumor cells may be responsible for the establishment and maintenance of a malignant state of growth.


Differences in Treatment Outcomes Between Patients with HER2-Low versus HER2-Zero, Hormone Receptor-Positive Advanced-Stage Breast Cancer Treated with Ribociclib.
Metastatic breast cancers (MBC) with no expression of human epidermal growth factor receptor-2 (HER2) are recently classified into two groups; HER2-zero [HER2-immunohistochemistry (IHC) score of 0 (IHC-0)] and HER2-low, defined as those with IHC score of 1+ or 2+ with negative in situ hybridization (ISH) assay. We investigate differences in treatment outcomes between both groups treated with endocrine therapy (ET) and the CDK4/6 inhibitor ribociclib. Data were retrospectively collected for patients with HR-positive+/HER2-negative MBC who received ribociclib with an aromatase inhibitor (AI) or fulvestrant and were divided into two groups: HER2-zero and HER2-low. A total of 257 patients, median age 48 (22-87) years, all with MBC who were treated with ET and ribociclib were enrolled. One hundred and thirty-seven (53.3%) patients had de novo MBC, and majority (n = 162, 63.0%) received ribociclib as a first-line therapy. In total, 114 (44.4%) patients had HER2-zero (IHC-0), while 143 (55.6%) others had HER2-low disease. The overall response rate (ORR) was 52.0% for the HER2-zero group compared to 39.4% for the HER2-low group, p = 0.005. The median PFS was 22.2 (95% confidence interval [CI], 19.4-NR) months for HER2-zero versus 17.3 (95% CI, 14.1-20.6) months for HER2-low, P = 0.0039. In multivariable analysis, HER2-low expression remained significant determinant of inferior PFS after adjusting for other factors, including the site of metastasis, prior chemotherapy, and the line of treatment. In patients with MBC treated with ET and ribociclib, level of HER2 negativity may affect treatment outcomes; patients with HER2-zero had better response rate and PFS compared to those with HER2-low disease. These findings, if confirmed in larger studies, may help oncologists select patients with HER2-low for better treatment options.


Chronic oligodendrocyte injury in central nervous system pathologies.
Myelin, the membrane surrounding neuronal axons, is critical for central nervous system (CNS) function. Injury to myelin-forming oligodendrocytes (OL) in chronic neurological diseases (e.g. multiple sclerosis) ranges from sublethal to lethal, leading to OL dysfunction and myelin pathology, and consequent deleterious impacts on axonal health that drive clinical impairments. This is regulated by intrinsic factors such as heterogeneity and age, and extrinsic cellular and molecular interactions. Here, we discuss the responses of OLs to injury, and perspectives for therapeutic targeting. We put forward that targeting mature OL health in neurological disease is a promising therapeutic strategy to support CNS function.


Bilateral giant intracavernous aneurysms. Technique of unilateral operation.
We report a case of bilateral intracavernous giant aneurysms of which the right side was clipped by direct surgery. Our case was a 74-year-old woman who developed bilateral abducens palsy. Computed tomography and angiography showed bilateral intracavernous giant aneurysms. This patient was followed up in the outpatient clinic. She developed headache and right trigeminal neuralgia 2 years later. The trigeminal pain was quite severe and very disturbing to her. Repeat angiography showed an increase in the size of the aneurysms. An operation was carried out after a balloon Matus test monitoring electroencephalogram, somatosensory evoked potential, and clinical symptoms. The cavernous sinus was opened and the aneurysm was clipped. There was no postoperative complication except right ophthalmoplegia which resolved after 3 months. Headache and trigeminal neuralgia also disappeared.


First on the List: Effectiveness at Self-Regulation and Prioritizing Difficult Exercise Goal Pursuit.
Identifying and understanding the goal pursuit strategies that distinguish effective self-regulators from less effective self-regulators is important for elucidating how individuals achieve their goals. We suggest that the timing of plans for difficult goal pursuits is one differentiation. A pilot study shows that effective self-regulators tend to believe they are best suited to pursue difficult goals earlier in the day, and two studies provide evidence that effective and less effective self-regulators differ in the timing of their plans for difficult goal pursuits. Results indicate that when exercising is perceived as difficult goal pursuit, effective self-regulators prioritize that difficult goal pursuit by planning to exercise earlier in the day whereas less effective self-regulators plan exercise for later in the day.


Nrf2 alleviates spaceflight-induced immunosuppression and thrombotic microangiopathy in mice.
Spaceflight-related stresses impact health via various body systems, including the haematopoietic and immune systems, with effects ranging from moderate alterations of homoeostasis to serious illness. Oxidative stress appears to be involved in these changes, and the transcription factor Nrf2, which regulates expression of a set of cytoprotective and antioxidative stress response genes, has been implicated in the response to spaceflight-induced stresses. Here, we show through analyses of mice from the MHU-3 project, in which Nrf2-knockout mice travelled in space for 31 days, that mice lacking Nrf2 suffer more seriously from spaceflight-induced immunosuppression than wild-type mice. We discovered that a one-month spaceflight-triggered the expression of tissue inflammatory marker genes in wild-type mice, an effect that was even more pronounced in the absence of Nrf2. Concomitant with induction of inflammatory conditions, the consumption of coagulation-fibrinolytic factors and platelets was elevated by spaceflight and further accelerated by Nrf2 deficiency. These results highlight that Nrf2 mitigates spaceflight-induced inflammation, subsequent immunosuppression, and thrombotic microangiopathy. These observations reveal a new strategy to relieve health problems encountered during spaceflight.


Difficult cases in heart failure: Expanding the therapeutic armamentarium in decompensated heart failure: using intravenous fenoldopam.
The authors report the clinical use of fenoldopam, a dopamine agonist, in a patient with decompensated heart failure and severe pulmonary hypertension. In addition, they explore the potential mechanisms by which fenoldopam exerts its beneficial effects and review the literature regarding the use of this agent in systolic heart failure. (c)2001 by CHF, Inc.


The effect of pH and hypoxia on function and intracellular pH of the rat diaphragm.
We studied the relationship between contractile function and intracellular pH (pHi) in the isolated rat diaphragm when superfusate PCO2 was changed during hyperoxia or hypoxia. Superfused diaphragm strips were field stimulated at 0.5 Herz, and twitch tension (TT) was recorded. The pHi was calculated from the volume distribution of a weak acid, dimethyl-oxazolidinedione. In hyperoxia, hypercapnic acidosis (pH 7.06-6.63) depressed diaphragm pHi and TT, whereas hypocapnic alkalosis (pH 7.82-8.15) increased pHi but did not significantly affect TT. TT was maximum at physiological pHi (7.06), but in hyperoxic hypercapnic muscles substantial force was still generated at pHi values as low as 6.44. Hypoxia (PO2 30-38 mm Hg) markedly reduced TT; this effect was slightly exacerbated by hypercapnia and attenuated by hypocapnia. Hypoxia lowered pHi by about 0.2 units, which was insufficient to account for the hypoxic contractile failure. Knowledge of the hyperoxic muscle TT/pHi relationship suggests that, in other contexts, caution should be exercised in attributing severe muscle fatigue or force loss to modest falls in pHi.


Effect of rifampicin pretreatment on the oral bioavailability of domperidone in healthy human volunteers.
Increased exsorption of domperidone was observed from different parts of the small intestine of the rat after pretreatment with rifampicin by the everted sac method. Based on the in vitro studies the effect of rifampicin pretreatment on the pharmacokinetics of domperidone was investigated in eight healthy male volunteers. After an overnight fast, 20 mg domperidone was administered to the volunteers, either alone or after 6 days pretreatment with a once daily dose of 600 mg rifampicin. Serum concentrations of domperidone were estimated by reverse phase HPLC. Pharmacokinetic parameters were determined based on non-compartmental model analysis using the computer program kinetica. Rifampicin pretreatment decreased Cmax, AUCo-∞, AUMC, MRT and t1/2 by 25.11%, 37.76%, 64.97%, 43.71% and 44.48%, respectively. This may be due to increased induction of cytochrome P450 enzymes and/or increased expression of P-glycoprotein. This interaction may have clinical significance when domperidone is co-administered with rifampicin in chronic treatment conditions, such as tuberculosis, leprosy and other infections of joints, bones, etc.


Intersectional Structural Stigma, Community Priorities, and Opportunities for Transgender Health Equity: Findings from TRANSforming the Carolinas.
In this manuscript, "Intersectional Structural Stigma, Community Priorities, and Opportunities for Transgender Health Equity," Poteat and Simmons outline the legal and policy barriers that impede efforts to end the HIV epidemic among transgender people in the South. They present qualitative and quantitative data from a community engaged research study conducted with transgender adults and other key stakeholders as well as finding from an analysis of policies impacting transgender people in both states. Violence prevention and decriminalization are highlighted as key policy initiatives that would advance health equity for transgender people.


Nucleotide sequence and structural analysis of the rat RT1.Eu and RT1.Aw3l genes, and of genes related to RT1.O and RT1.C.
A cDNA library was constructed using mRNA isolated from the R21 strain of rats which have the major histocompatibility complex (MHC) haplotype RT1.AlBlDlEu and the growth and reproduction complex (grc) genotype grc+. The cDNA clones that hybridized with the class I probes pAG64c and pARI.5 and were 1.3-1.7 kilobases were selected. Full-length clones were identified by sequencing partially the 5' and 3' ends of each clone, by the presence of a start codon at the 5' end, and by a polyadenylation sequence at the 3' end. The full-length cDNA clones were examined for in vitro transcription by transfection into human CIR cells using electroporation, and expression was detected by flow cytometry using monoclonal antibodies specific to the heavy chains and polyclonal antibody to beta 2-microglobulin. The RT1.Eu gene was transcribed and expressed optimally, and its nucleotide and deduced amino acid sequences differed significantly from the RT1.Aa, RT1.A(l), RT.Au, LW2, and 11/3R genes but only slightly from the RT1.K gene. The high level of sequence similarity between RT1.Eu and RT1.K suggests that the two genes may have originated from a common ancestral gene. In addition, three new genes (RT1.Aw3l, RT1.C-type, and RT1.O-type) were identified. The RT1.Aw3l gene is almost identical to RT1.A(l) with the exception of an in frame deletion of 21 nucleotides in exon 2 leading to a 7 amino acid deletion in the alpha 1 domain of the deduced amino acid sequence and 11 nucleotide substitutions and insertions in the rest of the sequence. It transcribed optimally, but no significant expression was detected. The RT1.C-type gene 119 is very similar (97%) to the LW2 gene in the 3' untranslated region, which suggests that it is in the RT1.C region. It transcribed optimally, but no significant expression was detected. The RT1.O-type gene 149 has all the features of a class Ib gene, but a premature stop codon in the alpha 1 domain causes incomplete translation. Its in vitro transcription was very low, and no expression was detected. These studies, combined with previous work, indicate that in the MHC of the R21 strain three class Ia genes (Eu, A(l), Aw3l) and three class Ib genes (C-type, O-type, N) are transcribed but only two class Ia genes (Eu, A(l)) are expressed.


[Clinical features and genetic analysis of a Chinese pedigree affected with X-linked adrenoleukodystrophy].
To analyze the clinical features and variants of ABCD1 gene in a Chinese pedigree affected with X-linked adrenoleukodystrophy. Clinical data of the proband were collected and analyzed. Potential variant of the ABCD1 gene were analyzed by PCR and Sanger sequencing of the proband, his parents and 100 unrelated healthy individuals. The prominent features of the proband included cerebellar and brainstem lesions, along with increased serum level of very-long chain fatty acids. He was found to harbor a hemizygous c.1509delG (p.L504Sfs*54) variant of the ABCD1 gene, for which his mother was heterozygous. The same variant was not detected in his father and 100 healthy controls. X-linked adrenoleukodystrophy has a variety of clinical manifestations. Discovery of the c.1509delG (p.L504Sfs*54), as a novel pathogenic variant of the ABCD1 gene, has enabled diagnosis and genetic counseling for this pedigree.


Matrix Metalloproteinase-9 as a Marker for Plaque Rupture and a Predictor of Adverse Clinical Outcome in Patients with Acute Coronary Syndrome: An Optical Coherence Tomography Study.
The present study sought to clarify the relationship between matrix metalloproteinase-9 (MMP-9) levels and plaque morphology demonstrated by optical coherence tomography (OCT), and to examine their prognostic impacts in patients with acute coronary syndrome (ACS). MMP-9 levels were measured for patients with ACS (n = 249). Among 249 patients, 120 with evaluable OCT images were categorized into patients with ruptured plaques (n = 65) and those with nonruptured plaques (n = 55) on the basis of culprit lesion plaque morphology demonstrated by OCT. MMP-9 levels on admission were significantly higher in the rupture group than in the nonrupture group (p = 0.029). Although creatine kinase-MB (CK-MB) on admission was comparable between the groups, peak CK-MB was higher in the rupture group than in the nonrupture group (p < 0.001). By receiver operating characteristic curve analysis, the optimal cut-off value of MMP-9 to detect ruptured plaques was 65.5 ng/ml (p = 0.029). There was a nonstatistically significant trend toward increased cardiac death at 2 years (5.9 vs. 1.0%, p = 0.059) in patients with high MMP-9 (≥65.5 ng/ml) compared to those with low MMP-9 (<65.5 ng/ml). MMP-9 can differentiate ACS with ruptured plaques from nonruptured plaques, and MMP-9 may be a valuable predictor of long-term cardiac mortality in patients with ACS reflecting plaque rupture.


Reovirus RNA transcriptase: evidence for a conformational change during activation of the core particle.
Reovirus cores contain an RNA transcriptase capable of synthesizing messenger RNA. When cores are suspended in 1 X SSC at 37 degrees they are quiescent and synthesize no product, but in the presence of the components of an RNA transcriptase reaction mixture they actively synthesize mRNA. Photochemical crosslinking has been used to investigate the arrangement of RNA and protein in both "quiescent" and "active" cores. Irradiation induces the formation of a noncovalent RNA:protein complex in "quiescent" but not in "active" cores. This difference is attributed to a conformational change in the reovirus core which results from the transition between the "quiescent" and "active" states of the particle.


Increase of large intramembranous particles in the presynaptic active zone after administration of 4-aminopyridine.
The effects of 4-aminopyridine (4-AP, 1 mg/kg i.v.) on the distribution of intramembranous particles in spinal motoneuronal synapses was examined in anesthetized (pentobarbital sodium, 50 mg/kg, i.p.) rats by freeze-etching electron microscopy. The particles were classified according to their size into small (4.2--10.5 nm in diameter) and large (10.5--18.9 nm in diameter). The active zone of the presynaptic membrane was identified on the basis of ultrastructural criteria. The large intramembranous particles in both protoplasmic (PF) and external fracture faces (EF) were aggregated more densely in the active zone as compared with its surroundings both in the control and 4-AP-treated group (P less than 0.001). The density of large particles in the PF rose from 300/sq.micron under the influence of 4-AP (P less than 0.001). The increased frequency of vesicle attachment sites at the presynaptic membrane (from 115/sq.micron in barbiturized controls to 150/sq.micron in 4-AP treated animals) seemed to be positively correlated with the increasing density of large particles. Based on these findings it is suggested that the large intramembranous particles of the presynaptic membrane may participate in the control of calcium fluxes which are essential to the transmitter release by exocytosis.


Development and testing of the Labor Support Scale.
Nurses use interventions and supportive strategies to help mothers throughout labor, yet little research examines intrapartum nurses' labor support techniques. The purpose of the study was to develop and test a self-report instrument, the Labor Support Scale (LSS), to describe the frequency with which nurses perform interventions and nurses' perceptions of the helpfulness of interventions. Steps for instrument development were item generation, content validity testing, piloting, refining, and administering the questionnaire in two studies (n = 307, n = 472). Internal consistency reliability was .90 and .92 for the frequency and helpfulness portions of the instrument (respectively). Exploratory factor analysis, known groups technique, content analysis, and discriminant analysis evaluated validity. In both phases, instrument psychometrics provided evidence of content, construct, and discriminant validity.


Continuous intra-articular infusion of bupivacaine for postoperative pain following total knee arthroplasty.
This study assessed the efficacy of local, continuous infusion of bupivacaine for pain control following total knee arthroplasty. Eleven men and 19 women with an average age of 65 years (range: 43-83 years) randomly received either 0.25% bupivacaine or normal saline by local infusion pump. Standard wound drainage also was implemented. Pain was assessed with a visual analog scale along with patient-controlled analgesia demand, narcotic delivery, and nonsteroidal anti-inflammatory administration. Drug lost to drainage also was assessed. Mean preoperative visual analog scores were similar between the saline and bupivacaine groups (6.5 +/- 1.4 and 6.1 +/- 2.0, respectively; P = .535). By the end of the second postoperative day, scores decreased to 3.4 +/- 3.2 for the saline group and 2.5 +/- 1.6 for the bupivacaine group. Although postoperative reductions were statistically significant (P = .007), the main treatment effect was not (P = .404). Mean narcotic demand and usage were 87 +/- 114.1 requests with usage of 11.8 +/- 12.3 mg for the saline group and 96 +/- 104.8 requests with usage of 7.5 +/- 3.8 mg for the bupivacaine group (P = .505). Cumulative ketorolac administration was 47 +/- 52.2 mg for the saline group and 83.6 +/- 64.9 mg for the bupivacaine group (P=.100). Hydrocodone-acetaminophen usage also was similar between the saline and bupivacaine groups (88 +/- 43.9 mg and 64.6 +/- 35 mg, respectively) (P = .112). Drug lost to drainage was estimated to be 27%. These findings suggest continuous local analgesic infusion after total knee arthroplasty does not offer significant improvements in either pain relief or medication use. Drug loss from drainage may exceed 25% and may compromise analgesic effectiveness.


Defining small-for-gestational-age: prescriptive versus descriptive birthweight standards.
Descriptive population-based birthweight standards possess low sensitivity in detecting infants with growth impairment. A prescriptive birthweight standard based on a 'healthy' subpopulation without risk factors for intrauterine growth restriction might be superior. We created two birthweight standards based on live born, singleton infants with gestational age 24-42 weeks and born in The Netherlands between 2000 and 2007. Inclusion criteria for the prescriptive birthweight standard were restricted to infants without congenital malformations, born to healthy mothers after uncomplicated pregnancies. We defined small-for-gestational-age (SGA) as birthweight <10th percentile and assessed the ability of both standards to predict adverse neonatal outcomes. The prescriptive birthweight standard identified significantly more infants as SGA, up to 38.0 % at 29 weeks gestation. SGA infants classified according to both standards as well as those classified according to the prescriptive birthweight standard only, were at increased risk of both major and minor adverse neonatal outcomes. The prescriptive birthweight standard was both more sensitive and less specific, with a maximum increase in sensitivity predicting bronchopulmonary dysplasia (+42.6 %) and a maximum decrease in specificity predicting intraventricular haemorrhage (-26.9 %) in infants aged 28-31 weeks. Prescriptive birthweight standards could improve identification of infants born SGA and at risk of adverse neonatal outcomes. • Descriptive birthweight standards possess low sensitivity in detecting growth restricted infants at risk of adverse neonatal outcomes. • Prescriptive standards could improve identification of very preterm small-for-gestational-age (SGA) infants at risk of intraventricular haemorrhage. What is New: • Prescriptive standards identify more preterm and term SGA infants at risk of major adverse neonatal outcomes. • Late preterm and term SGA infants classified according to the prescriptive standard are at increased risk of minor adverse neonatal outcomes with potentially harmful implications.


4-(Di-methyl-amino)-benzohydrazide.
The title compound, C9H13N3O, crystallizes in the monoclinic space group C2/c and all non-hydrogen atoms are within 0.1 Å of the mol-ecular mean plane. In the crystal, the hydrogen-bonding pattern results in [001] chains built up from fused R 2 2(6) and R 2 2(10) rings; the former consists of N-H⋯N bonds and the latter N-H⋯O bonds. Electrostatic and dispersion forces are major contributors to the lattice energy, which was estimated by DFT calculations to be -215.7 kJ mol-1.


Market conditions of international VET providers: a comparative analysis of Australia, UK, USA, and Germany.
VET (vocational education and training) is a highly complex, multidimensional worldwide phenomenon with diverse structures. Additionally, very different actors define the functions of a national (or even a regional) VET system. The paper contributes to a better understanding of the policy frameworks and current states of such systems. Therefore, we focus on selected VET systems in order to understand their specifics and thus, their market conditions. A qualitative approach is used to answer the research question regarding which conditions create or support market-based opportunities for the provision of commercial vocational training services. We find that the liberalism and deregulation of the VET sectors, as well as the marketisation of VET practices, lead to incentives to internationalise VET offers. Thinking in terms of skills, the kind of education system does not play a role. This is the case in liberal market-driven VET approaches (here, the UK, the USA and Australia) and is mirrored in the micro-analysis categories of curricula, learning location, content, and learning process.


Migrant women caregivers' experiences in end-of-life formal care.
To describe and understand the experience of Latin American migrant women as caregivers of elderly people in situations of advanced illness and end of life. Qualitative study using Gadamer's hermeneutic phenomenology. Data were collected in 2019 through 9 semi-structured interviews with Latin American women caregivers, who had cared for people at the end of life, in the Province of Granada (Spain). Two themes emerged: "Migrant caregiver at the end of life" and "And now, what should I do?": the impact of the loss at the economic, emotional and labor level. Care during the end of life of the cared person generates an additional overload to the situation of migrant women. The experience of this stage is related to the bond with the persons cared and their families, which may affect the development of complicated grief and personal problems related to the loss of employment and the absence of economic support.


Multilocus phylogeny of Crenicichla (Teleostei: Cichlidae), with biogeography of the C. lacustris group: species flocks as a model for sympatric speciation in rivers.
First multilocus analysis of the largest Neotropical cichlid genus Crenicichla combining mitochondrial (cytb, ND2, 16S) and nuclear (S7 intron 1) genes and comprising 602 sequences of 169 specimens yields a robust phylogenetic hypothesis. The best marker in the combined analysis is the ND2 gene which contributes throughout the whole range of hierarchical levels in the tree and shows weak effects of saturation at the 3rd codon position. The 16S locus exerts almost no influence on the inferred phylogeny. The nuclear S7 intron 1 resolves mainly deeper nodes. Crenicichla is split into two main clades: (1) Teleocichla, the Crenicichla wallacii group, and the Crenicichla lugubris-Crenicichla saxatilis groups ("the TWLuS clade"); (2) the Crenicichla reticulata group and the Crenicichla lacustris group-Crenicichla macrophthalma ("the RMLa clade"). Our study confirms the monophyly of the C. lacustris species group with very high support. The biogeographic reconstruction of the C. lacustris group using dispersal-vicariance analysis underlines the importance of ancient barriers between the middle and upper Paraná River (the Guaíra Falls) and between the middle and upper Uruguay River (the Moconá Falls). Our phylogeny recovers two endemic species flocks within the C. lacustris group, the Crenicichla missioneira species flock and the herein discovered Crenicichla mandelburgeri species flock from the Uruguay and Paraná/Iguazú Rivers, respectively. We discuss putative sympatric diversification of trophic traits (morphology of jaws and lips, dentition) and propose these species flocks as models for studying sympatric speciation in complex riverine systems. The possible role of hybridization as a mechanism of speciation is mentioned with a recorded example (Crenicichla scottii).


Systematic Review of the Effectiveness, Safety, and Acceptability of Mifepristone and Misoprostol for Medical Abortion in Low- and Middle-Income Countries.
Abortion-related complications remain one of the leading causes of maternal morbidity and mortality worldwide. Nearly half of all abortions are unsafe, and the vast majority of these occur in low- and middle-income countries. The use of mifepristone with misoprostol for medical abortion has been proposed and implemented to improve abortion safety. A systematic review of the literature was conducted in PubMed, Embase, Cochrane, and CINAHL. Criteria for study inclusion were first-trimester abortion, use of mifepristone with misoprostol, and low- or middle-income country status as designated by the World Health Organization. Results for effectiveness, safety, acceptability, and qualitative information were assessed. The literature search resulted in 181 eligible articles, 52 of which met our criteria for inclusion. A total of 34 publications reported effectiveness data on 25 385 medical abortions. The average effectiveness rate with mifepristone 200 mg and misoprostol 800 µg was 95% up to 63 days gestation. A sensitivity analysis was performed to assume that all women lost to follow-up failed treatment, and the recalculated effectiveness rate remained high at 93%. The average continuing pregnancy rate was 0.6%. A total of 22 publications reported safety and acceptability data on 17 381 medical abortions. Only 0.8% abortions required presentation to hospital, and 87% of patients found the side effects of treatment acceptable. Overall, 95% of women were satisfied with their medical abortion, 94% would choose the method again, and 94% would recommend this method to a friend. A total of 16 publications reported qualitative results and the majority supported positive patient experiences with medical abortion. Mifepristone and misoprostol is highly effective, safe, and acceptable to women in low- and middle-income countries, making it a feasible option for reducing maternal morbidity and mortality worldwide.


[Participation--oriented analysis of the anesthesia workplace. A work system for anesthesia in a multidisciplinary operating room].
The aim of this study was the detection and understanding of weak points in the ergonomic design of anaesthesia workplaces in a multidisciplinary operating room facility. Analysis of workplaces and of working processes by means of observations, computer-supported task recording and video-photo documentation. During guided interviews the participants were provided with material for naming-by-pointing and drawing. Subsequently, the background of the problems encountered and possible improvements were visualised. Important deficits were devices not positioned within reach and view, difficulties in operating the lines connecting the patient and the devices, and inconsistent workplace layouts. These were caused by erroneous planning of the facility and disregarding ergonomic principles in equipment design. The initial improvements implemented were the development of a new concept for a flexible equipment positioning and the design of a tool for cable handling. Although from the very beginning of the study the anaesthesia personnel quoted the handling of the lines connecting patients and devices as the main cause for working difficulties, the external ergonomist could contribute to a broader view of the problems. The method presented here initiated a mutual learning process between ergonomist and users and resulted in a common understanding of the problems and their causes. Compared to the traditional consulting process, more time and efforts were necessary but were offset by the users' acceptance of the improvements and the prevention of design errors.


Complementary and Integrative Approaches to Sleep Disorders in Children.
Sleep problems are very common in children and adolescents. Chronic insomnia is the leading cause of sleep disorders in children and adolescents. Adjunctive interventions that address low ferritin levels and vitamin D3 deficiency are helpful in children and adolescents. The addition of l-5-hydroxytryptophan, gabadone, l-theanine, Ashwagandha, omega 3 fatty acids, probiotics in bipolar disorder, and children with colic, meditation, and changing from a high-fat diet to a Mediterranean diet are also helpful adjunctive interventions. Actigraphy data should be collected in future sleep studies because subjective data may not indicate the true effect of the intervention.


Perception of cancer recurrence risk: more information is better.
Breast cancer is the most common cancer among women worldwide. Given the advances in extending survival, the number of recently diagnosed breast cancer patients and longer-term breast cancer survivors is growing. The goals of this study were to better understand (1) perceptions of provider cancer recurrence risk communication, (2) perceived risk of breast cancer recurrence in cancer patients and survivors, and (3) accuracy of perceived risk. A survey was conducted on women with a prior breast cancer (n=141). Approximately 40% of women perceived that providers had not talked about their breast cancer recurrence risk; although only 1 person reported not wanting a physician to talk to her about her risk. Women were largely inaccurate in their assessments of risk. Greater worry, living in a rural area, and longer time since diagnosis were associated with greater inaccuracy. Women tended to think about distal recurrence of cancer as often of local recurrence. Perceived risk of breast cancer recurrence was inaccurate, and patients desired more communication about recurrence risk. Consistent with findings from other studies, greater efforts are needed to improve the communication of cancer recurrence risk to patients. Attention should be paid to those from rural areas and to distal cancer recurrence in women with a previous history of breast cancer.


Analytical Performance and Validation of a Reliable Method Based on Graphite Furnace Atomic Absorption Spectrometry for the Determination of Gold Nanoparticles in Biological Tissues.
Gold nanoparticles (AuNPs) have a wide-ranging application and are widespread in samples with complex matrices; thus, efficient analytical procedures are necessary to identify and characterize this analyte. A sensitive analytical method for determination of AuNPs content in biological tissues, based on microwave-assisted acid wet digestion and graphite furnace atomic absorption spectrometry (GFAAS) validated in accordance with the requirements of Eurachem guideline and ISO 17025 standard, is presented in this study. The digestion procedure was optimized, and the figures of merit such as selectivity, limit of detection (0.43 µg L-1), limit of quantification (1.29 µg L-1, corresponding to 12.9 µg kg-1 in tissue sample, considering the digestion), working range, linearity, repeatability ((RSDr 4.15%), intermediate precision (RSDR 8.07%), recovery in accuracy study (97%), were methodically evaluated. The measurement uncertainty was assessed considering the main sources of uncertainties and the calculated relative expanded uncertainty (k = 2) was 12.5%. The method was applied for the determination of AuNPs in six biological tissues (liver, small intestine, heart, lungs, brain and kidneys) and the found concentrations were generally at low levels, close or lower than LOQ.


Saline at lower tonicity in cystic fibrosis (SALTI-CF) trial comparing 0.9% versus 3% versus 6% nebulised saline.
In people with cystic fibrosis (CF), regular nebulisation of 6% or 7% saline improves lung function; however, these concentrations are not always tolerable. Clinically, some CF patients report using lower concentrations of saline to improve tolerability, yet the effects of lower concentrations are unknown. This study therefore aimed to evaluate the relative effectiveness and tolerability of 0.9% versus 3% versus 6% saline nebulised twice daily with an eFlow rapid nebuliser. This was a randomised, blinded, placebo-controlled, parallel-group, multicentre study where subjects inhaled 4 mL of 0.9%, 3% or 6% saline twice daily for 16 weeks. The primary outcome was forced expiratory volume in 1 s. The secondary outcomes were: forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC; quality of life; exercise capacity; acquisition or loss of bacterial organisms in expectorated sputum; tolerability of nebulised saline; pulmonary exacerbations; and adverse events. 140 participants were randomised to 0.9% (n=47), 3% (n=48) or 6% (n=45) saline. 134 participants (96%) contributed to the intention-to-treat analysis. 3% saline significantly improved lung function and increased the time to first pulmonary exacerbation compared with 0.9% saline but did not improve quality of life. 6% saline had similar benefits to 3% saline but also significantly improved quality of life compared with 3% saline. Only 6% saline delayed the time to intravenous antibiotics for pulmonary exacerbation. Tolerability and adherence were similar. Dilution of 6% saline to 3% maintains the benefits for lung function and exacerbation prevention; however, the positive impacts of 6% saline on quality of life and time to i.v. antibiotics for pulmonary exacerbations are lost.


How the S-ICD (subcutaneous implantable cardiac defibrillator) senses cardiac signals to minimize cardiac over-sensing and maximize rhythm discrimination.
Transvenous Implantable Cardioverter Defibrillator (TV-ICD) and subcutaneous ICD (S-ICD) devices are available for patients at risk of sudden cardiac death (SCD). Both devices sense ventricular arrhythmias with near 100% sensitivity (Gold et al., 2012) and have similar rates of inappropriate shocks (IAS) (2.5-4.8%). IAS due to supraventricular tachycardias (SVT) is higher for TV-ICDs and IAS due to cardiac over-sensing is higher for S-ICDs (Basu-Ray et al., 2017). The S-ICD's sensing signal is morphologically rich, resembling the surface electrocardiogram (ECG) signal. As such, correlation waveform analysis (CWA) is used by the S-ICD to compare the morphology of two signals to minimize S-ICD cardiac over-sensing and rhythm discrimination errors. Early experience showed that the S-ICD had a comparable overall incidence of IAS compared to TV-ICDs. Progressive improvements in S-ICD algorithms and programming strategies have resulted in overall IAS rate reduction to 4.3% (Theuns et al., 2018), substantiating the S-ICD as a viable choice for patients at risk of SCD.


Region-specific differences in Achilles tendon cross-sectional area in runners and non-runners.
The present study examined the cross-sectional area (CSA) of the Achilles tendon in subjects who repeatedly exposed their tendons to large loads (habitual runners) compared to control subjects (non-runners). Six male habitual runners [36 (7) years, 70.9 (4.4) kg and 1.84 (0.05) m, +/-SD] who had performed distance running (approximately 80 km per week) for the last 5 years were compared to six non-runners [34 (3) years, 81.2 (8.7) kg and 1.81 (0.02) m, +/-SD]. Tendon CSA was obtained from MR images obtained with the ankle in a neutral position (90 degrees ). The most proximal aspect of the tuberosity of calcaneus was used as a landmark to standardize the levels of images: the most distal image (1) was obtained 10 mm above the proximal tuberosity of calcaneus, and the most proximal image (7) was obtained 70 mm above the proximal tuberosity of calcaneus. There was a significant difference in CSA along the length of the tendon both in runners ( P<0.001) and non-runners ( P<0.01). In non-runners and runners the CSA of the most distal part was 51% and 85% greater than the most proximal part of the tendon, respectively. Furthermore, there was a difference in tendon CSA between the groups, such that runners had a greater CSA (36%) than non-runners at the most distal part of the tendon ( P<0.05). The greater CSA in the distal tendon may reflect differences in structural properties along the length of the human Achilles tendon, while the greater CSA in runners compared to non-runners may indicate a region-specific hypertrophy in response to the habitual loading of running.


Post-buckling behaviour of a growing elastic rod.
We consider mechanically-induced pattern formation within the framework of a growing, planar, elastic rod attached to an elastic foundation. Through a combination of weakly nonlinear analysis and numerical methods, we identify how the shape and type of buckling (super- or subcritical) depend on material parameters, and a complex phase-space of transition from super- to subcritical is uncovered. We then examine the effect of heterogeneity on buckling and post-buckling behaviour, in the context of a heterogeneous substrate adhesion, elastic stiffness, or growth. We show how the same functional form of heterogeneity in different properties is manifest in a vastly differing post-buckled shape. Finally, a fourth form of heterogeneity, an imperfect foundation, is incorporated and shown to have a more dramatic impact on the buckling instability, a difference that can be qualitatively understood via the weakly nonlinear analysis.


Survey of Her2-neu Expression and its Correlation with Histology of Gastric Carcinoma and Gastroesophageal Junction Adenocarcinoma.
There is increasing evidence that HER2-neu is an important biomarker in gastric carcinomas (GC) and gastroesophageal junction (GEJ) adenocarcinomas. The aim of this study was to evaluate HER2-neu expression and also some clinicopathological features of these neoplasms. We selected 211 paraffin-embedded blocks, 193 GC and 18 GEJ. Then 4 micron sections were prepared for staining with hematoxylin and eosin and also for IHC (Her2-neu). The Chi-square test was used for significance between expression of HER2-neu and clinicopathological parameters. In patients with advanced cancer of GC and GEJ, HER2-neu overexpression was more associated with the intestinal cancer subtype. This could be a guide to new complementary therapy for affected patients.


Analysis of interactions between the corneal epithelium and liposomes: qualitative and quantitative fluorescence studies of a corneal epithelial cell line.
Transcorneal drug transport is normally limited by the intrinsic permeation characteristics of the corneal epithelium. However, liposomes, i.e., phospholipid vesicles composed of phospholipid membranes, have recently attracted attention as carriers of topically applied agents. The present study therefore describes a qualitative and quantitative laboratory investigation of interactions between corneal epithelial cells and liposomes. The lipid bilayers and interior spaces of liposomes were labelled with different fluorophores. Fluorescence microscopy revealed a rapid uptake of rhodamine B-labelled liposome bilayer components by the epithelial cell membrane and the cytoplasm. Simultaneously, intracellular uptake of aqueous liposome content was indicated by uniform fluorescence of the cytoplasm due to carboxyfluorescein (CF). The fluorimetric experiments showed that the uptake of liposomes by SIRC cells depended on liposome concentrations and the time of exposure of the cells to the liposomes, and that saturation effect characteristics were present. Cell fluorescence dropped by approximately 45% when the incubation temperature of the cells was reduced from 37 degrees C to 4 degrees C. Both this phenomenon and a significant reduction in liposome uptake (p < 0.05 and p < 0.01) after incubation with the metabolic inhibitors 2-deoxyglucose and sodium azide indicated active, energy-dependent processes. Phagocytosis in cell-liposome interactions was directly shown by a significant reduction in cell fluorescence (p < 0.05) after application of the actin inhibitor cytochalasin B. The results presented here give concrete data on interactions between liposomes and superficial cells of the eye in vitro.


[Earthquakes in Mexico in 1985. Their psychological repercussions and intervention by psychoanalysts].
Starting with a real event, the Mexican earthquake of 1985, this article describes a certain number of practices of Mexican psychoanalysts and their theoretical reflections which grew out of the experience of helping a disaster-struck population during a crisis period. The result of this intervention was that it enhanced the elaboration of the emotional and traumatic conflict created by this kind of natural phenomenon. This work, a; though not constituting a generalized practice within psychoanalysis, corroborates certain processes in Freud's second theory of drives.


Increased waking after intra-accumbens injection of m-chlorophenylbiguanide: prevention with serotonin or dopamine receptor antagonists.
Bilateral injection of the selective 5-HT3 receptor agonist m-chlorophenylbiguanide (5.0-40.0 micrograms) into the nucleus accumbens of the rat significantly increased waking and decreased slow wave sleep. Rapid eye movement (REM) sleep remained unchanged. Pretreatment with the 5-HT3 receptor antagonist MDL 72222 (1aH,3a,5a, H-tropan-3-yl-3,5-dichloro-benzoate) (0.5 mg/kg s.c.) reversed the effects of m-chlorophenylbiguanide (10.0-20.0 micrograms) on sleep and waking. Blockade of the dopamine D1 or D2 receptor with (+)-SCH 23390 (0.25 mg/kg s.c.) or YM-09151-2 (cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide) (0.5 mg/kg s.c.), respectively antagonized the increase of waking and reduction of slow wave sleep induced by m-chloro-phenylbiguanide (10.0 micrograms). Our results tend to indicate that the increase of wakefulness after injection of the selective 5-HT3 receptor agonist m-chlorophenylbiguanide into the nucleus accumbens is partly related to the release of endogenous dopamine. In addition, they suggest that concomitant stimulation of both accumbens dopamine D1 and D2 receptor-related mechanisms is a necessary prerequisite to increase wakefulness.


Surgical pinealectomy accelerates intervertebral disc degeneration process in chicken.
Despite the importance of intervertebral disc (IVD) degeneration both in research and clinical practice, the underlying biological mechanism of this phenomenon remains obscure. The current study investigated the effects of neonatal pinealectomy on the development of IVD degeneration process in chicken. Thirty chicks (3 days of age) were divided into two equal groups: unoperated controls (Group X) and pinealectomized chicks (Group Y). Pinealectomies were performed at the age of 3 days. At the age of 8 weeks, magnetic resonance imaging examination of one animal in each experimental group was taken. At the end of the study, serum melatonin level was determined by using ELISA method and histopathological or biochemical examination of specimens from all subjects was done. The results of biochemical analyses were compared using Mann-Whitney U test, whereas The Chi-square test was adopted for the histological findings. In this study, the serum melatonin levels in Group Y were significantly lower than those in Group X (P < 0.001). Similarly, scoliosis was developed in 14 out of 15 (93%) in Group Y. Hydroxyproline content of IVD tissue was high in Group Y compared with the values in Group X, although there was no significant difference. Histologically, an appearance of normal IVD was observed in Group X, while the presence of a degenerated IVD was observed in Group Y. From the results of the current study, it is evident that surgical pinealectomy in new-hatched Hybro Broiler chicks has a significant effect on serum melatonin level as well as on the development of IVD degeneration and spinal malformation. In the light of these results from present animal study, melatonin may play a role in the development of IVD degeneration in human beings, but this suggestion need to be validated in the human setting.


Clinical significance of no-reflow in different stages of primary angioplasty among patients with acute myocardial infarctions.
The coronary no-reflow (NR) phenomenon, which is associated with poor clinical outcomes, is usually referred to as a post-percutaneous coronary intervention (PCI) state. NR can occur in different stages of the PCI procedure, not only including the post-stenting stage, but from balloon pre-dilation to pre-stenting. The clinical significance of NR in the different stages of the PCI procedure is unclear. The purpose of the current study was to analyze the clinical and angiographic characteristics, the prognosis for NR patients in the aforementioned two stages and to determine the predictors of NR in the early stage. Between January 2009 and December 2013, a total of 420 consecutive patients with ST-segment elevation myocardial infarction (STEMI) underwent primary PCI. Sixty-three patients (15%) with NR constituted the study population. The patients were divided into an early NR group and a subsequent NR group. The clinical and angiographic findings were compared between the two groups. Multivariate logistic regression was used to determine the predictors for early NR. The long-term clinical outcomes after PCI were analyzed. Regarding the baseline characteristics, we identified that the early NR group had statistically significant effects on the higher percentage of diabetes mellitus (42.9% vs. 20%), lower admission systolic blood pressure (SBP) (102.2 ± 8.3 mmHg vs. 110.5 ± 7.6 mmHg), higher percentage of Killip classification III (71.4% vs. 45.7%,) and longer reperfusion time (7.1 ± 2.3 h vs. 5.88 ± 2.2 h) compared to the subsequent NR group.There were significant differences between the two groups with respect to the percentage of initial thrombolysis in myocardial infarction (TIMI) flow 0/1 (64.3% vs. 37.1%), target lesion length (31.4 ± 13.6 mm vs. 20.5 ± 17.3 mm) and thrombus score ⩾ 4 (67.9% vs. 42.9%; p < 0.05 for all). Multiple stepwise logistic regression analysis indicated that an admission SBP < 100 mmHg (OR = 4.580; 95% CI = 1.385-15.150; p = 0.0130), reperfusion time ⩾ 6 h (OR = 4.978; 95% CI = 1.468-16.882; p = 0.010) and a thrombus score ⩾ 4 (OR = 2.708; 95% CI = 0.833-8.799; p = 0.008) were the independent determinants of the early NR. During a 1-year follow-up, the all-cause mortality and overall major adverse cardiac events (MACEs) in the early NR group occurred significantly more often than in the subsequent NR group (28.6% vs. 5.7% and 35.7% vs. 14.3%, respectively, p ITALIC! <0.05). The early NR group had a lower left ventricular ejection fraction (LVEF) (42.5 ± 4.7 vs. 47.8 ± 3.5, p ITALIC! < 0.001) and a larger left ventricular end diastolic diameter (LVEDD) (56.0 ± 4.0 vs. 51.5 ± 4.7, p = 0.001) at the end of the follow-up. Early NR patients during primary PCI have more severe baseline clinical and angiographic characteristics, as well as a poorer long-term prognosis.


Comparison of six risk scores for in-hospital mortality in Chinese patients undergoing heart valve surgery.
To compare six risk scores with regard to their validity to predict in-hospital mortality after heart valve surgery in a single-centre patient population of China. From January 2006 to December 2011, 3479 consecutive patients who underwent heart valve surgery at our centre were collected and scored according to the EuroSCORE II, VA risk score, NNE risk score, Ambler risk score, NYC risk score, and STS risk score. Calibration of the six risk scores was assessed by the Hosmer-Lemeshow (H-L) test. Discrimination was tested by calculating the area under the receiver operating characteristic (ROC) curve. Observed mortality was 3.32% overall. The STS score showed good calibration in predicting in-hospital mortality (H-L: P = 0.126). The EuroSCORE II, VA score, NNE score, and NYC score underpredicted observed mortality (H-L: P < 0.0001, P < 0.0001, P = 0.001, and P < 0.0001, respectively) and the Ambler score overpredicted observed mortality (H-L: P = 0.005). The discriminative power (i.e. the area under the ROC curve) for in-hospital mortality was highest for the STS score (0.706), followed by the EuroSCORE II model (0.693), NNE score (0.684), NYC score (0.682), Ambler score (0.677) and VA score (0.643). Compared with the EuroSCORE II, VA score, NNE score, NYC score, and the Ambler score, the STS score gives an accurate prediction for individual operative risk in patients undergoing heart valve surgery at our centre. Therefore, the use of the STS score for risk evaluation maybe suitable in patients undergoing heart valve surgery at our centre in the future.


Ensemble of fuzzy-analytical hierarchy process in landslide susceptibility modeling from a humid tropical region of Western Ghats, Southern India.
The western flanks of the Western Ghats are one of the major landslide hotspots in India. Recent rainfall triggered landslide incidents in this humid tropical region necessitating the accurate and reliable landslide susceptibility mapping (LSM) of selected parts of Western Ghats for hazard mitigation. In this study, a GIS-coupled fuzzy Multi-Criteria Decision Making (MCDM) technique is used to evaluate the landslide-susceptible zones in a highland segment of the Southern Western Ghats. Fuzzy numbers specified the relative weights of nine landslide influencing factors that were established and delineated using the ArcGIS, and the pairwise comparison of these fuzzy numbers in the Analytical hierarchy process (AHP) system resulted in standardized causative factor weights. Thereafter, the normalized weights are assigned to corresponding thematic layers, and finally, a landslide susceptibility map is generated. The model is validated using the area under the curve values (AUC) and F1 scores. The result reveals that about 27% of the study area is classified as highly susceptible zones followed by 24% area in moderately susceptible zone, 33% in low susceptible, and 16% in a very low susceptible area. Also, the study shows that the plateau scarps in the Western Ghats are highly susceptible to the occurrence of landslides. Moreover, the predictive accuracy estimated by the AUC scores (79%) and F1 scores (85%) shows that the LSM map is trustworthy for future hazard mitigation and land use planning in the study area.


Highly selective removal of Zn(II) ion from hot-dip galvanizing pickling waste with amino-functionalized Fe3O4@SiO2 magnetic nano-adsorbent.
Amino-functionalized Fe3O4@SiO2 magnetic nano-adsorbent was used as a novel sorbent to highly selective removal of Zn(II) ion from hot-dip galvanizing pickling waste in the presence of Fe(II). These hot-dip galvanizing pickling waste mainly contain ZnCl2 and FeCl2 in aqueous HCl media. The properties of this magnetic adsorbent were examined by transmission electron microscopy (TEM), powder X-ray diffraction (XRD), infrared spectrometer (FT-IR) and BET surface area measurements. Various factors influencing the adsorption of Zn(II) ion such as initial concentration of metal ions, the amount of adsorbent, pH value of the solutions, the concentration of coexisting iron ion were investigated by batch experiments. The results indicated that the adsorption equilibrium data obeyed the Freundlich model with maximum adsorption capacities for Zn(II) to 169.5mg/g. The maximum adsorption occurred at pH 5±0.1 and Fe(II) interferences had no obvious influence. This work provides a potential and unique technique for zinc ion removal from hot-dip galvanizing pickling waste.


[Endoscopy on the surgical intensive care unit].
Endoscopy is most frequently performed in intensive care units (ICU) for gastrointestinal bleeding; however, there are other indications for performing an endoscopy on the ICU. This article shows the indications for this, the background and the peri-interventional and postinterventional management. The endoscopic placement of a postpyloric feeding tube is a well-established procedure. For anastomotic leakage in the esophagus and rectum, the endoscopic vacuum therapy is the treatment of choice. Gastrointestinal motility disorders are a frequent phenomenon in critically ill patients and are associated with increased mortality. With a cecal diameter > 9-12 mm, endoscopic decompression can be performed; however, this is associated with an increased risk of perforation and should only be carried out after the failure of conservative treatment.


Urine metabolomics insight into acute kidney injury point to oxidative stress disruptions in energy generation and H2S availability.
Acute kidney injury (AKI) is one of the main complications in acute care medicine and a risk factor for chronic kidney disease (CKD). AKI incidence has increased; however, its diagnosis has limitations and physiopathological mechanisms are underexplored. We investigated urine samples, aiming to identify major metabolite changes during human AKI evolution. Metabolic signatures found were further explored for a potential link to severity of injury. Twenty-four control subjects and 38 hospitalized patients with AKI were recruited and urine samples were collected at the time of diagnosis, during follow-up and at discharge. Nuclear magnetic resonance (NMR) was used in a first discovery phase for identifying potential metabolic differences. Target metabolites of interest were confirmed by liquid chromatography-mass spectrometry (LC-MS/MS) in an independent group. Underlying metabolic defects were further explored by kidney transcriptomics of murine toxic AKI. Urinary 2-hydroxybutyric acid, pantothenic acid, and hippuric acid were significantly downregulated and urinary N-acetylneuraminic acid, phosphoethanolamine, and serine were upregulated during AKI. Hippuric acid, phosphoethanolamine, and serine showed further downregulation/upregulation depending on the metabolite in acute tubular necrosis (ATN) AKI compared to prerenal AKI. Kidney transcriptomics disclosed decreased expression of cystathionase, cystathionine-β-synthase, and ethanolamine-phosphate cytidylyltransferase, and increased N-acetylneuraminate synthase as the potentially underlying cause of changes in urinary metabolites. A urinary metabolite panel identified AKI patients and provided insight into intrarenal events. A urine fingerprint made up of six metabolites may be related to pathophysiological changes in oxidative stress, energy generation, and H2S availability associated with AKI. The urinary metabolome reflects AKI evolution and severity of injury. Kidney transcriptomics revealed enzymatic expression changes. Enzymatic expression changes may be the potentially underlying cause of changes in urine metabolites. Identified metabolite changes link oxidative stress, energy generation, and H2S availability to AKI.


Polychlorinated biphenyls in settled dusts from an end-of-life vehicle processing area and normal house dusts in northern Vietnam: Occurrence, potential sources, and risk assessment.
Concentrations and congener-specific profiles of total 209 polychlorinated biphenyls (PCBs) were investigated in settled dust samples collected from end-of-life vehicle (ELV) processing, urban, and rural areas in northern Vietnam. Concentrations of total 209 PCBs, seven indicator congeners, and twelve dioxin-like PCBs decreased in the order: ELV working > ELV living ≈ urban > rural dusts. Penta- and hexa-CBs dominated the homolog patterns in all the samples with higher proportions in the ELV dusts compared to the urban and rural house dusts. The abundance and pattern of PCBs in the ELV dusts suggest on-going emissions of these compounds related to processing of vehicular oils and lubricants containing PCBs, whereas the presence of PCBs in the urban and rural house dusts indicate long-time releases. However, levels of some PCBs identified as by-products of pigment manufacturing (e.g., PCB-11 and PCB-209) were higher in the urban house dusts than those from other locations, resulting from human activities utilizing paints and pigments. Daily intake doses (ID), non-carcinogenic hazard quotient (HQ), and lifetime cancer risk (CR) of PCBs through dust ingestion were estimated for ELV workers and residents in the studied areas. The workers and children in the ELV sites were estimated to be at higher risk of PCB exposure, however almost all of the HQ < 1 and CR < 10-4 indicate no serious risk related to dust-bound PCBs.


Transient spine density increases in the mid-molecular layer of hippocampal dentate gyrus accompany consolidation of a spatial learning task in the rodent.
In previous studies, we observed a transient increase in dendritic spine frequency in the molecular layer of the dentate gyrus at 6h following passive avoidance training [O'Malley A., O'Connell C. and Regan C. M. (1998) Neuroscience 87, 607-613]. To determine if a similar change is associated with spatial forms of learning, we have estimated time-dependent modulations of spine number in the dentate gyrus of the adult rat following water maze training. All animals exhibited significant reductions in the latency to locate the platform over the five training sessions of the single trial (median and interquartile ranges of 60, 8 versus 8, 3 s for trials 1 and 5, respectively) and this improved performance was retained just prior to killing at the 6h post-training time. The unbiased dissector stereological procedure was used to estimate spine number in serial pairs of ultrathin coronal sections obtained at a point 3.3 mm caudal of Bregma. This analysis revealed a significant learning-associated increase in spine number at the 6h post-training time (1.32+/-0.18 spines/microm(3)) as it was not observed in paired controls exposed to the water maze for a similar swim-time (0.66+/-0.11 spines/microm(3)). The increase was transient as spine number returned to control levels at the 72 h post-training time. These spine frequency changes are proposed to reflect increased synapse turnover rate and concomitant change in connectivity pattern in the processing of information for long-term storage.


Anticancer properties of sodium selenite in human glioblastoma cell cluster spheroids.
Glioblastoma (GBM) is the most common type of primary tumor of the central nervous system with a poor prognosis, needing the development of new therapeutic drugs. Few studies focused on sodium selenite (SS) effects in cancer cells cultured as multicellular tumor spheroids (MCTS or 3D) closer to in vivo tumor. We investigated SS anticancer effects in three human GBM cell lines cultured in 3D: LN229, U87 (O(6)-methyguanine-DNA-methyltransferase (MGMT) negative) and T98G (MGMT positive). SS absorption was evaluated and the cytotoxicity of SS and temozolomide (TMZ), the standard drug used against GBM, were compared. SS impacts on proliferation, cell death, and invasiveness were evaluated as well as epigenetic modifications by focusing on histone deacetylase (HDAC) activity and dimethyl-histone-3-lysine-9 methylation (H3K9m2), after 24h to 72h SS exposition. SS was absorbed by spheroids and was more cytotoxic than TMZ (i.e., for LN229, the IC50 was 38 fold-more elevated for TMZ than SS, at 72h). SS induced a cell cycle arrest in the S phase and apoptosis via caspase-3. SS decreased carbonic anhydrase-9 (CA9) expression, invasion on a Matrigel matrix and modulated E- and N-Cadherin transcript expressions. SS decreased HDAC activity and modulated H3K9m2 levels. 3D model provides a relevant strategy to screen new drugs and SS is a promising drug against GBM that should now be tested in GBM animal models.


Psychoneurobiology Research and Personalized Treatment of Schizophrenia.
Psychoneurobiological approaches have been used to develop effective treatments for unmet needs in schizophrenia, e [...].


Studying the correlation between balance assessment by Biodex Stability System and Berg Scale in stroke individuals.
Balance disorders are considered to be a serious clinical manifestation after stroke. Therefore, to assess stroke patients' balance performance, use of a quantitative method appears essential. A fundamental step would be the approval of the efficiency of the measurement instruments. The current study aimed to investigate correlations between balance assessment as examined by Biodex Stability System (BSS) and the clinical Berg Balance Scale (BBS) in post-stroke hemiparesis. Twenty-five stroke survivors and 25 healthy age-sex matched subjects were recruited. The subjects were assessed using BSS during 3 days, with a 24-h interval. The high interclass correlation coefficient (ICC) values showed that the system was reliable enough to continue the study. The clinical evaluation was performed by the standard BBS. There was a significant moderate negative correlation between the Biodex overall indices and BBS scores in the stroke groups (ravg = -0.68) and in the healthy cohort (ravg = -0.55). Also, a significant moderate negative correlation was found between the Biodex antero-posterior stability indices and BBS scores in the stroke groups (ravg = -0.67) and in healthy cohort (ravg = -0.55). The correlation between the Biodex mediolateral stability indices and BBS scores was moderate to low in the stroke and healthy groups (ravg = -0.67 and -0.39 respectively). Moderate negative correlation between the stability indices of the Biodex Stability System and BBS scores indicates that dynamic balance status of the participants partially reflects their functional balance status.


Pharmacologic characterization of isolated canine bronchial smooth muscle.
The response of isolated canine bronchial smooth muscle to several agonists was investigated. Carbachol, serotonin, histamine and acetylcholine, in that order of potency, elicited a concentration-related contraction of bronchial smooth muscle. The maximal contractions produced by histamine and serotonin were somewhat less than those obtained with carbachol. Prostaglandin F2alpha and bradykinin failed to cause contraction. Bronchial smooth muscle strips in which a tone was induced with submaximal concentrations of carbachol underwent a concentration-related relaxation when exposed to prostaglandin E2,(+/-)-isoprenaline and (--)-norepinephrine, in that order of potency. Bradykinin, in three of four experiments, failed to relax the tissue.


Cultures of care? Animals and science in Britain.
It is becoming increasingly common to hear life scientists say that high quality life science research relies upon high quality laboratory animal care. However, the idea that animal care is a crucial part of scientific knowledge production is at odds with previous social science and historical scholarship regarding laboratory animals. How are we to understand this discrepancy? To begin to address this question, this paper seeks to disentangle the values of scientists in identifying animal care as important to the production of high quality scientific research. To do this, we conducted a survey of scientists working in the United Kingdom who use animals in their research. The survey found that being British is associated with thinking that animal care is a crucial part of conducting high quality science. To understand this finding, we draw upon the concept of 'civic epistemologies' (Jasanoff 2005; Prainsack 2006) and argue that 'animals' and 'care' in Britain may converge in taken-for-granted assumptions about what constitutes good scientific knowledge. These ideas travel through things like state regulations or the editorial policies of science journals, but do not necessarily carry the embodied civic epistemology of 'animals' and 'science' from which such modes of regulating laboratory animal welfare comes.


Repeat sentinel node biopsy should be considered in patients with locally recurrent breast cancer.
Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non-metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %; P < 0.001). In 230 patients (80.1 %), the retrieved SN was tumor negative; 17 SNs (5.9 %) contained a micrometastasis and 29 (10.1 %) a macrometastasis. Confirmation ALND in 31 repeat SN-negative patients revealed a macrometastasis in two patients (6.5 %). The negative predictive value (NPV) of repeat SNB was 93.6 %, and ALND was omitted in 109 of the 248 patients (44.0 %) with a negative repeat SN. In 29 of the 44 patients (63.0 %) with a positive SN, adjuvant treatment plans were altered based on the repeat SNB. Repeat SNB is a feasible procedure with a high NPV, leading to a change in management in a substantial proportion of patients. Therefore, repeat SNB should replace routine ALND and serve as the standard of care in recurrent breast cancer.


[Persistence of lymphocytic choriomeningitis virus in a transplantable line of Detroit-6 cells].
Defective LCM virus was found to persist in Detroit-6 cells. The persisting virus was not infectious for susceptible mice and some cell cultures. Its antigenic properties were enhanced to detectable levels in the CFT by cocultivation with LSV5 cells only. No reversion to its pathogenic properties, however, occurred either after 8 subpassages of the cocultivated cells or after blind passages of these cells in suckling mouse brains. The cytogenetic analysis, and the pattern of antigen fluorescence (IIF) revealed similarities between HeLa and D-6 cell lines persistently infected with LCM virus. The highest intensity of LCM virus antigen coincided with the period of maximum miotic activity of D-6-LCM cells, indicating a correlation between synthesis processes in the cells and reproduction of the persisting virus. Upon superinfection of D-6-LCM cells with homo- and isologous viruses no increase in the percentage of the antigen-containing cells was observed. No detectable interferon was found in the D-6-6CM system.


Use of Antibiotics during Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Hepatocellular Carcinoma.
Recent studies suggested that use of antibiotics may interfere with treatment responses to immune checkpoint inhibitors (ICIs). We determined whether concurrent use of antibiotics during ICI therapy was associated with adverse outcomes in patients with advanced hepatocellular carcinoma (HCC). This is a territory-wide retrospective cohort study including all advanced HCC patients who received ICIs (nivolumab, pembrolizumab, or ipilimumab) between January 2014 and December 2019. Exclusion criteria included prior liver transplantation and use of cabozantinib, regorafenib, or ramucirumab. The exposure of interest was concurrent antibiotic use within 30 days before or after the commencement of ICI. The adjusted hazard ratio (aHR) of cancer-related mortality and all-cause mortality with antibiotic use was derived by propensity score (PS) matching in 1:2 ratio of covariates including baseline characteristics, causes of cirrhosis, Child-Pugh status, prior HCC treatment, comorbidities, concurrent medications, and laboratory results including alpha fetoprotein. A total of 395 HCC patients who had received ICIs were included. During a median follow-up of 16.5 months (interquartile range [IQR]: 5.6-44.3), there were 286 (72.4%) deaths including 231 cancer-related deaths. The median time from the first ICI to event was 7.7 months (IQR: 4.0-16.8). PS matching of 56 antibiotic users with 99 nonusers showed that concurrent antibiotic use with ICI was associated with higher cancer-related (aHR: 1.66; 95% CI: 1.08-2.54) and all-cause mortality (aHR: 1.63; 95% CI: 1.17-2.28). Concurrent antibiotic use during immunotherapy was associated with higher mortality in patients with advanced HCC. Further studies should examine the role of gut dysbiosis on responses to ICI.


The effect of screw size and insertion technique on the stability of the mandibular sagittal split osteotomy.
The effect of screw size and insertion technique on the stability of sagittal split osteotomies was evaluated on 10 cadaver mandibles. The mandibles were osteotomized, and stabilized with either 2.0- or 2.7-mm stainless steel screws inserted as lag screws or position screws. All specimens were tested on an MTS servohydraulic testing machine (MTS Systems, Inc, Minneapolis, MN) to determine the strength and stability of the fixation. There were no statistically significant differences between the strengths achieved with the different screw sizes or fixation techniques. The primary variable that determined stability seemed to be the quality of the underlying bone.


Tumor necrosis factor alpha gene polymorphism is associated with cerebral infarction.
We examined whether promoter region polymorphism in the tumor necrosis factor-alpha (TNFalpha) gene at position -308 affects the odds of cerebral infarction (CI). We genotyped 366 CI patients and 610 healthy controls for the same polymorphism. A significant decrease was found for the TNFalpha A allele in CI patients compared with controls (P=0.003). Our finding suggests that TNFalpha promoter region polymorphism is responsible for susceptibility to CI in Koreans.


Lead selenide nanoparticles-induced oxidative damage of kidney in rats.
To investigate the effect of lead selenide nanoparticles (nano PbSe) on kidney in rats. Specific pathogen free SD rats were randomly divided into 4 groups (8 rats/group), and injected with of 0mg/kg (control group), 10mg/kg (low dose group), 20mg/kg (middle dose group), or 30mg/kg (high dose group) nano PbSe respectively. Seven weeks after injection, the serum was taken from rats for the detection of blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA). Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) levels were detected using renal tissue homogenate. Pathological examination was performed on kidney sections. The levels of BUN and Cr in three exposure groups were significantly increased compared with those of control group. Levels of UA in middle dose and high dose group were higher than those in the control group. Levels of SOD, GSH-Px and T-AOC in three exposure groups were markedly decreased compared with those in the control group. Levels of MDA in three exposure groups were higher than those in the control group. Pathological changes at different levels of kidneys were observed, and the damage was more serious with the increase of concentration. Nano PbSe can lead to oxidative damage to the kidney, with the toxicity positively correlates to the dosage.