Acclimation strategies of the green alga Chlorella vulgaris to different light regimes revealed by physiological and comparative proteomic analyses.
Acclimation to different light regimes is at the basis of survival for photosynthetic organisms, regardless of their evolutionary origin. Previous research efforts largely focused on acclimation events occurring at the level of the photosynthetic apparatus and often highlighted species-specific mechanisms. Here, we investigated the consequences of acclimation to different irradiances in Chlorella vulgaris, a green alga that is one of the most promising species for industrial application, focusing on both photosynthetic and mitochondrial activities. Moreover, proteomic analysis of cells acclimated to high light (HL) or low light (LL) allowed identification of the main targets of acclimation in terms of differentially expressed proteins. The results obtained demonstrate photosynthetic adaptation to HL versus LL that was only partially consistent with previous findings in Chlamydomonas reinhardtii, a model organism for green algae, but in many cases similar to vascular plant acclimation events. Increased mitochondrial respiration measured in HL-acclimated cells mainly relied on alternative oxidative pathway dissipating the excessive reducing power produced due to enhanced carbon flow. Finally, proteins involved in cell metabolism, intracellular transport, gene expression, and signaling-including a heliorhodopsin homolog-were identified as strongly differentially expressed in HL versus LL, suggesting their key roles in acclimation to different light regimes.


The development of a virtual reality training programme for ophthalmology: repeatability and reproducibility (part of the International Forum for Ophthalmic Simulation Studies).
To evaluate the variability of performance among novice ophthalmic trainees in a range of repeated tasks using the Eyesi virtual reality (VR) simulator. Eighteen subjects undertook three attempts of five cataract specific and generic three-dimensional tasks: continuous curvilinear capsulorhexis, cracking and chopping, cataract navigation, bimanual cataract training, anti-tremor. Scores for each attempt were out of a maximum of 100 points. A non-parametric test was used to analyse the data, where a P-value of <0.05 was considered statistically significant. Highly significant differences were found between the scores achieved in the first attempt and that during the second (P<0.0001) and third (P<0.0001) but not between the second and third attempt (P=0.65). There was no significant variability in the overall score between the users (P=0.1104) or in the difference between their highest and lowest score (P=0.3878). Highly significant differences between tasks were shown both in the overall score (P=0.0001) and in the difference between highest and lowest score (P=0.003). This study, which is the first to quantify reproducibility of performance in entry level trainees using a VR tool, demonstrated significant intra-novice variability. The cohort of subjects performed equally overall in the range of tasks (no inter-novice variability) but each showed that performance varies significantly with the complexity of the task when using this high-fidelity instrument.


[Vigilance in aesthetic dermatology].
As the acts in aesthetic dermatology are medical acts, they are under vigilance, i.e. the indesirable effects have to be declared to structures which centralize them for analysing their imputability. VigiDEC have been created by the gDEC, to be one of these structures: its objective is confraternal. A precise report of the act when it is make, allows to make a right declaration of the unwanted effect using the VigiDEC file.


Hippocampal and non-hippocampal correlates of physically active lifestyle and their relation to episodic memory in older adults.
Aging is associated with compromised neurocognition. While aerobic exercise has been linked with cognitive resilience, findings regarding its relationship with brain morphology are inconsistent. Furthermore, the biological underpinnings of the relationship between aerobic activity and memory in the aging human brain are unclear. To investigate these issues, we examined hippocampal and non-hippocampal structural correlates of aerobically active lifestyle and cardiorespiratory fitness in older adults. We then examined structural pathways which may potentially mediate the association between active lifestyle and memory. Fifty participants (aged 65-80) underwent structural and diffusion MRI, memory evaluation, were examined for active lifestyle and cardiorespiratory fitness. Morphological features of the hippocampus and fornix, white matter lesions, and brain atrophy were assessed. Active lifestyle and cardiorespiratory fitness correlated with all neurocognitive measures. An exploratory mediation analysis revealed hippocampal and white matter lesions pathways linking active lifestyle and cardiorespiratory fitness with memory. Our results support a neuroprotective role of aerobic exercise on the aging brain and suggest plausible morphological pathways that may underlie the relationship between aerobic exercise and memory.


A first Japanese case of Bartonella henselae-induced endocarditis diagnosed by prolonged culture of a specimen from the excised valve.
Bartonella henselae, the causative agent of cat scratch disease, is increasingly recognized as a cause of culture-negative endocarditis. This report describes the first Japanese case, which was diagnosed after a prolonged culture of the excised aortic valve. High IgG and IgM titers to B. henselae pointed to a subacute course of the disease.


Organ preservation strategies after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer: a multicenter retrospective cohort study.
Neoadjuvant chemoimmunotherapy has shown a good therapeutic effect on non-small cell lung cancer (NSCLC), which also opens up the possibility of applying organ preservation strategies. This study investigated the feasibility of modified surgery after potent neoadjuvant chemoimmunotherapy in central type NSCLC. In this multicenter retrospective cohort study, patients with central type NSCLC who received 2-4 cycles of neoadjuvant chemoimmunotherapy between January 2019 and June 2022 at Air Force Medical University Tangdu Hospital and Peking University People's Hospital were eligible. Patients were divided into modified and nonmodified groups according to the extent of surgery, after which, the safety and long-term prognosis of surgery were investigated. A total of 84 patients were enrolled. Of 36 (42.9%) patients who underwent modified surgery, 21 patients underwent lobectomy, 12 patients underwent lobectomy with bronchoplasty, 2 patients underwent sleeve lobectomy, and 1 patient underwent bilobectomy. The modification rate for the initially estimated pneumonectomy, sleeve lobectomy, and bilobectomy was 48.6, 44.8, and 30%, respectively. Grades II-V postoperative complications were found in 5 (13.9%) patients in the modified group and 17 (35.4%) patients in the nonmodified group (relative risk, 0.393; 95% CI, 0.016-0.963; P =0.026). No significant difference was observed regarding the surgical approach, operative duration, blood loss, or R0 resection rate. The 2-year local recurrence rate was 3.7% (95% CI, 0.004-0.175) and 5.2% (95% CI, 0.012-0.168) in the modified group and nonmodified group, respectively. The 1-year PFS rate of modified and nonmodified groups was 97.1% (95% CI, 83.7-99.8) and 86.9% (95% CI, 73.4-94.4), respectively, while 2-year PFS were 89.8% (95% CI, 74.1-96.9) and 71.8% (95% CI, 56.7-83.4), respectively. Applying organ preservation strategies, that is, undergoing modified surgery after neoadjuvant chemoimmunotherapy, is feasible for selected central type NSCLC patients with favorable safety and long-term survival.


Work Gains and Strains on Father Involvement: The Mediating Role of Parenting Styles.
The balance between work and family demands is one of the main challenges of contemporary parenting. However, most of the research has focused on mothers' perspectives, with fathers' perspectives about the links between work-family activities and father involvement, as well as the role of indirect effects, such as parenting styles, being less explored. This study aims to bridge these gaps by exploring whether work strains or gains are related to father involvement in childcare and the mediating role of parental styles, focusing on fathers' reports. Working, married fathers of preschoolers (n = 411) self-reported about work strains and gains, parental styles, and father involvement. Structural equation modeling, using maximum-likelihood estimation, provided good fit indices. Results of the bootstrap analysis revealed how fathers' gains indirectly increased involvement both in direct and indirect care through positive parental styles. Otherwise, fathers' strains at work had a negative indirect effect on direct care through negative parental styles. Findings contribute to work-family interface by showing how parental styles account for mediating environmental challenges on father involvement.


The amyloid-beta precursor-like protein APLP2 and its relative APP are differentially regulated during neuroendocrine cell activation.
The amyloid-beta precursor-like protein APLP2 is structurally and functionally related to the amyloid-beta precursor protein APP, the protein generally accepted to be involved in Alzheimer's disease. Since we previously observed that the levels of APP mRNA and protein were up-regulated threefold in the active intermediate pituitary melanotrope cells of black-adapted Xenopus laevis, we now decided to study the regulation of APLP2 in these physiologically inducible neuroendocrine cells. Interestingly, both the mRNA and protein levels of Xenopus APLP2 were similar in the melanotrope cells of black and white frogs. Newly synthesized APLP2 became glycosylated and sulfated, chondroitin sulfate glycosaminoglycan chains were added, and eventually the protein was proteolytically cleaved. Unlike for APP, no phosphorylated APLP2 was observed. Our results show that, although APP and APLP2 are thought to be functionally related, their responses to neuroendocrine cell activation differ, suggesting distinct roles for these proteins.


Pharmacy Survey on Patient Safety Culture: Benchmarking Results.
This study's objective was to assess the patient safety culture in a large, integrated health delivery system's pharmacy department to allow for benchmarking with other health systems. This was a cross-sectional survey conducted in a pharmacy department consisting of staff members who provide dispensing, clinical, and support services within an integrated health delivery system. The U.S. Agency for Healthcare Research and Quality's 11-composite, validated Pharmacy Survey on Patient Safety Culture questionnaire was transcribed into an online format. All departmental staff members were invited to participate in this anonymous survey. Cronbach α and overall results and contrasts between dispensing and clinical services staff and dispensing pharmacists and technicians/clerks as percentage positive scores (PPSs) are presented. Differences in contrasts were assessed with χ tests of association. Completed questionnaires were received from 598 (69.9%) of 855 employees. Cronbach α ranged from 0.55 to 0.90. Overall, the highest and lowest composite PPSs were for patient counseling (94.5%) and staffing and work pressure (44.7%), respectively. Compared with dispensing service, the clinical service participants had statistically higher PPSs for all composites except patient counseling, communication about mistakes, and staffing and work pressure (all P > 0.05). The technicians/clerks had a statistically higher PPS compared with the pharmacists for communication about mistakes (P = 0.007). All other composites were equivalent between groups. Patient counseling consistently had the highest PPS among composites measured, but opportunities existed for improvement in all aspects measured. Future research should identify and assess interventions targeted to improving the patient safety culture in pharmacy.


Influence of reduced nicotinamide adenine dinucleotide on the production of interleukin-6 by peripheral human blood leukocytes.
Recently, therapy with nicotinamide adenine dinucleotide (NADH) revealed positive effects on neurodegenerative disorders associated with inflammation of the CNS, such as Parkinson's disease or Alzheimer's disease. Pathophysiologically, focal CNS inflammation seems to be accompanied by an unbalanced cytokine production, pointing to an involvement of the immune system. Therefore, the aim of our study was to investigate whether NADH could influence cytokine release of peripheral blood leukocytes (PBLs) with special reference to interleukin-6 (IL-6). PBLs from 18 healthy donors were incubated in vitro with different concentrations of NADH to generate dose-response curves. As a control, mitogen-treated cells and unstimulated cells were included. In PBLs from the 18 healthy donors, NADH significantly stimulated the dose-dependent release of IL-6, ranging from 6.25 to 400 microg/ml, compared to medium-treated cells (p < 0.001). An amount of 1,000 pg/ml IL-6 was induced by NADH concentrations ranging from 3.1 to >25 microg/ml. It is concluded that NADH possesses cytokine-modulating effects on peripheral blood cells. The biological relevance of these data is discussed in the context of the recent use of NADH for the treatment of several neurodegenerative disorders.


A soluble angiotensin II-binding protein from rabbit liver.
An angiotensin II-binding activity has been detected in the 100,000 x g supernatant fraction of rabbit liver. The total amount of binding activity in this fraction was substantially greater than that which could be solubilized from hepatic particles by treatment with digitonin. The crude soluble binding activity resembled the binding protein which had been purified from the particles in several respects. First, binding required the presence of p-chloromercuriphenylsulfonic acid and bound angiotensin II was released by dithiothreitol. Second, the molecular weight of the responsible protein cross-linked to radioiodinated angiotensin II was about 75,000 in the reduced, denatured state. Finally, guinea pig antiserum raised against the binding protein that had been purified from particles reacted identically with the soluble and solubilized activities.


Coming out of the woods: do termites need a specialized worker caste to search for new food sources?
Most small-colony termites live confined within a single piece of wood on which they feed and do not possess permanent workers: Tasks are done by developmentally flexible immatures (pseudergates). By contrast, large-colony termites possess a specialized (true) worker caste and forage outside their nest for food. To shed light on possible transitional steps between these contrasting patterns of social organization, we studied an atypical Rhinotermitidae, Prorhinotermes inopinatus. In this species, despite the absence of a true worker caste, soldiers, pseudergates, and neotenic reproductives may leave the nest and explore their surroundings. Although evidence presented in this study indicates that termites recognize unknown areas, there is no directional recruitment toward them. The discovery of a food source, i.e., a piece of wood, is followed by the establishment of a long-lasting trail between the nest and the food source. A large fraction of the colony, including neotenic reproductives, ultimately migrates into the piece of wood. Our results thus demonstrate that multiple features of external foraging behavior can evolve independently of the existence of a true worker caste in termites. We suggest that large colonies with true workers, like those of most Rhinotermitidae, may easily have evolved from a Prorhinotermes-like pattern if submitted to increasing selective pressures for worker efficiency in a stable environment.


Carotid and brachial artery intima-media thickness is related to coronary atherosclerotic burden and may also represent high cardiovascular risk in patients with normal coronary angiograms.
Carotid and brachial artery intima-media thicknesses (IMT) determined using B-mode ultrasonography are validated surrogate markers of the severity and extent of coronary artery disease (CAD). The markers may also reflect the general vascular atherosclerotic involvement and cardiovascular risk in patients with normal coronary arteries (NCA). We aimed to investigate the relationship of carotid artery IMT (CIMT) and brachial artery IMT (BIMT) with CAD simultaneously, and also examined whether both markers represent cardiovascular risk determined by cardiovascular risk factors in patients with NCA. One hundred eligible patients who consecutively underwent coronary angiography under suspicion of CAD were included in this study. The patients were evaluated in terms of age, gender, and the risk factors for CAD, and their total cardiovascular risk was calculated. CIMT and BIMT measurements were performed by B-mode ultrasonography on all patients. The extent and severity of CAD were evaluated by the Gensini score, and the number of severely narrowed vessels was determined by coronary angiography. Sixty-three patients (47 males, 16 females) with a mean age of 62 ± 10 years had CAD, and 37 patients (20 males, 17 females) with a mean age of 51 ± 11 years had NCA on coronary angiography. The mean age and male ratio of patients with CAD were significantly higher as compared with the patients with NCA (p < 0.001, p = 0.035, respectively). The mean number of diseased vessels was 2.2 ± 0.9 (median 2.0), while the mean Gensini score was 25 ± 31 (median 14.0). The CIMT and BIMT were higher in patients with CAD than in those with NCA (0.9 ± 0.2 vs. 0.7 ± 0.2 mm and 0.5 ± 0.1 vs. 0.4 ± 0.1 mm, respectively; p < 0.001 for both). The cardiovascular risk score (CVRS) was also significantly higher in the CAD group (3.8 ± 1.1 vs. 2.9 ± 1.4, p < 0.001). CIMT, BIMT, and CVRS were significantly correlated with the Gensini score and number of diseased vessels. For the sensitivity and the specificity of CIMT, BIMT, and CVRS to detect the presence of CAD, the areas under the ROC curve were 0.785 (95% CI 0.687-0.883, p = 0.000), 0.842 (95% CI 0.764-0.920, p = 0.000), and 0.721 (95% CI 0.591-0.813, p = 0.001), respectively. When we compared the CVRSs between the groups, which were determined according to cutoff values for CIMT and BIMT (CIMT ≥0.9 vs. <0.9 and BIMT ≥0.4 vs. <0.4); among the patients with NCA, CVRSs were significantly different (3.5 ± 0.5 vs. 2.7 ± 1.4, p = 0.035 and 3.7 ± 1.1 and 2.7 ± 1.3, p = 0.073; respectively). The increases in both brachial and carotid IMT are positively correlated with the extent of CAD and the number of involved vessels, and have more predictive value for CAD than the traditional CVRS. In addition, carotid IMT is also related to high CVRS in patients with NCA, and this finding may represent general vascular involvement without coronary lesions determined by coronary angiography.


Teaching evidence-based practice: developing a curriculum model to foster evidence-based practice in undergraduate student nurses.
For the nature of the Evidence-Based Practice (EBP) and its relevance to nursing, the skills that it requires should be a component in the basic Nursing degree courses. For this reason, the EBP process should be introduced early on in nursing education to develop students' independence and ability to self-learning. the aim of this study is to describe the perception that newly graduated nurses have relative to the benefits of the skills learned during the laboratory's three-year EBP in consideration of the construction of the thesis, the research of evidence and usefulness of the EBP process for the development of their professional career. A descriptive study with a sample of 300 newly graduated nurses from the Degree Course in Nursing of the University of Modena and Reggio Emilia, venue of Reggio Emilia. The data collection instrument was an anonymous questionnaire. It was possible to answer through a 10 Likert scale. The sample considers effective the research of evidence carried out (mean 6, SD 2), related to the problems of patients (mean 7, SD 2); the sample considered the skills acquired during the laboratory's three-year EBP to be useful for career development (mean 7, SD 2). the decision to include the laboratory's three-year EBP in the curriculum of the Nursing degree promotes the development of skills relating to the use of the EBP process, competence that in the literature is indicated as one of the core competencies that all health professionals should develop and maintain throughout their professional career.


Joint analyses by laser-induced breakdown spectroscopy (LIBS) and Raman spectroscopy at stand-off distances.
Raman spectroscopy and laser-induced breakdown spectroscopy (LIBS) of solid samples have both been shown to be feasible with sample-to-instrument distances of many meters. The two techniques are very useful together, as the combination of elemental compositions from LIBS and molecular vibrational information from Raman spectroscopy strongly complement each other. Remote LIBS and Raman spectroscopy spectra were taken together on a number of mineral samples including sulfates, carbonates and silicates at a distance of 8.3 m. The complementary nature of these spectra is highlighted and discussed. A factor of approximately 20 difference in intensity was observed between the brightest Raman line of calcite, at optimal laser power, and the brighter Ca I LIBS emission line measured with 55 mJ/pulse laser power. LIBS and Raman spectroscopy have several obstacles to devising a single instrument capable of both techniques. These include the differing spectral ranges and required detection sensitivity. The current state of technology in these areas is discussed.


Speech register influences listeners' word expectations.
We utilized the N400 effect to investigate the influence of speech register on predictive language processing. Participants listened to long stretches (4 - 15 min) of naturalistic speech from different registers (dialogues, news broadcasts, and read-aloud books), totalling approximately 50,000 words, while the EEG signal was recorded. We estimated the surprisal of words in the speech materials with the aid of a statistical language model in such a manner that it reflected different predictive processing strategies; generic, register-specific, or recency-based. The N400 amplitude was best predicted with register-specific word surprisal, indicating that the statistics of the wider context (i.e., register) influences predictive language processing. Furthermore, adaptation to speech register cannot merely be explained by recency effects; instead, listeners adapt their word anticipations to the presented speech register.


Long-term efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma achieving a complete response with pixantrone.
The prognosis of diffuse large B-cell lymphoma (DLBCL) patients with refractory or multiply relapsed (R/R) disease is disappointing. Pixantrone is currently approved as third or fourth line regimen, with encouraging results, even if long-term follow-up data are limited. In this post-hoc analysis of our observational study, we retrospectively investigated disease outcome and clinical characteristics of 16 R/R DLBCL patients who achieved a complete response with pixantrone. Pixantrone was administered as third or fourth line in 12/16 (75%) and 4/16 (25%) cases. After a median follow-up of 24 months, 14/16 patients (87.5%) were alive (causes of death were progressive disease and secondary acute myeloid leukemia, one case each). Median progression-free survival was 23.8 months, median duration of response was 17.8 months and median overall survival (OS) was not reached (2-years OS was 84%). A significant proportion of patients achieved a long-lasting response >12 months (7/16 cases). Response to prior therapy did not influence long-term remission after pixantrone. In this real-life experience, pixantrone demonstrated long-term efficacy in a cohort of R/R DLBCL cases who had previously received at least two prior regimens; many of whom had characteristics associated with poor prognosis.


Children are not small adults: documentation of assent for research involving children.
Obtaining assent is an important part of research involving children, both from an ethical and regulatory perspective. Current practice for documenting assent is derived largely from documentation of informed consent for adults as there is little guidance in federal regulations. We propose a new approach to documenting assent.


Use of early hard palate closure using a vomer flap in cleft lip and palate patients.
The aim of the present study was to determine the influence of the vomer flap during cleft palate closure. A retrospective review was performed of all consecutive unilateral/bilateral complete cleft lip and palate (Veau III en IV) children who were treated by a simultaneous lip and hard palate closure using a vomer flap. Data were collected for sex, date of birth, syndrome, adoption, cleft palate type, type of repair, date of cleft repair, cleft width, lateral incisions, fistula and location of fistula. Ninety-one children (M = 62, F 29) were operated. Mean age at time of lip closure and vomer flap was 5.8 months (range 2.9 months to 49.2 months, SD 7.1) and the mean age at palate closure was 13.6 months (range 6.3 months to 79.9 months, SD 10.8). The mean cleft width at first assessment was 13.0 mm (range 7-22 mm) compared to 8.8 mm (range 4-15 mm) at second assessment (mean difference 4.6 mm, 95% CI 3.93-5.35, p < 0.01). One patient developed a fistula (1.1%) and required secondary surgery for closure. The vomer flap leads to a substantial decrease in cleft width, subsequently leading to a low fistula incidence (1.1%).


Otitis media with effusion and habitual mouth breathing in Dutch preschool children.
Habitual mouth breathing (HMB) is defined as the habit of in- and exhaling (part of) the air through the mouth, when an individual is at rest and the nose is sufficiently free. It is postulated that HMB is a risk factor for otitis media with effusion (OME) in preschool children. The results are presented of a prospective cohort study on 253 3-year-old children, free from OME, with a follow-up period of 3 months, to determine the role of HMB in the etiology of OME. The risk ratio for OME of habitual mouth breathers, compared to nose breathers, was found to be 2.4 (95% confidence interval (C.I.): 0.99-5.70). Moreover, there is a clear and significant linear trend in the proportion of OME in 3 breathing categories: nose breathing, intermediate and mouth breathing. This relation remains after correction for confounding. It is concluded that HMB is a risk factor for OME. It is estimated that about 20% of the incidence of OME is caused by HMB. The high incidence of OME means that HMB carries a great deal of impact. Suggestions are made for the prevention and treatment of HMB.


Development and Validation of a Novel LC-MS/MS Assay for C-Peptide in Human Serum.
C-peptide is used as a marker of endogenous insulin secretion in the assessment of residual β-cell function in diabetes and in the diagnostic workup of hypoglycemia. Previously developed LC-MS/MS methods to quantify serum concentrations of C-peptide have monitored intact peptide, which ionizes poorly. As a result, methods have leveraged immunoaffinity enrichment or two-dimensional chromatography. In this study, we aimed to use proteolysis during sample preparation to enhance the sensitivity of traditional LC-MS/MS. Due to the absence of arginine and lysine residues in C-peptide, we utilized Glu-C as the proteolytic enzyme in the method. After protein precipitation using acetonitrile and solid phase extraction with mixed anion exchange, lower molecular weight polypeptides were reduced, alkylated, and proteolyzed. The two amino-terminal peptide fragments, EAEDLQVGQVE and LGGGPGAGSLQPLALE, were monitored using multiple reaction monitoring in positive ion mode (Acquity ULPC-Xevo TQ-S, Waters). The former peptide was used for quantification and the latter for quality assurance. Glu-C was determined to be a reliable proteolytic enzyme with monotonic digestion kinetics. The assay was linear between 0.1 and 15 ng/mL and had a lower limit of quantification of 0.06 ng/mL. Total imprecision was 7.7 %CV and long-term imprecision at 0.16 ng/mL was 10.0%. Spike-recovery experiments demonstrated a mean recovery of 98.2 % (± 9.1 %) and the method compared favorably with a commercially available immunoassay and a reference measurement procedure. Protein precipitation with solid phase extraction and proteolysis with Glu-C is a robust sample preparation method for quantification of C-peptide in human serum by LC-MS/MS.


Knockdown of Mad2 induces osteosarcoma cell apoptosis-involved Rad21 cleavage.
Besides Mad2's role in carcinogenesis, recent study has shown that it is essential in cell survival. Here we found that knockdown of Mad2 causes osteosarcoma cell death through apoptosis, with the apoptotic signal resulting from Rad21 cleavage. U2OS and MG63 cells were divided into three groups: the Mad2 siRNA group, mock group and normal control group; the Mad2 siRNA group and mock group are transfected with Mad2 shRNA plasmid and mock plasmid, respectively. G418 was used to increase the transfection efficacy, which was evaluated by GFP fluorescence. Quantitative PCR and Western blotting analyses were used to detect the transcription and expression of Mad2, Rad21 and caspase-3, respectively. Flow cytometry assay using PE-labeled Annexin-V and PI, TUNEL assay and Hoechst 33258 staining were used to evaluate cell apoptosis. We successfully achieved knockdown of Mad2 expression in cancer cells using RNA interference. We observed obvious apoptosis in the Mad2 siRNA group compared with the Mock and control group. We found that the apoptosis induced by Mad2 knockdown correlated with Rad21 cleavage. These results confirmed that knockdown of Mad2 causes osteosarcoma cell death through apoptosis and provides evidence that the apoptotic signal resulted from Rad21 cleavage. This study suggested that Mad2 has potential to be a novel target for cancer therapy.


Psychometric properties of the Burnout Assessment Tool across four countries.
The Burnout Assessment Tool (BAT) is a new burnout measure developed to replace the Maslach Burnout Inventory (MBI). Studies have supported the psychometric properties and cross-cultural measurement invariance of the BAT. However, some unresolved questions remain. These questions are the appropriate level of score interpretation, convergent validity with the MBI, and measurement invariance using sample groups from countries outside of Europe. We used a cross-sectional survey approach to obtain 794 participants from Australia (n = 200), the Netherlands (n = 199), South Africa (n = 197), and the United States (n = 198). In brief, we used bifactor modelling to investigate the appropriate score interpretation and convergent validity with the MBI. Hereafter, we used the Rasch model and ordinal logistic regression to investigate differential item functioning. The bifactor model showed a large general factor and four small group factors, which suggests calculating and interpreting a general burnout score. This model further shows that the BAT and MBI measure the same burnout construct but that the BAT is a more comprehensive burnout measure. Most items fit the Rasch model, and few showed non-negligible differential item functioning. Our results support the psychometric properties and cross-cultural measurement invariance of the BAT in Australia, the Netherlands, South Africa, and the United States. Furthermore, we provide some clarity on the three previously mentioned unresolved questions.


Response pattern of visceral afferent fibres, supplying the colon, upon chemical and mechanical stimuli.
In the cat responses of afferent fibres in the inferior splanchnic nerves which innervate the colon and its mesentery were investigated upon intra-arterial bolus injection of bradykinin, of KCl- and of hypertonic NaCl-solution and upon ischaemia of the colon. One hundred and twenty-five units were analyzed. 1) Seventy-seven from 96 units with resting activity (80%) and 7 from 29 units without (24%) were excited by bradykinin. The exictation was present both when the colon wall contracted and when the contractions were prevented or when the colon was paralytic. 2) Fifty-two from 82 units with resting activity (67%) and 4 from 21 units without (19%) responded to KCl with short-lasting, high-frequency bursts. Injections of hypertonic NaCl-solutions had only small effects on the afferent units. 3) The responses of the units to distension of the colon (see [3]) and to the chemical stimuli were highly correlated. 4) Afferent units which responded to distension of the colon and to bradykinin were also excited by partial or complete ischaemia of the colon (produced by occlusion of both mesenteric arteries or of only the inferior mesenteric artery). During ischaemia the activity in the afferents increased and became burst-like. The response to distension of the colon increased in some of the afferent units. 5) Blood pressure responses to colon distension and to local bradykinin application also increased during ischaemia. 6) The results indicate that visceral afferent fibres from the colon in the inferior splanchnic nerves may be functionally homogeneous and may encode noxious stimuli applied to the colon.


Probiotic-fermented Portulaca oleracea L. alleviated DNFB-induced atopic dermatitis by inhibiting the NF-κB signaling pathway.
Probiotic fermentation is a mild and safe biological method to boost the performance of herbs. Portulaca oleracea L. (PO), with folklore records of purgative, anti-dermatological and anti-epidemic effects, has been demonstrated to possess anti-inflammatory, immunomodulatory, and antioxidant properties. However, the potential of PO for the treatment of atopic dermatitis (AD) has not been sufficiently explored. This study aimed to evaluate the therapeutic benefits of PO and fermented Portulaca oleracea L. (FPO) and explore their intrinsic mechanisms. By utilizing 2,4-dinitrofluorobenzene-induced AD mice as a model, the histopathology of the lesions was observed using H&E and toluidine blue staining methods; the levels of immunoglobulin E (Ig E), histamine (HIS), and thymic stromal lymphopoietin (TSLP) in serum were measured using ELISA, whereas, the expression of inflammatory cytokines in skin lesion was measured using ELISA and immunohistochemistry experiments. The expression of tumor necrosis factor-α (TNF-α), IKKα, NF-κB mRNA was measured using qPCR; and the expression of TNF-α、p-IKKα, p-IκBα, p-NF-κB was measured using western blotting. Both 20 mg/mL PO and FPO alleviated mast cell infiltration and lesion pathology, reduced serum levels of Ig E, HIS and TSLP, down-regulated the expression of AD-related inflammatory cytokines, such as, TNF-α, interferon-γ, and interleukin-4, and increased filaggrin expression. Furthermore, they inhibited the expression of TNF-α, IKKα, and NF-κB genes and TNF-α, p-IKKα, p-NF-κB and p-IκBα proteins associated with the NF-κB signaling pathway. PO and FPO has a positive therapeutic potential on AD, indicating that it may be employed as alternative therapies for AD.


Anti-inflammatory effects of interleukin-4, interleukin-10, and transforming growth factor-beta on human placental cells in vitro.
To determine the effects of anti-inflammatory cytokines on the production of inflammatory mediators by placental cells. Cells from term human placentas were isolated and cultured in vitro in the presence of anti-inflammatory cytokines interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-beta. Their effects on the production of IL-8 and prostaglandin E2 (PGE2) were investigated under basal conditions and after stimulation with IL-1 beta and tumor necrosis factor (TNF)-alpha. Both IL-10 and IL-4 inhibited IL-1 beta- and TNF-alpha-induced PGE2 production but had no significant effects on the production of PGE2 under basal conditions. TGF-beta 1 was without effect in stimulated cells, whereas under basal conditions TGF-beta 1 stimulated PGE2 production. Similar trends were seen for IL-8 production, with the exceptions that TGF-beta 1 decreased the TNF-alpha-induced production and IL-4 decreased basal IL-8 production. The anti-inflammatory effects shown by IL-4, IL-10, and (to lesser extent) TGF-beta may play a role in ameliorating the potentially harmful effects of pro-inflammatory mediators in the feto-placental unit.


The reciprocal effects of program evaluation on service delivery for the SPNS adolescent HIV outreach and treatment programs.
To describe the contexts within which the Special Projects of National Significance (SPNS) Adolescent HIV Outreach and Treatment programs were evaluated, the effects their evaluations had on their respective programs and, in turn, the effects the program delivery had on the evaluations. The full range of process evaluation heuristics were used to analyze the bi-directional effects of conducting field-based, service delivery data collection. Although data collection efforts sometimes interfered with service delivery, and vice versa, several notable positive effects were disclosed. Specific guidance and recommendations were provided to program designers, behavioral researchers and institutional funding decision makers. Primary amongst them was a call for research evaluation designs that allow for maximum flexibility.


The relationship of phosphodiesterase and cyclic AMP to the process of fluid secretion in the salivary glands of the ixodid tick Amblyomma americanum.
Phosphodiesterase (PDE) activity in the salivary glands of the female. Amblyomma americanum decreased as the tick progressed from a slow to a rapid phase of feeding, while the rate of fluid secretion increased when glands were stimulated with cyclic AMP and theophylline. Dopamine stimulated PDE activity and an 'inhibitory' factor was found in glands obtained from rapidly engorging ticks which decreased PDE activity. These findings are discussed as they relate to the process of fluid secretion by salivary glands of feeding ixodid ticks.


Response of Saccharomyces cerevisiae to severe osmotic stress: evidence for a novel activation mechanism of the HOG MAP kinase pathway.
The HOG/p38 MAP kinase route is an important stress-activated signal transduction pathway that is well conserved among eukaryotes. Here, we describe a novel mechanism of activation of the HOG pathway in budding yeast. This mechanism operates upon severe osmostress conditions (1.4 M NaCl) and is independent of the Sln1p and Sho1p osmosensors. The alternative input feeds into the HOG pathway MAPKK Pbs2p and requires activation of Pbs2p by phosphorylation. We show that, upon severe osmotic shock, Hog1p nuclear accumulation and phosphorylation is delayed compared with mild stress. Moreover, both events lost their transient pattern, presumably because of the absence of negative feedback mediated by Ptp2p tyrosine phosphatase, which we found to be localized in the nucleus. Under severe osmotic stress conditions, the delayed nuclear accumulation correlates with a delay in stress-responsive gene expression. Severe osmoshock leads to a situation in which active and nuclear-localized Hog1p is transiently unable to induce transcription of osmotic stress-responsive genes. It also appeared from our studies that the Sho1p osmosensor is less active under severe osmotic stress conditions, whereas the Sln1p/Ypd1p/Ssk1p sensor and signal transducer functions normally under these circumstances.


Binocular fields with lateral-eyed vision.
A simple geometrical model is constructed of the binocular field in animals with laterally directed eyes (such as the pigeon). Height and width are derived as a function of elevation, for eye-centred and for cyclopean co-ordinates. Stereoscopic vision in the frontal field is considered, and it is pointed out that convergence movements can facilitate stereopsis even in an afoveate periphery.


Office-based treatment of acute migraine with dihydroergotamine mesylate.
The Regional Migraine Field Trial assessed the efficacy and safety of dihydroergotamine mesylate (D.H.E. 45) for migraine in the office setting. Patients were admitted to the study provided they met the International Headache Society definition of migraine with or without aura. Thirty-eight neurologists enrolled 311 patients (274 women and 37 men) between the ages of 13 and 70 years in this open-design study. Ninety-five percent of the patients had moderate or severe headache pain at entry, and 62% had nausea. All patients received a single intramuscular injection of D.H.E. 45 1 mg. A second intramuscular injection of 1 mg was given 60 minutes after the first injection, if needed. An antiemetic was administered concomitantly with D.H.E. 45, if needed. Rescue therapy was given at the investigators' discretion. Efficacy was judged by the relief of pain, patients' ability to function, need for a second injection, need for rescue medication, and need for an antiemetic. At 30 and 60 minutes, 46% and 72% of patients had only mild or no head pain, respectively. At 24 hours, 77% of all patients had mild or no head pain. D.H.E. 45 also improved functional ability. At 30 and 60 minutes, 58% and 75% of patients had only mild or no disability, respectively. At 24 hours, 81% had mild or no impairment. Nausea was present in 62% of patients at the outset, 40% of patients at 30 minutes, and 30% at 60 minutes. An antiemetic was given to 43% of patients at the outset. The presence of nausea was similar whether or not patients received an antiemetic.(ABSTRACT TRUNCATED AT 250 WORDS)


The possible correlation between the patient's immune tolerance level during cesaerean section and the incidence of subsequent emergency peripartum hysterectomy.
Cesarean section is an independent risk factor for peripartum hysterectomy. As a method of delivery, cesarean section may interfere with a number of molecular changes that occur at the maternal-fetal interface during the course of labor. The level of CD3, CD56, CD25, and CD69 antigen immunoreactivity was assessed by immunohistochemistry in 26 decidual tissue samples. The tissue samples were obtained from 18 women who underwent cesarean sections at term and from 8 women who underwent cesarean hysterectomies. An increase in the activity and infiltration of immune cells in the decidua sampled during the spontaneous beginning of labor was observed. The further progression of labor was accompanied by a decrease in the number and activity of immune cells. The number of CD56+ and CD3+ cells in the decidua was statistically significantly lower in patients who had undergone cesarean hysterectomies than in those who had had cesarean sections at term. Abnormal immune response during labor may increase the risk for peripartum hysterectomy.


Tandem Achmatowicz-Knoevenagel protocol: diastereoselective synthesis and anticancer evaluation of cyclopenta[b]pyrane derivatives.
Synthesis of cyclopenta[b]pyrane derivatives via Achmatowicz oxidative cyclization of furanols followed by intramolecular Knoevenagel condensation of the β-ketoester arm is examined. The extent of diastereoselectivity was dependent on the nature of the chiral atom within the tethering carbon of the pyrenone ring. In some cases, this process proceeds with a high degree of stereoselectivity after protection of the anomeric hydroxyl group. Furthermore, the cytotoxic activity of pyrazolone derivatives thereof was studied against HCT116 (human colorectal cancer cells), SK-N-SH (human Caucasian bone marrow neuroblastoma) cells and the non-tumorigenic cells (MCF10A).


Conservative versus surgical treatment of 21 sports horses with osseous trauma in the proximal phalangeal sagittal groove diagnosed by low-field MRI.
To compare the outcome following conservative vs surgical management of sports horses with a diagnosis of subchondral bone trauma of the proximal aspect of the proximal phalanx (PP) by low-field MRI. Retrospective case series. Twenty-one mature sports horses with evidence of high water signal within the proximal sagittal groove of the PP according to low-field MRI of the fetlock, with no definitive radiographic evidence of fracture. Medical records (2010-2017) of horses admitted to 2 referral hospitals were reviewed. Historical, clinical, radiographic, and MRI findings and treatment choice were recorded. Conservative management consisted of confinement to a stall followed by gradual reintroduction to exercise. Surgical management consisted of cortical screw fixation across the proximal aspect of the PP. Long-term outcome was determined by telephone questionnaire or by clinical records review. Fisher's exact test was used to compare outcome between the 2 treatment groups. Follow-up was available in 17 of 21 horses in the study, including 8 horses treated conservatively and 9 treated surgically. No difference in outcome was detected in this study; 4 of 8 horses were sound after conservative management, and 5 of 9 horses were sound after surgery (P > .99). Approximately half of the horses that had a diagnosis of osseous trauma within the proximal aspect of PP returned to athletic activity, regardless of conservative or surgical management. The prognosis for return to athletic functions in horses with osseous trauma within the proximal aspect of the PP is guarded.


The role of primary surgery in the management of orofacial clefting.
Primary cleft surgery refers to the planned surgical procedure(s) necessary to reconstruct an orofacial defect according to a specified protocol; in the context of a unilateral cleft lip and palate, this would include lip repair (with vomer flap closure of the hard palate), subsequent repair of the residual soft palate cleft and finally, the alveolar bone graft. This paper will provide an overview of the goals of primary surgical reconstruction, including the utility of pre-surgical orthopaedic techniques, including nasoalveolar moulding. The surgical methods of primary lip repair in both unilateral and bilateral clefts will be outlined and the concept of a primary rhinoplasty will be introduced. The principal techniques of cleft palate reconstruction will be delineated for a variety of cleft phenotypes. The final element of the primary reconstructive sequence is the alveolar bone graft using cancellous bone harvested from the iliac crest at approximately 8-10 years of age. The role of optimising oral hygiene prior to bone grafting cannot be over-emphasised and the utility of pre-surgical orthodontic arch expansion is also discussed. In the UK, bone graft outcomes are audited using the Kindelan score, which is evaluated from the six-month postoperative upper standard occlusal radiograph.


[Infectious diseases--a permanent scourge to mankind?].
A synopsis of basic causes of the extended number of infectious diseases and changes of their clinical and epidemiological features is brought about in the article. The question is of changes of the pathogenic agents, their hosts and environment. Reasons of further evolution of infectious diseases are given.


Amphiprotism-Coupled Near-Infrared Emission in Extended Pyrazinacenes Containing Seven Linearly Fused Pyrazine Units.
Peripherally substituted tetradecaazaheptacene (N14Hp) compounds, exhibiting amphiprotism-coupled emission, have been synthesized. X-ray crystallography reveals a planar acene-like chromophore, and electronic absorption and emission occur in the near-infrared biological transparency window (650-900 nm). The compounds exhibit long-wavelength emission with photoluminescence quantum yields ΦPL up to ∼0.61 at 686 nm, with the monodeprotonated state ΦPL ≈ 0.58 at 712 nm. This unprecedented highly nitrogenous chromophore illustrates the stability and utility of the pyrazinacenes for different applications based on their photophysical properties and chemical structures.


Hepatosplenic gamma-delta T-cell malignant lymphoma: report of the first case in childhood, including molecular minimal residual disease follow-up.
We report the first case of T-cell gamma delta+ hepatosplenic malignant lymphoma in childhood. Tumour-specific oligoprobes were developed against the single V1-J1 rearrangement of the delta T-cell receptor (TCR) gene in order to perform minimal residual disease (MRD) studies. Molecular analysis in serial bone marrow samples proved to be of predictive value concerning the clinical outcome. Clonotypic DNA was not detected in peripheral blood during the course of the disease until a refractory terminal leukaemic phase took place 18 months after the diagnosis. This case demonstrates the usefulness of MRD studies to monitor the course of disease in at least some subsets of peripheral T-cell lymphomas.


Chemometrical identification of mutations in HIV-1 reverse transcriptase conferring resistance or enhanced sensitivity to arylsulfonylbenzonitriles.
A comparative binding energy (COMBINE) analysis on a series of nonnucleosidic reverse transcriptase inhibitors yields a QSAR model with high predictive ability and correctly identifies the effect of mutations on relevant protein residues.


Assessment of potential drug-drug interactions among outpatients in a tertiary care hospital: focusing on the role of P-glycoprotein and CYP3A4 (retrospective observational study).
Selecting a medicine has a significant impact on the quality of therapy including efficacy and safety. P-glycoprotein and CYP3A4 share several common substrates known as bi-substrates. Both play major role in the pharmacokinetics and pharmacodynamics when over or under expressed. The study aimed to assess the Drug-Drug Interaction (DDI) related to P-glycoprotein (P-gp) and Cytochrome P450-3A4 (CYP3A4), to predict their clinical outcomes and also to discover prospective predictors of pDDIs. The subjects in this retrospective study ranged in age from 18 to 95 years with polypharmacy prescriptions. Information was gathered through patient medical records. Based on Micromedex and previous literature studies, medications prescribed to the patients were observed for pDDIs according to risk rating scale for drug interactions. A total of 504 patients (160 males and 344 females) were included in the study. The mean of pDDI seen in the patients was 1.66 ± 1.48 and total 825 pDDIs were discovered. The factors significantly associated with having ≥1 pDDIs included: taking ≥5 medicines (OR 1.747), increased age (OR 1.026) increased comorbidities (OR 1.73). In prescriptions, a considerable number of probable DDI were discovered. Therefore, careful selection of drugs and identification of mechanisms for DDI is needed to lower the frequency of pDDI.


Immunoglobulin isotypes of anti-myeloperoxidase and anti-lactoferrin antibodies in patients with collagen diseases.
To investigate the prevalence and clinical relevance of immunoglobulin (Ig) isotypes of antimyeloperoxidase (MPO) and antilactoferrin (LF) antibodies in collagen diseases, enzyme-linked immunosorbent assay was employed to detect the Ig isotypes of both antibodies. The purified proteins of MPO and LF were used as two major representative antigens for anti-neutrophil cytoplasmic antibodies (ANCA) with a perinuclear staining pattern by an indirect immunofluorescent technique. We examined 131 serum samples from 79 patients with rheumatoid arthritis (RA), 32 with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM), and 5 with idiopathic crescentic glomerulonephritis who served as positive controls and 36 healthy subjects who served as controls. A limited number of patients with RA (4-10%), SLE (6-9%), and PSS (7-14%) but not PM/DM showed positive IgG or IgA anti-MPO antibody (MPO-ANCA) but not IgM MPO-ANCA. However, 10-20% of RA, 40-60% of SLE, 20-36% of PSS but none of the PM/DM patients showed positive IgG, IgA, or IgM anti-LF antibody (LF-ANCA). MPO- and LF-ANCA positivity in RA patients was correlated with markers of disease activity such as the erythrocyte sedimentation rate, C-reactive protein, and serum Ig levels. IgG LF-ANCA but not MPO-ANCA positivity in SLE patients also was correlated with the disease activity index but not with clinical features. Neither MPO- nor LF-ANCA positivity in PSS patients was correlated with any clinical features. Overall, both MPO- and LF-ANCA were found mainly in RA, SLE, and PSS patients but not in PM/DM patients. The Ig isotypes of MPO- and LF-ANCA frequently belonged to both IgG and IgA and rarely to the IgM class. Both MPO- and LF-ANCA positivity reflected disease activity in RA and SLE rather than specific organ involvement.


Discovery of a vezatin-like protein for dynein-mediated early endosome transport.
Early endosomes are transported bidirectionally by cytoplasmic dynein and kinesin-3, but how the movements are regulated in vivo remains unclear. Here our forward genetic study led to the discovery of VezA, a vezatin-like protein in Aspergillus nidulans, as a factor critical for early endosome distribution. Loss of vezA causes an abnormal accumulation of early endosomes at the hyphal tip, where microtubule plus ends are located. This abnormal accumulation depends on kinesin-3 and is due to a decrease in the frequency but not the speed of dynein-mediated early endosome movement. VezA-GFP signals are enriched at the hypha tip in an actin-dependent manner but are not obviously associated with early endosomes, thus differing from the early endosome association of the cargo adapter HookA (Hook in A. nidulans). On loss of VezA, HookA associates normally with early endosomes, but the interaction between dynein-dynactin and the early-endosome-bound HookA is significantly decreased. However, VezA is not required for linking dynein-dynactin to the cytosolic ∆C-HookA, lacking the cargo-binding C-terminus. These results identify VezA as a novel regulator required for the interaction between dynein and the Hook-bound early endosomes in vivo.


Brachioplasty after bariatric surgery: personal technique.
A review of the results of the standard technique for "batwing" deformity after massive weight loss led to the need to optimize the cost/benefit ratio in terms of maximal correction/less visible scars. Between 2001 and 2007, 29 patients were operated with a new technique based on a careful preoperative evaluation and markings, followed by an intraoperative skillful handling. This technique is not easy and needs plastic surgery experience and a long learning curve. The esthetic results are far better then those obtained with other techniques, especially the arm lower profile. The complication rate is similar to other techniques, even if a potential low risk for ulnar nerve damage is present.


Serotonin syndrome associated with MDPV use: a case report.
Serotonin syndrome is associated with use of certain street drugs, including methamphetamine, cocaine, and ecstasy. We describe a case of a woman who developed clinical findings consistent with serotonin syndrome after insufflation of 3,4-methylenedioxypyrovalerone (MDPV), a synthetic amphetamine. MDPV belongs to a group of substances called phenylethylamines, which are β-ketone analogs of other drugs of abuse, such as amphetamines and 3,4-methylenedioxymethamphetamine. She also received fentanyl initially during her hospitalization, which has also been associated with serotonin syndrome. In addition to benzodiazepines and supportive care, she was treated with cyproheptadine for 8 days, with slow resolution of her symptoms.


Segal crystallinity index revisited by the simulation of X-ray diffraction patterns of cotton cellulose Iβ and cellulose II.
The Segal method estimates the amorphous fraction of cellulose Iβ materials simply based on intensity at 18° 2θ in an X-ray diffraction pattern and was extended to cellulose II using 16° 2θ intensity. To address the dependency of Segal amorphous intensity on crystal size, cellulose polymorph, and the degree of polymorphic conversion, we simulated the diffraction patterns of cotton celluloses (Iβ and II) and compared the simulated amorphous fractions with the Segal values. The diffraction patterns of control and mercerized cottons, respectively, were simulated with perfect crystals of cellulose Iβ (1.54° FWHM) and cellulose II (2.30° FWHM) as well as 10% and 35% amorphous celluloses. Their Segal amorphous fractions were 15% and 31%, respectively. The higher Segal amorphous fraction for control cotton was attributed to the peak overlap. Although the amorphous fraction was set in the simulation, the peak overlap induced by the increase of FWHM further enhanced the Segal amorphous intensity of cellulose Iβ. For cellulose II, the effect of peak overlap was smaller; however the lower reflection of the amorphous cellulose scattering in its Segal amorphous location resulted in smaller Segal amorphous fractions. Despite this underestimation, the relatively good agreement of the Segal method with the simulation for mercerized cotton was attributed to the incomplete conversion to cellulose II. The (1-10) and (110) peaks of cellulose Iβ remained near the Segal amorphous location of cellulose II for blends of control and mercerized cotton fibers.


Hydrophobicity of Candida albicans related to their adherence to mucosal epithelial cells.
A total of 150 Candida albicans strains were examined, using a salt aggregation test (SAT) and an improved salt aggregation test (ISAT). The fungal strains were isolated from patients or taken from a collection. Out of 150 strains, 20.7% were autoaggregating in the ISAT. In the SAT, 12% of the strains were autoaggregating in saline and 14% in phosphate buffer. The remaining strains did not clump. Pretreatment of the autoaggregating strains with detergents (Tween 80 and ethylene glycol) prevented aggregation in some of them. The adherence capacity to buccal epithelial cells of the fungal strains autoaggregating in the SAT and ISAT, was compared to that of the nonaggregating ones. The autoaggregating strains revealed significantly higher adherence values (p less than 0.002). The adherence ability to buccal epithelial cells of the autoaggregating strains before and after their pretreatment with detergents was compared. The adherence values after pretreatment were significantly lower (p less than 0.001).


Analysis of morphological changes as a key method in studying psychiatric animal models.
A major interest in the analysis of animal models of psychiatric diseases is their underlying cellular pathology and to gain information regarding whether pharmacological treatments, genetic differences or an altered environment exert an impact upon the brain morphology or on the morphology or activity of single neurones. In this review, several key methods will be introduced that allow the analysis of morphological changes that are frequently observed in psychiatric animal models. An overview of the techniques that enable dendritic arborisation, alterations in dendritic spines and changes in fibre densities to be analysed are described. Moreover, methods for the analysis of adult neurogenesis and neurodegeneration and for the analysis of neuronal activity in fixed brain tissue are described. An important step during the analysis of morphological changes is the estimation of the number of stained cells. Since conventional cell counting methods have several limitations, two different approaches that permit an estimate of the number of stained cells within three-dimensional tissue are also discussed.


Dysregulation of circulating CDC42 and its correlation with demographic characteristics, comorbidities, tumor features, chemotherapeutic regimen and survival profile in non-small-cell lung cancer patients.
Cell division control protein 42 (CDC42) induces the immune escape, represses the CD8+ T-cell activation, and further leads to the tumor metastasis in various neoplasms, whereas the correlation of circulating CDC42 with clinical features and prognosis of non-small-cell lung cancer (NSCLC) remains elusive. Hence, the current study aimed to investigate this topic. Peripheral blood mononuclear cells from 263 NSCLC patients before treatment and 50 health controls (HC) were used for CDC42 determination by reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. CDC42 expression was higher in NSCLC patients than HCs (p < 0.001). Besides, elevated CDC42 expression was correlated with the occurrence of lymph node (LYN) metastasis (p = 0.003) and advanced TNM stage (p = 0.007), but not related to other tumor features, demographic characteristics, comorbidities, nor neoadjuvant/adjuvant chemotherapy (all p > 0.05). Additionally, elevated CDC42 expression was correlated with unfavorable accumulating disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.025). More importantly, multivariate Cox's proportional hazard regression analysis revealed that elevated CDC42 expression (hazard ratio (HR): 1.284, p < 0.001) and higher TNM stage (HR: 1.428, p = 0.003) were independently associated with shorter DFS, meanwhile elevated CDC42 expression (HR: 1.193, p = 0.035), higher pathological grade (HR: 1.558, p = 0.003), higher TNM stage (HR: 1.703, p = 0.001) and higher Eastern Cooperative Oncology Group performance status (ECOG PS) score (HR: 1.538, p = 0.038) were independently correlated with unsatisfying OS. Circulating CDC42 is highly expressed with its overexpression linked with LYN metastasis, poor DFS, and OS in NSCLC patients.


Subglottic stenosis associated with Wegener's granulomatosis.
To evaluate the outcomes of subglottic stenosis in patients with Wegener's granulomatosis. Retrospective chart review. A retrospective chart review was undertaken to review all patients evaluated in an otolaryngology-head and neck surgery department between 1993 and 2001 for active symptoms attributed to subglottic stenosis who had undergone cytoplasmic staining antineutrophil cytoplasm antibody and perninuclear staining antineutrophil cytoplasm antibody testing and who had a clinical diagnosis of Wegener's granulomatosis. Twenty-seven patients were identified with Wegener's granulomatosis and subglottic stenosis. Among these, 11 of 27 (40.7%) underwent tracheotomy; 13 of 27 (48.1%) required multiple surgical procedures. A history of open laryngotracheal repair was present in 7 of 27 patients (25.9%). CO(2) laser resection and dilation was used in 12 of 27 patients (44.4%). Three of 27 patients (11.1%) had a tracheotomy at last follow-up. Patients were followed for an average duration of 76.8 months (6.4 y) from the onset of symptoms attributed to subglottic stenosis. All patients who underwent open laryngotracheal reconstruction had successful decannulation. Wegener's granulomatosis is a necrotizing vasculitis that can involve the subglottis. Our approach to airway management in these patients involves a tracheotomy if obstruction occurs during acute inflammatory activity. We recommend minimizing airway manipulation during episodes of systemic disease activity. Once control of the disease process is obtained, consideration is given to either an endoscopic or an open approach based on the extent of stenosis. Either laryngotracheal reconstruction or CO(2) laser resection and dilation may be undertaken with safety and should result in favorable outcomes.


Discovery of potent, selective, and metabolically stable 4-(pyridin-3-yl)cinnolines as novel phosphodiesterase 10A (PDE10A) inhibitors.
We report the discovery of 6,7-dimethoxy-4-(pyridin-3-yl)cinnolines as novel inhibitors of phosphodiesterase 10A (PDE10A). Systematic examination and analyses of structure-activity-relationships resulted in single digit nM potency against PDE10A. X-ray co-crystal structure revealed the mode of binding in the enzyme's catalytic domain and the source of selectivity against other PDEs. High in vivo clearance in rats was addressed with the help of metabolite identification (ID) studies. These findings combined resulted in compound 39, a promising potent inhibitor of PDE10A with good in vivo metabolic stability in rats and efficacy in a rodent behavioral model.


Five years of phenological monitoring in a mountain grassland: inter-annual patterns and evaluation of the sampling protocol.
The increasingly important effect of climate change and extremes on alpine phenology highlights the need to establish accurate monitoring methods to track inter-annual variation (IAV) and long-term trends in plant phenology. We evaluated four different indices of phenological development (two for plant productivity, i.e., green biomass and leaf area index; two for plant greenness, i.e., greenness from visual inspection and from digital images) from a 5-year monitoring of ecosystem phenology, here defined as the seasonal development of the grassland canopy, in a subalpine grassland site (NW Alps). Our aim was to establish an effective observation strategy that enables the detection of shifts in grassland phenology in response to climate trends and meteorological extremes. The seasonal development of the vegetation at this site appears strongly controlled by snowmelt mostly in its first stages and to a lesser extent in the overall development trajectory. All indices were able to detect an anomalous beginning of the growing season in 2011 due to an exceptionally early snowmelt, whereas only some of them revealed a later beginning of the growing season in 2013 due to a late snowmelt. A method is developed to derive the number of samples that maximise the trade-off between sampling effort and accuracy in IAV detection in the context of long-term phenology monitoring programmes. Results show that spring phenology requires a smaller number of samples than autumn phenology to track a given target of IAV. Additionally, productivity indices (leaf area index and green biomass) have a higher sampling requirement than greenness derived from visual estimation and from the analysis of digital images. Of the latter two, the analysis of digital images stands out as the more effective, rapid and objective method to detect IAV in vegetation development.


Use of signature-tagged mutagenesis in pathogenesis studies.
From 2000-2001, over 10 studies have been completed, using signature-tagged mutagenesis, on a variety of bacterial pathogens. Investigators are examining the attenuated strains in additional in vivo, cell culture or in vitro assays to further characterize and catalog the mutants. Notable advances included screening of the attenuated mutants en masse in other assays, verification that mutant strains are defective for growth in specific host tissues, and identification of potential live-attenuated vaccine candidates. In addition, researchers are using signature-tagged strains to characterize the infection process, which is providing snapshots of bottlenecks and quantitative measurements of bacterial spread from tissue to tissue. This review focuses on themes emerging from signature-tagged mutagenesis studies completed on bacterial pathogens since mid-2000.


Nitroglycerin for portal hypertension. A controlled comparison of the hemodynamic effects of graded doses.
Nitroglycerin is reportedly an effective treatment for portal hypertension. However, the effects of graded doses have not been examined. We administered nitroglycerin intravenously to 10 patients with alcoholic cirrhosis, beginning at 10 micrograms/min and doubling the dose every 10 min thereafter until mean arterial pressure fell 10-15 mmHg. We compared the response to that of 10 patients receiving a control infusion. The median infusion rate of nitroglycerin was 40 micrograms/min (range 10-160 micrograms/min). Nitroglycerin significantly reduced cardiac output as well as pulmonary artery, pulmonary capillary and mean arterial pressure. The overall effects of nitroglycerin on the hepatic venous pressure gradient and azygous (gastroesophageal collateral) blood flow were heterogeneous. However, the hepatic venous pressure gradient significantly increased in nitroglycerin-treated patients with high pulmonary capillary pressures (greater than or equal to 12 mmHg) compared to control patients with similar cardiac filling pressures at both median and maximum rates of infusion. Nitroglycerin is therefore not a uniformly effective treatment for portal hypertension. Cardiac filling pressure may be a determinant of the splanchnic hemodynamic response to nitroglycerin.


Case report: Malignant peripheral nerve sheath tumor of the uterine cervix treated with radical vaginal trachelectomy.
Malignant peripheral nerve sheath tumors (MPNST) are rare tumors which occur primarily in major nerve trunks and most commonly in patients with neurofibromatosis. Only seven prior cases of these tumors arising in the uterine cervix have been reported, all of which were treated by hysterectomy. We report a 22-year-old woman with MPNST of the uterine cervix which recurred after loop electrocautery excision and had positive margins on cone biopsy. She was treated definitively with radical trachelectomy and is well with no sign of recurrence 20 months later. MPNST of the uterine cervix is a rare, but potentially aggressive neoplasm. This is the first case of such a tumor treated successfully with preservation of the patients fertility.


Distribution of bombesin, somatostatin, substance-P and vasoactive intestinal polypeptide in feline and porcine skin.
The content and distribution of several regulatory peptides in the skin of cats and pigs, freshly obtained at surgery, have been investigated. Immunoreactive bombesin was evenly distributed at low concentrations in both species, being below the detection limit in the body and nose of the cat, and showing a peak value of 1.6 +/- 0.7 pmol/g in the tip of the pig's ear. Similar concentrations of somatostatin-immunoreactivity (-IR) were found but greater regional variation occurred in the pig with a low in the mid back of 0.4 +/- 0.1 and the highest value in the snout of 3.1 +/- 0.8. Substance-P-IR in the pig showed a marked variation in concentration, apparently parallelling skin sensitivity, with a low in the back of 0.4 +/- 0.7 and higher values around the anus (8.1 +/- 1.6), legs (6.8 +/- 1.8) and snout (13.5 +/- 3.6) whilst in the cat values ranged from 0.3 +/- 0.06 in the body to 5.0 +/- 0.9 in the front footpads. In contrast, vasoactive intestinal polypeptide (VIP)-IR showed greater variability in the cat, being below the assay's detection in the body and highest in the front and rear footpads (17 +/- 7 and 29 +/- 6 respectively), but in the pig most regions exhibited low concentrations with the exception of the snout which peaked at 12.0 +/- 5.0. Immunocytochemical localisation showed the peptides to be present in nerve fibres. Substance-P-IR was particularly localised in the snout of the pig just below the epithelium while VIP-IR was more concentrated in deeper layers, often associated with sweat glands and blood vessels.


Trismus as a presenting symptom in nasopharyngeal carcinoma.
Trismus is a more common symptom in NPC patients with young age and an indicator of advanced primary tumour. Overall response rate after treatment was 88%. Trismus recovered in majority of patients at the end of treatment and patients with complete recovery of trismus may have a better survival.


US Parents' Acceptance of Learning About Mindfulness Practices for Parents and Children: National Cross-sectional Survey.
Mindfulness practices are associated with improved health and well-being for children. Few studies have assessed parents' acceptance of learning about mindfulness practices. This study aims to assess parents' beliefs and interest in learning about mindfulness, including from their health care provider, and differences across demographic backgrounds. We conducted a national cross-sectional survey of parents with children aged 0-18 years in October 2018. Measures included beliefs and interest in learning about mindfulness. These measures were compared across demographic backgrounds using chi-square analysis. Multivariate linear and logistic regression analyses were used to perform adjusted comparisons between demographic backgrounds. Participants (N=3000) were 87% (n=2621) female and 82.5% (n=2466) Caucasian. Most (n=1913, 64.2%) reported beliefs that mindfulness can be beneficial when parenting, 56.4% (n=1595) showed interest in learning about mindfulness to help their child stay healthy, and 40.8% (n=1214) reported interest in learning about mindfulness from their health care provider. Parents with a college degree 49.6% (n=444) were more likely to report interest in learning about mindfulness from a health care provider compared to those without 37.1% (n=768; P<.001). Parents interested in learning about mindfulness were more likely to be male 62.6% (n=223; P<.001). There was no significant difference in interest in learning about mindfulness from a health care provider based on race. This study indicates that many parents believe mindfulness can be beneficial while parenting and are interested in learning how mindfulness could help their child stay healthy. Findings suggest there is an opportunity to educate families about mindfulness practices.


Who uses telehealth? Setting a usage baseline for the early identification of pandemic influenza activity.
To describe Ontario Telehealth usage for respiratory complaints during normal (i.e., interpandemic) circumstances. Descriptive analyses were conducted on symptom calls of a respiratory nature made to Ontario (Canada) Telehealth during a 25-month period. Approximately 300,000 calls were made during the period under study, peaking annually in January/February. Calls were above average during the weekend and Mondays (p<0.0001). All-ages consultation rate was 0.21/1,000 (range, 0.11-0.43). Standardized call rates suggested an inverse relationship between age and call rate (except for >65 years of age). During peak activity, weekly telehealth call rates were up to more than twice the weekly mean and up to four times as high as the lowest weekly rate. Highest call rate was for under 5 years old (158.4/1,000). Male rates exceed female call rates in younger age groups; the pattern reversed in older age groups. The relationship between income and call pattern showed that income and call patterns were (1) directly related for under 5 years old, (2) inversely related for callers aged 45 years and above, and (3) bimodal (higher call rates in both the highest and lowest income groups) for callers 5-44 years old. The advent of annual respiratory illness seasons under study here resulted in surge capacity. Data such as these can and should be used for exercises such as seasonal and pandemic forecasting. Also, recent pandemic experience has showed us monitoring both overall exceedances in usage and deviances from established demographic patterns could enhance existing routine surveillance.


Toxicity of plant essential oils and their components against Lycoriella ingenua (Diptera: Sciaridae).
Plant essential oils from 20 plant species were tested for their insecticidal activity against larvae of Lycoriella ingenua (Dufour) (Diptera: Sciaridae) by using a fumigation bioassay. Good insecticidal activity (>90%) against larvae of L. ingenua was achieved with essential oils of caraway seed Carum carvi (L.)], lemongrass [Cymbopogon citratus (D.C.) Stapf.], mandarine (Citrus reticulate Blanco), nutmeg (Myristica fragrans Houtt), cade (Juniperus oxycedrus L.), spearmint (Mentha spicata L.), cumin (Cuminum cyminum L.), and thyme red [Thymus vulgaris (L.)] oils at 30 X 10-3 mg/1 air. Among them, caraway seed, spearmint, cumin, and thyme red essential oils were highly effective against L. ingenua at 20 x 10(-3) mg/ml air. Analysis by gas chromatography-mass spectrometry led to identification of 4, 9, 8, and 17 compounds from caraway seed, spearmint, cumin, and thyme red oils, respectively. These compounds were tested individually for their insecticidal activities against larvae of L. ingenua, and compared with the toxicity of dichlorvos. Carvacrol, thymol, linalool, cuminaldehyde, p-cymen, terpinen-4-ol, and carvone was effective at 10 x 10(-3) mg/l. The insecticidal activity of dichlorvos was 60% at 10 x 10(-3) mg/ml. Effects of four selected plant essential oils on growth of oyster mushroom, Pleurotus ostreatus, also were investigated.


Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice.
Prime-O-glucosylcimifugin is an active chromone isolated from Saposhnikovia root which has been reported to have various activities, such as anti-convulsant, anticancer, anti-inflammatory properties. The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. BALB/c mice received intraperitoneal injection of Prime-O-glucosylcimifugin 1h before intranasal instillation (i.n.) of lipopolysaccharide (LPS). Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary histological changes were evaluated by hematoxylin-eosin, myeloperoxidase (MPO) activity in the lung tissue and lung wet/dry weight ratios were observed. Furthermore, the mitogen-activated protein kinases (MAPK) signaling pathway activation and the phosphorylation of IκBα protein were determined by Western blot analysis. Prime-O-glucosylcimifugin showed promising anti-inflammatory effect by inhibiting the activation of MAPK and NF-κB signaling pathway.


Extracorporeal Membrane Oxygenation for Hypokalemia and Refractory Ventricular Fibrillation Associated with Caffeine Intoxication.
Caffeine has been reported as a cause of cardiac arrest after massive overdose. Here, we report the case of a patient with caffeine intoxication, which can cause fatal dysrhythmias and severe hypokalemia. They were successfully treated with extracorporeal membrane oxygenation (ECMO). A 43-year-old woman with a history of bipolar disorder presented to the emergency department after suicidal drug ingestion (caffeine and amitriptyline). Immediately after arrival, she experienced multiple episodes of ventricular fibrillation with severe hypokalemia requiring cardiopulmonary resuscitation and medical therapy. However, conventional treatment was not successful. We instituted ECMO early during resuscitation because prolonged hypokalemia refractory to aggressive potassium replacement precluded the use of antidysrhythmic medications for refractory circulatory compromise with ventricular fibrillation. The use of ECMO provided time to correct hypokalemia (19.3 g potassium) and reduce the caffeine level with hemodialysis. Although she had sustained cardiac arrest, she recovered fully and was discharged home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case indicates the potential effectiveness of ECMO in severely poisoned patients with fatal dysrhythmias. ECMO could provide time for removal of toxic drugs and correction of electrolyte abnormalities.


How should we tackle financial and prosocial biases against unattractive people?
The fact that attractive people benefit from their good looks is not bad per se. Rather, what is worrisome is the fact that unattractive people are discriminated against, and that such discrimination negatively affects many aspects of their lives. I focus on the moral implications of this discrimination and on the possible measures that could be taken to alleviate it.


Adult respiratory distress syndrome precipitated by massive salicylate poisoning.
Pulmonary oedema has been reported in severe cases of acetyl salicylic acid (ASA) poisoning. Liberal use of intravenous fluids, to establish a forced diuresis, is usually thought to be the precipitating cause. A case of severe ASA poisoning and respiratory failure was found to have increased pulmonary vascular resistance and signs of intravascular hypercoagulability. The patient recovered rapidly on mechanical ventilation with a positive endexpiratory pressure of 18 cm H2O and systemic steroids.


Cycloartanes, protolimonoids, a pregnane and a new ergostane from Trichilia reticulata.
The new ergostane steroid ergosta-5,24(24')-diene-3beta,4beta,22R-triol (1), a pregnane, (E)-volkendusin, characterised as the diacetate (3), cycloartanes 4-6 and protolimonoids 7-9 were obtained from the leaves and twigs of Trichilia reticulata.


Metastasectomy of Abdominal Wall Lesions due to Prostate Cancer Detected Through PET/CT Gallium 68-PMSA: First Case Report.
Introducing the topic of abdominal wall metastasis secondary to prostate cancer with a reminder of the disease's rarity, being the first published case. This article is about a 66 year old patient diagnosed with prostate cancer [cT2aNxMx iPSA: 5,6 ng/ml Gleason 3+3, (Grade 1 Group)], treated with radical prostatectomy as well as accompanied with amplified pelvic lymphadenectomy, who subsequently presented metastatic lesions to the abdominal wall diagnosed with PET/CT Gallium 68-PMSA technique and treated with abdominal metastasectomy with adequate short term results.


The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline.
LOTUS and Tudor domain containing proteins have critical roles in the germline. Proteins that contain these domains, such as Tejas/Tapas in Drosophila, help localize the Vasa helicase to the germ granules and facilitate piRNA-mediated transposon silencing. The homologous proteins in mammals, TDRD5 and TDRD7, are required during spermiogenesis. Until now, proteins containing both LOTUS and Tudor domains in Caenorhabditis elegans have remained elusive. Here we describe LOTR-1 (D1081.7), which derives its name from its LOTUS and Tudor domains. Interestingly, LOTR-1 docks next to P granules to colocalize with the broadly conserved Z-granule helicase, ZNFX-1. The Tudor domain of LOTR-1 is required for its Z-granule retention. Like znfx-1 mutants, lotr-1 mutants lose small RNAs from the 3' ends of WAGO and mutator targets, reminiscent of the loss of piRNAs from the 3' ends of piRNA precursor transcripts in mouse Tdrd5 mutants. Our work shows that LOTR-1 acts with ZNFX-1 to bring small RNA amplifying mechanisms towards the 3' ends of its RNA templates.


Comparative gene expression in hematopoietic progenitor cells derived from embryonic stem cells.
The aim of this study was to characterize at the molecular level the hematopoietic progenitor cells derived from rhesus monkey embryonic stem (ES) cell differentiation. We purified CD34(+) and CD34(+)CD38(-) cells from rhesus monkey ES cell cultures and examined the expression of a variety of genes associated with hematopoietic development, by semiquantitative polymerase chain reaction analysis. For comparison, we examined cell preparations from fresh or cultured rhesus monkey bone marrow (BM) and from mouse ES cells and BM. We observed a high degree of similarity in the expression patterns of these genes, with only a few exceptions. Most notably, the message of the flt3 gene was undetectable in rhesus monkey ES cell-derived CD34(+) and CD34(+)CD38(-) cells, whereas substantial flt3 expression was observed in the corresponding cells from fresh BM and in CD34(+) cells from cultured BM. The integrin alphaL and interleukin-6 (IL-6) receptor genes also were expressed in CD34(+)CD38(-) cells from BM, but there was little or no expression of these genes in CD34(+)CD38(-) cells derived from ES cells. Parallel analyses, using CD34(+)Lin(-) cells derived from murine ES cell cultures, showed no apparent expression of flt3, integrin alphaL, or IL-6 receptor, whereas corresponding cell preparations isolated from mouse BM expressed high levels of all of these genes. ES cell-derived hematopoietic progenitors, both from the rhesus monkey and from the mouse, exhibited the same alterations in gene expression compared with BM-derived cells from these animals. These observations could reflect the presence of different subpopulations in the cell fractions that were compared, or they may represent altered biologic properties of ES cell-derived hematopoietic stem cells.


Use of monoclonal antiacetylcholine receptor antibodies to investigate the macrophage inflammation of acute experimental myasthenia gravis: refractoriness to a second episode of acute disease.
The acute phase of experimental autoimmune myasthenia gravis (EAMG) is characterized by macrophage inflammation of muscle endplates and by muscle fiber necrosis. We induced acute EAMG by passive transfer of monoclonal antibodies (mAbs) directed against the acetylcholine receptor (AChR) to investigate this brief and self-limited disorder. After the initial acute phase, animals were refractory to induction of a second episode by subsequent injection of the same mAb, or another anti-AChR mAb of different idiotype and which binds to a separate epitope. Therefore, the refractory state was not caused by an anti-idiotypic response or epitopic modulation. Adoptive transfer of spleen cells from refractory animals had no effect, excluding a role of suppressor lymphocytes, and there was no evidence from experiments involving adoptive transfer of spleen cells from naive animals to refractory animals that refractory animals lacked effector cells.


Responsivity to pain in rats changed by the ingestion of flavored water.
Sprague-Dawley male rats drank flavored water and subsequent pain responsivity was assessed using a hot plate first after isotonic saline and later after either 2.75 (Experiment 1) or 2.5 (Experiment 2) mg/kg of morphine hydrochloride was injected. A 48-h exposure to any one of several different flavors resulted in a reduction of the analgesic effects of morphine as shown by an attenuation of the increased latency to paw lick caused by the morphine. This effect was independent of the amount consumed. A 26-h exposure to a flavor decreased pain reactivity before and after morphine as shown by an overall increase in latency to paw lick. This effect was not influenced by whether the normally preferred flavor was made aversive by a previous pairing with lithium chloride-induced illness. These findings are consistent with the idea that many flavors, independently of palatability and amount consumed, increase the release and utilization of endogenous opioids.


Oral copper absorption in men with morbid obesity.
Copper deficiency has been reported in patients with severe obesity, both before and after bariatric surgery, the latter at increased rates. However, little is known about the absorption of copper. Because of differences in copper dynamics between men and women in the limited available data, we evaluated copper absorption in men who were candidates for bariatric surgery. All patients gave informed consent, approved by the University of Pennsylvania Institutional Review Board, to participate in a pharmacokinetics study. After a 12-h fast, body composition was measured using air displacement plethysmography and a single oral dose of 4mg copper gluconate was given followed by serial measures of serum copper over 10h. Meals and snacks very low in copper were provided. The seven participants had age 52±8years, BMI 44.87±9.01kg/m2 and fat free mass 77.92±14.45kg. Baseline serum copper was 36.1±19.5μg/dL and ceruloplasmin was 50.86±4.58mg/dL. Peak copper absorption occurred within 1-2h. The AUC for six subjects was 254.6±151.3μg/100mLh. The estimated volume of distribution (1.98±0.36L) was ∼25mL/kg fat free mass. In these severely obese men, copper absorption occurred early in spite of their normal copper status, suggesting no impairment of absorption due to obesity. Further studies of copper absorption after the significant weight loss and possible malabsorption derived from bariatric surgery are needed.


Tris (1,3-dichloro-2-propyl) phosphate exposure disrupts the gut microbiome and its associated metabolites in mice.
Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) has been frequently detected in environmental media and biological samples. However, knowledge of its adverse health consequences is limited, and its impacts on the human gut microbiota, which play a key role in health and disease, remain unexplored. To better evaluate the potential risk of TDCIPP exposure in human health, we investigated the effects of TDCIPP on gut microbiome and gut metabolites in C57BL/6 mice. We applied an integrated analytical approach by combing 16S rRNA gene sequencing, metagenomic sequencing and 1H NMR metabolomics analysis in fecal samples collected from mouse with TDCIPP exposure as well as those from controls. Both 16S rRNA sequencing and metagenome sequencing showed that TDCIPP exposure significantly changed the gut microbiome, with a remarkable increased Firmicutes at the expense of Bacteroidetes after exposure. Perturbed gut metabolic profiles in the treated group were also observed and closely related with altered gut microbiome. Gene functional annotation analysis further suggested perturbed gut metabolites could be directly caused by altered gut microbiome. TDCIPP exposure has great influence on the gut ecosystem as reflected by perturbation of microbiome community structure, microbial species, gut microbe associated gene expression and gut metabolites, which may contribute to the progression of certain uncharacterized gut microbiota related host diseases. Our findings provide novel insights into adverse effects of TDCIPP exposure on human health.


Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study.
Both aspirin and warfarin when used alone are effective in the secondary prevention of vascular events and death after acute myocardial infarction. We tested the hypothesis that aspirin and warfarin therapy, when combined, would be more effective than aspirin monotherapy. Methods and Results- We conducted a randomized open-label study to compare the efficacy of warfarin (target international normalized ratio 1.5 to 2.5 IU) plus aspirin (81 mg daily) with the efficacy of aspirin monotherapy (162 mg daily) in reducing the total mortality in 5059 patients enrolled within 14 days of infarction and followed for a median of 2.7 years. Secondary end points included recurrent myocardial infarction, stroke, and major hemorrhage. Four hundred thirty-eight (17.3%) of 2537 patients assigned to the aspirin group and 444 (17.6%) of 2522 patients assigned to the combination group died (log-rank P=0.76). Recurrent myocardial infarction occurred in 333 patients (13.1%) taking aspirin and in 336 patients (13.3%) taking combination therapy (log-rank P=0.78). Stroke occurred in 89 patients (3.5%) taking aspirin and in 79 patients (3.1%) taking combination therapy (log-rank P=0.52). Major bleeding occurred more frequently in the combination therapy group than in the aspirin group (1.28 versus 0.72 events per 100 person years of follow-up, respectively; P<0.001). There were 14 individuals with intracranial bleeds in both the aspirin and combination therapy groups. In post-myocardial infarction patients, warfarin therapy (at a mean international normalized ratio of 1.8) combined with low-dose aspirin did not provide a clinical benefit beyond that achievable with aspirin monotherapy.


Rates of Sexually Transmitted Infection Diagnoses Among US Youth With Perinatally and Nonperinatally Acquired HIV.
Of new sexually transmitted infections (STIs) in the United States, 50% occur among youth aged 15 to 24 years. Previous studies among youth with HIV (YHIV) do not distinguish STI trends among individuals with perinatally (YPHIV) and nonperinatally (YNPHIV) acquired HIV. Among 3 Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) studies conducted between 2009 and 2015, we estimated incident diagnoses of trichomonal, bacterial, viral, and overall STIs stratified by sex assigned at birth, mode of HIV acquisition (perinatal [YPHIV] and nonperinatal [YNPHIV]), age (13-17 and 18-24 years), CD4 count (<200, 200-499, and ≥500/μL), and HIV viral load (VL) (<400 and ≥400 copies/mL). Among 3131 YHIV, across the 3 studies, mean (SD) age was 20.6 (2.6) years, 888 (28%) were female, 2498 (80%) had nonperinatal HIV acquisition recorded, and 2298 (73%) were African American/Black. Mean follow-up was 0.9 (0.3) years. Compared with YPHIV, YNPHIV spent less person-time with VL <400 copies/mL (47% vs. 53%) and more time off antiretroviral therapy (49% vs. 15%), and had higher overall STI rates (males, 65.9 vs. 8.5/100 person-years [PY]; females, 54.7 vs. 17.2/100 PY). Among YPHIV, bacterial STIs were higher during person-time spent with VL ≥400 vs. <400 copies/mL (male YPHIV, 10.9 vs. 0.6/100 PY; female YPHIV, 11.2 vs. 2.9/100 PY); no difference was observed among YNPHIV, which may be due to concurrent acquisition of HIV and other STIs and limited follow-up. Compared with YPHIV, YNPHIV spent less time on antiretroviral therapy and virologically suppressed; YNPHIV also had higher STI diagnosis rates. Very high STI diagnosis rates among YHIV, including among those without virologic suppression, highlight the importance of youth-focused efforts to support durable virologic suppression and identify and treat STIs.


Performance of Endoscopic Ultrasound-Guided Versus Percutaneous Liver Biopsy in Diagnosing Stage 3-4 Fibrosis.
Percutaneous liver biopsy (P-bx) is the gold standard for diagnosing advanced fibrosis. Despite the proven technical feasibility of EUS-guided liver bx (EUS-bx) as a novel alternative way of liver biopsy, the clinical applicability remains to be determined. The primary aim of this study is to evaluate if EUS-bx, compared to P-bx, can effectively and safely obtain adequate specimen and accurately predict hepatic fibrosis. This is a single center, retrospective chart review among patients with liver diseases at a tertiary endoscopy center from February 2011 to March 2020. We assessed the EUS-bx versus P-bx outcomes by success rate, performance, and safety profile. The primary outcome was the association between EUS-bx clinical variables and the presence of histologic liver fibrosis stage ≥ 3. The secondary outcomes were the associations between EUS-bx and variables indicative of fibrosis. Fifty-nine patients underwent EUS-bx; and 59, P-bx. All EUS-bx procedures were successfully completed. All 56/56 (100%) of EUS-bx vs. 50/52 (96.2%) P-bx were considered adequate samples. Tissue lengths were significantly longer in the EUS-bx cohort (p < 0.0001) with a trend towards a greater number of portal tracts. 46/56 (82.1%) cases of EUS-bx vs. 32/52 (61.5%) of P-bx had > 10 portal tracts; 21/56 (37.5%) cases of EUS-bx vs. 14/52 (26.9%) of P-bx had > 15 portal tracts. There were 6 (10.2%) EUS-bx vs. 1 (1.7%) P-bx related complication leading to a phone call (p = 0.061). EUS-bx can safely performed and accurately predict liver fibrosis stage as the standard P-bx without being influenced by procedure-related factors.


Urinary bladder carcinoma as apparent cause of antepartum haemorrhage in pregnancy.
A 34-year-old multipara presented with painless profuse genital bleeding during the third trimester of pregnancy in a state of hemorrhagic shock. Haematuria because of urinary bladder carcinoma was found to be the cause of bleeding. Cystoscopy was useful for accurate diagnosis as well as for achieving haemostasis. This case emphasizes the possibility and importance of haematuria when dealing with a patient with antepartum haemorrhage.


Metabolic control in a nationally representative diabetic elderly sample in Costa Rica: patients at community health centers vs. patients at other health care settings.
Costa Rica, like other developing countries, is experiencing an increasing burden of chronic conditions such as diabetes mellitus (DM), especially among its elderly population. This article has two goals: (1) to assess the level of metabolic control among the diabetic population age >or= 60 years old in Costa Rica, and (2) to test whether diabetic elderly patients of community health centers differ from patients in other health care settings in terms of the level of metabolic control. Data come from the project CRELES, a nationally representative study of people aged 60 and over in Costa Rica. This article analyzes a subsample of 542 participants in CRELES with self-reported diagnosis of diabetes mellitus. Odds ratios of poor levels of metabolic control at different health care settings are computed using logistic regressions. Lack of metabolic control among elderly diabetic population in Costa Rica is described as follows: 37% have glycated hemoglobin >or= 7%; 78% have systolic blood pressure >or= 130 mmHg; 66% have diastolic blood pressure >or= 80 mmHg; 48% have triglycerides >or= 150 mg/dl; 78% have LDL >or= 100 mg/dl; 70% have HDL <or= 40 mg/dl. Elevated levels of triglycerides and LDL were higher in patients of community health centers than in patients of other clinical settings. There were no statistical differences in the other metabolic control indicators across health care settings. Levels of metabolic control among elderly population with DM in Costa Rica are not that different from those observed in industrialized countries. Elevated levels of triglycerides and LDL at community health centers may indicate problems of dyslipidemia treatment among diabetic patients; these problems are not observed in other health care settings. The Costa Rican health care system should address this problem, given that community health centers constitute a means of democratizing access to primary health care to underserved and poor areas.