Uncoupling protein 3 as a mitochondrial fatty acid anion exporter.
In contrast to UCP1, the primary function of UCP3 is not the dissipation of energy. Rather, several lines of evidence suggest that UCP3 is related to cellular long-chain fatty acid homeostasis. If long-chain fatty acids enter the mitochondrial matrix in their non-esterified form, they cannot be metabolized and may exert deleterious effects. To test the feasibility that UCP3 exports fatty acid anions, we systematically interfered at distinct steps in the fatty acid metabolism pathway, thereby creating conditions in which the entry of (non-esterified) fatty acids into the mitochondrial matrix is enhanced. First, reducing the cellular fatty acid binding capacity, known to increase cytosolic concentrations of non-esterified fatty acids, up-regulated UCP3 5.3-fold. Second, inhibition of mitochondrial entry of esterified long-chain fatty acids up-regulated UCP3 by 1.9-fold. Third, high-fat diets, to increase mitochondrial supply of non-esterified long-chain fatty acids exceeding oxidative capacity, up-regulated UCP3 twofold. However, feeding a similar amount of medium-chain fatty acids, which can be oxidized inside the mitochondrial matrix and therefore do not need to be exported from the matrix, did not affect UCP3 protein levels. These data are compatible with a physiological function of UCP3 in facilitating outward transport of long-chain fatty acid anions, which cannot be oxidized, from the mitochondrial matrix.


Acute Myocardial Infarction in a Young Woman: Role of Cardiac Magnetic Resonance Imaging in Establishing the Diagnosis.
Evaluation of acute coronary syndromes (ACS) in young women presents a clinical challenge. An unremarkable coronary angiogram may not exclude ACS, as spontaneous lesion revascularization, resolved coronary spams, or spontaneous coronary dissection (SCAD) can often be missed. Cardiac magnetic resonance imaging (CMR) can provide useful information in acute myocardial infarction (MI) by confirming and sizing acute infarction and delineating the etiology when angiography is inconclusive. Here, we report a case of a 39-year-old postpartum woman with a history of hyperlipidemia who presented with a one-day history of atypical angina. On presentation, she was found to have transient ST-segment elevation in high lateral leads and elevated troponin. Coronary angiography revealed a nonobstructive lesion in the first obtuse marginal branch (OM1) distribution. The patient subsequently underwent cardiac magnetic resonance imaging (MRI) for further delineation of etiology, which confirmed acute infarction in the OM1 distribution. Diagnosis of myocardial infarction with no obstructive coronary artery disease (MINOCA) secondary to acute coronary artery dissection type 2 (SCAD-2) was made. The patient was managed conservatively with medical therapy. CMR has emerged as a front-line diagnostic imaging modality in acute MI and can provide invaluable information in the confirmation and sizing of infarction, delineating tissue characteristics, establishing the etiology of infarction, and prognostication.


Diagnostic performance of a point-of-care saliva urea nitrogen dipstick to screen for kidney disease in low-resource settings where serum creatinine is unavailable.
Kidney disease is prevalent in low-resource settings worldwide, but tests for its diagnosis are often unavailable. The saliva urea nitrogen (SUN) dipstick is a laboratory and electricity independent tool, which may be used for the detection of kidney disease. We investigated the feasibility and performance of its use in diagnosing kidney disease in community settings in Africa. Adult patients at increased risk of kidney disease presenting to three community health centres, a rural district hospital and a central hospital in Malawi were recruited between October 2016 and September 2017. Patients underwent concurrent SUN and creatinine testing at enrolment, and at 1 week, 1 month, 3 months and 6 months thereafter. Of 710 patients who presented at increased risk of kidney disease, 655 (92.3%) underwent SUN testing at enrolment, and were included (aged 38 (29-52) years, 367 (56%) female and 333 (50.8%) with HIV). Kidney disease was present in 482 (73.6%) patients and 1479 SUN measurements were made overall. Estimated glomerular filtration rate (eGFR) correlated with SUN (r=-0.39; p<0.0001). The area under the receiver operating characteristics curve was 0.61 for presenting SUN to detect acute or chronic kidney disease, and 0.87 to detect severe (eGFR <15 mL/min/1.73 m2) kidney disease (p<0.0001; sensitivity 82.3%, specificity 81.8%, test accuracy 81.8%). In-hospital mortality was greater if enrolment SUN was elevated (>test pad #1) compared with patients with non-elevated SUN (p<0.0001; HR 3.3 (95% CI 1.7 to 6.1). SUN, measured by dipstick, is feasible and may be used to screen for kidney disease in low resource settings where creatinine tests are unavailable.


Surgical and radiological decompression in malignant biliary obstruction: a retrospective study using multivariate risk factor analysis.
We performed a retrospective computer-aided statistical study of 228 patients who received treatment for malignant biliary obstruction to compare survival rates after surgical or radiological biliary decompression. To adjust for the selection bias produced by the clinical choice of surgical vs. catheter drainage, we examined differences in survival rates after controlling for various clinical and laboratory factors, which are predictive of short and long-term survival. These factors were selected by multivariate analysis. Short-term survival was significantly correlated with preoperative metabolic status as reflected in serum albumin, and blood urea nitrogen (BUN) levels. Elevated serum bilirubin values had no additional negative effect on survival. Long-term survival was influenced mainly by the extent of the primary cancer and the preoperative presence of leukocytosis. Although there was a difference in the raw data for hospital mortality between patients who underwent surgical drainage (11%) and those who underwent radiological drainage (30%), we found no real effect produced by the form of therapy after controlling for prognosis variables, i.e., eliminating selection bias. We propose a simple statistical model to predict short-term hospital survival. The application of objective risk factor analysis according to accepted statistical methods should permit the assessment of new radiologic therapeutic techniques with greater clinical validity.


Phase I/II study of bisantrene in childhood cancer: a report from the Childrens Cancer Study Group.
A phase I/II study of bisantrene using a 3-week schedule was undertaken in 171 children with refractory leukemias and solid tumors. The doses ranged from 190 to 430 mg/m2. The maximum tolerated dose for children with solid tumors and acute leukemias was 280 mg/m2 and 360 mg/m2 every 3 weeks, respectively. The dose limiting toxicities were hepatic and hematologic. One patient with ALL achieved a complete remission and partial responses were observed in three patients with soft-tissue sarcomas. The data indicate that bisantrene, at the doses and schedule used in this study, has limited antitumor activity in pretreated children with cancer.


Paroxysmal Sympathetic Hyperactivity in Children: An Exploratory Evaluation of Nursing Interventions.
Paroxysmal sympathetic hyperactivity (PSH) produces symptoms of autonomic instability and muscle over-activity; however, the majority of nursing interventions used in clinical practice are anecdotal and not evidenced based. The primary objective was to report nursing documentation of PSH events, and to describe the clinical nursing interventions and care provided to children who have suffered a severe brain injury and are exhibiting PSH. The secondary objective was to demonstrate how the Symptom Management Theory (SMT) can serve as a framework for research related to brain injury and PSH. The study consisted of a retrospective chart review of nursing progress notes using direct content analysis. The nested sample of ten randomly selected charts was chosen from a larger quantitative study of 83 children who had suffered severe brain injuries with and without PSH. Textual analysis of verbatim nursing progress notes was used to describe nursing interventions that were used and documented for this patient population. The priority nursing interventions to manage these symptoms included medication administration, facilitation of family presence, and strategies to target auditory, tactile, and visual stimuli. The sample received different individual interventions for PSH. Additionally, individual subjects demonstrated different patterns of interventions. While tactile interventions were documented most frequently, there was not a uniform approach to interventions. The SMT can be useful to provide a framework that organizes and tests clinical care and management of PSH strategies.


Culture, brain death, and transplantation.
From the social sciences, we know the space between life and death is historically and culturally constructed, fluid and open to dispute. The definition of death has cultural, legal, and political dimensions. As healthcare becomes more culturally diverse, the interface between culture and the delivery of healthcare will increase. In our increasingly pluralistic, interdependent society, there is a growing demand to integrate healthcare, including transplantation, into a broader context that respects both individual and cultural diversity. It is important that we first consider and explore what elements of Western healthcare practices including definitions and advances, such as brain death and organ donation, are culturally influenced. This article highlights some of the cultural influences on brain death by focusing on Western and Japanese perspectives on the permissibility of organ procurement from brain-dead persons. It also offers 4 recommendations for healthcare workers working cross-culturally.


Good luck rites in contemporary infertility.
To explore whether contemporary women use good luck rites in the infertility situation. Prospective study in a tertiary infertility center where women were asked to describe any type of good luck act performed on the day of critical medical intervention (either intrauterine insemination or embryo transfer) to achieve pregnancy. Four hundred thirty-eight consecutive infertile women participated. Good luck rituals, as defined by patients, included prayer, wearing of objects, fantasies and other acts performed specifically on the day of the medical intervention. While 40% of the study population reported engaging in a good luck act prior to intrauterine insemination of embryo transfer, there was no significant difference in pregnancy rates observed in women reporting utilization versus nonutilization of fertility rituals. This study indicated that good luck rites are commonly performed by women undergoing infertility procedures on the day of a critical intervention. The fact of their common presence attests to their importance for the well-being of the individual; however, there is no evidence of direct benefit in terms of higher pregnancy rates. The possibility of secondary benefits needs to be explored further.


Opening of the mouse zona pellucida by laser without a micromanipulator.
A contact-free laser system is described for ablation of the embryonic mouse zona pellucida using a pulsed excimer 308 nm laser. Effects on further embryonic development were evaluated. Zonae of 8- to 16-cell mouse embryos were either lased (n = 189), zona-drilled with acidified Tyrode's solution (n = 183) or left zona-intact (n = 188). Blastocyst formation (99-100%) was similar in the three groups. Hatching occurred earlier in lased embryos compared to those of the control group. These blastocysts hatched through the laser ablated area. Significantly more embryos were hatching on day 4 in the conventionally drilled group when compared to the laser treated group (50% versus 24% respectively). On day 7 of development, significantly (P < 0.05) more embryos conventionally zona-drilled (37%) were intact than those which were previously laser treated (10%). Abnormal development was also noted in a small group of embryos which were lased just on the outside of the zona in comparison to 1/3 of an embryonic width away from the zona. The current results suggest that apparently precise zona laser ablation with an excimer laser at 308 nm may have potential adverse effects which may only be manifested after a prolonged period of culture past the cavitation stage. However, implantation rates of morphologically normal laser abalated embryos were not impaired when compared to control embryos.


Antibacterial Properties of Chitosan Nanoparticles and Propolis Associated with Calcium Hydroxide against Single- and Multispecies Biofilms: An In Vitro and In Situ Study.
The aim of this study was to evaluate the efficacy of chitosan nanoparticles (CNPs) and ethanolic propolis extract (EPE) incorporated into a calcium hydroxide paste (Ca[OH]2) to kill bacterial biofilms. Human root canal dentin was infected with Enterococcus faecalis for 21 days and also intraorally for 48 hours followed by incubation in brain-heart infusion for 48 hours to standardize biofilm growth. Ca(OH)2 pastes associated or not with CNPs or EPE were tested on biofilms for 7 and 14 days. Distilled water was used for control purposes. After the treatment procedures, microbiological analysis was performed to determine the reduction in E. faecalis colonies. Confocal microscopy was used to determine the percentage of cell viability in polymicrobial biofilms before and after the exposure to the experimental intracanal medications. All experimental pastes were able to significantly reduce the E. faecalis colony-forming units (CFU) after 7 or 14 days (P < .05). However, the CFU reduction was significantly improved when CNPs were incorporated into the Ca(OH)2 paste (P < .05). The multispecies biofilms treated with Ca(OH)2 showed similar percentages of bacterial viability to the control regardless of the exposure time (P > .05). The viable cell count significantly dropped in the Ca(OH)2/CNPs groups for both 7 and 14 days (P < .05), whereas the Ca(OH)2/EPE groups were only effective in eliminating bacteria during the first 7 days of treatment (P < .05). Incorporating CNPs into pastes of Ca(OH)2 could potentially be beneficial when using interappointment intracanal medications because of their ability to kill bacteria in short- and long-term exposure.


High-dose chemotherapy for the treatment of breast and ovarian cancer.
Breast cancer is currently the primary indication for high-dose chemotherapy with autologous hematopoietic progenitor cell support. Recent advances include the first randomized trial comparing high-dose chemotherapy with conventional-dose chemotherapy in patients with metastatic disease, new and improved methods for detection of tumor cells in the autologous graft, new high-dose chemotherapy regimens, new trials exploring multicycle high-dose chemotherapy, and the development of prognostic factors that may predict the outcome of patients who receive this treatment. In patients with ovarian cancer, a recently activated intergroup randomized study of high-dose chemotherapy compared with conventional dose chemotherapy should help clarify the role of high-dose chemotherapy for the treatment of this disease.


Experimental and Computational Investigation of the Aerobic Oxidation of a Late Transition Metal-Hydride.
The rational development of homogeneous catalytic systems for selective aerobic oxidations of organics has been hampered by the limited available knowledge of how oxygen reacts with important organometallic intermediates. Recently, several mechanisms for oxygen insertion into late transition metal-hydride bonds have been described. Contributing to this nascent understanding of how oxygen reacts with metal-hydrides, a detailed mechanistic study of the reaction of oxygen with the IrIII hydride complex (dmPhebox)Ir(OAc)(H) (1) in the presence of acetic acid, which proceeds to form the IrIII complex (dmPhebox)Ir(OAc)2(OH2) (2), is described. The evidence supports a multifaceted mechanism wherein a small amount of an initially formed metal hydroperoxide proceeds to generate a metal-oxyl species that then initiates a radical chain reaction to rapidly convert the remaining IrIII-H. Insight into the initiation step was gained through kinetic and mechanistic studies of the radical chain inhibition by BHT (butylated hydroxytoluene). Computational studies were employed to contribute to a further understanding of initiation and propagation in this system.


Hand function assessment in patients receiving haemodialysis.
To assess the usefulness of Duruöz's Hand Index (DHI) in patients undergoing haemodialysis. Patients receiving haemodialysis for more than 2 months were recruited randomly. Demographic, clinical and functional characteristics of patients were evaluated. Functional assessment was performed with DHI, Hand Functional Index (HFI), Health Assessment Questionnaire (HAQ), Purdue Pegboard, grip strength and 3 kinds of pinch strengths. DHI was correlated (Spearman's) with the other functional parameters in assessing the convergent validity and with non-functional parameters in assessing the divergent validity. Sixty patients with a mean age of 50.05 were recruited. The average duration of haemodialysis was 55.02 months. DHI is significantly correlated with HAQ, HFI, Purdue Pegboard scores, grip strength and 3 types of pinch strengths while no significant correlation was found with non-functional parameters. DHI is a practical scale which is efficient in assessing accurately the functional disability of the hand in patients receiving haemodialysis.


Rapid infusion of streptokinase standard dose in acute myocardial infarction is followed by a higher rate of coronary reperfusion than standard protocol.
There are several opinions asserting that the accelerated t-PA is more efficient than the standard protocol of streptokinase (SK) administration in acute myocardial infarction (AMI). One hundred patients admitted within the first 6 hrs after the onset of the symptoms revealing AMI were divided in two subgroups, as follows: subgroup A (50 patients) in whom a dose of 1.5 M.U. SK was infused in 20 min (accelerated protocol) and subgroup B (50 patients) in whom the same dose was infused in 60 min (standard protocol). In order to assess the efficiency of thrombolytic therapy (TT), we used three noninvasive criteria: the rapid resolution of the chest pain, the rapid decreasing of the ST segment elevation by more than 50% from the initial value, and the rapid increasing of enzymes revealing necrosis. Using the above-mentioned criteria, we considered that coronary reperfusion appeared in 40 patients from subgroup A (80%) and in 29 patients from subgroup B (58%). The speed of coronary reperfusion was 40 +/- 26 min in patients with accelerated SK and this time was significantly shorter than the time of 60 +/- 24 min registered in the control group. No major hemorrhagic events appeared in both subgroups. Although hypotension appeared more frequently in subgroup A, this minor complication was well supported by our patients. The rapid infusion of the standard dose of SK was followed by a higher rate and speed of coronary reperfusion as compared to the standard protocol.


Association Of State Policies With Medicaid Disenrollment Among Low-Income Medicare Beneficiaries.
For some low-income Medicare beneficiaries, Medicaid provides financial protection against Medicare's out-of-pocket costs, but many Medicare beneficiaries who qualify for Medicaid are not continuously enrolled. We examined Medicaid disenrollment among fee-for-service Medicare beneficiaries and the relationship between disenrollment and state policies. In the period 2012-16, 18.2 percent of Medicare beneficiaries who received full or partial Medicaid disenrolled for reasons other than death. More than 50 percent of Medicare beneficiaries who remained without Medicaid one year after disenrolling continued to receive low-income subsidies for Medicare Part D coverage with eligibility requirements similar to those of Medicaid. Among Medicare beneficiaries with continuous Part D subsidies, the rate of Medicaid disenrollment was 24 percent lower in states that automatically enrolled recipients of the federal Supplemental Security Income program in full Medicaid, 33 percent lower in states with more generous provider payment policies, and 37 percent lower in states with less restrictive asset limits for partial Medicaid. Policies that make it easier for people to maintain Medicaid eligibility and that enhance access to care in Medicaid via higher provider reimbursements may reduce disenrollment.


An integrated risk predictor for pulmonary nodules.
It is estimated that over 1.5 million lung nodules are detected annually in the United States. Most of these are benign but frequently undergo invasive and costly procedures to rule out malignancy. A risk predictor that can accurately differentiate benign and malignant lung nodules could be used to more efficiently route benign lung nodules to non-invasive observation by CT surveillance and route malignant lung nodules to invasive procedures. The majority of risk predictors developed to date are based exclusively on clinical risk factors, imaging technology or molecular markers. Assessed here are the relative performances of previously reported clinical risk factors and proteomic molecular markers for assessing cancer risk in lung nodules. From this analysis an integrated model incorporating clinical risk factors and proteomic molecular markers is developed and its performance assessed on a subset of 222 lung nodules, between 8mm and 20mm in diameter, collected in a previously reported prospective study. In this analysis it is found that the molecular marker is most predictive. However, the integration of clinical and molecular markers is superior to both clinical and molecular markers separately. Registered at ClinicalTrials.gov (NCT01752101).


Posttranslationally modified proteins as mediators of sustained intestinal inflammation.
Oxidative and carbonyl stress leads to generation of N(epsilon)-carboxymethyllysine-modified proteins (CML-mps), which are known to bind the receptor for advanced glycation end products (RAGE) and induce nuclear factor (NF)-kappaB-dependent proinflammatory gene expression. To determine the impact of CML-mps in vivo, RAGE-dependent sustained NF-kappaB activation was studied in resection gut specimens from patients with inflammatory bowel disease. Inflamed gut biopsy tissue demonstrated a significant up-regulation of RAGE and increased NF-kappaB activation. Protein extracts from the inflamed zones, but not from noninflamed resection borders, caused perpetuated NF-kappaB activation in cultured endothelial cells, which was mediated by CML-mps including CML-modified S100 proteins. The resulting NF-kappaB activation, lasting 5 days, was primarily inhibited by either depletion of CML-mps or by the addition of sRAGE, p44/42 and p38 MAPKinase-specific inhibitors. Consistently, CML-mps isolated from inflamed gut areas and rectally applied into mice caused NF-kappaB activation, increased proinflammatory gene expression, and histologically detectable inflammation in wild-type mice, but not in RAGE-/- mice. A comparable up-regulation of NF-kappaB and inflammation on rectal application of CML-mps was observed in IL-10-/- mice. Thus, CML-mps generated in inflammatory lesions have the capacity to elicit a RAGE-dependent intestinal inflammatory response.


Effects of the sample preparation temperature on the nanostructure of compression moulded ultrahigh molecular weight polyethylene.
In this study, the effects of the sample sectioning temperature on the surface nanostructure and mechanical response of compression moulded ultrahigh molecular weight polyethylene (UHMWPE) at a nanometer scale (nanomechanical properties) have been characterized. The primary focus of this work was to determine if the sample sectioning temperature significantly changed the nanostructure of UHMWPE, while the secondary focus was to characterize the effect on the mechanical response due to the changes in the sectioned surface nanostructure. The goals of this study were: (a) to investigate the potential possibility of creating surface artefacts by the sample preparation technique by sectioning at different temperatures relative to the published range of glass transition temperatures, Tg, for PE (-12, -80 and -25 degrees C); (b) to determine the possibility of molecular orientation induced by plastic deformation of the UHMWPE sample during the process of sample preparation; (c) to measure the relative difference in nanomechanical properties owing to evolution of different nanostructures as a function of sample sectioning temperature. Field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM) and nanoindentation were used to demonstrate that the sectioning temperature caused a change in nanostructure of the compression moulded UHMWPE sectioned surface, explaining the change in mechanical response to indentation at a nanoscale. In this study, it was demonstrated that significant plastic deformation occurs when a shear stress is applied between the glass or diamond blade and the UHMWPE during sample preparation under ambient conditions at a temperature of 22 degrees C. These results also suggest that an optimum sample sectioning temperature should definitely be below the measured Tg of the polymer.


Utility of major leukocyte subpopulations for monitoring secondary cytomegalovirus infections in renal-allograft recipients by PCR.
The feasibility of the major peripheral blood leukocyte (PBL) subsets for use in qualitative and quantitative PCR to monitor secondary cytomegalovirus (CMV) infection and ganciclovir therapy was assessed with 188 blood samples derived from 40 CMV immunoglobulin G-positive renal-allograft recipients. In pp65 antigen-positive patients all leukocyte fractions, but only 79.5% of plasma preparations, were PCR positive. In pp65 antigen-negative samples from patients after antiviral treatment only 7.3% of polymorphonuclear cell (PMNL) samples, but 81.8% of peripheral blood mononuclear cells (PBMC), and 10.9% of plasma samples remained PCR positive. Similarly, in patients with latent infections only 5.0% of PMNL, but 51.7% of PBMC preparations, and 8.0% of plasma samples were PCR positive. Regarding patients with active CMV infection, CMV DNA copy numbers in PMNL correlated significantly with pp65 antigen-positive cell counts before and after onset of ganciclovir therapy. Significant differences in CMV DNA copy numbers in PMNL and plasma were observed (i) between patients with symptomatic infection and those with asymptomatic infection and (ii) between patients with active infection and those with latent infection. In contrast, PBMC harbored equally low CMV DNA levels both in patients with active infection and those with latent infections, and no decline of CMV DNA load in PBMC was observed during antiviral treatment. We conclude that detection of CMV DNA in PMNL, not in PBMC, is associated with active infections and is more sensitive than detection of CMV DNA in plasma. Negative PCR results for PMNL after antiviral therapy indicate recovery, and fewer unwanted positive results occur compared to PBMC and plasma. Therefore, purified PMNL should be preferred for analysis by qualitative CMV PCR to avoid unwanted positive results. The CMV DNA load in PBMC compared with that in PMNL is negligible during active infection, so mixed PBL are sufficient for use in quantitative PCR.


In situ observation of facet-dependent oxidation of graphene on platinum in an environmental TEM.
We performed a direct observation of a crystal facet-dependent oxidation of graphene layers on platinum nanocrystals at atomic resolution in an environmental transmission electron microscope. Combined with density functional theory calculations, our work provides a novel approach for the dynamical exploration of the facet-dependent reactions at the atomic level.


Acid-Suppressive Drugs and Risk of Fracture in Children and Young Adults: A Meta-Analysis of Observational Studies.
Background: Recent studies have suggested that proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs) may increase the risk of fracture. We performed a meta-analysis to evaluate the risk of fracture with PPIs and H2RAs use in children and young adults. Methods: PubMed, EMBASE database, Cochrane Library, and Web of Science for relevant articles published before May 2021 were searched. We included all the observational studies reporting on the risk of fracture with acid-suppressive drug (PPIs and H2RAs) use in children and young adults. We calculated pooled risk ratios (RRs) for fracture using random-effects models and conducted subgroup analyses. Results: A total of six studies were included in our analysis. Pooled analysis of PPIs use showed significant risk for fracture (RR = 1.23; 95% CI, 1.12-1.34; I 2 = 79.3), but not significant for PPIs combined with H2RAs use (RR = 1.22; 95% CI, 0.94-1.60; I 2 = 44.0%), as well as for H2RAs use alone (RR = 1.08; 95% CI, 0.94-1.24; I 2 = 84.1%). Grouping of studies by region showed a significantly increased fracture risk with PPIs use in North America (RR = 1.24; 95% CI, 1.16-1.32; I 2 =0.0%) than in Europe (RR = 1.23; 95% CI, 1.00-1.52; I 2 = 94.6%) and Asia (RR = 1.10; 95% CI, 0.96-1.25). However, there was no significant association between the H2RAs use and the fracture risk in North America (RR = 1.08; 95% CI, 1.00-1.09; I 2 = 0.0%). Moreover, PPIs use showed an increased risk of fracture in women (RR = 1.13; 95% CI, 1.07-1.19; I 2 = 0.0%), whereas there was no significant association between the PPIs use and the risk of fracture in men (RR = 0.93; 95% CI, 0.66-1.31; I 2 = 0.0%). Conclusion: PPIs use alone could increase the risk of fracture in children and young adults, but not for PPIs combined with H2RAs use or H2RAs use alone. Clinicians should exercise caution when prescribing PPIs for patients.


Taxanes Versus Androgen Receptor Therapy as Second-Line Treatment for Castrate-Resistant Metastatic Prostate Cancer After First-Line Androgen Receptor Therapy.
The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer (mCRPC) is still debated. This study aimed to compare activity of taxanes (TAX) versus that of androgen-receptor therapy (ART) in men with mCRPC treated with first-line ART. This retrospective study included all consecutive chemo-naive mCRPC patients who have received first-line ART treatment. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with second-line ART or TAX. Overall, 175 patients treated with first-line enzalutamide (ENZA, n = 75) or abiraterone (ABI, n = 100) were evaluated. Among them, 69 (39%) and 30 (17%) patients received second-line TAX and ART, respectively, while 76 (43%) patients did not receive further treatment. From the start of first-line therapy, the median PFS and OS were 13 months (95% CI: 11-15) and 34 months (95% CI: 29-39), respectively, without any significant difference between ENZA and ABI. From the start of second-line therapy, the median PFS and OS were 6 months (95% CI: 5-7) and 18 months (95% CI: 14-21), respectively. Compared with ART, docetaxel was associated with significantly higher prostate-specific antigen (PSA, ≥ 50%) (29% vs. 0%, P < .001) and radiological responses (21% vs. 0%, P < .001). PFS was longer in TAX than in ART (6.7 months vs. 4 months, HR: 0.63, 95% CI: 0.41-0.96, P = .034), but there was no significant difference in OS (19 months vs. 12 months, P = .1). After propensity score adjustment, PFS (P = .2) and OS (P = .1) were similar between second-line TAX and ART. In the second-line setting, TAX provides higher PSA and radiological responses than does ART for mCRPC patients who received first-line ART, but the PFS and OS are similar. This study provides new elements to help deciding the best treatment sequence.


Solid phase purification and SSCP analysis of amplified genomic DNA by capillary electrophoresis.
Detection and identification of point mutations in genomic DNA has proven increasingly important in biomedical research. A variety of methods for the analysis of single base substitutions have been proposed among which Single Strand Conformational Polymorphism (SSCP) quickly gained success due to its simplicity. In this work we present an analytical on-line tool which combines the ease of solid phase purification of amplified genomic DNA, the simplicity of SSCP and the significant potential advantages offered by capillary electrophoresis (CE).


Anisotropic shock responses of nanoporous Al by molecular dynamics simulations.
Mechanical responses of nanoporous aluminum samples under shock in different crystallographic orientations (<100>, <111>, <110>, <112> and <130>) are investigated by molecular dynamics simulations. The shape evolution of void during collapse is found to have no relationship with the shock orientation. Void collapse rate and dislocation activities at the void surface are found to strongly dependent on the shock orientation. For a relatively weaker shock, void collapses fastest when shocked along the <100> orientation; while for a relatively stronger shock, void collapses fastest in the <110> orientation. The dislocation nucleation position is strongly depended on the impacting crystallographic orientation. A theory based on resolved shear stress is used to explain which slip planes the earliest-appearing dislocations prefer to nucleate on under different shock orientations.


Charge separation in the aerodynamic breakup of micrometer-sized water droplets.
Charged water droplets generated by electrospray, sonic spray, and a vibrating orifice aerosol generator (VOAG) have been studied by digital macrophotography and image charge detection mass spectrometry. Image charge detection mass spectrometry provides information on the droplet size, charge, and velocity after transmission through a capillary interface. The digital images provide the droplet size distribution before they enter the capillary. Droplets with 10-100 microm radii generated by sonic spray and VOAG are reduced to 2-3 microm radii by transmission through the capillary interface. The droplets from sonic spray and VOAG are much more highly charged than expected for random charging, and positive droplets are much more prevalent than negative. For positive mode electrospray, >99% of the detected droplets carry a positive charge, whereas for negative mode electrospray, <30% of the detected droplets carry a negative charge (i.e., >70% carry a positive charge). These observation can all be accounted for by the aerodynamic breakup of the droplets in the capillary interface. This breakup reduces the droplets to a terminal size at which point further breakup does not occur. Charge separation during droplet breakup is responsible for the relatively high charges on the sonic spray and VOAG droplets and for the preference for positively charged droplets. The charge separation can be explained using the bag mechanism for droplet breakup and the electrical bilayer at the surface of water.


Upregulation of TLR4 via PKC activation contributes to impaired wound healing in high-glucose-treated kidney proximal tubular cells.
Acute kidney injury (AKI) leads to a worse prognosis in diabetic patients compared with prognoses in non-diabetic patients, but whether and how diabetes affects kidney repair after AKI remains unknown. Here, we used scratch-wound healing and transwell migration models to examine whether and how wound healing is affected by high glucose levels in cultured kidney proximal tubular cells (RPTC). The results show that scratch-wound healing and transwell migration were significantly slower in high-glucose-treated kidney tubular cells (30 mM glucose) than in low-glucose-treated cells (5.5 mM). Toll-like receptor 4 (TLR4), MyD88, phospho-protein kinase C (PKC), phospho-p38 MAPK and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were upregulated after high glucose treatments. Staurosporine, a selective PKC inhibitor, inhibited TLR4, MyD88 and p-p38 upregulation in the high-glucose-treated cells, indicating the involvement of PKC in high-glucose-induced TLR4 upregulation. The pharmacological inhibition of TLR4 or shRNA-mediated TLR4 knockdown improved wound healing and transwell migration in high-glucose-treated RPTC. In contrast, the overexpression of TLR4 in low-glucose-treated RPTC suppressed wound healing, mimicking the effects of high glucose levels. These results suggest that the upregulation of TLR4 expression via PKC activation contributes to defective wound healing in high-glucose-treated kidney tubular cells.


'They say God punishes people with HIV': experiences of stigma and discrimination among adults with HIV in Dili, Timor-Leste.
Little is known about the experiences of people with HIV in the small island nation of Timor-Leste. This study explored the HIV-related stigma experiences of adults aged between 18 and 40 living with HIV in Dili, Timor-Leste. Participants were interviewed on topics related to living with HIV, both as key informants describing the experience of others with HIV known to them, and also with respect to their own personal experiences. Findings suggest that people with HIV in Timor-Leste face stigma and discrimination in various contexts. In this predominantly Catholic country, perceptions of HIV and attitudes towards people with HIV appear to be commonly shaped by religious beliefs. In families and communities, participants encountered gossip, social exclusion and threats of violence. In health settings, participants experienced discrimination from health providers in the form of failing to maintain confidentiality and inappropriate treatment. The impact of stigma was profoundly negative and influenced participants' decision to disclose their status to others. Participants attributed stigma to a lack of information about HIV among the general public. Unless stigma reduction interventions also address the Church's role in shaping perceptions of HIV, education campaigns are unlikely to be effective in reducing HIV-related stigma.


Delayed Presentation of Isolated Adrenocorticotropin Insufficiency after Nivolumab Therapy for Advanced Non-small-cell lung carcinoma (NSCLC).
We describe a 73-year-old man who developed adrenal insufficiency 7 months after completing nivolumab therapy for advanced non-small cell lung cancer. He presented with non-specific symptoms of malaise and fatigue with an insidious 13.6 kilogram weight loss, prompting an evaluation for disease progression, which was negative. Subsequent evaluation revealed isolated adrenocorticotropin insufficiency as the aetiology, attributed to a delayed side effect of nivolumab therapy.


Quantifying the economic benefits of prevention in a healthcare setting with severe financial constraints: the case of hypertension control.
Hypertension significantly contributes to the increased cardiovascular morbidity and mortality, thus leading to rising healthcare costs. The objective of this study was to quantify the clinical and economic benefits of optimal systolic blood pressure (SBP), in a setting under severe financial constraints, as in the case of Greece. Hence, a Markov model projecting 10-year outcomes and costs was adopted, in order to compare two scenarios. The first one depicted the "current setting", where all hypertensives in Greece presented an average SBP of 164 mmHg, while the second scenario namely "optimal SBP control" represented a hypothesis in which the whole population of hypertensives would achieve optimal SBP (i.e. <140 mmHg). Cardiovascular events' occurrence was estimated for four sub-models (according to gender and smoking status). Costs were calculated from the Greek healthcare system's perspective (discounted at a 3% annual rate). Findings showed that compared to the "current setting", universal "optimal SBP control" could, within a 10-year period, reduce the occurrence of non-fatal events and deaths, by 80 and 61 cases/1000 male smokers; 59 and 37 cases/1000 men non-smokers; whereas the respective figures for women were 69 and 57 cases/1000 women smokers; and accordingly, 52 and 28 cases/1000 women non-smokers. Considering health expenditures, they could be reduced by approximately €83 million per year. Therefore, prevention of cardiovascular events through BP control could result in reduced morbidity, thereby in substantial cost savings. Based on clinical and economic outcomes, interventions that promote BP control should be a health policy priority.


Effects of prostaglandin A1 on renal handling of salt and water in congestive heart failure.
Prostaglandin A1 (PGA1) was infused at the rate of 1/microgram/kg/min in 10 patients with decompensated heart failure under conditions of water loading (5 patients) or water deprivation (5 patients). During water loading, PGA1 increased urinary excretion of sodium, potassium, chloride, calcium, and magnesium, as well as free-water clearance. During water deprivation, it increased free-water reabsorption. Gomerular filtration rate was increased slightly by PGA1 only when it was given with an infusion of hypertonic mannitol during water deprivation. This selective action of PGA1, which increased the excretion but not the reabsorption of free water, suggests its use to correct certain hypo-osmolar conditions. The site of action of PGA1 on the kidney seems to be in the tubules and mainly in the proximal tubules. These findings might be important in the understanding of the role of renal prostaglandins.


Dual effect of the presence of fruits on leaf gas exchange and water relations of olive trees.
The presence of fruits provokes significant modifications in plant water relations and leaf gas exchange. The underlying processes driving these modifications are still uncertain and likely depend on the water deficit level. Our objective was to explain and track the modification of leaf-water relations by the presence of fruits and water deficit. With this aim, net photosynthesis rate (AN), stomatal conductance (gs), leaf osmotic potential (Ψπ), leaf soluble sugars and daily changes in a variable related to leaf turgor (leaf patch pressure) were measured in olive trees with and without fruits at the same time, under well-watered (WW) and water stress (WS) conditions. Leaf gas exchange was increased by the presence of fruits, this effect being observed mainly in WW trees, likely because under severe water stress, the dominant process is the response of the plant to the water stress and the presence of fruits has less impact on the leaf gas exchange. Ψπ was also higher for WW trees with fruits than for WW trees without fruits. Moreover, leaves from trees without fruits presented higher concentrations of soluble sugars and starch than leaves from trees with fruits for both WW and WS, these differences matching those found in Ψπ. Thus, the sugar accumulation would have had a dual effect because on one hand, it decreased Ψπ, and on the other hand, it would have downregulated AN, and finally gs in WW trees. Interestingly, the modification of Ψπ by the presence of fruits affected turgor in WW trees, the change in which can be identified with leaf turgor sensors. We conclude that plant water relationships and leaf gas exchange are modified by the presence of fruits through their effect on the export of sugars from leaves to fruits. The possibility of automatically identifying the onset of sugar demand by the fruit through the use of sensors, in addition to the water stress produced by soil water deficit and atmosphere drought, could be of great help for fruit orchard management in the future.


[Application of an algorithm for the validation of congenital anomaly cases using hospital discharge records].
to evaluate and validate the adoption of an algorithm for the identification of cases of congenital anomalies (CAs) to improve the performance of the Congenital Malformations Registry of Sicily Region (Southern Italy). an algorithm was used to identify congenital anomalies on a sample of hospital discharge records (SDO) with ICD-9-CM code between 740-759 on any of the diagnoses within the first year of life, together with a sample of healthy births equal to 5% of total births for the same period. The identified cases were evaluated through the clinical record analysis. the analysed sample was composed of 4,271 cases identified between June 2013 and December 2014 along with 3,993 SDO without any code of MC (5% of the total volume of births in the same period). positive predictive value (VPP) and negative predictive value (VPN) were computed by means of the comparison between the algorithm outcomes and the clinical record verification. 4,271 potentially malformed records involving 3,381 subjects born in the Sicilian territory have been identified. Among the hospital discharge records that it was possible to verify, the application of the algorithm led to the exclusion of 924 cases: of these, 62 proved to be false negatives (VPN: 93.3). The valid cases were 1,179, while the cases to be evaluated 617: the comparison between algorithm and clinical record analysis led to a VPP of 91.7 and 72.1, respectively, for valid and to be evaluated. the tested algorithm proved to be a useful tool for identifying SDO potentially related to congenital anomalies. In the overall sample, the algorithm provided an outcome consistent with the clinical record assessment in 87.4% (2,379) of cases.


[Fasciitis with eosinophilia: Shulman syndrome. Report of a case and review of the literature].
A twelve year-old boy who developed, after a period of strenuous physical work, an illness characterized by thickened skin over his right thigh and hemiabdomen, flexion contractures in right wrist and elbow and in right metacarpophalangeal joints without Raynaud's phenomenon or other visceral symptoms is presented. Pertinent laboratory studies showed hypereosinophilia and hypergammaglobulinemia. Deep-fascia biopsy showed typical findings of fasciitis with eosinophilia. Prednisone therapy resulted in sustained improvement. Periarticular osteopenia of the right hand and mast cell infiltration in fascial biopsy are remarkable features. Authors stress striking differences between fasciitis with eosinophilia or Shulman's syndrome and scleroderma. Clinical picture, laboratory changes, typical histology and a usually rapid response to corticosteroids, as well as some autoimmune diseases possibly associated, suggest a different disease and an immunological pathogenesis. From literature review authors conclude that cases of Shulman's syndrome reported in children are very limited and that this disease should by ruled out in every child with thickened skin changes and articular flexion contractures.


Simultaneous Quantification of Gymnemic Acid as Gymnemagenin and Charantin as β-Sitosterol Using Validated HPTLC Densitometric Method.
Gymnemic acid and charantin are well-established antidiabetic phytosterols found in Gymnema sylvestre and Momordica charantia, respectively. The fact that these plants are often used together in antidiabetic poly-herbal formulations lured us to develop an HPTLC densitometric method for the simultaneous quantification of their bioactive compounds. Indirect estimation of gymnemic acid as gymnemagenin and charantin as β-sitosterol after hydrolysis has been proposed. Aluminum-backed silica gel 60 F254 plates (20 × 10 cm) were used as stationary phase and toluene-ethyl acetate-methanol-formic acid (60 : 20 : 15 : 5, v/v) as mobile phase. Developed chromatogram was scanned at 550 nm after derivatization with modified vanillin-sulfuric acid reagent. Regression analysis of the calibration data showed an excellent linear relationship between peak area versus concentration of the analytes. Linearity was found to be in the range of 500-2,500 and 100-500 ng/band for gymnemagenin and β-sitosterol, respectively. The suitability of the developed HPTLC method for simultaneous estimation of analytes was established by validating it as per the ICH guidelines. The limits of detection and quantification for gymnemagenin were found to be ≈60 and ≈190 ng/band, and those for β-sitosterol ≈30 and ≈90 ng/band, respectively. The developed method was found to be linear (r(2) = 0.9987 and 0.9943), precise (relative standard deviation <1.5 and <2% for intra- and interday precision) and accurate (mean recovery ranged between 98.43-101.44 and 98.68-100.20%) for gymnemagenin and β-sitosterol, respectively. The proposed method was also found specific and robust for quantification of both the analytes and was successfully applied to herbal drugs and in-house herbal formulation without any interference.


Hippocampal CA1 local field potential oscillations induced by olfactory cue of liked food.
Eating motivation is induced not only by negative energy balance but also food related cues. However, neural processing for acquisition of learned food preference remains to be established. This study aimed to identify hippocampal neural signaling in response to olfactory cue (chocolate scent) after completion of repetitive chocolate sessions. Male Swiss albino mice implanted with intracranial electrode into the hippocampus were used for local field potential (LFP) recording. Animals were given chocolate sessions (a piece of 2g chocolate per each mouse to eat on day 1, 3, 5 and 7). Hippocampal CA1 LFP signals and exploratory behavior of animals receiving chocolate scent were analyzed before and after chocolate sessions. The experiment was performed in a place preference-like apparatus with the zones of normal food pellet and chocolate (both kept in a small perforated cup for smell dispersion) at the opposite ends. Following chocolate sessions, time spent in a chocolate zone and CA1 LFP patterns were analyzed in comparison to control levels. Two-way ANOVA revealed significant increase in time spent seeking for chocolate. Frequency analysis of LFP power spectra revealed significant increases in delta and theta powers. Phase-amplitude analysis showed significant increase in maximal modulation index and decrease in frequency for phase of theta-high gamma coupling. Taken together, neural signaling in the hippocampus was sensitive to chocolate olfactory cue that might underlie learning process in response to repeated chocolate consumptions that primed intense food approaching behavior. Ultimately, these LFP patterns might reflect motivation to eat and predict feeding probability.


Functional outcome after shoulder arthroplasty for primary osteoarthritis: a multicenter study.
Shoulder arthroplasty outcomes have been reported in many case series. Typically, these series have followed either a single prosthesis used to treat a variety of arthritic disorders of the shoulder or experience in a single institution. In contrast, this report of a prospective study summarizes the experience of several surgeons with a single prosthetic design for treatment of primary osteoarthritis of the shoulder. A prospective, multicenter clinical outcome study evaluated 176 shoulders in 160 patients with primary osteoarthritis. This study evaluated a single prosthetic design (Global Shoulder) used by 19 contributing surgeons. Enrollment included 133 total shoulder replacements and 43 humeral head replacements (hemiarthroplasty) in 98 men and 62 women. Neither age nor sex affected whether hemiarthroplasty or total shoulder arthroplasty was performed. Patients with full-thickness cuff tears preferentially had hemiarthroplasty. The decision to perform total shoulder arthroplasty or hemiarthroplasty was based on the surgeon's preference. There were significant improvements (P <.001) in all evaluated and self-assessed outcome parameters from the preoperative baseline for both total shoulder arthroplasty and hemiarthroplasty. The results confirm that prosthetic arthroplasty leads to dramatic improvement in pain, function, and patient satisfaction. Intraoperative complications occurred in 5.4% of cases, and postoperative complications occurred in 7.8%. The most common intraoperative complications were intraoperative fractures, occurring in 9 cases. The most common postoperative complications were glenoid component loosening and humeral head subluxation. Almost all cases of humeral head instability were associated with rotator cuff tears or glenoid component loosening (or both). Seven shoulders underwent 9 additional surgeries during the 5-year study period. Thirteen shoulders in 11 patients were lost as a result of death unrelated to the procedure; 2 shoulders in 1 patient were lost within 3 days/3 months after the bilateral replacements as a result of death from pulmonary embolism. Nine percent of the shoulders (16/176) had full-thickness rotator cuff tears. Eight of the 16 shoulders with full-thickness supraspinatus cuff tears had hemiarthroplasty. All of these tears were isolated to the supraspinatus tendon, and all were repairable. There were no differences in postoperative pain, function, American Shoulder and Elbow Surgeons scores, or range of motion. There were no differences between total shoulder arthroplasty and hemiarthroplasty in those patients with a reparable rotator cuff tear. Total shoulder arthroplasty and hemiarthroplasty for treatment of primary osteoarthritis result in good or excellent pain relief, improvement in function, and patient satisfaction in 95% of cases. Avoiding intraoperative humeral shaft fractures through use of an uncemented, canal-filling prosthetic stem requires careful attention to reaming and component sizing. Postoperative humeral head subluxation is often associated with other factors including rotator cuff tears or glenoid component loosening.


Dental assistants of Indiana: comments from the front lines.
During the summer of 1996, a random sample survey of 1500 Indiana dental assistants licensed in radiology by the Indiana State Board of Health was conducted. Surveys were mailed to participants, and follow-up postcard reminders were sent out a few weeks later. There were 569 surveys returned, representing a 38 percent return rate. Numerical data were coded and entered in an SPSS program, and written comments were analyzed independently by the co-authors. Major demographic data and many categories of open-ended comments are summarized and analyzed in this paper. Results from this survey underscore the necessity for wages being improved in the dental assisting field. Comments underscore the fact that many dental assistants are not satisfied with their jobs and therefore may not be committed to either their careers or their employers. Office climate and relationships with the dentist are also described as being very important.


Induction of anti-thymocyte/T lymphocyte antibodies in mice injected with lipopolysaccharides from periodontopathic bacteria.
We examined the levels of anti-thymocyte/T lymphocyte autoantibody (ATA) in the serum of mice injected intraperitoneally with lipopolysaccharides (LPS) from periodontopathic bacteria; Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Capnocytophaga ochracea, and non-oral Escherichia coli. All of the LPS induced IgM-ATA. Among these, LPS from C. ochracea induced the highest level of IgM-ATA, whereas that of P. gingivalis induced the lowest. The peritoneal T lymphocytes of mice injected with LPS were bound by IgM-ATA. Peritoneal B-1 (CD5+B) cells stimulated by each LPS produced much more IgM-ATA than splenic B-2 (CD5-B) cells, suggesting that B-1 cells might be responsible for the production of these antibodies. Serum of mice injected with C. ochracea and F. nucleatum LPS showed cytotoxicity against thymocytes in the presence of rabbit complements. Binding and cytotoxicity were confirmed by IgM purified from serum of the mice injected with C. ochracea LPS. Furthermore, serum of mice treated with C. ochracea, F. nucleatum or A. actinomycetemcomitans LPS inhibited the proliferation of thymocytes. However, purified IgM from the serum of mice treated with C. ochracea LPS failed to produce the same inhibition. Our results suggest that LPS from certain species of periodontopathic bacteria can induce IgM-ATA in the serum and these antibodies may modulate the local immune network in periodontal tissues.


The CD300e molecule in mice is an immune-activating receptor.
CD300 molecules (CD300s) belong to paired activating and inhibitory receptor families, which mediate immune responses. Human CD300e (hCD300e) is expressed in monocytes and myeloid dendritic cells and transmits an immune-activating signal by interacting with DNAX-activating protein 12 (DAP12). However, the CD300e ortholog in mice (mCD300e) is poorly characterized. Here, we found that mCD300e is also an immune-activating receptor. We found that mCD300e engagement triggers cytokine production in mCD300e-transduced bone marrow-derived mast cells (BMMCs). Loss of DAP12 and another signaling protein, FcRγ, did not affect surface expression of transduced mCD300e, but abrogated mCD300e-mediated cytokine production in the BMMCs. Co-immunoprecipitation experiments revealed that mCD300e physically interacts with both FcRγ and DAP12, suggesting that mCD300e delivers an activating signal via these two proteins. Binding and reporter assays with the mCD300e extracellular domain identified sphingomyelin as a ligand of both mCD300e and hCD300e. Notably, the binding of sphingomyelin to mCD300e stimulated cytokine production in the transduced BMMCs in an FcRγ- and DAP12-dependent manner. Flow cytometric analysis with an mCD300e-specific Ab disclosed that mCD300e expression is highly restricted to CD115+Ly-6Clow/int peripheral blood monocytes, corresponding to CD14dim/+CD16+ human nonclassical and intermediate monocytes. Loss of FcRγ or DAP12 lowered the surface expression of endogenous mCD300e in the CD115+Ly-6Clow/int monocytes. Stimulation with sphingomyelin failed to activate the CD115+Ly-6Clow/int mouse monocytes, but induced hCD300e-mediated cytokine production in the CD14dimCD16+ human monocytes. Taken together, these observations indicate that mCD300e recognizes sphingomyelin and thereby regulates nonclassical and intermediate monocyte functions through FcRγ and DAP12.


Single-walled carbon nanotube thin film emitter-detector integrated optoelectronic device.
We use the suspended single-walled carbon nanotube (SWNT) thin film technology to assemble the first prototype of an integrated optoelectronic SWNT device, a SWNT optocoupler in which a SWNT emitter and a SWNT detector couple two electrical circuits by the transmission of a signal through the optical channel. Our experiments show that the integrated SWNT emitter/SWNT detector is an ideal couple in which the broadband wavelength character of the emission matches the broadband detection capabilities.


BES1 accumulates in the nucleus in response to brassinosteroids to regulate gene expression and promote stem elongation.
Plant steroid hormones, known as brassinosteroids (BRs), signal through a plasma membrane localized receptor kinase BRI1. We identified bes1, a semidominant suppressor of bri1, which exhibits constitutive BR response phenotypes including long and bending petioles, curly leaves, accelerated senescence, and constitutive expression of BR-response genes. BES1 accumulates in the nucleus in response to BRs. BES1 is phosphorylated and appears to be destabilized by the glycogen synthase kinase-3 (GSK-3) BIN2, a negative regulator of the BR pathway. These results establish a signaling cascade for BRs with similarities to the Wnt pathway, in which signaling through cell surface receptors leads to inactivation of a GSK-3 allowing accumulation of a nuclear protein that regulates target gene expression.


Composition and antibiotic resistance profile of microcosm dental plaques before and after exposure to tetracycline.
The aim of this study was to investigate the effects of tetracycline administration on the viability and antibiotic resistance profiles of microcosm dental plaques. A constant depth film fermenter was used to generate multi-species biofilms, which were grown for 216 h before tetracycline was added. The composition of the microcosm plaques was determined by viable counting on selective and non-selective media. The prevalence of antibiotic-resistant organisms was determined on antibiotic-containing media. Before administration of tetracycline, the biofilms had a total viable anaerobic count of 7 x 10(7) cfu per biofilm. They contained 7% lactobacilli, 19% streptococci and 2% Actinomyces spp. Immediately after pulsing with tetracycline, the composition of the biofilms changed and they consisted of 30% lactobacilli, 1.5% streptococci and 3% Actinomyces spp., with a total anaerobic count of 1 x 10(7) cfu per biofilm. The pre-valence and composition of the antibiotic-resistant microflora changed dramatically after the addition of tetracycline, with the proportion of the microflora displaying resistance to tetracycline increasing from 6% to 45%. Corresponding changes in the proportions of the microflora displaying resistance to other antibiotics were as follows: 5-28% for erythromycin, 1-5% for vancomycin and 0.4-3% for ampicillin. The results of this study have shown that the addition of tetracycline to microcosm dental plaques alters their composition and enriches for bacteria resistant to tetracycline and other unrelated agents.


Effect of an intramuscular injection of human leukocyte interferon on blood leukocyte counts and proportions of lymphocytes forming E, EA and EAC rosettes.
Following an intramuscular injection of human leukocyte interferon blood leukocyte counts decreased in most patients as tested 24 h after the injection. This decrease comprised lymphocytes, monocytes and granulocytes, 24 h after interferon injection, the proportion of lymphocytes forming E rosettes was incresed in most patients, whereas the proportion of lymphocytes forming EA and EAC rosettes was not significantly changed.


miR-422a inhibits osteosarcoma proliferation by targeting BCL2L2 and KRAS.
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. However, the underlying mechanism of osteosarcoma carcinogenesis and progression remains unknown. In the present study, we evaluated the expression profile of miRNAs in osteosarcoma tissues and the adjacent normal tissues. We found that the expression of miR-422a was down-regulated in osteosarcoma tissues and cell lines. In addition, we observed significantly elevated levels of repressive H3K9me3 and H3K27me3 and decreased active H3K4me3 on the promote region of miR-422a in osteosarcoma cells and clinical samples. Furthermore, up-regulation of miR-422a exhibited both in vitro and in vivo anti-tumor effects by inhibiting osteosarcoma cell growth and inducing apoptosis and cell cycle arrest. We also found that miR-422a targeted BCL2L2 and KRAS and negatively regulated their protein expression. Furthermore, restoration of miR-422a and knockdown of BCL2L2 and KRAS promoted apoptosis and induce cell cycle arrest in osteosarcoma cells. Taken together, the present study demonstrates that miR-422a may serve as a tumor suppressor in osteosarcoma via inhibiting BCL2L2 and KRAS translation both in vitro and in vivo Therefore, miR-422a could be developed as a novel therapeutic target in osteosarcoma.


Mono- and sesquiterpene release from tomato (Solanum lycopersicum) leaves upon mild and severe heat stress and through recovery: from gene expression to emission responses.
Plants frequently experience heat ramps of various severities, but how and to what degree plant metabolic activity recovers from mild and severe heat stress is poorly understood. In this study, we exposed the constitutive terpene emitter, Solanum. lycopersicum leaves to mild (37 and 41 °C), moderate (46 °C) and severe (49 °C) heat ramps of 5 min. and monitored foliage photosynthetic activity, lipoxygenase pathway volatile (LOX), and mono- and sesquiterpene emissions and expression of two terpene synthase genes, β-phellandrene synthase and (E)-β-caryophyllene/α-humulene synthase, through a 24 h recovery period upon return to pre-stress conditions. Leaf monoterpene emissions were dominated by β-phellandrene and sesquiterpene emissions by (E)-β-caryophyllene, and thus, these two terpene synthase genes were representative for the two volatile terpene classes. Photosynthetic characteristics partly recovered under moderate heat stress, and very limited recovery was observed under severe stress. All stress treatments resulted in elicitation of LOX emissions that declined during recovery. Enhanced mono- and sesquiterpene emissions were observed immediately after the heat treatment, but the emissions decreased even to below the control treatment during recovery between 2-10 h, and raised again by 24 h. The expression of β-phellandrene and (E)-β-caryophyllene synthase genes decreased between 2-10 h after heat stress, and recovered to pre-stress level in mild heat stress treatment by 24 h. Overall, this study demonstrates a highly sensitive heat response of terpenoid synthesis that is mainly controlled by gene level responses under mild stress, while severe stress leads to non-recoverable declines in foliage physiological and gene expression activities.


Insulin removal in man: in vivo evidence for a receptor-mediated process.
To evaluate the in vivo participation of insulin receptors in both hepatic and extrahepatic removal of insulin, compartmental kinetic analysis of insulin behavior was performed in a patient with blocked receptors due to endogenous antiinsulin receptor antibodies. Using the standard three-compartment simulation of insulin behavior, the responses to both a 5-U injection of exogenous insulin and a 4.2-U secretion of endogenous insulin subsequent to tolbutamide injection were examined. In response to both exogenous and endogenous insulin, hepatic removal of insulin was reduced to less than 18% of the insulin exposure (normal, 40-60%). The metabolic clearance of insulin was reduced from the normal level of 520 ml/min to less than 120 ml/min, consistent with a reduction in receptor-mediated removal of insulin from the blood. These studies propose quantitative parameters for insulin receptor function in hepatic and extrahepatic removal of insulin in man.


Hierarchical virtual screening of the dual MMP-2/HDAC-6 inhibitors from natural products based on pharmacophore models and molecular docking.
The dual-target inhibitors tend to improve the response rate in treating tumors, comparing with the single-target inhibitors. Matrix metalloproteinase-2 (MMP-2) and histone deacetylase-6 (HDAC-6) are attractive targets for cancer therapy. In this study, the hierarchical virtual screening of dual MMP-2/HDAC-6 inhibitors from natural products is investigated. The pharmacophore model of MMP-2 inhibitors is built based on ligands, but the pharmacophore model of HDAC-6 inhibitors is built based on the experimental crystal structures of multiple receptor-ligand complexes. The reliability of these two pharmacophore models is validated subsequently. The hierarchical virtual screening, combining these two different pharmacophore models of MMP-2 and HDAC-6 inhibitors with molecular docking, is carried out to identify the dual MMP-2/HDAC-6 inhibitors from a database of natural products. The four potential dual MMP-2/HDAC-6 inhibitors of natural products, STOCK1 N-46177, STOCK1 N-52245, STOCK1 N-55477, and STOCK1 N-69706, are found. The studies of binding modes show that the screened four natural products can simultaneously well bind with the MMP-2 and HDAC-6 active sites by different kinds of interactions, to inhibit the MMP-2 and HDAC-6 activities. In addition, the ADMET properties of screened four natural products are assessed. These found dual MMP-2/HDAC-6 inhibitors of natural products could serve as the lead compounds for designing the new dual MMP-2/HDAC-6 inhibitors having higher biological activities by carrying out structural modifications and optimizations in the future studies.


Eggshell conductance, embryonic growth, hatchability and embryonic mortality of broiler breeder eggs dipped into ascorbic acid solution.
1. Eggs from a broiler breeder flock between 25 and 29 weeks of age were dipped into solutions of various concentrations of ascorbic acid (AA) for up to 2 min, in order to evaluate its effects on eggshell conductance (EC), amniotic fluid pH, albumen height and pH, embryonic weight and hatchability. 2. Three experiments were conducted and the following treatments were used: control, non-dipped (CND); control, water-dipped (CWD); 10 g AA/l (AA1); 20 g AA/l (AA2) and 30 g AA/l (AA3). Measurements of EC before and after dipping were made in experiments 1 and 2 in eggs from hens at 25 and 27 weeks of age, respectively. Albumen height and pH were measured after dipping the eggs in experiment 2. In experiment 3, egg weight loss, embryonic weight and amniotic fluid pH at 14 d of age, hatchability percentage (HP), and embryonic mortality were measured in eggs from hens at 29 weeks of age. 3. AA treatment of eggs and dipping period of time (1, 1.5 and 2 min) increased EC of eggs from hens at 25 and 27 weeks of age. 4. AA3 treatment for 2 min reduced albumen height and increased albumen pH of eggs when compared with the CND treatment in eggs from hens at 27 weeks of age. 5. HP of AA1-treated eggs from hens at 29 weeks of age was higher than that of the CND treatment. AA2 and AA3 treatments of eggs reduced HP and increased the percentage of non-pips when compared with any of the other treatments. 6. AA2 and AA3 treatments of eggs increased egg weight loss when compared with the control treatments (CND and CWD). Dipping treatment did not influence amniotic fluid pH or embryo weight expressed as a percentage of initial egg weight. 7. It is concluded that dipping hatching eggs into AA solution increased EC of eggs. Dipping eggs into 10 g AA/l for a period of 2 min increased HP in eggs from hens at 29 weeks of age, although this was not associated with a significant increase in egg weight loss.


The monoclonal antibody GRC1 produced against human cornea recognizes a common determinant of collagen.
The monoclonal antibody GRC1 was obtained by immunizing BALB/c mice with human cornea. Screening was performed by indirect immunofluorescence in cryostatic sections of several tissues: cornea, skin, placenta, hyaline cartilage, blood vessels, and nerves. GRC1 was seen to recognize fibrillar structures in all of these tissues. The pattern of reaction was interstitial and membranous. On cornea, GRC1 reacts definitely with Bowman's membrane and diffusely with the stroma, while on skin it shows strongly positive reactivity with the papillary dermis and with the basement membrane. It also reacts on hyaline cartilage at the periphery of the condrocytic lacunae. These immunohistologic results suggest that GRC1 recognized human collagen. In order to investigate further the subtype of collagen defined by GRC1, an ELISA was performed with purified collagens of several types: I, II, III, IV, and V. The monoclonal antibody GRC1 defines a common determinant in types III, IV, and V.


Management of non-cognitive symptoms associated with dementia.
Up to 75% of patients with dementia will experience non-cognitive symptoms.1 These often present as psychotic symptoms, behavioural disturbances and changes in mood.1 Such symptoms provide a significant challenge for patients and their carers, and are often difficult to manage. Antipsychotic drugs have been widely used to treat non-cognitive symptoms of dementia. However, in 2004 data emerged linking the use of some antipsychotic drugs with an increased risk of stroke and death in patients with dementia.2 Since then, there has been a national drive to ensure that antipsychotic drugs are used appropriately. In 2007, we reviewed the safety of antipsychotics in people with dementia.3 Here, we provide an update on the evidence for the efficacy and safety of interventions used to manage non-cognitive symptoms of dementia.


Intestinal resistance to cholera toxin in mouse. Antitoxic antibodies and desensitization of adenylate cyclase.
Mice were immunized perorally with cholera toxin (CT), cholera B-subunit (CB), or buffer as control. The response of anti-CT antibodies of the IgG, IgA and IgM class in bile, IgA being predominating, were similar in both immunized groups. The same number of anti-CT containing plasma cells (ACC) were determined in the intestinal lamina propria of CT - as well as of CB-immunized mice 20 days after the last immunization, while ACC at day 4 in the CB group were 50% higher than in the CT group. In contrast to the vigorous antibody response to CT in both groups of immunized mice, only animals immunized with CT displayed resistance to CT-induced intestinal hypersecretion and to CT stimulation of adenylate cyclase. The CB-treated group responded to CT with fluid accumulation and enzyme activation similar to controls. The results suggest that intestinal resistance to CT in mouse is due to desensitization of adenylate cyclase rather than to CT-neutralizing antibodies.


Outcomes of Crowding in Emergency Departments; a Systematic Review.
Emergency Department (ED) crowding is a global public health phenomenon affecting access and quality of care. In this study, we seek to conduct a systematic review concerning the challenges and outcomes of ED crowding. This systematic review utilized original research articles published from 1st January 2007, to 1st January 2019. Relevant articles from the PubMed (MEDLINE), EMBASE, and Google scholar databases were extracted using predesigned keywords. Following the PRISMA guidelines, two reviewers independently evaluated the quality of the studies using Critical Appraisal Skills Programme for cohort studies and qualitative studies, and Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument for studies. Out of the total of 73 articles in the final record, we excluded 15 of them because of poor quality. This systematic review synthesized the reports of 58 original articles. The outcomes of multiple individual patients and healthcare-related challenges are comprehensively assessed. ED crowding affects individual patients, healthcare systems and communities at large. The negative influences of crowding on healthcare service delivery result in delayed service delivery, poor quality care, and inefficiency; all negatively affecting the emergency patients' healthcare outcomes, in turn.


Women commencing anastrozole, letrozole or tamoxifen for early breast cancer: the impact of comorbidity and demographics on initial choice.
Australian clinical guidelines recommend endocrine therapy for all women with hormone-dependent early breast cancer. Guidelines specify tamoxifen as first-line therapy for pre-menopausal women, and tamoxifen or an aromatase inhibitor (AI) for post-menopausal women depending on the risk of recurrence based on tumour characteristics including size. Therapies have different side effect profiles; therefore comorbidity may also influence choice. We examined comorbidity, and the clinical and demographic characteristics of women commencing different therapies. We identified the first dispensing of tamoxifen, anastrozole or letrozole for women diagnosed with invasive breast cancer in the 45 and Up Study from 2004-2009 (N = 1266). Unit-level pharmacy and medical service claims, hospital, Cancer Registry, and self-reported data were linked to determine menopause status at diagnosis, tumour size, age, comorbidities, and change in subsidy restrictions. Chi-square tests and generalised regression models were used to compare the characteristics of women commencing different therapies. Most pre-menopausal women commenced therapy with tamoxifen (91%). Anastrozole was the predominant therapy for post-menopausal women (57%), followed by tamoxifen (28%). Women with osteoporosis were less likely to commence anastrozole compared with tamoxifen (anastrozole RR = 0.7, 95% CI = 0.5-0.9). Women with arthritis were 1.6-times more likely to commence letrozole than anastrozole (95% CI = 1.1-2.1). Tamoxifen was more often initiated in women with tumours >1 cm, who were also ≥75 years. Subsidy restriction changes were associated with substantial increases in the proportion of women commencing AIs (anastrozole RR = 4.3, letrozole RR = 8.3). The findings indicate interplay of comorbidity and therapy choice for women with invasive breast cancer. Most post-menopausal women commenced therapy with anastrozole; however, letrozole and tamoxifen were more often initiated for women with comorbid arthritis and osteoporosis, respectively. Tamoxifen was also more common for women with tumours >1 cm and aged ≥75 years. Subsidy restrictions appear to have strongly influenced therapy choice.


Stem cell biology in thyroid cancer: Insights for novel therapies.
Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.


Mast cells and multiple sclerosis: a light and electron microscopic study of mast cells in multiple sclerosis emphasizing staining procedures.
In the brains of 7 patients with multiple sclerosis, mast cells were observed within the demyelinated plaques, in the border zone of the plaques as well as in seemingly normal white matter. The cells were mostly located in close connection with small vessels. The routine staining with toluidine blue for the demonstration of mast cells is not adequate as compared with staining of similar sections in pinacyanol erythrosine. Mast cells may be a hitherto underestimated contributor to the demyelinating process of multiple sclerosis.


The psychotherapeutic impasse.
A psychotherapeutic impasse can arise when the therapist's treatment goals differ from those of his patient, when the therapy prescribed is inappropriate, there is failure of rapport, or when an antitherapeutic alliance arises. Countertransference, adverse transference reactions, and transference gratification can stalemate therapy. For resolution, one must diagnose the cause of the impasse, and apply the appropriate treatment measure, which may be clarification, confrontation, interpretation, transfer, or some form of splitting the transference. Splitting of the transference is useful in the treatment of severely regressive transference reactions and allows for expression of the hostile feelings which were previously acted out or defended against by regression. Some impasse situations require consultation, ongoing supervision, or therapy for the therapist.


[Hemostatic problems in surgery].
In this study the authors analyse hemostatic problems in surgery, with particular reference to the perioperative management of the patient. They examine the numerous factors giving rise to hemorrhagic and thrombotic complications, namely, the hemostatic technique adopted, the use of drainages, patient risk factors, pharmacological prophylaxis, etc. Prevention of bleeding, however, depends essentially on adequate preparation of the patient at surgery and on the surgeon's skill and experience.


Analysis of loss of heterozygosity for tumor-suppressor genes can accurately classify and predict the clinical behavior of mucinous tumors arising from the appendix.
Pseudomyxoma peritonei is a rare heterogenous clinical syndrome with a variable clinical course. On the basis of the hypothesis that cumulative mutational damage can predict biological aggressiveness, we evaluated the utility of integrated histopathology and molecular analysis for patients with pseudomyxoma peritonei syndrome. Tissue specimens from 23 mucinous appendiceal tumors were analyzed. DNA samples from multiple sites were analyzed for loss of heterozygosity by using a panel of 15 allelic loss microsatellite markers and K-ras-2 point mutational damage. The fractional mutational rate (FMR), determined as the number of mutated markers divided by the total number of informative markers, was calculated by using the six most informative markers and the K-ras-2 gene. Kappa statistics were calculated to test the association between FMR and the histopathologic classification. Our study included 6 female and 17 male patients with a mean age of 53.6 years and a mean survival of 43.9 months. We found an association between tumor loss of heterozygosity markers and histopathologic classification (P < .05). In addition, there was also an association between the FMR and pathological classification as well as between the FMR and survival (P < .05). An FMR less than .25 indicated low-grade disease, an FMR of .25 to .50 indicated intermediate grade, and an FMR greater than .5 indicated a high-grade tumor. Mutational profiling of accumulated allelic loss and point mutational damage correlated strongly with histopathologic definitions of pseudomyxoma peritonei disease and helped to predict the prognosis of these patients. FMR, along with histopathology, offers a comprehensive classification of these rare tumors.


3D images as a field grader training tool for trachomatous trichiasis: A diagnostic accuracy study in Ethiopia.
Trachomatous trichiasis (TT) will continue to develop among those people who have had repeated infections after active trachoma is controlled. Detecting and treating affected individuals will remain necessary for years; a long "tail" of incident cases is anticipated. As the prevalence of TT declines, there will be fewer cases available for training trachoma graders (TG), necessitating alternative methods. Prospective, diagnostic accuracy study assessing sensitivity and specificity of 3D and 2D photography as a tool for training TG to detect TT. Individuals with TT in Ethiopia were examined, and 2D and 3D clinical images taken. Images were independently graded by four graders for presence or absence of trichiasis and compared to field grading. We recruited 153 participants. Clinical assessments and images were available for 306 eyes. Trichiasis was identified in 204 eyes by field grading. Image grading was performed on a selection of 262 eyes (131 with trichiasis). Most eyes with trichiasis had minor trichiasis (94/131). Pooled sensitivity was 88.3% (3D) and 98.0% (2D); pooled specificity was 59.8% (3D) and 26.8% (2D). 3D photo grading was 33.0% more specific than the 2D photo grading (p = 0.0002). The overall Kappa scores were 0.48 (3D) and 0.25 (2D). We trained 26 novice TG in Ethiopia using 3D images. They were tested on a 3D images set and had 71.4% agreement (kappa 0.46), relative to an expert. They were then tested examining 50 people, and had 86.8% agreement (kappa 0.75). We also tested 27 experienced TG on the same cases (86.4% agreement, kappa 0.75). There was no difference in performance between groups (p = 0.76). All participants preferred 3D over 2D images for training. The slightly higher sensitivity of 2D photos comes at considerable cost in specificity. Training with 3D images enabled novice TG to identify cases as well as experienced TG. 3D were preferred to conventional 2D photos for training. Standardized 3D images of TT could be a useful tool for training TG, in settings where there are now few TT cases.


Mesenchymal stem cells overexpressing integrin-linked kinase attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions.
Mesenchymal stem cells (MSCs) transfected by integrin-linked kinase (ILK) transplantation may improve the function and compliance of the post-infarct cardiac ventricle. We investigated the effect of ILK-modified MSC contiditioned medium (ILK-MSC-CM) on the proliferation of cardiac fibroblasts (CFBs) and collagen synthesis in vitro and in vivo. Myocardial infarction (MI)-induced animals received mesenchymal stem cell conditioned medium (MSC-CM), ILK-MSC-CM, or complete medium alone, subepicardially. A group of animals with MI and no other former intervention served as controls. ILK-MSC-CM inhibited CFB proliferation, reduced the gene expression of type I (Col1a1) and type III collagen (Col3a1), tissue inhibitors of metalloproteinase‑1 (TIMP-1) and ‑2 (TIMP-2), α smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF). It also increased the gene expression of matrix metalloproteinase‑2 (MMP‑2) and -9 (MMP‑9), as measured by qRT-PCR. Four weeks after the left anterior descending (LAD) coronary artery ligation, echocardiographic analysis demonstrated preserved cardiac geometry and contractility in the ILK-MSC-CM treated animals. Decreased infarct size and reduced fibrosis were observed in the ILK-MSC-CM group. Overexpression of ILK regulates paracrine actions of MSCs, and ILK-MSC-CM attenuates CFB proliferation and collagen synthesis through paracrine actions in vitro and in vivo.


Podoplanin expression in tumor-free resection margins of oral squamous cell carcinomas: an immunohistochemical and fractal analysis study.
Podoplanin is involved in tumorigenesis and cancer progression in head and neck malignancies and its expression is not restricted to lymphatic vessel endothelium. The aim of this study was to establish podoplanin expression in the tumor-free resection margins of oral squamous cell carcinomas (OSCCs) and to evaluate the geometric complexity of the lymphatic vessels in oral mucosa by utilizing fractal analysis. As concerns the podoplanin expression in noncancerous tissue, forty tumor-free resection margins from OSCCs were investigated utilizing immunohistochemistry for D2-40 antibody and image densitometry analysis. Podoplanin expression was extremely low in basal cells, especially in resection margins of OSCCs developed in the lower lip regions. However, a highly variable D2-40 expression in tumor-free resection margins associated with hyperplastic or dysplastic lesions was identified. Moreover, podoplanin expression also extended to the basal layer of the lower lip skin appendages, the myoepithelial cells of acini and ducts of minor salivary glands, and other structures from the oral cavity. As concerns the study of the density and complexity of oral lymphatic vessels architecture by means of immunohistochemistry (D2-40, CD31 and Ki-67 antibodies) and fractal analysis, we demonstrated that in normal oral mucosa the geometry of the lymphatic vessels was less complex at the level of the lower lip compared to the anterior part of the oral floor mucosa or the tongue. A comparative analysis between the normal and pathological aspects revealed statistically significant differences between the fractal dimension (FD) of the vessels' outline, especially in the tongue. Fractal analysis proved an increasing lymphatic network complexity from normal to premalignant oral mucosal lesions, providing additional prognostic information in oral malignant tumors.


Inotropic agents.
When fluid administration is not sufficient to restore hemodynamic stability, inotropic agents may be given to restore the tissue perfusion pressure and to increase oxygen delivery (DO2) to the cells. Dopamine remains the drug of choice in the resuscitation of septic shock but norepinephrine can also have a place in the treatment of profound cardiovascular collapse or severe right ventricular failure. Dobutamine has become the inotropic agent of choice to increase DO2 to the tissues. Unfortunately, the beneficial effects of these agents on the extraction capabilities of the tissues are questionable. The potential of other adrenergic agents (such as dopexamine) or nonadrenergic agents (such as phosphodiesterase inhibitors) is also discussed in this article. Inotropic therapy should be guided not only by measurements of systemic BP but also by repeated assessments of the metabolic function of organs.


Case report: management of tooth tissue loss from intrinsic acid erosion.
Acid erosive tooth wear is increasingly being reported in many western countries, and is also being recognised as a significant cause of tooth destruction in persons with xerostomia. The primary aetiology is related to a high consumption of dietary sources of acids and also to an increasing awareness of gastric acid as a significant factor in both children and adults. Recommended preventive dental treatments aim to neutralise the effects of acids, reduce the severity of xerostomia, stimulate salivary flow and buffering capacity, and increase the acid resistance of tooth substance. Initial restorative treatments should be conservative, using adhesive dentistry techniques. This treatment approach is illustrated by the oral rehabilitation of a severe erosion case using adhesive onlays, veneers and all ceramic crowns.


Controlled studies of intranasal immunotherapy for ragweed pollenosis.
During 1978 a double blind study compared the efficacy of preseasonal short ragweed (RW) extract intranasal immunotherapy with a histamine placebo; in 1979 more prolonged treatment with a larger dose of polymerized ragweed (PRW) was evaluated. In neither year did the placebo-treated patients show significantly more severe disease as assessed by daily symptom diaries, examination in season, comparison of overall symptom severity with previous years or changes in nasal challenge tests. Following treatment in 1979 there was a significantly greater amount of secretory IgA and IgG ragweed antibodies secreted by the nose of the PRW-treated group, but these titers did not correlate with clinical results.


Association of urinary sex hormones with mood and behavior changes in a community adolescent cohort.
To examine the contribution of variation in sex hormone excretion to mood and behavioral changes in adolescent females and males. Prospective, longitudinal observational cohort study. Participants were 342 volunteers aged 10-12 years living in rural Australia. Urinary estradiol and testosterone levels measured by liquid chromatography-mass spectrometry were obtained at three-month intervals for three years. Integrated measures (area-under-curve) of urinary steroid excretion summarised as absolute and variability during each 12-month period of the study. Psychosocial data were gathered annually with the primary outcome of depressive symptomatology. Secondary outcomes were the other subscales of the Youth Self-Report, impulsive-aggression, sleep habits, and self-harm. 277 (158 male) participants contributed data over the full duration of the study and could be included in the analyses. In females, analyses of absolute urine hormone levels found no relationship between estradiol and any outcome, but higher testosterone was significantly associated with depression and poorer sleep. Greater variability of both urine estradiol and testosterone was associated with lower total psychopathology, anxious/depressed and social problems scores. Greater variability in urine estradiol was associated with lower attention problems and impulsive aggression in females. In males, higher testosterone and estradiol levels were associated with rule-breaking, and poorer sleep, and no associations were found for gonadal hormone variability for males. Longitudinal measurement of both iso-sexual and contra-sexual gonadal hormones contributes to a more nuanced view of the impact of sex steroids on mood and behavior in adolescents. These findings may enlighten the understanding of the impact of sex steroids during normal male and female puberty with implications for hormone replacement therapies as well as management of common mood and behavioral problems.


Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells.
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T cell-mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigen-specific Treg from antigenically naive precursors in vitro using allogeneic nontransformed B cells as stimulators. By this approach naive CD4(+)CD25(-) T cells could be expanded 8-fold into alloantigen-specific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO(+)CCR7(-) memory cells, and had a CD4(high), CD25(+), Foxp3(+), and CD62L (L-selectin)(+) phenotype. Although these CD4(high)CD25(+)Foxp3(+) alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on cytotoxic T lymphocyte antigen-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases.


Western immunoblot analysis of the antigens of Haemobartonella felis with sera from experimentally infected cats.
Cats were experimentally infected with a Florida isolate of Haemobartonella felis in order to collect organisms and evaluate the immune response to H. felis. Cryopreserved organisms were thawed and injected intravenously into nonsplenectomized and splenectomized cats. Splenectomized animals were given 10 mg of methylprednisolone per ml at the time of inoculation. Blood films were evaluated daily for 1 week prior to infection and for up to 60 days postinfection (p. i.). Blood for H. felis purification was repeatedly collected from splenectomized animals at periods of peak parasitemias. Organisms were purified from infected blood by differential centrifugation, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and transferred to nitrocellulose membranes for immunoblot analysis. Serum was collected from nonsplenectomized animals prior to and for up to 60 days p.i. and was used on immunoblots to identify antigens. The combination of splenectomy and corticosteroid treatment resulted in marked, cyclic parasitemias without concurrent severe anemia, providing an opportunity to harvest organisms in a manner that was not lethal to the animals. Several antigens (150, 52, 47, 45, and 14 kDa) were identified. An antigen with a molecular mass of approximately 14 kDa appeared to be one of the most immunodominant and was consistently recognized by immune sera collected at various times during the course of infection. These data suggest that one or more of these antigens might be useful for the serologic diagnosis of H. felis infections in cats.


Construction of a Highly Selective Enrichment, Ionization, and Detection Platform Based on a Broad-Spectrum Antibody.
Ambient mass spectrometry (AMS) allows direct analysis of various raw food samples with minimal or no sample pretreatment, but the trace analytes in complex food samples still have problems with limitations. In this work, we developed a platform based on coated stainless steel sheet spray mass spectrometry for fast, in situ, high-throughput, and high selectivity multiresidue analysis of fluoroquinolone drugs (FQs). The sensitivity of the platform was enhanced via coupling broad-spectrum antibodies against FQs to graphene oxide coated blade spray (CBS)-MS through a streptavidin-biotin (SA-biotin) interaction. The prepared platform had sufficient loading capacity for SA (1.37 mg/piece) and the antibody (84.8 μg/piece), which is greater than that of physical mixing and the EDC/NHS covalent coupling strategy. With simplified sample pretreatment, this platform demonstrated comparable sensitivity to high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) (0.08-0.16 ng/mL in phosphate-buffered saline and 0.21-0.32 ng/mL in diluted milk). Meanwhile, compared with HPLC-MS/MS, the method is rapid (enrichment: 10 min, detection: <1 min) and acceptable recoveries (81.94-102.08%) can be obtained. The presence of analytes can be monitored by MS/MS spectra, and multiple analytes can be measured simultaneously in a single assay. This study is expected to provide a powerful and portable tool for rapid laboratory analysis and reliable screening in the field.


Improved results with selective distal splenorenal shunt in a highly selected patient population. A prospective study.
In a 5-year period 299 patients were admitted to the Heinz-Kalk Hospital with bleeding esophageal varices. Patients with acute bleeding were treated with endoscopic sclerotherapy. Sessions were performed as many times as needed for each individual case. One hundred seventy-eight patients in Child-Pugh class C were excluded from surgical treatment; the remaining 121 patients (Child AB) were selected using the following criteria: liver volume (ultrasound) between 1000 to 2500 ml, portal perfusion (sequential scintigraphy) more than 30%, no activity or progression of liver disease proved by biopsy, no stenosis of the hepatic arteries, and suitable anatomy to perform the Warren shunt. Only 32 patients fulfilled these criteria. In seven of these cases the shunt was technically impossible to perform. Operative mortality rate was 8% and the late mortality rate was 12%. No history of rebleeding, encephalopathy, and/or shunt thrombosis was recorded. Five-year survival rate, according to the method of Kaplan-Meier was 75%. We conclude that the Warren shunt is the treatment of choice for elective management of bleeding esophageal varices. The postoperative results can be improved with strict selection using the above criteria. The preoperative use of sclerotherapy has a positive influence. Prophylactic management to prevent encephalopathy is also recommended.