Lymphatic transport in rats of interesterified oils containing conjugated linoleic acids.
In this study we examined the lymphatic transport in rats of FA after administration of interesterified oils containing CLA, with emphasis on the location of CLA and octanoic acid in the TAG. The oils were produced by enzymatic interesterification. Eight oils with different structures or FA profiles were examined in this study: MCM, CMC, OCO, and COC, where M was expected to be octanoic acid and O oleic acid. In group 1, C was CLA as a mixture of the two CLA isomers c9, t11 or t10, c12, and in group 2, C was mainly the isomer t10, c12. Rats were subjected to cannulation of the mesenteric lymph duct, and the following day they were intragastrically administered one of the oils and lymph samples were collected for 24 h. The lymphatic transport of total FA from 0 to 8 h in group 1 was significantly (P < 0.05) higher for the OCO-1 and the COC-1 oils than for the CMC-1 oil. Similarly, in group 2 the transport was higher for the OCO-2 oil than for the CMC-2 oil. The recovery of both of the CLA isomers examined was similar (50-70%) and independent of the isomer, oil structure, and FA profile, whereas more octanoic acid was recovered from the CMC oils than from the MCM oils. The results indicated that the FA profiles and the position of octanoic acid had only a minor influence on the absorption of CLA.


Seed and seedling interactions in three tree species from Mediterranean forests as a knowledge base for ecological restoration.
The ecosystems of the Mediterranean regions are severely threatened by human activity, and although we have made progress in physical restoration measures, little is known about the interactions between the plants of these biomes. The objective of this study is to contribute to document interactions between seeds and seedlings of three woody species native to Chile (P. chilensis, Q. saponaria and A. caven), which could be used for restoration actions (e.g., after forest fires). In a first experiment, we evaluated the germination response, the initial elongation and the interactions between the seedlings that germinate exposed to the chemical compounds of the other species. In a second experiment, we compared the survival and growth of seedlings in monospecific versus bispecific mixtures, using a substrate similar to that which is present after a wildfire. Seed extracts of teguments promoted germination of P. chilensis, but cotyledons and whole seed extracts inhibited germination of only one species, Q. saponaria, with very high intensity. The effects of the extracts on initial seedling elongation were more variable, including five inhibitions and one facilitation. Negative effects on germination and elongation included two cases of autotoxicity. The survival of seedlings grown in mixtures showed only two differences between monospecific and bispecific mixtures, both positive, constituting a reciprocal effect between two species. Only in one case was there a significant difference in seedling growth, which was root growth inhibition. Indeed, these results reveal an interaction between species, the type and intensity of which varies according to the condition of the seed or seedling. The negative effect found in seedling root growth reflects an allelopathic interaction that conditions a vital aspect for the establishment of these species, so this information is an opportunity to improve the establishment conditions in future reforestation projects, by avoiding particular species or promoting their proportion in plantation mixtures, either by planting or direct seeding.


Bioassay of retinoids using cultured human conjunctival keratinocytes.
The biological action of retinoids has been assayed using the differentiated properties of cultured human conjunctival keratinocytes. The effects measured were the suppression of envelope cross-linking and the promotion of synthesis of a keratin of molecular weight 40,000. Among the retinoids tested, the most powerful was the arotinoid Ro 13-6298, which reduced envelope formation detectably at 10(-11) M and by 90% at a concentration of 2 X 10(-10) M. The arotinoid was about 15 times more potent than trans-retinoic acid. The order of effectiveness of the retinoids in suppressing envelope cross-linking was the same as the order of effectiveness in promoting the synthesis of the 40-kd keratin.


Immunodiagnosis of human anisakiasis by use of larval excretory-secretory antigen.
L3 larvae of Anisakis simplex, isolated from freshly caught herrings were cultured in Medium 199 at different temperatures to obtain excretory-secretory (ES) antigen. Larvae have been cultured in vitro for a period of 11 months. A crude extract of A. simplex larvae was compared with ES antigen obtained under 4 different culture conditions for the determination of IgG and IgE antibodies by ELISA and a modified RAST, respectively. 1 serum from a patient with histopathologically proved anisakiasis and 4 samples from persons with presumptive clinical disease were positive in the ELISA. Two sera were positive in the RAST. A combination of both tests is suggested for the serodiagnosis of human anisakiasis.


Chronic ethanol tolerance through free-choice drinking in the P line of alcohol-preferring rats.
The objective of this study was to determine if the selectively bred P line of alcohol-preferring rats would develop behavioral (neuronal) tolerance with free-choice drinking of ethanol. Adult, male P rats were divided into four groups. One group (FCE) received food, water and a 10% (v/v) ethanol solution ad lib, while the control group (C) had only food and water. The other two groups received either a liquid diet containing 5% (v/v) ethanol (LDE) or a control liquid diet (LDC). All groups were kept on their respective feeding regimens for 14 days. The mean (+/- SEM) ethanol intakes for the FCE and LDE groups were 6.8 +/- 0.5 and 9.9 +/- 0.4 g ethanol/kg body wt./day, respectively. A shock-motivated jumping task was used to test for tolerance. Each rat received an IP injection of 2.5 g ethanol/kg and was tested every 15 minutes for recovery to a criterion of 75% of the performance level achieved with training. All rats were tested twice, once on the day before beginning their feeding regimens (day 0) and again 14 days later. Tolerance was assessed from differences in time of recovery to criterion performance and in blood alcohol concentrations (BACs) at recovery on day 0 vs. day 14. The mean recovery times for the C, FCE, LDC, and LDE groups on day 0 were 177 +/- 6, 170 +/- 6, 143 +/- 10 and 153 +/- 13 minutes, respectively, and the BACs were 219 +/- 6, 222 +/- 5, 220 +/- 19 and 214 +/- 6 mg%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of minimal residual disease in childhood B-acute lymphoblastic leukemia by 4-color flowcytometry.
Monitoring of minimal residual disease (MRD) is currently considered the most powerful predictor of outcome in acute lymphoblastic leukemia (ALL). Achievement of a negative MRD state assessed by multicolor flowcytometry (MFC) is an important predictor of disease-free survival (DFS) and overall survival (OS) in ALL patients. We sought to determine whether panels of antibodies combination are more suitable for detection of MRD in Childhood ALL. Eighty-four (84) patients with ALL (B-lineage subtype) were enrolled in this study. Normal template for B cell precursors was established in 15 control participants using 4-four panels of monoclonal Antibodies (Mo Abs),{CD22, CD45, CD58 and CD97 in combination with CD10, CD19, CD34}. At diagnosis, CD22 exhibited the lowest incidence of expression in only 50% of all patients, while CD45, CD58, and CD97 were expressed in 80.9, 59.5 and 92.8%, respectively. Analysis of MRD was performed for each Mo Abs combination at day 0 and day 14 post-induction of chemotherapy by 4-color (FCM). The incidence of MRD was 61.9, 70.6, 60.0 and 55.1% for CD22, CD45, CD58 and CD97, respectively. In B-ALL patients, (CD10/CD19/CD34/CD45) + (CD10/CD19/CD34/CD97) represented the highest incidence of expression of leukemic cells markers with a significant correlation with blasts count, suggesting that these are more specific for MRD detection. Also FCM is relatively cost effective for detection of MRD in ALL patients and its applicability in routine leukemia lab is valuable. MRD evaluation at the end of the induction therapy (i.e. day 35 or 42 according to the different schedules) is advised. Also, Ig/T cell receptor gene rearrangements and gene fusions analyzed by polymerase chain reaction (PCR) are preferred.


[High frequency vibrations of human hollow bone (author's transl)].
For study of the functional structures in hollow bone were applicated longitudinal waves in form of ultrasonics. The findings have a great signification for the practical medicine, because we can demonstrate the elastic modul of the bone, the absorption of the longitudinal waves in the bone by a thickness more than 5 cm and the transformation of the ultrasonic amplitude in the bone.


Interfacial microrheology and tensiometry in a miniature, 3-d printed Langmuir trough.
We introduce a new approach for manipulating and studying complex fluid interfacial systems, that enables simultaneous tensiometry to measure surface pressure and high-performance interfacial shear microrheology. In contrast to existing techniques, we use a miniature Langmuir trough produced by 3-d printing methods, which fits on the stage of a conventional inverted microscope and which allows compression and stretching of the fluid-fluid interfaces at a constant bulk fluid volume. The tensiometry measurement relies on the quantitative imaging of a curved meniscus separate from the flat interface being imaged under the microscope. We first demonstrate that this approach can measure the interfacial tension of simple fluid-fluid and polymer-laden interfaces with an accuracy comparable to the pendant drop apparatus and Wilhelmy plates. We then study the mechanics of an adsorbed protein layer formed at an air-water (a-w) interface by simultaneously measuring its surface pressure and its interfacial viscosity. To perform two-point interfacial microrheology, micrometer-sized probes spread on the interface are tracked to 5 nm precision with very low drift, yielding measurements of interfacial viscosity having a wide dynamic range and high sensitivity (10-9-10-1Nsm-1).


Induction of intercellular adhesion molecule 1 gene expression by measles virus in human umbilical vein endothelial cells.
The expression of intercellular adhesion molecule 1 (ICAM-1) by endothelial cells is important for the regulation of adhesion and transendothelial migration of a variety of leukocytes that express the integrins lymphocyte function-associated antigen 1 (LFA-1) and/or Mac-1. Here, we demonstrate strain-specific differences in the ability of measles virus (MV) to induce ICAM-1 expression. The vaccine strain Moraten (Mor) rapidly induced high levels of ICAM-1 mRNA and protein expression, whereas the vaccine strain CAM-70 and the Edmonston wild type (Ed-wt) strain were far less effective, even when they were used at very high multiplicities of infection (MOIs). Strain-specific differences in the induction were not a consequence of differences in the ability to infect ECs. Furthermore, induction of ICAM-1 by Mor was not dependent on de novo expression of MV or cellular proteins. Dual-immunofluorescence analysis indicated that there was no association between the expression of either MV nucleocapsid or hemagglutinin protein and the induction of ICAM-1 expression. Some human umbilical vein endothelial cells (HUVECs) that expressed high nucleocapsid protein in response to either Mor or CAM-70 failed to express elevated ICAM-1, whereas some HUVECs that were incubated with Mor expressed high ICAM-1 prior to expression of MV nucleocapsid protein. Strain-specific differences in the ability of Mor and CAM-70 to induce ICAM-1 correlated with their ability to activate the latent transcription factor NF-kappaB. These studies suggest a preexisting component of MV particles that leads to strain-specific differences in the activation of NF-kappaB and the induction of ICAM-1 gene expression.


Spontaneous iliopsoas haemorrhage--an unusual complication of streptokinase therapy.
We report a case of spontaneous iliopsoas haemorrhage following intravenous streptokinase which serves to remind physicians of the potential dangers of this form of therapy.


Current treatment and molecular targets for axial spondyloarthritis: Evidence from randomized controlled trials.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that predominantly affects the axial skeleton and is characterized by inflammatory back pain. While much has been published regarding non-steroidal anti-inflammatory drugs and tumor necrosis factor inhibitors, other classes of medications which leverage alternate molecular mechanisms receive less attention. In this review, we summarize a few of the novel targets in axSpA, review the putative mechanism of action of therapies that focus on these targets, and reference the germane recently completed, ongoing, or proposed randomized controlled clinical trials. The agents addressed include inhibitors of interleukin-23, interleukin-17, janus kinases, granulocyte-macrophage colony-stimulating factor, macrophage migration inhibitory factor, antibodies recognizing T cell receptor beta variable 9 gene positive clones, as well as inhibitors of mitogen-activated protein kinase-activated protein kinase-2.


Identification of PECAM-1 association with sphingosine kinase 1 and its regulation by agonist-induced phosphorylation.
Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator generated from sphingosine by sphingosine kinase (SPHK). S1P acts both extracellularly and intracellularly as a signaling molecule, although its intracellular targets are still undefined. Intracellular level of S1P is under strict regulatory control of SPHK regulation, S1P degradation, and S1P dephosphorylation. Therefore, clarifying the mechanisms regulating SPHK activity may help us understand when and where S1P is generated. In this study, we performed yeast two-hybrid screening to search for SPHK1a-binding molecules that may be involved in the regulation of the kinase localization or activity. Platelet endothelial cell adhesion molecule-1 (PECAM-1) was identified as a protein potentially associating with SPHK1a. Their association was confirmed by co-immunoprecipitation analysis using HEK293 cells overexpressing PECAM-1 and SPHK1a. Moreover, the kinase activity appeared to be reduced in stable PECAM-1-expressing cells. PECAM-1 is expressed on the cell surface of vascular cells, and several stimuli are known to induce phosphorylation of its tyrosine residues. We found that such phosphorylation attenuated its association with SPHK1a. This association/dissociation of SPHK with PECAM-1, regulated by the phosphorylated state of the membrane protein, may be involved in the control of localized kinase activity in certain cell types.


Cell penetrating peptides fail to induce an innate immune response in epithelial cells in vitro: implications for continued therapeutic use.
Cell penetrating peptides (CPPs) offer the exciting potential of effectively delivering macromolecules to the cytoplasm of a cell that are otherwise impermeable to the plasma membrane. Although the use of these peptides has so far been well tolerated in clinical trials, it is important to remember that some of these CPPs were originally derived from pathogenic material. We therefore sought to determine if three of the most widely studied CPPs; HIV-TAT, Antennapedia and Transportan, initiated an immune response in epithelial cells. Using conditions where these peptides efficiently delivered a rhodamine tagged BSA cargo to the interior of epithelial cells, we failed to observe an effect on cell viability as determined by MTT assay (P>0.05). Further, CPP-mediated delivery of this protein cargo failed to activate NFκB, which would be indicative of toll-like receptor signalling. Finally, no significant increase in the release of the inflammatory cytokines interleukin (IL)-8 and IL-6 was detected in epithelial cells exposed to CPP complexes for 72 h (P>0.05). Together, these results indicate that these commonly used CPPs are passive carriers that do not initiate epithelial cell-associated 'danger signals' during the process of cytoplasmic delivery of a model protein cargo.


A longitudinal review of Scottish reporting radiographer output between 2015 and 2019.
Scottish radiographer reporting has been slow in its initiation compared with the wider UK. However, healthcare delivery imperatives require improvement in meeting seamless imaging acquisition and reporting. Initiatives supporting radiographer reporting could be extended to meet gaps in radiology and wider health service provision. Development drivers leading to a national reporting radiographer (RR) framework initiated this RR service analysis. All 14 Scottish health boards (and the waiting time centre) provided RR performance details, staffing make up and practice scopes between 2015 and 2019, with gap analyses performed via surveys to radiology managers in 2017 and 2019. Further expenditure data was provided by the National Procurement Directorate. A reporting radiographer census revealed details of changing levels of practice and areas of working within musculo-skeletal projection radiograph reporting. Gap analyses two years apart showed little wider service change and growing external reporting costs. Managers identified areas where RRs could reduce costs, shorten reporting timeframes and broaden service development potential across all staff. Scottish RRs have a growing cost effective role. To extend this, the radiographic workforce should embrace the various employment tiers and how this contributes to ideal patient pathway outcomes. Technical development and service transformation will drive future workforce change and has the potential to refocus radiographer roles with others to deliver seamless diagnostic and public health oriented services. Current service demand is supported by RRs identifying themselves as advanced practitioners. To meet deficiencies in service delivery, broadened practice scopes are required spanning the different grades of the profession, supported by education approaches to meet national geographic and staffing issues.


Leptomeningeal Neoplasms.
Leptomeningeal metastases are a late, devastating complication of systemic cancer that typically occurs in conjunction with other systemic relapse. The most common neurologic symptoms include headache, altered mentation, and difficult walking. Diagnosis is established by neuroimaging and cerebrospinal fluid analysis. The prognosis is poor with a median survival of 6 to 8 weeks; therefore most treatment interventions are palliative. Radiotherapy should be given to sites of bulky or symptomatic tumor. Intrathecal chemotherapy is most effective in patients with lymphoma, leukemia, and breast cancer. Systemic chemotherapy may be more effective in treating bulky leptomeningeal tumor. Ventriculoperitoneal shunting can be extremely useful in patients with obstructive hydrocephalus or increased intracranial pressure.


Superhydrophobicity for antifouling microfluidic surfaces.
Fouling of surfaces is often problematic in microfluidic devices, particularly when using protein or -enzymatic solutions. Various coating methods have been investigated to reduce the tendency for protein molecules to adsorb, mostly relying on hydrophobic surface chemistry or the antifouling ability of -polyethylene glycol. Here we present the potential use of superhydrophobic surfaces to not only reduce the amount of surface contamination but also to induce self-cleaning under flow conditions. The methodology is presented in order to prepare superhydrophobic surface coatings having micro- and nanoscale feature dimensions, as well as a step-by-step guide to quantify adsorbed protein down to nanogram levels. The fabrication of these surfaces as coatings via silica sol-gel and copper nano-hair growth is presented, which can be applied within microfluidic devices manufactured from various materials.


Biological responses to disasters.
The pathogenic effect of extreme events has been equated with their immediate stressfulness, and thereby with the biology of stress. This article extends this classical view to include, among other pathogenic factors the biological dimensions of learning, social interaction, territorial behavior, and a top-down brain process that links personal and cultural meanings with emotional and bodily responses. The paper depicts the way in which mechanisms related to stress and aversive learning trigger an initial response and those related to separation, loss and sensitization shape its long-term consequences. Traumatic events are followed by a critical period of increased brain plasticity, during which irreversible neuronal changes may occur in those who develop traumatic stress disorders.


Lipid metabolism dysfunction following symbiont elimination is linked to altered Kennedy pathway homeostasis.
Lipid metabolism is critical for insect reproduction, especially for species that invest heavily in the early developmental stages of their offspring. The role of symbiotic bacteria during this process is understudied but likely essential. We examined the role of lipid metabolism during the interaction between the viviparous tsetse fly (Glossina morsitans morsitans) and its obligate endosymbiotic bacteria (Wigglesworthia glossinidia) during tsetse pregnancy. We observed increased CTP:phosphocholine cytidylyltransferase (cct1) expression during pregnancy, which is critical for phosphatidylcholine biosynthesis in the Kennedy pathway. Experimental removal of Wigglesworthia impaired lipid metabolism via disruption of the Kennedy pathway, yielding obese mothers whose developing progeny starve. Functional validation via experimental cct1 suppression revealed a phenotype similar to females lacking obligate Wigglesworthia symbionts. These results indicate that, in Glossina, symbiont-derived factors, likely B vitamins, are critical for the proper function of both lipid biosynthesis and lipolysis to maintain tsetse fly fecundity.


Effectiveness of antibiotic removal by the antibiotic-binding blood culture systems.
The effectiveness of antibiotic removal by the BACTEC aerobic resin-containing blood culture medium (16B) and the Antimicrobial Removal Device (ARD) was compared for 12 antibiotics: ampicillin, cephalothin, cefoperazone, cefotaxime, moxalactam, nafcillin, gentamicin, tobramycin, azlocillin, mezlocillin, piperacillin, and ticarcillin. The ability to recover eight commonly encountered species of bacteria from antibiotic-containing serum by these two systems showed that recovery of antibiotic-exposed bacteria was dependent not only upon the amount and rate of the antibiotic removal but also upon the kinetics of bacterial killing by the antibiotic(s). The 16B medium had difficulty recovering organisms exposed to ticarcillin and moxalactam, whereas the ARD had difficulties with moxalactam and sometimes with cefotaxime and cefoperazone. Although neither system was able to recover all species of microorganisms tested, these in vitro results suggest that to use optimally these new culture systems, knowledge of the suspected pathogen(s), the amount and kind of antibiotic(s) administered, and the rate of bacterial killing by the antibiotic(s) is required.


The continuous quality improvement project for telephone-assisted instruction of cardiopulmonary resuscitation increased the incidence of bystander CPR and improved the outcomes of out-of-hospital cardiac arrests.
In 2007, the Ishikawa Medical Control Council initiated the continuous quality improvement (CQI) project for telephone-assisted cardiopulmonary resuscitation (telephone-CPR), which included instruction on chest-compression-only CPR, education on how to recognise out-of-hospital cardiac arrests (OHCAs) with agonal breathing, emesis and convulsion, recommendations for on-line or redialling instructions and feedback from emergency physicians. This study aimed to investigate the effect of this project on the incidence of bystander CPR and the outcomes of OHCAs. The baseline data were prospectively collected on 4995 resuscitation-attempted OHCAs, which were recognised or witnessed by citizens rather than emergency medical technicians during the period of February 2004 to March 2010. The incidence of telephone-CPR and bystander CPR, as well as the outcomes of the OHCAs, was compared before and after the project. The incidence of telephone-CPR and bystander CPR significantly increased after the project (from 42% to 62% and from 41% to 56%, respectively). The incidence of failed telephone-CPR due to human factors significantly decreased from 30% to 16%. The outcomes of OHCAs significantly improved after the projects. A multiple logistic regression analysis revealed that the CQI project is one of the independent factors associated with one-year (1-Y) survival with favourable neurological outcomes (odds ratio=1.81, 95% confidence interval=1.20-2.76). The CQI project for telephone-CPR increased the incidence of bystander CPR and improved the outcome of OHCAs. A CQI project appeared to be essential to augment the effects of telephone-CPR.


Altered clonogenic capability and stromal cell function characterize bone marrow of HIV-infected subjects with low CD4+ T cell counts despite viral suppression during HAART.
Inflammatory cytokines in bone marrow may impair hematolymphopoiesis in human immunodeficiency virus (HIV)-infected subjects who do not experience reconstitution of CD4(+) T cells despite suppression of virus replication while receiving highly active antiretroviral therapy (HAART) (immunological nonresponders). Bone marrow samples from 12 immunological nonresponders receiving HAART were studied and compared with samples from 11 immunological responders. The mean CD4(+) T cell count (+/- standard deviation) was 174 +/- 68 cells/mm(3) and plasma HIV RNA levels had been <50 copies/mL for at least 1 year for individuals enrolled in the study. The clonogenic capability of bone marrow samples was evaluated using the colony forming cell assay and the long-term culture-initiating cell assay. CD34(+) cells from the colony forming cell assay were pooled for real-time polymerase chain reaction analysis of Fas and Fas ligand. Bone marrow cytokine production (interleukin-2 and tumor necrosis factor-alpha) and stromal interleukin-7 levels were analyzed by enzyme-linked immunosorbent assay in both groups. Flow cytometric analysis of CD4(+) and CD8(+) T cell subsets was performed. A reduced clonogenic capability and a decrease in the level of more primitive progenitor cells were observed in parallel with lower production of interleukin-2 and increased tumor necrosis factor-alpha levels. A significant upregulation of Fas and Fas ligand on CD34(+) cells and a higher stromal interleukin-7 production were observed. Impairment of the naive T cell compartment and persistent T cell activation were observed in peripheral blood. Samples from immunological nonresponders show reduced growth of in vitro colonies and an altered cytokine production in bone marrow. The cytokine pattern observed and the altered Fas and Fas ligand pathway may determine stem cell apoptosis and low CD4(+) cell recovery. These features, which are similar to those observed in HIV-infected subjects before starting therapy, persist despite treatment.


Endometriosis and risk of ovarian cancer: what do we know?
Despite long and intensive research, endometriosis remains one of the leading causes of morbidity among premenopausal women. The majority of endometriosis-related ovarian carcinomas occur in the presence of atypical ovarian endometriosis. Nevertheless, despite the increased incidence of ovarian cancer in patients with endometriosis, our knowledge of the risk factors and mechanisms is still incomplete. Narrative overview, synthesizing the recent findings of literature retrieved from databases. Herein, we reviewed and summarized the most recent knowledge regarding endometriosis and ovarian cancer. The evidence showing that patients with endometriosis have a higher risk of developing ovarian cancer is compelling. However, the question of how much higher the absolute risk is, is not fully clear.


Point of care testing for group A streptococci in patients presenting with pharyngitis will improve appropriate antibiotic prescription.
History, clinical examination and throat culture may be inadequate to rule in or out the presence of group A streptococci (GAS) infection in patients with sore throat in a remote location. We correlated the diagnostic accuracy for guiding antibiotic prescription of clinical decision and physiological scoring systems to a rapid diagnostic point of care (POC) test result in paediatric patients presenting with sore throat. Prospective diagnostic accuracy study conducted between 30 June 2014 and 27 February 2015 in a remote Australian ED using a convenience sample. Among paediatric patients presenting with sore throat, the Centor criteria and clinical decision were documented. Simultaneously, patients without sore throat or respiratory tract infection were tested to determine the number of carriers. A throat swab on all patients was tested using a POC test (Alere TestPack +Plus Strep A with on board control), considered as reference standard to detect GAS infection. A total of 101 patients with sore throat were tested with 26 (25.7%) positive for GAS. One hundred and forty-seven patients without sore throat were tested with one positive POC test result (specificity 99%; 95% CI 96-100). Positive predictive value for clinician decision-making for a positive GAS swab (bacterial infection) was 29% (95% CI 17-43), negative predictive value 78% (95% CI 63-88). Area under ROC for the Centor score was 0.70 (95% CI 0.58-0.81). Clinician judgement and Centor score are inadequate tools for clinical decision-making for children presenting with sore throat. Adjunctive POC testing provides sufficient accuracy to guide antibiotic prescription on first presentation.


Nano-hydroxyapatite-evoked immune response synchronized with controllable immune adjuvant release for strengthening melanoma-specific growth inhibition.
Concerns about the potential systematic toxicity limit the extensive application of traditional therapeutic drugs for melanoma therapy, nano-hydroxyapatite (nHA) with good biocompatibility and anti-tumor ability could be an alternative choice. In this study, nHA was employed as an anti-tumor biomaterial due to its tumor-specific toxicity. Meanwhile, granulocyte-macrophage colony-stimulating factor (GM-CSF) served as the immune adjuvant to activate the immune response. The delivery platform was fabricated by co-encapsulation of both nHA and GM-CSF into a biocompatible thermosensitive PLGA-PEG-PLGA hydrogel. The results showed that the bio-activities of nHA and GM-CSF could be well-maintained within the hydrogel. Interestingly, the addition of nHA could attenuate the burst release of GM-CSF due to possible protein absorption capacity of nHA, which is beneficial for GM-CSF sustainable release at the tumor site, achieving boosted and prolonged anti-tumor immunity. The in vitro and in vivo data demonstrated that nHA/GM-CSF hydrogel exhibited greater potency to inhibit tumor growth via enhanced CD8+ T-cell response compared with hydrogel and nHA hydrogel groups, contributed by the synergistic effects of nHA and GM-CSF. Overall, the strategy combining nHA and immune adjuvant shows great promise, which largely broadens the choice of combinational therapies for melanoma. STATEMENT OF SIGNIFICANCE: Nano-hydroxyapatite (nHA) has been confirmed to specifically inhibit melanoma tumor growth and induce immune response. However, its antitumor efficiency and immunity-evoking capacity are limited. In this study, granulocyte-macrophage colony-stimulating factor (GM-CSF) was introduced to serve as the immune adjuvant. Both of them were encapsulated into a biocompatible thermosensitive PLGA-PEG-PLGA hydrogel. The addition of nHA could attenuate the burst release of GM-CSF due to the interaction with nHA, which is beneficial for GM-CSF sustainable release at tumor site, achieving boosted and prolonged anti-tumor immunity. Anti-tumor immune response could be activated due to the release of tumor-associated antigen and tumor debris induced by the specifically tumor inhibition effect of nHA and GM-CSF. The combination of nHA and GM-CSF could play synergistic inhibiting effect on tumor growth via boosting and prolonging anti-tumor immunity.


Expression of ER-resident selenoproteins and activation of cancer cells apoptosis mechanisms under ER-stress conditions caused by methylseleninic acid.
The aim of this work was to study changes in gene expression levels of 7 ER-resident selenoproteins under ER-stress caused by the action of a selenium-containing compound of organic nature, methylselenic acid using three human cancer cell lines DU 145 (prostate carcinoma), MCF 7 (breast adenocarcinoma)and HT-1080 (fibrosarcoma). According to the obtained results, we can speak of a synchronous changes in the expression of SELT and SEP15 mRNA depending on the concentration of MSA for 24 h, while the pattern of SELM expression was completely opposite and was radically different from other selenoproteins. It should be noted that in HT-1080 cells, the expression pattern of SELM differed from the expression pattern in two other cancer cells, while the expression patterns of other ER-resident selenoproteins (SELT, SEP15, SELK, SELS, SELN and DIO2) differed slightly depending on the cell line. Also we investigated the molecular mechanisms of UPR caused by MSA-induced ER stress in three cancer cell lines. According to the obtained results, it can be assumed that in DU 145 cells, MSA promotes activation of the PERK signaling pathway of UPR. In fibrosarcoma cells MSA was promoted the activation of ATF-6 UPR signaling pathway. In MCF 7 cells, MSA promoted the activation of two pro-apoptotic UPR signaling pathways at once: IRE1 and ATF-6.The results of this work once again demonstrate that the mechanisms of ER-stress regulation caused by the same agent, in this case, MSA, lead to the activation of different UPR signaling pathways in different cancer cells, and about their relationship.


Hyperactivity among white middle-class children. Psychogenic and other causes.
This paper investigates the problem of hyperactivity in school children and draws on the literature in the field, data collected from comprehensive examinations of 37 hyperactive children, and extensive field interviews with Chicago-area school nurses, social workers, psychologists, teachers, and principals. The research indicates that although constitutional factors are at times responsible for this problem, hyperactivity is due to psychogenic factors much more frequently than is often recognized. It also was found that school teachers seem overly inclined to identify hyperactivity in their students and to recomment that it be counteracted with prescribed drugs. The suggestion is offered that any child thought to be hyperactive undergo a comprehensive examination before such drugs as Ritalin and Dexedrine are prescribed.


Displacement of the Gent/1999 human-like swine H1N2 influenza A virus lineage by novel H1N2 reassortants in Germany.
A swine influenza survey was conducted between 2003 and 2015 in Germany. During this period, 8122 snout swabs or other respiratory specimens from pigs of 5178 herds, mainly from Germany, were investigated for the presence of swine influenza A virus (S-IAV). In total, 1310 S-IAV isolates were collected. Of this collection, the complete genome of 267 H1N2 S-IAV isolates was sequenced and phylogenetically analyzed. The data demonstrate the incursion of human-like swine H1N2 viruses (Gent/1999-like) in 2000 and prevalent circulation until 2010. From 2008 onward, a sustained and broad change of the genetic constellation of the swine H1N2 subtype commenced. The Gent/1999-like swine H1N2 viruses ceased and several new swine H1N2 reassortants emerged and became prevalent in Germany. Of these, the upsurge of the Diepholz/2008-like, Emmelsbuell/2009-like and Papenburg/2010-like viruses is notable. The data reveal the importance of reassortment events in S-IAV evolution. The strong circulation of S-IAV of different lineages in the swine population throughout the year underlines that pigs are important reservoir hosts.


Monitoring of methylglyoxal/indole interaction by ATR-FTIR spectroscopy and qTOF/MS/MS analysis.
Sugar derived reactive 1,2-dicarbonyl intermediates are considered important precursors for the formation of Maillard reaction products. Efficient strategies are needed to modulate their formation in food. Indole a major thermal degradation product of tryptophan, has been shown to scavenge such 1,2-dicarbonyls at high temperatures. In this study, the trapping of methylglyoxal by indole was monitored at various temperatures either by (a) ATR-FTIR spectroscopy or (b) in-solution using qTOF/MS/MS analysis. Information obtained through these studies have indicated that even at room temperature indole can quickly react with methylglyoxal forming an adduct as confirmed by the emergence of a new peak at 1729 cm-1 and by qTOF/MS/MS analysis. On the open surface of the ATR crystal this adduct underwent a fast oxidization into carboxylic acid as evidenced by the disappearance of the band at 1729 cm-1 and the formation of a new band at 1712 cm-1 and its subsequent conversion into a carboxylate band under basic conditions.


Dopamine autoreceptor mediation of the effects of apomorphine on serotonin neurons.
The effects of direct apomorphine (APO) infusion to the dorsal raphe and the substantia nigra on serotonergic neurons were examined in male rats. The results showed that APO infusion to the dorsal raphe failed to produce a significant effect on serotonin (5-HT) neurons in the dorsal raphe or 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the corresponding projection site, the striatum. Conversely, direct APO infusion to the substantia nigra mimicked the effects of systemic APO, namely, elevated 5-HT fluorescence in the dorsal raphe and increased 5-HT and 5-HIAA concentrations in the striatum. Serotonin neurons in the median raphe and its projection site, the hippocampus, were unaffected. Furthermore, horseradish peroxidase injection to the dorsal raphe resulted in specific cell labelling in the substantia nigra and fiber labelling in the ventral tegmental area. Together with previous findings that the serotonergic actions of systemic APO were antagonized by haloperidol or intraventricular 6-hydroxydopamine pretreatment; and the selective dopamine (DA) autoreceptor agonist 3-3-hydroxyphenyl-N-n-propyl-piperidine mimicked the effects of APO on 5-HT neurons, these results suggest that the observed effects of APO on the mesostriatal serotonergic system are probably mediated through DA autoreceptors in the substantia nigra and possibly by a direct nigroraphe pathway.


Mechanisms for inhibition of free fatty acid mobilization by nicotinic acid and sodium salicylate in canine subcutaneous adipose tissue in situ.
Mechanisms for reduced free fatty acids (FFA) mobilization effected by nicotinic acid (NA) and sodium salicylate (SS) were studied in canine adipose tissue in situ. Both drugs inhibited adipose tissue lipolysis as evidenced by reduced release of glycerol. In addition, although the total amount of FFA re-esterified was not significantly changed, the amount of FFA re-esterified relative to the amount of FFA liberated intracellularly was significantly increased by both drugs. These effects were most pronounced during isoprenaline-stimulated lipolysis. Thus NA and SS reduced mobilization of FFA from canine adipose tissue through a combined effect on re-esterification and lipolysis.


Particulate matter in the workplace: effects of a mental models-based folder combined with a practical assignment.
With increasing knowledge on the adverse health effects of certain constituents of PM (particulate matter), such as silica, metals, insoluble ions, and black carbon, PM has been under the attention of work safety experts. Previously, we investigated the perceptions of blue-collar workers in highly exposed areas of work. Subsequently, we developed an instruction folder highlighting the most important aspects of PM risk and mitigation, and tested this folder in a digital experiment. The digital experiment yielded positive results with regards to acquired knowledge about PM, but did not on risk perception or safety behavior. In this study, we investigate the effects of the folder when combined with a practical assignment involving a PM exposimeter, showing the amount of particulate matter in microgram per cubic meter in real time on its display for various activities. We tested this at six workplaces of four companies in the roadwork and construction branch. The results indicate that the folder itself yields an increased knowledge base in employees about PM, but the effects of the practical assignment are more contentious. Nevertheless, there is an indication that using the assignment may lead to a higher threat appraisal among employees for high exposure activities. We recommend implementing our folder in companies with high PM exposure and focusing further research on appropriate methods of implementation.


Arterial thrombosis in essential thrombocythemia.
The course of essential thrombocythemia has been observed in ten patients, ages 46 to 83, of whom nine were followed for a period of 4 months to 9 years. In contrast to the experience with essential thrombocythemia recorded in the literature, manifestations of arterial thrombosis were far more common than hemorrhage. In six of the ten patients, the presenting complaints were ascribable to incipient gangrene of the toes and several of these patients additionally developed occlusion of tibial and larger arteries while under our observation. All patients with incipient gangrene showed marked clinical improvement accompanying busulfan-induced reduction and normalization of the platelet count. Relapses in five patients after 2 to 87 months responded well to retreatment with busulfan. No patient has shown evolution to another myeloproliferative disorder. Essential thrombocythemia should be considered in the differential diagnosis of occlusive arterial disease.


The Correlation Between the Sonographic Course of Transobturator Slings and Sling-Related Pain.
To determine whether transobturator slings follow a consistent path and whether there is an association between ultrasonographically visualized sling pattern or position with sling-related pain. This was a cross-sectional retrospective pilot study. We evaluated women who were presented to our clinic for pain or other urogynecologic symptoms following transobturator sling placement between 2009 and 2014. Patients had undergone a 3-dimensional endovaginal pelvic floor ultrasound, assessing minimal levator hiatus, antero-posterior diameter, left-right diameter, and the hiatal shape. The mesh patterns were categorized as seagull patterns (normal), lopsided, flat, and convoluted. A total of 68 cases were reviewed. Fifty patients reported pain, and 18 did not. There were wide variations in the course of the slings. The sling center- minimal levator hiatus position ranged 14.8 mm below and 17.9 mm above the minimal levator hiatus. The lateral arm insertion points ranged between 17.1 mm below and 16.6 mm above the minimal levator hiatus. The right arm insertion points ranged between 9.6 mm below and 18.8 mm above the minimal levator hiatus. Thirty-five of 68 (70%) patients with pain and 13 of 18 (72.2%) without had abnormal sling patterns. The abnormal sling shape was not correlated with pain (P = 1). The levator shape trended toward a statistical significant correlation with sling shape abnormality (P = .084). This population of women with transobturator sling complications demonstrated wide variations in anatomic paths. Neither the abnormal sling shape nor the distance of the center of the tape from the minimal levator hiatus level were correlated with pain.


Magnetic-field-induced charge-stripe order in the high-temperature superconductor YBa2Cu3Oy.
Electronic charges introduced in copper-oxide (CuO(2)) planes generate high-transition-temperature (T(c)) superconductivity but, under special circumstances, they can also order into filaments called stripes. Whether an underlying tendency towards charge order is present in all copper oxides and whether this has any relationship with superconductivity are, however, two highly controversial issues. To uncover underlying electronic order, magnetic fields strong enough to destabilize superconductivity can be used. Such experiments, including quantum oscillations in YBa(2)Cu(3)O(y) (an extremely clean copper oxide in which charge order has not until now been observed) have suggested that superconductivity competes with spin, rather than charge, order. Here we report nuclear magnetic resonance measurements showing that high magnetic fields actually induce charge order, without spin order, in the CuO(2) planes of YBa(2)Cu(3)O(y). The observed static, unidirectional, modulation of the charge density breaks translational symmetry, thus explaining quantum oscillation results, and we argue that it is most probably the same 4a-periodic modulation as in stripe-ordered copper oxides. That it develops only when superconductivity fades away and near the same 1/8 hole doping as in La(2-x)Ba(x)CuO(4) (ref. 1) suggests that charge order, although visibly pinned by CuO chains in YBa(2)Cu(3)O(y), is an intrinsic propensity of the superconducting planes of high-T(c) copper oxides.


Retraction notice to: The optimality principle decreases hemodynamic stresses for aneurysm initiation at anterior cerebral artery bifurcations [WNEU 121 (2019) e379-e388/10317].
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care.


Repeating a dose of sucrose for heel prick procedure in preterms is not effective in reducing pain: a randomised controlled trial.
Oral sucrose is included in almost all recommendations for treatment of pain in newborns, but evidence if multiple doses might be more effective than a single standard dose is lacking. We designed a single-centre, double-blind, randomised, controlled trial. We enrolled preterm infants needing the heel prick procedure. Each enrolled infant was randomised to receive a single standard dose of sucrose 2 min before or a double dose of sucrose 2 min before, and 30 s after heel prick. Primary outcome was the efficacy of the two interventions tested by the premature infant pain profile-PIPP scale obtained at 30 s, 60 s, and 120 s after heel prick. Secondary outcome was the evaluation of the concordance between the PIPP scale and other pain scores more feasible in clinical practice. Seventy-two infants were randomised. No difference in pain perception as measured by the PIPP scale was found between the groups: median PIPP values 4.0(IQR 3.0-4.0) vs 3.0(IQR 3.0-4.0) at baseline; 6.0(IQR 5.0-10.0) vs 6.0(IQR 4.0-8.5) at 30 s; 6.0(IQR 4.0-7.0) vs 5.0(IQR 4.0-8.5) at 60 s and 5.0(IQR 4.0-7.0) vs 5.0(IQR 4.0-7.5) at 2 min, in the experimental and standard treatment groups, respectively (p = 0.9020). There was no correlation between PIPP scores and other pain scales.Conclusion: We do not recommend doubling the dose during heel prick.What is Known:• Oral sucrose is included in almost all international position papers and recommendations for the treatment of mild to moderate pain in newborns, associated with non-nutritive sucking and facilitated tucking• Premature infant pain profile (PIPP) scale is the gold standard for evaluation of pain in preterms but it is difficult to use in clinical practiceWhat is New:• Repeating a dose of 24% sucrose is not effective in reducing pain during the recovery phase of a skin breaking procedure• Other pain scales, easier to use in clinical practice, are not comparable with PIPP for the evaluation of procedural pain in preterms.


Cooperative equilibrium transitions coupled with a slow annealing step explain the sharpness and hysteresis of collagen folding.
Heat and guanidinium-induced denaturation curves of collagen III and its fragments were fitted by theoretical models to explain the extreme sharpness and the hysteresis between unfolding and refolding. It was shown that a recently proposed kinetic model for collagen denaturation does not account for the observed steepness, with physically reasonable values of activation energy and frequency factors in the Arrhenius equation. The extreme slope, which amounts to 0.38 per centigrade for collagen III at the midpoint of its transition, can only be explained by a highly cooperative equilibrium model. The refolding curve is shifted to lower temperatures by 6 degrees C for collagen III and reversible unfolding matching the initial profile of the native protein is observed only after long-time annealing. A simple formalism is proposed by which experimental denaturation and refolding curves are quantitatively described. The transition proceeds via many cooperative steps with slightly different equilibrium constants for unfolding and refolding. Hysteresis and annealing are caused by very slow steps, which are probably connected with a rearrangement of misfolded regions. These slow steps disappear with decreasing size of collagen fragments and hysteresis is not found for collagen model peptides.


Medical and psychosocial considerations in rehabilitation care of childhood neuromuscular diseases.
Most neuromuscular diseases (NMD) are rare inherited conditions presenting a relentlessly progressive course. Some NMD are associated with intellectual impairment and many are complicated by musculoskeletal, cardiac, or respiratory problems. Rehabilitation care of NMD is thus best provided by a team of medical specialists and health professionals working closely together in an interdisciplinary fashion. Rehabilitation for patients with NMD should include physical evaluation but also assessment of their ability to manage their daily activities or work and their need for assistive devices. With appropriate physical, psychological, and social support, those patients can maintain a good quality of life and an adequate level of well-being. Surgical management of musculoskeletal problems in children related to neuromuscular disorders remains a highly controversial subject. This review is based mainly on the author's personal experience with conservative and periopeporative rehabilitation care for neuromuscular diseases. A multidisciplinary approach is advocated. The importance of proactive respiratory care is emphasized. Rehabilitation after surgical treatment of spinal deformities is analyzed outlining the particular aspects in spinal muscular atrophy, Duchenne's muscular dystrophy, congenital muscular dystrophy, and congenital myopathies. A disease- specific approach is recommended as the wide variety of different neuromuscular pathologies requires careful planning of treatment strategies best managed in a team approach.


Retinal differentiation from multipotential pineal cells of the embryonic quail.
Pineal cells of the embryonic quail are multipotent stem cells which are able to differentiate in vitro into pigmented epithelial cells, lens cells and skeletal muscle fibers. Neuronal expression was added in this study in the repertory of differentiating potency of pineal cells. We used immunohistochemical methods to characterize neuronal properties with antibodies against serotonin, GABA, tyrosine hydroxylase and neuron-specific antigen (HPC-1) in addition to the enzyme histochemistry for acetylcholinesterase activity. Cells in the culture were found to be positively stained with these methods, suggesting that embryonic pineal cells are neuropotent to differentiate various types of neuronal cells. We have studied the culture conditions which favor increment of neuronal cells with extension of neuritic processes, and we have found that neuronal cells are maintained for quite a long period under suppressive conditions of DNA synthesis and under the effect of basic fibroblast growth factor (FGF). Suppression of DNA synthesis was achieved by the addition of aphidicolin, an inhibitor of DNA polymerase alpha, in the medium. Time lapse videograph revealed two different cell types participated in neurogenesis; a minor population of small round cells and a major one of flat epithelial cells. Since embryonic quail pineal cells have been shown to differentiate into two types of photoreceptors, the present results show wider retinal potency of cell differentiation by embryonic pineal cells. The cessation of DNA synthesis as well as growth factor(s) may be positively involved in the mechanisms of determination and differentiation of pineal neurons.


The isochore organization of the human genome and its evolutionary history--a review.
This review will first present some properties (including compositional pattern, correlations between isochores and chromosomal bands, and gene distribution) of the human genome, the most extensively studied among vertebrate genomes. It will then explain how these properties came about during the evolution of the vertebrates.


Resetting processes with noninstantaneous return.
We consider a random two-phase process which we call a reset-return one. The particle starts its motion at the origin. The first, displacement, phase corresponds to a stochastic motion of a particle and is finished at a resetting event. The second, return, phase corresponds to the particle's motion toward the origin from the position it attained at the end of the displacement phase. This motion toward the origin takes place according to a given equation of motion. The whole process is a renewal one. We provide general expressions for the stationary probability density function of the particle's position and for the mean hitting time in one dimension. We perform explicit analysis for the Brownian motion during the displacement phase and three different types of the return motion: return at a constant speed, return at a constant acceleration with zero initial speed, and return under the action of a harmonic force. We assume that the waiting times for resetting events follow an exponential distribution or that resetting takes place after a fixed waiting period. For the first two types of return motion and the exponential resetting, the stationary probability density function of the particle's position is invariant under return speed (acceleration), while no such invariance is found for deterministic resetting, and for exponential resetting with return under the action of the harmonic force. We discuss necessary conditions for such invariance of the stationary PDF of the positions with respect to the properties of the return process, and we demonstrate some additional examples when this invariance does or does not take place.


Effects of a human plasma fraction on the release of chemotactic factors and anaphylatoxin from complement.
A fraction prepared from normal human plasma inhibits the release of chemotactic factors and anaphylatoxin when complement is activated by the alternate but not by the classical pathway. The fraction gave no interference with the actions of the released substances on either leucocytes or guinea-pig isolated ileum. The possible relation of this effect to the mechanism of the anti-inflammatory actions of the plasma fraction is discussed.


The Nomenclature, Terminology and Lexicon of Breast Surgery: Are We Really Saying the Same Thing?
This study investigated inconsistencies in the use of descriptors in breast surgery and recommends a novel nomenclature that will be adopted and standardized among plastic surgeons. The study used a modified Delphi methodology to first identify redundant descriptors or those with multiple interpretations, and then achieve consensus on ideal recommended nomenclature in breast surgery. The Delphi panel agreed that there was misuse of and lack of a clear definition for several terms, and recommended removal of these subjective terms. Replacement with more anatomic nomenclature was suggested. Stretch deformity, pectoral banding, and implant-gland mismatch were introduced as new terms.


Rh-Endostatin Plus Irinotecan/Cisplatin as Second-Line Therapy for Advanced Esophageal Squamous Cell Carcinoma: An Open-Label, Phase II Study.
This open-label, phase II study aimed to investigate the efficacy and safety of recombinant human endostatin (Rh-endostatin) plus irinotecan/cisplatin as second-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). Eligible patients received 15mg/m2 Rh-endostatin as a continuous intravenous pump infusion (7 continuous days), 60mg/m2 irinotecan (days 1 and 8), and 60mg/m2 cisplatin (day 1) every 3 weeks. The primary endpoint was progression-free survival (PFS). A total of 50 patients were assessable for efficacy and safety analysis. The median follow-up was 10.97 months (95%CI: 7.03-19.42) as the data cutoff. Median PFS was 4.01 months (95% CI: 3.19-5.49), and median overall survival (OS) was 12.32 months (95% CI: 8.21-17.45); 13 (26%; 95% CI: 15.87-39.55) of 50 patients had an objective response, and 31 (62%; 95% CI: 48.15-74.14) had disease control. Grade 3 or greater treatment-related adverse events (AEs) occurred in 12 (24.0%) patients, and no deaths were reported. The common grade 3 or greater AEs were leucopenia (18.0%) and neutropenia (16.0%). Five (10%) patients discontinued treatment because of AEs. Rh-endostatin plus irinotecan/cisplatin showed promising anti-tumor activity in advanced ESCC patients with a good safety profile in the second-line setting, which warrants further study in this population. (ClinicalTrials.gov identifier: NCT03797625).


Stability of cocaine dose-response functions at different inter-dose intervals.
Past research has found that daily administration of cocaine can lead to tolerance to its behavioral effects, and that tolerance can develop even when the dose is varied from day to day. The present experiment examined effects of administering varied doses of cocaine at a variety of inter-dose intervals ranging from once per week to everyday. Pigeons pecked on a fixed-ratio 20 schedule of reinforcement. A dose-response function for cocaine was assessed eight consecutive times during each of four phases of the experiment to assess the stability of effects of each dose. In Phase 1, subjects were administered a dose of cocaine or saline vehicle every seventh day. One subject developed tolerance by the end of this phase and was not studied further. In Phase 2, doses were administered every fourth day. During Phase 3, doses were administered every 2 days. In the final phase, doses were administered everyday. Dose-response curves were generally similar both within and across phases, regardless of inter-dose interval. No subjects developed tolerance during Phases 2, 3, and 4, suggesting that some aspect of the drug regimen prevented the development of tolerance when cocaine was given frequently.


Successful treatment of a patient with recurrent furunculosis by vitamin C: improvement of clinical course and of impaired neutrophil functions.
Neutrophils play a critical role in host defense against a variety of microbial pathogens. There is much information to suggest a role for vitamin C in the physiology of neutrophils. Thus, the effects of vitamin C treatment were studied in a patient with a history of recurrent furunculosis who showed altered neutrophil functions. Superoxide generation was measured by cytochrome C reduction. Phagocytosis of opsonized zymosan by neutrophils and chemotaxis on agarose plates were determined. Chemotaxis, phagocytosis, and superoxide generation of the patient's neutrophils were significantly lower than those of the matched control. Treatment with vitamin C (500 mg/day) for 30 days caused a dramatic clinical response and a significant improvement of all three neutrophil functions to values similar to those of the controls. We suggest that the patient described here had a temporary defect in neutrophil functions. The treatment with vitamin C probably prevented neutrophil oxidation, thus contributing to recovery of neutrophil function and arrest of furunculosis.


Long-term stability of laboratory tests and practical implications for quality management.
Long-term stability of analytical performance is required for adequate patient management. We investigated the use of patient data to document test stability, and the relevance of observed instabilities on a surrogate medical outcome. We used multiyear patient and internal quality control (IQC) data from two laboratories for tests to monitor chronic kidney and thyroid disease. We plotted moving means of the 50th percentiles of stratified patient data and of the daily IQC means. We evaluated observed instabilities based on goals inferred from the analytes' biological variation and investigated their effect on classification of results against reference intervals. Patient and IQC data generally matched well, except for analytes, for which other than analytical variation sources prevailed. Analytical instabilities were predominantly due to reagent/calibrator lot changes, however, for immunoassays also to within-lot instabilities, urging frequent recalibrations. The relevance of biased results on medical decisions ranged from negligible to very pronounced, indicating the need for assessment of analytical performance in relation to quality goals inferred from biological variation. Patient percentiles offer great potential to assess/monitor the medium- to long-term analytical stability of a test within certain constraints. Differences in analytical quality between assays can significantly affect medical outcome.


Kinetics, energy efficiency and mathematical modeling of thin layer solar drying of figs (Ficus carica L.).
First convectional thin layer drying of two fig (Ficus carica L.) varieties growing in Moroccan, using partially indirect convective dryer, was performed. The experimental design combined three air temperatures levels (60, 70 and 80 °C) and two air-flow rates (150 and 300 m3/h). Fig drying curve was defined as a third-order polynomial equation linking the sample moisture content to the effective moisture diffusivity. The average activation energy was ranged between 4699.41 and 7502.37 kJ/kg. It raised proportionally with the air flow velocity, and the same pattern were observed for effective moisture diffusivity regarding drying time and velocity. High levels of temperature (80 °C) and velocity (300 m3/h) lead to shorten drying time (200 min) and improve the slices physical quality. Among the nine tested models, Modified Handerson and Pabis exhibited the highest correlation coefficient value with the lowest chi-square for both varieties, and then give the best prediction performance. Energetic investigation of the dryer prototype showed that the total use of energy alongside with the specific energy utilization (13.12 and 44.55 MWh/kg) were inversely proportional to the velocity and drying temperature. Likewise, the energy efficiency was greater (3.98%) higher in drying conditions.


Sequential injection system with multi-parameter analysis capability for water quality measurement.
A simple sequential injection (SI) system with capability to determine multi-parameter has been developed for the determination of iron, manganese, phosphate and ammonium. A simple and compact colorimeter was fabricated in the laboratory to be employed as a detector. The system was optimized for suitable conditions for determining each parameter by changing software program and without reconfiguration of the hardware. Under the optimum conditions, the methods showed linear ranges of 0.2-10 mg L(-1) for iron and manganese determinations, and 0.3-5.0 mg L(-1) for phosphate and ammonium determinations, with correlation coefficients of 0.9998, 0.9973, 0.9987 and 0.9983, respectively. The system provided detection limits of 0.01, 0.14, 0.004 and 0.02 mg L(-1) for iron, manganese, phosphate and ammonium, respectively. The proposed system has good precision, low chemical consumption and high throughput. It was applied for monitoring water quality of Ping river in Chiang Mai, Thailand. Recoveries of the analysis were obtained in the range of 82-119%.


Meatal-sparing dorsal onlay vaginal graft urethroplasty: widening the surgical horizons of female urethral stricture.
Female urethral stricture is an uncommon but challenging entity in the spectrum of female pelvic dysfunctions. There are various reconstructive techniques but none can be recommended over another. We present a case of meatal-sparing dorsal onlay vaginal graft urethroplasty as a surgical variation of the standard dorsal approach. This is a step to improve the results of the dorsal approach and overcome its limitations. In this video we present meatal-sparing dorsal onlay vaginal graft urethroplasty as a modification of the conventional dorsal approach. Sexual function can be preserved by dorsal plane dissection away from the clitoral neurovascular bundle. Excessive blood loss is avoided by limited mobilisation and dissection of the urethra. Meatal reconstruction is avoided by slitting the urethra directly over the strictured mid-urethral segment, thus averting a widened meatus and spraying of the urinary stream. Female urethroplasty provides excellent cure rates. Meatal-sparing dorsal onlay vaginal graft urethroplasty can be considered in mid- and proximal urethral strictures. This simple and effective approach can widen the surgical horizons in the treatment of female urethral stricture and reduce its complications.


Fractures of the mandible caused by stoning--return of an ancient entity.
Fifteen patients with mandibular fractures related to stone-throwing incidents are presented. Three illustrative cases are discussed in detail. Criteria for selecting management by early surgical intervention or a conservative approach are discussed. The ultimate aim in management is to preserve the greatest possible amount of function with the least risk and morbidity for the patients.


A simple method for accurately locating and cutting strips from the isoelectric focusing gel during two-dimensional electrophoresis using the PhastSystem.
A rapid and simple method has been developed for precisely locating and cutting 1-3 mm strips from the isoelectric focusing gel during two-dimensional electrophoresis using the PhastSystem. The protocol utilizes an easily constructed styrofoam template with marks to guide accurate cutting of the strips from the sample lanes. This system greatly enhances the reproducibility and quality of the two-dimensional patterns obtained.


Herpes simplex virus type 2 infection of neonatal mice.
We have demonstrated that newborn mice can be infected orally with herpes simplex virus type 2. Transplacental and transvaginal transmission of herpes simplex virus type 2 did not occur in our mice. Failure to produce natural transvaginal infection in mice may be explained by the relatively short period of exposure to the virus during parturition. These experiments demonstrate that high oral doses of herpes simplex virus type 2 can produce disseminate herpes neonatal infection in mice and therefore may be useful in future investigations into the mechanism and the treatment of this disease.


A cell fractionation approach for the quantitative analysis of subcellular drug disposition.
The purpose of this work was to develop and validate a method that can be used to quantify drugs associated with intracellular compartments. The human leukemic cell line U-937 was used to evaluate the distribution of model compounds with known and different subcellular distribution profiles. Lysotracker Red is a lysosomal vital stain and doxorubicin is an anticancer agent with a strong propensity for nuclear accumulation in U-937 cells. After incubation with compounds, cells were separated into fractions containing nuclei, cytosol, and cytoplasmic organelles (lysosomes, mitochondria, Golgi apparatus). Compounds contained within isolated fractions were subsequently extracted and analyzed by high-performance liquid chromatography. Diffusion of compounds from isolated organelles was also investigated. Using this approach we have shown that the model compounds Lysotracker Red and doxorubicin preferentially accumulated within lysosomes and nuclei, respectively. We have reproducibly determined concentrations of these compounds in each of the cellular fractions. We have also shown that diffusion of these compounds from isolated cellular compartments was minimal during the time required to complete the experimental procedure. The analytical approach described in this manuscript yielded reproducible quantitative data regarding the intracellular distribution of model compounds in U-937 cells. With the aid of a relatively sensitive analytical assay, this technique should be useful for most drugs that have a specific concentrative mechanism for organelle accumulation similar to Dox and LTR.


Occurrence, source apportionment and source-specific risk assessment of antibiotics in a typical tributary of the Yellow River basin.
The spatial distributions, sources, and source-specific risk apportionments of 26 antibiotics (5 categories) in the Fenhe River basin were determined based on sample data. The results showed that antibiotics were widely distributed in the surface water. There were significant differences between the different types of antibiotics, and the highest mean concentration was that of the sulfonamide category (33.74 ng/L), accounting for 36% of the total antibiotic concentration. Spatially, all antibiotics were mainly detected in the middle and downstream areas. The ecological risk assessment results showed that the significant risk rate of antibiotics accounted for 70% and was mainly distributed in the downstream area; however, the risks differed between the 5 categories. Quinolone antibiotics exhibited the highest significant risk rate, reaching 100%. The ecological risk associated with sulfamethoxazole was the highest among all detected antibiotics. The following five main factors influenced the antibiotic concentrations: aquaculture, pharmaceutical wastewater, livestock discharges, domestic sewage, and sewage treatment plants. Among these, pharmaceutical wastewater sources contributed the most (35%) to the total antibiotic concentration, and were distributed throughout the river. Although livestock discharges were not the main reason for the high level of ecological risk, these discharges were highest at certain sites in the midstream region. Different pollution sources posed different levels of ecological risk to the Fenhe River basin, the highest of which was pharmaceutical wastewater with a significant risk rate of 58%.


Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties.
Ionizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis. Rats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation. Serum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2'-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology. These results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.


Polyvinyl alcohol-based electrospun matrix as a delivery system for nanoemulsion containing chalcone against Leishmania (Leishmania) amazonensis.
Cutaneous leishmaniasis is a worldwide public health problem. Conventional therapies, in addition to the high cost, have many adverse effects and cases of parasite's resistance. Chalcones are secondary metabolites precursors in the flavonoid pathway and can be obtained naturally, but with low yield from plant raw material. Thus, the use of synthetic chalcones has been a promising strategy for the development of molecules with leishmanicidal activity. Thus, this work aimed to develop a controlled release system of two synthetic chalcone (trans-chalcones and 3'-(trifluormethyl)-chalcone) using polyvinyl alcohol nanofibers (PVA) as scaffold. The association of chalcones to the nanofibers was made by nanoemulsions (NE) thereof, i.e., a colloidal system on a nanometric scale, which allows compounds with opposite polarities to remain miscible and stable throughout their manipulation. Chalcone nanoemulsions were developed using the spontaneous emulsification technique. The NE were characterized regarding their particle size, polydispersion index (PDI), and zeta potential. The results showed NE with spherical shape, absolute values of zeta potential were higher than 30 mV and homogeneous distribution pattern (PDI < 0.3). Dynamics light scattering (DLS) analysis showed similar hydrodynamic rays, i.e., 180 nm (trans-chalcone NE) and 178 nm (NE containing 3'-(trifluormethyl)-chalcone, in addition to presenting encapsulation efficiency values close to 100 %. Subsequently, the NE were added to a polymeric solution of polyvinyl alcohol (PVA) and processed via the electrospinning technique affording a PVA matrix (15 %, w/v) nanofiber containing the chalcones NE at 1 mg.mL-1. In a follow-up experiment, the skin permeation assay of the PVA matrix-chalcone NE was performed in vitro using Franz type diffusion cells and porcine ear as biological model of study. The results showed that the treatments with the nanofibers containing the chalcone NE were retained mainly in the stratum corneum, while the NE suspensions containing chalcone were retained in the epidermis and dermis. This result is thought to be relevant, since parasites are located mainly in the dermis. Further, in vitro assay against the amastigote form of L. (L) amazonensis, showed IC50 values to trans-chalcone and 3'-(trifluormethyl)-chalcone of 24.42 ± 6.76 μg.mL-1 and 15.36 ± 4.61 μg.mL-1, respectively. In addition to improving the solubility of the compounds tested in culture medium without using organic solvents, chalcones in nano-emulsified form reduced the IC50 to 9.09 ± 1.24 μg.mL-1 (trans-chalcone) and 10.27 ± 2.27 μg.mL-1 (3'-(trifluormethyl)-chalcone) which confirmed the potential of the nanoemulsion containing chalcone for cutaneous leishmaniasis treatment.


Somatostatin analogue administration prevents increase in kidney somatomedin C and initial renal growth in diabetic and uninephrectomized rats.
In a previous study we demonstrated that the kidney content of somatomedin C was maximal one to two days after uninephrectomy or induction of diabetes, and that insulin treatment prevented an increase in kidney somatomedin C as well as kidney growth in diabetic animals. In the present study we have examined the effect of a somatostatin analogue on kidney somatomedin C and initial renal growth in the two experimental situations. The kidney hypertrophy in untreated diabetic animals amounted to 23% four days after streptozotocin injection and followed an increase in kidney somatomedin C content of 60% reaching the maximum after 48 h. In young and old uninephrectomized rats kidney growth was 19% and 16% after four days. In young animals a prompt increase of 50% in kidney somatomedin C was seen as reaching the maximum after 24 h, while the somatomedin C content in kidneys from old animals was maximal after 48 h (increase of 58%) in good accordance with the slightly slower kidney growth. The new findings of the present study are that administration of a long-acting somatostatin analogue (Sandostatin) effectively prevented the obligatory increase in kidney somatomedin C content as well as kidney growth both in experimental diabetes and after uninephrectomy. It is noteworthy that Sandostatin administration did not alter the metabolic state in diabetic animals indicating that the inhibition of kidney hypertrophy could not be attributed to improved metabolic control. The results thus support the concept that somatomedin C is involved in initial diabetic and post-nephrectomy renal growth.


Synthesis of p-trifluoroacetamidophenyl beta-D-glucopyranoside 4-(D-ribit-5-yl phosphate) corresponding to the Haemophilus influenzae type A capsular antigen.
The synthesis is described of the title glycoside which corresponds to the Haemophilus influenzae type a capsular antigen. The hydrogenphosphonate method was used with 3,3'-(chlorophosphonylidene)bis(2-oxo-1,3-oxazolidene) as the condensing agent.


Molecular characterization of hepatitis A virus isolates from environmental and clinical samples in Greece.
Hepatitis A virus (HAV) strains detected in environmental and clinical samples were analysed to characterize the genotypes of HAV circulating in Greece. Fifty (50) sewage samples were collected from Patras (South-Western Greece) and Alexandroupolis (North-Eastern Greece) from 2007 until 2009, accordingly. The clinical samples derived from an HAV outbreak involved populations from three neighbouring prefectures of North-Eastern Greece (Xanthi, Rodopi, and Evros). HAV particles were detected by nested RT-PCR, using a previously validated set of primers to amplify a 290-bp fragment encompassing the 5'-NTR. Positive HAV samples were confirmed by sequencing of the PCR product. To determine the relatedness between the different isolated sequences, a phylogenetic tree was constructed. Results showed a 100% prevalence of genotype I, and particularly subgenotype IA. The analyzed HAV strains were closely related between them with the percentage of nucleotide identity ranging between 96% and 100%. The study revealed the major prevalence of circulating strains of IA genotype in Greece and underlined the usefulness of molecular methods for the detection and typing of viruses in both environmental and clinical samples. The present study is, to our knowledge, the first in Greece to depict the simultaneous molecular characterization of HAV strains isolated from both clinical and environmental samples.


Occipital Intradiploic Pseudomeningocele - A Rare Complication of Pediatric Posterior Cranial Fossa Surgery: Case Report and Review of the Literature.
Intradiploic pseudomeningoceles, also called intradiploic cerebrospinal fluid (CSF) fistulas, are abnormal CSF collections between the two bony tables of the calvaria resulting from postsurgical CSF leakage. To date, only six cases of intradiploic pseudomeningocele have been reported, all occurring in the occipital area. In this paper, we report the seventh case of late-onset occipital intradiploic pseudomeningocele (OIP) occurring in a young female patient who underwent surgery for the removal of a cerebellar pilocytic astrocytoma. In this regard, we also review the literature on the few recognized cases of OIP. The case of an 18-year-old female patient known to our institute for an operation 12 years earlier to remove a pilocytic astrocytoma is illustrated. At admission, the patient complained only of occasional orthostatic headache. Brain imaging demonstrated a pseudomeningocele extended intradiploically from the occipital squama to the condylar and clivus regions, thinning both occipital bone tables and dilating the CSF-filled diploe. Watertight duroplasty and cranioplasty were effectively performed. Pediatric patients undergoing posterior cranial fossa craniotomy/craniectomy may postoperatively develop OIP. In this setting, treatment of any dural CSF fistula should be considered because of the risk of progressive extension and bone erosion.


Maternal smoking during pregnancy is associated with mitochondrial DNA methylation.
Maternal smoking during pregnancy (MSDP) has detrimental effects on fetal development and on the health of the offspring into adulthood. Energy homeostasis through ATP production via the mitochondria (mt) plays a key role during pregnancy. This study aimed to determine if MSDP resulted in differences in DNA methylation to the placental mitochondrial chromosome at the transcription and replication control region, the D-Loop, and if these differences were also present in an alternate neonatal tissue (foreskin) in an independent birth cohort. We investigated mtDNA methylation by bisulfite-pyrosequencing in two sections of the D-Loop control region and in long interspersed nuclear element-1 (LINE-1) genomic sequences in placenta from 96 mother-newborn pairs that were enrolled in a Rhode Island birth cohort along with foreskin samples from 62 infants from a Kentucky birth cohort. In both placenta and foreskin, mtDNA methylation in the light chain D-Loop region 1 was positively associated with MSDP in placenta (difference+2.73%) (P=0.001) and foreskin (difference+1.22%) (P=0.08). Additionally, in foreskin, a second segment of the D-Loop-heavy chain region 1 showed a small but significant change in methylation with MSDP (+0.4%, P=0.04). No methylation changes were noted in either tissue at the LINE-1 repetitive element. We identified a similar pattern of epigenetic effect to mitochondria arising in cells from different primordial lineages and in different populations, associated with MSDP. These robust and consistent results build evidence that MSDP may impact mt D-Loop methylation, as one mechanism through which this exposure affects newborn health.


A case of pancreatic walled-off necrosis successfully treated with endoscopic ultrasonography-guided drainage using Hot AXIOS System in a patient with severe hemophilia A.
Hemophilia A causes a bleeding tendency due to the congenital absence of coagulation factor VIII or the production of antibodies against it. It is challenging to perform invasive procedures in patients with hemophilia A. Walled-off necrosis (WON) is a serious complication of acute pancreatitis. Recently, a new metallic stent has been used to drain WON. We treated a 32-year-old man who developed WON due to acute pancreatitis and has severe congenital hemophilia A. Since conservative treatment was ineffective, he underwent endoscopic ultrasonography (EUS)-guided transgastric WON drainage using a new metallic stent Hot AXIOS System. The procedure was successful without any severe hemorrhagic complications. Before and after the procedure, his clotting factors were strictly monitored by a hemophilia specialist. EUS-guided pancreatic cyst drainage can be an effective option for WON in patients with severe congenital hemophilia, under adequate management.


The pathological features and circumstances of death of lethal crush/traumatic asphyxia in adults--a 25-year study.
A 25-year retrospective study of cases of crush/traumatic asphyxia autopsied at Forensic Science SA, Adelaide, Australia from 1980 to 2004 was undertaken. A total of 79 cases of crush asphyxia was found consisting of 63 males (80%) and 16 females (20%). The age range of the males was 19-86 years (mean=41.8 years) and of the females was 19-75 years (mean=38.6 years). In 18 cases the exact circumstances of death were unclear, leaving 61 cases in which details of the fatal episode were available. Major categories included vehicle crashes (N=37), industrial accidents (N=9), farm accidents (N=6) and entrapment beneath vehicles (N=5). Forty of the 79 victims (51%) had only very minor bruises and abrasions; 28 (35%) had evidence of chest compression with rib and sternal fractures and large areas of soft tissue bruising of the chest; 7 cases (9%) had other significant injuries or findings that had contributed to death. All of these victims had signs of crush asphyxia in the form of intense purple congestion and swelling of the face and neck, and/or petechial hemorrhages of the skin of the face and/or conjunctivae. The pattern of pathological findings of crush asphyxia was not influenced by the presence or absence of concomitant serious or lethal injuries. In 4 cases (5%) where the circumstances of the lethal episode were those of crush asphyxia there were no characteristic pathological findings. This study has shown that a high percentage of crush asphyxias may be caused by vehicle accidents. It has also demonstrated that on occasion fatal crush asphyxia may have to be a diagnosis of exclusion, made only when there are characteristic death scene findings, and no evidence of lethal natural diseases or injuries at autopsy, with negative toxicological screening.


Rectal intussusception and unexplained faecal incontinence: findings of a proctographic study.
The aetiology of faecal incontinence is multifactorial, yet there remains an approach to assessment and treatment that focusses on the sphincter. Rectal intussusception (RI) is underdiagnosed and manifests primarily as obstructed defecation. Yet greater than 50% of these patients admit to faecal incontinence on closer questioning. We aimed to evaluate the incidence of RI at evacuation proctography selectively undertaken in the evaluation of patients with faecal incontinence. Patients with faecal incontinence seen in a pelvic floor clinic were evaluated with anorectal physiology and ultrasound. Where the faecal incontinence was not fully explained by physiology and ultrasound, evacuation proctography was undertaken. Studies were classified as 'normal', 'low-grade RI' (recto-rectal), 'high-grade RI' (recto-anal) or 'anismus'. Forty patients underwent evacuation proctography (33 women, 83%). Median age was 63 years (range 34-77 years). Seven patients (17%) had a normal proctogram. Three (8%) had recto-rectal RI. Twenty-five (63%) demonstrated recto-anal RI. Five patients (12%) had anismus. Recto-anal intussusception is common in patients undergoing selective evacuation proctography for investigation of faecal incontinence. The role of recto-anal intussusception in the multifactorial aetiology of faecal incontinence has been largely overlooked. Evacuation proctography should be considered as part of routine work-up of patients with faecal incontinence.


Surgical exposures for distal humerus fractures: a review.
The majority of distal humerus fractures have complex fracture patterns, with displaced articular segments, requiring operative intervention. The goals of surgery are anatomic reduction and rigid internal fixation via an operative approach that balances maximum required exposure with minimum soft tissue or bony disruption that may necessitate postoperative protection. The selection of a surgical approach depends on multiple factors, including, fracture pattern, extent of articular involvement, associated soft tissue injury, rehabilitation protocols, and surgeon preference. This review focuses on the various surgical approaches to the distal humerus.


The layer concept: utilization in determining the pain generators, pathology and how structure determines treatment.
The level of understanding of pain in the non-arthritic hip has made significant strides in the last couple of decades beginning with the discoveries of Reinhold Ganz, MD. However, even with the detection of subtle bony abnormalities, including femoroacetabular impingement, a clinician's ability to differentiate pain generators in the hip has been ambiguous. Deciphering the etiology of the pathology versus the pain generator is essential in prescribing the proper treatment. The Layer Concept developed by Dr. Bryan Kelly, is a systematic means of determining which structures about the hip are the source of the pathology, which are the pain generators and how to then best implement treatment. Four layers will be discussed in this article. Layer I, the osseous layer, Layer II, the inert tissue layer, Layer III, the contractile layer and Layer IV, the neuromechanical layer.


Development of accreditation standards for midwifery clinical education in Iran.
Accreditation is one of the most important methods of quality assurance and improvement in medical education. In Iran, there are no specific midwifery education accreditation standards. This study was designed to develop accreditation standards for midwifery clinical education in Iran. This study was performed in Iran in 2021. It consisted of two phases. In the first phase, accreditation standards for midwifery education in the United Kingdom, the United States, Australia and the International Confederation of Midwives were thoroughly examined through a narrative review. The domains obtained from this phase were used as a framework for coding in the second phase. In the second phase, a qualitative study was conducted with a directed content analysis approach to determine standards and criteria for clinical midwifery education accreditation in Iran. Participants were policymakers and senior managers of midwifery education, faculty members of midwifery departments with clinical teaching experience, and final year undergraduate midwifery students. The participants were selected by purposive sampling method, and data collection continued until data saturation. The standards and accreditation criteria of midwifery education from the review study were formed 6 domains: Mission and goals; Curricula; Clinical instructors; Students, Clinical setting; and Assessment. In the second phase, data analysis led to the extraction of 131 codes, which were divided into 35 sub-subcategories, 15 sub-categories, and 6 main categories. Implementing the specific and localized standards of clinical midwifery education in Iran can lead to improved quality of clinical education programs.


Understanding the acceptability of e-mental health--attitudes and expectations towards computerised self-help treatments for mental health problems.
E-mental health and m-mental health include the use of technology in the prevention, treatment and aftercare of mental health problems. With the economical pressure on mental health services increasing, e-mental health and m-mental health could bridge treatment gaps, reduce waiting times for patients and deliver interventions at lower costs. However, despite the existence of numerous effective interventions, the transition of computerised interventions into care is slow. The aim of the present study was to investigate the acceptability of e-mental health and m-mental health in the general population. An advisory group of service users identified dimensions that potentially influence an individual's decision to engage with a particular treatment for mental health problems. A large sample (N = 490) recruited through email, flyers and social media was asked to rate the acceptability of different treatment options for mental health problems on these domains. Results were analysed using repeated measures MANOVA. Participants rated the perceived helpfulness of an intervention, the ability to motivate users, intervention credibility, and immediate access without waiting time as most important dimensions with regard to engaging with a treatment for mental health problems. Participants expected face-to-face therapy to meet their needs on most of these dimensions. Computerised treatments and smartphone applications for mental health were reported to not meet participants' expectations on most domains. However, these interventions scored higher than face-to-face treatments on domains associated with the convenience of access. Overall, participants reported a very low likelihood of using computerised treatments for mental health in the future. Individuals in this study expressed negative views about computerised self-help intervention and low likelihood of use in the future. To improve the implementation and uptake, policy makers need to improve the public perception of such interventions.


Fluid dynamics and forces in the HH25 avian embryonic outflow tract.
The embryonic outflow tract (OFT) eventually undergoes aorticopulmonary septation to form the aorta and pulmonary artery, and it is hypothesized that blood flow mechanical forces guide this process. We performed detailed studies of the geometry, wall motions, and fluid dynamics of the HH25 chick embryonic OFT just before septation, using noninvasive 4D high-frequency ultrasound and computational flow simulations. The OFT exhibited expansion and contraction waves propagating from proximal to distal end, with periods of luminal collapse at locations of the two endocardial cushions. This, combined with periods of reversed flow, resulted in the OFT cushions experiencing wall shear stresses (WSS or flow drag forces) with elevated oscillatory characteristics, which could be important to signal for further development of cushions into valves and septum. Furthermore, the OFT exhibits interesting double-helical flow during systole, where a pair of helical flow structures twisted about each other from the proximal to distal end. This coincided with the location of the future aorticopulmonary septum, which also twisted from the proximal to distal end, suggesting that this flow pattern may be guiding OFT septation.


Effects of occupational therapy on quality of life in breast cancer patients: A systematic review and meta-analysis.
The objective was to discuss the impact of occupational therapy on different domains of quality of life in breast cancer patients. We performed a literature search to identify articles published before June 27, 2023, using the following databases: PubMed, Embase, Web of Science, Cochrane Library, and Scopus. The objective was to discuss the impact of occupational therapy on different domains of quality of life in breast cancer patients. We performed a literature search to identify articles published before June 27, 2023, using the following databases: PubMed, Embase, Web of Science, Cochrane Library, and Scopus. This study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Randomized controlled trials that reported the effects of occupational therapy on quality of life in breast cancer patients were identified. Two reviewers independently assessed eligibility, extracted data, and determined risks of bias. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated using random-effects meta-analyses. Galbraith plots, meta-regression analysis, subgroup analysis, and sensitivity analysis were used to identify heterogeneity in treatment effects. Eight studies were included, with a total of 543 patients. The experimental group exhibited better global health (pooled SMD = 0.640, 95% CI = 0.251-1.028, P = .001), physical health (pooled SMD = 0.640, 95% CI = 0.251-1.028, P = .019), social health (pooled SMD = 0.251, 95% CI = 0.011-0.490, P = .040), and cognitive function (pooled SMD = 0.863, 95% CI = 0.266-1.460, P = .05) and improve fatigue (pooled SMD = -0.389, 95% CI = -0.586 to -0.192, P = .000), and role function (pooled SMD = 0.287, 95% CI = 0.029-0.546, P = .029) than the control group. The 2 groups exhibited comparable emotional health (pooled SMD = 0.243, 95% CI = -0.051 to 0.536, P = .105) and pain (pooled SMD = -0.312, 95% CI = -0.660 to 0.036, P = .079). The current evidence shows that occupational therapy can improve the quality of life of breast cancer patients, especially their global health, physical health, social health, cognitive function, fatigue, and role function.


DNA methylation and inflammatory skin diseases.
Epigenetics is the study of heritable changes in gene expression that do not originate from alternations in the DNA sequence. Epigenetic modifications include DNA methylation, histone modification, and gene silencing via the action of microRNAs. Epigenetic dysregulation has been implicated in many disease processes. In the field of dermatology, epigenetic regulation has been extensively explored as a pathologic mechanism in cutaneous T-cell lymphoma (CTCL), which has led to the successful development of epigenetic therapies for CTCL. In recent years, the potential role of epigenetic regulation in the pathogeneses of inflammatory skin diseases has gained greater appreciation. In particular, epigenetic changes in psoriasis and atopic dermatitis have been increasingly studied, with DNA methylation the most rigorously investigated to date. In this review, we provide an overview of DNA methylation in inflammatory skin diseases with an emphasis on psoriasis and atopic dermatitis.