Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.
Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients receiving high-dose inhaled corticosteroids (ICSs) is uncertain. We sought to determine whether airway type 2 inflammation persists in patients treated with ICSs and to evaluate the clinical features of patients with steroid-resistant airway type 2 inflammation. We used quantitative PCR to generate a composite metric of type 2 cytokine gene expression (type 2 gene mean [T2GM]) in induced sputum cells from healthy control subjects, patients with severe asthma receiving ICSs (n = 174), and patients with nonsevere asthma receiving ICSs (n = 85). We explored relationships between asthma outcomes and T2GM values and the utility of noninvasive biomarkers of airway T2GM. Sputum cell T2GM values in asthmatic patients were significantly increased and remained high after treatment with intramuscular triamcinolone. We used the median T2GM value as a cutoff to classify steroid-treated type 2-low and steroid-resistant type 2-high (srT2-high) subgroups. Compared with patients with steroid-treated type 2-low asthma, those with srT2-high asthma were older and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when body mass index was less than 40 kg/m2 but not when it was 40 kg/m2 or greater, whereas blood IgE levels strongly predicted srT2-high asthma when age was less than 34 years but not when it was 34 years or greater. Despite ICS therapy, many asthmatic patients have persistent airway type 2 inflammation (srT2-high asthma), and these patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type 2 inflammation.


A novel in-plane passive microfluidic mixer with modified Tesla structures.
An innovative in-plane passive micromixer using modified Tesla structures, which are used as passive valves, has been designed, simulated, fabricated and successfully characterized in this paper. Simulation and experimental results of the developed novel micromixer have shown excellent mixing performance over a wide range of flow conditions in the micro scale. The micromixer realized in this work has achieved even better mixing performance at a higher flow rate, and its pressure drop is less than 10 KPa at the flow rate of 100 microl min(-1). This micromixer shows characteristics similar to Taylor dispersion, with contributions from both diffusion and convection. The mixer has a diffusion domain region at low flow rate, but it moves to a convection domain region at high flow rate. Due to the simple in-plane structure of the novel micromixer explored in this work, the mixer can be easily realized and integrated with on-chip microfluidic devices and micro total analysis systems (micro-TAS).


Aggressive behavior of nonmelanotic skin cancers in solid organ transplant recipients.
The increased incidence of skin cancers in solid organ transplant recipients (OTR) has been well established. However, our understanding of the potential aggressive behavior of these cancers has been largely based on the findings of multiple different studies analyzing isolated indicators of aggressive behavior. The purpose of this study was to determine the aggressiveness of nonmelanotic skin cancers in a large transplant population compared with an immunocompetent control population with similar cancers. Immunosuppressed transplanted patients and an immunocompetent control group matched in size with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) were evaluated for the factors of aggressiveness. A retrospective chart review was performed. Data obtained included transplant type, number of cancers, local recurrence rate, lymph node involvement, lymphatic invasion, perineural invasion, deep spread, subsequent treatment with radiation or chemotherapy, and death from disease. Three hundred seven patients had SCC (OTR: 153, control: 154), and 246 patients had BCC (OTR: 123, control: 123). SCC in OTR was significantly more likely to have an increased number of primary tumors, deep tissue spread, perineural and lymphatic invasion, recurrence, and need for radiation or chemotherapy. BCC in OTR was not associated with more aggressive disease when compared with controls with BCC. SCC in OTR behaves significantly more aggressively than in immunocompetent patients. BCC in the OTR population does not seem to act more aggressively.


Biocompatibility of a New Antibacterial Compound and its Effect on the Mechanical Properties of Flowable Dental Composites (Animal Study).
Recently, new compound of 3, 5-dimethyl-1-thiocarboxamide pyrazole has been composed with excellent antibacterial property. Biocompatibility and its effects on mechanical properties of dental composites should be considered before clinical use. The purpose of this study was to evaluate the biocompatibility of 3, 5-dimethyl-1-thiocarboxamide pyrazole as a new antibacterial compound and its effect on the mechanical properties of dental composites. In this experimental study, a new antibacterial compound was synthesis by reaction between Thiosemicarbazide and 2, 4-Pentandione and tested on thirty male albino Wistar rats weighting 200-250gr. Rats were randomly divided into 3 groups of 10, each rat received 3 implants of 3,5-dimethyl-1-thiocarboxamide pyrazole, penicillin v and empty polyethylene tube. A pathologist, who was unaware of types of tested materials and timing, performed the examination of specimens. The depth of cure and flexural strength of resin composite was measured using Iso4049 standard technique. Compressive strength was determined according to Iso9917 standard. This compound was biocompatible and there was no significant difference in flexural strength and compressive strength of the composites containing 1% of this compound with the control group (p> 0.05). The 3, 5-dimethyl-1-thiocarboxamide pyrazole with a concentration of 1% in flowable composites can be very effective in preventing secondary caries.


Diffuse traumatic brain injury initially attenuates and later expands activation of the rat somatosensory whisker circuit concomitant with neuroplastic responses.
Traumatic brain injury can initiate an array of chronic neurological deficits, effecting executive function, language and sensorimotor integration. Mechanical forces produce the diffuse pathology that disrupts neural circuit activation across vulnerable brain regions. The present manuscript explores the hypothesis that the extent of functional activation of brain-injured circuits is a consequence of initial disruption and consequent reorganization. In the rat, enduring sensory sensitivity to whisker stimulation directs regional analysis to the whisker barrel circuit. Adult, male rats were subjected to midline fluid percussion brain or sham injury and evaluated between 1day and 42days post-injury. Whisker somatosensory regions of the cortex and thalamus maintained cellular composition as visualized by Nissl stain. Within the first week post-injury, quantitatively less cFos activation was elicited by whisker stimulation, potentially due to axotomy within and surrounding the whisker circuit as visualized by amyloid precursor protein immunohistochemistry. Over six weeks post-injury, cFos activation after whisker stimulation showed a significant linear correlation with time in the cortex (r(2)=0.545; p=0.015), non-significant correlation in the thalamus (r(2)=0.326) and U-shaped correlation in the dentate gyrus (r(2)=0.831), all eventually exceeding sham levels. Ongoing neuroplastic responses in the cortex are evidenced by accumulating growth associated protein and synaptophysin gene expression. In the thalamus, the delayed restoration of plasticity markers may explain the broad distribution of neuronal activation extending into the striatum and hippocampus with whisker stimulation. The sprouting of diffuse-injured circuits into diffuse-injured tissue likely establishes maladaptive circuits responsible for behavioral morbidity. Therapeutic interventions to promote adaptive circuit restructuring may mitigate post-traumatic morbidity.


Rhythmic visual stimulation as a window into early brain development: A systematic review.
Rhythmic visual stimulation (RVS), the periodic presentation of visual stimuli to elicit a rhythmic brain response, is increasingly applied to reveal insights into early neurocognitive development. Our systematic review identified 69 studies applying RVS in 0- to 6-year-olds. RVS has long been used to study the development of the visual system and applications have more recently been expanded to uncover higher cognitive functions in the developing brain, including overt and covert attention, face and object perception, numeral cognition, and predictive processing. These insights are owed to the unique benefits of RVS, such as the targeted frequency and stimulus-specific neural responses, as well as a remarkable signal-to-noise ratio. Yet, neural mechanisms underlying the RVS response are still poorly understood. We discuss critical challenges and avenues for future research, and the unique potentials the method holds. With this review, we provide a resource for researchers interested in the breadth of developmental RVS research and hope to inspire the future use of this cutting-edge method in developmental cognitive neuroscience.


Effect of redox mediators on nitrogenase and hydrogenase activities in Azotobacter vinelandii.
In bioelectrochemical studies, redox mediators such as methylene blue, natural red, and thionine are used to studying the redox characteristics of enzymes in the living cell. Here we show that nitrogenase activity in Azotobacter vinelandii is completely inhibited by oxidized methylene blue (MBo) when the concentration of this mediator in the medium is increased up to 72 microM. This activity in A. vinelandii is somewhat inhibited by a coenzyme, ascorbic acid (AA). However, the nitrogenase activity within the A. vinelandii cell is unchanged even for a high concentration of oxidized natural red (NRo) alone. Interestingly, these mediators and AA do not have the capacity to inhibit the H2 uptake activity of the hydrogenase in A. vinelandii. Average active rates of 66 nM H2 evolved/mg cell protein/min from the nitrogenase and 160 nM H2-uptake/mg cell protein/min from the hydrogenase in A. vinelandii are found in aid of the activities of the enzymes for H2 evolution and for H2 uptake are compared. The activities of both enzymes in A. vinelandii are strongly inhibited by thionine having high oxidative potential. Mechanisms of various mediators acting in vivo for both enzymes in A. vinelandii are discussed.


Iron-induced ascorbate oxidation in plasma as monitored by ascorbate free radical formation. No spin-trapping evidence for the hydroxyl radical in iron-overloaded plasma.
A study was made of the interaction of plasma ascorbate and ascorbate free radical (AFR) with exogenously added iron. The quantitative determination of AFR has the advantage that transient increases in ascorbate oxidation can be directly monitored by e.p.r. spectroscopy. An AFR signal was found in the plasma of all donors and was unaffected by superoxide dismutase, catalase and the strong iron chelator deferoxamine. These findings and the rapid decrease in AFR under a nitrogen atmosphere suggest that plasma AFR is probably a result of air auto-oxidation. Iron loading of plasma did not affect the intensity of the AFR signal until the iron concentration approached or exceeded the plasma latent iron-binding capacity. In iron-overloaded plasma, the intensity of the AFR signal increased to about 10 times the normal level before decreasing rapidly to undetectable levels after 15-20 min. Determination of plasma ascorbate showed that the disappearance of AFR was due to a complete loss of the vitamin. When 50 microM-ascorbate was loaded with iron in iso-osmotic phosphate buffer there was an increase in the AFR signal, independent of the iron concentration, which was stable at least for 15 min. Thus the rate of ascorbate loss in the iso-osmotic phosphate buffer was considerably lower than in iron-overloaded plasma. The addition of different iron chelators produced comparable effects on the intensity of the AFR signal in both iron-overloaded plasma and ascorbate solution. These results suggest that the characteristic behaviour of plasma AFR after iron loading is due to its specific iron-binding capacity and to plasma ferroxidase activity. The ferroxidase activity of plasma is important to promote the transfer of Fe2+ into transferrin without a transient ascorbate oxidation. Spin-trapping studies with 5,5-dimethyl-1-pyrroline N-oxide and N-t-butyl-alpha-phenylnitrone revealed that iron-overloaded plasma was unable to produce spin-trap adducts even in the presence of 50-300 microM-hydrogen peroxide or 100 microM-azide. Evidence of OH. radical formation was obtained only after the addition of EDTA. Therefore, iron-overloaded plasma itself does not produce a Fenton reaction and, if ascorbate does indeed have a free-radical-mediated pro-oxidant role, it is not detectable in plasma by spin-trapping experiments.


Increased Number and Distribution of Cerebral Microbleeds Is a Risk Factor for Cognitive Dysfunction in Hemodialysis Patients: A Longitudinal Study.
The aim of this study was to explore the risk factors associated with longitudinal changes in hemodialysis patients including the correlation between number and distribution of cerebral microbleeds (CMBs).Sixty-one hemodialysis patients were enrolled in this prospective study. Twenty-eight patients had follow-up examinations with a mean interval of 24.79 ± 5.17 months. The number of CMBs was manually counted on susceptibility-weighted imaging. Subjects were divided into 2 groups with and without CMBs. In the CMB group, 8 of 33 patients did not have a mini-mental state examination (MMSE) because of blurred vision. Multiple logistic regression was used to investigate the risk factors for CMBs. Partial correlation was used to explore the correlation between the increased number of CMBs and the change of MMSE scores.CMBs were seen in 33 (54%) hemodialysis patients. Both age and pre/postdialysis systolic blood pressure (SBP) positively correlated with CMBs. Serum iron (SI), and high-density lipoprotein cholesterol (HDL-c) negatively correlated with CMBs (all P < 0.05). Among 25 patients with CMBs and MMSE, 9 patients had scores <27, which was considered as subnormal and most CMBs in these patients were located in the brainstem and basal ganglia. Considering age and follow-up time as the co-confounding factors, the number of new CMBs over the 2 imaging time points negatively correlated with the change of MMSE scores (r = -0.673, P = 0.023).The presence of new CMBs was a risk factor for cognitive dysfunction and the location of CMBs may be correlated with cognitive impairment. Both SI and HDL-c were protective factors for the CMBs. The risk factors for CMBs included age, pre- and postdialysis SBP.


Evidence that the Pim1 kinase gene is a direct target of HOXA9.
The HOXA9 homeoprotein exerts dramatic effects in hematopoiesis. Enforced expression of HOXA9 enhances proliferation of primitive blood cells, expands hematopoietic stem cells (HSCs), and leads to myeloid leukemia. Conversely, loss of HOXA9 inhibits proliferation and impairs HSC function. The pathways by which HOXA9 acts are largely unknown, and although HOXA9 is a transcription factor, few direct target genes have been identified. Our previous study suggested that HOXA9 positively regulates Pim1, an oncogenic kinase. The hematologic phenotypes of Hoxa9- and Pim1-deficient animals are strikingly similar. Here we show that HOXA9 protein binds to the Pim1 promoter and induces Pim1 mRNA and protein in hematopoietic cells. Pim1 protein is diminished in Hoxa9(-/-) cells, and Hoxa9 and Pim1 mRNA levels track together in early hematopoietic compartments. Induction of Pim1 protein by HOXA9 increases the phosphorylation and inactivation of the proapoptotic BAD protein, a target of Pim1. Hoxa9(-/-) cells show increased apoptosis and decreased proliferation, defects that are ameliorated by reintroduction of Pim1. Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells. Since HOXA9 is frequently up-regulated in acute myeloid leukemia, Pim1 may be a therapeutic target in human disease.


Rapid melting curve analysis on monolayered beads for high-throughput genotyping of single-nucleotide polymorphisms.
This report describes a rapid solid-phase melting curve analysis method for single-nucleotide polymorphism (SNP) genotyping. The melting curve analysis is based on dynamic allele-specific hybridization (DASH). The DNA duplexes are conjugated on beads that are immobilized on the surface of a microheater chip with integrated heaters and temperature sensors. SNP on PCR products were scored, illustrating the sensitivity and robustness of the system. The method is based on random bead immobilization by microcontact printing. Single-bead detection and multiplexing were performed with a heating rate more than 20 times faster than conventional DASH. Analyses that took more than 15 min could be performed in less that 1 min, enabling ultrarapid SNP analysis. In addition, an array version of the chip was implemented enabling the preparation of an array of bead arrays for high-throughput and rapid SNP genotyping.


Nobiletin Ameliorates Hepatic Lipid Deposition, Oxidative Stress, and Inflammation by Mechanisms That Involve the Nrf2/NF-κB Axis in Nonalcoholic Fatty Liver Disease.
Nobiletin (NOB), a flavonoid with significant antioxidant potential, holds promise for treating nonalcoholic fatty liver disease (NAFLD). In this work, we aim to assess the effects and investigate the molecular mechanisms of NOB on NAFLD. After using a methionine choline-deficient diet to induce C57BL/6J mice, as well as oleic acid to induce HepG2 and L02 cells, we administered NOB as an intervention. The results indicated that the NOB significantly ameliorated lipid deposition, oxidative stress, and inflammation in NAFLD in both models. Its mechanism may involve the Nrf2, SREBP-1c, and NF-κB signaling pathways. Furthermore, Nrf2 is not only a direct target for NOB to improve oxidative damage but also indirectly involved in lipid-lowering and anti-inflammatory processes in NAFLD. By inhibiting Nrf2, we found that the regulatory role of Nrf2 in lipid metabolism is not related to SREBP-1c but is closely associated with NF-κB in terms of inflammation. Our results suggest that Nrf2 is one of the most critical targets for NOB against NAFLD in multiple aspects.


Thrombolysis in myocardial infarction risk score in an observation unit setting.
The Thrombolysis in Myocardial Infarction (TIMI) score is a validated tool for risk stratification of acute coronary syndrome. We hypothesized that the TIMI risk score would be able to risk stratify patients in observation unit for acute coronary syndrome. Retrospective cohort study of consecutive adult patients placed in an urban academic hospital emergency department observation unit with an average annual census of 65,000 between 2004 and 2007. Exclusion criteria included elevated initial cardiac biomarkers, ST segment changes on ECG, unstable vital signs, or unstable arrhythmias. A composite of significant coronary artery disease (CAD) indicators, including diagnosis of myocardial infarction, percutaneous coronary intervention, coronary artery bypass surgery, or death within 30 days and 1 year, were abstracted via chart review and financial record query. The entire cohort was stratified by TIMI risk scores (0-7) and composite event rates with 95% confidence interval were calculated. In total 2228 patients were analyzed. Average age was 54.5 years, 42.0% were male. The overall median TIMI risk score was 1. Eighty (3.6%) patients had 30-day and 119 (5.3%) had 1-year CAD indicators. There was a trend toward increasing rate of composite CAD indicators at 30 days and 1 year with increasing TIMI score, ranging from a 1.2% event rate at 30 days and 1.9% at 1 year for TIMI score of 0 and 12.5% at 30 days and 21.4% at 1 year for TIMI ≥ 4. In an observation unit cohort, the TIMI risk score is able to risk stratify patients into low-, moderate-, and high-risk groups.


Replacing the wild type loxP site in BACs from the public domain with lox66 using a lox66 transposon.
Chromatin adjoining the site of integration of a transgene affects expression and renders comparisons of closely related transgenes, such as those derived from a BAC deletion series retrofitted with enhancer-traps, unreliable. Gene targeting to a pre-determined site on the chromosome is likely to alleviate the problem. A general procedure to replace the loxP site located at one end of genomic DNA inserts in BACs with lox66 is described. Truncating insert DNA from the loxP end with a Tn10 transposon carrying a lox66 site simultaneously substitutes the loxP with a lox66 sequence. The replacement occurs with high stringency, and the procedure should be applicable to all BACs in the public domain. Cre recombination of loxP with lox66 or lox71 was found to be as efficient as another loxP site during phage P1 transduction of small plasmids containing those sites. However the end-deletion of insert DNA in BACs using a lox66 transposon occurred at no more than 20% the efficiency observed with a loxP transposon. Differences in the ability of Cre protein available at different stages of the P1 life cycle to recombine identical versus non-identical lox-sites is likely responsible for this discrepancy. A possible mechanism to explain these findings is discussed. The loxP/lox66 replacement procedure should allow targeting BACs to a pre-positioned lox71 site in zebrafish chromosomes; a system where homologous recombination-mediated "knock-in" technology is unavailable.


The impact of financial incentives on the implementation of asthma or diabetes self-management: A systematic review.
Financial incentives are utilised in healthcare systems in a number of countries to improve quality of care delivered to patients by rewarding practices or practitioners for achieving set targets. To systematically review the evidence investigating the impact of financial incentives for implementation of supported self-management on quality of care including: organisational process outcomes, individual behavioural outcomes, and health outcomes for individuals with asthma or diabetes; both conditions with an extensive evidence base for self-management. We followed Cochrane methodology, using a PICOS search strategy to search eight databases in November 2015 (updated May 2017) including a broad range of implementation methodologies. Studies were weighted by robustness of methodology, number of participants and the quality score. We used narrative synthesis due to heterogeneity of studies. We identified 2,541 articles; 12 met our inclusion criteria. The articles were from the US (n = 7), UK (n = 4) and Canada (n = 1). Measured outcomes were HbA1c tests undertaken and/or the level achieved (n = 10), written action plans for asthma (n = 1) and hospital/emergency department visits (n = 1). Three of the studies were part of a larger incentive scheme including many conditions; one focused on asthma; eight focussed on diabetes. In asthma, the proportion receiving 'perfect care' (including providing a written action plan) increased from 4% to 88% in one study, and there were fewer hospitalisations/emergency department visits in another study. Across the diabetes studies, quality-of-care/GP performance scores improved in three, were unchanged in six and deteriorated in one. Results for the impact of financial incentives for the implementation of self-management were mixed. The evidence in diabetes suggests no consistent impact on diabetic control. There was evidence from a single study of improved process and health outcomes in asthma. Further research is needed to confirm these findings and understand the process by which financial incentives may impact (or not) on care. Protocol registration number: CRD42016027411.


[Triple therapy of short-term with azithromycin, amoxycillin and omeprazole for the eradication of Helicobacter pylori].
The high cost and complexity of therapeutic schemes for the eradication of Helicobacter pylori has stimulated the search of simpler and cheaper treatment options. To evaluate the efficacy of 3 days of azithromycin 500 mg od, 7 days of amoxycillin 750 mg tid and omeprazole, 20 (Group A) or 40 mg (Group B) on randomization, as a treatment for Helicobacter pylori infection in patients with endoscopically diagnosed peptic ulcer. H. pylori status of peptic ulcer patients was pathologically confirmed by the examination of five gastric biopsies using the Giemsa stain and by rapid urease testing in two gastric biopsies. H. pylori status was reassessed not less than 28 days after completing treatment. Adverse events and compliance were evaluated. Fifty four patients (29 men, 25 women, mean age 48 years) were enrolled, 28 in Group A and 27 in Group B. Per protocol the infection was cured in 58.8% of patients (30/51; 95% CI: 45-73%). On an intention to treat basis, H pylori infection was cured in 55%. Minor side effects including diarrhea and nausea were reported by 32% of patients. Ninety-five per cent of patients consumed more than 95% of prescribed medications. H. pylori was successfully eradicated in 61% of group A and 57% of group B patients (p = NS). Short term therapy with azithromycin was poorly effective in curing H. pylori infection. The compliance was excellent. Increasing Omeprazole from 20 to 40 mg/day did not improve treatment effectiveness.


The basic biology of malignant melanoma: molecular mechanisms of disease progression and comparative aspects.
Malignant melanoma (MM) is a life-threatening disease characterized by a highly aggressive biologic behavior in both humans and dogs. Despite improvements in diagnosis and patient care, most deaths from MM are due to metastases that are resistant to conventional treatment modalities. To ultimately reduce the mortality associated with metastatic disease, it is necessary to better define the fundamental molecular mechanisms of malignant tumor progression. The progression of disease is a consequence of the complex interactions between malignantly transformed cells and host factors. Characterization of the stages of tumor progression and the changes occurring in highly malignant cells is important for the development of effective treatment regimens. The dys-regulated molecular mechanisms of transformed melanocytes are presently being characterized. In this review, we summarize the current understanding of the molecular phases in the progression of MM, which include genetic instability, dysregulated proliferation of melanocytes, increased invasion and metastasis, and angiogenesis.


Molecular mechanisms of hypertension--reactive oxygen species and antioxidants: a basic science update for the clinician.
Many factors have been implicated in the pathophysiology of hypertension such as upregulation of the renin-angiotensin-aldosterone system, activation of the sympathetic nervous system, perturbed G protein-coupled receptor signalling, inflammation, and altered T-cell function. Common to these processes is increased bioavailability of reactive oxygen species (ROS) (termed oxidative stress) due to excess ROS generation, decreased nitric oxide (NO) levels, and reduced antioxidant capacity in the cardiovascular, renal, and nervous systems. Although oxidative stress may not be the sole etiology of hypertension, it amplifies blood pressure elevation in the presence of other prohypertensive factors. In the cardiovascular system ROS play a physiological role in controlling endothelial function, vascular tone, and cardiac function, and a pathophysiological role in inflammation, hypertrophy, proliferation, apoptosis, migration, fibrosis, angiogenesis, and rarefaction, all of which are important processes contributing to endothelial dysfunction and cardiovascular remodelling in hypertension. A major source for cardiovascular ROS is a family of nonphagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox1, Nox2, Nox4, and Nox5). Other sources include mitochondrial enzymes, xanthine oxidase, and uncoupled NO synthase (NOS). Although convincing data from animal studies support a causative role for oxidative stress in the pathogenesis of hypertension, there is still no solid evidence that oxidative stress causes hypertension in humans. However, biomarkers of excess ROS are increased in patients with hypertension and oxidative damage is important in the molecular mechanisms associated with cardiovascular and renal injury in hypertension. Although clinical trials failed to show beneficial antihypertensive effects of antioxidants, strategies that combat oxidative stress by targeting Noxs in an isoform-specific manner may have therapeutic potential.


A systematic review of patient reported outcome measures for women with macromastia who have undergone breast reduction surgery.
Patient satisfaction and outcomes following reduction mammoplasty is important to measure, being a being a reconstructive procedure with physical and cosmetic benefits. This study aimed to evaluate patient satisfaction and the various questionnaires that have been devised for this measurement. A systematic search of literature was performed in PubMed, Cochrane Library, Medline and Scopus databases from 1966 to July 2018 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After application of pre-determined inclusion criteria by two authors, 95 articles were included. Data was extracted from included studies relating to demographics, surgical technique, questionnaires used and physical, psychological and aesthetic outcomes. Of the 95 studies included (9,716 patients), 58 studies (5,867 patients) reported on overall satisfaction with a mean rate of 90.26%. Researchers' own non-validated questionnaire was most commonly used in 52.6% of studies. Validated questionnaires used were most commonly the SF-36 (25.3%), Rosenberg self-esteem scale (RSES) (9.5%) and BREAST-Q (8.4%). All showed improvement in physical and mental health. Our findings suggest that women who have undergone reduction mammoplasty for breast hypertrophy report postoperative satisfaction and improvement in quality of life. Of the validated questionnaires used, a combination of those assessing both mental, physical and psychosocial health as well as breast-specific surveys were most commonly used and may provide an accurate assessment of patient outcomes.


[The characteristics of a differential approach to therapy in the stress syndrome taking into account the stages of the process].
Hereby is stated the data of the necessity of the differential approach to the therapy of stress-syndrome taking into consideration the stages of the process. Pharmacological corrections of the oscillations of the antioxidation system of protection during stress is carried out in the stage of quick adaptation and its conversion into long acting, i.e. into the period, when oscillations of biochemical indexes of the antiradical system of protection are compensated. In this an important role is played by using psychotropic substances, which have a quality of the antiradical protection.


The feline leukemia virus long terminal repeat contains a potent genetic determinant of T-cell lymphomagenicity.
Feline leukemia virus (FeLV) is an important pathogen of domestic cats. The most common type of malignancy associated with FeLV is T-cell lymphoma. SL3-3 (SL3) is a potent T-cell lymphomagenic murine leukemia virus. Transcriptional enhancer sequences within the long terminal repeats (LTRs) of SL3 and other murine retroviruses are crucial genetic determinants of the pathogenicities of these viruses. The LTR enhancer sequences of FeLV contain identical binding sites for some of the transcription factors that are known to affect the lymphomagenicity of SL3. To test whether the FeLV LTR contains a genetic determinant of lymphomagenicity, a recombinant virus that contained the U3 region of a naturally occurring FeLV isolate, LC-FeLV, linked to the remainder of the genome of SL3 was generated. When inoculated into mice, the recombinant virus induced T-cell lymphomas nearly as quickly as SL3. Moreover, the U3 sequences of LC-FeLV were found to have about half as much transcriptional activity in T lymphocytes as the corresponding sequences of SL3. This level of activity was severalfold higher than that of the LTR of weakly leukemogenic Akv virus. Thus, the FeLV LTR contains a potent genetic determinant of T-cell lymphomagenicity. Presumably, it is adapted to be recognized by transcription factors present in T cells of cats, and this yields a relatively high level of transcription that allows the enhancer to drive the requisite steps in the process of lymphomagenesis.


Water? What's so special about it?
What is so special about water? Why does it have the properties it has, and how might these reasons be relevant to its apparent biological importance? By exploring the structure and dynamics of water, from the isolated molecule and its interactions, through its many crystalline phases and to its so-called anomalous liquid phase, some of its apparently unusual behaviour is rationalized. The way in which it interacts with some relatively simple interfaces is also discussed. As a result of this exploration, a checklist of possible molecular-level reasons for its biological importance is devised.


[Biomechanical data regarding the socket-neck orientation of hip endoprosthesis].
On the basis of clinico-statistical, roentgenologic, morphological and spectral studies it is possible to draw the conclusion that the cause of the structural deformation of the bone tissue around the endoprosthesis parts and an approach of their instability is in the mechanical interaction of bone and explant. Under the influence of the biomechanical forces the socket of the endoprosthesis gradually changes its position from 45-90 degrees to 25-30 degrees. The original 25-30 degree positioning of the socket significantly decreases the moment of forces that it is subjected to and, as a rule, there is no socket displacement observed. That is why this socket positioning in the process of operation is a preferable one. But the angles of necks of the Sivash endoprosthesis and its modifications are equal to 130 degrees +/- 3 degrees and when the socket is positioned at an angle 25-30 degrees there can occur limitation of the limb abduction, the socket loosening, the structure fretting and metallosis of tissues due to the setting of the neck against the end of the insert. It is expedient to change the angle of the endoprosthesis neck to 150 degrees +/- 3 degrees and some shortening of the neck.


[Mirror, mirror of the wall: mirror therapy in the treatment of phantom limbs and phantom limb pain].
Phantom limb and phantom limb pain control are pivotal points in the sequence of intervention to bring the amputee to functional autonomy. The alterations of perception and sensation, the pain of the residual limb and the phantom limb are therefore aspects of amputation that should be taken into account in the "prise en charge" of these patients. Within the more advanced physical therapies to control phantom and phantom limb pain there is the use of mirrors (mirror therapy). This article willfocus on its use and on the possible side effects induced by the lack of patient selection and a conflict of body schema restoration through mirror therapy with concurrent prosthetic training and trauma acceptance. Advice on the need to select patients before treatment decisions, with regard to their psychological as well as clinical profile (including time since amputation and clinical setting), and the need to be aware of the possible adverse effects matching different and somehow conflicting therapeutic approaches, are put forward. Thus a coordinated sequence of diagnostic, prognostic and therapeutic procedures carried out by an interdisciplinary rehabilitation team that works globally on all patients' problems is fundamental in the management of amputees and phantom limb pain. Further studies and the development of a multidisciplinary network to study this and other applications of mirror therapy are needed.


Conceptual framework and research methods for migration and HIV transmission dynamics.
Migration and mobility have had a profound influence on the global HIV epidemic. We propose a network-dyadic conceptual model to interpret previous literature and inform the development of future research with respect to study design, measurement methods, and analytic approach. In this model, HIV transmission is driven by risk behaviors of migrants that emerges and is enabled by mobility, the bridging of sub-epidemics across space and time, and the displacement effects on the primary residential sending community for migrants. To investigate these causal pathways, empirical study designs must measure the relative timing of migratory events, sexual risk behaviors, and incident HIV infections. Network-based mathematical models using empirical data on partnerships help gain insight into the dynamic disease transmission systems. Although the network-dyadic conceptual model and related network methods may not address all questions related to migration and HIV, they provide a unified approach for future research on this important topic.


Environmental Deterioration of Biodegradable, Oxo-biodegradable, Compostable, and Conventional Plastic Carrier Bags in the Sea, Soil, and Open-Air Over a 3-Year Period.
There is clear evidence that discarded single-use carrier bags are accumulating in the environment. As a result, various plastic formulations have been developed which state they deteriorate faster and/or have fewer impacts on the environment because their persistence is shorter. This study examined biodegradable, oxo-biodegradable, compostable, and high-density polyethylene (i.e., a conventional plastic carrier bag) materials over a 3 year period. These materials were exposed in three natural environments; open-air, buried in soil, and submersed in seawater, as well as in controlled laboratory conditions. In the marine environment, the compostable bag completely disappeared within 3 months. However, the same compostable bag type was still present in the soil environment after 27 months but could no longer hold weight without tearing. After 9 months exposure in the open-air, all bag materials had disintegrated into fragments. Collectively, our results showed that none of the bags could be relied upon to show any substantial deterioration over a 3 year period in all of the environments. It is therefore not clear that the oxo-biodegradable or biodegradable formulations provide sufficiently advanced rates of deterioration to be advantageous in the context of reducing marine litter, compared to conventional bags.


Endothelial progenitor cells promote directional three-dimensional endothelial network formation by secreting vascular endothelial growth factor.
Endothelial progenitor cell (EPC) transplantation induces the formation of new blood-vessel networks to supply nutrients and oxygen, and is feasible for the treatment of ischemia and cardiovascular diseases. However, the role of EPCs as a source of proangiogenic cytokines and consequent generators of an extracellular growth factor microenvironment in three-dimensional (3D) microvessel formation is not fully understood. We focused on the contribution of EPCs as a source of proangiogenic cytokines on 3D microvessel formation using an in vitro 3D network model. To create a 3D network model, EPCs isolated from rat bone marrow were sandwiched with double layers of collagen gel. Endothelial cells (ECs) were then cultured on top of the upper collagen gel layer. Quantitative analyses of EC network formation revealed that the length, number, and depth of the EC networks were significantly enhanced in a 3D model with ECs and EPCs compared to an EC monoculture. In addition, conditioned medium (CM) from the 3D model with ECs and EPCs promoted network formation compared to CM from an EC monoculture. We also confirmed that EPCs secreted vascular endothelial growth factor (VEGF). However, networks cultured with the CM were shallow and did not penetrate the collagen gel in great depth. Therefore, we conclude that EPCs contribute to 3D network formation at least through indirect incorporation by generating a local VEGF gradient. These results suggest that the location of EPCs is important for controlling directional 3D network formation in the field of tissue engineering.


Adjuvants for human vaccines--current status, problems and future prospects.
Adjuvants help antigen to elicit an early, high and long-lasting immune response with less antigen, thus saving on vaccine production costs. In recent years, adjuvants received much attention because of the development of purified, subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. With the use of adjuvants immune response can be selectively modulated to major histocompatibility complex (MHC) class I or MHC class II and Th1 or Th2 type, which is very important for protection against diseases caused by intracellular pathogens such as viruses, parasites and bacteria (Mycobacterium). A number of problems are encountered in the development and use of adjuvants for human vaccines. The biggest issue with the use of adjuvants for human vaccines, particularly routine childhood vaccines, is the toxicity and adverse side-effects of most of the adjuvant formulations. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side-effects. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The most common adjuvants for human use today are still aluminum hydroxide and aluminum phosphate, although calcium phosphate and oil emulsions also have some use in human vaccinations. During the last 15 years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS). Other areas in adjuvant research which have received much attention are the controlled release of vaccine antigens using biodegradable polymer microspheres and reciprocal enhanced immunogenicity of protein-polysaccharide conjugates. Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. Reciprocal enhanced immunogenicity of protein-polysaccharide conjugates will be useful for the development of combination vaccines.


Hepatitis A, typhoid and malaria among travelers--surveillance data from Québec (Canada).
Analysis of epidemiological data on health problems related to international travel helps put into perspective preventive interventions for travelers. To document the epidemiological context of travel health interventions in Québec, we reviewed surveillance data for three infectious diseases. The analysis included data collected in the notifiable diseases surveillance system for hepatitis A, typhoid, and malaria cases reported from 2000 to 2002. Additional data were obtained from the provincial hepatitis risk factor database as well as from regional public health departments. More than 40% of cases of hepatitis A for which risk factor information is available are associated with international travel; 20% of these cases were contracted in Mexico and 22% in the West Indies. The risk of acquiring hepatitis A seems to be higher among travelers under 35 years of age; also, given the number of Quebecers traveling to all regions of the world, this risk is proportionally higher in Africa. Data gathered for typhoid indicate that the risk to travelers from Québec is proportionately higher for Quebecers traveling to the Indian subcontinent and whose purpose is to visit family and friends, and for those who stay abroad for 4 weeks or longer. The risk of malaria is greater in Africa (where contracted cases are mostly caused by Plasmodium falciparum). Over half of malaria cases involve individuals traveling abroad for business (including volunteerism), and almost 75% contracted the disease during a stay of a month or more. Nearly half of the cases had not taken chemoprophylaxis. Available data have limitations for infectious disease surveillance among Québec travelers: imprecise number of cases (underdiagnosis and underreporting), imprecise denominators (number of travelers), and lack of data on the characteristics of trips taken. However, despite its limitations, this profile of infectious diseases among travelers from Québec provides interesting data for preventive intervention.


Incorporating biomarkers into cancer and aging research.
The challenge in treating the older adult with cancer is accurately accounting for and adapting management to the heterogeneity in health status of the individual patient. Many oncologists recognize that chronological age alone should not be the determinant when deciding on a treatment regimen. Easily measurable markers that provide an assessment of functional age would be ideal to assess frailty, which may predispose the patient to complications from cancer treatment, including increased toxicity, functional decline, decreased quality of life, and poorer survival. Several categories of potential markers, including chronic inflammatory markers, markers of cellular senescence, and imaging to assess muscle mass to detect sarcopenia, may provide insight into the likelihood of treatment-related complications. This article discusses candidate markers and strategies to evaluate these markers in cancer treatment trials, with the aim of developing a method to assess risk of oncologic outcomes and guide management decisions for both the physician and patient.


No more tears? Maternal involvement during the newborn screening examination.
Babies often show signs of discomfort and distress by crying during the neonatal screening examination (NSE). The authors hypothesized that supporting the baby with maternal participation may reduce infant crying during NSE. The objective of this study was to document incidental infant crying during NSE, before and after training residents, on maternal involvement and infant comfort techniques to help. A total of 20 NSEs of normal newborn babies by pediatric residents were observed (video-recorded) following informed consent of the doctor and the baby's mother. The examining doctors were then taught how to use maternal participation and developmental care (MPDC) comfort techniques to support the baby during NSE. Mothers were shown how to focus on their baby's needs by supporting the baby's head (preventing atonic neck reflexes) and, if necessary, providing nonnutritive sucking to the baby and an encouraging, repetitive low-tone voices to sooth the baby. A further 14 NSEs on different babies were video-recorded using these techniques. The video recordings were analyzed by independent observers for total length of crying and duration of crying during specific components of the NSE. Mothers in both groups were given a questionnaire to assess their opinions of the NSE. The median length of crying was significantly longer in the pre-MPDC group (93.5 seconds; range 0-198 seconds) compared with the post-MPDC infants (0 seconds; range 0-123 seconds; P = .001). Only 1 of 20 infants in the pre-MPDC did not cry during NSE compared with 8 of 14 babies in the post-MPDC group. Newborn infants cry less and mothers were more satisfied with NSEs when shown simple support and comfort techniques for their babies.


Meniscal allograft transplantation improves patient-reported outcomes in both minimal and moderate knee osteoarthritis at 1 and 2 years postoperatively.
Severe cartilage damage and advanced knee osteoarthritis (OA) might be associated with poor outcomes of meniscal allograft transplantation (MAT). The purpose of this prospective follow-up study was to explore MAT survivorship and patient satisfaction among young patients with symptomatic meniscal deficiency and radiological OA of different Kellgren-Lawrence (K-L) grades. Thirty-five consecutive MAT patients were prospectively followed up for 2 years. The lateral meniscus was replaced in 29 patients and the medial meniscus in 6 patients. Outcomes were assessed using the KOOS4 composite score, KOOS subscales, Lysholm knee score, and OA K-L grade progression from weight-bearing knee radiographs. For the outcome analysis, patients were categorized into two groups: 19 in Group A (K-L classification 0-1) and 16 in Group B (K-L classification 2). In terms of KOOS4 and Lysholm scores, the patients showed a clinically significant improvement from baseline to the 1-year follow-up (22.2 points, 95% CI 16.6-27.8 for KOOS4 and 16.8 points, 95% CI 8.9-24.6 for Lysholm), and the improvement remained at 2 years (20.6 points, 95% CI 13.2-28.1 for KOOS4 and 21.5, 95% CI 12.5-30.7 for Lysholm). At the 6-month follow-up, this improvement was not yet observed. Minor between-group differences were observed in the KOOS4 and Lysholm scores for the K-L 0-1 and K-L 2 OA groups, but the estimates were imprecise with wide confidence intervals. A clinically relevant difference between these two study groups could not be found at any timepoint. The reoperation rate was higher in the K-L 2 group than in the K-L 0-1 group (31% vs. 11%). MAT yielded improved patient-reported outcomes and subjective satisfaction at 1 and 2 years postoperatively. The differences from baseline exceeded the minimal clinically important difference (MCID) at all timepoints. The severity of cartilage damage and knee OA in terms of the K-L grade at the time of surgery did not affect the KOOS and Lysholm scores after the MAT procedure. Knee OA progression in terms of K-L grade worsening was not observed in any patients. III.


Control of RecBCD enzyme activity by DNA binding- and Chi hotspot-dependent conformational changes.
Faithful repair of DNA double-strand breaks by homologous recombination is crucial to maintain functional genomes. The major Escherichia coli pathway of DNA break repair requires RecBCD enzyme, a complex protein machine with multiple activities. Upon encountering a Chi recombination hotspot (5' GCTGGTGG 3') during DNA unwinding, RecBCD's unwinding, nuclease, and RecA-loading activities change dramatically, but the physical basis for these changes is unknown. Here, we identify, during RecBCD's DNA unwinding, two Chi-stimulated conformational changes involving RecC. One produced a marked, long-lasting, Chi-dependent increase in protease sensitivity of a small patch, near the Chi recognition domain, on the solvent-exposed RecC surface. The other change was identified by crosslinking of an artificial amino acid inserted in this RecC patch to RecB. Small-angle X-ray scattering analysis confirmed a major conformational change upon binding of DNA to the enzyme and is consistent with these two changes. We propose that, upon DNA binding, the RecB nuclease domain swings from one side of RecC to the other; when RecBCD encounters Chi, the nuclease domain returns to its initial position determined by crystallography, where it nicks DNA exiting from RecC and loads RecA onto the newly generated 3'-ended single-stranded DNA during continued unwinding; a crevice between RecB and RecC increasingly narrows during these steps. This model provides a physical basis for the intramolecular "signal transduction" from Chi to RecC to RecD to RecB inferred previously from genetic and enzymatic analyses, and it accounts for the enzymatic changes that accompany Chi's stimulation of recombination.


How accurate are interpretations of curriculum-based measurement progress monitoring data? Visual analysis versus decision rules.
Curriculum based measurement of oral reading (CBM-R) is used to monitor the effects of academic interventions for individual students. Decisions to continue, modify, or terminate these interventions are made by interpreting time series CBM-R data. Such interpretation is founded upon visual analysis or the application of decision rules. The purpose of this study was to compare the accuracy of visual analysis and decision rules. Visual analysts interpreted 108 CBM-R progress monitoring graphs one of three ways: (a) without graphic aids, (b) with a goal line, or (c) with a goal line and a trend line. Graphs differed along three dimensions, including trend magnitude, variability of observations, and duration of data collection. Automated trend line and data point decision rules were also applied to each graph. Inferential analyses permitted the estimation of the probability of a correct decision (i.e., the student is improving - continue the intervention, or the student is not improving - discontinue the intervention) for each evaluation method as a function of trend magnitude, variability of observations, and duration of data collection. All evaluation methods performed better when students made adequate progress. Visual analysis and decision rules performed similarly when observations were less variable. Results suggest that educators should collect data for more than six weeks, take steps to control measurement error, and visually analyze graphs when data are variable. Implications for practice and research are discussed.


Utility of Thermographic Imaging for Callus Identification in Wound and Foot Care.
Calluses are thickened skin areas that develop due to repeated friction, pressure, or other types of irritation. While calluses are usually harmless and formed as a protective surface, they can lead to skin ulceration or infection if left untreated. As calluses are often not clearly visible to the patients, and some areas of dead skin can be missed during debridement, accessory tools can be useful in assessment and follow-up. The practical question addressed in this article is whether or not thermal imaging adds value to callus assessment. We have performed a theoretical analysis of the feasibility of thermographic imaging for callus identification. Our analytical calculations show that the temperature drop in the epidermis should be on the order of 0.1 °C for the normal epidermis in hairy skin, 0.9 °C for glabrous skin, and 1.5-2 °C or higher in calluses. We have validated our predictions on gelatin phantoms and demonstrated the feasibility of thermographic imaging for callus identification in two clinical case series. Our experimental results are in agreement with theoretical predictions and support the notion that local skin temperature variations can indicate epidermis thickness variations, which can be used for callus identification. In particular, a surface temperature drop on the order of 0.5 °C or more can be indicative of callus presence, particularly in callus-prone areas. In addition, our analytical calculations and phantom experiments show the importance of ambient temperature measurements during thermographic assessments.


Cyclooxygenase and atherosclerosis: a smoking area.
Chronic smoking is associated with functional and structural vascular changes underlying inflammatory processes responsible for plaque formation and rupture. Cyclooxygenase (COX) is the key enzyme linking smoking action to inflammatory damages: it is responsible for the conversion of arachidonic acid to prostanoids, and lipid mediators involved in most of pathological processes. Two COX isoenzymes have been characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity, and preferential coupling to upstream and downstream enzymes. The aim of this review is to highlight the pathogenetic role of chronic smoking in vasomotor dysfunction, inflammation, and modification of lipids underlying the initiation and the progression of atherosclerosis and to remark the hypothesis that plaque composition rather than plaque size is the real determinant of the plaque evolution toward rupture and the major responsible for acute ischemic syndromes. The concomitantly higher expression of EP4, COX-2, mPGES-1, MMP-2 and MMP-9 in unstable plaques is focused and the role of PGE(2) as pathophysiological link between smoking, COX-2 and MMP activity is stressed. Indeed, the intracellular pathways regulating COX-2 and the mechanisms suggested to clarify the role of COX-2 and downstream synthases in atherothrombosis are summarized.


The impact of generational change and retirement on psychiatry to 2025.
Australia is currently experiencing widespread shortages of psychiatrists. The changing nature of the workforce and increasing demand mean that these shortages are unlikely to ease. This study aims to identify demographic change and retirement patterns of the Australian psychiatry workforce from 1995 to 2003, and the implications of those changes for future workforce planning. Data from the Australian Institute of Health and Welfare (AIHW) Medical Labour Force Survey from 1995 to 2003 is used to examine ageing of the psychiatry workforce and attrition of psychiatrists aged 50 years and over. Future attrition from the workforce is projected to 2025. Sixty two percent of psychiatrists practicing in the year 2000 are predicted to have retired by 2025. Most psychiatrists continue to work until late in life, with only 18 per cent retiring before age 65. The psychiatry workforce aged significantly between 1995 and 2003 (p < 0.001), with men older than women in both years. A reduction in hours worked by psychiatrists reflects both the increasing proportion of females and the older members of the profession reducing their hours in preparation for retirement. The impact of ageing of the workforce may be more immediate for psychiatry than for some other health professions. With the growing proportion of females and their typically lower workforce participation, more than one younger psychiatrist will be required to replace each of the mostly male retirees.


Ghrelin suppresses tunicamycin- or thapsigargin-triggered endoplasmic reticulum stress-mediated apoptosis in primary cultured rat cortical neuronal cells.
Ghrelin functions as a neuroprotective agent and rescues neurons from various insults. However, the molecular mechanisms underlying ghrelin neuroprotection remains to be elucidated. An accumulation of unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress and then induces ER stress-mediated cell death. Here, we report that acylated ghrelin inhibited tunicamycin- or thapsigargin-triggered ER stress-induced apoptotic cell death in primary rat cortical neurons. An analysis using a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), LY294002, showed that ghrelin prevented apoptosis via the activation of PI3K signaling pathway. Ghrelin suppressed tunicamycin- or thapsigargin-induced upregulation and nuclear translocation of C/EBP homologous protein (CHOP). Ghrelin also inhibited tunicamycin or thapsigargin induction of PRK-like ER kinase (PERK), eukaryotic translation initiation factor-2α (eIF2α) and activating transcription factor (ATF) 4. Exposure of cells to tunicamycin or thapsigargin resulted in nuclear translocation of forkhead box protein O1 (Foxo1), which was reduced by pretreatment with ghrelin. The protective effect of ghrelin was accompanied by an increased phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. Furthermore, ghrelin phosphorylated and inactivated pro-apoptotic BAD and Foxo1. In addition, phospho-Akt was translocated to the nucleus in response to ghrelin and PI3K inhibition by LY294002 prevented ghrelin-induced effect on phospho-Akt localization. Our study suggests that suppression of CHOP activation via the inhibition of PERK/eIF2α/ATF4 pathway and prevention of Foxo1 activation and nuclear translocation may contribute to ghrelin-mediated neuroprotection during ER stress responses. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3β, BAD and Foxo1 may be associated with the anti-apoptotic effect of ghrelin.


[Use of magnesium sulfate for controlling postoperative shivering].
In intravenous administration of magnesium sulphate, the postoperative shivering was cupped off in 87.8% of the patients. The mean effective dosage of the preparation was 32.2 mg/kg of body weight. In rapid intravenous administration of the preparation, in 3% of the patients, the nausea and vomiting+ occurred. Hypotension (3% of cases) and ++re-curarization of the mandibular muscles (3%) were eliminated by means of the intravenous administration of calcium chloride. Cupping off the shivering permitted to prevent the hypothermal reaction after the operation and narcosis.


In vitro generation of tumoricidal properties in human alveolar macrophages following interaction with endotoxin.
Human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy nonsmoking donors exhibited primarily low levels of cytolytic activity against allogeneic tumor target cells. These AM acquired enhanced capacity to kill tumor cells following a 24-hr incubation in vitro with endotoxin [lipopolysaccharide (LPS)]. Maximal tumoricidal activity of LPS-activated AM as measured by lysis of tumor target cells was obtained after incubation with tumor cells for 72 hr. LPS-activated AM lysed allogeneic tumor cell lines of different origins but did not affect normal, nonneoplastic cells. We conclude that LPS induces human AM to become tumoricidal. This method should be useful in studies on therapeutic agents enhancing AM-mediated cytotoxicity in situ.


Object-Location Memory Training in Older Adults Leads to Greater Deactivation of the Dorsal Default Mode Network.
Substantial evidence indicates that cognitive training can be efficacious for older adults, but findings regarding training-related brain plasticity have been mixed and vary depending on the imaging modality. Recent years have seen a growth in recognition of the importance of large-scale brain networks on cognition. In particular, task-induced deactivation within the default mode network (DMN) is thought to facilitate externally directed cognition, while aging-related decrements in this neural process are related to reduced cognitive performance. It is not yet clear whether task-induced deactivation within the DMN can be enhanced by cognitive training in the elderly. We previously reported durable cognitive improvements in a sample of healthy older adults (age range = 60-75) who completed 6 weeks of process-based object-location memory training (N = 36) compared to an active control training group (N = 31). The primary aim of the current study is to evaluate whether these cognitive gains are accompanied by training-related changes in task-related DMN deactivation. Given the evidence for heterogeneity of the DMN, we examine task-related activation/deactivation within two separate DMN branches, a ventral branch related to episodic memory and a dorsal branch more closely resembling the canonical DMN. Participants underwent functional magnetic resonance imaging (fMRI) while performing an untrained object-location memory task at four time points before, during, and after the training period. Task-induced (de)activation values were extracted for the ventral and dorsal DMN branches at each time point. Relative to visual fixation baseline: (i) the dorsal DMN was deactivated during the scanner task, while the ventral DMN was activated; (ii) the object-location memory training group exhibited an increase in dorsal DMN deactivation relative to the active control group over the course of training and follow-up; (iii) changes in dorsal DMN deactivation did not correlate with task improvement. These results indicate a training-related enhancement of task-induced deactivation of the dorsal DMN, although the specificity of this improvement to the cognitive task performed in the scanner is not clear.


Transgenic plants: an historical perspective.
The development of technologies that allow the introduction and functional expression of foreign genes in plant cells has extended in less than two decades to the production of transgenic plants with improved insect and disease resistance, seeds and fruits with enhanced nutritional qualities, and plants that are better adapted to adverse environmental conditions. Vaccines against serious human diseases and other important products have also been developed using transgenic plants. Many more agronomic and quality traits are currently being engineered in both academic and industrial laboratories, which are limited only by our poor knowledge of plant gene function. The emergence of new functional genomic strategies for the identification and characterization of genes promises to provide a wealth of information with an enormous potential to enhance traditional plant breeding and to genetically engineer plants for specific purposes. This chapter describes some of the highlights in the development of these technologies and some of the major achievements in production and commercialization of transgenic crops. We also discuss some of the biosafety issues related to release of this novel class of plants into the environment.


Diversity and toxicity of the planktonic diatom genus Pseudo-nitzschia from coastal and offshore waters of the Southeast Pacific, including Pseudo-nitzschia dampieri sp. nov.
To expand knowledge of Pseudo-nitzschia species in the Southeast Pacific, we isolated specimens from coastal waters of central Chile (36°S-30°S), the Gulf of Corcovado, and the oceanic Robinson Crusoe Island (700 km offshore) and grew them into monoclonal strains. A total of 123 Pseudo-nitzschia strains were identified to 11 species based on sequencing of the ITS region of the nuclear rDNA and on ultrastructural and morphometric analyses of the frustule in selected representatives of each clade: P. australis, P. bucculenta, P. cf. chiniana, P. cf. decipiens, P. fraudulenta, P. hasleana, P. multistriata, P. plurisecta, P. cf. sabit, the new species P. dampieri sp. nov., and one undescribed species. Partial 18S and 28S rDNA sequences, including the hypervariable V4 and D1-D3 regions used for barcoding, were gathered from representative strains of each species to facilitate future metabarcoding studies. Results showed different levels of genetic, and at times ultrastructural, diversity among the above-mentioned entities, suggesting morphological variants (P. bucculenta), rapidly radiating complexes with ill-defined species boundaries (P. cf. decipiens and P. cf. sabit), and the presence of new species (P. dampieri sp. nov., Pseudo-nitzschia sp. 1, and probably P. cf. chiniana). Domoic acid (DA) was detected in 18 out of 82 strains tested, including those of P. australis, P. plurisecta, and P. multistriata. Toxicity varied among species mostly corresponding to expectations from previous reports, with the prominent exception of P. fraudulenta; DA was not detected in any of its 10 strains tested. In conclusion, a high diversity of Pseudo-nitzschia exists in Chilean waters, particularly offshore.


Respirator Testing Using Virus Aerosol: Comparison between Viability Penetration and Physical Penetration.
Viability, fluorescence (particle volume), photometric, viral RNA, and particle number penetration of MS2 bacteriophage through filter media used in three different models of respirators were compared to better understand the correlation between viability and physical penetration. Although viability and viral RNA penetration were better represented by particle volume penetration than particle number penetration, they were several-fold lower than photometric penetration, which was partially due to the difference in virus survival between upstream and downstream aerosol samples. Results suggest that the current NIOSH photometer-based test method can be used as a quick means to roughly differentiate respirators with different performance against virus aerosols.


Optimal sampling for pedigree analysis: sequential schemes for sibships.
Methods for inferring the mode of inheritance of a trait from familial data are becoming widely used. It is therefore important to assess alternative procedures for the collection of the relevant data. Cannings and Thompson (1977, Clinical Genetics 12, 208-212) and Thompson and Cannings (1979. In Genetic Analysis of Common Diseases, 363-382, New York: Liss) have advocated sequential schemes on the grounds that these admit simple methods for the correction of the likelihood function for ascertainment bias. Here it is shown that sequential procedures may also greatly increase efficiency, as measured by (statistical) information gained per individual sampled. Although attention is restricted to sampling sibships, and to a simple genetic model, the measures introduced are more widely applicable. A practical procedure for the construction of schemes, via a relationship between expected log likelihood and entropy, is also presented. This too is more widely applicable. A numerical example demonstrates the gains which can be achieved in practice, relative to alternative hypotheses which have been considered in several medical-genetic studies.


The acceptability and uptake of smartphone tracking for COVID-19 in Australia.
In response to the COVID-19 pandemic, many Governments are instituting mobile tracking technologies to perform rapid contact tracing. However, these technologies are only effective if the public is willing to use them, implying that their perceived public health benefits must outweigh personal concerns over privacy and security. The Australian federal government recently launched the 'COVIDSafe' app, designed to anonymously register nearby contacts. If a contact later identifies as infected with COVID-19, health department officials can rapidly followup with their registered contacts to stop the virus' spread. The current study assessed attitudes towards three tracking technologies (telecommunication network tracking, a government app, and Apple and Google's Bluetooth exposure notification system) in two representative samples of the Australian public prior to the launch of COVIDSafe. We compared these attitudes to usage of the COVIDSafe app after its launch in a further two representative samples of the Australian public. Using Bayesian methods, we find widespread acceptance for all tracking technologies, however, observe a large intention-behaviour gap between people's stated attitudes and actual uptake of the COVIDSafe app. We consider the policy implications of these results for Australia and the world at large.


Spinal reflex attenuation associated with spinal manipulation.
This study evaluated the effect of lumbosacral spinal manipulation with thrust and spinal mobilization without thrust on the excitability of the alpha motoneuronal pool in human subjects without low back pain. To investigate the effect of high velocity, low amplitude thrust, or mobilization without thrust on the excitability of the alpha motoneuron pool, and to elucidate potential mechanisms in which manual procedures may affect back muscle activity. The physiologic mechanisms of spinal manipulation are largely unknown. It has been proposed that spinal manipulation may reduce back muscle electromyographic activity in patients with low back pain. Although positive outcomes of spinal manipulation intervention for low back pain have been reported in clinical trials, the mechanisms involved in the amelioration of symptoms are unknown. In this study, 17 nonpatient human subjects were used to investigate the effect of spinal manipulation and mobilization on the amplitude of the tibial nerve Hoffmann reflex recorded from the gastrocnemius muscle. Reflexes were recorded before and after manual spinal procedures. Both spinal manipulation with thrust and mobilization without thrust significantly attenuated alpha motoneuronal activity, as measured by the amplitude of the gastrocnemius Hoffmann reflex. This suppression of motoneuronal activity was significant (P < 0.05) but transient, with a return to baseline values exhibited 30 seconds after intervention. Both spinal manipulation with thrust and mobilization without thrust procedures produce a profound but transient attenuation of alpha motoneuronal excitability. These findings substantiate the theory that manual spinal therapy procedures may lead to short-term inhibitory effects on the human motor system.


Mapping Quantitative Trait Loci (QTL) for Resistance to Late Blight in Tomato.
Late blight caused by Phytophthora infestans (Montagne, Bary) is a devastating disease of tomato worldwide. There are three known major genes, Ph-1, Ph-2, and Ph-3, conferring resistance to late blight. In addition to these three genes, it is also believed that there are additional factors or quantitative trait loci (QTL) conferring resistance to late blight. Precise molecular mapping of all those major genes and potential QTL is important in the development of suitable molecular markers and hence, marker-assisted selection (MAS). The objective of the present study was to map the genes and QTL associated with late blight resistance in a tomato population derived from intra-specific crosses. To achieve this objective, a population, derived from the crossings of NC 1CELBR × Fla. 7775, consisting of 250 individuals at F2 and F2-derived families, were evaluated in replicated trials. These were conducted at Mountain Horticultural Crops Reseach & Extension Center (MHCREC) at Mills River, NC, and Mountain Research Staion (MRS) at Waynesville, NC in 2011, 2014, and 2015. There were two major QTL associated with late blight resistance located on chromosomes 9 and 10 with likelihood of odd (LOD) scores of more than 42 and 6, explaining 67% and 14% of the total phenotypic variation, respectively. The major QTLs are probably caused by the Ph-2 and Ph-3 genes. Furthermore, there was a minor QTL on chromosomes 12, which has not been reported before. This minor QTL may be novel and may be worth investigating further. Source of resistance to Ph-2, Ph-3, and this minor QTL traces back to line L3707, or Richter's Wild Tomato. The combination of major genes and minor QTL may provide a durable resistance to late blight in tomato.


Publication rates of editorial board members in oral health journals.
The aim of this study was to measure the publication rate of editorial board members in their board journals and to evaluate associated variables. We evaluated the ten highest-ranked journals according to the 5-year impact factor under 'Dentistry, Oral Surgery & Medicine' subject category for 2010, 2011, and 2012. All original research papers with at least one member of the editorial board as author were counted. Final analyses assessed associated variables such as size of the editorial board, number of papers published each year, and each journal's impact factor. Overall, there was an increase in the average number of articles published from 2010 (115.2 ± 52.2) to 2012 (134.7 ± 47.4). The number and percentage of articles published with editorial board members as authors over the three years did not follow the same pattern, with a slight decrease from 2010 to 2011 and an increase in 2012. The number of articles with editorial board members as authors was significantly higher for journals with impact factors ≥4.0. Journals with a higher impact factor and larger editorial board were associated with higher chances of editorial board members publishing in their respective journals. Participation of editorial board members as authors in publishing varies significantly among journals.


Isolation and Identification of Phytocompounds from Maytenus dhofarensis and Their Biological Potentials.
Maytenus dhofarensis Sebsebe (Celestraceae) is a naturally growing shrub in Oman. It is not a reputed medicinal plant in Oman, but it is regionally endemic and causes shivering attacks on goats that graze on it. The chemical investigation of the hexane and chloroform extracts of the fruits and stems of M. dhofarensis afforded dihydro-β-agarofuran-type sesquiterpene pyridine alkaloid (1), lupanyl myristoate (2) and lignanolactone (3). Compounds (1-3) are new isolates from M. dhofarensis. The structures of these compounds were assigned through comprehensive IR, NMR, and ESI-MS analyses, and the relative configurations of compounds 1 and 3 were deduced from density function theory (DFT) calculations and NMR experiments. Compound 1 was assayed against the kinase enzyme and showed no inhibition activity for p38 alpha and delta at a 10 µM test concentration. Compound 3 inhibited the 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) by 69.5%, compared to 70.9% and 78.0% for gallic acid and butylated hydroxyanisole, respectively, which were used as positive controls.


Exocrine pancreatic insufficiency after esophagectomy: a systematic review of literature.
Complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are often attributed to an impaired exocrine pancreatic function. This review systematically summarizes all literature reporting on the presence of exocrine pancreatic insufficiency (EPI) after esophagectomy and the effect of treatment with pancreatic enzymes on gastrointestinal complaints, body weight, and quality of life. Databases of PubMed, Embase, and Wiley/Cochrane Library were searched systematically until July 2020. Studies reporting on EPI and pancreatic enzyme replacement therapy after esophagectomy were included. The Newcastle-Ottawa scale was used to assess study quality. Four studies, including 158 patients, were selected. The maximum score for study quality was six (range 4-6). Exocrine pancreatic function was investigated in three studies, measured by fecal elastase-1 and 72-hour fecal fat excretion. Fecal elastase-1 levels <200 μg/g were reported in 16% of patients at 4 months, 18% at 6 months, and 31% at 18-24 months postoperatively. A decreased fecal fat absorption was noticed in 57% 1 month postoperatively. Treatment with pancreatic enzymes was reported in two studies. In patients with fecal elastase-1 levels <200 μg/g, 90% of patients reported improvement in symptoms and 70% reported improvement in weight. In patients with complaints of steatorrhea, 87% noticed settlement of symptoms. Based on current literature, complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are common and can be related to an impaired exocrine pancreatic function. High-quality studies evaluating the presence of EPI and the effect of treatment with pancreatic enzymes after esophagectomy are needed to verify this conclusion.


CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium.
CDK8 and CDK19 form a conserved cyclin-dependent kinase subfamily that interacts with the essential transcription complex, Mediator, and also phosphorylates the C-terminal domain of RNA polymerase II. Cells lacking either CDK8 or CDK19 are viable and have limited transcriptional alterations, but whether the two kinases redundantly control cell proliferation and differentiation is unknown. Here, we find in mice that CDK8 is dispensable for regulation of gene expression, normal intestinal homeostasis, and efficient tumourigenesis, and is largely redundant with CDK19 in the control of gene expression. Their combined deletion in intestinal organoids reduces long-term proliferative capacity but is not lethal and allows differentiation. However, double-mutant organoids show mucus accumulation and increased secretion by goblet cells, as well as downregulation of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and functionality of the CFTR pathway. Pharmacological inhibition of CDK8/19 kinase activity in organoids and in mice recapitulates several of these phenotypes. Thus, the Mediator kinases are not essential for cell proliferation and differentiation in an adult tissue, but they cooperate to regulate specific transcriptional programmes.


Characterization of a sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin and lipoate in human placental choriocarcinoma cells.
The characteristics of the uptake of the vitamin pantothenate into JAr human placental choriocarcinoma cells were investigated and these cells were found to accumulate the vitamin against a concentration gradient by a Na(+)-dependent process. Substitution of Na+ with over other monovalent cations abolished the uptake completely. The transport process showed no preference for any particular anion. Kinetic analysis indicated the presence of a single saturable transport system with a Michaelis-Menten constant of 2.1 +/- 0.2 microM and a maximal velocity of 341 +/- 12 pmol/mg of protein per 10 min. The dependence of the uptake rate of pantothenate on Na+ concentration exhibited sigmoidal kinetics, indicating interaction of more than one Na+ ion with the transporter. The Hill coefficient for this process was calculated to be 1.6. The Na+/pantothenate coupling ratio being greater than unity suggests that the transport process is electrogenic, resulting in net transfer of positive charge across the membrane. This was confirmed in plasma membrane vesicles prepared from JAr cells where the uptake of pantothenate was found to be significantly stimulated by valinomycin-induced inside-negative K(+)-diffusion potential. Substrate specificity studies showed that, in addition to pantothenate, the transporter interacts with two other vitamins, namely biotin and lipoate. The characteristics of pantothenate uptake in the placental cell line BeWo was also investigated. These cells were also found to express a pantothenate transport system similar to that expressed in the JAr cells.


Intravenous Lidocaine: Old-School Drug, New Purpose-Reduction of Intractable Pain in Patients with Chemotherapy Induced Peripheral Neuropathy.
Background. Treatment of intractable pain due to chemotherapy induced peripheral neuropathy (CIPN) is a challenge. Intravenous (iv) lidocaine has shown to be a treatment option for neuropathic pain of different etiologies. Methods. Lidocaine (1.5 mg/kg in 10 minutes followed by 1.5 mg/kg/h over 5 hours) was administered in nine patients with CIPN, and analgesic effect was evaluated during infusion and after discharge. The immediate effect of lidocaine on pressure pain thresholds (PPT) and the extent of the stocking and glove distribution of sensory abnormalities (cold and pinprick) were assessed. Results. Lidocaine had a significant direct analgesic effect in 8 out of 9 patients (P = 0.01) with a pain intensity difference of >30%. Pain reduction persisted in 5 patients for an average of 23 days. Lidocaine did not influence mean PPT, but there was a tendency that the extent of sensory abnormalities decreased after lidocaine. Conclusion. Iv lidocaine has direct analgesic effect in CIPN with a moderate long-term effect and seems to influence the area of cold and pinprick perception. Additional research is needed, using a control group and larger sample sizes to confirm these results.


Lack of control over work and organizational citizenship behavior: overwork climate as a suppressor variable.
This study investigates a suppressor effect in the relationship between lack of control over work and organizational citizenship behavior (OCB). Suppressor effects operate when the addition of a predictor (in our study it is an overwork climate) increases the predictive power of another variable (lack of control over work) in predicting an outcome variable (OCB). Suppressor effects can play a valuable role in explicating the meaning of examined variables by bringing into clearer focus opposing elements that are inherent - but largely hidden - in the measurement of these variables. Data were collected through online questionnaires in a cross-sectional study. Using a sample of Polish employees (N = 580) we performed structural equation modelling (SEM) with robust maximum likelihood estimation to test our hypotheses. Confirming our hypothesis, we found that overwork climate, as a suppressor variable, in isolation is not correlated with OCB, but is strongly associated with lack of control over work, which is a significant predictor of OCB. In our study, we demonstrated that both lack of control over work and organizational citizenship behaviors encompass two dimensions simultaneously. The first, namely dedication to work (which they both share), constitutes the positive correlation between these two variables. The second dimension (which separates the two variables), which constitutes the negative correlation between them, is an attitude. Lack of control over work is rooted in the negative attitude and stems from the overwork climate, while organizational citizenship behaviors can be more widely associated with the positive attitude which generally stems from positive evaluation of the working environment.


Diversity of O Antigens within the Genus Cronobacter: from Disorder to Order.
Cronobacter species are Gram-negative opportunistic pathogens that can cause serious infections in neonates. The lipopolysaccharides (LPSs) that form part of the outer membrane of such bacteria are possibly related to the virulence of particular bacterial strains. However, currently there is no clear overview of O-antigen diversity within the various Cronobacter strains and links with virulence. In this study, we tested a total of 82 strains, covering each of the Cronobacter species. The nucleotide variability of the O-antigen gene cluster was determined by restriction fragment length polymorphism (RFLP) analysis. As a result, the 82 strains were distributed into 11 previously published serotypes and 6 new serotypes, each defined by its characteristic restriction profile. These new serotypes were confirmed using genomic analysis of strains available in public databases: GenBank and PubMLST Cronobacter. Laboratory strains were then tested using the current serotype-specific PCR probes. The results show that the current PCR probes did not always correspond to genomic O-antigen gene cluster variation. In addition, we analyzed the LPS phenotype of the reference strains of all distinguishable serotypes. The identified serotypes were compared with data from the literature and the MLST database (www.pubmlst.org/cronobacter/). Based on the findings, we systematically classified a total of 24 serotypes for the Cronobacter genus. Moreover, we evaluated the clinical history of these strains and show that Cronobacter sakazakii O2, O1, and O4, C. turicensis O1, and C. malonaticus O2 serotypes are particularly predominant in clinical cases.


Secretome analysis of multiple pancreatic cancer cell lines reveals perturbations of key functional networks.
The cancer secretome is a rich repository in which to mine useful information for both cancer biology and clinical oncology. To help understand the mechanisms underlying the progression of pancreatic cancer, we characterized the secretomes of four human pancreatic ductal adenocarcinoma (PDAC) cell lines versus a normal counterpart. To this end, we used a proteomic workflow based on high-confidence protein identification by mass spectrometry, semiquantitation by a label-free approach, and network enrichment analysis by a system biology tool. Functional networks significantly enriched with PDAC-dysregulated proteins included not only expected alterations within key mechanisms known to be relevant for tumor progression (e.g., cell-cell/cell-matrix adhesion, extracellular matrix remodeling, and cytoskeleton rearrangement), but also other extensive, coordinated perturbations never observed in pancreatic cancer. In particular, we highlighted perturbations possibly favoring tumor progression through immune escape (i.e., inhibition of the complement system, deficiency of selected proteasome components within the antigen-presentation machinery, and inhibition of T cell cytoxicity), and a defective protein folding machinery. Among the proteins found concordantly oversecreted in all of our PDAC cell lines, many are reportedly overexpressed in pancreatic cancer (e.g., CD9 and Vimentin), while others (PLOD3, SH3L3, PCBP1, and SFRS1) represent novel PDAC-secreted proteins that may be worth investigating.


Alterations in human muscle protein metabolism with aging: Protein and exercise as countermeasures to offset sarcopenia.
Aging is associated with a reduction in skeletal muscle mass-sarcopenia-the etiology of which is multifactorial. One mechanism is that aging has, as one of its hallmarks, a reduced sensitivity of skeletal muscle to the normally potent anabolic effects of protein feeding and resistance exercise, and to the anticatabolic effects of insulin, the combination of which has been termed "anabolic resistance." However, this reduced sensitivity of skeletal muscle to anabolic stimuli may, in some cases, be overcome by providing a greater quantity of the nutrition and/or exercise stimulus. Daily habitual physical activity appears to be a primary determinant of anabolic resistance as we have recently shown that as little as 14 days of reduced ambulatory activity was sufficient to induce anabolic resistance in the elderly by attenuating the postprandial increase in muscle protein synthesis (MPS). The etiology of anabolic resistance is complex and may include alterations in amino acid uptake/utilization, cell signaling status, muscle blood flow, and microvascular perfusion (impacting amino acid delivery and availability). Further, there appears to be sexual dimorphism with advancing age in the response of MPS to amino acid/insulin provision. Maintenance of physical activity during aging is of fundamental importance for skeletal muscle to allow it to appropriately respond to the anabolic effects of nutrition.


Clinical presentation and diagnosis of endometriosis.
Endometriosis is one of the most common conditions encountered in gynecology and the field of infertility. The clinical presentation depends on the location and the extent of disease, but the severity of symptoms does not correlate directly with the extent of disease. Symptoms of genital endometriosis may be categorized as menstrual dysfunction, ovulatory dysfunction, and reproductive dysfunction. With menstrual dysfunction, the frequent clinical symptoms are cyclic pelvic pain, dysmenorrhea, and dyspareunia. Endometriosis is commonly found to be the cause in younger patients with pain and dysmenorrhea, particularly when the clinician is aware of the appearance of atypical lesions. Types of ovulatory dysfunction reported to be associated with endometriosis include anovulation, premenstrual spotting, luteal phase defects, and LUF syndrome. The data are not sufficient to determine the prevalence of endometriosis, luteal phase defects, and hyperprolactinemia. With LUF syndrome, there are data to support an association, but more data on the frequency of LUF in consecutive normal cycles compared to consecutive cycles in women with endometriosis would be beneficial. A higher rate of infertility is reported in couples with endometriosis. Two approaches are used to evaluate spontaneous abortions and endometriosis. In retrospective studies, the abortion rates are higher in couples with endometriosis; however, when the pregnancy outcomes in untreated couples are studied, there is less evidence to support the association of a higher spontaneous abortion rate. Formerly, the diagnosis of endometriosis depended on the appearance of typical lesions. With the recognition of early or atypical lesions the histologic confirmation of glands and stroma is assuming a more prominent role. Noninvasive techniques such as assays of endometrial antibodies or CA-125 have certain limitations in terms of producing false-positive results and lacking predictability in early stages of disease. Ultrasonography and MRI give additional and confirmatory information. Most noninvasive techniques are ancillary in diagnosis and management. It still needs to be determined whether their routine use will give enough added information to justify their cost. Currently, the diagnosis of endometriosis is best made by histologic evidence of glands and stroma.


Increased expression of CD16, CD69, and very late antigen-1 on blood monocytes in active sarcoidosis.
Different types of immune cells are involved in the formation of granulomas, a hallmark of pulmonary sarcoidosis. Proinflammatory monocytes are activated circulating monocytes thought to be related to the initial events of granuloma formation. We tested the hypothesis that peripheral blood monocytes in patients with active pulmonary sarcoidosis have an activated phenotype and, secondly, that measuring this activation status can provide a new tool for monitoring disease activity. Blood was collected of 23 steroid-naive patients presenting with pulmonary sarcoidosis and 10 healthy control subjects. Expression of CD16 (Fc-gamma type III receptor), CD69 (a general activation marker of cells of the hematopoietic lineage), and the integrin very late antigen (VLA)-1 (on interaction with extracellular matrix compounds mediates cell adhesion) was measured by flow cytometry. Percentages of monocytes expressing CD16, CD69, and VLA-1 in patients vs control subjects were 56.2 +/- 4.1% vs 12.2 +/- 2.4% (p < 0.0001), 87.3 +/- 2.1% vs 8.6 +/- 3.3% (p < 0.0001), and 66.5 +/- 3.6% vs 11.2 +/- 2.3% (p < 0.0001), respectively. Moreover, the CD69+VLA-1+ monocyte subset, abundantly present at disease presentation, was found to decrease to normal levels during follow-up with disease remission. Peripheral blood monocytes from patients with pulmonary sarcoidosis show a highly activated phenotype. Phenotyping circulating monocytes might be a promising tool for monitoring sarcoidosis disease activity but needs further investigation.


Health promotion programme in the private workplaces in Singapore: a prevalence survey.
A postal survey was conducted in 4,479 private companies with at least 50 employees in 1998 to determine the prevalence and the scope of workplace health promotion programme in these companies in Singapore. The self-administered questionnaire mailed to the study population covered five areas viz, organisational details, workplace health policies, health promotion and related activities, workplace health facilities and the source of assistance for the programme. The overall response was 49.5%. Parkinson's definition of workplace health promotion was used in the analysis to determine the prevalence of the programme. The data was collated on DBase IV and analysed using SPSS computer programmes. About one third of the respondents covering an estimated 26% of the private sector workforce had a comprehensive workplace health promotion programme as defined by Parkinson. This prevalence was a function of workforce size and industry type. Workplaces with larger workforce size (p<0.001) and those from the manufacturing and human/health service sectors (p<0.001) were more likely to have such programmes compared to their smaller counterparts and other industries respectively. The management remained the main driver behind these programmes. Many of the programmes were centred around health promoting policies and facilities with emphasis on occupational healthl safety and smoking issues. A significant proportion of workplaces surveyed had in place a comprehensive workplace health promotion programme. However, more could still be done to encourage its uptake such as training for facilitators, consultation, grant provision etc. Small workplaces remained an untapped market for such programmes.


Hylan G-F 20 improves hip osteoarthritis: a prospective, randomized study.
We compared the efficacy and safety of intra-articular hylan G-F 20 with methylprednisolone acetate (MPA) for treating symptomatic Kellgren-Lawrence grade (KLG) 2 or 3 hip osteoarthritis in a prospective, randomized, multicenter, double-blind trial (N = 313). Two injections of hylan G-F 20 were administered 2 weeks apart (n = 150), or 1 injection of 40 mg MPA and 1 sham injection 2 weeks later (n = 155). The Western Ontario and McMaster Universities Arthritis Index (WOMAC) (total and subscale), clinician observations, and patient global assessments were collected at baseline and at weeks 4, 8, 12, 16, 20, and 26 (intent-to-treat population was analyzed; n = 305). Responder rates were assessed by WOMAC domain A, and criteria were established by the Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI). At week 26, WOMAC A improved by 16.6 mm for hylan G-F 20 versus 13.6 mm for MPA. Response rates were higher with hylan G-F 20 versus MPA in patients with more advanced disease (KLG 3) and were similar between hylan G-F 20 and MPA in patients with less advanced disease (KLG 2). Adverse events were similar between groups and between patients with KLG 2 or 3. Hylan G-F 20 provided clinically meaningful improvements in pain and function, comparable with those of MPA, with good safety and tolerability. Thus, we conclude it is an appropriate option for treating hip osteoarthritis.