Anhydrobiosis and freezing-tolerance: adaptations that facilitate the establishment of Panagrolaimus nematodes in polar habitats.
Anhydrobiotic animals can survive the loss of both free and bound water from their cells. While in this state they are also resistant to freezing. This physiology adapts anhydrobiotes to harsh environments and it aids their dispersal. Panagrolaimus davidi, a bacterial feeding anhydrobiotic nematode isolated from Ross Island Antarctica, can survive intracellular ice formation when fully hydrated. A capacity to survive freezing while fully hydrated has also been observed in some other Antarctic nematodes. We experimentally determined the anhydrobiotic and freezing-tolerance phenotypes of 24 Panagrolaimus strains from tropical, temperate, continental and polar habitats and we analysed their phylogenetic relationships. We found that several other Panagrolaimus isolates can also survive freezing when fully hydrated and that tissue extracts from these freezing-tolerant nematodes can inhibit the growth of ice crystals. We show that P. davidi belongs to a clade of anhydrobiotic and freezing-tolerant panagrolaimids containing strains from temperate and continental regions and that P. superbus, an early colonizer at Surtsey island, Iceland after its volcanic formation, is closely related to a species from Pennsylvania, USA. Ancestral state reconstructions show that anhydrobiosis evolved deep in the phylogeny of Panagrolaimus. The early-diverging Panagrolaimus lineages are strongly anhydrobiotic but weakly freezing-tolerant, suggesting that freezing tolerance is most likely a derived trait. The common ancestors of the davidi and the superbus clades were anhydrobiotic and also possessed robust freezing tolerance, along with a capacity to inhibit the growth and recrystallization of ice crystals. Unlike other endemic Antarctic nematodes, the life history traits of P. davidi do not show evidence of an evolved response to polar conditions. Thus we suggest that the colonization of Antarctica by P. davidi and of Surtsey by P. superbus may be examples of recent "ecological fitting" of freezing-tolerant anhydrobiotic propagules to the respective abiotic conditions in Ross Island and Surtsey.


Effects of tetrahydrobiopterin on cerebral infarction after transient focal ischemia in rats.
The present study investigated the effects of tetrahydrobiopterin (BH4) on cerebral infarction after transient focal ischemia in rats. Focal ischemia (1·5 hours) was created in male Sprague-Dawley rats (250-280 g) by middle cerebral artery occlusion. Some rats were treated with 20 mg/kg tetrahydrobiopterin by intraperitoneal injection 30 minutes before reperfusion. At 2, 6, and 12 hours of reperfusion, the brains were harvested for the nitric oxide synthase (NOS) activity and nitric oxide (NO) level assays. At 12 hours of reperfusion, the brains were harvested for infarct size measurement. NOS activity and NO level were all augmented after reperfusion. BH4 treatment significantly further increased NOS activity and NO level. Cerebral infarct size was significantly bigger in BH4 treatment group compared to that in no treatment group. The data indicate that BH4 enhances cerebral infarction after transient focal ischemia in rats, through NOS and NO pathway.


Reversible polyelectrolyte capsules as carriers for protein delivery.
A reversible drug delivery system based on spontaneous deposition of a model protein into preformed microcapsules has been demonstrated for protein delivery applications. Layer-by-Layer assembly of poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) onto polystyrene sulfonate (PSS) doped CaCO3 particles, followed by core removal yielded intact hollow microcapsules having a unique property to induce spontaneous deposition of bovine serum albumin (BSA) at pH below its isoelectric point of 4.8, where it was positively charged. These capsules showed reversible pH dependent open and closed states to fluorescence labeled dextran (FITC-Dextran) and BSA (FITC-BSA). The loading capacity of BSA increased from 9.1 x 10(7) to 2.03 x 10(8) molecules per capsule with decrease in pH from 4.5 to 3. The loading of BSA-FITC was observed by confocal laser scanning microscopy (CLSM), which showed homogeneous distribution of protein inside the capsule. Efficient loading of BSA was further confirmed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The interior capsule concentration was as high as 209 times the feeding concentration when the feeding concentration was increased from 1 to 10 mg/ml. The deposition was initially controlled by spontaneous loading mechanism at lower BSA concentration followed by diffusion controlled loading at higher concentration; which decreased the loading efficiency from 35% to 7%. Circular dichroism (CD) measurements and Fourier transform infrared spectroscopy (FTIR) confirmed that there was no significant change in conformation of released BSA in comparison with native BSA. The release was initially burst in the first 0.5 h and sustained up to 5 h. The hollow capsules were found to be biocompatible with mouse embryonic fibroblast (MEF) cells during in vitro cell culture studies. Thus these pH sensitive polyelectrolyte microcapsules may offer a promising delivery system for water soluble proteins and peptides.


Quantification of a Glucocorticoid Profile in Non-pooled Samples Is Pivotal in Stress Research Across Vertebrates.
Vertebrates are faced continuously with a variety of potential stressful stimuli and react by a highly conserved endocrine stress response. An immediate catecholamine mediated response increases plasma glucose levels in order to prepare the organism for the "fight or flight" reaction. In addition, in a matter of minutes after this (nor)adrenaline release, glucocorticoids, in particular cortisol or corticosterone depending on the species, are released through activation of the hypothalamic-pituitary-interrenal (HPI) axis in fish or hypothalamic-pituitary-adrenal (HPA) axis in other vertebrates. These plasma glucocorticoids are well documented and widely used as biomarker for stress across vertebrates. In order to study the role of glucocorticoids in acute and chronic stress and gain in-depth insight in the stress axis (re)activity across vertebrates, it is pivotal to pin-point the involved molecules, to understand the mechanisms of how the latter are synthesized, regulated and excreted, and to grasp their actions on a plethora of biological processes. Furthermore, in-depth knowledge on the characteristics of the tissues as well as on the analytical methodologies available for glucocorticoid quantification is needed. This manuscript is to be situated in the multi-disciplinary research topic of glucocorticoid action across vertebrates which is linked to a wide range of research domains including but not limited to biochemistry, ecology, endocrinology, ethology, histology, immunology, morphology, physiology, and toxicology, and provides a solid base for all interested in stress, in particular glucocorticoid, related research. In this framework, internationally validated confirmation methods for quantification of a glucocorticoid profile comprising: (i) the dominant hormone; (ii) its direct precursors; (iii) its endogenously present phase I metabolites; and (iv) the most abundant more polar excreted exogenous phase I metabolites in non-pooled samples are pivotal.


The role of clinical toxicologists and poison control centers in public health.
Poison control centers and clinical toxicologists serve many roles within public health; however, the degree to which these entities collaborate is unknown. The objective of this survey was to identify successful collaborations of public health agencies with clinical toxicologists and poison control centers. Four areas including outbreak identification, syndromic surveillance, terrorism preparedness, and daily public health responsibilities amenable to poison control center resources were assessed. An online survey was sent to the directors of poison control centers, state epidemiologists, and the most senior public health official in each state and selected major metropolitan areas. This survey focused on three areas: service, structure within the local or state public health system, and remuneration. Questions regarding remuneration and poison control center location within the public health structure were asked to assess if these were critical factors of successful collaborations. Senior state and local public health officials were excluded because of a low response rate. The survey was completed in October 2007. A total of 111 respondents, 61 poison control centers and 50 state epidemiologists, were eligible for the survey. Sixty-nine (62%) of the 111 respondents, completed and returned the survey. Thirty-three (54%) of the 61 poison control centers responded, and 36 of the 50 state epidemiologists (72%) responded. The most frequent collaborations were terrorism preparedness and epidemic illness reporting. Additional collaborations also exist. Important collaborations exist outside of remuneration or poison control centers being a formal part of the public health structure. Poison control centers have expanded their efforts to include outbreak identification, syndromic surveillance, terrorism preparedness, and daily public health responsibilities amenable to poison control center resources. Collaboration in these areas and others should be expanded.


Moderate- to long-term therapeutic outcomes of treated aggressive periodontitis patients without regular supportive care.
Risk for deterioration in treated aggressive periodontitis (AgP) individuals remained unclear. This retrospective cohort study investigated 7-26 years of periodontal outcomes and oral health-related quality of life (OHRQoL) of young adults with advanced periodontitis. Eighty-nine previously treated patients with AgP were re-examined. Clinical and radiographic parameters before treatment discontinuation and at re-examination were compared. OHRQoL at re-call was assessed with the short-form Oral Health Impact Profile (OHIP-14S). None of the subjects adhered to suggested periodontal therapy and maintenance after discharge. Mean percentage of sites with probing pocket depth (PPD) ≥6 mm at re-examination was 4.5 ± 5.9%. A total of 182 teeth had been lost over time. Tooth loss rate was 0.14/patient/year. From 68 subjects with documented favorable treatment outcomes, higher percentage of sites with PPD ≥6 mm at re-examination and higher radiographic proximal bone loss was associated with current smoking status. Patients with AgP with <20 teeth at re-call had worse OHRQoL than those with ≥20 teeth. Patients with higher full-mouth mean PPD also reported poorer OHRQoL. Treatment in patients with AgP who smoke and neglect proper supportive care, risk periodontal disease progression. Substantial tooth loss and higher full-mouth mean PPD led to poorer OHRQoL in this cohort.


A prospective study of risk factors and decision making in discontinuation of dialysis.
Discontinuation of dialysis is a common cause of death. We performed a prospective study to determine if a detailed description of patients could be used to identify those at risk for discontinuing dialysis. Two hundred thirty-five dialysis patients were studied for 3 1/2 years. Using questionnaires, medical chart analyses, and interviews, 300 sociodemographic, quality-of-life, medical and dialysis variables were prospectively obtained. The association of these variables with death from discontinuation of dialysis was studied in univariate and multivariate analyses. Seventy-six patients (32%) died during the follow-up period, 31 (41%) of cardiovascular problems, 13 (17%) of discontinuation of dialysis, and 32(42%) of other causes. Patients who discontinued dialysis were older (mean age, 66 vs 54 years), were more likely to be divorced or widowed (46% vs 16%), were more likely to live in nursing homes (31% vs 6%), spent less time outdoors (23% vs 53%), had twice as much comorbidity as other patients (major comorbidity score, 1.2 vs 0.6), had the same psychological quality-of-life score (60 vs 62) but a lower score on the Karnovsky Scale, and a higher physical discomfort index. In multivariate analysis, comorbidity, widowed or divorced status, and severe pain were independent predictors of discontinuation of dialysis, but no reliable predictive model could be created. A detailed analysis of the final event indicated that a relentless succession of problems often led nursing home patients to discontinue dialysis. These problems are common to all dialysis patients, especially those who have no one to support them in their suffering. Discontinuation of dialysis is common, and can been seen as a failure of and a relief from long-term dialysis. We believe mortality caused by discontinuation of dialysis could be decreased by better psychological support and improved management of ischemic problems and pain. We found no predictable model for such patients, but many successive acute problems in widowed and divorced patients seem to trigger the decision.


High throughput instrument to screen fluorescent proteins under two-photon excitation.
Two-photon microscopy together with fluorescent proteins and fluorescent protein-based biosensors are commonly used tools in neuroscience. To enhance their experimental scope, it is important to optimize fluorescent proteins for two-photon excitation. Directed evolution of fluorescent proteins under one-photon excitation is common, but many one-photon properties do not correlate with two-photon properties. A simple system for expressing fluorescent protein mutants is E. coli colonies on an agar plate. The small focal volume of two-photon excitation makes creating a high throughput screen in this system a challenge for a conventional point-scanning approach. We present an instrument and accompanying software that solves this challenge by selectively scanning each colony based on a colony map captured under one-photon excitation. This instrument, called the GIZMO, can measure the two-photon excited fluorescence of 10,000 E. coli colonies in 7 hours. We show that the GIZMO can be used to evolve a fluorescent protein under two-photon excitation.


Phylogenetic stratigraphy in the Guerrero Negro hypersaline microbial mat.
The microbial mats of Guerrero Negro (GN), Baja California Sur, Mexico historically were considered a simple environment, dominated by cyanobacteria and sulfate-reducing bacteria. Culture-independent rRNA community profiling instead revealed these microbial mats as among the most phylogenetically diverse environments known. A preliminary molecular survey of the GN mat based on only ∼1500 small subunit rRNA gene sequences discovered several new phylum-level groups in the bacterial phylogenetic domain and many previously undetected lower-level taxa. We determined an additional ∼119,000 nearly full-length sequences and 28,000 >200 nucleotide 454 reads from a 10-layer depth profile of the GN mat. With this unprecedented coverage of long sequences from one environment, we confirm the mat is phylogenetically stratified, presumably corresponding to light and geochemical gradients throughout the depth of the mat. Previous shotgun metagenomic data from the same depth profile show the same stratified pattern and suggest that metagenome properties may be predictable from rRNA gene sequences. We verify previously identified novel lineages and identify new phylogenetic diversity at lower taxonomic levels, for example, thousands of operational taxonomic units at the family-genus levels differ considerably from known sequences. The new sequences populate parts of the bacterial phylogenetic tree that previously were poorly described, but indicate that any comprehensive survey of GN diversity has only begun. Finally, we show that taxonomic conclusions are generally congruent between Sanger and 454 sequencing technologies, with the taxonomic resolution achieved dependent on the abundance of reference sequences in the relevant region of the rRNA tree of life.


Knockdown of translationally controlled tumor protein inhibits growth, migration and invasion of lung cancer cells.
To investigate the role of translationally controlled tumor protein (TCTP) in lung cancer development. A549 and HCC827 cells were transfected with shRNA specifically targeting TCTP mRNA. Cell growth was assessed by colony formation assay and cell counting kit-8. Cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion was measured by scratch and transwell assays. In vivo tumorigenicity was evaluated by tumor xenografts in nude mice. TCTP-silenced cells displayed a reduced ability of colony formation and a lower rate of proliferation in vitro. Knockdown of TCTP arrested cell cycle at G1 phase and led to downregulated expression of cyclins B1, D1 and E. Moreover, silencing of TCTP induced apoptosis and altered the levels of apoptosis-regulatory proteins such as cleaved caspase-3, Bcl-2, Bax and p53. Silencing of TCTP also inhibited migration and invasion of lung cancer cells. In addition, TCTP-silenced A549 cells, when subcutaneously inoculated in nude mice, formed tumors at a significantly slower rate. Our in vitro and in vivo data indicate that silencing of TCTP inhibits growth, migration and invasion of lung cancer cells. Thus, TCTP may be a potential target for lung cancer therapy.


Social competition, corticosterone and survival in female lizard morphs.
We examined the selective consequences of variation in behaviour and endocrine physiology in two female throat-colour morphs of the lizard, Uta stansburiana in the wild. Female morphs differed in home-range distribution patterns and corticosterone levels in relation to the density and frequency of their female neighbours. Levels of plasma corticosterone of yellow-throated females increased with increased density of both morphs. In contrast, orange-throated females had reduced levels of corticosterone in response to increased density of orange females. Additionally, females with lower corticosterone survived poorly, suggesting that social interactions and high local densities of orange females may be potentially costly for orange females. These results are consistent with decreased fitness effects and suppression of immune function previously reported for orange female morphs surrounded by more orange neighbours. These correlations, in conjunction with previous work in this system, indicate that corticosterone is likely to be an important physiological mechanism regulating female fitness in nature.


The ghost of Helioth and his stereoscope: the return of a phantom.
Among the myths surrounding the invention of the stereoscope, that of Helioth stands as a supreme example of shoddy scholarship and its subsequent dissemination. Helioth was said to have made a simple stereoscope before Wheatstone presented his mirror stereoscope to the public in 1838. There is no evidence of Helioth's existence prior to a report in the mid-twentieth century, and despite attempts to dispel his ghost it has recently resurfaced.


Alcohol, wine and mental health: focus on dementia and stroke.
The relative risks of coronary heart disease (CHD) and overall mortality are reduced by moderate consumption of alcoholic beverages, particularly wine, which has major implications for public health. It appears likely that this beneficial effect of alcohol will soon be extended to some mental disorders. Although data on psychosis and mood and anxiety disorders are currently lacking, it appears that the relative risks of developing ischaemic stroke and Alzheimer's or vascular dementia are also lowered by moderate alcohol consumption. Such findings are still tentative because of the inherent methodological problems involved in population-based epidemiological studies, and it is unclear whether the benefit can be ascribed to alcohol itself or to other constituents specific to wine such as polyphenols. Plausible biological mechanisms have been advanced for the protective effect of alcohol and wine against CHD, many of which will also play roles in their protective actions against cerebrovascular disease and dementia. The specific antioxidant properties of wine polyphenols may be particularly important in preventing Alzheimer's disease. Because of the substantially unpredictable risk of progression to problem drinking and alcohol abuse, the most sensible advice to the general public is that heavy drinkers should drink less or not at all, that abstainers should not be indiscriminately encouraged to begin drinking for health reasons, and that light to moderate drinkers need not change their drinking habits for health reasons, except in exceptional circumstances.


Combined use of the modified Hodge test and carbapenemase inhibition test for detection of carbapenemase-producing Enterobacteriaceae and metallo-β-lactamase-producing Pseudomonas spp.
We evaluated the combined use of the modified Hodge test (MHT) and carbapenemase inhibition test (CIT) using phenylboronic acid (PBA) and EDTA to detect carbapenemase-producing Enterobacteriaceae (CPE) and metallo-β-lactamase (MBL)-producing Pseudomonas spp. A total of 49 isolates of CPE (15 Klebsiella pneumoniae carbapenemase [KPC], 5 Guiana extended-spectrum β-lactamase [GES]-5, 9 New Delhi metallo-β-lactamase [NDM]-1, 5 Verona integron-encoded metallo-β-lactamase [VIM]-2, 3 imipenem-hydrolyzing β-lactamase [IMP], and 12 oxacillinase [OXA]-48-like), 25 isolates of MBL-producing Pseudomonas spp. (14 VIM-2 and 11 IMP), and 35 carbapenemase-negative controls were included. The MHT was performed for all isolates as recommended by the Clinical and Laboratory Standards Institute. Enhanced growth of the indicator strain was measured in mm with a ruler. The CIT was performed by directly dripping PBA and EDTA solutions onto carbapenem disks that were placed on Mueller-Hinton agar plates seeded with the test strain. Considering the results of the MHT with the ertapenem disk in Enterobacteriaceae and Pseudomonas spp., the CIT with the meropenem disk in Enterobacteriaceae, and the imipenem disk in Pseudomonas spp., three combined disk tests, namely MHT-positive plus PBA-positive, EDTA-positive, and MHT-positive plus PBA-negative plus EDTA-negative, had excellent sensitivity and specificity for the detection of KPC- (100% sensitivity and 100% specificity), MBL- (94% sensitivity and 100% specificity), and OXA-48-like-producing isolates (100% sensitivity and 100% specificity), respectively. Combined use of the MHT and CIT with PBA and EDTA, for the detection of CPE and MBL-producing Pseudomonas spp., is effective in detecting and characterizing carbapenemases in routine laboratories.


Development of a novel UV indicator and dosimeter film.
A novel UV indicator is described, comprising nanocrystalline particles of titania dispersed in a film of a polymer, hydroxyl ethyl cellulose (HEC), containing: a mild reducing agent, triethanolamine (TEOA) and a redox indicator, methylene blue (MB). The UV indicator film is blue-coloured in the absence of UV light and loses colour upon exposure to UV light, attaining within a few min a steady-state degree of bleaching that can provide a measure of the irradiance of the incident light. The original blue colour of the film returns once the source of UV light is removed. The spectral characteristics of a typical UV indicator film, and its components, are discussed and the UV-absorbing action of the titania particles highlighted. From the measured %bleaching undergone by a typical UV indicator as a function of light irradiance the indicator appears fully bleached, within 7 min, by a UV irradiance of 3 mW cm(-2) or greater. The mechanism by which the UV indicator works is described. The reversible nature of the UV indicator is removed by covering a typical UV indicator with a thin, largely oxygen impermeable, polymer film, such as the regenerated cellulose found in Sellotape. The product is a UV dosimeter, the response of which is related to the intensity and duration of the incident UV light, as well as the amount of titania in the film. A typical UV dosimeter film is fully bleached by 250 mJ cm(-2) of UV light. The possible use of these novel indicators to measure UV exposure levels, irradiance and dose, is discussed.


IFN-alpha/beta enhances BCR-dependent B cell responses.
Type I interferon (IFN-I) is constitutively produced in the bone marrow (BM), and induced at sites of inflammation and following infection by viruses or microorganisms. We have previously shown that IFN-I regulates the generation and selection of normal B cell populations in the BM. In the present work, we assess the effects of IFN-I on mature B cell function by monitoring the responses of IFN-alpha/beta-treated murine splenic B cells to apoptotic, mitogenic and activating stimuli. A similar analysis is performed on BM mature B cells obtained from wild-type or IFN-I receptor-deficient mice. IFN-alpha/beta is shown to induce B cells to a state of partial activation characterized by the up-regulation of CD69, CD86 and CD25 molecules in the absence of either proliferation or terminal differentiation. B cells treated with IFN-alpha/beta show an increased survival and resistance to Fas-mediated apoptosis. IFN-alpha/beta also enhances B cell responses to BCR ligation such as calcium fluxes, IgM internalization, induction of activation markers and proliferation. These results indicate that in addition to its inhibitory effect on viral replication and T cell apoptosis, IFN-alpha/beta plays an essential role during an inflammatory response by lowering the threshold for B cell induction, thereby promoting fast and polyclonal antibody responses.


Histology in the diagnosis of reflux esophagitis.
Esophageal biopsy remains an important procedure for the diagnosis of RE, as well as for the identification of other causes of esophagitis. Although grasp biopsy specimens obtained by fiberoptic endoscopy are routinely performed for patients suspected of having reflux disease, they are infrequently oriented prior to their submission to the surgical pathology laboratory. Basal zone thickness and height of papillae, parameters considered by most pathologists to be useful for the diagnosis of RE, cannot be evaluated in unoriented sections. Hence, the search for intraepithelial neutrophils, and especially intraepithelial eosinophils, is critically important in grasp biopsy specimens. The finding of only a few intraesophageal eosinophils is sufficient for the diagnosis of reflux esophagitis (in the proper clinical setting) in both children and adults. In any biopsy specimen, the identification of eosinophils is easier and more reliable than the determination of basal zone thickness and height of papillae. The significance of finding only balloon cells in esophageal biopsy specimens from patients with suspected RE needs to be clarified by further study.


Study of Pulmonary function tests in Type 2 Diabetes Mellitus and their correlation with glycemic control and systemic inflammation.
Background - Reduced lung function in diabetes has been described for long but its clinical importance is not yet clear. Also, limited literature is available regarding its association with sugar control, and its correlation with inflammatory markers. Thus, we aimed to study the pulmonary function test abnormalities and systemic inflammation in type 2 diabetes mellitus. Methods 100 patients of type 2 diabetes were divided into two groups depending on control of diabetes (group A-HbA1C≤7% and group B-HbA1C >7%). All the subjects selected underwent detailed evaluation including testing for HbA1C, HsCRP (high-sensitivity C-reactive protein), serum ferritin and serum fibrinogen, along with pulmonary function testing. Results Percentage predicted FVC (forced vital capacity), FEV1 (forced expiratory volume in 1 second) and SVC (slow vital capacity) were significantly reduced, while mean values of inflammatory markers [fibrinogen (p <0.001) and hsCRP (p 0.002)] were significantly higher in uncontrolled diabetes group. There was a significant negative correlation between FEV1 (r = -0.739, p<0.001), FVC ( r = -0.370, p<0.001), SVC (r = -0.635, p< 0.001) with HbA1C. HbA1C had a positive correlation with hsCRP (r = -0.308, p 0.002) and fibrinogen (r = 0.388 ,p 0.001). Conclusion Pulmonary functions were decreased and inflammatory markers like hsCRP, fibrinogen, and ferritin significantly increased in uncontrolled diabetics. Also, a potential association was seen between higher values of inflammatory markers like hsCRP and fibrinogen and decrease in lung function. This information, requiring confirmation with larger multicentre studies, remains important because of potential epidemiological, clinical and therapeutic implications.


Vaginal bromocriptine improves pain, menstrual bleeding and quality of life in women with adenomyosis: A pilot study.
Adenomyosis is a benign uterine disease where endometrial glands and stroma are found within the myometrium surrounded by an area of hypertrophic myometrium. Symptomatology includes heavy menstrual bleeding and pelvic pain. The pathogenesis of adenomyosis is not known; however, animal models have shown increased uterine concentration of prolactin as a risk factor. Prolactin acts as a smooth muscle cell mitogen. If prolactin is central to adenomyosis pathogenesis, reducing uterine prolactin could be a possible medical treatment option. In this pilot study, we aim to evaluate the effect of bromocriptine, a prolactin inhibitor, on menstrual bleeding and pain in women with adenomyosis. 23 women with diffuse adenomyosis were enrolled from a university hospital in Sweden and a tertiary care center in the USA. Nineteen patients completed 6 months of treatment with vaginal bromocriptine at a dose of 5 mg daily. Participants completed validated measures at baseline, 3 and 6 months of treatment, and at 9 months (3 months after cessation of bromocriptine). Validated measures utilized included Pictorial Blood Loss Assessment Chart (PBLAC), Aberdeen Menorrhagia Clinical Outcomes Questionnaire (AMCOQ), Visual Analog Scale for pain (VAS), McGill Pain Questionnaire (MPQ), Endometriosis Health Profile (EHP-30), Female Sexual Function Index (FSFI) and the Fibroid Symptom Quality of Life (UFS-QOL) symptom severity and health-related quality of life (HRQL) subscores. Scores were compared between baseline and 9 months using the Wilcoxon signed rank test. Mean age of participants was 44.8 years. About 77.8% reported PBLAC scores >250 and 68.4% reported moderate to severe pain at baseline. Compared with baseline, women had lower 9-month scores (median [interquartile range] for all) on PBLAC (baseline 349 [292-645] vs 9-month 233 [149-515], P = 0.003), VAS (5.0 [4-8.3] vs 2.5 [0-4.5], P < 0.001), EHP Core Pain (15.9 [9.1-50.0] vs 3.4 [2.3-34.1], P = 0.029), EHP Core Self-image (41.7 [16.7-58.3] vs 25 [0-5], P = 0.048) and Symptom Severity Score (60 [44-72] vs 44 [25-56], P < 0.001) and higher HRQL scores (57 [37-63] vs 72 [51-85], P < 0.001) following bromocriptine treatment. Other EHP core parameters and FSFI were not significantly different. Significant improvement in menstrual bleeding, pain and quality of life after vaginal bromocriptine treatment suggests a novel therapeutic agent for adenomyosis.


The site of cartilage matrix degradation.
1. A 'cavity' organ culture method was developed, which allowed the insertion within bovine nasal cartilage of 10 microliter of 35S-labelled proteoglycan aggregate. 2. Stimulation of the tissue with retinol or catabolin led to degradation of both the cartilage matrix and the proteoglycan within the cavity. 3. Proteoglycan aggregate trapped in polyacrylamide beads was not broken down in the cavities of living cartilage, except under autolytic conditions. 4. It is suggested that degradation of proteoglycan aggregate by chondrocytes occurs in a pericellular region.


Assessment of Outcomes of Inpatient or Clinic-Based vs Home-Based Rehabilitation After Total Knee Arthroplasty: A Systematic Review and Meta-analysis.
Recent publication of the largest trials to date investigating rehabilitation after total knee arthroplasty (TKA) necessitate an updated evidence review. To determine whether inpatient or clinic-based rehabilitation is associated with superior function and pain outcomes after TKA compared with any home-based program. MEDLINE, Embase, CINAHL, and PubMed were searched from inception to November 5, 2018. Search terms included knee arthroplasty, randomized controlled trial, physiotherapy, and rehabilitation. Published randomized clinical trials of adults who underwent primary unilateral TKA and commenced rehabilitation within 6 postoperative weeks in which those receiving postacute inpatient or clinic-based rehabilitation were compared with those receiving a home-based program. Two reviewers extracted data independently and assessed data quality and validity according to the PRISMA guidelines. Data were pooled using a random-effects model. Data were analyzed from June 1, 2015, through June 4, 2018. Primary outcomes were mobility (6-minute walk test [6MWT]) and patient-reported pain and function (Oxford knee score [OKS] or Western Ontario and McMaster Universities Osteoarthritis Index) reported at 10 to 12 postoperative weeks. The GRADE assessment (Grading of Recommendations, Assessment, Development, and Evaluation) was applied to the primary outcomes. Five unique studies involving 752 unique participants (451 [60%] female; mean [SD] age, 68.3 [8.5] years) compared clinic- and home-based rehabilitation, and 1 study involving 165 participants (112 [68%] female; mean [SD] age, 66.9 [8.0] years) compared inpatient and home-based rehabilitation. Low-quality evidence showed no clinically important difference between clinic- and home-based programs for mobility at 10 weeks (6MWT favoring home program; mean difference [MD], -11.89 m [95% CI, -35.94 to 12.16 m]) and 52 weeks (6MWT favoring home program; MD, -25.37 m [95% CI, -47.41 to -3.32 m]). Moderate-quality evidence showed no clinically important difference between clinic- and home-based programs for patient-reported pain and function at 10 weeks (OKS MD, -0.15 [95% CI, -0.35 to 0.05]) and 52 weeks (OKS MD, 0.10 [95% CI, -0.14 to 0.34]). Based on low- to moderate-quality evidence, no superiority of clinic-based or inpatient programs compared with home-based programs was found in the early subacute period after TKA. This evidence suggests that home-based rehabilitation is an appropriate first line of therapy after uncomplicated TKA for patients with adequate social supports.


Modifications of glyceraldehyde-3-phosphate dehydrogenase induced by increasing concentrations of peroxynitrite: early recognition by 20S proteasome.
Peroxynitrite, a potent oxidizing and nitrating species, induces covalent modifications of biomolecules in a number of pathological conditions. In previous studies with S. cerevisiae, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as being especially susceptible to nitration by peroxynitrite. The activity of this enzyme was strongly inhibited by low doses of peroxynitrite in yeast and in cultured rat astrocytes. Here, the sequence of modifications of isolated mammalian GAPDH induced by increasing concentrations of peroxynitrite is demonstrated to be as follows: (i) oxidation, leading to inactivation and to enhanced susceptibility of GAPDH for proteasomal degradation, (ii) oligomer formation, and (iii) nitration. In our study the susceptibility for degradation by isolated 20S proteasome was by far the most sensitive parameter for peroxynitrite-induced damage to GAPDH, implying that this might also occur under pathological conditions where peroxynitrite is generated at low concentrations in vivo.


A bronchoscopy-associated pseudo-outbreak of Mycobacterium mucogenicum traced to use of contaminated ice used for bronchoalveolar lavage.
Clonal Mycobacterium mucogenicum isolates (determined by molecular typing) were recovered from 19 bronchoscopic specimens from 15 patients. None of these patients had evidence of mycobacterial infection. Laboratory culture materials and bronchoscopes were negative for Mycobacteria. This pseudo-outbreak was caused by contaminated ice used to provide bronchoscopic lavage. Control was achieved by transitioning to sterile ice.


Chronic Melatonin Treatment Prevents Memory Impairment Induced by Chronic Sleep Deprivation.
Sleep deprivation (SD) has been associated with memory impairment through induction of oxidative stress. Melatonin, which promotes the metabolism of many reactive oxygen species (ROS), has antioxidant and neuroprotective properties. In this study, the effect of melatonin on memory impairment induced by 4 weeks of SD was investigated using rat animal model. Animals were sleep deprived using modified multiple platform model. Melatonin was administered via oral gavage (100 mg/kg/day). Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers in the hippocampus following treatments were measured using ELISA procedure. The result revealed that SD impaired both short- and long-term memory (P < 0.05). Use of melatonin prevented memory impairment induced by SD. Furthermore, melatonin normalized SD-induced reduction in the hippocampus activity of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, melatonin enhanced the ratio of reduced to oxidized glutathione GSH/GSSG in sleep-deprived rats (P < 0.05) without affecting thiobarbituric acid reactive substance (TBARS) levels (P > 0.05). In conclusion, SD induced memory impairment, which was prevented by melatonin. This was correlated with normalizing hippocampus antioxidant mechanisms during chronic SD.


Molecular nature of two nonconjugative plasmids carrying drug resistance genes.
Two nonconjugative R-plasmids, N-SuSm and N-Tc, have been characterized. Both were of relatively small size (5 x 10(6) to 6 x 10(6) daltons) and present in multiple copies within their respective bacterial hosts. N-SuSm possessed a guanine plus cytosine content of 55%, whereas N-Tc was 49% guanine plus cytosine. Although these plasmids were inherently nontransmissible they could be mobilized by a large variety of transfer agents including Ent, Hly, and K88. The fi(-) transfer factors tested were far more likely (about 200x) to mobilize these nonconjugative plasmids than were the fi(+) transfer factors tested. Although the mobilization phenomenon was not found to be associated with a detectable level of direct stable recombinational union between N-SuSm or N-Tc with a transfer factor, we were able to demonstrate a low level of recombination between these replicons and a transfer factor by P1-mediated transduction. The isolation of recombinants between transfer factors and nonconjugative plasmids presumably represents one means by which unitary molecular types of R-plasmids arise and by which existing R-plasmids may acquire new resistance determinants.


Genome-wide methylation patterns in papillary thyroid cancer are distinct based on histological subtype and tumor genotype.
Aberrant DNA methylation is known to be a major factor in oncogenesis and cancer progression, but effects of methylation in papillary thyroid cancer (PTC) are not well defined. The objective of the study was to identify altered methylation patterns, which may be associated with PTC disease behavior. This study was a genome-wide methylation analysis of PTC. The study was conducted at the National Institutes of Health Clinical Center. PTC tissue from 51 patients were analyzed and compared with normal thyroid tissue from seven patients. CpG methylation status was assessed using advanced genome-wide methylation bead chips. Altered methylation patterns in PTC were analyzed by stage, recurrence, histological subtype of tumor, and tumor genotype. PTC is globally hypomethylated compared with normal thyroid with 2837 differentially methylated CpG sites. The follicular variant of PTC demonstrated less differential methylation with only 569 differentially methylated CpG sites. Tumors with mutations in BRAF, RET/PTC, and RAS demonstrated a 3.6-fold increase in the number of differentially methylated sites compared with wild-type tumors. The differentially methylated genes were associated with oncological pathways including cellular movement, growth, and proliferation. PTC is epigenetically distinct from the follicular variant of PTC and by gene mutation status (BRAF, RET/PTC, and RAS).


Active Involvement of People with Dementia: A Systematic Review of Studies Developing Supportive Technologies.
Although there are promising benefits of supportive technology in dementia care, use of these technologies is still limited. It is challenging for researchers and developers in this field to actively involve people with dementia in development. This review updates and builds on existing knowledge by including a contemporary and relevant perspective. This perspective was gained by including search words and search databases from the field of Human Computer Interaction (HCI) and Design, as these fields were expected to supply novel insights in the complex task of actively involving people with dementia in developing supportive technologies. A total of 49 out of 3456 studies were included which describe the development of a great variety of technologies. Often people with dementia were involved in the generative or evaluative phase of the development. Interviews and observations were most commonly used methods. In seven articles the people with dementia were co-designers. This literature review reflects that people with dementia can influence the development of technology in regards to content, design, and even the initial idea, although the impact on how they experience their own involvement remains largely unknown. There is a lack of specific knowledge on appropriate methods and materials for active involvement of people with dementia in supportive technology development, even when including articles from the field of HCI and Design. Future research is needed to further appreciate and improve the desired role of people with dementia in meaningful technology development.


[Effects of SERMs on bone health. Discrimination of SERMs from bisphosphonates in the treatment of postmenopausal osteoporosis].
Since the aim of the treatment of osteoporosis is to prevent fractures, the first-line drugs must be chosen according to their antifracture efficacies. In postmenopausal women with osteoporosis, alendronate, risedronate, minodronate, and raloxifene are effective in preventing vertebral fractures, and alendronate and risedronate significantly prevent hip fractures. Because the antifracture efficacy of raloxifene against vertebral fractures is considered similar to that of bisphosphonates, the discrimination of raloxifene from bisphosphonates depends on the strategy of doctors (internal medicine, gynecology, and orthopaedics) for preventing vertebral fractures according to the possible side effects of drugs including upper gastrointestinal events, hot flash, and deep vein thromboembolism. Recent reports suggest that patients could be identified who are more responsive to raloxifene than bisphosphonates by evaluating collagen cross-links markers such as homocysteine. Because the incidence of vertebral fractures is higher in Japanese patients, raloxifene plays an important role in the prevention of vertebral fractures in postmenopausal Japanese women with osteoporosis.


A Survey of Intravenous Remifentanil Use for Labor Analgesia at Academic Medical Centers in the United States.
Remifentanil is most commonly offered when neuraxial labor analgesia is contraindicated. There is no consensus regarding the optimal administration, dosing strategy, or requirements for maternal monitoring, which may pose a patient safety issue. This exploratory survey evaluated the current practices regarding remifentanil use for labor analgesia at academic centers in the United States. Of 126 obstetric anesthesia directors surveyed, 84 (67%) responded. In 2014 to 2015, an estimated 36% (95% confidence interval: 25.7-46.3) of centers used remifentanil, most of which did so less than 5 times. Some serious maternal and neonatal respiratory complications occurred, emphasizing that clinical protocols and adequate monitoring are key to ensure maternal and neonatal safety.


Acetazolamide relieves concurrent episodic movement disorders encountered in Southern states.
Patients with episodic or paroxysmal movements or postures often are thought to have hysteric or psychosomatic illnesses. Kinesigenic (movement-induced) posturing similarly is usually misinterpreted. This case is notable because of the presence of symptoms of two distinct diseases with similar symptoms and changes from one dystonic posture to another during three different durations of attack. The condition improved with acetazolamide therapy. The effect of acetazolamide on sodium and potassium ionophores is discussed because of new genetic information about these illnesses.


[Dental manpower prediction in Israel for 2017].
A recent study published by the authors indicated that according to the Israeli Central Bureau of Statistics in 2008, Israel had 5800 active dentists, a figure well below the publication by the Ministry of Health. Based on this figure, using the manpower to population ratio method, the following results were obtained: The predicted number of dentist in 2017 would be 6090, based on, the estimated number of Israel: graduates, the estimated number of dentists who would arrive in Israel as immigrants or Israelis who studied abroad, based on an attrition rate of 3% and on the assumption that the number of dentists leaving the country is negligible. Table 2, based on manpower to population ratio, indicates that by 2017, Israel would have 1 dentist per 1400 population, a ratio which is still far above what many countries present, but high for Israel. This might reflect a dramatic change, from employment in public clinics, back to private practices. The results clearly indicate that a shortage of dentists is predicted in the near future and a major brainstorming is urgently required to evaluate these results.


Stevens-Johnson Syndrome associated with mogamulizumab treatment of adult T-cell leukemia / lymphoma.
We report an adult T-cell leukemia/lymphoma patient suffering from Stevens-Johnson Syndrome (SJS) during mogamulizumab (humanized anti-CCR4 monoclonal antibody) treatment. There was a durable significant reduction of the CD4(+) CD25(high) FOXP3(+) regulatory T (Treg) cell subset in the patient's PBMC, and the affected inflamed skin almost completely lacked FOXP3-positive cells. This implies an association between reduction of the Treg subset by mogamulizimab and occurrence of SJS. The present case should contribute not only to our understanding of human pathology resulting from therapeutic depletion of Treg cells, but also alert us to the possibility of immune-related severe adverse events such as SJS when using mogamulizumab. We are currently conducting a clinical trial of mogamulizumab for CCR4-negative solid cancers (UMIN000010050), specifically aiming to deplete Treg cells.


Lung Cancer Inhibition by Betulinic Acid Nanoparticles via Adenosine 5'-Triphosphate (ATP)-Binding Cassette Transporter G1 Gene Downregulation.
BACKGROUND Despite scientific advancement in radiotherapy and chemotherapy, the 5-year survival rate of lung cancer patients is around 15%. The present study explored the anticancer potential of betulinic acid nanoparticles against lung cancer cells. MATERIAL AND METHODS The proliferative changes in lung cancer cells by betulinic acid nanoparticles were measured by MTT assay. Cell cycle analysis was performed by flow cytometry using propidium iodide stain. Transwell and wound healing assay were used for determination of HKULC2 cell metastatic potential. RESULTS The betulinic acid nanoparticle treatment significantly (P<0.05) reduced proliferation of HKULC2, H1299, and H23 cells. The proliferation of HKULC2, H1299, and H23 cells was reduced to 33%, 28% and 24%, respectively on treatment with 10 µM of betulinic acid nanoparticles. The results from flow cytometry showed that betulinic acid nanoparticle exposure lead to cell cycle arrest in G1 phase in HKULC2 cells. Treatment with betulinic acid nanoparticles markedly decreased migration potential of HKULC2 cells. The invasive ability of HKULC2 cells was also suppressed markedly on exposure to betulinic acid nanoparticles. Western blotting of HKULC2 cells showed that betulinic acid nanoparticles promoted the expression of p21 and p53 and downregulated CD133, ALDH, BCL2, MCL1, and c-Myc expression. Betulinic acid nanoparticles reduced the expression of ABCG1 protein markedly. CONCLUSIONS The present study demonstrated that betulinic acid nanoparticles inhibit proliferation, metastatic ability, and arrest cell cycle in lung cancer cells through downregulation of ABCG1 oncogene expression. Therefore, betulinic acid nanoparticles may be used as therapeutic agent for the treatment of lung cancer.


Team Functioning And Beliefs About Team Effectiveness In Inter-Professional Teams: Questionnaire Development And Validation.
Few validated instruments are available to measure team functioning in acute and primary care teams. To address this, we developed a questionnaire measuring healthcare provider perceptions of team effectiveness (Provider-PTE) and assessed its psychometric properties. Empirical evidence and a conceptual model were used for item generation. The 41-item self-completed questionnaire was developed. A cross-sectional survey of healthcare providers (n=283) across a range of settings was performed. Psychometric properties were assessed for French and English language questionnaires using Cronbach alpha (α) for reliability, the feedback form for face validity, expert opinion for content validity, and the known-group technique for construct validity. Responsiveness was examined by comparing scores in high and low functioning teams. The mean time needed to complete the questionnaire was less than 9 mins. Respondents were typically female (84%), and employed full time (80%) in urban settings (82%). Cronbach α values were as follows: Team Processes = 0.88; PTE-Overall = 0.91; Outcomes = 0.72. Significant differences were found by professional group (p = 0.017), length of time in the team (p = 0.025), and presence of nurse practitioners. Responses to Outcomes varied by employment status (p = 0.017). Differences were identified in high and low functioning teams (p<0.001). Feedback indicated that two questions related to team meetings needed to be added. The study produced evidence of validity for English and French language Provider-PTE questionnaires. The revised 43-item instrument represents an important contribution by providing a validated questionnaire to measure team functioning across a range of settings that is consistent with a conceptual framework.


Muscle mechanoreflex overactivity in hypertension: a role for centrally-derived nitric oxide.
The cardiovascular response to exercise is abnormally large in hypertension. Over the past decade, it has become clear that the exercise pressor reflex (a peripheral feed-back mechanism originating in skeletal muscle) contributes significantly to the generation of this hyper-responsiveness. Further, it has been determined that overactivity of the mechanically (muscle mechanoreflex) and chemically (muscle metaboreflex) sensitive components of the exercise pressor reflex underpin its dysfunction. Given the recent attention in the literature, this review focuses upon the aberrant function of the muscle mechanoreflex in this disease. Evidence supporting a role for the mechanoreflex in the pathogenesis of the exaggerated cardiovascular response to physical activity is highlighted. The peripheral and central mechanisms that may be responsible for mechanoreflex overactivity in hypertension are likewise discussed. Particular attention is given to emerging evidence implicating a role for centrally-derived nitric oxide in this process.


Generation of induced pluripotent stem cell lines from a sister pair who suffered post-partum or recurrent Spontaneous Coronary Artery Dissections.
Spontaneous Coronary Artery Dissection (SCAD) results from a bleed within a coronary artery wall that impairs blood flow as it expands. It is the most common cause of myocardial infarction in pregnant women. Here, peripheral blood mononuclear cells from two sisters who had suffered SCADs were reprogrammed using Sendai Virus. Expression of pluripotency markers, capability to differentiate to the three germ layers, and cellular integrity were confirmed. This is the first report of a SCAD family induced pluripotent stem cell (iPSC) cohort, including a sister who suffered post-partum SCAD, and one who suffered from multiple recurrences.


Surgical repair of chronic rotator cuff tears. A prospective long-term study.
Rotator cuff disease or injury is one of the most frequently seen orthopaedic conditions, and surgical repair of rotator cuff tears is a common procedure. A prospective analysis of the operation, with consistent assessment of patient characteristics, variables associated with the rotator cuff tear and repair techniques, and outcome factors, was performed. One hundred and five shoulders with a chronic rotator cuff tear underwent open surgical repair and acromioplasty between 1975 and 1983. The patients were followed for an average of 13.4 years (range, two to twenty-two years). There were sixteen small tears, forty medium tears, thirty-eight large tears, and eleven massive tears. The tears were repaired directly (seventy-two tears), by V-Y plasty (twelve), by tendon transposition (twenty), or by reinforcement with a fascia lata graft (one). The long head of the biceps had been previously torn in eleven shoulders and was tenodesed in three other shoulders. In fifty-six shoulders, the distal part of the clavicle was excised for treatment of degenerative arthritic changes, often associated with osteophyte formation. Satisfactory pain relief was obtained in ninety-six shoulders (p < 0.0001). There was significant improvement in active abduction (p < 0.001) and external rotation (p < 0.007) as well as in strength in these directions of movement (p < 0.03 and p < 0.002, respectively). At the latest follow-up evaluation, the result was rated as excellent for sixty-eight shoulders, satisfactory for sixteen, and unsatisfactory for twenty-one. Tear size was the most important determinant of outcome with regard to active motion, strength, rating of the result, patient satisfaction, and need for a reoperation. Older age, less preoperative active motion, preoperative weakness, distal clavicular excision, and a transposition repair technique were all associated with larger tear size. There were eight reoperations; five were for rerepair of a persistent or recurrent rotator cuff tear. Standard tendon repair techniques combined with anterior acromioplasty, postoperative limb protection, and monitored physiotherapy can produce consistent and lasting pain relief and improvement in range of motion. Improving the results of this procedure will depend upon the development of new techniques to address the active motion and strength deficiencies following repair of massive rotator cuff tears.


Accumulation and release of adrenaline, and the modulation by adrenaline of noradrenaline release from rabbit blood vessels in vitro.
The accumulation of (-)-3H-adrenaline (3H-A) by rabbit isolated aorta was studied. In all experiments, monoamine oxidase and catechol-O-methyltransferase were inhibited by treatment with pargyline and 3',4'-dihydroxy-2-methyl-propiophenone, respectively. The relationship between the accumulation of 3H derived from 3H-A and the duration of incubation was linear. The 3H-accumulation after 3 h incubation was 22.5 ml/g. In reserpine-treated tissue, the 3H-accumulation levelled off after 30 min and was 8.5 ml/g after 3 h. The concentration of 3H-A or (-)-3H-noradrenaline (3H-NA) and the 3H-accumulation (ml/g) were inversely related. At 10(-8) M, the 1-hour accumulation of 3H derived from 3H-A and 3H-NA was 7.8 and 15.2 ml/g, respectively. With increasing concentrations the accumulation values approached each other. The accumulation of 3H derived from 3H-A by reserpine-treated tissue also showed an inverse relationship with concentration. The accumulation of 3H derived from 3H-A was dependent on the bath temperature. Storage of tissue (0-5 days in salt solution without equilibration with 95% O2/5% CO2; 4 degrees C) did not affect the accumulation of 3H derived from 3H-A. Thereafter (7-14 days), the accumulation decreased. The inhibitory potency (IC50; -log M) of desipramine, cocaine, propranolol, isoprenaline, and normetanephrine on accumulation of 3H derived from 3H-A was found to be 8.26; 6.50; 5.48; 4.88, and 4.02, respectively. The maximal degree of inhibition was almost the same for these drugs, while that of clonidine and corticosterone was 50 and 20%, respectively. In the presence of desipramine, either clonidine, corticosterone or isoprenaline reduces the accumulation of 3H derived from 3H-A. Ouabain and iodoacetic acid, but not sodium cyanide and 2,4-dinitrophenol, reduced the accumulation of 3H derived from 3H-A. Anoxia (95% N2/5% CO2; 37 degrees C; 1-24 h) did not alter the accumulation of 3H derived from 3H-A. Glucose deprivation alone or combined with anoxia markedly reduced the 3H-accumulation. The release of 3H-A from rabbit isolated aorta was studied. This release was compared with that of 3H-NA. The stimulation-evoked 3H-overflow from aorta preloaded with 3H-A decreased with repeated stimulation. In contrast, prestimulation enhanced subsequent stimulation-evoked 3H-overflows. For both 3H-amines, the 3H-overflow increased concomitantly to the same degree with the number of pulses. The time course of 3H-overflows with either 3H-A or 3H-NA was compared.(ABSTRACT TRUNCATED AT 400 WORDS)


[Role of severe anemia and hypoglycemia in severe malaria's mortality in children in a pediatric ward in Parakou (Benin)].
In this study, the objective was to determine the proportion of severe anemia and hypoglycemia in severe malaria in children and to identify factors influencing death. This is a descriptive and analytic cross-sectional study with prospectively collected data from January to December 2009. It included children from one month to fourteen years of age hospitalized in the Parakou Regional Hospital Center in Benin for severe malaria according to the World Health Organization (WHO) criteria. Among the 1838 cases, 968 cases (52.6%) had either severe anemia or hypoglycemia or both. Among these, 89% were under 5 years. Biologically, the mean parasite density was 40 062/mm3 and the mean hemoglobin rate was 4.94 g/dl. The average blood glucose was 0.45 g/l. The mortality rate was 8.2%. Death occurrence rate was significantly higher in under five children's group hospitalized for severe anemia and/or hypoglycemia compared to those of the same age group with others forms of severe malaria (p=0,000081). This work suggests the importance of hypoglycemia and anemia among factors associated with death in children's severe malaria.


Evaluation of the in vivo antimalarial activity of ethanolic leaf and stembark extracts of Anthocleista djalonensis.
To evaluate the in vivo antimalarial activities of ethanolic leaf and stembark extracts of Anthocleista djalonensis used traditionally as malarial remedy in Southern Nigeria in mice infected with Plasmodium berghei berghei. The ethanolic extracts of the A. djalonensis leaf (1000 - 3000 mg/kg/day) and stembark (220 - 660 mg/kg/day) were screened for blood schizonticidal activity against chloroquine-sensitive P. berghei in mice. The schizonticidal effect during early and established infections was investigated. The A. djalonensis leaf extract (1000 - 3000 mg/kg/day) exhibited a significant antiplasmodial activity both in the 4-day early infection test and in the established infection with a considerable mean survival time, which was incomparable to that of the standard drug, chloroquine (5 mg/kg/day). The stembark extract (220 - 660 mg/kg/day) also demonstrated a promising blood schizontocidal activity in early and established infections. These plant extracts possess considerable antiplasmodial activities, which justify their use in ethnomedicine and can be exploited in malaria therapy.


Current state of posterior chamber intraocular lenses after intracapsular and extracapsular cataract surgery.
The current posterior chamber lenses available for use after intracapsular and extracapsular cataract extraction, including the iris-centred and supported lenses, are reviewed. The relative advantages of rigid and flexible loop posterior chamber lenses used after extracapsular extraction are compared and it is concluded that there is little difference in the immediate visual results. The flexible posterior chamber lens is more difficult to insert in a collapsed anterior chamber and small pupil; conversely, capsular-fixed posterior chamber lenses face the problem of anterior capsular fibrosis and optic decentration if inaccurately placed.


A Novel Study of Comorbidity between Schizoaffective Disorder and Geschwind Syndrome.
Geschwind syndrome has been described in patients with temporal lobe epilepsy and is characterized by sexual behavioural disorders, hyperreligiosity, hypergraphia, and viscosity. Presented here is a case of a 53-year-old man with clinical findings consistent with Geschwind syndrome in the setting of a known diagnosis of schizoaffective disorder, with no identifiable comorbid illness of temporal lobe epilepsy or frontotemporal dementia. Brain MRI showed bilateral temporal lobe atrophy greater than would be expected for age and more prominent on the left side than the right. It is likely that these structural abnormalities may be related to this patient's clinical presentation of Geschwind syndrome. To our knowledge, this is the first reporting of a case of Geschwind syndrome in the setting of schizoaffective disorder. These symptoms of Geschwind syndrome were present irrespective of mental state status. The report highlights the importance in correct identification of underlying cause and differentiation between Geschwind syndrome and schizoaffective disorder in order to avoid mistreatment and consequent iatrogenic adverse events.


A novel biometric authentication approach using electrocardiogram signals.
In this work, we present a novel biometric authentication approach based on combination of AC/DCT features, MFCC features, and QRS beat information of the ECG signals. The proposed approach is tested on a subset of 30 subjects selected from the PTB database. This subset consists of 13 healthy and 17 non-healthy subjects who have two ECG records. The proposed biometric authentication approach achieves average frame recognition rate of %97.31 on the selected subset. Our experimental results imply that the frame recognition rate of the proposed authentication approach is better than that of ACDCT and MFCC based biometric authentication systems, individually.


A PCR assay for gender assignment in dugong (Dugong dugon) and West Indian manatee (Trichechus manatus).
Gender assignment for some aquatic mammals in the field is difficult. Molecular sexing from tissue biopsies is possible as males are heterogametic. Here we describe a multiplex PCR assay that amplifies the male specific SRY gene and differentiates ZFX and ZFY gametologues in two sirenian species, dugong (Dugong dugon) and West Indian manatee (Trichechus manatus). The assay was validated with animals of known gender and proved accurate and robust to experimental failure.


Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women.
Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.


Maxillary sinus carcinoma. Natural history and outcome.
To assess natural history, treatment outcome and pattern of relapse in patients with maxillary sinus carcinoma. A review was conducted of the medical records of all adult patients with maxillary sinus carcinoma, who were treated at King Faisal Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, between January 1990 and December 1999. A total of 60 patients were identified for analysis, 36 men and 24 women; the median age was 58-years (range 23-95). Major presenting symptoms were facial swelling 55%, facial pain 50%, and nasal obstruction 43.4%, with a median duration of 5-months (range 1-24). Histology was squamous cell carcinoma in 71.7% and adenoid cystic in 16.7%. They were restaged according to American Joint Committee on Cancer classification 1997 as II, III and IV in 1, 10 and 49. Thirty patients received treatment with curative intent (surgery in 4 patients, radiotherapy in 2, and combined modality in 24), 6 patients refused treatment and 24 were treated palliatively. With a median follow up of 50-months (range 2-128) in surviving patients treated with a curative intent, 12/30 failed locally, 4/30 in the regional neck nodes and 2/30 had systemic relapse. The actuarial 5-year overall survival (OS), relapse free survival (RFS) and local control rate (LC) were 55%, 39% and 51%. Treatment modality was the only significant prognostic factor for outcome, with 5 year OS, RFS and LC of 72%, 49% and 61%, for combined modality using surgery followed by radiotherapy compared to 0% for single approach (p=0.0003, p=0.0052 and p=0.0098) This study indicates that the majority of our patients presented with advanced disease, resulting in poor outcome to conventional treatment modalities. Efforts should be directed to minimize the delay in diagnosis at the primary care level. Combined modality treatment should be offered to all patients with locally advanced disease. New approaches such as neoadjuvant or concurrent chemoradiotherapy with or without surgery need to be considered and evaluated in prospective studies.


In vitro comparison of 3 techniques of prosthesis attachment to the muscular process of the equine arytenoid cartilage.
To determine the degree and ease of arytenoid abduction achieved with abaxial placement of a FASTak II suture anchor compared to 2 suture patterns with different directions of insertion-caudomedial to craniolateral and medial to lateral. Ex vivo experimental. Cadaveric larynges from 10 Standardbred racehorses. Each larynx was sequentially instrumented with all 3 arytenoid suture attachment in random order: (1) abaxial placement of a FASTak II suture, (2) caudomedial to craniolateral suture, and (3) medial to lateral suture placement. Each construct was abducted at 5N increments from 0 to 25N and the left to right quotient angle ratio (LRQ) measured from digital pictures acquired at each sequential increment. Arytenoid abduction (higher LRQ) was greater with FASTak II construct than either of the suture patterns. The largest difference occurred at 5N. Approximately 50% less force was required to achieve an LRQ of 1.0 with the FASTak II anchor compared to the suture patterns. No difference was detected between the 2 suture constructs throughout the study. Use of the FASTak II suture anchor improved arytenoid abduction compared to 2 suture patterns and minimized the suture loads required to achieve maximum arytenoid abduction. Use of the FASTak II anchor may decrease the suture load required to achieve arytenoid abduction in clinical cases. This may reduce the load placed on the laryngoplasty, thereby, minimizing postoperative loss of abduction.


Influenza vaccination in paediatric nurses: cross-sectional study of coverage, refusal, and factors in acceptance.
Influenza vaccination among health-care workers is poor, and the effectiveness of hospital vaccination programs remains unclear. Little is known about the effectiveness of intensive evidence-based vaccination programs in nursing staff. We determined whether the recommended vaccination rate could be achieved among paediatric nurses during an intensive promotional program for influenza vaccination. We also sought to identify the reasons for which nurses refuse the influenza vaccine and predictors of future vaccination intent. We offered influenza vaccination to nursing staff during an influenza season through a multi-component program that included intensive promotional activities. We analysed vaccination data to determine uptake rates. In a cross-sectional survey, self-administered questionnaires were distributed to all nurses with patient contact during that season. The questionnaire evaluated their vaccine use, site of work, absenteeism and physician visits due to respiratory illness, vaccination intent for the subsequent influenza season, and other items. We surveyed vaccinated nurses regarding their program experiences and the frequency and severity of adverse reactions. Unvaccinated nurses were asked their reasons for refusing vaccination. Multiple logistic-regression analysis was conducted to identify variables that predicted the likelihood of future vaccine acceptance. More than 75% (895/1,182) of applicable nurses were vaccinated in the program. The questionnaire response rate was nearly 48% (585/1,230). Vaccination in the program during the current season (odds ratio [OR] 101.99, 95% confidence interval [CI] 52.54-197.98), program convenience (OR 199.19, 95% CI 98.01-404.11), and a physician visit for respiratory illness (OR 2.44, 95% CI 1.29-4.61) were found to be independent predictors of intent to receive the vaccine the following season. A lack of perceived personal need was the most common reason for vaccine refusal, given in 30% (77/258) of unvaccinated respondents. Adequate coverage of nurses is achievable during an intensive voluntary immunisation program against influenza, using best-known practices. Perceived lack of personal benefit is a major deterrent, while program convenience and previous vaccination strongly predict future vaccine acceptance. Our findings support interventions that improve the convenience of hospital immunisation programs for influenza, particularly those that are aimed at nurses and that promote vaccine efficacy and benefits.


Initiation of dermatophyte pleomorphic strain sporulation by increased aeration.
A normally asporogenous pleomorphic strain of Microsporum gypseum was induced to sporulate by controlled aeration and dehydration. Aeration of the pleomorphic strain under optimal cultivation conditions caused the initiation of a sporulation cycle with equivalent growth parameters and percentage intracellular water loss as the wild-type strain. Initiation of sporulation was not due to alteration of the medium's nutrient concentration or consistency, concentration of fungal growth by-products, or removal of volatile "staling factors." Macroconidia formed by the pleomorphic colonies were of characteristic wildtype morphology, but germinated to form typical pleomorphic colonies, indicating that the induced sporulation was strictly phenotypic and reversible. Other asporogenous pleomorphic strains from different dermatophyte genera also were induced to form macroconidia by aeration, suggesting a similarity in sporulation induction in Microsporum sp., Epidermophyton floccosum, and Trichophyton violaceum. Initiation of sporulation by aeration further suggested that the pleomorphic mutation was one which affected the sensitivity of the pleomorphic aerial hyphae to natural sporulation inducers (i.e., decreased humidity) and did not represent a loss in the ability to form fertile macroconidia.


Biobehavioral approaches to cancer progression and survival: Mechanisms and interventions.
Over the last decade, there have been groundbreaking strides in our understanding of the multiple biological pathways by which psychosocial and behavioral factors can affect cancer progression. It is now clear that biobehavioral factors not only affect cellular immunity but both directly and indirectly modulate fundamental processes in cancer growth, including inflammation, angiogenesis, invasion, and metastasis. There is also an emerging understanding of how psychological and behavioral factors used in interventions can impact these physiological processes. This review outlines our current understanding of the physiological mechanisms by which psychological, social, and behavioral processes can affect cancer progression. The intervention literature is discussed, along with recommendations for future research to move the field of biobehavioral oncology forward.


BTEB2 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model.
Basic transcription element-binding protein 2 (BTEB2) is a regulator of the proliferation and phenotypic changes of vascular smooth muscle cells (SMCs). The aim of the present study was to determine whether or not BTEB2 knockdown inhibits balloon injury-induced neointimal hyperplasia attributed to the proliferation and phenotypic changes of vascular SMCs. We found that the knockdown of BTEB2 with antisense oligonucleotides (Ad-As-BTEB2) significantly reduced the intima/media ratio compared to uninjured arteries and vessels treated with Ad-LacZ. Knockdown of BTEB2 suppresses the proliferation of cultured vascular SMCs, concurrent with the down-regulation of proliferating cell nuclear antigen, angiotensin II type 1 receptor and platelet-derived growth factor BB. In addition, BTEB2 knockdown caused the up-regulation of the differentiation marker smooth muscle α-actin and down-regulation of the dedifferentiation marker embryonic smooth muscle myosin heavy chain. The present study provides direct evidence that BTEB2 plays a critical role in balloon injury-induced neointimal hyperplasia, which is closely linked to vascular SMC proliferation and phenotypic modulation. This study highlights the fact that BTEB2 may be a potential target for the prevention of restenosis after vascular intervention.


Exercise, sleep and cancer-related fatigue: Are they related?
Cancer-related fatigue (CRF) is a commonly reported and debilitating side effect of cancer and/or cancer treatment. Sleep disorders are also highly reported in the cancer population; however it is unknown if sleep is associated with fatigue. In the general population, exercise has been shown to improve sleep, however in the cancer population this idea is under investigation. The primary purposes of this review were to: (i) review the prevalence and causes of sleep disorders in cancer patients and survivors, (ii) examine the relationship between sleep and CRF and (iii) review the impact of exercise interventions on sleep in cancer patients and survivors. A scoping review of the literature was conducted regarding exercise interventions in cancer patients and survivors with sleep as at least one outcome measure. A search of the literature revealed limited studies (n=21) assessing the effect of exercise on sleep disorders in the cancer population. Methodological issues are evident because assessing sleep is often not the main outcome of interest. The reviewed studies revealed that exercise positively impacts sleep quality and quantity. There seems to be possible relationship between sleep disorders, exercise and CRF. Further investigation of this relationship is necessary, specifically using objective measurement tools, in large, controlled studies, focusing on sleep as the primary outcome.


Profound remission in Crohn's disease requiring no further treatment for 3-23 years: a case series.
Crohn's disease (CD) is rising in incidence and has a high morbidity and increased mortality. Current treatment use immunosuppressives but efficacy is suboptimal, and relapse is common. It has been shown that there is an imbalance present in the gut microbiome (dysbiosis) in CD with a possible infective aetiology-Mycobacterium avium subsp. paratuberculosis (MAP) being the most proposed. Antibacterial therapy and Faecal Microbiota Transplantation (FMT) are emerging treatments which can result in clinical and endoscopic remission, if employed correctly. The objective of this study was to report on the treatment and clinical outcomes of patients with CD in prolonged remission. Ten patients were identified to have achieved prolonged remission for 3-23 years (median 8.5 years). Of these, 7/10 took targeted Anti-MAP therapy (AMAT) for a median 36 months and then ceased AMAT treatment. After stopping AMAT five patients underwent Faecal Microbiota Transplantation (FMT) (average four infusions). In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6 months after fistulae resolution. One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for Clostridioides difficile Infection. Prolonged remission has been achieved for 3-23 years with individualised treatments, with the majority using AMAT ± infliximab and FMT. Treatment with antibiotics and/or FMT provides a potential new avenue for treatment of CD. These findings should stimulate thinking, investigations and better therapy against MAP and the dysbiosis of the gut flora, to enable higher rates of prolonged remission.


[Comparative study of immunomodulating properties of phenibut and gammoxin].
Experiments on CBA mice with model immunodepression induced by cyclophosphamide showed that phenibut (25 mg/kg) and gammoxin (25 mg/kg) recover both cellular and humoral immunoreactivity and restore lymphoproliferative processes in immunocompetent organs, which is evidence for pronounced immunocorrecting properties of these drugs. A comparative analysis of the immunomodulating activity of phenibut and gammoxin showed that the latter drug predominantly affects the process of immunocompetent cell maturation (growth in mass and cellularity of thymus and spleen--the central immunocompetent organs), while phenibut mostly influences the realization of the final reaction of the primary anti-erythrocyte immune response (significant correction of local infiltration delayed-type hypersensitivity reaction and antibody formation). This difference can be related to the fact that the drugs influence GABA receptors of different types, whereby gammoxin acts on these receptors in immunocompetent organs and phenibut acts on the receptors in lymphocytes.


Does the timing of suicide risk assessments influence ratings of risk severity?
Clinicians are often tasked with identifying and managing patients who are at risk for suicide. Therefore, greater understanding of factors that impact the efficacy of suicide risk assessments (SRA) are of critical importance. One potential factor that may affect assessments of risk severity is the timing of the evaluation during clinical interview. Given that some patients are reluctant to disclose suicide-related symptoms, it is possible that asking about suicide at the beginning of an interview elicits more false negatives. It is also possible that if risk assessments are conducted in a manner that is encouraging to the patient, timing does not significantly impact patient report. This study examined whether SRA timing within an initial intake interview affects risk severity ratings. Adult psychiatric outpatients (N=169) were randomly assigned to receive a SRA during the beginning or middle of a one-hour intake. We failed to find a significant difference in suicide risk ratings between those who were evaluated at the beginning as compared to the middle of intake (14% versus 15% rated at elevated risk). Findings were not moderated by age, gender, or attempt history. Our results provide preliminary evidence that the timing of SRA may not impact risk severity ratings.


Comparison between two- and three-dimensional quantitative coronary angiography bifurcation analyses for the assessment of bifurcation lesions: A subanalysis of the TRYTON pivotal IDE coronary bifurcation trial.
Three-dimensional (3D) quantitative coronary angiography (QCA) provides more accurate measurements by minimizing inherent limitations of two-dimensional (2D) QCA. The aim of this study was to compare the measurements between 2D and 3D QCA analyses in bifurcation lesions. A total of 114 cases with non-left main bifurcation lesions in the TRYTON pivotal IDE Coronary Bifurcation Trial (ClinicalTrials.gov: NCT01258972) were analyzed using a validated bifurcation QCA software (CAAS 5.10, Pie Medical Imaging, Maastricht, the Netherlands). All cases were analyzed in matched projections between pre- and post-procedure. The 2D analysis was performed using one of two angiographic images used for 3D reconstruction showing a larger distal bifurcation angle. In the treated segments (stent and balloon), there were no differences in minimal luminal diameter (MLD) between 2D and 3D, while diameter stenosis (DS) was significantly higher in 2D compared to 3D both pre-procedure and post-procedure (53.9% for 2D vs. 52.1% for 3D pre-procedure, P < 0.01; 23.2% for 2D vs. 20.9% for 3D post-procedure, P = 0.01). In the sub-segment level analysis, lengths of proximal main branch, distal main branch, and side branch were consistently shorter in 2D compared to 3D both pre-procedure and post-procedure. Using 3D QCA, the anatomic location of the smallest MLD or the highest DS was relocated to a different bifurcation sub-segment in a considerable proportion of the patients compared to when 2D-QCA was used (kappa values: 0.50 for MLD, 0.55 for DS). Our data showed differences in addressing anatomical severity and location of coronary bifurcation lesions between in vivo 2D and 3D QCA analyses. More studies are needed to investigate potential clinical benefits in using 3D approach over 2D QCA for the assessment of bifurcation lesions.


The attitudes of Canadian maternity care practitioners towards labour and birth: many differences but important similarities.
Collaborative, interdisciplinary care models have the potential to improve maternity care. Differing attitudes of maternity care providers may impede this process. We sought to examine the attitudes of Canadian maternity care practitioners towards labour and birth. We performed a cross-sectional web- and paper-based survey of 549 obstetricians, 897 family physicians (400 antepartum only, 497 intrapartum), 545 nurses, 400 midwives, and 192 doulas. Participants responded to 43 Likert-type attitudinal questions. Nine themes were identified: electronic fetal monitoring, epidural analgesia, episiotomy, doula roles, Caesarean section benefits, factors decreasing Caesarean section rates, maternal choice, fear of vaginal birth, and safety of birth mode and place. Obstetrician scores reflected positive attitudes towards use of technology, in contrast to midwives' and doulas' scores. Family physicians providing only antenatal care had attitudinal scores similar to obstetricians; family physicians practising intrapartum care and nurses had intermediate scores on technology. Obstetricians' scores indicated that they had the least positive attitudes towards home birth, women's roles in their own births, and doula care, and they were the most concerned about the consequences of vaginal birth. Midwives' and doulas' scores reflected opposing views on these issues. Although 71% of obstetricians supported regulated midwifery, 88.9% were against home birth. Substantial numbers of each group held attitudes similar to dominant attitudes from other disciplines. To develop effective team practice, efforts to reconcile differing attitudes towards labour and birth are needed. However, the overlap in attitudes between disciplines holds promise for a basis upon which to begin shared problem solving and collaboration.


Heat-shock proteins: chaperoning DNA repair.
Cells are repeatedly exposed to environmental or endogenous stresses that can alter normal cell behavior and increase cell vulnerability. In order to ensure tissue integrity and function, cells cope with cellular injuries by adapting their metabolism, protecting essential intracellular constituents, inhibiting cell death signaling pathways and activating those devoted to damage repair. The molecular chaperones of the heat-shock protein (HSP) family are critical effectors of this adaptive response. They protect intracellular proteins from misfolding or aggregation, inhibit cell death signaling cascades and preserve the intracellular signaling pathways that are essential for cell survival. Most HSPs are rapidly overexpressed in response to cellular injuries including genotoxic stress. DNA damage can dramatically alter cell behavior and contribute to a number of diseases including developmental defects, neurodegenerative disorders, and cancer. Thus, the ability of cells to repair DNA damage is essential for preserving cell integrity. DNA damage activates a coordinated response that includes detecting DNA lesions before their transmission to daughter cells, blocking cell cycle progression and DNA replication and repairing the damage. Although the role of HSPs in proteins homeostasis and cell death, especially apoptosis has been widely reported, much less is known about their function in DNA repair. This review aims to present the role of HSPs in DNA repair signaling pathways.


Optical analysis of biological hydrogen sulphide: an overview of recent advancements.
Determining the levels of endogenous hydrogen sulphide in real time has become increasingly crucial because of its important biological roles in various physiological and pathological processes. Optical methods allowing sensitive, multiplex and dynamic analysis in a non-invasive manner have attracted much attention in biological and biomedical analysis. This review provides an overview of recent advancements in optical analysis of biological hydrogen sulphide, with a focus on fluorescence and non-fluorescence optical strategies for sensing and imaging subcellular hydrogen sulphide in living biosystems.


Effects of Caregiver Sleep Disturbances on Relationship Quality with their Care Recipient.
Sleep problems are highly prevalent and disruptive for caregivers. While the connection between caregivers' sleep and outcomes like caregiver burden and quality of life are well established, the potential influence of caregivers' sleep on their reported relationship quality with the care recipient is not known. The current study sought to address this gap. We analyzed data from the 2017 National Health and Aging Trends Study and linked it with data from the 2017 National Study of Caregiving (NSOC). Our dependent variable was caregiver-reported relationship quality, and our predictor variable of interest was caregiver sleep problems. We also included several covariates related to the caregiver and care recipient. We used a generalized linear model to examine the relationship between caregiver sleep problems and relationship quality, controlling for other potentially influential factors. Sleep problems were significantly related to relationship quality. Compared to caregivers who reported no sleep problems, those who reported at least one sleep problem (β: -0.23, 95% CI: -0.46 to -0.01) had lower relationship quality with the care recipient. Other factors that remained related to relationship quality in the generalized linear model were negative aspects of caregiving, emotional difficulties, caregiver race, relationship type, care recipient depressive symptoms and care recipient sex. Sleep problems are influential health behaviors that are related to relationship quality for caregivers. Therefore, it is critical that sleep is more systematically assessed and addressed in caregiving populations.


Mn0.2Co0.8Fe2O4 and encapsulated Mn0.2Co0.8Fe2O4/SiO2 magnetic nanoparticles for efficient Pb2+ removal from aqueous solution.
Sol-gel auto-combustion technique was used to synthesize spinel ferrite nanoparticles of Mn0.2Co0.8Fe2O4 (MCF). Using the modified Stöber method, these magnetic nanoparticles were encapsulated with silica to form the core/shell Mn0.2Co0.8Fe2O4/SiO2 (MCFS). The phase composition, morphology, particle size, and saturation magnetization of the encapsulated nanoparticles were studied using X-ray diffraction (XRD), high resolution-transition electron microscopy (HR-TEM), and vibrating sample magnetometer (VSM). HR-TEM images indicated that particle size of the nanoparticles ranged from 15 to 40 nm, and VSM measurements showed that Ms of uncoated and coated samples were 65.668 emu/g and 61.950 emu/g and the Hc values were 2,151.9 Oe and 2,422.0 Oe, respectively. The effects of metal concentration, solution pH, contact time, and adsorbent dose of the synthesized nanoparticles on lead (Pb2+) ions removal from an aqueous solution were investigated. Based on Langmuir isotherm model, the results for peak adsorption capacity of the adsorbent under optimal conditions was 250.5 mg/g and 247 mg/g for MCF and MCFS, respectively. We concluded that Pb2+ adsorption occurred via a chemisorption mechanism based on the analysis of adsorption kinetics. The adsorbents displayed consistent adsorption efficiencies following three cycles of regeneration, indicating that these magnetic nanoparticles are promising candidates for wastewater purification.


'Abandoned by medicine'? A qualitative study of women's experiences with lymphoedema secondary to cancer, and the implications for care.
Lymphoedema secondary to cancer is a relatively neglected and under-researched condition. Few studies report people's experiences of care and treatment provision when living with the condition. Current practice focuses on the physical treatment yet psychosocial needs often remain unmet. A previous study examining the patient perspective identified the theme of being 'abandoned by medicine'. Perceived lack of support may result in a delayed adaptation and acceptance of this long-term condition and can significantly impact on psychological well-being. We explore this emerging theme alongside others in order to provide a guide to action for improvements for patient benefit. The central aim was to explore women's views of their care and treatment following a diagnosis with lymphoedema secondary to cancer. This forms part of a larger study aimed at assessing appropriate screening tools to measure psychosocial distress. A mixed-methods approach was used for the main study. Here we report the qualitative component, derived from in-depth semi-structured interviews conducted in the homes of the participants (n = 14) and focus group discussions (n = 15). In addition, qualitative comments from questionnaire data from a large-scale postal survey are included (n = 104). Participants identified considerable deficiencies in health care workers' knowledge and awareness of lymphoedema, which subsequently impacted on the patients' needs for information, support and understanding. Access to appropriate treatment was patchy and problems were identified with the process of obtaining compression garments, massage and other sources of help. Although lymphoedema is a long-term disfiguring condition, and much is known about how this impacts on patients' emotional well-being, little attention was paid by health professionals to potential psychosocial consequences. In essence women had to become experts of their own condition and cope as best as they could. We provide recommendations to improve service delivery and address these unmet needs.


The causal explanatory functions of medical diagnoses.
Diagnoses in medicine are often taken to serve as explanations of patients' symptoms and signs. This article examines how they do so. I begin by arguing that although some instances of diagnostic explanation can be formulated as covering law arguments, they are explanatory neither in virtue of their argumentative structures nor in virtue of general regularities between diagnoses and clinical presentations. I then consider the theory that medical diagnoses explain symptoms and signs by identifying their actual causes in particular cases. While I take this to be largely correct, I argue that for a diagnosis to function as a satisfactory causal explanation of a patient's symptoms and signs, it also needs to be supplemented by understanding the mechanisms by which the identified cause produces the symptoms and signs. This mechanistic understanding comes not from the diagnosis itself, but rather from the theoretical framework within which the physician operates.


Characterization of epitopes on zucchini yellow mosaic potyvirus coat protein permits studies on the interactions between strains.
Monoclonal antibodies (MAbs) raised against the coat protein of zucchini yellow mosaic potyvirus (ZYMV) were characterized by epitope mapping using synthetic oligopeptides. Two mutant viruses with a mutation in the amino acid sequence important for epitope recognition in vitro were obtained by site-directed mutagenesis of a full-length cDNA of ZYMV. Two MAbs, CC11 and DD2, could distinguish specifically between these mutants in mixed infections, or after sequential inoculations of muskmelons. Sequential inoculations of the mutants and analysis with MAbs CC11 and DD2 revealed that cross-protection was established between these quasi-isogenic strains within 48 h.


Size matters: non-numerical magnitude affects the spatial coding of response.
It is known that small and large numbers facilitate left/right respectively (the SNARC effect). Recently, it has been proposed that numerical magnitude is just one example of a range of quantities, which have a common cognitive/neural representation. To investigate this proposition, response congruency effects were explored for stimuli which differed according to their: (a) numerical size, (b) physical size, (c) luminance, (d) conceptual size and (e) auditory intensity. In a series of experiments, groups of undergraduate participants made two-alternative forced choice discriminations with their left or right hands. There were clear interactions between magnitude and responding hand whereby right hand responses were faster for stimuli with (a) large numbers, (b) large physical size, (c) low luminance, and (d) a reference to large objects. There was no congruency effect for the auditory stimuli. The data demonstrate that the response congruency effect observed for numbers also occurs for a variety of other non-numerical visual quantities. These results support models of general magnitude representation and suggest that the association between magnitude and the left/right sides of space may not be related to culture and/or directional reading habits.


Comparison of ICE (ifosfamide-carboplatin-etoposide) versus DHAP (cytosine arabinoside-cisplatin-dexamethasone) as salvage chemotherapy in patients with relapsed or refractory lymphoma.
High dose chemotherapy with autologous stem cell transplantation is currently the treatment of choice for relapsed or refractory lymphoma patients. However, its applicability is mostly restricted to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy and toxicity profiles of DHAP (cytosine arabinoside, cisplatin and dexamethasone) and ICE (ifosfamide, carboplatin and etoposide) regimens in the salvage treatment of relapsed and refractory lymphoma. In this retrospective analysis, 53 patients with primary refractory or relapsed Hodgkin's disease (HD) (n = 13) or non-Hodgkin lymphoma (NHL) (n = 40) who received ICE or DHAP salvage regimen were included. Of 53 patients, 21 (39,6%) were female and the median age was 43 years. A total of 73 courses of ICE and 59 courses of DHAP were administered. Response could be evaluated in 49 patients (36 NHL and 13 HD). Of 49 patients, 11 (22.5%) achieved complete remission (CR) and 17 (35%) achieved partial remission (PR), leading to an overall response rate (ORR: CR + PR) of 57.5%. In the evaluable ICE group (n = 22) rates of CR, PR, and ORR were 27%, 41% and 68% and in the DHAP group (n = 27) rates of CR, PR, and ORR were 18%, 30% and 48% (p = 0.24, for ORR). Toxicity with both regimens was within acceptable limits. The major grade III-IV toxicities for both groups were hematological (neutopenia and thrombocytopenia). The main non-hematological toxicity was renal and observed in 8 patients. Although the toxicity profiles of both ICE and DHAP regimens were similar in the treatment of patients with relapsed or refractory HD or NHL, ICE seems to have higher rates of response than DHAP regimen does.