Interventions for fatigue in inflammatory bowel disease.
Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of chronic, progressive inflammatory disorders of the digestive tract. Crohn's disease and ulcerative colitis are the two main types. Fatigue is a common, debilitating and burdensome symptom experienced by individuals with IBD. The subjective, complex nature of fatigue can often hamper its management. The efficacy and safety of pharmacological or non-pharmacological treatments for fatigue in IBD is not yet established through systematic review of studies. To assess the efficacy and safety of pharmacological and non-pharmacological interventions for managing fatigue in IBD compared to no treatment, placebo or active comparator. A systematic search of the databases Embase, MEDLINE, Cochrane Library, CINAHL, PsycINFO was undertaken from inception to July 2018. A top-up search was run in October 2019. We also searched the Cochrane IBD Group Specialized Register, the Cochrane Central Register of Controlled Trials, ongoing trials and research registers, conference abstracts and reference lists for potentially eligible studies. Randomised controlled trials of pharmacological and non-pharmacological interventions in children or adults with IBD, where fatigue was assessed as a primary or secondary outcome using a generic or disease-specific fatigue measure, a subscale of a larger quality of life scale or as a single-item measure, were included. Two authors independently screened search results and four authors extracted and assessed bias independently using the Cochrane 'Risk of bias' tool. The primary outcome was fatigue and the secondary outcomes included quality of life, adverse events (AEs), serious AEs and withdrawal due to AEs. Standard methodological procedures were used. We included 14 studies (3741 participants): nine trials of pharmacological interventions and five trials of non-pharmacological interventions. Thirty ongoing studies were identified, and five studies are awaiting classification. Data on fatigue were available from nine trials (1344 participants). In only four trials was managing fatigue the primary intention of the intervention (electroacupuncture, physical activity advice, cognitive behavioural therapy and solution-focused therapy). Electroacupuncture Fatigue was measured with Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (scores range from 0 to 52). The FACIT-F score at week eight was 8.00 points higher (better) in participants receiving electroacupuncture compared with no treatment (mean difference (MD) 8.00, 95% CI 6.45 to 9.55; 1 RCT; 27 participants; low-certainty evidence). Results at week 16 could not be calculated. FACIT-F scores were also higher with electroacupuncture compared to sham electroacupuncture at week eight (MD 5.10, 95% CI 3.49 to 6.71; 1 RCT; 30 participants; low-certainty evidence) but not at week 16 (MD 2.60, 95% CI 0.74 to 4.46; 1 RCT; 30 participants; low-certainty evidence). No adverse events were reported, except for one adverse event in the sham electroacupuncture group. Cognitive behavioural therapy (CBT) and solution-focused therapy Compared with a fatigue information leaflet, the effects of CBT on fatigue are very uncertain (Inflammatory Bowel Disease-Fatigue (IBD-F) section I: MD -2.16, 95% CI -6.13 to 1.81; IBD-F section II: MD -21.62, 95% CI -45.02 to 1.78; 1 RCT, 18 participants, very low-certainty evidence). The efficacy of solution-focused therapy on fatigue is also very uncertain, because standard summary data were not reported (1 RCT, 98 participants). Physical activity advice One 2 x 2 factorial trial (45 participants) found physical activity advice may reduce fatigue but the evidence is very uncertain. At week 12, compared to a control group receiving no physical activity advice plus omega 3 capsules, FACIT-F scores were higher (better) in the physical activity advice plus omega 3 group (FACIT-F MD 6.40, 95% CI -1.80 to 14.60, very low-certainty evidence) and the physical activity advice plus placebo group (FACIT-F MD 9.00, 95% CI 1.64 to 16.36, very low-certainty evidence). Adverse events were predominantly gastrointestinal and similar across physical activity groups, although more adverse events were reported in the no physical activity advice plus omega 3 group. Pharmacological interventions Compared with placebo, adalimumab 40 mg, administered every other week ('eow') (only for those known to respond to adalimumab induction therapy), may reduce fatigue in patients with moderately-to-severely active Crohn's disease, but the evidence is very uncertain (FACIT-F MD 4.30, 95% CI 1.75 to 6.85; very low-certainty evidence). The adalimumab 40 mg eow group was less likely to experience serious adverse events (OR 0.56, 95% CI 0.33 to 0.96; 521 participants; moderate-certainty evidence) and withdrawal due to adverse events (OR 0.48, 95%CI 0.26 to 0.87; 521 participants; moderate-certainty evidence). Ferric maltol may result in a slight increase in fatigue, with better SF-36 vitality scores reported in the placebo group compared to the treatment group following 12 weeks of treatment (MD -9.31, 95% CI -17.15 to -1.47; 118 participants; low-certainty evidence). There may be little or no difference in adverse events (OR 0.55, 95% CI 0.26 to 1.18; 120 participants; low-certainty evidence) AUTHORS' CONCLUSIONS: The effects of interventions for the management of fatigue in IBD are uncertain. No firm conclusions regarding the efficacy and safety of interventions can be drawn. Further high-quality studies, with a larger number of participants, are required to assess the potential benefits and harms of therapies. Future studies should assess interventions specifically designed for fatigue management, targeted at selected IBD populations, and measure fatigue as the primary outcome.


Absence of molecular defect in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene in premature pubarche children and hirsute female patients with moderately decreased adrenal 3 beta-HSD activity.
To date the molecular basis and hormonal criteria for inherited mild late-onset 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency congenital adrenal hyperplasia (CAH) have not been defined. We have thus investigated the presence or absence of mutation in the type II 3 beta-HSD gene encoding adrenal/gonadal 3 beta-HSD in each of five premature pubarche children and hirsute female patients manifesting moderately decreased adrenal 3 beta-HSD activity. ACTH-stimulated hormonal levels in all patients compared with mean levels in pubertal stage-matched normal subjects were between 2.5 and 6.5 SD for 17-hydroxypregnenolone levels, and between 2.5 and 7 SD for dehydroepiandrosterone levels in all except one patient. 17-Hydroxypregnenolone to cortisol ratios were between 2.5 and 4.3 SD, and dehydroepiandrosterone to androstenedione ratios were between 3 and 8.6 SD. The type II 3 beta-HSD gene regions of a putative promoter, exons I, II, III, and IV, and exon-intron boundaries in all subjects were amplified by polymerase chain reaction and then sequenced. All patients had normal sequences of the type II 3 beta-HSD gene in both alleles. Three female patients heterozygotic for severe 3 beta-HSD deficiency CAH with one allele mutation of the gene demonstrated normal ACTH-stimulated hormone profiles. These data indicate that moderately decreased adrenal 3 beta-HSD activity resulting in modestly increased delta 5 precursor steroid levels and delta 5 to delta 4 steroid ratios in premature pubarche and hirsute patients is not caused by a mutation in the type II 3 beta-HSD gene.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevention of hepatitis A infections: guidelines for use of hepatitis A vaccine and immune globulin. American Academy of Pediatrics Committee on Infectious Diseases.
The licensing of two inactivated hepatitis A vaccines for persons 2 years or older necessitates development of recommendations for pediatric use, as well as a review of the current indications for immune globulin (IG) in hepatitis A prophylaxis. Both vaccines are immunogenic and protective in children and adults. A single dose of vaccine induced antibody in 88% to 96% of subjects by 2 weeks and 97% to 100% by 1 month, and protected against subsequent hepatitis A virus (HAV) disease occurring 21 days after receipt of the dose in a community with endemic hepatitis A infection. However, completion of the full vaccine schedule is recommended to assure high antibody titers and likely long-term protection. The major pediatric indications for vaccine are: (1) travelers to areas with intermediate to high rates of endemic hepatitis A, (2) children living in defined and circumscribed communities with high endemic rates or periodic outbreaks of HAV infection, and (3) patients with chronic liver disease. Immune globulin is recommended for postexposure prophylaxis, as vaccine has not yet been demonstrated to be protective for this purpose. Except for travelers, recommendations for IG use are not changed from those in the current edition of the Red Book, and include contacts of cases in the home, child care centers, and other selected sites.


Tissue-engineering of the gastrointestinal tract.
The purpose of this review is to describe recent advancements in tissue-engineering of the gastrointestinal system. For some patients, a congenital or acquired defect in the alimentary system results in digestive or nutritional deficiencies requiring intervention. Unfortunately, these treatments are associated with morbid complications. Advances in the growth of tissue-engineered esophagus, stomach, small intestine, colon and anus have been made in recent years. The progress reviewed here hopefully will someday benefit patients with gastrointestinal organ loss by providing a tissue replacement with morphology and function similar to native tissue. In native gastrointestinal tissue, epithelial homeostasis is governed largely by the interaction of the stem cell and its surrounding cellular niche. In particular, the small intestinal stem cell populations identified as the crypt base columnar cell (CBCC) and at cell position 4 (cp4) are responsible for mucosal maintenance and response to injury. This work influences efforts to generate bioengineered tissues for both in-vitro mucosal models and full-thickness in-vivo tissue-engineered esophagus, stomach, intestine and colon. Gastrointestinal organ loss is a challenge to manage. Current therapy can be life-saving, but is associated with morbid complications. Tissue-engineering will someday restore normal gastrointestinal function and eliminate the need for nutritional supplementation or transplant.


Biodistribution profiling of the chemical modified hyaluronic acid derivatives used for oral delivery system.
A series of adipic acid dihydrazide (ADH)-modified hyaluronic acid (HA-ADH) compounds were synthesized and conjugated with QDots (QDots-HA conjugates) to assess the effects of the molecular weight (MW) and extent of chemical modification of HA on its biodistribution. Their physicochemical structures were confirmed by complementary application of GPC, (1)H NMR, FTIR, and UV-vis spectroscopic methods. In vivo imaging of QDots-HA conjugates after oral administration was analyzed to investigate their biodistribution in nude mice. Simultaneously, real-time bioimaging was confirmed by an anatomical analysis to investigate the organ-specific accumulation of conjugates. QDot-HA conjugates with a higher MW of HA or high modification presented relatively slow clearance leading to an extension of the retention time for up to 10 days, whereas those with lower MWs of HA or a low modification extent exhibited quick absorption and elimination after oral administration. Taken together, HA derivatives with suitable MWs and chemical modification extents can be used to design new, more-sophisticated, and intelligent HA-based vehicles for oral delivery with diverse characteristics.


Peer harassment, school connectedness, and academic achievement.
This study described peer harassment in a large, multiethnic sample of adolescents, and explored the relationship between experiencing peer harassment and both school connectedness and achievement. Survey data came from 4,746 students in grades 7-12 at 31 public schools in ethnically and socioeconomically diverse communities in a Midwestern state. Frequency of five types of harassment were analyzed with data on school connectedness and grades. Multivariate analysis controlled for gender, grade level, race/ethnicity, and socioeconomic status. Results indicate that most students periodically experience mistreatment; 10% to 17% report being treated disrespectfully, having others act superior, or being insulted at least once per week, and an additional 14% to 22% of students report suffering these behaviors a few times per month. Girls, Whites, Native Americans, and middle school students reported more harassment than boys, other ethnic groups, and high school students, respectively. Peer harassment related significantly to both aspects of school life; those who disliked school tended to suffer more mistreatment, and "B" students reported the least harassment on average. Young people mistreated by peers may not want to be in school and may thereby miss out on the benefits of school connectedness as well as educational advancement. The high prevalence of peer harassment and its association with school connectedness and school achievement provide justification for interventions aimed at prevention of peer harassment. A schoolwide approach using educational and policy components may provide an appropriate prevention strategy.


Design of primers and probes for quantitative real-time PCR methods.
Design of primers and probes is one of the most crucial factors affecting the success and quality of quantitative real-time PCR (qPCR) analyses, since an accurate and reliable quantification depends on using efficient primers and probes. Design of primers and probes should meet several criteria to find potential primers and probes for specific qPCR assays. The formation of primer-dimers and other non-specific products should be avoided or reduced. This factor is especially important when designing primers for SYBR(®) Green protocols but also in designing probes to ensure specificity of the developed qPCR protocol. To design primers and probes for qPCR, multiple software programs and websites are available being numerous of them free. These tools often consider the default requirements for primers and probes, although new research advances in primer and probe design should be progressively added to different algorithm programs. After a proper design, a precise validation of the primers and probes is necessary. Specific consideration should be taken into account when designing primers and probes for multiplex qPCR and reverse transcription qPCR (RT-qPCR). This chapter provides guidelines for the design of suitable primers and probes and their subsequent validation through the development of singlex qPCR, multiplex qPCR, and RT-qPCR protocols.


Neuroprotective and Anti-Obesity Effects of Tocotrienols.
Vitamin E is a natural lipophilic vitamin, and the most famous function of vitamin E is an antioxidant activity. Because we have α-tocopherol transfer protein, many vitamin E-related reports are about α-tocopherol. Recently, other vitamin E isoforms, tocotrienols are focusing. Because tocotrienols have unique biological functions such as induction of apoptosis, neuroprotective and anti-obesity effects. Tocotrienols contain in annatto, palm, whole wheat and rice bran. Rice is a typical food in the East Asian countries and Japan. Recently, intake of whole rice is a popular in young women of Japan. Previously, we demonstrated that treatment with tocotrienols on the neuronal cells shows a strong antioxidant effect compared to the tocopherols. In this review, I introduce about neuroprotective and anti-obesity effects of tocotrienols. I would like to show daily intake of whole rice is very good for our health in this review.


Interprofessional care in intensive care settings and the factors that impact it: results from a scoping review of ethnographic studies.
At the heart of safe cultures are effective interactions within and between interprofessional teams. Critical care clinicians see severely ill patients who require coordinated interprofessional care. In this scoping review, we asked: "What do we know about processes, relationships, organizational and contextual factors that shape the ability of clinicians to deliver interprofessional care in adult ICUs?" Using the 5-stage process established by Levac et al. (2010), we reviewed 981 abstracts to identify ethnographic articles that shed light on interprofessional care in the intensive care unit. The quality of selected articles is assessed using best practices in ethnographic research; their main insights evaluated in light of an interprofessional framework developed by Reeves et al (Interprofessional Teamwork for Health and Social Care. San Francisco, CA: Wiley-Blackwell; 2010). Overall, studies were of mixed quality, with an average (SD) score of 5.8 out of 10 (1.77). Insights into intensive care unit cultures include the importance of paying attention to workflow, the nefarious impact of hierarchical relationships, the mixed responses to protocols imposed from the top down, and a general undertheorization of sex and race. This review highlights several lessons for safe cultures and argues that more needs to be known about the context of critical care if quality and safety interventions are to succeed.


Detection of Anti-Toxoplasma gondii Antibodies in Human Sera Using Synthetic Glycosylphosphatidylinositol Glycans on a Bead-Based Multiplex Assay.
Toxoplasmosis, while often an asymptomatic parasitic disease in healthy individuals, can cause severe complications in immunocompromised persons and during pregnancy. The most common method to diagnose Toxoplasma gondii infections is the serological determination of antibodies directed against parasite protein antigens. Here we report the use of a bead-based multiplex assay containing a synthetic phosphoglycan portion of the Toxoplasma gondii glycosylphosphatidylinositol (GPI1) for the detection of GPI1-specific antibodies in human sera. The glycan was conjugated to beads at the lipid site to retain its natural orientation and its immunogenic groups. We compared the response against GPI1 with that against the protein antigen SAG1, a common component of commercial serological assays, via the detection of parasite-specific human IgG and IgM antibodies, respectively. The GPI1-based test is in excellent agreement with the results for the commercial ELISA, as the ROC analysis of the GPI1 test shows 97% specificity and 98% sensitivity for the assay. GPI1 was a more reliable predictor for a parasite-specific IgM response compared to SAG1, indicating that a bead-based multiplex assay using GPI1 in combination with SAG1 may strengthen Toxoplasma gondii serology, in particular in seroepidemiological studies.


The immobilized matrix buffer controls the rate of mitochondrial respiration in state 3P according to chance.
Preparations of coupled mitochondria were labeled with fluorescein isothiocyanate (FITC). Comparison of characteristics of FITC bound to mitochondria versus azolectin liposomes indicates that a significant part of the probe is bound to mitochondrial proteins including proteins of the matrix side of the inner membrane. The experiments with the probe indicate that mitochondrial proteins resemble typical polyelectrolytes with constant of dissociation close to 10(-7).H+ and K+ compete for binding to mitochondrial proteins at neutral pH. The slow deprotonation of matrix proteins is observed during equilibration of matrix protons with medium protons. This process is not restricted to the transmembrane proton transfer. The data are explained by the theory of immobilized buffer. Under certain conditions the extent of dissociation of the matrix immobilized buffer correlates with the rate of mitochondrial respiration in state 3P according to chance.


[Problems of the differential diagnosis and classification of liposarcomas (electron microscopy study)].
Ultrastructure of both liposarcomas of different histological types and those with non-verified diagnosis are studied. Liposarcomas are shown to contain a basic complex of ultrastructural features of lipid differentiation and different histological types of these tumours have, in principle, identical features varying in the degree of their expression. The questions of a differential diagnosis of liposarcomas and other tumours can be successfully solved on the basis of the above findings, and even more, a group of liposarcomas with a severe cataplasia that does not have histological analogues may be distinguished. The results allowed to work out an ultrastructural classification of liposarcomas in which the degree of cataplasia is directly taken into account.


The endangered Illidge's ant blue butterfly (Acrodipsas illidgei) from an intertidal habitat managed for mosquito control.
Acrodipsas illidgei is an endangered butterfly inhabiting mangrove forests in southeastern Queensland, Australia. Concern over the effects of mosquito control activities prompted a broad-scale survey for the species at Coomera Island, in southeastern Queensland. The butterfly was recorded on the edge of an old-growth mangrove forest in close proximity to mosquito control runnels. Other forms of mosquito control at Coomera Island are unlikely to impact on the species because of the mode of action of larvicides used and the fact larvae occur within ant colonies formed in hollow stems and branches of mangrove trees. Further studies are required to more fully understand the relationships between mosquito control activities and the population dynamics of endangered species such as A. illidgei.


Ceramides Mediate Insulin-Induced Impairments in Cerebral Mitochondrial Bioenergetics in ApoE4 Mice.
Alzheimer's disease (AD) is the most common form of neurodegenerative disease worldwide. A large body of work implicates insulin resistance in the development and progression of AD. Moreover, impairment in mitochondrial function, a common symptom of insulin resistance, now represents a fundamental aspect of AD pathobiology. Ceramides are a class of bioactive sphingolipids that have been hypothesized to drive insulin resistance. Here, we describe preliminary work that tests the hypothesis that hyperinsulinemia pathologically alters cerebral mitochondrial function in AD mice via accrual of the ceramides. Homozygous male and female ApoE4 mice, an oft-used model of AD research, were given chronic injections of PBS (control), insulin, myriocin (an inhibitor of ceramide biosynthesis), or insulin and myriocin over four weeks. Cerebral ceramide content was assessed using liquid chromatography-mass spectrometry. Mitochondrial oxygen consumption rates were measured with high-resolution respirometry, and H2O2 emissions were quantified via biochemical assays on brain tissue from the cerebral cortex. Significant increases in brain ceramides and impairments in brain oxygen consumption were observed in the insulin-treated group. These hyperinsulinemia-induced impairments in mitochondrial function were reversed with the administration of myriocin. Altogether, these data demonstrate a causative role for insulin in promoting brain ceramide accrual and subsequent mitochondrial impairments that may be involved in AD expression and progression.


Plasma and tissue concentrations of α-tocopherol and δ-tocopherol following high dose dietary supplementation in mice.
Vitamin E isoforms are essential nutrients that are widely used as dietary supplements and therapeutic agents for a variety of diseases. However, their pharmacokinetic (PK) properties remain poorly characterized, and high dosage animal studies may provide further information on their in vivo functions and pharmacological effects. In this study, alpha-tocopherol (α-toc) and delta-tocopherol (δ-toc) levels were measured in mouse plasma and tissues following their high dosage dietary supplementation. Average α-toc levels at 5, 10 and 20 g α-toc/kg diet increased over baseline levels 6-fold in plasma, 1.6-fold in brain, and 4.9-fold in liver. These elevated α-toc concentrations remained constant from 5 to 20 g α-toc/kg diet, rather than showing further increases across these dosages. No α-toc-related toxicity occurred at these high dosages, and strain-specific differences in liver and brain α-toc levels between Balb/cJ and C57Bl/6J mice were observed. Relatively high-dosage administration of dietary δ-toc for 1 or 4 weeks resulted in 6-30-fold increases in plasma and liver levels between dosages of 0.33 and 1.67 g δ-toc/kg diet. Co-administration of sesamin with δ-toc further increased δ-toc levels between 1.3- and 14-fold in plasma, liver, and brain. These results provide valuable PK information on high dosage α-toc and δ-toc in mouse and show that supplementation of sesamin with δ-toc further increases δ-toc levels over those seen with δ-toc supplementation alone.


Biodiversity of the microbial flora associated with two strains of Culexpipiens (Diptera: Culicidae).
Bacterial Flora from external surface and alimentary canal of wild and laboratory strains of Culex pipiens were isolated and investigated using quantitative bacterial cultures. Individual colonies were subcultured and identified to species level. Counts from alimentary canal differ significantly from those of the external surface. An increase in bacterial density was detected after feeding on mammalian and avian blood meal. Bacterial identification revealed a complex bacterial flora. In addition to members of family Enterobacteriaceae species of Bacillus, Staphylococcus, Streptococcus, and Acinetobacter are the most common in both strains investigated. Gram negative bacteria were increased significantly after feeding on blood meals than those detecting during the feeding on sugar after emergence of the adult female mosquitoes and vise versa with Gram positive bacteria. Bacterial isolates were tested for resistance to the most common commercial antibiotics.


Static axial overloading primes lumbar caprine intervertebral discs for posterior herniation.
Lumbar hernias occur mostly in the posterolateral region of IVDs and mechanical loading is an important risk factor. Studies show that dynamic and static overloading affect the nucleus and annulus of the IVD differently. We hypothesize there is also variance in the effect of overloading on the IVD's anterior, lateral and posterior annulus, which could explain the predilection of herniations in the posterolateral region. We assessed the regional mechanical and cellular responses of lumbar caprine discs to dynamic and static overloading. IVDs (n = 125) were cultured in a bioreactor and subjected to simulated-physiological loading (SPL), high dynamic (HD), or high static (HS) overloading. The effect of loading was determined in five disc regions: nucleus, inner-annulus and anterior, lateral and posterior outer-annulus. IVD height loss and external pressure transfer during loading were measured, cell viability was mapped and quantified, and matrix integrity was assessed. During culture, overloaded IVDs lost a significant amount of height, yet the distribution of axial pressure remained unchanged. HD loading caused cell death and disruption of matrix in all IVD regions, whereas HS loading particularly affected cell viability and matrix integrity in the posterior region of the outer annulus. Axial overloading is detrimental to the lumbar IVD. Static overloading affects the posterior annulus more strongly, while the nucleus is relatively spared. Hence, static overloading predisposes the disc for posterior herniation. These findings could have implications for working conditions, in particular of sedentary occupations, and the design of interventions aimed at prevention and treatment of early intervertebral disc degeneration.


The advanced practice nurse and physician relationship: considerations for practice.
Although physician and nurse relationships have traditionally been a challenge, evolving changes in health care delivery offer the advanced practice nurse (APN) on opportunity to redefine the scope. Several issues will have an impact on this course. Initially, the condition of employment, as well as the physician's perception of the APN's role and the physician's commitment to role preservation, will be primary influences. Secondary factors include defining the role, scope of practice, and mechanisms for practice evaluation. This process will require and ongoing dialogue and selected strategies to develop and maintain physician relationships.


Pressure-volume analysis of rat's micturition cycles in vivo.
Though the pressure-volume analysis (PVA), a method based on thermodynamics, is broadly used for assaying cardiac functions, its potential application on the physiology/pathophysiology of the urinary bladder, which processes resemble thermodynamic cycles to the heart, has not been established. Cystometry recording intravesical pressure (IVP) and intravesical volume (IVV) of rhythmic voiding contractions caused by a constant saline infusion (0.04 mL/min) were carried out in forty urethane-anesthetized female Sprague-Dawley rats, and the PVA was established by plotting IVP against IVV. Pressure-volume points shaped coincident enclosed loops, and loop-associated urodynamic parameters kept stable under a constant infusion rate (0.04 mL/min). Enhancing preload (by elevating infusion rates to 0.08 and 0.12 mL/min) increased the area enclosed by the loop (Apv) and shifted loops to the right and slightly upward. Augmenting afterload (by enhancing resistances using 1/4 and 1/2 urethra clamping) increased Apv and shifted loops markedly to the right and upward. Without affecting Apv, muscarine (0.01 and 0.1 mM)-induced inotropic states shifted loop to the left and upward that was as opposed to the atropine (0.01 and 0.1 mM)-induced anti-inotropic state. Not only consistently assayed baseline bladder functions, PVA but also validly measured modified bladder functions due to altered extrinsic environment and intrinsic contractility of the bladder itself. In accompanied by cystometry, PVA could provide a clear concept about the relationship between time, pressure, and volume in the voiding activity.


GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance.
Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice.


Predictors of multiple tooth loss among socioculturally diverse elderly subjects.
This study identifies clinical factors that predict multiple tooth loss in a socioculturally diverse population of older adults. A total of 193 participants from English-, Chinese-, or Punjabi-speaking communities in Vancouver, British Columbia, with low incomes and irregular use of dental services were followed for 5 years as part of a clinical trial of a 0.12% chlorhexidine mouthrinse. The participants were interviewed and examined clinically, including panoramic radiographs, at baseline and annually for 5 years. Binary logistic regression was used to test the hypothesis that there was no difference between incidence of multiple (≥ 3) tooth loss in older people with various biologic, behavioral, prosthodontic, and cultural variables over 5 years. Multiple tooth loss, which was distributed similarly among the groups in the trial, occurred in 39 (20%) participants over 5 years. The use of removable prostheses was the best predictor of loss, followed by the number of carious surfaces and number of sites with gingival attachment loss > 6 mm. The pattern of prediction was consistent across the three linguocultural groups. The use of removable dentures was the dominant predictor of multiple tooth loss in the three communities, but that tooth loss was not significantly associated with the cultural heritage of the participants.


Identification of the absorption processes in periodic plasmonic structures using energy absorption interferometry.
Power dissipation in electromagnetic absorbers is a quadratic function of the incident fields. To characterize an absorber, one needs to deal with the coupling that may occur between different excitations. Energy absorption interferometry (EAI) is a technique that highlights the independent degrees of freedom through which a structure can absorb energy: the natural absorption modes of the structure. The coupling between these modes vanishes. In this paper, we use the EAI formalism to analyze different kinds of plasmonic periodic absorbers while rigorously accounting for the coupling: resonant golden patches on a grounded dielectric slab, parallel free-standing silver wires, and a silver slab of finite thickness. The EAI formalism is used to identify the physical processes that mediate absorption in the near and far field. First, we demonstrate that the angular absorption, which is classically used to characterize periodic absorbers in the far field and which neglects the coupling between different plane waves, is only valid under stringent conditions (subwavelength periodicity, far-field excitation, and negligible coupling between the two possible polarizations). Using EAI, we show how the dominant absorption channels can be identified through the signature of the absorption modes of the structure, while rigorously accounting for the coupling. We then exploit these channels to improve absorption. We show that long-range processes can be exploited to enhance the spatial selectivity, while short-range processes can be exploited to improve absorptivity over wide angles of incidence. Finally, we show that by simply adding scatterers with the proper periodicity on top of the absorber, the absorption can be increased by more than 1 order of magnitude.


[Gender differences of at risk patients with overt heart failure in the real world of general practice. Data from the GIPSI (Gestione Integrata Progetto Scompenso in Italia) registry].
Controlled clinical trials have defined the characteristics of specialized world populations, different from the real world population. On this basis, the GIPSI registry was created, aiming to collect data from heart failure populations managed by general practitioners, focusing on gender differences. The registry was based on family history, clinical and laboratory data collection from general practitioners. Patients were considered as being at risk for heart failure if data applied to stage A/B, or presenting overt heart failure if data applied to stage C/D of the American College of Cardiology/American Heart Association classification. From June 2006 to October 2007, 757 consecutive patients (475 male, 62.7%) were enrolled from 260 general practitioner's practices; 227 patients (143 male, 63.0%) had overt heart failure. In the female population at risk, higher systolic and diastolic blood pressure values were observed, whereas males showed more frequently ischemic heart disease, hypercholesterolemia and hypertriglyceridemia, and were more often prescribed with statins and antiplatelet drugs. There were more heart failure females with diabetes and of advanced age. Moreover, females showed a higher pulse pressure and a significantly lower estimated glomerular filtration rate (by simplified MDRD equation) than males. The data collected in a real world population show that heart failure has significantly different gender characteristics, especially for risk factors, age, blood pressure and renal function. This kind of investigation should be extended to larger patient populations for a better understanding of the disease.


The effect of Insulin Degludec on glycemic control in diabetic cats over a 12-month period.
Insulin degludec (IDeg) is a long-acting basal insulin recently developed for use in humans. This study aimed to investigate the effects of IDeg on glycemic control in diabetic cats. Changes in body weight, IDeg dosage, and glycated albumin (GA) were evaluated at 0, 1, 3, 6, 9, and 12 months following initiation of IDeg. A significant decrease in GA was observed and a mean GA level below 25% was achieved between 3 and 12 months. Furthermore, a significant increase in body weight was observed between 3 and 12 months. The mean IDeg dose was 0.75 ± 0.68 IU/kg/day at 12 months. Taken together, long-term glycemic control was successfully achieved in diabetic cats using IDeg.


Patient-reported outcomes in melanoma survivors at 1, 3 and 5 years post-diagnosis: a population-based cross-sectional study.
There is a lack of population-based data describing patient reported outcomes (PROs) in melanoma survivors which could guide the development of interventions and resources. This study assessed overall quality of life (QoL), self-reported symptoms and unmet information needs in melanoma survivors 1, 3 or 5 years post-diagnosis. A cross-sectional postal survey was conducted in Victoria, Australia, with eligible melanoma survivors identified from a population-based cancer registry. Patient-reported outcome measures included the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), and self-reported symptoms, difficulties and information needs. Associations between demographic, disease and care-related factors and QoL were also assessed. A total of 476 melanoma survivors participated in the study (response rate 46.5%). Anxiety and depressive symptoms were more prevalent in survivors compared to the general population (30.7% vs 21.6%; p < 0.01). Fear of cancer recurrence (48.3%) and fear of cancer spreading (37.8%) were the most commonly reported symptom items, and approximately one in five melanoma survivors had unmet information needs related to psychological aspects of living with melanoma. Recurrent melanoma, living in a nursing home, chronic comorbidities, and melanoma diagnosed at > 2 mm thickness were associated with lower QoL. A large proportion of melanoma survivors reported ongoing quality of life deficits, fear of cancer recurrence, as well as unmet information needs up to 5 years after diagnosis. Patients may benefit from tailored informational resources and interventions that address the psychological aspects of living with and beyond melanoma.


[Impact of vaginal delivery after a previous cesarean section on perinatal outcomes].
To analyze the impact of vaginal delivery after a previous cesarean section on perinatal outcomes. Case-control study with selection of incident cases and consecutive controls. Maternal and perinatal variables were analyzed. We compared secundiparas who had a vaginal delivery after a previous cesarean delivery (VBAC) (n=375) with secundiparas who had a second cesarean section (CS) (n=375). Inclusion criteria were: secundiparas who underwent a cesarean section in the previous pregnancy; singleton and term pregnancy; fetus in vertex presentation, with no congenital malformation; absence of placenta previa or any kind of bleeding in the third quarter of pregnancy. The rate of vaginal delivery was 45.6%, and 20 (5.3%) women had forceps deliveries. We found a significant association between VBAC and mothers younger than 19 years (p<0.01), Caucasian ethnicity (p<0.05), mean number of prenatal care visits (p<0.001), time of premature rupture of membranes (p<0.01), labor duration shorter than 12 hours (p<0.04), Apgar score lower than seven at 5th minute (p<0.05), fetal birth trauma (p<0.01), and anoxia (p<0.006). In the group of newborns delivered by cesarean section, we found a higher frequency of transient tachypnea (p<0.014), respiratory disorders (p<0.048), and longer time of stay in the neonatal intensive care unit (p<0.016). There was only one case of uterine rupture in the VBAC group. The rate of neonatal mortality was similar in both groups. Vaginal delivery in secundiparas who had previous cesarean sections was associated with a significant increase in neonatal morbidity. Further studies are needed to develop strategies aimed at improving perinatal results and professional guidelines, so that health care professionals will be able to provide their patients with better counseling regarding the choice of the most appropriate route of delivery.


Composition and Stability of the Vaginal Microbiota of Pregnant Women With Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) is common in women of childbearing years, and active IBD during pregnancy is associated with increased rates of preterm delivery and low-birth-weight newborns. Changes in the vaginal microbiome have been associated with preterm delivery. We aimed to determine the taxonomic composition of the vaginal microbiota at 3 time points during pregnancy in a population of women with IBD. Participants were recruited from the patient registry of the Preconception and Pregnancy IBD Clinic at Royal University Hospital in Saskatoon, Canada. Self-collected vaginal swabs were obtained from patients at each trimester. Microbiota profiles were created by cpn60 amplicon sequencing. We characterized the vaginal microbiota of 32 pregnant participants with IBD (33 pregnancies) during each trimester. A total of 32 of 33 pregnancies resulted in a live birth with 43.8% (n = 14 of 32, 2 missing) by caesarean section; 2 of 32 were preterm. Microbiota compositions corresponded to previously described community state types, with most participants having microbiota dominated by Lactobacillus crispatus. In 25 of 29 participants in which samples were available for more than 1 time point, there was no change in the community state type over time. Prevalence of Mollicutes (Mycoplasma and/or Ureaplasma) was significantly higher in pregnant participants with IBD than in a previously profiled cohort of 172 pregnant women without IBD who delivered at term. The vaginal microbiome of participants with IBD was stable throughout pregnancy. Prevalence of Mollicutes, which has been associated with preterm delivery, warrants further study in this patient group.


An unusual cause of abrupt vessel closure.
A 60 year old woman presented with chest pain. An ECG showed ST depression across the anterior leads and lateral T wave inversion and angiography showed a significant proximal circumflex lesion. After percutaneous intervention to the circumflex artery she had a cardiac arrest and died. Postmortem examination found a stent blocked with a combination of thrombus and a tangle of translucent material. Embolic coronary artery occlusion is well described but this is the first report of embolisation of material arising from the lining of the guiding catheter as the cause.


Algorithm approach for revision surgery following late-onset bleb complications after trabeculectomy: long-term follow-up.
The aim of this study was to introduce a reproducible algorithm for the surgical management of late-onset (>2 months) bleb complications after trabeculectomy with mitomycin C. We performed a retrospective review of eyes treated using a reproducible algorithm approach by a single surgeon for the surgical management of late-onset bleb complications from July 2006 to April 2014. Exclusion criteria were bleb revision with less than 3 months of follow-up or bleb revision combined with other glaucoma procedures at the time of surgery. Success was evaluated using the Kaplan-Meier survival method and defined as achieving all of the following criteria: primary surgery indication resolved, no additional surgery required for decreasing the intraocular pressure (IOP), and IOP of ≥6 mmHg and ≤18 mmHg. Twenty-three eyes from 20 patients were evaluated. Indications for bleb revision were hypotonic maculopathy (47.8%), bleb leak (30.4%), and dysesthetic bleb (21.7%). The overall primary outcome success rate calculated using the Kaplan-Meier survival method was 65.2% at 48 months. When the IOP target was changed to ≤15 mmHg, the bleb survival rate was 47.8% at 48 months. At the most recent postoperative visit, 95.7% of eyes had an IOP of ≤15 mmHg and 56.5% were being treated with an average of one medication per eye. One eye (4.3%) required a second bleb revision for persistent hypotony and two eyes required glaucoma surgery to reduce IOP during follow-up. An algorithm approach for the surgical management of late-onset bleb complications with a success rate similar to those reported in specialized literature is proposed. Randomized trials are needed to confirm the best surgical approach.


Efficacy of laminar air flow room with or without clean nursing for preventing infection in patients with acute leukemia.
The clinical effectiveness of bioclean rooms was studied in relation to prevention of infection during treatment for induction of remission of acute leukemia. According to the steps in clean patient care, patients were divided into three groups, Group A consisting of 106 patients who were accommodated in laminar air flow (LAF) rooms under strictly clean nursing, Group B consisting of 99 patients who were treated in disinfected rooms with LAF without any clean nursing techniques and Group C consisting of 188 patients who stayed in conventional wards. Since all patients were treated with antileukemic drugs and preventive administration of antimicrobial drugs under the same regimen, any difference between groups should be attributable to LAF or LAF and clean nursing. A marked and stepwise reduction in the incidence of infection between Groups A, B and C was observed. A statistically significant reduction in pneumonia, upper respiratory tract infection, periproctitis and skin abscesses was also observed in Groups A and B. As to the causative organisms, a relative increase in incidence of infections caused by Pseudomonas aeruginosa and Escherichia coli and a decrease in those caused by Proteus and fungi were observed in Groups A and B, as compared with Group C. These data suggest that pneumonia etc. may be exogenous infections and that Proteus and fungi are exogenous organisms, while Pseudomonas aeruginosa and Escherichia coli are endogenous bacteria. These data seem very helpful for setting up several steps in bioclean rooms for effective and economic patient care.


A population-based study of the intersection of sexual identity and race/ethnicity on physiological risk factors for CVD among U.S. adults (ages 18-59).
Objectives: Sexual minorities face significant psychosocial stressors (such as discrimination and violence) that impact their health. Several studies indicate that sexual minority women (SMW) and bisexual men may be at highest risk for cardiovascular disease (CVD), but limited research has examined physiological CVD risk or racial/ethnic differences. This study sought to examine racial/ethnic differences in physiological risk factors for CVD among sexual minority and heterosexual adults.Design: We analyzed data from the National Health and Nutrition Examination Survey (2001-2016) using sex-stratified multiple linear regression models to estimate differences in physiological CVD risk. We compared sexual minorities (gay/lesbian, bisexual, 'not sure') to heterosexual participants first without regard to race/ethnicity. Then we compared sexual minorities by race/ethnicity to White heterosexual participants.Results: The sample included 22,305 participants (ages 18-59). Lesbian women had higher body mass index (BMI) but lower total cholesterol than heterosexual women. Bisexual women had higher systolic blood pressure (SBP). Gay men had lower BMI and glycosylated hemoglobin (HbA1c) relative to heterosexual men. White and Black lesbian women and bisexual women of all races/ethnicities had higher BMI than White heterosexual women; Black bisexual women had higher SBP and HbA1c. Black sexual minority men had higher HbA1c relative to White heterosexual men. Latino 'not sure' men also had higher SBP, HbA1c, and total cholesterol than White heterosexual men.Conclusions: Given evidence of higher CVD risk in sexual minority people of color relative to White heterosexuals, there is a need for health promotion initiatives to address these disparities. Additional research that incorporates longitudinal designs and examines the influence of psychosocial stressors on CVD risk in sexual minorities is recommended. Findings have implications for clinical and policy efforts to promote the cardiovascular health of sexual minorities.


Senior adult oncology, version 2.2014: clinical practice guidelines in oncology .
Cancer is the leading cause of death in older adults aged 60 to 79 years. The biology of certain cancers and responsiveness to therapy changes with the patient's age. Advanced age alone should not preclude the use of effective treatment that could improve quality of life or extend meaningful survival. The challenge of managing older patients with cancer is to assess whether the expected benefits of treatment are superior to the risk in a population with decreased life expectancy and decreased tolerance to stress. These guidelines provide an approach to decision-making in older cancer patients based on comprehensive geriatric assessment and also include disease specific issues related to age in the management of some cancer types in older adults.


Chlamydial serology: comparative diagnostic value of immunoblotting, microimmunofluorescence test, and immunoassays using different recombinant proteins as antigens.
To improve the reliability of the serodiagnosis of Chlamydia trachomatis infections, an immunoblot analysis, a microimmunofluorescence titration, and different immunoassays using synthetic peptides derived from species-specific epitopes in variable domain IV of the major outer membrane protein or recombinant antigens (heat shock protein 70 [hsp70], hsp60, hsp10, polypeptide encoded by open reading frame 3 of the plasmid [pgp3], macrophage infectivity potentiator, and a fragment of the total lipopolysaccharide) were evaluated. Because cross-reactions between chlamydial species have been reported, the microimmunofluorescence tests were also performed with Chlamydia pneumoniae and Chlamydia psittaci used as antigens, and C. pneumoniae-specific antibodies were also determined by immunoassays. Since the presence of antimicrobial antibodies must be interpreted in light of their prevalence in the general population, responses obtained with serum samples from patients with well-defined infection (i.e., with positive urethral or endocervical C. trachomatis DNA amplification) were compared to those obtained with samples from healthy blood donors. The best sensitivity (86%) with a specificity of 81% was obtained for immunoblotting results, when the number of individuals with > or =10 immunoglobulin G (IgG) and/or > or =2 IgM responses to the different C. trachomatis antigens was considered. A 13-kDa antigen was recognized by most of the samples (86% for IgG) from patients with acute urogenital infection but rarely (3%) by those from healthy blood donors (P < 0.0001). The sensitivity and specificity results obtained for serum antibodies to peptides or recombinant antigens were slightly lower than those results obtained for the number of responses to whole C. trachomatis antigens, which were 76 and 77%, respectively, when IgG responses to both recombinant hsp60 and pgp3 were considered.


Cellular Vimentin Interacts with Foot-and-Mouth Disease Virus Nonstructural Protein 3A and Negatively Modulates Viral Replication.
Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids that is in most FMDVs examined to date, and it plays important roles in virus replication, virulence, and host range. To better understand the role of 3A during FMDV infection, we used coimmunoprecipitation followed by mass spectrometry to identify host proteins that interact with 3A in FMDV-infected cells. Here, we report that cellular vimentin is a host binding partner for 3A. The 3A-vimentin interaction was further confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pull down, and immunofluorescence assays. Alanine-scanning mutagenesis indicated that amino acid residues 15 to 21 at the N-terminal region of the FMDV 3A are responsible for the interaction between 3A and vimentin. Using reverse genetics, we demonstrate that mutations in 3A that disrupt the interaction between 3A and vimentin are also critical for virus growth. Overexpression of vimentin significantly suppressed the replication of FMDV, whereas knockdown of vimentin significantly enhanced FMDV replication. However, chemical disruption of the vimentin network by acrylamide resulted in a significant decrease in viral yield, suggesting that an intact vimentin network is needed for FMDV replication. These results indicate that vimentin interacts with FMDV 3A and negatively regulates FMDV replication and that the vimentin-3A interaction is essential for FMDV replication. This study provides information that should be helpful for understanding the molecular mechanism of FMDV replication.IMPORTANCE Foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays important roles in virus replication, host range, and virulence. To further understand the role of 3A during FMDV infection, identification of host cell factors that interact with FMDV 3A is needed. Here, we found that vimentin is a direct binding partner of FMDV 3A, and manipulation of vimentin has a negative effect on virus replication. We also demonstrated that amino acid residues 15 to 21 at the N-terminal region of the FMDV 3A are responsible for the interaction between 3A and vimentin and that the 3A-vimentin interaction is critical for viral replication since the full-length cDNA clone harboring mutations in 3A, which were disrupt 3A-vimentin reactivity, could not produce viable virus progeny. This study provides information that not only provides us a better understanding of the mechanism of FMDV replication but also helps in the development of novel antiviral strategies in the future.


Stimulation of renal magnesium reabsorption by calcitonin in the rat.
The effect of salmon synthetic calcitonin (CT) on the renal excretion of water and electrolytes was investigated in thyroparathyroidectomized (TPTX) nondiuretic rats. CT did not significantly alter the excretion of either H2O, Na, Ca, phosphate (P), or K, but consistently decreased both fractional and absolute excretion rates of Mg. This latter effect was probably the result of enhanced reabsorption by the loop of Henle. The excretion rates of P and K were either increased or decreased by CT administration; the Mg response on both the whole kidney and loop of Henle was always observed, however, irrespective of the P and K response. In other experiments, the decrease in Mg excretion was still observed when the fall in the filtered load of P and Ca secondary to CT administration was prevented by an appropriate infusion of Ca and P. It is concluded that 1) CT can alter K and P excretion rates but this influence can be prevented by maintaining the filtered load of Ca and P constant, and 2) CT exerts a marked stimulatory effect on Mg reabsorption, presumably by enhancing reabsorption by the thick ascending limb.


Diversity of nontuberculous mycobacteria in Heater-Cooler Devices - results from prospective surveillance.
The international outbreak of cardiac surgery-associated Mycobacterium chimaera infections was traced back to infectious aerosols originating from contaminated water reservoirs of heater-cooler devices (HCD). In general, nontuberculous mycobacteria (NTM) frequently colonize water systems and can contaminate medical devices. Data on detection of NTM other than M. chimaera in samples gathered from HCDs are scarce. The present study summarizes prospective mycobacterial surveillance of five HCDs over more than four years. A cohort of five, in 2014 factory-new acquired, LivaNova 3T (London, UK) HCDs were prospectively followed. Until mid-April 2014 HCDs were maintained according to the manufacturer's recommendations, subsequently according to an intensified in-house protocol including exhaust air evacuation. Mycobacterial surveillance cultures consisted of monthly water samples gathered from patient and cardioplegia circuits, as well as airflow samples. Out of 441 water samples, 170 (38.6%) revealed NTM growth. The most frequently detected NTM were Mycobacterium chimaera (n=120 (67.4%)), Mycobacterium gordonae (n=35 (19.7 %)), and Mycobacterium paragordonae (n=17 (9.6%)). Growth of NTM, M. chimaera and M. paragordonae was significantly more common in water samples derived from the patient than the cardioplegia circuit of the HCD. Three (2.0%) out of 150 air samples grew NTM. Growth of NTM in HCD water samples was frequent. Diverse NTM species were detected, with M. chimaera being most common. The majority of air samples remained negative. The relevance of NTM other than M. chimaera contaminating HCDs is poorly defined, but a recent report on a HCD-associated outbreak with Mycobacterium abscessus confirms a potential threat.


An updated assessment of radon exposure in Canada.
Based on data from a national residential radon survey performed in 18 cities in Canada in the 1970s, an annual effective dose to the Canadian population due to indoor radon exposure was estimated at 0.71 mSv. An updated estimate of radon exposure in Canada has been made using additional indoor radon data from recent surveys in Ontario and Nova Scotia, and in 28 communities of British Columbia and 15 regions of Quebec. The associated annual effective dose to the Canadian population is now estimated to be 1.15 mSv. The percentage of homes in Canada with radon concentrations above the Canadian Radon Guideline of 200 Bq m(-3) is estimated to be about 3.3 %. As might be expected, this number varies significantly (from a low of 1 % of homes above the Guideline to a high of 19 %) from region to region. Because more radon data are included in the current assessment, and the data set covers broader geographical areas, the current assessment better represents the radon exposure in Canada.


Cell recovery during segmental intestinal perfusion in healthy subjects and patients with Crohn's disease.
The recovery of cells arising from small intestinal mucosa alone was studied during continuous perfusion of a closed segment of jejunum. The perfusion technique minimised the contamination of the perfused segment with, for example, proteolytic enzymes from pancreas, allowing recovery of viable cells. The use of hyaluronidase in the perfusion fluid increased the recovery of cells fivefold, the median recovery being 8 x 10(6) cells. The cells were analysed with monoclonal antibodies and flow cytometry. Nearly all cells (98-99%) recovered during perfusion of healthy control subjects and patients with Crohn's disease were epithelial cells. The jejunal cells expressed HLA-DR in similar proportions--around 30%--in patients and control subjects. The ratio between CD4+ and CD8+ lymphocytes was similar (0.2) in control subjects and patients with inactive Crohn's disease but decreased (0.03) in patients with active Crohn's disease in the ileum.


Medical students' perception of learning from patient encounters in primary health care; a qualitative interview study.
Clinical practice gives medical students opportunities to develop clinical skills and to gain insight into their future profession as a physician. Students in the medical programme at Karolinska Institutet in Sweden had clinical practice in primary health care in nine of their 11 semesters. The aim of this study was to explore medical students' perceptions of learning from patient encounters in a primary health care context. The study was a qualitative inductive interview study. The 21 participating medical students were from their 3rd, 4th and 5th (final year) year of the study programme. A semi-structured interview guide was used. The data analysis was performed with qualitative content analysis. The overarching theme of the study was: The individual patient encounters are the key to learning in primary health care. The patient encounters presented both useful opportunities and challenges that could contribute to the students' professional development. The following four categories were found: 1. Patient encounters in are instructive, rewarding and challenging. Practising in primary health care provided experience in meeting and communicating with a wide variety of patients. Students described it being challenging to trust in their own clinical competence and feeling a responsibility towards the patients. 2. Encounters with patients in primary health care provide opportunities for gradual professional development. Students had the opportunity of increasing independence based on their level of clinical competence. They experienced a progression in their professional development after each period in primary health care. 3. A committed supervisor plays a significant role in learning. Committed supervisors who set aside time for supervision, offered support, and encouraged the student, played an important role in the student's learning. 4. Learning in primary health care and learning in hospitals complement one another. It could be difficult for the students to sort out exactly where they learnt different things as they perceived that learning in primary health care and in hospitals complemented one another. The students' encounters with authentic patients in primary health care gave them recurring opportunities to develop communication skills and to be trusted to work on their own under supervision, giving them guidance on their way to becoming future physicians.


Evaluation of the protective immunity of a novel subunit fusion vaccine in a murine model of systemic MRSA infection.
Staphylococcus aureus is a common commensal organism in humans and a major cause of bacteremia and hospital acquired infection. Because of the spread of strains resistant to antibiotics, these infections are becoming more difficult to treat. Therefore, exploration of anti-staphylococcal vaccines is currently a high priority. Iron surface determinant B (IsdB) is an iron-regulated cell wall-anchored surface protein of S. aureus. Alpha-toxin (Hla) is a secreted cytolytic pore-forming toxin. Previous studies reported that immunization with IsdB or Hla protected animals against S. aureus infection. To develop a broadly protective vaccine, we constructed chimeric vaccines based on IsdB and Hla. Immunization with the chimeric bivalent vaccine induced strong antibody and T cell responses. When the protective efficacy of the chimeric bivalent vaccine was compared to that of individual proteins in a murine model of systemic S. aureus infection, the bivalent vaccine showed a stronger protective immune response than the individual proteins (IsdB or Hla). Based on the results presented here, the chimeric bivalent vaccine affords higher levels of protection against S. aureus and has potential as a more effective candidate vaccine.


Achieving Breastfeeding Equity and Justice in Black Communities: Past, Present, and Future.
Background: Breastfeeding is protective of maternal and infant health across the life course. Increasing breastfeeding rates in Black communities is an important public health strategy to address maternal and infant mortality and morbidity. Methods: Data trends for the past 10 years suggest that Black-led community efforts; local, state, and national initiatives; and maternity care practices that are supportive of breastfeeding have been effective in improving and increasing breastfeeding rates among Black women. Results: Yet breastfeeding disparities and inequities in Black communities persist. Systemic and structural barriers, such as racism, bias, and inequitable access to lactation resources and support continue to be issues in the United States. Conclusion: Going forward, significant investments are needed to decolonize breastfeeding research and clinical practice. Public health and policy priorities need to center on listening to Black women, and funding Black, Indigenous, and People of Color (BIPOC) organizations and researchers conducting innovative projects and research.


Efficacy of Second Generation Direct-Acting Antiviral Agents for Treatment Naïve Hepatitis C Genotype 1: A Systematic Review and Network Meta-Analysis.
The treatment of hepatitis C (HCV) infections has significantly changed in the past few years due to the introduction of direct-acting antiviral agents (DAAs). DAAs could improve the sustained virological response compared to pegylated interferon with ribavirin (PR). However, there has been no evidence from randomized controlled trials (RCTs) that directly compare the efficacy among the different regimens of DAAs. Therefore, we performed a systematic review and network meta-analysis aiming to compare the treatment efficacy between different DAA regimens for treatment naïve HCV genotype 1. Medline and Scopus were searched up to 25th May 2015. RCTs investigating the efficacy of second generation DAA regimens for treatment naïve HCV genotype 1 were eligible for the review. Due to the lower efficacy and more side effects of first generation DAAs, this review included only second generation DAAs approved by the US or EU Food and Drug Administration, that comprised of simeprevir (SMV), sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD). Primary outcomes were sustained virological response at weeks 12 (SVR12) and 24 (SVR24) after the end of treatment and adverse drug events (i.e. serious adverse events, anemia, and fatigue). Efficacy of all treatment regimens were compared by applying a multivariate random effect meta-analysis. Incidence rates of SVR12 and SVR24, and adverse drug events of each treatment regimen were pooled using 'pmeta' command in STATA program. Overall, 869 studies were reviewed and 16 studies were eligible for this study. Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of having SVR24 with pooled risk ratios (RR) of 1.98 (95% CI 1.24, 3.14), 1.46 (95% CI: 1.22, 1.75), and 1.68 (95% CI: 1.14, 2.46), respectively. Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR, i.e. SOF plus LDV with/without ribavirin, SOF plus SMV with/without ribavirin, SOF plus DCV with/without ribavirin, and PrOD with/without ribavirin, (pooled incidence of SVR12 ranging from 93% to 100%, and pooled incidence of SVR24 ranging from 89% to 96%) were much higher than the pooled incidence rates of SVR12 (51%) and SVR24 (48%) in PR alone. In comparing SOF plus LDV with ribavirin and SOF plus LDV without ribavirin, the chance of having SVR12 was not significantly different between these two regimens, with the pooled RR of 0.99 (95% CI: 0.97, 1.01). Regarding adverse drug events, risk of serious adverse drug events, anemia and fatigue were relatively higher in treatment regimens with PR than the treatment regimens without PR. The main limitation of our study is that a subgroup analysis according to dosages and duration of treatment could not be performed. Therefore, the dose and duration of recommended treatment have been suggested in range and not in definite value. Both DAA plus PR and dual DAA regimens should be included in the first line drug for treatment naïve HCV genotype 1 because of the significant clinical benefits over PR alone. However, due to high drug costs, an economic evaluation should be conducted in order to assess the value of the investment when making coverage decisions.


A Cost-Effectiveness Analysis of Surgery for Middle-Aged Men with Severe Obstructive Sleep Apnea Intolerant of CPAP.
Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Conventional OSA therapy necessitates indefinite continuous positive airway pressure (CPAP). Although CPAP is an effective treatment modality, up to 50% of OSA patients are intolerant of CPAP. We explore whether surgical modalities developed for those intolerant of CPAP are cost-effective. We construct a lifetime semi-Markov model of OSA that accounts for observed increased risks of stroke, cardiovascular disease, and motor vehicle collisions for a 50-year-old male with untreated severe OSA. Using this model, we compare the cost-effectiveness of (1) no treatment, (2) CPAP only, and (3) CPAP followed by surgery (either palatopharyngeal reconstructive surgery [PPRS] or multilevel surgery [MLS]) for those intolerant to CPAP. Compared with the CPAP only strategy, CPAP followed by PPRS (CPAP-PPRS) adds 0.265 quality adjusted life years (QALYs) for an increase of $2,767 (discounted 2010 dollars) and is highly cost effective with an incremental cost-effectiveness ratio (ICER) of $10,421/QALY for a 50-year-old male with severe OSA. Compared to a CPAP-PPRS strategy, the CPAP-MLS strategy adds 0.07 QALYs at an increase of $6,213 for an ICER of $84,199/QALY. The CPAP-PPRS strategy appears cost-effective over a wide range of parameter estimates. Palatopharyngeal reconstructive surgery appears cost-effective in middle-aged men with severe OSA intolerant of CPAP. Further research is warranted to better define surgical candidacy as well as short-term and long-term surgical outcomes. A commentary on this article appears in this issue on page 509.


Regulation of epithelial stem cell replacement and follicle formation in the Drosophila ovary.
Though much has been learned about the process of ovarian follicle maturation through studies of oogenesis in both vertebrate and invertebrate systems, less is known about how follicles form initially. In Drosophila, two somatic follicle stem cells (FSCs) in each ovariole give rise to all polar cells, stalk cells, and main body cells needed to form each follicle. We show that one daughter from each FSC founds most follicles but that cell type specification is independent of cell lineage, in contrast to previous claims of an early polar/stalk lineage restriction. Instead, key intercellular signals begin early and guide cell behavior. An initial Notch signal from germ cells is required for FSC daughters to migrate across the ovariole and on occasion to replace the opposite stem cell. Both anterior and posterior polar cells arise in region 2b at a time when approximately 16 cells surround the cyst. Later, during budding, stalk cells and additional polar cells are specified in a process that frequently transfers posterior follicle cells onto the anterior surface of the next older follicle. These studies provide new insight into the mechanisms that underlie stem cell replacement and follicle formation during Drosophila oogenesis.


Avoiding false positive diagnoses of motor neuron disease: lessons from the Scottish Motor Neuron Disease Register.
To describe the frequency and characteristics of those patients initially registered with the Scottish Motor Neuron Disease Register (SMNDR) but who subsequently had a diagnosis other than MND made (false positives), to analyse the features which led to a revised diagnosis, and to draw conclusions which might improve routine neurological practice. The Scottish Motor Neuron Disease Register is a community based, prospective disease register to identify and follow up all incident cases of motor neuron disease in Scotland. Fifty three patients out of a total of 552 registered are presented, who, after initial registration, were later excluded because they failed to satisfy the register's diagnostic criteria. Seven of these patients were labelled as "MND plus" syndromes and may represent a distinct subset of MND. The remaining 46 patients had an alternative diagnosis made (false positive group), accounting for 8% of the total. In half of these cases, potentially beneficial therapies are available. The predominant reasons which lead to a diagnostic revision were: failure of symptom progression, development of atypical clinical features for MND, and investigation results. Patients with MND should undergo thorough and relevant investigations at presentation with the emphasis on neuroradiological imaging and neurophysiology; all patients should be followed up by an experienced neurologist, particularly those in whom symptoms and signs are restricted to either the bulbar or spinal muscles; failure of symptom progression or development of atypical features should lead to an early reassessment; finally, patients should be informed of the diagnosis only when it is secure.


Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies.
Curcumin is the active ingredient of turmeric. It is widely used as a kitchen spice and food colorant throughout India, Asia and the Western world. Curcumin is a major constituent of curry powder, to which it imparts its characteristic yellow colour. For over 4000 years, curcumin has been used in traditional Asian and African medicine to treat a wide variety of ailments. There is a strong current public interest in naturally occurring plant-based remedies and dietary factors related to health and disease. Curcumin is non-toxic to human subjects at high doses. It is a complex molecule with multiple biological targets and different cellular effects. Recently, its molecular mechanisms of action have been extensively investigated. It has anti-inflammatory, antioxidant and anti-cancer properties. Under some circumstances its effects can be contradictory, with uncertain implications for human treatment. While more studies are warranted to further understand these contradictions, curcumin holds promise as a disease-modifying and chemopreventive agent. We review the evidence for the therapeutic potential of curcumin from in vitro studies, animal models and human clinical trials.


Bilingualism and specific language impairment in children attending language units.
Bilingual children were found to form a distinct subgroup within a large cohort of children with specific language-impairment (SLI) attending language units across England. They differed from the cohort as a whole, and from a language-matched monolingual 'control' group, on measures including language profile on entry to the unit, performance on standardised tests, emotional-behavioural state and probable future educational placement. This paper sets out the nature of these differences in more detail, and suggests some possible explanations for them.


[Chronic kidney diseases: common and harmful, but also preventable and treatable].
Chronic kidney disease (CKD) is a public health problem worldwide. In Brazil incidence and prevalence of end stage renal failure are increasing; prognosis is still poor and costs of disease treatment are very high. Regardless of the etiology, main outcomes in patients with CKD are its complications (anemia, metabolic acidosis, malnutrition and alteration in mineral metabolism), death (mainly due to cardiovascular causes) and loss of renal function. Recent studies indicate that these outcomes may be postponed with specific treatment if the CKD is diagnosed early and renoprotective and cardioprotective measures are implemented early in the course of the disease. The current definition and staging of CKD, as well as the discussion of the main preventive measures are addressed in this review.


Assessment of anaerobic bacterial diversity and its effects on anaerobic system stability and the occurrence of antibiotic resistance genes.
This study evaluated the link between anaerobic bacterial diversity and, the biodegradation of antibiotic combinations and assessed how amending antibiotic combination and increasing concentration of antibiotics in a stepwise fashion influences the development of resistance genes in anaerobic reactors. The biodegradation, sorption and occurrence of the known antibiotic resistance genes (ARGs) of erythromycin and tetracycline were investigated using the processes of UV-HPLC and qPCR analysis respectively. Ion Torrent sequencing was used to detect microbial community changes in response to the addition of antibiotics. The overall results indicated that changes in the structure of a microbial community lead to changes in biodegradation capacity, sorption of antibiotics combinations and occurrence of ARGs. The enhanced biodegradation efficiency appeared to generate variations in the structure of the bacterial community. The results suggested that controlling the ultimate Gram-negative bacterial community, especially Acinetobacter-related populations, may promote the successful biodegradation of antibiotic combinations and reduce the occurrence of ARGs.


An Approach to Minimising Risk of Adrenal Insufficiency When Discontinuing Oral Glucocorticoids.
Oral glucocorticoids are commonly used across every field of medicine; however, discontinuing them in patients can be challenging. The risk of acute adrenal crises secondary to glucocorticoid withdrawal can be fatal and arises from chronic suppression of the adrenal glands. Identifying risk factors for adrenal suppression in dermatological patients, such as doses greater than 5 to 7.5 mg of prednisone equivalent, duration of glucocorticoid use greater than 3 weeks, certain medications, and comorbidities, can help risk-stratify patients. The use of adrenal gland testing such as basal cortisol levels and adrenocorticotropic hormone stimulation tests can confirm adrenal suppression in patients. This review article provides an approach that dermatologists can use to minimise the risk of adrenal insufficiency in patients discontinuing glucocorticoids and when it may be appropriate to use adrenal gland testing.


Infectious nucleic acids, a new dimension in virology.
Viral nucleic acids have been found to be infectious for tissues and animals, yet are nonantigenic and resistant to antibodies against whole virus. Other unique properties, such as their host range and their susceptibility to nuclease action, render them a wholly new dimension to be reckoned with in virology. These properties may explain a number of conditions which at present are considered anomalous. The release from infected tissues of even a small proportion of total virus as free nucleic acid could, in an otherwise immune individual, lead to a low level of infection which would, perhaps, explain permanent immunity. If the proportion of nucleic acid is higher, or if the nucleic acid is resistant to nucleases because of an inert envelope, such conditions as "carrier" states-that is, viremias with or without antibodies-are possible. Note added in proof: The recent article by J. D. Ebert and F. H. Wilt (54) came to my attention after the present article was written. Ebert and Wilt's excellent article indicates the impact of the newer knowledge of viral nucleic acids on the ideas developing in the field of embryology.


[Myths concerning malarial transmission among Amazonian Indians and their relation with 2 types of transmission encountered in the Amazonian forest].
Among the Indians Desana's (Tukano amerindians) in the Upper Rio Negro, the interseasonal variation of the malarial fevers were associated with two myths (localised in two distinguishable places). One myth associates the malarial with the rivers which contain "malaria pots". Conception based on an observation of localised water collection in the banks and the rocky rapids ("banks and rocky's fever"). The transmission and the anophelian density present variation between the seasons in relation to the river's level. Another myth associates malarial fevers in the forest, with the song of a frog ("fever's frog") and the flowering and fructification of a tree (Poaqueira sericea Thul.). There is in South America a particular type of forest malaria, known as "Bromelia malaria" and denounced in human and/or simian transmission. This forest malaria is transmitted by the a sub-genus anopheles (Kerteszia) which larval breeding are areal in the canopy. The breeding places are found in the forest in the epiphyte bromeliads. To understand this type of transmission, we must take reference to the previous endomological data at the Upper Oyapock Wayâpi (Tupi amerindians). This Bromelia malaria could fluctuated according larval density variation, related to washing of epiphytes (end of the rainy season) or to their flowering (end of the dry season). The "fever's frog" myth collected at the Desana's in the Upper Rio Negro can be related to the existence of Bromelia malaria in this amazonian habitat. These myths showed the perfect adaptation of the amerindians to their environment and their complete knowledge of the neotropical forest.


Verification bias an underrecognized source of error in assessing the efficacy of medical imaging.
Diagnostic tests are validated by comparison against a "gold standard" reference test. When the reference test is invasive or expensive, it may not be applied to all patients. This can result in biased estimates of the sensitivity and specificity of the diagnostic test. This type of bias is called "verification bias," and is a common problem in imaging research. The purpose of our study is to estimate the prevalence of verification bias in the recent radiology literature. All issues of the American Journal of Roentgenology (AJR), Academic Radiology, Radiology, and European Journal of Radiology (EJR) between November 2006 and October 2009 were reviewed for original research articles mentioning sensitivity or specificity as endpoints. Articles were read to determine whether verification bias was present and searched for author recognition of verification bias in the design. During 3 years, these journals published 2969 original research articles. A total of 776 articles used sensitivity or specificity as an outcome. Of these, 211 articles demonstrated potential verification bias. The fraction of articles with potential bias was respectively 36.4%, 23.4%, 29.5%, and 13.4% for AJR, Academic Radiology, Radiology, and EJR. The total fraction of papers with potential bias in which the authors acknowledged this bias was 17.1%. Verification bias is a common and frequently unacknowledged source of error in efficacy studies of diagnostic imaging. Bias can often be eliminated by proper study design. When it cannot be eliminated, it should be estimated and acknowledged.


Multifunctional Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-Based Nanobomb against Carbapenem-Resistant Acinetobacter baumannii Infection through Cascade Reaction and Amplification Synergistic Effect.
Carbapenems have been considered to be the preferred antibiotics against Acinetobacter baumannii thus far. However, carbapenem-resistant Acinetobacter baumannii (CRAB) has gradually escalated worldwide, and it frequently causes respiratory and bloodstream infections. Its resistance may lead to high mortality. Thus, there is an urgent need to develop antibacterial drugs. In our research, the pH-sensitive sgRNA-I/L@ZS nanosystem delivered imipenem and better released it in infected tissues to synergistically damage bacteria with nanoparticles. Gene editing of the CRISPR-Cas9 nanosystem amplified the synergistic effect by reversing the drug-resistance of imipenem. Nitric oxide, which l-arginine reacted with ROS to produce in cascade reaction and bacterial infection sites, was beneficial to heal the infected tissues and induce bacteria death for further enhancing antibacterial effects. In addition, this nanocomposite influenced host-bacteria interactions and restrained and destroyed biofilms. The sgRNA-I/L@ZS nanosystem, similar to a nanobomb, was a high-efficiency bactericide against CRAB. Eventually, in acute pneumonia and peritonitis mouse models, the sgRNA-I/L@ZS nanosystem could combat bacteria and protect tissues from infection. It had marked suppressive effects on inflammation and promoted healing and proliferation of infected tissues. This multifunctional nanosystem is expected to be an effective antibacterial agent in the clinic based on good biocompatibility and no toxic side effects. Therefore, developing the nanocomposites will take a favorable step toward solving intractable public health issues.


An update of biochemical markers of hepatocellular carcinoma.
The definition of a tumor marker is broad, which covers a wide spectrum of biomacromolecules synthesized in excess concentration by a wide variety of neoplastic cells. Tumor markers can be normal endogenous products that are produced at a greater rate in cancer cells or the products of newly switched on genes that remained inactive in the normal cells. These markers consist of any products of either tumor itself or the host in reaction to tumor's presence that distinguishes malignant tissues from benign and is measurable in body fluids or tissues. They increase with progressive or recurrent disease, decrease with response to treatment, and normalize with remission. Clinical applications include screening in asymptomatic individuals, confirming a suspected diagnosis, assisting in tumor classification and staging, prognosis, monitoring treatment response, surveillance for residual disease, and early detection of recurrent disease.


Effective removal of inorganic and organic heavy metal pollutants with poly(amino acid)-based micromotors.
The increasing extent of heavy metal pollution all over the world has resulted in many serious environmental and public health problems. To solve these problems, effective technologies for water treatment are urgently needed. Recent efforts have focused on the development of self-driven micro/nanomotors for eliminating inorganic and organic pollutants in an aqueous system. These synthetic micro/nanomotors can increase mass transfer through the transportation of reactive species, leading to higher decontamination rates. Here, we report a surface-tunable poly(amino acid) (PAA)-based micromotor. The property of the outer layer can be adjusted by changing the type and proportion of amino acids according to real requirements. Three kinds of micromotors are fabricated, which consist of a microtube composed of PAAs (i.e., polyaspartic acid (PAsp), polycysteine (PCys) or a copolymer of both (PAsp-Cys)), a thin Ni intermediate layer, and a Pt inner layer. Due to the presence of various side-chain functional groups (e.g., amino, carboxyl, and sulfhydryl) on the surface of the poly(amino acid)s, these micromotors can be used as effective scavengers for the removal of heavy metals (i.e., Cd2+, Pb2+ and methylmercury). Compared with PAsp and PCys micromotors, the PAsp-Cys micromotor shows good acid resistance and can simultaneously adsorb various kinds of heavy metals with high removal efficiency. The outer layer of the surface-tunable micromotor has good biocompatibility and adsorption efficiency, which holds considerable promise for environmental and biomedical applications.


[Polycythemia caused by liver carcinoma in cattle and sheep].
Polycythemia associated with hepatic carcinoma was diagnosed in a 10-year-old cow, an 8-month-old heifer and a 3-year-old sheep. The cow was referred to our clinic because of weight loss, reduced appetite, hematuria, marked reddening of the mucosa of the tear canal, oral cavity and vestibule and an increased hematocrit. Clinical examination also revealed injected scleral vessels. The erythrocyte count, the PCV, hemoglobin concentration and the activities of the hepatic enzymes were increased. Ultrasonographic examination revealed a very large liver with a focal echogenic lesion. Based on all findings, a diagnosis of polycythemia associated with a liver tumor, was made. The cow was slaughtered. Multifocal liver tumors were diagnosed histologically as hepatocellular carcinoma. The heifer and sheep had similar clinical and hematological findings. Hepatocellular carcinoma was diagnosed in the heifer and cholangiocellular carcinoma in the sheep. It was concluded that in all three patients, polycythemia was caused by hepatic carcinoma.


Disparities by Race, Age, and Sex in the Improvement of Survival for Major Cancers: Results From the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program in the United States, 1990 to 2010.
Substantial progress has been made in cancer diagnosis and treatment, resulting in a steady improvement in cancer survival. The degree of improvement by age, race, and sex remains unclear. To quantify the degree of survival improvement over time by age, race, and sex in the United States. Longitudinal analyses of cancer follow-up data from 1990 to 2010, from 1.02 million patients who had been diagnosed as having cancer of the colon or rectum, breast, prostate, lung, liver, pancreas, or ovary from 1990 to 2009 and who were included in 1 of 9 population-based registries of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. Hazard ratios (HRs) and 95% CIs for cancer-specific death were estimated for patients diagnosed as having any of these cancers during 1995 to 1999, 2000 to 2004, and 2005 to 2009, compared with those diagnosed in 1990 to 1994. Significant improvements in survival were found for cancers of the colon or rectum, breast, prostate, lung, and liver. Improvements were more pronounced for younger patients. For patients aged 50 to 64 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.57 (95% CI, 0.55-0.60), 0.48 (95% CI, 0.45-0.51), 0.61 (95% CI, 0.57-0.69), and 0.32 (95% CI, 0.30-0.36), for cancer of the colon or rectum, breast, liver, and prostate, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. However, the corresponding HRs (95% CIs) for elderly patients (those 75-85 years old) were only 0.88 (95% CI, 0.84-0.92), 0.88 (95% CI, 0.82-0.95), 0.76 (95% CI, 0.69-0.84), and 0.65 (95% CI, 0.61-0.70), for the same 4 cancer sites, respectively. A similar, although weaker, age-related period effect was observed for lung and pancreatic cancers. The adjusted HRs (95% CIs) for lung cancer were 0.75 (95% CI, 0.73-0.77) and 0.84 (95% CI, 0.81-0.86), respectively, for patients aged 50 to 64 years and 75 to 85 years diagnosed between 2005 and 2009, compared with the same age groups of patients diagnosed between 1990 and 1994 (0.73 [95% CI, 0.69-0.77] and 0.90 [95% CI, 0.85-0.95], respectively. Compared with whites or Asians, African Americans experienced greater improvement in prostate cancer survival. From 1990 to 2009, ovarian cancer survival declined among African Americans but improved among whites. No apparent sex difference in the degree of improvement for any non-sex-specific cancer was noted. Younger patients experienced greater benefit from recent oncology advances than elderly patients. African Americans experienced poorer survival than whites for all cancers, and the racial difference decreased for prostate cancer but increased for ovarian cancer. Identifying factors associated with varied improvement in cancer survival can inform future improvements in cancer care for all.


Galcanezumab for the prevention of migraine.
Migraine is a common and disabling disorder affecting approximately 1.02 billion people worldwide. Calcitonin gene-related peptide (CGRP) has been identified as playing an important role in the pathophysiology of migraine and several migraine-specific therapies targeting the CGRP ligand or its receptor have been approved since 2018 for the acute and preventive treatment of migraine. This review focuses on the pharmacology, clinical efficacy and safety/tolerability of galcanezumab, an anti-CGRP monoclonal antibody approved for the prevention of migraine.


New York City social workers after 9/11: their attachment, resiliency, and compassion fatigue.
This study examines the relationship between attachment classification, resiliency, and compassion fatigue in New York social workers following 9/11. We used single occasion, quasi-random sampling, surveying 481 social workers living in Manhattan. Hierarchical regression analyses revealed that secure attachment is predictive of the ability to cope with secondary traumatic stress as well as capacity for resilience, explaining approximately 7% of the variance in both compassion fatigue and resiliency. These findings suggest that secure attachment may serve as a source of resilience for social workers, immunizing them from significant compassion fatigue. Such findings have significant implications for clinicians working with traumatized populations.


Phytosterols ameliorate clinical manifestations and inflammation in experimental autoimmune encephalomyelitis.
Using experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), the objective of this study was to examine the effect of phytosterol (PS) administration on inflammation-based EAE development. Female SJL mice were orally administered PS prior to disease induction and maintained throughout the experiment. EAE was induced with antigenic peptide (PLP(131-155)). Mice were clinically scored for disease and euthanized for biochemical and histological analysis of inflammation. PS delayed onset of EAE development by 2 days and decreased disease severity by 55%. Brain histological analysis revealed an 82% decrease in central nervous system (CNS) inflammatory infiltration and a 48% decrease in demyelination in PS-treated mice versus control. Immunohistochemistry (IHC) showed a 35% reduction in macrophages entering brains of PS-treated mice. Anti-inflammatory interleukin (IL)-10 was up-regulated by 10%, while pro-inflammatory CCL2 was inhibited by 50% with PS treatment. Additionally, PS slightly decreased other pro-inflammatory factors, such as tumor necrosis factor (TNF)-α, IL-6, and interferon (IFN)-γ. PS protects against development of EAE by reducing infiltration and inflammatory activity of immune cells into CNS of treated mice, thereby decreasing demyelination associated with EAE. These results provide evidence to support PS as a preventative agent that helps to protect against the development of inflammation-driven disease, such as MS.


A positive effect of p21cip1/waf1 in the colony formation from murine myeloid progenitor cells as assessed by retroviral-mediated gene transfer.
p21cip1/waf1 is a cyclin dependent kinase inhibitor. We have previously reported stimulation of p21cip1/waf1 by steel factor and GM-CSF in a factor dependent cell line and of p21cip1/waf1 involvement in hematopoiesis in vivo in p21cip1/waf1 gene knockout (-/-) mice. To further assess a role for increased p21cip1/waf1 in hematopoietic progenitor cells, we developed the retroviral vector L(p21cip1)SN to transcriptionally regulate p21cip1/waf1 from the Mo-MLV LTR. L(p21cip1)SN and the control vector LXSN were used to transduce murine bone marrow progenitor cells from p21cip1/waf1 (-/-) and littermate control (+/+) mice, as well as from other mouse strains. Hematopoietic colony formation by transduced cells was assessed in semi-solid culture medium with multiple growth factors. Myeloid colony formation by bone marrow cells from p21cip1/waf1 (-/-) mice was significantly lower than that by (+/+) mouse cells. Transduction of cells with LXSN had no effect on colony formation: however, (-/-) cells transduced with L(p21cip1)SN formed significantly greater numbers of colonies than either LXSN-transduced (-/-) or (+/-) cells. Moreover, L(p21cip1)SN-transduced (+/+) cells formed significantly more colonies than LXSN-transduced (+/+) cells. Increased cloning efficiency of progenitors from normal strains of mice induced by L(p21cip1)SN compared to LXSN-transduced cells was seen whether unseparated or highly purified populations of Sca1+ Lin- marrow cells were used. Gene transfer of L(p21cip1)SN increased the size and number of cells per colony, as well as the number of colonies compared to LXSN gene transfer. No colonies grew from non-transduced, LXSN-, or L(p21cip1)SN-transduced cells when no growth factors were added to the cultures. These results document the positive effect of p21cip1/waf1 in the proliferation and/or differentiation of the murine myeloid progenitor cells that lead to colony formation.


Role of genetic disorders in acute recurrent pancreatitis.
There was remarkable progress in the understanding of the role genetic risk factors in chronic pancreatitis. These factors seem to be much more important than thought in the past. The rare autosomal-dominant mutations N29I and R122H of PRSS1 (cationic trypsinogen) as well as the variant N34S of SPINK1 (pancreatic secretory trypsin inhibitor) are associated to a disease onset in childhood or youth. Compared to chronic alcoholic pancreatitis the progression is slow so that for a long time only signs of acute-recurrent pancreatitis are found. Only at later time points (more than 10-15 years) there is evidence for chronic pancreatitis in the majority of patients. Acute recurrent pancreatitis may therefore be regarded as a transition state until definite signs of chronic pancreatitis are detectable.