Cancer and breast cancer awareness interventions in an intellectual disability context: A review of the literature.

BACKGROUND: Women with an intellectual disability (ID) have a similar risk of developing breast cancer as women in the general population yet present with later stage breast cancers, which have poorer outcomes. AIM: To identify whether there is a need to develop a breast cancer awareness intervention for women with an ID. METHODS: Interventions aimed at increasing cancer awareness and breast cancer awareness for people with an ID were identified and critically appraised. RESULTS: Five interventions to increase cancer awareness or breast cancer awareness in people with an ID were identified. CONCLUSION: The review highlighted the paucity of theoretically underpinned breast cancer awareness interventions specifically aimed at women with an ID. Facilitating breast cancer awareness for women with an ID could potentially lead to earlier presentation of potential symptoms of breast cancer, earlier treatment, better prognosis and ultimately, improved survival. This article establishes that there is a need for an intervention underpinned by theory to increase breast cancer awareness in women with an ID.

Gepotidacin (GSK2140944) In Vitro Activity against Gram-Positive and Gram-Negative Bacteria.

Gepotidacin is a first-in-class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and has in vitro activity against susceptible and drug-resistant pathogens. Reference in vitro methods were used to investigate the MICs and minimum bactericidal concentrations (MBCs) of gepotidacin and comparator agents for Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli Gepotidacin in vitro activity was also evaluated by using time-kill kinetics and broth microdilution checkerboard methods for synergy testing and for postantibiotic and subinhibitory effects. The MIC90 of gepotidacin for 50 S. aureus (including methicillin-resistant S. aureus [MRSA]) and 50 S. pneumoniae (including penicillin-nonsusceptible) isolates was 0.5 µg/ml, and for E. coli (n = 25 isolates), it was 4 µg/ml. Gepotidacin was bactericidal against S. aureus, S. pneumoniae, and E. coli, with MBC/MIC ratios of ≤4 against 98, 98, and 88% of the isolates tested, respectively. Time-kill curves indicated that the bactericidal activity of gepotidacin was observed at 4× or 10× MIC at 24 h for all of the isolates. S. aureus regrowth was observed in the presence of gepotidacin, and the resulting gepotidacin MICs were 2- to 128-fold higher than the baseline gepotidacin MICs. Checkerboard analysis of gepotidacin combined with other antimicrobials demonstrated no occurrences of antagonism with agents from multiple antimicrobial classes. The most common interaction when testing gepotidacin was indifference (fractional inhibitory concentration index of >0.5 to ≤4; 82.7% for Gram-positive isolates and 82.6% for Gram-negative isolates). The postantibiotic effect (PAE) of gepotidacin was short when it was tested against S. aureus (≤0.6 h against MRSA and MSSA), and the PAE-sub-MIC effect (SME) was extended (>8 h; three isolates at 0.5× MIC). The PAE of levofloxacin was modest (0.0 to 2.4 h), and the PAE-SME observed varied from 1.2 to >9 h at 0.5× MIC. These in vitro data indicate that gepotidacin is a bactericidal agent that exhibits a modest PAE and an extended PAE-SME against Gram-positive and -negative bacteria and merits further study for potential use in treating infections caused by these pathogens.

In Vitro Activity of Gepotidacin (GSK2140944) against Neisseria gonorrhoeae.

Gepotidacin (formerly GSK2140944) is a novel, first-in-class, triazaacenaphthylene antibacterial that inhibits bacterial DNA gyrase and topoisomerase IV via a unique mechanism and has demonstrated in vitro activity against Neisseria gonorrhoeae, including drug-resistant strains, and also targets pathogens associated with other conventional and biothreat infections. Broth microdilution was used to evaluate the MIC and minimum bactericidal concentration (MBC) activity of gepotidacin and comparators against 25 N. gonorrhoeae strains (including five ciprofloxacin-nonsusceptible strains). Gepotidacin activity was also evaluated against three N. gonorrhoeae strains (including a ciprofloxacin-nonsusceptible strain) for resistance development, against three N. gonorrhoeae strains (including two tetracycline- and azithromycin-nonsusceptible strains) using time-kill kinetics and checkerboard methods, and against two N. gonorrhoeae strains for the investigation of postantibiotic (PAE) and subinhibitory (PAE-SME) effects. The MIC50 and MIC90 for gepotidacin against the 25 N. gonorrhoeae isolates tested were 0.12 and 0.25 µg/ml, respectively. The MBC50 and MBC90 for gepotidacin were 0.25 and 0.5 µg/ml, respectively. Gepotidacin was bactericidal, and single-step resistance selection studies did not recover any mutants, indicating a low rate of spontaneous single-step resistance. For combinations of gepotidacin and comparators tested using checkerboard methods, there were no instances where antagonism occurred and only one instance of synergy (with moxifloxacin; fractional inhibitory concentration, 0.375). This was not confirmed by in vitro time-kill studies. The PAE for gepotidacin against the wild-type strain ranged from 0.5 to >2.5 h, and the PAE-SME was >2.5 h. These in vitro data indicate that further study of gepotidacin is warranted for potential use in treating infections caused by N. gonorrhoeae.

Plate augmentation for femoral nonunion: more than just a salvage tool?

OBJECTIVE: The aim of the current study was to determine whether plate augmentation was a successful treatment algorithm for selected femoral nonunions initially managed with intramedullary nailing. MATERIALS AND METHODS: A total of 30 femoral nonunion cases were managed using the plate augmentation strategy with 13 primary cases and 17 multi-operated femurs (avg 2.8 ineffective procedures). Adjunctive strategies included autologous bone grafting and/or BMP for atrophic/oligotrophic and bone defect cases. Deformity correction was performed when required. RESULTS: Osseous union occurred in 29 of 30 cases. One multi-operated case with bone defect and prior infection required repeat autologous grafting prior to union. CONCLUSION: Plate augmentation should be added to the armamentarium for management of selected femoral nonunion that have failed initial intramedullary nailing.

Antimicrobial activity of solithromycin against serotyped macrolide-resistant Streptococcus pneumoniae isolates collected from U.S. medical centers in 2012.

Solithromycin, a next-generation macrolide and novel fluoroketolide, was tested against a 2012 collection of serotyped U.S. macrolide-resistant Streptococcus pneumoniae isolates associated with community-acquired bacterial pneumonia (CABP). Against all 272 isolates, solithromycin demonstrated high potency (MIC50/90, 0.06/0.25 µg/ml), and it inhibited all strains at MICs of ≤0.5 µg/ml, including the two most prevalent macrolide-resistant serotypes (19A and 35B). These data support the continued clinical development of solithromycin for the treatment of multidrug-resistant CABP.

Wedge effect following intramedullary hip screw fixation of intertrochanteric proximal femur fracture.

INTRODUCTION: The aim of the current study was to determine whether application of an intramedullary hip screw for definitive management of intertrochanteric fracture was associated with post-operative deformity. Specifically this study investigated whether nail insertion would cause a "wedge effect" of the intertrochanteric fracture manifesting as lateralization of the femoral shaft and varus malalignment. MATERIALS AND METHODS: The trauma database at the University of Pittsburgh Medical Center was investigated to identify all intertrochanteric fractures (AO/OTA 31A) over the past 3 years treated with an IMHS. Fractures eligible for inclusion were performed under the supervision of a fellowship trained orthopedic trauma surgeon. All fractures were reduced in optimal alignment using percutaneous or mini-open strategies during the reaming process and nail insertion. The entry portal was over-reamed by at least 1.5 mm. Cases selected for review of the "wedge effect" had optimal post-operative imaging allowing for assessment of discrepancy between the operative and normal hip. RESULTS: Forty six patients with an average age of 77 years were included for study. Fifty percent were classified as unstable patterns. Shaft lateralization following IMHS fixation of the fractured hip was found to be an average of 7 mm greater than the contralateral intact hip (p < 0.001) (range 0-30 mm). The neck-shaft angle of the operative hips was 129° as compared to 133° on the intact side (p = 0.009). The stability of the fracture pattern was not predictive for post-operative lateralization of the femoral shaft or varus angulation (p > 0.05) (Table 2). There was no difference in post-operative deformity among techniques used for maintenance of reduction during reaming and nail insertion (p > 0.05). Despite deformity, all cases demonstrated radiographic radiographic fracture union. CONCLUSION: Despite attention to detail, the application of an intramedullary hip screw for intertrochanteric fracture has the tendency to lateralize the shaft relative to the head/neck segment (The "wedge effect").

Head and neck cancer patients' experiences of percutaneous endoscopic gastrostomy feeding: a Q-methodology study.

Head and neck cancer patients are at high risk of malnutrition and its complications and therefore often undergo non-oral nasogastric or percutaneous endoscopic gastrostomy (PEG) nutrition support. However, there is little evidence that either approach is effective in this group. While one possible explanation for these findings relates to the relationship between artificial tube feeding and poor quality of life, there is little research that examines the patient's subjective experience of nutrition support. This study investigated the experiences of PEG tube feeding in head and neck cancer patients undergoing radical treatment. Conventional Q-methodology was used with 15 head and neck cancer patients, who rank-ordered 36 statements according to the extent to which these reflected their experiences of PEG tube feeding. The sorted statements were factor-analysed case-wise to provide clusters of similar experiences. Three perspectives emerged. Factor 1, labelled 'Constructive cognitive appraisal', focused around positive adaptation to, and acceptance of, PEG feeding. Factor 2, labelled 'Cognitive-affective dissonance', reflected ambivalence between cognitive acceptance and affective rejection of the PEG tube. Factor 3, labelled 'Emotion-focused appraisal', was characterised by tube-focused anxiety and fear. The findings broadly confirm Levanthal et al.'s Self-Regulatory Model of coping and support the need for genuine and individualised patient-centred nutritional care.

Early psychological interventions for prevention and treatment of post-traumatic stress disorder (PTSD) and post-traumatic stress symptoms in post-partum women: A systematic review and meta-analysis.

BACKGROUND: Pre-term or full-term childbirth can be experienced as physically or psychologically traumatic. Cumulative and trans-generational effects of traumatic stress on both psychological and physical health indicate the ethical requirement to investigate appropriate preventative treatment for stress symptoms in women following a routine traumatic experience such as childbirth. OBJECTIVE: The objective of this review was to investigate the effectiveness of early psychological interventions in reducing or preventing post-traumatic stress symptoms and post-traumatic stress disorder in post-partum women within twelve weeks of a traumatic birth. METHODS: Randomised controlled trials and pilot studies of psychological interventions preventing or reducing post-traumatic stress symptoms or PTSD, that included women who had experienced a traumatic birth, were identified in a search of Cochrane Central Register of Randomised Controlled Trials, MEDLINE, Embase, Psychinfo, PILOTS, CINAHL and Proquest Dissertations databases. One author performed database searches, verified results with a subject librarian, extracted study details and data. Five authors appraised extracted data and agreed upon risk of bias. Analysis was completed with Rev Man 5 software and quality of findings were rated according to Grading of Recommendation, Assessment, Development, and Evaluation. RESULTS: Eleven studies were identified that evaluated the effectiveness of a range of early psychological interventions. There was firm evidence to suggest that midwifery or clinician led early psychological interventions administered within 72 hours following traumatic childbirth are more effective than usual care in reducing traumatic stress symptoms in women at 4-6 weeks. Further studies of high methodological quality that include longer follow up of 6-12 months are required in order to substantiate the evidence of the effectiveness of specific face to face and online early psychological intervention modalities in preventing the effects of stress symptoms and PTSD in women following a traumatic birth before introduction to routine care and practice. PROSPERO REGISTRATION: CRD42020202576, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=202576.

Nonlinear mirror modelocking of a bounce geometry laser.

We present the investigation of nonlinear mirror modelocking (NLM) of a bounce amplifier laser. This technique, a potential rival to SESAM modelocking, uses a nonlinear crystal and a dichroic mirror to passively modelock a Nd:GdVO(4) slab bounce amplifier operating at 1063nm. At 11.3W, we present the highest power achieved using the NLM technique, using type-II phase-matched KTP, with a pulse duration of 57ps. Using type-I phase-matched BiBO, modelocking was achieved with a shorter pulse duration of 5.7ps at an average power of 7.1W.

Biomarkers of inflammation in cattle determining the effectiveness of anti-inflammatory drugs.

The impact of nonsteroidal anti-inflammatory drugs (NSAID) on prostaglandin E(2) (PGE(2)) production and cyclooxygenase 2 (COX-2) mRNA expression in bovine whole blood (WB) cultures stimulated by lipopolysaccharide (LPS) was determined, using the blood from six Holstein dairy cattle in various stages of lactation. Peak production of PGE(2) occurred 24 h after LPS stimulation but did not result in detectable concentrations of thromboxane B(2) (TXB(2)). The NSAID indomethacin, aspirin, flunixin meglumine, and 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide (PTPBS; celecoxib analogue), along with dexamethasone, were all equally effective in reducing the concentration of PGE(2) in the bovine WB culture supernatants. Bradykinin exhibited peak supernatant concentrations 1 h after LPS stimulation. Dexamethasone and the NSAID used in this study were equally effective at inhibiting bradykinin production. Peak induction of COX-2 mRNA occurred 3 h post-LPS stimulation. However, neither dexamethasone nor any of the NSAID used in this study altered COX-2 mRNA concentrations. In contrast, aspirin, flunixin meglumine, and PTPBS reduced tumor necrosis factor-alpha (TNFalpha) mRNA concentration. These results demonstrate that bovine blood cells respond to NSAID therapy like other mammalian cells with respect to inhibition of PGE(2) production and suppression of TNF mRNA induction, but do not inhibit induction of COX-2 mRNA.

Characterization of macrolide efflux pump mef subclasses detected in clinical isolates of Streptococcus pyogenes isolated between 1999 and 2005.

The macrolide efflux mechanism of resistance, mef, was characterized in community-acquired respiratory tract infections with Streptococcus pyogenes. Fifty-four (4.6%) M phenotype isolates were screen tested as negative for mef(A). Of these 54 isolates, 5 (0.4%), 27 (2.3%), and 1 (0.1%) were considered to be mef(I) positive, a novel mosaic variant of mef, or a novel subclass of mef, respectively. This study shows (i) the definitive presence of mef(E) in S. pyogenes and its global distribution, (ii) the presence of a mosaic variant of mef composed of mef(A) and mef(E), (iii) the previously undescribed presence of mef(I) in S. pyogenes, and (iv) the presence of a novel subclass of mef in S. pyogenes.

RNA polymerase activity in bovine spermatozoa.

Washed mature spermatozoa from bulls incorporate ribonucleoside triphosphates into RNA using an endogenous template. Maximum incorporation was observed at 31 degrees C in the presence of MgCl2, all four ribonucleoside triphosphates, beta-mercaptoethanol, and glycine sodium hydroxide buffer at pH 9.0. The amount of synthesis was linearly dependent upon the concentration of spermatozoa and continued for at least 4 h. Digestion studies revealed the RNA to be present in a protected (intracellular?) location in the spermatozoa. The RNA synthesis was inhibited by ethidium bromide, rifampicin, acriflavine, actinomycin D, and caffeine, but not by alpha-amanitine or rifamycin SV. Fractionation of the spermatozoa by sonication and separation of the heads and tails by centrifugation through a discontinuous gradient revealed that more than half of the total RNA polymerase activity was associated with the tail fraction.

Neuronal GM1 gangliosidosis in a Siamese cat with beta-galactosidase deficiency.

A juvenile Siamese cat with severe, progressive motor disability was shown to have extensive neuronal degeneration caused by accumulation of GM(1) ganglioside. Tissues from brain and kidney were markedly deficient in beta-galactosidase activity. The disease in this cat is thought to be inherited as an autosomal recessive trait, and is strikingly similar to juvenile GM(1) gangliosidosis of children.

Absence of pyruvate decarboxylase activity in man: a cause of congenital lactic acidosis.

A complete deficiency in the pyruvate dehydrogenase system activity contributed to the death of a 6-month-old infant with congenital lactic acidosis. The enzymatic block could be isolated to the first component, pyruvate decarboxylase (E1) of the pyruvate dehydrogenase complex. This enzymatic deficiency allowed a demonstration of an "intercomplex" exchange of the components of the mammalian pyruvate dehydrogenase system and indicated that the first component is normally present in an apparent excess.

Review: Beef-eating quality: a European journey.

This paper reviews recent research into predicting the eating qualities of beef. A range of instrumental and grading approaches have been discussed, highlighting implications for the European beef industry. Studies incorporating a number of instrumental and spectroscopic techniques illustrate the potential for online systems to non-destructively measure muscle pH, colour, fat and moisture content of beef with R 2 (coefficient of determination) values >0.90. Direct predictions of eating quality (tenderness, flavour, juiciness) and fatty acid content using these methods are also discussed though success is greatly variable. R 2 values for instrumental measures of tenderness have been quoted as high as 0.85 though R 2 values for sensory tenderness values can be as low as 0.01. Discriminant analysis models can improve prediction of variables such as pH and shear force, correctly classifying beef samples into categorical groups with >90% accuracy. Prediction of beef flavour continues to challenge researchers and the industry alike, with R 2 values rarely quoted above 0.50, regardless of instrumental or statistical analysis used. Beef grading systems such as EUROP and United States Department of Agriculture systems provide carcase classification and some indication of yield. Other systems attempt to classify the whole carcase according to expected eating quality. These are being supplemented by schemes such as Meat Standards Australia (MSA), based on consumer satisfaction for individual cuts. In Australia, MSA has grown steadily since its inception generating a 10% premium for the beef industry in 2015-16 of $187 million. There is evidence that European consumers would respond to an eating quality guarantee provided it is simple and independently controlled. A European beef quality assurance system might encompass environmental and nutritional measures as well as eating quality and would need to be profitable, simple, effective and sufficiently flexible to allow companies to develop their own brands.

CPHLN recommendations for the laboratory detection of Shiga toxin-producing Escherichia coli (O157 and non-O157).

Shiga toxin-producing Escherichia coli (STEC) are important enteric pathogens responsible for sporadic cases and outbreaks of gastroenteritis. E.coli O157:H7/NM (STEC O157) are the most commonly known STEC serotypes but it is now increasingly apparent that non-O157 STEC serotypes have been underreported in the past because they were not part of routine screening in many front-line laboratories. The Canadian Public Health Laboratory Network (CPHLN) has identified the need for improved detection and surveillance of non-O157 STEC and has developed the following recommendations to assist in the decision-making process for clinical and reference microbiology laboratories. These recommendations should be followed to the best of a laboratory's abilities based on the availability of technology and resources. The CPHLN recommends that when screening for the agents of bacterial gastroenteritis from a stool sample, front-line laboratories use either a chromogenic agar culture or a culture-independent diagnostic test (CIDT). CIDT options include nucleic acid amplification tests (NAATs) to detect Shiga toxin genes or enzyme immunoassays (EIAs) to detect Shiga toxins. If either CIDT method is positive for possible STEC, laboratories must have a mechanism to culture and isolate STEC in order to support both provincial and national surveillance as well as outbreak investigations and response. These CPHLN recommendations should result in improved detection of STEC in patients presenting with diarrhea, especially when due to the non-O157 serotypes. These measures should enhance the overall quality of healthcare and food safety, and provide better protection of the public via improved surveillance and outbreak detection and response.

Canadian recommendations for laboratory interpretation of multiple or extensive drug resistance in clinical isolates of Enterobacteriaceae, Acinetobacter species and Pseudomonas aeruginosa.

The goal of this document was to provide Canadian laboratories with a framework for consistent reporting and monitoring of multidrug resistant organisms (MDRO) and extensively drug resistant organisms (XDRO) for common gram-negative pathogens. This is the final edition of the interim recommendations, which were modified after one year of broad consultative review. This edition represents a consensus of peer-reviewed information and was co-authored by the Canadian Public Health Laboratory Network and the Canadian Association of Clinical Microbiology and Infectious Diseases. There are two main recommendations. The first recommendation provides standardized definitions for MDRO and XDRO for gram-negative organisms in clinical specimens. These definitions were limited to antibiotics that are commonly tested clinically and, to reduce ambiguity, resistance (rather than non-susceptibility) was used to calculate drug resistance status. The second recommendation identifies the use of standardized laboratory reporting of organisms identified as MDRO or XDRO. Through the broad consultation, which included public health and infection prevention and control colleagues, these definitions are ready to be applied for policy development. Both authoring organizations intend to review these recommendations regularly as antibiotic resistance testing evolves in Canada.

Elevated plasma fibrinogen gamma' concentration is associated with myocardial infarction: effects of variation in fibrinogen genes and environmental factors.

BACKGROUND: Fibrinogen gamma', a fibrinogen gamma-chain variant generated via alternative mRNA processing, has been associated with susceptibility to thrombotic disease. OBJECTIVE: The present case-control study searched for potential determinants of the plasma fibrinogen gamma' concentration and examined the relationship between this variant and risk of myocardial infarction (MI). PATIENTS AND METHODS: The Stockholm Coronary Artery Risk Factor study, comprising 387 postinfarction patients and 387 healthy individuals, was employed. The fibrinogen gamma (FGG) 9340T > C [rs1049636], fibrinogen alpha (FGA) 2224G > A [rs2070011] and fibrinogen beta (FGB) 1038G > A [rs1800791] polymorphisms were determined. The plasma fibrinogen gamma' concentration was measured by enzyme-linked immunosorbent assay. The multifactor dimensionality reduction method was used for interaction analyses on risk of MI. RESULTS: The FGG 9340T > C and FGA 2224G > A polymorphisms, total plasma concentrations of fibrinogen, insulin and high-density lipoprotein, and gender appeared to be independent determinants of plasma fibrinogen gamma' concentration in patients, and the corresponding determinants in controls included FGG 9340T > C and FGA 2224G > A polymorphisms and plasma fibrinogen concentration. An elevated plasma fibrinogen gamma' concentration proved to be an independent predictor of MI [adjusted odds ratio (OR) (95% CI): 1.24 (1.01, 1.52)]. The plasma fibrinogen gamma' concentration was involved in a high-order interaction with total plasma fibrinogen and the FGG 9340T > C and FGA 2224G > A polymorphisms, associated with a further increased risk of MI [OR (95% CI): 3.22 (2.35, 4.39)]. CONCLUSIONS: Plasma fibrinogen gamma' concentration influences the risk of MI, and this relationship seems to be strengthened by the presence of an elevated total plasma fibrinogen concentration and the FGG 9340T and FGA 2224G alleles.

High power scaling of a passively modelocked laser oscillator in a bounce geometry.

In this paper we present the first operation and power scaling of a modelocked Nd:YVO4 bounce laser oscillator at 1064 nm. We obtain up to 16.7 W of average output power from 38 W of pump power, in a continuous-wave modelocked pulse train with 30 ps pulses at a repetition rate of 78 MHz. We then use a Master Oscillator Power Amplifier (MOPA) configuration utilising another bounce amplifier, to achieve 60 W of modelocked output power.

Activity of telithromycin and comparators against isolates of Legionella pneumophila collected from patients with community-acquired respiratory tract infections: PROTEKT Years 1-5.

The in-vitro activity of telithromycin and comparator antibacterial agents was determined against clinical isolates of Legionella pneumophila collected in the PROTEKT surveillance study. In total, 133 isolates were collected between 1999 and 2004 from 13 countries (Australia, Belgium, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Portugal, Spain, Sweden and the USA). MICs were determined by broth microdilution. Telithromycin maintained activity between Year 1 (MIC(90) 0.015 mg/L) and Year 5 (MIC(90) 0.03 mg/L), as did the comparator antibacterial agents. Telithromycin appears to be a candidate for coverage of legionellosis in the empirical treatment of community-acquired respiratory tract infection.