IgG4-specific responses in patients with Staphylococcus aureus bone infections are not predictive of postoperative complications.

The most prevalent pathogen in bone infections is Staphylococcus aureus; its incidence and severity are partially determined by host factors. Prior studies showed that anti-glucosaminidase (Gmd) antibodies are protective in animals, and 93.3 % of patients with culture-confirmed S. aureus osteomyelitis do not have anti-Gmd levels > 10 ng/mL in serum. Infection in patients with high anti-Gmd remains unexplained. Are anti-Gmd antibodies in osteomyelitis patients of the non-opsonising, non-complement-fixing IgG4 isotype? The relative amounts of IgG4 and total IgG against Gmd and 7 other S. aureus antigens: iron-surface determinants (Isd) IsdA, IsdB, and IsdH, amidase (Amd), α-haemolysin (Hla), chemotaxis inhibitory protein from S. aureus (CHIPS), and staphylococcal-complement inhibitor (SCIN) were determined in sera from healthy controls (Ctrl, n = 92), osteomyelitis patients whose surgical treatment resulted in infection control (IC, n = 95) or an adverse outcome (AD, n = 40), and post-mortem (PM, n = 7) blood samples from S. aureus septic-death patients. Anti-Gmd IgG4 levels were generally lower in infected patients compared to controls; however, levels among the infected were higher in AD than IC patients. Anti-IsdA, IsdB and IsdH IgG4 levels were increased in infected patients versus controls, and Jonckheere-Terpstra tests of levels revealed an increasing order of infection (Ctrl < IC < AD < PM) for anti-Isd IgG4 antibodies and a decreasing order of infection (Ctrl > IC > AD > PM) for anti-autolysin (Atl) IgG4 antibodies. Collectively, this does not support an immunosuppressive role of IgG4 in S. aureus osteomyelitis but is consistent with a paradigm of high anti-Isd and low anti-Atl responses in these patients.

Performance of polymyxin B agar-based tests among carbapenem-resistant Enterobacterales.

Therapeutic options for infections caused by Carbapenem-resistant Enterobacterales (CRE) are restricted and include polymyxins-centred schemes. Evaluation of in vitro susceptibility is difficult and time consuming. Agar-based methodologies are an alternative to broth microdilution (BMD) and we aimed to evaluate the accuracy of those methods among Enterobacterales. A total of 137 non-duplicated CRE were subjected to polymyxin B BMD, agar screening test (Mueller Hinton plates containing 3 µg ml-1 of polymyxin B) and agar dilution (antibiotic serially diluted 0·25-64 µg ml-1 ). CRE of 42·3% were resistant to polymyxin B (MICs range: 0·25->64 µg ml-1 ) and 16·8% presented borderline MICs. Sensitivity, specificity, PPV and NPV were 86·2, 98·7, 98 and 90·7% for screening test and 86·2, 97·5, 96·1 and 90·6% for agar dilution. ME was 0·73 and 1·5% for screening and agar dilution respectively; VME was 5·8% for both techniques. In general, agar-based methods had a good performance. As far as we know, this is the first study to propose an agar screening test using polymyxin B instead of colistin.

Psychometric properties of the Weight Locus of Control Scale (MWLCS): study with Spanish individuals of different anthropometric nutritional status.

INTRODUCTION: The Multidimensional Weight Locus of Control Scale (MWLCS) measures a person's beliefs regarding the locus of control or lack of locus of control over his/her body weight. PURPOSE: We aim to evaluate the factorial structure and psychometric properties of the MWLCS with Spanish normal weight, overweight and obese samples. METHODS: The research was carried out in two different studies. The first included a sample of 140 normal weight participants, selected out of a 274 sample recruited with an online survey. Study 2 was carried out in a sample of 633 participants recruited from the PREDIMED-Plus study. Out of them, 558 participants fulfilled the weight criteria and were categorized into: overweight (BMI 25 - < 29.99; N = 170), obese class I (BMI 30 - < 34.99; N = 266), and obese class II (BMI 35 - < 39.99; N = 122). Exploratory (EFA) and confirmatory (CFA) factor analyses were used to evaluate the factor structure of the MWLCS, and reliabilities and Spearman's correlations were estimated. Invariance measurement was tested across the three subgroups of weight in Study 2. RESULTS: A three-factor structure indicating weight locus of control factors (internal, chance, and powerful others) was supported, both via EFA in the normal weight sample and CFA in the overweight and obese samples. In the normal weight sample, the powerful others dimension was positively related to BMI and the dimensions of the Dutch Eating Behaviors Questionnaire. Additionally, the scale showed evidence of scalar invariance across the groups with different weight conditions. CONCLUSIONS: This scale seems to be a psychometrically appropriate instrument and its use is highly recommended when designing interventions for overweight or obese individuals. LEVEL OF EVIDENCE: Level V, descriptive study.

Emergence of serotype 19A Streptococcus pneumoniae after PCV10 associated with a ST320 in adult population, in Porto Alegre, Brazil.

Use of pneumococcal conjugate vaccines has caused emergence of non-vaccine serotypes. No Brazilian data specifically about serotype 19A are available. We aimed to evaluate the frequency of occurrence, susceptibility profile and molecular epidemiology of serotype 19A before and after vaccine introduction in Brazil. Pneumococcal identification was performed by the conventional method. Strain serotype was determined by multiplex polymerase chain reaction (PCR) and/or Quellung reaction. Resistance was determined by Etest® and PCR was performed to determine the presence of macrolide resistance genes, ermB and/or mefA. Pneumococci were typed by Multilocus Sequence Typing. Thirty-eight serotype 19A Streptococcus pneumoniae were recovered, mostly from invasive diseases. Prevalence of serotype 19A increased following vaccination (from 3.5% before vaccination to 8.1% after, p = 0.04196). Non-susceptibility increased to most antimicrobials after vaccine introduction and was associated with clonal complex (CC)320. MLST showed nine different STs, which were grouped in one main CC: CC320 (63.9%). During the post-vaccination era, the frequency of this serotype increased significantly from 1.2% in 2011 to 18.5% in 2014 (p = 0.00001), with a concomitant decrease in the genetic variability: ST320 consistently predominated after vaccine-introduction (61.1%). Overall, our results showed a post-PCV10 increase in the frequency of serotype 19A. This was accompanied by a selection of CC320 and antimicrobial resistance.

Palauans who chew betel nut: social impact of oral disease.

BACKGROUND: Chewing betel nut is a tradition extending from Southeast Asia to the Pacific. Globally, betel nut is the fourth main psychotropic substance containing a stimulant, arecoline, that has a similar effect to nicotine. In Palau, there is broad acceptance of betel nut chewing. One of the largest immigrant groups in Hawaii is the Palauans. Chewing betel nut has significant social implications that make it difficult for those who engage in this practice to separate potential oral disease from the social importance. However, little is known about the social impact of oral disease from chewing betel nut on Palauans in Hawaii. AIM: The study aimed to describe the perceptions of betel-chewing Palauans in Hawaii regarding betel nut and to determine the social impact of oral disease among these individuals. METHODS: Descriptive study conducted on the island of Oahu, Hawaii with 30 adult Palauans. Data were collected using the Oral Health Impact Profile-14 to measure perceptions of social impact of oral disease on well-being. Demographic and general health information was collected. RESULTS: Participants perceived little negative social impact of oral disease on well-being. DISCUSSION: Families, peers and society exert a strong influence on the decision to chew betel nut, a known carcinogen. Participants in this study showed little concern on the impact of betel nut chewing on their oral health. They continue the habit in spite of the awareness of potential for oral disease. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurses face challenges in educating Palauans about the negative aspects of betel nut, particularly those related to oral health especially when they do not perceive problems. Nurses must be involved in the development of health policies to design and implement strategies to promote behavioural change, and to ensure clinical services that are culturally sensitive to betel nut chewers.

Relation of depot-specific adipose inflammation to insulin resistance in human obesity.

BACKGROUND: A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms of systemic metabolic dysfunction. However, the relation of clinical phenotypes to depot-specific inflammation has not been well examined in human obesity. OBJECTIVE: To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat. METHODS: We collected adipose tissue simultaneously from subcutaneous and visceral (omental and mesenteric) depots in 92 obese participants (age 42±11 years; BMI30 kg m(-2)) during planned bariatric surgery. Using immunohistochemistry, we categorized individuals as CLS(+) or CLS(-) based on the presence or absence, respectively, of macrophage CLS in subcutaneous (CLSs), omental (CLSo) and mesenteric (CLSm) adipose depots. RESULTS: The majority of participants exhibited adipose tissue inflammation manifest by the presence of CLS (CLS(+)) in both subcutaneous and intra-abdominal visceral depots. CLS status in subcutaneous fat was highly sensitive and modestly specific for inflammation of visceral fat. In multivariable models, plasma insulin and homeostatis model assessment levels were positively associated with CLS(+) status in all depots independent of age, waist circumference, BMI and type 2 diabetes, and worsened with the increasing number of adipose regions involved. CONCLUSIONS: In severely obese participants, systemic insulin resistance is linked to adipose inflammation in both subcutaneous and visceral depots. The findings suggest that examination of subcutaneous regions that are more easily accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease.

Identifying the molecular basis of functions in the transcriptome of the social amoeba Dictyostelium discoideum.

The unusual life cycle of Dictyostelium discoideum, in which an extra-cellular stressor such as starvation induces the development of a multicellular fruiting body consisting of stalk cells and spores from a culture of identical amoebae, provides an excellent model for investigating the molecular control of differentiation and the transition from single- to multi-cellular life, a key transition in development. We utilized serial analysis of gene expression (SAGE), a molecular method that is unbiased by dependence on previously identified genes, to obtain a transcriptome from a high-density culture of amoebae, in order to examine the transition to multi-cellular development. The SAGE method provides relative expression levels, which allows us to rank order the expressed genes. We found that a large number of ribosomal proteins were expressed at high levels, while various components of the proteosome were expressed at low levels. The only identifiable transmembrane signaling system components expressed in amoebae are related to quorum sensing, and their expression levels were relatively low. The most highly expressed gene in the amoeba transcriptome, dutA untranslated RNA, is a molecule with unknown function that may serve as an inhibitor of translation. These results suggest that high-density amoebae have not initiated development, and they also suggest a mechanism by which the transition into the development program is controlled.

Lifestyle behaviours of young adult survivors of childhood cancer.

This cross-sectional study collected baseline data on the health behaviours of a large population of survivors of childhood cancer in the UK, aged 18-30 years, compared with those of sex- and age-matched controls. Data from 178 young adult survivors of childhood cancer, diagnosed and treated at Bristol Children's Hospital, 184 peers from the survivors' GP practices and 67 siblings were collected by postal questionnaire. Conditional logistic regression analysis showed that, for matched sets of survivors and controls, survivors of a variety of childhood cancers reported lower levels of alcohol consumption (P=0.005), lower levels of cigarette smoking (P=0.027) and lower levels of recreational drug use (P=0.001) than controls. Analysis of matched sets of survivors and siblings showed similar trends but no significant differences. A health behaviour index for each participant was constructed from the data collected on five key health behaviours which influence future health status. Comparison of the means for each case group showed that survivors of childhood cancer were leading healthier lives than controls or siblings. This finding was expressed most clearly as the difference in the means of the health behaviour index for each case group, derived from five health behaviours (one-way ANOVA, P<0.001).

Exposure to power frequency electric fields and the risk of childhood cancer in the UK.

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one.

Ilioinguinal approach to manage benign pelvic and acetabular tumors.

Benign osteoblastic and cystic lesions involving the anterior column and wall of the pelvis and acetabulum are technically difficult areas to approach and achieve successful surgical outcomes. Tumors in this area are rare, leaving little information in the literature regarding how best to surgically approach them. Previous authors have reported small series of patients treated using anteromedial, iliofemoral, and intracapsular dissections. The ilioinguinal approach has been extensively described and used in the modern-day treatment of pelvic and acetabular fractures involving the anterior column and wall. Despite its use for acetabular trauma, application of the ilioinguinal approach in the treatment of benign pelvic and acetabular lesions has not been described. We reviewed the management of 5 patients with benign pelvic or acetabular tumors treated using the ilioinguinal approach. Diagnoses included aneurysmal bone cysts in 3 patients and osteoid osteomas in 2 patients, involving the pelvic anterior column and wall. The approach has permitted satisfactory exposure of the lesions for operative treatment. At an average follow-up of 3 years (range, 2-4 years), excellent functional outcome and no recurrences were noted. There were 2 patients with lateral femoral cutaneous nerve palsies, both of which resolved completely by 8 weeks. Encouraging results from our study demonstrate a new application for the ilioinguinal approach in the treatment of benign anterior column and wall lesions of the pelvis and acetabulum.

Ewing sarcoma vs lymphoblastic lymphoma. A comparative immunohistochemical study.

To develop a practical immunohistochemistry panel for distinguishing lymphoblastic lymphoma from Ewing sarcoma (ES), we evaluated 17 ES and 27 lymphoblastic lymphoma and leukemia cases with antibodies to CD99, terminal deoxynucleotidyl transferase (TdT), leukocyte common antigen (LCA), CD43, CD79a, CD20, CD3, vimentin, and neuron-specific enolase (NSE). Three cases were bone lymphomas, 2 initially misdiagnosed as ES. All cases were CD99+. All lymphomas and leukemias were TdT+ compared to none of the ESs. None of the ESs expressed other lymphocytic markers, which were inconsistently expressed in the lymphomas and leukemias: CD43, 33%; LCA, 30%; CD79a, 19%; CD3, 19%; and CD20, 7%. Of the ESs, 88% were vimentin positive compared with 23% of lymphomas and leukemias. Vimentin was stronger and more diffuse in ES. NSE did not reliably stain any cases. When faced with the differential diagnosis of ES vs lymphoblastic lymphoma, an immunohistochemical panel that includes antibodies to CD99 and TdT is useful. Both epitopes are well preserved in fixed and decalcified tissue. A panel composed of antibodies to CD99 and TdT, in conjunction with other lymphocytic markers and vimentin, is highly sensitive and specific.

Arthroplasty-associated malignant fibrous histiocytoma: two case reports.

AIMS: Sarcoma localized to the site of an arthroplasty procedure is a rare occurrence, and detailed histological depictions and descriptions are limited. We report the clinicopathological findings in two cases of arthroplasty-associated malignant fibrous histiocytoma (MFH) and review the literature. METHODS AND RESULTS: The patients were an elderly man and woman. Medical histories, radiographs and slides were reviewed. Immunohistochemistry, electron microscopy, cytogenetics, and electron dispersion spectroscopy were performed in one case. Both were destructive femoral bone tumours that appeared 2 and 8 years post-total hip arthroplasty, and pursued aggressive clinical courses. The histology was similar in both tumours, consisting of high-grade, pleomorphic sarcoma with numerous osteoclastic giant cells, prominent phagocytic activity, and entrapped particles of bone cement. Literature review disclosed 14 previous reports of arthroplasty-associated MFH, representing the most common phenotype. A number of materials and factors related to arthroplasty procedure, such as metal corrosion, wear debris, osteonecrosis, and chronic inflammation, have been implicated as causative agents. CONCLUSIONS: Arthroplasty-associated MFH is a rare and aggressive tumour. Although the aetiology remains unclear, the small number of arthroplasty-associated sarcomas compared with the large number of joint replacement operations performed over the past four decades suggests a coincidental as opposed to a causal relation.

Zygomycosis in relapsed acute leukaemia.

We would like to report the use of liposomal amphotericin in eradicating mucormycosis in two patients who had relapsed acute leukaemia. The first patient with relapsed acute myeloid leukaemia developed a rapidly expanding solitary necrotic neck lesion associated with opacity of maxilliary sinus at a time when he was profoundly pancytopenic following high dose chemotherapy. The second patient was a 3-year-old boy with pre-B acute lymphoblastic leukaemia who developed a central nervous system relapse whilst on his first line treatment and was treated with more aggressive chemotherapy on the Medical Research Council Relapse Protocol. During a period of profound pancytopenia following re-induction therapy, including high dose steroids and prolonged course of antibiotics for proven septicaemia, he developed periorbital swelling and proptosis and a clinical diagnosis of rhinocerebral mucormycosis was made. Both patients were treated with high doses of liposomal amphotericin (Ambisome Nexstar). The doses were escalated to 10 and 15 mg/kg/day, resulting in successful eradication of the mucormycosis.

Photopenic bone scan osteomyelitis: a clinical perspective.

Eighty-one pediatric patients had nuclear bone-imaging studies confirmatory of osteomyelitis during the past 10 years. Seven (8.6%) of 81 had "cold" osteomyelitis. These seven patients were all toxic [mean temperature (T), 39.9 degrees C; heart rate (HR), 145 beats/min], all had markedly elevated erythrocyte sedimentation rates (mean ESR, 76 mm/h), and six of seven had both confirmatory bone and blood cultures. All patients required surgical intervention. The average length of hospital stay for these seven patients was 32 days (range, 8-65 days). A control group of matched patients with "hot" osteomyelitis was constructed for statistical evaluation. This analysis confirmed significantly increased temperature, resting pulse rate, ESR, length of hospital stay, and rate of surgical intervention in patients with cold versus hot osteomyelitis. Patients with osteomyelitis presenting as a cold defect on bone imaging appeared to have a more aggressive type of bone infection, often requiring aggressive medical and surgical intervention adequately to control this infectious process.

The acid-labile subunit of the serum insulin-like growth factor-binding protein complexes. Structural determination by molecular modeling and electron microscopy.

The acid-labile subunit (ALS) is a glycosylated 85-kDa member of the leucine-rich repeat (LRR) protein superfamily and circulates in ternary complexes with the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs). These complexes are thought to regulate the serum IGFs by restricting IGF movement out of the circulation. However, little is known about how ALS binds to IGFBP-3 or -5, which link the IGFs to ALS. To investigate potential sites of interaction, the ALS structure has been modeled with the crystal structure of the LRR protein porcine ribonuclease inhibitor as a template. ALS is predicted to be a donut-shaped molecule with an internal diameter of 1.7 nm, an external diameter of 7.2 nm, and a thickness of 3.6 nm. These dimensions are supported by rotary shadowing electron microscopy of ALS. The internal face is lined with a substantial region of electronegative surface potential that could interact with the positively charged region on IGFBP-3 known to be involved in ALS binding. The model also predicts that three potential N-linked oligosaccharide sites within the LRR domain are clustered together, which may be important in light of recent studies showing ALS glycan involvement in complex formation with IGFBP-3.

Left ventricular diastolic filling patterns associated with progressive anthracycline-induced myocardial damage: A prospective study.

The objective of this study was to examine changes in diastolic function associated with progressive myocardial damage and their implications. We used prospective sequential Doppler echocardiographic studies of left ventricular (LV) function. The study included 125 consecutive children (median age 6.3 years) receiving anthracyclines to cumulative doses between 45 and 1150 mg/m2 (median 270 mg/m2). We measured peak early (E) and atrial (A) phase filling velocities, EA ratio, deceleration and isovolumic relaxation times (EDecT and IVRT), heart rate, and fractional shortening (SF). Results were compared serially and with individually paired control data matched for body surface area. Progressive myocardial damage was evidenced by a mean SF decrease of 1 absolute %/100 mg/m2 of anthracycline. Six patients developed cardiac failure. After 1-100 mg/m2 of anthracyclines, the EA ratio decreased (mean 1.54-1.40, p = 0.02) and IVRT became prolonged (54 vs 52 msec in controls, p = 0.03). EA ratio increased again with the next dose, usually normalizing thereafter. Twelve patients ended treatment with an EA ratio <1 (1 cardiac death) and 17 with EA ratio >2 (2 cardiac deaths). Diastolic abnormalities were not strongly predictive of reduced SF. Modest changes in left ventricular diastolic filling patterns occur during anthracycline treatment of childhood malignancies. Although 20% of patients have significant abnormalities of diastolic filling by the end of treatment, considerable individual variability renders the pathophysiological and clinical implications of the early changes uncertain.

A transfection compound series based on a versatile Tris linkage.

The family of cationic lipid transfection reagents described here demonstrates a modular design that offers potential for the ready synthesis of a wide variety of molecular variants. The key feature of these new molecules is the use of Tris as a linker for joining the hydrophobic domain to a cationic head group. The molecular design offers the opportunity to conveniently synthesise compounds differing in charge, the number and nature of hydrophobic groups in the hydrophobic domain and the characteristics of the spacer between the cationic and hydrophobic moieties. We show that prototype reagents of this design can deliver reporter genes into cultured cells with efficiencies rivaling those of established cationic lipid transfection reagents. A feature of these reagents is that they are not dependent on formulation with a neutral lipid for activity.