Direct and reflected self-concept show increasing similarity across adolescence: A functional neuroimaging study.

In adolescence, the perceived opinions of others are important in the construction of one's self-concept. Previous studies found involvement of medial Prefrontal Cortex (mPFC) and temporal-parietal junction (TPJ) in direct (own perspective) and reflected (perceived perspective of others) self-evaluations, but no studies to date examined differences in these processes across adolescence. In this study, 150 adolescents between 11 and 21 years old evaluated their traits from their own perspective and from the perceived perspective of peers in a fMRI session. Results showed overlapping behavioural and neural measures for direct and reflected self-evaluations, in mPFC, precuneus and right TPJ. The difference in behavioural ratings declined with age, and this pattern was mirrored by activity in the mPFC, showing a diminishing difference in activation for direct > reflected self-evaluations with increasing age. Right TPJ was engaged more strongly for reflected > direct evaluations in adolescents who were less positive about themselves, and those who showed who showed less item-by-item agreement between direct and reflected self-evaluations. Together, the results suggest that the internalization of others' opinions in constructing a self-concept occurs on both the behavioural and neural levels across adolescence, which may aid in developing a stable self-concept.

Transformation of serum-susceptible Escherichia coli O111 with p16Slux plasmid to allow for real-time monitoring of complement-based inactivation of bacterial growth in bovine milk.

Complement activity has only recently been characterized in raw bovine milk. However, the activity of this component of the innate immune system was found to diminish as milk was subjected to heat or partitioning during cream separation. Detection of complement in milk relies on a bactericidal assay. This assay exploits the specific growth susceptibility of Escherichia coli O111 to the presence of complement. Practical application of the assay was demonstrated when a reduction in complement activity was recorded in the case of pasteurized and reduced-fat milks. This presented an opportunity to improve the functionality of the bactericidal assay by incorporating bioluminescence capability into the target organism. Following some adaptation, the strain was transformed by correctly integrating the p16Slux plasmid. Growth properties of the transformed strain of E. coli O111 were unaffected by the modification. The efficacy of the strain adaptation was correlated using the LINEST function analysis [r=0.966; standard error of prediction (SEy)=0.957] bioluminescence with that of bactericidal assay total plate counts within the range of 7.5 to 9.2 log cfu/mL using a combination of raw and processed milk samples. Importantly, the transformed E. coli O111 p16Slux strain could be identified in milk and broth samples using bioluminescence measurement, thus enabling the bactericidal assay-viability test to be monitored in real time throughout incubation.

Optically isolated, 2 kHz repetition rate, 4 kV solid-state pulse trigger generator.

This paper presents the design and operation characteristics of a solid-state high voltage pulse generator. Its primary utilization is aimed at triggering a gaseous spark gap with high repeatability. Specifically, the trigger generator is designed to achieve a risetime on the order of 0.1 kV/ns to trigger the first stage, trigatron spark gap of a 10-stage, 500 kV Marx generator. The major design components are comprised of a 60 W constant current DC-DC converter for high voltage charging, a single 4 kV thyristor, a step-up pulse transformer, and magnetic switch for pulse steepening. A risetime of <30 ns and pulse magnitude of 4 kV is achieved matching the simulated performance of the design.

Effect of diabetes on tuberculosis presentation and outcomes in Kiribati.

OBJECTIVES: To determine the association between diabetes and the clinical features and treatment outcomes of TB in Kiribati. METHODS: We enrolled consecutive patients with TB who presented from August 2010 to February 2012 and compared clinical features and TB treatment outcomes for patients with and without diabetes, as measured by haemoglobin A1c assay. Poor outcome was defined as death, default or treatment failure, and good outcome as treatment success or cure. RESULTS: Two hundred and seventy-five eligible persons with TB disease were enrolled; 101 (37%) had diabetes. TB patients with diabetes were more likely to have acid-fast bacilli (AFB) seen on sputum smear microscopy (RR: 1.3; 95% CI: 1.03-1.62). The risk of poor outcome did not differ between patients with or without diabetes (RR: 1.1; 95% CI: 0.5-2.7). CONCLUSION: TB patients with diabetes are more likely than those without to have sputum with AFB on microscopy. This could increase transmission in the community. Early detection of TB by screening patients with diabetes, and the converse, could be important public health interventions where diabetes and TB are prevalent.

Tuberculosis and diabetes mellitus in the Republic of Kiribati: a case-control study.

OBJECTIVES: To better inform local management of TB-diabetes collaborative activities, we aimed to determine the prevalence of diabetes among persons with and without TB and to determine the association between TB and diabetes in Kiribati, a Pacific Island nation. METHODS: We compared consecutively enrolled TB cases to a group of randomly selected community controls without evidence of TB. Diabetes was diagnosed by HbA1c, and clinical and demographic data were collected. A tuberculin skin test was administered to controls. The chi-square test was used to assess significance in differences between cases and controls. We also calculated an odds ratio, with 95% confidence intervals, for the odds of diabetes among cases relative to controls. Unweighted multivariate logistic regression was performed to adjust for the effects of age and sex. RESULTS: A total of 275 TB cases and 499 controls were enrolled. The diabetes prevalence in cases (101, 37%) was significantly greater than in controls (94, 19%) (adjusted odds ratio: 2.8; 95% CI 2.0-4.1). Fifty-five percent (108) of all diabetic diagnoses were new; this proportion was higher among controls (64.8%) than cases (46.5%). Five patients with TB were screened to detect one patient with diabetes. CONCLUSIONS: There is a strong association between TB and diabetes in Kiribati and bidirectional screening should be conducted in this setting.

The anti-inflammatory potential of a moderately hydrolysed casein and its 5 kDa fraction in in vitro and ex vivo models of the gastrointestinal tract.

Bioactive peptides from milk can impart a wide range of physiological benefits without the allergies and intolerance associated with the consumption of whole milk. The objective of this study was to characterise the anti-inflammatory properties of intact sodium caseinate (NaCAS), a moderately hydrolysed NaCAS enzyme hydrolysate (EH) and its 5 kDa fraction (5kDaR), in both in vitro and ex vivo systems. In vitro, Caco-2 cells were stimulated with tumor necrosis factor (TNF) α and co-treated ± casein hydrolysates or dexamethasone (control). The inflammatory marker interleukin (IL)-8 was measured by ELISA in the supernatant at 24 h. Ex vivo, porcine colonic tissues were stimulated with lipopolysaccharide (LPS) and co-treated with casein hydrolysates for 3 h from which the relative expression of a panel of cytokines was measured in vitro. While the steroid dexamethasone brought about a 41.6% reduction in the IL-8 concentration in the supernatant, the 5kDaR reduced IL-8 by 59% (P < 0.05) when compared to the TNFα stimulated Caco-2 cells. In the ex vivo system, 5kDaR was associated with decreases in IL-1α, IL-1ß, IL-8 and TGF-ß expression and an increase in IL-17 expression (P < 0.05) relative to the LPS challenged tissues. We concluded, that a 5 kDa casein fraction demonstrates potent anti-inflammatory effects both in in vitro and ex vivo models of the gastrointestinal tract.

Congenital-infantile fibrosarcoma of the foot--avoidance of amputation.

Congenital-infantile fibrosarcoma is a rare entity with a five year survival rate of over 90%. Surgery is still the most common treatment modality with amputation often necessary. There have been reports supporting the use of neoadjuvant chemotherapy to debulk the tumour in an effort to facilitate limb sparing surgery. We report a case of a newborn who presented with a life threatening haemorrhage from a fibrosarcoma of the foot, successfully treated with Vincristine, Actinomycin and Cyclophosphamide (VAC) chemotherapy alone.

Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies.

For effective localization of functionalized nanoparticles at diseased tissues such as solid tumours or metastases through biorecognition, appropriate targeting vectors directed against selected tumour biomarkers are a key prerequisite. The diversity of such vector molecules ranges from proteins, including antibodies and fragments thereof, through aptamers and glycans to short peptides and small molecules. Here, we analyse the specific nanoparticle targeting capabilities of two previously suggested peptides (D4 and GE11) and a small camelid single-domain antibody (sdAb), representing potential recognition agents for the epidermal growth factor receptor (EGFR). We investigate specificity by way of receptor RNA silencing techniques and look at increasing complexity in vitro by introducing increasing concentrations of human or bovine serum. Peptides D4 and GE11 proved problematic to employ and conjugation resulted in non-receptor specific uptake into cells. Our results show that sdAb-functionalized particles can effectively target the EGFR, even in more complex bovine and human serum conditions where targeting specificity is largely conserved for increasing serum concentration. In human serum however, an inhibition of overall nanoparticle uptake is observed with increasing protein concentration. For highly affine targeting ligands such as sdAbs, targeting a receptor such as EGFR with low serum competitor abundance, receptor recognition function can still be partially realised in complex conditions. Here, we stress the value of evaluating the targeting efficiency of nanoparticle constructs in realistic biological milieu, prior to more extensive in vivo studies.

The 100 classic papers of pediatric orthopaedic surgery: a bibliometric analysis.

BACKGROUND: Pediatric orthopaedic surgery owes its development to many pioneering individuals, and the studies that these individuals have undertaken form the basis for the clinical decisions made on the modern pediatric orthopaedic service. The aim of our study was to use citation analysis to identify the top 100 papers in pediatric orthopaedic surgery. METHODS: Using the Thomson Reuters Web of Knowledge, we searched for citations of all papers relevant to pediatric orthopaedics. The number of citations, authorship, year of publication, journal of publication, and country and institution of origin were recorded for each paper. RESULTS: The most cited paper was found to be the classic paper from 1963 by Salter and Harris that introduced the now-eponymous classification system for physeal injuries in the skeletally immature patient. The second most cited was Salter's paper describing the widely used osteotomy for the treatment of developmental dysplasia of the hip, and the third most cited was Catterall's description of the natural history of Legg-Calvé-Perthes disease. Most papers originated in the U.S., and most were published in this journal. A number of authors including Salter, Ponseti, Graf, and Loder had more than one paper in the top-100 list. DISCUSSION: This paper's identification of the classic papers of pediatric orthopaedic surgery gives us a unique insight into the development of pediatric orthopaedic surgery in the twentieth and early twenty-first centuries and identifies those individuals who have contributed the most to the body of knowledge used to guide evidence-based clinical decision-making in pediatric orthopaedics today.

Whey protein isolate polydispersity affects enzymatic hydrolysis outcomes.

The effects of heat-induced denaturation of whey protein isolate (WPI) on the enzymatic breakdown of α-La, caseinomacropeptide (CMP), ß-Lg A and ß-Lg B were observed as hydrolysis proceeded to a 5% degree of hydrolysis (DH) in both unheated and heat-treated (80 °C, 10 min) WPI dispersions (100 g L(-1)). Hydrolysis of denatured WPI favoured the generation of higher levels of free essential amino acids; lysine, phenylalanine and arginine compared to the unheated substrate. LC-MS/MS identified 23 distinct peptides which were identified in the denatured WPI hydrolysate - the majority of which were derived from ß-Lg. The mapping of the detected regions in α-La, ß-Lg, and CMP enabled specific cleavage points to be associated with certain serine endo-protease activities. The outcomes of the study emphasise how a combined approach of substrate heat pre-treatment and enzymology may be used to influence proteolysis with attendant opportunities for targeting unique peptide production and amino acid release.

Enzymatic hydrolysis of heat-induced aggregates of whey protein isolate.

The effects of heat-induced denaturation and subsequent aggregation of whey protein isolate (WPI) solutions on the rate of enzymatic hydrolysis was investigated. Both heated (60 °C, 15 min; 65 °C, 5 and 15 min; 70 °C, 5 and 15 min, 75 °C, 5 and 15 min; 80 °C, 10 min) and unheated WPI solutions (100 g L(-1) protein) were incubated with a commercial proteolytic enzyme preparation, Corolase PP, until they reached a target degree of hydrolysis (DH) of 5%. WPI solutions on heating were characterized by large aggregate formation, higher viscosity, and surface hydrophobicity and hydrolyzed more rapidly (P < 0.001) than the unheated. The whey proteins exhibited differences in their susceptibility to hydrolysis. Both viscosity and surface hydrophobicity along with insolubility declined as hydrolysis progressed. However, microstructural changes observed by light and confocal laser scanning microscopy (CLSM) provided insights to suggest that aggregate size and porosity may be complementary to denaturation in promoting faster enzymatic hydrolysis. This could be clearly observed in the course of aggregate disintegration, gel network breakdown, and improved solution clarification.

Transmissibility of 2009 pandemic influenza A(H1N1) in New Zealand: effective reproduction number and influence of age, ethnicity and importations.

The first wave of pandemic influenza A(H1N1) has subsided in New Zealand as in other southern hemisphere countries. This study aimed to estimate the effective reproduction number (R) of 2009 pandemic influenza A(H1N1) taking into account imported cases. It also aimed to show the temporal variation of R throughout the New Zealand epidemic, changes in age- and ethnicity-specific cumulative incidence, and the effect of school holidays. Using a new modelling method to account for imported cases, we have calculated the peak R during the containment phase of the pandemic as 1.55 (95% confidence interval: 1.16 to 1.86). This value is less than previously estimated in the country early in the pandemic but in line with more recent estimates in other parts of the world. Results also indicated an increase in the proportion of notifications among school-age children after the school holiday (3-19 July 2009). This finding provides support for the potential effectiveness of timely school closures, although such disruptive interventions need to be balanced against the severity of the pandemic.

Chicken faeces garden fertilizer: possible source of human avian influenza H5N1 infection.

Avian influenza H5N1 infection in humans is typically associated with close contact with infected poultry or other infected avian species. We report on human cases of H5N1 infection in Indonesia where exposure to H5N1-infected animals could not be established, but where the investigation found chicken faeces contaminated with viable H5N1 virus in the garden fertilizer. Human cases of avian influenza H5N1 warrant extensive investigations to determine likely sources of illness and to minimize risk to others. Authorities should regulate the sale and transportation of chicken faeces as fertilizer from areas where H5N1 outbreaks are reported.

Pulmonary tuberculosis, impaired lung function, disability and quality of life in a high-burden setting.

SETTING: Tuberculosis treatment clinic in Papua, Indonesia. OBJECTIVE: To document the impact of pulmonary tuberculosis (PTB) on lung function, exercise tolerance and quality of life (QOL). DESIGN: A prospective cohort study of 115 patients with smear-positive PTB followed for 6 months. Demographics, disease history, sputum microbiology, spirometry, 6-minute weight.walk distance (6MWWD) and QOL (modified St George's Respiratory Questionnaire) were measured at diagnosis and at 2 and 6 months. Analysis was restricted to the 69/115 (60%) subjects who attended all follow-up visits. RESULTS: Subjects who attended all visits were less likely than the full cohort to be of Papuan ethnicity (P < 0.05), were more likely to be cured (P < 0.001) and had better lung function at diagnosis (P < 0.05). Significant lung function impairment (forced expiratory volume in 1 second [FEV(1)] <60% predicted) was found in 27/69 (39%) at diagnosis. Although this fell during treatment (P < 0.01), 17/69 (24.6%) had persisting significant lung function impairment at treatment completion. As lung function recovered, exercise tolerance (6MWWD) rose by 12.3% (P < 0.001) and QOL improved (P < 0.001). CONCLUSION: In a high-burden setting, PTB causes prolonged, significant impairment of lung function, exercise tolerance and QOL. Current measures of disease burden are likely to underestimate the true impact of disease. Earlier diagnosis and disease-modifying treatments may reduce the long-term impact of PTB.

An ethnographic study of barriers to and enabling factors for tuberculosis treatment adherence in Timor Leste.

BACKGROUND: Tuberculosis (TB) is a major public health problem in Timor Leste; treatment adherence was identified by the National TB Control Programme (NTP) as an impediment to TB control. OBJECTIVE: To identify barriers to and enabling factors for the successful implementation of the DOTS strategy in Timor Leste. METHOD: Qualitative research was carried out in the two districts (one rural and one urban) with the lowest treatment completion rates. Semi-structured interviews and focus group discussions were conducted with patients, health workers and community members in eight villages. RESULT: Good knowledge of TB, including a correct understanding of how it is cured, together with the provision of incentives, were important factors contributing to treatment completion. Defaulting patients and community members had less knowledge of TB. TB nurses had a good understanding of, and a high level of commitment to implementing the DOTS strategy. Obstacles to treatment completion included preference for traditional medicine, economic difficulties and geographic remoteness. CONCLUSION: Local cultural practices and knowledge as well as socio-economic factors contribute to less than optimal adherence to TB treatment. This study has assisted Timor Leste's NTP in modifying its DOTS expansion strategies to overcome barriers to treatment completion.

Ethical challenges in TB control in the era of XDR-TB.

Tuberculosis (TB) is the second leading cause of preventable illness worldwide and arguably the most important neglected topic in bioethics. This paper 1) explains the ethical importance of TB, 2) documents its neglect in bioethics discourse, 3) maps the terrain of ethical issues associated with TB, and 4) calls for ethicists, activists and socially concerned health professionals to raise and debate the full range of ethical issues associated with TB.

A public-private partnership for TB control in Timika, Papua Province, Indonesia.

SETTING: A district-level tuberculosis (TB) control programme in Papua Province, Indonesia. OBJECTIVE: To describe a successful partnership between the District Health Department, a private company and non-governmental health care providers. METHODS: Routinely collected surveillance data were analysed. A conceptual model was constructed to describe TB control in the district. Data were compared with the National TB Control Programme (NTP) performance indicators. RESULTS: Funding for the programme's TB clinic is provided by a private company (PT Freeport Indonesia). The NTP provides the policy framework, treatment guidelines and some supplies. TB clinic staff are included in training programmes and the TB laboratory in the provincial quality assurance system. TB clinic staff are responsible for diagnosis, treatment, default tracing, recording and reporting, health education and community mobilisation. The largest proportion of TB patient referrals came from the community hospital (41%). The TB notification rate (311/100000), TB-HIV (human immunodeficiency virus) co-infection (12%) and multidrug-resistant (MDR) TB (2%) are significantly higher in Mimika, but the treatment success rate for smear-positive patients (91%) is similar to Indonesian national figures. CONCLUSIONS: For true progress in attaining the United Nations Millennium Development Goals for TB in Indonesia, innovative local solutions utilising public-private partnerships are essential. The Mimika model is one such solution that should be tested elsewhere.

Tuberculosis control in conflict-affected East Timor, 1996-2004.

SETTING: East Timor has undergone major political changes in the past 10 years. Tuberculosis (TB) control has flourished, despite chronic low tension conflict, a brief but intense period of high-level conflict and post-conflict reconstruction. OBJECTIVE: To assess TB control in East Timor from 1996 to 2004. DESIGN: Data were collected from a variety of sources. Key TB programme indicators were analysed with reference to WHO targets to assess the performance of the three TB control programmes that operated during the study period. RESULTS: Before 1999, a non-governmental TB control programme was established in several districts in parallel with the government TB programme, and showed optimistic results. External donor funds, technical assistance and local control strategies were key components. In 1999, conflict led to complete disruption of both programmes. In 2000, a National Tuberculosis Control Programme (NTP) was established from the non-governmental programme in collaboration with other partners. The smear-positive TB case notification rate of 108 per 100000 population is the highest in the region and reflects high population coverage. The cure rate of 81% is close to reaching the WHO target. CONCLUSION: High-quality TB control has been introduced in conflict-affected East Timor. Further research is needed to examine Timorese approaches to inform other, similar settings.

Transforming growth factor-beta (TGF-beta) in acute injuries of the spinal cord.

Injuries to the spinal cord may be associated with increased healing of fractures. This can be of benefit, but excessive bone growth can also cause considerable adverse effects. We evaluated two groups of patients with fractures of the spinal column, those with neurological compromise (n=10) and those without (n=15), and also a control group with an isolated fracture of a long bone (n=12). The level of transforming growth factor-beta (TGF-beta), was measured at five time points after injury (days 1, 5, 10, 42 and 84). The peak level of 142.79 ng/ml was found at day 84 in the neurology group (p<0.001 vs other time points). The other groups peaked at day 42 and had a decrease at day 84 after injury (p

A community-based TB drug susceptibility study in Mimika District, Papua Province, Indonesia.

SETTING: A district level tuberculosis (TB) control programme in Papua Province, Indonesia. OBJECTIVE: To determine the nature and extent of drug-resistant TB in newly diagnosed sputum smear-positive patients. METHODS: Sputum was collected from previously untreated smear-positive pulmonary TB patients diagnosed in the district over a 10-month period. Sputum specimens were processed and inoculated into a BACTEC MGIT960 tube. Isolates were identified by Ziehl-Neelsen staining, hybridisation with nucleic acid probes and biochemical investigations. Susceptibility testing was performed using the radiometric proportion method. Pyrazinamide testing was performed using the Wayne indirect method. RESULTS: One hundred and seven patients had sputum sent to a reference laboratory; 101 (94.4%) were culture-positive for Mycobacterium tuberculosis, with 87 (86.1%) fully sensitive to first-line anti-tuberculosis drugs. Two per cent were multidrug-resistant (MDR-TB) and 12 (11.9%) had other drug resistance. Each of the MDR-TB isolates was susceptible to amikacin, capreomycin, ciprofloxacin and para-aminosalicylic acid (PAS), but were resistant to rifabutin. One isolate was also resistant to ethionamide. CONCLUSIONS: MDR-TB is present in Indonesia but is not a major problem for TB control in this district. Generalisability to other districts in Indonesia, particularly large urban areas, needs to be confirmed by future studies.