Cardiopulmonary and cerebrovascular acclimatization in children and adults at 3800 m.

Maturational differences exist in cardiopulmonary and cerebrovascular function at sea-level, but the impact of maturation on acclimatization responses to high altitude is unknown. Ten children (9.8 ± 2.5 years) and 10 adults (34.7 ± 7.1 years) were assessed at sea-level (BL), 3000 m and twice over 4 days at 3800 m (B1, B4). Measurements included minute ventilation ( V ̇ E ${\dot{V}}_{\rm{E}}$ ), end-tidal partial pressures of oxygen ( P ETO 2 ${P}_{{\rm{ETO}}_{\rm{2}}}$ ) and carbon dioxide, echocardiographic assessment of pulmonary artery systolic pressure (PASP) and stroke volume (SV) and ultrasound assessment of blood flow through the internal carotid and vertebral arteries was performed to calculate global cerebral blood flow (gCBF). At 3000 m, V ̇ E ${\dot{V}}_{\rm{E}}$ was increased from BL by 19.6 ± 19.1% (P = 0.031) in children, but not in adults (P = 0.835); SV was reduced in children (-11 ± 13%, P = 0.020) but not adults (P = 0.827), which was compensated for by a larger increase in heart rate in children (+26 beats min-1 vs. +13 beats min-1 , P = 0.019). Between B1 and B4, adults increased V ̇ E ${\dot{V}}_{\rm{E}}$ by 38.5 ± 34.7% (P = 0.006), while V ̇ E ${\dot{V}}_{\rm{E}}$ did not increase further in children. The rise in PASP was not different between groups; however, ∆PASP from BL was related to ∆ P ETO 2 ${P}_{{\rm{ETO}}_{\rm{2}}}$ in adults (R2  = 0.288, P = 0.022), but not children. At BL, gCBF was 43% higher in children than adults (P = 0.017), and this difference was maintained at high altitude, with a similar pattern and magnitude of change in gCBF between groups (P = 0.845). Despite V ̇ E ${\dot{V}}_{\rm{E}}$ increasing in children but not adults at a lower altitude, the pulmonary vascular and cerebrovascular responses to prolonged hypoxia are similar between children and adults. KEY POINTS: Children have different ventilatory and metabolic requirements from adults, which may present differently in the pulmonary and cerebral vasculature upon ascent to high altitude. Children (ages 7-14) and adults (ages 23-44) were brought from sea level to high altitude (3000 to 3800 m) and changes in ventilation, pulmonary artery systolic pressure (PASP) and cerebral blood flow (CBF) were assessed over 1 week. Significant increases in ventilation and decreases in left ventricle stroke volume were observed at a lower altitude in children than adults. PASP and CBF increased by a similar relative amount between children and adults at 3800 m. These results help us better understand age-related differences in compensatory responses to prolonged hypoxia in children, despite similar changes in pulmonary artery pressure and CBF between children and adults.

Social contributors to cardiometabolic diseases in indigenous populations: an international Delphi study.

OBJECTIVE: The objective of this study was to identify priority social factors contributing to indigenous cardiometabolic diseases. STUDY DESIGN: A three-round Delphi process was used to consolidate and compare the opinions of 60 experts in indigenous cardiometabolic health from Australia, New Zealand and the United States. METHODS: Round one: three open-ended questions: (i) historical, (ii) economic and (iii) sociocultural factor contributors to cardiometabolic disease risk. Round two: a structured questionnaire based on the results from the first round; items were ranked according to perceived importance. Final round: the items were reranked after receiving the summary feedback. RESULTS: Several key findings were identified: (i) an important historical factor is marginalisation and disempowerment; (ii) in terms of economic and sociocultural factors, the panellists came to the consensus that the socio-economic status and educational inequalities are important; and (iii) while consensus was not reached, economic and educational factors were also perceived to be historically influential. CONCLUSION: These findings support the need for multilevel health promotion policy. For example, tackling financial barriers that limit the access to health-promoting resources, combined with improving literacy skills to permit understanding of health education.

A trial of a self-assessment tool of problems following treatment of colorectal cancer: a prospective study in Australia primary care.

Patients treated for colorectal cancer (CRC) experience considerable physical, social and psychological morbidity. In this study, 66 participants with stages I-III CRC were enrolled in this study. Participants completed the self-assessment tool for patients (SATp) over a 5-month period and visited a general practitioner with a copy of their SATp to assist in the management of any problems associated with CRC treatment. General practitioners' notes were reviewed for management actions. Of the 66 participants, 57 visited a general practitioner over the 5-month study period. A total of 547 problems were identified (median 7; IQR: 3-12.25). Participants with physical problems were more likely to consult their general practitioner (OR: 1.84, CI: 1.05-3.21, P = 0.03) compared to those with psychological problems. The number of problems experienced by participants did not have any influence on the decision to visit a general practitioner. Psychological problems (P < 0.01) significantly reduced over the 5-month study period. Regular use of the SATp facilitates the identification of long-term CRC treatment-related problems. Some of these problems could then be addressed in primary care.

Help-seeking experiences of men diagnosed with colorectal cancer: a qualitative study.

Advanced-stage diagnosis of colorectal cancer (CRC) leads to poor prognosis and reduced survival rates. The current study seeks to explore the reasons for diagnostic delays in a sample of Australian men with CRC. Semi-structured interviews were conducted in a purposive sample of 20 male CRC patients. Data collection ceased when no new data emerged. Interviews were audiotaped, transcribed and thematically analysed using Andersen's Model of Total Patient Delay as the theoretical framework. Most participants (18/20) had experienced lower bowel symptoms prior to diagnosis. Patient-related delays were more common than delays attributable to the health-care system. Data regarding patient delays fit within the first four stages of Andersen's model. The barriers to seeking timely medical advice were mainly attributed to misinterpretation of symptoms, fear of cancer diagnosis, reticence to discuss the symptoms or consulting a general practitioner. Treatment delays were a minor cause for delayed diagnosis. Delay in referral and scheduling for colonoscopy were among the system-delay factors. In many instances, delays resulted from men's failure to attribute their symptoms to cancer and, subsequently, delay in diagnosis.

SCIPA Com: outcomes from the spinal cord injury and physical activity in the community intervention.

STUDY DESIGN: Quasi-experimental translational study with pre- and post-measures. OBJECTIVES: To determine the effects of the Spinal Cord Injury and Physical Activity in the Community (SCIPA Com) intervention on leisure-time physical activity (LTPA) and associated outcomes among participants with spinal cord injury (SCI). SETTING: Young Men's Christian Associations and community fitness centers, Australia and New Zealand. METHODS: SCIPA Com consisted of three stages: (i) training exercise professionals via the Train the Trainers Spinal Cord Injury course; (ii) implementation of supervised physical activity programs twice a week for 30 to 60 min for 8 to 12 weeks; and (iii) follow-up assessments on health outcomes over 9 months. Participants with SCI were classified as active or inactive by baseline LTPA levels and linear mixed methods compared LTPA between groups over time. RESULTS: Sixty-four community-dwelling participants with SCI completed customized physical activity programs. Compared with baseline, there were significant improvements in LTPA (26 min per day, 95% confidence interval (CI): 16.6-35.4; P<0.001), functional goals (2, 95% CI: 1.72-2.37; P<0.001), self-esteem (1.5, 95% CI: 0.72-2.27; P<0.001) and overall quality of life (P<0.05). Over time, LTPA participation was greater among the active compared with the inactive group, although LTPA levels among the inactive improved compared with baseline. CONCLUSIONS: Significant improvements in LTPA participation and health outcomes were observed, especially among inactive individuals with SCI. SCIPA Com is an ecologically valid intervention based on training and support provided to community exercise professionals who, although new to adapted training, delivered effective physical activity programs for those at risk of inactivity. SPONSORSHIP: Transport Accident Commission (Project Number DP172) and the International Postgraduate Research Scholarship (IPRS), Curtin University.

Evaluation of BSP expression and apoptosis in the periodontal ligament during orthodontic relapse: a preliminary study.

OBJECTIVE: To examine the expression of bone sialoprotein (BSP) and apoptosis in an in vivo orthodontic relapse model. MATERIALS AND METHODS: Male mice (10-12 weeks old), either transgenic [green fluorescent protein (GFP) driven by the BSP promoter] or wild type, were used in this study. To achieve orthodontic tooth movement (OTM), maxillary right first molars were moved mesially using closed-coil springs. Animals were divided into an OTM group (14 days continuous orthodontic force - 11 animals) or Relapse group (10 days of force application followed by 4 days of relapse - 8 animals). The control group was comprised of the contralateral maxillary molars. The periodontal ligament (PDL) was analyzed in areas of compression and tension for transgenic expression, osteoclast localization, and the presence of apoptotic cells. RESULTS: There was a significant decrease in GFP-labeled cells on the compression and tension sides of the PDL in the OTM group compared with control. In the relapse group, GFP-labeled cells were significantly decreased only on the old compression side. Osteoclasts were localized on the compression side of the OTM group, whereas in the Relapse group, they were present on both sides. PDL apoptosis significantly increased on the compression side in OTM and Relapse groups. CONCLUSION: Both OTM and Relapse groups exhibited a decreased number of GFP-labeled cells in areas of compression and tension. There was significant PDL apoptosis in regions under compressive forces following OTM and to a lesser extent following relapse.

Physical activity for children in special school environment.

1. We assessed children's physical activity (PA) in structured (physical education) and unstructured (recess, lunch, before and after school) periods in special schools and examined its association with modifiable area contextual characteristics. 2. Children with disabilities were not highly active, but were more active during recess and lunch periods than at other times including physical education classes. 3. Areas were often not accessible during unstructured settings. Children were more active in areas when supervision and organised activities were provided. 4. Providing an interactive game during free play did not significantly increase group's PA. 5. Children's PA accrual is influenced by contextual characteristics of the school environment. There is a need to make areas more accessible and to use social marketing and programming to attract more users. School and health professionals should modify contextual characteristics by providing more direct supervision and organised activities during free play.

Academic and personal problems among Australian university students who drink at hazardous levels: web-based survey.

ISSUE ADDRESSED: Australian university students consume large amounts of alcohol. There is little published information about personal and academic problems associated with this behaviour. We sought to estimate the prevalence, and identify variables associated with, alcohol-related problems among undergraduate hazardous drinkers. METHODS: The control group members (942 undergraduates, 53.3% male, mean age 19.4 years) of an internet-based intervention trial, who scored ≥8 on the Alcohol Use Disorders Identification Test, completed two validated questionnaires about their experience of alcohol-related problems in the preceding 4 weeks. Regression models were used to identify associations between individual characteristics and alcohol-related problems. RESULTS: One-quarter of participants had missed a class (25.6%) and/or had been unable to concentrate in class (25.7%), and 45% reported that their drinking had impacted negatively on their learning or grades. The most frequent non-academic problems were hangovers (74.8%), blackouts (44.8%), emotional outbursts (30.5%), vomiting (28.1%), arguments (20.2%) and drink-driving (23.2%). Male gender, lower age, being a smoker, being in the Faculty of Health (versus Humanities) and living in shared housing (versus with parents/guardians) were each associated with alcohol-related problems, whereas year of study had no association. CONCLUSIONS: There is a high prevalence of preventable alcohol-related problems among undergraduates drinking at hazardous levels and a need for restriction of the availability and promotion of alcohol as well as intervention for individuals at high risk. SO WHAT?: Universities have a duty of care to large populations of young people drinking at hazardous levels and should make greater efforts to address hazardous alcohol consumption.

Presence and identity of Babesia microti in Ireland.

Babesia microti is a tick-transmitted protozoan parasite of wildlife that can also cause serious disease in humans. It is now well established that B. microti represents an assemblage of different strains or species, only some of which are important zoonotic pathogens. Therefore, in order to assess the potential public health risk associated with B. microti in any given location, it is important to determine the strains that are present. This is the first study on the presence and identity of B. microti in Ireland. Overall, 314 wood mice (Apodemus sylvaticus), 243 bank voles (Myodes glareolus) and 634 questing Ixodes ricinus nymphs collected in various locations across Ireland were screened for the presence of B. microti by metabarcoding and nested PCR, respectively. Overall 8 rodent spleen samples (1.4%) were positive for B. microti, while all tick samples tested negative. Rodent isolates were identified as the 'Munich' strain which rarely causes human disease and is chiefly transmitted by the mouse tick, Ixodes trianguliceps. Together with reports from the UK these results suggest that B. microti does not represent a significant public health risk in Britain or Ireland.

How prepared is the retirement and residential aged care sector in Western Australia for older non-heterosexual people?

OBJECTIVE: To explore attitudes, knowledge and current practices of retirement and residential aged care providers in Western Australia towards accommodating older gay, lesbian, bisexual, transgender and intersex (GLBTI) individuals. GLBTI is used throughout as a general term to include people who are not exclusively heterosexual in identity, attraction and/or behaviour. METHODS: Postal surveys were sent to 329 providers of accommodation to ask about their attitudes, knowledge and current practices towards older GLBTI people. Two focus groups were also held with managers of accommodation facilities and GLBTI community members. RESULTS: Few respondents reported having experience with any older GLBTI residents in their retirement or residential aged care facility. There was poor inclusion of GLBTI issues in policy frameworks, and limited understanding regarding same-sex law reforms. CONCLUSION: Older non-heterosexual people are often obscured within ageing population discourses, and conceal their identity for fear of discrimination. GLBTI-sensitive practices can help to facilitate the disclosure of sexual orientation and/or gender identity that may assist in meeting the unique needs of this group.

Trunk muscle training, posture fatigue, and performance in laparoscopic surgery.

PURPOSE: To investigate the effect of trunk muscle endurance training on the perception of back postural fatigue and performance of a laparoscopic task. MATERIALS AND METHODS: Thirty-one medical students (28 men and 13 women) with no laparoscopic surgical experience were randomly assigned to either a training group or a control group. Participants in the training group underwent a 6-week, 18-session trunk (abdominal and back muscle) endurance training program, whereas participants in the control group did not. Performance by all participants was assessed on a simulated laparoscopic task under varying conditions of low back postural fatigue, both before and after the training program. RESULTS: Participants in the training group showed significant improvements in trunk endurance after the 6-week, trunk endurance training program (P<0.05), whereas those in the control group did not. The improvements in trunk endurance were accompanied by significantly reduced perceptions of discomfort (P< .001) and fewer errors during performance of the laparoscopic task. (P<0.02), whereas no significant changes occurred for the control group (P>0.05). CONCLUSION: Increasing trunk endurance can increase postural fatigue and discomfort during simulated laparoscopic tasks, which may assist in the management of errors during laparoscopy.

Incidence and risk factors for injury in non-elite netball.

This paper identifies the risk and protective factors for injury in non-elite netball. Three-hundred and sixty-eight non-elite netballers completed a baseline questionnaire at the commencement of the 1997 preseason. Participants were telephoned each month during the 1997 and 1998 playing seasons to provide details of their exposure at training and games and any injury experiences in the previous 4 weeks. The incidence of injury in this study was 14 injuries per 1000 player hours. The risk factors for injury were identified as: not warming up before a game (IRR 1.11, 95% CI 1.00-1.23) and not being open to new ideas (IRR 1.04, 95% CI 1.00-1.07). Training for 4 or more hours per week (IRR 0.66, 95% CI 0.45-0.98) and not sustaining an injury in the previous 12 months (IRR 0.58, 95% CI 0.43-0.79) were found to be protective against injury. The risk and protective factors for injury identified in this study can be used as the basis for the development of evidence-based injury prevention strategies that seek to reduce the risk of injury in sport. Injury prevention strategies should focus on the development of effective training programs that include netball-specific skills, activities and movements. Further investigation into the mechanisms associated with the risk and protective factors identified would provide further understanding of why these factors increase or decrease the risk of injury.

Gains, losses, and amplification of genomic material in rhabdomyosarcoma analyzed by comparative genomic hybridization.

In this study, 10 embryonal and 14 alveolar rhabdomyosarcoma (RMS) tumor samples, including 4 cell lines derived from tumors of the alveolar subtype, were analyzed by comparative genomic hybridization. In the embryonal tumors, the gain of whole or most of various chromosomes, notably chromosomes 2 (60% of cases), 13 (60%), 12 (60%), 8 (60%), 7 (50%), 17 (40%), 18 (40%), and 19 (40%), and the loss of chromosomes 16 (40%), 10 (30%), 15 (20%), and 14 (20%) were found. One case showed evidence of genomic amplification at 12q13-15. In contrast, the alveolar tumors and cell lines showed consistent evidence of genomic amplification, with multiple amplicons in some cases. The amplicons were localized to l2q13-15 (50%), 2p24 (36%), 13q14 (14%), l3q32 (14%), 1q36 (14%), 1q21 (7%), and 8q13-21 (7%). Four cases had additional copies of chromosome 17 or l7q. These changes were in addition to the presence of fusion gene transcripts that are associated with translocations specific to alveolar RMS. The results show that distinct patterns of primarily gains of specific chromosomal material are associated with the embryonal subtype of RMS, and that genomic amplification seems to play an important role in the alveolar subtype. Notably, these distinct changes predominantly involved chromosomes 2, 12, and 13 in both subtypes.

MiAMP1, a novel protein from Macadamia integrifolia adopts a Greek key beta-barrel fold unique amongst plant antimicrobial proteins.

MiAMP1 is a recently discovered 76 amino acid residue, highly basic protein from the nut kernel of Macadamia integrifolia which possesses no sequence homology to any known protein and inhibits the growth of several microbial plant pathogens in vitro while having no effect on mammalian or plant cells. It is considered to be a potentially useful tool for the genetic engineering of disease resistance in transgenic crop plants and for the design of new fungicides. The three-dimensional structure of MiAMP1 was determined through homonuclear and heteronuclear ((15)N) 2D NMR spectroscopy and subsequent simulated annealing calculations with the ultimate aim of understanding the structure-activity relationships of the protein. MiAMP1 is made up of eight beta-strands which are arranged in two Greek key motifs. These Greek key motifs associate to form a Greek key beta-barrel. This structure is unique amongst plant antimicrobial proteins and forms a new class which we term the beta-barrelins. Interestingly, the structure of MiAMP1 bears remarkable similarity to a yeast killer toxin from Williopsis mrakii. This toxin acts by inhibiting beta-glucan synthesis and thereby cell wall construction in sensitive strains of yeast. The structural similarity of MiAMP1 and WmKT, which originate from plant and fungal phyla respectively, may reflect a similar mode of action.

Insect peptides with improved protease-resistance protect mice against bacterial infection.

At a time of the emergence of drug-resistant bacterial strains, the development of antimicrobial compounds with novel mechanisms of action is of considerable interest. Perhaps the most promising among these is a family of antibacterial peptides originally isolated from insects. These were shown to act in a stereospecific manner on an as-yet unidentified target bacterial protein. One of these peptides, drosocin, is inactive in vivo due to the rapid decomposition in mammalian sera. However, another family member, pyrrhocoricin, is significantly more stable, has increased in vitro efficacy against gram-negative bacterial strains, and if administered alone, as we show here, is devoid of in vitro or in vivo toxicity. At low doses, pyrrhocoricin protected mice against Escherichia coli infection, but at a higher dose augmented the infection of compromised animals. Analogs of pyrrhocoricin were, therefore, synthesized to further improve protease resistance and reduce toxicity. A linear derivative containing unnatural amino acids at both termini showed high potency and lack of toxicity in vivo and an expanded cyclic analog displayed broad activity spectrum in vitro. The bioactive conformation of native pyrrhocoricin was determined by nuclear magnetic resonance spectroscopy, and similar to drosocin, reverse turns were identified as pharmacologically important elements at the termini, bridged by an extended peptide domain. Knowledge of the primary and secondary structural requirements for in vivo activity of these peptides allows the design of novel antibacterial drug leads.

Disruption of imprinted genes at chromosome region 11p15.5 in paediatric rhabdomyosarcoma.

Rhabdomyosarcomas are characterized by loss of heterozygosity (LOH) at chromosome region 11p15.5, a region known to contain several imprinted genes including insulin-like growth factor 2 (IGF2), H19, and p57(KIP2). We analyzed 48 primary tumour samples and found distinct genetic changes at 11p15.5 in alveolar and embryonal histological subtypes. LOH was a feature of embryonal tumours, but at a lower frequency than previous studies. Loss of imprinting (LOI) of the IGF2 gene was detected in 6 of 13 informative cases, all harbouring PAX3-FKHR or PAX7-FKHR fusion genes characteristic of alveolar histology. In contrast, H19 imprinting was maintained in 14 of 15 informative cases and the case with H19 LOI had maintenance of the IGF2 imprint indicating separate mechanisms controlling imprinting of IGF2 and H19. The adult promoter of IGF2, P1, was used in 5 of 14 tumours and its expression was unrelated to IGF2 imprinting status implying a further mechanism of altered IGF2 regulation. The putative tumour suppressor gene p57(KIP2) was expressed in 15 of 29 tumours and expression was unrelated to allele status. Moreover, in tumours with p57(KIP2) expression, there was no evidence for inactivating mutations, suggesting that p57(KIP2) is not a tumour suppressor in rhabdomyosarcoma.

Opportunistic infections in severely burned patients.

The risk of infection in burn patients, which is proportional to the extent of burn, reflects the combined effect of impairment of all aspects of the host defense system and microbial factors. The microbial flora colonizing the burn wound changes with time following injury and provides the organisms causing infections in burn patients. The temporal pattern of the predominant gram-negative organisms causing infections in a burn unit resembles that of a succession of mini-epidemics necessitating an active program of microbial surveillance to guide treatment of infections. Topical chemotherapy has significantly reduced the occurrence of invasive burn wound infections, but microbial control is imperfect and the burn wound, as well as the patient as a whole, must be closely monitored (using wound biopsies as indicated) to diagnose and treat infection in a timely manner. The treatment of burn wound infections is guided by extent and depth of microbial invasion, density of microorganisms, and systemic changes. As a manifestation of immunologic impairment, infection in sites other than the burn wound remains the most frequent cause of death in burn patients. The use of broad spectrum serologic agents to enhance immuno-competence in extensively burned patients may reduce the occurrence of life threatening opportunistic infections.

Replacement therapy with modified immunoglobulin G in burn patients: preliminary kinetic studies.

Suppression of serum immunoglobulin G for periods ranging from days to weeks following thermal injury may enhance the risk of infection in burn patients. In an initial trial, we attempted to determine whether intravenous pulses of Immunoglobulin G (IgG) will establish and maintain normal serum IgG concentrations in this interval. The levels of endogeneous serum IgG in eight control patients, mean total burn size 45 percent body surface area (no IgG infusions), were measured by radial immunodiffusion on various postburn days. Commercially available reduced alkylated IgG (5 percent Gamimune, Cutter Biological, Berkeley, California) was infused in doses of 500 mg/kg twice per week in four patients (total burn size 32 percent) and once per week in five patients (total burn size 47 percent), beginning during the first postburn week. Circulating IgG was measured prior to each infusion and at three postinfusion times: (1) 15 minutes (peak), (2) one day, and (3) either day 3, 4, or 6. Surgery or blood transfusions prior to one of these time points invalidated kinetic analysis of some infusions. Exponential two-point decay constants for total serum IgG after each of 24 infusions were calculated separately for early (day 0-1) and later (day 1-3 or 1-4) postinfusion intervals and assessed by stepwise regression analysis to determine sources of variation in decay. Early decay was seen to be faster with larger burn size after accounting for variation of decay with preinfusion and peak IgG values. Later decay was not related to burn size. Maltose, a constituent of the IgG preparation, was detectable in serum for only four to eight hours after each infusion and may have contributed to a 20 percent increase in total serum glucose between four and eight hours postinfusion. Mean serum IgG in patients given infusions twice weekly was in the normal range after one infusion, about a week earlier than in untreated patients. Such infusions maintained normal IgG levels.

Primitive neuroectodermal tumor of the kidney confirmed by fluorescence in situ hybridization.

Peripheral primitive neuroectodermal tumors (PNETs) are rare lesions that form part of the Ewing family of tumors, which includes osseous and extraosseous Ewing's sarcoma and Askins tumor of the thorax. All are characterized by translocations involving the EWS gene at 22q12, usually the translocation t(11;22)(q24;12). PNETs usually occur in soft tissues but occasionally arise within a visceral organ. We describe a PNET of the kidney that showed characteristic microscopic and immunohistochemical appearances of a small, round, dark blue cell tumor with focal rosette formation and strong membrane positivity for the MIC2 gene product. Interphase fluorescence in situ hybridization on touch imprints prepared from frozen tissue using cosmid probes flanking the EWS gene at 22q12 and the FLI1 gene at 11q24 indicated the presence of t(11; = +22)(q24; = +q12), confirming the diagnosis of PNET. This is the first reported PNET of the kidney supported by cytogenetic analysis. We also review the literature on this fascinating tumor in this unusual location.