Early-onset and recurrent depression in parents increases risk of intergenerational transmission to adolescent offspring.

BACKGROUND: To assess whether the age-of-onset or the recurrence of parents' major depressive disorder (MDD), measured prospectively in a longitudinal birth cohort study, predicted offspring depression at age 15. METHODS: A two-generation study of New Zealanders, with prospective, longitudinal data in the parents' generation (n = 375) and cross-sectional data from their adolescent offspring (n = 612). Parent and offspring depression was measured with structured clinical interviews. Parent depression was measured at six time points from age 11 to 38 years. Adolescent offspring depression was measured at age 15. RESULTS: Compared to adolescents whose parents were never depressed, those whose parents met criteria for MDD more than once and those whose parents first met criteria before adulthood had more symptoms of depression. The combination of early-onset and recurrent depression in parents made adolescents particularly vulnerable; their odds of meeting criteria for MDD were 4.21 times greater (95% CI = 1.57-11.26) than adolescents whose parents were never depressed. The strength of the intergenerational effect did not vary as a function of parent or offspring sex. The prevalence of adolescent depression was 2.5 times higher in the offspring than at age 15 in the parents' generation. CONCLUSIONS: Recurrent depression in both fathers and mothers increases offspring risk for depression, particularly when it starts in childhood or adolescence, but a single lifetime episode does not. Health practitioners should be aware of age-of-onset and course of depression in both parents when assessing their children's risk for depression.

Spiritual beliefs, practices, and needs at the end of life: Results from a New Zealand national hospice study.

OBJECTIVE: International studies have shown that patients want their spiritual needs attended to at the end of life. The present authors developed a project to investigate people's understanding of spirituality and spiritual care practices in New Zealand (NZ) hospices. METHOD: A mixed-methods approach included 52 semistructured interviews and a survey of 642 patients, family members, and staff from 25 (78%) of NZ's hospices. We employed a generic qualitative design and analysis to capture the experiences and understandings of participants' spirituality and spiritual care, while a cross-sectional survey yielded population level information. RESULTS: Our findings suggest that spirituality is broadly understood and considered important for all three of the populations studied. The patient and family populations had high spiritual needs that included a search for (1) meaning, (2) peace of mind, and (3) a degree of certainty in an uncertain world. The healthcare professionals in the hospices surveyed seldom explicitly met the needs of patients and families. Staff had spiritual needs, but organizational support was sometimes lacking in attending to these needs. SIGNIFICANCE OF RESULTS: As a result of our study, which was the first nationwide study in NZ to examine spirituality in hospice care, Hospice New Zealand has developed a spirituality professional development program. Given that spirituality was found to be important to the majority of our participants, it is hoped that the adoption of such an approach will impact on spiritual care for patients and families in NZ hospices.

Multisite phosphorylation of C-Nap1 releases it from Cep135 to trigger centrosome disjunction.

During mitotic entry, centrosomes separate to establish the bipolar spindle. Delays in centrosome separation can perturb chromosome segregation and promote genetic instability. However, interphase centrosomes are physically tethered by a proteinaceous linker composed of C-Nap1 (also known as CEP250) and the filamentous protein rootletin. Linker disassembly occurs at the onset of mitosis in a process known as centrosome disjunction and is triggered by the Nek2-dependent phosphorylation of C-Nap1. However, the mechanistic consequences of C-Nap1 phosphorylation are unknown. Here, we demonstrate that Nek2 phosphorylates multiple residues within the C-terminal domain of C-Nap1 and, collectively, these phosphorylation events lead to loss of oligomerization and centrosome association. Mutations in non-phosphorylatable residues that make the domain more acidic are sufficient to release C-Nap1 from the centrosome, suggesting that it is an increase in overall negative charge that is required for this process. Importantly, phosphorylation of C-Nap1 also perturbs interaction with the core centriolar protein, Cep135, and interaction of endogenous C-Nap1 and Cep135 proteins is specifically lost in mitosis. We therefore propose that multisite phosphorylation of C-Nap1 by Nek2 perturbs both oligomerization and Cep135 interaction, and this precipitates centrosome disjunction at the onset of mitosis.

A role for the Fizzy/Cdc20 family of proteins in activation of the APC/C distinct from substrate recruitment.

The Fizzy/Cdc20 family of proteins are essential activators of the anaphase-promoting complex/cyclosome (APC/C), a multisubunit E3 ubiquitin ligase. However, apart from the well-established role of the C-terminal WD40 domain in substrate recognition, the precise roles of the activators remain elusive. Here we show that Nek2A, which directly binds the APC/C, can be ubiquitylated and destroyed in Fizzy/Cdc20-depleted Xenopus egg extracts when only the N-terminal domain of Fizzy/Cdc20 (N-Cdc20) is added. This activity is dependent upon the C box and is conserved in the alternative activator, Fizzy-related/Cdh1. In contrast, canonical substrates such as cyclin B and securin require both the N-terminal and WD40 domains, unless N-Cdc20 is fused to substrates when the WD40 domain becomes dispensable. Furthermore, in Cdc20-depleted cells, N-Cdc20 can facilitate Nek2A destruction in a C box-dependent manner. Our results reveal a role for the N-terminal domain of the Fizzy/Cdc20 family of activators in triggering substrate ubiquitylation by the APC/C.

Oscillation of APC/C activity during cell cycle arrest promotes centrosome amplification.

Centrosome duplication is licensed by the disengagement, or 'uncoupling', of centrioles during late mitosis. However, arrest of cells in G2 can trigger premature centriole disengagement. Here, we show that premature disengagement results from untimely activation of the anaphase-promoting complex (APC/C), leading to securin degradation and release of active separase. Although APC/C activation during G2 arrest is dependent on polo-like kinase 1 (Plk1)-mediated degradation of the APC/C inhibitor, early mitotic inhibitor 1 (Emi1), Plk1 also has a second APC/C-independent role in promoting disengagement. Importantly, APC/C and Plk1 activity also stimulates centriole disengagement in response to hydroxyurea or DNA damage-induced cell-cycle arrest and this leads to centrosome amplification. However, the reduplication of disengaged centrioles is dependent on cyclin-dependent kinase 2 (Cdk2) activity and Cdk2 activation coincides with a subsequent inactivation of the APC/C and re-accumulation of cyclin A. Although release from these arrests leads to mitotic entry, the presence of disengaged and/or amplified centrosomes results in the formation of abnormal mitotic spindles that lead to chromosome mis-segregation. Thus, oscillation of APC/C activity during cell cycle arrest promotes both centrosome amplification and genome instability.

Growing health disparities for persons who are aging with intellectual and developmental disabilities: the social work linchpin.

Similar to the general population, adults with intellectual and developmental disabilities (IDD) are living into their 70s and beyond. Health care disparities have been well-documented for this vulnerable and underserved population. Social workers are often responsible for assessment, coordination of care, and negotiation of needed services for people with IDD. This article explores the challenges facing social workers in meeting the growing health and social needs of aging adults with IDD and their families. Trends in social work practice and gaps in education are discussed as they relate to addressing and reducing current health disparities.

Feasibility study of the prevalence of latent tuberculosis infection for Maori in the Waikato region, Aotearoa New Zealand.

OBJECTIVE: This study aimed to assess the feasibility of conducting a representative tuberculin skin test (TST) survey for Maori in Aotearoa New Zealand and to estimate the prevalence of latent tuberculosis (TB) infection. METHODS: Participants were Maori in the Waikato region, recruited by a Maori nurse, through: 1) random household selection from the Electoral Roll; 2) randomly selected prison inmates; and 3) community and health settings. A TB history and symptoms questionnaire was completed, TST performed and investigation of those with TST induration ≥10mm. RESULTS: Random household selection was resource intensive and only contributed 14 participants. Repeated random selection of prison lists were required to recruit 207 participants and there were no positive TST cases. Community and health settings yielded the highest participation (n=370) and the three people (0.5%) with TST ≥10mm. Age ≥45 years and history of contact with a TB case were associated with TST induration ≥5mm (n=39; 6.6%). CONCLUSIONS: The community and health settings were the only feasible options for recruitment. The overall prevalence of a positive TST in the study population was low. A 5mm cut-off may be best to maximise sensitivity for future studies. IMPLICATIONS FOR PUBLIC HEALTH: A mixture of sample selection processes that are more targeted are needed to identify Maori with latent TB infection.

Sealed with a Kiz: How Plk1 ensures spindle pole integrity.

The kinase Plk1 plays multiple roles in regulating mitotic progression, including stabilization of spindle poles, but its substrates are largely unknown. A new study by Yamamoto and coworkers has identified a centrosomal protein, Kizuna (Kiz), as a mitotic substrate of Plk1 (Oshimori et al., 2006). Phosphorylation of Kiz ensures the integrity of spindle poles in the face of severe pulling forces exerted by the chromosome-attached spindle microtubules.

Empowering equity: Striving for socio-economic equity in the Aotearoa New Zealand health workforce.

BACKGROUND: The lack of diversity in the health workforce is partly due to selection criteria for health professional programmes that have not selected students from a wide range of backgrounds. Consequently, health care professionals from minority groups and lower socio-economic backgrounds are under-represented in the workforce. APPROACH: The Socioeconomic Equity (EQ) support programme aims to increase the participation, retention and academic success of students from low socio-economic communities studying in health professional programmes at the University of Otago. At the start of the academic year, students who had attended a secondary school from a low socio-economic community were invited to take part in the EQ Programme. This includes group workshops on study skills, guidance from peer mentors, subject specific academic support, one-on-one course advice and pastoral support and activities to enhance self-esteem and self-efficacy. EVALUATION: Comparing the first two years of the EQ project with the previous year, there was an increase in the percentage of students from schools in low socio-economic communities that passed HSFY. It was also found that more EQ students were offered places in health professional programmes than in the previous year. IMPLICATIONS: The percentage of students passing HSFY has increased, and importantly, the percentage of students from low socio-economic backgrounds entering professional health programmes has doubled. This is a small start to building a health workforce that fairly reflects people from all communities.

Drinking and alcohol-related harm among New Zealand university students: findings from a national Web-based survey.

BACKGROUND: Alcohol-related harm is pervasive among college students in the United States of America and Canada, where a third to half of undergraduates binge drink at least fortnightly. There have been no national studies outside North America. We estimated the prevalence of binge drinking, related harms, and individual risk factors among undergraduates in New Zealand. METHODS: A web survey was completed by 2,548 undergraduates (63% response) at 5 of New Zealand's 8 universities. Drinking patterns and alcohol-related problems in the preceding 4 weeks were measured. Drinking diaries for the preceding 7 days were completed. Multivariate analyses were used to identify individual risk factors. RESULTS: A total of 81% of both women and men drank in the previous 4 weeks, 37% reported 1 or more binge episodes in the last week, 14% of women and 15% of men reported 2+ binge episodes in the last week, and 68% scored in the hazardous range (4+) on the AUDIT consumption subscale. A mean of 1.8 (95% confidence interval 1.4, 2.3) distinct alcohol-related risk behaviors or harmful consequences were reported, e.g., 33% had a blackout, 6% had unprotected sex, and 5% said they were physically aggressive toward someone, in the preceding 4 weeks. Drink-driving or being the passenger of a drink-driver in the last 4 weeks was reported by 9% of women and 11% of men. Risk factors for frequent binge drinking included: lower age, earlier age of drinking onset, monthly or more frequent binge drinking in high school, and living in a residential hall or a shared house (relative to living with parents). These correlates were similar to those identified in U.S. and Canadian studies. CONCLUSIONS: Strategies are needed to reduce the availability and promotion of alcohol on and around university campuses in New Zealand. Given the high prevalence of binge drinking in high school and its strong association with later binge drinking, strategies aimed at youth drinking are also a priority. In universities, high-risk drinkers should be identified and offered intervention early in their undergraduate careers.

Alcohol outlet density and university student drinking: a national study.

AIMS: To examine the geographic density of alcohol outlets and associations with drinking levels and related problems among university students. DESIGN: Cross-sectional survey study using geospatial data, with campus-level and individual-level analyses. PARTICIPANTS: A total of 2550 students (mean age 20.2, 60% women) at six university campuses in New Zealand (63% response). MEASUREMENTS: Counts of alcohol outlets within 3 km of each campus were tested for their non-parametric correlation with aggregated campus drinking levels and related problems. Generalized estimating equations were used to model the relation between outlet counts within 1 km and 3 km of student residences and individual drinking levels/problems, with control for gender, age, ethnicity and high school binge drinking frequency, and adjustment for campus-level clustering. FINDINGS: Correlations for campus-level data were 0.77 (P = 0.07) for drinking and personal problems, and 0.31 (P = 0.54) for second-hand effects. There were consistent significant associations of both on- and off-licence outlet densities with all outcomes in student-level adjusted models. Effects were largest for 1 km densities and off-licence outlets. CONCLUSIONS: There are positive associations between alcohol outlet density and individual drinking and related problems. Associations remain after controlling for demographic variables and pre-university drinking, i.e. the associations are unlikely to be due to self-selection effects. Increasing alcohol outlet density, and particularly off-licences, may increase alcohol-related harm among university students.

Coordinate regulation of the mother centriole component nlp by nek2 and plk1 protein kinases.

Mitotic entry requires a major reorganization of the microtubule cytoskeleton. Nlp, a centrosomal protein that binds gamma-tubulin, is a G(2)/M target of the Plk1 protein kinase. Here, we show that human Nlp and its Xenopus homologue, X-Nlp, are also phosphorylated by the cell cycle-regulated Nek2 kinase. X-Nlp is a 213-kDa mother centriole-specific protein, implicating it in microtubule anchoring. Although constant in abundance throughout the cell cycle, it is displaced from centrosomes upon mitotic entry. Overexpression of active Nek2 or Plk1 causes premature displacement of Nlp from interphase centrosomes. Active Nek2 is also capable of phosphorylating and displacing a mutant form of Nlp that lacks Plk1 phosphorylation sites. Importantly, kinase-inactive Nek2 interferes with Plk1-induced displacement of Nlp from interphase centrosomes and displacement of endogenous Nlp from mitotic spindle poles, while active Nek2 stimulates Plk1 phosphorylation of Nlp in vitro. Unlike Plk1, Nek2 does not prevent association of Nlp with gamma-tubulin. Together, these results provide the first example of a protein involved in microtubule organization that is coordinately regulated at the G(2)/M transition by two centrosomal kinases. We also propose that phosphorylation by Nek2 may prime Nlp for phosphorylation by Plk1.

Mental-physical comorbidity in an ethnically diverse population.

The relationship between mental disorders and chronic physical conditions is well established, but the possibility of ethnic group differences in mental-physical associations has seldom been investigated. This study investigated ethnic differences in associations between four physical conditions (chronic pain, cardiovascular disease, diabetes, and respiratory disease) and 12-month mood and anxiety disorders. A nationally representative face-to-face household survey was carried out in New Zealand from 2003 to 2004 with 12,992 participants aged 16 and older, achieving a response rate of 73.3%. The current study is of the subsample of 7,435 participants who were assessed for chronic physical conditions (via a standard checklist), and compares Maori, Pacific and Other New Zealanders. DSM-IV mental disorders were measured with the Composite International Diagnostic Interview (CIDI 3.0). The ethnic groups differed significantly in prevalences of both physical and mental disorders, but almost no ethnic differences in mental-physical associations were found. Independent of ethnicity, associations were observed between chronic pain and mood and anxiety disorders, cardiovascular disease and anxiety disorders, respiratory disease and mood and anxiety disorders. Despite differences in mental and physical health status between ethnic groups in New Zealand, mental-physical disorder associations occur with considerable consistency across the groups. These results suggest that whatever factors are conducive to the development of a mental disorder from a physical disorder (or vice versa), they are either unaffected by the cultural differences manifest in these ethnic groups, or, any cultural factors operating serve to both increase and decrease comorbidity such that they cancel each other out.

Management of distal radius fractures in the emergency department: A long-term functional outcome measure study with the Disabilities of Arm, Shoulder and Hand (DASH) scores.

OBJECTIVE: Distal radius fracture (DRF) is a common presentation to the ED. However, little is known about the long-term functional outcome of these patients following their initial management in the ED. METHODS: In order to evaluate the long-term functional outcome of DRF, we collected the Disabilities of Arm, Shoulder and Hand (DASH) scores from the patients who attended our ED with DRF between January 2014 and June 2015. We divided the patients into two groups based on their overall management: (i) conservative group who did not have any surgical interventions; and (ii) open reduction internal fixation (ORIF) group who needed surgical interventions in the theatre. Multiple linear regression models were used to identify the statistically significant predictor variables. RESULTS: Out of the 229 patients whom we contacted, 128 patients responded. The response rate was 56%. The majority of the patients belonged to the conservative group (n = 87, 75%), while one-quarter of the patients were in the ORIF group (n = 29, 25%). DASH score was higher in the ORIF group (median = 12.1, 95% confidence interval 5.6-25) than the conservative group (median = 6, 95% confidence interval 1.7-16.4). This difference between the groups was statistically significant (unadjusted P = 0.017, Wilcoxon test). Multiple linear regression models revealed that the management group and age of the patients were significant predictors for DASH score. CONCLUSION: Conservative management had lower DASH scores signifying better functional outcomes. Further prospective multicentre studies may be suggested to assess the generalisability of the study.

Short Communication: Diagnosis of Pneumocystis jirovecii Pneumonia by Detection of DNA in Blood and Oropharyngeal Wash, Compared with Sputum.

Molecular diagnostic methods on lower respiratory specimens for Pneumocystis pneumonia (PCP) are recommended, but specimens can be difficult to obtain. This study examined the diagnostic use of PCP polymerase chain reaction (PCR) on oropharyngeal wash (OPW) and blood versus sputum (spontaneous and induced) to find faster, simpler, and less invasive diagnostic methods. We prospectively recruited consenting adults with symptoms consistent with PCP. Real-time PCR targeted the Pneumocystis mitochondrial large subunit ribosomal RNA gene, using the aforementioned specimens. Clinical data were collected from routine records. Forty-five participants provided 45 sputa, 31 OPW, and 41 blood samples. Median age was 39 years and 41 (91%) were male, with median CD4 count being 64 cells/µL. Sputum PCR was positive in 27/45 (60%) participants. Comparative sensitivity of OPW was 9/19 (47%, 95% confidence interval [CI] 23-71) and blood 12/24 (50%, 95% CI 29-71) participants, both with specificity 100%. Including only samples obtained ≤2 days after start of treatment, sensitivity of OPW was 80% (8/10, 95% CI 51-100), that of blood was 57% (8/14, 95% CI 29-86), and that of combined tests was 88% (14/16, 95% CI 70-100). In 14/16 individuals with PCP and specimens obtained ≤2 days after start of treatment, diagnosis was possible using nonrespiratory samples. Despite moderate sensitivity of individual tests, combined PCP PCR on early blood and OPW specimens had high sensitivity and could reduce the need for invasive procedures. There were no false-positive results on nonrespiratory samples. Sampling and laboratory methods use routine technology and so require few additional resources.

Ethnic differences in acute hospitalisations for otitis media and elective hospitalisations for ventilation tubes in New Zealand children aged 0-14 years.

AIMS: This paper describes ethnic differences in acute hospitalisations for otitis media (OM) and elective hospitalisations for ventilation tube insertion in New Zealand children aged 0-14 years. Ethnic differences in first attendances at Ear Nose and Throat (ENT) outpatient clinics are also described. METHOD: The analysis included all hospital admissions of children aged 0-14 years during 2002-2008 which met the following criteria: Acute admissions with an ICD-10-AM primary diagnosis code of otitis media; and elective admissions with a primary procedure code of ventilation tube insertion. First attendances at ENT outpatient clinics during 2007-2008 were also reviewed. Explanatory variables included ethnicity, gender, age, and NZ Deprivation Index decile. RESULTS: Among 0-4 year olds, Maori and Pacific children were more likely to be admitted acutely for otitis media than European children. In contrast, both Maori and Pacific children had lower rates of elective admissions for ventilation tube insertion, with ethnic differences being most marked for children from the most deprived areas. Maori and Pacific children aged 5-14 years also had higher acute otitis media admission rates than European children. In contrast to their younger counterparts however, they also had higher rates of ventilation tube insertion. Exploration of ENT outpatient data for children 0-4 years revealed similar first appointment rates for European and Maori children, but lower rates for Pacific and Asian children. For the 5-14 age group, first appointment rates were higher for Maori and Pacific children than for European children. However, Maori and Pacific children in both age groups had higher rates of non-attendance at their first ENT appointments than European children. CONCLUSION: This study highlights ethnic differences in access to ventilation tubes amongst New Zealand's 0-4 year olds, with the greatest inequalities being seen for Maori, Pacific and Asian children living in the most deprived areas. For Maori and Pacific children, such differences cannot be attributed to lower rates of AOM or OME compared to European children. The fact that similar patterns are not seen for children aged 5-14 years potentially suggests that routine Well Child hearing screening may be playing a role in identifying unmet need in this older age group. Such disparities also suggest that factors over and above OM prevalence may be influencing access to ventilation tubes. Further research is required to determine why Maori and Pacific children (0-4 years) have similar/lower ENT appointment rates than European children, despite a higher burden of middle ear disease, as well as higher non-attendance rates at outpatient clinics. Given the importance of early detection and treatment of OM for children's ongoing well-being and education, a greater understanding of the reasons for these inequalities is urgently required.

Serious health events following involuntary job loss in New Zealand meat processing workers.

BACKGROUND: The association between unemployment and poor health outcomes is well documented. Significant debate exists as to whether unemployment causes ill health or whether those with poor health find it harder to obtain and maintain employment. Factory closure studies are well placed to comment on causation. The objective of this study was to investigate associations between involuntary job loss, mortality and serious illness. METHODS: An 8-year follow-up of workers from two meat-processing plants in the Hawkes Bay region of New Zealand. A cohort (n = 1945) made redundant in 1986 was compared with a cohort (n = 1767) from the neighbouring plant that remained open until 1994. Incidence rates for mortality, cancer registrations and admissions to public hospitals were derived from record linkage with routinely collected national data. RESULTS: Follow-up for the period 1986-1994 was 96% complete for both plants. Among the cohort made redundant in 1986, there was an increased risk of serious self-harm which led to hospitalization or death (adjusted for age, sex and ethnicity relative risk [RR] = 2.47; 95% CI: 1.04-5.89) compared to the employed cohort. The RR of admission to hospital with a mental health diagnosis was 1.17 (95% CI: 0.68-2.01). There were no other statistically significant findings. CONCLUSIONS: This study has most of the features of an 'ideal' factory closure study, in that it achieved near-complete follow-up of a large workforce made redundant and a similar employed workforce for 8 years. We found that exposure to involuntary job loss increased the risk of mental distress leading to serious self-harm. No other association was found.

The spiritual environment in New Zealand hospice care: identifying organisational commitment to spiritual care.

OBJECTIVES: Spiritual matters naturally arise in many people who have either a serious illness or are nearing end-of-life. The literature shows many examples of spiritual assessments, interventions and care; however, there is a lack of focus on organisational support for spiritual care. We aimed to ascertain the structural and operational capacity of New Zealand's hospices to attend to the spiritual needs and concerns of patients, families and staff. METHODS: As part of a larger study, a mail out cross-sectional survey was distributed to 25 New Zealand hospices and asked details from staff about facilities, practices and organisational aspects of spiritual care. Data were collated by creating a 'hospice setting spiritual score' based on an aggregate of eight items from the survey. RESULTS: There was a 66% response rate. Summary scores ranged from 2 to 7 indicating that while sites delivered a range of spiritual services, all could improve the level of spiritual care they provide. The two most common items missing were 'spiritual professional development' and 'formal spiritual assessment.' CONCLUSIONS: This simple setting spiritual score provides a snapshot of a hospice's commitment to spiritual care. It could be used as a preliminary auditing tool to assist hospices in identifying organisational and operational aspects that could be improved to enhance spiritual care delivery.

In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31)P-MRS) to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX) histochemistry). We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate) resynthesis) was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers): τ½ ADP (half-life of adenosine diphosphate clearance), HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3), HIV-uninfected 1.16±0.05×10(-3), p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX) defects within individual cells. Basal energy requirements may nevertheless be increased.