Cerebral tissue oxygenation response to brain irradiation measured during clinical radiotherapy.

Significance: Cancer therapy treatments produce extensive changes in the physiological and morphological properties of tissues, which are also individual dependent. Currently, a key challenge involves developing more tailored cancer therapy, and consequently, individual biological response measurement during therapy, such as tumor hypoxia, is of high interest. This is the first time human cerebral haemodynamics and cerebral tissue oxygenation index (TOI) changes were measured during the irradiation in clinical radiotherapy and functional near-infrared spectroscopy (fNIRS) technique was demonstrated as a feasible technique for clinical use in radiotherapy, based on 34 online patient measurements. Aim: Our aim is to develop predictive biomarkers and noninvasive real-time methods to establish the effect of radiotherapy during treatment as well as to optimize radiotherapy dose planning for individual patients. In particular, fNIRS-based technique could offer an effective and clinically feasible online technique for continuous monitoring of brain tissue hypoxia and responses to chemo- and radiotherapy, which involves modulating tumor oxygenation to increase or decrease tumor hypoxia. We aim to show that fNIRS is feasible for repeatability measuring in patient radiotherapy, the temporal alterations of tissue oxygenation induced by radiation. Approach: Fiber optics setup using multiwavelength fNIRS was built and combined with a medical linear accelerator to measure cerebral tissue oxygenation changes during the whole-brain radiotherapy treatment, where the radiation dose is given in whole brain area only preventing dosage to eyes. Correlation of temporal alterations in cerebral haemodynamics and TOI response to brain irradiation was quantified. Results: Online fNIRS patient measurement of cerebral haemodynamics during clinical brain radiotherapy is feasible in clinical environment, and results based on 34 patient measurements show strong temporal alterations in cerebral haemodynamics and decrease in TOI during brain irradiation and confirmed the repeatability. Our proof-of-concept study shows evidently that irradiation causes characteristic immediate changes in brain tissue oxygenation. Conclusions: In particular, TOI seems to be a sensitive parameter to observe the tissue effects of radiotherapy. Monitoring the real-time interactions between the subjected radiation dose and corresponding haemodynamic effects may provide important tool for the researchers and clinicians in the field of radiotherapy. Eventually, presented fNIRS technique could be used for improving dose planning and safety control for individual patients.

Physical activity and sitting time in occupational groups from Papua New Guinea.

PURPOSE: To assess physical activity and sitting time in workers from varied occupations in a regional urban population of Papua New Guinea (PNG), to identify priorities for worker health in a country experiencing rapid industrial development. METHODS: PNG workers from a variety of settings (office [n = 213], blue-collar [n = 131], and retail [n = 52]) completed an interviewer-administered demographic questionnaire, the International Physical Activity Questionnaire-short form (IPAQ) and the Occupational Sitting and Physical Activity Questionnaire (OSPAQ); and had height and weight measured. Comparison of activity and sitting time between occupational groups was undertaken using generalised linear equations, with models including demographic variables and sitting time/physical activity as appropriate. RESULTS: Participants reported median total physical activity (walking, moderate and vigorous PA) of 5025 MET-min/week (80% constituting walking) and over 97% of participants met physical activity guidelines (> 600 MET-min/week). Total sitting time was 7 hours/day (IPAQ) and workers sat for 50% of working hours (OSPAQ). There was no difference between groups total physical activity. Office workers reported more total sitting time and a greater proportion of their work time spent sitting than blue-collar and retail workers reported significantly less total sitting time both p < 0.001) and retail workers reported a greater proportion of their work hours standing than office workers and blue-collar workers. CONCLUSIONS: Sitting time in PNG office workers was high, similar to findings from high-income countries, but total physical activity was also high in all groups. As the PNG economy develops and office-based work becomes more prevalent, the challenge will be to minimise sitting time at work whilst maintaining high total physical activity.

Comprehensive genetic analysis of 961 unrelated Duchenne Muscular Dystrophy patients: Focus on diagnosis, prevention and therapeutic possibilities.

Recently DNA sequencing analysis has played a vital role in the unambiguous diagnosis of clinically suspected patients with Duchenne Muscular Dystrophy (DMD). DMD is a monogenic, X-linked, recessive, degenerative pediatric neuromuscular disorder affecting males, invariably leading to fatal cardiopulmonary failure. Early and precise diagnosis of the disease is an essential part of an effective disease management strategy as care guidelines and prevention through counseling need to be initiated at the earliest particularly since therapies are now available for a subset of patients. In this manuscript we report the DMD gene mutational profiles of 961 clinically suspected male DMD patients, 99% of whom were unrelated. We utilized a molecular diagnostic approach which is cost-effective for most patients and follows a systematic process that sequentially involves identification of hotspot deletions using mPCR, large deletions and duplications using MLPA and small insertions/ deletions and point mutations using an NGS muscular dystrophy gene panel. Pathogenic DMD gene mutations were identified in 84% of patients. Our data compared well with the frequencies and distribution of deletions and duplications reported in the DMD gene in other published studies. We also describe a number of rare in-frame mutations, which appeared to be enriched in the 5' proximal hotspot region of the DMD gene. Furthermore, we identified a family with a rare non-contiguous deletion mutation in the DMD gene where three males were affected and two females were deemed carriers. A subset of patients with mutations in the DMD gene who are likely to benefit therapeutically from new FDA and EMA approved drugs were found in our cohort. Given that the burden of care for DMD patients invariably falls on the mothers, particularly in rural India, effective genetic counseling followed by carrier screening is crucial for prevention of this disorder. We analyzed the carrier status of consented female relatives of 463 probands to gauge the percentage of patients with familial disease. Our analysis revealed 43.7% of mothers with DMD gene mutations. Our comprehensive efforts, involving complete genetic testing coupled with compassionate genetic counseling provided to DMD patients and their families, are intended to improve the quality of life of DMD patients and to empower carrier females to make informed reproductive choices to impede the propagation of this deadly disease.

Meningitis: is a major cause of disability amongst Papua New Guinea children?

PURPOSE: This article is intended to focus on the need for the use of rehabilitation services, for children with meningitis in Papua New Guinea, which is one of largest developing country in The Pacific with diverse culture and landscape. Meningitis is the fifth leading disease that results in disability in the country. The first line of treatment is usually antibiotics, administration of vaccination is also recommended. Currently community based rehabilitation workers and Physiotherapist offer the rehabilitation services. There is a need for the other rehabilitation professionals and appropriate education to the CBR workers, caregivers for providing effective Rehabilitation. METHOD: Articles related to meningitis were recruited through various electronic database such as Ovid SP, MEDLINE, CINHAL, Google Scholar and HINARI and EBSCOhost for full text. The search includes journal articles, editorials, research reports, systematic reviews and books. RESULTS: The neurological sequelae resulting from meningitis are increasing. There is a need for Hib vaccination to reduce the rate of mortality. Physiotherapists are new professionals that emerged since 2006 and are assisting in reducing the motor and neurological disability. CONCLUSIONS: A multidisciplinary approach is required to manage the child with meningitis. Adequate knowledge, resources and assistance about the condition among the health professionals, carers and teachers would enable the children to achieve the quality of life.