Assessment and predictors of fatigue in men with prostate cancer receiving radiotherapy and androgen deprivation therapy.

INTRODUCTION: Fatigue is a commonly reported symptom in men receiving radiation therapy and androgen deprivation therapy (ADT) for prostate cancer. Despite this, the complex mechanisms remain unclear. This study aims to investigate factors which correlate with development of fatigue. METHODS: Twenty-seven men with high-risk prostate cancer undergoing radiation therapy and 18 months of ADT were assessed for fatigue, haemoglobin (Hb), testosterone, magnetic resonance imaging (MRI) fat fraction (FF) and apparent diffusion coefficient (ADC), at baseline and at intervals after radiotherapy. Changes from baseline were analysed using paired t-tests. Linear time trends were assessed using linear mixed effect models. RESULTS: Overall, mean fatigue score increased from baseline to the 18-month time interval (difference 4.5, P = 0.0114). The mean value for Hb significantly decreased (P < 0.001) from baseline to 18 months. The mean value for testosterone significantly decreased (P < 0.001) from baseline to 12 months, and remained low. Mean for MRI FF showed a significant increase (P < 0.001) from baseline to 6 months. MRI ADC showed a non-significant decrease from baseline to 6 months (P = 0.4416). CONCLUSION: Radiotherapy and ADT resulted in a significant increase in fatigue scores. Statistically significant changes were noted in Hb, testosterone and MRI FF and ADC, however, none were shown to have a strong association with worsening fatigue. Further investigation in a larger cohort is required to assess the interaction between fatigue and possible biological factors.

Genetic population structure of the malaria vector Anopheles baimaii in north-east India using mitochondrial DNA.

BACKGROUND: Anopheles baimaii is a primary vector of human malaria in the forest settings of Southeast Asia including the north-eastern region of India. Here, the genetic population structure and the basic population genetic parameters of An. baimaii in north-east India were estimated using DNA sequences of the mitochondrial cytochrome oxidase sub unit II (COII) gene. METHODS: Anopheles baimaii were collected from 26 geo-referenced locations across the seven north-east Indian states and the COII gene was sequenced from 176 individuals across these sites. Fifty-seven COII sequences of An. baimaii from six locations in Bangladesh, Myanmar and Thailand from a previous study were added to this dataset. Altogether, 233 sequences were grouped into eight population groups, to facilitate analyses of genetic diversity, population structure and population history. RESULTS: A star-shaped median joining haplotype network, unimodal mismatch distribution and significantly negative neutrality tests indicated population expansion in An. baimaii with the start of expansion estimated to be ~0.243 million years before present (MYBP) in north-east India. The populations of An. baimaii from north-east India had the highest haplotype and nucleotide diversity with all other populations having a subset of this diversity, likely as the result of range expansion from north-east India. The north-east Indian populations were genetically distinct from those in Bangladesh, Myanmar and Thailand, indicating that mountains, such as the Arakan mountain range between north-east India and Myanmar, are a significant barrier to gene flow. Within north-east India, there was no genetic differentiation among populations with the exception of the Central 2 population in the Barail hills area that was significantly differentiated from other populations. CONCLUSIONS: The high genetic distinctiveness of the Central 2 population in the Barail hills area of the north-east India should be confirmed and its epidemiological significance further investigated. The lack of genetic population structure in the other north-east Indian populations likely reflects large population sizes of An. baimaii that, historically, were able to disperse through continuous forest habitats in the north-east India. Additional markers and analytical approaches are required to determine if recent deforestation is now preventing ongoing gene flow. Until such information is acquired, An. baimaii in north-east India should be treated as a single unit for the implementation of vector control measures.