The Effect of Photobiomodulation on the Treatment of Hereditary Mitochondrial Diseases

Introduction: Despite a wide variety of clinical presentations in hereditary Mitochondrial Diseases, muscle fatigue is a common theme and impairs a patient’s quality of life and ability to function. Current treatments are only supportive and include nutritional supplementation and physical therapy. Photobiomodulation therapy (PBMT) using low-intensity, narrow spectrum light in the red/near infrared (NIR) range, from a low-level laser or light-emitting diode sources, enhances mitochondrial function in preclinical and clinical studies on a range of conditions. However, little research has been done on the effectiveness of photobiomodulation in hereditary mitochondrial disorders. Methods: We performed a scoping review of the evidence of the beneficial effects of photobiomodulation for treating the muscle-related symptoms of hereditary mitochondrial disease. Results: No studies regarding photobiomodulation in hereditary mitochondrial disease were identified. However, in other clinical conditions featuring acquired mitochondrial impairment, we identified studies that suggested improved function, although sample sizes were small in number and statistical power. Conclusion: There is emerging evidence of efficacy for PBMT for diseases involving acquired mitochondrial insufficiency. We identified no published research on PBMT in hereditary mitochondrial disease, but this review confirms a theoretical rationale for a positive effect and suggests further research

Childhood-onset Leber hereditary optic neuropathy

Background The onset of Leber hereditary optic neuropathy (LHON) is relatively rare in childhood. This study describes the clinical and molecular genetic features observed in this specific LHON subgroup. Methods Our retrospective study consisted of a UK paediatric LHON cohort of 27 patients and 69 additional cases identified from a systematic review of the literature. Patients were included if visual loss occurred at the age of 12 years or younger with a confirmed pathogenic mitochondrial DNA mutation: m. 3460G>A, m. 11778G>A or m. 14484T>C. Results In the UK paediatric LHON cohort, three patterns of visual loss and progression were observed: (1) classical acute (17/27, 63%); (2) slowly progressive (4/27, 15%); and (3) insidious or subclinical (6/27, 22%). Diagnostic delays of 3-15 years occurred in children with an insidious mode of onset. Spontaneous visual recovery was more common in patients carrying the m. 3460G>A and m. 14484T>C mutations compared with the m. 11778G>A mutation. Based a meta-analysis of 67 patients with available visual acuity data, 26 (39%) patients achieved a final best-corrected visual acuity (BCVA) >= 0.5 Snellen decimal in at least one eye, whereas 13 (19%) patients had a final BCVA Conclusions Although childhood-onset LHON carries a relatively better visual prognosis, approximately 1 in 5 patients will remain within the visual acuity criteria for legal blindness in the UK. The clinical presentation can be insidious and LHON should be considered in the differential diagnosis when faced with a child with unexplained subnormal vision and optic disc pallor.Peer reviewe

Analysis of sampling clock phase noise in homodyne FMCW radar systems

In many contemporary electronic systems, phase noise sets the bound on the achievable performance. Radar systems are no exception, with the actual radar signals carrying significant amounts of phase noise due to the high transmit frequencies. In coherent radars, some of the phase noise sidebands on the received signal are cancelled due to mixing in the receiver. The sampling clock used to sample the intermediate frequency (IF) signals also introduces phase noise/jitter. This paper focuses on the contribution of the sampling clock's phase noise to the overall phase noise in the sampled signal in coherent homodyne FMCW radar systems. We develop a model relating the phase noise in the sampled signal to the phase noise in the radar signals and the jitter in the sampling clock. We apply our analysis to example FMCW radar systems. The derived model can be used to work out the phase noise requirement on the sampling clock for a given phase noise level in radar signals.</p

Phase noise analysis in FMCW radar systems

Phase noise in radar transmitters is known to raise the noise floor around large targets, making impossible the detection &amp; tracking of small targets nearby. This paper presents phase-noise modelling techniques, with a focus on homodyne FMCW radars, to accurately predict the level of phase noise expected in the radar display. Phase noise models of the sub-systems inside a typical radar are presented. We also discuss the cancellation of phase noise in coherent radar systems for short-ranges and analyse the situation for longer ranges. Practical measurements from a millimetre-wave radar system are presented to validate the theoretical modelling.</p

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The spread of marine anoxia on the northern Tethys margin during the Paleocene-Eocene Thermal Maximum

Records of the paleoenvironmental changes that occurred during the Paleocene-Eocene Thermal Maximum (PETM) are preserved in sedimentary rocks along the margins of the former Tethys Ocean and Peri-Tethys. This paper presents new geochemical data that constrain paleoproductivity, sediment delivery, and seawater redox conditions, from three sites that were located in the Peri-Tethys region. Trace and major element, iron speciation, and biomarker data indicate that water column anoxia was established during episodes when inputs of land-derived higher plant organic carbon and highly weathered detrital clays and silts became relatively higher. Anoxic conditions are likely to have been initially caused by two primary processes: (i) oxygen consumption by high rates of marine productivity, initially stimulated by the rapid delivery of terrestrially derived organic matter and nutrients, and (ii) phosphorus regeneration from seafloor sediments. The role of the latter process requires further investigation before its influence on the spread of deoxygenated seawater during the PETM can be properly discerned. Other oxygen-forcing processes, such as temperature/salinity-driven water column stratification and/or methane oxidation, are considered to have been relatively less important in the study region. Organic carbon enrichments occur only during the initial stages of the PETM as defined by the negative carbon isotope excursions at each site. The lack of observed terminal stage organic carbon enrichment does not support a link between PETM climate recovery and the sequestration of excess atmospheric CO2 as organic carbon in this region; such a feedback may, however, have been important in the early stages of the PETM

Differences in adiposity trajectories by birth cohort and childhood social class: evidence from cohorts born in the 1930s, 1950s and 1970s in the west of Scotland

Background Since the 1930s, the environment has become increasingly obesogenic, leading to rising rates of adiposity and socioeconomic inequalities in adiposity. Building on studies comparing body mass index (BMI) for cohorts born over a period of 20 years, we examine the social patterning of BMI and central adiposity for three cohorts born over a 40-year period. Methods Using data from the West of Scotland Twenty-07 study (n=4510), we investigate 20-year trajectories of adiposity for three cohorts born in the 1930s, 1950s and 1970s, allowing us to study 60 years of the lifecourse. Stratified by gender, we employed multilevel models to generate trajectories for BMI and waist-to-height ratio (WHtR) and explored how these trajectories varied by childhood social class. Results Adiposity increased most quickly with age in the youngest cohort, and cohort differences were greater than socioeconomic differences. For example, the smallest cohort difference for BMI, a comparison of men in the 1930s and 1950s cohorts at age 55, was 2.66 (95% CI 2.11 to 3.20) kg/m2, while the largest socioeconomic difference, a comparison of manual and non-manual women at age 64, was 1.18 (95% CI 0.37 to 1.98) kg/m2. Socioeconomic inequalities in adiposity increased with age and were greater for women than for men. The results for WHtR differed in that increases in WHtR accelerated with age while increases in BMI slowed. Conclusions Socioeconomic differences in adiposity accumulate slowly across the lifecourse and are approximately only a third of the adiposity differences between cohorts

A Phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults

Objectives Control of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults. Design This was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naïve subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon γ (IFN-γ) ELISpot assays and flow-cytometric analysis. Results MVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-γ response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable. Conclusion MVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB- and HIV-endemic areas is merited

High frequency of mitochondrial genome instability in human endometrial carcinomas

To investigate the occurrence of somatic mitochondrial DNA (mtDNA) mutations in human primary endometrial carcinomas, we sequenced the D-loop region, the 12S and 16S rRNA genes of mtDNA of cancer tissues and their matched normal controls. About 56% (28 out of 50) of cases carry one or more somatic changes in mtDNA including deletion, point mutation and mitochondrial microsatellite instability (mtMSI), namely the change in length of short base-repetitive sequences of mtDNA. In particular, mtMSI was frequently detected in 89% (25 out of 28) of all the cases carrying somatic changes followed by point mutations (25%; seven out of 28) and deletion (3.5%; one out of 28). The CCCCCTCCCC sequences located in the Hypervariable Regions I and II of the D-loop and 12S rRNA gene are instability hot spot regions in endometrial carcinomas. It is suggested that errors in replication may account for the high frequency of mtMSI in human endometrial carcinomas. The relatively high prevalence of mtMSI may be a potential new tool for detection of endometrial cancer. © 2003 Cancer Research UK.link_to_subscribed_fulltex

A Compilation of Global Bio-Optical In Situ Data for Ocean-Colour Satellite Applications

A compiled set of in situ data is important to evaluate the quality of ocean-colour satellite-data records. Here we describe the data compiled for the validation of the ocean-colour products from the ESA Ocean Colour Climate Change Initiative (OC-CCI). The data were acquired from several sources (MOBY, BOUSSOLE, AERONET-OC, SeaBASS, NOMAD, MERMAID, AMT, ICES, HOT, GeP&CO), span between 1997 and 2012, and have a global distribution. Observations of the following variables were compiled: spectral remote-sensing reflectances, concentrations of chlorophyll a, spectral inherent optical properties and spectral diffuse attenuation coefficients. The data were from multi-project archives acquired via the open internet services or from individual projects, acquired directly from data providers. Methodologies were implemented for homogenisation, quality control and merging of all data. No changes were made to the original data, other than averaging of observations that were close in time and space, elimination of some points after quality control and conversion to a standard format. The final result is a merged table designed for validation of satellite-derived ocean-colour products and available in text format. Metadata of each in situ measurement (original source, cruise or experiment, principal investigator) were preserved throughout the work and made available in the final table. Using all the data in a validation exercise increases the number of matchups and enhances the representativeness of different marine regimes. By making available the metadata, it is also possible to analyse each set of data separately. The compiled data are available at doi:10.1594/PANGAEA.854832 (Valente et al., 2015)