New Approaches to Photodynamic Therapy from Type I, II and III to Type IV Using One or More Photons

Photodynamic therapy (PDT) is an alternative cancer treatment to conventional surgery, radiotherapy and chemotherapy. It is based on activating a drug with light that triggers the generation of cytotoxic species that promote tumour cell killing. At present, PDT is mainly used in the treatment of wet age-related macular degeneration, for precancerous conditions of the skin (e.g. actinic keratosis) and in the palliative care of advanced cancers, for instance of the bladder or the oesophagus. PDT is still not used as a first line cancer treatment, which is surprising given the first clinical trials by Dougherty’s group dating back to the 1970’s. PDT has significant advantages over surgery or radiation therapy for low lying tumours due to better cosmetic outcome and localised treatment for the patients. However, despite these advantages and significant developments in optical technology that has enabled light penetration to deeper lying tumours, in excess of 5 cm, a lack of phase III clinical trials has slowed down the uptake of PDT by the healthcare sector as a frontline treatment in cancer. However research continues to demonstrate the potential benefits of PDT and the need to stimulate funding and uptake of clinical studies using next generation photosensitizers offering advanced targeted delivery, improved photodynamic dose combined with modern light delivery technologies. This review surveys the available PDT treatments and emerging novel developments in the field with a particular focus on two-photon techniques that are anticipated to improve the effectiveness of PDT in tissues at depth and on next generation drugs that work without the need of the presence of oxygen for photosensitization making them effective where hypoxia has taken hold

Behaviour in the hand predicts male natal dispersal distances in an establishing reintroduced hihi (Notiomystis cincta) population

Natal dispersal is a complex behaviour influenced by multiple factors that are often sex-specific and density-dependent. Reintroduced populations are typically low in density in the initial years of establishment; hence, understanding natal dispersal patterns in this context is a critical component of reintroduction biology. Natal dispersal is a key behaviour that influences both the probability of recruitment, and simultaneously dictates the spatial configuration of the reintroduced population as it establishes. Here, we examine natal dispersal in a reintroduced population of an endangered New Zealand forest passerine, the hihi, Notiomystis cincta, in the first 3 years after reintroduction to a large, mature forest reserve. We examined (1) differences between the sexes, and (2) the relationship between temperament and natal dispersal distances (NDD) in locally bred hihi over this time period. We found NDD varied widely in both sexes, with mean NDD significantly higher in males than females. There was a sex-specific effect of temperament, with males that distress-called during handling dispersing further than those that did not. Our results show that while clusters of individuals have established across the reserve due to conspecific attraction, there is movement between these clusters, primarily a consequence of dispersal of males of a distinct temperament. Continuing to monitor natal dispersal patterns as populations establish will provide further insights into the role of dispersal in shaping establishment patterns in reintroduced populations

Dietary supplements for consideration in elite female footballers

The physical demands of professional female football have intensified in recent years. Supplements are only advised in addition to a healthy, balanced diet, but may warrant a greater prevalence in the professional game to support well-being, recovery, and performance. Supplements used by players should be safe, legal, and scientifically proven to be effective. An individual approach should be taken to using supplements dependant on the needs and goals of the player. Female players should aim to improve the frequency of protein intake throughout the day, whilst tailoring doses to individual body mass. Vitamin D supplementation is vital throughout the winter months in countries with limited sun exposure, however doses should be administered based on individual blood test results. Iron is likely to be important to the well-being of female athletes throughout the season, in particular during the menses. Omega-3 and collagen may be of greater benefit to female than male athletes during recovery from soft tissue injury, whilst probiotics and creatine are beneficial throughout the season for reducing risk of illness and optimising recovery, respectively. Ergogenic supplements for football include beta-alanine, nitrate and caffeine. Caution should be taken with caffeine use due to the varying tolerance of difference athletes and sleep impairments that can follow

Learning the subtle dance: the experience of therapists who deliver mentalisation-based therapy for borderline personality disorder

Objectives: This study aimed to understand therapists’ lived experiences of delivering mentalisation-based therapy (MBT), including their experiences of service user change. / Method: One-to-one semi-structured interviews or focus groups were conducted with 14 MBT therapists and analysed using interpretative phenomenological analysis (IPA). / Results: Four superordinate themes were identified: 1) experiencing the challenges and complexities of being with service users during MBT; 2) being on a journey of discovery and change; 3) being an MBT therapist: a new way of working and developing a new therapeutic identity; and 4) being a therapist in the group: seeing it all come together / Conclusion: Our findings highlight the complexity, challenges and individualised experience of working therapeutically with service users with a diagnosis of BPD. The study provides a perspective of service use change that is enriched by idiosyncrasies within the therapeutic encounter. We conclude with a consideration of implications for MBT research and clinical practice

A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic

Sewage, a complex mixture of organic and inorganic chemicals, is considered to be a major source of environmental pollution. A random screen of 20 organic man-made chemicals present in liquid effluents revealed that half appeared able to interact with the estradiol receptor. This was demonstrated by their ability to inhibit binding of 17 beta-estradiol to the fish estrogen receptor. Further studies, using mammalian estrogen screens in vitro, revealed that the two phthalate esters butylbenzyl phthalate (BBP) and di-n-butylphthalate (DBP) and a food antioxidant, butylated hydroxyanisole (BHA) were estrogenic; however, they were all less estrogenic than the environmental estrogen octylphenol. Phthalate esters, used in the production of various plastics (including PVC), are among the most common industrial chemicals. Their ubiquity in the environment and tendency to bioconcentrate in animal fat are well known. Neither BBP nor DBP were able to act as antagonists, indicating that, in the presence of endogenous estrogens, their overall effect would be cumulative. Recently, it has been suggested that environmental estrogens may be etiological agents in several human diseases, including disorders of the male reproductive tract and breast and testicular cancers. The current finding that some phthalate compounds and some food additives are weakly estrogenic in vitro, needs to be supported by further studies on their effects in vivo before any conclusions can be made regarding their possible role in the development of these condition

Time-resolved nanosecond fluorescence lifetime imaging and picosecond infrared spectroscopy of combretastatin A-4 in solution and in cellular systems

Fluorescence lifetime images of intrinsic fluorescence obtained with two-photon excitation at 630 nm are shown following uptake of a series of E-combretastatins into live cells, including human umbilical vein endothelial cells (HUVECs) that are the target for the anticancer activity of combretastatins. Images show distribution of the compounds within the cell cytoplasm and in structures identified as lipid droplets by comparison with images obtained following Nile red staining of the same cells. The intracellular fluorescent lifetimes are generally longer than in fluid solution as a consequence of the high viscosity of the cellular environment. Following incubation the intracellular concentrations of a fluorinated derivative of E combretastatin A4 in HUVECs are up to between 2 and 3 orders of magnitude higher than the concentration in the surrounding medium. Evidence is presented to indicate that at moderate laser powers (up to 6 mW) it is possible to isomerize up to 25% of the combretastatin within the femtolitre focal volume of the femtosecond laser beam. This suggests that it may be possible to activate the E-combretastatin (with low cellular toxicity) to the Z-isomer with high anticancer drug activity using two-photon irradiation. The isomerization of Z- and E-combretastatins by 266 nm irradiation has been probed by ultrafast time-resolved infrared spectroscopy. Results for the E-isomer show a rapid loss of excess vibrational energy in the excited state with a lifetime of 7 ps, followed by a slower process with a lifetime of 500 ps corresponding to the return to the ground state as also determined from the fluorescence lifetime. In contrast the Z-isomer, whilst also appearing to undergo a rapid cooling of the initial excited state, has a much shorter overall excited state lifetime of 14 ps

Dietary supplements for consideration in elite female footballers

The physical demands of professional female football have intensified in recent years. Supplements are only advised in addition to a healthy, balanced diet, but may warrant a greater prevalence in the professional game to support well-being, recovery and performance. Supplements used by players should be safe, legal and scientifically proven to be effective. An individual approach should be taken to using supplements dependant on the needs and goals of the player. Female players should aim to improve the frequency of protein intake throughout the day, whilst tailoring doses to individual body mass. Vitamin D supplementation is vital throughout the winter months in countries with limited sun exposure, however doses should be administered based on individual blood test results. Iron is likely to be important to the well-being of female athletes throughout the season, in particular during the menses. Omega-3 and collagen may be of greater benefit to female than male athletes during recovery from soft tissue injury, whilst probiotics and creatine are beneficial throughout the season for reducing risk of illness and optimising recovery, respectively. Ergogenic supplements for football include beta-alanine, nitrate and caffeine. Caution should be taken with caffeine use due to the varying tolerance of difference athletes and sleep impairments that can follow

Genome sequence, population history, and pelage genetics of the endangered African wild dog (Lycaon pictus)

BACKGROUND: The African wild dog (Lycaon pictus) is an endangered sub-Saharan canid threatened by severe habitat fragmentation, human-wildlife conflict, and infectious disease. A highly specialized carnivore, it is distinguished by its social structure, dental morphology, absence of dewclaws, and colorful pelage. RESULTS: We sequenced the genomes of two individuals from populations representing two distinct ecological histories (Laikipia County, Kenya and KwaZulu-Natal Province, South Africa). We reconstructed population demographic histories for the two individuals and scanned the genomes for evidence of selection. CONCLUSIONS: We show that the African wild dog has undergone at least two effective population size reductions in the last one million years. We found evidence of Lycaon individual-specific regions of low diversity, suggestive of inbreeding or population-specific selection. Further research is needed to clarify whether these population reductions and low diversity regions are characteristic of the species as a whole. We documented positive selection on the Lycaon mitochondrial genome. Finally, we identified several candidate genes (ASIP, MITF, MLPH, PMEL) that may play a role in the characteristic Lycaon pelage

Author Correction: The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Three-dimensional imaging and uptake of the anticancer drug combretastatin in cell spheroids and photoisomerization in gels with multiphoton excitation

The uptake of E-combretastatins, potential pro-drugs of the anticancer Z-isomers, into multicellular spheroids has been imaged by intrinsic fluorescence in three dimensions using two-photon excited fluorescence lifetime imaging with 625 nm ultrafast femtosecond laser pulses. Uptake is initially observed at the spheroid periphery but extends to the spheroid core within 30 minutes. Using agarose gels as a three-dimensional model, the conversion of Z(trans) E(cis) via two-photon photoisomerization is demonstrated and the location of this photochemical process may be selected precisely within the micron scale in all three dimensions at depths up to almost 2 mm. We discuss these results for enhanced tissue penetration at longer near-infrared wavelengths for cancer therapy and up to three-photon excitation and imaging using 930 nm laser pulses with suitable combretastatin analogues