Analysis of Multiple Causes of Death: A Review of Methods and Practices.

BACKGROUND: Research and reporting of mortality indicators typically focus on a single underlying cause of death selected from multiple causes recorded on a death certificate. The need to incorporate the multiple causes in mortality statistics-reflecting increasing multimorbidity and complex causation patterns-is recognized internationally. This review aims to identify and appraise relevant analytical methods and practices related to multiple causes. METHODS: We searched Medline, PubMed, Scopus, and Web of Science from their incept ion to December 2020 without language restrictions, supplemented by consultation with international experts. Eligible articles analyzed multiple causes of death from death certificates. The process identified 4,080 items of which we reviewed 434 full-text articles. RESULTS: Most articles we reviewed (76%, n = 332) were published since 2001. The majority of articles examined mortality by "any- mention" of the cause of death (87%, n = 377) and assessed pairwise combinations of causes (57%, n = 245). Since 2001, applications of methods emerged to group deaths based on common cause patterns using, for example, cluster analysis (2%, n = 9), and application of multiple-cause weights to re-evaluate mortality burden (1%, n = 5). We describe multiple-cause methods applied to specific research objectives for approaches emerging recently. CONCLUSION: This review confirms rapidly increasing international interest in the analysis of multiple causes of death and provides the most comprehensive overview, to our knowledge, of methods and practices to date. Available multiple-cause methods are diverse but suit a range of research objectives. With greater availability of data and technology, these could be further developed and applied across a range of settings.

Observed and predicted premature mortality in Australia due to non-communicable diseases: a population-based study examining progress towards the WHO 25X25 goal.

BACKGROUND: The World Health Organization's (WHO) 25X25 goal aims for a 25% relative reduction in premature death due to four non-communicable diseases (NCD4)-cancer, cardiovascular disease, chronic respiratory diseases and diabetes-by 2025 compared to 2010. This study aimed to quantify the premature mortality in the Australian population due to NCD4, quantify the variation in mortality rates by age and sex, predict the premature mortality due to NCD4 in 2025 and evaluate the progress towards the WHO 25X25 goal. METHODS: A population-based study using cause-specific mortality data of all deaths which occurred in Australia from 2010 to 2016 and registered up to 2017, for adults aged 30-69 years, was conducted. Age-specific and age-standardised mortality rates (ASMR) and probability of death for NCD4 were calculated for each year. ASMRs in 2016 were calculated for men and women. Deaths and the probability of death in 2025 were predicted using Poisson regression based on data from 2006 to 2016. To assess the progress against the WHO 25X25 goal, the relative reduction in the probability of death from NCD4 conditions in 2025 compared to 2010 was calculated. RESULTS: ASMRs for NCD4 decreased from 2010 to 2016, except for diabetes which increased on average by 2.5% per year. Across sociodemographic factors, ASMRs were highest in males and increased with age. The projected probability of premature death in 2025 was 7.36%, equivalent to a relative reduction of 25.16% compared to 2010 levels. CONCLUSIONS: Premature mortality due to cancer, cardiovascular disease, respiratory diseases and diabetes declined in Australia from 2010 to 2016. This trend is consistent across age groups and by sex, and higher mortality rates were observed in males and at older ages. Nationally, if the current trends continue, we estimate that Australia will achieve a 25.16% relative reduction in premature deaths due to NCD4 in 2025 compared to 2010, signifying substantial progress towards the WHO 25X25 goal. Concerted efforts will need to continue to meet the 25X25 goal, especially in the context of the COVID-19 pandemic.

Tangerine tomatoes: origin, biochemistry, potential health benefits and future prospects.

BACKGROUND: Tomatoes and lycopene have been associated with the prevention of chronic diseases. Tetra-cis lycopene from tangerine tomatoes has been reported to be more bioavailable than the all-trans isomer found in red tomatoes. Therefore, tangerine tomatoes might contain superior health benefits compared to those of red tomatoes. SCOPE AND APPROACH: This review focuses on the origin, biochemistry, nutritional composition, and potential health benefits of tangerine tomatoes, as well as their comparison with those of the red and high-ß-carotene varieties. Information gathered from numerous studies on tomatoes, as well as conflicting perspectives, have been summarized to provide an unbiased review. KEY FINDINGS AND CONCLUSION: The origin of tangerine tomatoes is disputable, but they were reportedly present from as early as 1934. The carotenoid biosynthesis pathway underlying the accumulation of tetra-cis lycopene in tangerine tomatoes has been well defined. However, the nutritional composition of tangerine tomatoes is not currently publicly available. The carotenoid composition of tangerine tomatoes is unique not only because of the presence of tetra-cis lycopene, but also due to the relatively high content of phytoene, phytofluene, ζ-carotene, and neurosporene relative to other tomato varieties. Although a few in vitro and in vivo studies have shown promising results, further studies are required to validate the health benefits of tangerine tomatoes. Furthermore, published data regarding the potential health benefits of tangerine tomatoes on cardiovascular and bone health is currently lacking even though red tomatoes have shown promise in these areas.

Anticancer Characteristics of Fomitopsis pinicola Extract in a Xenograft Mouse Model-a Preliminary Study.

Introduction: Medicinal mushrooms have been used for the treatment of diseases and general promotion of health for many centuries. Recent pharmacological research into medicinal mushrooms has identified various therapeutic properties, with applications in modern medicine.Aim: To evaluate the anti-cancer activities of Fomitopsis pinicola (F. pinicola) alcoholic extract in an in vivo setting.Methods: The anti-tumour effect of the F. pinicola extract was tested in a xenograft immune-compromised Rag-1 mouse model. This was followed by RT-PCR and metabolomics analyses.Results: There were no observable differences in tumor growth between treated and non-treated groups. The bioactive components were not detected in the mouse plasma or the tumor site.Conclusions: The extract was poorly absorbed; this is likely due to the timing of treatment, dosage levels and modifications made to the extract where the alcohol-based solvent was replaced with water. This, in combination with fractionation studies which identified most anti-cancer compounds to be hydrophobic, largely explained the lack of anti-cancer activities in vivo.

Compositional Analysis and Aroma Evaluation of Feijoa Essential Oils from New Zealand Grown Cultivars.

Feijoa is an aromatic fruit and the essential oil from feijoa peel could be a valuable by-product in the juicing industry. An initial comparison of the essential oil extraction methods, steam-distillation and hydro-distillation, was conducted. The volatile compounds in the essential oils from four feijoa cultivars were identified and semi-quantified by GC-MS and the aroma active compounds in each essential oil were characterized using SPME-GC-O-MS. Hydro-distillation, with a material to water ratio of 1:4 and an extraction time of 90 min, was the optimized extraction method for feijoa essential oil. The Wiki Tu cultivar produced the highest essential oil yield among the four selected cultivars. A total of 160 compounds were detected, among which 90 compounds were reported for the first time in feijoa essential oils. Terpenes and esters were dominant compounds in feijoa essential oil composition and were also major contributors to feijoa essential oil aroma. Key aroma active compounds in feijoa essential oils were α-terpineol, ethyl benzoate, (Z)-3-hexenyl hexanoate, linalool, (E)-geraniol, 2-undecanone, 3-octanone, α-cubebene, and germacrene D. This is the first report on the optimization of the extraction method and the establishment of the aroma profile of feijoa essential oils, with a comparison of four New Zealand grown cultivars.

Risk of fracture in men with prostate cancer on androgen deprivation therapy: a population-based cohort study in New Zealand.

BACKGROUND: Androgen deprivation therapy (ADT) administered as a prostate cancer treatment is known to exert multiple side effects including bone deterioration leading to bone fracture. The current analysis is to evaluate the burden of fracture risk in the New Zealand prostate cancer (PCa) population treated with ADT, and to understand the subsequent risk of mortality after a fracture. METHODS: Using datasets created through linking records from the New Zealand Cancer Registry, National Minimal Dataset, Pharmaceutical Collection and Mortality Collection, we studied 25,544 men (aged ≥40 years) diagnosed with PCa between 2004 and 2012. ADT was categorised into the following groups: gonadotropin-releasing hormone (GnRH) agonists, anti-androgens, combined androgen blockade (GnRH agonists plus anti-androgens), bilateral orchiectomy, and bilateral orchiectomy plus pharmacologic ADT (anti-androgens and/or GnRH agonists). RESULTS: Among patients receiving ADT, 10.8 % had a fracture compared to 3.2 % of those not receiving ADT (p < 0.0001). After controlling for age and ethnicity, the use of ADT was associated with a significantly increased risk of any fracture (OR = 2.83; 95 % CI 2.52-3.17) and of hip fracture requiring hospitalisation (OR = 1.82; 95 % CI 1.44-2.30). Those who received combined androgen blockade (OR = 3.48; 95 % CI 3.07-3.96) and bilateral orchiectomy with pharmacologic ADT (OR = 4.32; 95 % CI 3.34-5.58) had the greatest risk of fracture. The fracture risk following different types of ADT was confounded by pathologic fractures and spinal cord compression (SCC). ADT recipients with fractures had a 1.83-fold (95 % CI 1.68-1.99) higher mortality risk than those without a fracture. However, after the exclusion of pathologic fractures and SCC, there was no increased risk of mortality. CONCLUSIONS: ADT was significantly associated with an increased risk of any fracture and hip fracture requiring hospitalisation. The excess risk was partly driven by pathologic fractures and SCC which are associated with decreased survival in ADT users. Identification of those at higher risk of fracture and close monitoring of bone health while on ADT is an important factor to consider. This may require monitoring of bone density and bone marker profiles.

CD8+ T-cell responses to different HIV proteins have discordant associations with viral load.

Selection of T-cell vaccine antigens for chronic persistent viral infections has been largely empirical. To define the relationship, at the population level, between the specificity of the cellular immune response and viral control for a relevant human pathogen, we performed a comprehensive analysis of the 160 dominant CD8(+) T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific responses were associated with lowering viremia. Env-specific and Accessory/Regulatory protein-specific responses were associated with higher viremia. Increasing breadth of Gag-specific responses was associated with decreasing viremia and increasing Env breadth with increasing viremia. Association of the specific CD8(+) T-cell response with low viremia was independent of HLA type and unrelated to epitope sequence conservation. These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation.

Accuracy of an accelerated, culture-based assay for detection of group B streptococcus.

OBJECTIVE: To determine the validity of a novel Group B Streptococcus (GBS) diagnostic assay for the detection of GBS in antepartum patients. STUDY DESIGN: Women were screened for GBS colonization at 35 to 37 weeks of gestation. Three vaginal-rectal swabs were collected per patient; two were processed by traditional culture (commercial laboratory versus in-house culture), and the third was processed by an immunoblot-based test, in which a sample is placed over an antibody-coated nitrocellulose membrane, and after a six-hour culture, bound GBS is detected with a secondary antibody. RESULTS: 356 patients were evaluated. Commercial processing revealed a GBS prevalence rate of 85/356 (23.6%). In-house culture provided a prevalence rate of 105/356 (29.5%). When the accelerated GBS test result was compared to the in-house GBS culture, it demonstrated a sensitivity of 97.1% and a specificity of 88.4%. Interobserver reliability for the novel GBS test was 88.2%. CONCLUSIONS: The accelerated GBS test provides a high level of validity for the detection of GBS colonization in antepartum patients within 6.5 hours and demonstrates a substantial agreement between observers.

Quantifying cause-related mortality in Australia, incorporating multiple causes: observed patterns, trends and practical considerations.

BACKGROUND: Mortality statistics using a single underlying cause of death (UC) are key health indicators. Rising multimorbidity and chronic disease mean that deaths increasingly involve multiple conditions. However, additional causes reported on death certificates are rarely integrated into mortality indicators, partly due to complexities in data and methods. This study aimed to assess trends and patterns in cause-related mortality in Australia, integrating multiple causes (MC) of death. METHODS: Deaths (n = 1 773 399) in Australia (2006-17) were mapped to 136 ICD-10-based groups and MC indicators applied. Age-standardized cause-related rates (deaths/100 000) based on the UC (ASRUC) were compared with rates based on any mention of the cause (ASRAM) using rate ratios (RR = ASRAM/ASRUC) and to rates based on weighting multiple contributing causes (ASRW). RESULTS: Deaths involved on average 3.4 causes in 2017; the percentage with >4 causes increased from 20.9 (2006) to 24.4 (2017). Ischaemic heart disease (ASRUC = 73.3, ASRAM = 135.8, ASRW = 63.5), dementia (ASRUC = 51.1, ASRAM = 98.1, ASRW = 52.1) and cerebrovascular diseases (ASRUC = 39.9, ASRAM = 76.7, ASRW = 33.5) ranked as leading causes by all methods. Causes with high RR included hypertension (ASRUC = 2.2, RR = 35.5), atrial fibrillation (ASRUC = 8.0, RR = 6.5) and diabetes (ASRUC = 18.5, RR = 3.5); the corresponding ASRW were 12.5, 12.6 and 24.0, respectively. Renal failure, atrial fibrillation and hypertension ranked among the 10 leading causes by ASRAM and ASRW but not by ASRUC. Practical considerations in working with MC data are discussed. CONCLUSIONS: Despite the similarities in leading causes under the three methods, with integration of MC several preventable diseases emerged as leading causes. MC analyses offer a richer additional perspective for population health monitoring and policy development.

Prospective investigation of second-trimester thrombin activation and preterm birth.

OBJECTIVE: We sought to determine if second-trimester amniotic fluid thrombin-antithrombin (TAT) complexes concentration correlates with subsequent preterm birth. STUDY DESIGN: A cohort of 550 women with singleton nonanomalous pregnancies undergoing second-trimester genetic amniocentesis was followed up to delivery and analyzed as a nested case-control study. Cases of preterm birth (n = 52) were compared with 104 term control subjects. Amniotic fluid collected at amniocentesis was tested for TAT. RESULTS: TAT concentrations were significantly higher in women who delivered preterm (median 115.9 µg/L) than in those who did not (median 62.2 µg/L; P < .001). This difference persisted when 31 spontaneous preterm births and 21 indicated preterm births were analyzed separately. The odds ratios for preterm birth in the highest TAT quartile relative to the lowest quartile was 4.98 (95% confidence interval, 1.17-22.01; P = .007). CONCLUSION: We found a difference in the pattern of intraamniotic thrombin generation between women destined to deliver at term and those who deliver preterm, regardless of the type of preterm birth.

Comparison of bactericidal properties of alcohol-based chlorhexidine versus povidone-iodine prior to amniocentesis.

OBJECTIVE: To compare the bactericidal properties of povidone-iodine versus alcohol-based chlorhexidine solution for cleansing the gravid abdomen prior to amniocentesis. METHODS: Fifty study participants were recruited from the University of Texas Women's Clinic in Houston, Texas. Two baseline swabs of the patients' abdomens were obtained to assess bacterial flora prior to treatment. A 10% povidone-iodine solution and 2% chlorhexidine gluconate with 70% isopropyl alcohol solution in a 3-mL prefilled applicator (Chloraprep, Cardinal Health, Inc., Leawood, KS) were then applied on different sides of the abdomen. After 30 seconds, cultures were obtained and plated on Trypticase Soy (PML Microbiologicals, Durham, NC) with sheep's blood agar for aerobic flora. Plates were incubated at 37°C for 48 hours for aerobic flora. Colony-forming units were counted and recorded. RESULTS: No statistically significant difference was detected between baseline colony counts between the left and right side of each patient's abdomen (p = 0.33) prior to cleansing. Postcleansing colony counts were evaluated, and a statistically significant difference was identified, favoring chlorhexidine as a more efficacious abdominal cleanser (p <0.001). CONCLUSION: We demonstrated that 2% chlorhexidine with 70% isopropyl alcohol had excellent bactericidal efficacy and was superior to povidone-iodine for cleansing the maternal abdomen.

Limited immunogenicity of HIV CD8+ T-cell epitopes in acute Clade C virus infection.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) responses contribute to the decline in acute peak viremia following infection. However, data on the relative immunogenicity of CD8(+) T-cell epitopes during and after acute viremia are lacking. METHODS: We characterized CD8(+) T-cell responses in 20 acutely infected, antiretroviral-naive individuals with HIV-1 subtype C infection using the interferon-γ enzyme-linked immunosorbent spot assay. Eleven of these had not fully seroconverted at the time of analysis. Viruses from plasma were sequenced within defined cytotoxic T-lymphocyte (CTL) cell epitopes for selected subjects. RESULTS: At approximately 28 days after estimated initial infection, CD8(+) T-cell responses were directed against an average of 3 of the 410 peptides tested (range, 0-6); 2 individuals had no detectable responses at this time. At 18 weeks, the average number of peptides targeted had increased to 5 (range 0-11). Of the 56 optimal Gag CTL epitopes sequenced, 31 were wild-type in the infecting viruses, but only 11 of 31 elicited measurable CD8(+) T-cell responses. CONCLUSIONS: These data demonstrate that the majority of CD8(+) responses are not elicited during acute HIV infection despite the presence of the cognate epitope in the infecting strain. There is a need to define factors that influence lack of induction of effective immune responses and the parameters that dictate immunodominance in acute infection.

Phenolic-rich feijoa extracts from flesh, peel and whole fruit activate apoptosis pathways in the LNCaP cell line.

This study aimed to explore the potential anticancer activity of phenolic-rich feijoa extracts from the flesh, peel, and whole fruit on the human prostate cancer cell line (LNCaP). Results showed that feijoa extracts had cancer-specific anti-proliferative activity on the LNCaP cell line. The anticancer activity of feijoa extracts was shown through activation of the caspase-dependent apoptosis pathway based on the increase of sub-G1 phase in the cell cycle, the decrease of mitochondrial membrane potential, as well as the elevated caspase 3, 8, and 9 activity in the treated LNCaP cells. The anti-cancer activity of feijoa extracts could be attributed to the high total phenolic contents (0.14-0.37 mg GAE/mg dw) and, in particular, the high ellagic acid content (2.662-9.119 µg/mg dw). The successful activation of the caspase-dependent apoptosis pathway indicates that phenolic-rich feijoa extracts have a good potential to be utilized as a functional ingredient in foods and nutraceuticals.

Education-related inequalities in cause-specific mortality: first estimates for Australia using individual-level linked census and mortality data.

BACKGROUND: Socioeconomic inequalities in mortality are evident in all high-income countries, and ongoing monitoring is recommended using linked census-mortality data. Using such data, we provide the first estimates of education-related inequalities in cause-specific mortality in Australia, suitable for international comparisons. METHODS: We used Australian Census (2016) linked to 13 months of Death Registrations (2016-17). We estimated relative rates (RR) and rate differences (RD, per 100 000 person-years), comparing rates in low (no qualifications) and intermediate (secondary school) with high (tertiary) education for individual causes of death (among those aged 25-84 years) and grouped according to preventability (25-74 years), separately by sex and age group, adjusting for age, using negative binomial regression. RESULTS: Among 13.9 M people contributing 14 452 732 person-years, 84 743 deaths occurred. All-cause mortality rates among men and women aged 25-84 years with low education were 2.76 [95% confidence interval (CI): 2.61-2.91] and 2.13 (2.01-2.26) times the rates of those with high education, respectively. We observed inequalities in most causes of death in each age-sex group. Among men aged 25-44 years, relative and absolute inequalities were largest for injuries, e.g. transport accidents [RR = 10.1 (5.4-18.7), RD = 21.2 (14.5-27.9)]). Among those aged 45-64 years, inequalities were greatest for chronic diseases, e.g. lung cancer [men RR = 6.6 (4.9-8.9), RD = 57.7 (49.7-65.8)] and ischaemic heart disease [women RR = 5.8 (3.7-9.1), RD = 20.2 (15.8-24.6)], with similar patterns for people aged 65-84 years. When grouped according to preventability, inequalities were large for causes amenable to behaviour change and medical intervention for all ages and causes amenable to injury prevention among young men. CONCLUSIONS: Australian education-related inequalities in mortality are substantial, generally higher than international estimates, and related to preventability. Findings highlight opportunities to reduce them and the potential to improve the health of the population.

Gag-protease-mediated replication capacity in HIV-1 subtype C chronic infection: associations with HLA type and clinical parameters.

The mechanisms underlying HIV-1 control by protective HLA class I alleles are not fully understood and could involve selection of escape mutations in functionally important Gag epitopes resulting in fitness costs. This study was undertaken to investigate, at the population level, the impact of HLA-mediated immune pressure in Gag on viral fitness and its influence on HIV-1 pathogenesis. Replication capacities of 406 recombinant viruses encoding plasma-derived Gag-protease from patients chronically infected with HIV-1 subtype C were assayed in an HIV-1-inducible green fluorescent protein reporter cell line. Viral replication capacities varied significantly with respect to the specific HLA-B alleles expressed by the patient, and protective HLA-B alleles, most notably HLA-B81, were associated with lower replication capacities. HLA-associated mutations at low-entropy sites, especially the HLA-B81-associated 186S mutation in the TL9 epitope, were associated with lower replication capacities. Most mutations linked to alterations in replication capacity in the conserved p24 region decreased replication capacity, while most in the highly variable p17 region increased replication capacity. Replication capacity also correlated positively with baseline viral load and negatively with baseline CD4 count but did not correlate with the subsequent rate of CD4 decline. In conclusion, there is evidence that protective HLA alleles, in particular HLA-B81, significantly influence Gag-protease function by driving sequence changes in Gag and that conserved regions of Gag should be included in a vaccine aiming to drive HIV-1 toward a less fit state. However, the long-term clinical benefit of immune-driven fitness costs is uncertain given the lack of correlation with longitudinal markers of disease progression.

Size of the nanovectors determines the transplacental passage in pregnancy: study in rats.

OBJECTIVE: The objective of the study was to examine whether the size of silicon nanovectors (SNVs) inhibits their entrance into the fetal circulation. STUDY DESIGN: Pregnant rats were intravenously administered with SNVs or saline. The SNVs were spherical particles with 3 escalating diameters: 519 nm, 834 nm, and 1000 nm. The maternal and fetal distribution of SNVs was assessed. RESULTS: In animals that received 1000 or 834 nm SNV, silicon (Si) levels were significantly higher in the maternal organs vs the saline group, whereas the silicon levels in fetal tissues were similar to controls. However, in animals receiving 519 nm SNVs, fetal silicon levels were significantly higher in the SNV group compared with the saline group (5.93 ± 0.67 µg Si per organ vs 4.80 ± 0.33, P = .01). CONCLUSION: Larger SNVs do not cross the placenta to the fetus and, remaining within the maternal circulation, can serve as carriers for harmful medications in order to prevent fetal exposure.

Rapid diagnostic test for identifying group B streptococcus.

Neonatal infection with Streptococcus agalactiae (group B streptococcus [GBS]) causes significant morbidity and mortality. A truly rapid diagnostic test for identifying GBS would allow for more timely initiation of antibiotic prophylaxis and also reduce the administration of antibiotics for the prevention of early onset neonatal GBS infection. A stock culture was formed from a laboratory reference strain of GBS and was diluted from 10 (7) to 10 (1) bacteria/mL. Specific concentrations were used to inoculate nitrocellulose membranes (NCMs) that had been coated previously with polyclonal rabbit antibody against GBS. After specific times, the NCMs were removed from the sheep blood agar medium, and horseradish-peroxidase conjugate polyclonal antibody against GBS was added. Bound antibody was detected with diaminobenzidine. After 6 hours of incubation, GBS was detected at concentrations from 10 (7) through 10 (4) bacterial/mL. After 4 hours of incubation, GBS was detected at concentrations from 10 (7) through 10 (5) bacteria/mL. GBS was not detected at 2 hours of incubation. Rapid growth and detection of GBS can be performed, and the results can be reliably attained as early as 4 hours. This is in marked contrast to the 48 to 72 hours required by current methods.

Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis.

Androgen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers-sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (- 10.06%, p = 0.0057), former-ADT (- 12.77%, p = 0.0239), and in PCa controls group (- 16.73, p = 0.0022); and OPG levels in chronic ADT (- 8.28%, p = 0.003) and PCa controls group (- 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

Characterisation of Extracts and Anti-Cancer Activities of Fomitopsis pinicola.

Fomitopsis pinicola (Sw. Karst) is a common bracket fungus, with a woody texture. It is found predominantly in coniferous forests in temperate regions throughout Europe and Asia. Fomitopsis pinicola has been extensively used for medicinal purposes, particularly in Chinese and Korean traditional medicine. In this mini-review, the anti-cancer characteristics of F. pinicola extracts were investigated. In vitro experiments revealed the pro-apoptotic, anti-oxidant and anti-inflammatory properties of extracts, whilst two of three in vivo studies reported an inhibition of tumour growth and prolonged survival. Only studies wherein fungal specimens were sourced from Europe or Asia were included in this review, as samples sourced as F. pinicola from North America were probably not F. pinicola, but a different species. Although not one of the most revered fungal species, F. pinicola has been used as a medicinal fungus for centuries, as well as consumed as a health food supplement. To date, the results from only three in vivo studies, investigating anti-cancer properties, have been published. Further studies, using comprehensively identified specimens, are required to fully elucidate the anti-cancer properties of F. pinicola extracts.