Pentadesma butyracea seed butter or fat (PBSB) is a vegetable fat extracted from the seeds of the P. butyracea plant. The butter has potential use in the food, pharmaceutical, and cosmetic industries. The study investigated traditional PBSB processing methods in Ghana and evaluated their effects on yield, physicochemical parameters, and fatty acid composition. Four traditional extraction methods were identified and evaluated, and these methods are direct wet extraction of PBSB from a fresh mixture of the seed paste and water (DEW); wet extraction of PBSB from a 12-hour fermented mixture of the seed paste and water (FWO); direct wet extraction of PBSB from a fresh mixture of the seed paste, salt, and water (DES); and wet extraction of PBSB from a 12-hour fermented mixture of the seed paste, salt, and water (FSO). Results of physicochemical properties of the PBSB samples showed moisture content of 0.06-0.07%, free fatty acid of 1.38-2.43%, iodine value of 56.50-56.85 Wijs, peroxide value of 5.58-8.52 mEq/kg, relative density of 0.91, refractive index of 1.462-1.464, percent impurities of 0.015-0.017%, saponification value of 165.57-178.02 mg KOH/g, and percent unsaponifiable matter of 2.60-3.18%. The PBSB yield varied in the range of 21.68-26.97%, with the highest average butter yield observed for FWO. Seventeen fatty acids were characterized in the PBSB samples, and they included ten saturated fatty acids, five monounsaturated fatty acids, and two polyunsaturated fatty acids. Key fatty acids found in the PBSB samples were oleic acid (51.21-51.31%), stearic acid (43.22-43.33%), palmitic acid (2.91-3.07%), linoleic acid (0.49-0.51%), linolenic acid (0.12-0.20%), and arachidic acid (0.14-0.15%). PBSB samples produced by the various traditional extraction methods in Ghana recorded similar physicochemical characteristics as unrefined shea butter per the Regional Standard for Unrefined Shea Butter (CXS 325R-2017) as well as Cook Brand Margarine, a common commercial baking fat, and thus, their potential food application such as an alternative shortening/ingredient could be explored in a future study.
Importance: Outcomes from protocol-directed active surveillance for favorable-risk prostate cancers are needed to support decision-making. Objective: To characterize the long-term oncological outcomes of patients receiving active surveillance in a multicenter, protocol-directed cohort. Design, Setting, and Participants: The Canary Prostate Active Surveillance Study (PASS) is a prospective cohort study initiated in 2008. A cohort of 2155 men with favorable-risk prostate cancer and no prior treatment were enrolled at 10 North American centers through August 2022. Exposure: Active surveillance for prostate cancer. Main Outcomes and Measures: Cumulative incidence of biopsy grade reclassification, treatment, metastasis, prostate cancer mortality, overall mortality, and recurrence after treatment in patients treated after the first or subsequent surveillance biopsies. Results: Among 2155 patients with localized prostate cancer, the median follow-up was 7.2 years, median age was 63 years, 83% were White, 7% were Black, 90% were diagnosed with grade group 1 cancer, and median prostate-specific antigen (PSA) was 5.2 ng/mL. Ten years after diagnosis, the incidence of biopsy grade reclassification and treatment were 43% (95% CI, 40%-45%) and 49% (95% CI, 47%-52%), respectively. There were 425 and 396 patients treated after confirmatory or subsequent surveillance biopsies (median of 1.5 and 4.6 years after diagnosis, respectively) and the 5-year rates of recurrence were 11% (95% CI, 7%-15%) and 8% (95% CI, 5%-11%), respectively. Progression to metastatic cancer occurred in 21 participants and there were 3 prostate cancer-related deaths. The estimated rates of metastasis or prostate cancer-specific mortality at 10 years after diagnosis were 1.4% (95% CI, 0.7%-2%) and 0.1% (95% CI, 0%-0.4%), respectively; overall mortality in the same time period was 5.1% (95% CI, 3.8%-6.4%). Conclusions and Relevance: In this study, 10 years after diagnosis, 49% of men remained free of progression or treatment, less than 2% developed metastatic disease, and less than 1% died of their disease. Later progression and treatment during surveillance were not associated with worse outcomes. These results demonstrate active surveillance as an effective management strategy for patients diagnosed with favorable-risk prostate cancer.
Background: Yoghurt is one of the most popularly consumed fermented products which provides several nutritional benefits. Yoghurt products often include flavour and colour additives however, growing awareness of the risks associated with synthetic food additives has necessitated the need to explore more natural colour and flavour as food additives. Methods: This study evaluated the effect of beetroot puree as flavouring and colourant in yoghurt production and quality. To develop the yoghurt product, incubation time and proportion of beetroot puree were optimized based on the resulting pH, titratable acidity, colour, and viscosity using response surface methods. Results: Optimum yoghurt formulations were obtained in products containing 2 %, 2.03 % and 8 % beetroot puree following an incubation of 2.5h. Increasing beetroot puree did not affect the pH and titratable acidity of the yoghurt samples but slightly influenced the viscosity of the yoghurt. The colour of yoghurt was mainly affected by the puree concentration. A consumer acceptance test was conducted on the optimized products compared to a control sample without beetroot. Yoghurt incorporated with 8 % beetroot puree was the least preferred with a mean score of 6.08, whereas yoghurt incorporated with 2.03 % beetroot puree was the most preferred (7.42), with a higher acceptance than the control (7.28). Conclusion: /Implications for industry: Findings from the study provide evidence for exploration of beetroot yoghurt as a natural product alternative to the use of synthetic flavour and colour additives in yoghurt.
Introduction: Strains of Leptospira interrogans belonging to two very closely related serovars, Icterohaemorrhagiae and Copenhageni, have been associated with disease in mammalian species and are the most frequently reported agents of human leptospirosis. They are considered the most pathogenic serovars and represent more than half of the leptospires encountered in severe human infections. Material and Methods: Nineteen such isolates from the United Kingdom - human, domestic and wildlife species - were typed using three monoclonal antibodies (F12 C3, F70 C14 and F70 C24) in an attempt to elucidate their epidemiology. They were further examined by restriction endonuclease analysis (REA), multiple-locus variable-number tandem repeat analysis (MLVA) and lic12008 gene sequence analysis. Results: Monoclonal antibody F12 C3, which is highly specific for Icterohaemorrhagiae and Copenhageni, confirmed that all the strains belonged to these two serovars. Sixteen strains were identified as Copenhageni and three as Icterohaemorrhagiae serovar. Only one restriction pattern type was identified, thus confirming that REA is not able to discriminate between the Icterohaemorrhagiae and Copenhageni serovars. Variable-number tandem-repeat analysis found three loci with differences in the repeat number, indicating genetic diversity between British isolates. Sequences of the lic12008 gene showed that all isolates identified as the Icterohaemorrhagiae serotype have a single base insertion, in contrast to the same sequences of the Copenhageni serotype. Conclusion: Copenhageni is the predominant serovar in the Icterohaemorrhagiae serogroup isolated in British Isles. There is a genetic diversity of MLVA patterns of the isolates but no genetic tool used in the study was able to determine serovars.
BACKGROUND: Pharmacists with specialized knowledge and skills are able to seek board certification from the Board of Pharmacy Specialties (BPS). In 2018, BPS conducted research to evaluate the relationship between eligibility pathways (i.e., completion of a postgraduate year 2 [PGY-2] specialty residency, completion of a postgraduate year 1 [PGY-1] residency plus 2 years of practice experience, or 4 years of practice experience) and certification examination pass rate. The study found statistically significant differences in pass rate based on eligibility criteria across all 6 specialties studied. There was a trend for higher pass rates in cohorts of examinees eligible for board certification based on completion of postgraduate residency training. OBJECTIVES: This study aimed to compare examination pass rates among different eligibility cohorts for board certification in recognized pharmacy practice specialties and compare contemporary findings with previously published findings. DESIGN: This cross-sectional study was conducted on data retrieved from BPS certification applications and examination administration records. SETTING AND PARTICIPANTS: Examinees in the United States and Canada for 9 BPS certification programs. OUTCOME MEASURES: A chi-square analysis was used to identify whether there were differences in pass rate among eligibility pathway cohorts. RESULTS: A total of 14,894 examinees met inclusion criteria; 6312 (42.4%) of the 14,894 examinees analyzed were eligible via practice experience, 5768 (38.7%) were eligible via PGY-1 completion, and 2814 (18.9%) were eligible via PGY-2 completion. A statistically significant difference was found for the relationship between pass rate and eligibility pathway for 8 of 9 BPS certification examinations analyzed (significant: ambulatory care pharmacy, critical care pharmacy, cardiology pharmacy, infectious diseases pharmacy, oncology pharmacy, psychiatric pharmacy, pediatric pharmacy, pharmacotherapy; not significant: solid organ transplantation pharmacy). Post hoc analyses showed that, in most cases, the PGY-2 eligibility cohort outperformed the PGY-1 eligibility cohort, which in turn outperformed the practice experience pathway cohort. CONCLUSION: Analysis of contemporary BPS certification examination administration data yields statistically significant differences among the pass rates by eligibility pathway, replicating previous findings and expanding the scope of the analysis.
Internship and Residency , Pharmacy , Humans , United States , Child , Specialty Boards , Pharmacists , Cross-Sectional Studies , Certification , Educational Measurement
Although parasites can kill their hosts, they also commonly cause nonlethal effects on their hosts, such as altered behaviors or feeding rates. Both the lethal and nonlethal effects of parasites can influence host resource consumption. However, few studies have explicitly examined the joint lethal and nonlethal effects of parasites to understand the net impacts of parasitism on host resource consumption. To do this, we adapted equations used in the indirect effects literature to quantify how parasites jointly influence basal resource consumption through nonlethal effects (altered host feeding rate) and lethal effects (increased host mortality). To parametrize these equations and to examine the potential temperature sensitivity of parasite influences, we conducted a fully factorial lab experiment (crossing trematode infection status and a range of temperatures) to quantify feeding rates and survivorship curves of snail hosts. We found that infected snails had significantly higher mortality and ate nearly twice as much as uninfected snails and had significantly higher mortality, resulting in negative lethal effects and positive nonlethal effects of trematodes on host resource consumption. The net effects of parasites on resource consumption were overall positive in this system, but did vary with temperature and experimental duration, highlighting the context dependency of outcomes for the host and ecosystem. Our work demonstrates the importance of jointly investigating lethal and nonlethal effects of parasites and provides a novel framework for doing so.
PURPOSE: Active surveillance is a safe and effective strategy for men with lower-risk prostate cancer who want to avoid local therapy; however, many patients on active surveillance progress to active treatment (eg, prostatectomy or radiation). We hypothesized that apalutamide would decrease active surveillance attrition rates through downstaging low-grade tumors. MATERIALS AND METHODS: This was an open-label, single-arm, phase II study testing 90 days of oral apalutamide 240 mg daily in men with low- to intermediate-risk prostate cancer on active surveillance. The primary objective was to determine the percentage of patients with a negative biopsy immediately following treatment. Secondary objectives were to assess long-term clinical outcomes, quality of life, safety, and biomarkers of response/resistance. RESULTS: Twenty-three patients enrolled and 22 completed 90 days of apalutamide with post-treatment biopsy. Fifteen (65%) had Grade Group 1 disease, and all others had Grade Group 2 disease. Seven (30%) had favorable- to intermediate-risk disease. Of 22 evaluable patients, 13 (59%) had no residual cancer on post-treatment biopsy. The median time to first positive biopsy was 364 days (95% CI: 91-742 days). The impact of apalutamide on quality of life was minimal and transient. Decipher risk classifier revealed a greater number of negative post-treatment biopsies in those with higher baseline genomic risk score (P = .01). CONCLUSIONS: The negative repeat biopsy rate following 90 days of apalutamide was high in men with prostate cancer followed on active surveillance. Apalutamide was safe, well tolerated, and had minimal impact on quality of life. Randomized studies evaluating the effects of apalutamide in men enrolled on active surveillance are warranted.
Prostatic Neoplasms , Quality of Life , Male , Humans , Prostatic Neoplasms/pathology , Thiohydantoins , Androgen Receptor Antagonists/adverse effects , Watchful Waiting
Modifiable lifestyle factors, such as following a healthy dietary pattern may delay or prevent prostate cancer (PCa) progression. However, few studies have evaluated whether following specific dietary patterns after PCa diagnosis impacts risk of disease progression among men with localized PCa managed by active surveillance (AS). 564 men enrolled in the Canary Prostate Active Surveillance Study, a protocol-driven AS study utilizing a pre-specified prostate-specific antigen monitoring and surveillance biopsy regimen, completed a food frequency questionnaire (FFQ) at enrollment and had ≥ 1 surveillance biopsy during follow-up. FFQs were used to evaluate adherence to the Dietary Guidelines for Americans (Healthy Eating index (HEI))-2015, alternative Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns. Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models. During a median follow-up of 7.8 years, 237 men experienced an increase in Gleason score on subsequent biopsy (grade reclassification). Higher HEI-2015, aMED or DASH diet scores after diagnosis were not associated with significant reductions in the risk of grade reclassification during AS. However, these dietary patterns have well-established protective effects on chronic diseases and mortality and remain a prudent choice for men with prostate cancer managed by AS.
Diet, Mediterranean , Prostatic Neoplasms , Male , Humans , Prostate/pathology , Neoplasm Grading , Watchful Waiting/methods , Prospective Studies , Prostatic Neoplasms/pathology
PURPOSE: To track and analyze the growth of 12 Board of Pharmacy Specialties (BPS) specialties from 2008 to 2020 and, subject to criteria, to project specialty numbers through 2025. The analysis considered residency data and Bureau of Labor Statistics projections. METHODS: BPS data were used to determine numeric growth, growth rates, and trends for 12 BPS specialties from 2008 to 2020. Specialties begun after 2008 were analyzed from their start date. For specialties with more than 2 data points and coefficients of determination greater than 0.80, we calculated projections through 2025. We also estimated the percentage of BPS-certified pharmacists with postgraduate year 1 training. RESULTS: BPS-certified pharmacists grew in number from 3,004 (2008) to 41,802 (2020), an over 13-fold increase. Currently, 4 of the 5 largest specialties (pharmacotherapy, ambulatory care, oncology, and critical care) continue to grow at a fast rate. Pharmacotherapy experienced the largest numeric growth (20,624) despite the ongoing introduction of new specialties. Critical care and infectious diseases had the highest growth rates (both 32%). We were able to make projections for 10 of 12 specialties, with greater than 62,000 certifications projected by 2025. Growth to these projected levels will require more residencies and more certification preparation opportunities. Residency-trained BPS specialists currently constitute slightly less than 50% of the BPS-certified population. CONCLUSION: Specialization in the pharmacy profession is growing at a rapid pace. As more clinical privileges are approved, the demand for more specialized pharmacists will likely continue to increase. Data from this study document the growth of the pharmacy specialty workforce. The data and analysis can be used to estimate potential pharmacist contributions across the healthcare spectrum in clinical areas where BPS-certified pharmacists practice.
Medicine , Pharmaceutical Services , Pharmacies , Pharmacy , Humans , Certification
PURPOSE: We assessed whether Prostate Health Index results improve prediction of grade reclassification for men on active surveillance. METHODS AND MATERIALS: We identified men in Canary Prostate Active Surveillance Study with Grade Group 1 cancer. Outcome was grade reclassification to Grade Group 2+ cancer. We considered decision rules to maximize specificity with sensitivity set at 95%. We derived rules based on clinical data (R1) vs clinical data+Prostate Health Index (R3). We considered an "or"-logic rule combining clinical score and Prostate Health Index (R4), and a "2-step" rule using clinical data followed by risk stratification based on Prostate Health Index (R2). Rules were applied to a validation set, where values of R2-R4 vs R1 for specificity and sensitivity were evaluated. RESULTS: We included 1,532 biopsies (n = 610 discovery; n = 922 validation) among 1,142 men. Grade reclassification was seen in 27% of biopsies (23% discovery, 29% validation). Among the discovery set, at 95% sensitivity, R2 yielded highest specificity at 27% vs 17% for R1. In the validation set, R3 had best performance vs R1 with Δsensitivity = -4% and Δspecificity = +6%. There was slight improvement for R3 vs R1 for confirmatory biopsy (AUC 0.745 vs R1 0.724, ΔAUC 0.021, 95% CI 0.002-0.041) but not for subsequent biopsies (ΔAUC -0.012, 95% CI -0.031-0.006). R3 did not have better discrimination vs R1 among the biopsy cohort overall (ΔAUC 0.007, 95% CI -0.007-0.020). CONCLUSIONS: Among active surveillance patients, using Prostate Health Index with clinical data modestly improved prediction of grade reclassification on confirmatory biopsy and did not improve prediction on subsequent biopsies.
Prostate , Prostatic Neoplasms , Biopsy , Humans , Male , Neoplasm Grading , Prostate/pathology , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Watchful Waiting/methods
AbstractPhysiological processes influence how individuals perform in various environmental contexts. The basis of such processes, metabolism, scales allometrically with body mass and nonlinearly with temperature, as described by a thermal performance curve. Past studies of thermal performance curves tend to focus on effects of temperature on a single body size or population, rather than variation in the thermal performance curve across sizes and populations. Here, we estimate intraspecific variation in parameters of the thermal performance curve in the salt marsh gastropod Littoraria irrorata. First, we quantify the thermal performance curve for respiration rate as a function of both temperature and body size in Littoraria and evaluate whether the thermal parameters and body size scaling are interdependent. Next, we quantify how parameters in the thermal performance curve for feeding rate vary between three Littoraria populations that occur along a latitudinal gradient. Our work suggests that the thermal traits describing Littoraria respiration are dependent on body mass and that both the thermal traits and the mass scaling of feeding vary across sites. We found limited evidence to suggest that mass scaling of Littoraria feeding or respiration rates depends on temperature. Variation in the thermal performance curves interacts with the size structure of the Littoraria population to generate divergent population-level responses to temperature. These results highlight the importance of considering variation in population size structure and physiological allometry when attempting to predict how temperature change will affect physiological responses and consumer-resource interactions.
Gastropoda , Vinca , Animals , Humans , Phenotype , Temperature , Wetlands
BACKGROUND: Pathogenic germline mutations in several rare penetrant cancer predisposition genes are associated with an increased risk of aggressive prostate cancer (PC). Our objectives were to determine the prevalence of pathogenic germline mutations in men with low-risk PC on active surveillance, and assess whether pathogenic germline mutations associate with grade reclassification or adverse pathology, recurrence, or metastases, in men treated after initial surveillance. METHODS: Men prospectively enrolled in the Canary Prostate Active Surveillance Study (PASS) were retrospectively sampled for the study. Germline DNA was sequenced utilizing a hereditary cancer gene panel. Mutations were classified according to the American College of Clinical Genetics and Genomics' guidelines. The association of pathogenic germline mutations with grade reclassification and adverse characteristics was evaluated by weighted Cox proportional hazards modeling and conditional logistic regression, respectively. RESULTS: Overall, 29 of 437 (6.6%) study participants harbored a pathogenic germline mutation of which 19 occurred in a gene involved in DNA repair (4.3%). Eight participants (1.8%) had pathogenic germline mutations in three genes associated with aggressive PC: ATM, BRCA1, and BRCA2. The presence of pathogenic germline mutations in DNA repair genes did not associate with adverse characteristics (univariate analysis HR = 0.87, 95% CI: 0.36-2.06, p = 0.7). The carrier rates of pathogenic germline mutations in ATM, BRCA1, and BRCA2did not differ in men with or without grade reclassification (1.9% vs. 1.8%). CONCLUSION: The frequency of pathogenic germline mutations in penetrant cancer predisposition genes is extremely low in men with PC undergoing active surveillance and pathogenic germline mutations had no apparent association with grade reclassification or adverse characteristics.
Germ-Line Mutation , Prostatic Neoplasms , Male , Humans , Watchful Waiting , Retrospective Studies , Prostatic Neoplasms/pathology , Genes, BRCA2 , Genetic Predisposition to Disease
Effective conservation strategies rely on knowledge of seasonal and social drivers of animal behaviour. Koalas are generally solitary and their social arrangement appears to rely on vocal and chemical signalling. Male koala vocalisations, known as bellows, are believed to be closely related to their breeding behaviour. Previous research suggests that oestrous female koalas use bellows to locate unique males to mate with, and that males can similarly use bellows to evaluate the physical attributes of their peers. We tested the behavioural responses of 20 free ranging koalas to bellow recordings collected from small (<6 kg) and large (>8.5 kg) adult male koalas. Individual koala movement was reported by hourly-uploaded GPS coordinates. We report evidence of intra-male competition, with adult males approaching bellow playbacks, particularly those from small-sized males. In contrast, males under three years of age were averse to the playbacks. No patterns in the response of females were detected. Our results provide the strongest evidence yet that bellows are primarily a means by which males occupy and control space during the breeding season. Future studies are required to see if female response to bellows depends on their reproductive status.
BACKGROUND: Maintaining men on active surveillance for prostate cancer can be challenging. Although most men who eventually undergo treatment have experienced clinical progression, a smaller subset elects treatment in the absence of disease reclassification. This study sought to understand factors associated with treatment in a large, contemporary, prospective cohort. METHODS: This study identified 1789 men in the Canary Prostate Cancer Active Surveillance Study cohort enrolled as of 2020 with a median follow-up of 5.6 years. Clinical and demographic data as well as information on patient-reported quality of life and urinary symptoms were used in multivariable Cox proportional hazards regression models to identify factors associated with the time to treatment RESULTS: Within 4 years of their diagnosis, 33% of men (95% confidence interval [CI], 30%-35%) underwent treatment, and 10% (95% CI, 9%-12%) were treated in the absence of reclassification. The most significant factor associated with any treatment was an increasing Gleason grade group (adjusted hazard ratio [aHR], 14.5; 95% CI, 11.7-17.9). Urinary quality-of-life scores were associated with treatment without reclassification (aHR comparing "mostly dissatisfied/terrible" with "pleased/mixed," 2.65; 95% CI, 1.54-4.59). In a subset analysis (n = 692), married men, compared with single men, were more likely to undergo treatment in the absence of reclassification (aHR, 2.63; 95% CI, 1.04-6.66). CONCLUSIONS: A substantial number of men with prostate cancer undergo treatment in the absence of clinical changes in their cancers, and quality-of-life changes and marital status may be important factors in these decisions. LAY SUMMARY: This analysis of men on active surveillance for prostate cancer shows that approximately 1 in 10 men will decide to be treated within 4 years of their diagnosis even if their cancer is stable. These choices may be related in part to quality-or-life or spousal concerns.
Prostatic Neoplasms , Watchful Waiting , Humans , Male , Neoplasm Grading , Prospective Studies , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Quality of Life
The Board Certified Psychiatric Pharmacist (BCPP) specialty certification was launched by the Board of Pharmacy Specialties in 1994. Candidates for the BCPP can qualify for the examination through 3 possible pathways: practice experience (4 years) in the specialty, completion of a PGY-1 residency plus an additional 2 years of practice experience, or completion of a PGY-2 specialty residency in psychiatric pharmacy. Recent fluctuations in the passing rate raised questions as to explanatory factors. This article represents the first published comprehensive study of candidate performance on the BCPP Examination. It describes a retrospective, observational study presenting (a) statistical trends of examination passing rates for biannual cohorts over the past 5 years, as well as (b) score distributions on the 3 performance domains of the certification. Pass-rate trend analyses suggest that variation in the proportion of eligibility pathway cohorts in the respective testing samples explains some of the fluctuation in passing rates. An analysis of variance of domain-level scores, using groups defined by eligibility pathway, yielded significant differences for nearly all group comparisons. Evaluation of the effect sizes suggest that the most disparate performance was observed on the core clinical domain, Patient-Centered Care. The results of this study are consistent with previously published research and will inform the upcoming role delineation study for the Psychiatric Pharmacy Certification.
BACKGROUND: Localized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP). METHODS: This was an open label, single-site, Phase II neoadjuvant trial in men with high to very-high-risk PC, as defined by NCCN criteria. Patients received 12 weeks of apalutamide (Apa), abiraterone acetate plus prednisone (AAP), degarelix, and Indo followed by RP. Primary objective was to determine the pathologic complete response (pCR) rate. Secondary objectives included minimal residual disease (MRD) rate, defined as residual cancer burden (RCB) ≤ 0.25cm3 (tumor volume multiplied by tumor cellularity) and elucidation of molecular features of resistance. RESULTS: Twenty patients were evaluable for the primary endpoint. Baseline median prostate-specific antigen (PSA) was 10.1 ng/ml, 4 (20%) patients had Gleason grade group (GG) 4 disease and 16 had GG 5 disease. At RP, 1 (5%) patient had pCR and 6 (30%) had MRD. Therapy was well tolerated. Over a median follow-up of 23.8 months, 1 of 7 (14%) men with pathologic response and 6 of 13 (46%) men without pathologic response had a PSA relapse. There was no association between prostate hormone levels or HSD3B1 genotype with pathologic response. CONCLUSIONS: In men with high-risk PC, pCR rates remained low even with combinatorial AR-directed therapy, although rates of MRD were higher. Ongoing follow-up is needed to validate clinical outcomes of men who achieve MRD.
Aldo-Keto Reductase Family 1 Member C3/antagonists & inhibitors , Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Neoadjuvant Therapy , Prostatectomy , Prostatic Neoplasms/drug therapy , Abiraterone Acetate/therapeutic use , Aged , Humans , Male , Middle Aged , Prostatic Neoplasms/surgery , Thiohydantoins/therapeutic use , Treatment Outcome
Fermented milk products are a major source of health-promoting microorganisms known as probiotics. To characterize the probiotic properties of lactic acid bacteria isolated from Ghanaian traditionally fermented milk, thirty (30) isolates comprising Enterococcus faecium (1), Lactobacillus fermentum (14), Lb. plantarum (2) and Pediococcus acidilactici (13) identified by 16S rRNA gene sequencing, were tested for survival at low pH (2.5) and bile salts (0.3% (w/v)), hydrophobicity, co-aggregation, auto-aggregation and antimicrobial activities against selected pathogens. Safety of potential probiotic bacteria was assessed by hemolytic activity on blood agar and susceptibility to nine different antibiotics. Majority (90%) of the strains showed survival rates above 80% at pH (2.5) and in bile salts (0.3% (w/v)). Hydrophobicity ranged from 5 to 61% while cell auto-aggregation ranged from 41 to 80% after 24 h. Co-aggregation with E. coli (3.7-43.9%) and S. Typhimurium (1.3-49.5%) were similar for the LAB strains at 24 h. Cell- free supernatants of all LAB strains inhibited E. coli while S. Typhimurium was not sensitive to cell-free supernatants of five Pd. acidilactici strains: OS24h20, OS18h3, OY9h19, OS9h8 and 24NL38. None of the LAB strains showed ß-hemolysis but 38% of strains showed α-hemolysis. Susceptibilities to antibiotics were strain-specific; only four strains, two Lb. fermentum and two Pd. acidilactici were susceptible to all nine antibiotics tested. Based on high survival rates in bile salts, low pH and generally good hydrophobicity, auto-aggregation, co-aggregation and inhibitory activities, 15 out of 30 strains tested were considered qualified candidates for development of probiotic cultures for fermented milk products in sub-Saharan Africa.
Cultured Milk Products/microbiology , Lactobacillales/classification , Probiotics/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Bile Acids and Salts , Drug Tolerance , Escherichia coli/genetics , Fermentation , Ghana , Hydrogen-Ion Concentration , Lactobacillales/drug effects , Lactobacillales/genetics , Lactobacillales/isolation & purification , Milk/microbiology , RNA, Ribosomal, 16S/genetics
The koala population in northern Australia has become increasingly fragmented due to natural and man-made barriers and interventions. This situation has created a unique opportunity to study both endogenous and exogenous koala retrovirus (KoRV). To determine the impact that population isolation has had on KoRV diversity in Queensland, 272 koalas from six fragmented koala populations were profiled for their KoRV provirus across two natural biogeographical barriers (the St Lawrence Gap and the Brisbane Valley Barrier), one man-made geographical barrier (the city of Brisbane) and two translocation events (the single movement of koalas to an island and the repeated movement of koalas into a koala sanctuary). Analysis revealed that all koalas tested were KoRV-A positive, with 90 - 96% of the detected KoRV provirus from each koala representing a single, likely endogenous, KoRV-A strain. The next most abundant proviral sequence was a defective variant of the dominant KoRV-A strain, accounting for 3 - 10% of detected provirus. The remaining KoRV provirus represented expected exogenous strains of KoRV and included geographically localized patterns of KoRV-B, -C, -D, -F, -G, and -I. These results indicate that lineage diversification of exogenous KoRV is actively ongoing. In addition, comparison of KoRV provirus within known dam-sire-joey family groups from the koala sanctuary revealed that joeys consistently had KoRV proviral patterns more similar to their dams than their sires in KoRV-B, -C and -D provirus composition. Collectively, this study highlights both the consistency of endogenous KoRV and the diversity of exogenous KoRV across the fragmented koala populations in northern Australia.IMPORTANCE KoRV infection has become a permanent part of koalas in northern Australia. With KoRV presence and abundance linked to more severe chlamydial disease and neoplasia in these koalas, understanding how KoRV exists throughout an increasingly fragmented koala population is a key first step in designing conservation and management strategies. This survey of KoRV provirus in Queensland koalas indicates that endogenous KoRV provirus is ubiquitous and consistent throughout the state while exogenous KoRV provirus is diverse and distinct in fragmented koala populations. Understanding the prevalence and impact of both endogenous and exogenous KoRV will be needed to ensure a future for all koala populations.
