Effect of tibolone on breast cancer cell proliferation in postmenopausal ER+ patients: Results from STEM trial

Purpose: Tibolone is a selective tissue estrogenic activity regulator, approved for the treatment of vasomotor symptoms in postmenopausal women. We have done an exploratory, double-blind, randomized, placebo-controlled pilot trial to investigate the tissue-specific effects of 2.5 mg tibolone on breast cancer in postmenopausal women, in particular on tissue proliferation (STEM, Study of Tibolone Effects on Mamma carcinoma tissue). Experimental Design: Postmenopausal women with initially stage I/II, estrogen receptor-positive (ER+) primary breast cancer, were randomly assigned to 14 days of placebo or 2.5 mg/d tibolone. Core biopsies of the primary tumor were obtained before and after treatment. Ki-67 and apoptosis index were analyzed in baseline and corresponding posttreatment specimen. Results: Of 102 enrolled patients, 95 had evaluable data. Baseline characteristics were comparable between both treatment groups. Breast cancer cases are mainly invasive (99%), stage I or II (42% and 50% respectively), and ER+ (99%). Median intratumoral Ki-67 expression at baseline was 13.0%, in the tibolone group and 17.8% in the placebo group, and decreased to 12.0% after 14 days of tibolone while increasing to 19.0% in the placebo group. This change from baseline was not significantly different between tibolone and placebo (Wilcoxon test; P = 0.17). A significant difference was observed between the treatment groups when the median change from baseline apoptosis index was compared between the treatment groups (tibolone, 0.0%; placebo, +0.3%; Wilcoxon test; P = 0.031). The incidence of adverse effects was comparable. Conclusions: In ER+ breast tumors, 2.5 mg/d tibolone given for 14 days has no significant effect on tumor cell proliferation

Investigation on Prevalence of Canine Trypanosomiasis in the Conservation Areas of Bwindi-Mgahinga and Queen Elizabeth in Western Uganda

Nowadays, despite the instauration of several control strategies, animal trypanosomiasis continues to be reported all over Uganda. Few canine African trypanosomiasis (CAT) studies have been carried out, yet dogs are known Trypanosoma reservoirs that share identical home ranges with livestock and serve as parasite link between livestock and humans. This study evaluates the prevalence of CAT in dogs in the Bwindi-Mgahinga and Queen Elizabeth conservation areas. This information will be useful to evaluate the possible role of dogs in the transmission cycle of Trypanosoma species in livestock and wild animals. Trypanosome tests using microhematocrit centrifugation/dark ground microscopy technique (MHCT) followed by conventional polymerase chain reaction (cPCR) were performed in blood samples collected from identified indigenous dogs (n = 124). Four (3.23%) out of 124 dogs were positive for CAT. One dog was positive with Trypanosoma congolense and three with T. vivax. There was no significant statistical difference in CAT prevalence rate in relation to dog's age, sex, and site (P > 0.05). This study reports what we believe is the first time detection of T. congolense and T. vivax in the indigenous dogs found in the Bwindi-Mgahinga and Queen Elizabeth conservation areas in western Uganda. The noticed T. congolense and T. vivax could be responsible for both canine and animal trypanosomiasis and represent a serious threat to the livestock industry. Therefore, there is a need for continuous trypanosomiasis surveillance and integrated management in contiguity to wildlife reserves

Evaluation of C-reactive protein, Haptoglobin and cardiac Troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome

Background: Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI), in dogs with brachycephalic upper airway obstructive syndrome (BAOS). Results: Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88%) had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%), stenotic nares (96%), everted laryngeal saccules (32%) and tracheal hypoplasia (29.1%). Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50) had values of CRP > 20 mg/L, 22.9% (11/48) had values of Hp > 3 g/L and 47.8% (22/46) had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p<0.02) and higher values of CRP (p<0.044). No other statistical association between biomarkers levels and severity of clinical signs was found. Conclusions: According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration

Welfare in farmed decapod crustaceans, with particular reference to Penaeus vannamei

The farming of decapod crustaceans is a key economic driver in many countries, with production reaching around 9.4 million tonnes (USD 69.3 billion) in 2018. These efforts are currently dominated by the farming of Pacific whiteleg shrimp, Penaeus vannamei, which translates into approximately 167 billion farmed P. vannamei being harvested annually. Further production growth is expected in the future and hence the need for more research into its health and welfare is required. Herein, from an extensive survey of the available literature, we scrutinise farming practices and the challenges associated with the production of P. vannamei from an animal-centric welfare perspective (1), we propose potential welfare indicators (2) and we critically review current scientific evidence of sentience in penaeid shrimp among other commercially important decapods (3), since it is plausible that in the near future not only the largest, but in fact all decapod crustaceans will receive welfare protection. This review highlights that despite the wide knowledge on crustacean stress physiology and immunology as well as disease control, still little is known about some key parameters related to the five welfare dimensions. We recommend that further research should focus on developing a systematic integrated welfare assessment encompassing all the different aspects of the crustaceans farming and life cycle up to slaughter. Furthermore, direct and indirect species-specific operational welfare indicators should be developed for all decapod crustaceans currently farmed, similar to the ones suggested in this review for P. vannamei

Circadian rhythm of preferred temperature in fish: Behavioural thermoregulation linked to daily photocycles in zebrafish and Nile tilapia

Ectothermic vertebrates, e.g. fish, maintain their body temperature within a specific physiological range mainly through behavioural thermoregulation. Here, we characterise the presence of daily rhythms of thermal preference in two phylogenetically distant and well-studied fish species: the zebrafish (Danio rerio), an experimental model, and the Nile tilapia (Oreochromis niloticus), an aquaculture species. We created a non-continuous temperature gradient using multichambered tanks according to the natural environmental range for each species. Each species was allowed to freely choose their preferred temperature during the 24h cycle over a long-term period. Both species displayed strikingly consistent temporal daily rhythms of thermal preference with higher temperatures being selected during the second half of the light phase and lower temperatures at the end of the dark phase, with mean acrophases at Zeitgeber Time (ZT) 5.37 h (zebrafish) and ZT 12.5 h (tilapia). Interestingly, when moved to the experimental tank, only tilapia displayed consistent preference for higher temperatures and took longer time to establish the thermal rhythms. Our findings highlight the importance of integrating both light-driven daily rhythm and thermal choice to refine our understanding of fish biology and improve the management and welfare of the diversity of fish species used in research and food production

Transcriptomic differences in MSA clinical variants

Background: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes. Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients. Results: Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies. Conclusions: In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results

Predictors of clinically significant quality of life impairment in Parkinson's disease.

Quality of life (QOL) plays an important role in independent living in Parkinson?s disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson?s disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ? 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 ± 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 ± 13 to 20.3 ± 16.4; p < 0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (OR = 0.896; 95% CI 0.829?0.968; p = 0.006), to be a female (OR = 4.181; 95% CI 1.422?12.290; p = 0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (OR = 1.139; 95% CI 1.053?1.231; p = 0.001) and NMSS (Non-Motor Symptoms Scale) (OR = 1.052; 95% CI 1.027?1.113; p < 0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (Hosmer?Lemeshow test, p = 0.665; R2 = 0.655). An increase in ?5 and ?10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663?17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975?22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patient

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease

Background: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. Methods: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. Results: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). Conclusions: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD