Long-term mental health and quality of life in women with a history of breast cancer

This thesis focused on the long-term mental health and quality of life of breast cancer survivors, compared to women with no prior cancer. The first study was a systematic review of studies that assessed adverse mental health outcomes in women who had breast cancer and non-cancer controls. This found evidence suggestive of an increased risk of anxiety, depression, suicide, and neurocognitive and sexual dysfunctions in breast cancer survivors. The second study systematically summarised the lists of Read codes and clinical definitions used in previous studies of mental health-related outcomes in primary care databases of electronic health records in the UK. The results showed substantial heterogeneity across studies and informed the definition of the outcomes in this thesis. The third study used data from the UK Clinical Practice Research Datalink (CPRD) GOLD primary care database to quantify the risk of adverse mental health-related outcomes in 57,571 breast cancer survivors and 230,067 women with no previous cancer. Breast cancer survivorship was positively associated with anxiety, depression, fatigue, pain, sexual dysfunction, sleep disorder and being prescribed opioid analgesics, but there was no evidence of association with cognitive dysfunction or fatal and non-fatal self-harm. The fourth study included 353 breast cancer survivors and 252 women with no prior cancer who replied to questionnaires assessing quality of life and mental health. Compared to women with no prior cancer, breast cancer survivors had poorer quality of life in the domains of cognitive problems, sexual function, and fatigue, but no evidence of difference in negative feelings, positive feelings, pain, or social avoidance. Women with advanced-stage cancer at diagnosis, and/or prior receipt of chemotherapy, had poorer quality of life and mental health. In conclusion, breast cancer survivorship is associated with impaired quality of life and raised risk of adverse mental health-related outcomes, persisting well into the survivorship period

Co‐existing monophasic teratoma and uterine adenocarcinoma in a female dog

Ovarian teratomas are occasionally reported in dogs; the rarest type is the monophasic teratoma,composed of tissues originating from only one germ layer. Canine endometrial adenocarcinomas are also rare in dogs and mainly affect geriatric females. This report describes case of co-existing ovarian teratoma and uterine adenocarcinoma in a 10-year old nulliparous female Boxer presented with lethargy, anorexia and purulent vaginal discharge. Abdominal ultrasonography evidenced pyometra and a mass in the left ovary. This was composed of a uniform whitish tissue with multiple cystic structures. The histology revealed an atrophy of the ovarian parenchyma, compressed by a proliferation of well-differentiated nervous tissue staining positively to vimentin, S100 and neuronal specific enolase (NSE), and negatively to keratin and inhibin. The left uterine horn, whose diameter was markedly increased, showed foci of endometrial cellular atypia, evident nucleoli and mitoses, at light microscopy. To our best knowledge, this is the first report of a coexisting ovarian monophasic teratoma and endometrial adenocarcinoma, two rare reproductive neoplasia in dogs

A Comparison of Phycocyanins from Three Different Species of Cyanobacteria Employing Resonance-Enhanced Coherent Anti-Stokes Raman Spectroscopy

Resonance-enhanced coherent anti-Stokes Raman spectra are recorded for monomers and trimers of phycocyanin from three different cyanobacteria: Westiellopsis prolifica, Mastigocladus laminosus and Spirulina platensis. It is shown that upon aggregation from monomer to trimer the electronic structures of both the α84 and β84 chromophores are changed. The spectra of the trimers originating from S. platensis and M. laminosus are very similar to each other, but distinctly different from the spectrum of W. prolifica

Factors associated with excess all-cause mortality in the first wave of the COVID-19 pandemic in the UK: A time series analysis using the Clinical Practice Research Datalink

BACKGROUND: Excess mortality captures the total effect of the Coronavirus Disease 2019 (COVID-19) pandemic on mortality and is not affected by misspecification of cause of death. We aimed to describe how health and demographic factors were associated with excess mortality during, compared to before, the pandemic. METHODS AND FINDINGS: We analysed a time series dataset including 9,635,613 adults (≥40 years old) registered at United Kingdom general practices contributing to the Clinical Practice Research Datalink. We extracted weekly numbers of deaths and numbers at risk between March 2015 and July 2020, stratified by individual-level factors. Excess mortality during Wave 1 of the UK pandemic (5 March to 27 May 2020) compared to the prepandemic period was estimated using seasonally adjusted negative binomial regression models. Relative rates (RRs) of death for a range of factors were estimated before and during Wave 1 by including interaction terms. We found that all-cause mortality increased by 43% (95% CI 40% to 47%) during Wave 1 compared with prepandemic. Changes to the RR of death associated with most sociodemographic and clinical characteristics were small during Wave 1 compared with prepandemic. However, the mortality RR associated with dementia markedly increased (RR for dementia versus no dementia prepandemic: 3.5, 95% CI 3.4 to 3.5; RR during Wave 1: 5.1, 4.9 to 5.3); a similar pattern was seen for learning disabilities (RR prepandemic: 3.6, 3.4 to 3.5; during Wave 1: 4.8, 4.4 to 5.3), for black or South Asian ethnicity compared to white, and for London compared to other regions. Relative risks for morbidities were stable in multiple sensitivity analyses. However, a limitation of the study is that we cannot assume that the risks observed during Wave 1 would apply to other waves due to changes in population behaviour, virus transmission, and risk perception. CONCLUSIONS: The first wave of the UK COVID-19 pandemic appeared to amplify baseline mortality risk to approximately the same relative degree for most population subgroups. However, disproportionate increases in mortality were seen for those with dementia, learning disabilities, non-white ethnicity, or living in London

Risk of fractures in half a million survivors of 20 cancers: a population-based matched cohort study using linked English electronic health records.

BACKGROUND: A history of multiple myeloma, prostate cancer, and breast cancer has been associated with adverse bone health, but associations across a broader range of cancers are unclear. We aimed to compare the risk of any bone fracture and major osteoporotic fractures in survivors of a wide range of cancers versus cancer-free individuals. METHODS: In this population-based matched cohort study, we used electronic health records from the UK Clinical Practice Research Datalink linked to hospital data. We included adults (aged ≥18 years) eligible for linkage, and we restricted the study start to Jan 2, 1998, onwards and applied administrative censoring on Jan 31, 2020. The cancer survivor group included survivors of the 20 most common cancers. Each individual with cancer was matched (age, sex, and general practice) to up to five controls (1:5) who were cancer-free. The primary outcomes were any bone fracture and any major osteoporotic fracture (pelvic, hip, wrist, spine, or proximal humeral fractures) occurring more than 1 year after index date (ie, the diagnosis date of the matched individual with cancer). We used Cox regression models, adjusted for shared risk factors, to estimate associations between cancer survivorship and bone fractures. FINDINGS: 578 160 adults with cancer diagnosed in 1998-2020 were matched to 3 226 404 cancer-free individuals. Crude incidence rates of fractures in cancer survivors ranged between 8·39 cases (95% CI 7·45-9·46) per 1000 person-years for thyroid cancer and 21·62 cases (20·18-23·18) per 1000 person-years for multiple myeloma. Compared with cancer-free individuals, the risk of any bone fracture was increased in 15 of 20 cancers, and of major osteoporotic fractures in 17 of 20 cancers. Effect sizes varied: adjusted hazard ratios (HRs) were largest for multiple myeloma (1·94, 95% CI 1·77-2·13) and prostate cancer (1·43, 1·39-1·47); HRs in the range 1·20-1·50 were seen for stomach, liver, pancreas, lung, breast, kidney, and CNS cancers; smaller associations (HR <1·20) were observed for malignant melanoma, non-Hodgkin lymphoma, leukaemia, and oesophageal, colorectal, and cervical cancers. Increased risks of major osteoporotic fracture were noted most substantially in multiple myeloma (2·25, 1·96-2·58) and CNS (2·12, 1·56-2·87), liver (1·62, 1·01-2·61), prostate (1·60, 1·53-1·67), and lung cancers (1·60, 1·44-1·77). Effect sizes tended to reduce over time since diagnosis but remained elevated for more than 5 years in several cancers, such as multiple myeloma and stomach, lung, breast, prostate, and CNS cancers. INTERPRETATION: Survivors of most types of cancer were at increased risk of bone fracture for several years after cancer, with variation by cancer type. These findings can help to inform mitigation and prevention strategies. FUNDING: Wellcome Trust

[Accepted Manuscript] Worldwide comparison of ovarian cancer survival: Histological group and stage at diagnosis (CONCORD-2)

Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15-99years) diagnosed with ovarian cancer during 1995-2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from 67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated age-standardised 5-year net survival by stage at diagnosis (localised or advanced). Survival from type I epithelial ovarian tumours for women diagnosed during 2005-09 ranged from 40 to 70%. Survival from type II epithelial tumours was much lower (20-45%). Survival from germ cell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology

Disponibilidad mensual de fitomasa aérea total y en distintos compartimentos de un pastizal bajo en la región de colinas de La Pampa

The work was done in a short grassland in the area of La Pampa hills (Toay department), to determine above ground standing crop, total and of the different compartments. Cuts were done monthly in -an area previously grazed, during a whole year's sampling. Total standing crop of aerial biomass was of 173 gDM/m2 of annual average. The most important valuable species were: Poa ligularis, Piptochaetium napoataense, Bothriochloa springfieldii y Rhynchoaia senna. Living biomasa compartment was at its maximum in summer months, with its greatest contribution in January (131 gDM/m2). The standing dead material increased in autumn reaching the maximum value in June (168 gDM/m2); while the litter had its highest value in September (288 gDM/m2) The grassland studied resulted being biseasonal with a period of greater growing by the end of spring-summer and another minor by the middle of autumn. The passage of the living material to the standing dead compartment was quick. It was also quick the convertion to litter in spring, as a consequence of the intensity of the winds.El trabajo fue realizado en un pastizal bajo, en la región de las colinas de La Pampa (Dpto. Toay), para determinar disponibilidad total aérea y de los distintos compartimentos. Los cortes se realizaron mensualmente en un área previamente pastoreada, a lo largo de un año de muestreo. La disponibilidad de fitomasa aérea total fue de 173 gMS/m2 de promedio anual. Las especies valiosas más importantes fueron Poa ligularis, Piptochaetium napostaense, Bothriochloa springfieldii y Rhynchosia senna. La fitomasa del compartimento vivo fue máxima en los meses de verano con el mayor aporte en Enero (131 gMS/m2). El material muerto en pie aumentó en otoño hasta alcanzar el máximo valor en Junio (168 gMS/m2); mientras que la broza tuvo el mayor valor en setiembre (288 gMS/m2). El pastizal estudiado resultó ser bi-estacional con un período de crecimiento mayor a fines de primavera-verano y otro menor a mediados de otoño. El pasaje de material vivo al compartimento muerto en pie fue rápido. También lo fue la aparici6n de broza en primavera a causa de la intensidad de los vientos

Relationship between Mediterranean Diet Adherence and Saliva Composition

Dietary polyphenol exposure is known to change protein saliva composition in rodents, but less is known in humans. The present study aimed to assess the relationship between saliva protein composition and adherence to Mediterranean Diet (MD) and polyphenol intake levels. Participants were assessed for their dietary habits, which were converted in Mediterranean adherence level, according to Mediterranean Diet Adherence Score (MEDAS) score. Total polyphenol and total flavanol intakes were extrapolated from dietary data, using Phenol explorer database. Whole saliva was collected, and proteins were separated by SDS-PAGE. Salivary S-type cystatins were highly expressed in the group with medium adherence to MD, being positively correlated with wine intake in overweight individuals. The association between salivary amylase and MD adherence also depended on Body Mass Index (BMI), with a positive association only in normal weight individuals. Polyphenol intake was positively associated with S-type cystatins levels, particularly when flavanols were considered separately. These results show that saliva relationship with MD adherence depend on BMI, suggesting that normal weight and overweight individuals may have different salivary responses to diet. Moreover, these results reinforce the link between saliva and dietary polyphenols (flavanols) levels, leading to the hypothesis that salivary proteome can have a role in polyphenol-rich foods acceptance

Impact of proximal cytoplasmic droplets on quality traits and in-vitro embryo production efficiency of cryopreserved bull spermatozoa

Background: Proximal cytoplasmic droplets (PCDs), a remnant of germ cell cytoplasm, are common non-specific morphological defects in bovine semen. This study evaluated the effect of higher percentages of PCDs on the quality of frozen-thawed bovine semen, embryo production and early embryo development.Methods: Three ejaculates from each of five (group 1: PCD <= 1%, control) and eight adult Bos indicus bulls (group 2: PCD >= 24%) were analysed. Semen samples were examined for: post-thaw motility, vigour of movement, concentration, sperm morphology, slow thermoresistance test (STT), membrane integrity, acrosome status, mitochondrial function using fluorescent probes association (FITC-PSA, PI and JC-1) and sperm chromatin integrity using acridine orange assay. Two bulls from group 2, with 28.5% and 48.5% PCD, respectively, and three bulls from the control group, each with 0% PCD, were selected for IVF (in vitro fertilisation).Results: Semen analyses revealed a significant correlation (P < 0.01) between increased rates of PCD and sperm quality traits. Nevertheless, no differences were observed in sperm motility and vigour either before or after the STT or in the percentage of intact acrosomes (analysed by differential interference contrast microscopy (DIC) after STT), but membrane integrity, acrosome status (evaluated with FITC-PSA staining method after thawing) and mitochondrial function were reduced, when compared with group 1 (P < 0.05). The higher incidence of PCD was positively correlated to chromatin damage, especially after three hours of incubation at 37 degrees C. IVF showed similar results for bull C2 (group 1, control) and bull P2 (group 2, group with higher PCDs).Conclusion: Higher PCD levels influenced spermatozoa quality traits. IVF and embryo development data showed that cleavage, blastocyst formation and blastocyst hatching may have been influenced by the interaction of morphology traits and individual bull effects