Adaptive significance of affiliative behaviour differs between sexes in a wild reptile population.

In recent years, we have begun to appreciate that social behaviours might exhibit repeatable among-individual variation. Such behavioural traits may even covary and have critical evolutionary implications. Importantly, some social behaviours such as aggressiveness have been shown to provide fitness benefits, including higher reproductive success and survival. However, fitness consequences of affiliative behaviours, especially between or among sexes, can be more challenging to establish. Using a longitudinal behavioural dataset (2014-2021) collected on eastern water dragons (Intellagama lesueurii), we investigated whether various aspects of affiliative behaviour (i) were repeatable across years, (ii) covaried with each other at the among-individual level, and (iii) influenced individuals' fitness. In particular, we considered affiliative behaviours towards opposite-sex and same-sex conspecifics separately. We found that social traits were repeatable and covaried with each other similarly for both sexes. More notably, we found that male reproductive success was positively correlated with the number of female associates and the proportion of time spent with females, while females' reproductive success was not correlated with any of the measured social behaviour metrics. Overall, these findings suggest that selection may be acting differently on social behaviour of male and female eastern water dragons.

What are the experiences of supportive care in people affected by brain cancer and their informal caregivers: A qualitative systematic review.

PURPOSE: To critically synthesise qualitative research to understand experiences of supportive care in people affected by brain cancer and their informal caregivers. METHODS: A qualitative systematic review was conducted according to the Joanna Briggs methodology and has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. Electronic databases were searched by an expert systematic review librarian for all qualitative studies irrespective of research design. All publications were double screened by two reviewers using a pre-determined exclusion and inclusion criteria. The review was managed using Covidence systematic review software. Methodological quality assessment and data extraction were performed. Qualitative findings accompanied by illustrative quotes from included studies were extracted and grouped into categories, which created the overall synthesised findings. RESULTS: A total of 33 studies were included which represented a total sample of 671 participants inclusive of 303 patients and 368 informal caregivers. There was a total of 220 individual findings included in this review, which were synthesised into two findings (1) caregivers and patients perceived supports which would have been helpful and (2) caregiver and patient experiences of unmet supportive care needs. CONCLUSION: This review highlighted the suffering and distress caused by brain cancer and associated treatments. Both patients and their informal caregivers experienced disconnect from themselves in renegotiating roles, and a profound sense of loneliness as the physical deterioration of the disease progressed. Both patients and informal caregivers reported similar unmet needs within the current service provision for brain cancer. However, what is apparent is that current cancer services are provided solely for patients, with little or no consideration to the support needs of both the patient and their informal caregiver. Service re-design is needed to improve care coordination with individualised informational support, implementation of holistic needs assessments for both the patients and their caregivers, better community support provision, improved opportunities for emotional care with early referral for palliative care services. IMPLICATIONS FOR CANCER SURVIVORS: It is recommended that members of the multidisciplinary brain cancer team reflect on these findings to target holistic needs assessments and develop shared self-management care plans for both the patient and the informal caregiver.

Evaluating the genetic consequences of population subdivision as it unfolds and how to best mitigate them: A rare story about koalas.

The genetic consequences of the subdivision of populations are regarded as significant to long-term evolution, and research has shown that the scale and speed at which this is now occurring is critically reducing the adaptive potential of most species which inhabit human-impacted landscapes. Here, we provide a rare and, to our knowledge, the first analysis of this process while it is happening and demonstrate a method of evaluating the effect of mitigation measures such as fauna crossings. We did this by using an extensive genetic data set collected from a koala population which was intensely monitored during the construction of linear transport infrastructure which resulted in the subdivision of their population. First, we found that both allelic richness and effective population size decreased through the process of population subdivision. Second, we predicted the extent to which genetic drift could impact genetic diversity over time and showed that after only 10 generations the resulting two subdivided populations could experience between 12% and 69% loss in genetic diversity. Lastly, using forward simulations we estimated that a minimum of eight koalas would need to disperse from each side of the subdivision per generation to maintain genetic connectivity close to zero but that 16 koalas would ensure that both genetic connectivity and diversity remained unchanged. These results have important consequences for the genetic management of species in human-impacted landscapes by showing which genetic metrics are best to identify immediate loss in genetic diversity and how to evaluate the effectiveness of any mitigation measures.

Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer.

The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation of the BRCA1/2 genes. We aimed to discover how BRCA1/2 mutations shape the cellular phenotypes and spatial interactions of the tumor microenvironment. Using a highly multiplex immunofluorescence and image analysis we generate spatial proteomic data for 21 markers in 124,623 single cells from 112 tumor cores originating from 31 tumors with BRCA1/2 mutation (BRCA1/2mut), and from 13 tumors without alterations in HR genes. We identify a phenotypically distinct tumor microenvironment in the BRCA1/2mut tumors with evidence of increased immunosurveillance. Importantly, we report a prognostic role of a proliferative tumor-cell subpopulation, which associates with enhanced spatial tumor-immune interactions by CD8+ and CD4 + T-cells in the BRCA1/2mut tumors. The single-cell spatial landscapes indicate distinct patterns of spatial immunosurveillance with the potential to improve immunotherapeutic strategies and patient stratification in HGSC.

Correction to: A framework for the identification of long-term social avoidance in longitudinal datasets.

[This corrects the article DOI: 10.1098/rsos.170641.][This corrects the article DOI: 10.1098/rsos.170641.].

Identifying the supportive care needs of men and women affected by chemotherapy-induced alopecia? A systematic review.

PURPOSE: To systematically evaluate evidence regarding the unmet supportive care needs of men and women affected by chemotherapy-induced alopecia (CIA) to inform clinical practice guidelines. METHODS: We performed a review of CINAHL, MEDLINE, PsychINFO, Scopus, the Cochrane Library (CCRT and CDSR) controlled trial databases and clinicaltrials.gov from January 1990 to June 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Twenty-seven publications were selected for inclusion in this analysis. RESULTS: Included reports used qualitative (ten) and quantitative (17) studies. Across these studies men and women reported the major impact that CIA had on their psychological well-being, quality of life and body image. Hair loss had a negative impact irrespective of gender, which resulted in feelings of vulnerability and visibility of being a "cancer patient". Men and women described negative feelings, often similar, related to CIA with a range of unmet supportive care needs. CONCLUSIONS: Some patients are not well-prepared for alopecia due to a lack of information and resources to reduce the psychological burden associated with CIA. Hair loss will affect each patient and their family differently, therefore, intervention and support must be tailored at an individual level of need to optimise psychological and physical well-being and recovery. IMPLICATIONS FOR CANCER SURVIVORS: People affected by CIA may experience a range of unmet supportive care needs, and oncology doctors and nurses are urged to use these findings in their everyday consultations to ensure effective, person-centred care and timely intervention to minimise the sequalae associated with CIA.

Tricuspid annular plane systolic excursion (TAPSE) in dogs: reference values and impact of pulmonary hypertension.

BACKGROUND: The impact of pulmonary hypertension (PH) on right ventricular systolic function is difficult to assess. Tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic measurement of right ventricular systolic function and a strong predictor of outcome in human PH patients. HYPOTHESIS/OBJECTIVES: Determine a reference range for TAPSE in healthy dogs, and quantify TAPSE in dogs with PH. It is hypothesized that TAPSE is lower in dogs with PH compared with a reference group, and decreases as PH worsens. ANIMALS: Fifty normal dogs and 30 dogs with PH. METHODS: TAPSE was measured by 2-dimensional echocardiography-guided M-mode from the left apical 4-chamber view. Peak systolic tricuspid valve regurgitation jet velocity was measured by continuous-wave Doppler to estimate right ventricular-to-right atrial pressure gradient. PH was subjectively classified as mild, moderate, and severe. RESULTS: There was a curvilinear correlation between TAPSE and body weight. The upper and lower limits of the 95% reference interval were determined by quantile regression. Interobserver and intraobserver agreement was adequate with a coefficient of variation <10%. There were significant differences when comparing dogs with PH and the healthy group, as well as between the PH subgroups (P < .01), except between dogs with mild and moderate PH (P = .99). Only dogs in the severe PH group had TAPSE values that were mostly below the lower limit of the reference interval. CONCLUSIONS AND CLINICAL IMPORTANCE: TAPSE is easily obtainable with acceptable inter and intraobserver agreement. TAPSE is decreased in PH and below the reference interval in most dogs with severe PH.

Canine and feline caval syndrome.

The caval syndrome is a serious complication of chronic heartworm (Dirofilaria immitis) disease in dogs and cats. The syndrome is characterized by acute anorexia, respiratory distress, weakness, right-sided cardiac murmur, anemia, hemoglobinuria, hepatic and renal dysfunction, signs of forward and backward heart failure, and, possibly, disseminated intravascular coagulation (DIC). Retrograde migration of adult heartworms from the pulmonary arteries to the right ventricle, right atrium, and venae cavae causes disruption of the tricuspid apparatus. Valvular insufficiency, with concurrent pulmonary hypertension, reduces cardiac output thus resulting in forward and backward heart failure. Additionally, red blood cells are traumatized and hemolyzed as they flow through the mass of worms. Therapy consists of supportive care and the removal of the heartworm mass from the right ventricular inflow tract. Caval syndrome in dogs and cats is associated with high mortality rates and generally has a guarded to poor prognosis.

Advances in antiarrhythmic therapy.

The therapy of cardiac arrhythmias in small animals can be confusing and challenging. This article reviews the current concepts of cardiac rhythm, including impulse generation, automaticity, and conduction in normal and diseased cardiac tissues. The mechanisms of arrhythmogenesis (abnormal automaticity and triggered events) and automatic modulation of cardiac arrhythmias are also discussed. Finally, a review of the clinical management of specific cardiac arrhythmias provides the practicing veterinarian with the current concepts of cardiac rhythm control.

Effects of spaceflight on rat erythroid parameters.

Hematologic studies were performed on 21 ground control rats and 21 rats flown during the Spacelab Life Sciences-2 14-day mission. Group A (n = 5) was used to collect blood in flight and 9 days postflight, group B (n = 5) was injected with recombinant human erythropoietin (rhEpo), group C (n = 5) received saline as a control, and group D (n = 6) was killed in flight and tissues were collected. Results indicated no significant changes in peripheral blood erythroid elements between flight and ground control rats. The nonadherent bone marrow on flight day 13 showed a lower number of recombinant rat interleukin-3 (rrIL-3)-responsive and rrIL-3 + rhEpo-responsive blast-forming unit erythroid (BFU-e) colonies in flight rats compared with ground control rats. On landing day, a slight increase in the number of rhEpo + rrIL-3-responsive BFU-e colonies of flight animals compared with ground control rats was evident. Nine days postflight, bone marrow from flight rats stimulated with rhEpo alone or with rhEpo + rrIL-3 showed an increase in the number of colony-forming unit erythroid colonies and a decrease in BFU-e colonies compared with ground control rats. This is the first time that animals were injected with rhEpo and subsequently blood and tissues were collected during the spaceflight to study the regulation of erythropoiesis in microgravity.

Lymphatic tissue changes in rats flown on Spacelab Life Sciences-2.

Thymus, spleen, inguinal lymph node, and bone marrow specimens from rats flown on the 14-day Spacelab Life Sciences-2 mission were examined after staining of tissue sections. The primary observation was a transient retrogressive change in lymphatic tissues in the rats within a few hours after landing. There was a diffuse increase in tingible body-containing macrophages in the cortex of the thymus, thymus-dependent areas of the splenic white pulp, and inguinal lymph node. This was not observed 9 days after recovery. The in situ labeling of fragmented DNA strands catalyzed by exogenous terminal deoxynucleotidyltransferase (TdT) with ApopTag reagents (Oncor, Gaithersburg, MD) inside the tingible body-containing macrophages indicated that the process was one of apoptosis. No increase in tingible body macrophage activity was noted in thymus and spleen tissue obtained from rats in flight on flight day 13. The reaction to gravitational stress from readaptation to 1 G is the most likely explanation of the transient retrogressive change in lymphatic tissues.

Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells.

The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to micro-gravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.

The relationship between breast cancer survival and prior postmenopausal estrogen use.

The growth of breast cancer may be mediated by endogenous or exogenous sex steroid hormones, particularly estrogen. However, neither contraceptive nor noncontraceptive estrogen use has been associated definitively with an increased risk of developing breast cancer. In this study, we addressed a corollary question: If a postmenopausal woman develops carcinoma of the breast, is her survival affected by previous use of replacement estrogen? Two hundred fifty-six postmenopausal women with breast cancer entered our Tumor Registry between 1972-1981, inclusive. Of these, 174 took no replacement estrogen before the diagnosis (never-users), 21 had used estrogen previously (past users), and 61 were taking estrogen at the time of diagnosis (current users). Survival analysis revealed a median survival of less than 84 months after diagnosis for never- and past users and greater than 143 months for current users, but these differences were not significant when controlled for stage of disease at diagnosis. We conclude that prior postmenopausal estrogen replacement therapy does not compromise survival in women who subsequently develop carcinoma of the breast.

The incidence of abnormal limb development in the Irish thoroughbred from birth to 18 months.

A two part survey was carried out in Irish Thoroughbred horses in 1988 and 1989 to establish the incidence and prevalence of developmental skeletal problems, particularly possible manifestations of developmental orthopaedic disease (DOD). Survey One was a retrospective study based on a questionnaire involving the foal crops of 46 stud farms for 3 successive seasons; the 1711 animals initially documented represented 10.46% of Irish foal registrations. The second survey involved repeated monitoring of the 1988 foal crop from birth to 18 months of age on 17 stud farms. The 248 foals initially examined represented 4.24% of foal registrations. Treatment for DOD was deemed necessary for 11.3% of the animals in Survey One. Angular limb deformities and physeal dysplasia ("epiphysitis") together constituted 72.9% of the cases treated. The peak incidence of DOD problems occurred between weaning and the end of December. More than half the animals treated (53.9%) recovered completely, ie achieved expected sale value as yearlings, 27.5% of those treated showed incomplete recovery and mild to moderate loss of sale value and the remaining 18.7% were killed or lost much of their sale value. In the second survey, while 67% of animals exhibited some form of DOD, the incidence and severity of problems treated were not significantly different from those of farms in Survey One. Again, physeal dysplasia and angular limb deformity were the predominant clinical conditions and their severity was greatest during the early winter. During the suckling phase colts had a significantly greater incidence of DOD. At all other stages the incidence and severity of DOD was similar in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Bovine brain microsomal CDP-diacylglycerol synthetase: solubilization and properties.

CDP-diacylglycerol(DAG) synthetase (EC 2.7.7.41) has been solubilized from bovine brain microsomes by the detergent CHAPS (3-[(3-cholamidopropyl) dimethylammonio] -1-propanesulfonate). Optimal solubilization with 1.5% CHAPS yielded 55-60% of the synthetase activity. The effect of CHAPS on the enzyme was biphasic inhibiting at 0.3% and giving maximal activity at 0.5% (the concentration used for all assays). The solubilized, but not the microsomal enzyme is activated by phosphatidylcholine (PC) and strongly inhibited by cardiolipin and lysoPC. Strong inhibition by N-ethylmaleimide, 5,5'-dithio-bis (2-nitrobenzoic acid) and p-chloromercuribenzoate supported a sulfhydryl requirement for the enzyme. Phosphatidic acid (PA) from egg lecithin and 1-stearoyl,2-arachidonoyl PA were preferred substrates for the microsomal synthetase. Solubilized synthetase showed selectivity for the latter PA which is consistent with this enzyme functioning to help form the preponderant 1-stearoyl,2-arachidonoyl species of phosphatidylinositol. Further attempts to purify the synthetase were unsuccessful. All findings suggested the enzyme exists as an unstable complex.

Triacylglycerol synthesis and diacylglycerol acyltransferase activity during skeletal myogenesis.

The role that diacylglycerol acyltransferase (DAGAT) may play in the switch in lipid metabolism from predominantly triacylglycerol- and phospholipid-synthesizing myoblasts to predominantly phospholipid-synthesizing myotubes has been studied during L6 skeletal myogenesis. Fatty acid induced triacylglycerol (TAG gamma accumulation in vivo was found to be optimal with long-chain, unsaturated fatty acids. The fatty acid induced TAG accumulation was significantly greater in myoblasts than that in myotubes. DAGAT activity in vitro was found to be associated with the particulate (membrane) fraction only. The inhibition by many thiol-specific reagents (N-ethylmaleimide, p-chloromercuribenzoate, iodoacetate, 5,5'-dithiobis (2-nitrobenzoic acid) suggest that a thiol group is at or near the active site. In general, optimal DAGAT activity in vitro was observed when long-chain unsaturated acyl-CoAs and diacylglycerols (DAGs) containing long acyl chains were used as substrates for in vitro TAG synthesis (although 1,2-didecanoin was also very effective). DAGAT activity (expressed relative to DNA) was shown to decline over twofold during skeletal myogenesis when measured in the absence of exogenous DAG. However, in the presence of exogenous (1 mM) DAG, there was no significant change in DAGAT activity, suggesting that the levels of this enzyme are not altered during skeletal myogenesis. These results indicate that endogenous DAG levels are limiting TAG synthesis in L6 myotubes. However, DAG content of myotubes was significantly greater than that of myoblasts, suggesting that there may be an increased competition for DAG (perhaps owing to enhanced phospholipid synthesis) during skeletal myogenesis. The combined effects of decreased synthesis and increased degradation (reported earlier) of TAG may account for the decrease in endogenous TAG contents observed during skeletal myogenesis.