Cancer SLC43A2 alters T cell methionine metabolism and histone methylation.

Abnormal epigenetic patterns correlate with effector T cell malfunction in tumours1-4, but the cause of this link is unknown. Here we show that tumour cells disrupt methionine metabolism in CD8+ T cells, thereby lowering intracellular levels of methionine and the methyl donor S-adenosylmethionine (SAM) and resulting in loss of dimethylation at lysine 79 of histone H3 (H3K79me2). Loss of H3K79me2 led to low expression of STAT5 and impaired T cell immunity. Mechanistically, tumour cells avidly consumed methionine and outcompeted T cells for methionine by expressing high levels of the methionine transporter SLC43A2. Genetic and biochemical inhibition of tumour SLC43A2 restored H3K79me2 in T cells, thereby boosting spontaneous and checkpoint-induced tumour immunity. Moreover, methionine supplementation improved the expression of H3K79me2 and STAT5 in T cells, and this was accompanied by increased T cell immunity in tumour-bearing mice and patients with colon cancer. Clinically, tumour SLC43A2 correlated negatively with T cell histone methylation and functional gene signatures. Our results identify a mechanistic connection between methionine metabolism, histone patterns, and T cell immunity in the tumour microenvironment. Thus, cancer methionine consumption is an immune evasion mechanism, and targeting cancer methionine signalling may provide an immunotherapeutic approach.

Genotyping-by-sequencing targets genic regions and improves resolution of genome-wide association studies in autotetraploid potato.

KEY MESSAGE: De novo genotyping in potato using methylation-sensitive GBS discovers SNPs largely confined to genic or gene-associated regions and displays enhanced effectiveness in estimating LD decay rates, population structure and detecting GWAS associations over 'fixed' SNP genotyping platform. Study also reports the genetic architectures including robust sequence-tagged marker-trait associations for sixteen important potato traits potentially carrying higher transferability across a wider range of germplasm. This study deploys recent advancements in polyploid analytical approaches to perform complex trait analyses in cultivated tetraploid potato. The study employs a 'fixed' SNP Infinium array platform and a 'flexible and open' genome complexity reduction-based sequencing method (GBS, genotyping-by-sequencing) to perform genome-wide association studies (GWAS) for several key potato traits including the assessment of population structure and linkage disequilibrium (LD) in the studied population. GBS SNPs discovered here were largely confined (~ 90%) to genic or gene-associated regions of the genome demonstrating the utility of using a methylation-sensitive restriction enzyme (PstI) for library construction. As compared to Infinium array SNPs, GBS SNPs displayed enhanced effectiveness in estimating LD decay rates and discriminating population subgroups. GWAS using a combined set of 30,363 SNPs identified 189 unique QTL marker-trait associations (QTL-MTAs) covering all studied traits. The majority of the QTL-MTAs were from GBS SNPs potentially illustrating the effectiveness of marker-dense de novo genotyping platforms in overcoming ascertainment bias and providing a more accurate correction for different levels of relatedness in GWAS models. GWAS also detected QTL 'hotspots' for several traits at previously known as well as newly identified genomic locations. Due to the current study exploiting genome-wide genotyping and de novo SNP discovery simultaneously on a large tetraploid panel representing a greater diversity of the cultivated potato gene pool, the reported sequence-tagged MTAs are likely to have higher transferability across a wider range of potato germplasm and increased utility for expediting genomics-assisted breeding for the several complex traits studied.

Small bite fascial closure technique reduces incisional hernia rates in gynecologic oncology patients.

BACKGROUND: The potential for the technique of small bite fascial closure in mitigating incisional hernias in gynecologic oncology patients still needs to be investigated. OBJECTIVE: To evaluate the impact of closure of small fascial bites compared with prior standard closure on incisional hernia rates in gynecologic oncology patients. METHODS: This is a retrospective cohort study comparing patient outcomes before and after the intervention at a single institution at a comprehensive cancer center. Patients who underwent laparotomy with a vertical midline incision for a suspected or known gynecologic malignancy with a 1-year follow-up were included. The pre-intervention cohort (large bites) had 'mass' or modified running Smead-Jones closure. In contrast, the post-intervention cohort had fascial bites taken 5-8 mm laterally with no more than 5 mm travel (small bites) closure using a 2-0 polydioxanone suture.The primary outcome was the incisional hernias rate determined by imaging or clinical examination within the first year of follow-up. Patient factors and peri-operative variates of interest were investigated for their association with hernia formation through univariate and multivariate analyses. These included age, body mass index (BMI), smoking history, estimated blood loss, pre-operative albumin, American Society of Anesthesia (ASA) physical status classification, or treatment with chemotherapy post-operatively. RESULTS: Of the 255 patients included, the total hernia rate was 12.5% (32/255 patients). Patient characteristics were similar in both cohorts. Small bite closure led to a significant reduction in hernia rates from 17.2% (22/128 patients) to 7.9% (10/127 patients), p=0.025. According to logistic regression modeling, small bite closure (OR=0.40, 95% CI 0.17 to 0.94, p=0.036) was independently associated with lower odds of hernia formation. Other factors associated with increased hernia rates were chemotherapy (OR=3.22, 95% CI 1.22 to 8.51, p=0.019) and obesity (OR=23.4, 95% CI 3.09 to 177, p=0.002). In obese patients, small bite closures led to maximal hernia rate reduction compared with large bites. CONCLUSIONS: The small bite closure technique effectively reduces hernia rates in gynecologic oncology patients undergoing midline laparotomy.

Decomposing the association of psychosocial wellbeing with all-cause mortality: the mediating role of physical health and lifestyle factors.

PURPOSE: This study quantified the effect of 48 psychosocial constructs on all-cause mortality using data from 7,698 individuals in the U.S. Health and Retirement Study. METHODS: Latent class analysis was used to divide participants into mutually exclusive psychosocial wellbeing groups (good, average, or poor) which was subsequently considered as the exposure. Mediation analysis was then conducted to determine the direct effect of the psychosocial wellbeing groups and the indirect (mediating) effects of physical health (functional status and comorbid conditions) and lifestyle factors (physical activity, smoking, and alcohol consumption) on overall survival. We also created a composite health index measure representing the summative effect of the mediators. RESULTS: We observed a strong and statistically significant total effect (TE) between survival time and psychosocial wellbeing group (survival time ratio (SR) = 1.73, 95% confidence interval (CI):1.50,2.01 when comparing good to poor). Mediation analysis revealed that the direct effect via psychosocial wellbeing group accounted for more than half of the TE (SR = 1.46, 95% CI:1.27,1.67). The composite health index measure mediated 36.2% of the TE with the natural indirect effect SR of 1.18 (95% CI:1.13,1.22). CONCLUSION: Our findings demonstrate the interconnectedness between psychosocial wellbeing and physical health and lifestyle factors on survival.

Provider compliance with a tailored opioid prescribing calculator in gynecologic surgery.

OBJECTIVE: To evaluate the impact a tailored opioid prescription calculator has on meeting individual patient opioid needs while avoiding opioid over prescriptions. METHODS: Our group previously developed and published an opioid prescribing calculator incorporating patient risk factors (history of depression, anxiety, chronic opioid use, substance abuse disorder, and/or chronic pain) and type of surgery (laparotomy or laparoscopy). This calculator was implemented on 1/1/2021 and its impact on opioid prescriptions was evaluated until 12/31/21. The primary outcome of the present study is to determine prescriber compliance with the calculator (defined as not overprescribing from the number of pills indicated by the calculator). The secondary outcome is to determine the excess prescription rate (defined as proportion of patients reporting more than 3 pills remaining at 30 days post-surgery). Refill rates and pain related patient phone calls were collected. Descriptive statistics were used to summarize the cohort. RESULTS: Of the 355 patients included, 54.7% (N = 194) underwent laparoscopy and 45.4% (N = 161) underwent laparotomy. One hundred and forty-two patients (40%) had at least one risk factor for opioid usage. The median number of opioid pills prescribed following laparoscopy was 3 (range 0-15) and 6 (0-20) after laparotomy. The prescriber compliance was 88.2% and the excess prescription rate was 25.1% (N = 89 patients). CONCLUSIONS: Our tailored opioid calculator has a high prescriber compliance. Implementation of this calculator led to a standardization of tailored opioid prescribing, while limiting the number of over prescriptions. A free web version of the calculator can be easily accessed at www.opioidcalculator.org.

Implementation of routine venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer.

OBJECTIVE: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis. METHODS: This is a quasi-experimental pre-post study evaluating the VTE rate in patients with ovarian cancer who received neoadjuvant chemotherapy following a quality improvement initiative of routine thromboprophylaxis within a single healthcare system that started in January 2017. Patients were excluded if VTE was diagnosed before initiating chemotherapy. Patient factors and perioperative variables of interest were investigated for their association with VTE through univariate and multivariate models. RESULTS: Of the 136 patients in the pre-implementation group, 3.7% (n = 5) received thromboprophylaxis. Of the 154 patients in the post-implementation group, 65.6% (n = 101) received thromboprophylaxis. Provider compliance varied from 51% in 2019 to 79.3% in 2021. The overall rate of VTE, from the start of chemotherapy to the end of treatment, was 21.3% (n = 29) pre- and 8.4% (n = 13) in the post-implementation group (p < 0.01). There was no difference in major bleeding events between groups (0% vs. 0.68%, p = 0.63). On univariate analysis, thromboprophylaxis (OR 0.19; 95% CI 0.07-0.52) and post-implementation period (OR 0.34; 95% CI 0.17-0.69) were associated with a decreased risk of any VTE during primary treatment. On multivariate analysis, only thromboprophylaxis remained significantly associated with reduced VTE rates (aOR 0.19; 95% CI 0.07-0.53). CONCLUSION: Routine thromboprophylaxis during neoadjuvant chemotherapy is associated with reduced risk of VTE throughout primary treatment and is not associated with increased bleeding events.

Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery.

OBJECTIVE: The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery. METHODS: This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS. RESULTS: Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53). CONCLUSIONS: The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Psychosocial assessment tools for children and young people aged 5-18 years: A rapid review of the literature.

AIM: Schools are a key platform for health promotion and a point of connection to local health-care services, with an almost universal reach across the child and adolescent population. This study sought to determine whether validated psychosocial assessment tools exist for a school-based nursing program that would assist in providing an initial health assessment to identify and understand the needs of children and young people referred to the nurse, with the outcome of appropriate connection to external health and wellbeing services. METHODS: Rapid evidence assessment methodology was utilised to identify validated tools that could identify psychosocial concerns in children and young people aged 5-18 years. We identified articles from peer-reviewed journals via three electronic bibliographic databases (PubMed, Embase and CINAHL). We then extended the search for evidence through a search of the grey literature. RESULTS: From 3963 peer-reviewed articles found in the database search, 10 relevant peer-reviewed publications met inclusion criteria. In combination with 12 grey literature sources, 33 tools were identified. These included self-report tools (typically for children aged 11 years and older), parent-report and teacher-report tools. We identified the six most promising psychosocial assessment tools. However, there was limited description about implementation within school-based nursing programs. CONCLUSIONS: Several tools exist that show promise in assisting school-based nursing programs to conduct preliminary psychosocial assessments for children and young people. The introduction of any tools into practice would require implementation guidance and evaluation, including how and when they should be used, and when referral and follow-up is required.

Endometriosis and menopausal hormone therapy impact the hysterectomy-ovarian cancer association.

OBJECTIVE: To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. METHODS: We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99). CONCLUSIONS: The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

Optimization of postoperative opioid prescriptions in gynecologic oncology: Striking a balance between opioid reduction and pain control.

OBJECTIVE: To implement a quality-improvement initiative to assess the impact various patient and procedural factors have on postoperative opioid use. To develop a tailored opioid prescribing algorithm for gynecologic oncology patients. METHODS: A retrospective cohort study was performed of patients who underwent a laparoscopy or laparotomy procedure for a suspected or known gynecologic malignancy between 3/2019-9/2020. Patients were assessed preoperatively for the presence of suspected risk factors for opioid misuse (depression, anxiety, chronic pain, current opioid use, or substance abuse). Patients completed a 30-day postoperative questionnaire assessing for total opioid pill use and refills requests. Multivariate models were developed to estimate the independent effect of sociodemographic characteristics, risk factors for opioid misuse and procedural factors on patient reported postoperative opioid use. RESULTS: A total of 390 patients were analyzed. Thirty-nine percent (N = 151/390) of patients reported not using opioids after discharge and 5% (N = 20/390) received an opioid refill. For both minimally invasive procedures and laparotomy procedures, body mass index, comorbidities, intraoperative or postoperative complications and final diagnosis of malignancy were not associated with the amount of opioid consumption. However, younger age and history of risk factors for opioid misuse significantly impacted postoperative opioid use. In multivariate analysis, age (p = 0.038) and risk factors (p < 0.001) remained significant after controlling for other factors. CONCLUSIONS: Two out of every five patients did not use opioids after surgery. Younger patients and those with risk factors for opioid misuse need a tailored approach to prescribing opioids to balance the need for adequate pain control with the risk of misuse.

Combining conventional QTL analysis and whole-exome capture-based bulk-segregant analysis provides new genetic insights into tuber sprout elongation and dormancy release in a diploid potato population.

Tuber dormancy and sprouting are commercially important potato traits as long-term tuber storage is necessary to ensure year-round availability. Premature dormancy release and sprout growth in tubers during storage can result in a significant deterioration in product quality. In addition, the main chemical sprout suppressant chlorpropham has been withdrawn in Europe, necessitating alternative approaches for controlling sprouting. Breeding potato cultivars with longer dormancy and slower sprout growth is a desirable goal, although this must be tempered by the needs of the seed potato industry, where dormancy break and sprout vigour are required for rapid emergence. We have performed a detailed genetic analysis of tuber sprout growth using a diploid potato population derived from two highly heterozygous parents. A dual approach employing conventional QTL analysis allied to a combined bulk-segregant analysis (BSA) using a novel potato whole-exome capture (WEC) platform was evaluated. Tubers were assessed for sprout growth in storage at six time-points over two consecutive growing seasons. Genetic analysis revealed the presence of main QTL on five chromosomes, several of which were consistent across two growing seasons. In addition, phenotypic bulks displaying extreme sprout growth phenotypes were subjected to WEC sequencing for performing BSA. The combined BSA and WEC approach corroborated QTL locations and served to narrow the associated genomic regions, while also identifying new QTL for further investigation. Overall, our findings reveal a very complex genetic architecture for tuber sprouting and sprout growth, which has implications both for potato and other root, bulb and tuber crops where long-term storage is essential.

Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

Foster and kinship carer survey: Accessing health services for children in out-of-home care.

AIM: To explore the experiences of Victorian foster and kinship carers in accessing health services for children in their care and to quantify the frequency of potential barriers to health care. METHODS: On-line survey co-designed with the Foster Care Association of Victoria measuring carer-reported health service engagement by a child/young person in their care, ease of service access, time to receiving Medicare number and out-of-pocket health-related costs. A total of 239 foster and 51 kinship carers were recruited through email and social media by carer support agencies. RESULTS: In total, 90% of children/young people had engaged with a general practitioner. Most had engaged with dental (75%), paediatric (72%), optometry (61%) and audiology (54%) services. Mental health services were most likely to be needed but not yet received. Neither carer education nor socio-economic status was associated with likelihood of service engagement. Carers reported that it was hardest to get appointments with mental health and paediatric services. Twenty-seven percent had waited to see a health service because of delays in carers receiving their Medicare number. Sixty percent of carers had paid out-of-pocket for health services; 78% of these had not been reimbursed. CONCLUSION: Victorian foster and kinship carers report high health service use for children and young people in their care. Mental health services were the hardest to access with the largest gap between identified need and service use. Timely access to Medicare numbers and financial support are barriers to access that could be addressed. The development of integrated paediatric health care and clinicians co-located with child protection could also assist.

Natural resistance to Potato virus Y in Solanum tuberosum Group Phureja.

KEY MESSAGE: Novel major gene resistance against Potato virus Y in diploid populations of Solanum tuberosum Groups Phureja and Tuberosum was biologically and genetically characterised. Named Ry(o)phu, it mapped to chromosome 9. A new source of genetic resistance derived from Solanum tuberosum Group Phureja against Potato virus Y (PVY) was identified and genetically characterised in three diploid biparental potato populations. Segregation data for two populations (05H1 and 08H1) suggested the presence of a single dominant gene for resistance to PVY which, following DaRT analysis of the 08H1 cross, was mapped to chromosome 9. More detailed genetic analysis of resistance utilised a well-characterised SNP-linkage map for the 06H1 population, together with newly generated marker data. In these plants, which have both S. tuberosum Group Phureja and S. tuberosum Group Tuberosum in their pedigree, the resistance was shown to map to chromosome 9 at a locus not previously associated with PVY resistance, although there is evidence for at least one other genetic factor controlling PVY infection. The resistance factor location on chromosome 9 (named as Ry(o)phu) suggests a potential role of NB-LRR genes in this resistance. Phenotypic analysis using a GUS-tagged virus revealed that a small amount of PVY replication occurred in occasional groups of epidermal cells in inoculated leaves of resistant plants, without inducing any visible hypersensitive response. However, the virus did not enter the vascular system and systemic spread was completely prevented.

Implementation of a standardized voiding management protocol to reduce unnecessary re-catheterization - A quality improvement project.

OBJECTIVE: To design and implement a standardized postoperative voiding management protocol that accurately identifies patients with urinary retention and reduces unnecessary re-catheterization. METHODS: A postoperative voiding management protocol was designed and implemented in patients undergoing major, inpatient, non-radical abdominal surgery with a gynecologic oncologist. No patients had epidural catheters. The implemented quality improvement (QI) protocol included: 1) Foley removal at six hours postoperatively; 2) universal bladder scan after the first void; and 3) limiting re-catheterization to patients with bladder scan volumes >150 ml. A total of 96 patients post-protocol implementation were compared to 52 patients pre-protocol. Along with baseline demographic data and timing of catheter removal, we recorded the presence or absence of urinary retention and/or unnecessary re-catheterization and postoperative urinary tract infection rates. Fisher's exact test and student's t-tests were performed for comparisons. RESULTS: The overall rate of postoperative urinary retention was 21.6% (32/148). The new voiding management protocol reduced the rate of unnecessary re-catheterization by 90% (13.5% vs 2.1%, p = 0.01), without overlooking true urinary retention (23.1% vs 20.8%, p = 0.83). Additionally, there was a significant increase in hospital-defined early discharge prior to 11:00 AM (4.0% vs 22.0%, p = 0.022). There was no difference in the postoperative urinary tract infection rate between the groups (p = 1.00). Risk factors associated with urinary retention included older age (p < 0.01), use of medications with anticholinergic properties (p < 0.01), and preexisting urinary dysfunction (p < 0.01). CONCLUSIONS: Implementation of this new voiding management protocol reduced unnecessary re-catheterization, captured and treated true urinary retention, and facilitated early hospital discharge.

Aromatase inhibitor use, side effects and discontinuation rates in gynecologic oncology patients.

OBJECTIVE: Aromatase inhibitors (AI) are frequently prescribed in gynecologic oncology. We sought to define the frequency and duration of AI use, characterize AI side effects and determine the reasons for discontinuation in these patients. METHODS: Uterine and ovarian cancer patients with AI use for gynecologic cancer therapy were identified retrospectively. Data were abstracted from the electronic medical record, including cancer type, stage, prior cancer treatments, body mass index, concurrent medications, prevalence of AI side effects before and during AI therapy, length of AI treatment and reason for AI discontinuation. RESULTS: 146 women received AI therapy, with 68 for ovarian cancer (46.6%) and 78 for uterine cancer (53.4%). The majority (71.9%) had advanced stage disease at diagnosis. 54.1% noted AI-associated side effects within the first three visits after starting AI therapy. The most common side effects were arthralgias (29.5%), hot flashes (25.3%), new/worsening fatigue (16.4%), muscle or joint stiffness (8.2%) and myalgias (6.8%). The mean duration of therapy was 14.7 months. Gabapentin or selective serotonin reuptake inhibitor (SSRI) use was associated with decreased musculoskeletal side effects (gabapentin: p < .001, OR 0.88, 95% CI 0.83-0.94; SSRI: p < .001, OR 0.82, 95% CI 0.77-0.89). The most common reason for AI discontinuation was disease progression (87.9%), with 5.0% discontinuing due to side effects and 7.1% for other reasons. CONCLUSION: AI therapy for gynecologic cancers is frequently associated with musculoskeletal side effects, but rarely leads to treatment discontinuation. Thus, AI side effects should be assessed in gynecologic cancer patients to allow potential mitigation of symptoms through adjunct therapies.

Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival.

PURPOSE: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival. METHODS: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery. RESULTS: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend <0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and survival. CONCLUSIONS: Pre-diagnosis MHT use for 5+ years was a favorable prognostic factor for women with ovarian cancer. This large study is consistent with prior smaller studies, and further work is needed to understand the underlying mechanism.

Brief evidence-based interventions for universal child health services: a restricted evidence assessment of the literature.

BACKGROUND: Universal child health services (UCHS) provide an important pragmatic platform for the delivery of universal and targeted interventions to support families and optimize child health outcomes. We aimed to identify brief, evidence-based interventions for common health and developmental problems that could be potentially implemented in UCHS. METHODS: A restricted evidence assessment (REA) of electronic databases and grey literature was undertaken covering January 2006 to August 2019. Studies were eligible if (i) outcomes related to one or more of four areas: child social and emotional wellbeing (SEWB), infant sleep, home learning environment or parent mental health, (ii) a comparison group was used, (iii) universal or targeted intervention were delivered in non-tertiary settings, (iv) interventions did not last more than 4 sessions, and (v) children were aged between 2 weeks postpartum and 5 years at baseline. RESULTS: Seventeen studies met the eligibility criteria. Of these, three interventions could possibly be implemented at scale within UCHS platforms: (1) a universal child behavioural intervention which did not affect its primary outcome of infant sleep but improved parental mental health, (2) a universal screening programme which improved maternal mental health, and (3) a targeted child behavioural intervention which improved parent-reported infant sleep problems and parental mental health. Key lessons learnt include: (1) Interventions should impart the maximal amount of information within an initial session with future sessions reinforcing key messages, (2) Interventions should see the family as a holistic unit by considering the needs of parents with an emphasis on identification, triage and referral, and (3) Brief interventions may be more acceptable for stigmatized topics, but still entail considerable barriers that deter the most vulnerable. CONCLUSIONS: Delivery and evaluation of brief evidence-based interventions from a UCHS could lead to improved maternal and child health outcomes through a more responsive and equitable service. We recommend three interventions that meet our criteria of "best bet" interventions.

A member of the TERMINAL FLOWER 1/CENTRORADIALIS gene family controls sprout growth in potato tubers.

Potato tuber bud dormancy break followed by premature sprouting is a major commercial problem which results in quality losses and decreased tuber marketability. An approach to controlling premature tuber sprouting is to develop potato cultivars with a longer dormancy period and/or reduced rate of sprout growth. Our recent studies using a potato diploid population have identified several quantitative trait loci (QTLs) that are associated with tuber sprout growth. In the current study, we aim to characterize a candidate gene associated with one of the largest effect QTLs for rapid tuber sprout growth on potato chromosome 3. Underlying this QTL is a gene encoding a TERMINAL FLOWER 1/CENTRORADIALIS homologue (PGSC0003DMG400014322). Here, we use a transgenic approach to manipulate the expression level of the CEN family member in a potato tetraploid genotype (cv. Désirée). We demonstrate a clear effect of manipulation of StCEN expression, with decreased expression levels associated with an increased rate of sprout growth, and overexpressing lines showing a lower rate of sprout growth than controls. Associated with different levels of StCEN expression were different levels of abscisic acid and cytokinins, implying a role in controlling the levels of plant growth regulators in the apical meristem.