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Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) establish latency in sensory and autonomic neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is strongly associated with HSV recurrences in humans and animal models. However, the mechanisms through which stress hormones act on the latent virus to cause reactivation are unknown. We show that the stress hormones epinephrine (EPI) and corticosterone (CORT) induce HSV-1 reactivation selectively in sympathetic neurons, but not sensory or parasympathetic neurons. Activation of multiple adrenergic receptors is necessary for EPI-induced HSV-1 reactivation, while CORT requires the glucocorticoid receptor. In contrast, CORT, but not EPI, induces HSV-2 reactivation in both sensory and sympathetic neurons through either glucocorticoid or mineralocorticoid receptors. Reactivation is dependent on different transcription factors for EPI and CORT, and coincides with rapid changes in viral gene expression, although genes differ for HSV-1 and HSV-2, and temporal kinetics differ for EPI and CORT. Thus, stress-induced reactivation mechanisms are neuron-specific, stimulus-specific and virus-specific. These findings have implications for differences in HSV-1 and HSV-2 recurrent disease patterns and frequencies, as well as development of targeted, more effective antivirals that may act on different responses in different types of neurons.

Vulture species worldwide play a key role in ecosystems as obligate scavengers, and several populations have had precipitous declines. Research on vulture health is critical to conservation efforts including free-living vultures and captive breeding programs, but is limited to date. In this systematic review, we determined the reported causes of free-living vulture species morbidity and mortality worldwide. The most commonly reported cause of mortality was from toxins (60%), especially lead and pesticides, followed by traumatic injury (49%), including collisions with urban infrastructure and gunshot. Neglected areas of research in free-living vulture health include infectious diseases (16%), endocrine and nutritional disorders (6%), and neoplasia (< 1%). Almost half of the studies included in the review were conducted in either Spain or the USA, with a paucity of studies conducted in South America and sub-Saharan Africa. The highest number of studies was on Griffon (Gyps fulvus) (24%) and Egyptian vultures (Neophron percnopterus) (19%), while half of all vulture species had five or fewer studies. Future investigations on free-living vulture health should focus on neglected areas of research, such as infectious diseases, and areas with gaps in the current literature, such as South America, sub-Saharan Africa, and under-studied vulture species.

Background Contrast-enhanced mammography (CEM) is more available than MRI for breast cancer staging but may not be as sensitive in assessing disease extent. We compared CEM and MRI in this setting. Methods Fifty-nine women with invasive breast cancer underwent preoperative CEM and MRI. Independent pairs of radiologists read CEM studies (after reviewing a 9-case set prior to study commencement) and MRI studies (with between 5 and 25 years of experience in breast imaging). Additional lesions were assigned National Breast Cancer Centre (NBCC) scores. Positive lesions (graded NBCC ≥ 3) likely to influence surgical management underwent ultrasound and/or needle biopsy. True-positive lesions were positive on imaging and pathology (invasive or in situ ). False-positive lesions were positive on imaging but negative on pathology (high-risk or benign) or follow-up. False-negative lesions were negative on imaging (NBCC < 3 or not identified) but positive on pathology. Results The 59 women had 68 biopsy-proven malignant lesions detected on mammography/ultrasound, of which MRI demonstrated 66 (97%) and CEM 67 (99%) ( p  = 1.000). Forty-one additional lesions were detected in 29 patients: six of 41 (15%) on CEM only, 23/41 (56%) on MRI only, 12/41 (29%) on both; CEM detected 1/6 and MRI 6/6 malignant additional lesions ( p  = 0.063), with a positive predictive value (PPV) of 1/13 (8%) and 6/26 (23%) ( p  = 0.276). Conclusions While MRI and CEM were both highly sensitive for lesions detected at mammography/ultrasound, CEM may not be as sensitive as MRI in detecting additional otherwise occult foci of malignancy. Trial registration Australian and New Zealand Clinical Trials Registry: ACTRN 12613000684729

Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG) and sympathetic superior cervical ganglia (SCG) after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF) deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN) and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons.

PurposeFertility treatments are available for women diagnosed with a gynecological malignancy, which is important for women who desire a biological family subsequent to treatment. The objective of this study was to report reproductive outcomes following fertility-sparing treatment for a gynaecological cancer.MethodsElectronic databases were searched to identify studies that reported on reproductive outcomes after treatment for a gynecological malignancy.ResultsIn total, 77 studies were included which reported on reproductive outcomes after treatment for cervical cancer, endometrial cancer, gestational trophoblastic disease, and ovarian cancer. The main treatments included vaginal or abdominal radical trachelectomy, progestin therapy, salpingo-oophorectomy, and chemotherapy. The mean age at diagnosis for the study population and at birth were 30.5 years and 30.3 years, respectively. There were 4749 pregnancies (42%) reported for the included studies, with a miscarriage rate of 15% and a medical termination rate of 5%. The live birth rate was 74% with a 10% preterm rate.Implications for Cancer SurvivorsPatients should be offered timely discussions, information, and counseling regarding the impact of gynecological cancer treatment on a patient’s fertility. Furthermore, fertility-sparing strategies and fertility preservation should be discussed prior to starting treatment.

Background Childhood cancer survivors (CCS) experience an elevated burden of health complications, underscoring the importance of understanding the patterns of multimorbidity to guide the management of survivors with complex medical needs. Methods We examined the patterns of hospitalisations with multimorbidity in 5-year CCS ( n  = 2938) and age- and sex-matched non-cancer comparisons ( n  = 24,792) using statewide records of inpatient admissions in Western Australia from 1987 to 2019. Results Multimorbidity rates were higher for CCS (10.6, 95%CI 10.2–10.9) than for non-cancer comparisons (3.2, 95%CI 3.2–3.3). CCS exhibited a significantly higher adjusted hazard ratio of multimorbidity, particularly when admitted for neoplasms (14.6, 95%CI 11.2–19.1), as well as blood (7.3, 95%CI 4.9–10.7), neurological and sensory (5.2, 95%CI 4.2–6.6), and cardiovascular (3.6, 95%CI 2.6–4.8) diseases. By the age of 55 years, chronic multimorbidity was more prevalent in survivors than in comparisons (14.5% vs. 5.3%). Psychiatric disorders were common comorbidities, particularly in those admitted for neurological and sensory (71.1%), endocrine (61.5%), and digestive (59.3%) diseases. Multimorbidity during hospitalisation increased the length of hospital stay ( p  < 0.05). Key condition clusters included (1) psychoactive substance  dependence, alcohol misuse, and other mental disorders; (2) hypertension, diabetes, kidney disease, and musculoskeletal diseases; (3) epilepsy, hypothyroidism, and other liver diseases; and (4) hypertension, kidney disease, and other liver diseases. Conclusions These findings suggest that exposure to cancer in childhood elevates the risk of multimorbidity. The reconfiguration of healthcare delivery to enhance personalised care and clinical integration is essential for effectively managing multimorbidity in this population.

Objectives To identify women who survived breast cancer and subsequently conceived and to determine the rate of pregnancy (proportion), management, outcome of the cancer, and outcome of the first subsequent pregnancy. Design Population based descriptive study with cases identified from the Western Australian data linkage system and validated by review of medical charts. Supplementary data obtained from hospital and clinician records. Setting Western Australia, 1982-2003. Participants Women aged <45 with a diagnosis of breast cancer who subsequently conceived. Main outcome measures Pregnancy outcome and rate, survival, time from diagnosis to pregnancy. Results Sixty two (54%) women with a diagnosis of breast cancer who subsequently conceived did so less than two years after their diagnosis: 29 of them had an abortion, 27 had a live birth, and six miscarried. Within a proportional hazards regression model subsequent pregnancy was associated with improved overall survival (hazard ratio 0.59, 95% confidence interval 0.37 to 0.95). When the model was stratified by time from diagnosis subsequent pregnancy was associated with improved overall survival in women who waited at least 24 months to conceive (0.48, 0.27 to 0.83) and a non-significant protective effect was seen for women who waited at least six months to become pregnant. Conclusions Our study does not support the current medical advice given to premenopausal women with a diagnosis of with breast cancer to wait two years before attempting to conceive. This recommendation may be valid for women who are receiving treatment or have systemic disease at diagnosis, but for women with localised disease early conception, six months after completing their treatment, is unlikely to reduce survival.

Compton Lymphoedema Care was established 21 years ago to support palliative and curative patients with a lifelong condition. It has been identified in the business plan that there’s a need to review lymphoedema referrals in terms of numbers and quality to provide optimum and timely patient care. If lymphoedema is recognised early, physical complications can be minimised (Cooper, 2010).AimsTo improve the referral process for our stakeholders. To improve stakeholders’ knowledge of lymphoedema. To improve patients’ experience by encouraging early intervention for best symptom management.MethodsAn audit of referrals was conducted during 22/05/2017 to 26/07/2017. This was achieved by logging all referrals, locality, referrer name and designation. This was to map what GP practices, community/secondary services were referring and identify gaps in areas across the city to ascertain engagement and training needs.A survey was undertaken through SurveyMonkey to measure stakeholders’ knowledge of the service, time limit 15/08/2017 – 30/08/2017. Five questions were identified, the name of the organisation was requested and job role but anonymity was respected.OutcomeFrom the audit 92 referrals were received during the time period from a combination of primary and secondary services clearly showing gaps in areas across the city. 200 surveys were sent out and 65 responses received. Key findings were:98% of people had heard of Compton Lymphoedema Care but knowledge and understanding of the services offered differed28% of professionals weren’t aware of the support group25% were unsure how or who could refer.ConclusionThe project was successful in identifying a snap-shot of demographic data across the city that has clearly identified gaps. Furthermore, the survey has identified a need for increased community engagement, improved communication, marketing strategies and education. Early intervention supports best patient management and reduces risks associated with long term swelling (British Lymphoedema Society, 2010).

PurposeThe use of high-dose chemotherapy and radiotherapy combined with haematopoietic stem cell transplantation (HSCT) may negatively affect a woman’s reproductive potential. Reproductive outcomes such as infertility are a major concern for women who undergo treatment for a haematological cancer diagnosis.ObjectiveThis systematic review and meta-analysis explores reproductive outcomes following a haematological cancer requiring HSCT.MethodsElectronic databases were searched to identify studies that reported on reproductive outcomes after treatment for a haematological cancer diagnosis. Studies were included that reported on pregnancy and reproductive outcomes following HSCT for a haematological malignancy.ResultsThe meta-analysis included 14 studies, collectively involving 744 female patients. The subgroup analysis showed an overall pooled estimated pregnancy rate, for autologous or allogeneic HSCT recipients, of 22.7% (n = 438). There were 25% (n = 240) of women who became pregnant after autologous HSCT compared with 22% (n = 198) who subsequently became pregnant following allogeneic HSCT.ConclusionsThis meta-analysis reflects low pregnancy rates for cancer survivors desiring a family. However, live births are improving over time with new technology and novel therapies. Hence, female cancer patients should be offered timely discussions, counselling and education around fertility preservation options prior to starting treatment with gonadotoxic therapy.

Purpose When a pregnant woman is diagnosed with cancer, she faces complex and unique challenges while navigating both obstetric and oncological care. Despite often being the primary support for women diagnosed with cancer during pregnancy (CDP), little is known about the experiences of their partners. We undertook an in-depth exploration of the experiences of partners of women diagnosed with CDP in Australia. Methods Semi-structured interviews were conducted with partners of women diagnosed with CDP treated in Australia. Interviews explored partners’ inclusion in decision making and communication with health professionals and their own coping experiences. Data were analysed thematically. Results Data from interviews with 12 male partners ( N  = 12) of women diagnosed with CDP were analysed. Two unique themes relevant to partners were identified: ‘Partners require support to adjust to changing roles and additional burdens’ and ‘Treating the couple as a team facilitates agency and coping, but partners’ needs are placed second by all’. Conclusion Partners of women diagnosed with CDP commonly experience unique stressors and a substantial shift in previously established roles across multiple domains including medical advocacy, household coordination and parenting. Partners’ coping is interlinked with how the woman diagnosed with CDP is coping. Inclusion of partners in treatment decisions and communications, and considering partners’ wellbeing alongside that of the woman with CDP, is likely to be supportive for partners. In turn, this is likely to enhance the quality of support that women diagnosed with CDP receive from their partners.