Aims2 dimensional (2D) strain analysis detects subclinical left ventricular (LV) systolic dysfunction. Our aim was to evaluate changes in LV systolic and diastolic function in breast cancer patients early after anthracycline chemotherapy, and to identify predisposing factors.Methods and results140 patients were assessed by detailed echocardiography before and within seven days post treatment. LV ejection fraction (LVEF), global longitudinal strain (GLS), strain rate and radial and circumferential strain were assessed. Additionally, left atrial volumes and LV diastolic parameters were evaluated. LVEF although reduced after treatment, remained within the normal range (60±3% vs. 59±3%, p = 0.04). Triplane GLS was significantly reduced after treatment (-20.0±1.6% vs. -19.1±1.8%, p<0.001). Subclinical LV dysfunction (>11% reduction in GLS compared to before therapy) occurred in 22% (29/135). Impaired diastolic function grade significantly increased from 46% to 57% (p<0.001) after treatment. Furthermore, diastolic dysfunction was more common in the subgroup group with reduced systolic GLS compared to those without changes in GLS (30% vs. 11%; p = 0.04). No risk factors or clinical parameters were associated with the development of subclinical LV dysfunction; however the percentage change in early diastolic strain rate and the E velocity were independent predictors of >11% reduction in GLS.ConclusionTwenty two percent of patients had subclinical LV dysfunction by GLS, whilst none had cardiotoxicity defined by LVEF, demonstrating that GLS is more sensitive for detection of subclinical LV systolic dysfunction immediately after anthracycline therapy. Diastolic dysfunction increased, particularly in the group with reduced GLS, demonstrating the close pathophysiological relationship between systolic and diastolic function.

The complexity of head and neck cancers (HNC) mandates a multidisciplinary approach and radiation therapy (RT) plays a critical role in the optimal management of patients with HNC, either as frontline or adjuvant treatment postoperatively. The advent of both definitive and post-operative RT has significantly improved the outcomes of patients with HNC. Herein, we discuss the role of postoperative RT in different subtypes of HNC, its side effects, and the importance of surveillance. The treatment regions discussed in this paper are the oral cavity, nasopharynx, paranasal sinus cavity, oropharynx, larynx and hypopharynx. Multiple studies that demonstrate the importance of definitive and/or postoperative RT, which led to an improved outlook of survival for HNC patients will be discussed.

Development of early follicles, especially the activation of primordial follicles, is strictly modulated by a network of signaling pathways. Recent advance in ovarian physiology has been allowed the development of several therapies to improve reproductive outcomes by manipulating early folliculogenesis. Among these, in vitro activation (IVA) has been recently developed to extend the possibility of achieving genetically related offspring for patients with premature ovarian insufficiency and ovarian dysfunction. This method was established based on basic science studies of the intraovarian signaling pathways: the phosphoinositide 3-kinase (PI3K)/Akt and the Hippo signaling pathways. These two pathways were found to play crucial roles in folliculogenesis from the primordial follicle to the early antral follicle. Following the results of rodent experiments, IVA was implemented in clinical practice. There have been multiple recorded live births and ongoing pregnancies. Further investigations are essential to confirm the efficacy and safety of IVA before used widely in clinics. This review aimed to summarize the published literature on IVA and provide future perspectives for its improvement.

Several substituted 2- and 4-hydroxyacetophenones are linked to Wang resin via a modified Mitsunobu protocol. These resin-bound acetophenones are condensed with aromatic aldehydes, and the resulting chalcones 5 are used for the synthesis of 2-dialkylamino- (9a-d) and 2-alkylamino-4,6-diarylpyridines (11a-f), and 2-alkyl-4,6-diaryl- (14a) and 2,4,6-triarylpyrimidines (14b,c) in a manner suitable for combinatorial applications.

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Recent advances in early detection and oncological therapies have ameliorated the survival rate of young cancer patients. Yet, ovarian impairment induced by chemotherapy and radiotherapy is still a challenging issue. This review, based on clinical and lab-based studies, summarizes the evidence of gonadotoxicity of chemoradiotherapy, the recent approaches, ongoing controversies, and future perspectives of fertility preservation (FP) in female patients who have experienced chemo- or radio-therapy. Existing data indicate that chemotherapeutic agents induce DNA alterations and massive follicle activation via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Meanwhile, the radiation causes ionizing damage, leading to germ cell loss. In addition to the well-established methods, numerous therapeutic approaches have been suggested, including minimizing the follicle loss in cryopreserved ovarian grafts after transplantation, in vitro activation or in vitro growing of follicles, artificial ovarian development, or fertoprotective adjuvant to prevent ovarian damage from chemotherapy. Some reports have revealed positive outcomes from these therapies, whereas others have demonstrated conflictions. Future perspectives are improving the live birth rate of FP, especially in patients with adverse ovarian reserve, eliminating the risk of malignancy reintroducing, and increasing society’s awareness of FP importance.

Context While 90% of former American Osteopathic Association (AOA) residency programs transitioned to Accreditation Council for Graduate Medical Education (ACGME) accreditation, surgical subspecialty programs such as ear, nose, and throat (ENT, 62%) and ophthalmology (47%) struggled to gain accreditation. Doctors of Osteopathic Medicine (DOs) actively participate in serving underserved communities, and the loss of AOA surgical specialty programs may decrease access to surgical care in rural and nonmetropolitan areas. Objectives To determine the challenges faced by former AOA-accredited surgical subspecialty programs during the transition to ACGME accreditation, particularly ENT and ophthalmology programs in underresourced settings. Methods A directory of former AOA ENT and Ophthalmology programs was obtained from the American Osteopathic Colleges of Ophthalmology and Otolaryngology-Head and Neck Surgery (AOCOO-HNS). A secured survey was sent out to 16 eligible ENT and ophthalmology program directors (PDs). The survey contained both quantitative and qualitative aspects to help assess why these programs did not pursue or failed to receive ACGME accreditation. Results Twelve of 16 eligible programs responded, com-prising six ophthalmology and six ENT PDs. Among the respondents, 83% did not pursue accreditation (6 ophthalmology and 4 ENT programs), and 17% were unsuccessful in achieving accreditation despite pursuing accreditation (2 ENT programs). Across 12 respondents, 7 (58%) cited a lack of hospital/administrative support and 5 (42%) cited excessive costs and lack of faculty support as reasons for not pursuing or obtaining ACGME accreditation. Conclusions The survey results reflect financial issues associated with rural hospitals. A lack of hospital/administrative support and excessive costs to transition to the ACGME were key drivers in closures of AOA surgical specialty programs. In light of these results, we have four recommendations for various stakeholders, including PDs, Designated Institutional Officials, hospital Chief Medical Officers, and health policy experts. These recommendations include expanding Teaching Health Center Graduate Medical Education to surgical subspecialties, identifying and learning from surgical fields such as urology that fared well during the transition to ACGME, addressing the lack of institutional commitment and the prohibitive costs of maintaining ACGME-accredited subspecialty programs in underresourced settings, and reconsidering the Centers for Medicare & Medicaid Services (CMS) pool approach to physician reimbursement.

STUDY QUESTION How is the localisation of ovarian follicles affected by ageing and chronic diseases? SUMMARY ANSWER Ovarian follicles shift deeper towards the medulla, due to thickening of the tunica albuginea (TA), with ageing and some major common chronic diseases. WHAT IS KNOWN ALREADY The ovary undergoes morphological and functional changes with ageing. The follicular pool follows these changes with alterations in the amount and distribution of residual follicles. Diseases causing a chronic inflammatory process are associated with morphological changes and impaired ovarian function. STUDY DESIGN, SIZE, DURATION We conducted a cross-sectional study, examining 90 ovaries from 90 female monkeys. The samples were collected from April 2018 to March 2019 at Tsukuba Primate Research Center in National Institutes of Biomedical Innovation, Health and Nutrition, Japan. PARTICIPANTS/MATERIALS, SETTING, METHODS Ovarian samples were obtained from cynomolgus monkeys that died from natural causes or were euthanised. Ovarian sections were stained with haematoxylin and eosin (H&E) for histological analyses. In ovarian sections from 64 female macaques aged 0–25 years, a total of 13 743 follicles at different developmental stages (primordial, intermediary, primary, early secondary and late secondary) were assessed to determine the depth of each follicle from the outer surface of the ovarian cortex to the far end of the follicle, by using a digital imaging software. TA thickness was measured as sum of basal membrane and tunica collagen layer for each ovary under H&E staining. To explore the possibility of age-related trends in ovarian morphometric characteristics, samples were divided into four different age groups (0–3 years (pre-menarche), 4–9 years, 10–14 years and 15–20 years). To evaluate the effect of common chronic diseases on ovarian morphometric characteristics, macaques with diabetes mellitus (DM) (n = 10), endometriosis (n = 8) or inflammatory bowel disease (IBD) (n = 8) were compared to age-matched controls without chronic diseases. MAIN RESULTS AND THE ROLE OF CHANCE Ovarian morphometric analysis revealed that the relative location of follicles became deeper in all age groups according to development of follicles (P &lt; 0.05). Total follicle distance from the ovarian surface was increased with ageing (P &lt; 0.05). In a sub-analysis according to developmental stage, only primordial and intermediary follicles were localised deeper with increasing age (P &lt; 0.05). TA thickness was also increased with ageing (P &lt; 0.05). The localisation of the total number of follicles became deeper in ovaries from monkeys with DM, endometriosis or IBD as compared to the control group (P &lt; 0.05). With DM, analysis of follicles distance at almost each developmental stage was significantly deeper compared to controls (P &lt; 0.05) with the exception of early secondary follicles. With endometriosis, follicles at primary and early and late secondary stages were significantly deeper compared to controls (P &lt; 0.05). Also with IBD, follicles at primary and early and late secondary follicles were significantly deeper compared to controls (P &lt; 0.001). The TA was thicker with DM and endometriosis compared to controls (P &lt; 0.05), but not with IBD (P = 0.16). LARGE SCALE DATA NA. LIMITATIONS, REASONS FOR CAUTION Two-dimensional histology was used to assess follicle localisation. The possibility of minimal variations between the measured distance to the actual distance in a spherical structure cannot be excluded. Additionally, the severity of disease was not assessed. WIDER IMPLICATIONS OF THE FINDINGS This study is the first step towards enhancing our understanding of how ageing and chronic diseases affect the relative localisation of dormant and developing follicles. These observations, combined with possible future human studies, may have managerial implications in the field of fertility preservation and other conditions involving ovarian tissue cryopreservation. STUDY FUNDING/COMPETING INTEREST(S) The present work was supported by the Grant-in-Aid for Scientific Research B (19H03801) (to K.K.), Challenging Exploratory Research (18K19624), Japan Agency for Medical Research and Development, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Takeda Science Foundation and Naito Foundation (to K.K.). All authors have no conflicts of interest directly relevant to the content of this article.