Oestrogens, adipose tissues and environmental exposures influence obesity and diabetes across the lifecycle.

Endogenous oestrogens regulate essential functions to include menstrual cycles, energy balance, adipose tissue distribution, pancreatic ß-cell function, insulin sensitivity and lipid homeostasis. Oestrogens are a family of hormones which include oestradiol (E2), oestrone (E1) and oestriol (E3). Oestrogens function by binding and activating oestrogen receptors (ERs). Phytoestrogens are plant-derived compounds which exhibit oestrogenic-like activity and can bind to ERs. Phytoestrogens exert potential oestrogenic-like benefits; however, their effects are context-dependent and require cautious consideration regarding generalised health benefits. Xenoestrogens are synthetic compounds which have been determined to disrupt endocrine function through binding to ERs. Xenoestrogens enter the body through various routes and given their chemical structure they can accumulate, posing long-term health risks. Xenoestrogens interfere with endogenous oestrogens and their functions contributing to conditions like cancer, infertility, and metabolic disorders. Understanding the interplay between endogenous and exogenous oestrogens is critical in order to determine their potential health consequences and requires further investigation. This manuscript provides a summary of the role endogenous oestrogens have in regulating metabolic functions. Additionally, we discuss the impact phytoestrogens and synthetic xenoestrogens have on biological systems across various life stages. We highlight their mechanisms of action, potential benefits, risks and discuss the need for further research to bridge gaps in understanding and mitigate exposure-related health risks.

The AANS Harvey Cushing Medal: a demographic and academic analysis of its recipients.

Background: The Harvey Cushing Medal, awarded by the American Association of Neurological Surgeons, is the premier accolade in neurosurgery. The study's purpose was to examine the qualities and accomplishments of previous winners, emphasizing potential selection biases, with the aim to promote social justice and guide young neurosurgeons in their career paths. Results: Predominantly, recipients graduated from top-ranked United States News and World Report institutions and specialized in cerebrovascular and neuro-oncologic/skull base neurosurgery. A significant proportion held roles as department or division chairs and led neurosurgical organizations. All awardees were male, and there was a notable trend of increasing publication counts among more recent recipients. Conclusions: Commonalities among Harvey Cushing Medal winners include graduating from top institutions, holding significant leadership roles, and having an extensive publication history. However, the absence of female and underrepresented minority awardees underscores an urgent need for greater diversity in the selection process.

The evolutionary impact and influence of oestrogens on adipose tissue structure and function.

Oestrogens are sex steroid hormones that have gained prominence over the years owing to their crucial roles in human health and reproduction functions which have been preserved throughout evolution. One of oestrogens actions, and the focus of this review, is their ability to determine adipose tissue distribution, function and adipose tissue 'health'. Body fat distribution is sexually dimorphic, affecting males and females differently. These differences are also apparent in the development of the metabolic syndrome and other chronic conditions where oestrogens are critical. In this review, we summarize the different molecular mechanisms, pathways and resulting pathophysiology which are a result of oestrogens actions in and on adipose tissues. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Pediatric pathology all grown up - An interesting case of adult tethered spinal cord.

BACKGROUND: Cervical myelopathy in an adult is typically the result of degenerative disease or trauma. Dysraphism is rarely the cause. CASE DESCRIPTION: The authors report the case of a 35-year-old male drywall installer who presented with 2 years of progressive left upper extremity weakness, numbness, and hand clumsiness. Only upon detailed questioning did he mention that he had neck surgery just after birth, but he did not know what was done. He then also reported that he routinely shaved a patch of lower back hair, but denied bowel, bladder, or lower extremity dysfunction. Magnetic resonance imaging of the cervical spine demonstrated T2 hyperintensity at C4-C5 with dorsal projection of the neural elements into the subcutaneous tissues concerning for a retethered cervical myelomeningocele. Lumbar imaging revealed a diastematomyelia at L4. He underwent surgical intervention for detethering and repaired of the cervical myelomeningocele. Four months postoperatively, he had almost complete resolution of symptoms, and imaging showed a satisfactory detethering. The diastematomyelia remained asymptomatic and is being observed. CONCLUSION: Tethered cervical cord is a rare cause for myelopathy in the adult patient. In the symptomatic patient, surgical repair with detethering is indicated to prevent disease progression and often results in clinical improvement.

Antibody Therapy Targeting RAN Proteins Rescues C9 ALS/FTD Phenotypes in C9orf72 Mouse Model.

The intronic C9orf72 G4C2 expansion, the most common genetic cause of ALS and FTD, produces sense- and antisense-expansion RNAs and six dipeptide repeat-associated, non-ATG (RAN) proteins, but their roles in disease are unclear. We generated high-affinity human antibodies targeting GA or GP RAN proteins. These antibodies cross the blood-brain barrier and co-localize with intracellular RAN aggregates in C9-ALS/FTD BAC mice. In cells, α-GA1 interacts with TRIM21, and α-GA1 treatment reduced GA levels, increased GA turnover, and decreased RAN toxicity and co-aggregation of proteasome and autophagy proteins to GA aggregates. In C9-BAC mice, α-GA1 reduced GA as well as GP and GR proteins, improved behavioral deficits, decreased neuroinflammation and neurodegeneration, and increased survival. Glycosylation of the Fc region of α-GA1 is important for cell entry and efficacy. These data demonstrate that RAN proteins drive C9-ALS/FTD in C9-BAC transgenic mice and establish a novel therapeutic approach for C9orf72 ALS/FTD and other RAN-protein diseases.