Autonomic brain functioning and age-related health concerns.

The autonomic nervous system (ANS) regulates involuntary bodily functions such as blood pressure, heart rate, breathing, and digestion, in addition to controlling motivation and behavior. In older adults, the ANS is dysregulated, which changes the ability of the ANS to respond to physiological signals, regulate cardiovascular autonomic functionality, diminish gastric motility, and exacerbate sleep problems. For example, a decrease in heart rate variability, or the variation in the interval between heartbeats, is one of the most well-known alterations in the ANS associated with health issues, including cardiovascular diseases and cognitive decline. The inability to perform fundamental activities of daily living and compromising the physiological reactivity or motivational responses of older adults to moving toward or away from specific environmental stimuli are significant negative consequences of chronic and geriatric conditions that pose grave threats to autonomy, health, and well-being. The most updated research has investigated the associations between the action responsiveness of older adults and the maintenance of their physiological and physical health or the development of mental and physical health problems. Once autonomic dysfunction may significantly influence the development of different age-related diseases, including ischemic stroke, cardiovascular disease, and autoimmune diseases, this review aimed to assess the relationship between aging and autonomic functions. The review explored how motivational responses, physiological reactivity, cognitive processes, and lifelong developmental changes associated with aging impact the ANS and contribute to the emergence of health problems.

Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high­incidence adult male cancers (Review).

The term 'cancer' refers to >100 disorders that progressively manifest over time and are characterized by uncontrolled cell division. Although malignant growth can occur in virtually any human tissue, the underlying mechanisms underlying all forms of cancer are consistent. The International Agency for Research on Cancer's annual GLOBOCAN 2020 report provided an update on the global cancer incidence and mortality. Excluding non-melanoma skin cancer, the report predicts that there will be 19.3 million new cancer cases and >10 million cancer-related fatalities in 2023. Lung, prostate, and colon cancers are the most prevalent and lethal cancers in males. It was recognized that post-translational modifications (PTMs) of proteins are necessary for almost all cellular biological processes, as well as in cancer development and metastasis to other bodily organs. Thus, PTMs have a considerable impact on how proteins behave. Various PTMs may have harmful roles by affecting the hallmarks of cancer, metabolism and the regulation of the tumor microenvironment. PTMs and genetic changes/mutations are essential in carcinogenesis and cancer development. A pivotal PTM mechanism is protein ubiquitination. Of note, the rate-limiting stage of the protein ubiquitination cascade is hypothesized to be E3-ligase-mediated ubiquitination. Numerous studies revealed that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) E3 ligase is among the E3 ubiquitin ligases that have essential roles in cellular processes. It regulates protein degradation and substrate ubiquitination. In addition, it has been shown that NEDD4 primarily functions as an oncogene in various malignancies but can also act as a tumor suppressor in certain types of tumor. In the present review, the roles of NEDD4 as an anticancer protein in various high-incidence male malignancies and the significance of NEDD4 as a potential cancer therapeutic target are discussed. In addition, the targeting of NEDD4 as a therapeutic strategy for the treatment of human malignancies is explored.

The effects of statin therapy on brain tumors, particularly glioma: a review.

Brain tumors account for less than 2% of all malignancies. However, they are associated with the highest morbidity and mortality rates among all solid tumors. The most common malignant primary brain tumors are glioma or glioblastoma (GBM), which have a median survival time of about 14 months, often suffer from recurrence after a few months following treatment, and pose a therapeutic challenge. Despite recent therapeutic advances, the prognosis for glioma patients is poor when treated with modern therapies, including chemotherapy, surgery, radiation, or a combination of these. Therefore, discovering a new target to treat brain tumors, particularly glioma, might be advantageous in raising progression-free survival and overall survival (OS) rates. Statins, also known as competitive HMG-CoA reductase inhibitors, are effective medications for reducing cholesterol and cardiovascular risk. The use of statins prior to and during other cancer treatments appears to enhance patient outcomes according to preclinical studies. After surgical resection followed by concurrent radiation and treatment, OS for patients with GBM is only about a year. Statins have recently emerged as potential adjuvant medications for treating GBM due to their ability to inhibit cell growth, survival, migration, metastasis, inflammation, angiogenesis, and increase apoptosis in-vitro and in-vivo studies. Whether statins enhance clinical outcomes, such as patient survival in GBM, is still debatable. This study aimed to explore the effects of statin therapy in the context of cancer treatment, with a particular focus on GBM.

Perforated Stress Ulcer of the Duodenum: a Case of an Unexpected Diagnosis in a COVID-19 Patient Following Dilatation and Curettage Procedure.

Background: Stress ulcers in the upper gastrointestinal tract can arise from pathologies related to erosive or inflammatory insults in critically ill patients. The relationship between stressful bodily events and the ischemia and perforation of stress ulcers is poorly understood. Objective: We present a case of perforated stress ulcer following an abortion that was treated by dilatation and curettage (D&C) and complicated by a coronavirus disease 2019 (COVID-19) infection. Case presentation: A 40-year-old lady presented to the emergency room complaining of diffuse abdominal pain, she was recently diagnosed with an incomplete abortion and managed via a D&C procedure in an external hospital. A computed tomography (CT) scan was done at our center for the abdomen and pelvis, showing extensive pneumoperitoneum, which brought the radiologist's attention to suspect a small bowel perforation presumably accompanying a uterine perforation secondary to the D&C. There were no obvious signs of pelvic small bowel perforation in the initial CT images. The perforated duodenal stress ulcer was diagnosed the next day by a new CT scan following oral contrast ingestion and managed surgically by repair and omental patch, and no other bowel perforations were found upon surgical exploration. After the surgery, the patient was diagnosed with COVID-19, and her clinical status deteriorated gradually during the following week, and she passed away from a cardiac arrest. Conclusion: It is unclear whether septic abortion or COVID-19 has resulted in stress ulcer perforation in our patient. This case report highlights the importance of raising early suspicion in the diagnosis of stress ulcer perforation in critically ill patients to reduce the risk of morbidity and mortality.

Granulomatous lobular mastitis: Clinical update and case study.

BACKGROUND: Granulomatous lobular mastitis (GM) is a rare chronic benign inflammatory breast condition. It can present a diagnostic challenge and mimic inflammatory carcinoma. It causes significant morbidity for affected patients. OBJECTIVE: The aim of this article is to provide a clinical update and case study for general practitioners, who are usually the first to see the patient. DISCUSSION: GM is usually idiopathic. The condition presents with a large painful lump with erythema. There is often ulceration, abscess and sinus formation. Triple assessment is needed to confirm diagnosis. GM may last for 12 months or more before healing occurs. Options for management are conservative/supportive care, oral prednisone or methotrexate, or surgical excision. At present, there is no universally accepted management strategy for GM; therefore, treatment will depend on the symptoms, extent of disease and patient preferences. Supporting the patient in coping with the long-term nature of GM and the chronic discharging lesions is essential.

Presentation, tumour and treatment features in immigrant women from Arabic-speaking countries treated for breast cancer in Australia.

BACKGROUND: Australia has a large population of immigrant women from Arabic-speaking countries. The aim of this study was to examine breast cancer tumour and surgical treatment features for women born in Arabic-speaking countries and compare them to women born in Australia and other countries. Another aim was to consider how this information can inform clinical care for this multicultural population. METHODS: This is a retrospective audit of an institutional breast cancer database. Demographic, tumour and surgical treatment data were extracted for the Arab women and compared to Australian-born women (comparison 1) and to women born in all other countries (comparison 2); chi-squared analysis was performed to test for differences between groups. RESULTS: A total of 2086 cases with country of birth information were identified, of whom 139 women (6.7%) were born in Arabic-speaking countries, 894 (42.8%) were born in Australia and 1053 (50.4%) were born in other countries (71 nations). Arab women tended to be younger (P = 0.013), more disadvantaged (P < 0.001), were more likely to have symptomatic rather than screen-detected breast cancer (P < 0.001), had a higher rate of high grade (P = 0.021), HER2-positive (P = 0.025) breast cancer compared to Australian-born women or others. There was no difference in tumour (pT) stage, rate of breast conservation versus mastectomy, re-excision and contralateral prophylactic mastectomy between groups. Australian-born women were more likely to undergo breast reconstruction after mastectomy (P < 0.001); reconstruction rate was >29% in all groups. CONCLUSION: Women born in Arabic-speaking countries were younger, more disadvantaged and showed more aggressive tumour features. This has implications for supportive care during treatment and survivorship.

Targeted axillary dissection after neoadjuvant systemic therapy in patients with node-positive breast cancer.

BACKGROUND: Over the last decade, neoadjuvant systemic therapy (NAST) has gained considerable popularity and its use has been extended to include breast cancer patients with operable node-positive disease. It may no longer be necessary to commit patients who are node-positive at presentation to axillary dissection if they become clinically node-negative after completing NAST. Targeted axillary dissection (TAD) is a technique where the marked pre-NAST positive node is excised along with the sentinel nodes and its response to chemotherapy is assessed and thus helps guide further treatment to the axilla. METHODS: The aim of this study was to determine the feasibility of marking positive axillary nodes with a clip and removing the clipped node after neoadjuvant treatment. We also assessed the concordance of the sentinel node with the clipped node. RESULTS: We prospectively evaluated 37 clinically and/or radiologically node-positive patients who underwent NAST. The overall identification rate of the clipped node was 78%. The identification rate was 100% if the clipped node was localized preoperatively and was much lower at 68% in patients who did not have the clipped node localized. The clipped node was not retrieved as the sentinel node in 14% of patients. CONCLUSION: We present the first Australian series on the feasibility of TAD. TAD is a feasible option in patients having NAST and with every new technique there is a learning curve. With the increasing experience globally and the refinement in marking and localization techniques, the accuracy of performing TAD will likely continue to improve.

Update on the management of early-stage breast cancer.

BACKGROUND: Breast cancer affects one in eight Australian women. While surgery, chemotherapy, radiotherapy and endocrine therapy are still the main treatments, there have been changes in the sequencing of treatment and advances in each therapy. The general practitioner (GP) is involved at each stage of the patient's journey. OBJECTIVE: This article discusses the current approach to the management of early breast cancer. It focuses on changes in recent years and discusses the role of the GP in supporting women in their decision-making and treatment. DISCUSSION: Key changes include the increasing use of neoadjuvant chemotherapy, the development of advanced oncoplastic surgery and breast reconstruction techniques, the use of gene expression profiling and the recommendation for extended adjuvant endocrine therapy for up to 10 years.