PC-A ( 1 ), a bromo nor-eremophilane, showed selective antiproliferative activity against a triple-negative breast cancer (TNBC) cell line. This unique activity prompted us to establish a total synthesis to facilitate a structure-activity relationship (SAR) study and selectivity optimization. An enantioselective first total synthesis of 1 was achieved starting from ( R )-carvone through a side chain extension with a Mukaiyama aldol reaction and decalin construction. The synthesized decalin derivatives and debromo PC-A ( 2 ) were evaluated for antiproliferative activity against five human tumor cell lines, including TNBC, to assess preliminary SAR correlations.

Total Synthesis of a TNBC-Selective Cytotoxic Bromo Nor-eremophilane, PC-A, and Its Preliminary Structure-Activity Relationships.

Journal of Natural Products

The prevalence of obesity in older adults (people aged &gt;60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced reduction in skeletal muscle and bone mass, and the awareness of the 'obesity paradox'. Obesity in the elderly contributes to various obesity-related complications from cardiometabolic disease and cancer, to functional decline, worsening cognition, and quality of life, that will have already suffered an age-related decline. Lifestyle interventions remain the cornerstone of obesity management in older adults, with emphasis on resistance training for muscle strength and bone mineral density preservation. However, in older adults with obesity refractory to lifestyle strategies, pharmacotherapy, using anti-obesity medicines (AOMs), can be a useful adjunct. Recent evidence suggests that intentional weight loss in older adults with overweight and obesity is effective and safe, hence a diminishing reluctance to use AOMs in this more vulnerable population. Despite nine AOMs being currently approved for the treatment of obesity, limited clinical trial evidence in older adults predominantly focuses on incretin therapy with glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and tirzepatide). AOMs enhance weight loss and reduce cardiometabolic events, while maintaining muscle mass. Future randomised controlled trials should specifically evaluate the effectiveness of novel AOMs for long-term weight management in older adults with obesity, carefully considering the impact on body composition and functional ability, as well as health economics.

Obesity pharmacotherapy in older adults: a narrative review of evidence.

International Journal of Obesity

Antibiotics have played a pivotal role in modern medicine, drastically reducing mortality rates associated with bacterial infections. Despite their significant contributions, the emergence of antibiotic resistance has become a formidable challenge, necessitating a re-evaluation of antibiotic use practices. The widespread belief in clinical practice that bactericidal antibiotics are inherently superior to bacteriostatic ones lacks consistent support from evidence in randomized controlled trials (RCTs). With the latest evidence, certain infections have demonstrated equal or even superior efficacy with bacteriostatic agents. Furthermore, within clinical practice, there is a tendency to indiscriminately order urine cultures for febrile patients, even in cases where alternative etiologies might be present. Consequently, upon obtaining a positive urine culture result, patients often receive antimicrobial prescriptions despite the absence of clinical indications warranting such treatment.&#xa0;Furthermore, it is a prevailing notion among physicians that extended durations of antibiotic therapy confer potential benefits and mitigate the emergence of antimicrobial resistance. Contrary to this belief, empirical evidence refutes such assertions. This article aims to address common myths and misconceptions within the field of infectious diseases.

''Myth Busting in Infectious Diseases'': A Comprehensive Review.

Curēus

Some of the most common conditions affecting people are kidney diseases. Among them, we distinguish chronic kidney disease and acute kidney injury. Both entities pose serious health risks, so new drugs are still being sought to treat and prevent them. In recent years, such a role has begun to be assigned to sodium-glucose cotransporter-2 (SGLT2) inhibitors. They increase the amount of glucose excreted in the urine. For this reason, they are currently used as a first-line drug in type 2 diabetes mellitus. Due to their demonstrated cardioprotective effect, they are also used in heart failure treatment. As for the renal effects of SGLT2 inhibitors, they reduce intraglomerular pressure and decrease albuminuria. This results in a slower decline in glomelular filtration rate (GFR) in patients with kidney disease. In addition, these drugs have anti-inflammatory and antifibrotic effects. In the following article, we review the evidence for the effectiveness of this group of drugs in kidney disease and their nephroprotective effect. Further research is still needed, but meta-analyses indicate SGLT2 inhibitors' efficacy in kidney disease, especially the one caused by diabetes. Development of new drugs and clinical trials on specific patient subgroups will further refine their nephroprotective effects.

SGLT2 Inhibitors in Kidney Diseases-A Narrative Review.

International Journal of Molecular Sciences

Albumin is commonly employed across a wide range of clinical settings to improve hemodynamics, facilitate fluid removal, and manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, kidney replacement therapy, or experiencing complications of cirrhosis.

Co-chairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception to November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The guideline was revised after public consultation.

The panel made 14 recommendations on albumin use in adult critical care (3 recommendations), pediatric critical care (1 recommendation), neonatal critical care (2 recommendations), cardiovascular surgery (2 recommendations), kidney replacement therapy (1 recommendation), and complications of cirrhosis (5 recommendations). Of the 14 recommendations, 2 had moderate certainty of evidence, 5 had low certainty of evidence, and 7 had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin is commonly transfused.

There are currently few evidence-based indications that support the routine use of albumin in clinical practice to improve patient outcomes. This guideline provides clinicians with actionable recommendations on the use of albumin.

Use of Intravenous Albumin: A Guideline from the International Collaboration for Transfusion Medicine Guidelines.

Chest

The role of aldosterone has yet to be well appreciated in chronic kidney disease (CKD). Two variables define CKD: an estimated glomerular filtration rate of &lt;60&#x2009;ml/min/1.73 m2 and a spot urine albumin-creatinine ratio of &gt;30&#x2009;mg/g. Both are needed for an accurate diagnosis. The presence of CKD at this level is associated with an elevated risk of cardiovascular death and a greater risk of CKD progression to kidney failure and subsequent dialysis. This paper presents an overview of aldosterone's importance in CKD and its contribution to the inflammatory processes involved in CKD development. Data on outcomes, both surrogate and hard, related to outcomes on CKD progression will also be discussed in the context of mineralocorticoid blockade. Based on recent epidemiological data as well as data examining markers of diabetic kidney disease progression, it is clear that use of both renin-angiotensin system inhibitors and aldosterone receptor antagonists have a significant role in altering the natural history of kidney disease progression itself, as well as reducing the risk of cardiovascular events that generally accompany long-standing kidney disease. This paper will discuss these issues and the management of consequent hyperkalaemia when both steroidal and non-steroidal mineralocorticoid receptor antagonists are used in detail.

Mineralocorticoid receptor antagonists and reno-protection: What's the evidence & where do they fit? A guide for non-specialists.

Diabetes, Obesity & Metabolism

Traumatic brain injury is one of the leading causes of morbidity and mortality worldwide and is one of the major public healthcare burdens in the US, with millions of patients suffering from the traumatic brain injury itself (approximately 1.6 million/year) or its repercussions (2-6 million patients with disabilities). The severity of traumatic brain injury can range from mild transient neurological dysfunction or impairment to severe profound disability that leaves patients completely non-functional. Indications for treatment differ based on the injury's severity, but one of the goals of early treatment is to prevent secondary brain injury. Hemodynamic stability, monitoring and treatment of intracranial pressure, maintenance of cerebral perfusion pressure, support of adequate oxygenation and ventilation, administration of hyperosmolar agents and/or sedatives, nutritional support, and seizure prophylaxis are the mainstays of medical treatment for severe traumatic brain injury. Surgical management options include decompressive craniectomy or cerebrospinal fluid drainage via the insertion of an external ventricular drain. Several emerging treatment modalities are being investigated, such as anti-excitotoxic agents, anti-ischemic and cerebral dysregulation agents, S100B protein, erythropoietin, endogenous neuroprotectors, anti-inflammatory agents, and stem cell and neuronal restoration agents, among others.

Total Synthesis of a TNBC-Selective Cytotoxic Bromo Nor-eremophilane, PC-A, and Its Preliminary Structure-Activity Relationships.

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