Early-life exposure to metabolic hormones may influence the development of taste acceptance and subsequent intake of hyperpalatable foods (HPF) in infants, but evidence integrating hormonal, behavioral, and dietary data in humans is limited. Therefore, our objective was to determine whether concentrations of insulin, leptin, cortisol, and liver-expressed antimicrobial peptide 2 (LEAP2) in human milk and infant plasma at 6 months predict infant sweet and fat taste acceptance and HPF intake later in infancy. In this prospective cohort study, human milk and infant plasma were collected at 6 months and analysed for insulin, leptin, cortisol, and LEAP2. At 18 months, sweet and fat taste acceptance were assessed using ingestion ratio (IR; motivational drive) and liking ratio (LR; hedonic response). HPF intake was quantified from standardized 24-h dietary recalls. Associations were evaluated using multivariable linear regression. Eighty two mother-infant pairs were enrolled, of which 28 completed follow-up and were included in the final analysis. Milk LEAP2 was positively associated with fat IR (p = .037). Milk insulin was inversely associated with sweet IR (p = .003) and LR (p = .020), while milk leptin was positively associated with sweet IR (p = .013) and LR (p = .018) and inversely associated with HPF intake consumption (p = .001). Milk cortisol was positively associated with fat (p = .043) and sweet IR (p = .014). In contrast, infant plasma LEAP2 was inversely associated with fat IR (p = .018) and HPF intake (p = .002) but positively associated with sweet IR (p = .005) and LR (p = .023). Infant plasma cortisol was directly associated with HPF intake (p = .006) and inversely associated with sweet and IR (p = .004) and fat LR (p = .009). Milk-derived and endogenous metabolic hormones were differentially associated with taste acceptance and HPF intake, identifying specific hormonal pathways that may shape early feeding behavior and later food intake. Clinical Trial Registry: This study was registered at clinicaltrials.gov as NCT05798676. https://clinicaltrials.gov/study/NCT05798676.

Adrenocortical carcinoma (ACC) is a rare malignancy, accounting for 0.05-2% of all malignant tumors. Most cases are sporadic and asymptomatic, often discovered incidentally via imaging. However, 50-60% present with autonomous hormonal secretion, with 45% producing excess cortisol, and only 1% exhibiting mineralocorticoid excess. We report a 43-year-old Filipino female with a 6-month history of abdominal bloating, proximal muscle weakness, edema, and hypertension. Laboratory tests showed hypokalemia (serum potassium 2.5-3.05 mmol/L; normal 3.3-5.0 mmol/L). Imaging revealed a neoplastic right suprarenal mass (adrenal origin vs confluent lymphadenopathy) described as an incidental, lipid-poor right adrenal mass measuring 4.7 x 3.6 x 6.1 cm, with contrast-enhanced Hounsfield units of 40, along with periportal and paraaortic lymphadenopathies. Biochemical evaluation indicated an intermediate probability of primary aldosteronism: suppressed plasma renin at 0.97 ug/L/hr (0.97 ng/mL/hr), normal plasma aldosterone 599.46 pmol/L (21.61 ng/dl), and aldosterone-renin ratio of 618 (pmol/L)/(ng/L/hr) (22.27 ng/dl/ng/mL/hr). Ideally, confirmatory testing with an aldosterone suppression test prior to imaging and adrenal vein sampling (AVS) should be performed to lateralize the lesion before surgery; however, the patient opted to proceed with surgery. The patient also had overt hypercortisolism, with non-suppressed serum cortisol of 31.88 µg/dL (reference <1.8 µg/dL) on a low-dose dexamethasone suppression test, suppressed ACTH at 2.81 pg/mL (reference 7.7-63.6 pg/mL) (Table 1), and clinical features of Cushing syndrome, including facial plethora, and proximal muscle weakness. While these findings support the diagnosis of an ACTH-independent hypercortisolism, current guidelines recommend confirmatory testing, including 24-hour urinary free cortisol or late-night salivary cortisol, before definitive evaluation to distinguish ACTH-dependent from ACTH-independent disease. Concomitant catecholamine and androgen excess were excluded with normal 24-hour urine metanephrines and serum DHEAS. Surgical removal via open adrenalectomy was performed. Histopathology confirmed ACC, supported by immunohistochemistry. Postoperative treatment included radiotherapy and planned adjuvant mitotane therapy. During follow-up, the patient's blood glucose and blood pressure worsened, requiring medication adjustments. Unfortunately, the patient succumbed to the disease seven months post-surgery. This case highlights the difficulties in assessing adrenal tumors that concurrently secrete cortisol and aldosterone, especially when biochemical results are inconclusive, emphasizing the need for careful assessment and prompt intervention in this rare coexistence.

Neogeometric copper nanoparticles (CuNPs) in drug delivery can be exploited for its cytotoxic effects and enhanced cellular uptake in dermatological conditions. The nanosystem, designed herein, is embedded in a Self-Oscillating Polymeric Network (SOPN) to stimulate the permeation of cubic CuNPs across the stratum corneum of induced psoriasiform-plaques in a BALB/c mouse model. Polymerization and cross-linking of the SOPN from NIPAM (N-isopropylacrylamide) and a metal salt exerted thermal and molecular differences of the resulting poly-NIPAM whilst maintaining inherent NIPAM thermo-responsive properties to control CuNP-permeation in an inflammatory environment. From an experimental design consisting of 15 formulations, it was found that thermo-responsive changes between 27-35˚C in the SOPN promoted the oscillatory behavior required for skin permeation of CuNPs where an oscillatory duration of 40 min was obtained. Viability analysis of the SOPN established biocompatible concentrations of the system for use in the in vivo model at reduced CuNP concentrations to control cytotoxicity (64.26-72.58%). The CuNP-loaded SOPN gel (60ug/mL) effectively promoted psoriatic-plaque resolution and hair growth, after 7 and 14 days of treatment, compared to the comparative (0.5% hydrocortisone cream). The geometric nanosystem embedded in an aqueous cream vehicle and the SOPN gel exhibited promising results in the reduction of in vivo psoriasiform-plaques compared to the gold standard.

Some of the immediate, medium-term, and long-term complications of acute community-acquired pneumonia are correlated with the degree of inflammation in the initial phase, particularly when it is dysregulated. Among the treatments designed to control this inflammation, corticosteroid therapy has been the most extensively studied. Randomized trials conducted in hospitalized patients have generally shown faster improvement with corticosteroids and prevention of subsequent worsening. In patients admitted to intensive care units, and despite conflicting trial results, meta-analyses conclude - with a low level of evidence - that there is a reduction in one-month mortality without an increase in the incidence of hospital-acquired infections. The incidence of hyperglycemia is increased with corticosteroid therapy and is likely a barrier to their use outside of intensive care units. In influenza, data from observational studies suggest excess mortality and lead to the contraindication of corticosteroids outside of therapeutic trials. In the future, treatment will likely need to be individualized based on clinical and biologic parameters, particularly the inflammatory syndrome and immunological phenotyping.

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) involving multiple organs. However, delayed-onset, multisystem irAEs after treatment discontinuation are uncommon. Here, we present a rare case of a man in his 50s with microsatellite instability-high colon cancer who developed multisystem irAEs following treatment with nivolumab plus ipilimumab. The patient developed adrenocorticotropic hormone deficiency after four cycles of combination therapy, which improved with hydrocortisone supplementation. Following eight cycles of nivolumab monotherapy, treatment was discontinued because no cancerous lesions were detected. Six months after the final nivolumab administration, the patient presented with bilateral knee arthritis and elevated hepatobiliary and pancreatic enzyme levels. No evidence of infectious, autoimmune, or IgG4-related disease was found. Liver biopsy revealed portal lymphocytic infiltration with a predominance of CD8-positive cells. The patient was diagnosed with delayed ICI-related arthritis, accompanied by asymptomatic cholangitis and pancreatitis. These irAEs improved rapidly after prednisolone administration. This case demonstrates that irAEs can occur in a delayed and multisystem manner, even after the cessation of ICIs. Thus, clinicians should consider irAEs in the differential diagnosis when new symptoms or unexplained laboratory abnormalities occur in patients with prior ICI exposure.

Dairy cows experience long-term stress during the pre- and postpartum period, as during this period they face extreme challenges related to their health, productivity and overall welfare. Recently, hair cortisol has gained attention as one of the most promising and non-invasive biomarkers for evaluating stress. However, the exact mechanism of its deposition in the hair remains unknown. This review combines the utility of hair cortisol as a tool for evaluating chronic stress and its effect on health status, lactation, parity, body condition score (BCS), and metabolic parameters, specifically glucose, β-hydroxybutyrate (BHBA), and non-esterified fatty acids in dairy cows. Emphasis is given to the transition period around parturition, where hormonal fluctuation, negative energy balance, and immunosuppression increase the animal's susceptibility to stress. Methodologically, tail hair exhibits a higher cortisol concentration than other regions due to a faster growth rate, making it an ideal site for maintaining a proper sampling interval during the transition period. Furthermore, regrown hair contains higher cortisol levels than native hair during parturition. In addition, hair cortisol level significantly elevated during peak lactation in multiparous cows and in cows with oversized or twin calves. Notably, newborn calves have higher cortisol than their dam during birth. Cows diagnosed with a disease condition display higher cortisol levels than healthy cows during the postpartum period. During the transition period, Glucose was found to be positively correlated with hair cortisol level, whereas β-hydroxybutyrate (BHBA) was negatively correlated with hair cortisol in multiparous cows. Ultimately, evaluating hair cortisol concentration alongside associated production and metabolic factors during the periparturient period can provide a proper framework for improving and monitoring dairy cattle welfare. However, further research is required on hair cortisol concentration and its connection with various stressors of the transition period, sampling and analytical methods, and a standardized reference range so that it can have practical use at the farm level.