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Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular diseases, and comprises obesity, hypertension, impaired glucose metabolism and dyslipidaemia. It is well recognised that the mineralocorticoid receptor (MR) plays an important role in blood pressure regulation via its effect on salt and water retention in renal tubules, with hypertension being a key feature in primary aldosteronism patients with excess adrenal production of aldosterone, the primary ligand for MRs in the epithelial tissues. MRs are also expressed in a number of non-epithelial tissues including adipose tissue; in these tissues, glucocorticoids or cortisol can also activate MRs due to low levels of 11-beta-hydroxysteroid-dehydrogenase type 2 (11-βHSD2), the enzyme which inactivates cortisol. There is increasing evidence suggesting that over-activation of MRs plays a role in the pathophysiology of the other components of metabolic syndrome, promoting adiposity, inflammation and glucose intolerance, and that MR antagonists may confer beneficial effects on energy and substrate homeostasis and cardiometabolic diseases. This review discusses the advances in the literature shedding light on the MR as an emerging player in metabolic syndrome.

Abstract Background In primary aldosteronism (PA), excessive, autonomous secretion of aldosterone is not suppressed by salt loading or fludrocortisone. For seated saline suppression testing (SSST), the recommended diagnostic cutoff 4-hour plasma aldosterone concentration (PAC) measured by high-performance liquid chromatography–mass spectrometry (HPLC-MS/MS is 162 pmol/L. Most diagnostic laboratories, however, use immunoassays to measure PAC. The cutoff for SSST using immunoassay is not known. We hypothesized that the cutoff is different between the assays. Methods We analyzed 80 of the 87 SSST tests that were performed during our recent study defining the HPLC-MS/MS cutoff. PA was confirmed in 65 by positive fludrocortisone suppression testing (FST) and/or lateralization on adrenal venous sampling and excluded in 15 by negative FST. PAC was measured by a chemiluminescence immunoassay (PACIA) in the SSST samples using the DiaSorin Liaison XL analyzer, and receiver operating characteristics (ROC) analysis was performed to identify the PACIA cutoff. Results ROC revealed good performance (area under the curve = 0.893; P < .001) of 4-hour postsaline PACIA for diagnosis of PA and an optimal diagnostic cutoff of 171 pmol/L, with sensitivity and specificity of 95.4% and 80.0%, respectively. A higher cutoff of 217 pmol/L improved specificity (86.7%) with lower sensitivity (86.2%). PACIA measurements strongly correlated with PAC measured by HPLC-MS (r = 0.94, P < .001). Conclusions A higher diagnostic cutoff for SSST should be employed when PAC is measured by immunoassay rather than HPLC-MS/MS. The results suggest that (i) PA can be excluded if 4-hour PACIA is less than 171 pmol/L, and (ii) PA is highly likely if the PACIA is greater than 217 pmol/L by chemiluminescence immunoassay. A gray zone exists between the cutoffs of 171 and 217 pmol/L, likely reflecting a lower specificity of immunoassay.

Abstract Context and Objective Posture-responsive and posture-unresponsive aldosterone-producing adenomas (APAs) account for approximately 40% and 60% of APAs, respectively. Somatic gene mutations have been recently reported to exist in approximately 90% of APAs. This study was designed to characterize the biochemical, histopathologic, and genetic properties of these 2 types of APA. Methods Plasma levels of aldosterone and hybrid steroids (18-oxocortisol and 18-hydroxycortisol) were measured by liquid chromatography-tandem mass spectrometry. Immunohistochemistry for CYP11B2 (aldosterone synthase) and CYP17A1 (17α-hydroxylase) and deoxyribonucleic acid sequencing (Sanger and next-generation sequencing) were performed on APA tissue collected from 23 posture-unresponsive and 17 posture-responsive APA patients. Results Patients with posture-unresponsive APA displayed higher (P < 0.01) levels of hybrid steroids, recumbent aldosterone and cortisol, larger (P < 0.01) zona fasciculata (ZF)-like tumors with higher (P < 0.01) expression of CYP17A1 (but not of CYP11B2) than patients with posture-responsive APA (most of which were not ZF-like). Of 40 studied APAs, 37 (92.5%) were found to harbor aldosterone-driving somatic mutations (KCNJ5 = 14 [35.0%], CACNA1D = 13 [32.5%], ATP1A1 = 8 [20.0%], and ATP2B3 = 2 [5.0%]), including 5 previously unreported mutations (3 in CACNA1D and 2 in ATP1A1). Notably, 64.7% (11/17) of posture-responsive APAs carried CACNA1D mutations, whereas 56.5% (13/23) of posture-unresponsive APAs harbored KCNJ5 mutations. Conclusions The elevated production of hybrid steroids by posture-unresponsive APAs may relate to their ZF-like tumor cell composition, resulting in expression of CYP17A1 (in addition to somatic gene mutation-driven CYP11B2 expression), thereby allowing production of cortisol, which acts as the substrate for CYP11B2-generated hybrid steroids.

Acute graft vs. host disease (aGVHD) results from newly transplanted donor immune cells recognizing recipient tissues as foreign, leading to end-organ damage. Diagnosing aGVHD typically involves a combination of clinical evaluation, histological examination, laboratory tests, and imaging studies. Although typically associated with allogeneic stem cells transplant and less frequently with liver or small bowel transplants, solid organ transplant GVHD (SOT-GVHD) associated with kidney-pancreas transplants is exceedingly rare. Our patient presented with pancytopenia unexplained by typical causes. He developed classical aGVHD findings of fever, diarrhea, rash, and abnormal liver tests. Our case underscores the importance of keeping a broad differential when evaluating solid organ transplant patients.

This study examines the intentions of foreign workers living in Okayama, Japan, to stay long-term in Japan. Utilizing a Bayesian multinomial logistic regression model, this research provides a novel analytical approach that captures parameter uncertainty and accommodates the categorical nature of migrants' settlement intentions using primary data collected via a questionnaire survey from January to March 2024. The findings reveal that residence status, previous experience of living in Japan, and graduation from a Japanese education institution significantly influence long-term settlement intentions. In addition, respondents aged 26-35 intend to stay longer than those of other ages, and those from less developed countries, such as Myanmar and Vietnam, intend to stay longer than those from China. Conversely, highly educated migrants express lower settlement intentions, suggesting a potential loss of skilled foreign labor in Japan. Notably, migrants in the Technical Intern Training Program are more likely to stay longer than those with other residence statuses, such as Highly Skilled Professional. In contrast, workers with higher education levels tend to have less intention to stay long-term, indicating a high probability of Japan losing educated foreign labor in the future. These findings contribute to understanding the dynamics of migrant workers in Japan, which is crucial for creating policies for foreign workers that can attract and support long-term settlement. These findings have important implications for policy, particularly in enhancing community integration, reducing workplace discrimination, and designing residence pathways that support long-term retention.

Abstract We report an Epstein-Barr virus–associated smooth muscle tumor in an adult male with AIDS. The patient had multiple lung nodules seen on computed tomography of the chest and an endobronchial lung tumor identified on bronchoscopy. Initiation of antiretroviral therapy slowed the progression of the tumors.

PET‐CT using 18F‐FDG is employed for detecting brown adipose tissue (BAT) in humans. Alternative methods are needed because of the radiation and cost of PET‐CT imaging. The aim was to evaluate the accuracy of infrared thermography (IRT) in detecting human BAT benchmarked to PET‐CT imaging. Seventeen individuals underwent a total of 29 PET‐CT scans, 12 of whom were studied twice, after 2 h of cold stimulation at 19°C, in parallel with measurement of skin temperatures overlying the supraclavicular (SCV) fossa and the lateral upper chest (control), before and after cold stimulation. Of the 29 scans, 20 were BAT positive after cold stimulation. The mean left SCV temperature tended to be higher in the BAT‐positive group before and during cooling. It was significantly higher (P = 0.04) than the temperature of the control area, which fell significantly during cooling in the BAT‐positive (−1.2 ± 0.3°C, P = 0.002) but not in the negative (−0.2 ± 0.4°C) group. The temperature difference (Δtemp) between left SCV and chest increased during cooling in the BAT‐positive (1.2 ± 0.2 to 2.0 ± 0.3°C, P < 0.002) but not in the negative group (0.6 ± 0.1 to 0.7 ± 0.1°C). A Δtemp of 0.9°C conferred a positive predictive value of 85% for SCV BAT, superior to that of SCV temperature. The findings were similar on the right. In conclusion, the Δtemp is significantly and consistently greater in BAT‐positive subjects. The Δtemp quantified by IRT after 2‐h cooling shows promise as a noninvasive convenient technique for studying SCV BAT function. e12167 Using infrared thermography (IRT), we observed the skin temperature of the supraclavicular fossa (SCV) where brown adipose tissue (BAT) is present, to be higher than that of a control BAT‐negative chest area. This temperature difference was greater in subjects with BAT and conferred a positive predictive value of 85% for BAT benchmarked to PET/CT imaging. IRT shows promise as a tool for detecting BAT function in humans.

In 2021, in the midst of a \"confluence of crises\" catalyzed by the Myanmar military's seizure of state power on February 1, the year 2015 will be viewed as the halfway point in Myanmar's now interrupted journey of reform and democratic transition.1 Bilateral relations between Myanmar and the United States, which started to normalize in the almost ten years between April 2011 and January 2021, are now \"paused\" at best, with Washington imposing and increasing targeted sanctions against the military regime in Myanmar since February. In 2015 I suggested that Myanmar would be engaged in an \"eternal balancing act\" between the United States and China.2 I continue that assessment in this essay, taking a closer look at how this balancing act is underpinned by domestic perceptions that motivate Burmese policymakers and diplomats to continue this policy of a \"delicate balance.\"4 Examining the domestic underpinnings to foreign policy takes on heightened relevance in the current geopolitical moment where major-power competition seizes imaginations globally, including in Southeast Asia. The current political moment in Myanmar, where the military coup has catalyzed a contest for foreign policy dominance and legitimacy assertion in the international arena, also calls for this additional lens of assessment. In this essay, I briefly assess Burmese domestic perceptions of the United States and its policy toward Myanmar along three broad themes: perceptions and expectations, the importance of legitimacy (to the Burmese), and revealed pragmatic preferences in bilateral interactions.

Myanmar's economic policymaking framework continued its shift away from the market orientation of the last decade or so towards a much more restrictive and state-centered approach. With the SAC's recent setbacks on the battlefield, this slide into dirigisme can be expected to continue for as long as the regime remains in power. A war economy does not reform make. With the current trends of rising inflation and poverty rates, foreign businesses continuing to exit Myanmar, more human capital outflows and fewer investment inflows, the hopes of Myanmar's people for improvements in employment, livelihoods and real incomes in the near future are fading. Anger and frustration have found different outlets, including a deepening distrust of power and authority structures. The SAC's economic miscalculations have created socio-economic implications of a magnitude that future administrations in Myanmar will need to tackle for years to come. The 2021 coup has catalyzed a negative cycle where the expertise and capacities necessary to tackle Myanmar's socio-economic challenges are unable to develop and thrive in the current environment, undoing the country's promising potential of the past decade.