GWAS-identified hyperuricemia-associated IGF1R variant rs6598541 has a limited role in urate mediated inflammation in human mononuclear cells.

Gout is a common autoinflammatory joint diseases characterized by deposition of monosodium urate (MSU) crystals which trigger an innate immune response mediated by inflammatory cytokines. IGF1R is one of the loci associated with both urate levels and gout susceptibility in GWAS to date, and IGF-1-IGF-1R signaling is implicated in urate control. We investigate the role of IGF-1/IGF1R signaling in the context of gouty inflammation. Also, we test the gout and urate-associated IGF1R rs6598541 polymorphism for association with the inflammatory capacity of mononuclear cells. For this, freshly isolated human peripheral blood mononuclear cells (PBMCs) were exposed to recombinant IGF-1 or anti-IGF1R neutralizing antibody in the presence or absence of solubilized urate, stimulated with LPS/MSU crystals. Also, the association of rs6598541 with IGF1R and protein expression and with ex vivo cytokine production levels after stimulation with gout specific stimuli was tested. Urate exposure was not associated with IGF1R expression in vitro or in vivo. Modulation of IGF1R did not alter urate-induced inflammation. Developing urate-induced trained immunity in vitro was not influenced in cells challenged with IGF-1 recombinant protein. Moreover, the IGF1R rs6598541 SNP was not associated with cytokine production. Our results indicate that urate-induced inflammatory priming is not regulated by IGF-1/IGF1R signaling in vitro. IGF1R rs6598541 status was not asociated with IGF1R expression or cytokine production in primary human PBMCs. This study suggests that the role of IGF1R in gout is tissue-specific and may be more relevant in the control of urate levels rather than in inflammatory signaling in gout.

Burnout, Depression, and Job Stress Factors in Healthcare Workers of a Romanian COVID-19 Dedicated Hospital, after Two Pandemic Years.

The COVID-19 pandemic put unprecedented pressure on all areas of activity, especially healthcare workers. Understanding the psychological response to the pandemic in healthcare workers is an important challenge. This study aims to investigate burnout, depression, and job stress factors in the medical personnel of a COVID-19-dedicated hospital, two years after the beginning of the pandemic. The survey was performed between the fifth and sixth pandemic waves in Romania. Employees of the Clinical Hospital for Infectious Diseases, Cluj-Napoca, completed an online survey using four tools: Maslach Burnout Inventory (MBI), Copenhagen Burnout Inventory (CBI), the Karasek Job factors questionnaire, and the Patient Health Questionnaire-9 (PHQ-9). A total of 114 employees completed the questionnaire (10.83% of total employees). The results showed 100% prevalence of Maslach burnout (56.1% moderate and severe burnout) and 63.1% prevalence of depression. The infectious disease resident doctors had the highest prevalence of burnout scores, depression, and perceived Karasek job demands. The 22- to 30-year-old age group and the group with fewer than ten years of professional experience had a significantly higher prevalence of burnout and depression than older employees or employees with more professional experience. The COVID-19 pandemic continues to have a high impact on the mental health of healthcare workers.

Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre.

The aim of this study was to ascertain patient characteristics, outcomes, and liver injuries in patients infected with different SARS-CoV-2 variants. Data from consecutive adult patients with severe/critical COVID-19 admitted to our hospital during the peak month of the Delta wave were compared to the ancestral, Alpha, and Omicron waves. The dataset of 551 hospitalized patients was similar in the Delta/non-Delta waves. At admission and discharge, the median aminotransferase levels were normal or slightly increased. During the Delta wave (172 vs. 379 non-Delta patients), more patients died (OR 1.69, 95%CI 1.09-2.56) or had liver injury at discharge (alanine aminotransferase, ALT ≥ 2 ULN) (OR 1.97, 95%CI 1.08-3.54). In-hospital mortality was associated with age, lung injury, intensive care unit admission, number of and cardiovascular comorbidities, diabetes, chronic kidney disease, and all inflammatory biomarkers. Serious liver injury at admission (ALT ≥ 5 × ULN) was significantly associated with in-hospital mortality (OR = 7.9, 95%CI 2-28.9). At discharge, drug-induced liver injury (DILI) was found in patients treated with remdesivir, ALT ≥ 2 ULN (OR = 2.62, 95%CI 1.22-5.75). Treatment with dexamethasone, remdesivir, and immunomodulators showed improved survival, OR = 0.50 (95%CI 0.33-0.77). Regardless of the variant and treatment options, less than 2% of patients displayed serious liver injury, which was not found to be a death predictor in multivariable analysis.

Wilkie's syndrome as a cause of anxiety-depressive disorder: A case report and review of literature.

BACKGROUND: Superior mesenteric artery syndrome is a disease with a complex diagnosis, and it is associated with complications that make it even harder to identify. Currently, a frequent association with psychiatric disorders has been noted. Despite numerous case reports and case series, the variability of the disease has not allowed the development of protocols regarding diagnosis and management. CASE SUMMARY: A 33-year-old woman presented with abdominal pain, nausea, and bile vomiting over the last 15 mo, associated with a 15-kg weight loss over the last three months. After the onset of the symptoms, the patient was diagnosed with anxiety-depressive disorder and treated appropriately. Standard examinations excluded an organic cause, and the cause of the symptoms was considered psychogenic. The persistence of symptoms, even under treatment, prompted a computer tomography angiography examination of the abdomen and pelvis. The examination identified emergence at a sharp angle of 13.7° of the superior mesenteric artery, with a reduced distance between the artery and the anterior wall of the aorta up to a maximum of 8 mm. A diagnosis of aortomesenteric clamp was established. Surgical treatment by laparoscopic duodenojejunostomy was performed. Postoperative evolution was marked by a patent anastomosis at 1 mo, with a 10-kg weight gain and improvement of the associated anxiety. CONCLUSION: This case report underlines two major aspects. One aspect refers to the predisposition of patients with superior mesenteric artery syndrome to develop psychiatric disorders, with an excellent outcome when proper treatment is administered. The second aspect underlines the key role of a multidisciplinary approach and follow-up.

Maternal/newborn genotype contribution of the renin-angiotensin system (Met235Thr, Thr174Met, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A- AT2R2, 83A/G-REN) to the risk of pre-eclampsia: a Romanian study.

INTRODUCTION: We evaluated the association of the mutated genotypes Met235Thr-AGT, Thr174Met-AGT, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A-AT2R2, (83)A/G-REN with the risk and outcome of pre-eclampsia; we also investigated whether genes in newborns increase maternal risk of pre-eclampsia. MATERIALS AND METHODS: Thirty-six pairs of pre-eclamptic women and their newborns were genotyped, along with 71 pairs of controls (mothers/newborns) using PCR-RFLP analysis. RESULTS: The Thr235/Thr235 (OR 3.44, p = 0.01), DD (OR 2.66, p = 0.039), CC1166 (OR 5.56, p = 0.04), AA3123 (OR 3.77, p = 0.03) and GG(83) (OR 8.32, p = 0.006) genotypes are significantly associated with pre-eclampsia. Women with pre-eclampsia positive for Met235Thr (34.64 ± 3.92 weeks vs. 38 ± 2 weeks), Thr174Met (32.58 ± 3.92 weeks vs. 36.38 ± 3.25 weeks), I/D (34.47 ± 3.67 weeks vs. 38.33 ± 3.5 weeks) delivered at a significant lower gestational age compared with pre-eclamptic women with a normal genotype. Newborns from women with pre-eclampsia positive for Thr174Met (2190 ± 820.21 g vs. 2702.08 ± 967.23 g), I/D (2399.33 ± 938.38 g vs. 3191.66 ± 684.40 g) had a significant lower birth weight compared with newborns from women with normal pregnancies. When both the mother and the newborn were positive for Met235Thr, I/D, A2350G, A1166C or (83)A/G polymorphisms, the risk for pre-eclampsia was significantly increased at 6.67 (p < 0.01), 5 (p < 0.01), 3.33 (p = 0.006), 2.72 (p = 0.04) and 7.8 (p < 0.01), respectively. CONCLUSIONS: The results of our study confirm that, in pre-eclampsia, both maternal and newborn genetic variations implicated in blood pressure regulation are important.

Effect of dietary isoflavones on plasma cholesterol.

The effects of dietary isoflavones on plasma cholesterol are discussed in order to find new diet therapies for hypercholesterolemia, which represents a cardiovascular risk factor. Isoflavones represent a class of biological substances with beneficial action in the reduction of cholesterol, LDL cholesterol, increase of HDL cholesterol and reduction of triglycerides as well as other risk factors of atherosclerotic cardiovascular diseases. The cholesterol-reducing effects of isoflavones have been demonstrated by numerous studies that started from the finding that the Japanese, consumers of more proteins of vegetal origin, present a lower incidence of ischemic heart disease, the mortality rate by cardiovascular disease being about half of that of the U.S.A. Subsequent studies were carried out in patient groups with high, average, small, or normal cholesterol levels, adults or children, all of them reporting that a diet containing vegetal isoflavones led to the reduction of cholesterol levels.