Parkmouritzen2550

Further studies to unravel the role of oligoclonal B-cells in (auto)immune-mediated kidney disease are warranted.Background In this study, we measured immunoglobulin free light chains (FLC), a biomarker of inflammation in the sera of patients with heart failure due to myocarditis. Methods FLC kappa and FLC lambda were assayed in stored serum samples from patients with heart failure with myocarditis from the US myocarditis treatment trial by a competitive-inhibition multiplex Luminex® assay. Calcium Channel chemical Results The median concentration of circulating FLC kappa/lambda ratio was significantly lower in the sera from patients with heart failure with myocarditis than in healthy controls, and FLC kappa/lambda ratio had good diagnostic ability for identification of heart failure with myocarditis. Further, FLC kappa/lambda ratio was an independent prognostic factor for overall survival, and allowed creation of three prognostic groups by combining with N-terminal pro-B-type natriuretic peptide. Conclusions This study suggests that FLC kappa/lambda ratio is a promising biomarker of heart failure with myocarditis.Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.The lymphopenia exhibited in patients with COVID-19 has been associated with a worse prognosis in the development of the disease. To understand the factors associated with a worse evolution of COVID-19, we analyzed comorbidities, indicators of inflammation such as CRP and the ratio of neutrophils/lymphocytes, as well as the count of blood cells with T-lymphocyte subtypes in 172 hospitalized patients with COVID-19 pneumonia. Patients were grouped according to their needs for mechanical ventilation (ICU care) or not. Within the comorbidities studied, obesity was the only associated with greater severity and ICU admission. Both the percentage and the absolute number of neutrophils were higher in patients needing ICU care than non-ICU patients, whereas absolute lymphocyte count, and especially the percentage of lymphocytes, presented a deep decline in critical patients. There was no difference between the two groups of patients for CD4 T-lymphocytes, neither in percentage of lymphocyte nor in absolute number, however for CD8 T-cells the differences were significant for both parameters which were in decline in ICU patients. There was a firm correlation between the highest values of inflammation indicators with the decrease in percentage of CD8 T-lymphocytes. This effect was not seen with CD4 cells. Obesity together with lymphopenia, especially whether preferentially affects to CD8 T- lymphocytes, are factors that can predict a poor prognosis in patients with COVID-19.Chemobrain is a well-established clinical syndrome that impairs patient's daily function, in particular attentiveness, coordination and multi-tasking. Thus, it interferes with patient's quality of life. The putative pharmacological intervention against chemobrain relies on understanding the molecular mechanisms underlying it. This study aimed to examine the potential neuroprotective effects of two immunomodulators Interferon-β-1a (IFN-β-1a), as well as Tumor necrosis function-alpha (TNF-α) inhibitor; Infliximab in doxorubicin (DOX)-induced chemobrain in rats. Besides, the current study targets investigating the possible molecular mechanisms in terms of neuromodulation and interference with different death routes controlling neural homeostasis. Herein, the two immunomodulators IFN-β-1a at a dose of 300,000 units; s.c.three times per week, or Infliximab at a dose of 5 mg/kg/week; i.p. once per week were examined against DOX (2 mg/kg/w, i.p.) once per week for 4 consecutive weeks in rats.The consequent behavioral tests and markers for cognitive impairment, oxidative stress, neuroinflammation, apoptosis and neurobiological abnormalities were further evaluated. Briefly, IFN-β-1a or Infliximab significantly protected against DOX-induced chemobrain. IFN-β-1a or Infliximab ameliorated DOX-induced hippocampal histopathological neurodegenerative changes, halted DOX-induced cognitive impairment, abrogated DOX-induced mitochondrial oxidative, inflammatory and apoptotic stress, mitigated DOX-induced autophagic dysfunction and finally upregulated the mitophagic machineries. In conclusion, these findings suggest that either IFN-β-1a or Infliximab offers neuroprotection against DOX-induced chemobrain which could be explained by their antioxidant, anti-inflammatory, pro-autophagic, pro-mitophagic and antiapoptotic effects. Future clinical studies are recommended to personalize either use of IFN-β-1a or infliximab to ameliorate DOX-induced chemobrain.The classical steroid receptors (nuclear receptors), including those for progesterone (nPRs), are thoroughly characterized. The knowledge about so-called non-genomic effects, which are mediated by extra-nuclear initiated signals, has increased immensely the last decades. In a previous clinical study of endometrial hyperplasia, we observed that the antiproliferative progestin effect persisted after 3 months treatment with levonorgestrel (LNG) intrauterine system (IUS) even with a complete downregulation of nPRs. This raised the question of what other mechanisms than signaling through nPRs could explain such an observation. In the present study, RT-qPCR was employed to characterize mRNA expression for nPRs, membrane progesterone receptors (mPRs) and progesterone receptor membrane components (PGRMCs) in women (n = 42) with endometrial hyperplasia that received intrauterine low dose LNG for 6 months. At the end of this period endometrial tissue showed that nPRs were virtually completely downregulated (≈ 10 % of baseline) whereas the levels of remaining mPRs, subtype-α, -β and -γ were 76 %, 59 % and 73 % of baseline, respectively. PGRMC1 was downregulated to 15 % of baseline, in contrast to PGRMC2, which was upregulated to about 30 % above baseline. We used human cancer cells from uterine cervix (C-4I cells) as control. Progesterone caused a concentration-dependent antiproliferative effect but in several and separate studies, we were unable to detect nPRs (immunocytochemistry) in the C-4I cells. The use of RT-qPCR showed that nPRs were undetectable in C-4I cells, in contrast to mPRs and PGRMCs with a distinct mRNA expression. The present study suggests that mPRs and/or PGRMCs preserve the antiproliferative effect of LNG in the human endometrium and are responsible for the concentration-dependent antiproliferative effect of progesterone in C-4I cells.Lymphedema are characterized by interstitial edema leading to swelling of extremities. They can be divided into primary and secondary lymphedema. Developmental abnormalities of the lymphatic system are responsible for the primary form of lymphedema. The secondary form of lymphedema is caused by damage of the lymphatic system due to external factors. Lymphedema can rarely be observed in patients with tuberous sclerosis complex (TSC), which is a neurocutaneous syndrome caused by pathogenic variants in the genes TSC1 or TSC2. Patients with TSC usually present with neurological manifestations and the development of multiple benign tumors of ectodermal origin. Typical onset for several symptoms is during the first year of life and in some cases lesions can be detected prenatally. Epilepsy is one of the most common manifestations, affecting up to 90% of TSC patients, and is associated with developmental delay. Early pharmacotherapy improves long term patient outcome. Trio exome sequencing was performed in a 3 weeks old girl with congenital lymphedema of the right lower extremity. Using a filter for de novo variants, the heterozygous missense variant c.2524C>T, p.(Gln842Ter) in TSC1 (NM_000368.4) could be identified. After the first onset of infantile spams at age 7 months treatment with vigabatrin was started immediately. We propose to include TSC1 and TSC2 analysis in the diagnostic work-up of patients with (isolated) congenital lymphedema as early diagnosis facilitates consequent treatment strategies potentially improving the prognosis of TSC patients.Background Increasing evidence suggests pernio-like lesions are cutaneous manifestations of COVID-19. Objective To describe clinical and pathologic findings of pernio-like lesions in confirmed or suspected COVID-19 cases. Methods An international dermatology registry was circulated to healthcare providers worldwide through the American Academy of Dermatology (AAD), International League of Dermatologic Societies (ILDS), and other organizations. Results We documented 505 patients with dermatologic manifestations associated with COVID-19, including 318 (63%) with pernio-like lesions. Patients with pernio-like lesions were generally young and healthy, with relatively mild COVID-19. Of 318 cases confirmed or suspected as COVID-19 by providers, twenty-three cases (7%) were laboratory-confirmed COVID-19 positive, and 20 others (6%) were close contacts of confirmed COVID-19 cases. Given current testing criteria, many patients lacked COVID-19 testing access. For 55% of patients, pernio-like lesions were their only symptom. In patients with other COVID-19 symptoms, pernio-like lesions typically appeared after other symptoms. Pernio-like lesions lasted a median of 14 days (IQR 10-21). Limitations A case series cannot estimate population level incidence or prevalence. Additionally, there may be confirmation bias in reporting. We cannot exclude an epiphenomenon. Conclusions Pernio-like skin changes of the feet and hands, without another explanation, may suggest COVID-19 infection and should prompt confirmatory testing.The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human C-C chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective.