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Background/Objectives: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages. Methods: Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients. Results: In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues. Conclusions: In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging. [ABSTRACT FROM AUTHOR]

Critical illness causes disturbances in lipid metabolism. Here, we investigated the levels of apolipoprotein A-IV (apoA-IV), a regulator of triglyceride and cholesterol metabolism, in human sepsis. ApoA-IV (analyzed in 156 patients with systemic inflammatory response syndrome (SIRS)/sepsis) and cholesteryl ester (CE) (analyzed in 121 of these patients) were lower in patients compared to 43 healthy controls. In contrast, triglyceride (TG) levels were elevated in patients. ApoA-IV levels in plasma of the patients did not correlate with these lipids. Patients with SIRS, sepsis or septic shock had comparable apoA-IV, TG, CE and free cholesterol (FC) levels. Patients on dialysis had significantly lower CE levels, whereas apoA-IV levels did not change much. CE levels were elevated in patients with viral sepsis due to SARS-CoV-2 infection in comparison to SIRS/sepsis patients not infected by this virus. CE levels correlated negatively with procalcitonin, interleukin-6 and bilirubin, while TGs were positively associated with bilirubin and C-reactive protein. ApoA-IV, TG, CE and FC levels were not associated with bacterial infection or survival. In conclusion, this analysis suggests that CE levels decline in sepsis-related renal failure and also shows that plasma apoA-IV and CE levels are early biomarkers of sepsis. [ABSTRACT FROM AUTHOR]

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 2019 (COVID-19), a disease with very heterogeneous symptoms. Dyslipidaemia is prevalent in at least 20% of Europeans, and dyslipidaemia before SARS-CoV-2 infection increases the risk for severe COVID-19 and mortality by 139%. Many reports described reduced serum cholesterol levels in virus-infected patients, in particular in those with severe disease. The liver is the major organ for lipid homeostasis and hepatic dysfunction appears to occur in one in five patients infected with SARS-CoV-2. Thus, SARS-CoV-2 infection, COVID-19 disease severity and liver injury may be related to impaired cholesterol homeostasis. These observations prompted efforts to assess the therapeutic opportunities of cholesterol-lowering medications to reduce COVID-19 severity. The majority of studies implicate statins to have beneficial effects on disease severity and outcome in COVID-19. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have also shown potential to protect against COVID-19. This review describes the relationship between systemic cholesterol levels, liver injury and COVID-19 disease severity. The potential effects of statins and PCSK9 in COVID-19 are summarised. Finally, the relationship between cholesterol and lung function, the first organ to be affected by SARS-CoV-2, is described. [ABSTRACT FROM AUTHOR]

Background: Resistance to chemotherapy is a major problem in the treatment of patients with triple-negative breast cancer (TNBC). Preclinical data suggest that TNBC is dependent on proteasomes; however, clinical observations indicate that the efficacy of proteasome inhibitors in TNBC may be limited, suggesting the need for combination therapies. Methods: We compared bortezomib and carfilzomib and their combinations with nelfinavir and lopinavir in TNBC cell lines and primary cells with regard to their cytotoxic activity, functional proteasome inhibition, and induction of the unfolded protein response (UPR). Furthermore, we evaluated the involvement of sXBP1, ABCB1, and ABCG2 in the cytotoxic activity of drug combinations. Results: Carfilzomib, via proteasome β5 + β2 inhibition, is more cytotoxic in TNBC than bortezomib, which inhibits β5 + β1 proteasome subunits. The cytotoxicity of carfilzomib was significantly potentiated by nelfinavir or lopinavir. Carfilzomib with lopinavir induced endoplasmic reticulum stress and pro-apoptotic UPR through the accumulation of excess proteasomal substrate protein in TNBC in vitro. Moreover, lopinavir increased the intracellular availability of carfilzomib by inhibiting carfilzomib export from cells that express high levels and activity of ABCB1, but not ABCG2. Conclusion: Proteasome inhibition by carfilzomib combined with nelfinavir/lopinavir represents a potential treatment option for TNBC, warranting further investigation. [ABSTRACT FROM AUTHOR]

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chemerin is an adipokine involved in inflammatory and metabolic diseases, and its circulating levels have been associated with inflammatory parameters in various patient cohorts. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which causes COVID-19, triggers inflammatory pathways. However, the association between serum chemerin levels and COVID-19 disease severity and outcomes has not been definitively established. Methods: In this study, serum chemerin levels were analyzed in 64 patients with moderate COVID-19 and 60 patients with severe disease. Results: The results showed that serum chemerin levels were comparable between these two groups and slightly higher than in healthy controls. Notably, COVID-19 patients with hypertension exhibited elevated serum chemerin levels, while those with liver cirrhosis had lower levels. When patients with these comorbidities were excluded from the analyses, serum chemerin levels in COVID-19 patients were similar to those in healthy controls. Positive correlations were observed between serum chemerin levels and markers such as alkaline phosphatase, C-reactive protein, eosinophils, and lymphocytes in the entire cohort, as well as in the subgroup excluding patients with hypertension and cirrhosis. Additionally, urinary chemerin levels were comparable between COVID-19 patients and controls, and neither hypertension nor dialysis significantly affected urinary chemerin levels. Both survivors and non-survivors had similar serum and urinary chemerin levels. Conclusions: In conclusion, this study suggests that comorbidities such as arterial hypertension and liver cirrhosis do have a more significant impact on serum chemerin levels than SARS-CoV-2 infection itself. [ABSTRACT FROM AUTHOR]

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Amyloid beta (Aβ) plays a major role in the pathogenesis of Alzheimer's disease and, more recently, has been shown to protect against liver fibrosis. Therefore, we studied Aβ-42 levels and the expression of genes involved in the generation, degradation, and transport of Aβ proteins in liver samples from patients at different stages of metabolic dysfunction-associated liver disease (MASLD) and under steatotic conditions in vitro/in vivo. Amyloid precursor protein (APP), key Aβ-metabolizing proteins, and Aβ-42 were analyzed using RT-PCR, Western blotting, Luminex analysis in steatotic in vitro and fatty liver mouse models, and TaqMan qRT-PCR analysis in hepatic samples from patients with MASLD. Hepatocytes loaded with palmitic acid induced APP, presenilin, and neprilysin (NEP) expression, which was reversed by oleic acid. Increased APP and NEP, decreased BACE1, and unchanged Aβ-42 protein levels were found in the steatotic mouse liver compared to the normal liver. Aβ-42 concentrations were low in MASLD samples of patients with moderate to severe fibrosis compared to the livers of patients with mild or no MASLD. Consistent with the reduced Aβ-42 levels, the mRNA expression of proteins involved in APP degradation (ADAM9/10/17, BACE2) and Aβ-42 cleavage (MMP2/7/9, ACE) was increased. In the steatotic liver, the expression of APP- and Aβ-metabolizing proteins is increased, most likely related to oxidative stress, but does not affect hepatic Aβ-42 levels. Consistent with our previous findings, low Aβ-42 levels in patients with liver fibrosis appear to be caused by the reduced production and enhanced non-amyloidogenic processing of APP. [ABSTRACT FROM AUTHOR]

Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9 regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC) were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival. The current study suggests that the imbalance between CE and FC levels is associated with disease severity and mortality in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Infectious diseases are associated with low iron levels and the induction of hepcidin, the primary protein regulating cellular iron export. Bone morphogenetic protein 6 (BMP6), a key regulator of hepcidin expression, has not yet been analyzed in the plasma of patients with systemic inflammatory response syndrome (SIRS) or sepsis. An analysis of 38 SIRS, 39 sepsis, and 78 septic shock patients revealed similar levels of BMP6 in sepsis and septic shock, which were lower compared to patients with SIRS and healthy controls. Plasma BMP6 levels did not correlate with procalcitonin and C-reactive protein levels in patients with SIRS or sepsis/septic shock. Neither bacterial nor SARS-CoV-2 infections affected plasma BMP6 levels. There was no difference in BMP6 levels between ventilated and non-ventilated patients, or between patients with and without dialysis. Vasopressor therapy did not alter BMP6 levels. Survivors had plasma BMP6 levels similar to non-survivors. Due to the high variability of plasma BMP6 levels, these analyses have limited clinical relevance. Iron, ferritin, and transferrin levels were known in at least 50% of patients but did not correlate with plasma BMP6 levels. In conclusion, this study showed normal BMP6 plasma levels in SIRS, which are reduced in patients with sepsis and septic shock. This suggests that the commonly observed increase in hepcidin levels and the decline in iron levels in SIRS, sepsis, and septic shock are not due to higher BMP6. [ABSTRACT FROM AUTHOR]

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections. [ABSTRACT FROM AUTHOR]

Predicting responses and monitoring the severity of inflammatory bowel disease (IBD) is challenging due to a lack of specific biomarkers. This study identifies urinary hydroxyproline, a marker of collagen turnover elevated in experimental colitis, as independent of conventional biomarkers like creatinine, glomerular filtration rate, C-reactive protein, and fecal calprotectin. Among 71 IBD patients, urinary hydroxyproline levels were significantly higher compared with 36 controls, with an area under the receiver operating characteristic curve of 0.814, highlighting its potential as a diagnostic tool. No significant difference in hydroxyproline levels was observed between the 50 Crohn's disease and 21 ulcerative colitis patients, nor was there a correlation with kidney function markers, gastrointestinal symptom severity, or stool consistency. Disease localization was not associated with urinary hydroxyproline levels. Interestingly, 14 patients with primary sclerosing cholangitis and IBD also exhibited elevated urinary hydroxyproline levels, comparable to IBD patients but higher than healthy controls. This underscores the role of urinary hydroxyproline as an independent biomarker for IBD diagnosis, without association with disease severity or established markers like fecal calprotectin. [ABSTRACT FROM AUTHOR]

The very existence of truth, let alone its worth, is currently under attack from many quarters. In the wider culture, disinformation and other forms of misrepresenting the truth spread far and wide, as information conduits proliferate. This paper suggests some reasons for the "anti-truth" trend. Mainstream media have played a role, as have theoreticians from fields as diverse as philosophy, psychoanalysis, science, and literary criticism. "Anti-truth" trends are having a serious impact on psychological treatment, affecting its content and the conception of its goals. This paper suggests some problematic outcomes of this phenomenon for practitioners and patients in various forms of psychotherapy. [ABSTRACT FROM AUTHOR]

The article "Social, disease and diagnostic factors associated with diagnostic delays in dermatomyositis: a retrospective cohort study" published in the British Journal of Dermatology discusses the challenges of diagnosing dermatomyositis (DM) promptly due to its varied clinical presentations and nonspecific laboratory findings. The study aimed to quantify diagnostic delays (DDs) and identify factors contributing to these delays. Conducted at an academic tertiary referral center, the retrospective cohort study analyzed adult patients with DM between 2009 and 2022, highlighting the importance of timely diagnosis in managing the condition and associated risks. [Extracted from the article]

Background: Metastatic Crohn's disease is a rare disorder characterized by various granulomatous skin lesions that occur independently of gastrointestinal tract involvement. However, currently there is no standardized care or specific treatment. Therapeutic approaches include immunosuppressive agents, such as corticosteroids, azathioprine, and monoclonal antibodies targeting inflammatory cytokines like tumor necrosis factor (TNF). Case presentation: We present a case of a 29-year-old western European woman with significant blind ending abdominal subcutaneous fistulas and abscesses, who sought evaluation in the dermatology department. Histological examination revealed multiple epithelioid cell granulomas. There was no evidence of infectious or rheumatologic diseases such as sarcoidosis. The tentative diagnosis was metastatic Crohn's disease, which was not related to an intestinal manifestation of the disease. The patient responded to infliximab but had to discontinue it due to an allergic reaction. Subsequent adalimumab treatment failed to induce clinical remission; thus, therapy was switched to ustekinumab, resulting in a positive response. Written informed consent for publication of their clinical details and clinical images was obtained from the patient. For our study more than 1600 publications were screened for cases of metastatic Crohn's disease on PubMed database. 59 case reports with 171 patients were included in the analysis and evaluated for localization, diagnostic and therapeutic approaches, and complications and were summarized in this review. Conclusion: The successful ustekinumab treatment of a patient with metastatic Crohn's disease underscores the potential of this minimally investigated therapeutic option, highlighting the need for future treatment guidelines given the increasing prevalence of such cases. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC. [ABSTRACT FROM AUTHOR]

Identical Lightning Imaging Sensors (LIS) aboard the Tropical Rainfall Measuring Mission satellite (TRMM LIS, 1998–2015) and International Space Station (ISS LIS, 2017–23) have provided over two decades of lightning observations over the global tropics, with ISS LIS extending coverage into the midlatitudes. Quantifying the detection performance of both LIS sensors is a necessary step toward generating a combined LIS climatological record and accurately combining LIS data with lightning detections from other sensors and networks. We compare lightning observations from both LIS sensors with reference sources including the Geostationary Lightning Mapper (GLM) and ground-based Earth Networks Total Lightning Network (ENTLN), Earth Networks Global Lightning Network (ENGLN), National Lightning Detection Network (NLDN), and Global Lightning Dataset (GLD360). Instead of a relative detection efficiency (DE) approach that assumes the perfect performance of the reference sensor, we employ a Bayesian approach to estimate the upper limit of the absolute DE (ADE) of each system being analyzed. The results of this analysis illustrate the geographical pattern of ADE as well as its diurnal cycle and yearly evolution. Reference network ADE increased by ∼15%–30% during the TRMM era, leading to a decline in TRMM LIS ADE. ISS LIS flash ADE has been relatively consistent at 61%–65%, about 4%–5% lower than TRMM LIS at the end of its lifetime. [ABSTRACT FROM AUTHOR]

Adiponectin is primarily known for its protective role in metabolic diseases, and it also possesses immunoregulatory properties. Elevated levels of adiponectin have been observed in various inflammatory diseases. However, studies investigating adiponectin levels in the serum of COVID-19 patients have yielded conflicting results. This study aimed to assess serum adiponectin levels in 26 healthy controls, as well as in 64 patients with moderate and 60 patients with severe COVID-19, to determine a potential association between serum adiponectin and the severity of COVID-19. Serum adiponectin levels in severe COVID-19 patients were significantly lower than in those with moderate disease and healthy controls, who exhibited similar serum adiponectin levels. Among patients with moderate disease, positive correlations were observed between serum adiponectin and C-reactive protein levels. Of note, serum adiponectin levels of severe COVID-19 cases were comparable between patients with and without dialysis or vasopressor therapy. Superinfection with bacteria did not exert a notable influence on serum adiponectin levels in patients with severe disease. Patients who were diagnosed with severe COVID-19 and vancomycin-resistant enterococci bacteremia showed a significant reduction in their serum adiponectin levels. An analysis conducted on the entire cohort, including both moderate and severe COVID-19 patients, showed that individuals who did not survive had lower serum adiponectin levels when compared to those who survived. In summary, this study highlights a decrease in serum adiponectin levels in severe COVID-19 cases, indicating the potential utility of adiponectin as an additional biomarker for monitoring disease severity in COVID-19 or critical illnesses in general. [ABSTRACT FROM AUTHOR]

Lauren Levine's book, "Risking Intimacy and Creative Transformation in Psychoanalysis," explores the integration of theory and clinical practice in psychoanalysis. Drawing from various sources, including psychoanalytic and artistic works, as well as non-psychoanalytic literature, Levine emphasizes the importance of clinical values such as curiosity, hope, purpose, courage, kindness, integrity, and the ability to bear loss. Through vignettes, Levine demonstrates how these values can impact the therapeutic process. The book also highlights the significance of courage, kindness, and empathy in effective psychoanalytic treatment. Levine's approach focuses on helping patients develop their own voice and personal agency, addressing complex issues such as race and politics. The text also delves into the challenges clinicians face in dealing with frequent endings and separations, as well as the role of creativity and the ongoing debate about giving direct guidance in treatment. Overall, Levine's work combines both intellect and emotion, offering impactful and thought-provoking insights. [Extracted from the article]

Shame and the fear of shame can play highly significant roles for each participant in treatment. For example, the analyst may feel afraid that doing treatment will expose their insufficiencies as a clinician, and, even more broadly, as a human being. This paper discusses a number of varieties of the experience of shame, including those tinged with anger, guilt, and anxiety. It also examines the shame about feeling shame, which can be particularly troubling in training. Aspects of the candidate's position that may elicit shame are explored, with some suggestions about ways they could be ameliorated. [ABSTRACT FROM AUTHOR]

Transforming growth factor beta (Tgfb) is a well-studied pro-fibrotic cytokine, which upregulates cellular communication network factor 2 (Ccn2), collagen, and actin alpha 2, smooth muscle (Acta2) expression. Obesity induces adipose tissue fibrosis, which contributes to metabolic diseases. This work aimed to analyze the expression of Tgfb, Ccn2, collagen1a1 (Col1a1), Acta2 and BMP and activin membrane-bound inhibitor (Bambi), which is a negative regulator of Tgfb signaling, in different adipose tissue depots of mice fed a standard chow, mice fed a high fat diet (HFD) and ob/ob mice. Principally, these genes were low expressed in brown adipose tissues and this difference was less evident for the ob/ob mice. Ccn2 and Bambi protein as well as mRNA expression, and collagen1a1 mRNA were not induced in the adipose tissues upon HFD feeding whereas Tgfb and Acta2 mRNA increased in the white fat depots. Immunoblot analysis showed that Acta2 protein was higher in subcutaneous and perirenal fat of these mice. In the ob/ob mice, Ccn2 mRNA and Ccn2 protein were upregulated in the fat depots. Here, Tgfb, Acta2 and Col1a1 mRNA levels and serum Tgfb protein were increased. Acta2 protein was, however, not higher in subcutaneous and perirenal fat of these mice. Col6a1 mRNA was shown before to be higher in obese fat tissues. Current analysis proved the Col6a1 protein was induced in subcutaneous fat of HFD fed mice. Notably, Col6a1 was reduced in perirenal fat of ob/ob mice in comparison to the respective controls. 3T3-L1 cells express Ccn2 and Bambi protein, whose levels were not changed by fatty acids, leptin, lipopolysaccharide, tumor necrosis factor and interleukin-6. All of these factors led to higher Tgfb in 3T3-L1 adipocyte media but did not increase its mRNA levels. Free fatty acids induced necrosis whereas apoptosis did not occur in any of the in vitro incubations excluding cell death as a main reason for higher Tgfb in cell media. In summary, Tgfb mRNA is consistently induced in white fat tissues in obesity but this is not paralleled by a clear increase of its target genes. Moreover, discrepancies between mRNA and protein expression of Acta2 were observed. Adipocytes seemingly do not contribute to higher Tgfb mRNA levels in obesity. These cells release more Tgfb protein when challenged with obesity-related metabolites connecting metabolic dysfunction and fibrosis. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection alters lysophosphatidylcholine (LPC) metabolism, enhancing viral infectivity and replication. Direct-acting antivirals (DAAs) effectively treat HCV and rapidly normalize serum cholesterol. In serum, LPC species are primarily albumin-bound but are also present in lipoprotein particles. This study aims to assess the impact of HCV eradication on serum LPC species levels in patients infected with HCV. Therefore, 12 different LPC species were measured by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the sera of 178 patients with chronic HCV infections at baseline, and in 176 of these patients after therapy with DAAs. All LPC species increased at 4 and 12 weeks post-initiation of DAA therapy. The serum profiles of the LPC species were similar before and after the viral cure. Patients with HCV and liver cirrhosis exhibited lower serum levels of all LPC species, except LPC 16:1, both before and after DAA treatment. Percentages of LPC 18:1 (relative to the total LPC level) were higher, and % LPC 22:5 and 22:6 were lower in cirrhotic compared to non-cirrhotic patients at baseline and at the end of therapy. LPC species levels inversely correlated with the model of end-stage liver disease score and directly with baseline and post-therapy albumin levels. Receiver operating characteristic curve analysis indicated an area under the curve of 0.773 and 0.720 for % LPC 18:1 (relative to total LPC levels) for classifying fibrosis at baseline and post-therapy, respectively. In summary, HCV elimination was found to increase all LPC species and elevated LPC 18:1 relative to total LPC levels may have pathological significance in HCV-related liver cirrhosis. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-binding protein (IGFBP)-2 is a regulator of anabolic pathways, which become inactivated in severe illness. Here, we measured the serum IGFBP-2 levels of COVID-19 patients with moderate and severe disease as well as healthy controls to identify the associations of serum IGFBP-2 levels with disease severity. Patients with severe COVID-19 had higher serum IGFBP-2 levels than those with moderate disease and healthy controls, who had similar levels. Non-survivors of COVID-19 tended to have elevated serum IGFBP-2 levels compared to survivors. Increased serum IGFBP-2 levels were observed in patients requiring dialysis and vasopressor therapy. Serum IGFBP-2 was positively correlated with procalcitonin in both patient groups. Bacterial co-infection in severe COVID-19 patients did not influence serum IGFBP-2 levels. Patients with liver cirrhosis and obesity, showing increased and decreased serum IGFBP-2 levels, respectively, were excluded from the study. The present analysis showed that higher serum IGFBP-2 levels are associated with increased disease severity in COVID-19 patients. The similarity in serum IGFBP-2 levels between patients with moderate COVID-19 and healthy controls suggests that elevated IGFBP-2 is associated with critical illness rather than SARS-CoV-2 infection itself. [ABSTRACT FROM AUTHOR]

Each psychoanalytic theory influences the clinician's focus. This paper examines the impact of Erich Fromm's writing on the analyst's attention to the material in sessions. Briefly, Fromm's work highlights the importance of the analyst's passion, courage, pursuit of truth, capacity to bear uncertainty and suffering, and dedication to helping people embrace their freedom and realize their full potential. Fromm has inspired generations of clinicians to become politically active citizens, maintain enlivening curiosity, and kindle the life force in themselves and those they treat. What role does theory play in the moment-by-moment behavior of the analyst in a session? I first address the general question of my view of the role of theory in clinical work. Then I turn to the more specific issue of Fromm's influence. [ABSTRACT FROM AUTHOR]

T cell depletion and functional impairment are characteristics of sepsis. CD137 is a costimulatory receptor on activated T cells, while soluble CD137 (sCD137) inhibits CD137 signaling. This study found elevated sCD137 levels in the plasma of patients with systemic inflammatory response syndrome (SIRS), sepsis, or septic shock compared to healthy controls. The sCD137 levels negatively correlated with the C-reactive protein and positively with procalcitonin and interleukin-6. There was no difference in sCD137 levels based on ventilation, dialysis, or vasopressor treatment. Patients with SARS-CoV-2, Gram-positive, or Gram-negative bacterial infections had similar sCD137 levels as noninfected individuals. Notably, higher plasma sCD137 levels were observed in non-survivors compared to survivors in both the SIRS/sepsis group and the SARS-CoV-2 subgroup. In conclusion, plasma sCD137 levels are associated with severe illness and survival in critically ill patients. [ABSTRACT FROM AUTHOR]

Lipedema is a chronic condition characterized by disproportionate and symmetrical enlargement of adipose tissue, predominantly affecting the lower limbs of women. This study investigated the use of metabolomics in lipedema research, with the objective of identifying complex metabolic disturbances and potential biomarkers for early detection, prognosis, and treatment strategies. The study group (n = 25) comprised women diagnosed with lipedema. The controls were 25 lean women and 25 obese females, both matched for age. In the patients with lipedema, there were notable changes in the metabolite parameters. Specifically, lower levels of histidine and phenylalanine were observed, whereas pyruvic acid was elevated compared with the weight controls. The receiver operating characteristic (ROC) curves for the diagnostic accuracy of histidine, phenylalanine, and pyruvic acid concentrations in distinguishing between patients with lipedema and those with obesity but without lipedema revealed good diagnostic ability for all parameters, with pyruvic acid being the most promising (area under the curve (AUC): 0.9992). Subgroup analysis within matched body mass index (BMI) ranges (30.0 to 39.9 kg/m2) further revealed that differences in pyruvic acid, phenylalanine, and histidine levels are likely linked to lipedema pathology rather than BMI variations. Changes in low-density lipoprotein (LDL)-6 TG levels and significant reductions in various LDL-2-carried lipids of patients with lipedema, compared with the lean controls, were observed. However, these lipids were similar between the lipedema patients and the obese controls, suggesting that these alterations are related to adiposity. Metabolomics is a valuable tool for investigating lipedema, offering a comprehensive view of metabolic changes and insights into lipedema's underlying mechanisms. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-binding protein (IGFBP)-2 regulates the bioactivity of the anabolic hormone's insulin-like growth factors, which are decreased in sepsis and contribute to the catabolic status of severely ill patients. The circulating levels of IGFBP-2 in critical illness have been rarely studied; therefore, we evaluated IGFBP-2 plasma levels in patients with systemic inflammatory response syndrome (SIRS) or sepsis as well as healthy controls. Our analysis of 157 SIRS/sepsis patients revealed higher plasma IGFBP-2 levels compared to 22 healthy controls. Plasma IGFBP-2 levels correlated positively with procalcitonin but not with C-reactive protein, interleukin-6, or the leukocyte count. Septic shock patients exhibited higher IGFBP-2 levels than those with SIRS. Bacterial or SARS-CoV-2 infection did not influence plasma IGFBP-2 levels. There was no difference in the IGFBP-2 levels between ventilated and non-ventilated SIRS/sepsis patients, and vasopressor therapy did not alter these levels. Dialysis patients had elevated plasma IGFBP-2 levels. Survivors had lower plasma IGFBP-2 levels than non-survivors. In conclusion, our study indicates that plasma IGFBP-2 levels are associated with disease severity, renal failure, and mortality in SIRS/sepsis patients. [ABSTRACT FROM AUTHOR]

Adiponectin is low in obesity, plays a crucial role in metabolic health, and, moreover, possesses immunoregulatory properties. However, studies examining its levels in patients with systemic inflammatory response syndrome (SIRS) or sepsis have yielded conflicting results. While females typically have higher systemic adiponectin levels than males, research on sex-specific associations in this context is limited. In this study of 156 SIRS/sepsis patients, including those with liver cirrhosis, we aimed to explore the relationship between plasma adiponectin, body mass index (BMI), gender, disease severity, and underlying etiological conditions. Our findings revealed that patients with liver cirrhosis, who are susceptible to infections, exhibited elevated circulating adiponectin levels, irrespective of sex. When excluding cirrhosis patients, plasma adiponectin levels were similar between male SIRS/sepsis patients and controls but lower in female patients compared to female controls. Plasma adiponectin was inversely related to BMI in female but not male patients. Further analysis within the non-cirrhosis subgroup demonstrated no significant differences in adiponectin levels between sexes among SIRS, sepsis, and septic shock patients. Ventilation, dialysis, and vasopressor therapy had no discernible impact on adiponectin levels in either sex. A negative correlation between adiponectin and C-reactive protein (CRP) existed in males only. Notably, patients with pancreatitis showed the lowest plasma adiponectin concentrations, although sex-specific differences were not significant. Infection with Gram-negative or Gram-positive bacteria had minimal effects on plasma adiponectin levels in both sexes. However, infection with the severe acute respiratory syndrome coronavirus type 2 led to decreased adiponectin levels in females exclusively. Multivariate analysis considering all factors affecting plasma adiponectin levels in males or females identified BMI in females and CRP levels in males to predict plasma adiponectin levels in SIRS/sepsis patients. Additionally, our study observed a trend where the 25 patients who did not survive had higher plasma adiponectin levels, particularly among males. In summary, our investigation highlights the influence of underlying diseases and sex on plasma adiponectin levels in SIRS/sepsis patients, shedding light on potential implications for disease management and prognosis. [ABSTRACT FROM AUTHOR]

Background: Disturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs). Whether fecal bile acids may emerge as biomarkers for IBD diagnosis and disease severity is less clear. Our study aimed to identify associations of 18 fecal bile acid species with IBD entity and disease activity. Methods: Stool samples of 62 IBD patients and 17 controls were collected. Eighteen fecal bile acid species were quantified by LC–MS/MS using stable isotope dilution. Lipid levels normalized to a dry weight of the fecal homogenates and ratios of single bile acid species to total bile acid levels were used for calculations. Results: IBD patients exhibited altered primary and secondary bile acid ratios in stool, with notable distinctions between ulcerative colitis (UC) compared to Crohn's disease (CD) and healthy controls. Fecal calprotectin was negatively correlated with glycolithocholic acid (GLCA) and hyodeoxycholic acid (HDCA) in UC. These bile acids were reduced in stool of UC patients with fecal calprotectin levels > 500 µg/g compared to UC patients with low calprotectin levels. Moreover, negative associations of six secondary bile acids with C-reactive protein (CRP) existed in UC. In CD patients, fecal bile acids did not correlate with CRP or fecal calprotectin. Diarrhoea is common in IBD, and UC patients with diarrhoea had reduced deoxycholic acid (DCA), glycine conjugated DCA (GDCA) and lithocholic acid in stool in contrast to patients with normal stool consistency. Fecal bile acid levels were not associated with diarrhoea in CD patients. UC patients treated with mesalazine had increased levels of fecal GDCA whereas no such changes were observed in CD patients. Bile acid levels of CD and UC patients treated with biologicals or corticosteroids did not change. Relative levels of GHDCA (specificity: 79%, sensitivity: 67%) and glycochenodeoxycholic acid (specificity: 74%, sensitivity: 63%) were the most specific to distinguish UC from CD. Conclusion: Disrupted fecal bile acid homeostasis is associated with disease severity and disease symptoms in UC but not in CD, potentially aiding in distinguishing IBD subtypes and classifying the pathophysiology of diarrhoea in UC. [ABSTRACT FROM AUTHOR]

This discussion focuses on the presence of traumatizing narcissists across eras and cultures, and some dilemmas encountered by survivors of cults and their therapists. It highlights the clinician's temptation to "other" survivors by pathologizing cult membership. Erich Fromm's cultural and psychoanalytic observations can be helpful in our understanding of these dynamics. The discussion comments on Shaw's conception of the role of shame at various points in the cult member's experience. It also outlines how the emotion of shame can vary in its impact, depending on the other feelings that are simultaneously present. Finally, the discussion suggests some clinical applications of our understanding of the role of shame as we participate in the cult survivor's recovery. [ABSTRACT FROM AUTHOR]

Background: Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with inflammatory bowel diseases (IBDs) and patients with primary sclerosing cholangitis (PSC), a disease closely associated with IBD, have decreased microbiome diversity. In this paper, the fecal SCFAs propionate, acetate, butyrate and isobutyrate of patients with IBD and patients with PSC-IBD and urinary 3-indoxyl sulfate of IBD patients were determined to study associations with disease etiology and severity. Methods: SCFA levels in feces of 64 IBD patients and 20 PSC-IBD patients were quantified by liquid chromatography with tandem mass spectrometry (LC–MS/MS). Urinary 3-indoxyl sulfate levels of 45 of these IBD patients were analysed by means of reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry. Feces of 17 healthy controls and urine of 13 of these controls were analyzed in parallel. These cohorts had comparable sex distribution and age. Results: Urinary 3-indoxyl sulfate concentrations (normalized to urinary creatinine levels) was increased (P = 0.030) and fecal isobutyrate levels (normalized to dry weight of the stool sample) of IBD patients were decreased (P = 0.035) in comparison to healthy controls. None of the analyzed metabolites differed between patients with Crohn´s disease (CD) and patients with ulcerative colitis (UC). Fecal acetate and butyrate positively correlated with fecal calprotectin (P = 0.040 and P = 0.005, respectively) and serum C-reactive protein (P = 0.024 and P = 0.025, respectively) in UC but not CD patients. UC patients with fecal calprotectin levels above 150 µg/g, indicating intestinal inflammatory activity, had higher fecal acetate (P = 0.016), butyrate (P = 0.007) and propionate (P = 0.046) in comparison to patients with fecal calprotectin levels < 50 µg/g. Fecal SCFA levels of PSC-IBD and IBD patients were comparable. Conclusions: Current findings suggest that analysis of urinary 3-indoxyl-sulfate as well as fecal SCFAs has no diagnostic value for IBD and PSC-IBD diagnosis or monitoring of disease severity. [ABSTRACT FROM AUTHOR]

Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. In this study, we aimed to gain new insights into the expression and functional role of FHL2 in VAT in diet-induced obesity. We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induced obesity and obese humans and identified macrophages as the cellular source of enhanced FHL2 expression in VAT. In mice with FHL2 deficiency (FHL2KO), WTD feeding resulted in reduced body weight gain paralleled by enhanced energy expenditure and uncoupling protein 1 (UCP1) expression, indicative of activated thermogenesis. In human VAT, FHL2 was inversely correlated with UCP1 expression. Furthermore, macrophage infiltration and the expression of the chemokine MCP-1, a known promotor of macrophage accumulation, was significantly reduced in WTD-fed FHL2KO mice compared with wild-type (wt) littermates. While FHL2 depletion did not affect the differentiation or lipid metabolism of adipocytes in vitro, FHL2 depletion in macrophages resulted in reduced expressions of MCP-1 and the neuropeptide Y (NPY). Furthermore, WTD-fed FHL2KO mice showed reduced NPY expression in VAT compared with wt littermates, and NPY expression was enhanced in VAT resident macrophages of obese individuals. Stimulation with recombinant NPY induced not only UCP1 expression and lipid accumulation but also MCP-1 expression in adipocytes. Collectively, these findings indicate that FHL2 is a positive regulator of NPY and MCP-1 expression in macrophages and herewith closely linked to the mechanism of obesity-associated lipid accumulation and inflammation in VAT. Thus, FHL2 appears as a potential novel target to interfere with the macrophage–adipocyte crosstalk in VAT for treating obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Copyright of Estudos e Pesquisas em Psicologia is the property of Editora da Universidade do Estado do Rio de Janeiro (EdUERJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver diseases, ranging from liver steatosis to metabolic dysfunction-associated steatohepatitis (MASH), increasing the risk of developing cirrhosis and hepatocellular carcinoma (HCC). Fibrosis within MASLD is critical for disease development; therefore, the identification of fibrosis-driving factors is indispensable. We analyzed the expression of interleukin 32 (IL-32) and chemokine CC ligand 20 (CCL20), which are known to be linked with inflammation and fibrosis, and for their expression in MASLD and hepatoma cells. RT-PCR, ELISA and Western blotting analyses were performed in both human liver samples and an in vitro steatosis model. IL-32 and CCL20 mRNA expression was increased in tissues of patients with NASH compared to normal liver tissue. Stratification for patatin-like phospholipase domain-containing protein 3 (PNPLA3) status revealed significance for IL-32 only in patients with I148M (rs738409, CG/GG) carrier status. Furthermore, a positive correlation was observed between IL-32 expression and steatosis grade, and between IL-32 as well as CCL20 expression and fibrosis grade. Treatment with the saturated fatty acid palmitic acid (PA) induced mRNA and protein expression of IL-32 and CCL20 in hepatoma cells. This induction was mitigated by the substitution of PA with monounsaturated oleic acid (OA), suggesting the involvement of oxidative stress. Consequently, analysis of stress-induced signaling pathways showed the activation of Erk1/2 and p38 MAPK, which led to an enhanced expression of IL-32 and CCL20. In conclusion, cellular stress in liver epithelial cells induced by PA enhances the expression of IL-32 and CCL20, both known to trigger inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Optical lightning observations from low-Earth orbit play an important role in our understanding of long-term global lightning trends. Lightning Imaging Sensors (LIS) on the Tropical Rainfall Measuring Mission (TRMM) satellite (1997-2015) and International Space Station (2017-present) capture optical emissions produced by lightning. This study uses the well-documented TRMM LIS performance to determine if the ISS LIS performs well enough to bridge the gap between TRMM LIS and the new generation of Geostationary Lightning Mappers (GLMs). The average events per group and groups per flash for ISS LIS are 3.6 and 9.9, which are 18% and 10% lower than TRMM LIS, respectively. ISS LIS has 30% lower mean group energy density and 30%-50% lower mean flash energy density than TRMM LIS in their common (6388) latitude range. These differences are likely the result of larger pixel areas for ISS LIS over most of the field of view due to off-nadir pointing, combined with viewing obstructions and possible engineering differences. For both instruments, radiometric sensitivity decreases radially from the center of the array to the edges. ISS LIS sensitivity falls off faster and more variably, contributed to by the off-nadir pointing. Event energy density analysis indicate some anomalous hotspot pixels in the ISS LIS pixel array that were not present with the TRMMLIS. Despite these differences, ISS LIS provides similar parameter values to TRMM LIS with the expectation of somewhat lower lightning detection capability. In addition, recalculation of the event, group, and flash areas for both LIS datasets are strongly recommended since the archived values in the current release versions have significant errors. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ) is an antimalarial agent that is commonly used in the management of rheumatic skin disease. Few reports exist documenting exacerbation of dermatomyositis (DM) related to HCQ. Herein, we describe three adult patients with worsening DM cutaneous disease after starting HCQ and resolution or improvement with cessation. The time to exacerbation ranged from two weeks to nine months after the initiation of HCQ 400mg/day. Two of the three patients had antibodies to transcription intermediary factor 1γ (TIF1γ) and the other had antibodies to anti-nuclear matrix protein 2 (NXP2). After discontinuation of HCQ, the time to improvement or resolution of cutaneous symptoms ranged from six weeks to six months. Hydroxychloroquine may be associated with worsening cutaneous features in DM. In patients who are not improving despite escalation of immunosuppressive medications, or are worsening, we recommend a trial of discontinuing HCQ. [ABSTRACT FROM AUTHOR]

This article explores the impact of medical comorbidities, smoking, and alcohol on the progression and mortality of mycosis fungoides (MF), a common form of cutaneous T‐cell lymphoma. The study reveals that certain factors, such as heart disease, large cell transformation, MF treatment escalation, Medicaid insurance, and not consuming alcohol, are associated with shorter progression-free survival (PFS). However, factors like hypertension, hyperlipidemia, diabetes, obesity, smoking, and autoimmune diseases do not significantly affect PFS. The study also highlights that the stage of MF at diagnosis is the only significant predictor of MF-specific death. Overall, the findings emphasize the importance of monitoring comorbidities in MF patients, while reassuring them that these conditions do not impact the progression of MF. [Extracted from the article]

This document discusses the pitfalls in testing for antiphospholipid antibodies (aPL), which are associated with antiphospholipid syndrome (APS). APS is an autoimmune condition characterized by blood clotting events and other symptoms. The document explains that laboratory testing for aPL can be challenging, particularly in patients taking anticoagulant medications. It describes the two types of tests commonly used to detect aPL and highlights the issues with false-positive results in patients on anticoagulants. The document also provides strategies to mitigate interference from anticoagulation in testing. Overall, it emphasizes the importance of understanding and addressing these challenges in order to accurately diagnose and manage APS. [Extracted from the article]

ARX788 is an anti-HER2 antibody drug conjugate (ADC) developed using Ambrx proprietary Engineered Precision Biologics technology. The manufacturing process of ARX788 has been optimized during the course of early to late-phase clinical development. A comprehensive evaluation of side-by-side comparability between pre- and post-change process for ARX788 drug substance and drug product from a quality perspective was conducted based on ICH Q5E guidelines consisting of batch release assays, physicochemical and biophysical characterization, biological characterization, and forced degradation studies. All results have substantiated a high degree of similarity between the pre- and post-change ARX788 drug substance batches and drug product lots, demonstrating that the process manufacturing changes did not impact product quality. [ABSTRACT FROM AUTHOR]

Chemerin is a chemoattractant protein abundantly expressed in hepatocytes. Chemerin exerts pro- and anti-inflammatory effects and acts as a pro-resolving protein. Chemerin levels are low in patients with liver cirrhosis and are increased in sepsis. The aim of this study was to identify associations between plasma chemerin levels and underlying diseases as well as causes of severe illness. The cohort included 32 patients with liver cirrhosis who had low systemic chemerin, and who were not considered for further evaluation. Plasma chemerin levels were similar between the 27 patients with systemic inflammatory response syndrome (SIRS), the 34 patients with sepsis and the 63 patients with septic shock. Chemerin in plasma correlated with C-reactive protein and leukocyte count but not with procalcitonin, a clinical marker of bacterial infection. Plasma chemerin did not differ among patients with and without ventilation and patients with and without dialysis. Vasopressor therapy was not associated with altered plasma chemerin levels. Infection with severe acute respiratory syndrome coronavirus 2 had no effect on plasma chemerin levels. Baseline levels of plasma chemerin could not discriminate between survivors and non-survivors. Notably, Gram-positive infection was associated with higher chemerin levels. In summary, the current study suggests that plasma chemerin might serve as an early biomarker for the diagnosis of Gram-positive infections in patients with sepsis. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces low density lipoprotein (LDL) uptake, leading to increased plasma levels of LDL. In addition, PCSK9 has been implicated in inflammation independently of the effects on cholesterol metabolism. The current analysis showed that our 156 patients with systemic inflammatory response syndrome (SIRS) or sepsis had higher plasma PCSK9 levels in contrast with the 68 healthy controls. COVID-19 sepsis patients had increased plasma PCSK9 levels in comparison to sepsis patients not infected by SARS-CoV-2. For further analysis, patients were divided in two groups based on COVID-19. In both sub-cohorts, plasma PCSK9 levels did not correlate with C-reactive protein, leukocyte count, and procalcitonin. Plasma PCSK9 levels of both patient groups did not significantly differ among SIRS/sepsis patients with and without dialysis and patients with and without ventilation. Furthermore, vasopressor therapy was not significantly associated with altered plasma PCSK9 levels. In the non-COVID-19 SIRS/sepsis group, patients with Gram-negative and Gram-positive infections had similar plasma PCSK9 levels as patients without a detectable pathogen in their blood. In conclusion, the current study suggests PCSK9 as a possible biomarker for COVID-19, but this needs to be validated in larger cohorts. [ABSTRACT FROM AUTHOR]

Copyright of Ricerca Psicoanalitica is the property of PAGEPress and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Experience as a trainee and as a supervisor has taught me how anxious novice clinicians can be. Early in our careers, we may have a broad knowledge of theory, but still lack confidence in our ability to help patients. How can supervisors address this issue? This paper focuses on helping novice clinicians develop what I call an 'internal chorus.' This inner object provides a resource to cope with the clinician's most vulnerable moments with patients. An illustration of an 'internal chorus' is provided. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) replication depends on cellular sphingomyelin (SM), but serum SM composition in chronic HCV infection has been hardly analyzed. In this work, 18 SM species could be quantified in the serum of 178 patients with chronic HCV infection before therapy with direct-acting antivirals (DAAs) and 12 weeks later, when therapy was completed. Six SM species were higher in the serum of females than males before therapy and nine at the end of therapy; thus, sex-specific analysis was performed. Type 2 diabetes was associated with lower serum levels of SM 36:2;O2 and 38:2;O2 in men. Serum SM species did not correlate with the viral load in both sexes. Of note, three SM species were lower in males infected with HCV genotype 3 in comparison to genotype 1 infection. These SM species normalized after viral cure. SM 38:1;O2, 40:1;O2, 41:1;O2, and 42:1;O2 (and, thus, total SM levels) were higher in the serum of both sexes at the end of therapy. In males, SM 39:1;O2 was induced in addition, and higher levels of all of these SM species were already detected at 4 weeks after therapy has been started. Serum lipids are related to liver disease severity, and in females 15 serum SM species were low in patients with liver cirrhosis before initiation of and after treatment with DAAs. The serum SM species did not correlate with the model of end-stage liver disease (MELD) score in the cirrhosis and the non-cirrhosis subgroups in females. In HCV-infected male patients, nine SM species were lower in the serum of patients with cirrhosis before DAA treatment and eleven at the end of the study. Most of the SM species showed strong negative correlations with the MELD score in the male cirrhosis patients before DAA treatment and at the end of therapy. Associations of SM species with the MELD score were not detected in the non-cirrhosis male subgroup. In summary, the current analysis identified sex-specific differences in the serum levels of SM species in HCV infection, in liver cirrhosis, and during DAA therapy. Correlations of SM species with the MELD score in male but not in female patients indicate a much closer association between SM metabolism and liver function in male patients. [ABSTRACT FROM AUTHOR]

Accumulating evidence implicates obesity as a risk factor for increased severity of disease outcomes in patients infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Obesity is associated with adipose tissue dysfunction, which not only predisposes individuals to metabolic complications, but also substantially contributes to low-grade systemic inflammation, altered immune cell composition, and compromised immune function. This seems to impact the susceptibility and outcome of diseases caused by viruses, as obese people appear more vulnerable to developing infections and they recover later from infectious diseases than normal-weight individuals. Based on these findings, increased efforts to identify suitable diagnostic and prognostic markers in obese Coronavirus disease 2019 (COVID-19) patients to predict disease outcomes have been made. This includes the analysis of cytokines secreted from adipose tissues (adipokines), which have multiple regulatory functions in the body; for instance, modulating insulin sensitivity, blood pressure, lipid metabolism, appetite, and fertility. Most relevant in the context of viral infections, adipokines also influence the immune cell number, with consequences for overall immune cell activity and function. Hence, the analysis of the circulating levels of diverse adipokines in patients infected with SARS-CoV-2 have been considered to reveal diagnostic and prognostic COVID-19 markers. This review article summarizes the findings aimed to correlate the circulating levels of adipokines with progression and disease outcomes of COVID-19. Several studies provided insights on chemerin, adiponectin, leptin, resistin, and galectin-3 levels in SARS-CoV-2-infected patients, while limited information is yet available on the adipokines apelin and visfatin in COVID-19. Altogether, current evidence points at circulating galectin-3 and resistin levels being of diagnostic and prognostic value in COVID-19 disease. [ABSTRACT FROM AUTHOR]