Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVES: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. METHODS: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions. RESULTS: 1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states. CONCLUSIONS: Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

Microbial transmission in the social microbiome and host health and disease.

Although social interactions are known to drive pathogen transmission, the contributions of socially transmissible host-associated mutualists and commensals to host health and disease remain poorly explored. We use the concept of the social microbiome-the microbial metacommunity of a social network of hosts-to analyze the implications of social microbial transmission for host health and disease. We investigate the contributions of socially transmissible microbes to both eco-evolutionary microbiome community processes (colonization resistance, the evolution of virulence, and reactions to ecological disturbance) and microbial transmission-based processes (transmission of microbes with metabolic and immune effects, inter-specific transmission, transmission of antibiotic-resistant microbes, and transmission of viruses). We consider the implications of social microbial transmission for communicable and non-communicable diseases and evaluate the importance of a socially transmissible component underlying canonically non-communicable diseases. The social transmission of mutualists and commensals may play a significant, under-appreciated role in the social determinants of health and may act as a hidden force in social evolution.

Gut complement induced by the microbiota combats pathogens and spares commensals.

Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization and is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host's specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as an innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.

Canadian patient experiences of lupus nephritis: a qualitative analysis.

OBJECTIVE: Lupus nephritis (LN) is one of the most severe manifestations of SLE; however, we know little about the lived experience of LN. This research investigates patient experiences and perspectives of (1) LN diagnosis; (2) living with LN; and (3) LN healthcare and treatment. METHODS: Patients aged ≥18 years with biopsy-proven pure or mixed International Society of Nephrology/Renal Pathology Society class III, IV or V LN were purposefully recruited from a Canadian lupus cohort to participate in semistructured in-depth interviews. RESULTS: Thirty patients with LN completed the interviews. The mean (SD) age was 42.1 (16.4) years, and 86.7% were female. Participants described challenges seeking, receiving and adjusting to a LN diagnosis, and some reported that their diagnosis process took weeks to years. While 16 participants were provided resources by healthcare providers to help them through the process of diagnosis, the need for accessible LN-specific information at diagnosis was highlighted (n=18). Participants also described the unpredictability of living with LN, particularly related to impacts on physical and mental health, relationships, leisure activities, employment and education, and family planning. While most (n=26) participants reported a positive impression of their care, the side effects of LN medications and the need to increase patient and societal awareness/understanding of LN were highlighted in the context of healthcare and treatment. CONCLUSIONS: The unpredictability of living with LN, the heavy treatment burden and a lack of patient/societal awareness substantially affect the lived experience of LN. These findings will inform the development of LN-specific patient resources to increase understanding of LN and improve well-being for patients.

Topical Finasteride: A Comprehensive Review of Androgenetic Alopecia Management for Men and Women.

The most prevalent kind of alopecia, androgenetic alopecia, commonly known as male or female pattern hair loss, affects both men and women, with the frequency rising with advancing years. Even though practicing dermatologists and hair experts frequently encounter it, it might be one of the most challenging disorders to treat since choosing a course of action frequently requires a comprehensive analysis of several variables and moral judgment. Effectiveness, side effect profiles, practicability, promoting compliance, and treatment cost are the most important factors to take into account, especially given the chronic nature of androgenetic alopecia. A clinician's ability to select the optimum course of treatment for each patient may be constrained and clouded by their knowledge base, experience, and financial compensation. A search was done to find research on the effectiveness of topical finasteride therapy, including clinically pertinent case reports and papers. Only topical minoxidil and oral finasteride are now approved by the Food and Drug Administration and the European Medicines Agency for the treatment of androgenetic alopecia. Despite being effective for hair regeneration, systemic use of finasteride is accompanied by adverse effects that prevent long-term use. Investigating topical finasteride as another possible treatment plan may be fruitful. Early research on the use of topical finasteride is safe and encouraging, despite its limitations. More research on drug distribution, ideal topical strength and usage regularity, adverse effects, and application for other alopecias would aid in elucidating the range of topical finasteride use.

Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy.

Our bodies are inhabited by trillions of microorganisms. The host immune system constantly interacts with the microbiota in barrier organs, including the intestines. Over decades, numerous studies have shown that our mucosal immune system is dynamically shaped by a variety of microbiota-derived signals. Elucidating the mediators of these interactions is an important step for understanding how the microbiota is linked to mucosal immune homeostasis and gut-associated diseases. Interestingly, the efficacy of cancer immunotherapies that manipulate costimulatory and coinhibitory pathways has been correlated with the gut microbiota. Moreover, adverse effects of these therapies in the gut are linked to dysregulation of the intestinal immune system. These findings suggest that costimulatory pathways in the immune system might serve as a bridge between the host immune system and the gut microbiota. Here, we review mechanisms by which commensal microorganisms signal immune cells and their potential impact on costimulation. We highlight how costimulatory pathways modulate the mucosal immune system through not only classical antigen-presenting cells but also innate lymphocytes, which are highly enriched in barrier organs. Finally, we discuss the adverse effects of immune checkpoint inhibitors in the gut and the possible relationship with the gut microbiota.

RETINAL DEPOSITS OF TRIAMCINOLONE-MOXIFLOXACIN AFTER DROPLESS CATARACT SURGERY.

PURPOSE: To report a case of epiretinal crystalline deposits observed on fundus examination and optical coherence tomography 2 years after transzonular intravitreal injection of triamcinolone-moxifloxacin (TriMoxi) during "dropless" cataract surgery. METHODS: Observational case report with literature review of toxic effects of intravitreal triamcinolone and differential diagnosis of retinal crystalline deposits. RESULTS: A 37-year-old asymptomatic pseudophakic man presented with refractile crystalline retinal deposits that had prompted an extensive systemic embolic workup. The systemic evaluation for emboli was negative. OCT imaging revealed that the crystalline deposits were confined to the anterior surface of the internal limiting membrane. Further historical inquiry determined that transzonular intravitreal triamcinolone-moxifloxacin injection had been performed at the time of cataract surgery 2 years earlier. CONCLUSION: Transzonular triamcinolone acetonide delivered during cataract surgery can deposit on the retinal surface for long periods. These epiretinal crystalline deposits are benign and generally do not interfere with visual acuity. Nevertheless, clinicians should be aware of this differential diagnosis because clinical misdiagnosis can lead to unwarranted evaluation and treatment.

NMDA Receptors in the Basolateral Amygdala Complex Are Engaged for Pavlovian Fear Conditioning When an Animal's Predictions about Danger Are in Error.

It is widely accepted that Pavlovian fear conditioning requires activation of NMDA receptors (NMDARs) in the basolateral amygdala complex (BLA). However, it was recently shown that activation of NMDAR in the BLA is only required for fear conditioning when danger occurs unexpectedly; it is not required for fear conditioning when danger occurs as expected. This study tested the hypothesis that NMDARs in the BLA are engaged for Pavlovian fear conditioning when an animal's predictions regarding danger are in error. In each experiment, rats (females in Experiment 1 and males in Experiments 2-5) were conditioned to fear one stimulus, S1, when it was paired with foot-shock (S1→shock), and 48 h later, a second stimulus, S2, when it was presented in sequence with the already-conditioned S1 and foot-shock (S2→S1→shock). Conditioning to S2 occurred under a BLA infusion of the NMDAR antagonist, D-AP5 or vehicle. The subsequent tests of freezing to S2 alone and S1 alone revealed that the antagonist had no effect on conditioning to S2 when the shock occurred exactly as predicted by the S1, but disrupted this conditioning when the shock occurred earlier/later than predicted by S1, or at a stronger/weaker intensity. These results imply that errors in the timing or intensity of a predicted foot-shock engage NMDARs in the BLA for Pavlovian fear conditioning. They are discussed in relation to theories which propose a role for prediction error in determining how experiences are organized in memory and how activation of NMDAR in the BLA might contribute to this organization.SIGNIFICANCE STATEMENT This study is significant in showing that prediction error determines how a new experience is encoded with respect to a past experience and, thereby, whether NMDA receptors (NMDARs) in the basolateral amygdala complex (BLA) encode the new experience. When prediction error is small (e.g., danger occurs as and when expected), the new experience is encoded together with a past experience as part of the same "mental model," and NMDAR activation in the BLA is not needed for this encoding. By contrast, when prediction error is large (e.g., danger occurs at an unexpected intensity or time), the new experience is encoded separately from the past experience as part of a new mental model, and NMDAR activation in the BLA is needed for this encoding.

Gut microbial fatty acid isomerization modulates intraepithelial T cells.

The human gut microbiome constantly converts natural products derived from the host and diet into numerous bioactive metabolites1-3. Dietary fats are essential micronutrients that undergo lipolysis to release free fatty acids (FAs) for absorption in the small intestine4. Gut commensal bacteria modify some unsaturated FAs-for example, linoleic acid (LA)-into various intestinal FA isomers that regulate host metabolism and have anticarcinogenic properties5. However, little is known about how this diet-microorganism FA isomerization network affects the mucosal immune system of the host. Here we report that both dietary factors and microbial factors influence the level of gut LA isomers (conjugated LAs (CLAs)) and that CLAs in turn modulate a distinct population of CD4+ intraepithelial lymphocytes (IELs) that express CD8αα in the small intestine. Genetic abolition of FA isomerization pathways in individual gut symbionts significantly decreases the number of CD4+CD8αα+ IELs in gnotobiotic mice. Restoration of CLAs increases CD4+CD8αα+ IEL levels in the presence of the transcription factor hepatocyte nuclear factor 4γ (HNF4γ). Mechanistically, HNF4γ facilitates CD4+CD8αα+ IEL development by modulating interleukin-18 signalling. In mice, specific deletion of HNF4γ in T cells leads to early mortality from infection by intestinal pathogens. Our data reveal a new role for bacterial FA metabolic pathways in the control of host intraepithelial immunological homeostasis by modulating the relative number of CD4+ T cells that were CD4+CD8αα+.

Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance.

The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice1-6. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma7,8. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and PD-L2 share PD-1 as a binding partner, but PD-L2 can also bind RGMb. We demonstrate that blockade of PD-L2-RGMb interactions can overcome microbiome-dependent resistance to PD-1 pathway inhibitors. Antibody-mediated blockade of the PD-L2-RGMb pathway or conditional deletion of RGMb in T cells combined with an anti-PD-1 or anti-PD-L1 antibody promotes anti-tumour responses in multiple mouse tumour models that do not respond to anti-PD-1 or anti-PD-L1 alone (germ-free mice, antibiotic-treated mice and even mice colonized with stool samples from a patient who did not respond to treatment). These studies identify downregulation of the PD-L2-RGMb pathway as a specific mechanism by which the gut microbiota can promote responses to PD-1 checkpoint blockade. The results also define a potentially effective immunological strategy for treating patients who do not respond to PD-1 cancer immunotherapy.

Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97.

Sigma-2 receptor (S2R) is a S2R ligand-binding site historically associated with reportedly 21.5 kDa proteins that have been linked to several diseases, such as cancer, Alzheimer's disease, and schizophrenia. The S2R is highly expressed in various tumors, where it correlates with the proliferative status of the malignant cells. Recently, S2R was reported to be the transmembrane protein TMEM97. Prior to that, we had been investigating the translocator protein (TSPO) as a potential 21.5 kDa S2R candidate protein with reported heme and sterol associations. Here, we investigate the contributions of TMEM97 and TSPO to S2R activity in MCF7 breast adenocarcinoma and MIA PaCa-2 (MP) pancreatic carcinoma cells. Additionally, the role of the reported S2R-interacting partner PGRMC1 was also elucidated. Proximity ligation assays and co-immunoprecipitation show a functional association between S2R and TSPO. Moreover, a close physical colocalization of TMEM97 and TSPO was found in MP cells. In MCF7 cells, co-immunoprecipitation only occurred with TMEM97 but not with PGRMC1, which was further confirmed by confocal microscopy experiments. Treatment with the TMEM97 ligand 20-(S)-hydroxycholesterol reduced co-immunoprecipitation of both TMEM97 and PGRMC1 in immune pellets of immunoprecipitated TSPO in MP cells. To the best of our knowledge, this is the first suggestion of a (functional) interaction between TSPO and TMEM97 that can be affected by S2R ligands.

Multitraits evaluation of a Solanum pennellii introgression tomato line challenged by combined abiotic stress.

Rising daily temperatures and water shortage are two of the major concerns in agriculture. In this work, we analysed the tolerance traits in a tomato line carrying a small region of the Solanum pennellii wild genome (IL12-4-SL) when grown under prolonged conditions of single and combined high temperature and water stress. When exposed to stress, IL12-4-SL showed higher heat tolerance than the cultivated line M82 at morphological, physiological, and biochemical levels. Moreover, under stress IL12-4-SL produced more flowers than M82, also characterized by higher pollen viability. In both lines, water stress negatively affected photosynthesis more than heat alone, whereas the combined stress did not further exacerbate the negative impacts of drought on this trait. Despite an observed decrease in carbon fixation, the quantum yield of PSII linear electron transport in IL12-4-SL was not affected by stress, thereby indicating that photochemical processes other than CO2 fixation acted to maintain the electron chain in oxidized state and prevent photodamage. The ability of IL12-4-SL to tolerate abiotic stress was also related to the intrinsic ability of this line to accumulate ascorbic acid. The data collected in this study clearly indicate improved tolerance to single and combined abiotic stress for IL12-4-SL, making this line a promising one for cultivation in a climate scenario characterized by frequent and long-lasting heatwaves and low rainfall.

Microbiome induced complement synthesized in the gut protects against enteric infections.

Canonically, complement is a serum-based host defense system that protects against systemic microbial invasion. Little is known about the production and function of complement components on mucosal surfaces. Here we show gut complement component 3 (C3), central to complement function, is regulated by the composition of the microbiota in healthy humans and mice, leading to host-specific gut C3 levels. Stromal cells in intestinal lymphoid follicles (LFs) are the predominant source of intestinal C3. During enteric infection with Citrobacter rodentium or enterohemorrhagic Escherichia coli, luminal C3 levels increase significantly and are required for protection. C. rodentium is remarkably more invasive to the gut epithelium of C3-deficient mice than of wild-type mice. In the gut, C3-mediated phagocytosis of C. rodentium functions to clear pathogens. Our study reveals that variations in gut microbiota determine individuals’ intestinal mucosal C3 levels, dominantly produced by LF stromal cells, which directly correlate with protection against enteric infection. Highlights: Gut complement component 3 (C3) is induced by the microbiome in healthy humans and mice at a microbiota-specific level.Gut stromal cells located in intestinal lymphoid follicles are a major source of luminal C3 During enteric infections with Citrobacter rodentium or enterohemorrhagic Escherichia coli, gut luminal C3 levels increase and are required for protection. C. rodentium is significantly more invasive of the gut epithelium in C3-deficient mice when compared to WT mice. In the gut, C3-mediated opsonophagocytosis of C. rodentium functions to clear pathogens.

Low dialysate sodium in children and young adults on maintenance hemodialysis: a prospective, randomized, crossover study.

BACKGROUND: The optimal dialysate sodium concentration (dNa) in children on hemodialysis (HD) is unknown. The aim of this study was to compare the effect on interdialytic weight gain (IDWG) and blood pressure (BP) of a low (135 mmol/l) and standard dNa (138 mmol/l) in children and young adults on maintenance HD. METHODS: This prospective single-blind randomized crossover study consisted of a randomized sequence of two phases: "standard dNa" of 138 mmol/L and "low dNa" of 135 mmol/L. Each phase lasted 4 weeks. Inclusion criteria were age < 25 years, hypertension, pre-HD serum Na (sNa) ≥ 130 mmol/L, and occurrence of symptoms in less than 25% of sessions. Primary outcomes were pre-HD systolic and diastolic BP and IDWG. RESULTS: Fifteen patients were recruited, mean age 17.8 ± 4.4 years. Pre-HD SBP and DBP were not different between the two treatments. Mean IDWG was significantly lower with low dNa than with standard dNa: 2.12 ± 1.39% vs. 2.77 ± 1.53%, respectively (p = 0.008). The first-hour refill index (a volume index based on blood-volume monitoring) was significantly lower with dNa 135 mmol/L (p = 0.018). The mean Na gradient (dNa-sNa) was - 2.53 ± 2.4 mmol/L with dNa 135 mmol/L and 0.17 ± 2.8 mmol/L with dNa 138 mmol/L (p = 0.0001). The incidence of symptomatic sessions was similar (1.0% vs. 1.0%). CONCLUSIONS: In a selected population of hypertensive pediatric and young adult HD patients, a dNa of 135 mmol/L was associated with a significant reduction of IDWG compared with a dNa of 138 mmol/L. Furthermore, long-term studies are needed to investigate the effect of lowering dNa on BP. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sharing the load in NAD metabolism.

Recently in Cell Metabolism, Challapa et al. used isotope labeling to track NAD metabolism in host tissues and the gut microbiota. They describe a symbiotic relationship in which the gut microbiota uses host-derived nicotinamide to generate NAD and in return, produces nicotinic acid for host NAD biosynthesis.

Health information use by patients with systemic lupus erythematosus (SLE) pre and during the COVID-19 pandemic.

OBJECTIVE: We conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic. METHODS: Patients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources. RESULTS: Surveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference -8.3%, 95% CI -10.2% to -6.5%; family physicians: 57.1% pre vs 50.0% post, difference -7.1%, 95% CI -9.2% to -5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted. CONCLUSIONS: Physicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

Economic burden of food allergy in Canada: Estimating costs and identifying determinants.

BACKGROUND: Limited data exist on the economic burden of food allergy (FA). OBJECTIVE: To assess FA-related direct (healthcare and out-of-pocket) and indirect (lost productivity) costs and their determinants in Canadian children and adults self-reporting FA. METHODS: FA-individuals self-reporting a convincing history or physician diagnosis were recruited through FA registries, an anaphylaxis registry, and advocacy associations, and electronically surveyed regarding FA-related healthcare use, out-of-pocket expenditures, and time lost from paid and unpaid labor. Direct and indirect costs (2020 Canadian dollars [CAD]) were stratified on severe reaction vs mild, moderate or no reaction, and children vs adults; multivariate regressions assessed the association between costs and sociodemographic and disease characteristics. RESULTS: Between May 2018 and July 2019, 2692 eligible individuals responded (2189 convincing history and 503 physician diagnosis only); 1020 experienced a severe reaction; 1752 were children. Per FA-individual, annual healthcare, out-of-pocket, and indirect costs were $1267, $2136, and $7950. Those with a severe reaction had higher healthcare and out-of-pocket costs than those with mild, moderate or no reaction. FA-children vs FA-adults had higher healthcare and out-of-pocket costs, and lower indirect costs. Multivariate results showed that lower age, a severe reaction ever, multiple FAs, and fair or poor general health were associated with higher healthcare and out-of-pocket costs. Higher age, lower household education and income, and fair or poor general health were associated with higher indirect costs. CONCLUSION: The economic burden of FA in Canada is substantial, particularly for those with a severe reaction ever, multiple FAs, and fair or poor general health. It is crucial that those most adversely affected are allocated appropriate resources to support disease management.

Cytokine autoantibodies in SARS-CoV-2 prepandemic and intrapandemic samples from an SLE cohort.

Cytokine autoantibodies, particularly those directed to type I interferon (T1IFN), have been reported to portend an increased risk of severe COVID-19. Since SLE is one of the conditions historically associated with T1IFN autoantibodies, we sought to determine the prevalence of cytokine autoantibodies in our local cohort of 173 patients with SLE prepandemic and intrapandemic, of which nine had confirmed exposure to SARS-CoV-2. Autoantibodies to 16 different cytokines, including T1IFN, were measured by an addressable laser bead immunoassay. None of the 9 patients with confirmed exposure to SARS-CoV-2 had autoantibodies to T1IFN and none had severe COVID-19 symptoms, necessitating hospitalisation. Hence, we could not confirm that TIIFN autoantibodies increase the risk for severe COVID-19. In addition, the cytokine autoantibody pattern did not differ between those with and without evidence of SARS-CoV-2 exposure.

New Pharmacological Strategies against Pancreatic Adenocarcinoma: The Multifunctional Thiosemicarbazone FA4.

A new sigma-2 (σ2) receptor ligand (FA4) was efficiently synthesized and evaluated for cytotoxic, proapoptotic, and antimigratory activity on pancreatic ductal adenocarcinoma (PDAC) primary cell cultures, which restrained the aggressive and chemoresistant behavior of PDAC. This compound showed relevant antiproliferative activity with half maximal inhibitory concentration (IC50) values ranging from 0.701 to 0.825 µM. The cytotoxic activity was associated with induction of apoptosis, resulting in apoptotic indexes higher than those observed after exposure to a clinically relevant concentration of the gemcitabine, the first-line drug used against PDAC. Interestingly, FA4 was also able to significantly inhibit the migration rate of both PDAC-1 and PDAC-2 cells in the scratch wound-healing assay. In conclusion, our results support further studies to improve the library of thiosemicarbazones targeting the σ-2 receptor for a deeper understanding of the relationship between the biological activity of these compounds and the development of more efficient anticancer compounds against PDAC.