Innate Factors Research Articles

The impact of ADHD genetic risk on educational achievement: a comparative cross-national study

Abstract Human capital accumulation is a key driver of economic development across countries. Although previous studies have shown that country-specific circumstances (e.g., cultural, health-related, and educational factors) are strongly related with the accumulation of human capital in society, few studies have explored the importance of innate ability factors in general and ADHD-related behavioral symptoms in particular for cognitive skill outcomes. This paper hypothesizes and empirically establishes the educational burden of the ADHD-related behavioral symptoms on aggregate cognitive achievement outcomes. We use a novel compilation of the 2- and 7-repeat allele variants of the human DRD4 exon III gene that candidate gene association studies have identified as an important biomarker in the etiology of childhood ADHD. We find that our indicator for the prevalence of ADHD genetic risk in society has a negative and statistically significant impact on educational achievement. Additional sensitivity tests and estimation methods further corroborate our main hypothesis.

Complement in autoimmune inflammatory myopathies, the role of myositis-associated antibodies, COVID-19 associations and muscle amyloid deposits

Introduction The inflammatory myopathies (IM) have now evolved into distinct subsets requiring clarification about their immunopathogenesis to guide applications of targeted therapies Areas covered Immunohistopathologic criteria of IM with focus on complement, anti-complement therapeutics and other biologic immunotherapies. The COVID19-triggered muscle autoimmunity along with the correct interpretation of muscle amyloid deposits are discussed. Expert opinion The IM, unjustifiably referred as idiopathic, comprise Dermatomyositis (DM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). In DM, complement activation with MAC-mediated endomysial microvascular destruction and perifascicular atrophy is the fundamental process, while innate immunity activation factors, INF1 and MxA, sense and secondarily enhance inflammation. Complement participates in muscle fiber necrosis from any cause and may facilitate muscle-fiber necrosis in NAM but seems unlikely that myositis-associated antibodies participate in complement-fixing. Accordingly, anti-complement therapeutics should be prioritized for DM. SARS-CoV-2 can potentially trigger muscle autoimmunity but systematic studies are needed as the reported autopsy findings are not clinically relevant. In IBM, tiny amyloid deposits within muscle fibers are enhanced by inflammatory mediators contributing to myodegeneration; in contrast, spotty amyloid deposits in the endomysial connective tissue do not represent “amyloid myopathy” but only have diagnostic value for amyloidosis due to any cause.

Welfare Assessment Tools in Zoos: From Theory to Practice.

Zoos are increasingly implementing formalized animal welfare assessment programs to allow monitoring of welfare over time, as well as to aid in resource prioritization. These programs tend to rely on assessment tools that incorporate resource-based and observational animal-focused measures. A narrative review of the literature was conducted to bring together recent studies examining welfare assessment methods in zoo animals. A summary of these methods is provided, with advantages and limitations of the approaches presented. We then highlight practical considerations with respect to implementation of these tools into practice, for example scoring schemes, weighting of criteria, and innate animal factors for consideration. It is concluded that there would be value in standardizing guidelines for development of welfare assessment tools since zoo accreditation bodies rarely prescribe these. There is also a need to develop taxon or species-specific assessment tools to complement more generic processes and more directly inform welfare management.

Cognitive model of phonological awareness focusing on errors and formation process through Shiritori

Language acquisition is supported by phonological awareness, which intentionally makes children aware of phonological units. By understanding the internal processes of children during language acquisition, this study aims to elucidate factors that can correct erroneous phonological generation. Therefore, we developed a cognitive model using innate and experiential factors of the memory retrieval in the cognitive architecture–ACT-R. Furthermore, we performed simulations using Shiritori, a Japanese word game, as an interaction task. The simulation included the observation of effects of the experiential factor of repeating a task and innate factors of different settings. It showed that repeating a single task causes incorrect convergence, and this convergence can be prevented by comprehensive activation of overall phonological knowledge during the interval of Shiritori tasks. Moreover, the simulation in specific innate settings exhibited commonalities with cases of developmental disorder by showing errors like consonant deletion. In the future, we will examine the correlation of the aforementioned findings with actual language development to realize the use of cognitive architecture in real world.

Survival analysis of African catfish and Nile tilapia briefly exposed to complex pesticide mixtures

BackgroundPulse exposures are the consequences of the intermittent release of pollutants in the environment. Brief exposure of aquatic organisms to high concentrations of pesticides simultaneously occurs, particularly in small watercourses during high flows. The effects of pulse exposure often include effects occurring during and after the exposure. Despite this, routine toxicity tests procedures often ignore brief exposure scenarios and the role of time in toxicity. We conducted a pulse toxicity test by briefly exposing African catfish and Nile tilapia fingerlings to pesticide mixtures of atrazine, mancozeb, chlorpyrifos, and lambda-cyhalothrin. The study aimed to estimate pesticide mixture interaction in pulse-exposed fish and elucidate the influence of species differences on the response of fish to the pesticide mixture.ResultsDespite the similarity in fingerlings weight, African catfish had a significantly higher survival probability than Nile tilapia after exposure to atrazine-mancozeb mixture. However, the survival probability of African catfish and Nile tilapia fingerlings were similar after exposure to atrazine-chlorpyrifos, atrazine-lambda cyhalothrin, mancozeb-chlorpyrifos, mancozeb-lambda cyhalothrin, chlorpyrifos-lambda cyhalothrin, and quaternary mixture (p > 0.05). The survival probability of exposed fingerlings was significantly lower for continuous than pulse exposure to the mixtures (p < 0.01). Nevertheless, the survival probability of 60 min of pulse exposure to 13.49 mg/L mancozeb-lambda cyhalothrin was similar to continuous exposure for 96 h. Atrazine-mancozeb, atrazine-chlorpyrifos, atrazine-lambda cyhalothrin, mancozeb-chlorpyrifos, mancozeb-lambda cyhalothrin, and the quaternary pesticide mixture were antagonists in African catfish but not in Nile tilapia. At the same time, chlorpyrifos-lambda-cyhalothrin was antagonistic in Nile tilapia but not African catfish.ConclusionsPesticide mixture interaction was antagonist but specie-dependent. Innate intrinsic and extrinsic deterministic factors and, to a limited extent, stochastic processes may have influenced the survival probability of African catfish, and Nile tilapia pulsed exposed to complex pesticide mixtures. Pulse toxicity assessment using survival analysis is relevant in ecotoxicology as it enables the study of factors that can influence pulse toxicity.

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection.

The natural process of human immunodeficiency virus type 1(HIV-1) infection is characterized by high viral load, immune cell exhaustion, and immunodeficiency, which eventually leads to the stage of acquired immunodeficiency syndrome (AIDS) and opportunistic infections. Rapidly progressing HIV-1 individuals often die of AIDS several years after infection without treatment. The promotion of ART greatly prolongs the survival time of HIV-infected persons. However, some patients have incomplete immune function reconstruction after ART due to latent storage of HIV-infected cells. Therefore, how to achieve a functional cure has always been the focus and hot spot of global AIDS research. Fortunately, the emergence of ECs/LTNPs who can control virus replication naturally has ignited new hope for realizing a functional cure for AIDS. Recently, a special category of infected individuals has attracted attention that can delay the progression of the disease more rigorously than the natural progression of HIV-1 infection described above. These patients are characterized by years of HIV-1 infection, long-term asymptomatic status, and normal CD4+T cell count without ART, classified as HIV-infected long-term nonprogressors (LTNPs) and elite controllers (ECs). Numerous studies have shown that the host and virus jointly determine the progression of HIV-1 infection, in which the level of innate immunity activation plays an important role. As the first line of defense against pathogen invasion, innate immunity is also a bridge to induce adaptive immunity. Compared with natural progressors, innate immunity plays an antiviral role in HIV-1 infection by inducing or activating many innate immune-related factors in the natural ECs. Learning the regulation of ECs immunity, especially the innate immunity in different characteristics, and thus studying the mechanism of the control of disease progression naturally, will contribute to the realization of the functional cure of AIDS. Therefore, this review will explore the relationship between innate immunity and disease progression in ECs of HIV-1 infection from the aspects of innate immune cells, signaling pathways, cytokines, which is helpful to provide new targets and theoretical references for the functional cure, prevention and control of AIDS, and development of a vaccine.

Evolutionary Landscapes of Host-Virus Arms Races.

Vertebrate immune systems suppress viral infection using both innate restriction factors and adaptive immunity. Viruses mutate to escape these defenses, driving hosts to counterevolve to regain fitness. This cycle recurs repeatedly, resulting in an evolutionary arms race whose outcome depends on the pace and likelihood of adaptation by host and viral genes. Although viruses evolve faster than their vertebrate hosts, their proteins are subject to numerous functional constraints that impact the probability of adaptation. These constraints are globally defined by evolutionary landscapes, which describe the fitness and adaptive potential of all possible mutations. We review deep mutational scanning experiments mapping the evolutionary landscapes of both host and viral proteins engaged in arms races. For restriction factors and some broadly neutralizing antibodies, landscapes favor the host, which may help to level the evolutionary playing field against rapidly evolving viruses. We discuss the biophysical underpinnings of these landscapes and their therapeutic implications.

Health equity & tribal populations: Challenges & way forward.

Health equity & tribal populations: Challenges & way forward.

The Effects of Resilience and Related Factors on Burnout in Clinical Nurses, Kagoshima, Japan.

Burnout, due to extreme mental and physical fatigue, and emotional exhaustion, leads to decreased nursing quality and turnover. However, not all nurses are observed as burnouts in the same work environment, and resilience and related factors may have effects on the development of burnouts. Therefore, we conducted a cross-sectional study to examine the effects of resilience and related factors on the burnout in clinical nurses, Kagoshima, Japan. Data for this cross-sectional study involving nurses (n = 98) was collected using the following questionnaire surveys: the Bidimensional Resilience Scale, The Workplace Social Support Scale, and the Japanese version of the Pine's Burnout Scale. Using burnout as a dependent variable, analyses were conducted using one-way analysis of variance and multiple regression analysis after adjusted for related factors. The prevalence of burnouts was 19.6% on the mainland and 36.1% on remote island. Innate resilience, acquired resilience, workplace social support, and burnout showed no significant difference between nurses on the mainland and remote island. In the mainland participants, innate resilience (β = -0.492, P < 0.001) and acquired resilience (β = -0.325, P = 0.007) showed a negative association with burnout, and similar associations were observed innate resilience (β = -0.520, P = 0.004) and acquired resilience (β = -0.336, P = 0.057) in the remote island participants. For all participants, innate resilience (β = -0.443, P = 0.001) and workplace social support (β = -0.204, P = 0.031) showed a negative association with burnout, and turnover intention was positively associated (β = 0.025, P = 0.021). A negative association between burnout and innate resilience factors was observed in the mainland and remote island. Further evaluation of innate resilience is necessary for burnout prevention in clinical nurses.

Soluble Factors and Receptors Involved in Skin Innate Immunity-What Do We Know So Far?

The pattern recognition receptors, complement system, inflammasomes, antimicrobial peptides, and cytokines are innate immunity soluble factors. They sense, either directly or indirectly, the potential threats and produce inflammation and cellular death. High interest in their modulation has emerged lately, acknowledging they are involved in many cutaneous inflammatory, infectious, and neoplastic disorders. We extensively reviewed the implication of soluble factors in skin innate immunity. Furthermore, we showed which molecules target these factors, how these molecules work, and how they have been used in dermatological practice. Cytokine inhibitors have paved the way to a new era in treating moderate to severe psoriasis and atopic dermatitis.

Introducing ‘Pragmatic Intelligence’ as a Prerequisite for Pragmatic Competence in Communication

There have been various approaches to the definition of the elusive term ‘intelligence’ from the perspectives of psychologists, computer language experts, natural scientists, linguists, philosophers, and others. However, no unanimous definition has so far been made for the term. On the contrary, new readings and understandings arise as the outcome of theoretical and experimental studies. This paper is an attempt to introduce the term ‘pragmatic intelligence’ as a prerequisite and a basic requirement for pragmatic competence to avoid pragmatic failure and secure a felicitous communication among interlocutors. The paper hypothesizes that ‘pragmatic intelligence’ is a prerequisite for ‘pragmatic competence’. In order to verify the hypothesis, the researcher theoretically analyzed the necessity of associating pragmatic competence with a mother concept of the same origin rather than connecting it to either Chomsky’s grammatical competence or Hymes’ communicative competence. The paper concluded that ‘pragmatic intelligence’ encompasses innate factors that human beings are born with, which could be shaped in the form of pragmatic competence depending on the quantity and quality of the obtained knowledge. Nonetheless, the paper also proposes for researchers to study the universal characteristics of ‘pragmatic intelligence’ and its pedagogical implications on first and second language acquisition

Physical Therapy Assessment of Baseline Function and Endurance Predicts Short Term Outcomes in Commercial CAR T Patients with Lymphoma

Introduction:CAR T-cell therapy has revolutionized the treatment of relapsed/refractory B cell lymphomas, providing hope to patients who previously faced dismal outcomes. Despite unprecedented efficacy including high response rates and a significant proportion of durable responses, significant toxicities are still prevalent. Toxicities related to immune therapy including cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) along with infections and hematologic toxicity, complicate the post CAR T-cell infusion course. Innate patient-related factors including presence of comorbidities, advanced physiologic age, and poor fitness, likely contribute to poor short-term outcomes, however no validated risk scores incorporating these factors have been validated in patients receiving CAR T-cell therapy for lymphoma. In the present study we identified the ability of a patient to walk 500 feet (ft) or more during the 6 Minute Walk Test (6MWT) at baseline as a predictive marker for poor short-term outcomes after CAR T-cell infusion.Methods:We retrospectively analyzed charts of 78 patients who received commercially available CAR T-cell products for the treatment of lymphoma between May, 2019 and March, 2021 who had baseline assessment by physical therapy at the time of admission for CAR T-cell therapy. CRS and ICANS were scored by ASTCT guidelines. Demographics were analyzed with descriptive statistics. Univariate analysis was performed by Chi Squared.Results:The analysis included 78 patients with a median age of 63 (range, 21-82), 37% (n=29) were female. Patients were treated for DLBCL (64%, n=50), transformed follicular lymphoma (tFL; 29%, n=23), primary mediastinal B cell lymphoma (PMBCL; 4%, n=3), and mantle cell lymphoma (MCL; 3%, n=2). Patients received axicabtagene ciloleucel (94%, n=73), tisagenlecleucel (4%, n=3), or brexucabtagene autoleucel (3%, n=2). Patients had a median of 3 prior lines of therapy (range 2-7) and 53% (n=42) received bridging chemotherapy.Among the 70 patients who completed the 6MWT, the mean distance was 909 ft (range, 20-2045), 8 patients were unable to compete the assessment due to debility and were included in the analysis as a 0 distance. Patients who were unable to complete 500 feet (n=17) were deemed to have poor endurance (PE). The PE group of patients were 3.6 times more likely to have a prolonged length of stay (p=0.02), while they were 1.5 times less likely to be alive at 100 days post CAR T infusion (p = 0.002). Patients also tended to have higher rates of ICANS (76% vs 41%), lower overall response rates (ORR) (78% vs 98%), and higher 30 day mortality (18% vs 2%), although these did not reach statistical significance, p=0.08, 0.06, and 0.07, respectively. CRS did not appear to be related to PE status, neither did age, or prior lines of therapy.Conclusions:Within the limitations of a retrospective study, we demonstrate that the baseline physical therapy-assessed measure of function and endurance, namely the 6MWT, correlates with several critical short-term outcomes in CAR T patients with lymphoma. These include prolonged length of stay, survival at day 100, and there is suggested correlation with ORR, ICANS, and 30-day survival as well. These findings illustrate the potential for early recognition of deconditioned patients that may do poorly after CAR T-cell therapy. Identification of these patients could allow for therapeutic interventions prior to CAR T infusion or during their post-infusion hospital stay, designed to enhance their strength and endurance, and potentially improve these short-term outcomes. Prospective intervention studies are planned based on these findings. DisclosuresShouse: Kite Pharma: Speakers Bureau; Beigene: Honoraria. Budde: Kite Pharma: Consultancy; AstraZeneca: Research Funding; Genentech: Consultancy, Research Funding.

Yellow fever vaccine protects mice against Zika virus infection.

Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public health priority. We describe the protective effect of an already licensed attenuated yellow fever vaccine (YFV, 17DD) in type-I interferon receptor knockout mice (A129) and immunocompetent BALB/c and SV-129 (A129 background) mice infected with ZIKV. YFV vaccination provided protection against ZIKV, with decreased mortality in A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in BALB/c mice. The A129 mice that were challenged two and three weeks after the first dose of the vaccine were fully protected, whereas partial protection was observed five weeks after vaccination. In all cases, the YFV vaccine provoked a substantial decrease in the cerebral viral load. YFV immunization also prevented hippocampal synapse loss and microgliosis in ZIKV-infected mice. Our vaccine model is T cell-dependent, with AG129 mice being unable to tolerate immunization (vaccination is lethal in this mouse model), indicating the importance of IFN-γ in immunogenicity. To confirm the role of T cells, we immunized nude mice that we demonstrated to be very susceptible to infection. Immunization with YFV and challenge 7 days after booster did not protect nude mice in terms of weight loss and showed partial protection in the survival curve. When we evaluated the humoral response, the vaccine elicited significant antibody titers against ZIKV; however, it showed no neutralizing activity in vitro and in vivo. The data indicate that a cell-mediated response promotes protection against cerebral infection, which is crucial to vaccine protection, and it appears to not necessarily require a humoral response. This protective effect can also be attributed to innate factors, but more studies are needed to strengthen this hypothesis. Our findings open the way to using an available and inexpensive vaccine for large-scale immunization in the event of a ZIKV outbreak.

The CCCH-Type Zinc Finger Antiviral Protein Relieves Immunosuppression of T Cells Induced by Avian Leukosis Virus Subgroup J via the NLP-PKC-δ-NFAT Pathway.

The CCCH-type zinc finger antiviral protein (ZAP) can recognize and induce the degradation of mRNAs and proteins of certain viruses, as well as exerting its antiviral activity by activating T cells. However, the mechanism of ZAP that mediates T cell activation during virus infection remains unclear. Here, we found a potential function of ZAP that relieves immunosuppression of T cell induced by avian leukosis virus subgroup J (ALV-J) via a novel signaling pathway that involves norbin-like protein (NLP), protein kinase C delta (PKC-δ), and nuclear factor of activated T cell (NFAT). Specifically, ZAP expression activated T cells by promoting the dephosphorylation and nuclear translocation of NFAT. Furthermore, knockdown of ZAP weakened the reactivity and antiviral response of T cells. Mechanistically, ZAP reduced PKC-δ activity by upregulating and reactivating NLP by competitively binding with viral protein. Knockdown of NLP decreased the dephosphorylation of PKC-δ by ZAP expression. Moreover, we show that knockdown of PKC-δ reduced the phosphorylation levels of NFAT and enhanced its nuclear translocation. Taken together, these data revealed that ZAP relieves immunosuppression caused by ALV-J and mediates T cell activation through the NLP-PKC-δ-NFAT pathway. IMPORTANCE The evolution of the host defense system is driven synchronously in the process of resisting virus invasion. Accordingly, host innate defense factors effectively work to suppress virus replication. However, it remains unclear whether the host innate defense factors are involved in antiviral immune responses against the invasion of immunosuppressive viruses. Here, we found that CCCH-type zinc finger antiviral protein (ZAP) effectively worked in resistance to immunosuppression caused by avian leukosis virus subgroup J (ALV-J), a classic immunosuppressive virus. Evidence showed that ZAP released the phosphatase activity of NLP inhibited by ALV-J and further activated NFAT by inactivating PKC-δ. This novel molecular mechanism, i.e., ZAP regulation of the antiviral immune response by mediating the NLP-PKC-δ-NFAT pathway, has greatly enriched the understanding of the functions of host innate defense factors and provided important scientific ideas and a theoretical basis for research on immunosuppressive viruses and antiviral immunity.

Altered expression of immune factors in sevenband grouper, Hyporthodus septemfasciatus following nervous necrosis virus challenge at optimal and suboptimal temperatures

The nervous necrosis virus (NNV) infection is generally observed in aquafarms when the seawater temperature is higher than 24 °C and the fishes seem to be refractory to disease at suboptimal temperatures below 20 °C suggesting a role of thermoregulation in NNV pathogenesis. The present study profiled the temperature-dependent regulation of cytokines (TNF-α, IL-1β and IFN-γ), innate antiviral factors (IFN-1, Mx, ISG-15), adaptive immune factors (CD-4, CD-8, IgM), signaling regulators (SOCS-1, SOCS-3), transcription factors (STAT-1, STAT-3) and microglial and NCC/NK specific cell markers (TMEM-119 and NCCRP-1) during NNV challenge in seven-band grouper, Hyporthodus septemfasciatus. The co-habitation challenge at 17 °C with showed a sustained expression of proinflammatory cytokines and following rechallenge with a dose of 104 TCID50/100μL/fish at optimal temperature, the survivors also exhibited a stable expression of immune factors. The 100% survival following the challenge at sub-optimal (17 °C) and rechallenge at optimal (25 °C) was due to the stable and sustained activation of the immune response. However, at 25 °C, the rechallenge displayed a priming effect with hyperactivation of the immune system evident from the immune gene expression profile. The mortality pattern observed is co-related with the cytokine storm as is evident from the gene expression profile. Whereas, neither of the adaptive immune markers was suggestive of humoral immune response in the 17 °C groups. Also, the data suggest a possible role of NK cell and microglia in mediating antiviral immune response following infection in the brain at different temperatures, where, former is beneficial in restricting viral infection with higher host tolerance.

Tofacitinib-Induced Modulation of Intestinal Adaptive and Innate Immunity and Factors Driving Cellular and Systemic Pharmacokinetics.

ObjectiveBy interfering with multiple cytokines, human Janus kinase inhibitors (JAKis) are of growing importance in the treatment of malignant and inflammatory conditions. Although tofacitinib has demonstrated efficacy as the first-in-class JAKi in ulcerative colitis many aspects concerning its mode of action and pharmacokinetics remain unresolved.DesignWe studied tofacitinib’s impact on various primary human innate and adaptive immune cells. In-depth in vivo studies were performed in dextran sodium sulfate–induced colitis in mice. Immune populations were characterized by flow cytometry and critical transcription factors and effector cytokines were analyzed. Pharmacokinetics of tofacitinib was studied by liquid chromatography–tandem mass spectrometry.ResultsTofacitinib inhibited proliferation in CD4+ and CD8+ T cells along with Th1 and Th17 differentiation, while Th2 and regulatory T cell lineages were largely unaffected. Monocytes and macrophages were directed toward an anti-inflammatory phenotype and cytokine production was suppressed in intestinal epithelial cells. These findings were largely reproducible in murine cells of the inflamed mucosa in dextran sulfate sodium colitis. Short-term treatment with tofacitinib had little impact on the mouse microbiota. Strikingly, the degree of inflammation and circulating tofacitinib levels showed a strong positive correlation. Finally, we identified inflammation-induced equilibrative nucleoside transporters as regulators of tofacitinib uptake into leukocytes.ConclusionsWe provide a detailed analysis of the cell-specific immune-suppressive effects of the JAKis tofacitinib on innate and adaptive immunity and reveal that intestinal inflammation critically impacts tofacitinib’s pharmacokinetics in mice. Furthermore, we describe an unappreciated mechanism—namely induction of equilibrative nucleoside transporters—enhancing baseline cellular uptake that can be inhibited pharmaceutically.

Prevalence of Psychological Distress and Associated Factors in Nursing Students during the COVID-19 Pandemic: A Cross-Sectional Study.

Little is known about psychological distress and its associated factors during the COVID-19 pandemic among nursing students, especially during the initial spread. The present study aimed to investigate the prevalence of psychological distress among Japanese nursing students after the first semester of 2020 with shifted classes and practice online. Furthermore, we examined whether factors such as health issues and resilience were associated with psychological distress. The data were obtained from a cross-sectional, self-administered questionnaire survey at a Japanese nursing college from September to November 2020 (n = 289). We collected data such as sociodemographic variables, medical history, insomnia, and resilience (Bidimensional Resilience Scale). Psychological distress was measured using the K6 scale (scores ≥ 5). The prevalence of psychological distress was 58.5%. The multivariate Poisson regression analysis found a negative association between innate resilience factors, and positive associations between medical history, insomnia, and psychological distress. The present study showed that more than half of the study participants experienced high levels of psychological distress. Our results suggest the importance of monitoring mental health among nursing students, focusing not only on health issues, but also personality components such as innate resilience during the prolonged COVID-19 pandemic.

To React or Not to React: The Dilemma of Fish Immune Systems Facing Myxozoan Infections.

Myxozoans are microscopic, metazoan, obligate parasites, belonging to the phylum Cnidaria. In contrast to the free-living lifestyle of most members of this taxon, myxozoans have complex life cycles alternating between vertebrate and invertebrate hosts. Vertebrate hosts are primarily fish, although they are also reported from amphibians, reptiles, trematodes, mollusks, birds and mammals. Invertebrate hosts include annelids and bryozoans. Most myxozoans are not overtly pathogenic to fish hosts, but some are responsible for severe economic losses in fisheries and aquaculture. In both scenarios, the interaction between the parasite and the host immune system is key to explain such different outcomes of this relationship. Innate immune responses contribute to the resistance of certain fish strains and species, and the absence or low levels of some innate and regulatory factors explain the high pathogenicity of some infections. In many cases, immune evasion explains the absence of a host response and allows the parasite to proliferate covertly during the first stages of the infection. In some infections, the lack of an appropriate regulatory response results in an excessive inflammatory response, causing immunopathological consequences that are worse than inflicted by the parasite itself. This review will update the available information about the immune responses against Myxozoa, with special focus on T and B lymphocyte and immunoglobulin responses, how these immune effectors are modulated by different biotic and abiotic factors, and on the mechanisms of immune evasion targeting specific immune effectors. The current and future design of control strategies for myxozoan diseases is based on understanding this myxozoan-fish interaction, and immune-based strategies such as improvement of innate and specific factors through diets and additives, host genetic selection, passive immunization and vaccination, are starting to be considered.

Genetic Determinants of Intrinsic Antibiotic Tolerance in Mycobacterium avium.

ABSTRACTThe Mycobacterium avium complex (MAC) is one of the most prevalent causes of nontuberculous mycobacteria pulmonary infection in the United States, and yet it remains understudied. Current MAC treatment requires more than a year of intermittent to daily combination antibiotic therapy, depending on disease severity. In order to shorten and simplify curative regimens, it is important to identify the innate bacterial factors contributing to reduced antibiotic susceptibility, namely, antibiotic tolerance genes. In this study, we performed a genome-wide transposon screen to elucidate M. avium genes that play a role in the bacterium’s tolerance to first- and second-line antibiotics. We identified a total of 193 unique M. avium mutants with significantly altered susceptibility to at least one of the four clinically used antibiotics we tested, including two mutants (in DFS55_00905 and DFS55_12730) with panhypersusceptibility. The products of the antibiotic tolerance genes we have identified may represent novel targets for future drug development studies aimed at shortening the duration of therapy for MAC infections.IMPORTANCE The prolonged treatment required to eradicate Mycobacterium avium complex (MAC) infection is likely due to the presence of subpopulations of antibiotic-tolerant bacteria with reduced susceptibility to currently available drugs. However, little is known about the genes and pathways responsible for antibiotic tolerance in MAC. In this study, we performed a forward genetic screen to identify M. avium antibiotic tolerance genes, whose products may represent attractive targets for the development of novel adjunctive drugs capable of shortening the curative treatment for MAC infections.

Putative Role of Vitamin D for COVID-19 Vaccination.

Severe acute respiratory syndrome coronavirus 2 is a new, highly pathogenic virus that has recently elicited a global pandemic called the 2019 coronavirus disease (COVID-19). COVID-19 is characterized by significant immune dysfunction, which is caused by strong but unregulated innate immunity with depressed adaptive immunity. Reduced and delayed responses to interferons (IFN-I/IFN-III) can increase the synthesis of proinflammatory cytokines and extensive immune cell infiltration into the airways, leading to pulmonary disease. The development of effective treatments for severe COVID-19 patients relies on our knowledge of the pathophysiological components of this imbalanced innate immune response. Strategies to address innate response factors will be essential. Significant efforts are currently underway to develop vaccines against SARS-CoV-2. COVID-19 vaccines, such as inactivated DNA, mRNA, and protein subunit vaccines, have already been applied in clinical use. Various vaccines display different levels of effectiveness, and it is important to continue to optimize and update their composition in order to increase their effectiveness. However, due to the continuous emergence of variant viruses, improving the immunity of the general public may also increase the effectiveness of the vaccines. Many observational studies have demonstrated that serum levels of vitamin D are inversely correlated with the incidence or severity of COVID-19. Extensive evidence has shown that vitamin D supplementation could be vital in mitigating the progression of COVID-19 to reduce its severity. Vitamin D defends against SARS-CoV-2 through a complex mechanism through interactions between the modulation of innate and adaptive immune reactions, ACE2 expression, and inhibition of the renin-angiotensin system (RAS). However, it remains unclear whether Vit-D also plays an important role in the effectiveness of different COVID-19 vaccines. Based on analysis of the molecular mechanism involved, we speculated that vit-D, via various immune signaling pathways, plays a complementary role in the development of vaccine efficacy.