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BackgroundNatural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us to define approaches to improve immune-mediate antitumor activity. In previous studies from our group, a genome-wide CRISPR-Cas9 screen identified Charged Multivesicular Body Protein 2A (CHMP2A) as a novel mechanism that mediates tumor intrinsic resistance to NK cell activity.MethodsHere, we use an immunocompetent mouse model to demonstrate that CHMP2A serves as a targetable regulator of not only NK cell-mediated immunity but also other immune cell populations. Using the recently characterized murine 4MOSC model system, a syngeneic, tobacco-signature murine head and neck squamous cell carcinoma model, we deleted mCHMP2A using CRISPR/Cas9-mediated knock-out (KO), following orthotopic transplantation into immunocompetent hosts.ResultsWe found that mCHMP2A KO in 4MOSC1 cells leads to more potent NK-mediated tumor cell killing in vitro in these tumor cells. Moreover, following orthotopic transplantation, KO of mCHMP2A in 4MOSC1 cells, but not the more immune-resistant 4MOSC2 cells enables both T cells and NK cells to better mediate antitumor activity compared with wild type (WT) tumors. However, there was no difference in tumor development between WT and mCHMP2A KO 4MOSC1 or 4MOSC2 tumors when implanted in immunodeficient mice. Mechanistically, we find that mCHMP2A KO 4MOSC1 tumors transplanted into the immunocompetent mice had significantly increased CD4+T cells, CD8+T cells. NK cell, as well as fewer myeloid-derived suppressor cells (MDSC).ConclusionsTogether, these studies demonstrate that CHMP2A is a targetable inhibitor of cellular antitumor immunity.

Purpose: To evaluate two pharmacologic antibiotic prophylaxis regimens and a control group of immunocompetent patients undergoing two-stage dental implant placement in a triple-blind randomized controlled clinical trial. Materials and Methods: From a group of 61 immunocompetent patients, 21 were randomly allocated into group 1 (G1) without antibiotic prophylaxis (control), 20 in group 2 (G2) with preoperative antibiotic prophylaxis (1 g amoxicillin 1 hour before the procedure), and 20 in group 3 (G3) with preoperative (1 g amoxicillin) and postoperative (500 mg every 8 hours for 5 days) antibiotic prophylaxis. Pain was assessed with the visual analog scale (VAS) and by considering the number of painkillers patients used. Infection was identified via the presence of pus and fistula. Patients were evaluated after 7, 14, 30, and 120 days. Implant failure (defined as mobility upon the application of manual torque) was evaluated after 120 days during the second surgical stage. Results: At the 7-day follow-up, pain intensity was less severe in the patients who had received antibiotics, with the G3 patients experiencing the least pain (P < .05). Infection was present in groups G1 (2 cases) and G3 (2 cases), but there was no statistically significant intergroup difference. Two implants failed, one in G1 and the other in G3. Conclusions: Based on the results of the present study, although the use of antibiotics reduced pain in the immediate postoperative period, it did not reduce infection rates and implant failure in immunocompetent patients. [ABSTRACT FROM AUTHOR]

Simple Summary: It is widely accepted that maternal stress can influence the behavior and immunity of F1 in the laboratory. However, surprisingly little is known about the replicated studies on the mechanisms by which maternal stress drives individual characteristics in wild animals. Therefore, to study the possible effect of DNA methylation of hypothalamic-pituitary-adrenal-axis (HPA-axis) genes of F1 induced by maternal density stress on behavior and immune traits in root voles, we measured mRNA and protein expression and DNA methylation of HPA-axis genes and assessed the depressive and anxiety-like behaviors and the immune traits. The F1 from high density had a lower DNA methylation level of corticotropin-releasing hormone (CRH) and a higher DNA methylation level of glucocorticoid receptor gene (NR3C1), accompanied by an increase in the expression levels of the CRH mRNA and protein expression, and a reduction in the expression levels of the NR3C1 mRNA and protein expression. The F1 from high density also reduced anti-keyhole limpet hemocyanin immunoglobulin G levels and phytohemagglutinin-delayed hypersensitivity, increased cytokines and depressive and anxiety-like behaviors, and increased coccidial infection. Our results indicate that altering the prenatal intrinsic stress environment can fundamentally impact behavior and immunity by DNA methylation of HPA-axis genes and can further drive population fluctuations in wild animals. The literature shows that maternal stress can influence behavior and immune function in F1. Yet, most studies on these are from the laboratory, and replicated studies on the mechanisms by which maternal stress drives individual characteristics are still not fully understood in wild animals. We manipulated high- and low-density parental population density using large-scale field enclosures and examined behavior and immune traits. Within the field enclosures, we assessed anti-keyhole limpet hemocyanin immunoglobulin G (anti-KLH IgG) level, phytohemagglutinin (PHA) responses, hematology, cytokines, the depressive and anxiety-like behaviors and prevalence and intensity of coccidial infection. We then collected brain tissue from juvenile voles born at high or low density, quantified mRNA and protein expression of corticotropin-releasing hormone (CRH) and glucocorticoid receptor gene (NR3C1) and measured DNA methylation at CpG sites in a region that was highly conserved with the prairie vole CRH and NR3C1 promoter. At high density, we found that the F1 had a lower DNA methylation level of CRH and a higher DNA methylation level of NR3C1, which resulted in an increase in the expression levels of the CRH mRNA and protein expression and further reduced the expression levels of the NR3C1 mRNA and protein expression, and ultimately led to have delayed responses to acute immobilization stress. Juvenile voles born at high density also reduced anti-KLH IgG levels and PHA responses, increased cytokines, and depressive and anxiety-like behaviors, and the effects further led to higher coccidial infection. From the perspective of population density inducing the changes in behavior and immunity at the brain level, our results showed a physiological epigenetic mechanism for population self-regulation in voles. Our results indicate that altering the prenatal intrinsic stress environment can fundamentally impact behavior and immunity by DNA methylation of HPA-axis genes and can further drive population fluctuations in wild animals. [ABSTRACT FROM AUTHOR]

Introduction: Facial attractiveness has recently been considered an indicator of underlying immunocompetence. However, studies examining this relationship have yielded mixed findings. Previous research suggested that these discrepant findings could be due to the common influence of lifestyle factors upon both rated facial attractiveness and health. Methods: Young men (N = 162) provided standardized facial photos with a neutral expression subsequently rated by eight women for overall attractiveness. Saliva was assayed for immunoglobulin A, testosterone (T) and cortisol (C), and body fat was measured using a skinfold caliper. Self-reports of poor health, and lifestyle factors that could influence health status (age, sleep habits, smoking, drinking alcohol, family stress, and exercising) were collected. Results: Results showed that symptoms of poor health and skinfold negatively predicted facial attractiveness. There was a modest but statistically nonsignificant T x C interaction where higher T lower C men trended toward having more attractive faces. A sequential mediation model examining the influence of lifestyle showed support for an indirect effect on facial attractiveness. Specifically, skinfold and poor health symptoms mediated the links between exercise, stress, and facial attractiveness. Discussion: These findings suggest links between facial attractiveness and immunocompetence could be linked to some common lifestyle and hormonal variables, but that more comprehensive research involving lifestyle indicators (such as nutrition) are necessary. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effects of Saccharomyces yeast postbiotics on cell turnover, immune responses, and oxidative stress in the jejunal mucosa of pigs. Thirty-two newly weaned pigs at 6.05 ± 0.24 kg were assigned to two dietary treatments based on a randomized complete block design. The treatments were control group receiving a basal diet and a group supplemented with Saccharomyces yeast postbiotics (175 g/ton diet) in the basal diet. After 35 d of the study, pigs were euthanized and jejunal mucosa were collected to assess immune status, oxidative stress, barrier markers, cell proliferation, and apoptosis. Saccharomyces yeast postbiotics reduced (P < 0.05) the fecal score from d 3 to d 7 and tended to increase the gene expression of interferon-γ (IFN-γ) (P = 0.071) and mammalian/mechanistic target of rapamycin (mTOR) (P = 0.080), decrease the gene expression of B-cell lymphoma 2-associated X protein 1 (BAX1) (P < 0.05), tended to decrease the gene expression of serum and glucocorticoid-induced protein kinase 1 (SGK1) (P = 0.066), increased (P < 0.05) cell proliferation in the crypts, and tended to increase the villus height (P = 0.078) and crypt depth (P = 0.052) in the jejunum. In conclusion, the supplementation of Saccharomyces yeast postbiotics in nursery diets reduced diarrhea within the first week after weaning and provided protection to the villi in the jejunum by enhancing the immune responses of nursery pigs, promoting crypt cell proliferation, and reducing the expression of genes associated with apoptosis without affecting inflammatory and oxidative stress status in the jejunum of the nursery pigs. [ABSTRACT FROM AUTHOR]

Recombinant zoster vaccine has been recommended by the US Advisory Committee on Immunization Practices (ACIP) for the prevention of herpes zoster (HZ) in immunocompetent adults aged at least 50 years since 2018. In January 2022, this was extended to immunodeficient/immunosuppressed adults aged at least 19 years. Key study objectives were to assess specialists' knowledge of the ACIP HZ vaccination recommendations, their attitudes toward HZ vaccination, and HZ vaccination practices/barriers. This cross-sectional, web-based survey (conducted in March 2022) included US dermatologists, gastroenterologists, infectious disease specialists, oncologists, and rheumatologists who treat patients with psoriasis, inflammatory bowel disease, human immunodeficiency syndrome, solid tumors/hematological malignancies, and rheumatoid arthritis, respectively. Although most of the 613 specialists correctly identified the ACIP HZ vaccination recommendations for adults aged at least 50 years (84%) and immunodeficient/immunosuppressed adults aged at least 19 years (67%), only 29% knew that recombinant zoster vaccine is recommended for individuals who have previously received zoster vaccine live, and only 18% knew all current ACIP recommendations. For patients with the diseases listed, 84% of specialists thought that HZ is a serious risk, 75% that HZ vaccination is extremely/very important, and 69% were extremely/very likely to recommend HZ vaccination. Only 36% administer vaccines themselves, mainly because patients receive vaccinations from others. Barriers to vaccination included more urgent/acute issues, insufficient time, and lack of patient motivation/willingness. Full knowledge of the ACIP HZ vaccination recommendations among the surveyed specialists was low. There may be a need to educate specialists to improve adherence to these recommendations. [ABSTRACT FROM AUTHOR]

Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience numerous complications, which are exacerbated by inflammatory dysregulation and infection. Understanding the immunological mechanisms is crucial for selecting medications that balance inflammation control and immunocompetence. In this cross‐sectional study, aiming to identify potential immunotherapeutic targets and inflammatory biomarkers, we delved into the interrelationship between clinical severity and systemic inflammatory parameters in a representative RDEB cohort. Encompassing 84 patients aged 1–67 and spanning all three Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) severity categories, we analysed the interrelationship of infection history, standard inflammatory markers, systemic cytokines and Ig levels to elucidate their roles in RDEB pathophysiology. Our findings identify C‐reactive protein as an excellent biomarker for disease severity in RDEB. A type 2 inflammatory profile prevails among moderate and severe RDEB patients, correlating with dysregulated circulating IgA and IgG. These results underscore the IL4/IL13 pathways as potential evidence‐based therapeutic targets. Moreover, the complete inflammatory scenario aligns with Staphylococcus aureus virulence mechanisms. Concurrently, abnormalities in IgG, IgE and IgM levels suggest an immunodeficiency state in a substantial number of the cohort's patients. Our results provide new insights into the interplay of infection and immunological factors in the pathogenesis of RDEB. [ABSTRACT FROM AUTHOR]

Newborns and young infants are at risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection. Passive immunity is the mainstay of infection prevention in this cohort. Transplacental transfer of maternal antibodies provides the newborn with immediate protection from life-threatening infections, however, is dependent upon gestational age, birth weight, mother's age, recent maternal vaccination, maternal nutritional status, maternal immunocompetence and medical conditions, and placental integrity. Efficient transplacental transfer of RSV-neutralizing antibodies have led to the development and approval of maternal RSV immunization for the protection of the newborn. Additionally, administration of RSV-specific antibodies to infants leads to high serum titers of RSV-neutralizing antibodies and further protection from severe disease. [ABSTRACT FROM AUTHOR]

Aging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age‐associated disease. Genetic manipulation of the nutrient‐sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age‐associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population. [ABSTRACT FROM AUTHOR]

Fanconi anemia, a rare disorder with an incidence of 1 in 300,000, is caused by mutations in FANC genes, which affect the repair of DNA interstrand crosslinks. The disease is characterized by congenital malformations, bone marrow failure within the first decade of life, and recurrent squamous cell carcinomas of the oral cavity, esophagus, and anogenital regions starting around age 20. In this review, we propose that Fanconi anemia should be considered a premature-aging syndrome. Interestingly, the onset and severity of the life-limiting clinical features of Fanconi anemia can be influenced by lifestyle choices, such as a healthy diet and physical activity. These factors shape the epigenetic status of at-risk cell types and enhance the competence of the immune system through nutritional signaling. Fanconi anemia may serve as a model for understanding the aging process in the general population, addressing research gaps in its clinical presentation and suggesting prevention strategies. Additionally, we will discuss how the balance of genetic and environmental risk factors—affecting both cancer onset and the speed of aging—is interlinked with signal transduction by dietary molecules. The underlying nutrigenomic principles will offer guidance for healthy aging in individuals with Fanconi anemia as well as for the general population. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to determine the effects of Saccharomyces yeast postbiotics on cell turnover, immune responses, and oxidative stress in the jejunal mucosa of pigs. Thirty-two newly weaned pigs at 6.05 ± 0.24 kg were assigned to two dietary treatments based on a randomized complete block design. The treatments were control group receiving a basal diet and a group supplemented with Saccharomyces yeast postbiotics (175 g/ton diet) in the basal diet. After 35 d of the study, pigs were euthanized and jejunal mucosa were collected to assess immune status, oxidative stress, barrier markers, cell proliferation, and apoptosis. Saccharomyces yeast postbiotics reduced (P

Immunoassays designed to detect SARS-CoV-2 protein antigens are now commercially available. The most widely used tests are rapid lateral flow assays that generate results in ~15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 antigen (Ag) assays have also been developed. The overall accuracy of SARS-CoV-2 Ag tests, however, is not well defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best-practice guidance related to SARS-CoV-2 Ag testing. This guideline is the third in a series of rapid, frequently updated COVID-19 diagnostic guidelines developed by IDSA. IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators, and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and nonmedical settings. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 5 diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals as well as assess single versus repeat testing strategies. Data on the clinical performance of US Food and Drug Administration SARS-CoV-2 Ag tests with Emergency Use Authorization are mostly limited to single, one-time testing versus standard nucleic acid amplification testing (NAAT) as the reference standard. Rapid Ag tests have high specificity and low to modest sensitivity compared with reference NAAT methods. Antigen test sensitivity is heavily dependent on viral load, with differences observed between symptomatic compared with asymptomatic individuals and the time of testing post-onset of symptoms. Based on these observations, rapid reverse transcriptase–polymerase chain reaction (RT-PCR) or laboratory-based NAAT remain the diagnostic methods of choice for diagnosing SARS-CoV-2 infection. However, when molecular testing is not readily available or is logistically infeasible, Ag testing can help identify some individuals with SARS-CoV-2 infection. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate. [ABSTRACT FROM AUTHOR]

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: The unrestricted usage of antibiotics led to the emergence of new antibiotic-resistant strains of pathogens, making it a concern in most countries. The restriction on the use of antibiotics in poultry has led to an increase in natural products that could serve as alternative antibiotics. Mushroom use in poultry nutrition is a major stride toward finding alternatives to antibiotics. This review aims to present a comprehensive overview of the role of different species of mushrooms commonly used in poultry in the performance, immunomodulatory actions, cholesterolemic properties, and meat quality of poultry birds. The restriction on the use of antibiotics in poultry has led to an increase in the use of natural products that could serve as alternatives to antibiotics. Mushrooms contain bioactive compounds that exhibit antifungal, antiparasitic, antibacterial, antioxidant, antiviral, anti-inflammatory, and cytotoxic properties. Hence, they are being tested, revealing as performance-enhancing natural feed additives for livestock. This review focused on the role of different species of mushrooms commonly used in poultry on the performance, immunomodulatory actions, cholesterolemic properties, and meat quality of poultry birds. Different studies reviewed show that mushrooms could positively impact poultry production, improve growth performance, modulate immune response, exert tissue antioxidant activity, influence intestinal morphology, enhance gut microbiome, and improve lipid profile. The variations in their efficacy could be attributed to the variations in physicochemical properties of different species and dosage levels applied in the experiments. However, the use of mushrooms as a natural product supplement is in its infancy, and more basic, pilot and large-scale research is required to make it a viable approach for improving immune responses in the poultry industry. [ABSTRACT FROM AUTHOR]

Purpose: Lung transplant recipients are at increased risk of severe disease following infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) due to high-dose immunosuppressive drugs and the lung is the main organ affected by Coronavirus disease 2019 (COVID-19). Several studies have confirmed increased SARS-CoV-2-related mortality and morbidity in patients living with lung allografts; however, detailed immunological studies of patients with SARS-CoV-2 infection in the early phase following transplantation remain scarce. Methods: We investigated patients who were infected with SARS-CoV-2 in the early phase (18–103 days) after receiving double-lung allografts (n = 4, LuTx) in comparison to immunocompetent patients who had not received solid organ transplants (n = 88, noTx). We analyzed SARS-CoV-2-specific antibody responses against the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), and immunoblot assays. T cell responses were investigated using Elispot assays. Results: One LuTx patient suffered from persistent infection with fatal outcome 122 days post-infection despite multiple interventions including remdesivir, convalescent plasma, and the monoclonal antibody bamlanivimab. Two patients experienced clinically mild disease with prolonged viral shedding (47 and 79 days), and one patient remained asymptomatic. Antibody and T cell responses were significantly reduced or undetectable in all LuTx patients compared to noTx patients. Conclusion: Patients in the early phase following lung allograft transplantation are vulnerable to infection with SARS-CoV-2 due to impaired immune responses. This patient population should be vaccinated before LuTx, protected from infection post–LuTx, and in case of infection treated generously with currently available interventions. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the methodological quality of published systematic reviews on randomized and non-randomized clinical trials to synthesize evidence on the association between IL-6, immunosenescence, and aerobic and/or resistance exercise. Method: The Preferred Reporting Items for Overviews of Systematic Reviews (PRIO-harms) guideline was used, with registration number CRD42022346142-PROSPERO. Relevant databases such as Cochrane Library, PubMed, Web of Science, Scopus, and Google Scholar were searched using English Medical Subject Headings terms. Inclusion criteria were systematic reviews analyzing aerobic exercise, resistance exercise, or a combination of both and assessing IL-6 as a biomarker of cellular immunosenescence in humans. The Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) was employed. Results: Out of 742 identified articles, 18 were eligible, and 13 were selected for analysis. Sample sizes ranged from 249 to 1421 participants, mostly female, with ages ranging from 17 to 95 years. Aerobic exercise was the most studied type (46.15%), followed by combined exercise (38.46%) and resistance exercise (15.38%). Aerobic exercise showed a statistically significant reduction in IL-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) levels. Among the 13 reviews analyzed using AMSTAR-2, 8 were rated as critically low quality, and 5 were classified as low quality. Conclusion: Aerobic exercise has anti-inflammatory properties and the potential to modulate IL-6, CRP, and TNF-α levels in immunosenescence. However, the limited methodological quality of the analyzed systematic reviews highlights the urgent need for robust, high-quality studies to improve access to information and facilitate evidence-based decision-making in healthcare. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course. Background: Histoplasma capsulatum is a spore-forming fungal organism found in soil that is considered endemic in Venezuela. Histoplasmosis has 3 different clinical presentations that primarily affect immunocompromised individuals. A type of injectable dermal cosmetic treatment uses platelet-rich plasma (PRP). This report is of a 35-year-old immunocompetent Venezuelan woman with primary cutaneous histoplasmosis (PCH) following cosmetic injection of PRP. Case Report: This report presents a rare case of PCH following a cosmetic procedure of PRP injection in a 35-year-old immunocompetent patient, who was initially treated with self-administered antibiotics. During her first appointment, an atypical mycobacterial infection was suspected, and empirical antibiotic therapy targeting these pathogens was initiated. Complementary tests were conducted, ruling out immunosuppression and systemic infections. After 1 month of treatment with trimethoprim-sulfamethoxazole, the lesions had completely resolved. Pathological examination confirmed the diagnosis of PCH with intracytoplasmic inclusions of Histoplasma. In this case, the patient had no evident risk factors for PCH, and it is suspected that the infection was likely introduced during the PRP procedure due to inadequate hygiene measures. Conclusions: This case demonstrates that PCH can arise in immunocompetent patients, emphasizing the need to include histoplasmosis as a diagnostic option, particularly in endemic locations. Direct inoculation of Histoplasma might occur following aesthetic procedures that do not follow basic hygiene precautions. Finally, trimethoprim-sulfamethoxazole can be considered an alternate therapy option, and additional research into this strategy may benefit patients with similar clinical circumstances or when optimal treatment options are unavailable. [ABSTRACT FROM AUTHOR]

Background: Fungal infections of the central nervous system usually affect immunocompromised patients. Primary Aspergillus myelitis has never been described. Report: A 45-year-old immunocompetent male with subacute paraplegia was treated for inflammatory myelitis before clinical deterioration requiring mechanical ventilation. Purulent meningitis preceded the formation of a paraspinal nodule biopsied by neurosurgery. Histopathological analysis revealed the presence of fungal hyphae, and polymerase chain reaction was positive for Aspergillus fumigatus. No cause of immunodeficiency was identified in this patient. Discussion: Primary Aspergillus myelitis may be confused with inflammatory myelitis and should be considered even in the absence of apparent immunosuppression. [ABSTRACT FROM AUTHOR]

Background. Granulomatous thyroiditis is usually viral and very rarely due to fungal infection. Fungal thyroiditis affects the severely immunocompromised and only rarely immunocompetent individuals. Case report. A 32-year-old man with known Hashimoto thyroiditis was consulted for a 1-week history of neck pain, dysphagia, cough, asthenia, loss of appetite, and night sweats. Imaging showed an enlarged right thyroid lobe. Laboratory studies confirmed hypothyroidism. He underwent a thyroid lobectomy. Microscopic examination showed granulomas in a background of Hashimoto thyroiditis. Silver stain revealed numerous yeasts consistent with Histoplasma. Subsequent serology was also positive. Further evaluations were negative for acquired or constitutional immunodeficiencies. He was started on oral itraconazole with resolution of all constitutional symptoms. Conclusions. We report a second case of concurrent Hashimoto and Histoplasma thyroiditis in an immunocompetent patient. Systemic manifestations of fungal infection are confounded by systemic symptoms of thyroid dysfunction. Fungal thyroiditis is a manifestation of systemic fungal infection requiring prolonged systemic therapy to prevent complications or fatal outcomes. [ABSTRACT FROM AUTHOR]

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Introduction. The development of combinatorial adjuvants is a promising strategy to boost vaccination efficiency. Accumulating evidence indicates that manganese exerts strong immunocompetence and will become an enormous potential adjuvant. Here, we described a novel combination of Mn2+ plus aluminum hydroxide (AH) adjuvant that significantly exhibited the synergistic immune effect. Methodology. Initially, IsdB3 proteins as the immune-dominant fragment of IsdB proteins derived from Staphylococcus aureus (S. aureus) were prepared. IsdB3 proteins were identified by western blotting. Furthermore, we immunized C57/B6 mice with IsdB3 proteins plus Mn2+ and AH adjuvant. After the second immunization, the proliferation of lymphocytes was measured by the cell counting kit-8 (CCK-8) and the level of IFN-γ, IL-4, IL-10, and IL-17 cytokine from spleen lymphocytes in mice and generation of the antibodies against IsdB3 in serum was detected with ELISA, and the protective immune response was assessed through S. aureus challenge. Results. IsdB3 proteins plus Mn2+ and AH obviously stimulated the proliferation of spleen lymphocytes and increased the secretion of IFN-γ, IL-4, IL-10, and IL-17 cytokine in mice, markedly enhanced the generation of the antibodies against IsdB3 in serum, observably decreased bacterial load in organs, and greatly improved the survival rate of mice. Conclusion. These data showed that the combination of Mn2+ and AH significantly acted a synergistic effect, reinforced the immunogenicity of IsdB3, and offered a new strategy to increase vaccine efficiency. [ABSTRACT FROM AUTHOR]

Immune responses can increase survival, but they can also incur a variety of costs that may lead to phenotypic trade‐offs. The nature of trade‐offs between immune activity and other components of the phenotype can vary and depend on the type and magnitude of immune challenge, as well as the energetic costs of simultaneously expressing other traits. There may also be sex‐specific differences in both immune activity and trade‐offs, particularly with regard to energy expenditure that might differ between males and females during the breeding season. Females are generally expected to invest less in nonspecific immune responses compared to males due to differences in the allocation of resources to reproduction, which may lead to sex differences in the metabolic costs of immunity. We tested for sex‐specific differences in metabolic costs of different types of immune challenges in Anolis carolinensis lizards, including lipopolysaccharide (LPS) injection and wounding. We also tested for differences in immune prioritization by measuring bacterial killing ability (BKA). We predicted males would show a greater increase in metabolism after immune challenges, with combined immune challenges eliciting the greatest response. Furthermore, we predicted that metabolic costs would result in decreased BKA. LPS injection increased the resting metabolic rate (RMR) of males but not females. Wounding did not affect RMR of either sex. However, there was an inverse relationship between BKA and wound healing in LPS‐injected lizards, suggesting dynamic tradeoffs among metabolism and components of the immune system. [ABSTRACT FROM AUTHOR]

Introduction: Mucormycosis of the head and neck region is a rare but aggressive fungal infection that usually involves immunocompromised patients. More infrequently, this infection can also occur in people with no otherwise known underlying immunological deficit. This rarity usually causes a delay in diagnosis and may severely decrease the chance of survival in these patients. In this study, we present an extreme case of mucormycosis in an immunocompetent patient. By conducting a thorough review of the literature, we aim to increase our knowledge on this matter. Our goal is to improve diagnosis and start treatment at an earlier stage. Case presentation and methods: Our patient was a 31-year-old man who presented with bilateral face numbness, neck pain, headache, and a necrotic palatal lesion 45 days after a dental root canal procedure. There was extensive involvement of facial and skull base bony and soft tissues. Through two debridement sessions and intravenous antifungal treatment, the patient was discharged with near-complete disease resolution. We identified 48 cases in the literature that matched our study criteria. We searched the current literature for proven cases of mucormycosis in the head and neck region who didn't have any underlying disease. We extracted their data and added the data of our patient. Then, we re-analyzed them using descriptive analysis, chi-square, and binary logistic regression to better understand the different factors for survival and disease burden in these patients. Results: 49 patients were analyzed in this study. The mean age was 46.93 ± 15.75 (min 16 and max78 years old). The most prevalent subsite to be involved was the sino-nasal mucosa, followed by the surrounding soft tissues and the orbit. While both orbit and intracranial tissue involvement differed significantly between surviving and deceased patients, only intracranial tissue involvement could be used to predict survival. The overall survival rate was 91.8%. Conclusion: Although very rare, mucormycosis can occur in immunocompetent patients. Physicians should consider mucormycosis when faced with refractory conditions and unusual symptoms such as exposed bones, facial numbness, headaches, and intractable pain. Complementary imaging (CT scan with or without MRI) and histopathological examination are critical for timely diagnosis or exclusion of this potentially fatal yet treatable disease. [ABSTRACT FROM AUTHOR]

IntroductionFacial attractiveness has recently been considered an indicator of underlying immunocompetence. However, studies examining this relationship have yielded mixed findings. Previous research suggested that these discrepant findings could be due to the common influence of lifestyle factors upon both rated facial attractiveness and health.MethodsYoung men (N = 162) provided standardized facial photos with a neutral expression subsequently rated by eight women for overall attractiveness. Saliva was assayed for immunoglobulin A, testosterone (T) and cortisol (C), and body fat was measured using a skinfold caliper. Self-reports of poor health, and lifestyle factors that could influence health status (age, sleep habits, smoking, drinking alcohol, family stress, and exercising) were collected.ResultsResults showed that symptoms of poor health and skinfold negatively predicted facial attractiveness. There was a modest but statistically non-significant T x C interaction where higher T lower C men trended toward having more attractive faces. A sequential mediation model examining the influence of lifestyle showed support for an indirect effect on facial attractiveness. Specifically, skinfold and poor health symptoms mediated the links between exercise, stress, and facial attractiveness.DiscussionThese findings suggest links between facial attractiveness and immunocompetence could be linked to some common lifestyle and hormonal variables, but that more comprehensive research involving lifestyle indicators (such as nutrition) are necessary.

ABSTRACT: The study examined the effects of successive feeding of sources of n-3 PUFA to broiler breeders (BB) and their progeny in broiler chickens challenged with Eimeria. The BB were fed: 1) control (CON), corn-soybean meal diet, 2) CON + 1 % microalgae (DMA), as a source of DHA and 3) CON + 2.50% co-extruded full fat flaxseed (FFF), as a source of ALA. Eggs were hatched at 34, 44, and 54 wk of age. Posthatch treatments (BB-progeny) were: CON-CON, DMA-CON, FFF-CON, DMA-DMA and FFF-FFF with diets formulated for starter (d 1–10) and grower/finisher (d 11–42) phases. All chicks were orally challenged with Eimeria (E. acervulina and E. maxima) on d 10. Relative to CON, DMA and FFF increased concentration of n-3 PUFA by ≥ 2-fold in hatching eggs and progeny diets. There were no (P > 0.05) interactions between treatment and BB age on d 0 to 10 growth. In general, BB age affected (P < 0.05) growth performance throughout the study. In the starter phase, successive exposure to DHA and ALA improved FCR over CON-CON (P < 0.01). The interaction between treatment and BB age in grower/finisher was such that DHA exposure to younger BB resulted in poor growth performance (P < 0.05) relative to exposure to older BB. In contrast, exposure to ALA had similar (P > 0.05) growth performance irrespective of BB age. Moreover, successive exposure to ALA resulted in higher BWG, breast weight and lower FCR compared to successive exposure to DHA (P < 0.05). There were no (P > 0.05) interactions between treatment and BB age on the intestinal lesion scores, lymphoid organ weights and concentration of plasma immunoglobulin A (IgA). Successive exposure to DHA resulted in higher (P = 0.006) jejunal lesion scores than CON-CON birds. The results showed that successive exposure of DHA and ALA improved FCR relative to non-exposed birds in the starter phase. However, responses in the grower/finisher phase depended on n-3 PUFA type, with birds on successive ALA exposure supporting better growth and breast yield than birds on successive DHA exposure.

Background: The immunocompetence handicap hypothesis suggests that males with a higher testosterone level should be better at developing male secondary traits, but at a cost of suppressed immune performance. As a result, we should expect that males with an increased testosterone level also possess a higher parasite load. However, previous empirical studies aimed to test this prediction have generated mixed results. Meanwhile, the effect of testosterone level on parasite load in female hosts remains poorly known. Methods: In this study, we tested this prediction by manipulating testosterone level in Daurian ground squirrels (Spermophilus dauricus), a medium-sized rodent widely distributed in northeast Asia. S. dauricus is an important host of ticks and fleas and often viewed as a considerable reservoir of plague. Live-trapped S. dauricus were injected with either tea oil (control group) or testosterone (treatment group) and then released. A total of 10 days later, the rodents were recaptured and checked for ectoparasites. Fecal samples were also collected to measure testosterone level of each individual. Results: We found that testosterone manipulation and sex of hosts interacted to affect tick load. At the end of the experiment, male squirrels subjected to testosterone implantation had an averagely higher tick load than males from the control group. However, this pattern was not found in females. Moreover, testosterone manipulation did not significantly affect flea load in S. dauricus. Conclusions: Our results only lent limited support for the immunocompetence handicap hypothesis, suggesting that the role of testosterone on regulating parasite load is relatively complex, and may largely depend on parasite type and gender of hosts. [ABSTRACT FROM AUTHOR]

Psoriasis is a common chronic inflammatory disease, but most of its current treatments come with a high risk of side effects. As one of the world's top three beverages, tea has a traditional history of being used as a treatment for skin conditions due to its high safety profile, anti-inflammatory and other properties. In this study, we investigated the anti-psoriasis effects of ethanol extracts of black tea, green tea and white tea from southeastern China. The compositions of the tea extracts (TEs) were first determined by UPLC-Q-Exactive-Orbitrap MS and then genetic analysis, antibacterial, anti-inflammatory, and immunocompetence assays were performed. Imiquimod was used to establish a mouse model of psoriasis-like dermatitis and treating with the extracts to examine their efficacy. A total of 88 chemical components, mainly phenols and organic acids, were identified from the TEs. These TEs ameliorated skin damage and they all reduced the expression of cytokines IL-17 and TNF-α. By analyzing the genes, TEs may affect the inflammatory signaling pathway by regulating the metabolic changes. In addition, TEs can significantly scavenge ROS, NO, and inhibit cellular inflammation. In conclusion, this study examined the inhibitory effects of three TEs on psoriasis and their potential as nutritional supplements for the treatment of skin inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary focus of this review revolves around actinic keratoses (AKs), common skin conditions primarily induced by prolonged sun exposure. These lesions are of particular concern due to their potential progression into skin cancer, thereby warranting in-depth investigation for effective treatment and prevention strategies. There are different approaches to treat AK; some of them target the dysplastic cells, whereas others act on the immunological response of the host to fight against abnormal cells. This review summarizes all the therapies used for AK and field cancerization, whose mechanism of action include the participation of the immune system. Moreover, the research extends to immunosuppressed individuals, mainly organ transplant recipients, who require tailored approaches due to their immune profiles. In essence, this research tries to update the therapeutic approaches for AKs, ultimately lowering the risk of malignant transformation and contributing to improved clinical management. This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use. [ABSTRACT FROM AUTHOR]

Herpesvirus of turkey (HVT) increases activation of T cells in 1-day-old chickens when administered in ovo. This study evaluated whether adding cytosine-guanosine oligodeoxynucleotides (CpG ODNs) to the HVT vaccine could enhance the adjuvant effect of HVT. We used a CpG ODN dose of 10 μg per egg. The experimental groups were (1) diluent-only control (sham), (2) HVT, (3) HVT+CpG ODN, (4) HVT+non-CpG ODN, (5) CpG ODN, and (6) non-CpG ODN control. Cellular response evaluation included measuring the frequencies of macrophages (KUL01+MHC-II+), gamma delta T cells (γδTCR+MHC-II+), CD4+, and CD8+ T cell subsets, including double-positive (DP) cells. In addition, CD4+ and CD8+ T cell activation was evaluated by measuring the cellular expression of major histocompatibility complex class II (MHC-II), CD44 or CD28 costimulatory molecules. An adjuvant effect was considered when HVT+CpG ODN, but not HVT+non CpG ODN, or CpG ODN, or non-CpG ODN, induced significantly increased effects on any of the immune parameters examined when compared with HVT. The findings showed that (1) HVT vaccination induced significantly higher frequencies of γδ+MHC-II+ and CD4+CD28+ T cells when compared with sham chickens. Frequencies of DP and CD4+CD28+ T cells in HVT-administered birds were significantly higher than those observed in the non-CpG ODN group. (2) Groups receiving HVT+CpG ODN or CpG ODN alone were found to have significantly increased frequencies of activated CD4+ and CD8+ T cells, when compared with HVT. Our results show that CpG ODN administration in ovo with or without HVT significantly increased frequencies of activated CD4+ and CD8+ T cells. [ABSTRACT FROM AUTHOR]

Embryo implantation induces the adaptive reprogramming of metabolism at the maternal-fetal interface, resulting in a hypoxic, mildly inflammatory, and slight acidic microenvironment. This type of microenvironment is conductive to establish endometrial receptivity, decidualization, trophoblast invasion and maternal-fetal immune tolerance by regulating the recruitment, activation, metabolism and polarization of immune cell. Successful embryo implantation necessitates the well -timed and suitable initiation and termination of the immune-inflammatory response and the glycolysis -dominated metabolic reprogramming. The dysregulation of immunometabolism caused by pathologic factors can result in adverse pregnancy outcomes, such as embryo implantation failure or post-implantation miscarriage. Macrophage as the most abundant antigen-presenting cell in the endometrium during the implantation window plays a crucial role in regulating immunometabolism at the maternal -fetal interface due to the remarkable immune plasticity and metabolic flexibility. We review the immunometabolic microenvironment and regulatory mechanisms at the maternal -fetal interface, to provide a reference for the advancement of clinical intervention approaches so as to improve the pregnancy outcomes in both natural conception and assisted reproduction. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aims to identify the outcomes of stem cell transplant (SCT) patients during the COVID-19 era. Pooled event rates (PER) were calculated, and meta-regression was performed. A random effects model was utilized. In total, 36 eligible studies were included out of 290. The PER of COVID-19-related deaths and COVID-19-related hospital admissions were 21.1% and 55.2%, respectively. The PER of the use of hydroxychloroquine was 53.27%, of the receipt of immunosuppression it was 39.4%, and of the use of antivirals, antibiotics, and steroids it was 71.61%, 37.94%, and 18.46%, respectively. The PER of the time elapsed until COVID-19 infection after SCT of more than 6 months was 85.3%. The PER of fever, respiratory symptoms, and gastrointestinal symptoms were 70.9, 76.1, and 19.3%, respectively. The PER of acute and chronic GvHD were 40.2% and 60.9%, respectively. SCT patients are at a higher risk of severe COVID-19 infection and mortality. The use of dexamethasone improves the survival of hospitalized SCT patients with moderate to severe COVID-19 requiring supplemental oxygen or ventilation. The SCT patient group is a heterogeneous group with varying characteristics. The quality of reporting on these patients when infected with COVID-19 is not uniform and further prospective or registry studies are needed to better guide clinical care in this unique setting. [ABSTRACT FROM AUTHOR]

Background Invasive fungal infections have been described throughout the COVID-19 pandemic. Cryptococcal disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in several isolated case reports and 1 larger case series. We sought to describe cryptococcal infections following SARS-CoV-2 through establishing a database to investigate underlying risk factors, disease manifestations, and outcomes. Methods We created a crowdsourced call for cases solicited through the Mycoses Study Group Education and Research Consortium, the Centers for Disease Control and Prevention Emerging Infectious Diseases Network, and infectious diseases Twitter groups. Data were collected in a web-based and secure REDCap survey without personal identifiers. Results Sixty-nine cases were identified and submitted by 29 separate institutional sites. Cryptococcosis was diagnosed a median of 22 days (interquartile range, 9–42 days) after SARS-CoV-2 infection. Mortality among those with available follow-up was 72% (26/36) for the immunocompetent group and 48% (15/31) for the immunocompromised group (likelihood ratio, 4.01; P =.045). We observed a correlation between disease manifestation (central nervous system infection, proven/probable disseminated disease, and respiratory) and mortality (P =.002). Conclusions The mortality rate of 59% for patients with cryptococcosis following SARS-CoV-2 is higher than that of modern Cryptococcus cohorts. There was an association between immunocompromised status and cryptococcal disease manifestations as well as mortality. Moreover, our series emphasizes the need for clinical and laboratory assessment of opportunistic infections beyond 30 days when concerning symptoms develop. [ABSTRACT FROM AUTHOR]

Background Fungal meningitis can be associated with epidural anesthesia procedures. Fusariosis is a rare infection typically affecting immunocompromised patients and rarely causes meningitis. During 2022–2023, public health officials responded to a large outbreak of Fusarium solani meningitis associated with epidural anesthesia in Durango, Mexico. Methods The public health response and epidemiological and clinical features of patients affected by this outbreak were described. Coordinated actions were addressed to identify the etiological agent, determine its drug susceptibility, develop diagnostic tests, and implement clinical and epidemiological protocols. Retrospective analyses of clinical variables and outcomes were performed to determine association with better patient survival. Results A total of 1801 persons exposed to epidural anesthesia were identified, of whom 80 developed meningitis. Fusarium solani was found in 3 brain biopsies and showed susceptibility to voriconazole and amphotericin B. After F solani polymerase chain reaction (PCR) implementation, 57 patients with meningitis were PCR-screened, and 31 (38.8%) had a positive result. Most patients were female (95%), and cesarean section was the most common surgical procedure (76.3%). The case fatality rate was 51.3% (41 patients) and the median hospitalization duration was 39.5 days (interquartile range, 18–86 days). Seventy-one patients (88.8%) received voriconazole/amphotericin B and 64 subjects (80%) additionally received steroids. Cox regression analysis showed an increased lethality risk in patients who received antifungal treatment after 5 days (hazard ratio, 2.1 [95% confidence interval, 1.01–4.48], P <.05). Conclusions The F solani meningitis outbreak in Durango was an unprecedented medical challenge. Timely treatment and effective healthcare management were associated with better survival outcomes. [ABSTRACT FROM AUTHOR]

Different studies suggest an impact of biofilms on carcinogenic lesion formation in varying human tissues. However, the mechanisms of cancer formation are difficult to examine in vivo as well as in vitro. Cell culture approaches, in most cases, are unable to keep a bacterial steady state without any overgrowth. In our approach, we aimed to develop an immunocompetent 3D tissue model which can mitigate bacterial outgrowth. We established a three-dimensional (3D) co-culture of human primary fibroblasts with pre-differentiated THP-1-derived macrophages on an SIS-muc scaffold which was derived by decellularisation of a porcine intestine. After establishment, we exposed the tissue models to define the biofilms of the Pseudomonas spec. and Staphylococcus spec. cultivated on implant mesh material. After 3 days of incubation, the cell culture medium in models with M0 and M2 pre-differentiated macrophages presented a noticeable turbidity, while models with M1 macrophages presented no noticeable bacterial growth. These results were validated by optical density measurements and a streak test. Immunohistology and immunofluorescent staining of the tissue presented a positive impact of the M1 macrophages on the structural integrity of the tissue model. Furthermore, multiplex ELISA highlighted the increased release of inflammatory cytokines for all the three model types, suggesting the immunocompetence of the developed model. Overall, in this proof-of-principle study, we were able to mitigate bacterial overgrowth and prepared a first step for the development of more complex 3D tissue models to understand the impact of biofilms on carcinogenic lesion formation. [ABSTRACT FROM AUTHOR]

The pro-hormone vitamin D3 is an important modulator of both innate and adaptive immunity since its biologically active metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates via the transcription factor VDR (vitamin D receptor) the epigenome and transcriptome of human immune cells and controls in this way the expression of hundreds of vitamin D target genes. Since the myeloid linage of hematopoiesis is epigenetically programmed by VDR in concert with the pioneer factors PU.1 (purine-rich box 1) and CEBPα (CCAAT/enhancer binding protein α), monocytes, macrophages, and dendritic cells are the most vitamin D-sensitive immune cell types. The central role of the immune system in various aging-related diseases suggests that immunocompetence describes not only the ability of an individual to resist pathogens and parasites but also to contest non-communicative diseases and the process of aging itself. In this review, we argue that the individual-specific responsiveness to vitamin D relates to a person's immunocompetence via the epigenetic programming function of VDR and its ligand 1,25(OH)2D3 during hematopoiesis as well as in the periphery. This may provide a mechanism explaining how vitamin D protects against major common diseases and, in parallel, promotes healthy aging. [ABSTRACT FROM AUTHOR]

Primary CNS lymphoma (PCNSL) is a rare lymphoma representing 3% of CNS malignancies. The diagnosis is complicated by the unique risks associated with brain biopsy, and the treatment is similarly complicated by the restriction of effective therapeutics able to cross the blood-brain barrier. Currently, the majority of individuals diagnosed with this disease are immunocompetent although immune deficiency related to HIV or immunosuppressive therapy remains an important risk factor. Improvements in both frontline therapy and consolidation options, including the use of hematopoietic stem-cell transplantation, have translated to improved survival. Unfortunately, patients experiencing relapsed or refractory disease often fare poorly. Here, we review key clinical, pathologic, and therapeutic aspects of PCNSL and highlight challenging clinical scenarios that may be encountered by the treating oncologist. [ABSTRACT FROM AUTHOR]

Sexes of a species may show different characteristics beyond the differences in their sexual organs and such sexual dimorphism often occurs in the level of immune response when exposed to pathogens (immunocompetence). In general, females have increased longevity relative to males, which is associated with higher immunocompetence. However, males have higher immunocompetence in some species, such as pipefishes and seahorses. Experimental evidence suggests that this could be because males, rather than females, carry fertilized eggs to birth in these species. This observation suggests that an increase in immunocompetence may be related to the level of parental investment and not to a particular sex. We use state‐dependent life‐history theory to study optimal investment in offspring production relative to parent immunocompetence, varying the relative time that a parent spends in brooding or pregnancy within a breeding cycle. When offspring is dependent on a parent's survival for a large part of the breeding cycle, we predict higher investments in immunity and longer life expectancies. [ABSTRACT FROM AUTHOR]

Torque Teno Virus (TTV), first discovered in 1997, is a non-pathogenic, highly prevalent virus with a notable presence in the human virome. TTV has garnered attention as a potential indicator of immunocompetence in recipients of solid organ transplants. In this review, we discuss the role of TTV as a potential marker for immunosuppression optimization, prediction of graft rejection, and as an indicator of opportunistic infections. We discuss TTV's behavior over the course of time after transplantation, TTV's implications in different immunosuppressive regimens, and potential utility in vaccinations. The review synthetizes findings from various studies depicting its potential clinical utility for future personalized patient care. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Pediatric Emergency & Intensive Care Medicine / Çocuk Acil ve Voğun Bakım Dergisi is the property of Galenos Yayinevi Tic. LTD. STI 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.)

Copyright of Revista de la Facultad de Medicina Humana is the property of Instituto de Investigaciones en Ciencias Biomedicas de la Universidad Ricardo Palma 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.)

The literature shows that maternal stress can influence behavior and immune function in F1. Yet, most studies on these are from the laboratory, and replicated studies on the mechanisms by which maternal stress drives individual characteristics are still not fully understood in wild animals. We manipulated high- and low-density parental population density using large-scale field enclosures and examined behavior and immune traits. Within the field enclosures, we assessed anti-keyhole limpet hemocyanin immunoglobulin G (anti-KLH IgG) level, phytohemagglutinin (PHA) responses, hematology, cytokines, the depressive and anxiety-like behaviors and prevalence and intensity of coccidial infection. We then collected brain tissue from juvenile voles born at high or low density, quantified mRNA and protein expression of corticotropin-releasing hormone (CRH) and glucocorticoid receptor gene (NR3C1) and measured DNA methylation at CpG sites in a region that was highly conserved with the prairie vole CRH and NR3C1 promoter. At high density, we found that the F1 had a lower DNA methylation level of CRH and a higher DNA methylation level of NR3C1, which resulted in an increase in the expression levels of the CRH mRNA and protein expression and further reduced the expression levels of the NR3C1 mRNA and protein expression, and ultimately led to have delayed responses to acute immobilization stress. Juvenile voles born at high density also reduced anti-KLH IgG levels and PHA responses, increased cytokines, and depressive and anxiety-like behaviors, and the effects further led to higher coccidial infection. From the perspective of population density inducing the changes in behavior and immunity at the brain level, our results showed a physiological epigenetic mechanism for population self-regulation in voles. Our results indicate that altering the prenatal intrinsic stress environment can fundamentally impact behavior and immunity by DNA methylation of HPA-axis genes and can further drive population fluctuations in wild animals.

Fanconi anemia, a rare disorder with an incidence of 1 in 300,000, is caused by mutations in FANC genes, which affect the repair of DNA interstrand crosslinks. The disease is characterized by congenital malformations, bone marrow failure within the first decade of life, and recurrent squamous cell carcinomas of the oral cavity, esophagus, and anogenital regions starting around age 20. In this review, we propose that Fanconi anemia should be considered a premature-aging syndrome. Interestingly, the onset and severity of the life-limiting clinical features of Fanconi anemia can be influenced by lifestyle choices, such as a healthy diet and physical activity. These factors shape the epigenetic status of at-risk cell types and enhance the competence of the immune system through nutritional signaling. Fanconi anemia may serve as a model for understanding the aging process in the general population, addressing research gaps in its clinical presentation and suggesting prevention strategies. Additionally, we will discuss how the balance of genetic and environmental risk factors—affecting both cancer onset and the speed of aging—is interlinked with signal transduction by dietary molecules. The underlying nutrigenomic principles will offer guidance for healthy aging in individuals with Fanconi anemia as well as for the general population.

Simple Summary: In Europe, seven out of eight patients with lung cancer die within 5 years after diagnosis. DDR1, a tyrosine kinase receptor, has emerged as a potential new therapeutic target for non-small cell lung cancer given its association with poor prognosis among affected patients. This study investigates the impact of DDR1 on tumor burden and immune cell infiltration into the tumor microenvironment. We found that pharmacological inhibition and knockout of DDR1 increased the tumor burden in an immunocompetent mouse model of lung adenocarcinoma. The absence of DDR1 reduced CD8+ cytotoxic T-cell infiltration but increased CD4+ helper and regulatory T-cell infiltration. Regulatory T cells, which promote tumorigenesis by suppressing the immune system, were also more common among The Cancer Genome Atlas (TCGA) lung adenocarcinoma patients with low DDR1 expression. These findings suggest that therapeutic inhibition of DDR1, in certain circumstances, might even have negative effects, although further studies are needed to confirm these findings. Lung cancer is the leading cause of cancer-related death worldwide. Discoidin domain receptor 1 (DDR1), a tyrosine kinase receptor, has been associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). However, its role in tumorigenesis remains poorly understood. This work aimed to explore the impact of DDR1 expression on immune cell infiltration in lung adenocarcinoma. Pharmacological inhibition and knockout of DDR1 were used in an immunocompetent mouse model of KRAS/p53-driven lung adenocarcinoma (LUAD). Tumor cells were engrafted subcutaneously, after which tumors were harvested for investigation of immune cell composition via flow cytometry. The Cancer Genome Atlas (TCGA) cohort was used to perform gene expression analysis of 509 patients with LUAD. Pharmacological inhibition and knockout of DDR1 increased the tumor burden, with DDR1 knockout tumors showing a decrease in CD8+ cytotoxic T cells and an increase in CD4+ helper T cells and regulatory T cells. TCGA analysis revealed that low-DDR1-expressing tumors showed higher FoxP3 (regulatory T-cell marker) expression than high-DDR1-expressing tumors. Our study showed that under certain conditions, the inhibition of DDR1, a potential therapeutic target in cancer treatment, might have negative effects, such as inducing a pro-tumorigenic tumor microenvironment. As such, further investigations are necessary. [ABSTRACT FROM AUTHOR]

The supplementation of cytosine phosphate guanosine-oligodeoxynucleotides (CpG-ODNs) in feeds to enhance the immune responses of crustaceans has been studied. However, the immunomodulatory effects of CpG-ODNs alone on prawn hepatopancreas and midgut remain unclear. Hence, we delivered CpG-ODNs directly into the midgut of Macrobrachium rosenbergii by reverse gavage (RG). In this study, M. rosenbergii was fasted before receiving different doses (0, 2, 4, and 10 μg) of CpG-ODN 2006. Furthermore, the hemolymph, hepatopancreas, and midgut were sampled at 2, 6, 12, and 24 h after RG. The results showed that administration of CpG-ODN 2006 could boost total hemocyte count (THC), transglutaminase (TG), phenoloxidase (PO), lysozyme-like (LYS), and respiratory burst (RB) responses in the hemolymph. In addition, the expression levels of prophenoloxidase (MrProPO), crustin (MrCrs), peroxinectin (MrPxt), and superoxide dismutase (MrSOD) in the hepatopancreas and midgut were also enhanced, in a dose- and time-dependent manner. Overall, our results indicate that administration of 4 μg CpG-ODN 2006 alone by RG elicited the most potent immunological response in the hemolymph, hepatopancreas, and midgut of M. rosenbergii. [ABSTRACT FROM AUTHOR]