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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Background: Chronic hepatitis E virus (HEV) infection may progress to end-stage liver disease in immunosuppressed individuals. Ribavirin therapy is efficient in most chronic HEV patients, but 10% remain without a sustained virological response (SVR). Objectives: We aimed to study whether zinc supplementation could represent a therapeutic approach in these patients. Methods: Antiviral properties of zinc salts were studied in vitro (subgenomic-replicon system), in vivo (rabbit model), and retrospectively in patients with chronic hepatitis E who did not achieve SVR under ribavirin monotherapy. Results: Zinc inhibited HEV genotype 3 replication in vitro. In a model of acute HEV infection in immunocompetent rabbits, zinc + ribavirin did not improve viral clearance compared to ribavirin monotherapy. In chronically HEV-infected patients not responding to ribavirin (n = 12), viral clearance was observed in 4/12 (33%) patients receiving additional zinc supplementation. Conclusions: Oral zinc, an inexpensive, harmless dietary supplement, could potentially represent a rescue treatment option for a few patients with chronic hepatitis E without SVR under ribavirin monotherapy. Further studies are needed to elucidate the role of zinc in HEV. [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]

Pulmonary carcinoma represents the second common cancer for human race while its mortality rate ranked the first all over the world. Surgery remains the primary option for early‐stage non‐small cell lung cancer (NSCLC) in some surgical traditions. Nevertheless, only less than half of patients are operable subjected to the limited lung function and multiple primary/metastatic lesions. Recent improvements in minimally invasive surgical techniques have made the procedure accessible to more patients, but this percentage still does not exceed half. In recent years, radiofrequency ablation (RFA), one of the thermal ablation procedures, has gradually advanced in the treatment of lung cancer in addition to being utilized to treat breast and liver cancer. Several guidelines, including the American College of Chest Physicians (ACCP), include RFA as an option for some patients with NSCLC although the level of evidence is mostly limited to retrospective studies. In this review, we emphasize the use of the RFA technique in patients with early‐stage NSCLC and provide an overview of the RFA indication population, prognosis status, and complications. Meanwhile, the advantages and disadvantages of RFA proposed in existing studies are compared with surgical treatment and radiotherapy. Due to the high rate of gene mutation and immunocompetence in NSCLC, there are considerable challenges to clinical translation of combining targeted drugs or immunotherapy with RFA that the field has only recently begun to fully appreciate. [ABSTRACT FROM AUTHOR]

Summary: The plant immune system features numerous immune receptors localized on the cell surface to monitor the apoplastic space for danger signals from a broad range of plant colonizers. Recent discoveries shed light on the enormous complexity of molecular signals sensed by these receptors, how they are generated and removed to maintain cellular homeostasis and immunocompetence, and how they are shaped by host‐imposed evolutionary constraints. Fine‐tuning receptor sensing mechanisms at the molecular, cellular and physiological level is critical for maintaining a robust but adaptive host barrier to commensal, pathogenic, and symbiotic colonizers alike. These receptors are at the core of any plant‐colonizer interaction and hold great potential for engineering disease resistance and harnessing beneficial microbiota to keep crops healthy. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroblastoma (NB) is the most common extracranial solid pediatric cancer, with highly observed metastasis at diagnosis. Primary NBs generally have favorable outcomes with current therapies; however, high-risk, metastatic NBs are resistant and result in relapsed disease. Patients with metastatic NBs, thus, have a lower overall survival. Thus, to develop effective therapies for metastatic NBs, it is essential to better understand the biology of metastasis in NB. This requires the utilization of pre-clinical animal models, importantly, immunocompetent models that have an intact immune system and better reflect the disease physiology. However, currently, there are few good animal models available for studying HR-NB metastasis. This study aimed to generate efficient and appropriate mouse models to study HR-NB metastasis. Our newly developed and validated mouse cell lines are relevant and promising tools to study (high-risk) HR-NB metastasis and identify novel therapeutic targets for metastatic NBs; thus, they could benefit the NB research community. NB, being a highly metastatic cancer, is one of the leading causes of cancer-related deaths in children. Increased disease recurrence and clinical resistance in patients with metastatic high-risk NBs (HR-NBs) result in poor outcomes and lower overall survival. However, the paucity of appropriate in vivo models for HR-NB metastasis has limited investigations into the underlying biology of HR-NB metastasis. This study was designed to address this limitation and develop suitable immunocompetent models for HR-NB metastasis. Here, we developed several highly metastatic immunocompetent murine HR-NB cell lines. Our newly developed cell lines show 100% efficiency in modeling experimental metastasis in C57BL6 mice and feature metastasis to the sites frequently observed in humans with HR-NB (liver and bone). In vivo validation demonstrated their specifically gained metastatic phenotype. The in vitro characterization of the cell lines showed increased cell invasion, acquired anchorage-independent growth ability, and resistance to MHC-I induction upon IFN-γ treatment. Furthermore, RNA-seq analysis of the newly developed cells identified a differentially regulated gene signature and an enrichment of processes consistent with their acquired metastatic phenotype, including extracellular matrix remodeling, angiogenesis, cell migration, and chemotaxis. The presented newly developed cell lines are, thus, suitable and promising tools for HR-NB metastasis and microenvironment studies in an immunocompetent system. [ABSTRACT FROM AUTHOR]

We report a case of bacteremia associated with Roseomonas mucosa isolated from an immunocompetent pediatric patient with no prior history of infection and bacteremia. [ABSTRACT FROM AUTHOR]

Post-pneumonectomy empyema (PPE) is an uncommon but serious complication that carries significant therapeutic challenges. We present a late-onset PPE due to Nocardia nova in an immunocompetent individual. Nine years after a right pneumonectomy for non-small cell lung cancer, surveillance scans revealed new right pleural thickening and FDG avidity concerning for recurrence. Thoracoscopic pleural biopsies were negative for malignancy, but tissue cultures grew N. nova. Nocardia empyema is rare with few reported cases. Most occur in immunocompromised hosts, and all were associated with pulmonary or disseminated nocardiosis. Our case describes the first report of a PPE secondary to Nocardia. [ABSTRACT FROM AUTHOR]

Background: Valine is an important amino acid and its deficiency may result in reduced growth and immunity. However, studies in turkeys are limited. Hence a study was conducted to assess the effect of supplemental L-valine (L-val) on growth performance, immunocompetence traits, carcass quality and meat composition of turkey poults. Methods: Day old turkey poults (n=96) were distributed into four dietary treatment groups: T1-basal diet, T2-T1+0.04% L-val, T3- T1+0.08% L-val, T4- T1+0.12% L-val, having three replicates of 8 birds each. Result: No significance difference observed in average weekly body weight (BW), body weight gain (BWG) and feed conversion ratio (FCR) of birds throughout experimental period except at 7th week where T2 and T3 poults had a significantly higher (P<0.05) BW, BWG and significantly better (P<0.05) FCR. HA titre was significantly higher (P<0.05) in T3. Per cent breast weight was significantly higher (P<0.05) in T3. Percent crude protein level in breast muscle of turkey poults was significantly higher (P<0.05) in T3. Thus, supplementation of L-val @ 0.08% in turkey poults resulted in significantly better humoral immune response, higher percent breast yield and higher percent crude protein in breast meat. [ABSTRACT FROM AUTHOR]

Background: Inorganic iron compounds have a positive effect on the health and growth of the broiler chickens. However, limited work has been done in Turkeys. Thus a study was conducted to assess the effect of dietary supplementation of ferrous sulphate on the growth, immunocompetence traits, carcass quality and meat composition of Turkey poults. Methods: Day old turkey poults (n=96) were distributed into four treatment groups (T1, T2, T3 and T4) having 3 replicates of 8 birds each. The poults in T1 were fed (control) basal diet, while for birds in T2, T3 and T4, FeSO4 was supplemented @ 80, 120 and 160 mg/kg of feed, respectively. Result: Weekly body weight gain was significantly higher in T4 than T1 and T2 birds at 6th (P<0.01) and 7th week (P<0.05). Phase wise body weight gain was also significantly higher (P<0.05) in T4 than T1 and T2 during 4 to 8 weeks and 0 to 8 weeks (P<0.01). Weekly feed conversion ratio of T4 group was significantly better (P<0.01) at 6th week and 7th week than T1 and T2 group birds. The birds fed with T4 had significantly (P<0.05) higher foot web index compared to T1 and T2 group birds. Iron supplemented groups had significantly (P<0.01) higher dressing per cent. T4 had significantly (P<0.05) higher deposition of iron in thigh muscle. Thus, dietary supplementation of FeSO4 @ 160 mg/kg resulted in better growth performance, immunity, significantly higher dressing per cent and significantly higher deposition of iron in thigh meat cuts. [ABSTRACT FROM AUTHOR]

The CD4 gene plays an important role in the immune process by producing CD4 molecules that aid in producing antibodies. IPB-D2 chickens are selected from IPB-D2 chickens based on IgY concentration and ND antibody titer. This study aimed to analyze the polymorphism of the CD4 gene, unravel the mRNA expression of CD4 gene in IPB-D2 chicken related to the immunocompetence index, and detect the CD4 gene pathway. The total samples used were 100 IPB-D2 G2 chickens aged 21 weeks. Blood samples were collected for ELISA test, HI test, sequencing test, and seca tonsil tissue for relative mRNA expression. Polymorphism and association data were analyzed using MEGAX, FinchTV, SNPstat, and DNAsp. The relative mRNA expression analysis was conducted using qRT-PCR. The pathway analysis of the CD4 gene was performed using the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. The result showed there were 4 SNPs of the CD4 gene in IPB-D2 chicken, i.e., g.7526 C>T, g.7825 C>T, g.8100 C>A, and g.8157 T>A. All CD4 SNPSs showed no association with IgY concentration and ND antibody titers. Relative mRNA expression shows that IPB-D2 chickens with high ND antibody titers have a higher level of expression when compared to IPB-D2 chickens with low ND antibody titers. Furthermore, pathway analysis showed the CD4 gene involved in the T cell receptor (TcR) signaling process. This study concludes that the CD4 gene is polymorphic and involved in the T cell receptor signaling process. This study demonstrated that polymorphisms of the CD4 gene in IPB-D2 chicken might not contribute to the IgY concentration and ND antibody titer but can serve as a reference in the study of CD4 genes in the other chicken breeds related to the other immunocompetence index. [ABSTRACT FROM AUTHOR]

Background: Human herpes virus-6 (HHV-6) is a ubiquitous virus known as an etiological agent of exanthem subitum. HHV-6-encephalitis in immunocompetent children is a rare complication of the primary infection. There are a lack of data on the prevalence of HHV-6-encephalitis in Russia. The aim of our study was to analyze the prevalence of HHV-6 DNA in the cerebrospinal fluid (CSF) of immunocompetent children with suspected acute meningoencephalitis. Materials and Methods: A total of 712 CSF samples were tested using qualitative PCR over 12 years at N.F. Filatov Children's City Clinical Hospital No.5, Saint-Petersburg, Russia. Results: HHV-6 DNA was detected in 20 (2.8%) of the samples. Retrospectively, we analyzed the medical records of 15 cases. There were seven boys and eight girls from 1 month to 7 years old; the mean age was 22.3 ± 5.6 months. Most HHV-6 DNA-positive cases were due to the primary form of HHV-6 infection. There were, in total, four cases of HHV-6-meningoencephalitis. All the children had a complete recovery, without neurological deficits or death. Conclusions: HHV-6 encephalitis is a very rare disease in immunocompetent children (four cases among 712 samples over 12 years). Additional studies are needed to develop accurate diagnostic criteria and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Immune traits are considered to serve as potential biomarkers for pig's health. Medium to high heritabilities have been observed for some of the immune traits suggesting genetic variability of these phenotypes. Consideration of previously established genetic correlations between immune traits can be used to identify pleiotropic genetic markers. Therefore, genome-wide association study (GWAS) approaches are required to explore the joint genetic foundation for health biomarkers. Usually, GWAS explores phenotypes in a univariate (uv), trait-by-trait manner. Besides two uv GWAS methods, four multivariate (mv) GWAS approaches were applied on combinations out of 22 immune traits for Landrace (LR) and Large White (LW) pig lines. Results: In total 433 (LR: 351, LW: 82) associations were identified with the uv approach implemented in PLINK and a Bayesian linear regression uv approach (BIMBAM) software. Single Nucleotide Polymorphisms (SNPs) that were identified with both uv approaches (n = 32) were mostly associated with immune traits such as haptoglobin, red blood cell characteristics and cytokines, and were located in protein-coding genes. Mv GWAS approaches detected 647 associations for different mv immune trait combinations which were summarized to 133 Quantitative Trait Loci (QTL). SNPs for different trait combinations (n = 66) were detected with more than one mv method. Most of these SNPs are associated with red blood cell related immune trait combinations. Functional annotation of these QTL revealed 453 immune-relevant protein-coding genes. With uv methods shared markers were not observed between the breeds, whereas mv approaches were able to detect two conjoint SNPs for LR and LW. Due to unmapped positions for these markers, their functional annotation was not clarified. Conclusions: This study evaluated the joint genetic background of immune traits in LR and LW piglets through the application of various uv and mv GWAS approaches. In comparison to uv methods, mv methodologies identified more significant associations, which might reflect the pleiotropic background of the immune system more accurately. In genetic research of complex traits, the SNP effects are generally small. Furthermore, one genetic variant can affect several correlated immune traits at the same time, termed pleiotropy. As mv GWAS methods consider strong dependencies among traits, the power to detect SNPs can be boosted. Both methods revealed immune-relevant potential candidate genes. Our results indicate that one single test is not able to detect all the different types of genetic effects in the most powerful manner and therefore, the methods should be applied complementary. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous mycoses, a disease of the tropics, are usually missed or misdiagnosed in immunocompetent individuals unless sought for. The study was designed to explore the experience of diagnosing subcutaneous mycoses by histopathological examination in our institute and to find out the epidemiology, clinical features, and histopathological findings of cases with subcutaneous mycosis. Methodology: We reviewed the cases reported as subcutaneous mycoses in the department of pathology over 6 years (2017-2022). The slides were stained with Hematoxylin and Eosin, Periodic acid Schiff (PAS), and Gomori's Methenamine silver (GMS) for identification of the fungi. Clinical details were obtained from the medical records. Results: Twenty-seven cases were retrieved from the archives, reported as subcutaneous mycoses from various sites. They presented with varying symptoms ranging from ulcers, discharging sinuses, nodular swellings, and cystic swelling. Histology from these revealed granulomas with suppuration, necrosis of subcutaneous fat, broad aseptate hyphae with angioinvasion, abscesses, and grains. Conclusion: Mycosis, a disease of the tropics, may manifest in immunocompetent individuals with varied clinical presentations and histology. The intact immune status of the individual results in granuloma formation along with suppuration and giant cells. Diagnosis is usually achieved by a meticulous search for fungus in such lesions. PAS and GMS stains help identify the fungus. [ABSTRACT FROM AUTHOR]

Primary cutaneous blastomycosis is very rare in non-endemic regions like India. Only few cases have been reported from India. Herein, we are reporting a rare case of chronic cutaneous blastomycosis in a young immunocompetent male presenting as mycetoma with multiple discharging sinuses in the anterior abdominal wall with no significant travel history. [ABSTRACT FROM AUTHOR]

Blastomycosis is a chronic systemic pyogranulomatous infection caused by the fungus Blastomyces dermatitidis, endemic to North America (Mazi et al. in Infect Dis Clin North Am 35(2):515–530, 2021). This is a dimorphic fungus, which exists as a non-pathogenic mycelial form in nature and converts to pathogenic yeast at body temperature. Although it primarily affects lungs, extrapulmonary involvement is reported in 20–30% cases and is very rare (Ballestas et al. in J Voice 36(6):881.e1-881.e3, 2022). We report an unusual case of blastomycosis involving the mediastinum, presented to us as an anterior neck swelling in an immunocompetent young male. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic rhinosinusitis (CRS) and immunoglobulin deficiencies (ID) have more recalcitrant sinonasal disease and a subset of these patients undergo surgical management for their CRS. However, there is a paucity of literature on the surgical outcomes in this patient population and appropriate treatment algorithms for CRS in patients with ID. The objective of this study was to better elucidate the outcomes of endoscopic sinus surgery (ESS) in patients with ID in terms of disease-specific quality-of-life scores and the need for revision surgery. Methods: A case–control study was performed comparing adult patients with ID and healthy controls that had undergone ESS for CRS. Patients were matched based on age, sex, CRS phenotype, and preoperative Lund-Mackay score. The revision surgery rates, time to revision surgery, and changes in sinonasal outcome tests (SNOT-22) were evaluated. Results: Thirteen patients with CRS and ID were matched to 26 control patients with CRS. The revision surgery rate for cases and controls was 31% and 12%, respectively, but there was no statistical difference (p > 0.05). There was a clinically meaningful reduction in SNOT-22 scores in both groups from the preoperative to postoperative period [mean of 12 points in patients with ID (p = 0.323) and 25 points in controls (p < 0.001)], however, there was again no significant difference between cases and controls (p > 0.05). Conclusion: Our data suggests that patients with ID have clinically meaningful improvement in SNOT-22 scores after ESS but may have higher revision rates than immunocompetent patients with CRS. ID are rare disease entities, thus most attempts at studying this cohort would be limited by sample size. Further homogenous data on immunoglobulin deficient patients is required for future meta-analysis to better understand the impact of ESS in patients with ID. [ABSTRACT FROM AUTHOR]

Photographic identification catalogs of individual killer whales (Orcinus orca) over time provide a tool for remote health assessment. We retrospectively examined digital photographs of Southern Resident killer whales in the Salish Sea to characterize skin changes and to determine if they could be an indicator of individual, pod, or population health. Using photographs collected from 2004 through 2016 from 18,697 individual whale sightings, we identified six lesions (cephalopod, erosions, gray patches, gray targets, orange on gray, and pinpoint black discoloration). Of 141 whales that were alive at some point during the study, 99% had photographic evidence of skin lesions. Using a multivariate model including age, sex, pod, and matriline across time, the point prevalence of the two most prevalent lesions, gray patches and gray targets, varied between pods and between years and showed small differences between stage classes. Despite minor differences, we document a strong increase in point prevalence of both lesion types in all three pods from 2004 through 2016. The health significance of this is not clear, but the possible relationship between these lesions and decreasing body condition and immunocompetence in an endangered, non-recovering population is a concern. Understanding the etiology and pathogenesis of these lesions is important to better understand the health significance of these skin changes that are increasing in prevalence. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 14-year-old girl who was admitted to the hospital with a fever of unknown origin. She had a history of migraines and presented with fevers, night sweats, myalgias, headache, nausea, chest pain, and a nonproductive cough.

Capnocytophaga canimorsus is a fastidious, capnophilic and facultative anaerobic Gram‐negative rod found commonly in the oral flora of dogs that may cause zoonotic infections such as cellulitis and eye infections. In immunocompromised patients, it may cause fulminant sepsis. Meningitis due to C. canimorsus is, however, a rare manifestation. This is the first reported case of C. canimorsus meningitis in Australia in an immunocompetent veterinarian diagnosed by 16s ribosomal RNA polymerase chain reaction. [ABSTRACT FROM AUTHOR]

Background and Design: Herpes zoster (HZ) is a viral infection characterized by dermatomal vesicles caused by the reactivation of the latent varicella-zoster virus (VZV). There are conflicting reports regarding the effects of VZV on bone marrow functions. In this study, we aimed to evaluate bone marrow function and systemic inflammation in immunocompetent HZ patients. Materials and Methods: This study included patients aged ≥18 yr diagnosed with HZ and admitted to a dermatology outpatient clinic between June 2011 and June 2021. Hematological parameters in routine hemogram tests of patients with HZ and new inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index, and platelet-neutrophil ratio (PNR), were determined and compared with healthy control groups. Results: Thrombocytopenia was observed in 6.1% and lymphopenia in 8% of 461 HZ patients. The mean leukocyte (white blood cell), lymphocyte, neutrophil, eosinophil, and platelet (PLT) counts in HZ patients were statistically significantly lower than in the control group (p<0.05). NLR and PLR values were statistically significantly higher in HZ patients than in the control group (p<0.05). PLT, eosinophil count, and PNR values were statistically lower in HZ patients aged ≥65 yr than in patients aged <65 yr, whereas mean platelet volume and NLR values were higher (p<0.05). Conclusion: Thrombocytopenia and lymphopenia may occur in immunocompetent HZ patients. NLR and PLR values increase in HZ patients. The increase in inflammatory markers and decrease in platelet count are more evident in HZ patients aged ≥65 yr. [ABSTRACT FROM AUTHOR]

Lazarine leprosy is an unusual expression of usually borderline tuberculoid (BT) form characterized by spontaneous ulceration of skin lesions. This is presumably the result of an exaggerated type 1 reaction. It commonly occurs in the BT, borderline lepromatous forms and rarely in the lepromatous forms of leprosy. We report two cases of lazarine leprosy in the BT and BT downgrading to borderline lepromatous spectrum in healthy and immunocompetent males. [ABSTRACT FROM AUTHOR]

Simple Summary: Over the years, the poultry industry has relied on the use of in-feed antibiotics as a growth-promoting agent and for the prevention of diseases. However, antibiotic use has brought about pathogens that are resistant to antimicrobials. To this end, spray-dried plasma (SDP), an animal blood by-product that is rich in protein-containing lipids, peptides, immunoglobulins, transferrin, and fibrinogen, is being explored as a replacement for in-feed antibiotics in poultry. We evaluated the immunological and biochemical profile of SDP in order to understand how it enhanced performance values when supplemented to a broiler diet. At the end of the four-week study, our findings demonstrated a decrease in the number of heterophils and an increase in immunoglobulin in circulation, with oxidative stress falling in the normal range. Bifidobacteria counts also increased in the SDP-supplemented treatment. This demonstrated that SDP supplementation prevented infection and caused an increase in immunoglobulin concentration required to support intestinal development and gut microbiota modulation. Spray-dried plasma (SDP) contain a variety of functional proteins that play an immunomodulatory role. To evaluate the potential of SDP to stimulate the immune system, day-old Ross 708 male broiler chicks (200) were allocated randomly to five dietary treatments. Treatment 1 (CX) comprised chicks fed basal unmedicated corn–soybean meal (SBM) without the addition of SDP. Treatment 2 (MX) includes chicks fed unmedicated corn–SBM basal containing Bacitracin methylene disalicylate (BMD) at 0.055 g/kg diet. Treatments 3 (SDP1), 4 (SDP2), and 5 (SDP3) contained chicks given unmedicated corn–SBM basal, into which SDP was included at 10, 20, and 30 g/kg diet, respectively. On d 7, 14, and 21, chicks' body weight and FCR were calculated. Additionally, leucocyte counts, oxidative status, and IgY concentrations were determined in blood. On d 23, fecal populations of selected indicator bacteria species were determined. Results showed that FCR for SP3 was superior (p < 0.05) to other treatments. Likewise, heterophil numbers decreased in MX and SDP treatments compared to CX. Circulating IgY concentration was higher for SDP dietary treatments (p < 0.05) compared to MX. In conclusion, dietary SDP at 30 g/kg enhanced immune surveillance by increasing circulating IgY levels, maintaining a normal oxidative state, and increasing gut Bifidobacteria, thereby improving chick growth performance. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor microenvironment (TME) is composed of various cell types and extracellular components and plays an important role in cancer development and progression, as well as in therapeutic resistance and metastasis. Cancer-associated fibroblasts (CAFs) are a key cell type in the TME and interact with cancer cells as well as with other TME cells, such as immune cells. Immunocompetent mouse cancer models that recapitulate the interactions of cancer cells with the TME have provided a better understanding of the TME network and support the development of new therapeutic strategies. In this review, we focus on cancer cell–TME interactions in heterogeneous tumor tissue, and we provide an overview of therapeutic strategies that target the TME. The tumor microenvironment (TME) plays a key role in cancer development and progression, as well as contributes to the therapeutic resistance and metastasis of cancer cells. The TME is heterogeneous and consists of multiple cell types, including cancer-associated fibroblasts (CAFs), endothelial cells, and immune cells, as well as various extracellular components. Recent studies have revealed cross talk between cancer cells and CAFs as well as between CAFs and other TME cells, including immune cells. Signaling by transforming growth factor-β, derived from CAFs, has recently been shown to induce remodeling of tumor tissue, including the promotion of angiogenesis and immune cell recruitment. Immunocompetent mouse cancer models that recapitulate interactions of cancer cells with the TME have provided insight into the TME network and support the development of new anticancer therapeutic strategies. Recent studies based on such models have revealed that the antitumor action of molecularly targeted agents is mediated in part by effects on the tumor immune environment. In this review, we focus on cancer cell–TME interactions in heterogeneous tumor tissue, and we provide an overview of the basis for anticancer therapeutic strategies that target the TME, including immunotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cryptococcosis is the most common cause of fungal meningitis worldwide and has a mortality of about 181,000 cases annually. It affects mainly HIV-positive patients or people with some cellular immune-response compromise. Even though it is an uncommon disease in immunocompetent subjects it may occur in apparently healthy hosts, in whom it must be recognized because the subacute presentation and the late diagnosis can increase morbidity and mortality on this group. CLINICAL CASE: A 67-year-old male patient, apparently immunocompetent, who consulted referring headache, fever and mental status altered. He was diagnosed with meningeal cryptococcosis by microbiological analyses and serum antigens, treated with fluconazole and liposomal amphotericin B and he had an adequate clinical response with no further complications (after finished the treatment) or neurological sequels. CONCLUSIONS: The clinical suspicion of this entity is very important because multiples causes of immunosuppression result in a major predisposition to the disease. [ABSTRACT FROM AUTHOR]

Background. Non-small-cell lung cancer (NSCLC) is a major health problem that endangers human health. The prognosis of radiotherapy or chemotherapy is still unsatisfactory. This study is aimed at investigating the predictive value of glycolysis-related genes (GRGs) on the prognosis of NSCLC patients with radiotherapy or chemotherapy. Methods. Download the clinical information and RNA data of NSCLC patients receiving radiotherapy or chemotherapy from TCGA and geo databases and obtain GRGs from MsigDB. The two clusters were identified by consistent cluster analysis, the potential mechanism was explored by KEGG and GO enrichment analyses, and the immune status was evaluated by estimate, TIMER, and quanTIseq algorithms. Lasso algorithm is used to build the corresponding prognostic risk model. Results. Two clusters with different GRG expression were identified. The high-expression subgroup had poor overall survival. The results of KEGG and GO enrichment analyses suggest that the differential genes of the two clusters are mainly reflected in metabolic and immune-related pathways. The risk model constructed with GRGs can effectively predict the prognosis. The nomogram combined with the model and clinical characteristics has good clinical application potential. Conclusion. In this study, we found that GRGs are associated with tumor immune status and can assess the prognosis of NSCLC patients receiving radiotherapy or chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer—ductal carcinoma of the breast and invasive ductal carcinoma (IDC)—arises within the confines of the mammary ductal epithelium. Progression to IDC can occur through a pre-invasive, ductal carcinoma in situ stage (DCIS), or in the absence of DCIS. The immune system has recently been identified as a factor in disease progression, highlighting the need for immune-competent mouse models of pre-invasive disease. To model early-stage disease, we tested six distinct murine mammary tumor cell lines injected directly into the mammary ducts of immune-competent mice. We find that all six mouse cell lines bypassed a stable DCIS stage, rapidly progressing to IDC. Similarly, in immune-compromised mice, we observed IDC in the absence of DCIS, suggesting an intact immune system may not play a primary role in early disease progression in these mouse models. These models may be useful for the study of IDC that occur in the absence of DCIS, and in the development of immune therapies. In breast cancer, progression to invasive ductal carcinoma (IDC) involves interactions between immune, myoepithelial, and tumor cells. Development of IDC can proceed through ductal carcinoma in situ (DCIS), a non-obligate, non-invasive stage, or IDC can develop without evidence of DCIS and these cases associate with poorer prognosis. Tractable, immune-competent mouse models are needed to help delineate distinct mechanisms of local tumor cell invasion and prognostic implications. To address these gaps, we delivered murine mammary carcinoma cell lines directly into the main mammary lactiferous duct of immune-competent mice. Using two strains of immune-competent mice (BALB/c, C57BL/6), one immune-compromised (severe combined immunodeficiency; SCID) C57BL/6 strain, and six different murine mammary cancer cell lines (D2.OR, D2A1, 4T1, EMT6, EO771, Py230), we found early loss of ductal myoepithelial cell differentiation markers p63, α-smooth muscle actin, and calponin, and rapid formation of IDC in the absence of DCIS. Rapid IDC formation also occurred in the absence of adaptive immunity. Combined, these studies demonstrate that loss of myoepithelial barrier function does not require an intact immune system, and suggest that these isogenic murine models may prove a useful tool to study IDC in the absence of a non-obligatory DCIS stage—an under-investigated subset of poor prognostic human breast cancer. [ABSTRACT FROM AUTHOR]

In ovo vaccination with herpesvirus of turkey (HVT) hastens immunocompetence in chickens and the recommended dose (RD) of 6080 plaque-forming-units (PFU) offers the most optimal effects. In previous studies conducted in egg-type chickens, in ovo vaccination with HVT enhanced lymphoproliferation, wing-web thickness with phytohemagglutinin-L (PHA-L), and increased spleen and lung interferon-gamma (IFN- γ) and Toll-like receptor 3 (TLR3) transcripts. Here, we evaluated the cellular mechanisms by which HVT-RD can hasten immunocompetence in one-day-old meat-type chickens, and also determined if HVT adjuvantation with a TLR3 agonist, polyinosinic-polycytidylic acid (poly(I:C)), could enhance vaccine-induced responses and provide dose-sparing effects. Compared to sham-inoculated chickens, HVT-RD significantly increased transcription of splenic TLR3 and IFN γ receptor 2 (R2), and lung IFN γ R2, while the splenic IL-13 transcription was found decreased. Additionally, these birds showed increased wing-web thickness following PHA-L inoculation. The thickness was due to an innate inflammatory cell population, CD3+ T cells, and edema. In another experiment, HVT-1/2 (3040 PFU) supplemented with 50 μ g poly(I:C) [HVT-1/2 + poly(I:C)] was administered in ovo and immune responses were compared with those produced by HVT-RD, HVT-1/2, 50 μ g poly(I:C), and sham-inoculated. Immunophenotyping of splenocytes showed HVT-RD induced a significantly higher frequency of CD4+, CD4+MHC-II+, CD8+CD44+, and CD4+CD28+ T cells compared to sham-inoculated chickens, and CD8+MHC-II+, CD4+CD8+, CD4+CD8+CD28+, and CD4+CD8+CD44+ T cells compared to all groups. Treatment groups, except HVT-1/2 + poly(I:C), had significantly higher frequencies of γδ T cells and all groups induced significantly higher frequencies of activated monocytes/macrophages, compared to sham-inoculated chickens. Poly(I:C)-induced dose-sparing effect was only observed in the frequency of activated monocytes/macrophages. No differences in the humoral responses were observed. Collectively, HVT-RD downregulated IL-13 transcripts (Th2 immune response) and had strong immunopotentiation effects on innate immune responses and the activation of T cells. However addition of poly(I:C) offered a minimal adjuvant/dose-sparing effect. [ABSTRACT FROM AUTHOR]

Prolactin and 11‐ketotestosterone (11‐KT) are important reproductive hormones in fishes, which may also influence immunocompetence. The immunocompetence handicap hypothesis states that higher androgen concentrations that support secondary sex traits are traded off against a decrease in immune system function. To test the relationships between these hormones and immunocompetence, we experimentally manipulated 11‐ketotestosterone and prolactin in the freshwater fish, bluegill (Lepomis macrochirus) during parental care using implants that contained either 11‐KT, prolactin, or an inert control. We vaccinated individuals to stimulate the acquired immune response, then measured immunocompetence as the number of granulocytes, lymphocytes and monocytes, and the expression of interleukin 8 in each sample. We did not observe any significant differences in the immune measures among the hormone treatments. Our results indicate that in bluegill, there is no trade‐off between androgens or prolactin and immunocompetence. Research Highlights: Prolactin or androgen (11‐KT) treatment did not affect immune responses in bluegill sunfish.We find no support the immunocompetence handicap hypothesis in fish.Increased 11‐KT affected behavior, but not the immune response to a vaccine. [ABSTRACT FROM AUTHOR]

The immune system of neonate piglets differs from adult pigs in structure and competence. Although piglets are born immunocompetent, they are genuinely immunologically defenseless. To survive in the environment, piglets need passive protection provided by sow's colostrum and milk when constantly exposed to numerous pathogens. Early assessment of piglets' immune status may enable rapid intervention in case of detection of any deficiencies or disorders. Moreover, awareness of the piglets' immunocompetence and the level of maternally-derived antibodies (MDA) may allow the creation of a proper vaccine schedule. Hence, extending knowledge of prenatal ontogeny of the porcine immune system, the immune status of neonate piglets' and the immunological components of porcine colostrum is crucial. Since animal welfare has become a more critical element of animal production, new, non-invasive sampling methodologies are highly desirable for the evaluation of piglets' immune status. [ABSTRACT FROM AUTHOR]

An 8-week study was carried out to examine the influence of dietary Biotronic Top3 (BTT3), which is a blend of short-chain fatty acids (formate, propionate, and acetate), a phytogenic agent (cinnamaldehyde), and a permeabilizer complex (Biomin), in whiteleg shrimp (Penaeus vannamei) juveniles. Five isonitrogenous (∼38%) diets were formulated and supplemented with BTT3 at 0 (control), 0.3, 0.6, 0.9, or 1.2 g/kg. Shrimps (2.7 g) were allocated into 15 circular fiberglass tanks filled with 150 L seawater (20 shrimp per tank) and each dietary treatment was in triplicate. Shrimps were handfed thrice a day at the rate of 7% of their initial biomass for 8 weeks. At the end of the feeding trial, hemolymph and hepatopancreas (HP) were sampled to evaluate plasma biochemical factors, immune-related genes, and digestive enzymes, respectively. The growth rate in shrimps fed with a 0.3 g BTT3/kg diet was markedly higher (∼1.6 g) than in the control (P < 0.05), but higher dietary BTT3 levels did not improve growth and feed utilization. Protein deposition in the whole body of shrimps fed with 0.3 or 0.6 g BTT3/kg diets was significantly increased (∼1.5%) compared to the control. Total alkaline proteases activity in BTT3 groups was significantly higher than in the control. The activity of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase, was increased in HP of shrimps fed BTT3-supplemented diets; meanwhile, malondialdehyde level was significantly reduced by increasing dietary BTT3 level. Shrimps fed diets supplemented with 1.2 g BTT3/kg, and the control had the highest and lowest plasma phenoloxidase activity, respectively. The plasma alkaline phosphatase content in BTT3 groups was higher than in the control. The highest relative abundance of prophenoloxidase gene mRNA transcript was in HP of shrimps fed a 1.2-g BTT3/kg diet. The relative abundance of lysozyme and penaeidin-3α genes mRNA transcript in HP of shrimps fed 0.9 and 1.2 g BTT3/kg diets was higher than in the other groups. Based on the abovementioned findings, the inclusion of aquafeeds with 0.3 g BTT3/kg can increase growth performance in P. vannamei juvenile by promoting the antioxidant capacity and immune responses. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 65-year-old geriatric patient with intracranial aspergilloma, a rare condition typically associated with immunocompromised states. Topics discussed include the diagnostic challenges in distinguishing fungal lesions from other intracranial pathologies, the significance of CSF galactomannan testing, and the effectiveness of Voriconazole therapy in managing intracranial aspergillosis in immunocompetent individuals.