Immune Depression Research Articles

Психические и соматические симптомы, связанные с эмоциональным выгоранием: систематический обзор исследований

<p>This article analyzes the scientific literature devoted to the study of the relationship of emotional burnout with symptoms of cardiovascular diseases, gastrointestinal diseases, immune system disorders, depression, and cognitive impairments. <strong>Methods:</strong> review and analytical method. Articles published in Russian and English in the period up to December 2023 in eLibrary, CyberLeninka, GoogleScholar, PubMed, ScienceDirect, Medline, ResearchGate were analyzed. <strong>Results:</strong> the analysis showed a link between emotional burnout and symptoms of cardiovascular diseases, gastrointestinal diseases and disorders of the immune system. Emotional burnout can also be associated with depression, asthenia, and cognitive impairment. <strong>Conclusion:</strong> mental and somatic symptoms associated with emotional burnout are highlighted.</p>

Targeting carbohydrate metabolism in colorectal cancer - synergy between DNA-damaging agents, cannabinoids, and intermittent serum starvation.

Chemotherapy is a therapy of choice for many cancers. However, it is often inefficient for long-term patient survival and is usually accompanied by multiple adverse effects. The adverse effects are mainly associated with toxicity to normal cells, frequently resulting in immune system depression, nausea, loss of appetite and metabolic changes. In this respect, the combination of chemotherapy with cannabinoids, especially non-psychoactive, such as cannabidiol, cannabinol and other minor cannabinoids, as well as terpenes, may become very useful. This is especially pertinent because the mechanisms of anticancer effects of cannabinoids on cancer cells are often different from conventional chemotherapeutics. In addition, cannabinoids help alleviate chemotherapy-induced adverse effects, regulate sleep and appetite, and are shown to have analgesic properties. Another component for achieving potential anti-cancer synergism is regulating nutrient availability and metabolism by calorie restriction and intermittent fasting in cancer cells. As tumours require a lot of energy to grow and because glucose is constantly available, malignant cells often opt to use glucose as a primary source of ATP production through substrate-level phosphorylation (fermentation) rather than through oxidative phosphorylation. Thus, periodic depletion of cancer cells of primary fuel, glucose, could result in a strong synergy in killing cancer cells by chemo- and possibly radiotherapy when combined with cannabinoids. This commentary will discuss what is known about such combinatorial treatments, including potential mechanisms and future protocols.

Self-reported immune status and COVID-19 associated subjective cognitive functioning in post-COVID-19 syndrome: Examination of an Irish cohort.

Cognitive changes are very frequently reported by people with post-COVID-19 syndrome (PCS), but there is limited understanding of the underpinning mechanisms leading to these difficulties. It is possible that cognitive difficulties are related to immune status and/or low mood. The aim of the present study was to examine the relationship between immune status and cognitive functioning in PCS, while considering whether depression symptoms also influence this association. Participants were recruited in an online study of cognitive and psychological consequences of PCS, involving individuals attending a post-COVID clinic in an acute general hospital in Ireland, and a comparison sample of age- and sex-matched community controls who had also been infected with COVID-19 but had not experienced PCS. Participants with PCS (n=71) and community controls (n=50) completed the immune status questionnaire, Cognitive Failures Questionnaire (CFQ), Hospital Anxiety and Depression Scale (HADS), and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F). Significant differences were observed between groups in terms of perceived immune status, perceived cognitive function, depression scores, and fatigue, with the "PCS" group reporting lower immune status, more cognitive difficulties, and higher levels of depression and fatigue. Regression analysis in the PCS group indicated that immune status and depression significantly contributed to variance in subjective cognitive functioning, with immune status remaining a significant predictor of cognitive functioning scores even when accounting for depression, fatigue, and other covariates related to PCS, such as Body Mass Index(BMI). Our findings suggest that subjective cognitive functioning is influenced by self-reported immune status in PCS, emphasising the importance of immune status, cognitive, and mood screening as part of routine clinical care in PCS.

Risk factors for prolonged infection and secondary infection in pediatric severe sepsis.

Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications. We performed a secondary analysis of clinical data from 401 subjects enrolled in the PHENOtyping sepsis-induced Multiple organ failure Study. We examined factors associated with prolonged infection, defined as infection that continued to be identified 7days or more from initial identification, and secondary infection, defined as new infections identified ≥ 3days from presentation. Multivariable adjustment was performed to examine laboratory markers of immune depression, with immunocompromised and immunocompetent subjects analyzed separately. Illness severity, immunocompromised status, invasive procedures, and site of infection were associated with secondary infection and/or prolonged infection. Persistent lymphopenia, defined as an absolute lymphocyte count (ALC) < 1000 cells/µL twice in the first five days, and persistent neutropenia, defined as absolute neutrophil count (ANC) < 1000 cells/µL twice in the first five days, were associated with secondary and prolonged infections. When adjusted in multivariable analysis, persistent lymphopenia remained associated with secondary infection in both immunocompromised (aOR = 14.19, 95% CI [2.69, 262.22] and immunocompetent subjects (aOR = 2.09, 95% CI [1.03, 4.17]). Persistent neutropenia was independently associated with secondary infection in immunocompromised subjects (aOR = 5.34, 95% CI [1.92, 15.84]). Secondary and prolonged infections were associated with worse outcomes, including death. Laboratory markers of immune suppression can be used to predict secondary infection. Lymphopenia is an independent risk factor in immunocompromised and immunocompetent patients for secondary infection.

Effect of nutritional status on occurrence of pneumonia after traumatic cervical spinal cord injury

Pneumonia after cervical spinal cord injury (CSCI) is a common and serious complication; however, its nutrition-related etiology has not yet been elucidated. This study aimed to elucidate the effects of nutritional factors on pneumonia after CSCI. Patients with acute traumatic CSCI who were admitted within 3 days after injury and followed up for at least 3 months were retrospectively examined. Occurrence of pneumonia, nutritional status, severity of dysphagia, vital capacity, use of respirators, and motor scores for paralysis were evaluated. Of 182 patients included in this study, 33 (18%) developed pneumonia. Multiple logistic regression analysis revealed that low nutritional status, severe paralysis, and low vital capacity were significant risk factors for pneumonia. The severity of paralysis, respiratory dysfunction, and poor nutritional status can affect the occurrence of pneumonia after CSCI. In addition to respiratory management, nutritional assessment and intervention may play key roles in preventing pneumonia associated with spinal cord injury-induced immune depression. Nutritional care should be provided as soon as possible when the nutritional status of a patient worsens after an injury.

Overview of Opportunistic Bacteria

The receptive patient and the bacterium serve as the two defining criteria for opportunistic bacteria. Theoretically, no saprophytic or typical commensal microbes can infiltrate a healthy receptive person. Only specific "undesirable" commensal species, "such as Vargues' Specific Pathogenic Bacteria", can infect this person. Several species from the typical commensal flora, or opportunistic bacteria in the wide meaning of the word, “may infiltrate an otherwise healthy host if their immune defences temporarily deteriorate”. Even species that were previously thought to be non-virulent may assault an immunosuppressed patient with a significant and protracted immune system depression, “including various saprophytic and commensal microbes”. Several bacteria that are typically found in water, food, and the air have recently become opportunistic pathogens in both people and animals. The issue is made more difficult by the introduction of many antibiotic-resistant strains of these opportunistic pathogens, which make hospital-acquired infections in susceptible hosts challenging to treat in the setting of illness.

Investigating the role of TGF-β and BDNF in cancer-related depression: a primary cross-sectional study.

Cancer-related depression is a well-documented condition that significantly impacts long-term quality of life. Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neurogenesis and neuronal plasticity, has been implicated in various neuropsychological disorders including depression associated with cancer. Cytokines, on the other hand, play a crucial role in regulating depression, potentially by influencing BDNF expression. Transforming growth factor-β (TGF-β), a key immune regulator within the tumor microenvironment, has been found to elevate BDNF levels, establishing a link between peripheral immune responses and depression. The study aims to investigate the correlation of TGF-β and BDNF in cancer-related depression. This study involved a cohort of 153 gynecological patients, including 61 patients with gynecological cancer and 92 patients without cancer. Depression levels were assessed using the subscale of Hospital Anxiety and Depression Scale (HADS-D), and TGF-β and BDNF plasma levels were measured using enzyme-linked immunosorbent assay (ELISA). The study revealed elevated plasma TGF-β levels in patients with cancer (32.24 ± 22.93 ng/ml) compared to those without cancer (25.24 ± 19.72 ng/ml) (P = 0.046). Additionally, reduced levels of BDNF were observed in patients presenting depression symptoms (44.96 ± 41.06 pg/ml) compared to those without depression (133.5 ± 176.7 pg/ml) (P = 0.036). Importantly, a significant correlation between TGF-β and BDNF was found in patients without cancer but with depression (correlation coefficient = 0.893, **P < 0.01). Interestingly, cancer appeared to influence the association between TGF-β and BDNF in patients with depression, as evidenced by a significant difference in the correlation of TGF-β and BDNF between cancer and non-cancer groups (P = 0.041). These findings underscore the active involvement of TGF-β and BDNF crosstalk in the context of cancer-related depression.

Therapeutic Effect of Music Therapy on Patients with End-stage Cancer: A Retrospective Study.

The aim of this study was to retrospectively analyze the effect of music therapy on patients with end-stage cancer in hospice care. This retrospective cohort study included 195 patients with end-stage cancer from January 2021 to December 2023. The conventional group comprised patients who received routine hospice care, whereas the combination group comprised those who received routine hospice care and music therapy. The immune indicators, anxiety and depression scores, quality of life scores, and sleep quality scores of both groups were compared before and after management. Before management, no significant differences were observed in the immune indicators, anxiety and depression scores, quality of life scores, and sleep quality scores between both groups (P > 0.05). However, after management, the immune indicators lymphocytes CD3+ and CD4+ were significantly higher in the combination group than in the conventional group (P < 0.05); in contrast, anxiety and depression and the Pittsburgh Sleep Quality Index scores were lower in the combination group than in the conventional group (P < 0.05). Lastly, the World Health Organization Quality of Life Brief Version scores were significantly higher in all domains in the combination group than in those in the conventional group; furthermore, the degree of decline in the physical, psychological, and social relationship domain scores was smaller in the combination group than in the conventional group (P < 0.05). For patients with end-stage cancer, music therapy can improve their immune status, quality of life, and sleep and ameliorate their anxiety and depression.

Single-cell RNA sequencing reveals peripheral blood leukocyte responses to spinal cord injury in mice with humanised immune systems

Next-generation humanised mouse models and single-cell RNA sequencing (scRNAseq) approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). We hypothesised that the use of such mice could help advance our understanding of spinal cord injury-induced immune depression syndrome (SCI-IDS), and also how human leukocytes change as they migrate from the circulation into the lesion site. Our scRNAseq experiments, supplemented by flow cytometry, demonstrate the existence of up to 11 human immune cell (sub-) types and/or states across the blood and injured spinal cord (7 days post-SCI) of humanised NSG-SGM3 mice. Further comparisons of human immune cell transcriptomes between naïve, sham-operated and SCI mice identified a total of 579 differentially expressed genes, 190 of which were ‘SCI-specific’ (that is, genes regulated only in response to SCI but not sham surgery). Gene ontology analysis showed a prominent downregulation of immune cell function under SCI conditions, including for T cell receptor signalling and antigen presentation, confirming the presence of SCI-IDS and the transcriptional signature of human leukocytes in association with this phenomenon. We also highlight the activating influence of the local spinal cord lesion microenvironment by comparing the transcriptomes of circulating versus infiltrated human immune cells; those isolated from the lesion site were enriched for genes relating to both immune cell activity and function (e.g., oxidative phosphorylation, T cell proliferation and antigen presentation). We lastly applied an integrated bioinformatics approach to determine where immune responses in humanised NSG-SGM3 mice appear congruent to the native responses of human SCI patients, and where they diverge. Collectively, our study provides a valuable resource and methodological framework for the use of these mice in translational research.

Quantitative PCR as a marker for preemptive therapy and its role in therapeutic control in Trypanosoma cruzi/HIV coinfection.

Trypanosoma cruzi and HIV coinfection can evolve with depression of cellular immunity and increased parasitemia. We applied quantitative PCR (qPCR) as a marker for preemptive antiparasitic treatment to avoid fatal Chagas disease reactivation and analyzed the outcome of treated cases. This mixed cross-sectional and longitudinal study included 171 Chagas disease patients, 60 coinfected with HIV. Of these 60 patients, ten showed Chagas disease reactivation, confirmed by parasites identified in the blood, cerebrospinal fluid, or tissues, 12 exhibited high parasitemia without reactivation, and 38 had low parasitemia and no reactivation. We showed, for the first time, the success of the timely introduction of benznidazole in the non-reactivated group with high levels of parasitemia detected by qPCR and the absence of parasites in reactivated cases with at least 58 days of benznidazole. All HIV+ patients with or without reactivation had a 4.0-5.1 higher chance of having parasitemia than HIV seronegative cases. A positive correlation was found between parasites and viral loads. Remarkably, treated T. cruzi/HIV-coinfected patients had 77.3% conversion from positive to negative parasitemia compared to 19.1% of untreated patients. Additionally, untreated patients showed ~13.6 times higher Odds Ratio of having positive parasitemia in the follow-up period compared with treated patients. Treated and untreated patients showed no differences regarding the evolution of Chagas disease. The main factors associated with all-cause mortality were higher parasitemia, lower CD4 counts/μL, higher viral load, and absence of antiretroviral therapy. We recommend qPCR prospective monitoring of T. cruzi parasitemia in HIV+ coinfected patients and point out the value of pre-emptive therapy for those with high parasitemia. In parallel, early antiretroviral therapy introduction is advisable, aiming at viral load control, immune response restoration, and increasing survival. We also suggest an early antiparasitic treatment for all coinfected patients, followed by effectiveness analysis alongside antiretroviral therapy.

Enhancing bovine immune, antioxidant and anti-inflammatory responses with vitamins, rumen-protected amino acids, and trace minerals to prevent periparturient mastitis.

Mastitis, the inflammatory condition of mammary glands, has been closely associated with immune suppression and imbalances between antioxidants and free radicals in cattle. During the periparturient period, dairy cows experience negative energy balance (NEB) due to metabolic stress, leading to elevated oxidative stress and compromised immunity. The resulting abnormal regulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with increased non-esterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA) are the key factors associated with suppressed immunity thereby increases susceptibility of dairy cattle to infections, including mastitis. Metabolic diseases such as ketosis and hypocalcemia indirectly contribute to mastitis vulnerability, exacerbated by compromised immune function and exposure to physical injuries. Oxidative stress, arising from disrupted balance between ROS generation and antioxidant availability during pregnancy and calving, further contributes to mastitis susceptibility. Metabolic stress, marked by excessive lipid mobilization, exacerbates immune depression and oxidative stress. These factors collectively compromise animal health, productive efficiency, and udder health during periparturient phases. Numerous studies have investigated nutrition-based strategies to counter these challenges. Specifically, amino acids, trace minerals, and vitamins have emerged as crucial contributors to udder health. This review comprehensively examines their roles in promoting udder health during the periparturient phase. Trace minerals like copper, selenium, and calcium, as well as vitamins; have demonstrated significant impacts on immune regulation and antioxidant defense. Vitamin B12 and vitamin E have shown promise in improving metabolic function and reducing oxidative stress followed by enhanced immunity. Additionally, amino acids play a pivotal role in maintaining cellular oxidative balance through their involvement in vital biosynthesis pathways. In conclusion, addressing periparturient mastitis requires a holistic understanding of the interplay between metabolic stress, immune regulation, and oxidative balance. The supplementation of essential amino acids, trace minerals, and vitamins emerges as a promising avenue to enhance udder health and overall productivity during this critical phase. This comprehensive review underscores the potential of nutritional interventions in mitigating periparturient bovine mastitis and lays the foundation for future research in this domain.

Psychological impact of the COVID-19 pandemic on chronic haemodialysis patients in eastern Morocco: a cross-sectional study

chronic haemodialysis patients are a vulnerable population significantly affected by the COVID-19 pandemic, which has had a severe impact on people with co-morbidities and immune system depression, which increases the risk of infection and of developing severe form of COVID-19. The purpose of this study is to assess the impact of the COVID-19 pandemic on the mental health and quality of life of chronic haemodialysis patients. we conducted a descriptive cross-sectional survey among 175 chronic hemodialysis patients using the Mini International Neuropsychiatric Interview Moroccan Arab Version 5.0.0 scale, the Perceived Stress Scale, and the Quality of Life Scale for Chronic Hemodialysis Patients (KDQOL-SFTM 1.3). one hundred and seventy-five (175) participants were recruited, of whom 76 patients had COVID-19. COVID-19 infection was significantly associated with age (p=0.018), psychiatric disorders (p=0.00), a history of suicide attempts (p=0.006) and high-stress levels (p=0.01). The quality of life of chronic haemodialysis patients was significantly impaired in patients with COVID-19 (p=0.00), especially in subjects who were elderly (p=0.034), lived alone (p=0.004), had a history of organic (p=0.04), psychiatric (p=0.00), or substance abuse issues (p=0.003), as well as in patients with a symptomatic form (p=0.001), complications (p=0.00), or hospitalisation secondary to COVID-19 (p=0.00), and those with severe stress (p=0.00). the mental health and quality of life of chronic haemodialysis patients were mainly negatively influenced during the COVID-19 pandemic.

Evolutionary proteogenomic landscape from pre-invasive to invasive lung adenocarcinoma

Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.

Association between Priority Conditions and Access to Care, Treatment of an Ongoing Condition, and Ability to Obtain Prescription Medications among Medicare Beneficiaries during the COVID-19 Pandemic

Several comorbid conditions have been observed to be associated with an increased risk of poor outcomes following a diagnosis of COVID-19. The purpose of this investigation was to assess associations between Centers for Medicare and Medicaid Services (CMS) designated priority conditions and an inability to access care, treat ongoing conditions, and obtain prescription medications among Medicare beneficiaries in the United States during the COVID-19 pandemic. Nationally representative CMS Medicare Current Beneficiary Survey (MCBS) COVID-19 Supplement Public Use Files (PUF) were analyzed via bivariable, binomial generalized linear models across three time periods: (1) Summer 2020; (2) Fall 2020; and (3) Winter 2021. Across an estimated 55.3–57.4 million Medicare beneficiaries, approximately one-fifth reported an inability to access at least one type of care at the onset of the pandemic. Significantly worse odds of an ability to get care across various time periods was observed among several priority conditions including immune disorders, cancer, depression, osteoporosis, diabetes, arthritis, and numerous cardiovascular and pulmonary conditions. Among those reporting an inability to access care, approximately one-third involved treatment of an ongoing condition, and under one-tenth involved prescription medications. To identify modifiable risk factors and to develop active interventions, future work should continue to assess the complex associations between outcomes, access to care, comorbidities, evolving healthcare infrastructures, computerization, and various public health initiatives.

Bidirectional Relationship between HIV/HBV Infection and Comorbid Depression and/or Anxiety: A Systematic Review on Shared Biological Mechanisms.

Mental disorders that are comorbid with chronic infectious diseases may worsen clinical outcomes and patients' quality of life. We hypothesized that depression and/or anxiety syndromes or symptoms comorbid with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) infection might stem from shared biological mechanisms. We conducted a systematic review applying the PRISMA statement by searching into the PubMed, APA PsycInfo, and Scopus databases. We examined the literature on HIV/HBV infection comorbid with depression and/or anxiety in adults ≥18 years. Thirty-one studies on HIV and three on HBV were analyzed. The Tat protein contributed to HIV-associated mood disorders due to the protein's ability to cause neurodegeneration and induce hypothalamic-pituitary-adrenal (HPA) axis dysregulation in response to natural stressors. The decreased brain-derived neurotrophic factor (BDNF) levels also emerged as a mechanism involved in HIV neuropathogenesis and the associated mood symptoms. Neuroinflammation was implicated in depression and/or anxiety onset in patients with HIV/HBV infections. Microglial activation and release of cytokines, in particular, appeared as potential pathogenetic mechanisms. Furthermore, an altered balance between quinolinic acid and kynurenic acid production emerged in HIV patients with comorbid depression, indicating a glutamatergic dysfunction. Inflammatory cytokine production and the downregulation of cellular immune responses contributed to persisting inflammation, delayed healing, and functional decline in patients with chronic hepatitis B (CHB) infection. A shift in type 1-type 2 cytokine balance might be implicated in HBV-related immune pathogenesis, and depression and anxiety might be considered immunomodulatory factors. Cytokines also caused HPA axis hyperactivity, frequently observed in HIV/HBV patients with comorbid depression/anxiety. The present systematic review showed, for the first time, that HIV/HBV and depression and/or anxiety might have several biological mechanisms as common denominators. The longitudinal course of the highlighted biological mechanisms should be explored to establish the causative interrelationship among the involved mechanisms. In addition, future research should investigate the possibility that a patient's clinical outcome might improve using pharmacological treatments acting on the biological mechanisms we described as common denominators of chronic inflammatory infective diseases and depression/anxiety.

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Truly Refractory Hodgkin Lymphoma Patients Is Highly Effective and Responses Are Mediated By NK Cells

Background In the relapsed/refractory Hodgkin Lymphoma (HL) setting (RHL), the achievement of complete remission (CR) is fundamental in order to proceed with allogeneic stem cell transplantation (HSCT) consolidation. Immune checkpoint inhibitors (CI) have demonstrated clinical activity in patients relapsing after ASCT, although only 20% CR rate is observed. In order to improve the efficacy of CI in RHL, we previously reported a salvage treatment based on early CI therapy following post-autologous stem cell transplantation (ASCT) with the reinfusion of unselected autologous lymphocytes infusions (ALI). The rationale of this approach is based on the achievement of a disease debulking through ASCT conditioning. Early administration of CI (nivolumab) is performed on a minimal disease burden, while reinfusions of ALI reduce post ASCT immune depression eliciting CI efficacy. Aims The aim of this study was to evaluate the efficacy of the procedure in terms of CR rates and overall survival (OS) after an extended follow up. Biological endpoint was to investigate the lymphocyte subpopulations involved in the mechanism of response and investigate the role of NK-cells mediating anti tumor responses in HL. Methods Patient were eligible to this study after failure to respond to first line treatment (i.e. positive PET2 or PET6 scan) and underwent autologous lymphocyte apheresis upon enrollment. All patients received conventional 2nd line chemo followed by 3rd line chemo-immunotherapy with Brentuximab-Vedotin (BV) in non-responding patients. Patient failing to achieve CR after BV were enrolled in the treatment arm and proceeded to ASCT + CI and ALI, whereas patients responding to 2nd- or 3rd treatment received ASCT followed by ALI alone, as a control cohort (figure 1A). NK cell degranulation assay was evaluated by staining for CD107a (LAMP-1) expression on healthy-donors derived NK cells exposed to HL cell lines (L428 and L250), in the presence or absence of monoclonal antibodies targeting inhibitory or activating receptors. Surface and intracellular staining was performed prior to flow cytometry and analysis was performed on the CD3-/CD56+ gated population. Results Twenty-one patients with RHL (median age 32 years; range 18-65) underwent lymphocyte apheresis after failure of 1st line chemo and then proceeded to salvage therapy. Thirteen patients failed to respond to 2nd and 3rd line therapy and thus received early post-transplant CI supported with four ALI. Eight patients responded to 2nd line chemo (n=6) or 3rd line BV (n=2) and received ASCT followed by ALI alone. No adverse events were recorded, specifically, no immune-related toxicity was observed. All patients receiving ALI + CI (treated patients) achieved negative PET scan CR. Eight of them received HSCT consolidation. One patient refusing HSCT after achieving CR in this study relapsed and responded to CI re treatment followed by HSCT. All patients in the treatment arm are alive and disease-free after a median follow-up of 32 months (95% CI 26.4-51.0). Median disease-free survival (DFS) was not reached in treatment arm (Fig 1B). Four of the patients in the control arm relapsed (50%). Three of them responded to 3rd line therapy and proceeded to HSCT. One patient achieved CR with conventional CI treatment but refused HSCT and the other relapsing patient died because of progressive lymphoma after failure to achieve CR with conventional single agent CI. Median DFS in the control arm was 22 months (Fig 1B). NK cells showed higher expansion and a faster maturation in the treatment arm, compared to the control arm (p&amp;lt;0.05). As expected, HL cells lines do not express HLA class I and II, but express activating NK cells receptors (aNKG2D, aNKp30, aNKp46, aDNAM-1). In vitro, the activation of each of those receptors was able to trigger NK cells degranulation. Similarly, PD-L1 and PD-L2 blockade on HL cell lines significantly increased NK cell degranulation (p&amp;lt;0.05). Taken together, those observations support the role of NK cells in this setting. Conclusions Our data show very high anti-tumor activity of ALI + CI for RHL, allowing most patients to proceed to HSCT. RHL patients in the treatment arm had an excellent outcome if compared to the control arm, which included patient who did respond to conventional treatment. Biological data suggests that this approach may accelerate NK cell development/maturation and suggest that NK cells may mediate response to CI in HL.

Microplastics in sediment of Indonesia waters : A systematic review of occurrence, monitoring and potential environmental risks

Microplastics, or plastic particles smaller than 5 mm, are a growing ecotoxicological problem for both human health and aquatic habitats. Even though microplastic pollution affects the air, water, and land widely, these habitats are often viewed as distinct from one another while in fact they are tightly related. The purpose of this work is to review the body of scientific literature on microplastic studies in Indonesian watershed sediment. Google Scholar has identified around 57 papers about microplastic pollution that were published between 2017 and 2023. Papers about sediment for rivers, lakes, marine, and estuaries are categorized further based on (i) their occurrence and characterization, (ii) their intake by and effects on species, and (iii) their fate and transport issues. Even at low concentrations of 10 μg/mL, microplastics cause harmful effects for people and animals, including cytotoxicity, immunological response, oxidative stress, barrier characteristics, and genotoxicity. When marine animals eat microplastics, their gastrointestinal tract physiology changes, and they also experience immune system depression, oxidative stress, cytotoxicity, differential gene expression, and growth inhibition. In addition, the bioaccumulation of microplastics in aquatic creatures' tissues may harm the aquatic ecosystem and may spread to people and birds. Through behavioural changes and policy changes, such imposing taxes, bans, or price increases on plastic carrier bags, plastic usage has been dramatically decreased to 8–85% in many different nations across the globe. The strategy for minimizing microplastics is structured like an upside-down pyramid: prevention is at the top, then reduction, reuse, recycling, recovery, and, as the least desirable alternative, disposal.Keywords:MicroplasticsSedimentIndonesia WatersEnvironmental RiskPollutant Aquatic

Evidence of a conserved mammalian immunosuppression mechanism in Lutzomyia longipalpis upon infection with Leishmania.

Sand flies (Diptera: Phlebotominae) belonging to the Lutzomyia genus transmit Leishmania infantum parasites. To understand the complex interaction between the vector and the parasite, we have been investigating the sand fly immune responses during the Leishmania infection. Our previous studies showed that genes involved in the IMD, Toll, and Jak-STAT immunity pathways are regulated upon Leishmania and bacterial challenges. Nevertheless, the parasite can thrive in the vectors' gut, indicating the existence of mechanisms capable of modulating the vector defenses, as was already seen in mammalian Leishmania infections. In this study, we investigated the expression of Lutzomyia longipalpis genes involved in regulating the Toll pathway under parasitic infection. Leishmania infantum infection upregulated the expression of two L. longipalpis genes coding for the putative repressors cactus and protein tyrosine phosphatase SHP. These findings suggest that the parasite can modulate the vectors' immune response. In mammalian infections, the Leishmania surface glycoprotein GP63 is one of the inducers of host immune depression, and one of the known effectors is SHP. In L. longipalpis we found a similar effect: a genetically modified strain of Leishmania amazonensis over-expressing the metalloprotease GP63 induced a higher expression of the sand fly SHP indicating that the L. longipalpis SHP and parasite GP63 increased expressions are connected. Immuno-stained microscopy of L. longipalpis LL5 embryonic cells cultured with Leishmania strains or parasite conditioned medium showed cells internalization of parasite GP63. A similar internalization of GP63 was observed in the sand fly gut tissue after feeding on parasites, parasite exosomes, or parasite conditioned medium, indicating that GP63 can travel through cells in vitro or in vivo. When the sand fly SHP gene was silenced by RNAi and females infected by L. infantum, parasite loads decreased in the early phase of infection as expected, although no significant differences were seen in late infections of the stomodeal valve. Our findings show the possible role of a pathway repressor involved in regulating the L. longipalpis immune response during Leishmania infections inside the insect. In addition, they point out a conserved immunosuppressive effect of GP63 between mammals and sand flies in the early stage of parasite infection.

Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023.

Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients. During its 2023 meeting in Bristol, the International Consultation on Incontinence-Research Society (ICI-RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think-tank. Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro-inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system-adipocyte-bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor-α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled. The think-tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High-priority research questions were identified.

A Study on Mycoplasmal and Viral Infections in Bovine Keratoconjunctivitis

Background: Infectious bovine keratoconjunctivitis (IBK or “pink eye”) is the most common infectious ocular disease in cattle worldwide. In addition to Moraxella bovis as the principal causative agent, infectious bovine rhinotracheitis virus (BHV-1) and Mycoplasma species probably act as risk factors for IBK. Objectives: This study aimed to evaluate the association between the detection of Mycoplasma sp., bovine herpesvirus 1 (BHV-1), and bovine viral diarrhea virus (BVDV) in the conjunctival sac of the eye and IBK. Methods: Polymerase chain reaction (PCR) was employed to detect Mycoplasma sp., BHV-1, and BVDV in samples collected from IBK-affected and healthy eyes. Results: Based on the PCR results, Mycoplasma sp. was detected in 63.6% and 47.2% of IBK-affected and healthy eyes, respectively. BHV-1 was detected in 59.1% and 36.1% of affected and healthy eyes, respectively. BVDV was detected in 65.9% and 58.3% of affected and healthy eyes, respectively. BHV-1 was the only agent significantly (P&lt;0.05) associated with IBK lesions (isolated from 59.1% of affected vs 36.1% of healthy eyes). Conclusion: Based on the study results, BHV-1 may be a risk factor in the pathogenesis of infectious bovine keratoconjunctivitis, and mechanisms other than immune depression might be involved in its pathogenicity.