Oxalate Alters Cellular Bioenergetics, Redox Homeostasis, Antibacterial Response, and Immune Response in Macrophages.

Individuals with calcium oxalate (CaOx) kidney stones can have secondarily infected calculi which may play a role in the development of recurrent urinary tract infection (UTI). Uropathogenic Escherichia coli (UPEC) is the most common causative pathogen of UTIs. Macrophages play a critical role in host immune defense against bacterial infections. Our previous study demonstrated that oxalate, an important component of the most common type of kidney stone, impairs monocyte cellular bioenergetics and redox homeostasis. The objective of this study was to investigate whether oxalate compromises macrophage metabolism, redox status, anti-bacterial response, and immune response. Monocytes (THP-1, a human monocytic cell line) were exposed to sodium oxalate (soluble oxalate; 50 µM) for 48 hours prior to being differentiated into macrophages. Macrophages were subsequently exposed to calcium oxalate crystals (50 µM) for 48 hours followed by UPEC (MOI 1:2 or 1:5) for 2 hours. Peritoneal macrophages and bone marrow-derived macrophages (BMDM) from C57BL/6 mice were also exposed to oxalate. THP-1 macrophages treated with oxalate had decreased cellular bioenergetics, mitochondrial complex I and IV activity, and ATP levels compared to control cells. In addition, these cells had a significant increase in mitochondrial and total reactive oxygen species levels, mitochondrial gene expression, and pro-inflammatory cytokine (i.e. Interleukin-1ß, IL-1ß and Interleukin-6, IL-6) mRNA levels and secretion. In contrast, oxalate significantly decreased the mRNA levels and secretion of the anti-inflammatory cytokine, Interleukin-10 (IL-10). Further, oxalate increased the bacterial burden of primary macrophages. Our findings demonstrate that oxalate compromises macrophage metabolism, redox homeostasis, and cytokine signaling leading to a reduction in anti-bacterial response and increased infection. These data highlight a novel role of oxalate on macrophage function.

Effects of Vaccination Against Coccidiosis on Gut Microbiota and Immunity in Broiler Fed Bacitracin and Berry Pomace.

Feeding practices have been found to influence gut microbiota which play a major role in immunity of poultry. In the present study, changes in cecal microbiota and humoral responses resulting in the 55 ppm bacitracin (BACI), 1% each of cranberry (CP1) and wild blueberry (BP1) pomace alone or in combination (CP+BP) feeding in broiler Cobb 500 vaccinated or not against coccidiosis were investigated. In the non-vaccinated group, no significant treatment effects were observed on performance parameters. Vaccination significantly affected bird's performance parameters particularly during the growing phase from 10 to 20 days of age. In general, the prevalence of coccidiosis and necrotic enteritis (NE) was reduced by vaccination (P < 0.05). BACI-treated birds showed low intestinal lesion scores, and both CP1 and BP1 feed supplementations reduced Eimeria acervulina and Clostridium perfringens incidences similar to BACI. Vaccination induced change in serum enzymes, minerals, and lipid levels in 21-day old birds while, levels of triglyceride (TRIG) and non-esterified fatty acids (NEFA) were higher (P < 0.05) in CP1 treated non-vaccinated group than in the control. The levels of NEFA were lower in BACI- and CP1-fed birds than in the control in non-vaccinated day 28 old birds. The highest levels of all estimated three immunoglobulins (IgY, IgM, and IgA) were found in the vaccinated birds. Metagenomics analysis of the cecal bacterial community in 21-day old birds showed the presence of Firmicutes (90%), Proteobacteria (5%), Actinobacteria (2%), and Bacteroidetes (2%). In the vaccinated group, an effect of BACI was noted on Proteobacteria (P = 0.03). Vaccination and/or dietary treatments influenced the population of Lactobacillaceae, Enterobacteriaceae, Clostridiaceae, and Streptococcaceae which were among the most abundant families. Overall, this study revealed that besides their beneficial effects on performance, alike bacitracin, berry pomaces in poultry feed have profound impacts on the chicken cecal microbiota and blood metabolites that could be influenced by vaccination against coccidiosis.

The role of the human gut microbiota in colonization and infection with multidrug-resistant bacteria.

About 100 years ago, the first antibiotic drug was introduced into health care. Since then, antibiotics have made an outstanding impact on human medicine. However, our society increasingly suffers from collateral damage exerted by these highly effective drugs. The rise of resistant pathogen strains, combined with a reduction of microbiota diversity upon antibiotic treatment, has become a significant obstacle in the fight against invasive infections worldwide.Alternative and complementary strategies to classical "Fleming antibiotics" comprise microbiota-based treatments such as fecal microbiota transfer and administration of probiotics, live-biotherapeutics, prebiotics, and postbiotics. Other promising interventions, whose efficacy may also be influenced by the human microbiota, are phages and vaccines. They will facilitate antimicrobial stewardship, to date the only globally applied antibiotic resistance mitigation strategy.In this review, we present the available evidence on these nontraditional interventions, highlight their interaction with the human microbiota, and discuss their clinical applicability.

Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections.

Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells that utilize a semi-invariant T cell receptor (TCR) α chain and are restricted by the highly conserved antigen presenting molecule MR1. MR1 presents microbial riboflavin biosynthesis derived metabolites produced by bacteria and fungi. Consistent with their ability to sense ligands derived from bacterial sources, MAIT cells have been associated with the immune response to a variety of bacterial infections, such as Mycobacterium spp., Salmonella spp. and Escherichia coli. To date, MAIT cells have been studied in humans, non-human primates and mice. However, they have only been putatively identified in cattle by PCR based methods; no phenotypic or functional analyses have been performed. Here, we identified a MAIT cell population in cattle utilizing MR1 tetramers and high-throughput TCR sequencing. Phenotypic analysis of cattle MAIT cells revealed features highly analogous to those of MAIT cells in humans and mice, including expression of an orthologous TRAV1-TRAJ33 TCR α chain, an effector memory phenotype irrespective of tissue localization, and expression of the transcription factors PLZF and EOMES. We determined the frequency of MAIT cells in peripheral blood and multiple tissues, finding that cattle MAIT cells are enriched in mucosal tissues as well as in the mesenteric lymph node. Cattle MAIT cells were responsive to stimulation by 5-OP-RU and riboflavin biosynthesis competent bacteria in vitro. Furthermore, MAIT cells in milk increased in frequency in cows with mastitis. Following challenge with virulent Mycobacterium bovis, a causative agent of bovine tuberculosis and a zoonosis, peripheral blood MAIT cells expressed higher levels of perforin. Thus, MAIT cells are implicated in the immune response to two major bacterial infections in cattle. These data suggest that MAIT cells are functionally highly conserved and that cattle are an excellent large animal model to study the role of MAIT cells in important zoonotic infections.

Parental experience of prophylactic antibiotics.

BACKGROUND AND OBJECTIVES: Long-term prophylactic antibiotics are often used to prevent bacterial infections. However, supporting evidence for this is not always robust. Including parents in decisions relating to medication is key to medicines optimisation. Parental concern regarding medication is a major determinant of poor adherence. This study explores parental experiences of having a child prescribed prophylactic antibiotics and how that affects their antibiotic use behaviour. METHODS: We conducted a prospective, single-centre, exploratory, qualitative study at Sheffield Children's Hospital. Through 15 interviews, involving 18 participants, we explored parental 'lived experiences' and attitudes towards azithromycin prophylaxis prescribed for various respiratory conditions. Thematic analysis was conducted. RESULTS: The overriding factor influencing parental decisions about the uptake of antibiotic prophylaxis is wanting their child to be well now. The main concern voiced by parents is that of antibiotic resistance given their children are high users of antibiotics. This is however seen as a problem for the future, not the present. Preparing families adequately helps prevent practical difficulties relating to medication. Facilitating 'normalisation' of prophylaxis through daily routines and minimising disruption to the family environment may reduce parental anxiety, promote adherence and result in easing of potential restrictions to the child's daily activities. CONCLUSION: Grounded in our deeper understanding, we propose a behavioural model that describes phases parents go through while having a child on prophylactic antibiotics. Time invested in holistically addressing the parental experience and having an awareness of potential issues parents face, may facilitate medication adherence, reduce anxieties and improve doctor-parent relationships.

Dietary Azomite, a natural trace mineral complex, improved the growth, immunity response, intestine health and resistance against bacterial infection in largemouth bass (Micropterus salmoides).

Azomite is a hydrated calcium sodium aluminosilicat rich in rare earth elements. To investigate the dietary effects of Azomite on growth, intestine microbiota and morphology, immunohematological changes and disease resistance, seven diets with Azomite supplementation of 0 (the control), 1.0, 2.0, 3.0, 4.0, 5.0 and 6.0 g/kg (A0, A1, A2, A3, A4, A5, A6), were prepared and fed to largemouth bass, Micropterus salmoides (7.96 ± 0.19) for 60 days. The results revealed that the weight gain (WG) increased first and then decreased with the increasing dietary Azomite, and the A2 group presented the highest WG and lowest feed conversion ratio among all the groups. The supplementation of 2.0 g/kg Azomite significantly increased the intestine protease activity, the crude protein of whole body and protein retention (P < 0.05), and high inclusion of Azomite (6.0 g/kg) significantly reduced the lipid retention (P < 0.05). The amounts of red blood cells in A5, A6 groups, white blood cells in A3, A5, A6 groups and lymphocyte in A2-A6 groups were all significantly higher than those in the control group (P < 0.05). In addition, serum superoxide dismutase and catalase activities in A5, A6 groups, and serum alkaline phosphatase and lysozyme activities in A2-A4 groups showed significantly higher values than the control group (P < 0.05). Intestinal microbiota analysis indicated that the Tenericutes abundance was increased, whereas Proteobacteria abundance was decreased in all Azomite supplemented groups. The villus height in A2-A4 groups, and the villus width in A2 group were significantly higher than those of the control group (P < 0.05). The cumulative mortality was reduced by the addition of 2.0-5.0 g/kg Azomite after challenging with A. hydrophila (P < 0.05). In conclusion, proper addition of Azomite in diets improved the growth, intestine morphology, immune response and disease resistance in largemouth bass, and the optimal inclusion was estimated to be 2.0-3.0 g/kg diet.

Future perspective: high-throughput construction of new ultrasensitive cytokine and virion liquid chips for high-throughput screening (HTS) of anti-inflammatory drugs or clinical diagnosis and treatment of inflammatory diseases.

Pathogen-host cell interactions play an important role in many human infectious and inflammatory diseases. Several pathogens, including Escherichia coli (E. coli), Mycobacterium tuberculosis (M. tb), and even the recent 2019 novel coronavirus (2019-nCoV), can cause serious breathing and brain disorders, tissue injury and inflammation, leading to high rates of mortality and resulting in great loss to human physical and mental health as well as the global economy. These infectious diseases exploit the microbial and host factors to induce serious inflammatory and immunological symptoms. Thus the development of anti-inflammatory drugs targeting bacterial/viral infection is an urgent need. In previous studies, YojI-IFNAR2, YojI-IL10RA, YojI-NRP1,YojI-SIGLEC7, and YojI-MC4R membrane-protein interactions were found to mediate E. coli invasion of the blood-brain barrier (BBB), which activated the downstream anti-inflammatory proteins NACHT, LRR and PYD domains-containing protein 2(NLRP2), using a proteomic chip conjugated with cell immunofluorescence labeling. However, the studies of pathogen (bacteria/virus)-host cell interactions mediated by membrane protein interactions did not extend their principles to broad biomedical applications such as 2019-nCoV infectious disease therapy. The first part of this feature article presents in-depth analysis of the cross-talk of cellular anti-inflammatory transduction signaling among interferon membrane protein receptor II (IFNAR2), interleukin-10 receptor subunit alpha (IL-10RA), NLRP2 and [Ca2+]-dependent phospholipase A2 (PLA2G5), based on experimental results and important published studies, which lays a theoretical foundation for the high-throughput construction of the cytokine and virion solution chip. The paper then moves on to the construction of the novel GPCR recombinant herpes virion chip and virion nano-oscillators for profiling membrane protein functions, which drove the idea of constructing the new recombinant virion and cytokine liquid chips for HTS of leading drugs. Due to the different structural properties of GPCR, IFNAR2, ACE2 and Spike of 2019-nCoV, their ligands will either bind the extracellular domain of IFNAR2/ACE2/Spike or the specific loops of the GPCR on the envelope of the recombinant herpes virions to induce dynamic charge distribution changes that lead to the variable electron transition for detection. Taken together, the combined overview of two of the most innovative and exciting developments in the immunoinflammatory field provides new insight into high-throughput construction of ultrasensitive cytokine and virion liquid chips for HTS of anti-inflammatory drugs or clinical diagnosis and treatment of inflammatory diseases including infectious diseases, acute or chronic inflammation (acute gouty arthritis or rheumatoid arthritis), cardiovascular disease, atheromatosis, diabetes, obesity, tissue injury and tumors. It has significant value in the prevention and treatment of these serious and painful diseases. Graphical abstract.

Vaccines Against Antimicrobial Resistance.

In the last century, life expectancy has increased considerably, thanks to the introduction of antibiotics, hygiene and vaccines that have contributed to the cure and prevention of many infectious diseases. The era of antimicrobial therapy started in the nineteenth century with the identification of chemical compounds with antimicrobial properties. However, immediately after the introduction of these novel drugs, microorganisms started to become resistant through different strategies. Although resistance mechanisms were already present before antibiotic introduction, their large-scale use and mis-use have increased the number of resistant microorganisms. Rapid spreading of mobile elements by horizontal gene transfer such as plasmids and integrative conjugative elements (ICE) carrying multiple resistance genes has dramatically increased the worldwide prevalence of relevant multi drug-resistant human pathogens such as Staphylococcus aureus, Neisseria gonorrhoeae, and Enterobacteriaceae. Today, antimicrobial resistance (AMR) remains one of the major global concerns to be addressed and only global efforts could help in finding a solution. In terms of magnitude the economic impact of AMR is estimated to be comparable to that of climate global change in 2030. Although antibiotics continue to be essential to treat such infections, non-antibiotic therapies will play an important role in limiting the increase of antibiotic resistant microorganisms. Among non-antibiotic strategies, vaccines and therapeutic monoclonal antibodies (mAbs) play a strategic role. In this review, we will summarize the evolution and the mechanisms of antibiotic resistance, and the impact of AMR on life expectancy and economics.

Pharmacodynamics of immune response biomarkers of interest for evaluation of treatment effects in bacterial infections.

This mini-review discusses the pharmacodynamics of immune-related biomarkers in the area of bacterial infectious diseases that could be of interest from a pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) perspective in the evaluation of treatment effects. The host response to an infection is often poorly defined both in preclinical assessments and in clinical practice when it comes to characterisation of PK and PK/PD relationships. Through population modelling, the time courses and variability of immune response variables can be quantified. Incorporation of such biomarker information into PK and PK/PD models may guide the evaluation of individual response to treatment (right antibiotic, more antibiotic, less antibiotic) and when to stop treatment. Furthermore, translation of results from preclinical systems to clinical scenarios may be improved with the incorporation of biomarker information. Potential biomarkers for these purposes are discussed and a few modelling examples are provided.

Differential effects of aminochlorin derivatives on the phagocytic and inflammatory potentials of mammalian macrophages.

Chlorin derivatives have been known for their biological activities. Especially due to their advanced electron transfer capacity they have been used as photodynamic therapy agent both at clinical and laboratory scales. Photodynamic therapy (PDT) against cancer or an infectious disease aims the development of less side effect on the patient since the activation of the inert drug molecule will start only after the light treatment. In order to increase our library of photodynamic therapy agents, we generated a set of chlorin derivatives and tested their PDT potential on the immune system cells; macrophages. Macrophages are known for their primary role as an inflammatory cell type that have been found in the inflamed tissues of the patients with autoimmune and inflammatory disorders as well as in the tumor environment as tumor associated macrophages. Our derivatives had anti-inflammatory PDT potential in the presence of a danger mimic but they lacked immunostimulatory effect. Moreover, these cells' ability to eliminate an infectious agent or present the danger molecules to the other immune cells were tested by phagocytosis assay in the presence of our compounds. Chlorin derivatives were able to differentially regulate the phagocytic activity of the mammalian macrophages.

Modulation of Gut Microbiota through Dietary Phytochemicals as a Novel Anti-infective Strategy.

Quorum Sensing (QS) is a phenomenon in which bacterial cells communicate with each other with the help of several low molecular weight compounds. QS is largely dependent on population density, and it triggers when the concentration of quorum sensing molecules accumulate in the environment and crosses a particular threshold. Once a certain population density is achieved and the concentration of molecules crosses a threshold, the bacterial cells show a collective behavior in response to various chemical stimuli referred to as "auto-inducers". The QS signaling is crucial for several phenotypic characteristics responsible for bacterial survival such as motility, virulence, and biofilm formation. Biofilm formation is also responsible for making bacterial cells resistant to antibiotics. The human gut is home to trillions of bacterial cells collectively called "gut microbiota" or "gut microbes". Gut microbes are a consortium of more than 15,000 bacterial species and play a very crucial role in several body functions such as metabolism, development and maturation of the immune system, and the synthesis of several essential vitamins. Due to its critical role in shaping human survival and its modulating impact on body metabolisms, the gut microbial community has been referred to as "the forgotten organ" by O`Hara et al. (2006) [1]. Several studies have demonstrated that chemical interaction between the members of bacterial cells in the gut is responsible for shaping the overall microbial community. Recent advances in phytochemical research have generated a lot of interest in finding new, effective, and safer alternatives to modern chemical-based medicines. In the context of antimicrobial research various plant extracts have been identified with Quorum Sensing Inhibitory (QSI) activities among bacterial cells. This review focuses on the mechanism of quorum sensing and quorum sensing inhibitors isolated from natural sources.

Systemic inflammation and the effects of short-term antibiotic treatment for PPM positive patients with stable COPD.

Objective: To evaluate patients with stable COPD for the presence of potentially pathogenic microorganisms (PPM), systemic inflammation and the effects of short-term antibiotic therapy in PPM positive patients. Methods: From January 2016 to June 2017, we enrolled 96 stable COPD patients. Bacterial cultures from sputum collections were quantitated, along with markers for systemic inflammation including serum C-reactive protein (CRP), interleukin-8 (IL-8) and plasma fibrinogen (FIB) in all patients. All enrolled patients were followed for 12 months. Forty patients were identified as PPM positive and were randomly divided into an antibiotic group and a control group. The antibiotic group was treated with moxifloxacin orally for 6 days. Lung function and markers for systemic inflammation were repeatedly measured at 30 days and 6 months in PPM positive subjects. Results: Binary logistic regression analysis showed that risk factors for PPM positive are bronchiectasis (OR 4.18, 95% CI 1.20-14.59; P=0.025), COPD assessment test (CAT) ≥20 (OR 17.55, 95% CI 2.82-109.18; P=0.002), spontaneous sputum (OR 15.09, 95% CI 1.36-168.02; P=0.027) and sputum purulence (OR 38.43, 95% CI 5.39-274.21; P=0.000). CRP and IL-8 were higher in PPM positive group than those in PPM negative group (P=0.001, P=0.007, respectively), but there were no differences of FIB between the two groups (P=0.086). Compared to the PPM negative group, the rate of acute exacerbation of COPD was higher (P=0.029) and time to next acute exacerbation was shorter (P=0.030) in PPM positive group. There were no differences in lung function and systemic inflammatory markers either in the control group or the antibiotic group at different time points of follow-up. Conclusion: PPM exists in stable COPD patients and can cause systemic inflammation and is associated with acute exacerbation of COPD. Short-term antibiotic therapy had no effect on systemic inflammation nor on acute exacerbation of COPD.China Clinical Trials Registry: ChiCTR-IOR-15006769.

Not by (Good) Microbes Alone: Towards Immunocommensal Therapies.

Commensal bacteria have been identified as critical drivers of host resilience to pathogen invasion. The resulting 'competitive exclusion' of pathogens by commensals can arise via multiple mechanisms, including direct competition for sites of colonization, production of metabolic products that inhibit pathogen growth, and modulation of host immune responses (including differential targeting of pathogens). Nonetheless, suppression of pathogens through the combined action of commensals and host immunity is far from inevitable. Here, we utilize a simple, within-host ecosystem model to explore the microbiological and immunological conditions that govern the fate of pathogen colonization. Model analysis leads to the hypothesis that robust elimination of pathogens requires a synergy between host immune defense and commensal bacteria. That is, pathogens can proliferate and establish persistent infections if either the state of the microbiota or the host immune defense falls below critical levels. Leveraging these findings, we advocate for improved integration of nonlinear dynamic models in efforts to understand infection dynamics in an immunological context. Doing so may provide new opportunities to establish baseline indicators for healthy microbiomes and to develop improved therapeutics through targeted modification of feedback amongst commensals and between commensals and the immune system.

The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies.

Mushrooms have been used for various health conditions for many years by traditional medicines practiced in different regions of the world although the exact effects of mushroom extracts on the immune system are not fully understood. AHCC® is a standardized extract of cultured shiitake or Lentinula edodes mycelia (ECLM) which contains a mixture of nutrients including oligosaccharides, amino acids, and minerals obtained through liquid culture. AHCC® is reported to modulate the numbers and functions of immune cells including natural killer (NK) and T cells which play important roles in host defense, suggesting the possible implication of its supplementation in defending the host against infections and malignancies via modulating the immune system. Here, we review in vivo and in vitro effects of AHCC® on NK and T cells of humans and animals in health and disease, providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC®.

Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions.

Patients with liver cirrhosis are susceptible to infections due to various mechanisms, including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine. Bacterial infections are common and represent a reason for progression to liver failure and increased mortality. Fungal infections, mainly caused by Candida spp., are often associated to delayed diagnosis and high mortality rates. High level of suspicion along with prompt diagnosis and treatment of infections are warranted. Bacterial and fungal infections negatively affect the outcomes of liver transplant candidates and recipients, causing disease progression among patients on the waiting list and increasing mortality, especially in the early post-transplant period. Abdominal, biliary tract, and bloodstream infections caused by Gram-negative bacteria [e.g., Enterobacteriaceae and Pseudomonas aeruginosa (P. aeruginosa)] and Staphylococcus spp. are commonly encountered in liver transplant recipients. Due to frequent exposure to broad-spectrum antibiotics, invasive procedures, and prolonged hospitalizations, these patients are especially at risk of developing infections caused by multidrug resistant bacteria. The increase in antimicrobial resistance hampers the choice of an adequate empiric therapy and warrants the knowledge of the local microbial epidemiology and the implementation of infection control measures. The main characteristics and the management of bacterial and fungal infections in patients with liver cirrhosis and liver transplant recipients are presented.

Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications.

Complement is a complex protein network of plasma, and an integral part of the innate immune system. Complement activation results in the rapid clearance of bacteria by immune cells, and direct bacterial killing via large pore-forming complexes. Here we review important recent discoveries in the complement field, focusing on interactions relevant for the defense against bacteria. Understanding the molecular interplay between complement and bacteria is of great importance for future therapies for infectious and inflammatory diseases. Antibodies that support complement-dependent bacterial killing are of interest for the development of alternative therapies to treat infections with antibiotic-resistant bacteria. Furthermore, a variety of novel therapeutic complement inhibitors have been developed to prevent unwanted complement activation in autoimmune inflammatory diseases. A better understanding of how such inhibitors may increase the risk of bacterial infections is essential if such therapies are to be successful.

Diabetes Shared Care Program (DSCP) and risk of infection mortality: a nationwide cohort study using administrative claims data in Taiwan.

OBJECTIVE: The Diabetes Shared Care Program (DSCP) is an integrated care model in Taiwan that has been proven to improve the care quality of patients with diabetes. We aimed to evaluate the efficacy of DSCP in decreasing the hospital mortality of infectious diseases. METHODS: From 1 662 929 patients with type 2 diabetes newly diagnosed between 1999 and 2013, we retrieved a total of 919 patients who participated in the DSCP with the first hospitalisation for an infectious disease as the study cohort and 9190 propensity score-matched patients with type 2 diabetes who did not participate as the comparison.The efficacy of DSCP was evaluated via the following comparisons between the DSCP and non-DSCP cohorts: hospital mortality, 1-year medical cost prior to and during the hospitalisation, and complications, such as receiving mechanical ventilation and intensive care unit admission. The ratio (OR) for hospital mortality of the DSCP participants was calculated by logistical regression. Further stratification analyses were conducted to examine which group of patients with type 2 diabetes benefited the most from the DSCP during hospitalisation for infectious diseases. RESULTS: The DSCP cohort had a lower hospital mortality rate than the non-DSCP participants (2.18% vs 4.82%, p<0.001). The total medical cost during the hospitalisation was lower in the DSCP cohort than in the non-DSCP cohort (NT$72 454±30 429 vs NT$86 385±29 350) (p=0.006). In the logistical regression model, the DSCP participants exhibited a significantly decreased adjusted OR for hospital mortality (adjusted OR=0.42, 95% CI 0.26 to 0.66, p=0.0002). The efficacy of the DSCP was much more prominent in male patients with type 2 diabetes and in patients with lower incomes. CONCLUSION: Participation in the DSCP was associated with a lower risk of hospital mortality for infectious diseases.

Reduction of respiratory infections in asthma patients supplemented with vitamin D is related to increased serum IL-10 and IFNγ levels and cathelicidin expression.

BACKGROUND: Vitamin D is a molecule that modulates the immune response and shows anti-inflammatory effects that are beneficial for the control of chronic diseases such as asthma. The trial aim was to explore the effect of vitamin D supplementation on the colonization of pathogenic bacteria in the upper respiratory tract of allergic asthmatic patients. METHODS: This study was conducted in 86 patients between 18 and 50 years of age who were randomly divided into two groups. Both groups received the treatment recommended by the Global Initiative for Asthma (GINA). One group also received calcitriol (1,25-(OH)2D3), and the other group received a placebo. At baseline and 6 months, skin prick tests were conducted, pharyngeal bacterial cultures were performed, and cathelicidin LL-37 was measured in sputum. Serum levels of IgE, eosinophils, IL-5, IL-9, IL-10, IL-13, and IFNγ were quantified at the beginning and the end of the study. RESULTS: Serum levels of IL-10 and IFNγ increased significantly in the group of patients with vitamin D supplementation, while IL-5, IL-9, and IL-13 decreased significantly. At the end of the trial, IgE and eosinophil levels significantly decreased but allergen sensitivity did not show any changes from baseline. Respiratory infections were drastically reduced, and this decrease was related to the number of patients who had high serum levels of IL-10 and IFNγ and expressed LL-37 in their sputum. CONCLUSION: Treatment of asthma patients with vitamin D reduced respiratory infections, and this effect was related to the increase of cathelicidin LL-37.

Role of divalent metals in infectious disease susceptibility and outcome.

BACKGROUND: Divalent metals play important roles in maintaining metabolism and cellular growth of both eukaryotic hosts and invading microbes. Both metal deficiency and overload can result in abnormal cellular function or damage. Given its central role in host-pathogen interactions, subtle alterations of divalent metal homeostasis can occur in the course of infectious diseases which aim, from the host perspective, either to reduce the availability of respective metals to microbes or to use toxic metal accumulation to eliminate pathogens. AIMS: To provide the reader with background information and clinical data on divalent metal homeostasis in host-pathogen interactions, how this affects the course of infectious disease and whether correction of metal disturbances has shown benefit in infections. SOURCES: An in-depth analysis of PubMed articles related to the topic of this review published in English between 1970 and 2016 was performed. CONTENT: From the microbial perspective, divalent metals are essential for growth and pathogenicity and to mount effective protection against antimicrobial host responses, including toxic radical formation. Microbes have evolved multiple strategies to control their access to divalent metals. From the clinical perspective, alterations of divalent metal levels may result in increased or decreased susceptibility to infection and often occur in response to infections. However, keeping in mind the strategies underlying such alterations, for which the term 'nutritional immunity' was coined, the uncritical correction of such divalent metal imbalances may cause harm to patients. This review addresses the role of the divalent metals iron, selenium, zinc, manganese and copper in infectious diseases from a mechanistic and clinical perspective. IMPLICATIONS: We point out areas of research needed to expand our limited knowledge, hoping to improve the clinical management of patients with infections and to identify promising new targets for treatment by modulation of host or microbe divalent metal metabolism.

Mineralization in newborn calves contributes to health, improve the antioxidant system and reduces bacterial infections.

The first phase of life of dairy calves has elevated mortality indices linked with low immunity and sanitary challenges, mainly bacterial infections are involved in the pathogenesis of diarrhea, the leading cause of death. Also, other important problem is the nutritional deficiencies, such as the mineral deficiency. Thus, the aim of this study was to evaluate whether an intramuscular mineral supplementation based on selenium, copper, potassium, magnesium and phosphorus possess beneficial effects on health of dairy calves. For this, ten calves were divided in two groups: the group A was supplemented with injectable mineral, while the group B was used as control group (without mineral supplementation). The mineral complex was administrated via intramuscularly at dose of 3 mL/animal on days 2 and 14 post-birth. The total blood was collected on days 2, 10, 20 and 30 of life of animals in order to analyze the antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)), blood count and seric biochemistry linked with proteic, lipid and carbohydrate metabolism. Feces samples were also collected on days 10, 20 and 30 of life of animals to perform the total bacterial count, parasitological exam and fecal consistency score. Moreover, the weight and corporal temperature were also evaluated. The mineral supplementation presented beneficial properties to calves from birth to the 30th of life through the increase on activity of antioxidant enzymes, improvement of immunity, and avoiding problems linked with diarrhea and anemia, can be considered an interesting approach to prevent these alterations linked with high mortality in the period of life.