Chronic Bacterial Infection Research Articles

Unmasked immune reconstitution inflammatory syndrome towards B-cell non-Hodgkin lymphoma during treatment of esophageal actinomycosis in a patient with advanced HIV: a case report

BackgroundActinomycosis is an unusual chronic bacterial infection, even rarer in people living with HIV. It is not considered an AIDS-defining disease. However, the role in co-presentation or overlap with other opportunistic conditions of advanced HIV is unknown.Case presentationA 49-year-old Peruvian male presented with a 4-month history of dysphagia, odynophagia, hyporexia and wasting. He underwent an upper digestive endoscopy, in which ulcers with a necrotic center were observed, therefore, the initial diagnostic assumption was esophageal cancer. Subsequent pathology report excluded neoplasms and confirmed the diagnosis of actinomycosis. Serology for human immunodeficiency virus was requested, yielding a positive result. Antimicrobial treatment with amoxicillin and antiretroviral therapy were indicated, with slow clinical improvement. After 4 months, epigastric discomfort presented, for which a new upper digestive endoscopy was performed, revealing a deep gastric ulcer, which was compatible with diffuse large B-cell non-Hodgkin lymphoma.ConclusionEsophageal actinomycosis in people living with HIV is very rare. We suggest HIV-associated immunosuppression is not enough to allow for actinomycosis to develop, and masked underlying entities should be sought. The existence of such entities in people living with HIV should raise awareness of the possibility of unmasked immune reconstitution inflammatory syndrome once treatment has started.

Association of ABO and Rh Blood Groups with Helicobacter pylori Seropositivity in Gonabad City, Iran: A Case-Control Study

Background: Helicobacter pylori infection is one of the most common chronic bacterial infections in humans, affecting large populations worldwide. Objectives: The aim of this study was to investigate the relationship between H. pylori infection prevalence with ABO and Rh blood groups. Methods: This descriptive-analytical study was conducted with a case-control design on individuals with anti-H. pylori positive test. Patients with IgG pylori were included in the study based on the inclusion criteria. The individuals were divided into two groups based on antibody titer. The case group included subjects with positive serological results with a titer greater than 12 u/mL IgG, and the control group entailed subjects with negative serological results with a titer less than 8 u/mL IgG. The ABO and Rh blood groups of both groups were examined based on case information. Finally, the data were entered into the SPSS software, and a significance level of 5% was considered for all analyses. Results: According to the results of this study, there was no significant relationship between the blood group and H. pylori infection (P > 0.05). However, the prevalence of blood type A was significantly higher in individuals with positive H. pylori IgG test. Conclusions: The current study suggests no association between ABO and Rh groups, but people with A blood group infected with H. pylori need more attention.

ORCHITIS and Chronic Granulomatous Disease

Chronic Granulomatous Disease (CGD) is a primary immunodeficiency disorder, which is almost always characterized by impairment of the function of leukocytes and generally presents with recurrent chronic relapsing bacterial or fungal infection. This study reported a three-year-old boy who was referred to the Pediatric Hematology and Oncology Center of Shohada Khalij-e-Fars general hospital, Bushehr with recurrent lymphadenitis, and orchitis, who suffered from this disease. Since confirmation of diagnosis, he is receiving Co-trimoxazole three times per week as prophylaxis, and the plan for him is hematopoietic stem cell transplantation (HSCT).

#6605 A CASE REPORT OF MEMBRANOUS NEPHROPATHY SECONDARY TO SYPHILIS: A STEROID-RESPONSIVE DISEASE?

Abstract Background and Aims Membranous Nephropathy (MN) is among the most common forms of nephrotic syndrome in the adults. MN in adults is most often primary (75-80%) and caused by circulating autoantibodies against podocyte antigens being PLA2R the most important target. In the remaining 20-25% of cases, the MN lesion is associated with various disorders, including infections, autoimmune diseases, thyroiditis, malignancies, and the use of certain drugs. Syphilis is a chronic bacterial infection caused by Treponema Pallidum that can present in the primary, secondary or tertiary forms. Kidneys can be involved during either the secondary or the tertiary phase and the most frequent clinical presentation is nephrotic syndrome underlying membranous nephropathy. Here, we present the case of a 47-year-old man who developed rapidly progressive acute kidney injury, nephrotic syndrome and a blotchy diffuse macular rash secondary to Treponema Pallidum infection. Method Data review and collection of clinical records, kidney biopsy evaluation, treatment and outcomes description. Results A 47-year-old man presented to our hospital complaining about asthenia and dizziness. He reported recent use of both antinflammatory drugs and antibiotics to treat an anal fissure. His past medical history was notable for previous drug abuse and alcohol consumption. Physical examination highlighted peripheral edema and a diffuse macular rash. Serum analysis showed serum creatinine of 2.06 mg/dL, urea 84 mg/dL, haemoglobin 13.8 g/dL, albumin 4 g/dL and protein/creatinine ratio of 17741 mg/g; urinary dipstick was positive for haemoglobinuria and proteinuria. Urine collection revealed 22 g proteins/24h. Kidney ultrasound showed normal kidneys with a preserved cortico-medullary differentiation and thickness. In the next days kidney function worsened (serum creatinine 3 mg/dL and urea 100 mg/dL) and daily proteinuria reached a peak of 35 g/24h. A complete panel of antibodies was searched. IgG4 against PLA2R were negative. ANA, ENA and ANCA were absent, C3 and C4 were in the normal range. Serologic testing for HBV, HCV and HIV were negative. Empiric steroid therapy with prednisone 1 mg/kg/day was started obtaining a rapid improvement in terms of proteinuria and kidney function (Fig. 1), the cutaneous rash fainted. Kidney biopsy was performed and demonstrated a membranous nephropathy. Serologic testing for syphilis revealed positive TPHA (titer, 1:2560; normal value, <1:80) and a positive Venereal Disease Research Laboratory test (VDRL) (titer, 1:32; normal value, <1:2). The presentation suggested the diagnosis of anti-PLA2R negative membranous nephropathy secondary to systemic syphilis. Because of the serious clinical manifestation and the unknown duration of the infection we decided to treat the patient with Benzathine penicillin G 2.4 million units administered as three doses at one week intervals (Schön & Bertsch, 2016). Oral steroid was maintained at a dose of 1mg/kg/body weight and descalation started after 30 days. The proteinuria also improved with a reduction in the 24-hour collection from 30 g to 200 mg and serum creatinine went back to normal. Clinical course according to treatment phases are summarized in Fig. 1. Conclusion As far as we know, this is the first case of PLA2R negative membranous nephropathy secondary to syphilis. Although, antibiotic therapy is pivotal in syphilis treatment, our patient showed a fast improvement of kidney function, proteinuria and fainting of the cutaneous erythema after steroid therapy and before starting antibiotic therapy. This suggested the possible role of steroids in treatment of secondary T. Pallidum infection complicated by anti-PLA2R negative membranous nephropathy. Further researches are needed to better define the possible role of steroids in the context of an infective but immune-complex mediated nephropathy.

A Novel Interleukin 17 Receptor A Mutation in a Child with Chronic Mucocutaneous Candidiasis and Staphylococcal Skin Infections.

Chronic mucocutaneous candidiasis leads to persistent or recurrent fungal infections of the nail, skin, oral, and genital mucosa. Impaired interleukin 17-mediated immunity is a cause of chronic mucocutaneous candidiasis. We aimed to show the pathogenicity of a novel interleukin 17 receptor A mutation through functional studies. After next-generation sequencing analysis showed the interleukin 17 receptor A variant, we confirmed the variant by Sanger sequencing and functional validation of the variant by flow cytometry. We present the case of a 6-year-old male patient who presented with recurrent oral and genital Candida infections and eczema. He had staphylococcal skin lesions, fungal susceptibility, and eczema. The patient carried a novel homozygous nonsense [(c.787C> T) (p.Arg263Ter)] mutation in the interleukin 17 receptor A gene. Sanger sequencing confirmed the variant and revealed the segregation of the variant in the family. We used flow cytometry to detect interleukin 17 receptor A protein expression in peripheral blood mononuclear cells from patients and measured Th17 cell percentage. We observed low interleukin 17 receptor A protein expression in patient peripheral blood mononuclear cells, decreased CD4+ interleukin 17+ cell percentage, and decreased interleukin 17F expression in CD4+ cells compared to healthy controls. Innate immune defects may lead to chronic recurrent fungal and bacterial infections of the skin, mucosa, and nails. Generally, genetic and functional analysis is needed in addition to basic immunological tests.

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates.

Introduction. One third of people with CF in the UK are co-infected by both Staphylococcus aureus and Pseudomonas aeruginosa. Chronic bacterial infection in CF contributes to the gradual destruction of lung tissue, and eventually respiratory failure in this group.Gap Statement. The contribution of S. aureus to cystic fibrosis (CF) lung decline in the presence or absence of P. aeruginosa is unclear. Defining the molecular and phenotypic characteristics of a range of S. aureus clinical isolates will help further understand its pathogenic capabilities.Aim. Our objective was to use molecular and phenotypic tools to characterise twenty-five clinical S. aureus isolates collected from mono- and coinfection with P. aeruginosa from people with CF at the Royal Victoria Infirmary, Newcastle upon Tyne.Methodology. Genomic DNA was extracted and sequenced. Multilocus sequence typing was used to construct phylogeny from the seven housekeeping genes. A pangenome was calculated using Roary, and cluster of Orthologous groups were assigned using eggNOG-mapper which were used to determine differences within core, accessory, and unique genomes. Characterisation of sequence type, clonal complex, agr and spa types was carried out using PubMLST, eBURST, AgrVATE and spaTyper, respectively. Antibiotic resistance was determined using Kirby-Bauer disc diffusion tests. Phenotypic testing of haemolysis was carried out using ovine red blood cell agar plates and mucoid phenotypes visualised using Congo red agar.Results. Clinical strains clustered closely based on agr type, sequence type and clonal complex. COG analysis revealed statistically significant enrichment of COG families between core, accessory and unique pangenome groups. The unique genome was significantly enriched for replication, recombination and repair, and defence mechanisms. The presence of known virulence genes and toxins were high within this group, and unique genes were identified in 11 strains. Strains which were isolated from the same patient all surpassed average nucleotide identity thresholds, however, differed in phenotypic traits. Antimicrobial resistance to macrolides was significantly higher in the coinfection group.Conclusion. There is huge variation in genetic and phenotypic capabilities of S. aureus strains. Further studies on how these may differ in relation to other species in the CF lung may give insight into inter-species interactions.

Antibacterial and antioxidant activity of catechin, gallic acid, and epigallocatechin-3-gallate: focus on nanoformulations

Up to one million secondary metabolites are found in plant species, some of which may have desirable therapeutic activities. Among these secondary metabolites, catechin, gallic acid, and epigallocatechin-3-gallate are natural phenolic compounds with promising antioxidant and antibacterial activity. However, these compounds have disadvantages of poor solubility, low bioavailability in physiological conditions, and side effects in patients. Therefore new strategies could rely on formulations with other synthetic and natural materials. Nanoformulations of secondary metabolites could be new efficient strategies to treat many chronic bacterial infections. Combinations and conjugates of catechin, gallic acid, and epigallocatechin-3-gallate with various antibiotics could reduce the dose of these compounds, increase their antibacterial activity, and decrease cytotoxicity against healthy cells. For instance, a smart combination of two or more secondary metabolites may improve therapeutic applications in physiological conditions. In this regard, the growth of antibiotic-resistant bacteria, specifically multidrug-resistant bacteria with overexpression of efflux pumps and expression of the penicillinase enzyme, has been inhibited significantly. According to recent investigations, this review will discuss the advances and challenges of new micro and nanoformulations of these natural products.

P190 Nanostructured formulation of a novel hybrid iminosugar/steroid agent for application in cystic fibrosis lung disease

Chronic bacterial infections and exaggerated inflammation of airways are hallmarks of Cystic Fibrosis (CF) and are significant causes of morbidity and mortality in CF patients. Accordingly, development of novel anti-inflammatory and anti-bacterial agents, to combine with CFTR modulators, is a key goal in CF drug discovery. Recent studies, granted by Italian Cystic Fibrosis Research Foundation, revealed the ability of two compounds, the iminosugar L-Miglustat and beta-sitosterol (BSS), to reduce both the levels of inflammation and the bacterial load in murine models of CF infection.

Optimization and physicochemical characterization of polymeric nanoparticles containing tinidazole

Background: Periodontitis is a chronic bacterial infection destroying tooth-supporting tissues. Like metronidazole, tinidazole (TNZ) is also effective in treating periodontitis. The preparation of polymeric nanoparticles containing TNZ helps to improve the solubility and increase the bioavailability of the drug. Objectives: This study aimed to formulate and optimize TNZ nanoparticles and evaluate their physicochemical properties. Materials and methods: TNZ, Eudragit RSPO polymer as a carrier were used in this study. TNZ-loaded nanoparticles (TNZ NPs) were prepared by the solvent evaporation - emulsion method. The influence of the factors in the formula and the preparation process of TNZ NPs was investigated and optimized using MODDE 13.0 software. The physicochemical properties of NPs were evaluated by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and in vitro drug release. Result: The optimal TNZ NPs were spherical in shape, mostly amorphous, with particle size of 179.60 ± 2.20 nm, polydispersity index of 0.149 ± 0.024, and encapsulation efficiency of 47.49 ± 0.02%. TNZ NPs showed prolonged drug release in phosphate buffer pH 6.8 for up to 24 hours. Conclusions: The optimal TNZ NPs would be a promising drug delivery system for periodontitis treatment. Key words: tinidazole, nanoparticle, periodontitis.

Intrahepatic cholelithiasis with gallbladder-like metaplasia of intrahepatic bile ducts associated with gallbladder agenesis in a wild boar.

An unknown-aged adult female wild boar (Sus scrofa) was brought to Kyungpook National University for postmortem examination. Gross examination revealed gallbladder agenesis. Histologically, the liver was cirrhotic and had intrahepatic cholelithiasis, the choleliths were yellow, brown, gray, and black, and had coffin-lid and pyramidal appearances. Fourier-transform infrared spectroscopy analysis revealed that the components were 80% struvite and 20% calcium oxalate monohydrate. Chronic inflammatory cell infiltration was observed, with hyperplastic hepatocellular nodules characterized by large nuclei, prominent nucleoli, and scant cytoplasm with frequent binucleation, surrounded by thick fibrous septa. The epithelium of intrahepatic bile ducts that contained choleliths had undergone gallbladder-like metaplasia, which might have been induced by chronic irritation from the stones or by the accompanying chronic bacterial infection that was observed in Gram stains.

Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

For those born with cystic fibrosis (CF), hyper-concentrated mucus with a dysfunctional structure significantly impacts CF airways, providing a perfect environment for bacterial colonization and subsequent chronic infection. Early treatment with antibiotics limits the prevalence of bacterial pathogens but permanently alters the CF airway microenvironment, resulting in antibiotic resistance and other long-term consequences. With little investment into new traditional antibiotics, safe and effective alternative therapeutic options are urgently needed. One gathering significant traction is bacteriophage (phage) therapy. However, little is known about which phages are effective for respiratory infections, the dynamics involved between phage(s) and the host airway, and associated by-products, including mucus. Work utilizing gut cell models suggest that phages adhere to mucus components, reducing microbial colonization and providing non-host-derived immune protection. Thus, phages retained in the CF mucus layer result from the positive selection that enables them to remain in the mucus layer. Phages bind weakly to mucus components, slowing down the diffusion motion and increasing their chance of encountering bacterial species for subsequent infection. Adherence of phage to mucus could also facilitate phage enrichment and persistence within the microenvironment, resulting in a potent phage phenotype or vice versa. However, how the CF microenvironment responds to phage and impacts phage functionality remains unknown. This review discusses CF associated lung diseases, the impact of CF mucus, and chronic bacterial infection. It then discusses the therapeutic potential of phages, their dynamic relationship with mucus and whether this may enhance or hinder airway bacterial infections in CF.

Comparative in vitro activities of eravacycline in combination with colistin, meropenem, or ceftazidime against various Achromobacter spp. strains isolated from patients with cystic fibrosis

The Achromobacter species is an emerging pathogen causing chronic bacterial infections in patients with certain conditions, such as cystic fibrosis (CF), hematologic and solid organ malignancies, renal failure, and certain immune deficiencies. In the present study, we assessed the in vitro bactericidal activities of eravacycline, either alone or in combination with colistin, meropenem, or ceftazidime, using 50 Achromobacter spp. strains isolated from CF patients. We also investigated the synergistic interactions of these combinations using microbroth dilutions against 50 strains of Achromobacter spp. Bactericidal, and we assessed the synergistic effects of the tested antibiotic combinations using the time-kill curve (TKC) technique. Our studies show that meropenem alone is the most effective antibiotic of those tested. Based on the TKCs, we found that eravacycline-colistin combinations display both bactericidal and synergistic activities for 24 h against 5 of the 6 Achromobacter spp. strains, including colistin-resistant ones, at 4xMIC of colistin. Although we did not observe synergistic interactions with eravacycline-meropenem or eravacycline-ceftazidime combinations, we did not observe antagonism with any combination tested. This study’s findings could have important implications for antimicrobial therapy with tested antibiotics.

Transcriptional regulatory signatures of systemic diseases in periodontitis with dyslipidemia

BackgroundPeriodontitis is a chronic bacterial infection of tooth that increases the risk of systemic diseases like diabetes, cancer, and cardiovascular diseases. Although it has been have found altered lipids in periodontitis patients, its gene regulation is largely unknown. This study aimed to examine the lipid meditated regulatory network in periodontitis that may helpful in early detection of periodontal mediated systemic diseases. MethodsWe employed a high-throughput gene expression data of 1) patients with periodontitis (n = 6); 2) the periodontitis patients with dyslipidemia (n = 6); and 3) healthy control group (n = 6). The over represented (DEGs) genes in SET-A (control vs. periodontitis) and SET-B (control vs. periodontitis with dyslipidemia) was identified. The protein interaction network was generated for the over represented genes in both the conditions. The constructed network was dissected into multiple regulatory clusters, containing over expressed transcription factors with its interacting proteins. Further the behavior of the clusters was determined through gene ontology and molecular pathways. ResultsOn expression analysis, 751 in SET-A and 561 in SET-B were over expressed compared to healthy control. Using over expressed genes, protein interaction networks were constructed for SET-A and SET-B, respectively. Topological analysis revel the difference in the complexity of both the network. Four regulatory clusters (ESR1, FOS, RUNX2, and SP1) from SET-A and six (ESR1, ESR2, FOS, JDP2, PBX1, and TAL1) from the SET-B network was extracted. Each cluster displayed a variety of molecular mechanism associated with immune system, cell cycle, and signal processing. Clusters from SET-B showed diverse regulatory pattern in associated with cancer, neurological, psychiatric and metabolic diseases. ConclusionOur findings demonstrate difference in regulatory patterns between periodontitis and periodontitis with dyslipidemia. These finding may provide evidence for dyslipidemia mediated periodontitis contribute to progressive systemic diseases. Further experiments are required to validate these regulators as biomarkers and drug targets.

Association Between Depression and Physical Conditions Requiring Hospitalization

Depression is associated with an increased risk of physical illness, but the most common causes of hospitalization among people with depression are unclear. To examine the association of depression with an array of physical conditions requiring hospital treatment. In this outcomewide prospective multicohort study, primary analysis was based on data from the UK Biobank, a population-based study in the United Kingdom. Analyses were repeated in an independent data set of 2 cohorts in Finland, a population-based study and an occupational cohort. Data analysis was conducted between April and September 2022. Self-reported depression, recurrent severe major depression, recurrent moderate major depression, and a single major depressive episode. A total of 77 common health conditions ascertained from linkage data to national hospital and mortality registries. The analytical sample of UK Biobank participants consisted of 130 652 individuals (71 565 women [54.8%]; 59 087 men [45.2%]; mean [SD] age at baseline, 63.3 [7.8] years). The pooled data from the Finnish replication cohorts included 109 781 participants (82 921 women [78.6%]; 26 860 men [21.4%]; mean [SD] age, 42 [10.8] years). In the main analysis, severe/moderately severe depression was associated with the incidence of 29 nonoverlapping conditions requiring hospital treatment during a 5-year follow-up. Twenty-five of these associations remained after adjustment for confounders and multiple testing (adjusted hazard ratio [HR] range, 1.52-23.03) and were confirmed in the analysis of the Finnish cohorts. These included sleep disorders (HR, 5.97; 95% CI, 3.27-10.89), diabetes (HR, 5.15; 95% CI, 2.52-10.50), ischemic heart disease (HR, 1.76; 95% CI, 1.36-2.29), chronic obstructive bronchitis (HR, 4.11; 95% CI, 2.56-6.60), bacterial infections (HR, 2.52; 95% CI, 1.99-3.19), back pain (HR, 3.99; 95% CI, 2.96-5.38), and osteoarthritis (HR, 1.80; 95% CI, 1.46-2.20). The highest cumulative incidence was observed for endocrine and related internal organ diseases (245 per 1000 persons with depression; risk difference relative to unaffected individuals: 9.8%), musculoskeletal diseases (91 per 1000 persons; risk difference, 3.7%), and diseases of the circulatory system and blood (86 per 1000 persons; risk difference, 3.9%). The cumulative incidence was lower for hospital-treated mental, behavioral, and neurological disorders (20 in 1000 persons; risk difference, 1.7%). Depression was also associated with disease progression in people with prevalent heart disease or diabetes, and for 12 conditions, there was evidence of a bidirectional relationship. In this study, the most common causes of hospitalization in people with depression were endocrine, musculoskeletal, and vascular diseases, not psychiatric disorders. These findings suggest that depression should be considered as a target for the prevention of physical and mental disease.

Myocarditis in a congenital STAT1 gain-of-function patient

Autosomal dominant Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations result in an inborn error of immunity characterized by chronic mucocutaneous candidiasis, recurrent viral and bacterial infections, and diverse autoimmune manifestations. Current treatment consists of chronic antifungal therapy, antibiotics for concomitant infections, and immunosuppressive therapy in case of autoimmune diseases. More recently, treatment with Janus kinases 1 and 2 (JAK1/2) inhibitors have shown promising yet variable results. We describe a STAT1 GOF patient with an incidental finding of elevated cardiac troponins, leading to a diagnosis of a longstanding, slowly progressive idiopathic myocarditis, attributed to STAT1 GOF. Treatment with a JAKinhibitor (baricitinib) mitigated cardiac inflammation on MRI but was unable to alter fibrosis, possibly due to the diagnostic delay, which finally led to fatal arrhythmia. Our case illustrates that myocarditis can be part of the heterogeneous disease spectrum of STAT1 GOF. Given the insidious presentation in our case, we recommend a low treshold for cardiac evaluation in all STAT1 GOF patients. [Display omitted] [Display omitted]

The effect of vitamin D supplementation on human airway epithelial antimicrobial activity, ion transport, and liquid absorption

Vitamin D deficiency is implicated in chronic lung disease. Given its popularity as a respiratory season supplement, we sought to characterize the effect of active vitamin D (calcitriol) on human airway epithelial cell innate immune properties, including ion transport in vitro. We hypothesized calcitriol supplementation would enhance epithelial antimicrobial properties and alter airway surface liquid (ASL) composition and volume.We assayed primary human airway epithelial cells (hAECs) pretreated with calcitriol (10 -7 M) for 22h vs. paired controls. ASL bactericidal activity was tested by quantifying bioluminescent Staphylococcus aureus incubated with ASL from hAECs ±calcitriol. Epithelial transcriptional changes were measured by RNA sequencing and RT-qPCR. We measured the final volume of an apical 60 μL bicarbonate solution after 4h to assess the rate of epithelial fluid absorption ( J v ). To evaluate ion transport properties, epithelia were mounted in Ussing chambers and short-circuit current ( I sc ) and transepithelial conductance ( G t ) recorded. We quantified the half-life of ENaC by blocking protein translation with cycloheximide, then measured amiloride-sensitive I sc or G t in the presence of anion channels inhibitors.ASL from epithelia supplemented with calcitriol exhibited enhanced bactericidal activity against S. aureus, due to enhanced cathelicidin expression. RNA sequencing analysis revealed calcitriol decreased mRNA transcripts of proteins involved in airway epithelial sodium and chloride transport ( SCNN1G and ATP1B1). Consistent with RNA sequencing data, calcitriol-treated epithelia had decreased J v , amiloride-sensitive I sc , and amiloride-sensitive G t . Electrophysiological responses from anion channel blockers were unaffected. We obtained similar results with prolonged calcitriol incubation (7-day), while acute treatment (≤20 min.) did not affect I sc or G t . After apically treating epithelia with nystatin, no differences were observed in ouabain-sensitive I sc ±calcitriol, indicating calcitriol did not alter Na-K pump activity. Supplementation also did not alter the half-life of amiloride-sensitive I sc . RT-PCR experiments demonstrated both 3h and 22h calcitriol treatment increased CYP24A1 and CAMP expression (Vitamin D response element controls). However, ENaC genes only trended down for both timepoints, indicating the VDR likely indirectly decreased ENaC activity.In summation, calcitriol increased hAEC cathelicidin expression and ASL bacterial killing, while reducing sodium and liquid absorption across the epithelia via decreased ENaC activity. Calcitriol supplementation may be useful in airway diseases involving chronic bacterial infection and mucus dehydration. The Bowers Emphysema Fund and P01 HL091842/HL/NHLBI NIH HHS/United States This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ACTINOMYCOSIS MIMICKING A CROHNS DISEASE

Actinomycosis is a slowly progressive chronic granulomatous bacterial infection caused by an anaerobic gram-positive bacillus: Actinomyces Israeli.Thinking about thisdiagnosis in the right iliac fossa is uncommonas it usually shows through a clinical aspect of acute appendicitis, a Crohns disease or even a tumor of the ileocolic region. We report the case of a young female patient admitted for an iliac fossa pain and a palpable mass, mimicking a Crohns disease during laparoscopic exploration, only to conclude its a retained diagnosis of actinomycosis, after doing an ileocecal resection and anatomopathological analysis The purpose of this case report is to focus on the different aspects of this infection in the ileocecal regionwhich can be mistaken at firstand that is only supposed to be treated medically by antibiotics for months, with a simple biopsy to confirm the diagnosissince surgery can be mutilating.

Early-life immune expression profiles predict later-life health and fitness in a wild rodent.

Individuals differ in the nature of the immune responses they produce, affecting disease susceptibility and ultimately health and fitness. These differences have been hypothesized to have an origin in events experienced early in life that then affect trajectories of immune development and responsiveness. Here, we investigate how early-life immune expression profiles influence life history outcomes in a natural population of field voles, Microtus agrestis, in which we are able to monitor variation between and within individuals through time by repeat sampling of individually marked animals. We analysed the co-expression of 20 immune genes in early life to create a correlation network consisting of three main clusters, one of which (containing Gata3, Il10 and Il17) was associated with later-life reproductive success and susceptibility to chronic bacterial (Bartonella) infection. More detailed analyses supported associations between early-life expression of Il17 and reproductive success later in life, and of Il10 expression early in life and later infection with Bartonella. We also found significant association between an Il17 genotype and the early-life expression of Il10. Our results demonstrate that immune expression profiles can be manifested during early life with effects that persist through adulthood and that shape the variability among individuals in susceptibility to infection and fitness widely seen in natural populations.

Serum Appetite-Regulating Hormone Levels in Cystic Fibrosis Patients: Influence of the Disease Severity and the Type of Bacterial Infection-A Pilot Study.

Cystic fibrosis (CF) belongs to the most common inherited diseases. The severity of the disease and chronic bacterial infections are associated with a lower body index, undernutrition, higher number of pulmonary exacerbations, more hospital admissions, and increased mortality. The aim of our study was to determine the impact of the severity of the disease and the type of bacterial infection in 38 CF patients on the serum level of appetite-regulating hormones including leptin, ghrelin, neuropeptide Y, agouti-signaling protein, proopiomelanocortin, kisspeptin, putative protein Y, and α-melanocyte-stimulating hormone. The patients were divided according to the severity of the disease according to spirometry and the type of chronic bacterial infection. We found that leptin level was significantly higher in patients with severe CF than in patients with mild disease (20.02 ± 8.09 vs. 12.38 ± 6.03 ng/mL, p = 0.028). Furthermore, leptin level was elevated in patients with chronic infection with Pseudomonas aeruginosa compared to uninfected participants (15.74 ± 7.02 vs. 9.28 ± 1.72 ng/mL, p = 0.043). The severity of the disease and the type of bacterial infection did not affect the levels of other appetite-regulating hormones. Moreover, we found a positive correlation between pro-inflammatory interleukin-6 and leptin level (p = 0.0426, R = 0.333). Taken together, our results indicate that both the severity of the disease and the type of bacterial infection are associated with elevated leptin levels in CF patients. Future CF treatment strategies should consider possible disturbances in the hormones that regulate appetite and the factors that influence their levels.

STUDY OF EXTENDED SPECTRUM BETA LACTAMASES & BIOFILM IN PSEUDOMONAS SPECIES ISOLATED FROM DIFFERENT CLINICAL SAMPLES

Background:-Pseudomonas species are Gram negative bacteria which are resistant to commonly used antibiotics. Due to the formation of biofilm antimicrobial therapy is reduced & leads to chronic bacterial infections. Therefore, we need to isolate species of Pseudomonas from different clinical samples, detect ESBL & biofilm production in them. Objective:-1. To determine percentage of Pseudomonas species isolated from different clinical samples. 2. To determine the antibiogram of Pseudomonas species isolated from the samples. 3. To detect ESBL & biofilm production in Pseudomonas species. 4. To correlate biofilm & ESBL production. Method:-The susceptibility of different clinical samples of Pseudomonas spp.was determined by using antibiotics on Muller Hinton Agar by the Kirby -Bauer disk diffusion method using Clinical & Laboratory Standards Institute (CLSI) standards. Confirmatory test for ESBL production was done as per Clinical and Laboratory Standards Institute (CLSI) 2021guidelines. For the detection of biofilm Tissue Culture Plate (TCP) method was used. TCP is considered as the gold-standard method for biofilm detection. Result:-Out of total 171 Pseudomonas aeruginosa samples 30 were ESBL producers (17.5%) & 141 were Non ESBL Producers (82.5%), 12.8% were ESBL Producers & Strong Biofilm producers, 82.45% were Strong biofilm producers & Non ESBL producers. Conclusion:-Phenotypic detection of ESBL & antibiotic resistance in P.aeruginosa should be done & both the results should be taken in consideration for better representation of resistant strains, this will help clinicians to give appropriate antibiotics so that they can treat the infections timely.