Complex Chronic Disease Research Articles

Surgical treatment of liver hydatid cyst in elderly patients: A propensity score-matching retrospective cohort study

BackgroundCystic echinococcosis is a clinically complex chronic parasitic disease and a major socioeconomic problem in endemic areas. The safety of liver resection in elderly patients is often debated among medical professionals. We analyzed the postoperative morbidity and mortality rates of elderly patients who underwent surgery at our unit. MethodsWe retrospectively evaluated patients with liver hydatid cysts which were surgically removed at our unit. Patients were divided into two groups: Group 1 (patients < 70 years), and Group 2 (patients ≥ 70 years). Propensity score matching (PSM) and comparative analyses between groups were performed. ResultsThe unmatched cohort consisted of 279 patients (Group 1: 244; Group 2: 35). After PSM, we compared the outcomes for 56 patients from Group 1 to 31 patients from Group 2. A higher rate of severe complications was observed in Group 2 (25.8% vs 5.36%, p = 0.014). No difference was found in the rates of infectious, cardiorespiratory, or hemorrhagic complications between both groups, and in the mortality rate either (0.00% vs 6.45%, p = 0.124). ConclusionsLiver surgery in selected elderly patients is safe and practicable. The low postoperative morbidity rate in these patients is acceptable, albeit higher, due to their comorbidities.

Emerging Roles of Platelets in Allergic Asthma.

Allergic asthma is a complex chronic inflammatory disease of the airways, driven by Th2 immune responses and characterized by eosinophilic pulmonary inflammation, airway hyperresponsiveness, excessive mucus production, and airway remodeling. Overwhelming evidence from studies in animal models and allergic asthmatic patients suggests that platelets are aberrantly activated and recruited to the lungs. It has been established that platelets can interact with other immune cells and secrete various biochemical mediators to promote allergic sensitization and airway inflammatory response, and platelet deficiency may alleviate the pathological features and symptoms of allergic asthma. However, the comprehensive roles of platelets in allergic asthma have not been fully clarified, leaving attempts to treat allergic asthma with antiplatelet agents questionable. In this review, we summarize the role of platelet activation and pulmonary accumulation in allergic asthma; emphasis is placed on the different interactions between platelets with crucial immune cell types and the contribution of platelet-derived mediators in this context. Furthermore, clinical antiplatelet approaches to treat allergic asthma are discussed. This review provides a clearer understanding of the roles of platelets in the pathogenesis of allergic asthma and could be informative in the development of novel strategies for the treatment of allergic asthma.

Collagen 3D matrices as a model for the study of cell behavior in pulmonary fibrosis

Purpose: Idiopathic pulmonary fibrosis (IPF) is a complex progressive chronic lung disease where epithelial to mesenchymal interaction, extracellular matrix (ECM) contact, and pro-fibrotic cytokines dynamics take part in the development of the disease. The study of IPF in the widespread in vitro two-dimensional (2 D) culture fails to explain the interaction of cells with the changing environment that occurs in fibrotic lung tissue. A three-dimensional (3 D) co-culture model might shed light on the pathogenesis of IPF by mimicking the fibrotic environment. Materials and Methods: Fibroblasts from nine IPF were isolated and embedded in collagen matrices with the alveolar epithelial human cell line (A549) on the top. Cells were also cultured in 2 D with and without TGF-β1 as a conventional model to compare with. Both types of cells were isolated separately. Protein and gene expression of the main fibrotic markers were measured by qPCR, Western blot, and ELISA. Results: IPF fibroblasts to myofibroblasts differentiation was observed in the 3 D model and in cells stimulated with TGF-β1. In addition, ECM-related genes were highly up-regulated in the 3 D collagen matrix. A549 co-cultured 3 D with IPF fibroblasts showed EMT activation, with down-regulation of E-cadherin (CDH1). However, other pro-fibrotic genes as VIM, TGFB1, and MMP7 were up-regulated in A549 co-cultured 3 D with fibroblasts. Conclusions: 3 D-collagen matrices might induce fibroblasts’ fibrotic phenotype as in the classic TGF-β1 model, by up-regulating genes associated with matrix production. In addition, IPF lung fibroblasts seem to exert a pro-fibrotic influence in A549 cells when they are co-cultured. These results suggest that an improved 3 D co-culture model might serve as an important tool to study the fibrotic process and its regulation.

Out-of-Network Care in Commercially Insured Pediatric Patients According to Medical Complexity.

Commercial health plans establish networks and require much higher cost sharing for out-of-network (OON) care. Yet, the adequacy of health plan networks for access to pediatric specialists, especially for children with medical complexity, is largely unknown. To examine differences in OON care and associated cost-sharing payments for commercially insured children with different levels of medical complexity. Cross-sectional study using a nationwide commercial claims database. Enrollees 0-18 years old in employer-sponsored insurance plans. The Pediatric Medical Complexity Algorithm was used to classify individuals into 3 levels of medical complexity: children with no chronic disease, children with non-complex chronic diseases, and children with complex chronic diseases. OON care rates, cost-sharing payments for OON care and in-network care, OON cost sharing as a proportion of total health care spending, and OON cost sharing as a proportion of total cost sharing. The study sample included 6,399,006 individuals with no chronic disease, 1,674,450 with noncomplex chronic diseases, and 603,237 with complex chronic diseases. Children with noncomplex chronic diseases were more likely to encounter OON care by 6.77 percentage points with higher cost-sharing by $288 for OON care, relative to those with no chronic disease. For those with complex chronic diseases, these differences rose to 16.08 percentage points and $599, respectively. Among children who saw behavioral health providers, rates of OON care were especially high. Commercially insured children with medical complexity experience higher rates of OON care with higher OON cost-sharing payments compared with those with no chronic disease.

Peer mentorship to improve outcomes in patients on hemodialysis (PEER-HD): a randomized controlled trial protocol

BackgroundPatients receiving in-center hemodialysis experience disproportionate morbidity and incur high healthcare-related costs. Much of this cost stems from potentially avoidable hospitalizations. Peer mentorship has been used effectively to improve outcomes for patients with complex chronic diseases. We propose testing the efficacy of peer mentorship on hospitalization rates among patients receiving hemodialysis.MethodsThis is a multicenter parallel group randomized controlled pragmatic trial of patients treated at hemodialysis facilities in Bronx, NY and Nashville, TN. The study has two phases. Phase 1 will enroll and train 16 hemodialysis patients (10 in Bronx, NY and 6 in Nashville TN) to be mentors using a program focused on enhancing self-efficacy, dialysis self-management and autonomy-supportive communication skills. Phase 2 will enroll 200 high risk adults receiving hemodialysis (140 in Bronx, NY and 60 in Nashville, TN), half of whom will be randomized to intervention and half to usual care. Intervention participants are assigned to weekly telephone calls with trained mentors (see Phase 1) for a 3-month period.The primary outcome of Phase 1 will be engagement of mentors with training and change in knowledge scores and autonomy skills from pre- to post-training. The primary outcome of Phase 2 will be the composite count of ED visits and hospitalizations at the end of study follow-up in patient participants assigned to intervention as compared to those assigned to usual care. Secondary outcomes for Phase 2 include the change over the trial period in validated survey scores measuring perception of social support and self-efficacy, and dialysis adherence metrics, among intervention participants as compared to usual care participants.DiscussionThe PEER-HD study will test the feasibility and efficacy of a pragmatic peer-mentorship program designed for patients receiving hemodialysis on ED visit and hospitalization rates. If effective, peer-mentorship holds promise as a scalable patient-centered intervention to decrease hospital resource utilization, and by extension morbidity and cost, for patients receiving maintenance in-center hemodialysis.Trial registrationClinicaltrials.gov identifier: NCT03595748; 7/23/2018.Trial sponsorNational Institutes of Diabetes, Digestive and Kidney Disease (NIDDK) 5R18DK118471.FundingFunding for this study was provided by the National Institutes of Diabetes, Digestive and Kidney Disease: R18DK118471.Study statusThis is an ongoing study and not complete. We are still collecting data for observational follow-up on participants.Related articlesNo related articles for this study have been submitted to any journal.The study sponsor and funders had no role in the design, analysis or interpretation of this data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The Role of Extracellular Non-coding RNAs in Atherosclerosis.

Atherosclerosis (AS) is a complex chronic inflammatory disease that leads to myocardial infarction, stroke, and disabling peripheral artery disease. Non-coding RNAs (ncRNAs) directly participate in various physiological processes and exhibit a wide range of biological functions. The present review discusses how different ncRNAs participate in the process of AS in various carrier forms. We focused on the role and potential mechanisms of extracellular ncRNAs in AS and examined their potential implications for clinical treatment.

A36 NON-PSYCHOTROPIC PHYTOCANNABINOIDS ATTENUATE VISCERAL HYPERSENSITIVITY IN DEXTRAN SULFATE SODIUM (DSS)-INDUCED COLITIS

BackgroundThe inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are complex chronic diseases that affect an increasing proportion of the population. Abdominal pain is a major clinical symptom, but current treatments are limited and a source of frustration for patients, many of whom seek alternatives such as cannabis. Cannabis contains many compounds with therapeutic potential that do not have the prohibitive psychotropic effects of tetrahydrocannabinol. These non-psychotropic cannabinoids (npCBs) have a variety of effects including analgesia and anti-inflammatory actions and show potentiating effects when administered in combination. The range of actions of these compounds potentially allows for their development as novel therapeutics for treatment of pain in IBD.AimsTo investigate the analgesic effects of cannabichromene (CBC), cannabidiol (CBD), cannabidivarin (CBDV), and cannabigerol (CBG), individually and in combination, in the treatment of colitis-evoked visceral hypersensitivity.MethodsThe analgesic effects of the npCBs were investigated in an acute dextran sodium sulfate model of colitis. Abdominal pain was quantified by electromyographic recordings of the reflexive contraction of the external oblique muscles in response to colorectal distension. Activation of the spinal cord was assessed using immunohistochemistry for the neuronal activity marker c-Fos in neurons of the spinal dorsal horn.ResultsCBD reduced pain responses in the functional assay and spinal cord c-Fos activity in a dose-dependent manner. A single intraperitoneal injection of 10 mg/kg, 30 minutes prior to application of the noxious stimulus, reduced pain responses to the level of non-DSS treated control animals. CBDV, and CBG were found to be ineffective in either assay at doses of 1, 5, and 10 mg/kg.ConclusionsThese results suggest CBD may be a promising therapeutic agent in the treatment of colitis–induced visceral hypersensitivity with rapid translational value due to the legalization of cannabis and rapidly growing cannabis industry in Canada. Additionally, CBDV, CBC, and CBG will be further investigated for their analgesic effects and any potentiating effects from administration of multiple npCBs examined.Funding AgenciesAlberta Innovates

An Evaluation of Online Cirrhosis-related Information Intended for Patients and Caregivers

With nearly 70% of American adults seeking online health information,1 the internet represents a powerful space to provide patients with evidence-based, usable education about their chronic conditions. Although effective patient-oriented communication recommendations are available, the accessibility, reliability, and accuracy of online health content is largely unmonitored or evaluated. In a complex chronic disease, such as cirrhosis, understanding the online information landscape specific to patients can provide insight into resources that are available to support their self-management behaviors and to fill knowledge gaps.

Effect of pharmaceutical care program on depression among women with epilepsy: A randomized controlled trial (IPHIWWE study)

Depression is the most frequent comorbidity of epilepsy, and they are both complex chronic diseases that affect health-related quality of life (HRQOL), especially in women. Pharmaceutical care may contribute significantly to the improvement of HRQOL in women with epilepsy (WWE), with the involvement of the pharmacist in the healthcare team treatments could be optimized and negative outcomes related to medication reduced.This was a randomized controlled trial involving WWE over 18 years of age. The intervention group (IG) received a Pharmaceutical care program consisting of medication review follow-up according to Dáder’s method, health education, aids for adherence to treatment, registration of seizures and possible triggers, and therapeutic drug monitoring of anticonvulsants. The control group (CG) received the usual care in the institution.The impact in depression was assessed by changes in the Center for Epidemiologic Studies Depression (CES-D) scale, which was applied both at the first and the last interviews, six months later.One hundred eighty-two WWE entered the study and 144 (79.1%) completed it. At the beginning of the study, 48.95% showed signs of depression, decreasing to 30.43% for the patients in the IG (p-value = 0.0238), while for the patients in the CG it remained at 47.30% (p-value = 0.8693). The Wilcoxon test for comparing the change (Δ) (before-after) in the CES-D scores, between groups, yielded a w = 3138.5, p-value = 0.01802 proving there were statistically significant differences.The study proved that the application of a Pharmaceutical Care program significantly decreases signs of depression in WWE. These results allow us to recommend the implementation of the Pharmaceutical care programs to improve the depression in WWE.Trial registration: Current Controlled Trials ISRCTN46864306 IPHIWWE study.

Impact of the COVID-19 Pandemic on Mental Health Outcomes of Healthy Children, Children With Special Health Care Needs and Their Caregivers-Results of a Cross-Sectional Study.

BackgroundSeveral studies have described widening inequalities as a result of the COVID-19 pandemic, mostly for adult populations. Children and adolescents are particularly impacted by the indirect effects of the pandemic and lockdown measures, such as reduced access to or delays in health care and school closures. National surveys in several countries also show a rising mental health burden in children and adolescents during the COVID-19 pandemic. Children with special health care needs are a particularly vulnerable group in this context as they rely on a wide range of services, which were mostly suspended during the first wave of the pandemic. This study aims: (1) to describe the mental health outcomes of children with and without special healthcare needs and of their caregivers following the first national lockdown in Germany; (2) to investigate variations in mental health outcomes and measures of pandemic burden according to socioeconomic status; (3) to assess the impact of socioeconomic status, disease complexity and psychosocial burden on parent-reported child mental health problems.MethodsWe conducted an online survey among 1,619 caregivers of children aged 1–18 years from August 11th until October 5th 2020. Participants were recruited both from families of children with special healthcare needs and of healthy children. Inequalities were analysed by descriptive statistics, simple and hierarchical logistic regression modelling to explore the association between socioeconomic status and psychological outcome measures, disease complexity and general burden related to COVID-19.ResultsThere was a high prevalence of 57.4% of parent-reported mental health problems in children and of a positive screening score for depression in 30.9% of parents. Parent-reported mental health problems were more likely to affect children with low socioeconomic status, with complex chronic disease and those whose parents screened positive for depression.ConclusionsThis study highlights inequalities in parent-reported child mental health outcomes by socioeconomic status and disease complexity in a large sample of German families with and without children with special health care needs. Political measures should put children at the centre and aim to mitigate the unequal impact of the COVID-19 pandemic, particularly on the mental health of vulnerable children.

“Association of Coronary Collateral Formation and Diabetes Patients with Ischaemic Heart Disease”

Background: Diabetes mellitus (DM) is a complex and heterogeneous chronic metabolic disease caused by elevated levels of blood glucose. Although myocardial ischemia is known to be significantly related to the development of coronary collateral vessels (CCVs), there is considerable variation between patients with ischemic heart disease in the presence of collateral development. Methods: This observational study was done in Department of Cardiology, Mymensingh Medical College Hospital, Bangladesh from January to December 2020. Out of 110 patients who had a stenosis of &gt;95% in any major coronary artery in angiograms were included in the study. Of these patients, 35 patients constitute the diabetic group. Remaining 75 patients were non-diabetic. For case-control matching, 35 non-diabetic patients (mean age, 52.03± 8.69 years) were selected randomly and were included in the control group. The CCVs were graded according to the Rentrop scoring system, and the collateral score was calculated by summing the Rentrop numbers of every patient. Results: There was no statistical difference between patients with and without DM in clinical baseline characteristics. The mean number of diseased vessels in the DM group (2.10±0.76) was higher than that in the nondiabetic group (1.63± 0.72 P.017). The mean collateral score was (1.13± 0.86) in the DM group and (1.97± 1.61) in the control group. After confounding variables were controlled for, the collateral score in the diabetic group was significantly different from that in the nondiabetic group (p=0.015). Conclusion: Our findings suggest that CCV development is poorer in patients with DM than in patients without DM. Thus, we can speculate that DM is an important factor affecting CCV development.

KdPT alleviates imiquimod-induced psoriasis-like skin lesion in mice via inhibiting proliferation and inflammation response.

Psoriasis is a complex chronic skin inflammatory disease characterized by abnormal proliferation, differentiation of keratinocytes and infiltration of lymphocytes and neutrophils. The tripeptide KdPT, structurally derived from the C-terminal amino acid of alpha-melanocyte-stimulating hormone, has shown a significant anti-inflammatory effect on mild-to-moderate active ulcerative colitis in previous reports. In this research, we investigated whether KdPT could consistently ameliorate disease in a mouse model of imiquimod (IMQ)-induced psoriasis by inhibiting proliferation and inflammation response. We demonstrated that KdPT in vitro significantly inhibited the proliferation of human keratinocytes and endothelial cells, and also downgraded the expression of inflammatory factors in LPS-induced RAW264.7, including IL-6, TNF-α and NO. In vivo, KdPT attenuates the severity of IMQ-induced psoriasis-like phenotype in mice. Such an effect was achieved by downregulating the expression of the inflammatory cytokines interleukin (IL)-6, TNF-α, and the proliferation marker Ki67. These results suggested that KdPT might be useful in the treatment for psoriasis.

P353 Agreement between patients, senior and junior physicians on disease activity and burden scoring in inflammatory bowel disease, using a tele-monitoring platform

Abstract Background Inflammatory bowel disease (IBD) are complex chronic disabling disease with variable disease activity. Physicians’ and patients’ perception of disease burden may vary considerably. The use of eHealth tools is a useful technique to monitor disease burden, but physicians- and patients-reported disease measurement do not overlap completely. Aim of this study was to perspectively explore agreement for rating disease activity and impact between patients, senior (consultants) and junior (residents) physicians. Methods Using a tele-monitoring platform (IBD Tool), 508 consecutive IBD patients filled disease activity (Harvey Bradshaw Index, HBI, for Crohn’s and Patient Simple Clinical Colitis Activity Index, P-SCCAI, as appropriate) and disease impact (Pictorial Representation of Illness and Self-Measure, PRISM) validated questionnaires at the time of outpatient visits. At the same timepoint also senior and junior physicians filled the same activity (HBI and Clinician SCCA, C-SCCAI) and impact (PRISM) questionnaires. Agreement between patients’ and physicians’ scores was analysed with intraclass and concordance correlation coefficients and Spearman’s rank correlation coefficient. Results A total of, 629 filled questionnaires regarding, 508 patients was available for analysis. Crohn’s patients were, 52%, and females were, 50%, median age of patients was, 44 years, and their median age at diagnosis was, 28 years, while median disease duration was, 12 years; overall, 39% of patients underwent surgery before being enrolled. Agreement for different scores among patients, senior and junior physicians was always significant and details are reported in Table, 1. Table, 1. Agreement among patients, senior and junior physicians for HBI, SCCAI and PRISM. A closer inverse relationship between activity indices and PRISM was found in physicians’ scores, while it was looser in patients’ scores. Senior physicians’ agreement was -0.774 and -0.793 for HBI and C-SCCAI, respectively, to PRISM (p&amp;lt;0.0001); Junior physicians’ agreement was -0.745 and -0.753 for HBI and C-SCCAI, respectively, to PRISM (p&amp;lt;0.0001); patients’ agreement was -0.414 and -0.498 for HBI and C-SCCAI, respectively, to PRISM (p&amp;lt;0.0001). Conclusion Agreement of patients’ and physicians’ scoring of disease activity on a tele-monitoring platform is good and significant, and it is optimal between junior and senior doctors. According to published data, physicians’ and patients’ agreement regarding the perception of disease impact on patients’ lives (measured with PRIMS) is slightly worse, although still significant, while it is good comparing junior and senior physicians’ rates. When exploring relationships between PRISM and disease activity scores it is good for physicians, and only average for patients.

Association of rheumatoid arthritis and its severity with human leukocytic antigen-DRB1 alleles in Kurdish region in North of Iraq

BackgroundRheumatoid arthritis is a complex multifactorial chronic disease, the importance of human leukocytic antigen (HLA) as a major genetic risk factor for rheumatoid arthritis was studied worldwide. The objective of this study is to identify the association of HLA-DRB1 subtypes with rheumatoid arthritis and its severity in Kurdish region.MethodsA case–control study recruited 65 rheumatoid arthritis patients and 100 healthy individuals as control group all over the Kurdistan region/Iraq. Both patient and control groups are genotyped using polymerase chain reaction with sequence specific primer. Anti-CCP antibodies were measured by ELISA test. Rheumatoid factor, C-reactive protein, and disease activity score 28 which measured by DAS-28 values were calculated. The DAS-28 was used to assess the clinical severity of the patients.ResultsHLA-DRB1-0404 and HLA-DRB1-0405 frequencies showed a strong association with disease susceptibility (P < 0.001). The frequency of HLA-DRB1-0411 and HLA-DRB1-0413 were significantly higher in control group (P < 0.001). The frequency of rheumatoid factor and Anti-CCP were significantly higher among shared epitope-positive patients compared to shared epitope-negative patients (P < 0.001). Regarding the disease activity by DAS-28, rheumatoid arthritis patients didn’t show significant difference between the shared epitope-positive and shared epitope-negative patients.ConclusionsHLA-DR0404 and HLA-DR0405 alleles are related to RA, while HLA-DR1-0411 and HLA-DRB1-0413 protect against RA in the Kurdistan region in the North of Iraq.

Complex Chronic Disease in Paediatrics – Needs in the Last Year of Life

Complex Chronic Disease in Paediatrics – Needs in the Last Year of Life

Home-based digital health technologies for older adults to self-manage multiple chronic conditions: A data-informed analysis of user engagement from a longitudinal trial.

BackgroundAgeing populations are resulting in higher prevalence of people with multiple chronic conditions (multimorbidity). Digital health platforms have great potential to support self-management of multimorbidity, increasing a person's awareness of their health and well-being, supporting a better understanding of diseases and encouraging behaviour change. However, little research has explored the long-term engagement of older adults with such digital interventions.MethodsThe aim of this study is to analyse how 60 older adults with multimorbidity engaged with digital symptom and well-being monitoring through a digital health platform over a period of approximately 12 months. Data analysis focused on user retention, frequency of monitoring, intervals in monitoring and patterns of daily engagement.ResultsOur findings show that the overall engagement with the digital health platform was high, with more than 80% of participants using the technology devices for over 200 days. The submission frequency for symptom parameters (e.g. blood glucose (BG), blood pressure (BP), etc.) was between three and four times per week which was higher than that of self-report (2.24) and weight (2.84). Submissions of exercise (6.12) and sleep (5.67) were more frequent. The majority of interactions happened in the morning time. The most common time of submission for symptom parameters was 10 am, whereas 8 am was the most common time for weight measurements.ConclusionsThe findings indicate the patterns of engagement of older adults with complex chronic diseases with digital home-based self-management systems.

Systemic Lupus Erythematosus and its major organ complications: a narrative review on available literature

Systemic lupus erythematosus (SLE) is a complex chronic autoimmune disease that is well-recognized by its dermal manifestations, like skin lesions, rash, and photosensitivity. Symptoms may vary among individuals ranging from mild to severe because of its erratic pattern of remission and flare. SLE is a systemic disease that has the tendency to influence multiple organs of the body like lungs, brain, heart, and blood, etc. which is also one of the most important reasons for SLE-mediated mortality in young and old age groups, apart from renal complications and various infections. Because SLE is an autoimmune ailment, the formation of autoantibodies is considered to be the main cause of multiple organ system effects and systemic inflammation. The presence of hyperactive B cells produces autoantibodies in combination with the removal of apoptotic cellular material, resulting in immune complex formation. This leads to an inflammatory reaction in the microvasculature – causing multi-organ complications. In this review article, the main focus is on the complications of SLE among which renal disorder is one of the most life-threatening complications. Apart from this, cardiovascular, neurological, gastrointestinal and hepatic, muscular, osteoarticular and pregnancy complications have also been discussed. It has been concluded that timely identification and targeted therapy to manage these patients is the only solution.

Gut microbiome dysbiosis in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a complex multi-factorial chronic relapsing disease of the digestive tract where dysbiosis of autochthonous intestinal microbiota, environmental factors and host genetics are implicated in the disease development, severity, course and treatment outcomes. The two clinically well-defined forms of IBD are Crohn's disease (CD) and ulcerative colitis (UC). The CD affects the local immune response of the entire gastrointestinal tract whereas the inflammation in UC is mainly restricted to the colonic mucosa. Prolong progressive inflammation due to CD and UC often lead to colonic cancer. In healthy individuals, the enormous taxonomic diversity and functional potency of gut microbiota including members from the bacterial and fungal microbiota tune the host immunity and keep the gastric environment beneficial and protective. However, expansion of pathobionts, autochthonous microbes with the potency of pathogenicity in dysbiotic condition, in the gastrointestinal tract and subsequently enriched inflammatory microbial products in the gastrointestinal milieu attract different immune cells and activate aberrant host immune response which leads to excessive production and secretion of different cytokines that damage the colonic epithelial cells and manifest chronic inflammatory digestive disease. In the current chapter, we provided our updated understanding about the different bacterial and fungal pathobionts, their genomic and metabolic signatures, and geo-specific diversity of gut microbes linked with IBD across the globe at the molecular resolution. An improved understanding of IBD and the factors associated with the disease will be a boost for therapeutic development and disease management.

Роль генов иммунного ответа в развитии сахарного диабета 2 типа

Type 2 diabetes mellitus (T2D) is a complex chronic disease resulting from a lot of factors, including insulin resistance. One of the causes of the insulin resistance is the presence of chronic inflammation. This study aimed to analyze polymorphisms of genes of pro-inflammatory cytokines and their receptors (the gene coding tumor necrosis factor receptor superfamily member 1B TNFRSF1B, the genes coding A and B subunits of interleukin 12 IL12A, IL12B) and C-reactive protein (CRP) with T2D in Tatars. The single nucleotide polymorphism (SNP) rs568408 in IL12A (PFDR=0.00005, OR=5.28) was significantly associated with type 2 diabetes. Regression analysis revealed that rs3212227 in IL12В associated with the glycated hemoglobin HbA1c level and fasting blood glucose (Р=0.0017 and Р=0.03, respectively).

Allosteric inhibition of SHP2 uncovers aberrant TLR7 trafficking in aggravating psoriasis

Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. We found that the Src homology‐2 domain‐containing protein tyrosine phosphatase‐2 (SHP2) was highly expressed in both psoriatic patients and imiquimod (IMQ)‐induced psoriasis‐like mice. Also, the SHP2 allosteric inhibitor SHP099 reduced pro‐inflammatory cytokine expression in PBMCs taken from psoriatic patients. Consistently, SHP099 significantly ameliorated IMQ‐triggered skin inflammation in mice. Single‐cell RNA sequencing of murine skin demonstrated that SHP2 inhibition impaired skin inflammation in myeloid cells, especially macrophages. Furthermore, IMQ‐induced psoriasis‐like skin inflammation was significantly alleviated in myeloid cells (monocytes, mature macrophages, and granulocytes)—but not dendritic cells conditional SHP2 knockout mice. Mechanistically, SHP2 promoted the trafficking of toll‐like receptor 7 (TLR7) from the Golgi to the endosome in macrophages by dephosphorylating TLR7 at Tyr1024, boosting the ubiquitination of TLR7 and NF‐κB‐mediated skin inflammation. Importantly, Tlr7 point‐mutant knock‐in mice showed an attenuated psoriasis‐like phenotype compared to wild‐type littermates following IMQ treatment. Collectively, our findings identify SHP2 as a novel regulator of psoriasis and suggest that SHP2 inhibition may be a promising therapeutic approach for psoriatic patients.