Early Immunomodulatory Program Triggered by Protolerogenic Bifidobacterium pseudolongum Drives Cardiac Transplant Outcomes.

BACKGROUND: Despite ongoing improvements to regimens preventing allograft rejection, most cardiac and other organ grafts eventually succumb to chronic vasculopathy, interstitial fibrosis, or endothelial changes, and eventually graft failure. The events leading to chronic rejection are still poorly understood and the gut microbiota is a known driving force in immune dysfunction. We previously showed that gut microbiota dysbiosis profoundly influences the outcome of vascularized cardiac allografts and subsequently identified biomarker species associated with these differential graft outcomes. METHODS: In this study, we further detailed the multifaceted immunomodulatory properties of protolerogenic and proinflammatory bacterial species over time, using our clinically relevant model of allogenic heart transplantation. RESULTS: In addition to tracing longitudinal changes in the recipient gut microbiome over time, we observed that Bifidobacterium pseudolongum induced an early anti-inflammatory phenotype within 7 d, whereas Desulfovibrio desulfuricans resulted in a proinflammatory phenotype, defined by alterations in leukocyte distribution and lymph node (LN) structure. Indeed, in vitro results showed that B pseudolongum and D desulfuricans acted directly on primary innate immune cells. However, by 40 d after treatment, these 2 bacterial strains were associated with mixed effects in their impact on LN architecture and immune cell composition and loss of colonization within gut microbiota, despite protection of allografts from inflammation with B pseudolongum treatment. CONCLUSIONS: These dynamic effects suggest a critical role for early microbiota-triggered immunologic events such as innate immune cell engagement, T-cell differentiation, and LN architectural changes in the subsequent modulation of protolerant versus proinflammatory immune responses in organ transplant recipients.

Rapid intestinal and systemic metabolic reprogramming in an immunosuppressed environment.

Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes.

Rapid intestinal and systemic metabolic reprogramming in an immunosuppressed environment.

Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes.

Management of Non-union Distal Femur Fractures With Augmentation Nail Plate Construct.

Background and objective A non-union distal femur fracture is a challenging fracture to treat. Common treatment modalities for non-union distal femur fractures include dual plating, intramedullary nails, ilizarov, and hybrid fixators. Despite the availability of a wide armamentarium of constructs, the clinical and functional outcome of these modalities is often complicated by significant morbidity, joint stiffness, and delayed union. The augmentation of the intramedullary nail with a locking plate results in a robust architecture, improving the likelihood of union. The use of this nail plate construct improves biomechanical stability and restores limb alignment, which enables early rehabilitation and weight bearing and lowers the likelihood of fixation failure. Methodology A prospective study was conducted at the Government Institute of Medical Science, Greater Noida, from January 2021 to January 2022 on 10 patients with non-union of the distal femur. All the patients were operated on with nail plate construct. The minimum follow-up period was 12 months. Results A total of 10 patients with a mean age of 55 years were included. Six were earlier treated with an intramedullary nail and four with extramedullary implants. All patients were managed with implant removal and fixation with nail plate construct and bone grafting. The average duration of the union was 10.3 months. The International Knee Documentation Committee (IKDC) score improved from 30.6 preoperatively to 67.3 postoperatively. Only one patient developed a superficial infection, which was managed by wound debridement and targeted antibiotic therapy. Conclusion In our experience, this relatively novel technique of combining nail plate constructs offers encouraging outcomes in the management of non-union of distal femur fractures, especially in elderly and osteopenic patients.

FRC transplantation restores lymph node conduit defects in laminin α4-deficient mice.

Fibroblastic reticular cells (FRCs) play important roles in tolerance by producing laminin α4 (Lama4) and altering lymph node (LN) structure and function. The present study revealed the specific roles of extracellular matrix Lama4 in regulating LN conduits using FRC-specific KO mouse strains. FRC-derived Lama4 maintained conduit fiber integrity, as its depletion altered conduit morphology and structure and reduced homeostatic conduit flow. Lama4 regulated the lymphotoxin ß receptor (LTßR) pathway, which is critical for conduit and LN integrity. Depleting LTßR in FRCs further reduced conduits and impaired reticular fibers. Lama4 was indispensable for FRC generation and survival, as FRCs lacking Lama4 displayed reduced proliferation but upregulated senescence and apoptosis. During acute immunization, FRC Lama4 deficiency increased antigen flow through conduits. Importantly, adoptive transfer of WT FRCs to FRC Lama4-deficient mice rescued conduit structure, ameliorated Treg and chemokine distribution, and restored transplant allograft acceptance, which were all impaired by FRC Lama4 depletion. Single-cell RNA sequencing analysis of LN stromal cells indicated that the laminin and collagen signaling pathways linked crosstalk among FRC subsets and endothelial cells. This study demonstrated that FRC Lama4 is responsible for maintaining conduits by FRCs and can be harnessed to potentiate FRC-based immunomodulation.

Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation.

Antigen-specific tolerance is a key goal of experimental immunotherapies for autoimmune disease and allograft rejection. This outcome could selectively inhibit detrimental inflammatory immune responses without compromising functional protective immunity. A major challenge facing antigen-specific immunotherapies is ineffective control over immune signal targeting and integration, limiting efficacy and causing systemic non-specific suppression. Here we use intra-lymph node injection of diffusion-limited degradable microparticles that encapsulate self-antigens with the immunomodulatory small molecule, rapamycin. We show this strategy potently inhibits disease during pre-clinical type 1 diabetes and allogenic islet transplantation. Antigen and rapamycin are required for maximal efficacy, and tolerance is accompanied by expansion of antigen-specific regulatory T cells in treated and untreated lymph nodes. The antigen-specific tolerance in type 1 diabetes is systemic but avoids non-specific immune suppression. Further, microparticle treatment results in the development of tolerogenic structural microdomains in lymph nodes. Finally, these local structural and functional changes in lymph nodes promote memory markers among antigen-specific regulatory T cells, and tolerance that is durable. This work supports intra-lymph node injection of tolerogenic microparticles as a powerful platform to promote antigen-dependent efficacy in type 1 diabetes and allogenic islet transplantation.

Valorisation of fruit peel bioactive into green synthesized silver nanoparticles to modify cellulose wrapper for shelf-life extension of packaged bread.

Fruit peels are rich source of bioactive compounds such as polyphenols, flavonoids, and antioxidants but are often discarded as waste due to limited pharmaceutical and nutraceutical applications. This study aimed to valorise pomegranate and citrus fruit peel into green synthesised silver nanoparticles (AgNPs) in order to modify cellulose-based wrapping material for prospective food packaging applications and propose an alternate and sustainable approach to replace polyethene based food packaging material. Four different concentrations of AgNO3 (0.5 mM, 1 mM, 2 mM, and 3 mM) were used for green synthesis of AgNPs from fruit peel bioactive, which were characterised followed by phytochemical analysis. Ultraviolet-Visible spectroscopy showed surface plasmon resonance at 420 nm, XRD analysis showed 2θ peak at 27.8°, 32.16°, 38.5°, 44.31°, 46.09°, 54.76°, 57.47°, 64.61° and 77.50° corresponding to (210), (122), (111), (200), (231), (142), (241), (220) and (311) plane of face centred cubic crystal structure of AgNPs. Fourier-transform infrared spectroscopy analysis of AgNPs green synthesised from pomegranate and kinnow peel extract showed a major peak at 3277, 1640 and 1250-1020 1/cm while a small peak at 2786 1/cm was observed in case of pomegranate peel extract which was negligible in AgNPs synthesized from kinnow peel extract. Particle sizes of AgNPs showed no statistically significant variance with p > 0.10 and thus, 2 mM was chosen for further experimentation and modification of cellulose based packaging material as it showed smallest average particle size. Zeta potential was observed to be nearly neutral with a partial negative strength due to presence of various phenolic compounds such as presence of gallic acid which was confirmed by ultrahigh performance liquid chromatography-photodiode array(UHPLC-PDA) detector. Thermal stability analysis of green synthesised AgNPs qualified the sterilisation conditions up to 100 °C. AgNPs green synthesized from both the peel extracts had higher polyphenolic content, antioxidant and radical scavenging activity as compared to peel extracts without treatment (p < 0.05). The cellulose based food grade packaging material was enrobed by green synthesised AgNPs. The characterisation of modified cellulose wrappers showed no significant difference in thickness of modified cellulose wrappers as compared with untreated cellulose wrapper (p > 0.42) while weight and grammage increased significantly in modified cellulose wrapper (p < 0.05). The colour values on CIE scale (L*, a* and b*) showed statistically significant increase in yellow and green colour (p < 0.05) for modified cellulose wrappers as compared to control wrapper. The oxygen permeability coefficient, water vapour permeability coefficient, water absorption capacity and water behaviour characteristics (water content, swelling degree and solubility) showed significant decrease (p < 0.05) for modified cellulose wrapper as compared to control wrapper. A uniform distribution and density of green synthesised AgNPs across cellulose wrapper matrix was observed through scanning electron microscopy (SEM) images with no significant aggregation, confirming successful enrobing and stable immobilisation of nanoparticles from cellulose matrix. A seven-day storage study of bread wrapped in modified and control cellulose wrappers showed delayed occurrence of microbial, yeast and mould count in bread packaged in modified cellulose wrappers and thus, resulting in shelf life extension of bread. The results are encouraging for the potential applications of modified cellulose wrappers to replace polyethene based food packaging.

Strain-specific alterations in gut microbiome and host immune responses elicited by tolerogenic Bifidobacterium pseudolongum.

The beneficial effects attributed to Bifidobacterium are largely attributed to their immunomodulatory capabilities, which are likely to be species- and even strain-specific. However, their strain-specificity in direct and indirect immune modulation remain largely uncharacterized. We have shown that B. pseudolongum UMB-MBP-01, a murine isolate strain, is capable of suppressing inflammation and reducing fibrosis in vivo. To ascertain the mechanism driving this activity and to determine if it is specific to UMB-MBP-01, we compared it to a porcine tropic strain B. pseudolongum ATCC25526 using a combination of cell culture and in vivo experimentation and comparative genomics approaches. Despite many shared features, we demonstrate that these two strains possess distinct genetic repertoires in carbohydrate assimilation, differential activation signatures and cytokine responses signatures in innate immune cells, and differential effects on lymph node morphology with unique local and systemic leukocyte distribution. Importantly, the administration of each B. pseudolongum strain resulted in major divergence in the structure, composition, and function of gut microbiota. This was accompanied by markedly different changes in intestinal transcriptional activities, suggesting strain-specific modulation of the endogenous gut microbiota as a key to immune modulatory host responses. Our study demonstrated a single probiotic strain can influence local, regional, and systemic immunity through both innate and adaptive pathways in a strain-specific manner. It highlights the importance to investigate both the endogenous gut microbiome and the intestinal responses in response to probiotic supplementation, which underpins the mechanisms through which the probiotic strains drive the strain-specific effect to impact health outcomes.

STING controls T cell memory fitness during infection through T cell-intrinsic and IDO-dependent mechanisms.

Stimulator of interferon genes (STING) signaling has been extensively studied in inflammatory diseases and cancer, while its role in T cell responses to infection is unclear. Using Listeria monocytogenes strains engineered to induce different levels of c-di-AMP, we found that high STING signals impaired T cell memory upon infection via increased Bim levels and apoptosis. Unexpectedly, reduction of TCR signal strength or T cell-STING expression decreased Bim expression, T cell apoptosis, and recovered T cell memory. We found that TCR signal intensity coupled STING signal strength to the unfolded protein response (UPR) and T cell survival. Under strong STING signaling, Indoleamine-pyrrole 2,3-dioxygenase (IDO) inhibition also reduced apoptosis and led to a recovery of T cell memory in STING sufficient CD8 T cells. Thus, STING signaling regulates CD8 T cell memory fitness through both cell-intrinsic and extrinsic mechanisms. These studies provide insight into how IDO and STING therapies could improve long-term T cell protective immunity.

Artificial intelligence-based prediction of lycopene content in raw tomatoes using physicochemical attributes.

INTRODUCTION: Lycopene consumption reduces risk and incidence of cancer and cardiovascular diseases. Tomatoes are a rich source of phytochemical compounds including lycopene as a major constituent. Lycopene estimation using high-performance liquid chromatography is time-consuming and expensive. OBJECTIVE: To develop artificial intelligence models for prediction of lycopene in raw tomatoes using 14 different physicochemical parameters including salinity, total dissolved solids (TDS), electrical conductivity (EC), firmness, pH, total soluble solids (TSS), titratable acidity (TA), colour values on Hunter scale (L, a, b), total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity (AOA). MATERIAL AND METHODS: The post-harvest data acquisition was collected through investigation for more than 100 raw tomatoes stored for 15 days. Linear multivariate regression (LMVR), principal component regression (PCR) and partial least squares regression (PLSR) models were developed by splitting data set into train and test datasets. The training of models was performed using 10-fold cross validation (CV). RESULTS: Principal component analysis showed strong positive association between lycopene, colour value 'a', TPC, TFC and AOA. The R2 (CV), root mean square error (RMSE) (CV) and RMSE (Test) for best LMVR model was observed to be at 0.70, 8.48 and 9.69 respectively. The PCR model revealed R2 (CV) at 0.59, RMSE (CV) at 8.91 and RMSE (Test) at 10.17 while PLSR model revealed R2 (CV) at 0.60, RMSE (CV) at 9.10 and RMSE (Test) at 10.11. CONCLUSION: Results of the present study show that epidemiological studies suggest fully ripened tomatoes are most beneficial for consumption to ensure recommended daily intake of lycopene content.

Delivery of costimulatory blockade to lymph nodes promotes transplant acceptance in mice.

The lymph node (LN) is the primary site of alloimmunity activation and regulation during transplantation. Here, we investigated how fibroblastic reticular cells (FRCs) facilitate the tolerance induced by anti-CD40L in a murine model of heart transplantation. We found that both the absence of LNs and FRC depletion abrogated the effect of anti-CD40L in prolonging murine heart allograft survival. Depletion of FRCs impaired homing of T cells across the high endothelial venules (HEVs) and promoted formation of alloreactive T cells in the LNs in heart-transplanted mice treated with anti-CD40L. Single-cell RNA sequencing of the LNs showed that anti-CD40L promotes a Madcam1+ FRC subset. FRCs also promoted the formation of regulatory T cells (Tregs) in vitro. Nanoparticles (NPs) containing anti-CD40L were selectively delivered to the LNs by coating them with MECA-79, which binds to peripheral node addressin (PNAd) glycoproteins expressed exclusively by HEVs. Treatment with these MECA-79-anti-CD40L-NPs markedly delayed the onset of heart allograft rejection and increased the presence of Tregs. Finally, combined MECA-79-anti-CD40L-NPs and rapamycin treatment resulted in markedly longer allograft survival than soluble anti-CD40L and rapamycin. These data demonstrate that FRCs are critical to facilitating costimulatory blockade. LN-targeted nanodelivery of anti-CD40L could effectively promote heart allograft acceptance.

Self-Assembly of Immune Signals to Program Innate Immunity through Rational Adjuvant Design.

Recent clinical studies show activating multiple innate immune pathways drives robust responses in infection and cancer. Biomaterials offer useful features to deliver multiple cargos, but add translational complexity and intrinsic immune signatures that complicate rational design. Here a modular adjuvant platform is created using self-assembly to build nanostructured capsules comprised entirely of antigens and multiple classes of toll-like receptor agonists (TLRas). These assemblies sequester TLR to endolysosomes, allowing programmable control over the relative signaling levels transduced through these receptors. Strikingly, this combinatorial control of innate signaling can generate divergent antigen-specific responses against a particular antigen. These assemblies drive reorganization of lymph node stroma to a pro-immune microenvironment, expanding antigen-specific T cells. Excitingly, assemblies built from antigen and multiple TLRas enhance T cell function and antitumor efficacy compared to ad-mixed formulations or capsules with a single TLRa. Finally, capsules built from a clinically relevant human melanoma antigen and up to three TLRa classes enable simultaneous control of signal transduction across each pathway. This creates a facile adjuvant design platform to tailor signaling for vaccines and immunotherapies without using carrier components. The modular nature supports precision juxtaposition of antigen with agonists relevant for several innate receptor families, such as toll, STING, NOD, and RIG.

A Cross-Sectional Study of the Impact of the COVID-19 Pandemic on Previously Diagnosed Patients With Fibromyalgia.

Introduction Coronavirus disease 2019 (COVID-19) was a one-of-its-kind pandemic due to its high infectivity and mortality rate. Prolonged lockdown periods imposed during the pandemic saved many lives but, on the other hand, had a huge psychological and clinical impact on patients suffering from chronic medical illnesses. Aims This study aimed to find the impact of the COVID-19 pandemic on patients with previously diagnosed fibromyalgia. Methods A prospective observational study including the cohort of previously diagnosed cases of fibromyalgia as per American College of Rheumatology (ACR) 2010 criteria where the patients were evaluated by an online survey for socio-demographic profile, subjective improvement, and objective improvement in quality of life by the Fibromyalgia Impact Questionnaire-Revised (FIQR). Pre and post-COVID-19 scores were analyzed. The statistical procedure used included the chi-square test. Results A total of 78 subjects were recruited for the study, with a female preponderance (75%) and mean (SD) age of 37.2 (9.2) years. The duration of symptoms was nine to 12 months followed by more than 12 months at the time of the first consultation for the majority of subjects. Sixty-five percent (65%) of subjects had no improvement or deterioration on FIQR. Statistical analysis This included mean, standard deviation, proportions, percentages, and the chi-square test. Conclusion COVID-19 had a significant negative impact on patients with fibromyalgia even on continued pharmacological treatment. However, there was no statistically significant data on the comparison of the overall mean score of FIQR and each domain individually with the continuation of treatment and improvement of symptoms.

Lymph node fibroblastic reticular cells preserve a tolerogenic niche in allograft transplantation through laminin α4.

Lymph node (LN) fibroblastic reticular cells (FRCs) define LN niches and regulate lymphocyte homeostasis through producing diverse extracellular matrix (ECM) components. We examined the role of ECM laminin α4 (Lama4) using FRC-Lama4 conditional KO Pdgfrb-Cre-/- × Lama4fl/fl mice. Single-cell RNA-sequencing (scRNA-Seq) data showed the promoter gene Pdgfrb was exclusively expressed in FRCs. Depleting FRC-Lama4 reduced Tregs and dendritic cells, decreased high endothelial venules, impaired the conduit system, and downregulated T cell survival factors in LNs. FRC-Lama4 depletion impaired the homing of lymphocytes to LNs in homeostasis and after allografting. Alloantigen-specific T cells proliferated, were activated to greater degrees in LNs lacking FRC-Lama4, and were more prone to differentiate into effector phenotypes relative to the Treg phenotype. In murine cardiac transplantation, tolerogenic immunosuppression was not effective in FRC-Lama4 recipients, which produced more alloantibodies than WT. After lung transplantation, FRC-Lama4-KO mice had more severe graft rejection with fewer Tregs in their LNs. Overall, FRC-Lama4 critically contributes to a tolerogenic LN niche by supporting T cell migration, constraining T cell activation and proliferation, and promoting Treg differentiation. Hence, it serves as a therapeutic target for immunoengineering.

PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration.

Programmed death-1 (PD-1) and its ligand PD-L1 are checkpoint molecules which regulate immune responses. Little is known about their functions in T cell migration and there are contradictory data about their roles in regulatory T cell (Treg) function. Here we show activated Tregs and CD4 effector T cells (Teffs) use PD-1/PD-L1 and CD80/PD-L1, respectively, to regulate transendothelial migration across lymphatic endothelial cells (LECs). Antibody blockade of Treg PD-1, Teff CD80 (the alternative ligand for PD-L1), or LEC PD-L1 impairs Treg or Teff migration in vitro and in vivo. PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to up-regulate VCAM-1 expression on LECs. CD80/PD-L1 signaling up-regulates VCAM-1 through ERK and NFκB-p65. PD-1 and CD80 blockade reduces tumor egress of PD-1high fragile Tregs and Teffs into draining lymph nodes, respectively, and promotes tumor regression. These data provide roles for PD-L1 in cell migration and immune regulation.

Treg tissue stability depends on lymphotoxin beta-receptor- and adenosine-receptor-driven lymphatic endothelial cell responses.

Regulatory T cell (Treg) lymphatic migration is required for resolving inflammation and prolonging allograft survival. Focusing on Treg interactions with lymphatic endothelial cells (LECs), we dissect mechanisms and functional consequences of Treg transendothelial migration (TEM). Using three genetic mouse models of pancreatic islet transplantation, we show that Treg lymphotoxin (LT) αß and LEC LTß receptor (LTßR) signaling are required for efficient Treg migration and suppressive function to prolong allograft survival. Inhibition of LT signaling increases Treg conversion to Foxp3loCD25lo exTregs. In a transwell-based model of TEM across polarized LECs, non-migrated Tregs become exTregs. Such conversion is regulated by LTßR nuclear factor κB (NF-κB) signaling in LECs, which increases interleukin-6 (IL-6) production and drives exTreg conversion. Migrating Tregs are ectonucleotidase CD39hi and resist exTreg conversion in an adenosine-receptor-2A-dependent fashion. Human Tregs migrating across human LECs behave similarly. These molecular interactions can be targeted for therapeutic manipulation of immunity and suppression.

Artificial intelligence-assisted blockchain-based framework for smart and secure EMR management.

Healthcare professionals, patients, and other stakeholders have been storing medical prescriptions and other relevant reports electronically. These reports contain the personal information of the patients, which is sensitive data. Therefore, there exists a need to store these records in a decentralized model (using IPFS and Ethereum decentralized application) to provide data and identity protection. Many patients recurrently visit doctors and undergo treatments while receiving different prescriptions and reports. In case of an emergency, the doctors and attendants may need and benefit from the patients' medical history. However, they are unable to go through medical history and a wide range of previous reports and prescriptions due to time constraints. In this paper, we propose an AI-assisted blockchain-based framework in which the stored medical records (handwritten prescriptions, printed prescriptions, and printed reports) are stored and processed using various AI techniques like optical character recognition (OCR) to form a single patient medical history report. The report concisely presents only the crucial information for convenience and perusal and is stored securely over a decentralized blockchain network for later use.

Mortality in patients with Coronavirus disease 2019 (COVID- 19) and its clinicoradiological and laboratory correlates: A retrospective study.

Aim: To delineate and analyze the mortality from COVID -19 in our institute during the devastating second wave of pandemic. Settings and Design: A retrospective cohort analysis. Methods and Materials: A comprehensive mortality analysis of 142 laboratory-confirmed severe acute respiratory syndrome coronavirus 2-infected deceased patients from our hospital's medical records was done. These patients presented with severe disease at the time of admission and were managed in intensive care units. Statistical Analysis Used: Statistical Package for Social Sciences software, IBM manufacturer, Chicago, USA, version 21.0 was used. Results: The number of deceased males (82, 62.6%) was higher than females (53, 37.3%). Median age of deceased patient was 57 (44.25-69.75) years. Most frequent comorbidities were diabetes mellitus (42, 29.6%) and hypertension (41, 28.9%). Most common symptoms being shortness of breath (137, 96.5%), fever (94, 66.2%) and cough (73, 51.4%). Median peripheral capillary oxygen saturation (SpO2) at time of admission was 86% (77.25-90). Median time interval from symptom onset to admission in hospital was 3 (2.25-5) days. Neutrophil lymphocyte ratio was more than 5 in 117 (90.7%) patients. Complications seen were acute respiratory distress syndrome in 82.3%, acute liver injury in 58.4%, acute kidney injury in 26.7%, sepsis in 13.3% and acute cardiac injury in 12% patients. The median high-resolution computed tomography score was 20 (17-22). Conclusions: Male and elderly patients with underlying comorbidities had poorer outcome and involvement of multiple organ systems was common. A short time interval between symptom onset and admission/mortality, particularly encountered was worrisome.

Chronic rejection as a persisting phantom menace in organ transplantation: a new hope in the microbiota?

PURPOSE OF REVIEW: The microbiota plays an important role in health and disease. During organ transplantation, perturbations in microbiota influence transplant outcome. We review recent advances in characterizing microbiota and studies on regulation of intestinal epithelial barrier function and mucosal and systemic immunity by microbiota and their metabolites. We discuss implications of these interactions on transplant outcomes. RECENT FINDINGS: Metagenomic approaches have helped the research community identify beneficial and harmful organisms. Microbiota regulates intestinal epithelial functions. Signals released by epithelial cells or microbiota trigger pro-inflammatory or anti-inflammatory effects on innate and adaptive immune cells, influencing the structure and function of the immune system. Assessment and manipulation of microbiota can be used for biomarkers for diagnosis, prognosis, and therapy. SUMMARY: The bidirectional dialogue between the microbiota and immune system is a major influence on immunity. It can be targeted for biomarkers or therapy. Recent studies highlight a close association of transplant outcomes with microbiota, suggesting exciting potential avenues for management of host physiology and organ transplantation.