Chronic State Research Articles

Dialectical Medicine: Z Syndrome and Use of Pathological Substances, The Clinical Case

Since the beginning of humanity man develops without stimulation for internal consciousness, although technological evolution grows in a linear sense, the human mind remains stagnant, exchanging the ancient human slavery for the mental slavery of money and fear. Z Syndrome was described in September 2022 as a family neuroadaptation disease, dearly childhood, as central dysfunction to biological family asynchrony, with multiple neuroendocrine, neuro epigenetic alterations, associated with chronic filial hypodopaminergic state, all unconscious, in which family disease is harmful among family members. This is a dysfunction common to every human being, and Z Syndrome has initial dopaminergic pathophysiology, and is connected to other medical areas. The dialectic function of the reality of the religious, of the doctor, of the legal professional, of a political leader, who now has the choice between the biological truth of his diagnoses, of his families, and of his countries, whether a disease, disorder or just dysfunction, directly influences the collective future. All children to this day, are growing and developing neuro adapted, without biological family synchrony, and without real free will. Statistics will hardly solve studies of the human mind, which is always limited to linearity without clinical coding in the field of medicine. Dissecting intimately the love of attachment, the sublimation of charity and gaining fluid intelligence, is the result of the unique and REAL CHANGE, which is the treatment of Z Syndrome. The reflection and evaluation of the work performed to any addition should be revaluated, as many are being harmed. With a lot of love and joy that I dedicate this work to all professional specialists, scientists and my parents, because without you, this diagnosis would not be possible.

Angiotensin-Converting Enzyme 2 Expression and Severity of SARS-CoV-2 Infection.

Angiotensin-converting enzyme 2 (ACE2), first discovered in 2000, serves as an important counterregulatory enzyme to the angiotensin II-mediated vasoconstrictive, pro-inflammatory, and pro-fibrotic actions of the renin-angiotensin system (RAS). Conversion of angiotensin II to the peptide angiotensin 1-7 (ANG 1-7) exerts protective vasodilatory, anti-inflammatory, and anti-fibrotic actions through interaction with the MasR receptor. There are many important considerations when noting the role of ACE2 in the pathogenesis and sequelae of COVID-19 infection. ACE2, in the role of COVID-19 infection, was recognized early in 2020 at the beginning of the pandemic as a cell membrane-bound and soluble binding site for the viral spike protein facilitating entering into tissue cells expressing ACE2, such as the lungs, heart, gut, and kidneys. Mechanisms exist that alter the magnitude of circulating and membrane-bound ACE2 (e.g., SARS-CoV-2 infection, viral variants, patient characteristics, chronic disease states, and the degree of cell surface expression of ACE2) and the influence these mechanisms have on the severity of disease and associated complications (e.g., respiratory failure, systemic inflammatory response syndrome, acute myocarditis, acute kidney injury). Several medications alter the ACE2 receptor expression, but whether these medications can influence the course of the disease and improve outcomes is unclear. In this review, we will discuss what is known about the interrelation of SARS-CoV-2, ACE2 and the factors that may contribute to the variability of its expression and potential contributors to the severity of COVID-19 infection.

Bioactive Compounds as Inhibitors of Inflammation, Oxidative Stress and Metabolic Dysfunctions via Regulation of Cellular Redox Balance and Histone Acetylation State.

Bioactive compounds (BCs) are known to exhibit antioxidant, anti-inflammatory, and anti-cancer properties by regulating the cellular redox balance and histone acetylation state. BCs can control chronic oxidative states caused by dietary stress, i.e., alcohol, high-fat, or high-glycemic diet, and adjust the redox balance to recover physiological conditions. Unique functions of BCs to scavenge reactive oxygen species (ROS) can resolve the redox imbalance due to the excessive generation of ROS. The ability of BCs to regulate the histone acetylation state contributes to the activation of transcription factors involved in immunity and metabolism against dietary stress. The protective properties of BCs are mainly ascribed to the roles of sirtuin 1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (NRF2). As a histone deacetylase (HDAC), SIRT1 modulates the cellular redox balance and histone acetylation state by mediating ROS generation, regulating nicotinamide adenine dinucleotide (NAD+)/NADH ratio, and activating NRF2 in metabolic progression. In this study, the unique functions of BCs against diet-induced inflammation, oxidative stress, and metabolic dysfunction have been considered by focusing on the cellular redox balance and histone acetylation state. This work may provide evidence for the development of effective therapeutic agents from BCs.

Stool biomarkers as measures of enteric pathogen infection in infants from Addis Ababa informal settlements.

Frequent enteric infections in children may be an important cause of growth faltering; however, we do not fully understand the mechanisms by which pathogen infections and the physiological responses to these infections result in poorer growth. Commonly used protein fecal biomarkers (anti-alpha trypsin, neopterin, and myeloperoxidase) provide broad immunological information on an inflammatory response; however, they do not provide information on non-immune processes (e.g., gut integrity) that may be important indicators of chronic end states such as environmental enteric dysfunction (EED). To explore how additional biomarkers will better inform which physiological pathways (both immune and non-immune) are impacted by pathogen exposure we added to the traditional panel of 3 protein fecal biomarkers 4 novel fecal mRNA transcript biomarkers (sucrase isomaltase, caudal homeobox 1, S100A8, and mucin 12) and analyzed stool samples from infants living in informal settlements in Addis Ababa, Ethiopia. To test how this expanded biomarker panel captures distinct pathogen exposure processes we used two different scoring systems. First, we used a theory-based approach to assign each biomarker to specific physiological attributes based on prior understanding of each biomarker. Second, we used data reduction methods to categorize biomarkers and then assign physiological attributes to those categories. We used linear models to examine the association between the derived biomarker scores (based on mRNA and protein levels) and stool pathogen gene counts to determine pathogen specific effects on gut physiology and immune responses. Inflammation scores were positively associated with Shigella and enteropathogenic E.Coli (EPEC) infection, while gut integrity scores were negatively associated with Shigella, EPEC and, shigatoxigenic E.coli (STEC) infection. Our expanded panel of biomarkers hold promise as tools to measure systemic outcomes of enteric pathogen infection. mRNA biomarkers complement established protein biomarkers by providing important cell-specific physiological and immunological consequences of pathogen carriage that can lead to chronic end states such as EED.

The syndromic triad of COVID-19, type 2 diabetes, and malnutrition.

The coronavirus disease 2019 (COVID-19) pandemic challenges our collective understanding of transmission, prevention, complications, and clinical management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Risk factors for severe infection, morbidity, and mortality are associated with age, environment, socioeconomic status, comorbidities, and interventional timing. Clinical investigations report an intriguing association of COVID-19 with diabetes mellitus and malnutrition but incompletely describe the triphasic relationship, its mechanistic pathways, and potential therapeutic approaches to address each malady and their underlying metabolic disorders. This narrative review highlights common chronic disease states that interact epidemiologically and mechanistically with the COVID-19 to create a syndromic phenotype-the COVID-Related Cardiometabolic Syndrome-linking cardiometabolic-based chronic disease drivers with pre-, acute, and chronic/post-COVID-19 disease stages. Since the association of nutritional disorders with COVID-19 and cardiometabolic risk factors is well established, a syndromic triad of COVID-19, type 2 diabetes, and malnutrition is hypothesized that can direct, inform, and optimize care. In this review, each of the three edges of this network is uniquely summarized, nutritional therapies discussed, and a structure for early preventive care proposed. Concerted efforts to identify malnutrition in patients with COVID-19 and elevated metabolic risks are needed and can be followed by improved dietary management while simultaneously addressing dysglycemia-based chronic disease and malnutrition-based chronic disease.

NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress-induced anhedonia-like behavior and reductions in excitatory synapses.

Chronic stress can produce reward system deficits (i.e., anhedonia) and other common symptoms associated with depressive disorders, as well as neural circuit hypofunction in the medial prefrontal cortex (mPFC). However, the molecular mechanisms by which chronic stress promotes depressive-like behavior and hypofrontality remain unclear. We show here that the neuronal activity-regulated transcription factor, NPAS4, in the mPFC is regulated by chronic social defeat stress (CSDS), and it is required in this brain region for CSDS-induced changes in sucrose preference and natural reward motivation in the mice. Interestingly, NPAS4 is not required for CSDS-induced social avoidance or anxiety-like behavior. We also find that mPFC NPAS4 is required for CSDS-induced reductions in pyramidal neuron dendritic spine density, excitatory synaptic transmission, and presynaptic function, revealing a relationship between perturbation in excitatory synaptic transmission and the expression of anhedonia-like behavior in the mice. Finally, analysis of the mice mPFC tissues revealed that NPAS4 regulates the expression of numerous genes linked to glutamatergic synapses and ribosomal function, the expression of upregulated genes in CSDS-susceptible animals, and differentially expressed genes in postmortem human brains of patients with common neuropsychiatric disorders, including depression. Together, our findings position NPAS4 as a key mediator of chronic stress-induced hypofrontal states and anhedonia-like behavior.

Butyrate: More Than a Short Chain Fatty Acid.

The mechanistic understanding of the importance and the potential benefits of the gut microbiome has exploded in potential roles in human health and disease. Short chain fatty acids (SCFAs), including butyrate, are one of the key metabolic end products that has been a major focus of microbiome understanding. This brief review aims to describe butyrate's relation to certain biological concepts and their clinical application. Butyrate has reportedly been described as a potent pro-resolution molecule that has a significant role in maintaining gut immunity, supporting gut barrier function, regulation of histone deacetylase (HDAC), and numerous systemic roles. Further research is needed to explore potential benefits of adding SCFAs for patients receiving total parenteral nutrition. Butyrate plays several biological roles in intestinal epithelium anti-inflammatory pathways with clear benefits in numerous acute and chronic disease states and overall human health helping to maintain homeostasis.

Chronic ocular small vessel disease: An overview of diabetic retinopathy and its relationship with cardiovascular health

Diabetic retinopathy (DR) is a potentially blinding disease originating from small vessel damage in the retina in chronic hyperglycemic states. DR has a complex multi-pathway driven pathogenesis resulting in diabetic macular edema and retinal ischemia, the former being the most common cause of vision impairment in DR. Hypoxia induced cytokines stimulate vascular endothelial growth factor (VEGF) production and subsequent angiogenesis with resultant mechanical retinal damage over time. Anti-VEGF therapy is effective for the treatment of center-involving diabetic macular edema. There is evolving evidence showing the effectiveness of anti-VEGF as both adjuvant and monotherapy in the treatment of proliferative DR, however laser photocoagulation continues to remain the standard of care. DR in large cohort studies has been shown to be an independent risk factor for the development of cardiovascular disease and mortality. In addition, changes in retinal vascular caliber ratios may have implications for risk of macrovascular events with a gender discrepancy towards women.

Applying Next-Generation Sequencing and Multi-Omics in Chronic Obstructive Pulmonary Disease.

Microbiomics have significantly advanced over the last decade, driven by the widespread availability of next-generation sequencing (NGS) and multi-omic technologies. Integration of NGS and multi-omic datasets allow for a holistic assessment of endophenotypes across a range of chronic respiratory disease states, including chronic obstructive pulmonary disease (COPD). Valuable insight has been attained into the nature, function, and significance of microbial communities in disease onset, progression, prognosis, and response to treatment in COPD. Moving beyond single-biome assessment, there now exists a growing literature on functional assessment and host-microbe interaction and, in particular, their contribution to disease progression, severity, and outcome. Identifying specific microbes and/or metabolic signatures associated with COPD can open novel avenues for therapeutic intervention and prognosis-related biomarkers. Despite the promise and potential of these approaches, the large amount of data generated by such technologies can be challenging to analyze and interpret, and currently, there remains a lack of standardized methods to address this. This review outlines the current use and proposes future avenues for the application of NGS and multi-omic technologies in the endophenotyping, prognostication, and treatment of COPD.

Chronic water restriction reduces sensitivity to brain stimulation reward in male and female rats

States of physiological need motivate individuals to seek and consume stimuli that restore homeostatic balance. This goal-directed behavior is driven, in part, by pathways that process reward and are sensitive to changes in physiological state, including the mesolimbic dopamine system. The effects of hunger and its physiological markers have been more widely studied for their role in modulating reward signaling pathways. However, fluid need produces robust goal-directed behavior and has also been shown to affect neural substrates of reward processing. To test how acute and chronic states of thirst might alter reward sensitivity, we used the intracranial self-stimulation (ICSS) rate-frequency paradigm (Carlezon & Chartoff, 2007) with male and female Long Evans rats. We hypothesized that sensitivity to ICSS would increase under an acute need state for water and would decrease under chronic deprivation. We found that acute water deprivation for 22-hours prior to the ICSS session did not alter any parameters of reward sensitivity. To elicit motivated behavior toward water in the absence of physiological need, we chemogenetically activated glutamatergic neurons of the subfornical organ (SFO). Despite eliciting more water consumption than acute deprivation, acute chemogenetic activation of SFO neurons also did not alter reward sensitivity. Finally, subjects underwent a five-day chronic water restriction protocol with daily ICSS sessions to determine the effects of sustained physiological need. Chronic water restriction resulted in reduced sensitivity to ICSS. Together, these results indicate that persistent changes in physiological state alter the responsiveness of reward circuitry that could potentially exacerbate maladaptive reward-seeking behaviors.

The immune paradox of SARS-CoV-2: Lymphocytopenia and autoimmunity evoking features in COVID-19 and possible treatment modalities.

SARS-CoV-2 causes multiorgan damage to vital organs and tissue that are known to be due to a combination of tissue tropisms and cytokine-mediated damage that it can incite in COVID-19. The effects of SARS-Co-2 on the lymphocytes and therefore on the immune response have attracted attention recently in COVID-19 to understand its effects in causing a chronic state of ongoing infection with Long-COVID. The associated lymphopaenia and autoimmune disease state, which is an apparent paradox, needs to be researched to dissect possible mechanisms underlying this state. This paper attempts to unravel the aforesaid immune paradox effects of SARS-CoV-2 on the lymphocytes and discusses appropriate treatment modalities with antiviral drugs and nutraceuticals which could prove virucidal in SARS-CoV-2 seeding monocytes and lymphocytes in patients with COVID-19 and Long-COVID. Importantly it proposes a new in vitro treatment modality of immune regulating cells that can help patients fight the lymphopaenia associated with COVID-19 and Long-COVID.

Development of a value-based care and population health internship for student pharmacists

IntroductionPharmacists assist in achieving desired outcomes and reducing costs of care within newer value-based payment models. The purpose of this article is to describe a summer internship for first- and second-year student pharmacists to gain exposure to value-based care. MethodsUniversity Health Network is a clinically integrated health network and accountable care organization in East Tennessee. Two student interns completed consecutive seven-week programs alongside clinical pharmacist specialists in the primary care settings of the network. Program requirements included direct patient care for chronic disease state management, topic discussions, formal writing assignments and presentations, and a quality improvement project. Student perception of internship activities was measured using a Likert type survey and free response questionnaire. ResultsStudent interns responded positively to program requirements with feelings of enhanced preparedness for advanced pharmacy practice experiences and post-graduate residency positions. Additionally, interns perceived themselves as more competitive for post-graduate positions having completed the internship. ConclusionsAs the US continues to move toward value-based payment models, student pharmacists must be well prepared to contribute to quality and population health initiatives. Student pharmacists benefit from an internship in a clinically integrated health network by gaining an improved understanding of the future of United States healthcare, an expanded clinical skillset, experience in demonstrating a pharmacist's value to the healthcare team, and the ability to overcome barriers to pharmacy services. A pharmacy internship within a clinically integrated health network may help prepare students to successfully contribute to value-based models of healthcare.

Predictability of Nailfold Capillaroscopic Score in Diagnosing Retinopathy in Patients with Type 2 Diabetes Mellitus and its Utility as a Non-Invasive Tool for Differentiating from those Not Having Retinopathy: A Pilot Observational Cross-Sectional Analytical Study.

Diabetes mellitus (DM) is a chronic hyperglycaemic state associated with microvascular structural alterations. Nailfold capillaroscopy (NFC) is an in vivo study of microvascular circulation. This study aimed to investigate the diameters of capillary loops and morpho-structural changes using a handheld dermatoscope in patients with type 2 DM (T2DM) with and without diabetic retinopathy (DR) and to establish nailfold capillary changes and NFC score as a non-invasive method to identify microvascular complication in T2DM patients. A cross-sectional observational study was conducted in AIIMS Rishikesh for 6 months from August 2022 to February 2023. Our study participants were 100 adults more than 18 years of age diagnosed with T2DM, based on the American Diabetes Association (ADA) criteria. All patients were evaluated thoroughly for the presence of microvascular complications in the form of retinopathy. Based on this, they were divided into two groups-group 1 (T2DM with retinopathy) and group 2 (T2DM without retinopathy). Both groups were further subdivided into three subgroups based on haemoglobin A1c (HbA1c): the first group with HbA1c <7%, the second group with HbA1c 7-8.9% and the third group with HbA1c >=9%. For all the study participants, a detailed NFC was done for all 8 fingernails (excluding the thumb), using a handheld dermatoscope. Abnormal capillary shapes (ACS) were recorded by semi-quantitative score (NFC score). A significant association was seen in capillary density (loops/mm) (5.83 ± 0.72 in the DR group and 6.3 ± 0.89 in the no-DR group) (P value = 0.005), capillary density (loops/3 mm) (P value = 0.005), total number of microhaemorrhages/3 mm (P value < .0001), total number of giant capillaries/3 mm (P value = 0.0004), total number of avascular areas/3 mm (P value = 0.0005), enlarged capillaries/3 mm (P value = 0.002), tortuous capillaries/3 mm (P value < .0001), abrogated/bushy capillaries/3 mm (P value = 0.004), number of fingers involved excluding the thumb (P value < .0001) and total nailfold capillaroscopic score (P value < .0001) between the two groups, one with DR and another without DR. Furthermore, the proportion of patients with abnormal nailfold capillaroscopic findings, abnormal NFC score, was significantly higher in patients with DR as compared to patients without DR (51.85% vs 4.35%, respectively) (P value < 0.0001). Our results suggest that NFC could possibly be used as an adjunctive tool in diabetics for diagnosing or monitoring microvascular complications with total NFC score being the significant predictor of DR at a cut-off point of >0 with the area under the curve (AUC) of 0.745 for correctly predicting DR.

Recent Research Advancements in Interventions and Assessments Related to Chronic Obstructive Pulmonary Disease Rehabilitation

The Global Initiative for Chronic Obstructive Pulmonary Disease states that pulmonary rehabilitation (PR) can improve patients’ health and prevent progression of chronic obstructive pulmonary disease (COPD). By searching the relevant literature on lung ventilation both in China and abroad, and reviewing the impact of physical exercise, nutrition intervention, physical education, and psychological intervention on lung ventilation measures in COPD patients, this paper aims to provide guidance for clinical nurses in implementing PR in COPD patients.

The Interplay between α-Synuclein and Microglia in α-Synucleinopathies.

Synucleinopathies are a set of devastating neurodegenerative diseases that share a pathologic accumulation of the protein α-synuclein (α-syn). This accumulation causes neuronal death resulting in irreversible dementia, deteriorating motor symptoms, and devastating cognitive decline. While the etiology of these conditions remains largely unknown, microglia, the resident immune cells of the central nervous system (CNS), have been consistently implicated in the pathogenesis of synucleinopathies. Microglia are generally believed to be neuroprotective in the early stages of α-syn accumulation and contribute to further neurodegeneration in chronic disease states. While the molecular mechanisms by which microglia achieve this role are still being investigated, here we highlight the major findings to date. In this review, we describe how structural varieties of inherently disordered α-syn result in varied microglial receptor-mediated interactions. We also summarize which microglial receptors enable cellular recognition and uptake of α-syn. Lastly, we review the downstream effects of α-syn processing within microglia, including spread to other brain regions resulting in neuroinflammation and neurodegeneration in chronic disease states. Understanding the mechanism of microglial interactions with α-syn is vital to conceptualizing molecular targets for novel therapeutic interventions. In addition, given the significant diversity in the pathophysiology of synucleinopathies, such molecular interactions are vital in gauging all potential pathways of neurodegeneration in the disease state.

Implementation of pharmacist recommendations in patients with type 2 diabetes enrolled in an employer-sponsored health plan

BackgroundThe new, employee health plan (EHP) focused, population health initiative was established at Atrium Health Wake Forest Baptist in October 2020. The initiative’s goals are to reduce health care costs and optimize patient care by providing patient-specific recommendations to help manage chronic disease states in the ambulatory care setting. This project’s purpose is to quantify and categorize pharmacist recommendations implemented and not implemented. ObjectiveDescribe the implementation of pharmacist recommendations in a new, population health program. MethodsEligible patients: >18 years of age, diagnosed with type 2 diabetes, baseline HbA1c > 8%, and enrolled in the EHP. Patients were identified retrospectively through an electronic health record report. The primary endpoint assessed the proportion of pharmacist recommendations implemented. Interventions implemented and not implemented were categorized and reviewed for timely optimization of patient care and quality improvement. ResultsOverall, 55.7% of pharmacist recommendations were implemented. The most common reason recommendations were not implemented was that they were not addressed by the provider. The most common pharmacist recommendation was a drug therapy addition. Recommendations were implemented in a median time of 44 days. ConclusionOver half of pharmacist recommendations were implemented. Provider communication and awareness was identified as a barrier for this new initiative. Increasing provider education and advertisement of pharmacist services should be considered to increase future implementation rates. The project identified a need for optimization of timely patient care by prioritizing patient charts prior to their next applicable provider visit.

Incident edentulism and number of comorbidities among middle-aged and older Americans.

Certain chronic non-communicable diseases have been associated with the loss of all natural permanent teeth, referred to as edentulism. It has been suggested that edentulism, a chronic dental state, involving the loss of all teeth and poorer masticatory efficiency, could be associated with multiple chronic conditions as people age. In this study, we describe the association between the number of comorbidities and incident edentulism in a representative sample of older Americans. We took data from the Health and Retirement Study (HRS). Dentate participants aged 50 or older at the baseline of 2006 (N=13 221) and 2012 (N=13 938) were linked to their dentate and survival status at the follow-up interviews in 2012 and 2018, respectively. The association between the number of comorbidities and incident edentulism was investigated by using multinomial logistic regression models. Over the two observation periods, the number of selected chronic conditions was predictive of edentulism 6 years later. A 10% higher chance of becoming edentulous by 2012 (OR=1.10, 95% CI=1.01, 1.20) was found for every additional comorbid condition to those who remained dentate in 2012. A similar association was identified for the 2012-2018 period. Among older adults, the number of comorbidities was predictive of incident edentulism, and the same association pattern was found across two longitudinal study periods. Older adults with an increase in the number of comorbidities may experience a higher chance of tooth loss later in time.

An automated platform for Assessing Working Memory and prefrontal circuit function

Working memory is a process for actively maintaining and updating task-relevant information, despite interference from competing inputs, and is supported in part by sustained activity in prefrontal cortical pyramidal neurons and coordinated interactions with inhibitory interneurons, which may serve to regulate interference. Chronic stress has potent effects on working memory performance, possibly by interfering with these interactions or by disrupting long-range inputs from key upstream brain regions. Still, the mechanisms by which chronic stress disrupts working memory are not well understood, due in part to a need for scalable, easy-to-implement behavioral assays that are compatible with two-photon calcium imaging and other tools for recording from large populations of neurons. Here, we describe the development and validation of a platform that was designed specifically for automated, high-throughput assessments of working memory and simultaneous two-photon imaging in chronic stress studies. This platform is relatively inexpensive and easy to build; fully automated and scalable such that one investigator can test relatively large cohorts of animals concurrently; fully compatible with two-photon imaging, yet also designed to mitigate head-fixation stress; and can be easily adapted for other behavioral paradigms. Our validation data confirm that mice could be trained to perform a delayed response working memory task with relatively high-fidelity over the course of ∼15 days. Two-photon imaging data validate the feasibility of recording from large populations of cells during working memory tasks performance and characterizing their functional properties. Activity patterns in >70% of medial prefrontal cortical neurons were modulated by at least one task feature, and a majority of cells were engaged by multiple task features. We conclude with a brief literature review of the circuit mechanisms supporting working memory and their disruption in chronic stress states—highlighting directions for future research enabled by this platform.

USING A REAL TIME DASHBOARD TO SUPPORT POPULATION HEALTH IN INFLAMMATORY BOWEL DISEASE

Abstract The Phoenix Children’s Hospital (PCH) Inflammatory Bowel Disease (IBD) Clinic provides care for nearly 500 patients. As a group, PCH is part of the ImproveCareNow (ICN) network—a collaboration of over 100 centers worldwide to improve IBD care. Patient care has followed ICN guidelines including a weekly pre-visit planning (PVP) session. PVP is a time intensive process of manual chart review and data gathering for upcoming clinic patients. To improve this process and patient care, our group created a real-time IBD dashboard. OBJECTIVES: The aims of the dashboard were to identify and validate our patient population, improve efficiency by automating data gathering for PVP, and create a visual representation . Secondary aim, was to optimize processes including documentation, order entry and timely follow-up. METHODS: Data is sourced from the Allscripts electronic medical record (EMR). Data retrieval is contingent upon documentation. Our population of patients with IBD was identified based on a charted ICD-10 diagnosis of CD, UC or IC. PCH has a data warehouse of orders, results, Admission-Discharge-Transfer documentation, and flowsheets from the EMR and external data sources. Data is harvested and hosted using Microsoft Power BI for live review at weekly PVP. Once desired data points were hosted, focus was on process improvement (proper documentation, follow-up orders, and patient visits every 200 days). RESULTS: The dashboard hosts patients seen within the last 200 days, provider follow-up order placement, and physician global assessment (PGA) since January 2021. The percent of patients with follow-up orders placed was 61% in 2021. With dashboard enhancements and data visibility, this improved to 99% as of October 17, 2022. Physician global assessment (PGA) was recorded in 81% of encounters in 2021. Our most recent documentation rate is 92% on October 17, 2022. Our group had seen 82% of patients within the 200 days in 2021. Currently we have seen 89% of patients within 200 days as of October 17, 2022 (of these 91% of patients with active disease have been seen). We have instituted a work-flow process with schedulers to ensure patients are contacted and scheduled and not transitioned or moved. Figure 1 Historical Data from 1/2021-10/2021 Figure 2 Current Data as of 10/17/2022 CONCLUSIONS: With time, the IBD dashboard has proven to be a powerful tool in improving process measures. Our hope is these improvements will lend themselves to improved patient outcomes. With the ability to view data in real time in an automated fashion, staff hours have been saved and reallocated to other patient care needs. With continuous review of the data and introduction of accountability, we continue to see improvement. We now have the capacity to add additional metrics to the dashboard and our this can be viewed as a proof of concept for use in other specialties and chronic disease states.

EphH, a unique epoxide hydrolase encoded by Rv3338 is involved in the survival of Mycobacterium tuberculosis under in vitro stress and vacuolar pH-induced changes.

Mycobacterium tuberculosis (Mtb), one of the deadliest human pathogen, has evolved with different strategies of survival inside the host, leading to a chronic state of infection. Phagosomally residing Mtb encounters a variety of stresses, including increasing acidic pH. To better understand the host-pathogen interaction, it is imperative to identify the role of various genes involved in the survivability of Mtb during acidic pH environment. Bio-informatic and enzymatic analysis were used to identify Mtb gene, Rv3338, as epoxide hydrolase. Subsequently, CRISPRi knockdown strategy was used to decipher its role for Mtb survival during acidic stress, nutrient starvation and inside macrophages. Confocal microscopy was used to analyse its role in subverting phagosomal acidification within macrophage. The present work describes the characterization of Rv3338 which was previously known to be associated with the aprABC locus induced while encountering acidic stress within the macrophage. Bio-informatic analysis demonstrated its similarity to epoxide hydrolase, which was confirmed by enzymatic assays, thus, renamed EphH. Subsequently, we have deciphered its indispensable role for Mtb in protection from acidic stress by using the CRISPRi knockdown strategy. Our data demonstrated the pH dependent role of EphH for the survival of Mtb during nutrient starvation and in conferring resistance against elevated endogenous ROS levels during stress environment. To the best of our knowledge, this is the first report of an EH of Mtb as a crucial protein for bacterial fitness inside the host, a phenomenon central to its pathogenesis.