Investigating ticagrelor in a preclinical pipeline as a novel therapeutic to prevent preterm birth.

In brief: Preterm birth is the leading cause of perinatal morbidity and mortality, and new therapies that delay preterm birth and improve neonatal outcomes are urgently needed. This study investigates whether ticagrelor inhibits uterine contractility and inflammation in preclinical in vitro, ex vivo (human) and in vivo (mouse) studies, to explore the potential of repurposing ticagrelor for the prevention of preterm birth. Abstract: Preterm birth remains a significant global health challenge, affecting approximately 10% of pregnancies and resulting in one million deaths globally every year. Tocolytic agents, used to manage preterm labour, have considerable limitations including lack of efficacy, and adverse side effects, emphasising the urgent need for innovative solutions. Here, we explore repurposing an antiplatelet cardioprotective drug, ticagrelor, as a potential treatment to prevent preterm birth. Ticagrelor has demonstrated pleiotropic actions beyond platelet inhibition, including relaxant effects on smooth muscle cells and anti-inflammatory effects in models of diabetes and sepsis. As preterm birth is underscored by inflammatory processes triggering uterine contractions, these actions position ticagrelor as an attractive candidate for prevention or delay of preterm birth. Utilising primary human myometrial tissue, human myometrial cells, and a mouse model of preterm birth, we investigated ticagrelor's potential as a safe and effective therapy for preterm birth. We showed that ticagrelor did not reduce the frequency or strength of spontaneous muscle contractions of ex vivo myometrial tissue nor did it reduce in vitro inflammation-induced contractility in myometrial cells. Additionally, ticagrelor did not exhibit the anticipated anti-inflammatory effects in myometrial cell culture experiments. In our mouse model of preterm birth, ticagrelor neither improved the preterm birth rate or fetal survival outcomes. Gene expression of pro-inflammatory cytokines and contraction-associated proteins in postpartum mouse uteri were unaltered by ticagrelor. In conclusion, ticagrelor is not a strong candidate to continue investigations in clinical trial for the treatment of preterm labour and prevention of preterm birth.

Child Opportunity Index and Pediatric Intensive Care Outcomes: A Multicenter Retrospective Study in the United States.

OBJECTIVES: To evaluate for associations between a child's neighborhood, as categorized by Child Opportunity Index (COI 2.0), and 1) PICU mortality, 2) severity of illness at PICU admission, and 3) PICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Fifteen PICUs in the United States. PATIENTS: Children younger than 18 years admitted from 2019 to 2020, excluding those after cardiac procedures. Nationally-normed COI category (very low, low, moderate, high, very high) was determined for each admission by census tract, and clinical features were obtained from the Virtual Pediatric Systems LLC (Los Angeles, CA) data from each site. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 33,901 index PICU admissions during the time period, median patient age was 4.9 years and PICU mortality was 2.1%. There was a higher percentage of admissions from the very low COI category (27.3%) than other COI categories (17.2-19.5%, p < 0.0001). Patient admissions from the high and very high COI categories had a lower median Pediatric Index of Mortality 3 risk of mortality (0.70) than those from the very low, low, and moderate COI groups (0.71) ( p < 0.001). PICU mortality was lowest in the very high (1.7%) and high (1.9%) COI groups and highest in the moderate group (2.5%), followed by very low (2.3%) and low (2.2%) ( p = 0.001 across categories). Median PICU LOS was between 1.37 and 1.50 days in all COI categories. Multivariable regression revealed adjusted odds of PICU mortality of 1.30 (95% CI, 0.94-1.79; p = 0.11) for children from a very low versus very high COI neighborhood, with an odds ratio [OR] of 0.996 (95% CI, 0.993-1.00; p = 0.05) for mortality for COI as an ordinal value from 0 to 100. Children without insurance coverage had an OR for mortality of 3.58 (95% CI, 2.46-5.20; p < 0.0001) as compared with those with commercial insurance. CONCLUSIONS: Children admitted to a cohort of U.S. PICUs were often from very low COI neighborhoods. Children from very high COI neighborhoods had the lowest risk of mortality and observed mortality; however, odds of mortality were not statistically different by COI category in a multivariable model. Children without insurance coverage had significantly higher odds of PICU mortality regardless of neighborhood.

Discerning novel drug targets for treating Mycobacterium avium ss. paratuberculosis-associated autoimmune disorders: an in silico approach.

Mycobacterium avium subspecies paratuberculosis (MAP) exhibits 'molecular mimicry' with the human host resulting in several autoimmune diseases such as multiple sclerosis, type 1 diabetes mellitus (T1DM), Hashimoto's thyroiditis, Crohn's disease (CD), etc. The conventional therapy for autoimmune diseases includes immunosuppressants or immunomodulators that treat the symptoms rather than the etiology and/or causative mechanism(s). Eliminating MAP-the etiopathological agent might be a better strategy to treat MAP-associated autoimmune diseases. In this case study, we conducted a systematic in silico analysis to identify the metabolic chokepoints of MAP's mimicry proteins and their interacting partners. The probable inhibitors of chokepoint proteins were identified using DrugBank. DrugBank molecules were stringently screened and molecular interactions were analyzed by molecular docking and 'off-target' binding. Thus, we identified 18 metabolic chokepoints of MAP mimicry proteins and 13 DrugBank molecules that could inhibit three chokepoint proteins viz. katG, rpoB and narH. On the basis of molecular interaction between drug and target proteins finally eight DrugBank molecules, viz. DB00609, DB00951, DB00615, DB01220, DB08638, DB08226, DB08266 and DB07349 were selected and are proposed for treatment of three MAP-associated autoimmune diseases namely, T1DM, CD and multiple sclerosis. Because these molecules are either approved by the Food and Drug Administration or these are experimental drugs that can be easily incorporated in clinical studies or tested in vitro. The proposed strategy may be used to repurpose drugs to treat autoimmune diseases induced by other pathogens.

Social Determinants of Health in Pediatric Rehabilitation for Children with Traumatic Injury: A Systematic Review.

OBJECTIVE: To examine the current evidence regarding health care disparities in pediatric rehabilitation after hospitalization with traumatic injury. STUDY DESIGN: This systematic review utilized both PubMed and EMBASE, and each was searched with key MESH terms. Studies were included in the systematic review if they (1) addressed social determinants of health including, but not limited to, race, ethnicity, insurance status, and income level; (2) focused on inpatient and outpatient rehabilitation services posthospital stay; (3) were based in the pediatric population; and (4) addressed traumatic injury requiring hospitalization. Only studies from within the US were included. RESULTS: From 10 169 studies identified, 455 abstracts were examined for full-text review, and 24 studies were chosen for data extraction. Synthesis of the 24 studies revealed 3 major themes: (1) access to services; (2) outcomes from rehabilitation; and (3) service provision. Patients with public insurance had decreased availability of service providers and had longer outpatient wait times. Non-Hispanic Black and Hispanic children were more likely to have greater injury severity and decreased functional independence after discharge. Lack of interpreter services was associated with decreased utilization of outpatient services. CONCLUSIONS: This systematic review identified significant effects of health care disparities on the rehabilitation process in pediatric traumatic injury. Social determinants of health must be thoughtfully addressed to identify key areas of improvement for the provision of equitable health care.

Melamine-Formaldehyde Polymer-Based Nanocomposite for Sunlight-Driven Photodegradation of Multiple Dyes and Their Mixture.

Cadmium sulfide (CdS)-decorated, cross-linked melamine-formaldehyde polymer-based nanocomposite (MFP-CdS) has been synthesized. MFP-CdS is utilized here as a photoactive material for the photodegradation of six model organic dyes and their mixture in an aqueous medium in the presence of sunlight. The half-life values from the kinetic study of multiple dyes strongly support the importance of sunlight on the fast degradation of all six dyes compared to bulb light and control (dark) conditions. A comparative 1H NMR analysis of the dyes and their degraded products has been performed to support the breakdown of the aromatic framework of organic dyes using MFP-CdS in sunlight. The mechanisms involved in the photodegradation of dyes have been investigated based on radical trapping studies that support the significant involvement of superoxide radicals along with holes. Moreover, the dye removal efficiency using MFP-CdS from real industrial wastewater samples is evaluated via the external spiking of organic dyes and their mixture in unknown industrial effluents where they showed similar photodegradation results. Based on the high recyclability of MFP-CdS, these are used for multiple cycles.

Outcomes of Patients Receiving Thrombolysis in a Mobile Stroke Unit: A 4-Year Retrospective, Observational, Single-Center Study.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke (AIS) eligible for thrombolysis benefit when thrombolysis is administered quickly, and mobile stroke units (MSU) can facilitate timely thrombolysis. We sought to compare time metrics and clinical outcomes of AIS patients receiving thrombolysis in an MSU compared with patients arriving via local emergency medical services (EMS). METHODS: We performed a retrospective, non-randomized, cohort study comparing MSU-arriving to EMS-arriving AIS patients from January 20, 2017 through November 30, 2020. The primary outcome was rate of return to baseline functional status as measured by the modified Rankin Score (mRS) 90 days after thrombolysis. Secondary outcomes included evaluation and treatment intervals from last known well, treatment rate in the first hour of symptoms, hospital length of stay, and mortality. Chi square and Student's t-test were used to compare groups. RESULTS: Of 1752 total patients with prehospital suspected stroke, 975 (55.7%) were transported via MSU, of whom 431 (44.2%) were diagnosed with stroke, including 368 (85.4%) with AIS, and 69 AIS patients (18.8%) received thrombolysis. Of 777 (44.3%) EMS-arriving patients, 373 (48%) were diagnosed with stroke, including 305 (81.8%) with AIS, and 74 (24.3%) received thrombolysis. Though not statistically significant, point estimates of the proportion of AIS patients treated with thrombolysis returning to baseline functional status were more commonly observed for MSU than for EMS transports when the baseline mRS was 0-2 (45.8% vs 33.3%), 0-3 (41.9% vs 33.3%), and 4-5 (71.4% vs 20.0%). MSU patients were more likely to receive thrombolysis in the first 60 minutes of symptom onset (31.9% vs 12.2%, p = 0.006). Overall mortality rates regardless of baseline mRS were similar between groups. CONCLUSIONS: AIS patients received thrombolysis faster in the MSU compared with EMS and more frequently within 60 minutes of stroke onset. Point estimates for 90-day clinical outcomes of AIS patients treated with thrombolysis favored MSU without a statistically significant difference.

Pulmonary Manifestations in Patients of Rheumatoid Arthritis and its Correlation with Severity of Disease.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology marked by symmetric, peripheral polyarthritis. RA has a prevalence of 1-2% in the general adult population. The mortality rate in patients with RA increases during the course of the disease, with a tendency to accelerate after 15 yearsAim: To study the pulmonary manifestations and their severity using [Disease Activity Score (DAS)-28 score] in patients of RAMaterials and methods: Present study was conducted in the Department of Medicine, Sardar Patel Medical College and Associated Group of Hospitals Bikaner, Bikaner, Rajasthan, India, on 100 patients. This study was a cross-sectional, observational study conducted over 1 year. Consecutive cases of RA patients attending the outpatient department or admitted to the medicine wards were selected according to the inclusion and exclusion criteriaResults: Pulmonary manifestation was present in a total of 38% of cases, while the remaining 62% of cases had no pulmonary manifestation. The presence of comorbidity and C-reactive protein (CRP) was significantly associated with pulmonary manifestation in RA patients. On high-resolution computed tomography (HRCT), the most common finding was interstitial lung disease (ILD) (60.5%), with usual interstitial pneumonia (UIP) as the most common pattern. On performing a pulmonary function test (PFT), 33 patients (86.84%) had an abnormal result, with restrictive as the most common patternConclusion: The patients of RA, especially those with advanced age, long duration of disease, male sex, and associated comorbidity, should be screened for pulmonary complications of RA using X-ray chest and PFT, supplemented by HRCT chest wherever required.

Sodium channel expression and transcript variation in the developing brain of human, Rhesus monkey, and mouse.

Genetic variation in voltage-gated sodium (NaV) channels is a significant contributor to neurodevelopmental disorders. NaV channel alpha subunits are encoded by the SCNxA family and four are predominately expressed in the brain: SCN1A, SCN2A, SCN3A, and SCN8A. Gene expression is developmentally regulated, and they are known to express functionally distinct transcript variants. Precision therapies targeting these genes and their transcript variants are currently in preclinical development, yet the developmental expression of these transcripts in the human brain is yet to be fully understood. Additionally, the functional consequences of some mutations differ depending on the studied channel isoform, suggesting differential transcript variant expression can affect disease prognoses. We characterise the expression of the four SCNxAs and their transcript variants in human, Rhesus monkey and mouse brain using publicly available RNA-sequencing data and analysis tools, demonstrating that this approach can be used to answer important biological questions of gene and transcript developmental regulation. We find that gene expression and transcript variant regulation are conserved across species at similar developmental stages and determine the developmental milestones for transcript variant expression. Our study provides a guide to researchers testing therapies and clinicians advising prognoses based on the expression of channel isoforms.

Insights into the human gut virome by sampling a population from the Indian subcontinent.

Gut virome plays an important role in human physiology but remains poorly understood. This study reports an investigation of the human gut DNA-virome of a previously unexplored ethnic population through metagenomics of faecal samples collected from individuals residing in Northern India. Analysis shows that, similar to the populations investigated earlier, majority of the identified virome belongs to bacteriophages and a smaller fraction (<20 %) consists of viruses that infect animals, archaea, protists, multiple domains or plants. However, crAss-like phages, in this population, are dominated by the genera VI, VII and VIII. Interestingly, it also reveals the presence of a virus family, Sphaerolipoviridae, which has not been detected in the human gut earlier. Viral families, Siphoviridae, Myoviridae, Podoviridae, Microviridae, Herelleviridae and Phycodnaviridae are detected in all of the analysed individuals, which supports the existence of a core virome. Lysogeny-associated genes were found in less than 10 % of the assembled genomes and a negative correlation was observed in the richness of bacterial and free-viral species, suggesting that the dominant lifestyle of gut phage is not lysogenic. This is in contrast to some of the earlier studies. Further, several hundred high-quality viral genomes were recovered. Detailed characterization of these genomes would be useful for understanding the biology of these viruses and their significance in human physiology.

Assessing the effect of COVID-19 stay-at -home orders on firearm injury in Maryland.

This study sought to characterize frequency and demographic characteristics of firearm injury and penetrating trauma in Maryland over the first year of the pandemic, by comparing these characteristics to those of the three years prior to stay-at-home order issuance. Patients were identified in the Maryland Health Services Cost Review Commission database using ICD-10 codes for firearm injury by all intents and assaults by penetrating trauma. Cases from July 1, 2017 to March 31, 2020 ("pre-stay-at-home") were compared to those from April 1, 2020 to March 31, 2021 ("post-stay-at-home") using descriptive statistics. There was no significant change overall in frequency or demographics of firearm injury or penetrating trauma in the year after stay-at-home orders were issued. Youth between ages 15 and 24, overwhelmingly male, comprise a disproportionately high percentage of firearm injuries and assaults, and most penetrating trauma occurs in urban environments where Black non-Hispanic youth and children of low socioeconomic status are at high risk. Our study also found unintentional firearm injury among adults was significantly increased during the pandemic. While increased unintentional firearm injury among adults was the major significant change found in our study, the persistence of firearm injury, particularly in youth, racial and ethnic minority groups, and those in urban environments, should be deeply concerning. Stay-at-home policies did not keep youth safer from firearm injury. With continued high rates of firearm injury and the national debate over how to prevent these incidents, increased education and comprehensive strategies for prevention are needed.

Non-aqueous onion like nano-carbons from waste diesel-soot used as FRET-based sensor for sensing of nitro-phenols.

Herein, a simple-functionalization method is described to prepare the oleylamine functionalized non-aqueous version of onion-like nanocarbons (ONC-OA), where ONC was isolated from the waste pollutant soot exhausted from the diesel engine. The surface group analysis of ONC-OA has been investigated via Nuclear Magnetic Resonance and X-ray Photoelectron Spectroscopy. ONC-OA shows blue fluorescence with a quantum yield of ∼6% in tetrahydrofuran (THF). The fluorescence-based sensing applications of ONC-OA has been investigated for selective sensing of toxic aromatic nitro-phenols compounds (para-nitro, dinitro, and trinitro phenols) from the tested many nitro organic compounds. Based on the limit of detection values, ONC-OA shows much better results for tri-nitro phenol compared to di and mono nitrophenol. To understand the quenching mechanism, a time-resolved photoluminescence analysis of the sensor with and without the addition of quenchers is performed. The effective lowering in fluorescence lifetime of the sensor after the addition of quenchers concludes that the quenching observed is majorly due to the Förster Resonance Energy Transfer (FRET) mechanism. The real-life application of ONC-OA was analyzed by external spiking of N-PhOHs in soil samples.

mRNALoc: a novel machine-learning based in-silico tool to predict mRNA subcellular localization.

Recent evidences suggest that the localization of mRNAs near the subcellular compartment of the translated proteins is a more robust cellular tool, which optimizes protein expression, post-transcriptionally. Retention of mRNA in the nucleus can regulate the amount of protein translated from each mRNA, thus allowing a tight temporal regulation of translation or buffering of protein levels from bursty transcription. Besides, mRNA localization performs a variety of additional roles like long-distance signaling, facilitating assembly of protein complexes and coordination of developmental processes. Here, we describe a novel machine-learning based tool, mRNALoc, to predict five sub-cellular locations of eukaryotic mRNAs using cDNA/mRNA sequences. During five fold cross-validations, the maximum overall accuracy was 65.19, 75.36, 67.10, 99.70 and 73.59% for the extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. Assessment on independent datasets revealed the prediction accuracies of 58.10, 69.23, 64.55, 96.88 and 69.35% for extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. The corresponding values of AUC were 0.76, 0.75, 0.70, 0.98 and 0.74 for the extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. The mRNALoc standalone software and web-server are freely available for academic use under GNU GPL at http://proteininformatics.org/mkumar/mrnaloc.

Proportion and Clinical Relevance of Intraspinal Air in Patients With Pneumomediastinum.

OBJECTIVE: The purposes of this study were to determine the incidence of pneumorrhachis among patients with pneumomediastinum, determine whether its proportion correlates with the extent of pneumomediastinum, and ascertain its clinical relevance. MATERIALS AND METHODS: The radiologic database was searched for CT reports between January 2009 and September 2013 containing the term "pneumomediastinum" or "mediastinal air." Scans were examined for pneumomediastinum, pneumorrhachis, pneumothorax, sternotomy, and distribution of pneumomediastinum. The age and sex of the patient and probable cause of the abnormality were recorded. Cases that might have had another cause were excluded. RESULTS: The search yielded 422 CT scans. Among these, 242 instances of pneumomediastinum in 241 patients were found. Fifteen of these patients had pneumorrhachis. One was excluded because of recent traumatic spinal penetration. There was no significant difference in age or sex between patients with and those without pneumorrhachis. After application of the exclusion criteria, there were 14 cases of pneumorrhachis, yielding a proportion of 5.8%. Pneumorrhachis was observed more frequently in cases of the most severe grade (grade C) of pneumomediastinum; however, that relationship was not statistically significant (11 cases [8.2%]; p = 0.304). Pneumorrhachis was found significantly more frequently in patients with distribution of air in all three mediastinal compartments (13 cases, 16.2%, p < 0.001). Pneumorrhachis was overrepresented among subjects with spontaneous compared with those with secondary pneumomediastinum, although the trend did not reach statistical significance. CONCLUSION: Pneumorrhachis was present in 5.8% of patients. It is significantly more common in patients with the broadest distributions of mediastinal air and nonsignificantly more common in association with spontaneous as opposed to secondary pneumomediastinum. Pneumorrhachis in patients with pneumomediastinum is a generally benign, self-resolving condition.

Association Between Opioid Abuse/Dependence and Outcomes in Hospitalized Heart Failure Patients.

Opioid use is associated with unintentional and intentional overdose and is one of the leading causes of emergency room visits and accidental deaths. However, the association between opioid abuse/dependence and outcomes in hospitalized patients has not been well studied. Congestive heart failure (HF) is the fourth most common cause of hospitalization in the United States. The purpose of this study was to examine the effect of opioid abuse/dependence on outcomes in patients hospitalized with HF. We queried the 2002-2010 Nationwide Inpatient Sample databases to identify all patients aged 18 years and older admitted with the primary diagnosis of HF. Multivariate logistic regression analysis was used to compare the frequency of hospital-acquired conditions (HACs) and in-hospital mortality between patients with and without a history of opioid abuse/dependence. Of 9,993,240 patients with HF, 29,014 had a history of opioid abuse or dependence. Opioid abusers/dependents were likely to be younger men of poor socioeconomic background with self pay or Medicaid as their primary payer. They had a lower prevalence of dyslipidemia, diabetes mellitus, coronary artery disease, prior myocardial infarction, and peripheral vascular disease (P < 0.001 for all). They were more likely to be smokers and have chronic pulmonary disease, depression, liver disease, and obesity (P < 0.001 for all). Patients with a history of opioid abuse/dependence had lower incidence of HACs (14.8% vs. 16.5%, adjusted odds ratio: 0.71, P < 0.001) and lower in-hospital mortality (1.3% vs. 3.6%, adjusted odds ratio: 0.64, P < 0.001) as compared with patients without prior opioid abuse/dependence. In conclusion, among adult patients aged 18 years and older hospitalized with HF, opioid abuse/dependence was associated with lower frequency of HACs and lower in-hospital mortality.

Association of the Child Opportunity Index and Inpatient Illness Severity in the United States, 2018-2019.

OBJECTIVE: Children residing in impoverished neighborhoods have reduced access to health care resources. Our objective was to identify potential associations between Child Opportunity Index (COI), a composite score of neighborhood characteristics, and inpatient severity of illness and clinical trajectory among United States (US) children. METHODS: This retrospective cohort study assessed data using the Pediatric Health Information System Registry from 2018 to 2019. Primary exposure variable was COI level (range: very low [CO1 1], low [COI 2], moderate [COI 3], high [COI 4], and very high [COI 5]). Markers of inpatient clinical severity included index mortality, Pediatric Intensive Care Unit (PICU) admission, invasive mechanical ventilation (IMV), and hospital length of stay (LOS). Subgroup analysis of COI and clinical outcome variation by United States Census Geographic Regions was conducted. Adjusted regression analysis was utilized to understand associations between COI and inpatient clinical severity outcomes. RESULTS: Of the 132,130 encounters, 44% resided in very low or low COI neighborhoods. In adjusted models, very low COI was associated with increased mortality (aOR: 1.35, 95% CI: 1.05-1.74, P = .018), PICU admission (aOR: 1.06, 95% CI: 1.02-1.11, P = 0.014), IMV (aOR: 1.12, 95% CI: 1.04-1.21, P = .002), and higher hospital LOS (P = .045). Regional variation by COI depicted the East North Central region having the highest rate of mortality (20.5%), P < .001, and PICU admissions (23%), P = .014. CONCLUSIONS: Our multicenter, retrospective study highlights the interaction between neighborhood-level deprivation and worsened health disparities, indicating a need for prospective study.

Exploring Cellular Heterogeneity: Single-Cell and Spatial Transcriptomics of Alzheimer Disease Brains and iPSC-Derived Microglia.

Background Substantial evidence has established the critical role of microglia, the brain's resident immune cells, in the pathogenesis of Alzheimer's disease (AD). Microglia exhibit diverse transcriptional states in response to neuroinflammatory stimuli, and understanding these states is crucial for elucidating the underlying mechanisms of AD. Methods In this work, we integrated single-cell and spatially resolved transcriptomics data from multiple cohorts and brain regions, including microglia from experimental and human brains. Results This comprehensive atlas revealed a great heterogeneity of microglial states, with a significant enrichment of specific states, including activated microglia, in AD brains compared to controls. Further integration of spatial transcriptomics and immunohistochemistry showed that activated microglia are predominantly located in the external cortical layers near amyloid plaques, while homeostatic microglia are more prevalent in the internal cortical layers and further away from the plaques. These spatial patterns were further validated using P2RY12 immunostaining, which confirmed the reliability of the transcriptomic data. Conclusion By integrating single-cell and spatial transcriptomics, we have provided a detailed atlas of microglial diversity, revealing the regional and pathological specificity of microglial states.

Therapeutic Potential of Plant-Derived Compounds and Plant Extracts in Rheumatoid Arthritis-Comprehensive Review.

Rheumatoid arthritis (RA) is a persistent autoimmune disorder that is characterized by joint inflammation, discomfort, and impairment. Despite the existence of several therapeutic approaches, their effectiveness is often restricted and may be linked to unfavorable side effects. Consequently, there has been growing interest in investigating naturally derived compounds as plausible therapeutic agents for RA disease. The objective of this review is to summarize the existing preclinical and clinical evidence regarding the efficacy of naturally extracted compounds and plant extracts in the treatment of RA, focusing on their anti-inflammatory, anti-oxidative, and immunomodulatory properties. Some of the problems with using natural chemicals are the uneven quality of commercially available preparations and the poor bioavailability of these compounds. Future investigations should focus on improving the formulations, conducting thorough clinical trials, and exploring different techniques to fully utilize the intrinsic potential of naturally derived chemicals in treating RA.

The Haven Clinic: The Planning and Implementation of a Medical Home for Child Trafficking Survivors.

The authors describe the planning and implementation of a survivor-informed medical home for child trafficking survivors. Key partnerships necessary for establishing clinical infrastructure are highlighted. The trauma-informed clinical practices are described in detail. An overview of next steps for evaluation of this clinical program is provided.