¿No Hay Racismo?: application of the levels of racism framework to Latinx perspectives on barriers to health and wellbeing.

BACKGROUND: The purpose of this study is to increase understanding of the forms of systemic racism experienced by Latinx communities in North Carolina during the COVID-19 pandemic as identified by Latinx community health workers (CHWs) and community-based organization (CBO) leaders. METHODS: We held three focus groups in July 2022 (N = 16) with CHWs and CBO leaders in Spanish to discuss policy and community interventions that improved access to resources during the COVID-19 pandemic; policy or community interventions needed to improve care of Latinx communities; and lessons learned to improve the health of Latinx communities in the future. We performed directed and summative qualitative content analysis of the data in the original language using the Levels of Racism Framework by Dr. Camara Jones to identify examples of implicitly and explicitly discussed forms of systemic racism. RESULTS: Latinx CHWs and CBO leaders implicitly discussed numerous examples of all levels of racism when seeking and receiving health services, such as lack of resources for undocumented individuals and negative interactions with non-Latinx individuals, but did not explicitly name racism. Themes related to institutionalized racism included: differential access to resources due to language barriers; uninsured or undocumented status; exclusionary policies not accounting for cultural or socioeconomic differences; lack of action despite need; and difficulties obtaining sustainable funding. Themes related to personally-mediated racism included: lack of cultural awareness or humility; fear-inciting misinformation targeting Latinx populations; and negative interactions with non-Latinx individuals, organizations, or institutions. Themes related to internalized racism included: fear of seeking information or medical care; resignation or hopelessness; and competition among Latinx CBOs. Similarly, CHWs and CBO leaders discussed several interventions with systems-level impact without explicitly mentioning policy or policy change. CONCLUSION: Our research demonstrates community-identified examples of racism and confirms that Latinx populations often do not name racism explicitly. Such language gaps limit the ability of CHWs and CBOs to highlight injustices and limit the ability of communities to advocate for themselves. Although generally COVID-19 focused, themes identified represent long-standing, systemic barriers affecting Latinx communities. It is therefore critical that public and private policymakers consider these language gaps and engage with Latinx communities to develop community-informed anti-racist policies to sustainably reduce forms of racism experienced by this unique population.

Treatment of Acute Myeloid Leukemia in the Community Setting.

The treatment landscape for acute myeloid leukemia (AML) is rapidly changing. Many new agents and lower-intensity regimens have been approved and can be safely used by hematologists and oncologists in both academic and community settings. The US Food and Drug Administration (FDA) held a virtual symposium on AML treatment in the community in November 2022. Several members of the FDA, along with practicing hematologists and oncologists in both academic and community settings, participated in the symposium. The goal of the symposium was to discuss challenges and opportunities in the treatment of patients with AML in community oncology settings. A summary of these discussions and key considerations are presented here.

Usability and Tolerability of Virtual Reality-Based Cognitive Stimulation in Healthy Elderly Volunteers-A Feasibility Clinical Trial.

Background: The aim of the current pilot study was to evaluate the usability, acceptability, and tolerability of virtual reality (VR)-based cognitive stimulation exercises (CSEs) in healthy young versus old populations before health care integration. A secondary aim was to assess the accuracy of VR games as a proxy for cognitive stimulation, specifically for attention. VR-based CSEs promise to improve attention and brain function through varied learning systems. Methods: This is a Phase 1 feasibility clinical trial at a single center. It involves 30 healthy volunteers randomly selected using the American Society of Anesthesiologists (ASA) physical status classification system. Participants fall into ASA 1 (age >18-35 years, n = 15) or ASA 2 (age >60 years, n = 15) categories. All participants tested the ReCognitionVR-based CSEs. Feasibility criterion: Participants in each group were monitored for completion of 20 minutes of VR-based CSEs. Acceptability criterion: Proportion of participants with system usability scale (SUS) >35 or SUS score of 87.5. Safety (tolerability) monitoring: Sessions were monitored for neurological, cardiovascular, or pulmonary adverse events (AEs). Safety criterion: No more than 10% of sessions stopped due to neurological, cardiovascular, or pulmonary AEs. Results: The primary outcome (feasibility) of ReCognitionVR-based CSEs was 100%. For the secondary outcome (acceptability), there was no group difference in SUS scores (ASA 1 = 88.17 ± 12.83 vs. ASA 2 = 88.39 ± 10.22, P = 0.81). For the tertiary outcome (safety), mild transient uneasiness was reported by two (13.4%) ASA 1 participants (resolved in 2 minutes), and one (6.67%) ASA 1 participant experienced a temporary >20% increase in blood pressure from baseline. No ASA 2 participants had AEs. Conclusion: The feasibility, acceptability, and safety of ReCognitionVR-based CSEs in healthy elderly volunteers are acceptable, indicating that the evaluation of the ReCognitionVR-based CSEs in hospitalized patients is reasonable.

Rapid postradiation malignant transformation of a pilocytic astrocytoma in an adult with neurofibromatosis type 1: illustrative case.

BACKGROUND: Juvenile pilocytic astrocytoma (JPA) is the most common primary brain tumor of childhood and is rarely seen in adults. Neurofibromatosis type 1 (NF1), a common tumor predisposition syndrome, demonstrates a strong association with low-grade gliomas, most notably pilocytic astrocytoma, which are relatively indolent. Unlike its juvenile counterpart, reports of adult pilocytic astrocytoma (APA) vary widely in terms of disease progression from benign to much more malignant courses. Moreover, current studies discussing APA report different treatment approaches and outcomes (e.g., malignant transformation of JPA and APA with or without radiation), as little is known regarding the management of recurrent tumors and how adjuvant therapies may alter disease progression. OBSERVATIONS: The authors report the unique case of an adult male with NF1 and APA who underwent rapid malignant conversion after intensity-modulated radiation therapy. LESSONS: The authors demonstrate that caution should be taken in utilizing radiotherapy instead of resection in cases of APA and NF1, with close monitoring for posttreatment recurrence. https://thejns.org/doi/10.3171/CASE24241.

A Novel, Low-Cost Alternative to Traditional Glaucoma Surgeries.

Purpose: To investigate the real-world efficacy of a novel, low-cost glaucoma drainage device in canine and human patients. Methods: A retrospective case series of 17 eyes in 14 canines and one eye of a human patient who each underwent novel drainage device implantation is described. This device was constructed by insertion and advancement of a 24-gauge cannula (canine) or 23-gauge cannula (human) perpendicularly through five adjacent tubes of a 25-mm Yeates surgical drain. Results: Of the canine patients, the average follow-up period was 362 days (range, 27-863). The mean preoperative intraocular pressure (IOP) was 50.9 ± 17.9 mm Hg. Following tube surgery, IOP was maintained at <20 mm Hg in 81.3%, 100%, 100%, 85.7%, 100%, and 75.0% of eyes at 1, 2, 3, 6, 9, and 12 months, respectively. Bleb needling and/or revisions were required in five eyes. Enucleations and/or device explantations were performed in five eyes at mean day 140. In the human case, the device was implanted in the right eye of a 64-year-old male with refractory raised IOP (55 mm Hg) despite maximum medical therapy. IOP was well controlled until day 818, when eventual tissue breakdown necessitated device removal. Conclusions: This design represents a novel, low-cost, effective alternative to traditional glaucoma tube devices. Translational Relevance: This device has great potential for use in regions where the needs for glaucoma drainage devices and surgical alternatives to trabeculectomy have not been met. Further development may include tube crimping or fenestration and preoperative loading of slow-release antibiotics and/or anti-metabolite medications within the non-draining lumens.

Ascertainment of Helicobacter pylori Infection and Eradication Treatment Using a Nationwide Electronic Health Record Database.

Background and Aims: There are limited contemporary population-based data on Helicobacter pylori epidemiology and outcomes in the United States. Our primary aim was to create a validated cohort of veterans with H pylori testing or treatment using Veterans Health Administration data. Methods: Using Veterans Health Administration structured and unstructured data, we developed and validated 4 algorithms for H pylori infection (3 algorithms) and treatment status (1 algorithm). During the development phase, we iteratively modified each algorithm based on a manual review of random sets of electronic health records (reference standard). The a priori validation goal was to achieve a one-sided 95% confidence lower bound (LB) for positive predictive value (PPV) and/or negative predictive value (NPV) >90%. We applied the Bonferroni correction when both PPV and NPV were relevant. Results: For H pylori infection, we achieved 99.0% PPV (LB = 94.6%) and 100% NPV (LB = 96.4%) for discriminating H pylori positive vs negative status using structured (ie, laboratory tests) and 95% PPV (LB = 90.3%) and 97.9% NPV (LB = 93.9%) using unstructured (ie, histopathology reports) data. Diagnostic codes achieved 98% PPV (LB = 93.0%) for H pylori diagnosis. The treatment algorithm was composed of multiple antimicrobial combinations and overall achieved ≥98% PPV (LB = 93.0%) for H pylori treatment, except for amoxicillin/levofloxacin (PPV<60%). Application of these algorithms yielded nearly 1.2 million veterans with H pylori testing and/or treatment between 1999 and 2018. Conclusion: We assembled a validated national cohort of veterans who were tested or treated for H pylori infection. This cohort can be used for evaluating H pylori epidemiology and treatment patterns, as well as complications of chronic infection.

Quantified trends in provider reimbursement and utilization volume in colorectal cancer screenings: analysis of Medicare claims from 2000 to 2019.

AIM: Colorectal cancer (CRC) screening rates in the United States remain persistently below guideline targets, partly due to suboptimal patient utilization and provider reimbursement. To guide long-term national utilization estimates and set reasonable screening adherence targets, this study aimed to quantify trends in utilization of and reimbursement for CRC screenings using Medicare claims. METHOD: Inflation-adjusted reimbursements and utilization volume associated with each CRC screening code were abstracted from Medicare claims between 2000 and 2019. Screenings, screenings/100 000 enrolees and reimbursement/screening were analysed with linear regression and compared with the equality of slopes tests. Average reimbursement per screening was compared using analysis of variance with Dunnett's T3 multiple comparisons test. RESULTS: The growth rate of multitarget stool DNA tests (mt-sDNA)/100 000 was the highest at 170.4 screenings/year (R2 = 0.99, p ≤ 0.001), while that of faecal occult blood tests/100 000 was the lowest at -446.4 screenings/year (R2 = 0.90, p ≤ 0.001) (p ≤ 0.001). Provider reimbursements averaged $546.95 (95% CI $520.12-$573.78) per mt-sDNA screening, significantly higher than reimbursements for all invasive screenings. Only FOBTs significantly increased in reimbursement per screening at $0.62/year (R2 = 0.91, p ≤ 0.001). CONCLUSION: We derived forecastable trend numbers for utilization and provider reimbursement. Faecal immunochemical tests/100 000 and mt-sDNA screenings/100 000 increased most rapidly during the entire study period. The number of nearly all invasive screenings/100 000 decreased rapidly; the number of colonoscopies/100 000 increased slightly, probably due to superior diagnostic strength. These trends indicate the that replacement of other invasive modalities with accessible noninvasive screenings will account for much of future screening behaviour and thus reductions in CRC incidence and mortality, especially given providers' reimbursement incentive to screen average-risk patients with stool-based tests.

Helicobacter pylori Burden in the United States According to Individual Demographics and Geography: A Nationwide Analysis of the Veterans Healthcare System.

BACKGROUND & AIMS: There are no contemporary large-scale studies evaluating the burden of Helicobacter pylori in the United States according to detailed demographics. The primary objective was to evaluate H pylori positivity in a large national healthcare system according to individual demographics and geography. METHODS: We conducted a nationwide retrospective analysis of adults in the Veterans Health Administration who completed H pylori testing between 1999 and 2018. The primary outcome was H pylori positivity overall, as well as according to zip code-level geography, race, ethnicity, age, sex, and time period. RESULTS: Among 913,328 individuals (mean, 58.1 years; 90.2% male) included between 1999 and 2018, H pylori was diagnosed in 25.8%. Positivity was highest in non-Hispanic black (median, 40.2%; 95% confidence interval [CI], 40.0%-40.5%) and Hispanic (36.7%; 95% CI, 36.4%-37.1%) individuals and lowest in non-Hispanic white individuals (20.1%; 95% CI, 20.0%-20.2%). Although H pylori positivity declined in all racial and ethnic groups over the timeframe, the disproportionate burden of H pylori in non-Hispanic black and Hispanic compared with non-Hispanic white individuals persisted. Approximately 4.7% of the variation in H pylori positivity was explained by demographics, with race and ethnicity accounting for the vast majority. CONCLUSIONS: The burden of H pylori is substantial in the United States among veterans. These data should (1) motivate research aimed at better understanding why marked demographic differences in H pylori burden persist so that mitigating interventions may be implemented and (2) guide resource allocation to optimize H pylori testing and eradication in high-risk groups.

Applying the RE-AIM framework to evaluate an educational model to "close the gap" and improve health equity in uncontrolled hypertension.

OBJECTIVES: To use the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to evaluate an educational model addressing self-management of uncontrolled hypertension. METHODS: We used a pre-post single cohort design to identify minoritized patients with uncontrolled hypertension (systolic > 160 mmHg and/or diastolic > 100 mmHg). Trained Ambassadors provided telephone outreach, skill-based blood pressure (BP) monitoring, and goal-setting for 4 months. Follow-up occurred at 7 months. We evaluated the initiative using the RE-AIM framework and quantitative analysis for process and outcome measures post-intervention. RESULTS: Among Black patients (n = 345), the average age was 55.4 years (8.7), half identified as male (n = 173, 50.1 %); many were uninsured (n = 159, 46.1 %). Engagement in calls occurred for 67.8 % (n = 234) of the cohort; monitor distribution was 22.9 % (n = 79); and goal setting occurred for 64 patients. BP improved for 40 % of the cohort (mean pre: 168/98 mmHg, mean post: 150/89 mmHg; p < 0.0001) and 40 % of patients' last known BP was < 140/90. CONCLUSIONS: RE-AIM evaluation of the Closing the Gap initiative suggests that the model is associated with BP reduction in high-risk Black patients. PRACTICE IMPLICATIONS: An educational model for patient-centered hypertension management in low-income populations is feasible and addresses self-monitoring barriers.

Systemic Racism Affecting Latinx Population Health During the COVID-19 Pandemic and Beyond: Perspectives of Latinx Community Health Workers and Community-Based Organization Leaders.

Introduction: The purpose of this study is to identify forms of systemic racism experienced by Latinx communities in North Carolina during the COVID-19 pandemic as identified by Latinx community health workers (CHWs) and community-based organization (CBO) leaders. Methods: We conducted three focus groups in July 2022 (N=16). We performed qualitative analysis of data using an iterative inductive approach of the original language in Dedoose. Results: Four central themes emerged: (1) Access to resources for Latinx individuals; (2) Immediate, transitional, and future fears; (3) Benefits of CHWs; and (4) Lessons learned. Discussion: Institutional and state policies often do not involve community members, such as CHWs and CBO leaders, at the start of the development process, leading to ineffective interventions that perpetuate health disparities and systemic racism. Health Equity Implications: Community-informed policy recommendations can improve alignment of community and policy priorities to create more effective interventions to address systemic racism and promote health equity.

Delayed presentation of traumatic supra- and infratentorial extradural hematoma: illustrative case.

BACKGROUND: Supra- and infratentorial epidural hematomas (SIEDHs) are a rare subtype of epidural hematoma (EDH), showing expanding bleeding on both sides of the tentorium, and account for <2% of EDHs (Aji, Apriawan, and Bajamal, 2018). These lesions can typically expand and decompensate quickly, making immediate diagnosis and surgical intervention crucial. OBSERVATIONS: The authors' patient presented >48 hours from a blunt trauma to the right side of the head with progressive vomiting and bruising behind the right ear. He had a Glasgow Coma Scale score of 15 on arrival. Head computed tomography showed an SIEDH measuring approximately 3 cm, and, given the hematoma's size and mass effect, the patient was taken emergently to the operating room for decompression, where the source of bleeding was noted to be an emissary vein from the transverse sinus. The linear parietooccipital fracture was mended with mesh cranioplasty. Patient imaging and follow-up showed an excellent recovery. LESSONS: Although SIEDH is rare, patients can present in a delayed fashion and be neurologically intact. The threshold to obtain imaging to rule out delayed hemorrhage should be low in any patient with a history of trauma in the region of a dural venous sinus.

Sync for Genes Phase 5: Computable artifacts for sharing dynamically annotated FHIR-formatted genomic variants.

Introduction: Variant annotation is a critical component in next-generation sequencing, enabling a sequencing lab to comb through a sea of variants in order to hone in on those likely to be most significant, and providing clinicians with necessary context for decision-making. But with the rapid evolution of genomics knowledge, reported annotations can quickly become out-of-date. Under the ONC Sync for Genes program, our team sought to standardize the sharing of dynamically annotated variants (e.g., variants annotated on demand, based on current knowledge). The computable biomedical knowledge artifacts that were developed enable a clinical decision support (CDS) application to surface up-to-date annotations to clinicians. Methods: The work reported in this article relies on the Health Level 7 Fast Healthcare Interoperability Resources (FHIR) Genomics and Global Alliance for Genomics and Health (GA4GH) Variant Annotation (VA) standards. We developed a CDS pipeline that dynamically annotates patient's variants through an intersection with current knowledge and serves up the FHIR-encoded variants and annotations (diagnostic and therapeutic implications, molecular consequences, population allele frequencies) via FHIR Genomics Operations. ClinVar, CIViC, and PharmGKB were used as knowledge sources, encoded as per the GA4GH VA specification. Results: Primary public artifacts from this project include a GitHub repository with all source code, a Swagger interface that allows anyone to visualize and interact with the code using only a web browser, and a backend database where all (synthetic and anonymized) patient data and knowledge are housed. Conclusions: We found that variant annotation varies in complexity based on the variant type, and that various bioinformatics strategies can greatly improve automated annotation fidelity. More importantly, we demonstrated the feasibility of an ecosystem where genomic knowledge bases have standardized knowledge (e.g., based on the GA4GH VA spec), and CDS applications can dynamically leverage that knowledge to provide real-time decision support, based on current knowledge, to clinicians at the point of care.

Emerging trends in post-translational modification: Shedding light on Glioblastoma multiforme.

Recent multi-omics studies, including proteomics, transcriptomics, genomics, and metabolomics have revealed the critical role of post-translational modifications (PTMs) in the progression and pathogenesis of Glioblastoma multiforme (GBM). Further, PTMs alter the oncogenic signaling events and offer a novel avenue in GBM therapeutics research through PTM enzymes as potential biomarkers for drug targeting. In addition, PTMs are critical regulators of chromatin architecture, gene expression, and tumor microenvironment (TME), that play a crucial function in tumorigenesis. Moreover, the implementation of artificial intelligence and machine learning algorithms enhances GBM therapeutics research through the identification of novel PTM enzymes and residues. Herein, we briefly explain the mechanism of protein modifications in GBM etiology, and in altering the biologics of GBM cells through chromatin remodeling, modulation of the TME, and signaling pathways. In addition, we highlighted the importance of PTM enzymes as therapeutic biomarkers and the role of artificial intelligence and machine learning in protein PTM prediction.

Automated HL7v2 LRI informatics framework for streamlining genomics-EHR data integration.

While VCF formatted files are the lingua franca of next-generation sequencing, most EHRs do not provide native VCF support. As a result, labs often must send non-structured PDF reports to the EHR. On the other hand, while FHIR adoption is growing, most EHRs support HL7 interoperability standards, particularly those based on the HL7 Version 2 (HL7v2) standard. The HL7 Version 2 genomics component of the HL7 Laboratory Results Interface (HL7v2 LRI) standard specifies a formalism for the structured communication of genomic data from lab to EHR. We previously described an open-source tool (vcf2fhir) that converts VCF files into HL7 FHIR format. In this report, we describe how the utility has been extended to output HL7v2 LRI data that contains both variants and variant annotations (e.g., predicted phenotypes and therapeutic implications). Using this HL7v2 converter, we implemented an automated pipeline for moving structured genomic data from the clinical laboratory to EHR. We developed an open source hl7v2GenomicsExtractor that converts genomic interpretation report files into a series of HL7v2 observations conformant to HL7v2 LRI. We further enhanced the converter to produce output conformant to Epic's genomic import specification and to support alternative input formats. An automated pipeline for pushing standards-based structured genomic data directly into the EHR was successfully implemented, where genetic variant data and the clinical annotations are now both available to be viewed in the EHR through Epic's genomics module. Issues encountered in the development and deployment of the HL7v2 converter primarily revolved around data variability issues, primarily lack of a standardized representation of data elements within various genomic interpretation report files. The technical implementation of a HL7v2 message transformation to feed genomic variant and clinical annotation data into an EHR has been successful. In addition to genetic variant data, the implementation described here releases the valuable asset of clinically relevant genomic annotations provided by labs from static PDFs to calculable, structured data in EHR systems.

New era of artificial intelligence and machine learning-based detection, diagnosis, and therapeutics in Parkinson's disease.

Parkinson's disease (PD) is characterized by the loss of neuronal cells, which leads to synaptic dysfunction and cognitive defects. Despite the advancements in treatment strategies, the management of PD is still a challenging event. Early prediction and diagnosis of PD are of utmost importance for effective management of PD. In addition, the classification of patients with PD as compared to normal healthy individuals also imposes drawbacks in the early diagnosis of PD. To address these challenges, artificial intelligence (AI) and machine learning (ML) models have been implicated in the diagnosis, prediction, and treatment of PD. Recent times have also demonstrated the implication of AI and ML models in the classification of PD based on neuroimaging methods, speech recording, gait abnormalities, and others. Herein, we have briefly discussed the role of AI and ML in the diagnosis, treatment, and identification of novel biomarkers in the progression of PD. We have also highlighted the role of AI and ML in PD management through altered lipidomics and gut-brain axis. We briefly explain the role of early PD detection through AI and ML algorithms based on speech recordings, handwriting patterns, gait abnormalities, and neuroimaging techniques. Further, the review discuss the potential role of the metaverse, the Internet of Things, and electronic health records in the effective management of PD to improve the quality of life. Lastly, we also focused on the implementation of AI and ML-algorithms in neurosurgical process and drug discovery.

Long-term effect of seasonal and constant low temperatures on mesophilic biomass treating sewage in continuously stirred tank anaerobic granular reactor.

A Continuously Stirred Tank Anaerobic Granular Reactor seeded with mesophilic biomass was studied for 1733 days analysing the impact of seasonal (12-23 °C) and controlled (8-15 °C) low temperatures on anaerobic treatment of sewage. Aided by intermittent dosing of 0.04% (v/v) methanol, the microbiota quickly adapted to temperature fluctuations. Chemical oxygen demand (COD) removal efficiency was high but low temperatures affected methane production. Under low-temperature stress, the Methanomythylovorans and Methanosaeta-dominated methanogenic community shifted focus to cellular repair and transport, with carbon diversion towards assimilative pathways, thereby decreasing methane yields. Specific methanogenic activity at 15 °C and 30 °C increased by five and four times, respectively, from their initial values indicating microbiota retained its mesophilic properties. Despite lower methane yield, stable and high COD removals, along with low dissolved methane and volatile fatty acids indicated that low-temperature anaerobic sewage treatment using mesophilic biomass in the long run is sustainable.

Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.

Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes. Mounting evidence demonstrated that NDDs and NPDs share an overlapping mechanism, which includes post-translational modifications, the microbiota-gut-brain axis, and signaling events. Mounting evidence demonstrated that various drug molecules, namely, natural compounds, repurposed drugs, multitarget directed ligands, and RNAs, have been potentially implemented as therapeutic agents against NDDs and NPDs. Herein, we highlighted the overlapping mechanism, the role of anxiety/stress-releasing factors, cytosol-to-nucleus signaling, and the microbiota-gut-brain axis in the pathophysiology of NDDs and NPDs. We summarize the therapeutic application of natural compounds, repurposed drugs, and multitarget-directed ligands as therapeutic agents. Lastly, we briefly described the application of RNA interferences as therapeutic agents in the pathogenesis of NDDs and NPDs. Neurodegenerative diseases and neuropsychiatric diseases both share a common signaling molecule and molecular phenomenon, namely, pro-inflammatory cytokines, γCaMKII and MAPK/ERK, chemokine receptors, BBB permeability, and the gut-microbiota-brain axis. Studies have demonstrated that any alterations in the signaling mentioned above molecules and molecular phenomena lead to the pathophysiology of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and neuropsychiatric disorders, such as bipolar disorder, schizophrenia, depression, anxiety, autism spectrum disorder, and post-traumatic stress disorder.

A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing.

Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor (PR), retinal pigment epithelium (RPE), and choriocapillaris (CC) degeneration. Recent work suggests that RPE-based cell therapy may slow down vision loss in late stages of age-related macular degeneration (AMD), a polygenic disease induced by RPE atrophy. However, accelerated development of effective cell therapies is hampered by the lack of large-animal models that allow testing safety and efficacy of clinical doses covering the human macula (20 mm2). We developed a versatile pig model to mimic different types and stages of retinal degeneration. Using an adjustable power micropulse laser, we generated varying degrees of RPE, PR, and CC damage and confirmed the damage by longitudinal analysis of clinically relevant outcomes, including analyses by adaptive optics and optical coherence tomography/angiography, along with automated image analysis. By imparting a tunable yet targeted damage to the porcine CC and visual streak - with a structure similar to the human macula - this model is optimal for testing cell and gene therapies for outer retinal diseases including AMD, retinitis pigmentosa, Stargardt, and choroideremia. The amenability of this model to clinically relevant imaging outcomes will facilitate faster translation to patients.

Multiple therapeutic approaches of glioblastoma multiforme: From terminal to therapy.

Glioblastoma multiforme (GBM) is an aggressive brain cancer showing poor prognosis. Currently, treatment methods of GBM are limited with adverse outcomes and low survival rate. Thus, advancements in the treatment of GBM are of utmost importance, which can be achieved in recent decades. However, despite aggressive initial treatment, most patients develop recurrent diseases, and the overall survival rate of patients is impossible to achieve. Currently, researchers across the globe target signaling events along with tumor microenvironment (TME) through different drug molecules to inhibit the progression of GBM, but clinically they failed to demonstrate much success. Herein, we discuss the therapeutic targets and signaling cascades along with the role of the organoids model in GBM research. Moreover, we systematically review the traditional and emerging therapeutic strategies in GBM. In addition, we discuss the implications of nanotechnologies, AI, and combinatorial approach to enhance GBM therapeutics.

Celebrating 50 years of microbial granulation technologies: From canonical wastewater management to bio-product recovery.

Microbial granulation technologies (MGT) in wastewater management are widely practised for more than fifty years. MGT can be considered a fine example of human innovativeness-driven nature wherein the manmade forces applied during operational controls in the biological process of wastewater treatment drive the microbial communities to modify their biofilms into granules. Mankind, over the past half a century, has been refining the knowledge of triggering biofilm into granules with some definite success. This review captures the journey of MGT from inception to maturation providing meaningful insights into the process development of MGT-based wastewater management. The full-scale application of MGT-based wastewater management is discussed with an understanding of functional microbial interactions within the granule. The molecular mechanism of granulation through the secretion of extracellular polymeric substances (EPS) and signal molecules is also highlighted in detail. The recent research interest in the recovery of useful bioproducts from the granular EPS is also emphasized.