Gold Nanoparticle-Based Drug Delivery System for the Diagnosis and Treatment of Bacterial Meningitis.

Managing bacterial pathogens in the central nervous system is an immense issue for researchers all around the globe. The problem of these infections remains throughout the population, regardless of the discovery of several possible medicines. The major obstacle to drug delivery is the BBB, but only a few medicines that fulfill demanding requirements can penetrate it. Considering inadequate antibiotic alternatives and the increasing development of resistance, it is more important than ever to find new approaches to address this worldwide problem. Medical nanotechnology has evolved as a cutting-edge and effective means of treating many of the most difficult CNS illnesses, including bacterial meningitis. Various metallic nanoparticles, such as gold, silver, and titanium oxide, have shown bactericidal potential. Gold nanoparticles have gotten a great deal of interest due to their excellent biocompatibility, simplicity of surface modification, and optical qualities. The current study described AuNP-based detection and therapy options against meningitis-- causing bacteria, including bacterial pathogens' mechanisms for crossing BBB and AuNPs' mode of Action against those bacteria. The current study looked into green synthesized bactericidal gold nanoparticles-based therapy techniques for diagnosing and intervening in bacterial meningitis. Nevertheless, more research is needed before these laboratory findings can be translated into therapeutic trials. Nonetheless, we can confidently assert that the knowledge acquired and addressed in this study will benefit neuro-nanotechnology researchers.

CRISPR and Gene Editing: A Game-Changer in Drug Development.

CRISPR and gene editing technologies have emerged as transformative tools in medicine, offering unprecedented precision in targeting genetic disorders and revolutionizing drug development. This review explores the multifaceted impact of CRISPR across various medical domains, from hereditary diseases to infectious diseases and cancer. The potential of CRISPR in personalized medicine, therapeutic innovation, and pandemic prevention is highlighted, along with its role in reshaping traditional drug development processes. However, alongside its promise, ethical considerations loom large, particularly regarding germline editing and equitable access to treatments. The commercialization of CRISPR poses further challenges, raising questions about affordability and healthcare equity. Collaboration among scientists, policymakers, and the public is emphasized to navigate the ethical and societal implications of CRISPR responsibly. As the field advances, it is essential to ensure that the benefits of CRISPR are realized while addressing potential risks and maintaining a commitment to the well-being of future generations.

Recent Trends in Nanocarrier-Based Drug Delivery System for Prostate Cancer.

Prostate cancer remains a significant global health concern, requiring innovative approaches for improved therapeutic outcomes. In recent years, nanoparticle-based drug delivery systems have emerged as promising strategies to address the limitations of conventional cancer chemotherapy. The key trends include utilizing nanoparticles for enhancing drug delivery to prostate cancer cells. Nanoparticles have some advantages such as improved drug solubility, prolonged circulation time, and targeted delivery of drugs. Encapsulation of chemotherapeutic agents within nanoparticles allows for controlled release kinetics, reducing systemic toxicity while maintaining therapeutic efficacy. Additionally, site-specific accumulation within the prostate tumor microenvironment is made possible by the functionalization of nanocarrier with targeted ligands, improving therapeutic effectiveness. This article highlights the basics of prostate cancer, statistics of prostate cancer, mechanism of multidrug resistance, targeting approach, and different types of nanocarrier used for the treatment of prostate cancer. It also includes the applications of nanocarriers for the treatment of prostate cancer and clinical trial studies to validate the safety and efficacy of the innovative drug delivery systems. The article focused on developing nanocarrier-based drug delivery systems, with the goal of translating these advancements into clinical applications in the future.

Association of eGFR with stages of diabetic retinopathy and age-related macular degeneration in Indian population.

PURPOSE: To investigate the influence of glomerular filtration rate in renal disease decline and its association with diabetic retinopathy (DR) and age-related macular degeneration (ARMD) in patients in South India. METHODS: A population-based cross-sectional study was conducted including participants with DR and ARMD recruited from urban and rural populations. The data collection included medical history, anthropometric measurements, and ophthalmic work-up. The estimated glomerular filtration rate (eGFR) was calculated using the equation of chronic kidney disease-epidemiology collaboration (CKD-EPI). The grading of AMD was done by a single experienced (more than 5 years) vitreoretinal surgeon as per the International ARM Epidemiological Study Group and it was staged based on grading in the worsened eye. RESULTS: A decline in eGFR was observed as the severity of DR increased (P < 0.001). Baseline characteristics such as age (P < 0.001), duration of diabetes (P < 0.001), gender (P < 0.001), creatinine (P < 0.001), albumin to creatinine ratio (ACR; P < 0.001), albuminuria (P = 0.023), blood urea (P < 0.001), and high-density lipoprotein (HDL; P = 0.003) were found to be statistically significant. The risk for developing DR with CKD was found to be 5 times higher in male patients compared to female patients. Age and high blood urea level, diastolic blood pressure, mild and moderate DR were the risk factors associated with CKD. A decline in eGFR was observed as the severity of ARMD increased (P < 0.001). The risk factors associated with CKD were age, gender, smoking, alcohol consumed, presence of hypertension, duration of diabetes, systolic and diastolic blood pressure, history of diabetes, body mass index (BMI), serum triglycerides, and serum HDL cholesterol. CONCLUSION: Reduced eGFR values were associated with an increase in the severity of DR and ARMD.

Osteonecrosis in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: The relationship of inflammatory bowel disease (IBD) with osteonecrosis or avascular necrosis (AVN) is uncertain. METHODS: Systematic review to estimate the frequency of osteonecrosis in IBD was performed. Electronic databases were searched on 12 December 2022 to identify relevant studies. We planned to estimate the pooled prevalence of AVN in IBD, the risk in IBD when compared to the healthy population (without any chronic disease), and the impact of steroid use on osteonecrosis (IBD with and without steroid use). The risk of Bias was assessed with the Joanna Briggs Institute appraisal tool. RESULTS: Fifteen studies including 105 154 individuals were included. The pooled rate AVN was 10.39 per 1000 patients (95% confidence interval, 4.44-24.11, I 2  = 97%). Subgroup analysis suggested that the prevalence was lower in larger studies (>1000 participants) at 3.10, 1.07; 8.98, I 2  = 98% versus 21.03, 8.69; 50.01, I 2  = 83%. The use of steroids did not seem to increase the risk of osteonecrosis in the included studies (pooled odds ratio: 1.88, 0.55-6.41, I 2  = 39%). The systematic review was limited by the absence of comparison with the control population free of chronic disease. CONCLUSION: IBD may be associated with a risk of osteonecrosis. Future studies should assess the risk in comparison to the healthy population and the impact of disease activity and IBD therapies on the risk.

Fiber-connectorized ultrafast-laser-inscribed K-band integrated optics beam combiner for the CHARA telescope array.

A fiber-connectorized K-band integrated-optics two-telescope beam combiner was developed for long-baseline interferometry at the CHARA telescope array utilizing the ultrafast laser inscription (ULI) technique. Single-mode waveguide insertion losses were measured to be ∼1.1d B over the 2-2.3 µm window. The development of asymmetric directional couplers enabled the construction of a beam combiner that includes a 50:50 coupler for interferometric combination and two ∼75:25 couplers for photometric calibration. The visibility of the bare beam combiner was measured at 87% and then at 82% after fiber-connectorization by optimizing the input polarization. These results indicate that ULI technique can fabricate efficient fiber-connectorized K-band beam combiners for astronomical purposes.

A DNA aptamer-based assay for the detection of soluble ST2, a prognostic biomarker for monitoring heart failure.

Heart failure (HF) is emerging as a leading cause of death worldwide. Estimation of BNP levels is a routine diagnosis in these patients. However, in patients having high body-mass index (BMI), renal disease or in geriatric patients, BNP level is reported to be noisy and leads to incongruous conclusion. Thus, for better risk stratification among heart failure patients, it is imperative to look for a superior biomarker. In recent times, sST2 has shown promise as a biomarker. Identifying such biomarkers in peripheral blood of HF patients, need an affine and selective molecular recognition element. Thus, in the current study an aptamer (sS9_P) against sST2 was identified from an aptamer library. Systematic Evolution of Ligands through Exponential enrichment (SELEX) derived aptamer evinced role of its primer binding domains in maintaining its selectivity. This aptamer candidate demonstrated dissociation constant (Kd) in low nanomolar range, and the Limit of Detection (LOD) was ~4 ng. Circular dichroism confirms the formation of complex stem-loop like structure. The well characterized sS9_P aptamer was used in an Aptamer Linked Immobilized Sorbent Assay (ALISA) to detect sST2 level in patients' serum (n = 99). Aptamer sS9_P has shown significant discrimination to differentiate HF patients and healthy volunteers with a reasonable specificity (~83 %) with a modest sensitivity of ~64 %. While sST-2 antibody has shown poor specificity of ~44% but good sensitivity (~87%). The insight obtained from this study indicates that a combination of aptamer and antibody-based assay can be used to design a point-of-care assay for the rapid detection of HF patients in emergency settings.

Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT): Subanalysis of Referral to Ophthalmology.

PURPOSE: The Manhattan Vision Screening and Follow-up Study aims to provide access to eye care for underserved populations, detect native rates of ocular pathology, and refer participants with eye disease to ophthalmology. This subanalysis describes the reasons for referral to ophthalmology and identifies risk factors associated with being referred. METHODS: Enrolled participants were aged ≥40 years, living independently in public housing developments and able to provide consent for eye health screenings. Those with habitual visual acuity 20/40 or worse, intraocular pressure (IOP) 23-29 mmHg, or an unreadable fundus image failed and were scheduled with the on-site optometrist. The optometric exam determined whether further referral to ophthalmology for a clinic exam was warranted. Those with an abnormal image or IOP ≥30 mmHg were referred directly to ophthalmology. Main outcome was factors associated with referral to ophthalmology. RESULTS: A total of 708 individuals completed the eye health screening over 15 months. A total of 468 participants were referred to ophthalmology (250 had an abnormal image and 218 were referred by the optometrist). Those referred were predominantly older adults (mean age 70.0 ± 11.4 years), female (66.7%), African American (55.1%) and Hispanic (39.5%). Seventy percent of participants had not had a recent eye exam. Stepwise multivariate logistic regression analysis showed that participants with pre-existing glaucoma (OR 3.14, 95% CI 1.62 to 6.08, p = 0.001), an IOP ≥23 mmHg (OR 5.04, 95% 1.91 to 13.28, p = 0.001), or vision impairment (mild) (OR 2.51, 95% CI 1.68 to 3.77, p = 0.001) had significantly higher odds of being referred to ophthalmology. CONCLUSION: This targeted community-based study in Upper Manhattan provided access to eye care and detected a significant amount of ocular pathology requiring referral to ophthalmology in this high-risk population.

ProGlycProt V3.0: updated insights into prokaryotic glycoproteins and their glycosyltransferases.

ProGlycProt is a comprehensive database of experimentally validated information about protein glycosylation in prokaryotes, including the glycoproteins, glycosyltransferases, and their accessory enzymes. The first release of ProGlycProt featured experimentally validated information on glycoproteins only. For the second release in 2019, the size and scope of the database were expanded twofold, and experimental data on cognate glycosyltransferases and their accessory proteins was incorporated. The growing research and technology interest in microbial glycoproteins and their enzymes is evident from the steady rise in academic publications and patents in this area. Accordingly, the third update comprises a new section on patents related to glycosylation methods, novel glycosyltransferases, and technologies developed therefrom. The structure gallery is reorganized, wherein the number and quality of the models are upgraded with the help of AlphaFold2. Over the years, the influx of experimental proteomics data into public repositories like PRIDE has surged. Harnessing this legacy data for in-silico glycoprotein identification is a smart approach. Version 3.0 adds 45 N-glycoprotein entries annotated from MS datasets available on PRIDE and reviewed by independent research groups. With a 67% rise in entries corresponding to 119 genera of prokaryotes, the ProGlycProt continues to be the exclusive database of experimentally validated comprehensive information about protein glycosylation in prokaryotes.

Mapping vision loss of patients in a glaucoma backlog following the COVID-19 pandemic: a real-world analysis using the Glauc-Strat-Fast risk stratification tool.

INTRODUCTION: Glauc-Strat-Fast is a clinical tool recommended by The Royal College of Ophthalmologists to classify glaucoma patients into strata of risk for significant future sight loss and an estimate of resource requirement. The aim of this study was to map the movement of glaucoma patients across stratification boundaries on Glauc-Strat-Fast during the COVID-19 pandemic. SUBJECTS AND METHODS: Glauc-Strat-Fast was applied to a consecutive sample of 100 primary open angle glaucoma patients in a backlog at Worcestershire Acute Hospitals NHS Trust. Stratification outcomes were compared between clinic visits prior to the COVID-19 pandemic versus the follow-up visit. Patients were stratified twice separately based on their worse eye (i.e., most affected) and better eye (i.e., least affected) according to Glauc-Strat-Fast. RESULTS: Amount of slippage (difference between target follow-up and actual follow-up) ranged from 2 to 32 months. There was a statistically significant average reduction in visual field mean deviation for better and worse eyes between visits (p = <0.001). At follow-up, no worse eyes were classified as being low risk (green), while 96 were classified as high risk (red). For better eyes, elevation of risk into the highest strata of Glauc-Strat-Fast observed a three-fold increase in patients (19 versus 56) between visits. DISCUSSION: This retrospective real-world analysis highlights patients' movement into the highest strata on the Glauc-Strat-Fast tool and demonstrates a significant deterioration in visual outcomes during a period of extensive appointment slippage. The findings demonstrate the utility of Glauc-Strat-Fast as a tool for improved patient management.

DiabeticSense: A Non-Invasive, Multi-Sensor, IoT-Based Pre-Diagnostic System for Diabetes Detection Using Breath.

Diabetes mellitus is a widespread chronic metabolic disorder that requires regular blood glucose level surveillance. Current invasive techniques, such as finger-prick tests, often result in discomfort, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named DiabeticSense, an affordable digital health device for early detection, to encourage immediate intervention. The device employed electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differed between diabetic and non-diabetic individuals. The system merged vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used clinical breath samples from 100 patients at a nationally recognized hospital to form the dataset. Data were then processed using a gradient boosting classifier model, and the performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, indicating an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. This has the potential to increase patient adherence to regular monitoring.

Patient perspectives on tapering biologic or targeted synthetic therapy in well-controlled rheumatoid arthritis and comparison with providers' perspectives.

OBJECTIVE: We examined patient and providers' perspectives on tapering biologic or targeted synthetic disease modifying antirheumatic drugs (bDMARD or tsDMARD) in well-controlled RA to determine which factors influence their long-term treatment decisions. METHODS: A standardized phone survey was administered to patients with well-controlled RA based on electronic health record review. Providers were also surveyed. Univariate and multivariable regression analysis was performed with odds ratios (OR) and 95% CI. RESULTS: Sixty-two patients and 11 providers completed the survey. In total, 39 (63%) patients would consider a bDMARD/tsDMARD taper. Patients were more likely to consider a taper if they thought their RA was well-controlled (OR 8.02, 95% CI 2.15-29.99, P = 0.002) and of shorter duration (OR 0.94, 95% CI 0.89-0.99, P = 0.02). Patients were less likely to consider a taper if older (OR 0.95, 95% CI 0.91-1.0, P = 0.05), if they were being treated with conventional synthetic DMARDs (OR 0.25, 95% CI 0.07-0.86, P = 0.0275) or daily glucocorticoids (OR 0.08, 95% CI 0.02-0.44, P = 0.0033). Patients' and providers' top concerns about long-term bDMARD/tsDMARD use were malignancy and infection. Their concerns about tapering were worsening pain, flare and loss of function. Patients were more likely to consider a bDMARD/tsDMARD taper than providers (63% vs 36%). CONCLUSION: Patients who have had well-controlled RA are more likely to consider tapering bDMARD/tsDMARD when not being treated with csDMARDs or glucocorticoids. Patients and providers shared similar concerns regarding long-term use and tapering of bDMARD/tsDMARD, but patients were more likely to consider a taper.

A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort.

OBJECTIVES: This study had two aims: (i) to investigate outcomes of medication tapering in stable RA patients on biologic or targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) and conventional synthetic DMARDs (csDMARDs) in a real-world prospective cohort; and (ii) to evaluate possible predictors of flare with medication taper. METHODS: A prospective cohort of patients with RA in sustained remission or low disease activity while on stable bDMARD/tsDMARDs +/- csDMARDs for at least 6 months underwent medication tapering/stopping and was tracked for 2 years. Patients were evaluated for flares in four groups: no taper, only bDMARD/tsDMARD taper, only csDMARD taper and both csDMARD and bDMARD/tsDMARD taper. RESULTS: The RHEUMTAP cohort included 131 patients that met eligibility criteria, of which 52 patients underwent a medication taper. Flare was experienced by 15 patients in the taper and two in the no-taper groups. Patients undergoing any taper/stop overall were 10 times more likely to experience a flare compared with those not tapered (HR 10.43, 95% CI 2.98-36.53, P = 0.0002). The group tapering bDMARD/tsDMARD had 31 times higher risk of flare (HR 31.43, 95% CI 6.35-155.55, P <0.0001) than the no-taper group. Patients tapering both csDMARDs and bDMARD/tsDMARDs had 18 times higher risk of flare than the no-taper group (HR 18.45, 95% CI 2.55-133.37, P = 0.0039). The only csDMARD taper group had a 91% lower risk of flare than the bDMARD/tsDMARD taper group (HR 0.09, 95% CI 0.01-0.69, P = 0.0213). CONCLUSION: In our real-world prospective RHEUMTAP cohort study on the outcomes of different medication tapering groups in well-controlled RA, patients who tapered or stopped bDMARDs/tsDMARDs with or without background therapy were more likely to experience a flare than patients that did not taper any medications and those that tapered only csDMARDs.

Rapid diagnosis of TB using Aptamer-based assays for Mycobacterium tuberculosis antigens in children and adolescents.

Background: Despite advances establishing microbiological evidence of tuberculosis (TB) is still a concern in children due to the limitation of availability of sample and predominance of extrapulmonary TB, there is unmet need for diagnostic tests which are low cost, rapid and sensitive and specific. Methods: This study evaluated the utility of aptamer-based assay for detecting mycobacterium tuberculosis antigens HspX and MPT 64 in rapid diagnosis of TB in children up to 18 years of age in a tertiary medical college. A total of 100 children were sequentially enrolled with presumptive pulmonary (n = 52 and extrapulmonary n = 48) TB based on clinico-radiological characteristics. The samples were evaluated with ALISA technique for TB antigens and compared with the results of ZN microscopy, GeneXpert and mycobacterial culture MGIT. Results: The enrolled children had mean age (11.7 + 4.4 years) with both pulmonary (n = 52) and extrapulmonary TB (n = 48). Our study results concluded poor results of smears (11% positivity, sensitivity: 17.7%, NPV: 42.7%) and better of GeneXpert (positivity: 42%, sensitivity of 67.4%, NPV: 65.5%) and culture (positivity 57%, sensitivity 91.9%, NPV 88.3%). HspX antigen by ALISA had comparable results (positivity: 49%, sensitivity: 62.9%; NPV: 54.9%). MPT 64 antigen by ALISA also had similar results (positivity: 45%, sensitivity: 58% and NPV 52, 3%). Sensitivity and specificity were higher in pulmonary TB compared to EPTB for both antigens. HspX antigen assay by ALISA and MPT 64 ALISA over existing microbiological diagnostic methods had additional of 13%. Conclusion: ALISA technique for mycobacterium antigens HspX and MPT 64 was rapid, low-cost test (1-3$/test) high sensitivity and specificity and comparable to currently available methods.

Manhattan Vision Screening and Follow-Up Study: (NYC-SIGHT)Tele-Retinal Image Findings and Importance of Photography.

Purpose: To describe tele-retinal abnormality image findings from the Manhattan Vision Screening and Follow-up Study (NYC-SIGHT), which aims to investigate whether community-based eye health outreach strategies using telemedicine can improve visual outcomes among at-risk populations in Upper Manhattan. Methods: A 5-year prospective, cluster-randomized clinical trial was conducted. Eligible individuals aged 40 years and older were recruited from affordable housing developments and senior centers in New York City. Participants underwent on-site eye health screening (best-corrected visual acuity, intraocular pressure [IOP] measurements, and fundus photography). Fundus images were graded via telemedicine by a retina specialist. Multivariate logistic regression modeling was used to assess the factors associated with abnormal retinal findings requiring referral to ophthalmology. Results: Participants with a retinal abnormality on fundus photography (n = 157) were predominantly older adults, with a mean age of 68.4 ± 11.1 years, female (63.7%), African American (50.3%), and Hispanic (43.3%). A total of 32 participants in our study passed the vision and IOP screening but had an abnormal retinal image and ocular pathology that would have been missed without fundus photography. Individuals who self-identified as having preexisting glaucoma (odds ratio [OR] = 3.749, 95% confidence interval [CI] = 1.741-8.074, p = 0.0001) and had severe vision impairment (OR = 4.1034, 95% CI = 2.0740-8.1186, p = 0.000) at the screening had significantly higher odds of having an abnormal retinal image. Conclusion: This community-based study targeted populations at-risk for eye disease, improved access to eye care, detected a significant number of retinal image abnormalities requiring follow-up by using telemedicine, and provided evidence of the importance of fundus photography during eye health screenings. CTR number: NCT04271709.

G-quadruplex motifs in Neisseria gonorrhoeae as anti-gonococcal targets.

Neisseria gonorrhoeae is an obligate human pathogen that causes gonorrhea and has shown a vast emergence of multidrug resistance in recent times. It is necessary to develop novel therapeutic strategies to combat this multidrug-resistant pathogen. The non-canonical stable secondary structures of nucleic acids, G-quadruplexes (GQs), are reported to regulate gene expressions in viruses, prokaryotes, and eukaryotes. Herein, we explored the whole genome of N. gonorrhoeae to mine evolutionary conserved GQ motifs. The Ng-GQs were highly enriched in the genes involved in various important biological and molecular processes of N. gonorrhoeae. Five of these GQ motifs were characterized using biophysical and biomolecular techniques. The GQ-specific ligand, BRACO-19, showed a high affinity towards these GQ motifs and stabilized them in both in vitro and in vivo conditions. The ligand showed potent anti-gonococcal activity and modulated the gene expression of the GQ-harboring genes. Strikingly, BRACO-19 also altered the biofilm formation in N. gonorrhoeae and its adhesion and invasion of the human cervical epithelial cells. In summary, the present study showed a significant role of GQ motifs in N. gonorrhoeae biology and put forward a step closer towards the search for therapeutic measures in combating the emerging antimicrobial resistance in the pathogen. KEY POINTS: •Neisseria gonorrhoeae genome is enriched in non-canonical nucleic acid structures-G-quadruplexes. •These G-quadruplexes might regulate bacterial growth, virulence, and pathogenesis. •G-quadruplex ligands inhibit biofilm formation, adhesion, and invasion of the gonococcus bacterium.