The Association between Glymphatic System and Perivascular Macrophages in Brain Waste Clearance.

The glymphatic system suggests the convective bulk flow of cerebrospinal fluid (CSF) through perivascular spaces and the interstitial spaces of the brain parenchyma for the rapid removal of toxic waste solutes from the brain. However, the presence of convective bulk flow within the brain interstitial spaces is still under debate. We first addressed this argument to determine the involvement of the glymphatic system in brain waste clearance utilizing contrast-enhanced 3D T1-weighted imaging (T1WI), diffusion tensor imaging (DTI), and confocal microscopy imaging. Furthermore, perivascular macrophages (PVMs), which are immune cells located within perivascular spaces, have not been thoroughly explored for their association with the glymphatic system. Therefore, we investigated tracer uptake by PVMs in the perivascular spaces of both the arteries/arterioles and veins/venules and the potential association of PVMs in assisting the glymphatic system for interstitial waste clearance. Our findings demonstrated that both convective bulk flow and diffusion are responsible for the clearance of interstitial waste solutes from the brain parenchyma. Furthermore, our results suggested that PVMs may play an important function in glymphatic system-mediated interstitial waste clearance. The glymphatic system and PVMs could be targeted to enhance interstitial waste clearance in patients with waste-associated neurological conditions and aging.

Antimicrobial Potential of Polyphenols: An Update on Alternative for Combating Antimicrobial Resistance.

The last decade has encountered an increasing demand for plant-based natural antibiotics. This demand has led to more research-based investigations for natural sources of antimicrobial agents and published reports demonstrating that plant extracts are widely applied in modern medicine, reporting potential activity that may be due to polyphenol compounds. Interestingly, the effects of polyphenols on the sensitivity of bacteria to antibiotics have not been well-studied. Hence, the current review encompasses the prospective application of plant-based phenolic extracts from plants of Indian origin. The emergence of resistance to antimicrobial agents has increased the inefficacy of many antimicrobial drugs. Several strategies have been developed in recent times to overcome this issue. A combination of antimicrobial agents is employed for the failing antibiotics, which restores the desirable effect but may have toxicity-related issues. Phytochemicals such as some polyphenols have demonstrated their potent activity as antimicrobial agents of natural origin to work against resistance issues. These agents alone or in combination with certain antibiotics have been shown to enhance the antimicrobial activity against a spectrum of microbes. However, the information regarding the mechanisms and structure-activity relationships remains elusive. The present review also focuses on the possible mechanisms of natural compounds based on their structure- activity relationships for incorporating polyphenolic compounds in the drug-development processes. Besides this work, polyphenols could reduce drug dosage and may diminish the unhidden or hidden side effects of antibiotics. Pre-clinical findings have provided strong evidence that polyphenolic compounds, individually and in combination with already approved antibiotics, work well against the development of resistance. However, more studies must focus on in vivo results, and clinical research needs to specify the importance of polyphenol-based antibacterials in clinical trials.

An Effective Flux Framework for Linear Irreversible Heat Engines: Case Study of a Thermoelectric Generator.

We consider an autonomous heat engine in simultaneous contact with a hot and a cold reservoir and describe it within a linear irreversible framework. In a tight-coupling approximation, the rate of entropy generation is effectively written in terms of a single thermal flux that is a homogeneous function of the hot and cold fluxes. The specific algebraic forms of the effective flux are deduced for scenarios containing internal and external irreversibilities for the typical example of a thermoelectric generator.

Mixed-methods study exploring health service access and social support linkage to the mental well-being of Canadian Indigenous pregnant persons during the COVID-19 pandemic.

OBJECTIVES: This study aimed to explore how the unprecedented stressors associated with the COVID-19 pandemic may have contributed to heightened levels of depression and anxiety among pregnant Indigenous persons, and identify protective individual-level factors. DESIGN: The current study used a mixed-methods design including standardised questionnaires and open-ended response questions. Using hierarchical regression models, we examined the extent to which COVID-19-related factors of service disruption (ie, changes to prenatal care, changes to birth plans and social support) were associated with mental well-being. Further, through qualitative analyses of open-ended questions, we examined the coping strategies used by pregnant Indigenous persons in response to the pandemic. SETTING: Participants responded to an online questionnaire consisting of standardised measures from 2020 to 2021. PARTICIPANTS: The study included 336 self-identifying Indigenous pregnant persons in Canada. RESULTS: Descriptive results revealed elevated rates of clinically relevant depression (52.7%) and anxiety (62.5%) symptoms among this population. 76.8% of participants reported prenatal care service disruptions, including appointment cancellations. Thematic analyses identified coping themes of staying informed, social and/or cultural connections and activities, and internal mental well-being strategies. Disruptions to services and decreased quality of prenatal care negatively impacted mental well-being of Indigenous pregnant persons during the COVID-19 pandemic. CONCLUSIONS: Given the potential for mental well-being challenges to persist and long-term effects of perinatal distress, it is important to examine the quality of care that pregnant individuals receive. Service providers should advance policies and practices that promote relationship quality and health system engagement as key factors linked to well-being during the perinatal period for Indigenous persons.

Clinical magnetic resonance imaging evaluation of glymphatic function.

The glymphatic system is a system of specialized perivascular spaces in the brain that facilitates removal of toxic waste solutes from the brain. Evaluation of glymphatic system function by means of magnetic resonance imaging (MRI) has thus far been largely focused on rodents because of the limitations of intrathecal delivery of gadolinium-based contrast agents to humans. This review discusses MRI methods that can be employed clinically for glymphatic-related measurements intended for early diagnosis, prevention, and the treatment of various neurological conditions. Although glymphatic system-based MRI research is in its early stages, recent studies have identified promising noninvasive MRI markers associated with glymphatic system alterations in neurological diseases. However, further optimization in data acquisition, validation, and modeling are needed to investigate the glymphatic system within the clinical setting.

Cerebrospinal Fluid Viral Escape on Highly Active Antiretroviral Therapy: Analysis from Single Tertiary Care Centre.

HIV-infected individuals receiving regular antiretroviral therapy (ART) can present with a high viral load in cerebrospinal fluid (CSF) at times when it is suppressed in blood. This study presents data of HIV-infected patients who had undetectable or low plasma viral load in blood but presented with neurological signs and symptoms and were diagnosed to have CSF HIV viral escape. Records were reviewed for clinical manifestations, details of opportunistic or coinfection, and HIV viral copies in plasma and CSF at time of diagnosis of CSF escape. A total of 10,200 HIV-infected individuals were registered in HIV care till December 31, 2021. Nineteen individuals (14 virologically confirmed and 5 clinically) were diagnosed with high viral copies in CSF from June 2014 to December 2021. Mean age was 41.5 ± 9.2 (median, 39.5; range, 30-62) years. Average duration of antiretroviral treatment received at the time of diagnosis of CSF escape was 10.1 years. Median plasma HIV-viral copies were 2,469.8 (undetectable to 29,418) and in CSF were 12,773.7 (n = 14, range, 1,340-48,530) copies/mL. HIV viral copies in CSF were significantly higher than in plasma at the time of presentation (p = .003). ART regimen switch was done after identification of HIV CSF escape. Seventeen patients were alive with a regular follow-up of average 35 (range 7-66) months. All had documented clinical improvement with reversal of neurological impairment after ART switch. There was one death and one lost to follow-up. Early identification and timely intervention in CSF viral escape could revert severe neurological impairment and improves treatment outcome.

What is the impact of artificial intelligence-based chatbots on infodemic management?

Artificial intelligence (AI) chatbots have the potential to revolutionize online health information-seeking behavior by delivering up-to-date information on a wide range of health topics. They generate personalized responses to user queries through their ability to process extensive amounts of text, analyze trends, and generate natural language responses. Chatbots can manage infodemic by debunking online health misinformation on a large scale. Nevertheless, system accuracy remains technically challenging. Chatbots require training on diverse and representative datasets, security to protect against malicious actors, and updates to keep up-to-date on scientific progress. Therefore, although AI chatbots hold significant potential in assisting infodemic management, it is essential to approach their outputs with caution due to their current limitations.

The Glymphatic Response to the Development of Type 2 Diabetes.

The glymphatic system has recently been shown to be important in neurological diseases, including diabetes. However, little is known about how the progressive onset of diabetes affects the glymphatic system. The aim of this study is to investigate the glymphatic system response to the progressive onset of diabetes in a rat model of type 2 diabetic mellitus. Male Wistar rats (n = 45) with and without diabetes were evaluated using MRI glymphatic tracer kinetics, functional tests, and brain tissue immunohistochemistry. Our data demonstrated that the contrast agent clearance impairment gradually progressed with the diabetic duration. The MRI data showed that an impairment in contrast clearance occurred prior to the cognitive deficits detected using functional tests and permitted the detection of an early DM stage compared to the immuno-histopathology and cognitive tests. Additionally, the quantitative MRI markers of brain waste clearance demonstrated region-dependent sensitivity in glymphatic impairment. The improved sensitivity of MRI markers in the olfactory bulb and the whole brain at an early DM stage may be attributed to the important role of the olfactory bulb in the parenchymal efflux pathway. MRI can provide sensitive quantitative markers of glymphatic impairment during the progression of DM and can be used as a valuable tool for the early diagnosis of DM with a potential for clinical application.

Diabetic Retinopathy - Pathophysiology to Treatment: A Review.

Diabetic retinopathy (DR) is a microvascular disease affecting the eyes of diabetic patients, and is the most prevalent complication of diabetes mellitus. Vision improvement is not possible in the majority of DR patients. Several studies have indicated that microvascular changes, inflammation, oxidative stress, and retinal neurodegeneration are involved in the pathogenesis of DR. Therefore, there is an urgent need for the development of new and effective treatment for DR. Understanding the molecular mechanisms involved in the pathogenesis of disease will pave a way for better treatment and management of DR. This article has emphasized the molecular pathogenesis and treatment of DR.

Key Insights on the Classification and Theranostic Applications of Magnetic Resonance Imaging Contrast Agents.

Magnetic resonance imaging (MRI) is a non-invasive molecular imaging tool being extensively employed in clinical and biomedical research for the detection of a broad spectrum of diseases. This technique offers remarkable spatial resolution, good tissue penetration and a high soft tissue contrast. Contrast agents (CAs) have been regularly used in MRI tests to enhance the resolution of MR images and to visualize the diseased sites in the body. In the past years, considerable efforts have been devoted towards developing new theranostic MRI agents that can be tailored to integrate the targeting and therapeutic functions in a single agent. In this review, we have underlined the role of the MRI CAs in the developing field of 'theranostics' and their recent applications in the combined imaging and therapy of different types of tumors. In addition, this review also outlines the different categories of MRI CAs and their comprehensive classification based on different criteria such as chemical composition, relaxation mechanism and biodistribution with clinically relevant examples.

Cloud Native Remote Monitoring Data Ecosystem for Aging Population based on Commercial AAL Sensors.

In the recent years, Active Assisted Living (AAL) technologies used for autonomous tracking and activity recognition have started to play major roles in geriatric care. From fall detection to remotely monitoring behavioral patterns, vital functions and collection of air quality data, AAL has become pervasive in the modern era of independent living for the elderly section of the population. However, even with the current rate of progress, data access and data reliability has become a major hurdle especially when such data is intended to be used in new age modelling approaches such as those using machine learning. This paper presents a comprehensive data ecosystem comprising remote monitoring AAL sensors along with extensive focus on cloud native system architecture, secured and confidential access to data with easy data sharing. Results from a validation study illustrate the feasibility of using this system for remote healthcare surveillance. The proposed system shows great promise in multiple fields from various AAL studies to development of data driven policies by local governments in promoting healthy lifestyles for the elderly alongside a common data repository that can be beneficial to other research communities worldwide.Clinical Relevance- This study creates a cloud-based smart home data ecosystem, which can achieve the remote healthcare monitoring for aging population, enabling them to live more independently and decreasing hospital admission rates.

Molecular characterization of Orientia tsutsugamushi causing fatal scrub typhus in a young male affected by so-called "mystery fever" in North India.

Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi. Although the presence of eschar is considered pathognomic, diagnosis of scrub typhus is challenging due to overlapping presentation. The diagnosis is based on the serological and molecular assay. Here, we describe a case of a young male patient who was diagnosed with scrub typhus and developed complications in the course of the disease. We also performed molecular characterization of the strain which revealed a close relatedness to Karp-like Linh.DT strains were previously reported from Vietnam.

A Rare Association of Pituitary Macroadenoma With Nasopharyngeal Angiofibroma: A Case Report.

Pituitary macroadenoma and angiofibroma are two distinct and diverse types of tumors that can develop in different anatomical locations and clinical characteristics and are not typically related to each other in terms of their hormonal or developmental aspects. This case describes an adult male with pituitary macroadenoma with nasal angiofibroma. A 35-year-old male was diagnosed with pituitary macroadenoma and incidentally found to have juvenile nasopharyngeal angiofibroma (NPA). The patient underwent a diagnostic workup, including imaging studies and hormonal assays, which confirmed the concomitant presence of both tumors. The patient underwent successful endoscopic surgical excision of the NPA and transnasal transsphenoidal endoscopic pituitary macroadenoma excision as a two-stage operation. The patient was followed up postoperatively and had no evidence of tumor recurrence or hormonal imbalances. The importance of complete and comprehensive diagnostic workup and multidisciplinary management in achieving successful and optimum treatment outcomes for coexisting NPA and pituitary macroadenoma in an adult patient is highlighted in the present report.

Imaging glymphatic response to glioblastoma.

BACKGROUND: The glymphatic system actively exchanges cerebrospinal fluid (CSF) and interstitial fluid (ISF) to eliminate toxic interstitial waste solutes from the brain parenchyma. Impairment of the glymphatic system has been linked to several neurological conditions. Glioblastoma, also known as Glioblastoma multiforme (GBM) is a highly aggressive form of malignant brain cancer within the glioma category. However, the impact of GBM on the functioning of the glymphatic system has not been investigated. Using dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) and advanced kinetic modeling, we examined the changes in the glymphatic system in rats with GBM. METHODS: Dynamic 3D contrast-enhanced T1-weighted imaging (T1WI) with intra-cisterna magna (ICM) infusion of paramagnetic Gd-DTPA contrast agent was used for MRI glymphatic measurements in both GBM-induced and control rats. Glymphatic flow in the whole brain and the olfactory bulb was analyzed using model-derived parameters of arrival time, infusion rate, clearance rate, and residual that describe the dynamics of CSF tracer over time. RESULTS: 3D dynamic T1WI data identified reduced glymphatic influx and clearance, indicating an impaired glymphatic system due to GBM. Kinetic modeling and quantitative analyses consistently indicated significantly reduced infusion rate, clearance rate, and increased residual of CSF tracer in GBM rats compared to control rats, suggesting restricted glymphatic flow in the brain with GBM. In addition, our results identified compromised perineural pathway along the optic nerves in GBM rats. CONCLUSIONS: Our study demonstrates the presence of GBM-impaired glymphatic response in the rat brain and impaired perineural pathway along the optic nerves. Reduced glymphatic waste clearance may lead to the accumulation of toxic waste solutes and pro-inflammatory signaling molecules which may affect the progression of the GBM.

The Association between Glymphatic System and Perivascular Macrophages in Brain Waste Clearance.

The glymphatic system suggests the convective bulk flow of cerebrospinal fluid (CSF) through perivascular spaces and the interstitial spaces of the brain parenchyma for the rapid removal of toxic waste solutes from the brain. However, the presence of convective bulk flow within the brain interstitial spaces is still under debate. We first addressed this argument to determine the involvement of the glymphatic system in brain waste clearance utilizing contrast-enhanced 3D T1-weighted imaging (T1WI), diffusion tensor imaging (DTI), and confocal microscopy imaging. Furthermore, perivascular macrophages (PVMs), which are immune cells located within perivascular spaces, have not been thoroughly explored for their association with the glymphatic system. Therefore, we investigated tracer uptake by PVMs in the perivascular spaces of both the arteries/arterioles and veins/venules and the potential association of PVMs in assisting the glymphatic system for interstitial waste clearance. Our findings demonstrated that both convective bulk flow and diffusion are responsible for the clearance of interstitial waste solutes from the brain parenchyma. Furthermore, our results suggested that PVMs play an important function in glymphatic system-mediated interstitial waste clearance. The glymphatic system and PVMs could be targeted to enhance interstitial waste clearance in patients with waste-associated neurological conditions and aging.

Telephone Virtual Versus In-Person Pharmacotherapy-Based Obesity Care: A COVID-19-Related Experience at a Veterans Administration Facility.

Background: Most of the Veterans Administration (VA) population is either overweight or obese, which is a serious health concern. Medical weight management visits have traditionally occurred through in-person clinics. However, the COVID-19 pandemic forced care delivery to virtual platforms. Methods: We compared weight loss with in-person versus telephone-based medical weight management (lifestyle counseling coupled with pharmacotherapy) delivered by physician and nurse practitioner visits during the pandemic. We designed a program evaluation utilizing a naturalistic (pragmatic) observational study structure, including both newly enrolled and previously established participants in the Minneapolis VA MOVE! program between 2017 and 2021. A "transition" cohort (n = 74) received in-person care from March 2019 to March 2020, and then transitioned to virtual care. A "new start" virtual care cohort (n = 149) enrolled after March 2020 was compared to a separate historical group (n = 180) that received in-person care between January 2017 and December 2019. Weight loss was accessed over a 9-month period in both cohorts. Results: Mean weight loss over 9 months was -6.5 ± 18.2 and -2.5 ± 13.3 lbs in the in-person and virtual phases of the transition cohort, respectively, without significant difference between the two phases (p = 0.22). Mean weight loss over 9 months in the new start (virtual) cohort was -14.4 ± 17.0 lbs compared to -16.7 ± 21.0 lbs in the historical cohort, without significant difference between groups (p = 0.44). Conclusions: In our naturalistic study in a single-site VA clinic setting, weight loss with telephone-based medical weight management during the pandemic was comparable to in-person care. These findings are important for veterans living in rural and/or underserved areas.

Pathogenesis of Alzheimer's Disease and Diversity of 1,2,3-Triazole Scaffold in Drug Development: Design Strategies, Structural Insights, and Therapeutic Potential.

Alzheimer's disease is a most prevalent form of dementia all around the globe and currently poses a significant challenge to the healthcare system. Currently available drugs only slow the progression of this disease rather than provide proper containment. Identification of multiple targets responsible for this disease in the last three decades established it as a multifactorial neurodegenerative disorder that needs novel multifunctional agents for its management and the possible reason for the failure of currently available single target clinical drugs. 1,2,3-Triazole is a miraculous nucleus in medicinal chemistry and the first choice for development of multifunctional hybrid molecules. Apart from that, it is an integral component of various drugs in clinical trials as well as in clinical practice. This review is focused on the pathogenesis of Alzheimer's disease and 1,2,3-triazole containing derivatives developed in recent decades as potential anti-Alzheimer's agents. The review will provide (A) precise insight of various established targets of Alzheimer's disease including cholinergic, amyloid, tau, monoamine oxidases, glutamate, calcium, and reactive oxygen species hypothesis and (B) design hypothesis, structure-activity relationships, and pharmacological outcomes of 1,2,3-triazole containing multifunctional anti-Alzheimer's agents. This review will provide a baseline for various research groups working on Alzheimer's drug development in designing potent, safer, and effective multifunctional anti-Alzheimer's candidates of the future.

Encaved optical fiber nano-probe exciting whispering gallery mode resonance with focused far off-axis beam.

This paper demonstrates whispering gallery mode (WGM) resonance with the help of an encaved optical nano-probe developed inside an optical fiber tip cavity. The nano-probe generates a tightly focused beam with a spot-size of ∼3 µm. A barium titanate microsphere is placed besides the optical axis inside the cavity. The focused beam remains off-axis of the microresonator and excites the WGM. The off-axis excitation shows unique resonating properties depending on the location of the resonator. A resonant peak with quality factor as high as Q ∼7 × 104 is achieved experimentally. Another design with a shorter cavity length for a bigger resonator is also demonstrated by embedding a bigger microsphere on the cleaved fiber tip surface. The optical probe holds great potential for photonic devices and is ideal for studying morphology-based scattering problems.

First detection and genetic identification of Rickettsia spp. from ticks collected from rodents in north India.

BACKGROUND: Changing climatic conditions and invasion of ticks in urban areas have led to a greater number of cases of tick-borne diseases, thus, becoming a matter of increasing concern. Tick borne rickettsioses are one of the important emerging diseases worldwide. Knowledge of epidemiology of the vector and pathogen in the community is essential in order to understand and prevent the transmission of the disease to healthy population. METHODS: In our present study, we trapped rodents in selected areas of Chandigarh and Punjab in north India. The rodents were screened for the presence of ticks which were further screened for the presence of rickettsial agents. PCRs targeting 17 â€‹kDa and gltA genes were carried out followed by Sanger sequencing of the positive amplicons followed by phylogenetic analysis of the sequences. RESULTS: A total of 17 ticks were collected out of which one (Rhipicephalus sanguineus) was found to be harboring a Rickettsia sp. PCR targeting gltA and 17 â€‹kDa genes of rickettsia were put up and Sanger sequencing was performed. Phylogenetic analysis revealed the sequences to be closely related to Rickettsia rhipicephali. CONCLUSION: The current study establishes the presence of rickettsial agents in the community. Although Rickettsia rhipicephali is a non-pathogenic agent, the study encourages more vigorous community surveillance should be carried out in order to determine the exact burden of rickettsial agents in our community. To our knowledge, this is the first study reporting Rickettsia rhipicephali in India.