Assessing Interest in a Peer Support Person for Patients Experiencing Early Pregnancy Loss: Results from a National Survey.

Introduction: The use of a peer support person as an intervention for early pregnancy loss (EPL) is not well studied. In addition, limited literature exists regarding the type of support patients need when experiencing EPL. The objective of this study is to quantify interest in a peer EPL support person intervention, to assess the types of support desired following EPL, and to investigate if there is an association between self-compassion or resilience and coping ability post-EPL. Methods: We conducted a cross-sectional, web-based survey with 110 individuals who experienced EPL in the past 2 years. Questions explored interest in a peer EPL support person and different types of support, as well as perceived self-compassion and resilience. Analyses of variance were used to test if interest in the peer support intervention and in different types of support varied by demographics, while linear regression modeling was used to test the relationship between self-compassion, resilience, and coping ability. Results: Nearly all participants (98.2%, n = 108) were interested in peer support. The majority (31.8%, n = 35) of participants prioritized informational and educational support at the time of their EPL and in the months following. There was a positive relationship between self-compassion scores and ability to cope with EPL (p = 0.2) and between resilience scores and coping ability (p < 0.05). Conclusions: Almost all participants were interested in a peer support person for coping with EPL. Given the types of support participants identified in this study, a peer support person may provide emotional and informational support as well as resilience training.

HuM195 and its single-chain variable fragment increase Aß phagocytosis in microglia via elimination of CD33 inhibitory signaling.

CD33 is a transmembrane receptor expressed on cells of myeloid lineage and regulates innate immunity. CD33 is a risk factor for Alzheimer's disease (AD) and targeting CD33 has been a promising strategy drug development. However, the mechanism of CD33's action is poorly understood. Here we investigate the mechanism of anti-CD33 antibody HuM195 (Lintuzumab) and its single-chain variable fragment (scFv) and examine their therapeutic potential. Treatment with HuM195 full-length antibody or its scFv increased phagocytosis of ß-amyloid 42 (Aß42) in human microglia and monocytes. This activation of phagocytosis was driven by internalization and degradation of CD33, thereby downregulating its inhibitory signal. HumM195 transiently induced CD33 phosphorylation and its signaling via receptor dimerization. However, this signaling decayed with degradation of CD33. scFv binding to CD33 leads to a degradation of CD33 without detection of the CD33 dimerization and signaling. Moreover, we found that treatments with either HuM195 or scFv promotes the secretion of IL33, a cytokine implicated in microglia reprogramming. Importantly, recombinant IL33 potentiates the uptake of Aß42 in monocytes. Collectively, our findings provide unanticipated mechanistic insight into the role of CD33 signaling in both monocytes and microglia and define a molecular basis for the development of CD33-based therapy of AD.

Natural Flavonoids: Fortifying Renal Defence Mechanism.

BACKGROUND: The kidneys, intricate organs responsible for maintaining fluid and electrolyte balance, are susceptible to damage from diverse nephrotoxic insults, including drugs, toxins, and metabolic disorders. In recent years, flavonoids, bioactive compounds abundant in fruits, vegetables, and herbal extracts, have emerged as promising candidates for renal protection due to their potent antioxidant and anti-inflammatory properties. METHODS: We have collected the data that supported this idea to conduct a comprehensive review by using scientific databases, such as Pub Med ®, ScienceDirect ®, Google Scholar ®, and MEDLINE ®. An attempt was made to refer to all English-language articles published between 2000 to 2020 using keywords like flavonoids potential in nephrotoxicity and nephrotoxicity treatment approaches with herbal remedies. CONCLUSION: This comprehensive review delves into the molecular mechanisms underlying the reno-protective effects of flavonoids. By scavenging reactive oxygen species, inhibiting inflammatory mediators, and modulating intracellular signalling pathways, flavonoids can mitigate oxidative stress and inflammation, thereby preserving renal function and integrity. Preclinical studies have demonstrated the potential of specific flavonoids in ameliorating drug-induced nephrotoxicity, renal ischemia-reperfusion injury, diabetic nephropathy, and other kidney diseases. Furthermore, epidemiological evidence highlights the inverse relationship between flavonoid intake and the risk of developing kidney diseases. Nevertheless, understanding the molecular mechanisms of flavonoids in nephroprotection offers exciting prospects for developing novel therapeutic strategies to combat kidney diseases and promote kidney health.

Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy.

BACKGROUND: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. METHODS: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. RESULTS: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. CONCLUSIONS: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

The design, implementation, and impact of an automated patient-reported outcome data collection and adverse event surveillance tool: a randomized trial.

BACKGROUND: Incorporating patient-reported outcome measures into routine clinical care can improve the patient experience, increase engagement, and establish a structured method for gathering adverse event (AE) data. Systematically collecting this information on a large scale can also inform new solutions for removing treatment barriers like medication nonadherence. This study evaluated whether implementing a patient-reported outcome data collection and adverse event surveillance tool would result in greater treatment continuation for patients receiving care on a telehealth platform. METHODS: We used iterative plan-study-do-act cycles to evaluate how this data collection and surveillance tool-a short prompt for patients to provide information on treatment satisfaction and side effects-impacted treatment continuation, the outcome of interest. We tested two cycles in n = 2,000 patients receiving care for erectile dysfunction on a telehealth platform as a randomized controlled trial, and accounted for incidents where true randomization was not possible during implementation. The first cycle tested the tool alone, while the second cycle tested the tool in conjunction with a messaging template system that provided standardized side effect counseling. RESULTS: Compared to patients in the control group, patients in the intervention group were more likely to refill their prescription over the duration of the study period (75% vs. 71%, Kaplan Meier log-rank test, p = 0.04). Receiving standardized counseling as part of the AE response system was positively associated with treatment continuation (p = 0.0005). CONCLUSIONS: Prompting patients to report side effects and outcomes outside of routine clinical visits has the potential to improve quality of care in virtual treatment. TRIAL REGISTRATION: This trial has been retrospectively registered as a clinical trial (ClinicalTrials.gov Identifier: NCT05895539, registered June 8, 2023).

Single-Cell Spatial MIST for Versatile, Scalable Detection of Protein Markers.

High-multiplex detection of protein biomarkers across tissue regions has been an attractive spatial biology approach due to significant advantages over traditional immunohistochemistry (IHC) methods. Different from most methods, spatial multiplex in situ tagging (MIST) transfers the spatial protein expression information to an ultrahigh-density, large-scale MIST array. This technique has been optimized to reach single-cell resolution by adoption of smaller array units and 30% 8-arm PEG polymer as transfer medium. Tissue cell nuclei stained with lamin B have been clearly visualized on the MIST arrays and are colocalized with detection of nine mouse brain markers. Pseudocells defined at 10 µm in size have been used to fully profile tissue regions including cells and the intercellular space. We showcased the versatility of our technology by successfully detecting 20 marker proteins in kidney samples with the addition of five minutes atop the duration of standard immunohistochemistry protocols. Spatial MIST is amenable to iterative staining and detection on the same tissue samples. When 25 proteins were co-detected on 1 mouse brain section for each round and 5 rounds were executed, an ultrahigh multiplexity of 125 proteins was obtained for each pseudocell. With its unique abilities, this single-cell spatial MIST technology has the potential to become an important method in advanced diagnosis of complex diseases.

Interest in peer support persons among patients experiencing early pregnancy loss.

BACKGROUND: Limited data exist regarding the type of support patients need when experiencing early pregnancy loss (EPL). The objective of this study is to explore how patients emotionally cope with EPL and to assess if there is interest in a peer EPL support program with a self-compassion component. METHODS: We conducted semi-structured interviews with patients who experienced EPL in the past two years. We evaluated the kinds of support that patients felt were most helpful, interest in a possible peer EPL support person, and suggestions for the creation of such a program. Content analysis was utilized to analyze the data and identify themes. RESULTS: Twenty-one individuals participated in the study. Approximately 52.3% (n = 11) of interviewees reported expectant management of their EPL, 23.8% (n = 5) reported medication management, and 23.8% (n = 5) reported undergoing dilation and curettage. We identified five themes: (1) therapy and in-person support groups are helpful when experiencing EPL, but are sometimes inaccessible; (2) social media support groups are initially advantageous for creating a sense of solidarity, but in the long term can be triggering; (3) support from a peer who has also experienced EPL is uniquely valuable; (4) developing self-compassion is important in emotionally coping with EPL; and (5) there is a demand for emotional and informational support following EPL. CONCLUSIONS: Given the unique support participants identified receiving from a peer with shared lived experience, there is interest in a peer EPL support program with a self-compassion component for emotional and informational support following EPL.

Circadian protein TIMELESS regulates synaptic function and memory by modulating cAMP signaling.

The regulation of neurons by circadian clock genes is thought to contribute to the maintenance of neuronal functions that ultimately underlie animal behavior. However, the impact of specific circadian genes on cellular and molecular mechanisms controlling synaptic plasticity and cognitive function remains elusive. Here, we show that the expression of the circadian protein TIMELESS displays circadian rhythmicity in the mammalian hippocampus. We identify TIMELESS as a chromatin-bound protein that targets synaptic-plasticity-related genes such as phosphodiesterase 4B (Pde4b). By promoting Pde4b transcription, TIMELESS negatively regulates cAMP signaling to modulate AMPA receptor GluA1 function and influence synaptic plasticity. Conditional deletion of Timeless in the adult forebrain impairs working and contextual fear memory in mice. These cognitive phenotypes were accompanied by attenuation of hippocampal Schaffer-collateral synapse long-term potentiation. Together, these data establish a neuron-specific function of mammalian TIMELESS by defining a mechanism that regulates synaptic plasticity and cognitive function.

Gut microbes modulate neurodegeneration.

Microbiota mediate neuroinflammation in a genetic- and sex-specific manner in mice.

An Augmented Method for Collecting PLGA Nanoparticles and the Fabrication of 1, 3, 4, 6-Tetra-O-acetyl-2-azido-2-deoxy-D-glucopyranose (Ac42AzGlc)-Loaded PLGA Nanoparticles for Efficient and Prospective in Vivo Metabolic Processing.

We investigated two ways for fabricating 1, 3, 4, 6-tetra-O-acetyl-2-azido-2-deoxy-D-glucopyranose (Ac42AzGlc)-loaded poly (lactic-co-glycolic acid) PLGA nanoparticles in this article : 1) single emulsion solvent evaporation and 2) the nanoprecipitation method. Among the available methods of collecting nanoparticles using an ultra-high-speed centrifuge, we improvised a less-known method for collecting synthesized nanoparticles without a high-speed centrifuge, based on molecular weight (MW)-dependent centrifugal filters. These nanoparticles were collected in a tabletop centrifuge at a meager centrifugal force in the range of 200-300 xg whereas the conventional high-speed centrifuge method for nanoparticle recovery results in a hard nanoparticle pellet with poor resuspendability which hampers the yield and outcomes of the product. The Ac42AzGlc-loaded PLGA nanoparticles were spherical in shape with consistent and reliable nanometric particle size. The polydispersity indices were well within the acceptable limits. The preliminary studies in RAW 264.7 cell and C57BL/6 mice advocated efficient engineering in the former; however, the latter needs further confirmatory investigations. Preliminary in vivo studies with un-encapsulated Ac42AzGlc showed poor engineering of cardiac glycoproteins, opening up avenues for Ac42AzGlc-loaded nanoparticles for improved bioavailability and efficient metabolic engineering.

Cyclic microchip assay for measurement of hundreds of functional proteins in single neurons.

Despite the fact that proteins carry out nearly all cellular functions and mark the differences of cells, the existing single-cell tools can only analyze dozens of proteins, a scale far from full characterization of cells and tissue yet. Herein, we present a single-cell cyclic multiplex in situ tagging (CycMIST) technology that affords the comprehensive functional proteome profiling of single cells. We demonstrate the technology by detecting 182 proteins that include surface markers, neuron function proteins, neurodegeneration markers, signaling pathway proteins, and transcription factors. Further studies on cells derived from the 5XFAD mice, an Alzheimer's Disease (AD) model, validate the utility of our technology and reveal the deep heterogeneity of brain cells. Through comparison with control mouse cells, we have identified differentially expressed proteins in AD pathology. Our technology could offer new insights into cell machinery and thus may advance many fields including drug discovery, molecular diagnostics, and clinical studies.

Retinal manifestations of ophthalmic artery occlusion with ischemic stroke in a young patient with COVID-19.

COVID-19-associated coagulopathy (CAC) has led to an increase in the incidence of large vessel stroke and cryptogenic shock. We present a case of a 30-year-old COVID-19-positive patient who developed an internal carotid artery (ICA) thrombosis, which led to ischemic stroke, aphasia, and unilateral blindness. Ophthalmic artery occlusion (OAO) was found to be the cause of vision loss. We thereby aim to highlight the detailed ophthalmic manifestations of OAO with features of posterior ciliary artery occlusion (PCAO) in this patient with proven ICA thrombosis.

Functional insight into LOAD-associated microglial response genes.

Alzheimer's disease (AD) is characterized by the presence of amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs), neuronal and synaptic loss and inflammation of the central nervous system (CNS). The majority of AD research has been dedicated to the understanding of two major AD hallmarks (i.e. Aß and NFTs); however, recent genome-wide association studies (GWAS) data indicate neuroinflammation as having a critical role in late-onset AD (LOAD) development, thus unveiling a novel avenue for AD therapeutics. Recent evidence has provided much support to the innate immune system's involvement with AD progression; however, much remains to be uncovered regarding the role of glial cells, specifically microglia, in AD. Moreover, numerous variants in immune and/or microglia-related genes have been identified in whole-genome sequencing and GWAS analyses, including such genes as TREM2, CD33, APOE, API1, MS4A, ABCA7, BIN1, CLU, CR1, INPP5D, PICALM and PLCG2. In this review, we aim to provide an insight into the function of the major LOAD-associated microglia response genes.

Cataract surgery in eyes with associated coloboma: Predictors of outcome and safety of different surgical techniques.

Purpose: The aim of this study was to report the outcome of cataract surgery with different surgical techniques in eyes with coexisting coloboma and to define factors of prognostic importance. Methods: Retrospective case sheet review of patients presenting between January 2016 and December 2018, who underwent cataract surgery in eyes with coexisting coloboma. Results: Of the 3,30,231 cases operated during the study period, 280 eyes of 276 patients had associated colobomatous malformation. The prevalence of coloboma in eyes undergoing cataract surgery was 0.085%. The mean age of the patients was 46.4 years (range 19 -88 years). Phacoemulsification (PE) was performed in 130 eyes (46.4%), manual small incision cataract surgery (M-SICS) was done in 115 eyes (41.1%), and 35 eyes (12.5%) underwent intra capsular cataract extraction. Intra-operative complications were noted in 26 (9%) eyes. Incidence of intra-operative and post-operative complications was comparable between PE and M-SICS groups (p = 0.94). The mean corrected distance visual acuity (CDVA) improved from logMAR 1.71 ± 0.62 to 0.87 ± 0.61 (p = 0.00009). On multivariate analysis, microcornea (p = 0.002), type 1 and 2 coloboma (p < 0.001), and intraoperative complications (p = 0.001) were associated with poor visual outcome. Conclusion: Favorable functional outcomes can be achieved with phacoemulsification in eyes with softer cataract and corneal diameter >8 mm and with M-SICS in eyes with hard cataracts and corneal diameter of 6-8 mm. PE should be considered as the primary choice whenever permissible by the corneal diameter and severity of nuclear sclerosis. Poor functional outcomes were seen in eyes with smaller corneal diameter, extensive chorioretinal coloboma, and intraoperative complications.

Subacute Sclerosing Panencephalitis manifesting as Bell's palsy and bilateral macular necrotizing retinitis: an atypical presenting feature.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a potentially lethal complication of measles infection. Neurological complications take years to manifest after primary viral infection of brain and can lead to blindness in some individuals. FINDINGS: A 13-year-old female patient with history of Bell's palsy 2 months prior, presented with rapidly progressing necrotizing retinitis in both eyes. Soon after, she was unable to walk, developed myoclonic jerks, altered sensorium and loss of bowel and bladder control. Her clinical history, CSF IgG measles antibody analysis, MRI brain and EEG findings confirmed the diagnosis of SSPE. CONCLUSION: SSPE in our case presented as Bell's palsy and sudden painless diminution of vision due to ocular involvement, and developed full blown disease within 2 months. SSPE can present as a diagnostic challenge and warrants early identification and referral for timely diagnosis and management.

The quality of online consumer health information at the intersection of complementary and alternative medicine and arthritis.

BACKGROUND: Complementary and alternative medicine (CAM) use is prevalent among patients living with arthritis. Such patients often seek information online, for the purpose of gaining a second opinion to their healthcare provider or even self-medication. Little is known about the quality of web-based consumer health information at the intersection of CAM and arthritis; thus, investigating the quality of websites containing this information was the purpose of this study. METHODS: Four unique search terms were searched on Google across four English-speaking countries. We assessed the first 20 results of each search, including them if they contained CAM consumer health information for the treatment and/or management of arthritis. Eligible websites were assessed in duplicate using the DISCERN instrument, which consists of 16-items designed to assess quality. RESULTS: Of total of 320 webpages, 239 were duplicates, and a total of 38 unique websites were deemed eligible and assessed using the DISCERN instrument. The mean summed  DISCERN scores across all websites was 55.53 (SD = 9.37). The mean score of the overall quality of each website was 3.71 (SD = 0.63), thus the majority of websites are ranked as slightly above 'fair' quality. CONCLUSION: Eligible websites generally received scores better than 'moderate' in terms of overall quality. Several shortcomings included a lack of transparency surrounding references used and underreporting of risks associated with treatment options. These results suggest that health providers should be vigilant of the variable quality of information their patients may be accessing online and educate them on how to identify high quality resources.

The quality of online consumer health information at the intersection of complementary and alternative medicine and arthritis

Abstract Background: Complementary and alternative medicine (CAM) use is prevalent among patients living with arthritis. Such patients often seek information online, for the purpose of gaining a second opinion to their healthcare provider or even self-medication. Little is known about the quality of web-based consumer health information at the intersection of CAM and arthritis; thus, investigating the quality of websites containing this information was the purpose of this study. Methods: Four unique search terms were searched on Google across four English-speaking countries. We assessed the first 20 results of each search, including them if they contained CAM consumer health information for the treatment and/or management of arthritis. Eligible websites were assessed in duplicate using the DISCERN instrument, which consists of 16-items designed to assess quality. Results: Of total of 320 webpages, 239 were duplicates, and a total of 38 unique websites were deemed eligible and assessed using the DISCERN instrument. The mean summed DISCERN scores across all websites was 55.53 (SD = 9.37). The mean score of the overall quality of each website was 3.71 (SD = 0.63), thus the majority of websites are ranked as slightly above 'fair' quality. Conclusion: Eligible websites generally received scores better than 'moderate' in terms of overall quality. Several shortcomings included a lack of transparency surrounding references used and underreporting of risks associated with treatment options. These results suggest that health providers should be vigilant of the variable quality of information their patients may be accessing online and educate them on how to identify high quality resources.(AU)

To Study the Barriers in Palliative Care to Nonmalignant Cases in COVID-19 Crisis in a Tertiary Health-Care Center.

INTRODUCTION: COVID-19, the new pandemic faced by the world, is a novel betacoronavirus causing severe respiratory coronavirus syndrome. Elderly patients, people with underlying chronic illnesses, cancer patients, and those who are immunocompromised are at higher risk and account for higher mortality rate. Unfortunately, there is no approved medication for treatment, till date, thereby supporting triage management and difficult decision-making. Thus, there should be a substantial increase in the palliative care in times of pandemic. There should be an increase in the availability of palliative care services in different care settings. Due to a surge in the number of cases of COVID-19, it has been reported on how palliative care is being delayed, discontinued, or deprioritized. AIM: The aim of this study is to evaluate the barriers occurring in providing the palliative care to the patients with nonmalignant illness. METHODOLOGY: A questionnaire was designed after studying previous work over palliative care and pandemic crisis and was distributed among the physicians, surgeons, and the residents; a total of 95 health-care workers were involved. The survey was done through mails. The response then was evaluated and analyzed. RESULTS: As seen by the responses we got from the health-care workers, the main issue is the nonavailability of the personal protective equipment during this pandemic. Keeping the current scenario in mind, regarding COVID-19, the patients are at fear of coming to the hospital at first place, and even if they come then the fear of being alone haunts them. One of the biggest fears of the patient is dying alone, without being in contact with their loved ones. CONCLUSION: Palliative care should be an essential part of any health-care service in any humanitarian crisis, including the COVID-19 pandemic. Thus, effort should be made to remove the barriers and provide palliative care to the patient.

Multiple retinal astrocytic hamartomas in siblings with lebers congenital amaurosis: a case series and review of literature.

BACKGROUND: Leber's congenital amaurosis (LCA) is a known inherited retinal disease (IRD) associated with severe visual loss, nystagmus, amaurotic pupils, oculo-digital sign and markedly reduced or absent electroretinograms (ERG). Retinal astrocytic hamartomas (RAH) is a benign vascularized glial tumor of the retina. There is no known association of these two entities, more so in siblings. CASE PRESENTATION: A pair of siblings diagnosed as LCA who presented with RAH with no extraocular symptoms or signs of phakomatosis were imaged. Multimodal imaging was performed and are elaborately described in this article. CONCLUSION: LCA in siblings with multiple RAHs is an extremely rare association. Recent advances in retinal imaging tools have aided in diagnosing even subtle and early RAH with high sensitivity using Infrared imaging (IRI) and Optical coherence tomography (OCT).