Selenium Nanoparticles as Neuroprotective Agents: Insights into Molecular Mechanisms for Parkinson's Disease Treatment.

Oxidative stress and the accumulation of misfolded proteins in the brain are the main causes of Parkinson's disease (PD). Several nanoparticles have been used as therapeutics for PD. Despite their therapeutic potential, these nanoparticles induce multiple stresses upon entry. Selenium (Se), an essential nutrient in the human body, helps in DNA formation, stress control, and cell protection from damage and infections. It can also regulate thyroid hormone metabolism, reduce brain damage, boost immunity, and promote reproductive health. Selenium nanoparticles (Se-NPs), a bioactive substance, have been employed as treatments in several disciplines, particularly as antioxidants. Se-NP, whether functionalized or not, can protect mitochondria by enhancing levels of reactive oxygen species (ROS) scavenging enzymes in the brain. They can also promote dopamine synthesis. By inhibiting the aggregation of tau, α-synuclein, and/or Aß, they can reduce the cellular toxicities. The ability of the blood-brain barrier to absorb Se-NPs which maintain a healthy microenvironment is essential for brain homeostasis. This review focuses on stress-induced neurodegeneration and its critical control using Se-NP. Due to its ability to inhibit cellular stress and the pathophysiologies of PD, Se-NP is a promising neuroprotector with its anti-inflammatory, non-toxic, and antimicrobial properties.

Anti-psychotic Nature of Antibiotics: Vancomycin and Omadacycline Combination Ameliorating Stress in a Zebrafish Model.

Background Stress affects mental health significantly and is a ubiquitous feature of contemporary living. Among the possible antibiotics are omadacycline and vancomycin, whose anti-inflammatory properties have also been thoroughly documented in recent research. The goal of the current study was to examine their complex involvement in the brain's stress response circuits and how they modulate stress. An established model organism that provides a useful platform for examining stress-induced behaviors and possible therapeutic approaches is the zebrafish. To investigate how dopamine affects the stress response, we used a zebrafish model that was exposed to stress. Methodology For three minutes, zebrafish were continually subjected to chasing stress. They were then given antibiotic combinations of 50 µg/mL each of vancomycin and omadacycline at various ratios of 1:1, 3:1, and 3:1. Behavior alterations, including freezing bouts, top-bottom ratios, and latency periods, were analyzed and contrasted with control groups. ImageJ software was utilized to analyze the video footage of the fish. Results The study showed that the combination of omadacycline and vancomycin greatly reduced the behaviors in zebrafish caused by stress. They chose their concentration (50 µg/mL) according to the lethal concentration 50% result. By shortening the latency time and increasing the intensity of breezing sessions, these chemicals restored almost normal activity. There was statistical significance in the outcomes. The results show that the combination of vancomycin and omadacycline may have an anti-psychotic impact on zebrafish behaviors brought on by stress. Their control of stress reactions is consistent with their known roles in the reward and stress circuits of the brain. These results emphasize the complex interactions between neurotransmitter systems and the control of stress, highlighting the therapeutic potential of dopamine in the treatment of stress-related mental illnesses. Conclusions The combination of vancomycin and omadacycline has been shown to have anti-psychotic effects, which presents potential opportunities for the development of new treatment strategies for mental diseases associated with stress. To fully understand the specific processes underpinning their involvement in stress management and how they relate to mental illnesses in humans, more investigation is necessary.

Exploring Tumor-Promoting Qualities of Cancer-Associated Fibroblasts and Innovative Drug Discovery Strategies With Emphasis on Thymoquinone.

Tumor epithelial development and chemoresistance are highly promoted by the tumor microenvironment (TME), which is mostly made up of the cancer stroma. This is due to several causes. Cancer-associated fibroblasts (CAFs) stand out among them as being essential for the promotion of tumors. Understanding the fibroblastic population within a single tumor is made more challenging by the undeniable heterogeneity within it, even though particular stromal alterations are still up for debate. Numerous chemical signals released by tumors improve the connections between heterotypic fibroblasts and CAFs, promoting the spread of cancer. It becomes essential to have a thorough understanding of this complex microenvironment to effectively prevent solid tumor growth. Important new insights into the role of CAFs in the TME have been revealed by recent studies. The objective of this review is to carefully investigate the relationship between CAFs in tumors and plant secondary metabolites, with a focus on thymoquinone (TQ). The literature published between 2010 and 2023 was searched in PubMed and Google Scholar with keywords such as TQ, TME, cancer-associated fibroblasts, mechanism of action, and flavonoids. The results showed a wealth of data substantiating the activity of plant secondary metabolites, particularly TQ's involvement in blocking CAF operations. Scrutinized research also clarified the wider effect of flavonoids on pathways related to cancer. The present study highlights the complex dynamics of the TME and emphasizes the critical role of CAFs. It also examines the possible interventions provided by secondary metabolites found in plants, with TQ playing a vital role in regulating CAF function based on recent literature.

OCTA Signal Quality Augmentation Using the Isometric Handgrip Test to Maximize Vascular Flow (SQUEEZE): A Randomized Crossover Trial.

Purpose: To determine if performing the isometric handgrip test (IHGT) can augment optical coherence tomography angiography (OCTA) vascular signal quality in eyes with macular abnormalities. Methods: A randomized, single-blinded crossover trial was conducted including 36 participants with macular abnormalities, randomized to undergo OCTA with or without the IHGT, then crossed over to the alternate "intervention" after 1 minute. The primary outcome was OCTA signal quality after 1 minute of squeezing at 50% maximum grip strength. Secondary outcomes were other measures of vascular flow and systemic blood pressure (BP), also regressed against person- and eye-level covariables. Results: Primary analysis of OCTA signal quality with versus without the IHGT was nonsignificant (P = 0.73). Nested analyses showed that the IHGT resulted in increased OCTA B-scan retinal vascular flow signal (2.95 [-1.64 to 7.55] Δ%, P < 0.05) and increased systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (4.94 [0.41 to 9.47] to 12.38 [8.01 to 16.75] mm Hg, P < 0.05). OCTA signal quality and en face vessel density and perfusion changes were associated with sex, refraction, race/ethnicity, and right-hand IHGT use (P < 0.05). Greater increases in systolic and diastolic BP and mean arterial pressure were generally associated with right-hand IHGT use and greater maximum grip strength (P < 0.09). Conclusions: The IHGT can temporarily increase OCTA B-scan retinal vascular flow signal in participants with macular abnormalities. IHGT-induced changes to systemic BP appear to be linked to absolute (rather than relative) grip strength, implying that the IHGT may be ineffective with low grip strength. Further research in larger populations is warranted. Translational Relevance: This study provides early validation that the IHGT may augment OCTA output, which may lead to improved noninvasive detection of pathologic vascular changes.

Multifunctional curcumin mediated zinc oxide nanoparticle enhancing biofilm inhibition and targeting apoptotic specific pathway in oral squamous carcinoma cells.

BACKGROUND: Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties. METHODS: In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity. RESULTS: ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40 µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10 µg/mL, 20 µg/mL, 40 µg/mL, and 80 µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells. CONCLUSIONS: This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.

Zinc oxide nanoparticles functionalized with cinnamic acid for targeting dental pathogens receptor and modulating apoptotic genes in human oral epidermal carcinoma KB cells.

BACKGROUND: Oral diseases are often attributed to dental pathogens such as S. aureus, S. mutans, E. faecalis, and C. albicans. In this research work, a novel approach was employed to combat these pathogens by preparing zinc oxide nanoparticles (ZnO NPs) capped with cinnamic acid (CA) plant compounds. METHODS: The synthesized ZnO-CA NPs were characterized using SEM, FTIR, and XRD to validate their composition and structural features. The antioxidant activity of ZnO-CA NPs was confirmed using DPPH and ABTS free radical scavenging assays. The antimicrobial effects of ZnO-CA NPs were validated using a zone of inhibition assay against dental pathogens. Autodock tool was used to identify the interaction of cinnamic acid with dental pathogen receptors. RESULTS: ZnO-CA NPs exhibited potent antioxidant activity in both DPPH and ABTS assays, suggesting their potential as powerful antioxidants. The minimal inhibitory concentration of ZnO-CA NPs against dental pathogens was found 25 µg/mL, indicating their effective antimicrobial properties. Further, ZnO-CA NPs showed better binding affinity and amino acid interaction with dental pathogen receptors. Also, the ZnO-CA NPs exhibited dose-dependent (5 µg/mL, 15 µg/mL, 25 µg/mL, and 50 µg/mL) anticancer activity against Human Oral Epidermal Carcinoma KB cells. The mechanism of action of apoptotic activity of ZnO-CA NPs on the KB cells was identified through the upregulation of BCL-2, BAX, and P53 genes. CONCLUSIONS: This research establishes the potential utility of ZnO-CA NPs as a promising candidate for dental applications. The potent antioxidant, anticancer, and effective antimicrobial properties of ZnO-CA NPs make them a valuable option for combating dental pathogens.

Marine-derived κ-carrageenan-coated zinc oxide nanoparticles for targeted drug delivery and apoptosis induction in oral cancer.

BACKGROUND: Kappaphycus alvarezii, a marine red algae species, has gained significant attention in recent years due to its versatile bioactive compounds. Among these, κ-carrageenan (CR), a sulfated polysaccharide, exhibits remarkable antimicrobial properties. This study emphasizes the synergism attained by functionalizing zinc oxide nanoparticles (ZnO NPs) with CR, thereby enhancing its antimicrobial efficacy and target specificity against dental pathogens. METHODS: In this study, we synthesized ZnO-CR NPs and characterized them using SEM, FTIR, and XRD techniques to authenticate their composition and structural attributes. Moreover, our investigation revealed that ZnO-CR NPs possess better free radical scavenging capabilities, as evidenced by their effective activity in the DPPH and ABTS assay. RESULTS: The antimicrobial properties of ZnO-CR NPs were systematically assessed using a zone of inhibition assay against dental pathogens of S. aureus, S. mutans, E. faecalis, and C. albicans, demonstrating their substantial inhibitory effects at a minimal concentration of 50 µg/mL. We elucidated the interaction between CR and the receptors of dental pathogens to further understand their mechanism of action. The ZnO-CR NPs demonstrated a dose-dependent anticancer effect at concentrations of 5 µg/mL, 25 µg/mL, 50 µg/mL, and 100 µg/mL on KB cells, a type of Human Oral Epidermal Carcinoma. The mechanism by which ZnO-CA NPs induced apoptosis in KB cells was determined by observing an increase in the expression of the BCL-2, BAX, and P53 genes. CONCLUSION: Our findings unveil the promising potential of ZnO-CR NPs as a candidate with significant utility in dental applications. The demonstrated biocompatibility, potent antioxidant and antiapoptotic activity, along with impressive antimicrobial efficacy position these NPs as a valuable resource in the ongoing fight against dental pathogens and oral cancer.

Activation of Nuclear Factor Kappa B (NF-kB) Signaling Pathway Through Exercise-Induced Simulated Dopamine Against Colon Cancer Cell Lines.

Introduction Dopamine is an important neuroregulatory hormone and is secreted during exercise. Its role in physiological regulation is not fully uncovered. Recent studies showed that it suppresses inflammation. Colon cancer is one of the most predominant cancers in the population and is influenced by prolonged inflammation. The anti-inflammatory effect of dopamine using the colon cancer model was analyzed in KB cells. Methods KB cells were cultured using Dulbecco's Modified Eagle Medium and Inhibitory Concentration- 50 (IC50) was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. BCl-2, tumour necrosis factor-α (TNF-α), nuclear factor kappa- B (​​​​​NF-kB), and interleukin (IL)-6 were assessed using reverse transcription polymerase chain reaction (RT-PCR)(at 50 and 100 µg/ ml < IC50). Schrödinger was used for docking analysis using nuclear factor Kappa B (NF-kB) (Protein Data Bank: 5T8O) and dopamine (CID 681). Results Results were represented as mean ± standard deviation and statistically evaluated. Dopamine showed severe growth inhibition in KB cells (IC50- 225±3.1µg/ ml). It downregulated the expression of BCl-2, NF-k, and IL-6, but increased TNF-α expression. Dopamine bonded with NF-kB by two hydrogen bonds with aspartic acid​​-53and alanine-54, respectively). Conclusion The present study revealed that dopamine has a significant anti-cancer potential by blocking NF-kB pathways in KB cells.

Advancements of fish-derived peptides for mucormycosis: a novel strategy to treat diabetic compilation.

Mucormycosis, an extremely fatal fungal infection, is a major hurdle in the treatment of diabetes consequences. The increasing prevalence and restricted treatment choices urge the investigation of novel therapeutic techniques. Because of their effective antimicrobial characteristics and varied modes of action, fish-derived peptides have lately emerged as viable options in the fight against mucormycosis. This review examines the potential further application of fish-derived peptides in diagnosing and managing mucormycosis in relation to diabetic complications. First, we examine the pathophysiology of mucormycosis and the difficulties in treating it in diabetics. We emphasize the critical need for alternative therapeutic methods for tackling the limitations of currently available antifungal medicines. The possibility of fish-derived peptides as an innovative approach to combat mucormycosis is then investigated. These peptides, derived from several fish species, provide wide antimicrobial properties against a variety of diseases. They also have distinct modes of action, such as rupture of cell membranes, suppression of development, and modification of the host immunological response. Furthermore, we investigate the problems and prospects connected with the clinical application of fish-derived peptides. Ultimately, future advances in fish-derived peptides, offer interesting avenues for the management of mucormycosis in the context of diabetic comorbidities. More research and clinical trials are needed to properly investigate these peptide's therapeutic potential and pave the way for their adoption into future antifungal therapies.

Abandoning the word Caucasian.

Traditionally, the field of genetics has used patient-reported genetic ancestry to assist in risk assessment, calculate detection rates, and understand residual risks for recessive or X-linked genetic diseases. Patient-reported genetic ancestry is useful for variant curation, based on practice guidelines from medical societies. Words used to describe a person's race, ethnicity, and genetic ancestry have changed over the last few centuries, especially in the last few decades. The origin and use of Caucasian to describe people of European ancestry have come into question. With recommendations from the Department of Health and Human Services (HHS) and the American College of Medical Genetics and Genomics (ACMG), among other organizations, the medical and genetics communities are moving away from using this term altogether. The purpose of this article is to review the history of the word Caucasian and to provide evidence that it should be avoided when documenting genetic ancestry in medical records, laboratory forms, and medical research.

Interactions between FUS and the C-terminal Domain of Nup62 are Sufficient for their Co-phase Separation into Amorphous Assemblies.

Deficient nucleocytoplasmic transport is emerging as a pathogenic feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including in ALS caused by mutations in Fused in Sarcoma (FUS). Recently, both wild-type and ALS-linked mutant FUS were shown to directly interact with the phenylalanine-glycine (FG)-rich nucleoporin 62 (Nup62) protein, where FUS WT/ Nup62 interactions were enriched within the nucleus but ALS-linked mutant FUS/ Nup62 interactions were enriched within the cytoplasm of cells. Nup62 is a central channel Nup that has a prominent role in forming the selectivity filter within the nuclear pore complex and in regulating effective nucleocytoplasmic transport. Under conditions where FUS phase separates into liquid droplets in vitro, the addition of Nup62 caused the synergistic formation of amorphous assemblies containing both FUS and Nup62. Here, we examined the molecular determinants of this process using recombinant FUS and Nup62 proteins and biochemical approaches. We demonstrate that the structured C-terminal domain of Nup62 containing an alpha-helical coiled-coil region plays a dominant role in binding FUS and is sufficient for inducing the formation of FUS/Nup62 amorphous assemblies. In contrast, the natively unstructured, F/G repeat-rich N-terminal domain of Nup62 modestly contributed to FUS/Nup62 phase separation behavior. Expression of individual Nup62 domain constructs in human cells confirmed that the Nup62 C-terminal domain is essential for localization of the protein to the nuclear envelope. Our results raise the possibility that interactions between FUS and the C-terminal domain of Nup62 can influence the function of Nup62 under physiological and/or pathological conditions.

Anti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons.

ALS-linked mutations induce aberrant conformations within the SOD1 protein that are thought to underlie the pathogenic mechanism of SOD1-mediated ALS. Although clinical trials are underway for gene silencing of SOD1, these approaches reduce both wild-type and mutated forms of SOD1. Here, we sought to develop anti-SOD1 nanobodies with selectivity for mutant and misfolded forms of human SOD1 over wild-type SOD1. Characterization of two anti-SOD1 nanobodies revealed that these biologics stabilize mutant SOD1 in vitro. Further, SOD1 expression levels were enhanced and the physiological subcellular localization of mutant SOD1 was restored upon co-expression of anti-SOD1 nanobodies in immortalized cells. In human motor neurons harboring the SOD1 A4V mutation, anti-SOD1 nanobody expression promoted neurite outgrowth, demonstrating a protective effect of anti-SOD1 nanobodies in otherwise unhealthy cells. In vitro assays revealed that an anti-SOD1 nanobody exhibited selectivity for human mutant SOD1 over endogenous murine SOD1, thus supporting the preclinical utility of anti-SOD1 nanobodies for testing in animal models of ALS. In sum, the anti-SOD1 nanobodies developed and presented herein represent viable biologics for further preclinical testing in human and mouse models of ALS.

Development of Immersive Virtual Reality Environment for Assessment of Functional Vision in people with Low Vision: A Pilot Study.

INTRODUCTION: Virtual Reality technology helps in creating virtual environments for evaluation of visual performance of low vision individuals with holistic experience. The purpose of this study was to develop a virtual reality (VR) platform for the objective assessment of functional vision in patients with low vision in two categories, central and peripheral vision loss . MATERIALS AND METHODS: Focus group discussions (FGD) were organized to understand the difficulties faced on a day to day basis by patients with low vision. Based on the results of the focus group discussions, a virtual bank scenario incorporating specific visual tasks was developed. A pilot study was conducted which involved people with normal vision; low vision Patients secondary to central field loss (CFL) and peripheral field loss (PFL). Each subject completed all the tasks in the objective assessment; the data obtained from the assessment were further analyzed to understand the pattern. RESULTS: Comparing the three groups, there was a significant difference in distance (central field loss was lowest) and near visual angle, and three visual search tasks (peripheral field loss was lowest). In assessing the time taken, peripheral field loss group was again found to take the most time to complete tasks. CONCLUSION: Based on a newly developed virtual reality platform, assessment of functional vision of specially abled persons could be tested and was inferior to that of normal sighted persons. in a close to realistic environment. Multiple visual tasks were performed in the virtual environment and the visual performance was compared among all three groups of participants. Participants were matched for age and gender. Irrespective of the nature of tasks, visual performance of the normal group seemed significantly better than people with CFL and PFL.

Excessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons.

Non-cell-autonomous mechanisms contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), in which astrocytes release unidentified factors that are toxic to motoneurons (MNs). We report here that mouse and patient iPSC-derived astrocytes with diverse ALS/FTD-linked mutations (SOD1, TARDBP, and C9ORF72) display elevated levels of intracellular inorganic polyphosphate (polyP), a ubiquitous, negatively charged biopolymer. PolyP levels are also increased in astrocyte-conditioned media (ACM) from ALS/FTD astrocytes. ACM-mediated MN death is prevented by degrading or neutralizing polyP in ALS/FTD astrocytes or ACM. Studies further reveal that postmortem familial and sporadic ALS spinal cord sections display enriched polyP staining signals and that ALS cerebrospinal fluid (CSF) exhibits increased polyP concentrations. Our in vitro results establish excessive astrocyte-derived polyP as a critical factor in non-cell-autonomous MN degeneration and a potential therapeutic target for ALS/FTD. The CSF data indicate that polyP might serve as a new biomarker for ALS/FTD.

Clinical explainable differential diagnosis of polypoidal choroidal vasculopathy and age-related macular degeneration using deep learning.

BACKGROUND: This study aims to achieve an automatic differential diagnosis between two types of retinal pathologies with similar pathological features - Polypoidal choroidal vasculopathy (PCV) and wet age-related macular degeneration (AMD) from volumetric optical coherence tomography (OCT) images, and identify clinically-relevant pathological features, using an explainable deep-learning-based framework. METHODS: This is a retrospective study with data from a cross-sectional cohort. The OCT volume of 73 eyes from 59 patients was included in this study. Disease differentiation was achieved through single-B-scan-based classification followed by a volumetric probability prediction aggregation step. We compared different labeling strategies with and without identifying pathological B-scans within each OCT volume. Clinical interpretability was achieved through normalized aggregation of B-scan-based saliency maps followed by maximum-intensity-projection onto the en face plane. We derived the PCV score from the proposed differential diagnosis framework with different labeling strategies. The en face projection of saliency map was validated with the pathologies identified in Indocyanine green angiography (ICGA). RESULTS: Model trained with both labeling strategies achieved similar level differentiation power (>90%), with good correspondence between pathological features detected from the projected en face saliency map and ICGA. CONCLUSIONS: This study demonstrated the potential clinical application of non-invasive differential diagnosis using AI-driven OCT-based analysis, with minimal requirement of labeling efforts, along with clinical explainability achieved through automatically detected disease-related pathologies.

Identifying Peripheral Neuropathy in Colour Fundus Photographs Based on Deep Learning.

The aim of this study was to develop and validate a deep learning-based system to detect peripheral neuropathy (DN) from retinal colour images in people with diabetes. Retinal images from 1561 people with diabetes were used to predictDN diagnosed on vibration perception threshold. A total of 189 had diabetic retinopathy (DR), 276 had DN, and 43 had both DR and DN. 90% of the images were used for training and validation and 10% for testing. Deep neural networks, including Squeezenet, Inception, and Densenet were utilized, and the architectures were tested with and without pre-trained weights. Random transform of images was used during training. The algorithm was trained and tested using three sets of data: all retinal images, images without DR and images with DR. Area under the ROC curve (AUC) was used to evaluate performance. The AUC to predict DN on the whole cohort was 0.8013 (±0.0257) on the validation set and 0.7097 (±0.0031) on the test set. The AUC increased to 0.8673 (±0.0088) in the presence of DR. The retinal images can be used to identify individuals with DN and provides an opportunity to educate patients about their DN status when they attend DR screening.

Interactions between ALS-linked FUS and nucleoporins are associated with defects in the nucleocytoplasmic transport pathway.

Nucleocytoplasmic transport (NCT) decline occurs with aging and neurodegeneration. Here, we investigated the NCT pathway in models of amyotrophic lateral sclerosis-fused in sarcoma (ALS-FUS). Expression of ALS-FUS led to a reduction in NCT and nucleoporin (Nup) density within the nuclear membrane of human neurons. FUS and Nups were found to interact independently of RNA in cells and to alter the phase-separation properties of each other in vitro. FUS-Nup interactions were not localized to nuclear pores, but were enriched in the nucleus of control neurons versus the cytoplasm of mutant neurons. Our data indicate that the effect of ALS-linked mutations on the cytoplasmic mislocalization of FUS, rather than on the physiochemical properties of the protein itself, underlie our reported NCT defects. An aberrant interaction between mutant FUS and Nups is underscored by studies in Drosophila, whereby reduced Nup expression rescued multiple toxic FUS-induced phenotypes, including abnormal nuclear membrane morphology in neurons.

Comparison of ringer's lactate and plasmalyt-a as cardiopulmonary bypass prime for bypass associated acidosis in valve replacement surgeries.

Introduction: A wide range of acid base fluctuations are seen during Cardiopulmonary bypass (CPB) and the development of metabolic acidosis is well recognized. We conducted a study tocompare the metabolic effects of Ringer lactate and Plasmalyte-A as CPB prime in causing bypass associated acidosis in valve replacement surgeries. Methods: We performed a prospective, randomized controlled study on a total of 80 adult patients undergoing CPB for valvular heart surgeries. The patients were randomized into two groups: Group I (Ringer Lactate) and Group II (Plasmalyte-A). Arterial blood samples were taken before initiating CPB, 30 minutes after starting CPB, then every half hourly till termination of CPB and after half an hour stay in the ICU post operatively to analyze primarily H+ ions, bicarbonates, lactate and strong ion difference. Results and Discussion: The results were analyzed in a quantitative manner. In Ringer Lactate group, during CPB, there was reduction in pH from 7.428 ± 0.029 at T1 to 7.335 ± 0.06 (P < 0.01) and 7.358 ± 0.06 (P < 0.01) at T2 and T3 respectively. Mean bicarbonates decreased in Ringer Lactate group during CPB from 24.28 ± 1.65 mEq/L at T1 to 20.98 ± 2.97 mEq/L at T2 (P < 0.01). In Plasmalyte-A group, mean pH, bicarbonate, strong ion difference (SID) were comparable at all time intervals (P > 0.05). In Ringer Lactate group, maximum surge in mean blood lactate levels was seen from 0.85 ± 0.35 mmol/l at T1 to 4.29 ± 1.78 mmol/L (P < 0.01) and 4.17 ± 1.28 mmol/L (P < 0.01) at T2 and T3, respectively. Such surge was not seen in Plasmalyte-A group. The mean SID decreased during the CPB in Ringer Lactate group from 41.102 mEq/L at T1 to 35.66 mEq/L (P = 0.033) at T2 implying metabolic acidosis. Numbered patients having hypotension and arrhythmias were also higher in Ringer Lactate group again indicating higher acidosis. Conclusion: The different composition of Plasmalyte-A and Ringer Lactate have different metabolic implications for patients undergoing cardiac surgery. Patients who received Plasmalyte-A as cardiopulmonary bypass prime developed less metabolic acidosis. Hence we conclude that Plasmalyte-A is the preferred cardiopulmonary bypass prime in adult patients undergoing valve replacement surgeries.