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BACKGROUND: There are no recent estimates for hypertension-associated medical expenditures. This study aims to estimate hypertension-associated incremental medical expenditures among privately insured US adults. METHODS: We conducted a retrospective cohort study using IQVIA's Ambulatory Electronic Medical Records-US data set linked with PharMetrics Plus claims data. Among privately insured adults aged 18 to 64 years, hypertension was identified as having ≥1 diagnosis code or ≥2 blood pressure measurements of ≥140/90 mm Hg, or ≥1 antihypertensive medication in 2021. Annual total expenditures (in 2021 $US) were estimated using a generalized linear model with gamma distribution and log-link function adjusting for demographic characteristics and cooccurring conditions. Out-of-pocket expenditures were estimated using a 2-part model that included logistic and generalized linear model regression. Overlap propensity score weights from logistic regression were used to obtain a balanced sample on hypertension status. RESULTS: Among the 393 018 adults, 156 556 (40%) were identified with hypertension. Compared with individuals without hypertension, those with hypertension had $2926 (95% CI, $2681-$3170) higher total expenditures and $328 (95% CI, $300-$355) higher out-of-pocket expenditures. Adults with hypertension had higher total inpatient ($3272 [95% CI, $1458-$5086]) and outpatient ($2189 [95% CI, $2009-$2369]) expenditures when compared with those without hypertension. Hypertension-associated incremental total expenditures were higher for women ($3242 [95% CI, $2915-$3569]) than for men ($2521 [95% CI, $2139-$2904]). CONCLUSIONS: Among privately insured US adults, hypertension was associated with higher medical expenditures, including higher inpatient and out-of-pocket expenditures. These findings may help assess the economic value of interventions effective in preventing hypertension.

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Terminal myelocystocele (TMC) is a rare form of spinal dysraphism which arises due to aberration in the secondary neurulation process involving the caudal cell mass. Terminal myelocystocele has been defined by Pang et al. based on essential and non-essential features. One of the non-essential features includes non dysraphic lipomas which do not tether to the neural placode. We are presenting two cases which meets all the essential criteria outlined by Pang et al. for TMC but also show the presence of a lipomatous component tethering to the neural placode, similar to a dysraphic lipoma. Through this article, we want to showcase a subset which represents "true" terminal lipomyelocystocele (TLMC), bridging the spectrum of spinal dysraphism between TMC and lipomyelomeningocele (LMM).

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Diabetic neuropathy (DN) is one of the major microvascular complications of diabetes mellitus affecting 50% of the diabetic population marred by various unmet clinical needs. There is a need to explore newer pathological mechanisms for designing futuristic regimens for the management of DN. There is a need for post-transcriptional regulation of gene expression by non-coding RNAs (ncRNAs) to finetune different cellular mechanisms with significant biological relevance. MicroRNAs (miRNAs) are a class of small ncRNAs (~ 20 to 24 nucleotide length) that are known to regulate the activity of ~ 50% protein-coding genes through repression of their target mRNAs. Differential expression of these miRNAs is associated with the pathophysiology of diabetic neuropathy via regulating various pathways such as neuronal hyperexcitability, inflammation, axonal growth, regeneration, and oxidative stress. Of note, the circulating and extracellular vesicular miRNAs serve as potential biomarkers underscoring their diagnostic potential. Recent pieces of evidence highlight the potential of miRNAs in modulating the initiation and progression of DN and the possibility of developing miRNAs as treatment options for DN. In this review, we have elaborated on the role of different miRNAs as potential biomarkers and emphasized their druggable aspects for promising future therapies for the clinical management of DN.

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Multidomain proteins with flexible linkers and disordered regions play important roles in many cellular processes, but characterizing their conformational ensembles is difficult. We have previously shown that the coarse-grained model, Martini 3, produces too compact ensembles in solution, that may in part be remedied by strengthening protein-water interactions. Here, we show that decreasing the strength of protein-protein interactions leads to improved agreement with experimental data on a wide set of systems. We show that the 'symmetry' between rescaling protein-water and protein-protein interactions breaks down when studying interactions with or within membranes; rescaling protein-protein interactions better preserves the binding specificity of proteins with lipid membranes, whereas rescaling protein-water interactions preserves oligomerization of transmembrane helices. We conclude that decreasing the strength of protein-protein interactions improves the accuracy of Martini 3 for IDPs and multidomain proteins, both in solution and in the presence of a lipid membrane.

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Neuroinflammation is a pivotal factor in the progression of both age-related and acute neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. Mitochondria, essential for neuronal health due to their roles in energy production, calcium buffering, and oxidative stress regulation, become increasingly susceptible to dysfunction under conditions of metabolic stress, aging, or injury. Impaired mitophagy in aged or injured neurons leads to the accumulation of dysfunctional mitochondria, which release mitochondrial-derived damage-associated molecular patterns (mtDAMPs). These mtDAMPs act as immune checkpoints, activating pattern recognition receptors (PRRs) and triggering innate immune signaling pathways. This activation initiates inflammatory responses in neurons and brain-resident immune cells, releasing cytokines and chemokines that damage adjacent healthy neurons and recruit peripheral immune cells, further amplifying neuroinflammation and neurodegeneration. Long-term mitochondrial dysfunction perpetuates a chronic inflammatory state, exacerbating neuronal injury and contributing additional immunogenic components to the extracellular environment. Emerging evidence highlights the critical role of mtDAMPs in initiating and sustaining neuroinflammation, with circulating levels of these molecules potentially serving as biomarkers for disease progression. This review explores the mechanisms of mtDAMP release due to mitochondrial dysfunction, their interaction with PRRs, and the subsequent activation of inflammatory pathways. We also discuss the role of mtDAMP-triggered innate immune responses in exacerbating both acute and chronic neuroinflammation and neurodegeneration. Targeting dysfunctional mitochondria and mtDAMPs with pharmacological agents presents a promising strategy for mitigating the initiation and progression of neuropathological conditions.

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Dopamine is a neurotransmitter in the central nervous system that is essential for many bodily and mental processes, and a lack of it can cause Parkinson's disease. DNA tetrahedral (TD) nanocages are promising in bio-nanotechnology, especially as a nanocarrier. TD is highly programmable, biocompatible, and capable of cell differentiation and proliferation. It also has tissue and blood-brain barrier permeability, making it a powerful tool that could overcome potential barriers in treating neurological disorders. In this study, we used DNA TD as a carrier for dopamine to cells and zebrafish embryos. We investigated the mechanism of complexation between TD and dopamine hydrochloride using gel electrophoresis, fluorescence and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and molecular dynamic (MD) simulation tools. Further, we demonstrate that these dopamine-loaded DNA TD nanostructures enhanced cellular uptake and differentiation ability in SH-SY5Y neuroblastoma cells. Furthermore, we extended the study to zebrafish embryos as a model organism to examine survival and uptake. The research provides valuable insights into the complexation mechanism and cellular uptake of dopamine-loaded DNA tetrahedral nanostructures, paving the way for further advancements in nanomedicine for Parkinson's disease and other neurological disorders.

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Aneurysms of the distal anterior cerebral artery (DACA) are rare but surgically challenging. Despite a known therapeutic implication of the aneurysm location on the DACA territory, the literature is unclear about its clinical and prognostic significance. Our surgical experience over the last 5 years was reviewed to compare the clinical, operative, and outcome characteristics between aneurysms located below the mid portion of the genu of the corpus callosum (called proximal aneurysms) to those distal to this point (called distal aneurysms). A prognostic factor analysis was done using uni and multivariable analysis. A total of 34 patients were treated (M: F = 1:2.3). The distal group had a higher frequency of poor clinical grade at presentation (n = 9, 47.4%) in contrast to (n = 2, 13.3%) proximal aneurysms (p = 0.039). Despite an overall tendency for a delayed functional improvement in these patients, the results were mainly due to favorable outcomes in the proximal group (favourable functional outcomes at discharge and at last follow-up being 80% and 86.7% respectively). On the multivariable analysis, only WFNS grade (> 2) at presentation (OR = 13.75; 95CI = 1.2-157.7) (p = 0.035) and application of temporary clips (AOR = 34.32; 95CI = 2.59-454.1) (p = 0.007), both of which were more in the distal group, independently predicted a poor long term functional outcome. Thus, the aneurysm location impacts the preoperative clinical grade, the intraoperative aneurysm rupture risk rate as well as the temporary clipping requirement. A combination of these factors leads to worse short and long-term functional outcomes in the distal DACA aneurysms.

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BACKGROUND: Congenital spondylolisthesis is characterized by dysplasia of the facet joint or congenital defect in the pars. OBJECTIVE: Our study highlights the clinical and radiological profile, various treatment options, and outcomes in patients with pediatric congenital lumbar and lumbosacral spondylolisthesis. METHODS: A retrospective analysis and follow-up of 22 patients were conducted presented with radiological diagnosis of congenital lumbar/lumbosacral spondylolisthesis (2018-2021). RESULTS: Twenty patients (91%) had L5-S1 listhesis and two patients (9%) had L4-L5 listhesis. Six (27.3%) patients had low-grade listhesis (grades 1-2), 16 (72.7%) had high-grade listhesis (grades 3-5). Seventeen (77.3%) had S1, three (13.6%) had L5, and two (9%) had both L4-L5 radiculopathy. All patients had neurogenic claudication. One had an associated spina bifida occulta. Six (27.3%) patients underwent two-level fixation, and 16 (72.7%) underwent three-level fixation. Minimally Invasive Transforaminal Lumbar Interbody Fusion (MIS TLIF) was done in two patients. Revision of at least one screw was done in three patients. After one year of follow-up, all the patients had 75-100% relief in radicular pain and neurogenic claudication. The Oswestry Disability Index (ODI) score in preop for all patients was 41-60% and postoperatively they showed an improvement in ODI score (0-20). The postoperative low back pain score on the Numeric Rating Scale was 0-1 for all patients. CONCLUSION: Congenital lumbar spondylolisthesis usually presents with high-grade listhesis. Management of such cases is a surgical challenge but posterior decompression resulted in relief of pain in all patients. However, in situ fixation without reduction is also effective in selective cases where attempts to reduce the listhesis result in a decline in intraoperative neuromonitoring parameters.

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Rheumatoid arthritis (RA) is a progressive autoimmune disease that mainly affects the inner lining of the synovial joints and leads to chronic inflammation. While RA is not known as lethal, recent research indicates that it may be a silent killer because of its strong association with an increased risk of chronic lung and heart diseases. Patients develop these systemic consequences due to the regular uptake of heavy drugs such as disease-modifying antirheumatic medications (DMARDs), glucocorticoids (GCs), nonsteroidal anti-inflammatory medicines (NSAIDs), etc. Nevertheless, a number of these medications have off-target effects, which might cause adverse toxicity, and have started to become resistant in patients as well. Therefore, alternative and promising therapeutic techniques must be explored and adopted, such as post-translational modification inhibitors (like protein arginine deiminase inhibitors), RNA interference by siRNA, epigenetic drugs, peptide therapy, etc., specifically in macrophages, neutrophils, Treg cells and dendritic cells (DCs). As the target cells are specific, ensuring targeted delivery is also equally important, which can be achieved with the advent of nanotechnology. Furthermore, these nanocarriers have fewer off-site side effects, enable drug combinations, and allow for lower drug dosages. Among the nanoparticles that can be used for targeting, there are both inorganic and organic nanomaterials such as solid-lipid nanoparticles, liposomes, hydrogels, dendrimers, and biomimetics that have been discussed. This review highlights contemporary therapy options targeting macrophages, neutrophils, Treg cells, and DCs and explores the application of diverse nanotechnological techniques to enhance precision RA therapies.

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BACKGROUND:  Surgical resection is the cornerstone of treatment for low-grade tumors, albeit total excision is beneficial. As the thalamus is surrounded by vital neurovascular system, lesions here present a surgical challenge. METHOD: This article aims to demonstrate the trans-temporal, trans-choroidal fissure approach's effective surgical therapy on patients with thalamic lesions. With this approach, we were able to remove the tumor completely in three patients and almost completely in six more. Here we discuss a few technical details and potential hazards of the procedure with an operative video. CONCLUSION: This approach  provides excellent access to the deep areas of brain.

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Cloud computing is an on-demand virtual-based technology to develop, configure, and modify applications online through the internet. It enables the users to handle various operations such as storage, back-up, and recovery of data, data analysis, delivery of software applications, implementation of new services and applications, hosting websites and blogs, and streaming of audio and video files. Thereby, it provides us many benefits although it is backlashed due to problems related to cloud security like data leakage, data loss, cyber attacks, etc. To address the security concerns, researchers have developed a variety of authentication mechanisms. This means that the authentication procedure used in the suggested method is multi-levelled. As a result, a better QKD method is offered to strengthen cloud security against different types of security risks. Key generation for enhanced QKD is based on the ABE public key cryptography approach. Here, an approach named CPABE is used in improved QKD. The Improved QKD scored the reduced KCA attack ratings of 0.3193, this is superior to CMMLA (0.7915), CPABE (0.8916), AES (0.5277), Blowfish (0.6144), and ECC (0.4287), accordingly. Finally, this multi-level authentication using an improved QKD approach is analysed under various measures and validates the enhancement over the state-of-the-art models.

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A series of donor-acceptor (D-π-A) substituted diphenylbutadienes exhibiting solvatochromic emission and a large Stokes shift (100-200 nm) were designed and synthesized for distinctive organelle labelling, enabling real-time monitoring of organelle behaviour such as lysosomal dynamics, mitophagy monitoring, and stress responses. The morpholine-substituted D-A-D diphenylbutadiene (M2) was employed to investigate selective imaging of lysosomes, the uptake of damaged mitochondria through mitophagy, and monitoring lysosomal viscosity or pH changes. Other diphenylbutadiene derivatives (M1, M3, M4) selectively accumulated in lipid droplets. All the synthesized derivatives demonstrated significant uptake in 5-day post-fertilization zebrafish larvae, with M2 showing maximum uptake in the enterocyte-containing heart and intestinal regions, which include the lysosomes.

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INTRODUCTION: This study seeks to estimate health care expenditures and use associated with hypertension, focusing on differences among racial and ethnic groups. METHODS: Data were from the 2019 Medical Expenditure Panel Survey, analyzed in 2023. The study sample included noninstitutionalized U.S. adults aged ≥18 years. Outcome variables were health care expenditures and events. Hypertension was determined by a self-reported diagnosis or diagnosis codes. Race and ethnicity were self-reported. A 2-part model was used to estimate expenditures associated with hypertension. A zero-inflated negative binomial model was used to estimate events associated with hypertension. Sampling designs were applied to generate nationally representative estimates. RESULTS: Hypertension was associated with $2,759 (95% confidence interval [CI]: $2,039, $3,479) in health care expenditures and 10.3 (95% CI: 9.3, 11.3) health care events, including prescriptions filled, in 2019 per person. Compared with non-Hispanic White adults, hypertension-associated health care expenditures were significantly lower among Hispanic adults (difference: -$1,877; 95% CI: -$3,389, -$364) and Asian adults (difference: -$2,452; 95% CI: -$4,093, -$811), and hypertension-associated health care events were significantly lower among Hispanic adults (difference: -3.8; 95% CI: -6.1, -1.6) and non-Hispanic Asian adults (difference: -4.1; 95% CI: -6.9, -1.2). Differences between non-Hispanic White adults and non-Hispanic Black adults were not statistically significant in health care expenditures (difference: -$954; 95% CI: -$2,849, $941) and events (difference: 0.3; 95% CI: -2.1, 2.8). CONCLUSIONS: This study reveals differences in health care expenditures and use associated with hypertension among racial and ethnic groups. Future studies are needed to examine potential drivers of these differences.

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BACKGROUND: The ruptured anterior communicating artery aneurysm is the most frequent intra-cranial aneurysm treated at any neurosurgical department. These aneurysms arise from either the A1-A2-Acom artery junction or Acom artery. The surgical outcome depends on the age of the patient, time duration between ictus and surgery, and Hunt and Hess grade at admission. In this article, we intend to analyze the surgical outcome based on our proposed classification with our overall experience of Acom aneurysm. METHODS: A retrospective review of our surgical database with 250 patients of ruptured Acom was done, and the location, morphology, and direction of aneurysm, along with other clinical parameters including the demographic profile, radiological findings, and intra-operative details, were studied. We classified the Acom based on both site of origin and morphology (Type I, junctional on the dominant side; Type II, fusiform with an ill-defined neck and branching pattern; Type III, saccular true Acom A) and secondarily as described in the literature on the basis of the direction of fundus (Type A-E). The clinical parameters were compared among the above groups using Fischer-exact and one-way analysis of variance test. RESULTS: A total of 250 patients (M: F =113:137) were included (mean age 52.1 ± 11.5 standard deviation years). 55.2% patients had left A1 dominance. Type I Acom A was commonly found on the left dominant circulation (P = 0.00). The difference in aspect ratio of Type I (2.0 ± 0.8) and Type II (1.8 ± 0.52) aneurysms was insignificant (P = 0.28). However, a significant difference in post-operative vasospasm among different types of aneurysms was found (P < 0.05). The Type I Acom A were anteriorly directed, while Type II and III were posteriorly directed (P = 0.001). The mean follow-up of the study was 44.4 ± 25.7 months, with age (P = 0.007) and Hunt and Hess grade (P = 0.001) at admission correlating with surgical outcome. CONCLUSION: Classifying the Acom A pre-operatively based on site and morphology, location, and direction of fundus helps in surgical planning and prognosis. The junctional 'Type IA aneurysms' are most common and possess a high intra-operative rupture rate. The anteriorly directed aneurysms have a better prognosis, and visual complaints are usually associated with anterior-inferiorly directed aneurysms.

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BACKGROUND/OBJECTIVE: Visual impairment affects 55%-80% of medial sphenoid wing meningiomas (mSWMs) patients, making optic nerve decompression a critical surgical goal. Complete resection often leads to better visual outcomes. However, involvement of critical neurovascular structures increases postoperative morbidity and mortality, with vascular injury reported in 18%-20% of cases. This study aims to evaluate the relationship between the extent of resection (EOR), visual outcomes, and the incidence of vascular injury, seeking to identify the optimal surgical approach for mSWMs. METHODS: We retrospectively analyzed data from patients undergoing surgery for mSWM at our tertiary care center from January 2001 to December 2021. Inclusion criteria included histopathologically confirmed globoid mSWMs (N = 89). Patients with recurrent tumors (n = 14) or lost to follow-up (n = 9) were excluded. We classified patients into 2 groups based on EOR using Simpson's grade: Group 1 (good-resection,Simpson Grade-I/II,n = 51) and Group 2 (poor-resection,Simpson Grade III/IV, n = 15). RESULTS: Among 66 (=N) patients, visual impairment was the most common symptom (81.8%), followed by headaches (77.3%) and seizures (27%). T2-hyperintensity on magnetic resonance imaging [(OR:5.4, 95%CI:1.5-18.6) (P-value<0.01)] and cavernous sinus-extension [(OR:3.9, 95%CI:1.1-13.1) (p-value-0.02)] were independent significant predictors of poor resection. Visual status was preserved in 90.3% of Group-1 and 86.6% of Group-2, with no significant difference based on EOR. Vascular involvement was noted in 87.9%, higher than the vessel encasement (>1800) (57.6%, P = 0.04). Vessel injury occurred in 7.8% of Group-1 and 6.6% of Group-2, with no significant impact on EOR. CONCLUSIONS: Cavernous sinus-extension and T2-hyperintensity predict poor resection rates in mSWMs. While visual outcomes are not directly affected by EOR, long-term visual status may decline due to tumor recurrence and radiotherapy. Vascular injury incidence is not associated with EOR. Thus, the "maximal safe resection" of mSWMs involves a surgical strategy balancing targeted aggressive and conservative resection for maximal cytoreduction and functional preservation.

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BACKGROUND: Encephalocele represent a group of disorders which is characterised by extracranial herniation of the leptomeninges, brain, and CSF through a structural defect in the cranium. They are usually associated with other intracranial anomalies which may impact the neurological development. AIM: This study aimed to assess the predictors of neurological development of patients undergone surgical excision of occipital encephalocele. METHODS: All patients with occipital encephaloceles operated over the last decade (2012-2022). The sac size, presence of hydrocephalous, and associated anomalies were noted. The biopsy of these patients were reviewed and categorised as those which contains mature neural tissue and those without. The neurological outcomes were assessed by social, language, cognitive, and motor milestone and has been stratified into no delay, mild (1 of 4), moderate (2 or 3 of 4), and severe development delay (4 of 4). RESULTS: Total of 35 patients were included with median age of 10 months (IQR = 5-20 months). Fifteen (42.9%) patients had sac size of ≥ 5 cm, and 23 (65.7%) patients had mature neural tissues on biopsy. The median follow-up period was 6.4 years (IQR = 4.38-10.65) years. Seventeen (49.6%) patients had moderate to severe developmental delay. The sac size of ≥ 5 cm (AOR = 33.5; 95%CI = 3.35-334.8) (p = 0.003) and presence of mature neural content in the sac (AOR = 13.32; 95%CI = 1.1-160.36) (p = 0.041) were associated with significant neurodevelopmental delay. CONCLUSION: The presence of a large sac of ≥ 5 cm and the presence of mature neural tissues on histopathological specimen of patients with encephalocele point towards the possibility of poor neurological development.

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PURPOSE: Somatic missense mutations in the phosphodegron domain of the MYC gene (MYC Box I or MBI) are detected in the dominant clones of a subset of patients with acute myeloid leukemia (AML), but the mechanisms by which they contribute to AML are unknown. EXPERIMENTAL DESIGN: To investigate the effects of MBI MYC mutations on hematopoietic cells, we employed a multi-omic approach to systematically compare the cellular and molecular consequences of expressing oncogenic doses of wild type, threonine-58 and proline-59 mutant MYC proteins in hematopoietic cells, and we developed a knockin mouse harboring the germline MBI mutation p.T58N in the Myc gene. RESULTS: Both wild-type and MBI mutant MYC proteins promote self-renewal programs and expand highly selected subpopulations of progenitor cells in the bone marrow. Compared with their wild-type counterparts, mutant cells display decreased cell death and accelerated leukemogenesis in vivo, changes that are recapitulated in the transcriptomes of human AML-bearing MYC mutations. The mutant phenotypes feature decreased stability and translation of mRNAs encoding proapoptotic and immune-regulatory genes, increased translation of RNA binding proteins and nuclear export machinery, and distinct nucleocytoplasmic RNA profiles. MBI MYC mutant proteins also show a higher propensity to aggregate in perinuclear regions and cytoplasm. Like the overexpression model, heterozygous p.T58N knockin mice displayed similar changes in subcellular MYC localization, progenitor expansion, transcriptional signatures, and develop hematopoietic tumors. CONCLUSIONS: This study uncovers that MBI MYC mutations alter RNA nucleocytoplasmic transport mechanisms to contribute to the development of hematopoietic malignancies.

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