Randomized Placebo-Controlled Trial of 60-Day Percutaneous Peripheral Nerve Stimulation Treatment Indicates Relief of Persistent Postoperative Pain, and Improved Function After Knee Replacement.

OBJECTIVES: Total knee arthroplasty (TKA) is an effective surgery for end-stage knee osteoarthritis, but chronic postoperative pain and reduced function affect up to 20% of patients who undergo such surgery. There are limited treatment options, but percutaneous peripheral nerve stimulation (PNS) is a promising nonopioid treatment option for chronic, persistent postoperative pain. The objective of the present study was to evaluate the effect of a 60-day percutaneous PNS treatment in a multicenter, randomized, double-blind, placebo-controlled trial for treating persistent postoperative pain after TKA. MATERIALS AND METHODS: Patients with postoperative pain after knee replacement were screened for this postmarket, institutional review board-approved, prospectively registered (NCT04341948) trial. Subjects were randomized to receive either active PNS or placebo (sham) stimulation. Subjects and a designated evaluator were blinded to group assignments. Subjects in both groups underwent ultrasound-guided placement of percutaneous fine-wire coiled leads targeting the femoral and sciatic nerves on the leg with postoperative pain. Leads were indwelling for eight weeks, and the primary efficacy outcome compared the proportion of subjects in each group reporting ≥50% reduction in average pain relative to baseline during weeks five to eight. Functional outcomes (6-minute walk test; 6MWT and Western Ontario and McMaster Universities Osteoarthritis Index) and quality of life (Patient Global Impression of Change) also were evaluated at end of treatment (EOT). RESULTS: A greater proportion of subjects in the PNS groups (60%; 12/20) than in the placebo (sham) group (24%; 5/21) responded with ≥50% pain relief relative to baseline (p = 0.028) during the primary endpoint (weeks 5-8). Subjects in the PNS group also walked a significantly greater distance at EOT than did those in the placebo (sham) group (6MWT; +47% vs -9% change from baseline; p = 0.048, n = 18 vs n = 20 completed the test, respectively). Prospective follow-up to 12 months is ongoing. CONCLUSIONS: This study provides evidence that percutaneous PNS decreases persistent pain, which leads to improved functional outcomes after TKA at EOT.

Multi-institutional review of characteristics and management of gunshot wounds to the spine.

BACKGROUND CONTEXT: Gunshot wounds (GSWs) to the vertebral column represent an important cause of morbidity and mortality in the United States, constituting approximately 20% of all spinal injuries. The management of these injuries is an understudied and controversial topic, given its heterogeneity and lack of follow-up data. PURPOSE: To characterize the management and follow-up of GSWs to the spine. STUDY DESIGN/SETTING: A multi-institutional retrospective review of the experience of two urban Level 1 trauma centers. PATIENT SAMPLE: Patients with GSWs to the spine between 2010-2021. OUTCOME MEASURES: Measures included work status, follow-up healthcare utilization, and pain management were collected. METHODS: Charts were reviewed for demographics, injury characteristics, surgery and medical management, and follow-up. Statistical analysis included T-tests and ANOVA for comparisons of continuous variables and chi-square testing for categorical variables. All statistics were performed on SPSS v24 (IBM, Armonk, NY). RESULTS: 271 patients were included for analysis. The average age was 28 years old, 82.7% of patients were black, 90% were male, and 76.4% had Medicare/Medicaid. The thoracic spine (35%) was most commonly injured followed by lumbar (33.9%) and cervical (25.6%). Cervical GSW was associated with higher mortality (p<0.001); 8.7% of patients developed subsequent osteomyelitis/discitis, 71.3% received prophylactic antibiotics, and 56.1% of cervical GSW had a confirmed vertebral or carotid artery injury. ASIA scores at presentation were most commonly A (26.9%), D (20.7%), or E (19.6%), followed by C (7.4%) and B (6.6%). 18.8% of patients were unable to be assessed at presentation. ASIA score declined in only 2 patients, while 15.5% improved over their hospital stay. Those who improved were more likely to have ASIA B injury (p<0.001). Overall, 9.2% of patients underwent spinal surgery. Of these, 33% presented as ASIA A, 21% as ASIA B, 29% as ASIA C, and 13% as ASIA D. Surgery was not associated with an improvement in ASIA score. CONCLUSIONS: Given the ubiquitous and heterogeneous experience with GSWs to the spine, rigorous attempts should be made to define this population and its clinical and surgical outcomes. Here, we present an analysis of 11 years of patients presenting to two large trauma centers to elucidate patterns in presentation, management, and follow-up. We highlight that GSWs to the cervical spine are most often seen in young black male patients. They were associated with high mortality and high rates of injury to vertebral arteries and that surgical intervention did not alter rates of discitis/osteomyelitis or propensity for neurologic recovery; moreover, there was no incidence of delayed spinal instability in the study population.

External Vs Internal e-Referrals: Results from a Nationwide Epidemiological Study Utilizing Secondary Collected Data.

Background: E-referral systems, streamlining patient access to specialists, have gained global recognition yet lacked a comparative study between internal and external referrals in Saudi Arabia (KSA). Methods: This retrospective study utilized secondary data from the Saudi Medical Appointments and Referrals Centre system. The data covers 2020 and 2021, including socio-demographic data, referral characteristics, and specialties. Logistic regression analysis was used to assess factors associated with external referrals. Results: Out of 645,425 e-referrals from more than 300 hospitals, 19.87% were external. The northern region led with 48.65%. Males were 55%, and those aged 25-64 were 56.68% of referrals. Outpatient clinic referrals comprised 47%, while 61% of referrals were due to a lack of specialty services. Several significant determinants are associated with higher rates of external referral with (p-value <0.001) and a 95% Confidence interval. Younger individuals under 25 exhibit higher referral rates than those aged 25-64. Geographically, compared to the central region, in descending order, there were increasing trends of external referral in the northern, western, and southern regions, respectively (OR = 19.26, OR = 4.48, OR 3.63). External referrals for outpatient departments (OPD) and dialysis services were higher than for routine admissions (OR = 1.38, OR = 1.26). The rate of external referrals due to the lack of available equipment was more predominant than other causes. Furthermore, in descending order, external referrals for organ transplantation and oncology are more frequent than for medical specialties, respectively (OR = 9.39, OR = 4.50). Conclusion: The study reveals trends in e-referrals within the KSA, noting regional differences, demographic factors, and types of specialties regarding external referrals, benefiting the New Model of Care for the 2030 Vision. Findings suggest expanding virtual consultations to reduce external referrals. Strengthening primary care and preventive medicine could also decrease future referrals. Future studies should assess resource distribution, including infrastructure and workforce, to further inform healthcare strategy.

Occurrence and significance of elevated D-dimer levels in different types of osteomyelitis: a clinical study.

OBJECTIVE: Plasma D-dimer levels >0.5 mg/L are encountered in various conditions besides venous thromboembolism (VTE). Recent studies use them as a prognostic indicator for systemic and inflammatory diseases. The clinical significance of abnormal levels is unclear in osteomyelitis patients with baseline elevation. Our study reviews the occurrence and significance of >0.5 mg/L D-dimer levels in different types of osteomyelitis. PATIENTS AND METHODS: This study involved 125 individuals, out of which 94 were male and 31 were female. The patients were divided into two groups based on the results of bacterial culture testing. Group A comprised those who tested positive for bacterial culture, while group B included those who tested negative. Out of 68 samples tested, 56% were found to have Staphylococcus aureus. All 125 patients underwent blood testing, which included measuring the D-dimer levels, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and MHR monocyte to high-density lipoprotein cholesterol (HDL-C) ratio in different types of osteomyelitis. The statistical analysis of these tests was carried out. RESULTS: Although there were no significant differences in white blood cell (WBC) count, Neutrophil count, Lymphocyte count, or erythrocyte sedimentation rate (ESR) as well as the NLR, PLR, LMR, MHR, HDL-C ratio. The C-reactive protein (CRP) levels were significantly higher in group A (26.13±50.30) than in group B (10.76±18.70) (p<0.05). D-dimer levels were elevated in 40.8% of patients with bacterial culture-positive osteomyelitis, negative culture osteomyelitis, implants with fractures, and no trauma osteomyelitis. No correlation was found between the increase in D-dimer levels and the presence of bacterial culture or implant-related osteomyelitis in patients. CONCLUSIONS: No significant correlation was found between D-dimers and osteomyelitis, including positive bacterial cultures, implant-related osteomyelitis, or osteomyelitis without trauma. However, 40% of the patients had higher D-dimer levels.

Capacity for the management of kidney failure in the International Society of Nephrology Middle East region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The highest financial and symptom burdens and the lowest health-related quality-of-life scores are seen in people with kidney failure. A total of 11 countries in the International Society of Nephrology (ISN) Middle East region responded to the ISN-Global Kidney Health Atlas. The prevalence of chronic kidney disease (CKD) in the region ranged from 4.9% in Yemen to 12.2% in Lebanon, whereas prevalence of kidney failure treated with dialysis or transplantation ranged from 152 per million population (pmp) in the United Arab Emirates to 869 pmp in Kuwait. Overall, the incidence of kidney transplantation was highest in Saudi Arabia (20.2 pmp) and was lowest in Oman (2.2 pmp). Chronic hemodialysis (HD) and peritoneal dialysis (PD) services were available in all countries, whereas kidney transplantation was available in most countries of the region. Public government funding that makes acute dialysis, chronic HD, chronic PD, and kidney transplantation medications free at the point of delivery was available in 54.5%, 72.7%, 54.5%, and 54.5% of countries, respectively. Conservative kidney management was available in 45% of countries. Only Oman had a CKD registry; 7 countries (64%) had dialysis registries, and 8 (73%) had kidney transplantation registries. The ISN Middle East region has a high burden of kidney disease and multiple challenges to overcome. Prevention and detection of kidney disease can be improved by the design of tailored guidelines, allocation of additional resources, improvement of early detection at all levels of care, and implementation of sustainable health information systems.

Energy gap and aromatic molecular rings.

The manuscript combines rational density functional theory simulations and experimental data to investigate the electrical properties of eight polycyclic aromatic hydrocarbons (PAHs). The optimized geometries reveal a preference for one-row, two-row and three-row ring distributions. Band structure plots demonstrate an inverse correlation between the number of aromatic rings and band gap size, with a specific order observed across the PAHs. Gas phase simulations support these findings, though differences in values are noted compared to the literature. Introducing a two-row ring distribution concept resolves discrepancies, particularly in azulene. The B3LYP function successfully bridges theoretical and experimental gaps, particularly in large PAHs. The manuscript highlights the potential for designing electronic devices based on different-sized PAHs, emphasizing a multi-ring distribution approach and opening new avenues for practical applications.

Biosensors for psychiatric biomarkers in mental health monitoring.

Psychiatric disorders are associated with serve disturbances in cognition, emotional control, and/or behavior regulation, yet few routine clinical tools are available for the real-time evaluation and early-stage diagnosis of mental health. Abnormal levels of relevant biomarkers may imply biological, neurological, and developmental dysfunctions of psychiatric patients. Exploring biosensors that can provide rapid, in-situ, and real-time monitoring of psychiatric biomarkers is therefore vital for prevention, diagnosis, treatment, and prognosis of mental disorders. Recently, psychiatric biosensors with high sensitivity, selectivity, and reproducibility have been widely developed, which are mainly based on electrochemical and optical sensing technologies. This review presented psychiatric disorders with high morbidity, disability, and mortality, followed by describing pathophysiology in a biomarker-implying manner. The latest biosensors developed for the detection of representative psychiatric biomarkers (e.g., cortisol, dopamine, and serotonin) were comprehensively summarized and compared in their sensitivities, sensing technologies, applicable biological platforms, and integrative readouts. These well-developed biosensors are promising for facilitating the clinical utility and commercialization of point-of-care diagnostics. It is anticipated that mental healthcare could be gradually improved in multiple perspectives, ranging from innovations in psychiatric biosensors in terms of biometric elements, transducing principles, and flexible readouts, to the construction of 'Big-Data' networks utilized for sharing intractable psychiatric indicators and cases.

A paper-based dual functional biosensor for safe and user-friendly point-of-care urine analysis.

Safe, accurate, and reliable analysis of urinary biomarkers is clinically important for early detection and monitoring of the progression of chronic kidney disease (CKD), as it has become one of the world's most prevalent non-communicable diseases. However, current technologies for measuring urinary biomarkers are either time-consuming and limited to well-equipped hospitals or lack the necessary sensitivity for quantitative analysis and post a health risk to frontline practitioners. Here we report a robust paper-based dual functional biosensor, which is integrated with the clinical urine sampling vial, for the simultaneous and quantitative analysis of pH and glucose in urine. The pH sensor was fabricated by electrochemically depositing IrOx onto a paper substrate using optimised parameters, which enabled an ultrahigh sensitivity of 71.58 mV pH-1. Glucose oxidase (GOx) was used in combination with an electrochemically deposited Prussian blue layer for the detection of glucose, and its performance was enhanced by gold nanoparticles (AuNPs), chitosan, and graphite composites, achieving a sensitivity of 1.5 µA mM-1. This dual function biosensor was validated using clinical urine samples, where a correlation coefficient of 0.96 for pH and 0.98 for glucose detection was achieved with commercial methods as references. More importantly, the urine sampling vial was kept sealed throughout the sample-to-result process, which minimised the health risk to frontline practitioners and simplified the diagnostic procedures. This diagnostic platform, therefore, holds high promise as a rapid, accurate, safe, and user-friendly point-of-care (POC) technology for the analysis of urinary biomarkers in frontline clinical settings.

The functional and molecular roles of p75 neurotrophin receptor (p75NTR) in epilepsy.

Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75NTR in epilepsy has not been completely elucidated. Therefore, this review aimed to revise the mechanistic pathway of p75NTR in epilepsy.

Roles of p75 neurotrophin receptor (p75NTR) in epilepsy: Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75NTR in epilepsy has not been completely elucidated.

The effect of transcranial ultrasound pulse repetition frequency on sustained inhibition in the human primary motor cortex: A double-blind, sham-controlled study.

BACKGROUND: Non-invasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation hold promise for inducing brain plasticity. However, their limited precision may hamper certain applications. In contrast, Transcranial Ultrasound Stimulation (TUS), known for its precision and deep brain targeting capabilities, requires further investigation to establish its efficacy in producing enduring effects for treating neurological and psychiatric disorders. OBJECTIVE: To investigate the enduring effects of different pulse repetition frequencies (PRF) of TUS on motor corticospinal excitability. METHODS: T1-, T2-weighted, and zero echo time magnetic resonance imaging scans were acquired from 21 neurologically healthy participants for neuronavigation, skull reconstruction, and the performance of transcranial ultrasound and thermal modelling. The effects of three different TUS PRFs (10, 100, and 1000 Hz) with a constant duty cycle of 10 % on corticospinal excitability in the primary motor cortex were assessed using TMS-induced motor evoked potentials (MEPs). Each PRF and sham condition was evaluated on separate days, with measurements taken 5-, 30-, and 60-min post-TUS. RESULTS: A significant decrease in MEP amplitude was observed with a PRF of 10 Hz (p = 0.007), which persisted for at least 30 min, and with a PRF of 100 Hz (p = 0.001), lasting over 60 min. However, no significant changes were found for the PRF of 1000 Hz and the sham conditions. CONCLUSION: This study highlights the significance of PRF selection in TUS and underscores its potential as a non-invasive approach to reduce corticospinal excitability, offering valuable insights for future clinical applications.

Achieving Well-Oriented FAPbI3 Perovskite Photovoltaics by Cyclohexane Modification.

It is essential and challenging to develop green and cost-effective solar cells to meet the energy demands. Solar cells with a perovskite light-harvesting layer are the most promising technology to propel the world toward next-generation solar energy. Formamidinium lead tri-iodide (FAPbI3)-based perovskite solar cells (F-PSCs), with their considerable performance, offer cost-effective solar cells. One of the major issues that the PSC community is now experiencing is the stability of α-FAPbI3 at relatively low temperatures. In this study, we fabricated FAPbI3-PSCs using cyclohexane (CHX) material via a two-step deposition method. For this purpose, CHX is added to the formamidinium iodide:methylammonium chloride (FAI:MACl) solution as an additive and used to form a better FAPbI3 layer by controlling the reaction between FAI and lead iodide (PbI2). The CHX additive induces the reaction of undercoordinated Pb2+ with FAI material and produces an α-FAPbI3 layer with low charge traps and large domains. In addition, the CHX-containing FAPbI3 layers show higher carrier lifetimes and facilitate carrier transfer in F-PSCs. The CHX-modified F-PSCs yield a high champion efficiency of 22.84% with improved ambient and thermal stability behavior. This breakthrough provides valuable findings regarding the formation of a desirable FAPbI3 layer for photovoltaic applications and holds promise for the industrialization of F-PSCs.

Sleep disorders cause Parkinson's disease or the reverse is true: Good GABA good night.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative brain disease due to degeneration of dopaminergic neurons (DNs) presented with motor and non-motor symptoms. PD symptoms are developed in response to the disturbance of diverse neurotransmitters including γ-aminobutyric acid (GABA). GABA has a neuroprotective effect against PD neuropathology by protecting DNs in the substantia nigra pars compacta (SNpc). It has been shown that the degeneration of GABAergic neurons is linked with the degeneration of DNs and the progression of motor and non-motor PD symptoms. GABA neurotransmission is a necessary pathway for normal sleep patterns, thus deregulation of GABAergic neurotransmission in PD could be the potential cause of sleep disorders in PD. AIM: Sleep disorders affect GABA neurotransmission leading to memory and cognitive dysfunction in PD. For example, insomnia and short sleep duration are associated with a reduction of brain GABA levels. Moreover, PD-related disorders including rigidity and nocturia influence sleep patterns leading to fragmented sleep which may also affect PD neuropathology. However, the mechanistic role of GABA in PD neuropathology regarding motor and non-motor symptoms is not fully elucidated. Therefore, this narrative review aims to clarify the mechanistic role of GABA in PD neuropathology mainly in sleep disorders, and how good GABA improves PD. In addition, this review of published articles tries to elucidate how sleep disorders such as insomnia and REM sleep behavior disorder (RBD) affect PD neuropathology and severity. The present review has many limitations including the paucity of prospective studies and most findings are taken from observational and preclinical studies. GABA involvement in the pathogenesis of PD has been recently discussed by recent studies. Therefore, future prospective studies regarding the use of GABA agonists in the management of PD are suggested to observe their distinct effects on motor and non-motor symptoms. CONCLUSION: There is a bidirectional relationship between the pathogenesis of PD and sleep disorders which might be due to GABA deregulation.

Plasmonic Contact Lenses Based on Silver Nanoparticles for Blue Light Protection.

Constant exposure to blue light emanating from screens, lamps, digital devices, or other artificial sources at night can suppress melatonin secretion, potentially compromising both sleep quality and overall health. Daytime exposure to elevated levels of blue light can also lead to permanent damage to the eyes. Here, we have developed blue light protective plasmonic contact lenses (PCLs) to mitigate blue light exposure. Crafted from poly(hydroxyethyl methacrylate) (pHEMA) and infused with silver nanoparticles, these contact lenses serve as a protective barrier to filter blue light. Leveraging the plasmonic properties of silver nanoparticles, the lenses effectively filtered out the undesirable blue light (400-510 nm), demonstrating substantial protection (22-71%) while maintaining high transparency (80-96%) for the desirable light (511-780 nm). The maximum protection level reaches a peak of 79% at 455 nm, aligned with the emission peak for the blue light sourced from LEDs in consumer displays. The presence of silver nanoparticles was found to have an insignificant impact on the water content of the developed contact lenses. The lenses maintained high water retention levels within the range of 50-70 wt %, comparable to commercial contact lenses. The optical performance of the developed lenses remains unaffected in both artificial tears and contact lens storage solution over a month with no detected leakage of the nanoparticles. Additionally, the MTT assay confirmed that the lenses were biocompatible and noncytotoxic, maintaining cell viability at over 85% after 24 h of incubation. These lenses could be a potential solution to protect against the most intense wavelengths emitted by consumer displays and offer a remedy to counteract the deleterious effects of prolonged blue light exposure.

Biosensors for melanoma skin cancer diagnostics.

Skin cancer is a critical global public health concern, with melanoma being the deadliest variant, correlated to 80% of skin cancer-related deaths and a remarkable propensity to metastasize. Despite notable progress in skin cancer prevention and diagnosis, the limitations of existing methods accentuate the demand for precise diagnostic tools. Biosensors have emerged as valuable clinical tools, enabling rapid and reliable point-of-care (POC) testing of skin cancer. This review offers insights into skin cancer development, highlights essential cutaneous melanoma biomarkers, and assesses the current landscape of biosensing technologies for diagnosis. The comprehensive analysis in this review underscores the transformative potential of biosensors in revolutionizing melanoma skin cancer diagnosis, emphasizing their critical role in advancing patient outcomes and healthcare efficiency. The increasing availability of these approaches supports direct diagnosis and aims to reduce the reliance on biopsies, enhancing POC diagnosis. Recent advancements in biosensors for skin cancer diagnosis hold great promise, with their integration into healthcare expected to enhance early detection accuracy and reliability, thereby mitigating socioeconomic disparities.

The priority of mesenchymal stem cells treated with melatonin in ameliorating thyroid impairment induced by amiodarone. Thorough look on the apoptotic pathway.

Amiodarone treatment has been associated with thyroid alterations. This work was planned to consider therapeutic outcome of MSCs versus MSCs treated with melatonin in minimizing amiodarone -induced deviations in thyroid. We handed-down 50 male Wistar rats, then distributed them into 5 groups; I, II, III, IV, V; control, sham control, amiodarone treated, amiodarone and MSCs treated, and amiodarone, MSCs and melatonin treated groups respectively. Light microscopic examination; levels of T3, T4 and TSH, Oxidative/antioxidative tissue markers, immune-histochemical staining (Bcl2, BAX, iNOS) and real time PCR (IL-6 and VEGF and Caspase 3) were done. Results of group III showed degenerated follicles, decreased follicular cell count and diminished colloid. Some of the follicles were dilated with signs of inflammatory response and apoptosis. Increased collagen deposition in group III was marked. The positive immune-reactive cells of Bcl-2 was decreased and that of BAX and iNOS was increased, also T3 and T4 levels were significantly decreased, but TSH was significantly increased in group III comparing it to the group I. There were highly significant diminution in both SOD and GPx and upsurge in MDA intensities in groups III, IV when correlated to the control. In group IV and V the aforementioned values were restored. The PCR results showed significant increase in IL-6 and VEGF and Caspase 3 in group III compared to the control one, whereas, their values in groups IV and V were reestablished. It is concluded that stem cells can to a great extent ameliorate the thyroid damage induced by amiodarone.But, Adding melatonin to the stem cells culture was found to have auxiliary beneficial effect in the improving the thyroid structure and function.

Role of ketogenic diet in neurodegenerative diseases focusing on Alzheimer diseases: The guardian angle.

The ketogenic diet (KD) is a low-carbohydrate, adequate protein and high-fat diet. KD is primarily used to treat refractory epilepsy. KD was shown to be effective in treating different neurodegenerative diseases. Alzheimer disease (AD) is the first common neurodegenerative disease in the world characterized by memory and cognitive impairment. However, the underlying mechanism of KD in controlling of AD and other neurodegenerative diseases are not discussed widely. Therefore, this review aims to revise the fundamental mechanism of KD in different neurodegenerative diseases focusing on the AD. KD induces a fasting-like which modulates the central and peripheral metabolism by regulating mitochondrial dysfunction, oxidative stress, inflammation, gut-flora, and autophagy in different neurodegenerative diseases. Different studies highlighted that KD improves AD neuropathology by regulating synaptic neurotransmission and inhibiting of neuroinflammation and oxidative stress. In conclusion, KD improves cognitive function and attenuates the progression of AD neuropathology by reducing oxidative stress, mitochondrial dysfunction, and enhancing neuronal autophagy and brain BDNF.

Patient-reported outcome measure use among older adults after emergency department care: A systematic review.

BACKGROUND: Patient-reported outcome measures (PROMs) are gaining favor in clinical and research settings given their ability to capture a patient's symptom burden, functional status, and quality of life. Our objective in this systematic review was to summarize studies including PROMs assessed among older adults (age ≥ 65 years) after seeking emergency care. METHODS: With the assistance of a medical librarian, we searched Ovid MEDLINE, PubMed, Embase, CINAHL, Web of Science-Core Collection, and Cochrane CENTRAL from inception through June 2023 for studies in which older adult ED patients had PROMs assessed in the post-emergency care time period. Independent reviewers performed title/abstract review, full-text screening, data extraction, study characteristic summarization, and risk-of-bias (RoB) assessments. RESULTS: Our search strategy yielded 5153 studies of which 56 met study inclusion criteria. Within included studies, 304 unique PROM assessments were performed at varying time points after the ED visit, including 61 unique PROMs. The most commonly measured domain was physical function, assessed within the majority of studies (47/56; 84%), with measures including PROMs such as Katz activities of daily living (ADLs), instrumental ADLs, and the Barthel Index. PROMs were most frequently assessed at 1-3 months after an ED visit (113/304; 37%), greater than 6 months (91/304; 30%), and 4-6 months (88/304; 29%), with very few PROMs assessed within 1 month of the ED visit (12/304; 4%). Of the 16 interventional studies, two were determined to have a low RoB, four had moderate RoB, nine had high RoB, and one had insufficient information. Of the 40 observational studies, 10 were determined to be of good quality, 20 of moderate quality, and 10 of poor quality. CONCLUSIONS: PROM assessments among older adults following an ED visit frequently measured physical function, with very few assessments occurring within the first 1 month after an ED visit.

Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3ß) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue.

Parkinson's disease (PD) is a progressive neurodegenerative disease of the brain due to degeneration of dopaminergic neurons in the substantia nigra (SN). Glycogen synthase kinase 3 beta (GSK-3ß) is implicated in the pathogenesis of PD. Therefore, the purpose of the present review was to revise the mechanistic role of GSK-3ß in PD neuropathology, and how GSK-3ß inhibitors affect PD neuropathology. GSK-3 is a conserved threonine/serine kinase protein that is intricate in the regulation of cellular anabolic and catabolic pathways by modulating glycogen synthase. Over-expression of GSK-3ß is also interconnected with the development of different neurodegenerative diseases. However, the underlying mechanism of GSK-3ß in PD neuropathology is not fully clarified. Over-expression of GSK-3ß induces the development of PD by triggering mitochondrial dysfunction and oxidative stress in the dopaminergic neurons of the SN. NF-κB and NLRP3 inflammasome are activated in response to dysregulated GSK-3ß in PD leading to progressive neuronal injury. Higher expression of GSK-3ß in the early stages of PD neuropathology might contribute to the reduction of neuroprotective brain-derived neurotrophic factor (BDNF). Thus, GSK-3ß inhibitors may be effective in PD by reducing inflammatory and oxidative stress disorders which are associated with degeneration of dopaminergic in the SN.

SCANED: Siamese collateral assessment network for evaluation of collaterals from ischemic damage.

This study conducts collateral evaluation from ischemic damage using a deep learning-based Siamese network, addressing the challenges associated with a small and imbalanced dataset. The collateral network provides an alternative oxygen and nutrient supply pathway in ischemic stroke cases, influencing treatment decisions. Research in this area focuses on automated collateral assessment using deep learning (DL) methods to expedite decision-making processes and enhance accuracy. Our study employed a 3D ResNet-based Siamese network, referred to as SCANED, to classify collaterals as good/intermediate or poor. Utilizing non-contrast computed tomography (NCCT) images, the network automates collateral identification and assessment by analyzing tissue degeneration around the ischemic site. Relevant features from the left/right hemispheres were extracted, and Euclidean Distance (ED) was employed for similarity measurement. Finally, dichotomized classification of good/intermediate or poor collateral is performed by SCANED using an optimal threshold derived from ROC analysis. SCANED provides a sensitivity of 0.88, a specificity of 0.63, and a weighted F1 score of 0.86 in the dichotomized classification.