Atheroprotective role of vinpocetine: an old drug with new indication.

Endothelial dysfunction is considered one of the main causes of atherosclerosis and elevated blood pressure. Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatment toward endothelial dysfunction is vinpocetine (VPN). VPN is an ethyl apovincaminate used in the management of different cerebrovascular disorders and endothelial dysfunction through inhibition of atherosclerosis formation. VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE1) as well it has anti-inflammatory and antioxidant effects through inhibition of the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present narrative review was to clarify the mechanistic role of VPN in AS. Most of pro-inflammatory cytokines released from macrophages are inhibited by the action of VPN via NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by inhibiting the expression of pro-inflammatory cytokines. As well, VPN is effective in reducing oxidative stress, a cornerstone in the pathogenesis of AS, through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevent erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress with plaque stability effects could be effective agent in the management of endothelial dysfunction through inhibition of atherosclerosis mediators.

Blunted Melatonin Circadian Rhythm in Parkinson's Disease: Express Bewilderment.

Melatonin (MTN) is a neuro-hormone released from the pineal gland. MTN secretion is regulated by different neuronal circuits, including the retinohypothalamic tract and suprachiasmatic nucleus (SCN), which are affected by light. MTN is neuroprotective in various neurodegenerative diseases, including Parkinson's disease (PD). MTN circulating level is highly blunted in PD. However, the underlying causes were not fully clarified. Thus, the present review aims to discuss the potential causes of blunted MTN levels in PD. Distortion of MTN circadian rhythmicity in PD patients causies extreme daytime sleepiness. The underlying mechanism for blunted MTN response may be due to reduction for light exposure, impairment of retinal light transmission, degeneration of circadian pacemaker and dysautonomia. In conclusion, degeneration of SCN and associated neurodegeneration together with neuroinflammation and activation of NF-κB and NLRP3 inflammasome, induce dysregulation of MTN secretion. Therefore, low serum MTN level reflects PD severity and could be potential biomarkers. Preclinical and clinical studies are suggested to clarify the underlying causes of low MTN in PD.

A Meta-Analysis of Medication Reduction and Motor Outcomes After Awake Versus Asleep Deep Brain Stimulation for Parkinson Disease.

BACKGROUND AND OBJECTIVES: There remains significant debate regarding the performance of deep brain stimulation (DBS) procedures for Parkinson disease (PD) under local or general anesthesia. The aim of this meta-analysis was to compare the clinical outcomes between "asleep" DBS (general anesthesia) and "awake" DBS (local anesthesia) for PD. METHODS: We conducted a comprehensive literature review of all published studies on DBS for PD following PRISMA guideline on PubMed and Cochrane library from January 2004 to April 2023. Inclusion criteria included cohort ≥15 patients, clinical outcomes data which included Unified Parkinson's Disease Rating Scale (UPDRS) score and levodopa equivalent daily dosage (LEDD), and ≥3 months of follow-up. Analysis was conducted using Stata software. RESULTS: There were 18 articles that met inclusion criteria. On meta-analysis, there were no significant differences between awake or asleep DBS with regard to percent change in UPDRS III "off" med/"on" DBS condition (P = .6) and LEDD score (P = .99). On subgroup analysis, we found that the choice of target had no significant effect on improvement of UPDRS III (P = 1.0) or LEDD (P = .99) change for the asleep vs awake operative approach. There were also no statistically significant differences between microelectrode recording (MER) use and no MER use in postoperative UPDRS III (P = 1.0) or LEDD improvement (P = .90) between awake and asleep surgery. CONCLUSION: There was no significant difference in the primary motor outcomes and LEDD improvement between asleep vs awake DBS. The variables of target selection and MER use had no statistically significant impact on outcome. We find that asleep techniques are both safe and effective compared with the awake technique.

Pharmacological characterization of the antidiabetic drug metformin in atherosclerosis inhibition: A comprehensive insight.

BACKGROUND: Atherosclerosis (AS) is a progressive disease that interferes with blood flow, leading to cardiovascular complications such as hypertension, ischemic heart disease, ischemic stroke, and vascular ischemia. The progression of AS is correlated with inflammation, oxidative stress, and endothelial dysfunction. Various signaling pathways, like nuclear erythroid-related factor 2 (Nrf2) and Kruppel-like factor 2 (KLF2), are involved in the pathogenesis of AS. Nrf2 and KLF2 have anti-inflammatory and antioxidant properties. Thus, activation of these pathways may reduce the development of AS. Metformin, an insulin-sensitizing drug used in the management of type 2 diabetes mellitus (T2DM), increases the expression of Nrf2 and KLF2. AS is a common long-term macrovascular complication of T2DM. Thus, metformin, through its pleiotropic anti-inflammatory effect, may attenuate the development and progression of AS. AIMS: Therefore, this review aims to investigate the possible role of metformin in AS concerning its effect on Nrf2 and KLF2 and inhibition of reactive oxygen species (ROS) formation. In addition to its antidiabetic effect, metformin can reduce cardiovascular morbidities and mortalities compared to other antidiabetic agents, even with similar blood glucose control by the Nrf2/KLF2 pathway activation. CONCLUSION: In conclusion, metformin is an effective therapeutic strategy against the development and progression of AS, mainly through activation of the KLF2/Nrf2 axis.

Recovery of Verbal Working Memory Depends on Left Hemisphere White Matter Tracts.

Researchers propose that the recovery of language function following stroke depends on the recruitment of perilesional regions in the left hemisphere and/or homologous regions in the right hemisphere. Many investigations of recovery focus on changes in gray matter regions, whereas relatively few examine white matter tracts and none address the role of these tracts in the recovery of verbal working memory (WM). The present study addressed these gaps, examining the role of left vs. right hemisphere tracts in the longitudinal recovery of phonological and semantic WM. For 24 individuals with left hemisphere stroke, we assessed WM performance within one week of stroke (acute timepoint) and at more than six months after stroke (chronic timepoint). To address whether recovery depends on the recruitment of left or right hemisphere tracts, we assessed whether changes in WM were related to the integrity of five white matter tracts in the left hemisphere which had been implicated previously in verbal WM and their right hemisphere analogues. Behavioral results showed significant improvement in semantic but not phonological WM from the acute to chronic timepoints. Improvements in semantic WM significantly correlated with tract integrity as measured by functional anisotropy in the left direct segment of the arcuate fasciculus, inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. The results confirm the role of white matter tracts in language recovery and support the involvement of the left rather than right hemisphere in the recovery of semantic WM.

Challenges to Early Detection of Brain Tumors in LMICs: A Systematic Review.

BACKGROUND AND OBJECTIVES: While early diagnosis of brain tumors is essential for improving prognoses, several challenges prevent early diagnosis of these illnesses in low- and middle-income countries. The objective of this systematic review is to identify and evaluate the barriers and challenges to early detection of brain tumors in Low- and Middle-Income Countries (LMICs), as well as to propose potential solutions. METHOD: A thorough search of the literature was carried out with the aid of multiple databases, including Google Scholar, CINAHL, PubMed, and Scopus. Studies focusing on the early detection of brain tumors in low- and middle-income countries met the inclusion criteria for this review. Articles were screened independently by two reviewers. National Surgical, Obstetric, and Anesthesia plan (NSOAP) framework was used to extract relevant data and develop themes. Microsoft Excel was then used to arrange and analyze these themes. RESULTS: Out of 21 articles included in the final analysis, notable challenges to early detection of brain tumors included healthcare providers' lack of awareness of early signs and symptoms of brain tumors (21%), limited diagnostic facilities (38%), misdiagnosis by healthcare providers (33%) and financial constraints (46%). Potential strategies for addressing these barriers and challenges include educating healthcare providers on early warning signs (50%), improving the early referral system (25%) and establishing local clinical guidelines (19%). CONCLUSION: Significant barriers to early detection persist in LMICs. Collaboration between stakeholders, legislators, health ministries, and governmental organizations is essential for developing and implementing focused interventions, such as establishment of referral pathways and specialized centers, adapting guidelines to local cultural contexts and raising public and professional awareness.

Follow-Up Care for Brain Tumors in Low- and Middle-Income Countries: A Systematic Review of Existing Challenges and Strategies for the Future.

BACKGROUND AND OBJECTIVES: Brain tumors have a poor prognosis and a high death rate. Sufficient aftercare is necessary to enhance patient results. But follow-up care provision is fraught with difficulties in low- and middle-income countries (LMICs), where a variety of variables can impede access to care. Therefore, our systematic review aimed to identify challenges to follow-up care for brain tumors and possible solutions in LMICs. METHODS: A thorough search of the literature was performed from the beginning until October 20, 2022, using Google Scholar, PubMed, Scopus, and CINAHL. Studies focusing on the aftercare of brain tumors in LMICs met the inclusion criteria. Two reviewers used the National Surgical, Obstetric, and Anesthesia Plan categories to identify themes, extract relevant data, and evaluate individual articles. After being discovered, these themes were arranged in Microsoft Excel to make reporting and comprehension simpler. RESULTS: A total of 27 studies were included in the review. Among the studies included, the most frequently cited barriers to follow-up care were financial constraints (54%), long-distance travel (42%), and a lack of awareness about the importance of follow-up care (25%). Other challenges included preference for traditional or alternative medications (4%) and high treatment costs (8%). Proposed strategies included implementing mobile clinics (20%), establishing a documentation system (13%), and educating patients about the importance of follow-up care (7%). CONCLUSION: In LMICs, several issues pertaining to personnel, infrastructure, service delivery, financing, information management, and governance impede the provision of follow-up treatment for patients with brain tumors. As established by the suggested techniques found in the literature, addressing these issues will necessitate concurrent action by stakeholders, legislators, health ministries, and government agencies.

Adjuvant therapy for brain tumors in LMICs: A systematic review of barriers and possible solutions.

BACKGROUND: Adjuvant therapy is an important tool in the arsenal of brain tumor management and can improve patients' outcomes significantly but low- and middle-income countries (LMICs) often face challenges in provision. Therefore, our study aims to highlight barriers and strategies to adjuvant therapy of brain tumors in low-resource settings. METHOD: A comprehensive search of literature was conducted using PubMed, CINAHL, Google Scholar, and Scopus, from inception to October 20, 2022. The review included studies on adjuvant therapy for brain tumors in LMICs and identified themes using the National Surgical, Obstetric, and Anesthesia Plan (NSOAP) domains. RESULTS: 32 studies were included in the review. The most reported barriers to adjuvant care were limited access to healthcare (14 %), limited access to chemotherapy and radiation equipment (25 %), and traditional or alternative medications (11 %). Strategies for improvement include improving the availability of specialized radiation oncology training (8 %) and improving access to neuro-diagnostics and neurotherapeutics (12 %). In addition, efforts to subsidize treatment (4 %) and provide financial coverage through the Ministry of Health (4 %) can help to address the high cost of care and improve access to funding for chemotherapy. Finally, establishing documentation systems and registries (16 %), implementing standardized national treatment guidelines (8 %) can help to improve overall care for brain tumor patients in LMICs. CONCLUSION: A multimodal approach of strategies targeting workforce, infrastructure, service delivery, financing, and information management is needed to improve adjuvant care for brain tumors. International collaboration and partnerships can also play a key role in addressing barriers and improving care in LMICs.

Information Management for the Neurosurgical Care of Brain Tumors: A Scoping Review of Literature from Low- and Middle-Income Countries.

BACKGROUND: Health care in developing countries often lacks adequate bookkeeping and national cancer registries, means of information that have proven to impact disease research and care. The true burden of brain tumors therefore remains unchecked and so does the extent of the problem. Therefore, this study aims to explore the challenges and potential strategies related to information management of brain tumors in low- and middle-income countries (LMICs). METHODS: A comprehensive literature search conducted using databases such as PubMed, Scopus, Google Scholar, and Cumulated Index in Nursing and Allied Health Literature, without any language restrictions, from inception to October 20, 2022. Following screening and extraction of data, themes were generated using the information management domain of the National Surgical, Obstetric, and Anesthesia Plan framework. RESULTS: The final analysis includes 23 studies that highlighted the challenges to managing information to the surgical care given to brain tumors in LMICs, including lack of proper hospital record system (43%), lack of national brain tumor registry (67%), lack of local management guidelines (10%), and low research output (33%). Some of the proposed strategies in the literature to address these barriers include improving data management systems (45%), developing a population-based brain tumor registry (64%), and formulating local treatment guidelines (9%) for the management of brain tumors. CONCLUSIONS: In LMICs, improving patient outcomes and quality of life postneurosurgical intervention for brain tumors requires coordinated efforts to enhance information systems. The support of the government and public health professionals is vital in implementing strategies to achieve this goal.

Role of uric acid in neurodegenerative diseases, focusing on Alzheimer and Parkinson disease: A new perspective.

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD) and Parkinson disease (PD) are group of diseases affecting the central nervous system (CNS) characterized by progressive neurodegenerations and cognitive impairment. Findings from different studies highlighted the beneficial and detrimental effects of serum uric acid on the development and progression of NDs. Therefore, this mini-review aims to discuss the beneficial and detrimental effects of uric on NDs. The neuroprotective effect of uric acid is mainly related to the antioxidant effect of uric acid which alleviates oxidative stress-induced neurodegeneration in AD and PD. However, long-term effect of hyperuricemia prompts for the development and progression of cognitive impairment. Hyperuricemia is associated with cognitive impairment and dementia, and gout increases dementia risk. In addition, hyperuricemia can cause cerebral vascular injury which is a risk factor for vascular dementia and cognitive impairment. Taken together, the relationship between uric acid and NDs risk remains conflicting. Hence, preclinical and clinical studies are indicated in this regard.

Governance Challenges to the Neurosurgical Care of Brain Tumors in LMICs: A Systematic Review.

BACKGROUND: Low- and middle-income countries (LMICs) often struggle to provide adequate neurosurgical care due to poor governance and institutional efforts, making access to care difficult. Therefore, our review of literature aims to identify gaps in government, national, and institutional efforts to combat barriers to neurosurgical care of brain tumors in LMICs, to inform future policy and action planning. METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Google Scholar, and CINAHL without language restrictions from inception to October 20, 2022. After screening and data extraction, a thematic analysis based on the National Surgical, Obstetric, and Anesthesia Plan (NSOAP) systematically identified and classified notable themes, which were then quantified and presented as percentages. RESULTS: A total of 12 studies were included in the final analysis. The review highlighted some of the barriers to providing surgical care of brain tumors in LMICs, including political instability (14%), inadequate national budget for healthcare (43%), poor government support (14%), lack of support of hospital management (14%), and no coverage under national insurance plans (14%). Strategies that can be implemented to address the barriers include strengthening the local health system (17%), advocating for health ministry support (33%), developing national treatment guidelines (17%), making neurosurgery a part of the national surgical plan (17%), fostering collaborations across various levels of government (17%), changing national insurance policy to include neurosurgical care (17%), and advocating for more resources and changes in global care (33%). CONCLUSION: Effective governance plays a critical role in addressing challenges as it shapes the availability of resources and policies that affect the quality of care provided. Our study outlines key challenges and strategies reported within literature in an attempt to drive government attention and thereby policy to support the neurosurgical care of brain tumors, particularly in the developing world.

Mediterranean diet and associations with the gut microbiota and pediatric-onset multiple sclerosis using trivariate analysis.

BACKGROUND: The interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS. METHODS: We conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample. RESULTS: Here we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%-53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet. CONCLUSIONS: Our findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS.

Multiple sclerosis (MS) is a disease where the immune system attacks the protective covering of nerve cells in the brain. There may be a relationship between diet and bacteria within the gut and MS, however this is not well understood. We investigated how diet and gut bacteria are linked to MS in young people. We examined the diet and types of bacteria in stool samples from those with and without MS. We found that a diet richer in fiber and Mediterranean foods were less common in those with MS. This dietary pattern was linked to certain differences in the gut bacteria. These findings raise the possibility, but cannot prove, that what we eat may help prevent MS by influencing our gut bacteria. This research opens the door to further studies on how diet can impact MS through our gut bacteria.

Awareness and Knowledge of the Physical Activity Guidelines and Their Association with Physical Activity Levels.

BACKGROUND: Physical activity guidelines recommend that adults engage in aerobic exercise and activities that preserve or increase muscle mass. The primary aim of this study was to assess the awareness and knowledge of these guidelines among adults in the Jazan region of Saudi Arabia. A secondary objective was to examine the role of awareness and knowledge in the adherence to physical activity guidelines. METHODS: In this cross-sectional observational study, 1018 participants were recruited through a self-administered online survey. Participants' awareness and knowledge about physical activity guidelines were assessed using a prompted questionnaire. Physical activity levels and weekly energy expenditures were evaluated using the International Physical Activity Questionnaire. RESULTS: The proportion of the participants who reported being aware of the guidelines was approximately 48%, whereas the proportion of the participants who correctly identified the guidelines for moderate-intensity physical activity was 38%. However, only 23% correctly identified the muscle strength guidelines. Those who were aware of the guidelines were most likely to meet the physical activity recommendations (OR = 2.03; 95% CI = 1.55-2.65). Participants who reported being aware of the guidelines exhibited a significantly higher energy expenditure, measured in MET minutes per week (p < 0.01). Similarly, participants who correctly identified the guidelines had greater energy expenditure (p = 0.03). CONCLUSIONS: We found that adults in Jazan have a moderate level of awareness and knowledge of PA guidelines and that awareness is a predictor of adherence to these guidelines. Individuals who are aware of PA guidelines or have knowledge of them tend to have higher levels of physical activity. These findings suggest that public health campaigns that promote awareness and knowledge of the physical activity guidelines may accelerate the progress in engaging the Saudi population with these guidelines.

Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment and cognitive dysfunctions. It has been shown that hypoglycemia can adversely affect AD neuropathology. It is well-known that chronic hyperglycemia in type 2 diabetes (T2D) is regarded as a potential risk factor for the development and progression of AD. However, the effect of recurrent hypoglycemia on the pathogenesis of AD was not deeply discussed, and how recurrent hypoglycemia affects AD at cellular and molecular levels was not intensely interpreted by the previous studies. The underlying mechanisms for hypoglycaemia-induced AD are diverse such as endothelial dysfunction, thrombosis, and neuronal injury that causing tau protein hyperphosphorylation and the accumulation of amyloid beta (Aß) in the brain neurons. Of note, the glucagon hormone, which controls blood glucose, can also regulate the cognitive functions. Glucagon increases blood glucose by antagonizing the metabolic effect of insulin. Therefore, glucagon, through attenuation of hypoglycemia, may prevent AD neuropathology. Glucagon/GLP-1 has been shown to promote synaptogenesis, hippocampal synaptic plasticity, and learning and memory, while attenuating amyloid and tau pathologies. Therefore, activation of glucagon receptors in the brain may reduce AD neuropathology. A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology.

Pedunculated Nasopharyngeal Mass: A Case of Squamous Cell Carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the rarest malignancies and carries a high risk of morbidity and mortality. The presentation of the disease depends on the stage and the anatomical relation of the lesion. In this case report, we present a case of a young female patient, who was found to have a pedunculated nasopharyngeal mass upon examination. The patient presented with nasal obstruction, which improved after surgical removal of the lesion. A histopathological examination of the resected mass revealed an undifferentiated squamous cell carcinoma type, which usually arises as an exophytic raised mass and not a pedunculated mass as in this case.

Assessment of quality of life in patients with neurogenic bladders who undergone urinary system reconstruction (Mitrofanoff).

OBJECTIVE: The purpose of this study was to evaluate the additional contribution of the Mitrofanoff channel to health-related quality of life (HRQoL). METHODS: Between 2005 and 2009, we conducted a retrospective study on 10 pediatric patients who underwent Mitrofanoff surgery for neurogenic bladder and 11 control patients using urethral catheterization. We evaluated HRQoL using questionnaires tailored for various age groups, with higher scores indicating better QoL. RESULTS: The mean age in the patient group was 12.8 years and 10.7 years in the control group (p = 0.103). Shunt use and wheelchair dependency were similar between groups (p = 0.217 and p = 0.505, respectively). Diaper use showed no significant difference (p = 0.256). Notably, 50% of the patient group performed self-catheterization compared to 9.1% in the control group, a significant difference (p = 0.038). Prophylaxis application was significantly higher in the control group (p = 0.049). HRQoL scores were not significantly different between surgery and control groups in children (p = 0.251) and adolescents (p = 0.831), with Cronbach's α values indicating high reliability of the HRQoL scale. CONCLUSIONS: Although the procedure shows potential in enhancing independence, particularly in self-catheterization, the impact on overall HRQoL is not significantly different from the control group.

OBJETIVO: Evaluar la contribución adicional del canal de Mitrofanoff a la calidad de vida relacionada con la salud (CVRS). MÉTODO: Evaluamos la CVRS utilizando cuestionarios adaptados para varios grupos de edad, con puntuaciones más altas indicando una mejor calidad. RESULTADOS: La edad media de los pacientes fue de 12.8 años y la del grupo control fue de 10.7 años (p = 0.103). El uso de derivaciones y la dependencia de silla de ruedas fueron similares entre los grupos (p = 0.217 y p = 0.505, respectivamente). Es notable que el 50% del grupo de pacientes realizaron autocateterización, en comparación con el 9.1% del grupo control (diferencia significativa, p = 0.038). La aplicación de profilaxis fue significativamente mayor en el grupo control (p = 0.049). Las puntuaciones de CVRS no fueron significativamente diferentes entre los grupos de cirugía y control en niños (p = 0.251) y adolescentes (p = 0.831), con valores alfa de Cronbach indicando una alta fiabilidad de la escala de CVRS. CONCLUSIONES: Aunque el procedimiento muestra potencial en mejorar la independencia, en particular en la autocateterización, el impacto en la CVRS general no es significativamente diferente del grupo de control.

Exploring the Antioxidant and Anti-inflammatory effect of Rhoifolin Extracted from Teucrium polium in Rats' Lungs Exposed to Tobacco Smoke.

Cigarette smoking exacerbates respiratory diseases, while plant-derived polyphenols offer antioxidant and anti-inflammatory benefits. This study explores the effects of Rhoifolin (ROF), a polyphenol from Jordanian Teucrium polium, on lung health in rats exposed to tobacco smoke. Male rats were divided into two groups: one exposed to cigarette smoke (CS), and the other to ROF treatment alongside smoke exposure (ROF/CS). ROF was administered orally for 21 days before smoke exposure. Results showed smoke-induced lung inflammation and oxidative stress, mitigated by ROF treatment. Histological examination revealed smoke-related morphological changes in lung tissue. ROF treatment reduced oxidative stress and inflammation, as evidenced by decreased proinflammatory cytokines. In silico docking demonstrated ROF's potential as an inhibitor. This study suggests the therapeutic potential of ROF and similar polyphenols in mitigating the harmful effects of cigarette smoke on lung health.

The potential role of brain renin-angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?

Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin-angiotensin system (RAS) is intricate in the PD neuropathology through modulation of oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, modulation of brain RAS by angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may be effective in reducing the risk and PD neuropathology. It has been shown that all components including the peptides and enzymes of the RAS are present in the different brain areas. Brain RAS plays a critical role in the regulation of memory and cognitive function, and in the controlling of central blood pressure. However, exaggerated brain RAS is implicated in the pathogenesis of different neurodegenerative diseases including PD. Two well-known pathways of brain RAS are recognized including; the classical pathway which is mainly mediated by AngII/AT1R has detrimental effects. Conversely, the non-classical pathway which is mostly mediated by ACE2/Ang1-7/MASR and AngII/AT2R has beneficial effects against PD neuropathology. Exaggerated brain RAS affects the viability of dopaminergic neurons. However, the fundamental mechanism of brain RAS in PD neuropathology was not fully elucidated. Consequently, the purpose of this review is to disclose the mechanistic role of RAS in in the pathogenesis of PD. In addition, we try to revise how the ACEIs and ARBs can be developed for therapeutics in PD.

The Subscapularis Healing Index: A New Scoring System for Predicting Subscapularis Healing After Arthroscopic Repair.

BACKGROUND: Previous research has emphasized the effect of prognostic factors on arthroscopic rotator cuff repair (ARCR) success, but a specific focus on subscapularis (SSC) tendon repair healing is lacking. PURPOSE: To identify prognostic factors for SSC healing after ARCR and develop the Subscapularis Healing Index (SSC-HI) by incorporating these factors. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: This was a retrospective study using prospectively maintained data collected from patients with isolated or combined SSC tears who underwent ARCR between 2011 and 2021 at a single institution with a minimum 2-year follow-up. Functional outcomes were assessed using the American Shoulder and Elbow Surgeons (ASES) score, Subjective Shoulder Value (SSV), and visual analog scale (VAS) pain scale. SSC tendon healing was evaluated via ultrasound at the final follow-up. Multivariate logistic regression analysis was performed to determine the factors affecting SSC healing, and based on these factors, the SSC-HI, which ranges from 0 to 15 points, was developed using odds ratios (ORs). RESULTS: Among 1018 ARCR patients, 931 met the inclusion criteria; 279 returned voluntarily for postoperative SSC ultrasound assessment. The overall healing failure rate was 10.8% (30/279). Risk factors for healing failure included female sex (P = .008; OR, 3.119), body mass index (BMI) ≥30 (P = .053; OR, 2.323), supraspinatus fatty infiltration ≥3 (P = .033; OR, 3.211), lower SSC fatty infiltration ≥2 (P = .037; OR, 3.608), and Lafosse classification ≥3 (P = .007; OR, 3.224). A 15-point scoring system comprised the following: 3 points for female sex, 2 points for BMI ≥30, 3 points for supraspinatus fatty infiltration ≥3, 4 points for lower SSC fatty infiltration ≥2, and 3 points for Lafosse classification ≥3. Patients with ≤4 points had a 4% healing failure rate, while those with ≥9 points had a 55% rate of healing failure. Patients with a healed SSC reported significantly higher ASES (healed SSC: ΔASES, 44.7; unhealed SSC: ΔASES, 29; P < .01) and SSV (healed SSC: ΔSSV, 52.9; unhealed SSC: ΔSSV, 27.5; P < .01) and lower VAS (healed SSC: ΔVAS, -4.2; unhealed SSC: ΔVAS, -3; P < .01) scores compared with those with an unhealed SSC. CONCLUSION: The SSC-HI scoring system integrates clinical and radiological factors to predict SSC healing after surgical repair. Successful SSC healing was found to be associated with enhanced functional outcomes, underscoring the clinical relevance of SSC healing prediction in the management of these tears.

Assessing Residual Gastric Fluid Volume after Administering Diluted Oral Contrast until One Hour Prior to Anesthesia in Children: An Observational Cohort Study.

Background: Gastric fluid volume has been used as a surrogate marker for pulmonary aspiration risk in studies evaluating fasting protocol safety. This study measured residual gastric fluid volume in children using a protocol in which diluted oral contrast medium was administered up until one hour before anesthesia. Methods: This was a single-center prospective observational cohort trial of 70 children for elective abdominal/pelvic computed tomography (CT). Imaging was performed after diluted enteral contrast medium administration, beginning two hours before and ending at least one hour before induction. For each patient, gastric fluid volume was calculated using an image region of interest. The primary outcome measure was gastric fluid volume measured using the computed tomography image. Results: The median time from the end of contrast administration to imaging was 1.5 h (range: 1.1 to 2.2 h). Residual gastric volume, measured using CT was <0.4 mL/Kg in 33%; ≥0.4 mL/Kg in 67%; and ≥1.5 mL/Kg in 44% of patients. Residual gastric volumes measured using CT and aspiration were moderately correlated (Spearman's correlation coefficient = 0.41, p = 0.0003). However, the median residual gastric volume measured using CT (1.17, IQR: 0.22 to 2.38 mL/Kg) was higher than that of aspiration (0.51, IQR: 0 to 1.58 mL/Kg, p = 0.0008 on differences in paired measures). Three cases of vomiting were reported. No evidence of pulmonary aspiration was identified. Conclusions: Children who receive large quantities of clear fluid up to one hour before anesthesia can have a significant gastric residual volume.