Long-term Control Research Articles

11. Cervicogenic headache and occipital neuralgia.

Cervicogenic headache (CEH) and occipital neuralgia (ON) are headaches originating in the occiput and that radiate to the vertex. Because of the intimate relationship between structures based in the occiput and those in the upper cervical region, there is significant overlap between the presentation of CEH and ON. Diagnosis starts with a headache history to assess for diagnostic criteria formulated by the International Headache Society. Physical examination evaluates range of motion of the neck and the presence of tender areas or pressure points. The literature for the diagnosis and treatment of CEH and ON was searched from 2015 through August 2022, retrieved, and summarized. Conservative treatment includes pain education and self-care, analgesic medication, physical therapy (such as reducing secondary muscle tension and improving posture), the use of TENS (transcutaneous electrical nerve stimulation), or a combination of the aforementioned treatments. Injection at various anatomical locations with local anesthetic with or without corticosteroids can provide pain relief for a short period. Deep cervical plexus block can result in improved pain for less than 6 months. In both CEH and ON, an occipital nerve block can provide important diagnostic information and improve pain in some patients, with PRF providing greater long-term pain control. Radiofrequency ablation of the cervical facet joints can result in improvement for over 1 year. Occipital nerve stimulation (ONS) should be considered for the treatment of refractory ON. The treatment of CEH preferentially consists of radiofrequency treatment of the facet joints, while for ON, pulsed radiofrequency of the occipital nerves is indicated. For refractory cases, ONS may be considered.

Radiosurgery for Facial Pain: A Narrative Review.

The surgical treatment of pain has been an integral part of neurosurgery since the early 20th century when Harvey Cushing pioneered ganglionectomy for trigeminal neuralgia. Over the ensuing years, as anatomic and physiologic knowledge of pain systems grew, new techniques aimed at new targets were developed for various pain conditions. Our objective was to provide an informative and up-to-date summary of radiosurgery for chronic facial pain, emphasizing trigeminal neuralgia and discussing the advantages and challenges of this modality. A PubMed search with keywords ("trigeminal neuralgia" or "cluster headache" or "glossopharyngeal neuralgia") and ("radiosurgery") and ("systematic review" or "review") was conducted. Relevant publications in English published from January 2000 to May 2022 were screened manually for their title, abstract, and even full text to determine their relevance. References from the searched articles were also searched as other supplementary articles. We excluded original articles and personal series from the analysis and only considered systematic reviews to maintain the transparency in the record. A total of 19 studies for trigeminal neuralgia (n > 100), 52 cases of cluster headache, and 42 cases of glossopharyngeal neuralgia were found. Radiosurgery remains the safest among various treatment options with equitable pain control with other percutaneous procedures. MVD remains the gold standard for long-term pain control. There is no difference in efficacy or tolerance between patients treated with gamma knife, linear accelerator, or CyberKnife. The minimum recommended prescription dose was 70 Gy (level of evidence II), and the maximum dose was 90 Gy (level of evidence III) in a single fraction. Radiosurgery provides 5-year pain control in 50% of patients without medication (85% of patients with/without medication) with an average latency period of 1-3 months. Approximately 8-15% of patients will experience a recurrence of pain after an average period of 1 year. Prospective pain relief will be about 60% at 3 years, 40% at 7 years, and 37% in 10 years. The main complication was facial hypoesthesia occurring in 25-50% of patients within 6 months-3 years and disabling in 10% of cases. Cluster headache and glossopharyngeal neuralgia are emerging conditions for treatment with GKRS, although long-term efficacy remains to be studied. Having searched PubMed and other databases and summarized the application of radiosurgery for facial pain, we concluded that radiosurgery is undoubtedly a promising tool for chronic facial pain, but further studies are needed to realize its long-term efficiency and advanced applications of the same.

Estimation of life history parameters of the Gangetic leaffish, Nandus nandus from southern coastal waters of Bangladesh: Implications for sustainable management

The Nandus nandus (Hamilton, 1822) is a highly prized food fish that possesses significant nutritional and commercial worth. Bangladesh, India, Pakistan, Malaysia, Myanmar, Thailand and Viet Nam are the countries where it is endemic. The IUCN Bangladesh has classified this species as near endangered due to its current progressive decline. Hence, immediate actions are necessary to efficiently manage the fishery in this country. To address this issue, a comprehensive understanding of its life history parameters is required. This study aimed to examine the growth characteristics, recruitment length, sexual maturity, mortality, exploitation rate, and maximum sustainable production of N. nandus in Bangladesh's southern coastal waters. Samples were taken every month from January through December of 2021. Our study indicates that N. nandus grows in an isometric manner. The estimated asymptomatic length of this species is 18.0 cm in total length (TL), growing at a rate of 1.30 year−1. The growth performance index of this species was determined to be 2.62, and the projected lifespan was calculated to be 2.31 years. The initial length at recruitment was measured to be 9.5 cm TL, whie the size at first sexual maturity was recorded to be 9.4 cm TL. With the contributions of the natural mortality rate (2.26 year−1) and the fishing mortality rate (1.86 year−1) the total mortality rate was found to be 4.12 year−1. The exploitation rate, determined to be 0.45, surpasses the upper limit of sustainable yield criteria set at 0.37. Therefore, it is imperative to implement strategies to avoid excessive fishing and guarantee the long-term control of N. nandus populations.

Long-term Visual Acuity Outcomes of Deep Sclerectomy in Pediatric Glaucoma.

This study provides evidence of the long-term efficacy and safety of Deep Sclerectomy as a successful surgical intervention option in cases with childhood glaucoma. The primary objective was to evaluate the long-term visual acuity outcomes of Deep Sclerectomy in pediatric glaucoma and identify factors predicting poor prognosis. The secondary objective was to evaluate the long-term success rate of Deep Sclerectomy in controlling intraocular pressure. A retrospective review was conducted of all pediatric patients who underwent deep sclerectomy at King Abdulaziz University Hospital (KAUH) between 2001 and 2016. We included all patients who had valid visual acuity tests. The preoperative findings and long-term visual and intraocular pressure outcomes were analyzed. A total of 83 eyes of 68 patients were included. The mean (SD) age of participants was 11.1 (4.0) years (range: 5-25 years). The mean age at surgery was 5.9 months, and the mean follow-up period was 10.75 years. The majority of cases (83.1%) were primary congenital glaucoma. Visual acuity was ≥ 20/40 in 56.6% of cases, ranged between 20/40 and 20/200 in 18.1%, and was ≤ 20/200 in 25.3% of the operated eyes. Complete success rate (IOP ≤ 21mmHg without medications) after one surgery was achieved in 53 eyes (63.86%). Qualified success rate (IOP ≤ 21 mmHg with medications) was achieved in 8 eyes (9.6%), while 22 eyes (26.5%) failed to achieve target IOP of ≤ 21 mmHg or needed additional surgery to achieve it. Nine eyes (10.74%) had post-operative complications. Deep sclerectomy is a reasonable option for pediatric glaucoma that can provide good long-term visual outcomes and IOP control with a lower risk of surgical complications.

Analytical performance evaluation of the GreenCare A1c and Cera-Stat HbA1c point-of-care testing assays.

The escalating prevalence of diabetes underscores the need for precise diagnostic tools to facilitate effective management. Hemoglobin A1c (HbA1c) is a crucial biomarker for long-term glycemic control in diabetic patients. Point-of-care testing (POCT) for HbA1c offers rapid, accessible alternatives to conventional laboratory methods, but uncertainties persist regarding the accuracy and reliability of POCT assays. This study evaluates the analytical performance of two boronate-affinity based HbA1c POCT assays, the GreenCare A1c and Cera-Stat HbA1c. Various analytical parameters including precision, linearity, comparison, and accuracy are assessed following guidelines from Clinical and Laboratory Standards Institute (CLSI), with results applied to certification criteria from the National Glycohemoglobin Standardization Program (NGSP) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Furthermore, 52 and 13 frozen EDTA whole blood samples were respectively used for additional evaluation of accuracy and interference due to Hb variants for the GreenCare A1c assay. Both GreenCare and Cera-Stat demonstrated good precision (repeatability CV% 1.5-1.9 and total imprecision CV% 1.6-2.2), linearity (R2 = 0.9996 & 0.9990), and correlation (r = 0.982 & 0.978) with an established HbA1c analyzer, the Bio-Rad D100. The GreenCare also exhibited good accuracy with frozen EDTA samples with known HbA1c values. Both assays met the certification criteria from NGSP and IFCC, classifying them as "standard" according to IFCC model for quality targets for HbA1c. This evaluation affirms the reliability of GreenCare and Cera-Stat POCT assays for HbA1c measurements, which can potentially reduce unnecessary referrals and enhance the overall quality of diabetes diagnosis and treatment.

A thirty-year time series analyses identifies coherence between oscillations in Anthrax outbreaks and El Niño in Karnataka, India

Anthrax is an economically important zoonotic disease affecting both livestock and humans. The disease is caused by a spore forming bacterium, Bacillus anthracis, and is considered endemic to the state of Karnataka, India. It is critical to quantify the role of climatic factors in determining the temporal pattern of anthrax outbreaks, so that reliable forecasting models can be developed. These models will aid in establishing public health surveillance and guide strategic vaccination programs, which will reduce the economic loss to farmers, and prevent the spill-over of anthrax from livestock to humans. In this study, correlation and coherence between time series of anthrax outbreaks in livestock (1987–2016) and meteorological variables and Sea Surface Temperature anomalies (SST) were identified using a combination of cross-correlation analyses, spectral analyses (wavelets and empirical mode decomposition) and further quantified using a Bayesian time series regression model accounting for temporal autocorrelation. Monthly numbers of anthrax outbreaks were positively associated with a lagged effect of rainfall and wet day frequency. Long-term periodicity in anthrax outbreaks (approximately 6–8 years) was coherent with the periodicity in SST anomalies and outbreak numbers increased with decrease in SST anomalies. These findings will be useful in planning long-term anthrax prevention and control strategies in Karnataka state of India.

Biological effective dose as a predictor of local tumor control in stereotactic radiosurgery treated parasellar meningioma patients

IntroductionThe radio-surgical literature increasingly uses biological effective dose (BED) as a replacement for absorbed dose to analyze outcome of stereotactic radiosurgery (SRS). There are as yet no studies which specifically investigate the association of BED to local tumor control in para-sellar meningioma.Methodswe did a retrospective analysis of patients underwent stereotactic radiosurgery (SRS) for para-sellar meningioma during the period of 1995–2022. Demographic, clinical, SRS parameters, and outcome data were collected. The target margin BED with and without a model for sub-lethal repair was calculated, as well as a ratio of BED at the target margin to the absorbed dose at the target margin. Factors related to local control were further analyzed.ResultsThe study was comprised of 91 patients, 20 (22.0%) and 71 (78.0%) of whom were male and female, respectively. The median age was 55.0 (interquartile range Q1, Q3:47.5,65.5years). 34 (37%) patients had a resection of their meningioma prior to SRS. The median interval from SRS to last clinical follow up or progression was 89 months. 13 (14.3%) patients were found to have progression. 3-, 5- and 10-years local tumor control were 98%, 92% and 77%, respectively. In cox univariate analysis, the following factors were significant: Number of prior surgical resections (Hazard Ratio [HR] = 1.82, 95% CI = 1.08–3.05, p = 0.024), BED (HR = 0.96, 95% CI = 0.92-1.00, p = 0.03), and BED/margin (HR = 0.44, 95% CI = 0.21–0.92, p = 0.028). A BED threshold above 68 Gy was associated significantly with tumor control (P = 0.04).ConclusionBED and BED /margin absorbed dose ratio can be predictors of local control after SRS in parasellar meningioma. Optimizing the BED above 68Gy2.47 may afford better long-term tumor control.

A single institution retrospective study of efficacy and complications perspective of Gamma Knife Radiosurgery for benign skull base meningioma: A 12-year follow-up

Background and Objectives: Gamma knife radiosurgery (GKRS) has established its role as an effective treatment modality for inaccessible, recurrent, and residual benign skull base meningioma. Therefore, it is necessary to study the outcome in the long term. The current retrospective study aims to analyze and report the clinical and radiological outcomes after long-term follow-up of GKRS for skull base meningiomas >= 12 years. Patients and methods: The present study was conducted on 106 consecutive patients harboring benign skull base meningiomas treated by GKRS at our IMC center between 2005 and 2012 and was followed till the end of 2023. Results: After a median follow-up of 13 years (3.6-18 years), a tumor control rate was reported in 88.7% of patients (n 94/106). Recurrences and tumor progression occurred in 11.3% (n 12/106) at a median follow-up period of 5.4 years (3–10.3 years). The 3, 5-, 10-, 12-and 15-year actuarial tumor control rate was 100%, 95.3%, 89.7%, 88.7%, and 78.1% respectively. Conclusions: The current retrospective study provides a long-term 12-year follow-up and comprises one of the longest follow-up studies of GKRS-treated benign skull base meningiomas. The current series documents a persistent long-term high local tumor control and an acceptable low incidence of neurological deficits. Benign skull base meningioma volume variant at the time of GKRS is a statistically significance predictor factor for tumor control at long-term outcomes.

Predictive Factors for Long-Term Disease Control in Systemic Treatment-Naïve Oligorecurrent Renal Cell Carcinoma Treated with Up-Front Stereotactic Ablative Radiotherapy (SABR).

Stereotactic ablative radiotherapy (SABR) is emerging as a potential local treatment option for oligometastatic RCC. This study aims to evaluate the efficacy of SABR in patients with oligorecurrent RCC. A total of 50 patients with histologically confirmed RCC underwent SABR for oligorecurrence between 2006 and 2022. Eligible patients had up to five extracranial metastases and were systemic treatment-naïve at the time of irradiation. The primary endpoints of the analysis were overall survival (OS), local control (LC), distant metastasis-free survival (DMFS), and time to systemic therapy initiation. The median OS was not reached, with 1- and 3-year OS rates of 93.8% and 77.5%, respectively. LC rates at one and three years were 95.8% and 86.5%, respectively. The median time to systemic therapy initiation was 63.8 months, and the median DMFS was 17.9 months, with one- and three-year rates of 63.4% and 36.6%, respectively. Multiple metastases were a negative predictive factor for DMFS (HR 2.39, p = 0.023), whereas lung metastases were associated with a more favorable outcome (HR 0.38, p = 0.011). SABR offers a valuable treatment option for oligometastatic RCC, demonstrating significant potential for achieving long-term disease control and delaying the need for systemic therapy.

Organic Waste from the Management of the Invasive Oxalis pes-caprae as a Source of Nutrients for Small Horticultural Crops.

The management of invasive plants is a challenge when using traditional control methods, which are ineffective for large areas, leading to the abandonment of invaded areas and the subsequent worsening of the situation. Finding potential uses for waste resulting from invaders' management could motivate their control in the long-term, concurrently providing new bio-based resources with different applications. Oxalis pes-caprae is an invasive plant, widely distributed worldwide, which spreads aggressively through bulbils, creating a dense ground cover. This study was designed to assess the potential of Oxalis aboveground waste for use as fertilizer and in ameliorating deficit irrigation effects in growing crops. Diplotaxis tenuifolia (wild rocket) seedlings were planted in pots with soil mixed with Oxalis waste at 0, 2.2 and 4.3 kg m-2 or with commercial fertilizer, left to grow for 27 days and then irrigated at 100% or 50% field capacity for 14 days. The incorporation of the Oxalis waste improved the biomass, photosynthesis, sugars, total phenols and total antioxidant capacity in the crop, achieving commercial fertilization values, as well as increasing the phosphorus in soils. However, Oxalis waste seems not to directly affect plants' relative water contents. Our results support the use of Oxalis waste as fertilizer, which can encourage the long-term control of this invasive species.

Tolerability and long-term disease control by IGHV mutation status among patients with CLL on ibrutinib arm of E1912

Tolerability and long-term disease control by IGHV mutation status among patients with CLL on ibrutinib arm of E1912

Pembrolizumab and Cabozantinib in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Long-term Survival Update with a Biomarker Analysis.

Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) have immunomodulatory properties and improve clinical outcomes in combination with anti-PD-1 therapy in different malignancies. We report the long-term efficacy and safety of pembrolizumab and cabozantinib in patients with RMHNSCC and include a correlative biomarker analysis. This open-label, single-arm, multicenter, phase 2 study screened 50 patients with RMHNSCC, of whom 36 received pembrolizumab and cabozantinib. The primary endpoint was overall response rate (ORR), safety, and tolerability. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and correlative studies of tissue and blood. We report the long-term PFS, OS, and safety of treated patients and describe correlative biomarkers evaluating p-MET expression and tumor immune microenvironment (TIME) using multiplex immunohistochemistry. With median follow-up of 22.4 months, the median PFS was 12.8 months with a 2-year PFS of 32.6% (95% CI, 18.8%-56.3%) and the median OS was 27.7 months with a 2-year OS of 54.7% [95% confidence interval (CI), 38.9%-76.8%]. The median duration of response was 12.6 months with a 2-year rate of 38.5% (95% CI, 30.8%-81.8%). Long-term treatment-related adverse events included manageable hypothyroidism (5.5%) and grade 1 elevated aspartate aminotransferase and alanine aminotransferase (2.8%). Baseline tumor p-MET expression correlated with ORR (P = 0.0055). Higher density of CD8+, CD103+, and CSF1-R+ cells at baseline correlated with improved OS [hazard ratio (HR) = 5.27, P = 0.030; HR = 8.79, P = 0.017; HR = 6.87, P = 0.040, respectively]. Pembrolizumab and cabozantinib provided prolonged encouraging long-term disease control and survival with a maintained favorable safety profile. The prognostic significance of higher density of CD8+, CD103+, and CSF1-R+ cells in TIME deserve further evaluation in similar clinical settings.

IOS-1002, a Stabilized HLA-B57 Open Format, Exerts Potent Anti-Tumor Activity.

HLA-B27 and HLA-B57 are associated with autoimmunity and long-term viral control and protection against HIV and HCV infection; however, their role in cancer immunity remains unknown. HLA class I molecules interact with innate checkpoint receptors of the LILRA, LILRB and KIR families present in diverse sets of immune cells. Here, we demonstrate that an open format (peptide free conformation) and expression- and stability-optimized HLA-B57-B2m-IgG4_Fc fusion protein (IOS-1002) binds to human leukocyte immunoglobulin-like receptor B1 and B2 (LILRB1 and LILRB2) and to killer immunoglobulin-like receptor 3DL1 (KIR3DL1). In addition, we show that the IgG4 Fc backbone is required for engagement to Fcγ receptors and potent activation of macrophage phagocytosis. IOS-1002 blocks the immunosuppressive ITIM and SHP1/2 phosphatase signaling cascade, reduces the expression of immunosuppressive M2-like polarization markers of macrophages and differentiation of monocytes to myeloid-derived suppressor cells, enhances tumor cell phagocytosis in vitro and potentiates activation of T and NK cells. Lastly, IOS-1002 demonstrates efficacy in an ex vivo patient-derived tumor sample tumoroid model. IOS-1002 is a first-in-class multi-target and multi-functional human-derived HLA molecule that activates anti-tumor immunity and is currently under clinical evaluation.

A scoping review on control strategies for Echinococcus granulosus sensu lato.

Cystic echinococcosis (CE) is a widespread neglected zoonotic disease caused by Echinococcus granulosus sensu lato (EG) with a global burden of control in the billions of dollars. E. granulosus' life cycle involves definitive, intermediate, and humans as dead-end hosts. Echinococcosis control programs use strategies that focus on any of these hosts. We aimed to provide a comprehensive and up-to-date overview of the EG control interventions worldwide. We conducted a scoping review by mapping all studies on interventions for EG control following the Arksey and O'Malley Framework. We screened identified articles, and charted and coded selected papers. We classified the data based on target host, type of study, and control mechanism. We described the efficacy or safety outcomes, and the associated barriers/facilitators for the intervention. Critical appraisal was conducted. From 7,853 screened studies, we analyzed 45: seven centered on human interventions, 21 on animals, and 17 on both. Studies on humans focused on educational strategies and human CE monitoring. The studies on animals were field trials and most were based on Praziquantel (PZQ) for dogs. Studies focused on both animals and humans had, in general, more participants, lasted longer, and covered larger geographical areas. Overall, the quality of studies was moderate to low. Available evidence suggests that long-term interventions aimed at both animals and humans can achieve significant reduction in EG transmission, particularly when PZQ treatment for dogs is included. Higher quality evidence, standardization of methodologies, and better reporting on post-intervention outcomes are necessary for drawing stronger conclusions. Further evidence is needed to assess the sustainability and scalability of control measures. Nonetheless, an integrative One Health approach is essential for overcoming the multiple challenges associated with sustaining long-term control efforts for Echinococcosis.

Advancements in Newcastle Disease Vaccination: Evaluating Traditional and Thermostable Vaccines for Enhanced Control and Efficacy

Newcastle disease (ND) is a critical viral disease in poultry, affecting various avian species worldwide and causing substantial economic losses annually in commercial and backyard poultry operations. Despite its global prevalence, ND can be controlled through proper vaccination and biosecurity management. Over the past 60-65 years, both live attenuated and inactivated ND virus vaccines have been extensively used to mitigate the economic impact of ND. Although live vaccines demonstrate high efficacy against the disease, achieving comprehensive control of ND outbreaks and their financial consequences remains challenging. The primary limitation of most commercially available live vaccines is their heat sensitivity, necessitating a cold chain for quality maintenance, which poses difficulties in village conditions or remote areas of developing tropical countries. This review discusses various methods of ND vaccine administration, their efficacy, and immunogenicity, focusing on the efficacy and stability of thermostable ND vaccines. A thorough understanding of these factors is essential for the long-term control and eradication of ND.

Predicting Locust Invasions in Eastern India: Strategies and Awareness for Long-Term Control

Predicting Locust Invasions in Eastern India: Strategies and Awareness for Long-Term Control

Interventions to improve glycaemic control in people living with, and at risk of developing type 2 diabetes.

Type 2 diabetes mellitus is one of the most prevalent health conditions worldwide, affecting millions of individuals and posing significant public health challenges. Understanding the nature of type 2 diabetes, its causes, symptoms and treatments is crucial for managing and preventing its complications. Many different dietary strategies are used by individuals to treat and manage diabetes. This review provides an overview of popular dietary strategies that have evidence for improving long-term glycaemic control or achieving diabetes remission, as well as strategies that may be useful to reduce postprandial hyperglycaemia, which may be of use in the prevention of diabetes, but also as strategies for those already diagnosed but trying to manage their condition better. Recent clinical trials have provided evidence that in people living with type 2 diabetes who also live with overweight or obesity, using a total diet replacement weight loss programme results in significant and substantial weight loss, and as a result, many people can achieve remission from their diabetes. There has been considerable interest in whether similar effects can be achieved without reliance on formula foods, using real diet approaches. Reduced or low-carbohydrate diet approaches hold some promise, with observational or preliminary findings suggesting beneficial effects, but evidence from robust trials or systematic reviews of randomized controlled trials is still lacking. The Mediterranean dietary pattern, low in saturated fat and high in monounsaturated fat, also has some potential, with evidence to suggest some people can lose weight and achieve remission using this approach, which may be easier to adhere to longer term than more intensive total diet replacement and low-carbohydrate strategies. Plant-based diets that advocate for the elimination of animal-based and/or animal-derived foods have increased in popularity. There is evidence from epidemiological studies that people who follow these diets have a lower risk of developing type 2 diabetes, and evidence from trials and systematic reviews of trials that changing to a dietary pattern lower in animal-based and animal-derived foods has benefits on glycaemic control and other markers of cardiovascular disease. While these approaches all provide food or nutrient prescriptions, approaches that incorporate periods of fasting do not provide rules on the types of foods that can or cannot be consumed, but rather provide time windows of when to eat. Evidence suggests that these approaches can be as effective in achieving energy restriction and weight loss as approaches that advocate continuous energy restriction, and there is evidence for benefits on glycaemic control independent of weight loss. Finally, popular dietary strategies that may be useful to use or combine to help prevent postprandial hyperglycaemia include reducing the glycaemic index or glycaemic load of the diet, high-fibre diets, eating foods in a meal in the order vegetables > protein > carbohydrates, preloading or combining acids such as vinegar or lemon juice with meals and engaging in low-intensity aerobic exercise immediately after meals.

A hybrid Bi-level management framework for caching and communication in Edge-AI enabled IoT

The proliferation of IoT devices has led to a surge in network traffic, resulting in higher energy usage and response delays. In-network caching has emerged as a viable solution to address this issue. However, caching IoT data faces two key challenges: the transient nature of IoT content and the unknown spatiotemporal content popularity. Additionally, the use of a global view on dynamic IoT networks is problematic due to the high communication overhead involved. To tackle these challenges, this paper presents an adaptive management approach that jointly optimizes caching and communication in IoT networks using a novel bi-level control method called BC3. The approach employs two types of controllers: a global ILP-based optimal controller for long-term timeslots and local learning-based controllers for short-term timeslots. The long-term controller periodically establishes a global cache policy for the network and sends specific cache rules to each edge server. The local controller at each edge server solves the joint problem of bandwidth allocation and cache adaptation using deep reinforcement learning (DRL) technique. The main objective is to minimize energy consumption and system response time with utilizing the global and local observations. Experimental results demonstrate that the proposed approach increases cache hit rate by approximately 12% and uses 11% less energy compared to the other methods. Increasing the cache hit rate can lead to a reduction in about 17% in response time for user requests. Our bi-level control approach offers a promising solution for leveraging the network's global visibility while balancing communication overhead (as energy consumption) against system performance. Additionally, the proposed method has the lowest cache eviction, around 19% lower than the lowest eviction of the other comparison methods. The eviction metric is a metric to evaluate the effectiveness of adaptive caching approach designed for transient data.

Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?

Metformin is a widely employed drug in type 2 diabetes. In addition to warranting good short- and long-term glycemic control, metformin displays many intriguing properties as protection against cardiovascular and neurodegenerative diseases, anti-tumorigenic and longevity promotion. In addition to being a low-cost drug, metformin is generally well tolerated. However, despite the enthusiastic drive to aliment these novel studies, many contradictory results suggest the importance of better elucidating the complexity of metformin action in different tissues/cells to establish its possible employment in neurodegenerative diseases. This review summarises recent data identifying lysosomal-dependent processes and lysosomal targets, such as endosomal Na+/H+ exchangers, presenilin enhancer 2 (PEN2), the lysosomal pathway leading to AMP-activated protein kinase (AMPK) activation, and the transcription factor EB (TFEB), modulated by metformin. Lysosomal dysfunctions resulting in autophagic and lysosomal acidification and biogenesis impairment appear to be hallmarks of many inherited and acquired neurodegenerative diseases. Lysosomes are not yet seen as a sort of cellular dump but are crucial in determining key signalling paths and processes involved in the clearance of aggregated proteins. Thus, the possibility of pharmacologically modulating them deserves great interest. Despite the potentiality of metformin in this context, many additional important issues, such as dosing, should be addressed in the future.

Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension.

The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as chronic renal failure, which is frequently observed in hypertensive patients. Therefore, new approaches that may improve the control of arterial blood pressure should be considered to prevent serious cardiovascular disorders. The contribution of purinergic receptors has been acknowledged in the pathophysiology of hypertension; this review describes the participation of these receptors in the alteration of kidney function in hypertension. Elevated interstitial ATP concentrations are essential for the activation of renal purinergic receptors; this becomes a fundamental pathway that leads to the development and maintenance of hypertension. High ATP levels modify essential mechanisms implicated in the long-term control of blood pressure, such as pressure natriuresis, the autoregulation of the glomerular filtration rate and renal blood flow, and tubuloglomerular feedback responses. Any alteration in these mechanisms decreases sodium excretion. ATP stimulates the release of vasoactive substances, causes renal function to decline, and induces tubulointerstitial damage. At the same time, a deleterious interaction involving angiotensin II and purinergic receptors leads to the deterioration of renal function.