Evaluating Load Balancing in Peer-to-Peer Resource Sharing Algorithms for Wireless Mesh Networks

Wireless mesh networks are a promising area for the deployment of new wireless communication and networking technologies. In this paper, we address the problem of enabling effective peer-to-peer resource sharing in this type of networks. In particular, we consider the well-known Chord protocol for resource sharing in wired networks and the recently proposed MeshChord specialization for wireless mesh networks, and compare their performance under various network settings for what concerns total generated traffic and load balancing. Both iterative and recursive key lookup implementation in Chord/MeshChord are considered in our extensive performance evaluation. The results confirm superiority of MeshChord with respect to Chord, and show that recursive key lookup is to be preferred when considering communication overhead, while similar degree of load unbalancing is observed. However, recursive lookup implementation reduces the efficacy of MeshChord cross-layer design with respect to the original Chord algorithm. MeshChord has also the advantage of reducing load unbalancing with respect to Chord, although a moderate degree of load unbalancing is still observed, leaving room for further improvement of the MeshChord design

Pragmatic Use of Planetary Health and Nature-Based Solutions for Future Pandemics Using COVID-19 Case Scenario

https://www.frontiersin.org/article/10.3389/fpubh.2021.62012

Gluconeogenic Signals Regulate Iron Homeostasis via Hepcidin in Mice.

Hepatic gluconeogenesis provides fuel during starvation, and is abnormally induced in obese individuals or those with diabetes. Common metabolic disorders associated with active gluconeogenesis and insulin resistance (obesity, metabolic syndrome, diabetes, and nonalcoholic fatty liver disease) have been associated with alterations in iron homeostasis that disrupt insulin sensitivity and promote disease progression. We investigated whether gluconeogenic signals directly control Hepcidin, an important regulator of iron homeostasis, in starving mice (a model of persistently activated gluconeogenesis and insulin resistance).|We investigated hepatic regulation of Hepcidin expression in C57BL/6Crl, 129S2/SvPas, BALB/c, and wild-type and Creb3l3-/- null mice. Mice were fed a standard, iron-balanced chow diet or an iron-deficient diet for 9 days before death, or for 7 days before a 24- to 48-hour starvation period; liver and spleen tissues then were collected and analyzed by quantitative reverse-transcription polymerase chain reaction and immunoblot analyses. Serum levels of iron, hemoglobin, Hepcidin, and glucose also were measured. We analyzed human hepatoma (HepG2) cells and mouse primary hepatocytes to study transcriptional control of Hamp (the gene that encodes Hepcidin) in response to gluconeogenic stimuli using small interfering RNA, luciferase promoter, and chromatin immunoprecipitation analyses.|Starvation led to increased transcription of encodes phosphoenolpyruvate carboxykinase 1 (a protein involved in gluconeogenesis) in livers of mice, increased levels of Hepcidin, and degradation of Ferroportin, compared with nonstarved mice. These changes resulted in hypoferremia and iron retention in liver tissue. Livers of starved mice also had increased levels of Ppargc1a messenger RNA and Creb3l3 messenger RNA, which encode a transcriptional co-activator involved in energy metabolism and a liverspecific transcription factor, respectively. Glucagon and a cyclic adenosine monophosphate analog increased promoter activity and transcription of Hamp in cultured liver cells; levels of Hamp were reduced after administration of small interfering RNAs against Ppargc1a and Creb3l3. PPARGC1A and CREB3L3 bound the Hamp promoter to activate its transcription in response to a cyclic adenosine monophosphate analog. Creb3l3-/- mice did not up-regulate Hamp or become hypoferremic during starvation.|We identified a link between glucose and iron homeostasis, showing that Hepcidin is a gluconeogenic sensor in mice during starvation. This response is involved in hepatic metabolic adaptation to increased energy demands; it preserves tissue iron for vital activities during food withdrawal, but can cause excessive iron retention and hypoferremia in disorders with persistently activated gluconeogenesis and insulin resistance

Advancing One Health:Updated core competencies

International audienceAbstract One Health recognises the interdependence between the health of humans, animals, plants and the environment. With the increasing inclusion of One Health in multiple global health strategies, the One Health workforce must be prepared to protect and sustain the health and well-being of life on the planet. In this paper, a review of past and currently accepted One Health core competencies was conducted, with competence gaps identified. Here, the Network for Ecohealth and One Health (NEOH) propose updated core competencies designed to simplify what can be a complex area, grouping competencies into three main areas of: Skills; Values and Attitudes; and Knowledge and Awareness; with several layers underlying each. These are intentionally applicable to stakeholders from various sectors and across all levels to support capacity-building efforts within the One Health workforce. The updated competencies from NEOH can be used to evaluate and enhance current curricula, create new ones, or inform professional training programs at all levels, including students, university teaching staff, or government officials as well as continual professional development for frontline health practitioners and policy makers. The competencies are aligned with the new definition of One Health developed by the One Health High-Level Expert Panel (OHHLEP), and when supported by subjectspecific expertise, will deliver the transformation needed to prevent and respond to complex global challenges. One Health Impact Statement Within a rapidly changing global environment, the need for practitioners competent in integrated approaches to health has increased substantially. Narrow approaches may not only limit opportunities for global and local solutions but, initiatives that do not consider other disciplines or social, economic and cultural contexts, may result in unforeseen and detrimental consequences. In keeping with principles of One Health, the Network for Ecohealth and One Health (NEOH) competencies entail a collaborative effort between multiple disciplines and sectors. They focus on enabling practitioners, from any background, at any level or scale of involvement, to promote and support a transformation to integrated health approaches. The updated competencies can be layered with existing disciplinary competencies and used to evaluate and enhance current education curricula, create new ones, or inform professional training programs at all levels-including for students, teachers and government officials as well as continual professional development for frontline health practitioners and policymakers. The competencies outlined here are applicable to all professionals and disciplines who may contribute to One Health, and are complimentary to, not a replacement for, any discipline-specific competencies. We believe the NEOH competencies meet the need outlined by the Quadripartite’s (Food and Agriculture Organisation, United Nations Environment Programme, World Health Organisation, World Organisation for Animal Health) Joint Plan of Action on One Health which calls for cross-sectoral competencies

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Towards a self-adjuvanting and cross-protective vaccine against human papilloma virus

La scoperta che l’infezione persistente da tipi oncogeni del virus del papilloma umano (HPV) è causa necessaria per l’insorgenza di neoplasia cervicale ha guidato lo sviluppo di strategie di prevenzione primaria. Nonostante la dimostrata efficacia dei vaccini attualmente in commercio contro infezioni dai sierotipi più comuni di HPV, la limitata multivalenza contro tipi virali non inclusi nelle formulazioni, l’elevato costo di ciascuna dose e la necessità di personale paramedico per la somministrazione, rendono necessario lo sviluppo di preparati di seconda generazione. La presente ricerca, nata dalla collaborazione tra il Dipartimento di Biochimica e Biologia Molecolare dell’Università degli Studi di Parma, ‘International Agency for Research on Cancer’, WHO (Lione) e ‘German Cancer Research Center’ (Heidelberg), si è posta come obiettivo lo sviluppo di un vaccino economico, stabile e in grado di fornire una protezione a lungo termine a livello mucosale contro la maggiorparte dei tipi oncogeni di HPV. Nella prima fase della ricerca è stata esaminata l’immunogenicità e il potenziale di neutralizzazione virale di sei peptidi appartenenti alla regione N-terminale della proteina capsidica minore L2 (aa 1-120) di HPV16, utilizzando la proteina batterica Tioredossina (Trx) come scaffold strutturale. La strategia TDMI (Thioredoxin Displayed Multipeptide Immunogens) utilizzata, ha permesso l’identificazione dell’antigene ricombinante trimerico Trx-L2(20-38) come il miglior candidato per lo sviluppo di un vaccino cross-protettivo. Questo infatti si è rivelato un eccellente immunogeno, in grado di indurre non solo una forte risposta immunitaria, ma anche la produzione di anticorpi a protezione crociata in grado di neutralizzare fino a quattro diversi sierotipi virali, inclusi quelli a più alta cancerogenicità (HPV 16, 18, 58, 45). Avendo identificato l’antigene più promettente, la fase successiva ha riguardato l’ulteriore ottimizzazione dello stesso in vista di una sua utilizzazione come vaccino peptidico ricombinante. La dimostrazione che la porzione di epitopo effettivamente riconosciuta dagli anticorpi monoclonali, prodotti a partire dai topi precedentemente immunizzati, era quella compresa tra gli aminoacidi 20 e 31, ha portato alla generazione di antigeni ‘miniaturizzati’ costituiti dalla fusione della Trx con più copie dell’epitopo ridotto, con l’obiettivo di indurre una maggiore focalizzazione del sistema immunitario e quindi di potenziare ulteriormente la performance del vaccino in termini di cross-neutralizzazione. Con lo stesso scopo, sono state progettate proteine potenzialmenti multivalenti, presentanti diverse combinazioni strutturali dell’epitopo candidato di differenti sierotipi virali. Nota l’importanza di particolari ponti disolfuro per l’infettività dei virioni, è stata inoltre valutata l’immunoreattività dei monoclonali verso la forma ossidata o artificialmente ridotta dell’antigene Trx-L2(20-38) in esame, al fine di incrementare il potere neutralizzante degli anticorpi generati. L’ulteriore miglioramento dell’immunogeno candidato è stato diretto alla realizzazione di derivati ad elevata stabilità termica e conformazionale, con costi di produzione il più possibile ridotti, in grado di garantire una risposta immunitaria di lunga durata, con un numero minimo di somministrazioni. Tali obiettivi sono stati perseguiti valutando, da una parte, le proprietà di scaffold molecolare di varianti della Tioredossina provenienti da batteri ipertermofili, dall’altra esaminando la performance immunologica, soprattutto in termini di immunogenicità e capacità autoadiuvante, di proteine chimeriche contenenti forme modificate della Trx fuse alla Flagellina (Fli), uno dei più potenti stimolatori dell’immunità innata. Oltre alla fusione Fli-Trx di Escherichia coli già disponibile, sono stati realizzati costrutti chimerici della Flagellina di Salmonella typhi, con la Trx posta in una posizione più apicale e quindi verosimilmente più esposta. Le corrispondenti proteine di fusione verranno somministrate in animali da laboratorio in diverse formulazioni (con e senza adiuvante) per valutare l’effettiva potenzialità adiuvante della Flagellina. La presente ricerca si è inoltre posta come obiettivo secondario e futuro la valutazione di vaccini TDMI alternativi potenzialmenti autoadiuvanti, tra i quali i vaccini ‘vivi’ in ospiti batterici approvati per uso umano (e.g., Salmonella typhi) e strutture sovramolecolari ottenute utilizzando la parete di batteri lattici, non viventi e non geneticamente modificati, come sistemi di display di multiple copie dell’antigene. L’analisi della risposta immune generata negli animali vaccinati, a cui le differenti formulazioni verranno somministrate mediante metodiche alternative (orale e intranasale) all’iniezione, fornirà importanti indicazioni circa l’approccio migliore per fornire una protezione più efficace e duratura contro il virus del papilloma umano, con l’obiettivo finale di sviluppare un vaccino di seconda generazione, multivalente, auto-adiuvante e a basso costo