The mammalian olfactory system has an amazing ability to distinguish thousands of odorant molecules at the trace level. Scientists have made great achievements on revealing the olfactory sensing mechanisms in decades; even though many issues need addressing. Optogenetics provides a novel technical approach to solve this dilemma by utilizing light to illuminate specific part of the olfactory system; which can be used in all corners of the olfactory system for revealing the olfactory mechanism. This article reviews the most recent advances in olfactory optogenetics devoted to elucidate the mechanisms of chemical sensing. It thus attempts to introduce olfactory optogenetics according to the structure of the olfactory system. It mainly includes the following aspects: the sensory input from the olfactory epithelium to the olfactory bulb; the influences of the olfactory bulb (OB) neuron activity patterns on olfactory perception; the regulation between the olfactory cortex and the olfactory bulb; and the neuromodulation participating in odor coding by dominating the olfactory bulb. Finally; current challenges and future development trends of olfactory optogenetics are proposed and discussed. As one of the oldest sensory systems, the mammalian olfactory system is capable of recognizing thousands of different odorant molecules, which can help creatures avoiding danger, looking for food, identifying spouses. The olfactory system has evolved a mature and perfect odor information processing mechanism. Odorant molecules are firstly sensed by olfactory sensory neurons (OSNs) of the olfactory epithelium (OE), where odorant receptors (ORs) are expressed in OSNs and interact specifically with odorant molecules. An OSN expresses only one type of OR protein, which belongs to the superfamily of G protein-coupled receptors (GPCRs). The specific interactions of ORs and odorant molecules cause OSNs to generate an electrical signal, which can be transmitted to the glomerular layer of the OB. The odor information is then projected by the mitral/cluster (M/T) cells of the OB through the lateral olfactory tract into the olfactory cortex (OC), including the anterior olfactory nucleus (AON), the piriform cortex (PC), the amygdaloid cortex (AOC), the olfactory tubercle (OT), and the lateral entorhinal cortex (LEC) . At presNatromonas pharaonis halorhodopsin (NpHR) , a, a92], aIn earlier studies, anti-mitotic drugs  and tranThe OB acts as a relay between the olfactory epithelial sensory input and the advanced olfactory brain area. A large number of neural activities related to olfactory information processing are compressed and completed in the OB. Optogenetics provides a bridge to explore a variety of interneurons and complex circuits in the OB. In the glomerular layer, PGCs mediate the difference in inhibition of MCs and TCs, resulting in different spike latency of the two output neurons, and the inhibition mediated by superficial short-axon cells can reduce the response of M/T cells to the sensory input. The EPL interneurons are widely connected with MC, and one of the interneuron subgroups inhibits the activity of MCs while receiving excitatory input from MCs. A small number of interneurons in the IPL are also involved in the regulation of the OB output neurons. The microcircuit formed by the most abundant granule cells in the OB and MT cells plays a unique role in information processing and participates in pattern separation and odor recognition through this interconnection. Reviewing these studies, it was found that various types of interneurons jointly modulate the activity of the main output neurons in the OB through different methods of inhibition to realize the fine processing of olfactory information, and the role of optogenetics was throughout.M/T cells transmit the odor information from the OB to the OC area through the lateral olfactory tract (LOT), where the odor information is integrated. How the cerebral cortex network recognizes and responds to these different synaptic inputs is an important topic. In order to clarify these mechanisms, researchers use optogenetics to study how the projection of OB to OC and the feedback projection affects the OB circuit, thereby participating in olfactory coding. The related olfactory cortex includes the anterior and posterior piriform cortices (aPC and pPC), the anterior olfactory nucleus (AON), the olfactory tubercle, and other related regions.The piriform cortex (PCx), the largest olfactory area with a simple three-layer structure, participate in the recognition and memory of smell , which rPyramidal cells of PCx receive sensory input from OB, and ipsilateral OB receives centrifugal input from PCx. This cortical feedback directly stimulates GABAergic GCs and short axon cells, thereby inhibiting OB output neurons ,101. TheThe axons of the pyramidal cells in piriform cortex project to the ipsilateral OB of the cortical projection, while the neurons in the anterior olfactory nucleus project axons to the ipsilateral and contralateral OB. The cortical input of the OB is believed to mainly dominate the granule cell layer ,106, andThe use of optogenetics for investigating the OC mainly involves the aforementioned parts: the piriform cortex and the anterior olfactory nucleus. In addition to the olfactory tubercle, the periamygdaloid cortex and the anterior part of the entorhinal cortex are also considered to be main parts of the OC. The extensive olfactory network also includes the orbitofrontal cortex, thalamus, and insular cortex . While tThe olfactory cortex is involved in all aspects of odor perception, including odor intensity, odor recognition, and odor memory . The corIn addition to receiving centrifugal feedback regulation from OC, OB is also regulated by the neuromodulation system, including cholinergic ,120 and The OB receives centrifugal input from both cholinergic and GABA neurons in the horizontal diagonal band of Broca (HDB), one BF nucleus. As such, light stimulation is needed to selectively activate target neurons and study their respective mechanisms of modulation. In order to examine the special functions of cholinergic neurons projecting to the OB, many in-depth studies have been carried with the help of optogenetic tools. Recently, by injecting AAV-ChR2-EYEP into the HDB to selectively activate the projection of cholinergic neurons expressing vesicular glutamate transporter 3 (VGLUT3) to the OB, Case et al., investigated the modulation effect of this subset of BF neurons on the OB circuit . FluoresAnother centrifugal projection of the basal forebrain to the OB comes from GABAergic neurons in the HDB. Yet, GABAergic BF-OB projections have received relatively little attention. Diez et al., studied the target neurons of GABAergic BF-OB projections  by injec5-Hydroxytriptamine (5-HT), a neurotransmitter released by neurons in raphe nuclei, is related to various brain functions, including sensory processing in the olfactory system. Optogenetic tools have played an irreplaceable role in studying how 5-HT affects OB odor information processing. Researchers injected virus expressing ChR2 to the raphe nuclei to study the mechanisms of 5-HT OB projections . The resAnother interesting study investigated the regulation of 5-HT activation on the OC of mice, specifically the anterior piriform cortex (aPC) c 65]. R. R65]. RNorepinephrine from the locus coeruleus (LC) plays a key role in olfactory perception learning. A combination of optogenetic and behavioral studies in mice investigated the value of norepinephrine in olfactory learning tasks by representing odors through OB oscillations d 66]. T. T66]. TNeurotransmitters play an important role in the signal processing of the OB. Together with the neurons in the OC, these modulatory neurons input a large amount of centrifugal feedback to the OB . They paStudies revealed the modulating effect of neurotransmitters on the olfactory bulb with the help of optogenetics. Firstly, the photogenic activation of HDB cholinergic neurons increased the spiking response of M/T cells to odors, suggesting cholinergic neurons improve the possibility of olfactory recognition and participation in olfactory perception learning. Different studies have observed inconsistent cholinergic stimulation to enhance  or inhibThe mammalian olfactory system has a powerful ability to process olfactory information, including the ability to recognize and distinguish thousands of odors, distinguish different intensities of odor stimuli, and even perceive the difference in the duration of odor stimuli in milliseconds, all of which requires the orderly coordination between different parts of the olfactory system. Therefore, decrypting the mechanism of the functional connections in the olfactory system is the focus of olfactory research. Optogenetics has become one of the most suitable and powerful tools for olfactory research. The general strategy of this method is to activate or silence target neurons in the olfactory system through light stimulation, and then combine electrophysiology to measure downstream neuron responses, or combine behavior to measure animal olfactory perception, to study the projection from one area to another and the impact of the target area on olfactory perception. Odor information is directly input from the OSNs in OE to OB, adjusted by the inhibitory circuit and centrifugal modulation, and projected into the cortex for characterization. Such a complex process involves the participation of many neurons, and optogenetics has played an instrumental role in illuminating these pathways. Haloarcula  salinarum exhibit robust inhibition of neuron activity noninvasively [Blastocladiella emersonii [Some key issues need to be focused on in the application of optogenetic technology to study the olfactory system. The first is the choice of optical probes, which are used to activate or silence olfactory neurons according to needs. As we can see, a wild variety of virus vectors and transgenic animal models allows scientists to target ChR2 to almost all neurons in the olfactory system, including OSNs in the OE, M/T cells, and inhibitory neurons in the OB, and neurons in the OC. The mutations of ChR2 (ChETA) provide higher precision control and faster spiking frequency, and may be more suitable for research requiring accurate spike times. Transgenic Drosophila models of ChR2 and ReaChR are both broadly applied in studying the insect olfactory system, while some scientists believe that ReaChR works better in adult Drosophila owing. Interestingly, the application of optogenetic silencing tools is far less extensive than the activation tools in the olfactory research, considering that silencing neurons is harder to trace its origin than exciting neurons, but there is still a certain demand. Optogenetic neuronal silencing tools (ArchT and NpHR) have been used to target M/T cells and inhibitory neurons in the OB by virus vectors. Despite the development and progress of the ChR2 targeting strategies for olfactory neurons, other optogenetic tools and efficient targeting strategies remain to be developed. For instance, the mutations of ChR excel ChR2 in precision control and spiking frequency, so these are needs for generating transgenic animal models to target these tools to various neurons in the olfactory system. Similarly, the silencing tools needs potent target strategies for not only neurons in the OB but also neurons in the OE and the OC. In addition to eNpHR3.0, some other excellent optogenetic silencing tools with enhanced functions have been generated, which have not been used in the olfactory study due to the lack of cell type-specific promotors and transgenic animal models. Jaws derived from vasively , which cvasively , which ivasively . The avamersonii . TherefoThe research progress of optogenetics in the olfactory bulb provides ideas for the next direction. First, the mitral cells and the secondary cells receive different OSN signals in the odor information processing in the glomerulus, which indicates the difference in their odor information processing functions, and these two types of cells may be further subdivided into different functional subtypes with the help of optogenetics. Secondly, researchers use optogenetics to link the spatiotemporal activities of the olfactory bulb with olfactory perception and behavior. A meaningful direction is to use this connection to construct biosensors for odor recognition and concentration estimation, which requires the combination of optogenetics and electrophysiology. Furthermore, olfactory bulb interneurons mediate different inhibitory circuits. These OB interneurons are constantly being replaced. Among them, the role of newborn PGCs in odor information processing has not yet been elucidated. Their specific light activation can help explain this problem. In addition, the input from the olfactory bulb indicates that PCx plays an important role in odor characterization, while other areas in the olfactory cortex, such as olfactory tubercle, also receive olfactory input from OB. It is necessary to further determine the performance of olfactory tubercle. In short, optogenetics is expected to solve other important problems in the olfactory system in the future.


Applications of natural hyaluronic acid (HYH) for the fabrication of organic-inorganic composites for biomedical applications are described. Such composites combine unique functional properties of HYH with functional properties of hydroxyapatite, various bioceramics, bioglass, biocements, metal nanoparticles, and quantum dots. Functional properties of advanced composite gels, scaffold materials, cements, particles, films, and coatings are described. Benefiting from the synergy of properties of HYH and inorganic components, advanced composites provide a platform for the development of new drug delivery materials. Many advanced properties of composites are attributed to the ability of HYH to promote biomineralization. Properties of HYH are a key factor for the development of colloidal and electrochemical methods for the fabrication of films and protective coatings for surface modification of biomedical implants and the development of advanced biosensors. Overcoming limitations of traditional materials, HYH is used as a biocompatible capping, dispersing, and structure-directing agent for the synthesis of functional inorganic materials and composites. Gel-forming properties of HYH enable a facile and straightforward approach to the fabrication of antimicrobial materials in different forms. Of particular interest are applications of HYH for the fabrication of biosensors. This review summarizes manufacturing strategies and mechanisms and outlines future trends in the development of functional biocomposites. Hyaluronic acid (HYH) is a natural polymer that plays a vital role in many physiological processes in humans and other organisms ,2. HYH iHYH is of significant interest for the fabrication of organic-inorganic composites for biomedical applications. Many natural materials, such as bone, are organic-inorganic nanocomposites. Natural composites combine the unique biomedical properties of biopolymers with properties of inorganic materials. Advanced functional properties of such composites also result from design features, such as multilayer and hierarchical structural organization, containing various building blocks at different dimensional scales . The mosInnovative studies during recent years have led to various applications of HYH for the fabrication of composite materials. The chemical structure of HYH facilitates the adsorption of this polymer on different inorganic surfaces. HYH has attracted attention for surface modification of inorganic particles and is used as a capping or structure-directing agent for the synthesis of inorganic nanoparticles and their dispersion ,19,20. MThis review is focused on the functional properties of organic-inorganic composites containing HYH as an organic phase and their applications .Our goal is to emphasize innovative ideas in biocomposite technology that are based on the unique properties of HYH. We describe recent advances in surface modification methods, which have enriched the science and technology of biomaterials. This review covers advanced functional materials for biomedical applications, such as scaffolds, gels, biocements, and materials for wound dressing. Another important area covered by this review is the application of HYH for the fabrication of composite films by electrochemical and colloidal methods. Special attention is paid to the synthesis and colloidal processing of functional inorganic materials using HYH as a capping and dispersing agent and their incorporation in the HYH matrix. Conceptually, new methods are described for the fabrication of composite materials for drug delivery and materials with antimicrobial properties. The unique microstructure and functional properties of HYH-based composites are key factors for new emerging developments in various fields of advanced biomaterials.HYH is a natural biopolymer distributed widely throughout the human body. The HYH content in the human body was estimated as ~15 g for a body mass of 70 kg . It is a- groups , ca, ca57], 2+ and PO43− ions. The anionic HYH and cationic Chit were added by alternately dipping the matrix into solutions of these polymers, starting with Chit. The developed films were highly hydrophilic and became more hydrophilic with an increasing number of individual layers. The addition of HYH increased the mechanical strength. Greater numbers of film layers decreased the hardness of the film. The cell viability increased with the LBL deposition on the surface, as there is an increased surface area and surface affinity following the LBL assembly [Huang et al.  developeassembly .HYH can be adsorbed onto HAP or CaP surfaces to create a polyelectrolyte-based composite coating ,62,63. TScaffolds have been found  to be exHYH was also combined with other biopolymers in order to improve porosity and biocompatibility ,71,72,73Calcium phosphate cements (CPCs) containing HYH (CPC-HYH) have generated significant interest  for variThe HYH microparticles were incorporated into the cement to make the cement more porous and, therefore, make it more degradable, as the highly interconnected structure facilitates its degradation. The addition of platelet lysate proteins was used to further increase the macroporosity. The HYH microparticles found in this cement have a very low degradability due to their crosslinking and encasement in the cement surface . In anot2+ and PO43− ions [The addition of HYH to CPC to form a paste greatly increased the injectability of the paste ; however43− ions . The add43− ions .2+ ions on the HAP surface promoted HAP crystal interlocking. The injectability, setting time, and mechanical strength were varied by changing the HYH phase content in the composite cement. HYH was functionalized with bisphosphonate [Another interesting strategy was based on the use of composite HYH–alginate microbeads, which were incorporated into the CPC matrix and facilitated the cement’s injectability . The addsphonate  to enhanInvestigations in this area also reported the application of HYH–tyramine (Tyr) conjugates for the fabrication of a HAP–HYH–Tyr cement, which was hardened by enzyme-mediated coupling of Tyr moieties . This ceComposite HYH–CaP and HYH–HAP particles  are undeHYH-functionalized pH-responsive CaP nanoparticles showed a promising performance for application in tumor targeted therapy . Surface2) have been developed  [2 microparticles have high loading amounts of RB, as the microparticles have a large surface area. During the drug release, RB first diffuses from the silica particles into the HYH matrix, then diffuses from the HYH matrix into the surrounding media. As the RB diffuses from the gel, the gel swells as water molecules can then be adsorbed by the gel [2 nanoparticles. Near-infrared radiation can be used to further degrade the hydrogel, allowing doxorubicin to be released more easily [HYH–SiOgal (RB)  or doxorgal (RB) . The amo the gel . To relee easily . Injectae easily .2 films have been developed by anodic EPD [HYH–SiOodic EPD . The devodic EPD .- onto the surface of the silica particles. This adsorption then stabilizes the silica suspensions [Increasing the amount of silica in the solution allows the silica nanoparticles to cover a greater surface area of the film, increasing the surface roughness. The silica nanoparticles have also been shown to increase the mechanical properties of the gel. The solution is stable in suspension due to hydrogen bonding between HYH and silica . The silpensions . The incpensions .HYH–poly(6-lysine)–silica films have also been developed by polyelectrolyte multilayer formation followed by immersion of the film into a solution containing a silica precursor of sodium silicate . The mulThe material system of HYH–titania  offers m2+-modified HYH–titania composite irradiated under visible light resulted in changes in electrical resistance and fluorescence intensity, which could be recorded by an optical microscope and a wireless device.HYH–titania composites showed improved antifungal activity compared with the individual components . It was 3 composites  , chitosaspersion . The comspersion ,159, whispersion .Another LBL self-assembly technique  involvedThe use of HYH–Au composites  has emerHYH was loaded with semiconducting quantum dots (QDs)  to studyHYH–QDs composites were prepared using LBL self-assembly for sensors, based on fluorescent properties of QDs, and for other applications . CdS/HYHThe literature data described in this review indicate that HYH gels loaded with HAP or CaP are promising materials for bone tissue regeneration and the treatment of bone and skin defects. Further progress in this area can be achieved by the optimization of the HYH molecular size, chemical modifications of HYH molecules, the development of advanced crosslinking techniques, and the optimization of the size and shape of HAP or CaP particles and their dispersion. Moreover, composite gels can be loaded with other functional materials for the fabrication of new composites with advanced functionality.New film deposition mechanisms based on the pH-dependent charge and solubility of HYH as well as HYH adsorption on HAP are key factors for emerging developments in the field of surface modification of biomedical implants. Further advances can be achieved by the development of film crosslinking techniques to improve the chemical stability of the films. EPD offers the potential for co-deposition of HYH and HAP with other functional biomaterials. One of the remaining challenges in this area is related to charge reversal of HYH at a low pH and solubilization of HYH gel, which are detrimental to the formation of adherent films by anodic EPD.Investigations demonstrated the promising performance of HYH–HAP and HYH–CaP scaffolds, which combine properties of organic and inorganic components. The primary research focus in this area is the development of composites containing other polymers and functional materials. Significant interest has been generated in the development of efficient crosslinkers, application of BCaP, microstructure control, and development of advanced fabrication techniques.Many examples herein suggest that HYH-CPCs are promising materials for various biomedical applications. The most important advancements are related to the optimization of the composition of the inorganic CPC phase, modification of the HYH, and optimization of the microstructure and chemical interactions of CPC and HYH phases. Various properties have been optimized, such as mechanical properties, the setting time, the injectability, and the degradation rate. This fast-growing field is exciting on several applied and fundamental levels.The synergy of functional properties of HYH and HAP/CaP offers a strong potential for applications of composite particles in drug delivery and tumor treatment. From the available literature, it is obvious that further development of fabrication procedures, particle microstructures, and compositions will result in new important advances in this field. Bioceramic particles with a HYH-modified surface chemistry have also been used to expand the functionality of HYH-based composites. The ability to modify a bioceramic’s surface chemistry opens up new opportunities for the fabrication of advanced scaffolds and materials for drug delivery. Of particular interest are applications of HYH as a biocompatible dispersing, capping, and structure-directing agent for the synthesis of bioceramic particles. The bioactivity of HYH provides a platform for advanced implant applications.From the available literature, it is obvious that the development of material processing techniques will play an important role in the fabrication of HYH–AgNPs, HYH–AuNPs, and HYH–QDs composites. It is expected that further progress in this area will result in the development of advanced materials with antibacterial products for various biomedical applications and advanced biosensors.


A stomach was considered ineligible to be an ideal conduit conventionally if its right gastroepiploic artery (RGEA) were injured. However, both sufficient blood flow and good venous return are crucial to the success of reconstruction. And there lacks robust evidence regarding the surgical techniques of reconstructing RGEA and right gastroepiploic vein (RGEV) and performing cervical anastomosis with gastric conduit simultaneously. Herein, we summarized the key surgical techniques for simultaneous vascular reconstruction and gastric conduit anastomosis in McKeown esophagectomy. McKeown esophagectomy is the primary surgical procedure for esophageal malignancies. As RGEA is the primary source of blood supply of the gastric conduit , the unaA midline incision was made in the epigastrium to ensure adequate relaxation of the gastric tissues and immediate exploration of the injured vessels. If the vascular deficit is small, the soft tissues around the vascular stumps should be fully dissociated, and then the tension of the vascular stumps should be accurately assessed. Once acceptable tension was identified at the vascular stumps, the injured vessels could be reconstructed via direct anastomosis promptly.The principles for vascular anastomosis: (1) Both arteries and veins should be anastomosed by vein-first surgical technique; (2) The vessel stumps should be trimmed into an oblique section, after which continuous suture could be performed from the posterior wall of the vessel stumps using a 7-0 polypropylene thread ; (3) No The blood flow after anastomosis could be accurately assessed intraoperatively with coronary blood flow measuring instrument. Once poor blood flow was found, the vascular reconstruction must be abandoned. Postoperative assessment of blood supply was performed by contrast-enhanced CT  or angioOnce the blood perfusion of the anastomosed vessels was disturbed, it will greatly increase the risk of anastomotic leakage. Surgeons should pay attention to preventing thrombosis. Intra-operative anticoagulation therapy should be implemented with diluted heparin (5000 U/single dose), post-operative anticoagulation therapy with low molecular weight heparin (4000 AxaIU/qd), and followed by aspirin (100 mg/qd) for 1 year .During the early postoperative period, sufficient blood capacity should be maintained to achieve appropriate blood pressure. Drugs that constrict peripheral blood vessels should be used with caution, so as to ensure adequate perfusion to the reconstructed RGEA.Minimized tension of vascular anastomosis and gastric conduit anastomosis as follows may be effective to avoid postoperative complications, such as esophageal anastomotic fistula and vascular anastomosis hemorrhage.Before anastomosis, the tissues around the vascular stump should be fully freed to reduce the tension of the vascular stumps. To extend the length of the gastric conduit and to reduce the tension of esophageal anastomosis, the fundus of stomach should not be clipped during the gastric conduit construction until cervical anastomosis was completed , while tAfter the operation, the gastric tube was placed in the lowest position of the gastric conduit to avoid gastric fluid retention. Enteral nutrition support via jejunostomy was recommended to avoid the physical stimulates from the nutrient tube. Those strategies can eliminate excessive internal tension in the gastric conduit, especially in the pylorus, so as to avoid the local expansion of gastric conduit which may increase the tension of vascular anastomosis.Hitherto, there have been no convincing reports that revealed the feasibility and safety to reconstruct RGEA and RGEV and to perform cervical anastomosis using gastric conduit simultaneously. Given that a previous study introduced the cases on whom RGEA reconstruction was performed in Ivor-Lewis esophagectomy , the preIn addition to cancerous involvement, anatomical variations  or previBased on the literature review and clinical experience, we would like to underscore 2 points of the surgical techniques in McKeown esophagectomy, in which reconstruction of RGEA and RGEV and cervical anastomosis using gastric conduit were performed simultaneously: (1) Immediate reconstruction of the RGEA and RGEV and long-term maintenance of the blood flow effectively. (2) Effective tension reduction of gastric conduit anastomosis and vascular anastomosis.The short-term ischemia reperfusion process can help the gastric conduit adapt to the transient hypoxia environment, which may lower the risk of postoperative anastomotic leakage . HoweverIn terms of the anticoagulation therapy after vascular construction, we suggest that anticoagulation therapy should be administered intraoperatively as no previous reports available. Since the average inner diameter of the proximal end of RGEA is similar to that of the coronary artery, we referred to the anticoagulation guideline for coronary artery bypass graft surgery .There are several inherent limitations in the present study. First, the number of patients who underwent vascular reconstruction and cervical anastomosis in McKeown esophagectomy was limited. Second, whether RGEA reconstruction alone could be an alternative to both RGEA and RGEV reconstruction should arouse more attention.It is recommended to reconstruct the RGEA and RGEV immediately in the vein-first order, after which the simultaneous cervical anastomosis is feasible and reliable in McKeown esophagectomy.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by The ethics committee of the Second Affiliated Hospital of Soochow University. The patients/participants provided their written informed consent to participate in this study.LC, JZ, and DC: manuscript writing/editing and data analysis. LC and JZ: data collection. YS and WY: protocol/project development and manuscript writing/editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In this Special Issue we will consider the impact of obesity on health in order to review the latest findings on the risk factors associated with cardiometabolic diseases in children with overweight and obesity as well as to explore the pathogenic mechanisms and potential therapeutic targets. The role of weight-management strategies, including exercise, dietary changes and nutritional education, in preventing obesity-related complications will be considered. The improvement of many obesity-associated complications following bariatric surgery will also be reported. The timely implementation of preventive strategies in pediatric patients with overweight and obesity may ameliorate the future burden of weight-related diseases and the future of healthcare. Pediatric obesity represents a significant issue of public health ,2,3. AccChildhood obesity is a result of genetics, environmental factors and developmental influences in addition to the complex interactions between them . PediatrThe spectrum of cardiometabolic disorders begins with relative insulin resistance (IR). IR is expressed early in life, progressing from prediabetes and metabolic syndrome to T2DM or CVD ,2,6,7. SThe initiating events, including metabolic and cardiovascular derangement, in obesity-induced inflammation start early in childhood, and the adverse effects of obesity on cardiometabolic health in adult ages are independent from adult weight, suggesting the fundamentality of prevention ,2.The promotion of an active lifestyle alongside the modification of behavioral movements , dietaryConsidering that the acquisition of a healthy lifestyle could track to later ages, a proposal of a preventive approach starting in pediatric ages could preserve children’s health . The earEarly childhood education is one of the best investments a country can make to prepare children for learning and give them a chance to thrive later in life. The timely implementation of preventive strategies targeted at reducing the prevalence of obesity during the early years of life can also address health and economic burdens in adult ages .In this Special Issue we will consider the impact of obesity on health in order to review the latest findings on the risk factors associated with cardiometabolic diseases in pediatric subjects with overweight and obesity in addition to explore the pathogenic mechanisms and potential preventive as well as therapeutic targets. The relevant role of weight-management strategies, including behavioral movements, dietary changes and nutritional education, in preventing obesity-related complications will be considered. The improvement of many obesity-associated complications following bariatric surgery will also be reported. Preventive interventions in pediatrics must be proposed in order to ameliorate the future burden of weight-related diseases and the future of healthcare.


To determine the effect of the COVID-19 pandemic on referrals to mental health and physical health services.We analysed referral data from three psychiatric services in the boroughs of Camden and Islington across 2018-2020: Early Intervention Services (for patients with a 1st episode of psychosis), Crisis Resolution Teams and inpatient admissions. We also analysed GP referral data to Cancer Services  to Whittington Hospital, Royal Free Hospital and University College Hospital . We examined the impact of the COVID-19 pandemic on these referrals and compared the findings between physical and mental health. We chose to use EIS and Cancer services as comparable services since they both operate with the two-week target of achieving diagnosis of psychosis and cancer respectively.The number of referrals to EIS and CRT both decreased to 61% in April 2020 with respect to their baseline; EIS referrals continued to decrease to 48% in May before starting to recover. Inpatient admissions saw a smaller reduction to 87% in April 2020. The number of cancer two-week wait referrals similarly decreased and reached a trough of 37% in April 2020. The rate of recovery back to the baseline number of referrals and admissions relative to previous years differed between services, with acute care recovering faster. Referrals to CRT and inpatient admissions recovered by 98% and 115% respectively by June 2020; comparatively, referrals to EIS recovered to 102% by December 2020. In contrast, cancer two-week wait referrals returned to 106% by September 2020, a rate faster than EIS, but slower than CRT and inpatient admissions.The reduction in the number of referrals across all examined services correlated with the first wave of the COVID-19 pandemic. The rate of decrease was similar across all services, coinciding with the peak of COVID-19 infections. However, the ultimate degree of decrease and following rate of recovery in numbers differed across both psychiatric and non-psychiatric services. These differences likely have multifactorial origins. The authors discuss contributing factors, such as changes in health seeking behaviours observed during the pandemic, potential impact of reduction in face to face consultations in primary care, as well as temporary changes in the population demographic of Camden and Islington resulting in absent target groups . It remains important to not neglect mental health and face a hidden epidemic once COVID-19 pandemic settles.


The uses of nanofluid in cooling technology is growing. The nanofluid is made up of metallic and nonmetallic particles that are distributed in a base fluid. This research provides a summary of fuel cell models, uses, and how they function. Researchers have made significant contributions in the following era due to the importance of bioconvection in nanotechnology and a variety of biological systems. The idea of the recent work is to evaluate the aspects of the Cattaneo–Christov (C–C) heat and mass flux model, the second-order boundary with melting phenomenon on the bioconvective flow of viscoelastic nanofluid across a cylinder. The nature of the activation energy, thermal conductivity is also taken into account. Appropriate similarity transformations are utilized to reframe the PDEs of the modeled system into a system of ODEs. The governing equations for the renovated system of ODEs are treated by a shooting function. Here bvp4c built-in function computational tool MATLAB is used. The two-dimensional flow has ceased application in several areas, such as polymer industry, material synthesis technology, nano-biopolymer computer graphics processing, industry, mechanical engineering, airplane structures, and scientific research, which is much more useful in nanotechnology. The results of emerging important flow-field parameters are investigated with the aid of graphs and numerical results. Information on the incorporation of materials into continuous phase fluid for the delivery of improved means of transport is then implemented. Nanofluids are a combination of microscopic nanoparticles and liquid bases. Various critical liquids, like water, fuel oil, and ethylene glycol, are used for the manufacture of the flow of nanofluid. It helps to augment the thermal of the fluid and to enhance the rate of heat transformation. Owing to the high potential of nanofluid, it has a range of uses in engineering, including energy processing, wiring, sheet metal, deformation, lubricant, optical fiber processing, heating roll, and cooling. Nanofluids can also be used in a range of vital fields of scientific and technological development, namely nuclear power stations, electronics, bioengineering, and transport. Choi and Eastman2 first proposed the concept of nanofluid. Buongiorno3 studied the influence of Brownian diffusion and thermophoresis on energy diffusion and mass conversion. Tiwari and Das4 also established a simplified model in which the thermophysical properties of volume fraction substances have been investigated. Kuznetsov and Nield5 used the Buongiorno model to explain the transfer of thermophoresis motion and Brownian diffusion on the flow of nanofluid that corresponds to the heating vertical surface via the pervious layer, noting that these movements of thermophoresis and Brownian motion result in a reduction of the heat development initiatives via the surface. Shafiq et al.6 discussed convective boundary value and thermal slip meaning in 3-D Darcy-Forchheimer nanofluid flowing across the stretching surface. Waini et al.7 addressed the issue of steady flow and thermal transition of a porous spinning thin needle in such a nanofluid. Yang et al.8 defined the forced convection heat transformation of water/aluminum nanofluid in a rectangular microchannels model. Irfan et al.9 reviewed the mathematical method of unsteady Carreau nanoliquids flow via variable conductivity through a bi-directional stretched surface. Albojamal et al.10 have proposed numerically nanomaterials aggregation for flow through a partially filled medium due to constant limits on heat flux. Patil et al.11 define the continuous nonlinear mixed convection nanofluid flow of a surface layer with hydrogen gas diffusion. Izadi et al.12 mathematically investigated the nanofluid heat transfer via an open-cell mechanical heat sink under a uniform heat flux. Many other researchers26 studied the nanofluid flow with the C–C heat and mass flux. Akinshilo et al.27 analyzed the flow and thermal transfer of nanofluids via the converging or diverging channels via the porous tube. The influences of the magnetic field implementation on the heat transmission and entropy output of nanofluids through the triangular microchannels sheet wall were examined by Nguyen et al.28. Varzaneh et al.29 studied the hydrodynamic and thermal transition parameters of nanoparticles using Numerical simulations in a smooth curved microtube. Bestman30 first created an analytical model flowing in the presence of energy linked to chemical reactions on the fitted sheet using a disruption approach. Khan et al.31 discussed non-Newtonian material rheology via the use of electromagnetic, MHD nanofluid, and the influence of activation energy. Khan et al.32 examined the effect of variable thermal conductivity with Arrhenius activation energy on the 2nd-grade nanofluid flow by nanomaterials.Pertinently, investigators and technologists have carried out many scientific and computational studies to increase the efficiency of industrial applications. Scientists and researchers have experimentally shown that heat transport is necessary for the dominance of multi-scale growth. Continuous phase fluids usually gain thermal properties33 used the term bioconvection and polygonal rotating systems were studied in dense Tetrahymena societies. Kuznetsov34 established the important findings for the absorption of nanomaterials. Chu et al.35 examined the steady flow of incompressible and two-dimensional laminar results of the non-Newtonian system on the expandable surface by motile microorganisms. Li et al.36 investigated the aspects of swimming bioconvection on nanoliquids containing gyrotactic microorganisms and Wu slip characteristics. Nadeem et al.37 investigated the efficiency of drag tolerance, heat, and mass transformation in the boundary layer flowing via the density of microorganisms. Khan et al.38 studied the relationship of motile microorganisms on the nonlinear mixed convection Magnetohydrodynamic flow of thyrotrophic nanoparticles. Sohail et al.39 examined the Maxwell nanoliquids, including the gyrotactic motile microorganism, in the absence of homogeneous means that the model by modified mass and heat flow systems. Elanchezhian et al.40 explored gyrotactic microorganism’s effects in bioconvection Oldroyd-B nanofluid past a vertical stretching sheet comprising mixed convection and also a magnetic field inclination. Abbasi et al.41 examined the migration of viscoelastic nanoliquids, including a gyrotactic motile microorganism, through a rotating expanding disc with a convective boundary as well as zero mass flow constraints. Also, some relevant studies on the bioconvective model may be linked to research48.Bioconvection happens as the normal microbe swims upwards, so the bacteria are denser than the foundation fluids. As the top surface of the base liquid gets so dense due to the multitude of bacteria, it becomes fragile, then the microorganisms decrease and create bioconvection as well as the return of the microbes to swim sustain the bioconvection process. This migration of microorganisms inside the water increases the temperature and the converted mass of the environment as a whole. Microscopic species have played an important role in improving human life, especially because of medical applications. Life is impossible to contribute without the use of microorganisms. Continuum numerical models are built by denying the length of the chambers as well as cell resistance. It is often believed that the distribution of the concentration of nanoparticles is immense relative to the cell axis. Bioconvection happens as biochemical and mixed nanoliquids are treated employing heat and mass conversion. In the first position, PlattThe main aim of this research work is to evaluate the aspects of the Cattaneo–Christov (C–C) heat and mass flux model, the second-order boundary with melting phenomenon on the bioconvection flow of viscoelastic nanofluid past the cylinder. The nature of the activation energy, thermal conductivity is also taken into account. Appropriate similarity transformations are used to reframe the PDEs of the modeled system into a system of ODEs. The governing equations for the renovated system of ODEs are treated by a shooting function. Here bvp4c built-in function MATLAB computational tool is used. The heat profile decays for a larger estimation of Prandtl number and thermal conductivity parameter. The concentration profile upsurges the magnitude of activation energy and microorganisms profile decreases bioconvection Lewis number. The This study deals with the 2D Bioconvectional flow of incompressible viscoelastic nanofluid having motile microorganisms via a stretched cylinder with thermal conductivity and activation energy impacts as illustrated in Fig. 50.The governing equations areContinuity equationVelocity equationTemperature equationConcentration equationMicroorganism swimming equation48:The following boundary conditions are as followsIn the above equations 48:The similarity transformations are as followsBy after implementing similarity transformation in Eqs. –7, we geThrough the boundary restrictionsIn this division, the physical aspects of the temperature profile, concentration of nanoparticles profile, and gyrotactic microorganisms’ profile. Here The local Reynolds number The dimensionless ODEs –13 with LetNr, K and Nc while declined Me and Lb and Pe. Table Table entclass1pt{minimaIn this slice, the significance of this analysis is to explore the properties of 2D Bioconvectional flow of nanofluid through a cylinder in the occurrence of second-order boundary condition and activation energy with melting phenomenon. The aim of this section focuses on the attained numerical result associated with the velocity profile, thermal distribution profile, nanoparticles concentration profile, and motile microorganisms profile for the important involved parameters  that are displayed in Figs. Figure mentclasspt{minimaThe study scrutinizes the aspects of thermal conductivity, Fourier and Fick’s laws, and activation energy on the bioconvection viscoelastic nanofluid via a stretching sheet. The second-order boundaries with melting phenomenon are used with appropriate similarity transformations. Mathematical findings computed via shooting scheme with bvp4c (Lobatto-IIIa formula) built-in function MATLAB.An augmentation in viscoelastic fluid parameters and mixed convection parameter lead to the diminished flow of fluid velocity profile.The temperature profile declines for a greater variation of thermal conductivity parameter and Prandtl number.The temperature profile improves for larger Biot number and melting parameter while opposite Aspects of curvature parameter.The concentration profile of nanoparticles increases with a greater value of activation energy while the opposite trend is analyzed for the Prandtl number.The microorganisms profile reduces significantly with booming the variation of bioconvection Lewis number and Peclet number.The main points of communication are given below.


Ceratitis capitata, is a pest of fruit and vegetables in many parts of the world. The Sterile Insect Technique (SIT) is used as an environmentally friendly method for the control and/or eradication of this pest. A critical step in the production of sterile insects in biofactories is when the larvae complete their development and begin metamorphosis to become pupae. Artificial substrates are used to facilitate pupation, but little research has been devoted to this critical moment in the life cycle of the insect. We tested seven pupation substrates and five substrate volumes for a reproductive colony of C. capitata VIENNA 8 genetic sexing strain for SIT application in Mexico. One type of cellulose and sawdust at relatively low ratios of substrate:larvae enhanced pupation and were more cost-effective to produce one million pupae than other substrates including fine wheat bran currently used in a SIT mass-rearing facility in Mexico. Our study contributes to improving rearing processes involved in SIT-based pest control.The Mediterranean fruit fly, Ceratitis capitata (Wiedemann) VIENNA 8 genetic sexing strain, we first examined pupation in cellulose from recycled paper (cellulose I), sawdust, fine wheat bran, vermiculite and coconut fiber using a volume of 2.5–12.5 mL of substrate for each 5 mL volume of fly larvae. We found a positive relationship between substrate volume and pupation, with cellulose I generating the highest proportions of pupation and coconut fiber the lowest. Higher proportions of female flies (white pupae) pupated in sawdust. The proportion of female fliers increased as substrate volume rose in sawdust and coconut fiber, whereas it decreased in vermiculite and cellulose. In a second experiment, we tested three types of cellulose differing in physicochemical characteristics , sawdust, and fine wheat bran using a substrate:larvae ratio of 1:1. The three types of cellulose produced the highest pupation levels. The highest proportions of female fliers were observed in sawdust, and cellulose types III and II. Cellulose III and sawdust at relatively low volumes were more cost-effective to produce one million pupae than other substrates, including fine wheat bran used in a mass-rearing facility in Mexico.Adequate pupation substrates and substrate volume are critical factors in the mass-rearing of insects for Sterile Insect Technique (SIT) applications. To identify an ideal pupation substrate for a reproductive colony of  Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), is a highly polyphagous species native to Africa that has invaded most tropical and subtropical regions of the world  × Selected substrate volume/5 mL of larvae.C. capitata VIENNA 8 GSS larvae that pupated differed significantly as a function of the substrate type  and substrate volume . Substrate volume had a positive effect on pupation ; the highest proportions of females that pupated  were observed in sawdust (0.723), followed by fine wheat bran (0.672) and cellulose I (0.672), vermiculite (0.653), and coconut fiber (0.631) with the lowest proportion of female pupation , volume , or their interaction , and the model simplification led to a null model indicating that an overall mean proportion of 0.533 provided the best description of female emergence ; the proportion of female fliers increased as a function of the volume of substrate only in the case of sawdust and coconut fiber, whereas in the case of cellulose and vermiculite the proportion of female fliers decreased as a function of the volume of substrate used, and in the case of fine wheat bran the proportion of female fliers was similar across the range of substrate volumes used . The highest proportions of pupation were observed with the three types of cellulose and the lowest with sawdust and fine wheat bran , and the mean pupal weight was more than 9 mg in all cases . Our study did not include a pupation treatment in the absence of a substrate, but instead we tested several pupation substrates and substrate to larvae ratios in a single study. Notably, this is the first report on the use of cellulose and coconut fiber as pupation substrates for a reproductive colony of C. capitata VIENNA 8 GSS. The three types of cellulose we tested yielded the highest proportions of pupation  of the pupation rooms to influence fly pupation and other traits of flies of relevance for SIT applications, such as the time to emergence. A cost-effectiveness optimization perspective ,51 couldC. capitata VIENNA 8 GSS in terms of pupation, female pupal weight, female fliers, and estimated cost to produce one million pupae compared to the fine wheat bran substrate currently used in the Moscamed facility. Sawdust was more economical than cellulose III to produce one million pupae with a higher proportion of female pupae, which is very important, but with the drawback that it requires additional handling and has a potential cost associated with larval loss during pupation. We believe that both cellulose III and sawdust have potential for further testing at a larger scale considering other variables associated with production costs such as the recovery of female flies, the larvae that do not pupate and the possibility of recycling substrates. The study of pupation substrates is an issue that could improve the mass-rearing process of fruit flies for SIT applications by enhancing fly pupation and quality, and reducing substrate-associated costs.We conclude that cellulose III at relatively low volumes was an ideal pupation substrate for a reproductive colony of


Dentistry is confronted with the functional and aesthetic consequences that result from an increased prevalence of misaligned and discrepant dental occlusal relations in modern industrialised societies. Previous studies have indicated that a reduction in jaw size in response to softer and more heavily processed foods during and following the Industrial Revolution  was an important factor in increased levels of poor dental occlusion. The functional demands placed on the masticatory system play a crucial role in jaw ontogenetic development; however, the way in which chewing behaviours changed in response to the consumption of softer foods during this period remains poorly understood. Here we show that eating more heavily processed food has radically transformed occlusal power stroke kinematics. Results of virtual 3D analysis of the dental macrowear patterns of molars in 104 individuals dating to the Industrial Revolution , and 130 of their medieval and early post-medieval antecedents  revealed changes in masticatory behaviour that occurred during the early stages of the transition towards eating more heavily processed foods. The industrial-era groups examined chewed with a reduced transverse component of jaw movement. These results show a diminished sequence of occlusal contacts indicating that a dental revolution has taken place in modern times, involving a dramatic shift in the way in which teeth occlude and wear during mastication. Molar macrowear suggests a close connection between progressive changes in chewing since the industrialization of food production and an increase in the prevalence of poor dental occlusion in modern societies. Devehominins .A reduction in jaw dimensions and an increase in poor dental occlusion among modern groups has been discussed as an adaptive consequence of the reduced dental processing of the softer diet that emerged during and following the Industrial Revolution (1760–1840 CE) –14. ThisClinical feeding studies indicate that human chewing behaviours adapt to the mechanical properties of the food consumed, such as toughness and hardness, as well as their extrinsic surface characteristics, such as stickiness, particle size and roughness –23. DiffIn humans, the chewing cycle begins with puncture-crushing cycles in which the teeth come together in a vertically directed squashing action comparable to the crushing action of a pestle and mortar , 29. LatDuring the power stroke, a layer of particles suspended in saliva, likely including a combination of food particles, abrasives and detached enamel, is present between the tooth surfaces. This results in the development of dental wear facets, highly polished planar surfaces, at specific areas of the occlusal surface against which abrasive particles are repeatedly moved across and trapped against as the dental surfaces slide past one another during the power stroke. Each wear facet that develops as a result of the masticatory power stroke has a corresponding wear facet in the teeth of the opposing dental arch , 33. TheBread was the principal dietary staple in both the pre-industrial and industrial groups. In the medieval period, cereals formed up to 80% of calorific intake . SimilarThe aim of this paper is to determine whether changes in chewing behaviour occurred as a result of the consumption of more heavily processed staple foods during the Industrial Revolution. A method of three-dimensional dental macrowear pattern analysis , 35, 48,An association between changes in chewing behaviour and the increased prevalence of poor occlusion evident in industrialised societies may inform functional and preventative treatments in the context of contemporary dental practice.https://www.bradford.ac.uk/archaeological-forensic-sciences/facilities/barc/BARC_human_remains_policy.pdf, https://www.sheffield.ac.uk/polopoly_fs/1.573395!/file/Guidelines_for_conduct_in_osteology_labs.pdf, https://www.museumoflondon.org.uk/application/files/5714/8129/0350/Museum_of_London_Policy_for_the_Care_of_Human_Remains.pdf). No permits were required for the described study beyond the written permissions given by the individual institutions responsible for the human remains. The study complied with all relevant regulations.Specimens were selected from five British cemetery assemblages dating to the medieval and early post-medieval periods (n = 130) and from four industrial era British cemeteries (n = 103) . The ethThe principal research question sought to identify differences in masticatory behaviours following the introduction of more heavily processed and softer dietary staples in the industrial period. Historical and archaeological evidence indicated that the majority of assemblages selected were largely representative of the average diet and lifestyle in either the medieval, early post-medieval or industrial periods . A rangeEach assemblage was dated to either the medieval and early post-medieval periods (1100–1700 CE) or the industrial period (1700–1900 CE). Where inhumations at a single cemetery overlapped both periods, contextual information for each burial had to be adequate to disentangle the earlier from the later burials. The only cemetery selected that required separation into early and later phases was St Michael’s Litten, Chichester (ESC11), which dated from 1550–1900 CE.Sufficient contextual information for each assemblage had to be available to characterise the general profile of the individuals interred at the site.Most of the assemblages included were selected because they were drawn from cemeteries of a substantial size  and likely reflected the average demographic for the period and region.If assemblages from approximately the same geographic region were available in the medieval, early post-medieval and industrial periods these assemblages were prioritised.The assemblage had to be available for examination within a suitable timeframe for data collection to be completed (September 2017 to September 2019).At least five individuals within the assemblage had to satisfy the individual selection criteria below. Larger assemblages were prioritised to increase the likelihood that this condition would be met.Many of the individuals examined dating to the medieval period were derived from lay cemeteries. The cemetery of All Saint’s Church, Fishergate, was situated south of the medieval city walls of York on the east side of the River Foss. The occupants of the cemetery were likely civilians drawn from a range of socioeconomic groups. It was likely established in the late 11th century and fell out of use shortly after 1585 CE . The skeOther medieval cemetery assemblages assessed also included monastic burials. The cemetery at Box Lane, Pontefract was likely associated with St John’s Priory, which was founded in about 1090 CE. Pottery recovered supports burial dates from the 13th to the 14th century. It is uncertain whether the cemetery served the Cluniac monks themselves or the lay population of the monastery and the community of nearby settlements. The cemetery included both women and men, with relatively few children, infants and adolescents, supporting the latter interpretation. Burials were modest and bodies were likely placed in shrouds without the use of coffins . The assth to the 17th centuries. Individuals with leprosy and males were concentrated in the southwestern portion of the excavation area whilst females, subadults and non-leprous individuals became more frequent in the northern area of the site. It has been proposed that the earliest portion of the cemetery is the southwestern portion where the prevalence of leprosy is greatest [A subset of the medieval material analysed was associated with the medieval leprosarium and later post-medieval almshouse of St James and St Mary Magdalene, Chichester, likely dated from the 12greatest .The industrial group was similarly drawn from a wide socioeconomic spectrum and included London, Chichester and the more northerly industrial centres of Wolverhampton and South Shields. The Litten cemetery, encountered during the excavation of Eastgate square, Chichester, was estimated to have been in use from 1100–1850 CE. Although, most burials date from the 17th-19th centuries. This cemetery likely represented a broad cross-section of the socioeconomic groups present at Chichester and could be divided between the pre-industrial and industrial groups in the current research using burial type . The earThe skeletal assemblages examined were drawn from a range of geographic locations and social backgrounds within England. Consequently, post-hoc pairwise testing was performed to determine whether any differences observed between the two groups were particularly driven by any of the assemblages examined. These factors are explored further in .Second lower molars were selected for OFA as it has been shown to provide an effective representation of masticatory behaviours in primates . OFA canIndividuals were prioritised if they had relatively good representation of the dentition, preferably with some representation of both the upper and lower dental arcades. The best-preserved side was chosen and in cases of an equivalent state of preservation the right side was analysed. Dental pathology, including ante-mortem tooth loss and dental caries, was present in many of the dentitions examined. Carious lesions were marked as present if a cavity involving the crown was observed on the tooth. The impact of these confounding factors  was previously assessed  and consIndividuals for whom sex and age-at-death estimates could be made were also prioritised. Sex was estimated by assessing the morphology of the pubic bone, cranium and greater sciatic notch of the innominate bone , 64. TheTo conduct dynamic OFA analysis, one individual was selected from the pre-industrial group and one from the industrial group to simulate power stroke kinematics. Individuals were selected with adequate preservation of the upper and lower tooth rows and who presented lower second molar wear facet patterns characteristic of each period; their wear facet area proportions approximated the centre values for either the pre-industrial or industrial group. 3D models of antagonistic upper and lower molar rows were required and generated using the methods outlined below.A dental gypsum model of one of the lower second molars was produced for each individual. The reflective and lustrous qualities of the enamel rendered the direct generation of 3D models from the original dental surfaces problematic , therefoet al. [Wear facet analysis was performed using GOM Inspect (Version 2018 Hotfix 6) based on the method of Kullmer et al.  Fig 2)..et al. [et al. , 70. Thiet al. , 72, modet al. . The areet al. , 39, 40.Differences in wear facet area composition were visualised using a ternary plot. A ternary plot is a diagram that displays three variables which sum to a constant (1 or 100%). Each axis corresponds to one of the three variables that form the composition . Observations are plotted within the equilateral triangle formed by the three axes. The ratio of the three variables for a given observation are graphically displayed based on the position of the plotted point within the triangle and the proximity of the point to the apex associated with that element of the composition. Ternary diagrams were produced in R statistical software (v.3.6.1) using the package ‘compositions’.In addition, the occlusal relief index (ORI) was calculated for each lower second molar, which provides a measure of the complexity and steepness of occlusal topography , 73, 74.https://www.for771.uni-bonn.de/for771-en/ofa) on one individual from the medieval and early post-medieval periods and one from the industrial period. It provides a complementary approach to the static analysis of the molar wear pattern by indicating the directions of occlusal movements involved in wear facet development. The software enables the simulation of the occlusal phase of the power stroke between antagonistic teeth and can be used to infer the kinematic relationship between sets of wear facets. The user can set a trajectory pathway for the lower teeth which approximates their movement during the power stroke. The software detects collisions between the teeth as they come into contact and are deflected along the surface relief of each other. Contact areas can be recorded and assessed as they develop during the power stroke enabling comparisons to be made between individuals, groups and taxa. For further details on the operation of the Occlusal Fingerprint Analyser software refer to Kullmer et al. [Kinematic simulations of the power stroke were conducted using the Occlusal Fingerprint Analyser software package developed by DFG Research Unit 771  was calculated for each lower second molar examined. Wear facet dip angle values satisfied the assumptions of normality and homogeneity of variance , therefore, differences in dip angle inclination between the two human groups were tested using the independent sample t-tests. Independent sample t-tests were also used to determine the effect of sex and age-at-death on wear facet dip angle in each of the human groups.The wear facet area composition in the molars differs significantly between the two groups  values were observed in the lower second molars of individuals dating to the industrial period  and homogeneity of variance could be assumed . Null hypothesis: ORI did not differ significantly between the two periods.Wear facet expression was not found to differ significantly between males and females in either the pre-industrial or industrial group   . The oldBPI dip angles were significantly less steep in the older age-at-death category . LPI andThe molars in the pre-industrial group performed a greater lateral displacement during phase I of the power stroke resulting in a more gradual increase in crown contact area relative to the industrial period  Videos. The study aimed to assess whether the dental occlusal pattern typical of individuals from the Industrial Revolution indicated changes in the occlusal power stroke when compared to their medieval antecedents. This was framed in terms of the dietary changes that took place during the Industrial Revolution, which were inferred from archaeological, historical and bioarchaeological evidence. Nine British cemetery assemblages were included and compared. Evidence for changes in the power stroke were inferred from the dental wear facet patterns of the lower second molars using OFA. Significant differences were found between the dental wear facet patterns of individuals dating from the industrial era and those from the medieval and early post-medieval periods.The dental macrowear patterns of the lower second molars of the pre-industrial group are characterised by significantly greater proportions of buccal phase I and lingual phase I wear when compared to the industrial group. This indicates differences in chewing behaviours between the two groups. A greater transverse jaw movement has been associated with the enlargement of lingual phase I wear facet areas in some modern hunter-gatherers . This inThe variance in dental wear facet patterns did not differ significantly between the two periods. Nevertheless, variance values are relatively large in both. This might derive from the inclusion of individuals of both higher and lower social status within the pre-industrial and industrial samples. In the medieval period, the quality and type of bread consumed varied between social classes. The upper classes ate fine wheaten bread while the lower classes would consume darker and coarser loaves of rye, barley and oats . For thest century [The increasingly steep wear facets and greater occlusal relief in the molars of the industrial group reflects a reduction in the transverse component of the masticatory stroke as well as a reduction in abrasive particles within the food eaten , 62, 85. century , 89–91.No significant differences in dental wear facet expression were found between the sexes in the industrial period. The bulk of the dietary staples consumed in the 18th-19th centuries would have been consistent between the sexes. Both sexes would have derived most of their calories from bread, potatoes, vegetables and sweetened tea. Men, within a lower-class urban setting, however, would receive the majority of meat that could be afforded. Even so, the quantity would likely be meagre and would therefore be less likely to impact habitual masticatory behaviours , 43, 92.2 value was associated with the differences in wear facet proportions between age-at-death categories in the industrial period when compared to the R2 value associated with the differences in wear facet proportions between the two periods  in individuals from the industrial period contrast with previous studies that have examined wear facet area proportions in modern hunter-gatherers and Palaeolithic anatomically modern humans and Neanderthals , 40 and % in indiSome authors have associated phase II facets with a grinding function, combining a flat-angled shearing and crushing action, during phase II of the power stroke , 36. ExpIn this model of food breakdown during phase I of the power stroke, material is cut initially along the edges of phase I wear facets. In addition, food particles are compressed against phase II wear facets, formed along the lingual slopes of the buccal cusps far down into central fossa of the lower molars, during the terminal part of phase I and during maximum intercuspation, proximate to or during the peak in jaw adductor muscle force. The extensive development of phase II wear facets when compared to the size of phase I wear facets in the industrial-era may, therefore, indicate that food breakdown during the power stroke may principally have occurred as a result of the crushing action against phase II facets during the terminal part of phase I.Dentists often desire predictable and stable outcomes for their patients during and following treatment . Dental st century have moved increasingly towards ultra-processed foods; they form the principal source of dietary calories in the USA and UK [As food properties are modified further in the future by both technological changes and social factors, more frequent and perhaps more marked disturbances related to dental occlusion might be anticipated. Diet in the 21A and UK –118. TheA and UK , 120. AnA and UK . Little A and UK –123. As S1 Text(DOCX)Click here for additional data file.S1 VideoThe movement trajectory of the lower teeth is more shallowly inclined and begins from a more laterally shifted position during phase I of the power stroke when compared to the industrial individual. Phase II occurs over a more elongated time segment and involved greater medial movement of the lower teeth.(MP4)Click here for additional data file.S2 VideoThis simulation showcases the movement trajectory of the lower teeth during the power stroke. Note an oblique angle of approach during phase I of the power stroke and a very brief phase II movement following maximum intercuspation.(MP4)Click here for additional data file.S1 File(PDF)Click here for additional data file.S1 Data(CSV)Click here for additional data file.


The overarching aim of the National Institute on Aging funded Adherence Promotion with Person-centered Technology (APPT) Project is to promote adherence to technology-based solutions designed to enhance the early detection and treatment of cognitive decline. The goal is to build and evaluate adaptive, tailored, and integrated technology-based adherence support systems for mobile software platforms that assess and train cognitive skill. The symposium describes the various steps of the development process of the APPT smart adherence support system. N. Charness will present an overview of the APPT project, its aims, and the clinical trials designed to assess the effectiveness of the APPT smart reminder system compared to typical reminder systems. S. Chakraborty will present detailed analyses of past cognitive intervention data to inform understanding of who is likely at risk for poor adherence and how adherence lapses might be predicted in advance to provide just-in-time adherence support. D. Carr will present an exploration of motivating factors for participants to engage in research, and these motivations will be tapped to help develop motivational messages for the APPT adherence support system to be used in the two planned clinical trials. M. Dieciuc will provide additional insights into motivations for engaging in home-based cognitive assessment and training derived from a focus group study. Finally, S. Zhang will describe the results of an initial pilot study examining the effectiveness of motivational reminder messages that match vs. mismatch participants’ own motivations. All results inform the design of the APPT system to maximize adherence.


However, it is unclear how the coronavirus disease (COVID-19) pandemic has affected this outcome and whether it can be reasonably used as an outcome for ongoing cohort studies. Understanding this will provide suggestions for handling this outcome in cohort studies and also indicate support measures for older adults. Thus, we report the impact of the first wave of the COVID-19 pandemic on new applications for LTCI in our metropolitan cohort.In epidemiological studies of older Japanese adults, new certifications for long-term care insurance (LTCI)3 Using these data, we calculated the number of new applications for LTCI per 10,000 people every month from January 2018 to July 2020. The World Health Organization (WHO) declared COVID-19 a global pandemic on March 11, 2020. In Japan, the national government declared a nationwide state of emergency from April 7 to May 25, 2020. Thus, we compared the number of new LTCI applications in the period up to February 2020 with the period after March 2020. We applied regression analysis to the number of new LTCI applications from January 2018 to February 2020 and predicted the number of new LTCI applications after March 2020 using the regression equation. Finally, we compared the predicted and actual numbers of new LTCI applications.We investigated the applications and certifications for LTCI and mortality information of 15,500 stratified and randomly sampled residents aged 65–84 years of Ota City, Tokyo, in 2016 to verify the effectiveness of community-wide intervention.Figure These results indicate a clear trade-off between the number of new LTCI applications and the waves of the COVID-19 pandemic. In the valley of the first and second waves of the pandemic (June 2020), the number of applications jumped more than the previous trend. The new LTCI application may have been simply postponed until the nationwide state of emergency was lifted. However, it should be noted that the number of outcomes regarding LTCI may be underestimated during the waves of the COVID-19 pandemic in ongoing cohort studies.A major explanation for this phenomenon may be that older adults and their families avoided applying for LTCI due to concerns about COVID-19 infections. Future investigations are necessary to clarify the reasons for the decrease in applications. Investigations of regional differences are also required because the COVID-19 pandemic has spread from metropolitan areas to local areas, causing regional differences in infection status, including a time lag. Finally, we should continue to carefully monitor the transition of LTCI applications after the second wave of the pandemic because refraining from various activities due to the COVID-19 pandemic for long periods may lead to functional decline in older adults. As the pandemic continues, it is necessary to discuss how to handle health outcomes regarding LTCI in ongoing cohort studies during the COVID-19 pandemic. Although we cannot generalize conclusions from our results alone, we believe this report can lay the groundwork for further discussion.


Despite growing milk demand and imports, market-oriented milk production and formal processing in Ethiopia is limited to areas around Addis Ababa, notwithstanding its competing land use demand. This study assessed biophysical and market potential for developing the dairy sector, characterizing Ethiopian dairy clusters. Biophysical data from geographic information system (GIS) sources and information from key informants were combined in mapping and ranking these clusters on milk production potential. Twenty-four indicators in six major categories were applied for this assessment: feed availability, environmental conditions for dairy cattle, current production status, access to inputs and services, output market access, and production expansion potential. Feed availability  were the main drivers for dairy development, followed by the current production status, mainly driven by number of (improved) dairy cattle and  milk volumes. Dairy clusters close to Addis Ababa had the highest overall scores for development potential, mainly determined by local demand and access to inputs. For dairy sustainable dairy development in Ethiopia, companies seeking long-term opportunities may avoid the Addis Ababa area and develop dairy production and processing in other clusters especially in Amhara and Tigray regions, with good milk production potential but less developed market infrastructure. The combination of biophysical data and key informant knowledge offered key strengths in delivering valuable results within a short time span. It however requires a careful selection of knowledgeable key informants whose expertise cover a broad scope of the dairy value chain.The online version contains supplementary material available at 10.1007/s11250-021-02695-2. Ethiopia has great opportunities for development of its dairy sector, as many parts of the country have a favorable agro-ecology for dairy cows. As second most populated country in Africa, Ethiopia is also one of the fastest-growing economies in the world  in the area SAI Platform . For susIn this component, social and human capital are considered: the skills of workers and the incentives they are offered. Socially sustainable farms should provide a positive impact within their local community SAI Platform . The govCurrent production conditions are subject to various changes that could affect future production potential. For example, Ethiopian woodlands are subject to serious environmental impacts due to heavy pressure causing them to shrink over time due to extraction of fuel and construction wood and expansion of cash crops like sesame in the northwest , Amhara (Metema area), and Benishangul-Gumuz (Sherkole area) over the 25-year period of 1985–2010 , giving an overview of dairy production and marketing chains and identifying a first draft list of indicators for distinguishing areas with a good dairy potential  within the clusters. Assessment of all primary data collected leads to a final delineation of the borders of clusters and to adjustments in the initial scores.Primary 5.Maps were created using the new data collected from districts, showing the current milk production per square kilometer for the different clusters. The clusters were characterized using the biophysical potential data collected in step 2 and the primary data collected in step 4.6.Review meetings involving regional and national key informants validated the results. These meetings provided additional information about strengths and weaknesses of the various clusters and performed a scoring on the potential of their region based on a list of 24 indicators described in Table 7.report  in Table Dry matter productivity (DMP), an indicator for the biomass production per ha. This indicator is strongly related to main category a (feed availability) in Table Percentage of agricultural land cover. This is an indicator for the percentage of land used for agriculture. Low percentages denote limited agricultural activities, limiting the availability of local crop residues and by-products for dairy production.Figure The combination of these three indicators delineates areas where dairy cattle can endure in terms of climatic conditions, and at the same time, their owners could easily access feed. Such areas are represented by the greenish shade in Fig. 2 in most cases is higher inside the selected clusters than outside them. Figures 7From Figs. This section assessed the dairy potential of all fourteen clusters based on two sources of data: (i) scoring of each cluster based on the 24 indicators of Table Based on the average scores per category of indicators Table , the NorThe highest scoring clusters Fig.  are stroAll identified clusters are within 100 km distance zones from cities with over 50,000 inhabitants, showing a linkage between potential production and possible markets for both inputs and outputs. Most of the clusters identified in this study are similar to those identified by Brandsma et al. , confirm2) and Fig. From Figs. From Fig. Table Figure Milk production and processing is most strongly developed in areas in the proximity of Addis Ababa. Figure In Amhara, the score for market is higher in Bahir Dar-Debre Markos as compared to Gondar-Debre Tabor Table , as low The approach of combining biophysical data and key informants assessments to identify and to estimate potential milk production areas was successful in generating large and useful datasets. The presentation in maps using several layers is an easy way to show different indicators in one picture, helping in demarcating high potential areas from low potential ones. Open GIS-databases can cost-effectively provide a large share of the required data. Additionally, the use of key informants creates opportunities for interaction between them, reducing bias and harmonizing outputs.The collection of actual data on dairy cattle numbers and milk volumes within districts from the investigation area was very time-consuming. The data collected was incomplete, and in some cases, the data format varied between districts, making comparability difficult. This made us use more data from reputable open sources.The process to optimize and standardize the scoring of indicators in all the dairy clusters took more time than was expected. The lack of dairy specialists able to oversee many aspects of dairy production across all regions has complicated the process of standardizing the assessment scores. We concluded that, to make the process of scoring more efficient and to make the scoring more uniform, selected key informants should have a broad overview of the dairy sector, including knowledge of regional aspects of the clusters.The addition of strengths and weaknesses of the dairy clusters compensates for the somewhat limited expressiveness of the key informant assessment. We have therefore aligned the outcome of this assessment with the identified strengths and weaknesses.Despite the abovementioned advantages of the applied methodology, some weaknesses were also perceived:Considering the aforementioned characteristics of this key informant approach, we recommend its application in other countries whenever a quick and cost-effective assessment of the potential of the dairy sector is desired. This should be adapted to the biophysical and socioeconomic context of the country and should also identify the strengths and weaknesses of each region.The developed assessment approach was successfully applied: the combination of data collection and key informant assessments leads to identification of clusters in Ethiopia with a potential to increase milk production in the future. These clusters have been ranked, and their strengths and weaknesses elaborated in such a way that both public and private investors could find the results useful in planning future investments in the dairy sector.It will pave the way for future investments in other potential areas next to central part of the country where dairy production, processing, and marketing could be intensified. The study could also contribute knowledge that fosters public-private partnerships targeting the development of input and service provision systems, in order to fully realize the biophysical potential of identified dairy production clusters.Companies seeking for opportunities in the long term may choose to invest in other clusters further away from Addis Ababa, which have a good milk production potential but less developed markets. This will require development of dairy infrastructure (a reliable milk transportation chain) and additional interventions to improve services for dairy farmers.The applied methodology has strengths in its geographical presentation, using several layers of maps from open GIS databases to demarcate potential areas, and in its triangulation with key informant knowledge, which ranked and generated more information on strengths and weaknesses of specific clusters. This approach could also be adapted and applied in other countries or regions globally, whenever a cost-effective option for identifying areas for sustainable dairy or agricultural development is solicited.ESM 1(DOCX 16 kb)ESM 2(PDF 402 kb)ESM 3(XLSX 24 kb)ESM 4(XLSX 25 kb)


This paper presents the development of a life-cycle assessment (LCA) framework for quantifying the carbon footprint of individual households based on detailed household survey data. According to household consumption and production patterns, the comprehensive life-cycle assessment framework is designed with clarified life-cycle boundaries. The framework covers eight types of specific living activities of rural households generated from a large-scale household survey in the Three Gorges Reservoir area in China. Both carbon emissions and carbon sequestrations of households’ consumption and production activities can be assessed, and eventually the integrative carbon footprint is evaluated. The LCA framework enables comprehensive and relatively precise assessment of carbon footprint at a household level and thus adds value to studies in the fields of carbon emission reduction, carbon neutrality and climate policies.  Specifications table1The approach of life-cycle assessment (LCA) facilitates a systematical view in environmental evaluation of a product from raw material extraction, manufacturing, and utilization to ultimate disposal Overall, LCA is widely applied to evaluate the environmental impacts of product, process, or activity. First, an individual product's environmental impact could be assessed within a LCA framework, such as the different environmental impacts of various building materials Despite the broad application of LCA in specific individual production processes or aggregated activities, no explicit framework has been designed to assess the carbon footprint of overall household activities based on survey data. The existing research has either focused on specific household activities This study developed an improved LCA framework for quantifying the carbon footprint of rural households. The framework aims to assess carbon emissions and carbon sequestrations of households' living and production activities and eventually evaluate their integrative carbon footprint. The present paper introduces especially the methodology framework, the assessment process and the data requirements. A separate co-submission paper covers the application of the method in the Three Gorges Reservoir (TGR) area in China, where details of the data collection, data analysis, research area, results analysis, and relevant policy indications were introduced.2•Process LCA for agriculture and livestock related processes.•Input–output LCA for consumptions of energy, food, housing and transportation.•Hybrid LCA for afforestation processes in production and the clothing in household consumptions.This study designed a framework for calculating the carbon footprint based on households' consumption and production patterns . In the The consumption activities of a rural household cover direct energy consumption  and other consumption of food, housing, transport, and clothes. The production and processing stages of these goods all involve energy consumption and associated carbon emissions. The household production activities include agriculture, livestock rising and economic afforestation according to a field survey with the households. On the one hand, carbon-capturing processes occurred through biomass growth and soil carbon sink in agriculture and forestry. On the other hand, these production activities also emit carbon through the material inputs, including fertilizers, pesticides and plastic films during the crop planting process. Both emission and sequestration processes are assessed separately in the present LCA framework  to evaluThe household carbon footprint is assessed in the scope of living consumptions, household production, and the production chain of the consumed products. A specific application of the framework was carried out using households survey data in the Three Gorges Reservoir (TGR) area in western China, and the results are presented in a separate co-submission paper.3–––The overall carbon footprint of households is calculated using 3.1Carbon emissions of direct energy are mainly generated from the consumption of fossil fuel, biofuel and electricity. The annual carbon emission of household i from the direct energy thus depends on the fuel type d, the amount of fuel consumption  emission factors and the amount of consumed products . For theThe carbon emission factors of various indirect consumption are adopted from literature references. Specifically, carbon emissions from both self-produced food and purchased food are all considered in the calculation by different types and with different emission factors. In addition, the consumption data in the transportation category are mostly the spending of fuels or public transportation, which should be first transformed into the amount of fuel according to the average price of the fuel or the ticket price of the public transportation in the same year. Afterwards, the carbon emission of transportation can be calculated by the amount of the consumed fuels and its relevant emission factors.The calculation of carbon emissions from clothing follows the carbon emission functions of durable consumer products in response to the long lifetime of clothes (2–10 years varied by different clothes). The detergents and electricity consumed in the washing processes are also considered as short-lived products. Besides, electricity consumption is not repetitively included in the category of clothing consumption because the overall household electricity consumption has been included in the direct energy consumption category. The other durable consumer products and housing were also approximately calculated according to different housing structures 3.3Carbon footprint processes were assessed in many agricultural activities . Though with large amount of labor migrations, crop productions have been keeping increasing in West China –In summary, the annual carbon emissions and sequestration of household production activities are illustrated in In addition, at the final harvesting stage, the produced grains might be consumed or stored by the household or sold to others. The storage processes are assumed with no carbon emissions, while the sold grains are potentially consumed in other regions and thus emit carbon. Since the sold parts are no longer relevant to the surveyed households or the studied area, they are not considered in this research.3.4–Afforestation and economic tree plantation is another major carbon sequestration section in the mountain areas of west China As reported in the study of 3.5The carbon footprint of livestock raising by households was assessed with consideration of its four stages : fodder –The annual carbon footprint of livestock raising are calculated according to equation 7:The final livestock trading stage is the same as the trade process of crops, which is thus neglected in the present study.4The LCA framework developed in this study was applied to a case study in the Three Gorges Reservoir area in west China, which acts as a validation process. We utilized the household survey data collected from the case area to test the feasibility of the framework.4.1The input data was taken from a large-scale household survey in selected districts and villages at the TGR area in 2016 and 2017. The TGR area has a subtropical monsoon humid climate with an average annual temperature of approximately 18 °C. The annual rainfall is approximately 1000–1200 mm, which is abundant but temporally and spatially uneven A survey household is defined as a group of people living together in one house that is considered as their primary home. Out-migrant workers who do not have another independent home are considered members of the household. Accordingly, the annual household income is the sum of incomes from all household members, including their employment, private enterprise, agricultural income, pension and government subsidies. The survey relies on the accounting of households’ daily spending and incomes. To ensure the data accuracy, the survey thus targeted to talk with the head of a household, who is in charge of the household economic management. In total, 422 valid questionnaires were collected from the TGR area.1)Basic characteristics of the household, including all members’ age, gender, marriage status, education level, profession, health status, etc.2)Socioeconomic characteristics, including the main sources and amounts of household income as well as the investments and benefits of their economic activities.3)Household consumption, including mainly the direct and indirect energy consumption associated with transportation, housing, clothing, food consumption, and other daily living expenses. The survey relies on people's memory and awareness. Thus the survey targeted to talk with the head of a household to obtain annual household data.4)Household production activities, such as crop production, livestock raising and forestry. The detail in terms of all the input materials, land size, crop type, tillage method, irrigation method and all yield production are required in the survey data.The survey data covers 100 questions of four major aspects  regardin4.2The detailed survey data could apply to the comprehensive life cycle assessment framework to evaluate a household's environmental influences (carbon footprint). Without the comprehensive life cycle assessment framework, the survey data might be failed to present the household carbon footprint. First, the detailed survey would record the same data in different categories, such as the gasoline consumption data might be re-collected in the transportation category. Second, the output products through one production category might be re-consumed by other consumption or production activities. For example, crop production output might be consumed in the food consumption or livestock feeding processes. Third, the survey data could be recorded by different units in terms of amount or spending which need to be converted to a uniform form.The household life cycle assessment framework sets up a scope for the carbon footprint calculation with a clear boundary of each consumption and production activities. The innovation of presenting the clear corresponding life-cycle for each household activities firstly improves the explicitness of consumption and production in each category; secondly avoids the duplicate carbon footprint calculation of same consumption from different category and offset the value both existing in the consumption and production categories. For example, the agricultural production activity is exhibited by the whole processes from the preparation stage to the handling stage, and its relevant carbon footprint LCA will be the LCA processes. Another very inspired improvement of this research is the inclusion of household afforestation activities, which rarely existed in former studies. The household LCA framework described in this article could be widely used for households in urban or rural areas because it covers both consumption and production activities.Despite these clear advantages, the household LCA framework does not include household received service goods. Future research could further expand the household LCA framework by including the carbon footprint of consumed service categories, which might be mostly characterized by urban households, such as take-away food delivery, online shopping delivery, etc. Assessing the carbon footprint of these modern service activities would provide an insight into the household environmental influence differences between urban and rural households.4.3•Include the carbon footprint of service products, which are expected to increase fast in the rural areas along with the general social-economic development.•Apply the LCA framework in various regions with diverse rural livelihoods, e.g. in geographically plain areas in East China, and in developed countries in Europe.•Compare the carbon footprint of rural households and urban households, and thus to enable an integrated assessment of carbon footprint in a rural–urban system.As shown in the co-submission paper, the improved LCA framework produced valuable information on the carbon footprint of rural households in the mountainous west China. To reach a further enhancement of the study, next research steps are expected to:The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.