Monkeypox virus, the causative agent of monkeypox. Subsequent real-time PCR testing at CDC on May 18 confirmed that the patient was infected with the West African clade of Monkeypox virus. Since then, confirmed casesOn May 17, 2022, the Massachusetts Department of Public Health (MDPH) Laboratory Response Network (LRN) laboratory confirmed the presence of orthopoxvirus DNA via real-time polymerase chain reaction (PCR) from lesion swabs obtained from a Massachusetts resident. Orthopoxviruses include Monkeypox virus, West African, and Congo Basin, the latter causing more severe illness  announced a confirmed monkeypox case on May 7, 2022, in a traveler returning from Nigeria. On May 14 and 16, UKHSA announced a second unrelated cluster of two cases and a third clustered group of four cases identified at sexual health clinics; the four-case cluster involved persons who identify as gay, bisexual, or MSM.Massachusetts. On May 4, a Massachusetts resident developed an anogenital rash 3 days after returning from international travel. This rash progressed to vesicles and pustules and spread to the face and trunk; the patient sought medical care four times at outpatient clinics during May 4–12, during which time common causes were ruled out. The patient was hospitalized on May 12 for management of refractory perianal pain from the rash. Prompted by UKHSA’s announcement regarding the recent monkeypox cases, clinicians notified the MDPH and CDC for testing. On May 17, the patient received a diagnosis of confirmed Orthopoxvirus by the Massachusetts LRN laboratory, and CDC confirmed Monkeypox virus West African clade the following day. The local hospital infection prevention team, MDPH, and CDC responded to identify contacts and determine exposure risk, facilitate PEP with one of two orthopoxvirus vaccines  was evaluated for an oral lesion, and a new painful, perianal rash; the patient was tested and treated for a presumed common STI and sent home. The rash spread, progressing to pustules, and the patient was seen again and treated for a different STI; all testing results were ultimately negative. On May 19, after the announcement of the monkeypox case in Massachusetts, a clinician caring for the NYC patient notified the NYC Department of Health and Mental Hygiene (NYC DOHMH) about the possibility of monkeypox. The patient received a positive orthopoxvirus test result at the NYC LRN laboratory and continued to isolate at home. NYC DOHMH began identifying contacts, determining exposure risk, and facilitating PEP for at-risk contacts.Other U.S. states. Over the next 5 days from the identification of the NYC case, multiple states received notifications from clinicians about suspected monkeypox cases; on May 23, an incident command structure was created within CDC’s National Center for Emerging and Zoonotic Infectious Diseases to respond to this outbreak. As of May 31, nine states  have reported 17 patients with confirmed orthopoxvirus infections, which until proven otherwise, are considered to be Monkeypox virus during this outbreak response .https://stacks.cdc.gov/view/cdc/117900). In addition to skin rash, patients commonly reported chills (12), fatigue or malaise (11), and lymphadenopathy (nine); fever was reported in seven patients , and all had rash onset dates during May 1–27; three patients were immunocompromised. Diagnosis of an orthopoxvirus infection occurred an average of 11 days after rash onset (range = 0–21 days) . One patient was treated with tecovirimat, an antiviral agent from the strategic national stockpile with antiorthopoxvirus activity, licensed for smallpox but available from CDC under an expanded access Investigational New Drug protocol  for 21 days following last exposure.Genome sequencing results from virus recovered from the patient in Massachusetts display similarities to other published genomes in this outbreak from Europe (Nextstrain/monkeypox)***Monkeypox virus infection in human monkeypox outbreaks  is the most significant risk factor for The following measures can be taken by the public to prevent infection with monkeypox: 1) isolate ill persons from uninfected persons; 2) practice good hand hygiene and use appropriate personal protective equipment to protect household members if ill or caring for ill persons at home ; 3) use an Environmental Protection Agency–registered disinfectant with an emerging viral pathogens claim that is found on EPA’s List Q for disinfection of surfaces.Orthopoxvirus at an LRN laboratory is presumed to be monkeypox and is actionable for antiorthopoxviral treatment, and by public health authorities to initiate isolation, contact tracing, monitoring, investigation, and PEP of exposed contacts. PEP with smallpox vaccines remains available from the strategic national stockpile for eligible exposed persons.CDC urges health care providers in the United States to be alert for patients who have rash illnesses consistent with monkeypox, regardless of a patient’s gender or sexual orientation or a history of international travel or specific risk factors for monkeypox. Clinicians should contact their local or state health department if they suspect a case of monkeypox. There are 110 LRN laboratories available and equipped for rapid diagnostic testing of emerging pathogens across the United States; currently 68 test for orthopoxviruses. The prolonged interval from rash onset to positive test result was reflective of delays in clinical suspicion of an unfamiliar illness; all patients had results within 0–2 days after specimens were collected. During this outbreak, a positive test result for an As the source and spread of this outbreak are being investigated, it is crucial to assess all possible modes of transmission and identify risk groups, as well as institute appropriate public health preventive measures. CDC is providing guidance on case definitions, identification of contacts, clinical management, and infection control and prevention within health care facilities and the home, creating resources for disseminating information on monkeypox, and supporting laboratory testing infrastructure domestically and globally.Monkeypox virus, is endemic in several Central and West African countries. Cases in persons outside Africa are often linked to international travel or imported animals.Monkeypox, a rare disease caused by infection with CDC is tracking multiple reported U.S. monkeypox cases, and monitoring cases in persons in countries without endemic monkeypox and with no known travel links to an endemic area; current epidemiology suggests person-to-person community spread.CDC urges health departments, clinicians, and the public to remain vigilant, institute appropriate infection prevention and control measures, and notify public health authorities of suspected cases to reduce disease spread.


Several global initiatives put parent involvement at the forefront of enabling children’s well-being and development and to promote quality of care for newborns and hospitalized young children aged 0–24 months. Scanty evidence on mistreatment such as delays or neglect and poor pain management among newborns exists, with even less exploring the experience of their parents and their hospitalized young children. To address this gap, authors reviewed research on experience of care for hospitalized young children and their parents, and potential interventions that may promote positive experience of care.A scoping review of English language articles, guidelines, and reports that addressed the experiences of care for newborns and sick young children 0–24 months in health facilities was conducted. Multiple databases: PubMed, PROSPERO, COCHRANE Library and Google Scholar were included and yielded 7,784 articles. Documents published between 2009 and November 2020, in English and with evidence on interventions that addressed family involvement and partnership in care for their sick children were included.The scoping review includes 68 documents across 31 countries after exclusion. Mistreatment of newborns comprises physical abuse, verbal abuse, stigma and discrimination, failure to meet professional standards, poor rapport between providers and patients, poor legal accountability, and poor bereavement and posthumous care. No literature was identified describing mistreatment of hospitalized children aged 60 days– 24 months. Key drivers of mistreatment include under-resourced health systems and poor provider attitudes. Positive experience of care was reported in contexts of good parent-provider communication. Three possible interventions on positive experience of care for hospitalized young children (0–24 months) emerged: 1) nurturing care; 2) family centered care and 3) provider and parental engagement. Communication and counseling, effective provider-parental engagement, and supportive work environments were associated with reduced anxiety and stress for parents and hospitalized young children. Few interventions focused on addressing providers’ underlying attitudes and biases that influence provider behaviors, and how they affect engaging with parents.Limited evidence on manifestations of mistreatment, lack of respectful care, drivers of poor experience and interventions that may mitigate poor experience of care for hospitalized young children 0–24 months especially in low resource settings exists. Design and testing appropriate models that enhance socio-behavioral dimensions of care experience and promote provider-family engagement in hospitals are required. The United Nations’ Sustainable Development Goals include targets the reduction of neonatal mortality to 12 deaths per 1,000 live births and under five mortality to 25 deaths per 1,000 live births by 2030 [The quality of care for hospitalized newborns and young children is intrinsically linked to experience of care across the life-course continuum (starting from their mothers’ pregnancy through her childbirth experience and thereafter) and recognized in global frameworks that view quality as a combination of service delivery and experience of patient care –6. QualiTo fill this gap, the authors conducted a scoping review to map the research on experience of care and related interventions for young children from birth to 24 months and their parents in hospitalized and outpatient settings. The focus was on manifestations of mistreatment and their drivers during care for young children up to 24 months, positive and negative experiences of care and, potential interventions that reduce mistreatment, promote provider communication and family engagement in their children’s care globally, including in low- and middle-income countries. Evidence from this scoping review alongside formative research in select hospitals in Kenya (not presented in this paper) will be used to identify a contextually relevant model to improve experience of care for parents and families seeking services for hospitalized newborns, infants and young children up to 24 months in a low-income setting. For the purpose of this paper, we use the term “young children” for those who are 0 to 24 months unless otherwise specified.Scoping reviews map key concepts within a research area, the main sources and types of evidence available, and can be used for concurrent pragmatic aims, including summarizing and describing a particular concept (e.g. experience of care for young children and their parents or related-interventions), its characteristics, and identification of gaps and areas of future research and practice , 18. GivOur search strategy drew on guidance from the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) . Five reNurturing Care for Small and Sick Newborns: Evidence Review and Country Case Studies” [The search terms and their corresponding definitions are presented in Studies” . DocumenTwo reviewers (CN and CO) extracted data by reading the full text articles, guidelines and reports that met the eligibility criteria and retained through the iterative charting process. Reviewers extracted information, using Microsoft Excel, on each document’s publication-related data , geography and context, study and data type, manifestations and types of mistreatment and positive experiences of newborns and sick young children, of family centered care (FCC), quality of care, intervention elements—including partners and funders. They reviewed the relevance and type of evidence and summarized these broad emerging themes to map out areas for future programmatic research.The initial search in PubMed, PROSPERO, COCHRANE Library and Google Scholar yielded 7,784 results and after exclusions, 246 were retrieved as potentially eligible papers.After exclusions, 68 published papers, grey literature, guidelines and strategy documents aimed at defining normative practices among young children 0–24 months of age were included. The analysis synthesized findings from single- and multi-country studies conducted across 31 countries, including Global (n = 18); high income countries in Europe (n = 13), North America (n = 15) and Australia (n = 2); low- and middle-income countries (LMICs) in South America (n = 2); Asia (n = 6) and sub-Saharan Africa (n = 13). Many papers focused on newborns aged between 0–28 days including stillbirths, premature babies, and neonatal deaths (n = 42). The remaining literature centered on children 59 days and older (n = 26); of these, very few papers had evidence that was exclusive to young children up to 24 months old (n = 4). The remaining 19 (of the 26) addressed under five or pediatric care in older children but were retained as they met the other inclusion criteria and featured learnings on interventions around the 0-24-month age group.The results from the scoping review are described under three main domains: 1) experience of care for hospitalized young children and their caregivers; 2) drivers of negative experience of care of hospitalized young children and their caregivers; and 3) interventions to promote positive experience of caregivers and their hospitalized young children. Where possible, each domain describes issues pertaining to hospitalized newborns and young infants (0–59 days) and infant/young child (60 days– 24 months) separately. We found 15 articles on experience of care , 11 on dNegative experiences of care manifest in various forms and were described in eight studies . MistreaNegative provider attitudes manifest as unfriendly verbal expressions or lack of attendance to parents when they complain about care. This may lead to distrust in the health system and influence women’s future care-seeking decisions for future childbirth at facilities, postnatal care, and accessing essential child health services . Health Negative experiences also occur as a result of poor provider communication with parents on caring for their hospitalized young children (n = 9). Studies show that women, were often poorly informed about clinical practices and procedures, lack autonomy to make treatment choices for their newborns; in cases of small and sick newborns, this can lead to emotional crises including maternal post-traumatic stress, anxiety and depression , 25–27. Positive experiences of care, across (n = 12) studies, were reported where parents were able to express their opinions’ on care given to their newborns and when there was good communication between providers and parents , 33, 34.Twelve studies describe the various factors influencing or “driving” negative experiences of care within health systems and among communities, and from individual providers.Under-resourced health systems, and specifically at facility level, contribute to drivers of patient mistreatment. Often due to weak infrastructure and limited equipment, including lack of such basic elements such as running water, crowded units with limited bed capacity (where newborns are often sharing incubators or cots), noisiness, lack of privacy, lack of life saving commodities and facility policies, poor adherence to policies and guidelines and poorly trained staff are especially acute factors.In a multi-country study, readiness for skin-to-skin implementation in newborn units was extremely rare , and faiThis scoping review found 40 studies of interventions that may improve experiences of care, reduce mistreatment, or improve provider and parent communication and partnership whereby parents are central to caregiving. Of these, 14 were review articles, three were randomized control trials three pilot interventions, one was an implementation study, and two were evaluations.In this review we refer to the WHO’s Nurturing Care Framework , as it pThe interventions discussed in this review are not mutually exclusive but focus on encouraging positive interactions between providers and parents. Some interventions emphasize the use, adaptation, or development of policy guidance, care protocols and job aids, parental or provider trainings, and use of technology to support an implementation. Nurturing care emerged as an approach that enhance physical, emotional and cognitive development. To effectively implement nurturing care three main interventions that can enhance nurturing care emerge from this review that may improve the experiences of care for newborns and young children: nurturing care, family-centered care, strategies to enhance parental/family engagement which all underscores provider communication and counseling skills.“a stable environment that is sensitive to children’s health and nutritional needs, with protection from threats, opportunities for early learning, and interactions that are responsive, emotionally supportive, and developmentally stimulating” [Three studies; all of which are global reviews and one WHO framework describe approaches to ensure nurturing care. Nurturing care is defined by Britto et al. as ulating” . InterveIn the long term, nurturing care promotes a child’s physical and cognitive development, reduces morbidities and mortalities, and prevents disability injuries and deaths , 20, 48.This review shows that nurturing care during management of pre-term births and those born with complications is associated with outcomes such as early bonding, facilitated by skin-to-skin contact, and early initiation of breastfeeding, facilitated by a companion to support the new mother , 20. OthFamily-centered care (FCC), described in 14 studies, places parents, families and caregivers at the center of newborn and young childcare. Family centered care is an approach to care delivery that promotes a mutually beneficial partnership among parents, families and healthcare providers to support health-care planning, delivery and evaluation. The principles of family-centered care include: dignity and respect; information sharing; participation; and collaboration . This moFCC involves time-sensitive dual communication between parents and multi-disciplinary team members who coordinate care transition through emotional, educational, medical, and home visit support for families. FCC is also an approach that promotes mutual benefit among parents, their families and providers through dignity and respect; information sharing; participation; and collaboration . ImplemeFCC promotes a healing and nurturing environment that fosters care and protection for better linguistic, cognitive, motor, social, and emotional development, and improved psycho-social outcomes of young children under five years of age. FCC depends on providers’ knowledge and abilities to apply FCC core concepts during their interactions with parents. A randomised controlled trial evaluating FCC of sick newborns admitted in a NICU showed that babies of mothers or families trained and involved in FCC showed lower rates of nosocomial infections than a control group (not trained in FCC) though not significant . FCC impStudies show that family members report satisfaction with their health care experiences involving FCC due to the transparency of care, allowing parents to be at the infant’s bedside , and proEight (n = 13) studies describe parental engagement as a promising strategy to enhance effective parent and provider communication for meaningful participation in their hospitalized child’s care. WHO’s Framework for Improving the Quality of Pediatric Care recommends effective provider and parent communication and meaningful parental participation . Parent Models, which educate health providers on how to communicate and provide end-of-life care, are particularly beneficial in dealing with bereavement or events after the death of a child , 55, 60.Family and parental engagement has also been associated with greater acceptability of exclusive breastfeeding, immediate breastfeeding after birth, and skin-to-skin care and infant warmth. Parental engagement also enhances families’ involvement in decisions, when parents are well-informed of what is expected of them for the care of their children in newborn units . The eleOne challenge to parental engagement strategies is the power imbalances between parents, families and their clinicians, with providers’ values and preferences potentially hindering consideration of families in decisions during care . A studyCentral to nurturing care, family centered care and family/ parental engagement as well as other child health interventions is the quality of provider communication and counselling. Several studies (n = 13) focused on strategies to improve communication between providers and parents. Effective communication between providers and parents is integral to improve health care, reduce medical errors, and better health care seeking. Parents play unique and integral roles in judging their child’s symptoms, and they need to be given information on care during their child’s hospital stay to ensure adequate care and follow up at home .A global systematic review found that parental capacity, confidence, and communication with providers is key for joint decisions for pre-term and acutely ill infants as they transition within or between health care settings . Few stuharmful errors (preventable adverse events) such as delay in treatment or skin breakdown from oxygen tubing decreased significantly, by 38 percent post-intervention [A pediatric unit study found that although a structured communication intervention for families and providers did not change, the overall rate of medical errors  such as administering penicillin to a patient with a known penicillin allergy, rvention . A reviervention .A study in Brazil and a systematic review conducted in the United States found that involving parents during medical ward rounds, in discussions with clinicians about their sick children’s care, was instrumental in improving communication and understanding of information—and confidence in the medical team , 80. ParMost interventions on communication counselling centered around information-sharing and provider development of parental capacities for specific skills through routine clinical counseling, observation and recommendations for care practices, and use of technology to promote follow up. A meta review observed that health workers should receive training in communication skills during their pre- and in-service health education. Implementation of most parent-targeted interventions emphasize regular interpersonal communication between parents and providers, with respect, confidentiality, comfort and support during care, engaging clients in care decisions, with continuity of care and audit and client response mechanisms .A study in the Middle East on implementation of the Integrated Management of Newborn and Child Initiative (IMNCI) for children under five years of age found that, although clinician competency improved for assessing, classifying, and treating illnesses according to IMNCI guidelines, transferring complementary skills to parents required more attention . InadequThis scoping review describes literature on experience of care for sick young children (24 months of age and younger) and the experiences of their parents or caregivers, the factors driving negative experience of care, and interventions to improve these experiences and address the emotional needs of parents with sick young children. The 68 published and grey literature documents assessed from the last 10 years reveal that findings on mistreatment of young children, positive experiences, and interventions in a hospital setting emerged primarily from Asia, Europe, or North America, while most literature on the drivers of mistreatment is from sub-Saharan Africa. Overall, the literature on experiences of care is limited; there is little on mistreatment of newborns and young children (particularly infants and young children of ages 60 days to 24 months) and even less on how to mitigate mistreatment broadly. Interventions to improve the experience of care—nurturing care, FCC, parental engagement, and provider communication—are generally implemented in high income settings, with a paucity of evidence on how such models can be implemented in low income settings, with a focus on small and sick newborns and young children with chronic illnesses or conditions. Existing models do not sufficiently distinguish how provider norms and attitudes toward parents affect their interactions and behaviors.All children have a right to respectful and adequate health care that considers their behavioral and developmental needs, and is sensitive to the emotional and psychological needs of their caregivers –88. AuthThis scoping review shows that the drivers of negative experience of care are well documented, especially for newborns (n = 10), but little evidence exists for young children up to 24 months (n = 1). Factors driving inadequate provider care include inadequate knowledge, poor communication and interaction with parents, and poor personal and professional attitudes. Factors affecting care at facilities include high workloads with inadequate staffing, commodities, equipment, and general infrastructure. These factors are well described in high income countries, but there is little recorded evidence on negative experiences of care especially in sub-Saharan Africa –91.This review reveals a wide range of interventions (n = 32) for improving quality of care, especially those involving families. These strategies are mainly articulated for small and sick newborns and premature infants including children with long term or chronic illnesses, with limited evidence on older children ages 60 days to 24 months.This scoping review identified three inter-related frameworks that have been introduced in high income countries: 1) Family-Centered Care (FCC), 2) Family and Parent Engagement, and 3) Nurturing Care. The three frameworks put the child’s family at the center of childcare during hospitalization. Each emphasizes family education, coaching, and full partnership with health care providers for a child’s care, which is found to improve understanding and adherence to plan of care in addition to follow up care at home, resulting in better newborn and child health outcomes. Supporting parents psychosocially while at the hospital and continually once back in society–particularly in cases of perinatal loss remains an area for future adaptation and refinement. Good provider communication and counseling also enhance the experience of care with improved mutual understanding of care measures and enhanced respect among caregivers, families, and providers.Factors that influence family engagement include beliefs about the family/of child’s role, health literacy and education, organizational culture, societal norms, policy, practice and regulation . WHO staSeveral studies show that a conducive policy environment, facility preparedness, and improved provider and parental knowledge play critical roles in successful implementation of health care interventions , 96, 98.This scoping review adds to the existing body of evidence on experience of care and the factors that drive mistreatment of newborn and young children up to 24 months of age. It also describes promising intervention models to improve the experience of care and reduce mistreatment. The process of interpreting evidence from the interventions in this review was complicated since many studies did not consistently nor adequately measure outcomes. Although the authors conducted an extensive in-depth literature review, it is possible not all available literature was identified, as only those studies published in English and within the last 10 years were included. Moreover, similar to other scoping reviews and in line with the debate around quality assessment constraints, the study did not assess quality of evidence to the extent possible in a in a systematic review with tighter criteria and sufficient research in the topic area , 100. DeThis scoping review will be used in two ways: 1) with formative research in select hospitals in Kenya for developing a contextually-relevant model to improve experience of care for parents and families seeking services for sick young children up to 24 months in a low income setting, and 2) to develop and test a provider behavior change approach to enhance provider and parent communication and engagement for the promotion of respectful, nurturing and health system responsive care to newborns, infants, and young children in a low resource setting.Experience of care is an integral component of quality care for hospitalized newborns and young children up to 24 months of age. There is limited evidence on the implementation of models of care that sufficiently consider provider-centric norms and attitudes while involving parents and families in the care of hospitalized newborns and young children globally, and in sub-Saharan Africa. A focus on addressing norms and values of health providers that may drive poor quality of care is critical. Improving provider performance is crucial to accelerating progress in child survival—and to thrive—and meeting the sustainable development goal targets.S1 Checklist(TIF)Click here for additional data file.S1 File(ZIP)Click here for additional data file.S2 File(TIF)Click here for additional data file.S1 Table(TIF)Click here for additional data file.


Communities are powerful and necessary agents for defining and pursuing their health, but outside organizations often adopt community health promotion approaches that are patronizing and top-down. Conversely, bottom-up approaches that build on and mobilize community health assets are often critiqued for tasking the most vulnerable and marginalized communities to use their own limited resources without real opportunities for change. Taking into consideration these community health promotion shortcomings, this article asks how communities may be most effectively and appropriately supported in pursuing their health. This article reviews how community health is understood, moving from negative to positive conceptualizations; how it is determined, moving from a risk-factor orientation to social determination; and how it is promoted, moving from top-down to bottom-up approaches. Building on these understandings, we offer the concept of ‘resourcefulness’ as an approach to strengthen positive health for communities, and we discuss how it engages with three interrelated tensions in community health promotion: resources and sustainability, interdependence and autonomy, and community diversity and inclusion. We make practical suggestions for outside organizations to apply resourcefulness as a process-based, place-based, and relational approach to community health promotion, arguing that resourcefulness can forge new pathways to sustainable and self-sustaining community positive health. The role of communities in promoting health and wellbeing is a tenet of public health research and practice. While recognizing that communities are not homogenous or static , communiHow health is conceptualized instructs where, when, and how it is promoted. Yet, the concept of health is under-scrutinized and often used uncritically in the field of public health . The bioSeveral theories of health provide for a deeper understanding of positive health. Nordenfelt  proposed11These ideas complement those from diverse cultures and places. For example, various Indigenous conceptualizations of health emphasize culture, spirituality, interdependence, and interconnections between the individual and their wider environment. In Australia, Aboriginal and Torres Strait Islander social and emotional wellbeing sits across mental, physical, family, community, cultural, spiritual, and environmental and place-based health factors . In FirsThese approaches not only resist reductionist and individualistic  notions of health, but they also articulate the value of collective community health outcomes. While mainstream global health practice tends to treat community health as individual-level health data in aggregate, collective notions of wellbeing are greater than the sum of individual health achievements alone and even call into question the strict delineation between individual, interpersonal, and family health in more collectivist societies . CommuniHealth is commonly seen as being determined by interactions between internal biology, human behavior, the external physical environment, and social conditions ,19. The determinants of health enable some understanding of complex salutogenic systems, critical epidemiologists such as Spiegel et al.  further recognizes and supports the power within rather than beyond the community by emphasizing process. CM is ‘a capacity-building process through which community individuals, groups, or organizations plan, carry out, and evaluate activities on a participa-tory and sustained basis to improve their health and other needs, either on their own initiative or stimulated by others (participation (community and other stakeholders), partnerships (with supportive outside actors), and power  conceptualize what constitutes their health and health assets and (b) pursue and sustain health agendas driven by local priorities, needs, and learning, while they also work to (c) change power imbalances that drive inequitable patterns of material resource distribution, and (d) nurture ecologically sound relationships with their local environment. Communities pursue their health through their internal strengths and supplement them through strategic partnerships: partners may include other communities with similar priorities and/or complementary resources and other actors at higher institutional scales with additional resources and power. By creating ‘genuinely deliberative democratic dialogue’ and developing ‘contestable alternative agendas’ , communiResourcefulness-based approaches offer insights into three interrelated aspects within community health promotion:1) Resources and sustainability: a community’s resourcefulness has the potential to offset certain material resource deficits , but nat2) Interdependence and autonomy: unlike purely agency-based approaches that focus on a community’s self-reliance and determination, the relational lens of resourcefulness recognizes the interconnectivity of communities with larger institutional and/or spatial scales  as well as other communities . Strengthening progressive translocal connections may help to challenge inequitable relationships within broader systems of power, like dominant economic systems , and adv3) Community diversity and inclusion: communities are not homogenous and bounded entities, and community members do not share entirely unified values and goals . MembersThe potential usefulness and usability of resourcefulness-based approaches for outside organiza-tions promoting community positive health can be found in diverse communities, settings, and issues, alongside their complications and shortcomings in practice. For example, resourcefulness may be leveraged to break dependencies that are harmful to the short- and long-term health of marginalized communities and forge more equitable power relations and interactions that are conducive to community positive health. Yet, systems are characteristically resistant to change, especially when some actors gain from inequitable resource distribution.Community activism may be met with violence, which was the case with Honduran environmental activist and Indigenous leader Berta Cáceres. Cáceres organized local communities to peacefully resist the building of the internationally funded Agua Zarca Dam on the Gualcarque River, which is integral to the positive health of the Lenca People. Her coordination was recognized with a Goldman Environmental Prize in 2015, but her efforts also resulted in her assassination in 2016 . After tOther situations highlight how outside organizations play a complicated hand in creating health challenges that play out in communities while also supporting community solutions. For example, the structural adjustment programs (SAPs) of the 1980s reduced public spending on health systems in economically marginalized countries, and international non-governmental organizations stepped in to patch the widening cracks . MeanwhiThe 2014–2016 Ebola outbreak in West Africa brought the important and enduring role of community health workers to the fore, as they were more effective than outsiders at Ebola response and were able to continue providing maternal and child health services alongside traditional birth attendants, community health committees, and traditional healers . This exThese vignettes shed light on how communities demonstrate resourcefulness in developing necessary place-based community health strategies, but not without costs and complications. Communities can and do navigate a dynamic stream of challenges and creatively seize opportunities embedded within these challenges to strengthen their community positive health. At the same time, the combination of these multiscalar challenges most often leaves the most socially, politically, economically, and envi-ronmentally marginalized communities with increasingly fewer opportunities, resources, and capabilities to realize their health goals. Thus, these examples illustrate that while communities are powerful and necessary agents in determining and advancing their own health, they also benefit from partnerships and alliances – including with outside organizations – that collectively wield greater power and influence to create necessary changes. Resourcefulness as a process-based and relational practice depends on long-term relationships that adapt to the changing needs, goals, and conditions of communities as well as the dynamic challenges and opportunities they face.Practical resourcefulness-based strategies for outside practitioners and policymakers to support community positive health may take many forms, including the following non-exhaustive list:1) developing long-term relationships with com-munities that build trust over time through learning from and respecting community leaders and community mechanisms for problem-solving and planning;2) supporting bonding within communities, con-necting with other communities, and linking with larger institutional scales to coordinate health strategies;3) providing support in advocacy and lending perceptions of legitimacy to increase broader recognition of community health initiatives and strategies;4) fostering awareness and knowledge about current and expected future environmental conditions and their impacts on natural resources;5) providing seed funding or financial backing for experimentation, as well as continuing support for ongoing initiatives and the maintenance of relationships between communities and organi-zations over time;6) assisting with problem-solving when health initiatives encounter barriers and challenges; and7) providing a platform for inclusive internal and translocal knowledge creation and sharing.The overarching purpose of these distilled resourcefulness-based strategies is to offer inroads for outside organizations to help support and strengthen community positive health in ways that complement and do not supplant existing community strengths, knowledge, and initiatives. Yet, recogni-zing that health challenges and constraints can stem from or intertwine with community-level factors, resourcefulness-based strategies may also include bringing to light new information, ideas, and other opportunities and resources to help forge new pathways to community positive health.Outside organizations adopting a resourcefulness mindset may be better able to link their efforts and investments to health processes and changes that are locally meaningful and self-sustaining. Despite these benefits, outside community health promotion organizations and donors may be reluctant to embrace these roles, because they entail that communities retain or gain control of health promotion processes. Best practices that emerge in a specific context may not be appropriate to import into another context, and this constant learning process may challenge an organization’s ability to solidify evidence-based approaches and streamline projects. Community goals may not align neatly with the global public health agenda, progress toward them may not be linear or take place over the short term, and achieving them may not be easily captured through standard monitoring and evaluation tools.Nevertheless, resourcefulness may be a viable way forward in light of health disasters like the COVID-19 pandemic. Resourcefulness-based strategies could arguably help with pandemic prevention and mitigation in the future by supporting the objects and processes of community positive health directly. When global prevention fails, local resourcefulness could be leveraged to keep integrated formal–informal health systems running, prevent health workers and others from dying from the disease and other treatable ailments, and mitigate its effects on other essential aspects of community positive health . It might also then galvanize global and multiscalar resourcefulness for positive health.This paper has applied and adapted the concept of resourcefulness as a process-based, place-based, and relational approach to understand and pursue community positive health, with the goal of strengthening health opportunities and choices. Resourcefulness builds on bottom-up approaches by strengthening and mobilizing community assets, but it also seeks to address the structural factors that determine health by forging tools and partnerships through long-term cooperative actions at multiple scales. Recognizing the importance of material factors and natural resources in community positive health, resourcefulness-based approaches also emphasize the cultivation of socially and environmentally sustainable practices and relationships, and they challenge the inequitable power relations and environmental practices that degrade local resources and capacities for health. Future research may explore how resourcefulness-based approaches to community health promotion can be leveraged in applied settings to make meaningful gains in narrowing health equity gaps.


The biomimetic olfactory and gustatory biosensing devices have broad applications in many fields, such as industry, security, and biomedicine. The development of these biosensors was inspired by the organization of biological olfactory and gustatory systems. In this review, we summarized the most recent advances in the development of detection strategies for chemical sensing based on olfactory and gustatory biomimetic biosensors. First, sensing mechanisms and principles of olfaction and gustation are briefly introduced. Then, different biomimetic sensing detection strategies are outlined based on different sensing devices functionalized with various molecular and cellular components originating from natural olfactory and gustatory systems. Thereafter, various biomimetic olfactory and gustatory biosensors are introduced in detail by classifying and summarizing the detection strategies based on different sensing devices. Finally, the future directions and challenges of biomimetic biosensing development are proposed and discussed. Olfaction and gustation are two of the most important senses in mammals. Olfaction, as a physiological sense, can perceive chemical odorant molecules in the environment. The olfactory system can discriminate different types of odorant molecules with extremely high sensitivity, specificity, and the wide response range ,2,3,4. IAs another important biological system, the gustatory system provides five basic tastes: sour, sweet, bitter, salty, and umami , which cWith the development of science and technology, several researches have designed many detection strategies on odorants and tastants detection, such as patch clamp technique, gas chromatography-mass spectrometry (GC-MS), various sensors and so on. Patch clamp is the golden technique to detect the electrophysiological activity of cells ,37, and Mammals’ olfactory and gustatory systems have ultra-excellent characteristics of genetic diversity and a high performance in recognizing odorants and tastants, which can provide the most excellent sensitive materials for the construction of smell and taste sensory sensors. Many studies have successfully used animals to achieve high-sensitivity perception of the external chemical environment, such as well-trained canines for the detection of explosives ,48,49,50In the past decade, different biomimetic detection strategies have been developed, which exhibited many excellent characteristics, including high sensitivity and selectivity, good stability, and practicability, offering an effective platform for application in food safety ,15,45,55This review will summarize the development of biomimetic olfactory and gustatory biosensors in the past 10 years and the possible direction of future research from the following four sections. The first section will introduce sensing mechanisms and principles of olfaction and gustation in mammals. The second section will introduce the immobilization strategies used for coupling between biomolecules and biomimetic sensory. The third section will elaborate various biomimetic sensors used for the detection of targets ligands with highlights. Finally, the current challenges and the possible direction of future research is discussed.The working principles of biological olfaction and gustation are the important basis of biomimetic biosensing construction. Only by mastering and understanding their most basic working mechanism and principle can we simulate its basic working state as much as possible and develop the most effective, reliable biosensors in the process of utilization. Therefore, in this section, olfactory and gustatory sensing mechanisms are introduced as shown in The olfactory system starts from the interactions between the odorant molecules and the olfactory receptors located on the cilia of the olfactory receptor neurons, which transduce chemical information of odorants into action potentials of neurons A. Then, αolf-GTP and Gβγ formation. Then, the activated Gαolf protein will combine with adenyl cyclase III (AC III) to form a complex, which converts ATP into cyclic AMP (cAMP). Sustained increases of cAMP can trigger the opening of cyclic nucleotide-gated channels (CNGCs), resulting in the influx of Na+ and Ca2+ across the membrane. Simultaneous calcium influx opens calcium-activated chloride channels (CACCs) and allows chloride efflux across the membrane, eventually resulting in the “depolarization” on the membrane [In olfactory receptor neurons, once the olfactory receptors bind with specific odorants, a cascade of cellular reactions will take place. As shown in membrane .However, the olfactory receptors cannot be directly exposed to odorants in the air, but animals can still achieve highly sensitive odorant recognition. Several studies have found that odor-binding proteins (OBPs) may play an important role in the transport of odorants from air phase to liquid phase ,59,60. OTaste substances dissolve in saliva and active the taste buds in the mouth to stimulate the response of taste cells. These gustatory signals are transmitted to the high-level processing center through intracellular and extracellular signal transduction and afferent neurotransmission. After integrated coding, they are projected to the taste cortex of the cerebral cortex, and finally they produce taste sensation A,D.α, Gβ, and Gγ). The guanosine diphosphate (GDP) on the Gα subunit is replaced by guanosine triphosphate (GTP). Then, the complex dissociates into Gα-GTP and Gβγ subunits and activates the calcium ion channel, leading extracellular calcium influx and simultaneous endoplasmic reticulum releasing calcium  is an important field-effect device with excellent characteristics including high input resistance, low noise, low power consumption, large dynamic range, and ease of integration. It consists of the source electrode, drain electrode, and gate electrode. When no voltage is applied to the gate, the current channel between the source and the drain is not turned on, and the FET is at the cut-off state. Once the applied voltage of the gate exceeds the threshold voltage, the current channel between the source and the drain will be turned on to form a leakage current. The leakage current can be tuned by the voltage of the gate with an internal amplification effect.–12 M indicated the high affinity between VFT and sweet tastants and the similar constant of sucrose and sucralose contributed to their similar structure. Recently, CNT as sensitive material carriers have been widely used to combine with FETs for the development of biomimetic biosensors, which can be attributed to: (1) the tubular structure providing abundant binding sites and a wider detection range, (2) the high electrical conductivity and large carrier mobility providing effective direction for improving the interfacial properties of transducer devices, and (3) the excellent chemical stability and elastic mechanical properties being beneficial to improving the specificity, selectivity, and stability of the sensor. In addition, many studies usually utilized equilibrium constant K to reflect the dissociation rate of the combination between proteins and small molecules so as to achieve quantitative evaluation of protein affinity level with small molecules. FET-based biosensors were developed by coupling olfactory receptors as sensitive materials to recognize different specific ligands, which can be widely applied in food quality analysis, disease diagnosis and environmental assessment. A single-walled carbon nanotubes-field effect transistor (swCNT-FET) was coated with polyethylene glycol (PEG) for the prevention of nonspecific absorption and functionalized with the human olfactory receptor 2AG1 (hOR2AG1), which was used to detect amyl butyrate (AB) selectively with ultrahigh sensitivity down to concentrations as low as 1 fM . Carbon Graphene has a large specific surface area, good stability, electrical conductivity and excellent absorbability, which has been widely used to modify and perfect the transducer surface. A bioelectronic tongue was established based on graphene-FET platform with VFT domain of human taste receptor type 1 member 1 (T1R1) as sensing elements and the disodium 5′-inosinate (IMP) as the enhancing element for the specific detection of umami taste in real time . This pldK value, the responsive range was calculated through Langmuir isotherm to be from 3.05 × 1010 M−1 to 7.53 × 1012 M−1, indicating the high affinity binding of the adopted receptors with different corresponding ligands. Such a detection strategy provides a new effective research direction for simulating human olfactory and gustatory perception. The developed biosensors have high resolution in distinguishing corresponding target molecules. Notably, the production of receptor proteins has the characteristics of simple, rapid and high-yield extraction, which provides a strong and beneficial basis for simulating human olfactory/gustation system. In 14 confirmed the perfect affinity between receptors and ligands.Although olfactory and gustatory receptors can simultaneously detect and recognize different ligands in real time, the processing and effective analysis of large amounts of data is time-consuming and error-prone. The combination of biosensor and machine learning has become the mainstream of current researches. Among these methods, principal component analysis (PCA) was especially suitable for dimensionality reduction of large quantities of data, effective and quick extraction of data features and rapid realization of visual research, which have been widely used in data analysis for distinguishing various smells and taste substances. As shown in In addition to receptors, OBPs are another effective alternative sensitive material with hydrophobic β-barrel cavity, successfully providing a useful model system to study binding affinity with odor compounds. 11 M–1, showing the high affinity between ligands and receptors and different periods of spoilage experiments, indicating the excellent practical application value for evaluations in food safety environments [dK between hOR1A2 and geraniol was changing from 8.37 × 1011 M−1 to 1.64 × 1015 M−1 after the addition of enhancer materials, which indicated that the benzyl salicylate as the enhancer could obviously improve the binding affinity between ligands and receptors [8 M–1 to 2.30 × 109 M–1 in this developed biomimetic gustatory biosensor. Based on the similar detection strategies, another research proposed a new specific human olfactory receptor (OR) found using a cyclic adenosine monophosphate (cAMP) response element (CRE)-reporter gene assay and successfully achieved high sensitivity real-time detection of fungal contamination in grain down to 1 fM and high selectivity toward other interference including 1-octanol, 1-octanal, 3-octanol, and 1-octene [–3 M, showing that the developed sweet biosensor have great potential application in detection and monitoring sweeteners in real samples [E. coli) [Although the solution to extract receptor or binding proteins may be very simple and fast, the conformation and biological activity of membrane proteins are still easily damaged during extraction due to various problems. In addition, it was still difficult to keep the activity, conformation maintenance and stability of extracted proteins in vitro. To challenge this problem, nanodiscs were reported and successfully extracted with a phospholipid bilayer structure composed of membrane scaffold proteins (MSPs) and phospholipids, providing powerful technical support for membrane protein research and olfactory and gustatory detection. Yang et al. developed a biomimetic olfactory biosensor based on oriented-immobilization nanodiscs embedded with trace-amine-associated receptor 13c (TAAR13c) as a sensitive element and CNT-FET with floating gold electrodes as a transducer element for highly-sensitive detection of death-associated odor, cadaverine (CV). The developed system successfully achieved detection on CV with a concentration range over five orders of magnitude and showed good selectivity toward other interference including diaminodecane, trimethylamine, ethanolamine, and glutamine. The equilibrium constant K between T13NDs and CV was estimated as 3.63 × 10ronments . To impreceptors . Recentleceptors , and theeceptors . Notably1-octene . Notably samples . However samples . This wo13, which suggested high affinity between peptides and targets. Unlike previous studies that used chromatographic instruments and strain counts to evaluate seafood freshness, a bioelectronic nose was developed based on CNT-FET functionalized with a synthetic peptide horp61m for rapid and non-invasive detection of gas trimethylamine (TMA). In order to evaluate the effectiveness of the biological electronic nose more accurately, the study adopted the sensory evaluation and gas chromatography-mass spectrometry (GC-MS) as a standard for comparison as shown in Since an increasing number of micro-biomolecules was discovered and used as the sensing element, artificial synthetic peptide derived from receptors or the binding proteins’ specific binding sites can be synthesized as another substitution of protein due to its high yield and stability. Detection of salmonella infection is relatively difficult and meaningful. A bioelectronic nose was proposed based on CNT-FET functionalized with odorant binding protein (OBP)-derived peptide expressed in Drosophila for the rapid detection of salmonella contamination in ham . The sysE. coli in this work, providing an effective method for batch production of sensitive materials. The system has characteristics of miniaturization, stability, and easy access to sensitive materials, and it provides a potential development direction for portable olfactory or gustatory detection device construction.Electrolyte-insulator-semiconductor (EIS) sensors are another type of field effect device, which has been widely used in chemical and biological sensing applications due to its small size and simple fabrication method, as shown in E. coli expressing hT2R4 as a sensing element without any additional steps of protein extraction and cell/protein immobilization for successful bitter substances detection through monitoring of the variation of space charge capacitance [LAPS are another type of field effect device with an EIS structure. As the transducer element, LAPS has excellent light-addressable ability, making it suitable for the signal capture of single cell and tissue in response to specific ligands, obviously except patch-clamp technology. In the development of biomimetic sensors, olfactory and gustatory epithelium were used as sensitive materials and LAPS as the detection device for the determination of specific ligand combinations through change of photocurrent acquisition ,97. A duacitance .A microelectrode array (MEAs) system can record the electrophysiological signals of sensitive materials in vitro and in vivo . IsolateWhen the olfactory and gustatory systems are stimulated by external odorants and tastants, a cascade of reactions will occur in the corresponding cell and transport to respective intermediate stations for integration and procession. Direct utilization of in vivo mammalian system is a very effective strategy for olfactory and gustatory detection. An olfactory biosensor in vivo was proposed based on an array of mitral/tufted cells (M/Ts) as sensing elements coupled with MEAs as transducer elements for odorant discrimination . The resIn addition, an in vivo gustatory system can also achieve effective detection for the high-quality detection of bitter compounds in food and medicine. In Utilization of high sensitivity of the mammalian olfactory system directly can achieve supernal value in multi-type odor discrimination and can avoid the complex means of extracting cell tissues and proteins. However, the development of biomimetic biosensing systems based on in vivo animals requires researchers with excellent experimental skills and experience, laboratories with sophisticated equipment, as well as the difficult to solve electrode stability, which seriously hinders its extensive development and application. An effective alternative on balance to resolve this problem and simultaneously implement spatiotemporal analysis is to isolate the primary olfactory and gustatory epithelium and plate it on the surface of planar integrated MEA system. The extracted primary tissues or cells contain their biological characteristics without completely changing and simulating the process of odorant and tastant sensing in vivo to reflect the state of the body in a certain extent. What’s more, spatiotemporal methods involving time-domain and frequency-domain analysis were proposed and developed as the auxiliary analysis solution in such a sensing system to analyze the correlation between different channels and furtherly verify detection performance of the MEA system as the transducer element. In earlier work,  successfElectric Cell-substrate Impedance Sensing (ECIS) can simultaneously measure the resistance changes and membrane capacitance changes of multiple groups of cells, as well as cultured cells and basement membranes, which was also summarized in The electrochemical analysis method has been widely used in application of biomimetic olfactory and gustatory biosensors due to its simple instrument, high sensitivity, high detection efficiency, and accuracy, as shown in Ka) was usually used to evaluate the affinity of receptors with ligands. The smaller the Ka value is, the higher the signal output efficiency produced by the ligand-receptor interaction. In addition, molecular docking can search the best matching pattern between molecules and ligands through geometric matching and energy matching mutual recognition, providing an effective analysis platform for exploring the combination pattern and affinity of olfactory and gustatory receptors and ligands. Ka through the sensing kinetics method showed that GMP have the highest affinity combined with hT1R1. Additionally, the analysis results of molecular docking model showed that the tight binding of TIR1 to the ligands depends on the formation of hydrogen bonds between its two rings (Asp147 and Ala170) and the amino/imino groups of the ligands. Notably, the hydrogen bond also formed between the phosphate group in GMP and IMP and the amino group at Asn69 to render the VFT active bag more tightly with ligands, which explained the reason why IMP and GMP can perform as enhancers for promoting umami perception [T. flavidus. The quantum chemistry and molecular docking results demonstrated that aspartic acid was the active site in the umami peptides. The meaningful work revealed the umami mechanism of peptides and provided a reasonable tool for rapid screening of umami peptides in food. Another interesting research, as shown in −15 showed capsaicine has the highest affinity with hTRPV1. Molecular docking simulation analysis demonstrated that Glu570 in the active pocket of hTRPV1 has a vital function in identifying spicy substances [Glassy carbon electrodes (GCE) are commonly used as working electrodes in biomimetic biosensor construction due to its excellent characteristics of good electrical conductivity, high chemical stability, and small thermal expansion coefficient ,110,111.rception . What’s bstances . FurtherKa showed that the umami receptors in different tongue regions have different perceptions of MSG and IMP as shown in −18 M and also analgesic compounds up to the attomole-level. Its related competition experiments and quantitatively the antagonistic strengths and inhibition constants investigation showed that capsaicin, AMG 517, lurelin B and tetrahydropalmatine are competitive allosteric regulatory ligands of capsaicin, while aconitine and anandamide are non-competitive and competitive mixed allosteric regulatory ligands. Results of these studies showed that such primary taste bud biosensors can precisely mimic the ligand-receptor interaction environment in biological taste systems to quantitatively illustrate the dynamic characteristics of cell or tissue receptor interaction with its ligand, the effect of cell signal cascade, and the amounts of receptors and signal transmission pathways. However, GCE is easily polluted by some organic and metal compounds. Screen printing electrode also has been widely used in environmental security detection, auxiliary clinical diagnosis, and food composition detection [Recently, taste buds were extracted from different regions of rabbit tongue tissue to construct a biomimetic biosensor, and its auxiliary analysis indicator etection ,114. It etection . For theetection . The resThe interdigitated electrode (IDE), another alternative type of electrode, is a finger-shaped or comb-shaped electrode with periodic patterns in the surface obtained by electrochemical processing. As the core component of electrical signal transmission, it has been widely utilized in various applications, such as biomedical, environmental monitoring, and food safety due to its high collection rate, high signal-to-noise ratio and feedback effect similar to amplification. When the receptor immobilized on the IDE electrode surface binds to the corresponding ligand, its conformational change might increase the contact area between the mobile ion and the electrode, thereby making the electron transfer process easier, which has a great influence on the dielectric and conductive properties of the staggered electrodes. In Intracellular calcium ions have temporal and spatial properties in neurocyte communication. In the resting state, the calcium ion concentration in most neuronal cells is approximately 50 to 100 nM. Once the cell is excited, intracellular calcium ion concentrations will instantaneously rise to 10 to 100 times. Therefore, detection of the variation of intracellular calcium ion concentration could be an effective way to monitor the cell mobility through special fluorescent dye or a calcium ion indicator. The influx of extracellular calcium ions includes voltage-gated calcium ion channels, ionic glutamine receptors, and nicotinic cholinergic receptors. The olfactory or taste biosensors introduced here were mainly based on calcium influx of ligand-gated channels as shown in 2+ imaging principle and innovative combination with flow cytometry to capture the green fluorescence for successfully bitter substance detection  is a plasma wave-based optical measurement method, which has the excellent characteristics of real-time, label-free, and high-throughput monitoring for target detection. The signal is proportional to the refractive index (RI) of the medium near the gold metal film, indicating that any changes in the medium environment at a distance of 300 nm from the surface can be captured, which can perform an effective highly-sensitive transducer element for biomimetic olfactory and gustatory biosensor construction. When sensitive materials combine with specific ligands on the SPR surface, the changes of properties of the surface medium or the amount of attachment would cause resonance angle variation. A biomimetic olfactory biosensor was functionalized with liposome containing hOR3A1 as the sensitive material and based on SPR as the transducer element for the detection of helional . NotablyHigh-throughput analysis has always been an important work of mass component detection in life science research. Surface plasmon resonance imaging (SPRi) offered a very promising multi-functional high-throughput research platform for complex odorant and tastant recognition. SPRi can be developed based on microarray device, which has all the advantages of SPR and can successfully realize real-time monitoring of various molecular action processes. A biomimetic olfactory biosensor was successfully developed based on SPRi as the transducer element for β-ionone and hexanal detection . In thisThe luciferase reporter gene system is another efficient fluorescence measurement method which uses luciferin as a substrate to detect firefly luciferase activity. A bioluminescence system consists of luciferin and luciferase, which is an effective detection method for detecting the interactions between transcription factors and DNA in the promoter region of the target gene. It was used to develop a dataset for other researchers to analyze olfactory coding information . The in-In addition, interferometer imaging can realize the combination of one or more light waves and produce interference patterns. The interference patterns produced by different light wave combinations produced by different types of receptor-ligand binding on the working elements may be different. The contained olfactory and taste coding information may be very abundant and worth analyzing. Aryballe Corporation developed a novel portable olfactory biosensor based on Michelson interferometer functionalized with different types of functional peptides and equipped with machine learning as the fast analysis method, which has been commercialized and widely used in the automotive industry .C. elegances, ODR-10 onto QCM for effective detection of diacetyl [Quartz crystal microbalances (QCM) is a typical quality sensitive sensor based on the piezoelectric effect of quartz crystal. With its high sensitivity, good chemical stability, and quantitative detection of high precision, it has been widely applied in many fields of biosensor technology, such as detection of the interactions between biological macromolecules, gaseous material analysis, etc. The interactions between the biomolecule and the target ligand can be monitored by detecting the output of the variation frequency. diacetyl . The bitdiacetyl . The desdiacetyl ,129. Thediacetyl . In a fodiacetyl . TherefoThe high-detection performance pursuit of biomimetic biosensors used for olfactory and gustatory molecular detection has drawn great attention in academic research. Based on existing research strategies, different detection strategies are summarized in the The enhanced elements were added into the medium to improve the responses of sensitive materials to specific ligands via the allosteric modulation mechanism. For example, zinc nanoparticles located in the interface between the guanine nucleotide binding protein and the receptor proteins to improve signal transmission when responding to odorants . PreviouMammalian olfactory and gustatory systems can simultaneously identify and detect various odorant and tastant ligands with high sensitivity and specificity and wider response range, owing to the abundant diversity of functional elements of biological olfaction and gustation in mammals. Truly, infinitely imitating and approaching the functional characteristics of biological sensing of olfaction and gustation or even replacing their functional roles in the fields of medical, environmental safety, and food safety are the ultimate goals of many biomimetic biosensing platform construction. To greatly simulate the functional diversity of biological olfactory and gustatory systems, numerous biomimetic biosensors were widely developed based on more emphasis on the imitation effect of sensitive materials for complex odorant and tastant diversity detection, such as creative recombination of olfactory and gustatory functional elements including the co-culture of olfactory or gustatory functional cells with nerve cells , olfactoRecently, the construction of organoids has provided the most efficient and potentially sensitive materials for the construction of biomimetic biosensing of olfaction  and gustThe smart portable devices construction has run through the development process of the entire sensor field, being the ultimate goal of different types of sensor development including a biomimetic biosensor for odorant and tastant detection. Its excellent characteristics including miniaturization, intelligence, excellent detection index , allow for fast, accurate, and on-site detection, which have already been pursued by high-quality sensor research and development. Recently, the rapid development of microfluidic integrated devices has provided a potential platform for the intelligent and portable design and construction of biomimetic biosensors. The microfluidic technology with precise control and manipulation of micro-scale fluids characteristics integrates biological, chemical, and medical analysis processes on micro-scale chips and automatically completes the entire analysis process, which has been widely used in clinical diagnosis model construction in vitro ,138, druNotably, the integrated combination of microfluidic devices with other functional detection platforms, such as electrochemical sensors  and an eHowever, the utilization of conventional two-dimensional planar electrodes may have a limitation in formation of the complete bio-interface system and measurement of high-quality and reliable electrophysiological recordings due to the existing multiple 3D structural features of different types of excitable tissues and organs. To challenge this dilemma, many studies have proposed and designed different types of 3D bioelectrodes system by changing the 3D geometry and microscopic size and lowering the Young’s modulus biocompatible materials to achieve a high resistance sealing and low impedance of the cell-electrode interval . The intIn conclusion, this review summarized the progress of biomimetic olfactory and gustatory sensing systems based on detection strategies in the past 10 years. In pursuit of olfactory and gustatory systems approaching that of the mammalian, abundant biomaterials were used as sensitive materials, including nanovesicles, nanodiscs, membrane receptor proteins, binding proteins, cells, and tissues for offering diverse options in the construction of biomimetic biosensors with high detection performance. In addition, the detection devices used as transducer elements, including FETs, MEAs, electrochemical sensors, QCM and optical devices, etc., have been widely used in olfaction and gustation detection and have provided a rich research background for portable development.


Aim: The objective of this paper is to demonstrate that structural alterations of the nasal cavity, e.g. septal deviation and conchal hypertrophy have high incidence in patients with sleep apnea and hypopnea syndrome and must be addressed with associated specific procedures of the syndrome. Type of Study: Clinical retrospective. Casuistic and Method: A retrospective study of 200 patients was performed, with 196 male and 4 female, attended at the otorhinolaryngology ambulatory of Hospital Prof. Edmundo Vasconcelos and Unidade Paulista de Otorrinolaringologia, all of them subjected to polysomnography, otorhinolaryngological physical exam, endoscopy exam, and surgical treatment with nasal and pharyngeal procedures. Results: All of them were subjected to pharyngeal procedure: uvulopalatopharyngoplasty or uvulopalatoplasty and nose procedure: 176 septoplasty with partial turbinectomy (88%) and 24 isolated turbinectomy, with satisfactory results. Conclusion: We can see that structural alterations of the nasal cavity have high incidence in patients with OSA. The obstructive sleep apnea syndrome (OSA) is a chronic and evolution disease presenting high morbidity and mortality rates, affecting 4% of men and 2% of women. It presents a wide range of symptoms, among which we have snoring (90% of cases), increased daytime somnolence, mood changes, daytime headache, sexual impotence, decreased intellectual performance and cardiologic and neurological disorders as the most important signsPatient’s evaluation with suspected OSA must include anamnesis comprehending graded scale for snoring and sleepiness. Regarding complementary exams, anterior and posterior rhinoscopy, oroscopy and nasofibrolaryngoscopy with rigid and/or flexible endoscopes to establish the possible site of structural alterations related to the syndromeOSA’s treatment may be clinical or surgical and is directly related to AHR, which classifies the disease into mild (AHR 5 to 15), moderate (AHR 15 to 30) and severe (AHR above 30). In patients up to AHR 15, auxiliary methods should be considered important in the treatment of this pathology, as well as behavioral attitudes such as losing weight, avoiding alcohol beverages and sedatives, as well as smoking cessationCurrently, the most adopted clinical treatment for OSA is mask application, with continuous positive airway pressure (CPAP) bound to an air compressor. Apnea and snoring respond well to CPAP in patients with AHR above 30, once they present immediate improvement and high mask toleranceSurgical treatment of nasal structural alterations, such as septoplasty, turbinectomy and polypectomy, offers limited efficiency in the treatment of adults with OSA, although it improves tolerance to CPAP Several surgical approaches have been proposed and the type chosen is related to severity of OSA, as well as to nasal, pharyngeal and craniofacial alterations previously found. The procedures performed include: pharyngeal ; nasal ; maxillary-facial (maxillo-mandibular advancement).The present study aims at demonstrating that structural alterations of the nasal cavity, such as septal deviation and conchal hypertrophy, are highly frequent among OSA patients and should be referred for surgical approaches (septoplasty and/or turbinectomy) associated with other specific procedures of this syndrome.Hospital Prof. Edmundo Vasconcelos (SP) and at Unidade Paulista de Otorrinolaringologia due to sleep disordered breathing, in the period of March 1992 and December 2003. All patients were submitted to directed anamnesis, comprehensive otorhinolaryngological exam and nasofibroscopy with Muller maneuver and polysomnography. Treatment was indicated after outcome analysis. Other evaluated disorders included cranio-maxillofacial disorders, obesity, body mass index (BMI), arterial hypertension, diabetes mellitus and behavioral habits.This is a retrospective study comprehending 200 patients that were assisted at Surgical treatment was indicated based on the structural alterations of the upper airways, facial skeleton and polysomnographic classification, to which apnea-hypopnea rate (AHR) and oxyhemoglobin saturation are greatly relevant. Nasal surgical procedures included septoplasty and/or turbinoplasty, while pharyngeal surgeries included uvulopalatopharyngoplasty, uvulopalatoplasty with cautery or laser.Out of 200 patients, 196 were men (98%) and 4 were women (2%)  within tThese procedures were grouped according to nasal structural disorders: 176 septoplasties with turbinoplasties (88%) and 24 turbinoplasties (12%) .Table 2SEven though some authorsA mouth breather has a lower tongue posture, in close contact with the mouth floor, and low pressure over the palate. This results in high palate and maxillary narrowing and consequent deviation of the upper dental arch, leading to cross bite. Tongue posture disorders, muscular tonus and inadequate dental occlusion also cause suction alterations, atypical chewing and deglutition. Persistence of these disorders in adolescence and adult age is firstly related to important cause of snoringConsidering these issues, we believe that those data are relevant in OSA’s genesis, in which nasal obstruction is a very important factor that should be treated.This study shows evidences of nasal disorders in patients with OSA. All patients (200) were submitted to surgical procedures in order to enhance the retro-palatine space  and nasaAnother important aspect is that some patients, along OSA’s evolution, even after undergoing surgery, may eventually use CPAP for a more effective control. In addition, surgical treatment may probably improved CPAP tolerance since patients with nasal obstruction have enhanced positive pressureFinally, it is our opinion that diagnostic approach of nasal structural alterations - particularly septal deviation and/or conchal hypertrophy, polyps or other pathology leading to obstruction of natural air flow, is of great relevance in the assessment of patients with suggestive symptomatology of sleep disordered breathing.Concomitant treatment of these disorders and of OSA has proved to be feasible and, when associated with surgical and/or clinical procedures, such as CPAP, it offers great chances to reach improved outcomes in these patients.


Because of its composition diversity and disease-specific expression characteristics, gut microbiota holds strong promise as novel biomarkers and therapeutic targets for NAFLD. Intervening intestinal microbiota, such as antibiotic/probiotic treatment and fecal transplantation, has been a novel strategy for preventing and treating NAFLD. In this article, we have reviewed the emerging functions and association of gut bacterial components in different stages of NAFLD progression and discussed its potential implications in NAFLD diagnosis and therapy.The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one of the most common clinical liver diseases. Since the pathogenesis of NAFLD has not been completely elucidated, few effective therapeutic drugs are available. As the “second genome” of human body, gut microbiota plays an important role in the digestion, absorption and metabolism of food and drugs. Gut microbiota can act as an important driver to advance the occurrence and development of NAFLD, and to accelerate its progression to cirrhosis and hepatocellular carcinoma. Growing evidence has demonstrated that gut microbiota and its metabolites directly affect intestinal morphology and immune response, resulting in the abnormal activation of inflammation and intestinal endotoxemia; gut dysbiosis also causes dysfunction of gut-liver axis  Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury disease worldwide, with a broad spectrum ranging from simple steatosis, nonalcoholic steatohepatitis (NASH) to cirrhosis and even hepatocellular carcinoma (HCC). Epidemiological investigation shows that NAFLD has become one of the most common liver diseases, with a global prevalence of 25.2%, 27.4% in Asia , but morThe popular theory for the pathological progression of NAFLD is “multi-hit” theory . AccordiThe gut microbiota is a complex community that exist in the human gastrointestinal tract in a symbiotic manner and maintain 3 important physiological functions of the human digestive system, namely digestion, metabolism, and protection . GrowingThe gut microbiota breaks down undigested polysaccharides into monosaccharides and dietary fibers into SCFAs by utilizing a variety of enzymes, both of which provides energy support for the host cells. Most notably, SCFAs exert multiple benefits in the regulation of metabolism and immune, and could be emerged as a potential therapeutic agent against various diseases. Beside the main source of energy for host colonocytes, SCFAs have distinctive pharmacological and physiological functions, such as promoting colonic motility, protecting intestinal mucosal barrier, altering carbohydrate and lipid metabolism, participating in immune regulation, and improving the absorption of electrolytes and nutrients as well as anti-inflammatory and antitumor activities . Dependivia the activation of fibroblast growth factor (FGF) 15/19, PPARγ, GLUT-4 and GLP-1 to improve insulin sensitivity (BAs are the main components of bile and can be divided into primary and secondary bile acids. Primary bile acids (PBAs), including cholic acid (CA) and chenodeoxycholic acid (CDCA), are produced from cholesterol in hepatocytes and excreted to the bile duct. Secondary bile acids (SBAs), including lithocholic acid (LCA), deoxycholic acid (DCA), ursodeoxycholic acid (UDCA) and their respective isoforms (such as isolithocholic acid), are then transformed from the primary bile acids by bacteria in the small intestine. PBAs not only maintain intestinal microbiota homeostasis through directly inhibiting overgrowth of pathogenic bacteria, but also act as the naturally occurring agonists of intestinal FXR  and subsequently activate its downstream defense genes in ileal mucosa  to protesitivity . TGR5 issitivity . Activatsitivity . Howevervia the portal vein and converted by flavin-containing monooxygenases into TMAO, which promotes the accumulation of activated leukocytes into human endothelial cells, leading to endothelial dysfunction and significantly increases the risk of atherosclerosis and cardiovascular diseases , and more interestingly, transplantation of this HiAlc-Kpn isolated from the feces of NASH patients could induce NAFLD in the mice  . There aStreptococcus, Lactobacillus, and Bifidobacterium improve the gut inflammatory microenvironment, promote the growth and survival of intestinal epithelial cells, and inhibit pathogenic bacteria by modulating the immune system and host defense , Key research projects of Hangzhou Medical College (No. KYZD202106), and Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province (No.2019E10021).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.