COVID-19 has disrupted maternal and child health services. Community Health Workers (CHWs) supported the women by visiting pregnant women's homes and providing the MCH services as required. This study attempts to understand the role of CHW and its impact on the Ante-Natal Care (ANC) services pre-pandemic and post-Pandemic in the poor resource setting.Swabhimaan programme interventions were carried out in the selected blocks in the Indian States of Bihar, Odisha and Chhattisgarh with the objective to improve the nutritional status of mothers, pregnant women and adolescents living in resource-poor blocks of three selected states during 2016–2022. Cross-sectional surveys, namely pre-pandemic (2018–19) and post-pandemic (2021–22) of pregnant and mothers of under two children, utilised to fulfil the objectives of this study. These surveys are part of Swabhimaan evaluation, a community-based non-randomised controlled study.The The ANC services received by women have increased over time from 2015 to 2022. Our findings confirm that the ground-level community and health systems were active during the pandemic, and the results show significant improvement. Additionally, the women supported by the CHW have substantially improved pregnancy registration, first ANC, Tetanus injection, consumption of Iron Folic Acid, Calcium and deworming tablets than those who did not. Propesnsity Score Matching analysis shows that the average treatment effect on the various ANC services of having the support of CHW is significant.This study shows the vital role of CHWs in utilising various Maternal and Child Health services. Better linkage and networking of the CHWs with the community will ensure health service delivery regularly and in an emergency like a pandemic and develop resilience. The COVID-19 pandemic posed unprecedented challenges by straining the under-resourced health systems in low- and middle-income countries (LMICs) . DisruptPregnant women are a vulnerable group who need special consideration during any health emergency . During Swabhimaan is an initiative of UNICEF India in collaboration with the National Rural Livelihoods Mission (NRLM), Government of India. It was launched in 2016 to improve the nutritional status of adolescent girls, pregnant women, and mothers of children under two years in the selected resource-poor blocks of three Indian states, namely Odisha, Chhattisgarh, and Bihar [India announced a nationwide lockdown on 24 March 2020, which continued for more than six months and was later extended with a few relaxations here and there. Despite the mitigation measures, India was at the top among the LMICs regarding the number of confirmed COVID-19 cases . Forced nd Bihar .Given the nature of COVID-19, literature that scientifically quantifies the implications of the pandemic on the use of maternal health care in LMICs is limited . One of Swabhimaan midline and endline impact evaluation surveys.To achieve Sustanable Development Goals even at local level, the health workers from the communities play a vital role in providing ground level services. ASHA , ANM (Auxiliary nurse midwife), and AWW (Anganwadi worker) are a part of the continuum of care for women and play a crucial role in it. ASHA, generally a woman, is an interface between the community and the public health system and is accountable for ensuring the smooth implementation of the National Health Mission (NHM) at the lowest level, that is, village or slum pocket. ANMs are a crucial component of NHM, connecting ASHAs and communities with the public health system and delivering specific services through camps, home visits, and PHCs. As community members, Anganwadi workers (AWWs) assist ANMs and ASHAs provide services, executing programs, and maintaining records under the Integrated Child Development Scheme (ICDS). The government of India implemented a lockdown to curtail the spread of COVID-19, with sealed boundaries and restrictions of movement. Only local-level community health workers could provide ANC services to pregnant women during this situation. Therefore, this study assesses the role of community health worker during the pandemic by using Swabhimaan programme has three cross-sectional surveys: baseline (2016–17), midline (2018–19), and endline (2021–22). During all three rounds, data was collected from the Kasba and Jalalgarh blocks in the Purnea district of Bihar, the Pallahara (Angul district) and Koraput (Koraput district) blocks of Odisha, and the Bastar and Bakawand blocks in the Bastar district of Chhattisgarh. The present study evaluates the data from the midline survey carried out before the pandemic in 2018–19 (Sep’18-Jun’19) and the endline survey conducted after the onset of COVID-19 during 2021–22 (Jan’21-Jan’22).The In designing this cross-sectional study, we took into account the Swabhimaan strategy and the outcome indicators, as well as the changes anticipated. The sample selection was based on two-stage systematic sampling and was designed to provide the estimates of key indicators at block levels across the three selected states. The representative sample in each round was derived using the simple random sampling after adjusting for non-response rate and the required women were selected from sampling frame using the sysytematic sampling. The detailed information on survey design of this prospective, non-randomised controlled study is available elsewhere . The numIn all rounds of surveys, trained field investigators administered pretested bilingual questionnaires to pregnant and MU2 women through face-to face computer-assisted personal interviews (CAPI). This data collection application used in the CAPI ensures quality data collection in timely manner with inbuilt soft and hard checks. Further, the quality control checks on several issues including ANC services were done for 10 percent of the sampled women in every state and in each round to maintain the quality of the data.The variables representing maternal health care services were pregnancy registration, seeking ANC in the first trimester, and receipt of Tetanus (TT) injection, Iron Folic Acid (IFA) tablets, calcium tablets, and deworming tablets in the second and third trimesters of pregnancy.Community workers providing advice about ANC services, helping with early pregnancy registration, counselling on birth preparedness, and supporting ANC services during COVID-19 were treated as independent variables. Other covariates, such as state, age, education, religion, caste, family size, and return of migrant members during COVID-19, were included to understand the differentials. The return of a migrant member was considered a possible covariate as households with such members may have been left out by community health workers (CHWs) due to COVID-19, which may have impacted mothers or pregnant women in those households.The utilisation of ANC services for pregnant women of second and third trimesters is examined. In the case of mothers under two years, these services are completed; hence, there are no exclusion criteria for the analysis. The trend of ANC service utilisation is based on three rounds of surveys, to show the impact of intervention. Authors analysed the involvement of community health workers like ASHAs, ANMs, and AWWs in creating awareness regarding ANC, providing counselling, and supporting women while seeking ANC during the pre and post-pandemic periods separately for PW and MU2(2018–19 and 2021–2022). ANOVA is used to understand the differentials in exposure and outcome variables by womens varying characteristics post-covidLastly, the role of the CHWs in utilising ANC by women was explored using bivariate analysis, and the impact of the services provided by the CHWs was analysed using the propensity score method (PSM). The matching technique was used because the beneficiaries were not randomly selected, as a result of which selection bias could be introduced in the estimated impact of the programme. The covariates matched in the present study encompassed categorical variables like caste, education, religion, type of house, and availability of land. The analysis was carried out in the following steps.Firstly, the logit model was used to estimate the propensity score for the covariates presenting mothers' demographic and socio-economic characteristics. Next, we used the k-match command to calculate the difference, known as the average treatment effect (ATE), in the utilisation of maternal health services between the control group (those who didn't receive or avail services through CHWs) and the treatment group (those who received assistance from the CHWs). The difference is presented in terms of proportion.There are basic assumptions that need to be satisfied for using PSM. The first is that the potential outcomes must be determined in a way that they are independent of the treatment assignment, possibly carried out by including all the covariates that affect the outcome or the treatment. The second is a common support or overlap condition; that is, the treatment units will have to be similar to control units in observed characteristics unaffected by the participation of CHWs. The data was collected using CS Pro (Census and survey processing system) and extracted and analysed using STATA 15.1.In Bihar and Odisha, an endline survey was conducted after the first wave of COVID-19. In the state of Chhattisgarh, the survey was conducted after the second wave of COVID-19. Most of the women in both groups are below 30 years Table . The eduIn the Swabhimaan area, essential ANC indicators have improved from 2015 to 2022 for pregnant women and mothers of under two children  to improve access to maternal health care, family planning services, and micro-nutrient supplementation.The findings of this study reveal that in the study area, despite the pandemic, the proportion of pregnant women utilising various components of ANC increased from pre-pandemic 2019) to post-pandemic (2022) After the pandemic's breakout, pregnancy registration in the first trimester increased by 15 percent, micronutrient supplementation like IFA recorded an about 20 percent increase, and compliance with deworming tablets increased from 11 to 31 percent. Corroborating our findings, Nguyen et al. elaborated that although fewer health facilities provided ANC services amid the lockdown, most services for pregnant women continued to be offered, except for anthropometric measurements, which registered a decline 19 to pos. The impOur results show that in Bihar, a significantly lower proportion of pregnant women sought ANC in the first trimester compared to other states. Further, socio-economic disparities in utilization of ANC services still exists as shown in earler research . Women fThe present study established that sensitisation, counselling, and support extended to pregnant women by existing community health workers like ASHAs, ANMs, and AWWs increased after the onset of the pandemic. About 40–60 percent of the pregnant women reported that the health workers supported them in receiving ANC during the lockdown. Government guidelines to make essential services available at door step were issued . During Swabhimaan study area witnessed improvements during the COVID-19 lockdown periods. Pregnant women who got interaction with community health workers like ASHA had better exposure to these services than those who were not a part of these community platforms. Other Indian studies related to ANC and PNC service delivery during this period show that the services were disrupted due to the overburdening of the local health system due to the pandemic [Swabhimaan study areas while also ensuring patient safety by following the guidelines of the global health agencies [Various global health guidelines emphasise the importance of community participation in health delivery . Health pandemic , 28–30. agencies .Our findings confirm that the ground-level community and health systems were active during the pandemic. Policies and interventions should focus on effectively using ground-level health workers to create a source of health information and access to health services, thereby reducing the impact of health emergencies in the future. Increasing the community health workforce, especially in underserved resource-poor communities, can meet the urgent demand to educate and connect people to healthcare services during emergencies. In developing countries like India, participatory community programmes such as VHSND serve as promising platforms for delivering maternal health care with the help of ASHAs, ANMs, and AWWs.The major strength of this study is that it addresses the gap in the utilisation of ANC services before and after the pandemic based on women who were pregnant at the time of the midline and endline surveys, thus addressing the recall bias. However, it should be noted that the study was limited to selected areas. An earlier study pointed out that measuring community participation and social involvement factors will be essential to more adequately and accurately .The study highlights the importance of Community Health Workers in providing maternal and child healthcare services during the pandemic.This study is not a follow-up of women from the baseline to endline. All three rounds of cross-sectional surveys were representative samples of the community. Hence, an attempt has been made to show the overall impact of CHW on ANC services. These findings are applicable to the rural areas of poor resourse setting communities in India. Further, the study could not see the impact of COVID-19 pandemic over time due to non-availability representative data over time.This study invites policymakers' attention to the new healthcare service delivery culture that supports community participation to link as many people to community health workers as possible since these platforms can potentially promote last-mile delivery of health and nutrition services in the community. The present findings suggest the positive outcomes of antenatal care supported by the CHWs during pandemic, a perfect example of community engagement that build health system resilence for health emergency. Their role in pregnancy registration, motivating for seeking ANC and distributing IFA and calcium tablets are noticeable. Women from households with return migrants did not show any bareer in access to ANC. However, the socio-economic gaps in utilization of ANC services still exist which require further attention to women from lower socio-economic starta. Furthermore, the existing ground-level community health workers network should be strengthened to ensure coproduction. These measures may form a new institutional culture to ensure the continuity of health service delivery during a pandemic, minimise the impact of a health emergency, and build resilience.


We here summarize the major points of the complex scenario involving monoclonal gammopathies and MM clinical management in view of advantages derived for the use of Hevylite®.The antibody-related immune response is mediated by immunoglobulins (Igs), soluble circulating glycoproteins produced by activated B cells that, upon the recognition of specific epitopes on pathogen surfaces, activate, proliferate, and differentiate into antibody-secreting plasma cells. Although the antibodies are effectors of the humoral immune adaptive response, their overproduction in response to a dysregulated proliferation of clonal plasma cell production in tumoral conditions , enriches the serum and urinary matrices, assuming the crucial role of biomarkers. Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the expansion and accumulation of clonally activated plasma cells in bone marrow, determining the release of high amounts of monoclonal component (MC) that can be detected as intact immunoglobulin (Ig), immunoglobulin fragments, or free light chains (FLCs). The importance of detecting biomarkers for the diagnosis, monitoring, and prognosis of diseases is highlighted by the international guidelines that recommend specific assays for the analysis of intact Igs and FLC. Moreover, a developed assay called Hevylite A dysregulated proliferation of clonal plasma cells in bone marrow gives rise to a tumor burden as in multiple myeloma . MultiplAbnormal B-cell clone expansion and the secretion of monoclonal proteins may indicate a clinically quiescent state for a prolonged period, defining monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic monoclonal gammopathy ,6 that m®), which is able to detect the involved immunoglobulin heavy/light pair chain (iHLC) and the corresponding uninvolved immunoglobulin heavy/light pair chain (uHLC) [Therefore, through these parameters, it is possible to conduct frequent monitoring of patients at higher risk, and those at lower risk can be reassured and followed less frequently ,8. Specin (uHLC) . Thus, tn (uHLC) ,10. Thern (uHLC) , acquiriA wide range of clinical signs may be associated with the presence of monoclonal gammopathies ,11,12. QRecently, the international guidelines for the definition of MM have been updated, identifying valid biomarkers, in addition to the CRAB criteria, in patients who would otherwise be considered as having smoldering multiple myeloma (SMM): an intermediate condition between MGUS and MM without CRAB signs, as wells as MGUS, but with higher levels of clonal bone marrow plasma cells (≥30 g/L) ,16. MM pAs suggested by Mateos et al., the treatment of asymptomatic high-risk patients leads to a decrease in the rate of malignant transformation and improvement in overall survival ). Early In the development of MM from MGUS and/or smoldering MM (SMM), a wide range of events take place involving both the plasma cell clone and the bone marrow microenvironment. Among these, heterogeneous genetic lesions, interactions between myeloma cells in the bone marrow niche, osteoblasts, osteoclasts, and components of the immune system, mediated by the hyperproduction of cytokines and growth factors, play a crucial role, together with alterations in bone remodeling and the bone marrow angiogenesis process ,20.This biological and genetic heterogeneity relates to the difficulty of identifying laboratory and clinical parameters with defined prognostic roles. In fact, most of the factors still used in clinical practice no longer have a predictive role after the introduction of new drugs. The reason for the poor prognostic reliability of both the clinical and biological parameters is the persistence of residual clonal myeloma cells in patients who have experienced complete remission after chemotherapy and/or stem cell transplantation .The introduction of novel therapeutic strategies including autologous stem cell transplantation changed the natural history of the disease, leading to new manifestations of relapse. Although MM is characterized by the proliferation of an abnormal plasma cell clone, the genetic heterogeneity of the disease is both interclonal and intraclonal . This biBased on this evidence, mandatory molecular events are not achieved in a linear way for the development of MM, but through branching or non-linear pathways, typical of the evolutionary model proposed by Darwin ,23. ThisIn 2009, a new immunoassay to measure heavy/light chains (HLCs) was introduced ,27. ImmuFurthermore, this assay exploits the ability of antibodies to bind directly to target epitopes at the junctional region between bound k or λ light chains and their respective heavy-chain molecules  Figure .Ig chains are assessed in pairs to produce the HLC ratio in the same manner as the κ/λ sFLC ratio, being an indicator of clonal expansion ,10. HLC The sensitivity of the HLC ratio (rHLC) in detecting monoclonal intact immunoglobulins is dependent upon the concentration of both the involved  and uninvolved  immunoglobulin HLC of the same isotype, which also provides accurate information about isotype-matched immunoparesis (IMI) ,10. The Abnormalities in HLC are associated with various clonal or reactive B-cell disorders, including plasma cell disorders, B-cell lymphoma, and B-cell hyperplasia after immune stimulation; preliminary multivariate analysis indicates that the IgMκ/IgMλ HLC ratio is predictive of PFS as it is exhibited in multiple myeloma . The assThe Guidelines of the International Myeloma Working Group (IMWG), together with scientific reports, state that the HLC test has an important role to play throughout the management of a patient with MM, from diagnosis to prognosis and up to the assessment of the response to therapy ,32,33,34The Hevylite assay provides additional key data for diagnosing patients with MM. Compared to serum protein electrophoresis (SPE), this assay is more sensitive, less laborious, processes a quantitative result avoiding the subjective interpretation of the gel, and can overcome many of the known limitations of the SPE, such as co-migration and migration diffusion of the monoclonal component (MC), dye saturation, and non-linearity ,34,35,36The IMWG guidelines for the standard investigative work-up of patients state that, “For patients with measurable monoclonal protein in serum, both electrophoretic studies and quantitative immunoglobulins are recommended to assess response, although electrophoretic measurements to follow monoclonal protein are preferred” . HoweverThe quantitative measurement of total Igs is also recommended by the IMWG criteria , but, alThe IMWG criteria for the therapy response and definition of minimal residual disease (MRD) recognize the Hevylite method as an additional assay for the management and monitoring of patients with oligosecretory MM  or with an IgA MC migrating in the β-zone of electrophoretic trace . TherefoSeveral studies, in fact, have also shown that rHLC could indicate residual disease in MM patients with normalized SPE after therapy, allowing for relapse detection earlier than traditional methods ,46,47,48Through periodic Hevylite monitoring, Ludwig et al. detected the presence of disease in patients who achieved a complete response (CR) with traditional methods and the conversion of the iHLC ratio. Normal to abnormal uHLC has been shown to be an early biomarker of disease progression , based oAs shown in As a tumor grows, there is often a reduction in polyclonal plasma cells and, consequently, polyclonal immunoglobulins. Thus, the measurement of a Hevylite pair that is the same immunoglobulin class but the alternate light-chain type to that produced by the tumor (uHLC) results in a reduced concentration. When the concentration of the uHLC is below the normal range and an abnormal rHLC is present, it is referred to as HLC pair suppression .It is possible to obtain important information about tumor clonality from the relationship between iHLC and uHLC. In addition, the detection of uHLC values lower than the normal range with an altered iHLC/uHLC ratio provides important information regarding the level of suppression of the immune system, which is induced by the myeloma itself .The mechanisms of suppression of normal Igs in plasma cell dyscrasias remain poorly understood: uHLC suppression below normal levels and an altered iHCL/uHLC ratio have been observed to be associated with an increased risk of progression to myeloma in patients with MGUS ,31,34,52The greater prevalence of IMI (immunoparesis matched isotype) over the suppression of uninvolved isotypes , along with the lower proportional values for IMI, supports an isotype specificity of early suppression mechanisms for IgG and IgA isotype smoldering multiple myeloma (SMM). Immunoparesis is associated with other recognized risk factors for progression, but, especially in case of IgM, it appears to develop in advanced disease and could correspond to different suppression mechanisms. These mechanisms are involved at the time of the initial evaluation and during the follow-up assessments of patients with SMM using the serum Hevylite assay ,53.Altered values of HLC indicate the presence of an early relapse compared to traditional tests, associating with a lower survival rate of MM patients and a likely increased progression from MGUS to MM. Together with the free light-chain test and other serum markers, the Hevylite test guarantees the excellent monitoring of patients with plasma cell dyscrasias . InteresRecently, the effect of HLC pair suppression has been studied as a risk factor for bloodstream infections (BSI) and early death in a Spanish clinical trial, which included 115 newly diagnosed intact immunoglobulin MM patients with measurable disease . The BSI® is capable of quantifying both the immunoglobulins involved in the tumor process and the immunoglobulins that are not involved  with relative comparisons analysis (rHLC and dHLC) [In the general context of monoclonal gammopathies, the FLC assay represents the progenitor among the biomarkers in the analysis of MC variation. Nevertheless, a recently developed assay called Hevylitend dHLC) . The cornd dHLC) ,58 and, nd dHLC) .Interestingly, the Hevylite assay has also been widely applied in other diagnostic areas, since the identification of sensitive and specific biomarkers is crucial for prognostic diseases analysis. For instance, in patients with chronic hepatitis C virus, related mixed cryoglobulinemia (HCV-related MC), and increased risk of B-cell non-Hodgkin Lymphoma (B-NHL), HLC may represents a serum biomarker that is able to identify patients with overt B-NHL associated with mixed cryoglobulinemia vasculitis in chronic HCV infection ,59. The Therefore, biomarkers play pivotal roles in the evaluation and measurement of specific parameters in physiological processes, pathogenesis, and response to therapy. In this context, Hevylite, with other serum assay biomarkers, might display a predictive and prognostic ability to improve treatment outcomes, by which patients could receive multiple competing drug options or other treatment administrations modalities . Thus, the diagnostic potential of innovative assays helps to implement the paradigm of precision medicine: ‘the right treatment to the right patient at the right time’, adding, “the right assay to the right patient at the right time”.


Scoliosis is a three-dimensional deformity of lateral bending and rotation of the spine. Artificial intelligence (AI) is a set of theories and techniques for studying artificial intelligence, which realizes machine intelligence by simulating and expanding human intelligence. With the continuous development of the multidisciplinary integration trend of modern medicine, artificial intelligence is used more and more in the diagnosis and treatment of scoliosis. Artificial intelligence has been widely used in the study of scoliosis and has penetrated into all fields of clinical practice of scoliosis. At present, artificial intelligence has shown good application prospects in early screening, diagnosis, treatment decision making, intraoperative operation, and prognosis prediction of scoliosis. This paper mainly summarizes the application of artificial intelligence in the clinical practice of scoliosis, and briefly introduces the AI model and its specific applications. In addition, this paper also discusses the limitations and future development of artificial intelligence. In the future, artificial intelligence will bring greater convenience to the diagnosis and treatment of scoliosis and provide better therapeutic effects for patients. Scoliosis refers to a three-dimensional deformity of the spine with lateral curvature and vertebral rotation, which covers some characteristics including rib hump, shoulder imbalance, waist asymmetry ,2. The IIn recent years, artificial intelligence (AI) has developed rapidly and has been widely used in various medical fields. AI aims to imitate, extend, and expand human intelligence by studying artificial methods and technologies. This endeavor leads to the realization of machine intelligence . The intEarly screening is the most effective way to find spinal deformity early, and early screening and diagnosis will contribute to the early intervention and treatment of spinal deformity . CurrentIn 2000, Jaremko et al.  firstly In the realm of AIS, the application of large language models (LLMs), such as advanced AI-based chatbots, is revolutionizing patient education and information dissemination. These AI-driven systems are adept at delivering personalized, comprehensible, and medically accurate information to patients and their families. The integration of LLMs in AIS management is particularly beneficial, given the condition’s complexity and the diverse treatment options available. LLMs provide a convenient and accessible platform for patients and families to address their questions, grasp the nuances of different treatment strategies, and participate actively in decision-making processes . FurtherBeyond educational purposes, LLMs also work well in assessing the severity of scoliosis. Contrastive language-image pretraining (CLIP)  is an AIThe key to the early screening of scoliosis by AI is to obtain human trunk information. Currently, the methods of AI for the early screening of scoliosis are constantly being updated, and its reliability and accuracy are constantly improving. In addition to these advancements, it is crucial to implement regular evaluations and updates to these AI models to ensure their effectiveness in clinical settings. This involves rigorous performance monitoring to assess accuracy, sensitivity, and specificity in different populations and under varying clinical conditions. Moreover, model recalibration is essential to adjust algorithms in response to new findings or shifts in epidemiological trends. This recalibration should be an ongoing process, adapting the models to maintain their relevance and accuracy over time. Equally important is the incorporation of new data, which can come from recent clinical studies, patient demographics, or novel imaging techniques. By continually integrating this new information, AI models can evolve to become more robust and reflective of the current state of scoliosis presentations and treatments. It is believed that AI will become a common means for screening and monitoring scoliosis in the near future.Quantitative analysis of scoliosis is a necessary step in the diagnosis and treatment of scoliosis . The autAutomatic image analysis of spinal deformity mainly includes direct estimation and segmentation-based methods . The acqThe segmentation-based method extracts the vertebral contour, and then measures scoliosis according to the segmentation results. Previous studies have developed a variety of segmentation-based methods for evaluating scoliosis, such as Hough transform ,36, actiIn the realm of scoliosis diagnosis and treatment, AI has revolutionized the automatic evaluation of related parameters, particularly in quantitative analysis, which is crucial for accurate diagnosis and treatment planning. The advancement of AI has led to the development of various automatic analysis programs for spinal deformity images, showcasing a trend towards greater intelligence and precision. These include direct estimation methods like ResU-Net, BoostNet, MVC-Net, and MVE-Net, which have demonstrated a high reliability for measuring spinal parameters such as the Cobb angle from X-ray images. In parallel, segmentation-based methods, evolving from traditional techniques like Hough transform and active contour models to advanced deep learning approaches like various U-Net models, have significantly improved in vertebral segmentation and Cobb angle estimation. For instance, Horng et al.  and ZhaoThe classification of scoliosis can help surgeons classify curve types and guide them to make treatment decisions . CurrentWith the support of big data and image recognition technology, AI assists orthopedic surgeons to diagnose and treat diseases by learning massive knowledge and experience. Phan et al.  applied Early prediction of the progression risk of scoliosis has significant clinical value, so as to help ensure that patients at risk of progression receive early supportive treatment and to strengthen treatment compliance. An AI algorithm can be applied to automatically predict the risk of scoliosis progression. Yahara et al.  developeThe procedure of surgical instrumentation for scoliosis is complicated, in which the choice of a fusion region is very challenging. Currently, the Lenke classification model is used in the surgical planning of spinal deformity to determine the appropriate fusion region. Mezghani et al.  trained Incorporating the prediction of surgical results into treatment decisions can improve patients’ satisfaction and reduce the occurrence and risk of reoperation. Pasha et al.  used theAI plays a pivotal role in therapeutic decision making in scoliosis, enhancing the classification, progression prediction, and surgical planning processes. AI facilitates rapid and accurate scoliosis classification, as seen in the works of Phan et al.  and ChenPedicle screw insertion is a key step in scoliosis correction surgery. Pedicle localization and identification play an important role in screw insertion for spinal deformity. The AI algorithm contributes to the localization and identification of pedicles. Esfandiari et al.  establisCorrection simulation and intraoperative functional detection of spinal deformity can gain profit from the contribution of AI. By considering preoperative spinal alignment and possible complications during operation, it will help shorten the operation time and reduce the risk of blood loss, nerve injury, and infection. The bending of the rods during operation needs repeated comparison, which is not only time consuming, but also increases the risk of infection. Solla et al.  obviouslIn recent years, robot-assisted technology has been applied in scoliosis correction surgery. Orthopedic robots use intraoperative image guidance technology and surgical navigation data to map surgical space and plan surgical paths, which has the functions of active positioning and coordinated human−computer movement . In spinHowever, the robot device is controlled by the surgeon, and its surgical effect is influenced by the learning curve stage of the manipulator. Therefore, solid surgical skills and knowledge are still essential for surgeons to ensure the safety of patients.Employing machine learning algorithms to anticipate the prognosis and potential complications following scoliosis surgery can significantly enhance the assurance of patient recovery in the postoperative phase. Imaging complications of scoliosis patients mainly include proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). Scheer et al.  used theIn recent years, AI has made remarkable progress in the diagnosis and treatment of scoliosis. In addition, AI has been gradually applied in case management and postoperative rehabilitation of patients. At present, AI technology is in the early stage of development, and there are still the following limitations and problems: ① AI has missed diagnosis and misdiagnosis in disease screening and diagnosis, and its accuracy is not 100% effective. ② Limited data and lack of multi-center verification in diverse clinical environments. ③ Lack of a perfect model integration platform, and lack of stability and limited generalization ability of the model. ④ Multi-professional collaboration to support and develop AI may pose economic challenges. ⑤ The execution rate of surgical robot programs is limited, and the operating systems are not fully intelligent. ⑥ AI involves patients’ data privacy and security, and its ethical issues cannot be ignored.Ethical Issues of Artificial Intelligence in Medicine and Healthcare” [When evaluating the transformative potential of AI in the management of scoliosis, it is paramount to consider its impact on the standard of healthcare. AI methodologies, particularly advanced imaging algorithms and machine learning techniques, promise a paradigm shift in both diagnosis and treatment strategies. For instance, AI can enhance the accuracy of scoliosis detection and curve progression prediction, leading to more timely and personalized interventions. Moreover, AI’s ability to integrate and analyze vast datasets can aid in developing more effective treatment modalities, potentially reducing the need for invasive procedures such as surgery. However, the integration of AI into clinical practice also raises significant ethical considerations. The use of AI in medical decision making must ensure patient privacy, data security, and mitigate biases inherent in algorithmic processes. As highlighted in the article “lthcare” , there iIn terms of models, the simulation system and future planning of AI need to be continuously optimized in many details, and clinical problems should be solved in combination with doctors’ clinical experience when designing the model. In terms of data, future AI algorithms need to be verified on the multi-center database platform to continuously improve the number and diversity of samples. Furthermore, it is imperative to underscore the importance of long-term studies for validating AI applications in diverse clinical environments. The effectiveness and safety of AI-driven interventions in scoliosis care must be demonstrated over extended periods and across varied healthcare settings. This is not only essential to ensure that these innovative technologies provide immediate clinical benefits, but also to maintain their efficacy and safety in the long term. Longitudinal studies will allow for the comprehensive assessment of AI’s impact on long-term patient outcomes, including quality of life and functional status post-treatment. Additionally, deploying AI tools in a variety of clinical settings, from specialized scoliosis centers to general hospitals, will enable the evaluation of their adaptability and generalizability across different patient populations and healthcare infrastructures. This approach aligns with the calls for rigorous validation in medical AI research, as is emphasized by Chen et al. . By commThe development of AI needs the joint efforts of bioinformaticians, computer scientists, data engineers, and doctors. Facing the rapid development of science and technology, doctors should know and be familiar with the theoretical knowledge and operating system of AI as much as possible, and gain the initiative in clinical use in the combination of AI and medical technology, so as to serve human society more effectively.AI plays an important role in the clinical practice of scoliosis, which aims to assist the diagnosis of scoliosis and improve the treatment efficiency. At present, the application of AI in scoliosis mainly uses ML and DL algorithms for image segmentation to assist its diagnosis and treatment. In addition, the emergent spinal robotic technology also allows the surgical treatment of scoliosis to be more minimally invasive and intelligent, which can significantly improve its surgical outcomes. Although AI has made gratifying progress in early imaging screening, automatic evaluation of imaging parameters, treatment decision making, surgical assistance, and prognosis prediction of scoliosis, it still has some problems such as limited generalization ability and limited data sources. Looking ahead, several promising directions can further advance AI’s role in scoliosis management. First, there is a critical need for developing AI systems with enhanced generalization capabilities, capable of accurately functioning across diverse patient populations and varied clinical settings. This requires the collection and integration of large, varied datasets that reflect the spectrum of scoliosis presentations. Second, interdisciplinary collaborations between AI researchers, clinicians, and biomechanical engineers can foster innovative solutions, particularly in the realm of personalized medicine. Customized treatment plans based on AI-driven predictions could significantly improve patient outcomes. Third, exploring the potential of AI in patient monitoring and postoperative care can optimize long-term treatment strategies and enhance patient quality of life. Finally, as AI technology evolves, ethical considerations and the development of robust guidelines for its application in clinical practice must be a priority to ensure patient safety and data privacy. We believe that with the continuous development and optimization of AI, it can achieve revolutionary changes in the diagnosis and treatment of spinal surgery. In the future, AI will present more new methods and more reliable prediction models and infiltrate into all aspects of clinical practice related to scoliosis.


Animal diarrhea is a prevalent issue in animal production globally and causes significant economic losses to animal husbandry. Typically, the occurrence of diarrhea is closely related to imbalances in intestinal microbiota. Animals with diarrhea have an altered intestinal microbiota balance, and infection by pathogens can result in a diarrhea phenotype . DiarrheZong et al. explored the effect of the oral milk-derived bioactive tripeptide, VPP , on the degree of diarrhea and intestinal inflammation in pre-weaning Holstein calves. In this study, 18 calves with similar birth dates, weights, and genetic backgrounds were selected. The calves were randomly assigned to two groups (n = 9): the control group  and the VPP group . The test lasted for 17 days. The findings revealed that oral administration of VPP resulted in decreased levels of pro-inflammatory factors in the blood, increased concentrations of short-chain fatty acids  in stool, and altered the intestinal microbiota of calves. Consequently, VPP reduced the severity of calf diarrhea prior to weaning. In this study, the author found that administering VPP to calves before weaning was a practical strategy to reduce the degree of intestinal inflammation and diarrhea in calves, which is essential to improve the future production performance of calves and cultivate excellent reserve cattle.Neonatal calf diarrhea is a globally recognized disease in the cattle industry. With its high incidence rate, mortality, growth retardation, treatment costs, and severe long-term consequences, it has caused significant economic losses . AntibioWang et al. explores ways to treat rumen swelling through nutritional regulation. The results showed that supplementation with concentrated tannins and other additives can effectively prevent and treat rumen swelling caused by feeding with high-concentration diets.Rumen bloating is a common digestive system disease in ruminants, characterized by gas accumulation in the rumen and reticular rumen, and may damage digestive and respiratory functions (including diarrhea). Changes in modern feeding methods have led to an increase in the incidence of abdominal bloating in grazing and enclosed ruminants . The secEscherichia coli (ETEC) is the primary cause of post-weaning diarrhea (PWD) in piglets , ETEC-challenge (PC), ETEC-challenge accepting garlic and apple pomace (GA), and ETEC challenge accepting garlic and blackcurrant (GB). The results showed that the incidence of diarrhea in piglets in the GA and GB groups was significantly lower than that in ETEC-infected piglets, and the Prevotella and Lactobacillus in the GB group were more abundant than those in the PC group. In summary, dietary supplementation with GA and GB limits ETEC proliferation, reduces PWD, and beneficially affects the diversity, composition, and stability of fecal microbiota.Modern intensive breeding systems frequently utilize early weaning technology to enhance sow productivity, leading to an increased annual litter size for sows . However piglets . The thiBonetti et al. conducted a similar study in vitro. The author explored the protective effects of a group of essential oils and natural extracts on intestinal Caco-2 cells infected with Escherichia coli F4 infection. The experimental results indicated that thyme essential oil (ThyEO) and grape seed extract (GSE) can effectively protect the epithelial integrity of Caco-2 cells under the infection of Escherichia coli F4; GSE effectively reduces the inflammatory response, and ThyEO and ginger essential oil significantly reduce the adhesion of Escherichia coli F4. These in vitro and in vivo experimental results support the use of dietary supplements and plant extracts to manage PWD in piglets.The fourth article written by This Research Topic strengthens our understanding of various strategies for preventing post-weaning diarrhea in young animals and provides new ideas for further research in this field. Although these four articles have proposed feeding strategies to alleviate gastrointestinal diseases in animals, there are still some areas of knowledge that need to be explored. In order to optimize nutritional regulation and promote the healthy development of young animals, future research should focus on exploring the role of nutrition in improving the intestinal health of pre-weaning calves and piglets. It is crucial to explore potential mechanisms for alleviating gastrointestinal diseases in animals through advanced technologies such as metagenomics and metabolomics to identify new biomarkers. In addition, future research should study the long-term impact of nutrition control measures on the growth and development of young animals in order to develop more effective nutrient management strategies, prevent digestive tract problems in animals, and promote the development of the livestock industry.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Among central nervous system structures, the cerebral cortex is widely recognized as the hub of higher cognitive functions that distinctly characterize humans. With its intricate network of connections, bewildering variety of cell types, and peculiar multilaminated structure, the cerebral cortex has undergone a dramatic evolution over time accompanied primarily by an increase in proportions in relation to body size. Indeed, the gyrification process is a result of the expansion of novel classes of progenitor cells, especially the outer radial glia, that produce and provide migration guidance for upper-layer cortical neurons, many of which are characteristic of the most evolved species and define the neocortex, underlining its recent phylogenetic origin.This Research Topic aims to present a comprehensive overview of the latest advancements in cerebral cortex development. Special attention is given to the role of the molecular mechanisms that coordinate its assembly, the involvement of non-neuronal cells in its development and in the acquisition of cognitive abilities, and the evolutionary factors influencing its cytoarchitecture.per se may not be sufficiently informative, as translation into proteins may be delayed, depending on mRNA stability, localization, and editing  and microRNAs during corticogenesis. Both RBPs and microRNAs operate as translational repressors exerting control over various processes, including neural proliferation and differentiation  in five mammalian orders: human and non-human primates , rodents , Eulipotyphla (Erinaceous europeus), Artiodactyla (Sus scrofa), and Carnivora (Mustela putorius). The authors describe a spatial arrangement of minicolumnar bundles of the primary visual cortex (V-1) in linear or branched strings with variable intra-layer length, density, and intracolumnar distance, depending on the species . In general, V-1 minicolumns spanned from the base of layer 3 to the white matter in all great apes including humans, and carnivores, whereas other mammalian orders had a diverse structure made of repeating modules or microcolumns with a shorter layer extension and more irregularity in the spatial patterning. There was a strong association between the abundance of minicolumns and visual acuity, thus indicating the existence of a relationship between a numerical parameter in cortical cytoarchitecture and an indicative function of the computational power.The arrangement of minicolumns is another crucial aspect of cortical structure that has undergone evolutionary changes across different species (Buxhoeveden and Casanova, Degl'Innocenti and Dell'Anno summarized prevalent astrocyte differences between mice and humans in an overview that starts with cortical astrogliogenesis and includes morphological and functional differences. Compared with rodents, human astrocytes have a higher degree of complexity in size, morphology, and extension of intercellular interactions, all aspects that reflect their increased capacity in fostering synaptic transmission and increasing mouse cognitive capacities upon engraftment (Han et al., Several observations have supported the notion that non-neuronal cells, specifically astroglia, may affect cortex development and evolution. Findings included unique characteristics of primate astroglia, implying a potential contribution to cortical processes (Oberheim et al., In summary, the findings in this Research Topic offer a comprehensive overview of factors participating in cortex development and key divergences that have led to the acquisition of distinctive species-specific features. These elements collectively contribute to our understanding of the intricate processes shaping the cortex and its evolutionary trajectory. The data in these five articles, in conjunction with studies outside this Research Topic, should provide clues for uncovering the logic behind the vast heterogeneity of the human cerebral cortex, not only to reveal underlying mechanisms in neurological or psychiatric disorders but also to disclose the neurobiological elements conferring the uniqueness, multifaceted talents, and capacities of the human brain.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Nanosystems provide an attractive approach to pharmacological therapy, with the possibility of enhancing the performance and overcoming the constraints of conventional therapies, thus adding substantial value to some of the already available formulations. Among these, lipid-based nanosystems  possess enormous potential due to their ability to improve drug delivery, enhance therapeutic efficacy, and enable the targeted and controlled release of bioactive compounds. Their unique properties make them suitable for an extensive range of applications owing to their lipid biocompatibility, low toxicity, and versatility. Currently, the development of nanomedicines that are based on lipid nanosystems capable of delivering therapeutic agents to a desired site in the body is an attractive area of pharmaceutical research. The major advantage of local drug delivery is that drug/bioactive concentrations can be enhanced in a specific desired site, minimizing toxicity to other nontargeted locations. Local drug delivery using nanosystems can be accomplished via various means: direct local placement  or systemic administration, which can be either targeted or triggered.Pharmaceutics, entitled Lipid Nanosystems for Local Drug Delivery, presents a collection of ten innovative works—seven original research studies and three review papers—describing recent advances in the development of lipid nanosystems suitable for local drug delivery, employing various strategies , and highlighting their advantages in this research area.This Special Issue of Concerning localized drug delivery lipid-based nanosystems, Smoleński et al. , in a coAlthough the topical administration of therapeutic agents to the skin appears to be preferable when aiming to manage skin conditions due to the lower likelihood of systemic adverse effects, the stratum corneum restricts their penetration. Therefore, lipid-based nanosystems have been demonstrated as one of the most effective strategies for improving skin permeability by fluidizing the lipid matrix of the stratum corneum without interfering with the skin barrier’s functions. In this regard, a team of researchers from the University of Huddersfield, UK, formulated a stable nanoemulsion for the topical delivery of mupirocin, a topical antibacterial agent, to the skin . The autIn another study involving Romanian researchers, Scomoroscenco et al.  preparedResearchers from different institutes in Jordan  proposed a combined system of prednisolone-loaded microemulsion and thermoresponsive in situ microgels in order to achieve sustained local drug delivery to the eye . The devIn terms of cancer therapy, several researchers are focusing on therapeutic delivery systems that regulate chemotherapeutic release and uptake, specifically in the tumor site, while limiting toxicity in healthy cells. With this perspective, a collaboration of Portuguese researchers developed and optimized pH-triggered hybrid (polymeric/lipid) lyotropic non-lamellar liquid crystalline nanoassemblies for drug delivery that exhibited the sustained and significantly higher release of doxorubicin in a pH of 5.5—i.e., an acidic environment typical of cancer cells and endosomal vesicles—compared to the release of doxorubicin under a pH of 7.5—i.e., typical of normal physiological conditions [Furthermore, in a collaboration between the Humboldt University and the Potsdam Institute for Climate Impact Research, Germany, the Saratov State University and the Russian Academy of Sciences, Russia, and Aston University, UK, Semyachkina-Glushkovskaya et al.  proved tAs is well known, different variables, such as the resistance mechanisms and physicochemical properties of antiviral agents, have a negative impact on the efficacy of antiviral therapeutic strategies. Therefore, researchers from Rhodes University in South Africa and from the University of Kinshasa and the Official University of Bukavu in the Republic of the Congo produced stable lipid nanocapsules in order to enhance the biopharmaceutical properties of efavirenz, a non-nucleoside reverse-transcriptase inhibitor . The autThis Special Issue’s review papers have addressed significant themes for researchers working in the following areas of interest: (i) the application of microfluid technology to prepare lipid-based nanosystems ; (ii) thVoogelar et al. , from thThe editors of this Special Issue are very grateful and express their appreciation to all of the authors, who are experts in the field of lipid-based nanosystems and have responded to our invitation to share the findings of their excellent quality research, as well as for the critical assessments of their manuscripts.


The allocation of the midwife-led care unit (MLCU), a midwifery-led care model in which midwives carry out eminent roles to enrich maternal and newborn outcomes with minimal standard interventions, has appeared to be productive in furthering the quality of care and positive childbirth experiences. In the present article, we review the investments needed in MLCUs for their inclusion into the public health system by describing their advantages, the latest trends in maternal mortality, the roles of midwives, the relevant background, and the current advances in midwifery practices in India. Midwifery-led care is directed by a philosophy that considers pregnancy and childbirth as normal physiological events for women. Making use of a midwife, especially in low-risk pregnancies, extends satisfactory and cost-effective care. The Government of India has begun to introduce midwifery services to the country to improve the quality, righteousness, and worthiness in the provision of care and to offload higher-level hospitals. The year 2020 was designated as the "Year of the Nurse and the Midwife" by the WHO, highlighting the importance of nurses' and midwives' roles in sustaining quality health care. Further, the acceptability among clinicians and the public is crucial for the future advancement and implementation of MLCUs in India. Advancing maternal-child health is pivotal to any nation's healthcare development . HoweverSevere maternal outcomes: globallyThe maternal mortality ratio (MMR) remains high across the world. Approximately 295,000 women died from complications related to pregnancy and childbirth in 2017. Most of these 94%) deaths occurred in low-resource settings. Sub-Saharan Africa and Southern Asia reported approximately 254,000 (86%) of the figured global maternal deaths. Sub-Saharan Africa singly reported about two-thirds of the maternal deaths, whereas Southern Asia reported about one-fifth. These high MMRs in some countries accentuate the wide gap between the MMR of developed and developing countries . The MMR% deaths Severe maternal outcomes: IndiaIndia shares 15% of global maternal deaths . India mMidwife-led care unitsEvidence shows that midwifery-led maternal health services were efficacious as an adjunct in reducing severely negative maternal outcomes. Midwife-led care includes comprehensive obstetric and newborn care provided by a midwife either at an in-site hospital-based care unit or as a stand-alone care unit outside the institutional referral center. In-hospital care units have proven to be beneficial in improving poor access to maternal health care and difficult referral systems . The proSearch strategyWe executed an extensive literature review by browsing several databases, namely PubMed, Scopus, Web of Science, Google Scholar, several obstetrics and gynecology organizations, associations' web pages, and the Government of India Guidelines, using the following keywords and phrases: "maternal health," "newborn health," "midwifery practice," "nurse practitioner in midwifery," "midwives," "severe maternal outcome," and "midwife-led care unit." We also screened the reference list of selected articles to examine other relevant articles. We subsequently assessed the selected literature and synthesized the findings to include them in the present review article under the following subthemes: severe maternal outcomes in India and globally, the role of midwives in maternal and newborn health, midwifery practices in India and globally, and the future of midwifery in India.Literature reviewCompared to other countries, India's healthcare system offers little independent midwifery-led care for women during pregnancy, childbirth, and the puerperium period . In the MLCU componentsMidwifery-led care is an evidence-based practice that involves improved maternal care. Ideal MLCUs involve midwives adequately skilled to aid childbearing women, providing care that promotes normal physiological pregnancy and childbirth and encourages and defends non-intervention during vaginal delivery . MidwiveRole of midwives in promoting maternal health and reducing adverse outcomesThe capacity of midwives to achieve SDGs has expanded over the past few decades. Midwifery lies at the core of health systems intended to improve maternal and child health, and efforts to improve such systems will be invigorated by strengthening midwifery care. Midwives ensure that women, newborns, and families receive adequate and timely care -20. The The Lancet Series on Midwifery revealed that implementing full-scope midwifery can improve over 50 aftereffects of childbirth for women, newborns, and families by mitigating risk, improving emotional and mental health, and preserving resources. Table MLCUs' utilitarian approachMLCUs satisfy clients using a multipronged strategy . The preAlthough MLCUs are cost-effective and sustainable for low-risk populations, their efficacy is questionable for high-risk cases. Evidence supports a higher usage of non-pharmacological pain relief methods in the context of MLCUs rather than instrumentation to promote patient satisfaction . A systeMany childbearing women seek freedom of selection for their desired birthing place or method. To make such a decision, clients should be provided with all relevant information and requisite knowledge of available choices and a comprehensive explanation of the advantages and disadvantages of each. Demographic patterns, geography, risks, and availability influence a client's decision . AlthougFurther, the presence of someone who is both empathic and skilled during the process of childbearing has benefits. Women may feel secure and emotionally comfortable in the presence of a midwife ,19. MidwMLCUs must employ competent midwives equipped with the requisite skill sets and knowledge to provide optimal care. To supplement this, frequent obstetrician-led education programs and workshops aimed at conducting safe vaginal deliveries and newborn care should be organized. Additionally, midwives should be able to identify impending danger early and make timely referrals to higher centers . The autImproving patients' confidence and feelings of self-efficacy during childbirth and newborn care consistently minimizes the associated negative impact and augments mood elevation and overall satisfaction. A US-based correlational descriptive study found that women using a midwife during childbirth possessed a greater level of personal control over and satisfaction with their experience . There iMidwifery practices globallyMidwives have historically contributed to dwindling MMRs. Since the 1600s, Sweden has been the foremost innovator among Nordic countries in midwifery education. Sweden's land mass is extensive compared to its relatively small population, making the availability of doctors in rural areas a challenge. Midwifery as an educated and paid profession was developed and expanded throughout the country . CurrentMidwifery practices in IndiaSeveral studies have highlighted the origin of midwifery in India, which dates to British control, and the challenges in nursing and midwifery education, regulation, organization, and policy-making since. Presently, India's healthcare system necessitates competent, independent midwives . In 2005Rajasthan is the first Indian state that has sought to organize and regulate nurse practitioners (NPs). Although there are many NPs in the region, particularly in rural areas, their recognition by the population has not yet been legitimatized. In 2002, the state of West Bengal pioneered the adoption of a nurse practitioner in midwifery (NPM) course under the India-Aus AID project; this program provided 18 months of training for diploma and graduate nurses, sanctioned those nurses at 12 posts around their state and afforded them their due recognition in 2010 . SimilarMoreover, the Government of India developed a constructed role for registered nurse practitioners (RNPs) as community health officers (CHOs), which could be achieved after participating in a six-month training program. These CHOs are scheduled to provide healthcare services, leadership, supervision, and management and play a dynamic role in India's healthcare system .Various midwifery-led care models have been introduced in India to explore variations in childbirth experiences, such as RN training programs, ICM standard compliance, and childbirth outcomes, in contrast to physician-led care models . These iEffective implementation of midwifery practices in IndiaRole of NPMs and Integration Into the Existing Healthcare SystemThe recognition of midwives, auxiliary nurse midwives, and staff nurses is necessary to generate evidence-based policies . There iNPM Career ProgressionA career progression pathway for NPMs has not been suitably planned after introducing midwives into the existing healthcare system, making it challenging for those newly appointed to proceed as members of an autonomous profession. Moreover, the midwifery profession is not yet regulated and is consequently proscribed to work as a separate cadre in the health system. Thus, even after completing midwifery training, midwives are often not allowed to work within their scope of practice and competence. It is of key importance to deploy midwives in their determined professional areas so they can engage in their full scope of practice and promote positive health outcomes for women, newborns, and families .Strengthening of Legal and Regulatory FrameworkA lack of regulatory framework is a primary factor negatively affecting midwifery in India. The Indian healthcare system confronts various hurdles in healthcare provisions, including poor standards, unspecific regulatory functions, and insufficient amends. These deficits have hindered the creation of leadership posts, thereby debilitating the progress of the midwifery profession. Many studies have evidenced the significance of midwifery for maternal and neonatal health, indicating the necessity of making lawful attempts to legitimize NPMs as an autonomous profession independent of generalized nursing .Midwife TrainingThe National Midwifery Task Force, led by various experts, revealed that further post-basic education  will be required to harness competent midwives. Additionally, the Indian Nursing Council stated that a range of innovative educational strategies can be practiced in both academic and clinical settings to foster learning experiences . It is iThe suggested solution to address the challenges (Author's own creation based on reviews) includes the establishment of a separate Directorate for Midwifery Education and Practice; the establishment of a separate Midwifery Council at both Central and state levels to regulate Midwifery Practice in India; the framing of a Midwifery Bill to standardize Midwifery Practices throughout the nation; the formulation of job specifications and descriptions for Nurse Midwives at all levels of care after adequate brainstorming; the building of supervision mechanisms across the healthcare system; the provision of adequate investment for Midwifery education and practice in India; the legitimization of NPMs as an autonomous and independent profession; networking and collaboration with Central and State government agencies and local administrative authorities to implement and facilitate midwifery practice; ensuring that trainee midwives are adequately trained by maintaining student and case load ratios, with the adoption of innovative strategies in academic and clinical settings to foster their learning experiences; and the timely review of the scope of midwifery practices.There is adequate evidence to support the beneficial aspects of midwifery care in promoting maternal and newborn health. Governmental leadership in enhancing midwife education, employment, and effective utilization in health centers is crucial to improving maternal and newborn care in India. Respectful treatment for clients and collaboration among obstetricians are other vital factors in sustaining high-quality midwifery practices. Additionally, clinicians and researchers should strengthen MLCU participation through evidence-based research. Moreover, cooperative interdisciplinary training and the development of effective skill sets among midwives can be promoted by involving experts in the fields of obstetrics and gynecology, pediatrics, and public health.


Diabetes is a chronic metabolic disease caused by a reduction in the production and/or action of insulin, with consequent development of hyperglycemia. Diabetic patients, especially those who develop neuropathy, presented dysbiosis, with an increase in the proportion of pathogenic bacteria and a decrease in the butyrate-producing bacteria. Due to this dysbiosis, diabetic patients presented a weakness of the intestinal permeability barrier and high bacterial product translocation to the bloodstream, in parallel to a high circulating levels of pro-inflammatory cytokines such as TNF-α. In this context, we propose here that dysbiosis-induced increased systemic levels of bacterial products, like lipopolysaccharide (LPS), leads to an increase in the production of pro-inflammatory cytokines, including TNF-α, by Schwann cells and spinal cord of diabetics, being crucial for the development of neuropathy. Diabetes is a chronic metabolic disease characterized by hyperglycemia due to a reduction in the production and/or action of insulin.,Neuropathy is the most prevalent complication of diabetes, occurring in up to half of all people living with this disease.Pathogenesis of diabetic neuropathy,,,,,,In diabetic patients, the development of neuropathy is multifactorial and involves uncontrolled glycemia, diabetes duration, and age-related neuronal attrition.,,,,The exact mechanism that promotes alterations in the peripheral nervous system and, consequently, neuropathic pain in diabetic patients is not fully elucidated. Nonetheless, several evidences showed that hyperglycemia and dyslipidemia induce pathological changes in neurons, glia, and vascular cells that culminate in nerve dysfunction and neuropathy.,,,,In diabetes, the overproduction of ROS induces activation of PARP-1 with a concomitant decrease in ATP formation.,,,,,,,,,Several pre-clinical and clinical studies showed upregulation of pathways involved in inflammation in peripheral nerves.Diabetes and gut microbiota,The human gut microbiota contains up to 100 trillion of microbes, including commensal, symbiotic, and pathogenic bacteria, as well as archaea, fungi, and viruses.,,Diet, early-life microbiota exposure, antibiotic therapy, changing hygiene status, pollution, socioeconomic status, and other environmental factors can directly influence the composition of gut microbiota and its metabolic products, making it unique to each individua.,,,,,,In early stages of life, the extensive exposure to antibiotics may lead to dysbiosis, resulting in underweight or overweight.,Firmicutes and Bacteroidetes is unbalanced in these patients.,,Prevotella copri and Bifidobacterium longum, probiotic bacteria, and enrichment of families like Ruminococcaceae, Clostridiaceae, Clostridiales, and Oscillibacter, bacteria associated with infection and inflammation.It is well known that diabetic patients showed dysbiosis.,,Faecalibacterium prausnitzii, improved the intestinal barrier permeability and reduced circulating levels of LPS.The maintenance of homeostasis in gut environment is important not only to slow-down diabetes development but it is also central in the control of its complications.,In diabetic patients, the gut leakiness is accompanied by a low-grade inflammation, with increased levels of IL-1β, IL-6, and TNF-α in the blood.,,,,,Lactobacillus rhamnosus NCDC17 improved the insulin resistance, in parallel to a reduction in IL-6 and TNF in the epididymal fat.Remarkably, treatment with probiotics is one of the most used strategies to modulate intestinal microbiota and their used can prevent diabetes establishment and is effective as adjuvant in insulin resistance therapies.Gut microbiota and neuropathic pain,,,,,,,,,,The gut microbiota plays a role in the maintenance of nervous system function, through immunological, hormonal, and neuronal signals.Furthermore, the gut microbiota is also involved in the pathophysiology of neuropathic pain. For instance, some chemotherapy drugs, including paclitaxel and oxaliplatin, cause chemotherapy-induced peripheral pain (CIPN) during anti-cancer treatment,Since the development of neuropathic pain can be related to changes in the gut microbiota and diabetic patients presented dysbiosis in association with neuropathy, a central question arises: can dysbiosis and the consequent pro-inflammatory status be critical for the development of neuropathic pain in diabetes?Dysbiosis is important to the establishment and aggravation of diabetic neuropathyIn diabetes, dysbiosis occurs in parallel to a break in the epithelial-intestinal barrier and translocation of bacterial contents to the bloodstream.Interestingly, the incubation of Schwann cells in a high glucose environment induced an increase in the apoptosis of those cells in association with overexpression of TLR4, the receptor activated by LPS, and a rise in the TNF-α production.,,,,,TNF-α is produced primarily by endoneurial macrophages and Schwann cells,Sodium butyrate has anti-inflammatory and neuroprotective effects in spinal cord injury, including the improvement of motor function and the reduction of neutrophils accumulation and pro-inflammatory cytokine expression.,The composition of the gut microbiota can change during the development of diabetes. Interestingly, the diversity of gut microbiota from patients with type 2 diabetes with gastrointestinal autonomic neuropathy was modified compared to type 2 diabetic patients without this condition. Diabetic patients with neuropathy presented an increase in the relative abundance of pathogenic bacteria of phyla Proteobacteria,Furthermore, the flavonoid quercetin reversed mechanical pain and intraepidermal nerve fiber density in streptozotocin-induced diabetic rats, in clear association with the reduction of pathogenic bacteria species and the enrichment of two prebiotic species.In conclusionIn conclusion, we postulate that the increase in the richness of pathogenic bacteria and a reduction in the abundance of butyrate-producing bacteria in the gut microbiota of diabetic patients may be responsible for the onset of peripheral neuropathy. The dysbiosis in diabetes triggers a break in the intestinal barrier with consequent increase in the bacterial products, such as LPS, into the bloodstream. Possibly, the activation of TLR4 in the Schwann cells and spinal cord of diabetics induces an overproduction of TNF-α, resulting in the increase of pain . In this


The use of natural antimicrobials in the food industry is being proposed as an eco-friendly postharvest technology to preserve fruit-derived foods. In this context, this systematic review aims to describe and discuss the application of naturally occurring antimicrobial compounds in the processing of fruit-derived foods by the PRISMA methodology. In a first step, the use of free natural antimicrobials was investigated as an approach to identify the main families of bioactive compounds employed as food preservatives and the current limitations of this dosage form. Then, the use of immobilized antimicrobials, in an innovative dosage form, was studied by distinguishing two main applications: addition to the food matrix as preservatives or use during processing as technological aids. Having identified the different examples of the immobilization of natural antimicrobial compounds on food-grade supports, the mechanisms of immobilization were studied in detail to provide synthesis and characterization guidelines for future developments. Finally, the contribution of this new technology to decarbonization and energy efficiency of the fruit-derived processing sector and circular economy is discussed in this review. The consumption of natural healthy products, such as fruit and their derivatives , has increased in recent years owing to their convenience and acknowledged nutritional and functional properties. These properties are the result of their high content of vitamins , antioxidants, polyphenols, and fiber, and their low sodium and fat contents .Alicyclobacillus acidoterrestris) and pose public health problems  according to the U.S. FDA . However, heat treatments cause loss of water-soluble and oxygen-labile nutrients, such as vitamins [2/L of juice in a 96% heat recovery thermal system [2/L of juice. With these data, the carbon footprint that results from the pasteurization of liquid foods in Europe can be estimated at 1 × 105 tons CO2/year. Moreover, the addition of synthetic preservatives, such as sorbates, benzoates, or sulfur dioxide, is very much questioned because their use can lead to dangerous health problems or antimicrobial resistance [As fruit-derived foods are perishable, their processing plays a crucial role in guaranteeing their safety and extending their shelf life. Fruit preservation techniques are based mainly on the use of heat treatments or synthetic preservatives. Heat treatments  enable a product’s microbial load to be reduced or eliminated, and allow the enzymes present in food to be deactivated and, thus, contribute to greater stabilization. Thermal pasteurization is considered the most appropriate methodology for some fruit-derived foods, such as juices, to ensure a 5-log reduction in the microorganisms that can cause spoilage  to fruit-derived products, and their use after covalent immobilization on the surface of different food-grade supports, to be employed as food preservatives or food processing aids to avoid modifying the sensory properties of the food. This review includes the advantages and disadvantages of utilizing natural antimicrobials according to their formulation (free or immobilized forms) and their application form on the food product (preservative or processing aid). A description of the main methodologies for the covalent immobilization of natural antimicrobials and the most relevant characterization techniques to verify covalent grafting and bioactivity is also included. Finally, future perspectives of these alternative preservation technologies are proposed.A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines  was condThe selection process proposed by Bhardwaj et al. (2023)  and RifaThe search results were exported to Mendeley reference manager and duplicates were removed.Documents were screened according to the inclusion and exclusion criteria in the title and abstract. Eligible articles were evaluated by three reviewers after considering the inclusion and exclusion criteria for the full text .Variations in the number or records in each stage were checked and any discrepancies were assessed by the reviewers to make a final decision.Information about the number of records included in this review and the summary of the selection process of the included articles are shown in The systematic review on the use of natural antimicrobials in fruit-derived foods revealed that essential oil components (EOCs), bacteriocins, polysaccharides, organic acids, or bacteriophages are the most frequent molecules employed as preservatives in fruit-derived foods, probably due to their consideration as GRAS  products by the U.S. FDA . EOCs are a mixture of different compounds, such as terpenes, alcohols, phenols, etc., generated from plants. Free hydroxyl functional groups (-OH) are mostly responsible for their antimicrobial activity . BacteriEscherichia coli, Salmonella enterica, and Listeria monocytogenes, yeasts, such as Zygosaccharomyces bailii, Zygosaccharomyces rouxii, and Saccharomyces cerevisiae. In the reviewed studies, the authors reported remarkable efficacy for the microbiological control of all the fruit-derived foods. The antimicrobial activity of the naturally occurring compounds was tested in different fruit-derived products  against bacteria, such as Despite the demonstrated in vivo inhibitory efficacy of antimicrobials, some studies have revealed that their direct addition to food presents certain limitations that stem from their intrinsic physico-chemical properties. Mitropoulou et al. (2020)  and Thomp < 0.05) by incorporating thymol at concentrations up to 2 mM. Further research rated the appearance, odor, taste, aftertaste, viscosity, and overall acceptance parameters at different concentrations of isoeugenol (0–1 µL/mL) added to pineapple juice [p < 0.05) in the odor, taste, aftertaste, and overall acceptance scores, while no changes were recorded for the appearance and viscosity characteristics. Using EOs from Citrus medica and Cinnamomum zeylanicum for microbiological wine stabilization [In addition to all these limitations, some reports have shown that the incorporation of these compounds modifies some food sensory attributes. The study of Beristaín-Bauza et al. (2018)  evaluatele juice . The reslization , aroma aThe interaction of antimicrobial compounds with food matrix components also limits their application in food products ,28,29,30For all these reasons, research is currently exploring new alternative dosage forms of natural antimicrobials to be used as food preservatives or processing aids, such as encapsulation of immobilization. The first alternative consists of trapping an active agent  in a carrier material to enhance its later release in the food or in the gastrointestinal tract. Immobilization, in contrast, consists of anchoring the active biomolecule on the surface of the support. This technology not only makes it possible to preserve the native antimicrobial properties of the active biomolecule but also prevents its leaching into the food matrix due to the creation of covalent bonds between the support and the antimicrobial compound. Having this in mind, covalent immobilization is presented in this work as an eco-friendly postharvest technology with great possibilities for application in the preservation of fruit-derived foods.The use of immobilized natural antimicrobials to preserve or extend the shelf life of fruit-derived products has increased in recent years owing to their marked antimicrobial effectiveness and good capacity to cushion their sensory and stability impact on foods after grafting ,49,50.Immobilization refers to the chemical, physico-chemical, or electrostatic binding of bioactive molecules to a surface. Chemical immobilization involves the formation of at least one covalent bond between the surface and the target biomolecule, which represents the most permanent and irreversible form of coupling. Covalent linkage involves strongly bounding the compound of interest with a potentially longer shelf life, greater bioactivity, and lower toxicological risk . The immAccording to this systematic review, these antimicrobial systems can be applied to fruit-derived foods in different processing stages: (i) as a food additive (preservative) present in the final product and (ii) as food processing aids that are absent in the final product see . This seIn the last few years, the design of immobilized antimicrobial systems as food preservatives to control or prevent microbial spoilage in fruit-derived foods has grown. In this context, Ribes et al. (2017)  conducteFinally, it is worth mentioning that all these reviewed systems present common characteristics: (i) the bioactive compound is covalently immobilized on the surface of the support; (ii) immobilized bioactive compounds exhibit greater antimicrobial or antifungal activity than their free form; (iii) the use of these novel preservatives does not modify the final product’s physico-chemical or sensory properties.The second approach of using immobilized natural antimicrobials in fruit-derived foods does not imply the permanence of particles in food to exert their antimicrobial effect. So in this case, instead of considering the antimicrobial supports to be food preservatives, they should be taken as processing aids.A. acidoterrestris growth in apple juice and recovered particles after treatment. After demonstrating that the juices treated with functionalized magnetic particles were not influenced in physico-chemical and sensory terms, as well as the non-toxicity and biosecurity of composites, the authors highlighted this innovative antimicrobial system as a promising tool to control A. acidoterrestris contamination in the juice industry. In the systematic review of this application, four works used immobilized antimicrobials as processing aids. Within this framework, Song et al. (2019)  employedA. acidoterrestris contamination from apple juice due to the antibacterial action of nisin and the retention of spores on the membrane surface. In a different approach, Peña-Gomez et al. (2019) [E. coli load inoculated in pasteurized apple juice of at least 5 logarithmic reduction values (LRVs). In addition, employing antimicrobial particles for the filtration of fresh juices was able to microbiologically stabilize the non-thermally treated apple juice, which resulted in juice with high microbial stability and quality. This suggests that this filtration technology is a promising alternative to existing pasteurization technologies that apply heat. In another work, Ruiz-Rico et al. (2021) [Conversely, the other three studies applied the immobilization of natural antimicrobial compounds on food-grade supports as a strategy to create filtration systems for the cold pasteurization of liquid fruit-derived foods. The main objective of these filtration systems was to remove spoilage or pathogenic microorganisms from liquid fruit-derived products (juices or wine) through the retention and/or the disruption of the bacterial cell wall after the interaction with the antimicrobial compound . Zhang e. (2019)  develope. (2021)  evaluateThese described filtration systems differ from micro- and ultrafiltration techniques, which have been extensively studied and implemented for the cold pasteurization of drinks on an industrial scale, in terms of removal capacity and their impact on the properties of filtered drinks. The mechanism of action of micro- and ultrafiltration  is the physical retention of all the molecules and organisms bigger than the pore size. In contrast, filtration systems based on membranes or particles functionalized with natural antimicrobials exhibit a larger pore size or filtration channels that only allow the partial retention of microorganisms and food matrix components. Therefore, they act by the combined effect of cell retention and cell damage due to the specific interaction with the antimicrobial compound by preserving the nutritional, functional, and sensory properties of the filtered drink.After identifying and analyzing the different examples of applying immobilized natural antimicrobials, this section describes the immobilization approaches in detail to provide a guideline of the synthesis and characterization of these antimicrobial systems for future developments.Chemical immobilization can be a complex process for preserving the antimicrobial properties of the target molecule on a specific surface. The specific properties of the substrate surface, such as composition, charge, hydrophilicity/hydrophobicity, chemical stability, roughness, and geometry, as well as antimicrobial characteristics, including molecular structure, charge, and molecular size, should be considered for the bonding process. In addition, covalent immobilization can alter the conformational molecule structure by altering its mechanism of action. Therefore, coupling strategies should be carefully evaluated to optimize the attachment and maintenance of antimicrobial properties .The substrate surfaces for the immobilization of biomolecules are diverse in terms of their features and properties, but the main characteristic they must present for coupling is the presence of sufficient functional groups for attaching the target molecule . OtherwiSurface activation is a set of methods used to alter the chemistry of a substrate surface by introducing chemical groups or charges on the surface. Different techniques are available to make surface modifications to supports prior to immobilization, including silanization as the main strategy . SilanizFor covalent immobilization purposes, the functional moieties of the biomolecule must be compatible with the reactive groups present, either spontaneously or occurring after a previous surface modification on the substrate surface. The biomolecule chemical structure should be studied to preserve antimicrobial properties. The main drawback of covalent immobilization is the potential disruption of antimicrobial activity after bond formation. Immobilized biomolecules can be attached to the surface by a specific site that is responsible for the inhibitory potential, or in a rigid spatial orientation that can significantly change antimicrobial properties. In addition, the grafting process should ensure suitable coating density and uniformity to guarantee the reproducibility and scale up of immobilization, as well as the preservation of the grafted biomolecule’s efficient antimicrobial activity . TherefoBiomolecules that contain intrinsic chemically reactive groups, such as carboxylic acid, amino, sulfhydryl, and hydroxyl groups, can be covalently immobilized onto activated surfaces through chemical interfacial reactions by non-selective immobilization. This type of grafting can result in more than one type of covalent bonding with different biomolecule orientations . In contThe aim of antimicrobial immobilization approaches is to design antimicrobial-coated substrates that should exert their biocidal properties after grafting without apparent release, and result in increased stability, a longer shelf life, and enhanced bioactivity . To ensuSurface chemistry should be characterized by analytical techniques to establish the coating’s coverage and the effect of coating on the substrate microstructure, surface charge, surface morphology, porosity, and size . These tThe biocidal properties of the immobilized antimicrobial are characterized by in vitro antimicrobial performance testing against microorganisms of interest in different microbial life stages . These vThe simulation of the other parameters relevant to the real application of the developed immobilized antimicrobials is another important factor for characterization. Shelf life, cleaning, and stability requirements should be characterized to establish adequate durability . Prior tSeeking new technologies capable of preserving fruit-derived foods and minimizing the impact of processing on the sensory, nutritional, and functional properties of fruit-derived foods, while reducing the carbon footprint of thermal processing, are major challenges for today’s food industry. With such tasks, the solution could come from a new approach to the application of natural antimicrobials: their immobilization on food-grade supports. The immobilization of different natural antimicrobials (mostly EOCs) on silica particles is a proven excellent strategy to create effective food preservatives (direct use) or processing aids (indirect use) capable of improving the microbiological quality of fruit-derived foods by extending their shelf life, but without altering nutritional, functional, and sensory properties.Beyond these advantages, this alternative approach to traditional heat treatment is also seen as an eco-friendly postharvest technology. On the one hand, it could contribute to improving the decarbonization and energy efficiency of the fruit-derived processing sector because it avoids using heat. On the other hand, it provides solutions based on nature, such as natural antimicrobial biomolecules. Moreover, as most of these proposed natural antimicrobials are obtained from plant and animal by-products, their valorization will comply with bioeconomy principles by reducing waste and generating added value to the agri-food sector. Finally, this technology might be used to preserve fruit-derived foods in developing countries with restricted access to other complex and expensive technologies or electricity. As limitations to the immediate use of this technology, it should be noted that all the applications shown in this work have been exclusively investigated on a laboratory scale, and the immobilization processes described in the different works are laborious and require energy and solvents. These limitations could be reduced by employing green chemistry to reduce the use of solvents and photocatalysis by resorting to solar or white light as a source of energy for the immobilization steps. In either case, this review demonstrates how the immobilization of natural antimicrobial compounds on food-grade supports possesses all the features required to be proposed as an eco-friendly postharvest technology that is capable of preserving fruit-derived foods.