Globally, obesity is on the rise. Research over the past 20 years has highlighted the far-reaching multisystem complications of obesity, but a better understanding of its complex pathogenesis is needed to identify safe and lasting solutions. Globally, obesity is on the rise. This Perspective looks at how research over the past 20 years has changed the way we view obesity and what the future might hold for further mechanistic understanding and treatment and prevention options. PLOS Biology 20th anniversary collection.This article is part of the Obesity is a multifaceted disorder, affecting individuals across their life span, with increased prevalence in persons from underrepresented groups. The complexity of obesity is underscored by the multiple hypotheses proposed to pinpoint its seminal mechanisms, such as the “energy balance” hypothesis and the “carbohydrate–insulin” model. It is generally accepted that host (including genetic factors)–environment interactions have critical roles in this disease. The recently framed “fructose survival hypothesis” proposes that high-fructose corn syrup (HFCS), through reduction in the cellular content of ATP, stimulates glycolysis and reduces mitochondrial oxidative phosphorylation, processes that stimulate hunger, foraging, weight gain, and fat accumulation . The marThe past few decades of scientific progress have dramatically transformed our understanding of pathogenic mechanisms of obesity . FundameBeyond intercellular communication mediated by extracellular vesicles, the discovery of interactions between the host and the gut microbiome has suggested important roles for this interkingdom axis in obesity. Although disturbances in commensal gut microbiota species and their causal links to obesity are still debated, transplantation studies have demonstrated relationships between Firmicutes/Bacteroidetes ratios and obesity . EvidencAlthough the above discoveries focus largely on perturbations in energy metabolism (energy intake and expenditure) as drivers of obesity, a recently published study suggests that revisiting the timeline of obesogenic forces in 20th and 21st century society may be required. The authors tracked 320,962 Danish schoolchildren (born during 1930 to 1976) and 205,153 Danish male military conscripts (born during 1939 to 1959). Although the overall trend of the percentiles of the distributions of body mass index were linear across the years of birth, with percentiles below the 75th being nearly stable, those above the 75th percentile demonstrated a steadily steeper rise the more extreme the percentile; this was noted in the schoolchildren and the military conscripts [First, in terms of endogenous factors relevant to individuals, stressors such as insufficient sleep and psychosocial stress may impact substrate metabolism, circulating appetite hormones, hunger, satiety, and weight gain . ReducedIn addition to the effects of exposure to endogenous and exogenous stressors on the risk of obesity, transgenerational (passed through generations without direct exposure of stimulant) and intergenerational (direct exposure across generations) transmission of these stressors has also been demonstrated. A leading proposed mechanism is through epigenetic modulation of the genome, which then predisposes affected offspring to exacerbated responses to obesogenic conditions such as diet. A recent study suggested that transmission of disease risk might be mediated through transfer of maternal oocyte-derived dysfunctional mitochondria from mothers with obesity . AdditioStrikingly, the work of the past few decades has resulted in profound triumphs in the treatment of obesity. Multiple approved glucagon-like peptide 1 (GLP1) and gastric inhibitory polypeptide (GIP) agonists  (alone oWhere might efforts in combating obesity lie in the next decades? At the level of basic and translational science, the heterogeneity of metabolic organs could be uncovered through state-of-the-art spatial “omics” and single-cell RNA sequencing approaches. For example, analogous to the deepening understanding of the great diversity in immune cell subsets in homeostasis and disease, adipocyte heterogeneity has also been suggested, which may reflect nuances in pathogenesis and treatment approaches. Further, approaches to bolster brown fat and thermogenesis may offer promise to combat evolutionary forces to hoard and store fat. A better understanding of which interorgan communications may drive obesity will require intensive profiling of extracellular vesicles shed from multiple metabolic organs to identify their cargo and, critically, their destinations. In the three-dimensional space, the generation of organs-on-a-chip may facilitate the discovery of intermetabolic organ communications and their perturbations in the pathogenesis of obesity and the screening of new therapies.Looking to prevention, recent epidemiological studies suggest that efforts to tackle obesity require intervention at multiple levels. The institution of public health policies to reduce air pollution and the vast employment of EDCs in common household products could impact the obesity epidemic. Where possible, the availability of fresh, healthy foods in lieu of highly processed foods may be of benefit. At the individual level, focused attention on day-to-day behaviors may yield long-term benefit in stemming the tide of obesity. “Wearable” devices that continuously monitor the quantity, timing, and patterns of food intake, physical activity, sleep duration and quality, and glycemic variability might stimulate on-the-spot and personalized behavior modulation to contribute to the prevention of obesity or of maintenance of the weight-reduced state.Given the involvement of experts with wide-ranging expertise in the science of obesity, from basic science, through clinical/translational research to epidemiology and public health, it is reasonable to anticipate that the work of the next 2 decades will integrate burgeoning multidisciplinary discoveries to drive improved efforts to treat and prevent obesity.


The decarboxylative pathways are activated for two main physiological reasons. Decarboxylation is one of the responses of cells to acid stress and it has been demonstrated that the transcription of many decarboxylase genes is induced by low pH and improves cell performances in acid conditions. Moreover, these pathways can bring supplementary energy to the cells by energizing the proton motive force associated with the membrane.Biogenic amines (BAs) are non-volatile low-molecular-weight nitrogenous organic bases that can be found in nearly all types of foods in a wide and variable range of concentrations. The most significant BAs occurring in food are histamine, tyramine, putrescine, cadaverine, tryptamine, 2-phenylethylamine, spermine, spermidine, and agmatine. BAs are produced by microorganisms, mainly bacteria, through the action of decarboxylases, which act selectively on precursor amino acids in which they remove the carboxyl group with the formation of the correspondent biogenic amine and COBAs can be produced both by Gram-positive and Gram-negative bacteria which occur naturally in food products, are introduced by contamination, or are added as a starter culture. Among Gram-negative bacteria, spoilage microorganisms belonging to Enterobacteriaceae and Pseudomonas are known as the major producers of cadaverine, histamine, and putrescine. The ability to produce BAs is widespread also among Gram-positive bacteria. The decarboxylase activity has been found in strains belonging to the genera Bacillus and Staphylococcus. However, attention has been mainly focused on lactic acid bacteria (LAB), which are commonly present or intentionally used in fermented food.Ingestion of food containing BAs represents a considerable toxicological risk for consumer health since these compounds can cause headaches, heart palpitations, vomiting, diarrhea, and hypertensive crisis. However, their toxic effect depends on the type of BAs, individual sensitivity or health status, and on the consumption of ethanol or monoamine oxidase inhibitory drugs, which interact with amino oxidase enzymatic systems responsible for the detoxification process of exogenous BAs.Microorganisms  that are able to produce biogenic amines in models or real systems may be evaluated. Furthermore, such subjects could include descriptions of novel knowledge and strategies for aminogenesis control: use of bioprotective cultures producing bacteriocins or other antimicrobial substances, technological additives, effects of packaging, other non-thermal treatments, and use of microbial cultures able to degrade BAs and detoxifying them through the action of amino oxidases.The Aminobiogenic Potential of Fermented Food Microbiota”. The topic collected four research articles from international researchers. This Research Topic is focused on the aminobiogenic potential of fermented food microbiota, taking into consideration the conditions affecting biogenic amine accumulation and the enzymes and genes involved in the biosynthetic mechanisms.In this context, we organized this Research Topic on “Sang et al. aimed to evaluate the ability to produce BAs of halophilic bacteria isolated from grasshopper sub shrimp paste. The authors analyzed and discussed the bacterial and fungal diversities and BAs contents in grasshopper sub shrimp paste at different fermentation times. They concluded that the actual production of BA by a particular strain was closely related to other species present in the complex fermentation system. The experiment carried out provided important insights into the microbiota and BAs content of grasshopper sub shrimp paste.The study of Yang et al. evaluated the amine production abilities of strains of enteric bacteria screened from Chinese traditional fermented fish. The genotypic diversity of amino acid decarboxylase and the effect of pH were explored on strains of high-yield BAs. They reported that all tested strains carried the corresponding amino acid decarboxylase genes of putrescine and cadaverine. In addition, almost half of the strains carried the histidine decarboxylase gene. The research demonstrates that acid stress causes growth delay but can increase the contents of putrescine, histamine, and cadaverine.Yu et al. presented a study on the change in BA content and microbes involved in BA formation during mustard fermentation. They showed that diverse bacterial species harbored genes associated with the production of various BAs. Four BAs  were generated during mustard fermentation. According to the metagenome sequencing, the predominant genus was Bacillus followed by Lactobacillus, Weissella, and Leuconostoc in the initial fermentation stage, while Lactobacillus became the most dominant genus in the late stage.Hernández-Macias et al. investigated whether the use of cava lees can help to control biogenic amine formation in bread and fermented sausages. The authors showed that cava lees and their phenolic extract are an effective strategy to control the undesirable accumulation of high levels of biogenic amines during the production of fermented products. However, the effect of reducing the high levels of biogenic amines was not as effective as the use of starter cultures.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Thumb base osteoarthritis (OA) is a prevalent hand OA phenotype, associated with specific risk factors, treatment strategies, and requiring a distinct subset of evaluative approaches. This paper aimed at surveying our clinical evaluative methods and identifying gaps in our ability to capture the thumb’s unique attributes and how they could impact our treatment recommendations.A scoping review was conducted in accordance with the Joanna Briggs Institute methodology to gather relevant published and non-published articles regarding clinical tests currently available to assess the physical presentation of thumb base OA with special consideration of its specific multifactorial parameters namely architecture, ligaments, biomechanics, neuromuscular control, and proprioception. A full search strategy of MEDLINE, CINAHL, EMBASE, Scopus, Google Scholar, and Clinical Trials.gov from their inception through May 2020 was performed.Of 1936 citation identified, 54 met the inclusion criteria. Fifty-two clinical physical tests for the evaluation of thumb base OA were extracted, most of which well suited to address research questions regarding efficacy of clinical intervention, however providing limited information regarding the underlying impairments of ligaments, biomechanics, neuromuscular or proprioceptive components.The tests and measures specific to the basal thumb OA phenotype, and capable of isolating its multifactorial contributors are scarce. Our limited physical assessment repertoire impedes our ability to describe and answer explicative research questions. Without these we cannot evaluate the effect of conservative management and provide specific treatment recommendations. Further research is needed to develop and validate distinct clinical tools for this debilitating pathology. Hand OA encompasses three different phenotypes  each associated with different risk factors requiring different treatment strategies.Thumb base osteoarthritis (OA) is a prevalent distinct hand OA subset that results in considerable clinical burden.35 Although the clinical diagnosis of OA may be reached in the at-risk population using the classification criteria for OA of the hand developed by the American College of Rheumatology (ACR),7 the classification does not distinguish between OA in interphalangeal and thumb base joints.The risk factors for thumb base OA include mechanical load, hypermobility, systemic factors such as obesity, hormones and other yet unclear potential metabolic contributors, as well as genetic influence.9 which challenges our understanding of its pathomechanics.The thumb's broad range of performance from strong grip to very precise manipulations is a testimony to its complex nature. With its kinematic structure organized in a serial chain of five, invariant, nonorthogonal and nonintersecting rotational degrees of freedom , nine activating muscles , and elaborate neuromuscular and proprioceptive network, it translates into a diverse crowd of kinematic model types affecting its functionality,1014 Despite confirmation of improvement in pain and function, their conclusions regarding the effect of non-surgical therapies for the management of OA of the hand and thumb remain unable to provide specific treatment guidance due to the heterogeneity of the study designs and outcome parameters.Several recent systematic and scoping reviews have shown that the ability to effectively isolate and assess the efficacy of rehabilitative interventions for thumb base OA is limited. and recent primary research study on the OA classification's inter and intra-rater reliability found that the Eaton method had low to moderate reliability, suggesting that it should be used with caution when correlating with clinical findings and making treatment decisions. The authors propose that other qualitative factors, such as reported symptoms and physical examination are more important for choosing treatment modalities than Eaton radiographic classification. Although the Osteoarthritis Research Society International (OARSI) identified some core outcome measurement sets for studies in hand OA and a list of methods and instruments that should be used to measure symptoms or structures, to our knowledge no recommendations have yet been proposed in consideration of the recognized multifactorial nature of thumb stability and mobility. The existence of a broad variety of presentations of thumb kinematic models, resulting from its multifactorial nature,9 requires the establishment of an expended evaluative approach considering its unique characteristics; architectural, ligamentous, biomechanical, neuromuscular, and proprioceptive.Patient selection of many rehabilitation clinical trials is based on the radiographic disease state through different grading classifications of articular degeneration. A systematic review For example, the benefits of the use of a thumb orthosis may be measured through functional performance or with a patient-reported outcome measure, which makes it difficult to determine the ideal type of orthosis, as the primary outcome measure does not target the underlying aspects of the intervention such as the biomechanical rationale. To move the research efforts towards the explanatory end of the spectrum, we propose to refine the physical function and hand strength domains and associated outcome measures specific to the thumb base OA phenotype, looking at clarifying the presentation of the problematic thumb chain.Another explanation for the limited treatment guidance of conservative management of thumb base OA could reside in the selection of rehabilitation trial designs, perhaps leaning more toward the pragmatic versus explanatory side of the design continuum, where the primary outcome although meaningful, may not be the direct result of the intervention, as described in the OARSI clinical trials recommendations for rehabilitation intervention for OA. As the American population above the age of 65 is projected to increase from 16% to 22% by 2050, the expected influx of incidences compels us to revise our approach to the assessment of thumb base OA, as a better definition of the problem could help lay the foundational blocks of preventative treatment.Current statistics on occurrence of thumb base OA in males and females in their fifth and sixth decade of life reaches 11% and 33%, respectively.A preliminary search of PROSPERO, MEDLINE, the Cochrane Database of Systematic Reviews, and the Joanna Briggs Institute (JBI) Database of Systematic Reviews and Implementation Reports was conducted and no current or underway systematic reviews on the topic were identified.The objective of this scoping review was to map the current evidence on clinical physical tests to assess thumb base OA and provide an analysis of their coverage of the multifactorial components specific to the thumb. The review aims to address the following questions: i) what are the current clinical physical tests of thumb base OA; ii) which thumb dimensions are considered by current tests; and iii) what are the gaps in the approach to assessment of the multifactorial nature of thumb OA?22 The Institute and its international collaborating entities promote and support the synthesis, transfer and implementation of evidence through identifying feasible, appropriate, meaningful and effective healthcare practices to assist in the improvement of healthcare outcomes globally. Scoping reviews, like systematic reviews focus on rigor, reproducibility, and transparency. They draw on evidence from any research methodology and may also include evidence from non-research sources. In this manner, scoping reviews provide a comprehensive overview to address broader review questions than traditionally more specific systematic reviews of effectiveness or qualitative evidence. Scoping reviews are particularly helpful when the literature is complex and heterogeneous, as is the case regarding clinical tests for thumb base OA.This scoping review was conducted in accordance with the Joanna Briggs Institute methodology.The review considered literature including information on current physical assessment tools used in clinical settings, targeting human adult population above 50 years of age, presenting with thumb base OA. We selected the term thumb base OA as it refers to a defined hand OA phenotype. The assessment selection included however the entire thumb chain components when presented in connection to thumb base OA. Documents referring to pre-existing conditions that were known to influence joint morphology or kinematics, such as traumatic injury, thumb or hand surgery, inflammatory arthritis, metabolic bone disease were excluded.Extracted clinical tests of the thumb and its kinematic chain were mapped to underline their respective affinities to the thumb-specific dimensions namely architectural, ligamentous, biomechanical, neuromuscular, and proprioceptive.Studies conducted in orthopedic out-patient clinics, hand therapy clinics, occupational and physical therapy outpatient clinics, rehabilitation clinics, universities, and hospitals.Experimental and quasi-experimental study designs including randomized controlled trials, non-randomized controlled trials, before and after studies and interrupted time-series studies, analytical observational studies including prospective and retrospective cohort studies, case-control studies and analytical cross-sectional studies, descriptive observational study designs including case series, individual case reports and descriptive cross-sectional studies.The search strategy aimed to locate both published and non-published studies. An initial limited search of MEDLINE (Pubmed) and CINAHL was undertaken to identify articles on the topic. The text words contained in the titles and abstracts of relevant articles, and the index terms used to describe the articles were used to develop a full search strategy. The search strategy, including all identified keywords and index terms, was adapted for each included information source, and restricted to articles published in English and French. The reference lists of all studies selected for critical appraisal were screened for additional studies. For each database, we used words and expressions from controlled vocabulary  and free-text searching. The search combined words and expressions of four conceptual groups: Trapeziometacarpal (TMC) joint, OA, physical examination, and different aspects of thumb stability and mobility including kinematics, kinematic chain, biomechanics, ligament, strength, neuromuscular control, and proprioception.Six databases were searched from inception until May 2020 (Appendix 1). They included MEDLINE (Pubmed), CINAHL, EMBASE, and Scopus. Sources of unpublished studies and gray literature included Google Scholar, and Clinical Trials.gov. The full text of selected citations was assessed in detail against the inclusion criteria by two independent reviewers. Any disagreements that arose between the reviewers at each stage of the study selection process was resolved through discussion, or with a third reviewer. The results of the search were presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram.Following the search, all identified citations were collated and uploaded into Endnote X9 version 3.1 and duplicates removed. Titles and abstracts were then screened by two independent reviewers for assessment against the inclusion criteria for the review. Potentially relevant studies were retrieved in full and their citation details imported into the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI) . relative to architecture, ligaments, biomechanics, neuromuscular control, and proprioception. Although most instruments' ability to isolate single contributors to the thumb's performance is limited by the inherent simultaneous activation of many systems, certain tests and measures have greater affinity toward some of them. We classified the affinity based on the thumb dimensions definition/affinity criteria presented in Data were extracted from papers included in the scoping review by two independent reviewers using a data extraction tool developed by the first author. Any disagreements that arose between the reviewers was resolved through discussion, or with a third reviewer. The third reviewer, who speaks French, served as one of the main two reviewers for the French documents. Authors of papers were contacted to request additional data, when required. The two reviewers further organized the extracted tests and measures based on their respective evaluative focus of this global joint disorderThe initial search identified 1936 documents, 1912 from different databases and 24 from extended search of cited references. Following the removal of duplicates and screening of titles and abstracts, 95 documents were selected for full text assessment. Forty-one of them did not meet the selection criteria, leaving 54 suitable for inclusion .Fifty-four documents containing information on clinical physical tests and measures of thumb base OA were retained for analysis. Data regarding the participants, concept, context, type of evidence source, applied tests/instruments, and psychometric validation were extracted (Characteristics of Included Studies can be found in the online Supplementary file I). The types of evidence source included systematic reviews, randomized control trials, test re-test study, cross-sectional study, prospective comparative pre-experimental study, cross-control study, prospective case control study, case-control study, prospective within patient repeated measures study, prospective cohort study, cross-sectional observational pilot study, practice guidelines, clinical trial recommendations, textbook chapter, expert opinion, and poster presentation. Some applied tests and measures were not considered in the final compilation in accordance with our selection criteria. The rejected tests and rationales are listed in From the 54 analysed documents, 52 clinical physical tests and measures for the evaluation of thumb base OA were extracted . The mosArchitectural: Nine tests and measures presented affinity to the architectural aspect of thumb stability. Tests included in this category provided information regarding anatomical location of the disease through pain/tenderness or crepitus provocation, and deductive assessment of the degree of articular cartilage degeneration. Psychometric validation was not available for 4 of them. There was an overlap with some of these tests with those of the architectural group due to their combined detection of crepitus along with laxity. Psychometric validation was not available for 9 of the 15 tests.Ligamentous: Fifteen tests and measures presented affinity to the ligamentous aspect of the thumb. Tests included in this category primarily informed the observer on the subjective general laxity of the trapeziometacarpal (TMC) joint and the irritability of the joint capsule. Several different testing techniques were depicted and were mainly assessing the TMC joint, except for the Metacarpophalangeal (MCP) joint Instability Test and Degree of Laxity of Interphalangeal (IP) and MCP joints as their names indicate. The Screw Home Torque proposed a method of assessment of the integrity of the dorsal ligament complex more specifically. Six of those tests did not provide psychometric validation, including the latter.Biomechanical: Nine tests and measures presented affinity for the biomechanical aspect of the thumb. Tests of this category provided information on mobility of the thumb and wrist, span of the first web space, MCP joint rigidity or hyperextension, as well as arc position and muscle recruitment of the thumb under load. The Colditz Tear Test was the only one assessing mechanical behaviour under load.Neuromuscular: Thirteen tests and measures presented affinity for the neuromuscular aspect of the thumb. Information gathered from those tests included thumb and finger flexor muscles strength, simultaneous thumb abduction and index extension strength, speed of grasp and release of objects, adjustability of grasp to different size objects, precision grip, and general motor control and speed of thumb and fingers. Few of those tests overlapped with the previous category due to their simultaneous consideration of joint mobility and muscular control. Five of those tests did not provide psychometric validation.Proprioceptive: Seven tests and measures presented affinity for the proprioceptive aspect of the thumb. Information obtained from those tests included sensory discrimination, sensory perception, as well as joint position sense of the TMC joint, and functional performance of the hand based on proprioception of the upper limb and tactile input of fingertips. Psychometric validation was not available for three of them.Inclusive: Ten of the 52 tests were categorized as inclusive due to the functional nature of their performance and did not allow for discrimination of their relative affinity. Half of them did not report psychometric validation.The gaps and their clinical and research implications are summarized in 28 TMC joint stability requires integrity of its primary stabilizing ligament, which the Screw Home Torque targets, however there is no psychometric confirmation of its validity for clinical use. Considering that the posterior ligament complex also plays an important role as proprioceptive organ, imparted by the density of its mechanoreceptors, the implication of our ability to determine its status could influence the direction of treatment.Data from the ligamentous test category provide us with subjective appreciation of the laxity of the thumb joint capsules, which is of questionable usefulness, as debate carries on regarding the causal relationship between laxity and development of basal thumb OA.30 little is recorded regarding the thumb's kinetics, or behaviour under load. The Colditz Tear test was the only one to propose a way to clinically assess this feature, nevertheless it is an observational test without quantifiable results and does not have psychometric validation data. Interestingly, four distinct functional patterns of thumb key pinch were identified in healthy subjects, which were independent from the level of strength and hyperextension availability at the MCP joint. However, these patterns have not been studied with the basal thumb OA population.Data from the biomechanical test category inform us primarily on kinematics of the thumb joints, however, does not encompass the broader thumb chain, which includes the wrist. Although thumb base OA is considered more biomechanically driven,33 Additionally, we are unaware of a quantifiable method for assessment of muscular imbalances which has been identified as a risk factor. Although motion capture and load cell technologies can quantify motion and force with high accuracy and repeatability in research laboratory, this technology is unavailable in the clinical setting.Data from the neuromuscular test category do not provide information on isolated voluntary control of individual thumb muscles. The pinch and grip strength, although appearing more precise, represent a combination of muscular actions and remain devoid of information on the quality of the execution specific to the thumb. Some instruments measuring intrinsic muscular force have been identified; however, they have not been validated with all thumb muscles or with the basal thumb OA population. The strength dexterity test proposes an instrument that provides some insight on the subject however, the instrument is not currently available for clinical use.Regarding the proprioceptive data, as suggested in a review of current concepts regarding the proprioception of the wrist joint, when considering the proprioceptive senses under the conscious and unconscious umbrellas, data collected from our available tests is richer in the former which includes somatosensory information such as tactile, pain, joint position sense. The neuromuscular senses reflect the unconscious control in joint proprioception and include joint stability and feed-forward control that has not yet been isolated for quantitative appreciation. Several clinical tools, in particular self-administered questionnaires meet those criteria and have been extensively studied. Conversely, the few performance-based instruments recommended for the assessment of our domains of interest i.e. physical function and hand strength, were described as not disease specific, less studied, with variable metric properties for the hand OA population, and overlapping investigated domains. Overall, performance-based and self-reported functional assessments were quoted as evaluating different domains of disability and unable to identify certain specific underlying impairments. Five years later, the results of our scoping review reflect ongoing shortcomings of validated assessments and measures of characteristics specific to thumb base OA phenotype.Fifty-two clinical tests for the evaluation of thumb base OA were identified and classified into 5 thumb dimensions recognized as pillars of stability and mobility of the thumb, namely architecture, ligaments, biomechanics, neuromuscular control, and proprioception. Despite a large number of assessments, the information provided remains insufficient regarding quantification of ligamentous laxity, performance under load, individual thumb muscle strength, joint stability and feed-forward control, which are needed to answer questions related to therapeutic interventions efficacy. The OARSI recommendations for design and conduct of clinical trials for hand OA presented in 2015 supported the study of thumb base OA as a specific phenotype. They advocated the use of instruments that are valid, reliable, responsive to change, feasible and publicly available. Most evidence regarding the evaluation and treatment of basal thumb OA continues to trend toward the pragmatic end of the design spectrum. The questions answered by this design relate to the effectiveness of a given intervention in real-life routine, practice, or conditions. For example: Do thumb orthoses or exercises help decrease pain and improve function of people with basal thumb OA? In contrast, the explanatory trials answer questions related to the if and how an intervention works. For example: What is the best orthosis design for thumb base OA and why? Unfortunately, this type of inquiry requires different outcome measures that are not currently available. As it pertains to basal thumb OA phenotype, the need for measures of thumb specific parameters is evident and the development and validation of new tests and instruments is required to deepen our understanding of this debilitating condition and to improve the specificity and justification of our treatment recommendations.Pragmatic trials measure a wide spectrum of outcomes, mostly patient-centered, whereas explanatory trials focus on measurable symptoms or markers .Despite adherence to a systematic search process, eligible studies may have been inadvertently excluded due to the exclusion of surgical cases in our selection criteria. However, we think that the diagnostic process is uniform and independent from conservative or surgical management. Our selection criteria also excluded tests and measures that are not clinically available, which did not allow for consideration of tools currently in developmental stage. Mention of those is made in our results section, nevertheless the official tabulation is true to the current clinical situation. Finally, although important to the development of outcome measures, assessing methodological quality of included papers was outside the scope of this review.As the thumb basal OA emerges as a distinct hand OA subset supported by its distinct joint type, clinical burden, risk factor profile, clinical relevance of synovial inflammation and therapeutic interventions, it underlines the need for specific outcome measures in addition to the general hand OA assessments.The present scoping review has highlighted the scarcity of clinical tests and measures for basal thumb OA phenotype distinct features. We should continue to build on new ideas to translate our experimental knowledge into the applied clinical environment. It is imperative to consider the multifactorial aspect of thumb stability and mobility to better assess their contribution and analyse the impact of conservative management. Moving the research strategies toward the explanatory end of the spectrum, by developing new tests and measures to capture and selectively isolate the components of the thumb multifactorial presentation would improve the target of therapy and furthermore, provide evidence of its benefits or lack thereof.Click here for additional data file.Supplemental material, sj-pdf-1-hth-10.1177_17589983211002560 for Clinical evaluation of thumb base osteoarthritis: A scoping review by Mirka Normand, Tiffany S Tang, Jean-Michel Brismée Stéphane Sobczak in Hand Therapy


Pneumatosis intestinalis is a condition characterized by the presence of gas or air pockets within the walls of the intestines. It can occur in any section of the gastrointestinal tract but it is most commonly found in the colon. Etiology and pathogenesis of PI are not yet fully understood, but several potential factors have been suggested to play a pivotal role in the development of this pathologic condition. Pneumatosis intestinalis seems to arise from a complex interplay between various factors, such as the integrity of the intestinal lining, pressure within the portal vein, the composition of the microbiological flora in the gut. Pneumatosis intestinalis can be caused by a variety of underlying conditions, such as bowel obstruction, intestinal ischemia, infection, inflammatory bowel disease, or certain medications. Symptoms may include abdominal pain, bloating, diarrhea, vomiting, and bloody stools. We present a case report of a 63-year-old male patient who underwent laparoscopic cholecystectomy for symptomatic cholelithiasis with recurrent cholecystitis. Following the surgery, the patient experienced a rapid drop in hemoglobin levels, necessitating an urgency regimen laparoscopic abdominal exploration which revealed Meckel's diverticulitis with active bleeding leading to diverticulectomy. The next day, the patient developed a radiological condition characterized by the co-presence of intermittent pneumatosis intestinalis, Portal pneumatosis and intermittent small bowel obstruction. Pneumatosis intestinalis (PI) is a condition characterized by the presence of gas-filled collections within the wall of the digestive tract. They can be found throughout the digestive system, from the stomach to the rectum, although they are most frequently observed in the small intestine Primary pneumatosis intestinalis, also known as idiopathic pneumatosis intestinalis, occurs without an identifiable cause. It is often seen in newborns and infants but can also occur in adults. The exact mechanism behind primary PI is unknown, but it is thought to be associated with bowel wall inflammation or ischemia Secondary pneumatosis intestinalis, on the other hand, is associated with a variety of conditions or factors. These include gastrointestinal disorders such as inflammatory bowel disease, intestinal obstruction, intestinal infections, and certain medications like immunosuppressants. Other underlying causes can include mechanical trauma to the bowel wall, such as due to surgery or endoscopy, as well as respiratory conditions like chronic obstructive pulmonary disease (COPD) that can cause gas to migrate into the digestive tract The clinical presentation of PI can vary depending on the severity and location of the gas collections ,6. Mild Diagnosis of PI is primarily done through imaging studies such as abdominal X-ray, computed tomography (CT), or ultrasound. These can reveal the presence of gas within the intestinal wall or lumen. In some cases, additional diagnostic procedures like endoscopy or biopsy may be required to determine the underlying cause Treatment of PI depends on the underlying cause and the severity of the condition Escherichia and Clostridia species, may invade intraluminal compartments Pneumatosis intestinalis can be associated with various conditions, including bowel ischemia, bowel obstruction, inflammatory bowel disease, infections, and certain connective tissue disorders We present a case report of a 63-year-old male patient who went under laparoscopic cholecystectomy for symptomatic cholelithiasis with recurrent cholecystitis. Following the surgery, the patient experienced a rapid drop in hemoglobin levels, necessitating an abdominal CT scan with intravenous iodinated contrast.A 63-year-old male was admitted to the Radiology Department of University Hospital Luigi Vanvitelli in Naples for laparoscopic cholecystectomy due to a history of complicated biliary colic and cholecystitis. Shortly after the surgery, the patient experienced a rapid decline in hemoglobin levels, necessitating an emergency laparotomy to investigate potential iatrogenic source of active bleeding. During the exploratory laparotomy, a bleeding Meckel’s diverticulum was identified and surgically removed.Less than 24 hours after the surgery, the patient presented with diffuse abdominal pain, abdominal distension, and reduced intestinal peristalsis, raising suspicion of intestinal obstruction. An abdominal X-ray revealed subdiaphragmatic free air, a ladder-like pattern of fluid levels consistent with mechanical ileus, and radio transparency corresponding to the biliary tree . A contrGiven the stability of the patient and his comorbidities, a follow-up CT scan was scheduled 24 hours later, this time with oral contrast administration. The subsequent CT scan showed increased fluid and fluid-gas levels in the duodenum, jejunum, and ileum, with contrast passing beyond the ileocecal valve and presence of the surgical clips. Mild fluid distention of the right colon and sigmoid colon was also noted . After aThis case highlights a rare occurrence of intestinal pneumatosis and pneumobilia following laparoscopic cholecystectomy. The development of intestinal pneumatosis, characterized by the presence of gas within the intestinal walls, is a relatively uncommon finding, and its association with pneumobilia further adds to the complexity of the case. While the exact pathophysiology of these conditions in this particular case remains speculative, we hypothesize that dysfunction of the ileocecal valve clip played a role in the development of intestinal pneumatosis and subsequent pneumobilia. The presence of the surgical clips at the ileocecal valve raises the possibility of mechanical obstruction and impaired intestinal motility. This dysfunction could lead to stasis and distension of the intestinal lumen, creating a favorable environment for bacterial overgrowth and subsequent gas production. The resulting pneumatosis may have caused the escape of intramural gas nuclei through the compromised intestinal mucosa, leading to the observed pneumobilia.Furthermore, the calcified atherosclerosis involving the aorta, superior mesenteric artery, and celiac trunk observed in the arterial phase of the CT scan suggests potential vascular compromise. Although it is unclear whether this atherosclerosis directly contributed to the development of intestinal pneumatosis, it may have impaired the intestinal blood supply, further exacerbating the compromised intestinal motility.The resolution of the obstructive pattern and recurrent ileus seen in the follow-up imaging further support the hypothesis of ileocecal valve clip dysfunction as a contributing factor. The intermittent nature of the obstruction and its resolution suggest mechanical factors rather than a structural abnormality as the underlying cause. The subsequent resolution of symptoms and absence of recurrence after conservative management further support this hypothesis.While this case report provides insight into a rare occurrence, further research and similar case reports are needed to establish a definitive causal relationship between ileocecal valve clip dysfunction and the development of intestinal pneumatosis and pneumobilia. Moreover, additional studies should explore potential predisposing factors, such as patient-specific anatomical variations or surgical technique, that may contribute to this complication. A better understanding of these factors will aid in the identification and management of similar cases in the future.This case report highlights the challenges encountered in managing a patient with intestinal pneumatosis complicated by portal pneumatosis. The successful use of conservative management in our patient, despite the poor prognosis indicated by radiological findings, emphasizes the importance of individualized treatment approaches based on the patient’s condition and contraindications. Further studies are warranted to elucidate optimal management strategies for similar cases.Imaging diagnosis performed by integrating abdominal X-ray and contrast-enhanced CT with intravenous iodinated contrast allows for the diagnosis of intestinal complications, provides indications for follow-up, and identifies the presence of any post-surgical complications. The radiologist plays a crucial role in the procedural process and must therefore be aware of the type of surgery performed and the potential post-surgical complications. The clinical signs of abdominal discomfort and other nonspecific gut symptoms make it common for PI to be misdiagnosed as intestinal polyps, carcinoma, or colitis. As the number of surgeries increases, healthcare professionals must also increase their knowledge of PI. The diagnosis of PI heavily relies on the results of colonoscopy and abdominal CT. Treatment options for PI vary from observation and medication to oxygen therapy and surgery, depending on the patient’s symptoms and endoscopic findings. To avoid unnecessary surgery, the treatment approach should be tailored to the individual patient. If there are no significant complications, the prognosis is generally favorable.Informed written consent was obtained from the patient for publication of the case report and all imaging studies.


We also focus on the different wavelengths with respect to the lasers that are applied in endodontics. High-power lasers perform well as operative instruments; in addition, low-level lasers lead to the regulation of pulp inflammation, and the promotion of pulp healing. This narrative review provides a summary of the advanced applications of lasers in conjunction with various devices in the practice of endodontics, and aims to inspire innovative perspectives on lasers in the context of the treatment of dental diseases, especially pulp diseases, in the future.The utilization of lasers has been regarded as a novel technique for the purposes of clinical use in the dental field. Recently, numerous studies have been conducted on the potential applications of laser therapy in endodontics. Moreover, due to their ablation, penetrability, and disinfection capabilities, lasers have performed well with respect to endodontic treatments, including root canal treatment, vital pulp therapy (pulp capping and pulpotomy), dentinal hypersensitivity treatment, and management of dental pain related to pulp and periradicular disease. In particular, the superiorities of laser-aided pulp therapy are emphasized through condensed clinical controlled trials, and histological studies, in this review. Moreover, the ingenious use of laser applications with respect to aiding in the acceleration of root development and the extraction of foreign matters  in canals has quickly become the cutting-edge trend of current research. This review offers a summary and discussion of the current literature on all the aforementioned laser applications. Moreover, the characteristics of laser devices, including erbium lasers, neodymium-doped lasers, CO Endodontic treatment in dentistry involves decimating bacterial contamination, cleansing the root canal system, as well as regaining favorable morphology, and the functions of the tooth . MechaniDue to their characteristics regarding debridement, ablation, the regulation of inflammation, and the acceleration of healing, the application of lasers with different wavelengths and devices was introduced to dentistry, and has been conducted for decades . Laser tIn this review, we summarize the advanced applications of lasers in the context of endodontic treatment , includi2) lasers; and diode lasers. The mechanism of action and application in dentistry of these lasers are summarized in The types of lasers commonly used in clinical endodontic treatment include: erbium:yttrium–aluminum–garnet (Er:YAG) lasers; erbium, chromium-doped yttrium scandium gallium garnet  lasers; neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers; neodymium: yttrium–aluminum–perovskite (Nd:YAP) lasers; carbon dioxide  in order to remove debris and biofilms, which is still the most favored form of irrigation protocol in clinical practices . DespiteLaser-activated irrigation (LAI) was applied as an adjunctive method for root canal irrigation many years ago . The mecIntroduced for the purposes of clinical use in 2012, photon-induced photoacoustic streaming (PIPS) is an example of one of the emerging LAI techniques. When compared with conventional LAI methods, it renders features of low energy (10 or 20 mJ) and short pulse length (50 μs) . FurtherAccumulated hard tissue debris is a type of byproduct from root canal shaping, which should be removed during irrigation. A comparative experiment used 30 extracted human mandibular molars to compare the effectiveness of three different auxiliary means for removing accumulated hard tissue debris, including ultrasonically activated irrigation, PIPS, and SWEEPS. In addition, the evaluation was performed by microcomputed tomography. The PIPS and SWEEPS groups were performed with special fiber tips (PIPS 600/9 and SWEEPS 600) using a 2940 nm Er:YAG laser. The results showed that there was less remaining debris after SWEEPS than after ultrasonically activated irrigation and PIPS, especially in regard to complicated structures, such as isthmuses .As for the elimination of biofilm and calcium hydroxide, multiple studies have shown that LAI performed significantly better than SNI ,38,39. TNonetheless, the comparison between the efficiency of ultrasonically activated irrigation and LAI, engendered different results and views. The results of a comparative study, which used transparent resin blocks in two standardized root canals as the test models, demonstrated that LAI using a 2940 nm Er:YAG laser resulted in greater biofilm-mimicking hydrogel removal than ultrasonically activated irrigation . AnotherWhen the coronal loss is so severe that the remaining dental hard tissue cannot offer adequate support, while the teeth should be preserved for functional or aesthetic reasons, dentists will use fiber posts during endodontic treatment as intracanal retainers in order to disperse the forces transmitted to the roots, as well as to provide better retention and support . Due to The lifespan of endodontically treated teeth using fiber posts is connected with the effectiveness of bonding among the posts, the dentin, and the resin cement, due to the fact that debonding is a major cause of failure . In ordeGomes et al.  conducteAs for quartz fiber posts, an in vitro experiment showed that the irradiation of the Er,Cr:YSGG laser increased the PBS between quartz and dentin; additionally, an output power of 1.0 W was recommended in order to minimize the damage, and to maximize the PBS . FurtherThe controversial efficiency of fiber post surface treatment with lasers varies with different laser systems, and fiber post materials. Further research should be conducted in order to determine whether the laser’s energy, frequency, potency, pulse duration, irradiation time, and acting distance, influence the results of fiber post surface treatment. Completely removing the filling materials in root canals is an essential step in retreatment. This is due to the fact that the remnants can breed bacteria and block the apical area of root canals, thereby leading to retreatment failure. However, the filling materials are placed deep and dense in order to exert the biological effects fully around the periapical area, which renders the complete removal of the remnants a great challenge . SNI, paWe summarized the research on the application of lasers in root canal treatment. Meanwhile, details and parameters of the samples in the in vitro experiments and the application of the laser devices are listed in The preservation of pulp vitality is a critical target during endodontic treatment. In contrast with root canal treatment, vital pulp therapies, including pulp capping and pulpotomy, are available as options, offering less invasion and a higher cure rate for the carious exposed pulps . Pulp caMineral trioxide aggregate, calcium hydroxide, and formocresol, are all commonly used drugs. For the purposes of pulp capping treatment, calcium hydroxide has been widely used for decades. However, it must be noted that this practice often results in diverse and unpredictable outcomes . FurtherThe utilization of laser irradiation could accelerate the formation of the fibrous matrix and the dentin bridge. Further, the use of laser irradiation could also promote the expression of lectins and collagens in the exposed dental pulp tissues, thereby resulting in wound healing in respect of the pulp . A low-pClinical research on laser applications in pulp capping was carried out. A pilot study proved that the diode 808 nm laser-assisted procedure, including hemostasis and decontamination, could enhance the outcomes of pulp capping treatment for the purposes of carious exposures . Similar2 laser irradiation could inhibit the formation of dentin bridges by creating heat-denatured tissue around the exposed pulp. The thermal-induced denaturation was aggravated in proportion to the intensity of the lasers. Therefore, the selection of the wavelength or the frequency of the irradiation was deemed to be noteworthy [In this respect, through various histological studies in animals, a consensus was reached. The histopathology of pulpal and periapical tissue after direct pulp capping with a low-level 980 nm laser application was analyzed. The laser-aided group showed mild inflammation, organized odontoblasts, thicker predentin in the pulp tissue, and more fibrosis in the periapical area. The histologic sections were evidence that lasers could enhance healing after direct pulp capping . Howeverteworthy . In geneIn conventional pulpotomy treatment, the dentist amputates the putrescent coronal pulp with a round bur at a low speed, and removes this portion with a spoon excavator. After flushing and drying the pulp chamber, moist cotton pellets with ferric sulfate, formocresol, or other coagulative agents, are placed in it . After cThe clinical success of the pulpotomy treatment for primary teeth could be influenced by laser application. In order to face the challenges of various degrees of cooperation and the behavior management of children undergoing dental procedures, the laser was introduced on account of its low noise, as well as the reduced contact between tooth and mechanical instrumentation, which was especially attractive to pediatric dentists . As suchClinical evidence shows that lasers could perform as an alternative for primary teeth pulpotomy, with better patient compliance and outcomes. However, the selection of the devices and wavelength of the lasers still needs to be researched. Meanwhile, as certain trials showed no statistical significance, more survey samples and longer follow-up periods are expected and encouraged for the purposes of further research. The parameters and details of the above-mentioned clinical trials on the application of lasers in vital pulp therapy are listed in Pain is a major concern of patients; the prevention and management of pain during or after endodontic treatment are often critical for the patient’s comfort and quality of life . EndodonLasers were found to reduce pain-inducing substances , as well as increase the synthesis of lymphokines, immunoglobulins, anti-inflammatory prostaglandins, and beta-endorphins ,84. The Clinical trials have been carried out for different endodontic diseases. Patients with apical periodontitis suffer from typical spontaneous pain or pain on percussion when undergoing endodontic treatment. The associated pain intensity may be mitigated after the sources of inflammation and infection are removed using proper procedures. Lasers with different wavelengths or applying methods have also been introduced to treatment modalities for the purposes of decontamination and debridement of the root canal system. Yeon-Jee et al. utilized a 1440 nm Nd:YAG laser in order to treat teeth with symptomatic apical periodontitis via intracanal irradiation. The 300 μm fiber optic tip was dangled at the apical 3 mm level of the root canals for 10 s in the experimental group. By combining the assessment of the patient’s subjective pain level and the quantification of pain-related substances, they found that the irradiation group performed significantly better at the alleviation of pain and reduction in substance P, calcitonin gene-related peptide, and matrix metalloproteinase levels than what was found in the control group . AnotherPhotobiomodulation therapy is an alternative therapeutic strategy for dealing with safe and non-invasive features in order to reduce pain and inflammation . PhotobiPhotodynamic therapy, also known as antimicrobial photodynamic therapy, performs using antimicrobial properties via an interaction between a light source at a specific wavelength and a photosensitizer . FurtherHowever, clinical research depends on various factors, for instance, the effects of laser irradiation in relation to biological tissue, the complex causes of post-operative pain, and the individual differences in respect to pain perception. Recently, Fatma and colleagues paid attention to the lasers’ efficiency in respect of the post-operative discomfort of a patient with irreversible pulpitis and necrotic pulps. In their investigation, Nd:YAG and diode lasers were applied as adjuvant to the standard procedures, while a visual analogue scale was recorded in order to quantify the pain intensity. However, the use of the Nd:YAG and diode lasers showed no obvious improvement or deterioration of the pain level in patients with irreversible pulpitis and necrotic pulps. Furthermore, they advised that the body’s immune system will take major responsibility for healing as long as the contaminant removal and dense sealing have been executed properly . The definition of dentinal hypersensitivity is the pain arising from the exposure of open dentinal tubules to various stimuli including thermal, chemical, or tactile factors . The sti2) irradiation reached similar consequences at the end of the respective therapies [Numerous clinical research studies have compared laser-based therapy with drug-based protocols. Sgreccia et al. performed a randomized clinical trial, aimed at evaluating the low-power laser and potassium oxalate gel treatment for the purposes of cervical dentin hypersensitivity. Although the potassium oxalate resulted in immediate symptom reduction, the GaAlAS laser  showed superior dentin tubule occlusion, less intrapulpal temperature change, and hardly any morphological alterations of the pulps [2 had a significant effect on the diameter change in dentinal tubule orifices and caused less of an increase in temperature [In parallel, several researchers have accounted for the optimal parameters of laser treatment via in vitro studies; further, this was achieved by compromising between therapeutic effect and pulp safety. Zhuang and colleagues analyzed the performance of an Er:YAG laser with different parameters in the context of dentin tubule occlusion via scanning electron microscopy. Meanwhile, the assessment of the intrapulpal temperature stabilization and pulp tissue morphological invariability was also conducted. In addition, the extracted human molars after Er:YAG laser irradiation at 0.5 W  irradiation and calcium hydroxide without laser irradiation, respectively. According to the findings of this study, the combination of calcium hydroxide and laser irradiation had beneficial effects on the apexogenesis process. Therefore, lasers possess the potential to be utilized as an adjunctive method to promote the root development process. However, more clinical studies and several animal studies are needed in order to validate their effectiveness in the future.Trauma and decay can cause necrosis of the pulp tissue, which can lead to the obstruction of normal root development and an open apex . MTA is Lasers stimulate atoms or molecules in order to emit a specific wavelength of light and amplify it, resulting in coherent, monochromatic, well controlled, and precisely directed light beams. These characteristics render them useful in a wide range of fields, such as transmission, imaging, measurement, etc. When a laser interacts with biological tissues, it produces special biological effects, including thermal, photochemical, electromagnetic, and biological stimulation effects, which are the basis of its use in medicine. The rapid development of laser technology can usher in a new era for the diagnosis, prevention, and treatment of multiple diseases. More and more attention has been directed to its application and prospects in dentistry, and its clinical implications are mainly divided into two parts: hard tissue applications and soft tissue applications. Caries prevention, cavity preparation and dentinal hypersensitivity treatment are examples of hard tissue applications of lasers in dentistry, while soft tissue applications include gingivectomy, gingivoplasty, labial frenectomy, lingual frenum release, mucositis, and so on. In recent years, the literature has fully proved that laser treatment is an effective adjunctive method for endodontic treatment.In this review, we summarized the novel applications of lasers in endodontics and certain common dental procedures, regarding laser-based therapy as a potential option for dental treatment. However, the review is narrative; thus, no comprehensive analysis of the literature has been performed. Some conclusions related to the ideal type of laser and parameters for certain clinical purposes still required deliberations. Moreover, there are certain drawbacks to lasers, including the potential for causing erythema, skin hyperpigmentation, thermal injury, and eye injury. As a result, the clinical use of lasers must be performed by professionally trained dentists, which is also a barrier to their application in clinical practice. Another major drawback that hinders the application of lasers is the cost factor.There is no doubt that, in the future, lasers will be used more frequently in endodontics. As a result, future research in this field will focus on the issue of how to overcome the shortcomings, prevent treatment-related accidents, and apply it to more clinical examinations and treatments.


The objective of bioimplant engineering is to develop biologically compatible materials for restoring, preserving, or altering damaged tissues and/or organ functions. The variety of substances used for orthopedic implant applications has been substantially influenced by modern material technology. Therefore, nanomaterials can mimic the surface properties of normal tissues, including surface chemistry, topography, energy, and wettability. Moreover, the new characteristics of nanomaterials promote their application in sustaining the progression of many tissues. The current review establishes a basis for nanotechnology-driven biomaterials by demonstrating the fundamental design problems that influence the success or failure of an orthopedic graft, cell adhesion, proliferation, antimicrobial/antibacterial activity, and differentiation. In this context, extensive research has been conducted on the nano-functionalization of biomaterial surfaces to enhance cell adhesion, differentiation, propagation, and implant population with potent antimicrobial activity. The possible nanomaterials applications  may resolve a variety of issues  associated with conventional metallic or non-metallic grafts, primarily for optimizing implant procedures. Future developments in orthopedic biomaterials, such as smart biomaterials, porous structures, and 3D implants, show promise for achieving the necessary characteristics and shape of a stimuli-responsive implant. Ultimately, the major barriers to the commercialization of nanotechnology-derived biomaterials are addressed to help overcome the limitations of current orthopedic biomaterials in terms of critical fundamental factors including cost of therapy, quality, pain relief, and implant life. Despite the recent success of nanotechnology, there are significant hurdles that must be overcome before nanomedicine may be applied to orthopedics. The objective of this review was to provide a thorough examination of recent advancements, their commercialization prospects, as well as the challenges and potential perspectives associated with them. This review aims to assist healthcare providers and researchers in extracting relevant data to develop translational research within the field. In addition, it will assist the readers in comprehending the scope and gaps of nanomedicine’s applicability in the orthopedics field. Nanotechnology is a multidisciplinary field that manipulates the nanometer-scale chemical, physical, and biological properties and structures of materials. Nanomaterials have size-dependent characteristics that are not typically observed in large quantities of materials. The advancements in nanotechnology have opened up new possibilities for diverse applications in the fields of medicine , moleculNanomaterials are viable means for the development of future orthopedic implants  because Bone and its components, for example, Haversian systems, hydroxyapatite (HA), and collagen fibrils, are nano-compounds. Therefore, orthopedics is a fascinating nanotechnology application field. Orthopedic procedures commonly involve intricate interactions at the microscopic level between the host tissue and nanomaterials. Enhancing the efficiency of connections can be achieved by employing biomaterials comprising nanoparticles and structures to modify nanoscale materials. The statement mentioned above forms the foundation for a considerable portion of nanotechnology applications within the medical field of orthopedics. The application of nanotechnology in the field of orthopedic research demonstrates significant promise due to its ability to enhance the mechanical characteristics and biocompatibility of implantable orthopedic devices. Nanostructured grafts and prostheses offer several advantages, including enhanced mechanical durability, improved resistance to wear and corrosion, the potential for drug delivery, and the ability to serve as scaffolds for tissue regeneration. The two main classifications of biological tissues are hard tissues, which include teeth, cartilage, nails, and bone, and soft tissues, which encompass the epidermis, fibrous tissues, ligaments, and synovial membranes. These tissues may or may not contain mineral elements. The scarcity of organ donors prompted scientists to develop innovative techniques to mimic or replicate organs. Bioimplants have been specifically engineered to address the need for restoring, maintaining, or enhancing the functionalities of human tissues. Nevertheless, biomaterials designed for implants exhibit distinct characteristics compared to those found in natural tissues and bones. Biomaterials are synthetic or naturally occurring compounds developed for use in biological systems.The bioimplant market is expanding at an exponential rate as a result of an aging population, lifestyle changes (particularly those that induce and prolong chronic diseases such as osteoarthritis and cardiac disorders), bioengineering technological advancements, and increased cosmetic implant awareness. According to market research, the global bioimplant market is expected to reach $115.8 billion by 2020, expanding at a compound annual growth rate (CAGR) of 10.3% over the period projected (2014–2020) . BioimplThe impact of nanotechnology on the field of grafting has grown significantly in recent years. Researchers are encouraged to investigate the function of nanoparticles (NPs) in enhancing the performance of conventional grafts due to their biologically-inspired properties. This study investigated the evolution of orthopedic biomaterials from conventional  components to nanomaterials. In addition, this article discusses a variety of surface modification techniques, including surface structuring and nanotechnology-based therapies. This evaluation also focuses on antibacterial surface therapeutic interventions for bioimplants. The identification of treatment sites and their successful implantation are the primary focuses of orthopedic treatments. Despite the recent success of nanotechnology, numerous obstacles remain in the way of nanomedicine’s implementation in orthopedics. The purpose of this review is to offer a comprehensive examination of recent advancements, their commercial viability, obstacles encountered, and potential future opportunities. This analysis will assist healthcare professionals and researchers in synthesizing this information to design translational research in the field. Furthermore, this will support the readers in understanding the extent of applicability and constraints of nanomedicine in the field of orthopedics.Since ancient times, humans have used a variety of foreign substances for medical purposes, such as sutures made of hair or cellulose, as well as horns or wood for bone fracture repair . Metals The most essential criteria for implant materials are their clinical and production qualities. Regarding therapeutic requirements, implant materials must not be rejected by the body or produce hazardous byproducts . As a maThe mechanical requirements of an implant are determined by its intended use, such as its loading strength and shear stress flexibility. In orthopedics, graft materials must withstand multiple upload/download cycles under torsional, bending, and shear stresses. In addition, implantable devices are frequently exposed to corrosive environments, which can modify their properties. Therefore, an accurate evaluation of mechanical characteristics is necessary to maintain fracture reductions. The material’s mechanical properties are measured in terms of the distortion (strain) brought on by an applied force (stress) . The appThe primary stress experienced in a pelvic fracture is the loading stress. The load-deformation curve can be obtained by deriving it from the general load curve, as demonstrated in prior research . The traThe most important quality of an orthopedic device is its biological inertness or lack of response to its surrounding biological environment. Several reactions occur at the material surface in physiological circumstances; consequently, implant degradation is possible. This is permitted if the process does not compromise the mechanical strength or produce hazardous residues . In contIn vivo stimulation of the production of a hydroxyapatite layer on the implant surface is believed to enhance the mineralization, fixation, and bone regeneration processes  have greater potential applicability in orthopedics, according to research  were investigated for cartilage tissue . Surgical procedures frequently require the removal of the damaged bone cartilage region by creating an osteochondral defect.Microfracture is another common surgical treatment for comparable injuries, in which calcified cartilage is separated and the subchondral bone is perforated to create a defect. Through the creation of small openings, the defects are filled with bone marrow components containing stem cells. It is one of the most commonly used treatments for cartilage damage , despitein vitro confirmation of cellular responsiveness to the stepped scaffold. The investigation also encompassed the examination of agarose gels and alginate combined with nHAp as potential materials for the regeneration of the osteochondral interface  are commonly used in osteochondral and osteogenic restoration techniques. In a separate investigation , collagenterface . The usenterface . Hypertrnterface . The incnterface . Moreoventerface . Howevernterface . Future nterface .Tendons serve the purpose of connecting muscles to bones and exhibit structural similarities to ligaments. The majority of tendon injuries or ruptures commonly manifest in joints such as the knee or shoulder, and the resulting damage can be severe enough to disrupt the interface between the tendon and bone. Traditionally, these injuries have been stabilized through surgical intervention, as previously indicated, which can potentially lead to further complications. The predominant techniques employed for tendon healing typically encompass the utilization of artificial tendon implants, as well as the implantation of allogenic or xenogeneic grafts. For instance, arthroscopic treatment of irreparable rotator cuff injuries is performed with irreparable rotator cuff tears , TissueMIn vitro, the erratically aligned fibers demonstrated an accelerated degradation profile. This study also demonstrates that the cells in these soft tissue regions are capable of recognizing fiber alignment and directing their proliferation. In addition to being more physiologically relevant than microfibers, nanofibers possess enhanced biomimetic capability  exhibited remarkable characteristics such as exceptional biocompatibility, stability, prolonged joint retention, and effective infiltration into cartilage. After the administration of intra-articular injection, the TGF-NPs demonstrated a high degree of effectiveness in mitigating the deterioration of OA cartilage, the sclerosis of the subchondral bone plate, and the post-surgical joint discomfort (Significant advancements have been observed in the field of nanotechnology-driven drug delivery systems (DDS) designed for the localized, sustained, and targeted administration of pharmaceutical agents. These advancements have demonstrated enhanced therapeutic efficacy and reduced the occurrence of adverse effects, rendering them particularly advantageous in the field of orthopedics. Numerous nanomaterials derived from nanotechnology with distinct chemical, physical, and biological properties have been used to develop innovative DDS for protecting, transporting, and precisely releasing pharmaceutical compounds. Traditional pharmaceuticals are limited by a lack of specific selectivity accompanied by severe side effects, the inability to traverse certain biological barriers, and inefficacy due to poor solubility . Nanotecscomfort . Alternascomfort . NanotecDrug delivery from metal surfaces plays an important role in orthopedic applications as well. Using an extract of green tea polyphenols , the surface of a Ti alloy (Ti6Al4V) was functionalized to promote the precipitation of HA from body fluids . Using a laser microscope, a greater quantity of extracellular matrix was observed on operational specimens, and fluorescence images revealed that these specimens contained more viable cells and osteocalcin. These findings demonstrate the ability of polyphenols to promote cell differentiation and biological mineralization, indicating that surface functionalization of graft metals may be a viable strategy for enhancing osteointegrability  Jäger e.NPs can incorporate ligands that selectively bind to specific molecules present on the surfaces of target cells. This enables the NPs to attach to the cells, thereby enhancing their biocompatibility and facilitating their integration into the host tissue microenvironment with greater efficiency. By the incorporation of contrast agents into ligand complexes, precise imaging of tumors at the cellular level can be attained . In addivia specific ligands produced by tumor cells has the potential to enhance treatment parameters for primary bone cancers. Tumor cells possess surface proteins characterized by multidrug resistance, which effectively diminish the intracellular concentration of pharmaceutical compounds by actively transporting them out of the cells. Nanotechnology has the potential to not only effectively transport anticancer drugs to cancer cells, but also facilitate the delivery of specific genes aimed at countering proteins associated with multidrug resistance. Due to their diminutive size (passive targeting) and their ability to permeate cancer cells, NPs also facilitate increased drug concentrations within tumor cells. The prevention of osteogenic malignancies can be achieved through the downregulation of specific target genes and the use of specific NPs. Certain fusion oncogenes and molecular markers associated with osteogenic tumors can have their expression downregulated by targeted NPs. In addition to this, a considerable number of patients diagnosed with bone tumors necessitate orthopedic implants due to extensive bone resection. Nevertheless, it is worth noting that only a limited range of conventional implant materials are specifically designed to facilitate proper bone growth or mitigate the risk of tumor recurrence. Nanotechnology advancements have revealed an optimistic possible context. Nanomaterials are widely regarded as highly suitable for addressing substantial bone deformities  and the Environmental Protection Agency (EPA) have evaluated NPs for environmental sustainability throughout their life cycle, as well as the difficulty of obtaining and interpreting scientific data to establish the safety of manufactured nanomaterials, over the past two decades. In addition, international governance institutions are being established to address the benefits of nanotechnologies and mitigate their potential risks to human health and the environment. These institutions utilize various voluntary, standard-setting, regulatory, statutory, and other governance platforms.Nanotechnology has only recently been used in orthopedic research, diagnostics, and treatment. Nanotechnology has changed the science and practice of orthopedic treatment in the brief period that it has been studied and implemented. Nanotechnology offers potential advantages in terms of infection rates, reoperation necessity, and the enhancement of bone development, thereby presenting a theoretically safer approach to medical interventions in the human body. In addition to expanding research on current nanotechnology methodologies, benefits, and risks, it is imperative to thoroughly analyze and address the regulatory, production, and pricing challenges. The manufacturing process of nanotechnology products poses challenges due to their inherent characteristics and intricate nature. These items may be inaccessible due to their high cost, and the current regulatory systems can be time-consuming, thereby delaying the implementation of research. If these issues are resolved, nanomaterials will become more accessible and their use in orthopedics will be promoted more effectively.1 Nanotechnology has the potential to provide personalized therapies for musculoskeletal ailments. By customizing patient care, it is possible to enhance outcomes and decrease complications.2 Nanotechnology has the potential to be utilized in the advancement of novel methods for tissue rejuvenation and renewal. This may entail the application of growth factors and nanofibrous scaffolds to induce the proliferation of new tissue.3 Nanotechnology has the potential to be utilized in the development of materials that possess properties comparable to those of real bone tissue. This could potentially lead to the development of biocompatible grafts that exhibit improved mechanical properties.4 Intelligent Implants: Nanotechnology can be employed to create grafts that react to their surroundings. This might comprise using sensors to monitor graft performance or DDS that respond to variations in the body.In the future years, orthopedic surgery might be transformed by nanotechnology. Future research directions in this field include:Nanotechnology is promising for regulating the chemistry and topography of bioimplant surfaces to (i) realize biological relations and (ii) make a new implant nanosurface that recapitulates organ or tissue interactions. Biomaterials based on nanotechnology have the potential to offer advantageous properties for osteoblast functions, tissue regeneration, and bone development, thereby enhancing their function in orthopedic implants. Nanomaterials implants can be utilized in a variety of ways using functional nanocoatings or nanostructured surfaces on the implant surface. The future of nanophase biomaterials is dependent on the development of enhanced design techniques that can combine the advantages of nanomaterials with modern manufacturing processes. Prior to the clinical/commercial application of nanotechnology-based orthopedic grafts, it is crucial to investigate the potential health risks associated with cell-nanophase biomaterial interactions. In the near future, nanotechnology holds great promise for the development of innovative orthopedic implants in the field of medicine.Hence, the utilization of nanotechnology in the development of conventional implants with specific attributes is deemed more favorable compared to the utilization of nanoparticle-based transplants. This effectively prevents the potential for nanomaterials to disperse and impact the toxicity of tissues. Given the aforementioned concerns, the implementation of regulation has been proposed as imperative. The development of nanostructured implants and prostheses is met with caution by companies, primarily due to the lack of established therapeutic advantages, potential toxicity concerns, and the associated high costs. Despite being in its early stages of development, nanotechnology holds significant promise in improving orthopedic diagnosis, management, and research. The performance of the commercial and service sectors validates the idea that nanotechnology will play a crucial role in the future of treatment. Additional research is required to fully comprehend the safety and usefulness of this innovative technology. Utilizing nanomaterials and other fabrication technologies, future research will almost undoubtedly concentrate on enhancing design techniques. It is essential to understand the molecular processes that underlie cell–nanobiomaterial interactions. Additionally, care must be taken when validating the biosafety of nanomaterials and mitigating their effects.Current research focuses on the development of novel materials and strategies for surface modification. The development of novel coating techniques and strategies that more closely resemble the structure of human bone would result in a new generation of orthopedic implants with enhanced integration and bone regeneration. The recent development and use of 3D printing technology are becoming increasingly valuable to the field of orthopedics; however, the field of orthopedic implants has not been thoroughly investigated. Polymers are widely employed in the fabrication of 3D-printed bone replacements due to their suitability as filaments for fused deposition modeling, compatibility with stereolithography equipment, and applicability as mediums for direct ink writing. To reduce implant costs, maintain patient safety, optimize surgical techniques, and reduce the risk of infection, materials used in orthopedics will continue to evolve.


Twenty neglected tropical diseases (NTDs) are currently prioritised by the World Health Organization for eradication, elimination as a public health problem, elimination of transmission or control by 2030. This issue celebrates progress made since the 2012 London Declaration on NTDs and discusses challenges currently faced to achieve these goals. It comprises 14 contributions spanning NTDs tackled by intensified disease management to those addressed by preventive chemotherapy. Although COVID-19 negatively affected NTD programmes, it also served to spur new multisectoral approaches to strengthen school-based health systems. The issue highlights the needs to improve impact survey design, evaluate new diagnostics, understand the consequences of heterogeneous prevalence and human movement, the potential impact of alternative treatment strategies and the importance of zoonotic transmission.This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’. They prevail in tropical and subtropical conditions of the world, and 1.65 billion people are estimated to be infected with at least one NTD worldwide. Currently, the World Health Organization (WHO) prioritises 20 NTDs . While NTaenia solium taeniasis/cysticercosis and hydatid disease). In 2019, the WHO embarked on a consultation with the broader NTD community to revise the goals previously proposed for the 2012–2020 roadmap . This waThis timely collection of papers marks 10 years since the London Declaration and the first WHO roadmap on NTDs and celebrates the progress made over the last decade. The first paper traces the evolution of the NTD concept, its formal emergence and adoption in the year 2000, and the impetus that ensued to establish a new WHO department for NTD control in 2005 .The collection goes on to discuss the challenges and opportunities that lie ahead in the journey to achieve the revised goals set in the second WHO roadmap. Three pillars provide the foundations to this roadmap: (i) accelerate programmatic action; (ii) intensify cross-cutting approaches, and (iii) facilitate country ownership. This volume brings examples of studies that can contribute to strengthening these pillars, such as the modelling analysis on the use of moxidectin mass drug administration (MDA) to accelerate onchocerciasis EOT based on clinical trial data generated by country actors , and mulThe most recent WHO report on NTDs celebrates the vast gains that have been made, with more than one billion people treated for NTDs every year between 2016 and 2019. However, it also highlights the challenges for health systems which have arisen owing to the COVID-19 pandemic, changes in the funding landscape, and the unequal progress on NTDs, with some countries or populations being left behind, often owing to poverty, climate change and lack of infrastructure [One encouraging trend towards the change in operating models and culture to facilitate country ownership that constitutes the third pillar of the WHO roadmap is the funding of country-wide control programmes by philanthropic organizations, which support much of the NTD control programmes in resource-constrained countries. The purpose is to increase support for local implementers with the aim of strengthening local capacity in NTD control. The ultimate goal is to gradually encourage local Ministries of Health to take over the NTD control programmes and support them within their own budgets, reducing dependency from foreign assistance, which up until now has been a major catalytic force . As thiset al. argues that an alternative approach, based on geospatial statistical modelling, can lead to efficiency gains by exploiting spatial correlation in the underlying prevalence, and advocates for the use of a predictive inferential framework which naturally accommodates context-specific information in the form of georeferenced covariates that have been shown to be predictive of disease prevalence. They exemplify this approach by reporting on ongoing collaborative work with the Guyana Ministry of Health NTD programme for the design of an ivermectin + diethylcarbamazine + albendazole impact survey of LF [To this end, it is essential that NTD surveys used to measure progress are optimally designed. Current WHO guidelines set prevalence thresholds below which EPHP may have been achieved, and specify how surveys to assess this target should be designed and analysed, based on classical survey sampling methods. The paper by Diggle ey of LF .. 2The strategies to combat NTDs are broadly categorized into two groups, those which are tackled by innovative and intensified disease management (IDM), and those that rely on preventive chemotherapy (PC) ,14. For Schistosoma mansoni endemic areas in Uganda [et al. presents an evaluation of Kato-Katz and multiplex qPCR performance for the diagnosis of helminth infections  in Thailand, using a Latent Class Analysis [In fact, an issue linked to sustaining the successes gained in the fight against the PC NTDs is the need for better and more sensitive point-of-care diagnostics to ensure that pockets of low-intensity infections can be detected. Exciting opportunities exist in research laboratories based on parasite secretions detectable in blood, urine or faeces. However, the challenge is to convert these technical advances into low-cost diagnostics suitable for use in resource-constrained settings. The contribution of Kabbas-Piñango and co-authors discusses the importance of reproducibility and intra- and inter-sample variation of the point-of-care circulating cathodic antigen (POC-CCA) test in high and low n Uganda , and theAnalysis .For IDM diseases, such as leprosy (targeted for EOT in the second WHO roadmap), there may be a long delay between infection and detection, and therefore, evaluating the relationship between observed cases and underlying transmission can be challenging. Due to long incubation periods, it may take many years for the final cases to be observed, making it difficult to assess progress towards elimination goals in the interim period. Davis and colleagues  provide . 3R0) or where infection is most prevalent in adults, as is the case for hookworm, the target coverage is too low to interrupt transmission [In 2021, 1.65 billion people were reported to require mass or individual treatment and care for NTDs, down from 2.19 billion in 2010, and about 80 million fewer than reported in 2020. Treatment and care is broadly defined to include preventive, curative, surgical or rehabilitative interventions. These figures include the average annual number of people requiring MDA for at least one PC-NTD; and the number of new cases requiring individual treatment and care for other NTDs [smission  and may smission .Ascaris, Trichuris, hookworm, and in the 2021–2030 WHO roadmap also Strongyloides [Trichuris) exhibits generally lower egg reduction rates following benzimidazole treatment, Strongyloides is not greatly affected by it (requiring ivermectin), and the prevalence of hookworm  increases with age rather than peaking in childhood [Although the name STH is used as an umbrella term to include a group of intestinal nematode infections transmitted by exposure to soil contaminated with parasite eggs or larvae, the component species (gyloides ) can havhildhood ,24.Bundy and colleagues open this collection with a two-part paper . This beAnother paper directly related to MDA campaigns for STH and schistosomiasis and their broader impact is that by Bartlett and colleagues . They reChandrasena and colleagues discuss the challenges of eliminating remaining LF and STH pockets of infection in Sri Lanka , a countMore generally, even in regions where geographical and therapeutic coverage of PC-based interventions is on average good, much heterogeneity exists within households and between villages in adherence to the treatment offered at repeated rounds of MDA. As such, even in high average coverage regions, pockets of high infection may thus persist with the implications that they can re-seed infection once PC ceases. The contribution of Collyer and collaborators to this collection highlights the importance of considering human movement in STH models to explain declines in prevalence owing to MDA and bounce-back of hookworm infection using data from the TUMIKIA trial in Kenya .The paper by Kura and colleagues investigates the potential of moxidectin MDA (a drug hailing from the field of veterinary medicine but recently approved for treatment of human onchocerciasis) compared to ivermectin for accelerating onchocerciasis EOT in African settings of varying endemicity, coverage, adherence and frequency .. 4et al. in this volume discusses the challenges for determining the relationship between cumulative pathogen exposure and morbidity at the individual and population levels, drawing on case studies for trachoma, schistosomiasis and foodborne trematode infections, and explores potential frameworks for explicitly incorporating long-term morbidity into NTD transmission models [Although it is considered that infection intensity is the main determinant of NTD-associated morbidity, for some NTDs , the most severe clinical manifestations develop over many years of chronic or repeated infection. For these diseases, the association between infection and risk of long-term pathology is generally complex and poorly understood. The paper by Borlase n models . These fn models .. 5Recognizing that many of the NTDs are vector-borne, zoonotic or directly related to the interaction between the environment and human behaviour has led to a growing emphasis on the importance of animal-human-environmental interface by the NTD community. In particular, One Health is an approach that recognizes the connection between the health of people, animals and the environment and the need to build strong partnerships between these sectors. The tripartite collaboration between the WHO, the World Organisation of Animal Health and the United Nations Food and Agriculture Organization was formed to help countries to implement a One Health approach . The pap. 6During the decade following the first WHO roadmap on NTDs , mathemaIn an effort to synthesize and present the status of NTD models during the 2012–2020 period, two of the guest editors of this issue (M.G.B. and R.M.A.) edited two collections of comprehensive reviews of the then state-of-the-art mathematical models for NTDs as essential tools for control and elimination. These were published in 2015 and 2016 ,35, and https://www.ntdmodelling.org/), and with contributions by other modelling consortia and groups gave rise to a collection of published pieces on dengue, rabies, trachoma, yaws, Chagas disease, gHAT, visceral leishmaniasis (VL), T. solium taeniasis, schistosomiasis, STH, LF, onchocerciasis and scabies (https://gatesopenresearch.org/collections/ntd), covering 13 of the 20 NTDs currently prioritized by the WHO [During the WHO consultation process with the broad NTD community, initiated in 2019, NTD modellers were asked to provide insights, using improved models, into the revised targets for the 2021–2030 horizon, inform the technical feasibility of achieving them with current methods, ascertain the most salient risks, and identify the need for alternative and complementary strategies and novel tools. This endeavour, partly coordinated by the NTD Modelling Consortium  and to identify mitigation strategies that would help bringing programmes against these NTDs back on track for reaching the proposed goals by 2030 [In 2020, the COVID-19 pandemic severely disrupted health systems, MDA programmes, supply chains for NTD medicines and health products, and surveillance activities. These disruptions jeopardized support for prompt diagnosis, treatment and care, as well as provision of essential interventions such as vector control and veterinary public health [ by 2030 ,37,38.Also in 2020, the NTD Modelling Consortium proposed the PRIME-NTD guidelines for Policy-Relevant Items to be included in Models for the Epidemiology of NTDs, based on the five principles of: (i) ensuring stakeholder engagement throughout the modelling process; (ii) providing complete model documentation and code; (iii) presenting complete description of the data used to fit/validate the model; (iv) quantifying and communicating uncertainty; and (v) reporting model outcomes in the form of testable hypotheses . Some ofFor this issue, NTD modellers have contributed seven papers (50% of the contributions), including the potential of alternative treatment strategies for accelerating programmatic action towards attaining interruption of transmission ; the deset al. [Going forward, complex (stochastic) models should be fitted to baseline and longitudinal data , and used to analyse the significance of spatial heterogeneity in both infection prevalence and intervention coverage. The model described by Collyer et al.  is the fFurther developments are also required in several other areas, including modelling prevalence data derived from diagnostic tools not reliant on microscopy-based detection of parasite stages ; understanding how the performance of different diagnostics influences the interpretation of surveys for assessing control impact, post-treatment, post-validation and post-elimination surveillance; quantifying the epidemiological impact of adopting new drugs or new drug combinations and their cost-effectiveness, and reflecting how treatment adherence by individuals varies over a long sequence of MDA rounds.. 7This collection has shared some of the complex challenges faced as the NTD community works to achieve the targets set by the WHO to control, eliminate or eradicate its prioritized 20 NTDs by 2030 and beyond. As the three fundamental pillars of the new roadmap comprise accelerating programmatic action, intensifying cross-cutting approaches, and increasing country ownership, this volume has explored how these issues can only be addressed by international and multidisciplinary research teams working in tandem and in dialogue with national control programmes. Some papers have discussed the problem of long-term persistence of low prevalence for some NTDs, the need to account for spatial heterogeneity and to identify hot spots of infection prevalence, and the challenges for NTDs which slowly approach low incidence as transmission declines, as well as the need for alternative/complementary intervention strategies and more sensitive, diagnostic tools and techniques as we move closer to elimination.Besides, most NTDs do not occur in isolation, but rather they are co-endemic with others, requiring integrated approaches to their diagnosis, treatment and control. The end is in sight for some NTDs, but issues related to the roles of surveillance and residual infection after MDA, verification/validation of elimination, and post-elimination surveillance, must be considered now to continue supporting, in the coming years, the investments made and the gains accrued .Ten years have passed since the London Declaration on NTDs, and in 2022 the Kigali Declaration on NTDs, generated in consultation with stakeholders around the world, reaffirmed a global commitment to put individuals, communities, and countries at the centre of the NTD response . Much pr