The complement system is part of the innate immune response system, which comprises more than 50 distinct plasma and serum proteins that interact to opsonize pathogens  and induce inflammatory responses to fight infection. The role of the complement system is 2-fold: immune surveillance and host defense. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, acquired, hematologic disease caused by somatic mutations in the gene PIGA in the hematopoietic stem cells. These stem cells produce abnormal clone blood cells that lack the complement regulatory proteins CD55 and CD59, causing the body to recognize these otherwise healthy red blood cells as damaged. The complement system destroys cells without these protective proteins, resulting in general hemolysis. PNH is characterized by fatigue; hemolytic anemia that can be severe and debilitating; increased lactic dehydrogenase level, reticulocyte count, and bilirubin level; propensity for thrombotic events; and renal dysfunction. Epidemiologic data, while sparse, suggest that an estimated 5,000-6,000 individuals in the United States are affected by PNH. If left untreated, PNH has a 10-year mortality rate of 29%, although the natural history of this disease has been recently altered by the introduction of complement inhibitors for the treatment of PNH. The complement system is part of the innate immune response system, composed of more than 50 distinct plasma and serum proteins that interact to opsonize pathogens and induce inflammatory responses to fight infection. Opsonization is the process of marking pathogens for destruction by recognizing and targeting invading particles for phagocytosis by coating them with antibodies or complement components.4 After a trigger, a complement protein is cleaved into its active form, which then cleaves other proteins into their active forms in a cascade-like manner  gene cause the production of abnormal clone red blood cells (RBCs) that lack the complement regulatory proteins CD59  and CD55 .1 Defensive effects of the complement cascade are to tag or mark pathogens (opsonization) with activated complement proteins for removal by phagocytes, to induce a series of inflammatory responses that help to fight infection, and to recruit and activate more phagocytes to the site of complement activation, and to damage bacteria by creating pores in the bacterial membrane  leads to the destruction of the enzyme C3-convertase, an enzyme that leads to the activation of complement factors C3 and C5, both necessary in the MAC. Complement regulatory proteins such as CD55 and CD59 on the surface of the host cells inhibit formation of the C3 convertases and prevent formation of MAC, respectively, thereby preventing self-targeted complement activation.1A complement-initiated membrane attack complex (MAC) is assembled through the association of several complement proteins. The host cell protein CD59 (MIRL) on the cell surface prevents the aggregation of the complement factor C9 and, hence, the lytic pores.5 In RBCs, CD59 and CD55 are cell-surface proteins that are part of the host’s self-recognition mechanism; this mechanism protects the cells from being destroyed if the complement system is activated to fight an infection.7Aside from pathogens and damaged host cells, RBCs are potentially sensitive to lysis because they do not have a nucleus.8 However, hemoglobin in the urine may not always be visible to the eye, and not every patient with PNH presents with frank hemoglobinuria. While the specific symptoms of PNH vary from one person to another, the most common symptom of PNH is debilitating fatigue.9PNH is a rare, chronic, acquired , somatic mutation of the PIGA gene. The mutation occurs randomly and sporadically. In PNH, this mutation occurs in a single hematopoietic stem cell, which then multiplies and expands, manifesting with episodic complement-mediated hemolysis that can result in life-threatening complications, including anemia and venous thrombosis. The classic presentation of PNH is characterized by sudden, episodic , at night  hemoglobin occurring in the urine .10 The classification of PNH subtype helps to categorize the clinical manifestations and severity of hemolysis, and it informs immunological treatment approaches. The IPIG developed a 3-subcategory classification method for PNH that incorporates variations in the presenting features, clinical manifestations, and natural history among patients.10 Although IPIG has suggested this classification scheme, distinction between the 3 categories may be difficult since varying degrees of bone marrow failure underlie almost all cases of PNH.10Classification of PNH is not well defined, and the disorder is difficult to diagnose. While no universally accepted classification system is available for PNH, a classification scheme has been proposed by the International PNH Interest Group (IPIG) and the PNH International Registry.Classic or clinical PNH is characterized by significant intravascular hemolytic anemia with no signs of bone marrow failure, an elevated reticulocyte count, high lactic dehydrogenase (LDH) levels, and large PNH clones (> 50% of glycosylphosphatidylinositol-anchored protein [GPI-AP]–deficient granulocytes). PNH in the setting of a bone marrow disorder is defined by a history of associated bone marrow disease, karyotypic abnormalities typical of bone marrow disorders , and < 50% of GPI-AP–deficient granulocytes. Conversely, subclinical PNH is asymptomatic, with no clinical or laboratory evidence of hemolysis and < 10% of GPI-AP–deficient granulocytes.13 Aplastic anemia is a known risk factor for PNH. In patients with aplastic anemia, the risk of developing clinical PNH is 15%-25%.13 If left untreated, 10-year mortality rates among patients with PNH are 29%.14PNH can affect any age group, with a median age of diagnosis in the 30s, and is estimated to affect males and females equally.15 However, for stakeholders to best estimate how many patients may have the condition, 2 available studies, which include 1 model and 1 known epidemiological study, are summarized. Given the paucity of U.S. epidemiological data, researchers have attempted to model the U.S. incidence and prevalence of PNH. In a study of the evolutionary dynamics of PNH, the prevalence of clinical PNH cases, both monoclonal and multiclonal , was estimated in the United States. Using the stochastic evolutionary model and Markov chain model and population age distribution data obtained in 2010 by the U.S. Census Bureau, the researchers estimated that prevalence of clinical PNH for U.S. monoclonal and multiclonal cases was 1.76 cases per 100,000 individuals. For the U.S. population, this would result in an estimate of approximately 3,000 patients with a single clone and 2 patients with biclonal disease based on historical (2010) U.S. population data.16Because of the rarity of PNH, the incidence and prevalence rates have been poorly reported and have likely been underestimated.17 Seventy-six patients with PNH were diagnosed during this time period, resulting in an annual incidence of 0.13 per 100,000. Based on this incidence rate and additional data on survival, the estimated 15-year prevalence of PNH in this study was 1.59 per 100,000, resulting in a predicted prevalence of 59 patients in the study region. The estimate for the United States based on the same incidence and prevalence estimates and the same assumption about disease occurrence and survival was 4,713 cases of PNH based on the July 1, 2005, U.S. Census Bureau population estimate of 296,410,404.17 Based on 2020 U.S. Census Bureau population data, the number of U.S. PNH cases estimated from these United Kingdom data is likely to be 5,000-6,000.18To better define the incidence and prevalence of PNH in the United Kingdom, researchers collected survival data on all patients diagnosed with PNH in the strategic health authorities of North and East Yorkshire, Northern Lincolnshire, and West Yorkshire between January 1991 and July 2006.17 which can be used by payers as they assess prevalence in their managed care populations.In summary, the 2 known epidemiologically related references containing data about the prevalence of PNH provide an estimate that the number of U.S. patients ranges between 3,000 and 6,000 per 100,000,7 Fatigue is the most commonly reported symptom of PNH, occurring in 80.9% of patients.9 Other common symptoms include hemoglobinuria (45.0%), dyspnea (45.3%), renal dysfunction (42.8%), abdominal pain (35.2%), erectile dysfunction (24.2%), dysphagia (16.5%), and thrombosis (13.3%).9 If left untreated, patients with PNH experience major adverse vascular events (18.8%), thrombotic events (13.3%), and impaired renal function (42.8%) and must undergo RBC transfusions (61.3%).9 Hemoglobinuria, thrombosis, severe anemia, and debilitating fatigue have a significant effect on daily living due to loss of independence, decreased physical activity, and functional decline.20While the specific symptoms, progression, and severity of PNH vary from one person to another, chronic hemolysis is central to the symptoms and clinical manifestations of the disorder.10 Hemolysis can occur intravascularly , releasing cellular content into the surrounding environment and leading to an increase in serum LDH level, which can be up to 10 times the upper limit of normal.21 Extravascular lysis occurs outside of circulation in the spleen or liver due to RBC opsonization. Extravascular hemolysis is caused by C3d deposition on the PNH red cells.6 PNH results in abnormal hematologic parameters, including decreased hemoglobin and increased LDH, reticulocyte, and bilirubin levels.22 The premature destruction of RBCs in patients with PNH may result in hemolytic anemia  driven by underlying bone marrow failure.6 Anemia associated with PNH is often chronic and can lead to symptoms including shortness of breath, headache and chest pain, as well as an increased risk of morbidity and mortality.24In patients with PNH, hemolysis is chronic but may worsen during periods of infection, trauma, or stress.25 as free hemoglobin in the serum reacts irreversibly with and depletes nitric oxide (NO), which regulates smooth muscle cells.26 Low NO levels can cause dyspnea, erectile dysfunction, gastrointestinal spasms, and abdominal pain, as well as pain in other parts of the body. Depletion of NO can also precipitate thrombosis, as it can activate and, thus, cause aggregation of platelets.4An estimated 25%-35% of patients with PNH also experience smooth muscle dystonia,27 Clinical presentation of thrombosis may vary and be difficult to distinguish from general PNH symptomatology, which includes fatigue, abdominal pain, and chest pain.28 In patients with PNH, platelets appear to be more susceptible to terminal complement-induced prothrombin effects, potentially explaining the tendency toward thrombosis.29 The most common sites of thrombosis are venous thrombosis of the liver (Budd-Chiari syndrome); abdomen ; and the brain . The risk of developing thrombosis is correlated with the proportion of PNH clones and the severity of intravascular hemolysis.30 Thrombosis is a significant source of morbidity and accounts for up to 50% of mortality in untreated patients.30Thrombosis occurs in 13.3% of patients with PNH before treatment initiation and in 40% of patients overall.31 Renal failure is likely caused by iron deposits and free plasma hemoglobin, manifesting as acute kidney injury or chronic kidney disease. Chronic kidney disease potentially stems from intravascular hemolysis, while renal tubular damage can occur from microvascular thrombosis. It is estimated that 42.8% of untreated patients have renal dysfunction,9 and it is a significant source of mortality if untreated, contributing to 8%-18% of deaths.31Renal failure is a significant complication of PNH.18 PNH is characterized by intravascular and extravascular hemolysis,21 leading to severe anemia and other debilitating symptoms.24 Patients are at risk of fatal disease complications, including thrombotic and hemorrhagic events,9 with a 10-year mortality rate of 29%, if left untreated.14PNH is an extremely rare, chronic, life-threatening blood disease with an estimated prevalence of 5,000-6,000 in the U.S. population.


A one-unit increase in the lifestyle score was associated with a 0.33-times reduction in the risk of developing multimorbidity . A combination of lifestyle factors can influence a variety of multimorbidity among the Chinese adults in Macau. Thus, comprehensively assessing the combined contribution of several lifestyle factors in predicting multimorbidity is important.Multimorbidity has become one of the most pressing public health concerns worldwide. The objectives of this study were to understand the prevalence of multimorbidity and its relationship with lifestyle factors among Chinese adults in Macau, and to investigate the combined contribution of common lifestyle factors in predicting multimorbidity. Data were collected through face-to-face interviews using a self-reported questionnaire on common chronic diseases, lifestyle factors and sociodemographics. BMI, physical activity, drinking status, smoking status and sleep quality were assessed, and a composite lifestyle score (0 to 9 points) was calculated, and the higher the score, the healthier the lifestyle. A total of 1443 participants were included in the analysis, of whom 55.2% were female, 51.8% were middle aged or elderly and 30.5% completed tertiary education or higher. The prevalence of multimorbidity was 10.3%. The combination of hypertension and hyperlipidaemia was the most common (22.2%) multimorbidity among the participants with multimorbidity. After the adjustment of the covariates, it was found that the participants who were overweight (OR: 1.95, 95% CI: 1.18–3.20,  Multimorbidity is defined as the coexistence of two or more chronic diseases in a single individual . The preMany lifestyle factors are associated with multimorbidity. Unhealthy lifestyles, such as physical inactivity ,17, smokMacau, which is located south of the Pearl River Delta, is a special administrative region of China that is known as the ‘Las Vegas of the East’ because it is home to some of the largest and most popular casinos in the commercial gambling industry in the world . Macau iOur study was part of the ‘Healthy Life, Longer Lives’ (HLLL) project, which conducted a community-based cross-sectional survey on a representative sample of community-dwelling people in Macau, from 2017 to 2019. The HLLL project was designed to investigate the lifestyle behaviours of Macau residents in terms of their dietary habits, sleep patterns, physical activity (PA), electronic device usage, smoking, drinking and health information seeking, and to identify the barriers to a healthy lifestyle in vulnerable groups. We obtained data from adults (aged ≥ 18 years) to identify the multimorbidity situation and related lifestyle factors in the population. This project was approved by the institutional review boards of The Hong Kong Polytechnic University (HSEARS20180516001), the Kiang Wu Nursing College of Macau (REC-2017.3) and the Macau Polytechnic Institution (07/PSC/ESS/2017). All the participants provided their written informed consent.Our target population was adults of Chinese descent residing in Macau. The inclusion criteria included individuals who (1) were 18 years old or older, (2) could read and write Chinese and speak Cantonese or Putonghua and (3) were currently residing in one of the seven parishes of Macau. The exclusion criteria were (1) individuals of mixed descent, that is, Chinese and other ethnicities; (2) nonpermanent residents; (3) individuals who were unable to communicate owing to psychological or physical illnesses; and (4) individuals who were unable to provide written informed consent.We invited a total of 1623 Macau residents to participate in the study, 122 of whom declined our invitation. Of the 1501 individuals who agreed to participate in the study, 57 were below the age of 18 years, and 1 refused to provide written informed consent. Ultimately, a total of 1443 individuals completed the questionnaire and were included in the analysis .We estimated the sample size using the formula was 1.3% , and setwas 1.3% , we deteBy referencing the classification of chronic diseases of previous studies ,30,31, wMultimorbidity was defined as the coexistence of two or more chronic diseases in a single person ,32. We cPA. We measured PA using the International Physical Activity Questionnaire-Short Form (IPAQ-SF) [IPAQ-SF) , which iIPAQ-SF) : enough IPAQ-SF) .Drinking. We evaluated their drinking status by asking the participants whether they had a habit of drinking alcohol. We grouped the participants into three categories according to their drinking status: current drinker, former drinker who has quit drinking and has never drunk alcohol. If a participant was a current drinker, then we asked their drinking frequency, consumption amount and preferred type of drink [of drink . We asseof drink . Smoking. We collected information on the participants’ smoking status and classified them as nonsmokers, former smokers or current smokers [ smokers . In addi smokers .Sleep quality. We used the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality [ quality . The PSQ quality .BMI. We asked the participants to report their current weight and height measured by standard scales. We recorded their height to the nearest 0.1 cm and weight to the nearest 0.1 kg. The BMI is calculated as weight in kilograms (kg) divided by height in meters (m) squared BMI (kg/m2). We classified BMI into four levels according to the WHO standards for Asian populations [2), normal weight (18.5–22.9 kg/m2), overweight (23.0–24.9 kg/m2) and obese (≥25.0 kg/m2). We further grouped the four categories as underweight/normal weight (<23.0 kg/m2), overweight (23–24.9 kg/m2) and obese (≥25 kg/m2) for the analysis.ulations : underwe2, 23–24.9 kg/m2 and ≥25 kg/m2. With regard to TOPA, 0 min was considered as poor, and less than 150 min and 150 min or more were considered as intermediate and optimal, respectively. For drinking, ≥ 8 drinks/week for the women and ≥ 15 drinks/week for the men were considered as poor, and no drinking and 1–7 drinks/week for the women and 1–14 drinks/week for the men were considered as intermediate and optimal, respectively [We calculated the total lifestyle score using an algorithm that summarised the subscores of BMI, TOPA, drinking, smoking and sleep quality . We cateectively ,39. For We obtained the participants’ sociodemographic information, including their gender, age, education level, marital status, employment status and monthly family income. We recorded age as a continuous variable (years) and categorised it into three groups: 18–44 years, 45–64 years and ≥65 years. We defined education level as primary or lower, secondary and tertiary or higher. We dichotomised marital status as single  or coupled . We classified employment status as employed, unemployed and other . Finally, we grouped monthly family income into four categories (MOP): 29,999 or less, 30,000–59,999, 60,000 or more and unknown (USD 1 = MOP 8.03).t-test for the continuous variables to compare the variable differences between the different multimorbidity statuses.We performed the descriptive analysis using the mean and standard deviation (SD), frequency and percentage for the continuous variables and categorical variables. We used the chi-squared test for the categorical variables and independent We employed logistic regression models to examine the associations between the lifestyle factors and lifestyle score and multimorbidity of the Macau population. Model 1 was the univariate logistic regression model, with only one lifestyle factor or lifestyle score as the independent variable, and Model 2a was the multivariable logistic regression model. We included BMI, VPA, MPA, drinking status, smoking status and insomnia in one model for the analysis and made adjustments for gender, age, employment status, education level, marital status and monthly family income. The adjustment variables in Model 2b were the same as those in Model 2a, and we included the lifestyle score in the model for the analysis. Additionally, we performed priori stratification analyses by gender and age (stratified by 45 years) to assess the potential moderating effect of such factors on the association between the lifestyle characteristics and multimorbidity.We conducted several sensitivity analyses to test the robustness of our findings by (1) excluding the participants with only one chronic disease from the analysis, (2) excluding the participants with no chronic disease from the analysis and (3) constructing a multivariable logistic regression model that included BMI, TOPA, drinking status, smoking status, insomnia and the other covariates for the analysis.p < 0.05 was considered to be statistically significant.We conducted all the statistical analyses using R 4.2.1 . A two-sided p < 0.05).We summarised the basic and lifestyle characteristics of the participants based on their multimorbidity status in In terms of their lifestyle characteristics, around one-fifth of the participants were obese (19.9%) and had enough VPA (19.8%) and MPA (20.9%), 31.5% had enough TOPA, 25.3% were current drinkers, 8.0% were current smokers and 32.3% reported poor sleep quality. The mean lifestyle score was 6.09. The distribution of single chronic diseases according to gender are shown in The prevalence of multimorbidity was 10.3%. Among the participants with multimorbidity, 71.1% experienced the co-occurrence of two conditions, 21.5% had three conditions, 5.4% had four conditions and only 2.0% had five or more conditions. In addition, among the participants with multimorbidity, the most common disease combination was the co-occurrence of hypertension and hyperlipidaemia (22.2%), followed by the co-occurrence of hypertension and diabetes (18.1%); hypertension and osteoporosis (7.4%); hypertension, hyperlipidaemia and diabetes (5.4%); and hypertension, hyperlipidaemia and osteoporosis 4.7%; .p < 0.05; p < 0.001) times more likely to have multimorbidity (p = 0.008) times higher odds of having multimorbidity than those who had never drunk alcohol, whereas no significant difference existed between the participants who were drinkers and those who have never drunk alcohol  times higher odds of having multimorbidity than those who did not suffer from insomnia (p < 0.001; In the univariate analysis, BMI, VPA, drinking, smoking, sleep quality and the lifestyle score were positively significantly associated with multimorbidity (all orbidity . The parinsomnia . For theIn the stratification analysis by gender, we found a significant association between BMI, insomnia, the lifestyle score and multimorbidity in the men and women, but drinking status was associated with multimorbidity only in the men and not in the women . The resThe exclusion of the participants with only one chronic disease or no chronic disease did not qualitatively alter the association between BMI, drinking status, insomnia and the lifestyle score and multimorbidity . FurtherTo the best of our knowledge, our study is the first to use a comprehensive and population-based approach to estimate the prevalence of multimorbidity in a large sample of the Macau population. The findings can help raise awareness of the burden of multimorbidity and the importance of addressing its risk factors. In addition to a few common lifestyle factors, such as BMI, drinking and sleep quality, we found that the overall lifestyle score can quantify the combined impact of the lifestyle factors on the health of the participants from Macau. Our findings can serve as a basis for the development and implementation of effective interventions to prevent and manage multimorbidity and thus alleviate people’s suffering and social burden.Overweight and obese people have a higher risk of having multimorbidity than those with normal weight. The number of overweight individuals has increased over the years, and obesity is considered to be a chronic disease; therefore, such factors may have a considerable negative effect on future disease incidence. Our investigation pointed out that BMI contributed to multimorbidity, which is consistent with the finding of multimorbidity being highly associated with an increasing BMI and obesity ,22,40,41In this study, we demonstrated the correlation between drinking and multimorbidity, that is, the participants who had quit drinking were likely to have multimorbidity; however, some studies showed no correlation between such variables ,44. Our Our results also demonstrated that poor sleep quality was related to the prevalence of multimorbidity in older adults. Several studies reported the same findings ,47,48. SIn our study, the most common disease combination was hypertension and hyperlipidaemia, followed by hypertension and diabetes. Hypertension, hyperlipidaemia and diabetes were the main chronic conditions among our study population, with a higher prevalence in the men than in the women, which is consistent with the findings in Macau  and MainThe participants were likely to have multimorbidity if they were older than 65 years, completed primary education or lower, were coupled and were retired/a housewife. Our results are consistent with those of a previous study that found that age, a low socioeconomic status and gender are important determinants of multimorbidity. As a literature review, the study included 39 studies conducted in 12 countries and involved more than 70 million patients . As a spOur study has several limitations. Firstly, though the hierarchical model seemed to account for the variables that may have reverse causality, the cross-sectional design did not allow us to establish a causal relationship between exposure and outcome. Secondly, we did not consider measures of common mental health disorders in our study. Finally, the cross-sectional design could not establish causality; thus, our findings may not be generalisable to populations with characteristics that differ from those of our research population. Despite such limitations, the findings of our community assessment can provide relatively reliable information about the health conditions of the Macau population. Our study is the first to investigate multimorbidity in a representative sample of Macau residents. Our use of a comprehensive lifestyle score to demonstrate the overall lifestyle status can provide local community stakeholders with quantitative evidence to recommend positive changes in lifestyle behaviours. The important implications of our study for individuals and society include the use of a simple and quantitative approach and education of people to change their lifestyle to avoid multimorbidity.Our study highlights the heavy burden of multimorbidity among Chinese adults in Macau, which can help raise awareness among healthcare professionals and policymakers about the need to prevent and manage chronic diseases. The BMI, drinking, sleep quality and composite lifestyle score were significantly associated with multimorbidity, and the healthier the lifestyle, the lower the risk of multimorbidity. Our research findings can help guide the development of multimodal and efficient health promotion programmes that can target multiple lifestyle factors simultaneously to minimise the incidence of multimorbidity.


The digital revolution has made its way into the highly regulated field of clinical trials. With an increase in the use of digital technologies in clinical trials decentralised digital clinical trials (DDCTs) are disrupting the way evidence is generated for new medical treatments ,2. Recen2 emissions.Since climate warming poses a multifaceted threat, impacting the environment and economy ,8, it isInformed consent forms, data protection information, test forms, questionnaires, registration forms, and visits to the study centres consume a lot of paper and energy in traditional clinical trials. Hence, digitising clinical trials not only improves the clinical trial system, but is also less harmful for the environment. But how much do we really save by fully digitising a clinical trial?2 emissions of DDCTs compared to traditional trials. To address this topic, we estimated the CO2 savings of various scenarios involving decentralised and digital elements in comparison to a traditional middle-sized clinical trial from our institution.The aim of this opinion article was to add an additional and moreover, the most sustainable argument for DDCTs, namely the large reduction of energy and CO2 [2 would be emitted into the atmosphere as estimated using the model by [Assuming a 25% dropout rate, a typical clinical trial with 2000 patients visiting one of the ten study sites nine times would require a total of 164,800 sheets of paper for case reports and patient forms, the study master file, and site files. This corresponds to a stack of paper higher than 16m and 799 kg COmodel by .2 will be emitted into the atmosphere. Finally, study documents need to be sent back and forth between the monitor and the centres over the course of the study. With one letter per patient and 20 g of CO2 per letter [2. In total, this exemplary traditional, paper-based, clinical trial produced 4,885 kg of CO2.Further, when study participants are required to travel to the study centres, an additional 237 kg of COr letter , this ad2. In our exemplary study above, however, this amounts to just 486 kg CO2. Noteworthy, even this seemingly small proportion of CO2 emission should make us aware of our responsibility and drive us to formulate precise scientific questions, which are then implemented consistently with high data quality in order to achieve meaningful results.Of course, DDCTs also need energy. Reading documents, filling out questionnaires on computers or smartphones (1 minute per page) , video c2 and the full digitisation of a clinical trial saves 4,399 kg (90.1% reduction) of CO2. That is equivalent to a long-distance flight of 24,000 km [Hence, a classical clinical trial needs about 10 times more CO4,000 km . ClearlyAs regulations rightfully stipulate, the rights, safety, dignity, and well-being of study participants should always be prioritised. Any additional burden placed on participants must be carefully weighed against the benefits of digitization . Therefo2 per year Click here for additional data file.


In conclusion, based on the studied anthropometric, nutritional, and functional variables, CD patients were not diagnosed with sarcopenia in the present study. Body composition patterns were related to the inflammatory burden, underlying the interplay of inflammation and malnutrition, even in remission states. Further studies on older populations and during disease exacerbation are necessary to explore the potential link between CD, inflammation, and sarcopenia. Patients with Crohn’s disease (CD) face malnutrition risk, which, combined with inflammation, can lead to sarcopenia, associated with a worse prognosis. The purpose of the present study was to assess malnutrition and sarcopenia in patients with CD. Fifty-three patients (26 women) participated . Body composition, physical performance, nutritional questionnaires, and biomarkers were performed. Malnutrition was screened with the Mini Nutritional Assessment (MNA) and the Malnutrition Inflammation Risk Tool (MIRT) and was assessed with the Global Leadership Initiative on Malnutrition (GLIM) tool using etiologic along with three different phenotypic criteria: low Body Mass Index (BMI), low Calf Circumference (CC), and low Fat-Free Mass Index (FFMI). To find cases and evaluate sarcopenia, the Sarcopenia Questionnaire (SARC-F) and European Working Group on Sarcopenia2 (EWGSOP2) criteria were used. Malnutrition rates were 11.3% (n = 6), 7.5% (n = 4), and 5.6% (n = 3) based on low FFMI, CC, and BMI, correspondingly. Four (7%) patients had low Hand-Grip Strength (HGS), n = 8 (14.8%) had low Appendicular Lean Mass (ALM), and n = 3 (5.6%) had low gait speed. No-one had sarcopenia. A high albumin and triceps skinfold pattern, identified by principal component analysis, was related to reduced C-Reactive Protein (CRP) levels (B = −0.180, SE = 0.085,  Inflammatory Bowel Disease (IBD) represents a severe and complex spectrum of gastrointestinal diseases characterized by chronic or recurrent inflammation , impactiRegarding the nutritional status of patients with CD, they are at risk of malnutrition due to reduced food intake, malabsorption, increased gastrointestinal losses, and side effects of medication ,9. PatieMalnutrition can result in loss of muscle mass and function and possibly sarcopenia , definedHowever, there are severe biases and flaws in that kind of study. A main flaw is the heterogeneity of the sarcopenia assessment because of the plethora of existing detection tools . AdditioThe early detection and management of both malnutrition and sarcopenia are of utmost importance since they are both connected to postoperative complications, increased infection rates, and worse prognosis ,21. ThusParticipants  were recruited from a public Greek hospital and were assessed without comparisons with a control group. Inclusion criteria were (a) confirmed CD patients in remission or mild or moderate symptoms, (b) aged ≥18 years old and (c) capable to self-serve in their daily routine activities, (d) physical activity at least two times per week, (e) controlled diet and (f) in pharmaceutical treatment . ExclusiBefore proceeding to the measurements, all the patients were informed about the study’s process and the safety of the study. Then, a consent form was signed to ensure patients’ participation. The protocol was carried out in accordance with the Declaration of Helsinki (1989) of the World Medical Association. The protocol of the study was approved by the Scientific Board of Theageneio Hospital with approval code: 3734/2-3-2022.Considering the extensive array of screening tools ,23 and mThe body weight was measured on a scale without shoes and wearing minimal clothes to the nearest 0.01 kg, and the height was measured to the nearest 0.1 cm with a stadiometer  . The cir® 1500MDD Bodystat 1500 . The participants, during the measurement, stayed relaxed in the supine position, connecting the two electrodes on the hand and feet, respectively, as proposed by the manufacturer. The appendicular lean mass (ALM) was estimated from published equations by using weight, height, sex, and raw Resistance values measured from bioelectrical impedance analysis [Patients came to the hospital refraining from any type of exercise, caffeine , and alcohol the day before the body composition measurements. In addition, they had fasted for at least 2–3 h . Moreover, shoes, socks, tights, or everything else which could affect the measurement was removed, and females were in the middle period of menstruation . Body coanalysis .A physical performance assessment was conducted in a separate room of the hospital and included four tests. Before the measurements, patients completed a standardized eight minutes warm-up, which included two cycles of five full-body dynamic stretching exercises. The duration and the interval of each exercise were 30 and 15 s, respectively. Afterward, the patients started the following performance tests. 30-s Chair Stand TestTo perform the 30-s chair stand test, the participants were seated on a chair with their arms crossed at the chest level and their hands over their shoulders. They had to stand up from this seated position until they reached a complete knee extension and then sit down again until the back touched the backrest of the chair. This procedure was repeated as many times as they could in 30 s .One Leg Standing Test (OLST) for Both LegsParticipants were asked to stand on either their left or right leg and were instructed to keep their legs from touching and to maintain a single-leg stance for as long as possible, recording each try with a stopwatch. The try began once the foot was lifted off the floor and ended when the lifted foot was placed on the floor or with arm movements and the placement of their hand on the wall, which was in front of them for support if they needed it. Each leg was tested three times unless subjects performed perfectly on the first two trials .6-m Walk Test (Slow and Fast)Each participant completed two trials, a slow and a fast, starting at the standing position. Patients were instructed to stand with their toes touching the taped start line and walk at their usual (slow) and fast pace to a few steps beyond the taped finish line. Patient’s performance was recorded from the moment their foot crossed the start line to the moment their foot crossed the finish line .Hand-grip Strength Test (HGS)HGS was measured using a digital hand-grip strength meter  with a range of 5 to 99.9 kg. Before the test, participants adapted to the grip with some probationary tries. They performed three maximal intensity tries, with 45″ intervals between them, for each hand, calculating the average kilos. During the measurement, participants kept their bodies upright, feet naturally apart, arms diagonally down, palms facing inward, and maintaining an upright posture .Global Leadership Initiative on Malnutrition (GLIM) tool(i)2 if <70 yrs or BMI < 22 kg/m2 if ≥70 yrs, indicating moderate malnutrition; BMI < 18.5 kg/m2 if <70 yrs or BMI< 20 kg/m2 if ≥70 yrs, indicating severe malnutrition) [low BMI  .(ii)low CC.(iii)2 for men and <15 kg/m2 for women [low FFMI < 17 kg/mor women .Malnutrition Inflammation Risk Tool (MIRT)The nutritional status was assessed with the GLIM tool . In orde(i)2 (0 points), 28.5–20 kg/m2 (1 point), <18.5 kg/m2 (2 points).BMI: >20 kg/m(ii)Weight loss in the previous 3 months: <5% (0 points), 5–10% (2 points), ≥10% (3 points).(iii)CRP: <5 (0 points), 5–50 (2 points), ≥50 (3 points).The MIRT tool was developed by Jansen et al. in 2016 and was found to predict clinical outcomes in CD patients, including CD-related flares, hospitalizations, and surgeries . It is aTo evaluate sarcopenia, the European Working Group on Sarcopenia2 in Older People (EWGSOP2) criteria were used, namely hand strength , peripheral lean body mass  (<20 kg and <15 kg for men and women respectively) and gait speed (speed ≤ 0.8 m/s) .The participants, during their therapy with biological agents, answered the questionnaires, which were read and filled out by one volunteer, making it easier for them to give the answers. The following questionnaires were used: (i) the modified Harvey Bradshaw Index (MHBI)  to examiCRP (high sensitivity), albumin, and creatinine were measured. Data on the disease activity, duration, localization, and behavior were recorded. Moreover, data regarding the extended small intestine disease, peri-proctal disease, enterectomy, extra-intestinal manifestations, endoscopic response, and endoscopic healing were recorded . Smoking habits were also recorded as a dichotomous variable . t-test  or Mann-Whitney test  was used for possible differences between the genders. Pearson’s or Spearman correlation coefficients were used, for normally distributed and skewed variables/patterns, respectively. Also, linear regression analysis was conducted to find out the percentage of prediction of independent to dependent variables.The Kolmogorov-Smirnoff test was used to test the normality. The values are shown as means, standard deviation (SD) for normally distributed variables, or median with interquartile range (IQR) for non-normally distributed variables. The independent sample a = 0.05.A Principal Components Analysis (PCA) was applied for the identification of body composition/function patterns. More than one component with eigenvalues (originating from the correlation matrix of the standardized variables) was retained for the data analyses. The scree plot was also used to check the previous decision. The orthogonal varimax rotation was applied to generate optimal, non-correlated patterns. Five components of body composition/function patterns were identified based on the principle that the higher absolute scores indicate the variables contributing most to a particular component . Linear regression models were developed to evaluate the association of the extracted body composition/function components (independent variables) on log CRP (dependent variable) after adjustment for age. It is noted that CRP was transformed in a log form to achieve normality. Moreover, Spearman correlation coefficients were applied to test the association of the derived patterns with the MNA score. The analysis was performed with the statistical software IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY, USA: IBM Corp. The level of significance was set at The prediction of the sample size (n) occurred with G*Power 3.1.9.7  for Windows . Determip < 0.05). No differences were observed in OLST (R), and phase angle  for the LIADLS and ADLS was 8 (8–8) and (6–6), respectively. Indeed, all patients achieved the maximum score on both scales, suggesting a good functional ability for complex and basic daily activities. It is noted that disability was defined as an exclusion criterion. Moreover, they were physically active at least two times per week with activities such as walking, running, swimming, football, volleyball, tennis, etc.In In 2 = 23.7%). It is noted that the model remained significant after further adjustment for disease severity. The linear regression model was also applied to a subsample of patients being in remission in order to avoid potential bias pertaining to disease severity. The pattern of increased albumin and TSF was significant logCRP “prediction” after adjustment for age . Furthermore, a Spearman correlation was performed between the identified body composition/function patterns and MNA total score as well its constructive components (MNA sub-scores) (p = 0.043), the MNA sub-score for food intake was related to Pattern 5  , the MNA sub-score of weight loss was associated to Pattern 1   and the MNA sub-score pertaining to BMI was also related to Pattern 1  (In -scores) . As show< 0.001) .In the present study, the rate of malnutrition varied according to the GLIM criteria used, and its detection rate increased with the use of more accurate indicators, such as the FFMI. Sarcopenia was not detected in the present sample, while a pattern with high albumin and TSF identified with the use of PCA analysis was related to reduced CRP levels.In general, patients with CD have a high risk of malnutrition due to loss of appetite, reduced food intake, impaired absorption, increased gastrointestinal losses, possibly increased energy requirements, and side effects of medication ,9. The e2 or (iii) albumin < 30 g/L [In the present study, the rate of malnutrition was relatively low compared to other studies . This fi< 30 g/L . In the It is noted that in other studies, including patients in remission, participants were also characterized as well-nourished . PatientWomen presented higher rates of malnutrition according to the GLIM criteria in the present sample. Gender differences have not adequately been addressed in the literature, but women with CD have been reported to have lower FFMI  and to b2), but with the BMI-based GLIM phenotypic criteria, three subjects still had problematic values. Compared to other studies, including IBD patients in remission, our results are comparable to a study reporting a mean BMI of 26.2 kg/m2 [2) [2 [2 in our study vs. 17.3 kg/m2) [Regarding BMI, body composition values and physical performance measurements may be adversely affected in patients with CD, even in patients in remission in some  but not .2 kg/m2  or higheg/m2 [2)  or other2 [2) [2 . Regardi3 kg/m2) . Women h3 kg/m2) . Fat mas3 kg/m2) , which m3 kg/m2) . The sam3 kg/m2) .The assessment of muscle functionality is crucial in both CD , and sarRegarding sarcopenia, which combines the phenotypes of muscle quantity and function in its definition, it is estimated that fifty percent of patients with CD have sarcopenia . Howevera (TNF-α) can increase muscle breakdown and reduce protein synthesis, while in cachexia and sarcopenia, the inflammatory burden is increased, implying a bi-directional relationship [CRP correlates with IBD activity, and it is related to postoperative complications, especially in patients with CRP > 10 mg/L. . In the tionship ,88,89,90tionship  and CD ationship , and thetionship . Thus, tIt is also noted that several body composition/function patterns were detected instead of fewer that would simply categorize patients into those with bad/good function. This may be explained by the sample size and the sample characteristics. It is, however, also possible that each test reflects different angles of nutritional status. This hypothesis is in line with the fact that only selected correlations were significant regarding the identified patterns and MNA-score and its components. The strengths of the present study include the assessment of a plethora of anthropometric, body composition, and function parameters related to malnutrition and sarcopenia. In parallel, certain biochemical indices were measured, which enabled the association of inflammatory fluctuations with body composition/function patterns. 2, which is implicated in PAF metabolism [2 in cachexia [Limitations of the present study include the relatively small but adequate sample size, as suggested by the power analysis performed. Given that certain variables had zero variability, no other comparisons/correlations could be performed. The cross-sectional nature of the present work cannot imply causality in the observed associations. In addition, the data-driven by nature of identified patterns limits the repeatability and “translation” of the present results in a different clinical context. It is also possible that other inflammatory indices may have been affected by alterations in body composition, such as Lp-PLAtabolism , is altetabolism ,96,97, atabolism . Such dacachexia ,87 and tcachexia ,100. In cachexia . MoreoveThe present study is the first to be conducted using a variety of sarcopenia detection tools to determine the presence of sarcopenia in a sample of patients with CD in remission without making comparisons to a control group. This is in contrast to many studies where the prevalence of sarcopenia among patients with CD exceeds 40%. Furthermore, when comparing genders, females had a higher percentage of malnutrition compared to males. However, this difference was not related to the presence of sarcopenia in either gender.Future research should be directed toward exploring novel perspectives that could streamline the detection of both sarcopenia and CD. One promising avenue is the utilization of the Mendelian randomization method, which assesses genetic variations and investigates the causal impact of a modifiable factor on disease within observational studies ,102,103.In conclusion, based on the studied anthropometric, nutritional, and functional variables, CD patients were not diagnosed with sarcopenia in the present study. Body composition patterns were related to the inflammatory burden, underlying the interplay of inflammation and malnutrition, even in remission states. Further studies on older populations and during disease exacerbation are necessary to explore the potential link between CD, inflammation, and sarcopenia.


Information was obtained from 19 patients using the State-Trait Anxiety Inventory (STAI) and analysis of BDNF, NSE and S100B serum levels.the pre-intervention anxiety score in the IDATE-Trait was 52.11±6.691 (CV 12.84%) and the assessment after auriculotherapy was significantly lower . S100B levels were significantly reduced after auriculotherapy .auriculotherapy effectively reduced anxiety levels. It proved to be safe and easy to apply, allowing nurses to perform this technique autonomously. A reduction of S100B was also evidenced, demonstrating possible prevention of neuronal damage. A 2017 World Health Organization (WHO) report estimated that approximately 264 million people in the world suffer from anxiety disorders, mainly affecting women between 40 and 49 years of age and appearing as the sixth cause of loss of quality of life for years lived with disability. In Brazil, the prevalence of anxiety disorders in the population reaches 9.3%, which is the highest rate among all those recorded in the report.Mental health is currently a much discussed topic, as the proportion of people who have some type of mental disorder has grown exponentially around the world, pointing to several consequences in terms of loss of quality of life. Aiming to overcome these altered emotional states, people seek Integrative and Complementary Practices (ICP) as a means of controlling and treating their illness, thus improving their quality of life.Anxiety, as a nursing diagnosis, is defined as: “a vague and uncomfortable feeling of discomfort or fear, accompanied by an autonomic response, a feeling of apprehension, caused by the anticipation of danger”Sistema Único de Saúde) called the Brazilian National Policy on Integrative and Complementary Practices , published as Ministerial Ordinance 971 on May 3, 2006 and later in a new Ordinance 1600, on July 17, 2006. The treatments offered, a priori, included Traditional Chinese Medicine (TCM)/acupuncture, homeopathy, phytotherapy, medicinal plants, social thermalism/crenotherapy, and anthroposophical medicine. In 2017 and 2018 the PNPIC was expanded and now covers 29 ICPs-6. The Federal Council of Nursing (COFEN) determined and certified, through Resolution 326/2008, acupuncture as a specialty that can be performed by nurses, subject to proof of specific technical training and that must be applied complementarily in their activities, always aiming at the promotion and recovery of health and rehabilitation in illness.ICPs are therapeutic resources that aim to promote and restore health through the stimulation of natural mechanisms, using effective and safe technologies. Currently, there is a specific resource for implementing these practices in Brazil within the Brazilian Health System  levels. BDNF is a protein widely distributed by the central nervous system (CNS) that has a neurotrophic effect on the development and function of neurons, in particular on serotoninergic neurotransmission, having antidepressant and anxiolytic effects. Research shows that the extracellular presence of NSE is indicative of neuronal damage in pathological situations, in addition to pointing to the emergence of alterations in serum levels of this enzyme in individuals with mood disorders. S100B is a calcium-binding protein present mainly in the cytoplasm of astrocytes, and its levels in biological fluids also indicate neural damage. According to controlled scientific experiments, elevated S100B serum levels are directly related to significantly higher states of anxiety as well as impaired cognitive functions-19.Studies have also investigated the importance of other anxiety-related biomarkers, such as neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B). NSE is a glycolytic enzyme found mainly in neurons and neuroendocrine cells, which can perform neuroinflammation, neurodegeneration, and neuroprotection functions. Knowledge of these data reinforces the importance of using auriculotherapy as a nursing intervention, highlighting the relevance of nursing consultations and diagnoses, as nurses are professionals who can carry out specializations to apply this therapy according to the COFEN Resolution 585/2018. According to a study carried out with Primary Health Care (PHC) nurses, a nursing consultation is an extremely important means for developing clinical practice, anchored on the principle of comprehensiveness and evidence-based practice, contributing to improving the quality of care provided and recognizing nurses’ autonomy. Reinforcing this idea, a survey carried out with workers at a Basic Health Unit (BHU) evidenced professionals’ willingness to implement ICPs in PHC for treating mental disorders. Thus, 73.9% claim to know an IPC ; 94.2% acknowledge that BHU users with mental health issues would benefit from the therapies offered; 91.3% claim they would like to receive training in ICPs; and 92.8% report that they consider ICPs as a way to perform mental health care.With the increase in anxiety in the population, there is a growing search for treatments that alleviate symptoms and bring better quality of life for these people. A survey carried out in a psychology service-school from 2009 to 2014 showed that anxiety together with depressive symptoms, among other complaints, were the main reasons for seeking careThe present study aims to apply auriculotherapy as a tool in anxiety control and treatment, being a safe, low-cost, non-invasive, and quick-to-perform technique, which can be applied autonomously by nurses. It is necessary to highlight the evidence of its effect on improving quality of life as well as greater knowledge about the technique among PHC professionals, in order to favor the implementation of the procedure and promote the prevention and early treatment of anxiety and related harms.To assess the effects of auriculotherapy on anxiety and BDNF, NSE, and S100B serum levels in adults in PHC in a BHU in the city of Palhoça, Santa Catarina.Universidade do Sul de Santa Catarina and Certificate of Presentation for Ethical Consideration (CAAE - Certificado de Apresentação para Apreciação Ética), whose opinion is attached to this submission. This clinical trial was published in the Brazilian Registry of Clinical Trials (ReBEC) under RBR-35n9nkj. The written Informed Consent Form was obtained from all individuals involved in the study.The study was conducted in accordance with national and international ethics guidelines, approved by the Research Ethics Committee of the This study is characterized as a pre-experimental pilot clinical trial with a quantitative approach, carried out at a BHU in the city of Palhoça, Santa Catarina, in which the period of data collection was from July to September 2019. The study was carried out over six weeks: in the first meeting, the ICF was read and signed, and STAI was applied to assess anxiety levels and eligibility in the sample; in the second meeting, a sociodemographic questionnaire was applied, blood was collected for analysis of serum BDNF, NSE, and S100B, and treatment with auriculotherapy was started; in the third, fourth, and fifth meetings, auriculotherapy sessions were repeated; in the sixth meeting, STAI was applied again to reassess anxiety levels and blood was collected for post-intervention BDNF, NSE, and S100B analysis . The resFor sample selection, the survey was disclosed at the BHU among users and 25 participants voluntarily agreed to be part of the study. Participants over 18 years, of both sexes, with medium (from 41 to 60 points) and high (from 61 to 80 points) anxiety levels, measured using the State-Trait Anxiety Inventory (STAI), not being on psychotropic drugs, antibiotics, corticosteroids, or anabolic steroids, not being in the first trimester of pregnancy, and not being illiterate were included.In order to characterize the sample, a sociodemographic questionnaire was applied, including the following variables: age, sex, education level, religion, family income, alcohol consumption, consumption of caffeinated beverages, use of illicit drugs, physical activity, and use of natural substances such as plants and phytotherapy., translated and validated to Portuguese by Biaggio and Natalício, was used to assess anxiety before and after the intervention with auriculotherapy. It is an instrument composed of two self-assessment subscales: the STAI-Trait (STAI-T), which defines an individual’s anxiety trait, pointing out the tendency to react to situations identified as threatening, with the objective of becoming more stable, proposing that individuals describe how they generally feel. The second subscale is the STAI-State (STAI-S), which identifies the state of anxiety in relation to a specific situation considered to be worrying or distressing and intends to be a transitory characteristic, asking individuals to describe how they feel at the time they respond to the questionnaire. Each of the subscales has 20 questions, with four possible degrees of response intensity, ranging from 1 to 4, so that the scores for each volunteer range from 20 to 80 points, which may indicate low (20 to 40), medium (41 to 60), and high (61 to 80) anxiety levels.The STAI, developed by Spielberger. In the auriculotherapy intervention, the following materials were used: mustard seeds ; tweezers suitable for applying the seeds; cotton, and 70% ethyl alcohol. The procedure was performed after inspection and choice of the dominant auricle of each participant, applying the seeds in a set of points in the following order of application: Shenmen; Kidney; Neurovegetative System; Heart; Joy; and Anxiety II . This stimulus provokes responses that help in therapeutic treatment, forming the triple relationship: auricular point, brain, and organsxiety II . After t® SST® II, BD) without anticoagulant, and left to stand at room temperature for 20 minutes. Next, they were centrifuged at 3,000 rpm for 10 minutes and stored at a temperature of 4º C for a maximum of 4 hours. Subsequently, aliquots of the supernatant (serum) were stored at -80°C until the time of assay.Blood collection was performed before and after the auriculotherapy intervention. Blood samples were placed in vacutainer tubes . For the assay, 100 µl of sample was used to measure the concentrations of BDNF, S100B, and NSE , according to the kit manufacturer’s instructions. The values obtained were estimated by interpolating the data with a standard curve for each biomarker using a colorimetric assay, measured at 450 nm (wavelength correction 540 nm) in a spectrophotometer , and the results were expressed in picograms per milliliter (pg/mL).® spreadsheets and analyzed using the Graph Pad Prism® program . Initially, the normal data distribution was assessed by the Shapiro-Wilk test and, therefore, the results were presented as mean ± standard deviation (SD) and coefficient of variation (CV). Parametric data from biochemical and STAI assessments before and after the auriculotherapy intervention were compared using the paired Student’s t test. To analyze the correlation between BDNF, NSE, and S100B serum levels and anxiety levels, the Pearson correlation test was used, in addition to the confidence interval (CI) and the coefficient of determination (R2). The correlation strength will be interpreted within the range of -1 to +1. Sociodemographic variables were presented as absolute numbers and percentages. Multiple linear regression was performed using the backward stepwise method. The validity of final multiple regression models required the following assumptions: (a) no heteroskedasticity (Breusch-Pagan hettest); (b) no multicollinearity (variance inflation factor); (c) residuals normality distributed . Multiple linear regression was performed on Stata 14.0  statistical package. In all analyses, p-values less than 0.05 were considered statistically significant.The information obtained through STAI, sociodemographic questionnaire, and serum concentrations of BDNF, NSE, and S100B were organized in ExcelInitially, 25 participants were recruited. After applying the eligibility criteria, 20 participants met the inclusion criteria and were allocated to the intervention, however there was a loss of 1 participant following the research, thus 19 participants were analyzed .versus 12 were female (63.15%). As for education, 1 had from 6 to 9 years of study (5.26%); 2 had from 9 to 12 years of study (10.53%); 9 had from 12 to 15 years of study (47.36% ); 7 had more than 15 years of study (36.85%). Also, 11 had a religion (57.89%); 8 had no religion (42.11%); 13 did not use illicit drugs (68.43%); 5 used them once a week (26.31%); 1 used them five times a week (5.26%); 10 did not practice physical activity regularly (minimum 30min per day) (52.63%); 4 practiced twice a week (21.06%); 3 practiced three times a week (15.79%); 1 practiced four times a week (5.26%); and 1 practiced five times a week (5.26%). Other sociodemographic characteristics of the sample are shown in With respect to sociodemographic data, 4 participants were between 18 and 25 years of age (21.05%); 10 were between 26 and 35 years (52.63%); 2 were between 36 and 45 years (10.53%); and 3 were over 45 years (15.79%). Moreover, 7 were male (36.85%) Neuronal biomarker analyses were compared using pre-treatment versus post-treatment, as shown in 2=0.0076; 2 = 0.017; 2 = 0.0492; 2 = 0.004; 2 = 0.0032; 2 = 0.080; 2 = 0.45, P = 0.007). Thus, the final regression model suggests that sex (P = 0.022), family income (P = 0.004) and use of natural substances (P = 0.023) are significantly associated with 58% of change in STAI-Trait difference after treatment . STAI-State and NSE and S100B biochemical markers are not associated with sociodemographic variables in the final regression model  after physical exercise causes morphological and functional changes in the spinal cord, substantia nigra and in the neurons of the hypothalamic nuclei, responsible for: the alteration of the functional properties of the motoneurons that innervate the skeletal muscles; the increase in the release of dopamine in the brain; and the modulation of hormone levels involved in the regulation of metabolic processes supporting the benefits of exercise on brain health for its neuroprotective effect. In the present study, no statistically significant alteration was found in serum levels of NSE preversus post-intervention with auriculotherapy as well as no correlation of anxiety levels with this biomarker. This finding is in line with research in which NSE levels and the severity of anxiety symptoms were not associated.Studies indicate that NSE is an enzyme associated with neuronal damage in pathological situations, in addition to pointing to the emergence of alterations in serum levels of this enzyme in individuals with mood disorders. In the current study, it was pointed out that S100B serum levels significantly reduced preversus post-intervention with auriculotherapy, suggesting a possible benefit of treatment. When we correlated S100B serum levels with anxiety, there was no statistically significant evidence. Although high S100B levels are related to schizophrenic patients as well as patients with major depression, to date, the correlation between S100B levels and anxiety has not been found in the literature, and it is not possible to compare our results with previous studies.S100B is a calcium-binding protein produced and secreted mainly by astrocytes, demonstrating that increased serum levels are indicative of neuronal injury or deathAs for the limitations of this study, the number of participants may have been insufficient to demonstrate better results from auriculotherapy treatment with seeds as well as to show significant correlations between anxiety levels and biomarkers. It is suggested that future studies do not exclude symptomatic patients undergoing drug treatment, as many symptoms of high anxiety cause great suffering in these individuals, and auriculotherapy should be integrated with first-choice drug treatments. Thus, the inclusion of these patients could have increased our sample size. Further studies using other materials are recommended, such as crystal spheres, gold, silver, magnets, or even needles as well as longer treatment times, which could lead to an even greater reduction in anxiety levels. In the current study, a standardized treatment protocol was used for all participants, which may have limited the results in reducing anxiety levels. It is possible an individualized protocol, considering the specific demands of each participant, could have presented better results. It is also suggested that other studies be carried out in a randomized manner, using a control group for better observations of treatment effects. Furthermore, it was not possible in this study to better control the data of participants who used illicit drugs and who consumed alcoholic beverages.Auriculotherapy was shown to be an effective intervention in reducing anxiety levels as well as related signs and symptoms, proving to be a safe, non-invasive, easy-to-apply practice, with minimal side effects and low cost, enabling nurses to perform this technique with autonomy in PHC. A reduction in S100B serum levels was also evidenced, demonstrating possible prevention of neuronal damage.The importance of nursing consultations fostered in evidence-based practice is reinforced, observing people as a whole, meeting all their needs. It is considered essential that PHC provide ICPs, such as auriculotherapy, which is a practice that can be used as an adjunct in first-line treatment, aiming at health promotion and the prevention, control, and treatment of anxiety, among other illnesses.0034-7167-reben-76-06-e20220728-suppl01Click here for additional data file.0034-7167-reben-76-06-e20220728-suppl02Click here for additional data file.0034-7167-reben-76-06-e20220728-suppl03Click here for additional data file.


This article introduces a technical solution for investigating the movement of gases in the atmosphere through the turbulent pulsation method. A comprehensive control system was developed to measure and record the concentrations of carbon dioxide and methane, temperature, humidity, atmospheric air pressure, wind direction, and speed in the vertical plane. The selection and validation of sensor types and brands for each parameter, along with the system for data collection, registration, and device monitoring, were meticulously executed. The AHT21 + ENS160 sensor was chosen for temperature measurement, the BME680 was identified as the optimal sensor for humidity and atmospheric pressure control, Eu-M-CH4-OD was designated for methane gas analysis, and CM1107N for carbon dioxide measurements. Wind direction and speed are best measured with the SM5386V anemometer. The control system utilizes the Arduino controller, and software was developed for the multicomponent gas analyzer. Currently, the method of turbulent pulsations is extensively employed in studying gas movement within the atmosphere ,2,3. Thea—air density, kg/m3;ρw—vertical wind speed covariance, s—ratio of gas density to air density.When using the turbulent pulsation method, it is assumed that changes in air density are negligible, and there is no divergence and convergence of the vertical airstream.Researchers globally widely employ the pulsation method. For instance, the carbon cycle of the Middle Tien Shan pasture ecosystem has been analyzed, revealing fluctuations in carbon balance during daylight hours and days. Gross primary productivity and ecosystem respiration have been determined, along with months of carbon dioxide sources and absorbers. Notably, soil respiration is significantly influenced by temperature . SimilarThe foundation of the turbulent pulsation method lies in its instrumentation, allowing requisite parameter recording ,8. To ac2, H2O, and CH4 measurements [A predominant solution on the market is the vortex covariance system by LiCor (USA) ,11,12,13urements ,15. LiCoThese devices are currently used across the Eurasian continent, as well as in North and South America, and within research laboratories such as the Natural Resource Ecology Laboratory at Colorado State University in Fort Collins, Colorado, the Pacific Northwest National Laboratory, ICOS Atmospheric Thematic Centre, Laboratoire des Sciences du Climat et de l’Environnement ,17, as wDepending on the customer’s requirements, the systems are equipped with sensors for temperature, humidity, rain, illumination, and a radiometer . The sys2O), methane (CH4), carbon dioxide (CO2), ammonia (NH3), and water vapor (H2O). Its specifications are detailed in Picarro introduced the G2508 analyzer to the market, offering simultaneous and accurate measurement of nitrous oxide  , this meThe G2508 measures and records atmospheric gases. To implement the turbulent pulsation method, supplementary instruments for measuring meteorological parameters are necessary.The equipment market for conducting pulsation studies primarily comprises control devices designed to measure and record climatically active gases in most cases. These devices lack the capability to expand the roster of controlled gases; they solely monitor the concentration of a specific gas. Expanding research objectives and measuring other substances necessitate acquiring new control devices. Consequently, this approach hampers the swiftness of responding to novel research challenges.Thus, the development of flexible new technical capacities for research becomes imperative. One plausible approach involves employing separate devices and integrating them into a unified monitoring system.The aim of the study is to devise a technical solution for conducting comprehensive investigations into the motion of climatically active gases using the turbulent pulsation method.Development of a prototype for a multicomponent gas analyzer;Selection of discrete and analog input modules to receive unified signals from sensors;Design of a data transmission system in a multicomponent gas analyzer.The study has the following objectives:This work employs the fundamentals of constructing an automated process control system (APCS) as its research methodology ,26,27. ATo construct a gas analyzer, sensors are indispensable. The selection of sensors, essential for a multicomponent gas analyzer, was performed by examining the array of sensors available on the global market.Temperature sensors, namely CJMCU-811, GY-SGP30, and AHT21 + ENS160, were considered. These sensors exhibit distinct characteristics, with the choice hinging on specific requirements and objectives. A comparative analysis of temperature measurement sensors was conducted .2 and VOC (volatile organic compounds), while the GY-SGP30 sensor measures CO2 and TVOC . These sensors have found utility in indoor air quality monitoring.CJMCU-811 and GY-SGP30 are sensors designed for measuring air quality, with temperature measurement being an additional function. However, their primary purpose is not temperature measurement. The CJMCU-811 sensor measures COThe AHT21 + ENS160 sensor was selected for measuring atmospheric air temperature. The AHT21 and ENS160 sensors boast a broader operating temperature range, elevated measurement precision, and reduced noise levels. Furthermore, these sensors consume less power, enhancing their efficiency. They also offer support for the I2C interface, facilitating their integration with the Arduino platform.To measure humidity, temperature, and air pressure, sensors like BMP280, LPS22HB, and BME680 are employed. Each of these sensors has distinct characteristics and applications. A comparative analysis of humidity and pressure measurement sensors was undertaken .Additional Dimension. The BME680 introduces an additional dimension—air quality assessment. This sensor gauges gas concentrations such as nitrogen oxides, ammonia, ethanol, and carbon dioxide to evaluate air quality. This capability is absent in BMP280 and LPS22HB.Enhanced Precision. The BME680 exhibits superior humidity, pressure, and temperature measurement accuracy compared to BMP280 and LPS22HB. It also delivers enhanced measurement stability with reduced noise in output signals.Wide Measurement Range. The BME680 covers a wide measurement range—from 0 to 100% for humidity, from 300 to 1100 hPa for pressure, and from −40 to +85 °C for temperature. This wide range allows the sensor to be used for a variety of purposes.Multiple Interfaces. The BME680 supports a variety of interfaces, including I2C, SPI, and UART, rendering it compatible with an array of microcontrollers and devices.User-Friendly. Compact and lightweight, BME680 facilitates easy integration into diverse systems. Additionally, it consumes less power, making it suitable for energy-constrained mobile devices.The BME680 sensor brings forth several advantages:2 sensors that can be employed for atmospheric CO2 detection, along with their characteristics.Most sensors available on the market are optical sensors. Depending on the intended application, sensors with an error range of 50 ppm + 3% to 1% can be procured. The CM1107N is a favorable choice for carbon dioxide measurement in terms of its price-to-performance ratio. It operates effectively across a wide temperature range, providing sufficient accuracy and response time for measurements.Sensors for measuring methane in atmospheric air were also considered: MSH-P/HCP, Eu-M-CH4-OD, F3-042107-05000, and Gasboard-2500. A comparative analysis of these methane sensors is presented in As depicted in Anemometer sensors, namely SM5386V, RK100-02, and BGT-FSI-RS485, possess distinct specifications, with the ideal choice depending on specific requirements and applications. A comparative analysis of these anemometers was conducted .Both SM5386V and RK100-02 are analog air speed sensors, which gauge air speed in meters per second and yield an analog voltage signal contingent on the air speed. In contrast, the BGT-FSI-RS485 sensor quantifies air speed in m/s and generates a digital signal utilizing the RS485 interface.Extensive Measurement Range. With a measurement range from 0.5 m/s to 30 m/s, the SM5386V accommodates a wide spectrum of conditions.High Precision. The SM5386V ensures accurate air velocity measurement, down to 0.1 m/s, making it suitable for scientific research.User-Friendly. Compact and easily interfaced with microcontrollers through analog inputs, the SM5386V stands out, while RK100-02 and BGT-FSI-RS485 require additional hardware for signal processing.Reliability. The SM5386V boasts minimal noise and an extended service life, enhancing its reliability. In contrast, RK100-02 and BGT-FSI-RS485 may encounter noise-related issues and signal processing requirements.Among these, the SM5386V anemometer was preferred for the following reasons:The Arduino Mega 2560  was chosFurthermore, the device mandates a power supply, a power protection module, and a data communication module for operation. The SIM800L GSM data transmission module was employed.The multi-component measuring tool consists of the Arduino controller, AHT21 + ENS160 temperature sensor, BME680 air pressure and humidity sensor, Eu-M-CH4-OD methane sensor, CM1107N carbon dioxide sensor, SM5386V anemometer, SIM800L GSM communication module, DC power supply, and power board protection module.Measurement and recording of greenhouse gas concentrations;Measurement and registration of atmospheric air temperature;Measurement and registration of wind speed and direction in the vertical plane;Measurement and registration of atmospheric air humidity;Measurement and registration of atmospheric air pressure.A prototype of a device for monitoring the parameters required for research using the turbulent pulsation method was developed. It performs the following functions:1—sensor for measuring the concentration of carbon dioxide, 22—sensor for measuring the concentration of methane, 23—sensor for measuring the humidity of atmospheric air, 24—sensor for measuring the temperature of atmospheric air, 25—sensor for measuring the atmospheric air pressure, 26—sensor for measuring the speed wind in the horizontal direction, 27—sensor for measuring the wind direction in the horizontal plane, 28—sensor for measuring the direction of vertical air movement, and 29—sensor for measuring the speed of vertical air movement. An external memory module (11) (SD card module) is connected to controller 1.The developed system consists of a personal computer with an installed automated control system, 1—controller , 2—relay with connected sensors, 3—power supply, 4—sampling pump, and 5—communication module  . The com1, 22, …, 29.The automated system 1 collects, registers, and displays data recorded by the sensors 2The output voltage of power supply 3 must match the required voltage of the controller and relay 2 (most devices require 7–12 V).1, 22, …, 29 to relay 2 occurs via I2C, UART, SPI, and other Modbus protocol interfaces.Data transfer from modules 2Data transfer from controller 1 to PC occurs through the RS-232 interface.1, 22, …, 29 are fed to relay 2, which collects information from all the control devices. Experimental data is then transmitted from relay 2 to controller 1 via the Modbus protocol. The data are recorded in registers and sent to a PC via the RS-232 interface. On the PC, in the automated control system (SCADA-system), the current values from the control devices are displayed and recorded in the database. Measurement data of sensors 21, 22, …, 29 are stored on an external storage device  using module 11. Data arrays are recorded in table formats. File format: *.txt, *.csv, *.xls, etc. Communication module 5 transfers information according to the Groupe Special Mobile digital mobile cellular communication standard to external information storage .The principle of operation of the device is as follows: When pump 4 is operational, signals from sensors 2To connect the BME680 temperature, humidity, and pressure sensor, use the following steps: The BME680 sensor has four pins: VCC, GND, SLA, and SDA, which serve as the analog signal output . This seThe ENS160 + AHT21 sensor is connected to the pins, the SDA and SCL contacts . The modTo connect the SIM800L GSM communication module, a separate 4.0 V supply voltage regulator is required . A resisBoosting DC–DC Converter XL6009: The XL6009 module has input and output voltage terminals. LEDs are placed on the board, indicating its operating status.Since this is a boost converter, the supply potential at the input of the module will always be less than at the output. Therefore, it is quite possible to obtain a voltage at the output greater than at the input using XL6009. To increase its voltage (current), it is necessary to rotate the corresponding knob of the potentiometers located on the board clockwise. To decrease, turn it in the other direction. This allows for the adjustment of the required values of the output parameters.Out of all 12 pins, only 4 are needed: VCC, RXD, TXD, and GND.To ensure the stable operation of the SIM800L module, a power supply with an output voltage of 3.4–4.4 V and a maximum operating current of 2 A is required. Thus, connect the VCC and GND contacts to the plus and minus terminals of the 5 V power supply, and then connect RXD and TXD to the pins.To create an equal-arm voltage divider, use a pair of resistors of the same rating within the range of 1–10 KΩ. This configuration will provide a voltage of 2.5 V, which fits within the required range of 2.1–3.1 V.It is not possible to power the module from the Arduino. The module can draw up to 2A, and the Arduino is not capable of supplying such a current. Attempting to power the module from the Arduino or the USB port of the computer could result in damage to one or both components. This is particularly relevant in the active operation mode when transferring data to the database, as the current consumption increases significantly.Connecting the wind speed sensor and the 18650 Li-ion battery protection board. First, short wires with a cross section of 0.5–0.75 mm should be prepared. It is necessary to solder them to the board pads for added reliability and to reduce the risk of accidental short-circuits of the battery leads . First, Next, the connection of the middle output is carried out, where the cross-section of the wire is not critical as it does not carry a large current. Finally, all the components should be connected together using the appropriate wires and terminal blocks.In summary, the VIN and GND contacts are connected to the plus and minus of the p+ and p- protection board and to the plus and minus of the 5 V power supply. Power is supplied to the device and connected to the analog input.Connect the +V pin of the sensor to the 5 V pin on the Arduino Mega 2560.Connect the GND pin of the sensor to the GND pin on the Arduino Mega 2560.Connect the AO analog input pin of the sensor to the AO pin on the Arduino Mega 2560.Connect the Rx pin of the sensor to the Rx pin on the Arduino Mega 2560.Connect the Tx pin of the sensor to the Tx pin on the Arduino Mega 2560.To connect the Eu-M-CH4-OD methane sensor to the Arduino board, it is necessary to:The wiring diagram for connecting the Eu-M-CH4-OD methane sensor is illustrated in Connect the VCC pin of the sensor to the 5 V pin on the Arduino Mega 2560.Connect the GND pin of the sensor to the GND pin on the Arduino Mega 2560.Connect the SDA pin of the sensor to the SDA pin on the Arduino Mega 2560.Connect the SCL pin of the sensor to the SCL pin on the Arduino Mega 2560.To connect the CM1107N carbon dioxide sensor to the Arduino board, it is necessary to:The wiring diagram for connecting the CM1107N carbon dioxide sensor is illustrated in The wiring diagram of the device prototype was developed and is illustrated in The measurement system  consistsThe developed control device is illustrated in The program for managing the greenhouse gas control process was created using the Arduino IDE. The variables for the controlled and adjustable parameters of the technological process are defined in the variable editor window .Field tests of the developed control device were conducted in urbanized areas with low-growing mixed vegetation at a height of 110 mm from the ground level during the period from 4 to 6 in the afternoon. The anemometer was positioned to register a 0° angle when air moved vertically upwards and 180° when moving vertically downwards.Time series data on the concentration of carbon dioxide, methane, temperature, humidity, atmospheric air pressure, wind direction, and speed in the vertical direction were collected .2 and CH4, with CO2 exhibiting greater intensity.According to the data obtained, the turbulent flow of carbon dioxide, calculated by formula 1, is −63.478 This paper proposes a technical solution for measuring and recording the parameters necessary for conducting scientific studies on the movement of gas flows in atmospheric air using the method of turbulent pulsations. This solution consists of a complex device, including a controller and connected measuring elements. The system can be easily upgraded to accommodate additional sensors, enabling rapid adaptation to changes in the goals and objectives of scientific research, which provides a competitive advantage over existing market solutions.The article also discusses organizational and technical considerations during the installation of automation systems. It justifies the choice of technical and software components for automation, including the selection of the Arduino controller and sensors such as AHT21 + ENS160, BME680, Eu-M-CH4-OD, CM1107N, and SM5386V. Furthermore, it explains the rationale behind the selection of mounting and auxiliary automation and electrical equipment. The programming of the Arduino Mega 2560 controller is performed using the Arduino IDE software, resulting in the successful creation of a greenhouse gas control system with real-time technological parameters.Field tests of the developed measuring device were conducted, yielding valuable data on the turbulent flow of carbon dioxide and methane.The developed measuring tool is technically straightforward to implement and user-friendly. It offers cost-effectiveness, and its characteristics can be easily customized by adding new sensors as needed.


This review highlights the importance of perilipins in lipid metabolism and their potential as therapeutic targets for lipid-associated diseases like cancer and obesity. Perilipins are proteins found in lipid droplets that regulate lipase activity and play a crucial role in maintaining the balance between lipid synthesis and breakdown. Modulating perilipins could improve existing treatments or offer new therapeutic opportunities for addressing these diseases.Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1–5), each with specific expression patterns and metabolic activation, but all capable of regulating the activity of lipases on LD. This plurality creates a complex orchestrated mechanism that is directly related to the healthy balance between lipogenesis and lipolysis. Given the essential role of PLINs in the modulation of the lipid metabolism, these proteins can become interesting targets for the treatment of lipid-associated diseases. Since reprogrammed lipid metabolism is a recognized cancer hallmark, and obesity is a known risk factor for cancer and other comorbidities, the modulation of PLINs could either improve existing treatments or create new opportunities for the treatment of these diseases. Even though PLINs have not been, so far, directly considered for pharmacological interventions, there are many established drugs that can modulate PLINs activity. Therefore, the aim of this study is to assess the involvement of PLINs in diseases related to lipid metabolism dysregulation and whether PLINs can be viewed as potential therapeutic targets for cancer and obesity. Canxidation . To prevxidation ,5,6,7,8;xidation .LDs are nano- to micro-sized organelles, composed of a neutral lipid core surrounded by a phospholipid monolayer ,11. For Perilipins (PLINs), the most abundant proteins in LDs, regulate LD stability and lipid turnover, consequently controlling the overall lipid metabolism . Given tThe biogenesis of LDs mainly takes place within the endoplasmic reticulum (ER), culminating in the creation of a fully functional structure . A schemde novo synthesis [The LD structure comprises a core of neutral lipids enveloped by a single layer of phospholipids with proteins . The corynthesis .The uptake of FA occurs through transporters such as CD36, the fatty acid transport protein family (FATP), and plasma membrane fatty acid-binding proteins (FABPpm) . CD36 isDe novo lipogenesis, the process of producing new FAs, originates from citrate and acetate, which are produced by pyruvate oxidation via the TCA cycle [CA cycle . This prCA cycle . HoweverCA cycle .Within the ER, FAs are transformed into neutral lipids, specifically in the form of TAG . The synThe TAG synthesized by DGAT starts to accumulate between the bilayer membrane of the ER, marking the beginning of LD biogenesis ,25. ContA group of other proteins, the PLINs, also participate in the regulation of the rate of lipolysis in the LD . These pThe balance between lipogenesis and lipolysis is directly influenced by the accessibility of lipases to the lipid core of the LD . PLINs pPLINs, also known as PAT proteins, represent the most prevalent proteins found in LD membranes . Five PLPLIN1 is mainly found in mature adipocytes, where it acts as a lipolysis modulator, thereby regulating lipid redistribution from adipose tissues to other organs and tissues . PLIN1 rThe lipolytic pathway of PLIN1 is controlled by receptors linked to the cAMP-dependent protein kinase (PKA) pathway . PhosphoPLIN1 is an important regulator of lipolysis in white adipose tissue (WAT) and it is associated with both basal and adrenergic-induced lipolysis . The PLIIn cancer, PLIN1 overexpression has been reported to favor cancer development in tissues which normally express PLIN1 (adipose tissue) , being hPLIN2, also known as adipophilin, is ubiquitous and continuously expressed ,57,58. PExpression of PLIN2 is induced by peroxisome proliferator-activated receptor gamma (PPARγ) activation ,62,63. PThe ubiquitin–proteasome pathway consistently degrades expressed PLIN2, a process that involves the E3 ubiquitin ligase (Ubr1) ,71. Ubr1PLIN2 bound to the LD membrane is degraded by chaperone-mediated autophagy (CMA), as illustrated in CMA of PLIN2 may be increased by its phosphorylation by AMP-activated protein kinase (AMPK) . Under chilpda), the gene that encodes the hypoxia-inducible protein 2 (HIG-2) [Hypoxia induces an extensive metabolic reprogramming of the cell to face the decrease in nutrients and oxygen supply. The metabolic reprogramming is coordinated by the hypoxia-inducible factors (HIF) 1-alpha (HIF-1α) and 2-alpha (HIF-2α) . Under n (HIG-2)  whose fu (HIG-2) ,85. Hypohilpda and, therefore, the increase in LD load promoted by hypoxia [The interplay between PLIN2 and hypoxia seems to be particularly relevant as PLIN2 has been shown to be involved in a positive loop that further inhibits the degradation of HIF-1α and sustains its expression and that of  hypoxia . The pat hypoxia ,88 or ca hypoxia . The ass hypoxia ,91, brea hypoxia ,93, pros hypoxia ,95, lung hypoxia ,97, blad hypoxia ,104,105, hypoxia , gastric hypoxia , and mel hypoxia .PLIN2 was also shown to be involved in the interaction between LDs and the plasma membrane ,110,111,PLIN3, also known as TIP47, is ubiquitously expressed . During PLIN3 seems to play a pivotal role in promoting the transition from brown to WAT and, consequently, in obesity. The depletion of PLIN3 in WAT triggers the generation of brown adipocytes and the expression of genes responsible for thermogenesis .PLIN3 also appears to play a significant role in cancer pathogenesis. Studies have reported abnormal PLIN3 expression in several types of cancer, including cervical , clear cPLIN4, also known as S3-12, is the least studied protein of the perilipin family . It is mThe depletion of PLIN4 has been linked to diminished PLIN5 expression in the heart and a reduction in heart LDs. This suggests that the functions of PLIN4 and PLIN5 may be closely interconnected .The most solid evidence pointing to a relationship between PLIN4 and obesity was provided by the observation that single nucleotide polymorphisms of PLIN4 were correlated with obese phenotypes . In cancPLIN5, also known as OXPAT, predominantly occurs in tissues that rely on β-oxidation for energy generation, such as skeletal muscle, cardiac muscle, and brown adipose tissue . Its expPLIN5 is found at the contact site between LDs and mitochondria ,37. The Therefore, the function of PLIN5 seems to participate in a delicate balance to preserve lipid homeostasis . It favoIn the context of cancer, the overexpression of PLIN5 has been observed in patients with breast cancer, renal carcinomas, liposarcoma, rhabdomyosarcoma, and leiomyosarcoma ,143. It The diverse roles and tissue distribution of PLINs raise the question about how their actions are coordinated to act both as gatekeepers of LD and to allow the release of LD contents when required . The orcPeroxisome proliferator-activated receptors (PPARs) are transcriptional factors that control the expression of genes that code for proteins involved in FA storage, glucose metabolism, and adipocyte differentiation , includiPPARγ activity can be influenced by substances like polyunsaturated FAs, eicosanoids, and oxidized lipid components . ElevateTwo specific mechanisms seem to underpin the enhancement of LD loading mediated by PPARγ. One is the upregulation of PLIN1 expression, which improves the capacity to restrict lipolytic enzymes from acting primarily on LDs in adipocytes . The othIn addition to the influence on PPARγ, free FAs also stimulate PPARα, resulting in increased β-oxidation in skeletal muscle and the liver ,159. ThuAny stimulus that activates PKA can lead to PLIN1 phosphorylation by PKA . PLIN1 pThe key distinction between PKA-induced regulation and PPARγ-induced regulation lies in the effect on adipocytes’ ability to store FAs in LDs. Under PKA regulation, this ability is diminished due to PKA’s action on PLIN1 . This reIn situations where a cell has the necessary conditions for proliferation (such as the availability of sufficient amino acids), this mechanism may also be triggered. By sensing the abundance of these anabolic components, the cell promotes PLIN2 degradation as well . This prThis coordinated regulation can fail if either the sensitivity of PLIN1 to phosphorylation decreases or the control over PLIN2 degradation lessens. In such cases, obesity or ectopic fat deposits may occur, leading to dysfunctions in lipid metabolism and the potential development of associated diseases . In factIn the context of cancer, the overexpression of PLIN2 and PLIN3 is often observed ,163,164.Several prevalent types of cancer, such as breast, colorectal, esophageal, kidney, gallbladder, uterine, pancreatic, and liver, have been associated with obesity, which also increases the likelihood of cancer mortality ,166. TheAdipocytes and cancer cells appear to establish a metabolic symbiosis, transforming adipocytes into cancer-associated adipocytes and promoting cancer growth . This tr2-adrenoceptors, which are prototypically coupled to the Gs/cAMP/PKA pathway [Adrenaline is the endogenous ligand of β pathway . Both ou pathway ,171 and  pathway ,173 haveUltimately, the accumulation of FAs in the LDs of cancer cells, along with their ability to mobilize FAs from adipocytes in the tumor microenvironment, may enhance the ability of cancer cells to resist the starvation conditions signaled by AMPK activation .The significance of PLINs in regulating lipid metabolism is undeniable. However, they have not yet been prioritized as targets for pharmacological intervention. Nevertheless, there are a variety of drug categories, some of which are approved for clinical use, that operate on the regulators of PLIN function or expression. This repertoire includes PPAR activators , SIRT1 ,176, andThese regulatory pathways exert unique influences on different PLINs ,153,154.As previously described, PPARs play a significant role in maintaining nutrient homeostasis and they are the main regulators of PLIN expression ,153,154.Fibrates are high affinity PPARα activators used for the treatment of dyslipidemias ,182. ThrThiazolidinediones (TZDs), recognized as PPARγ activators, are utilized in the management of diabetes . ConsideSome cancer types are known to express PLIN2 ,163,164.TZDs are also known to have anti-inflammatory properties ,194. WheGiven AMPK function in promoting the CMA of PLIN2, PLIN3, and the increasing expression of PLIN5 , the stiPharmacologically, AMPK may be activated by drugs such as salicylic acid or by its precursor, acetylsalicylic acid  and metfMetformin was also shown to reduce LD accumulation in human chorionic villous mesenchymal stem cells , an obseAdiponectin is a glycoprotein primarily produced in adipocytes . The expSIRT1 is a post-translational regulator that affects multiple biological processes according to the cell energy status , and itsResveratrol is one of the first SIRT1 activators studied, but the list of SIRT activators is being extended with the inclusion of other activators of natural  and synthetic origin  ,176. SulThe cAMP/PKA pathway is a complex pathway that presents several possibilities of pharmacological intervention. One of the most obvious and extensively explored is the intervention at the membrane G-protein coupled receptors that lead to adenylyl cyclase activation . The β-aβ-AR activation promotes the lipolysis of stored triglyceride in both white and brown adipocytes . The mecIn cancer, activation of the PKA pathway may also provide the energy to fuel the higher anabolic activity associated with these cells. This assumption is supported by the observation that clenbuterol, a long-acting β-AR agonist, was shown to induce cell proliferation  and thatKnowing the relevance of PLINs in controlling FA distribution and use, its putative involvement may be considered when trying to explain the effects caused by several drugs on body weight. For instance, the chronic use of antipsychotic drugs, such as olanzapine, clozapine, and chlorpromazine, causes an increase in body weight and fat mass ,245. TheThe opposite may also occur. The following clinically approved drugs were described to decrease lipid accumulation or cause weight loss as an adverse drug reaction by a mechanism that involves a reduction of PLIN1 expression or an increase PLIN1 degradation: adapalene, used for topical treatment of mild to moderate acne ; artesunOther drugs may cause a reaction pattern more complex than an increase/decrease of body weight. For instance, vitamin D  or dihydThis review summarizes the role of LDs and PLINs in the management of lipids in our body. The coordinated activity of PLINs promotes a healthy balance between storage, when supply exceeds demand, and release, when demand increases. However, this coordination is very fragile and can be easily disrupted.Alterations in the balance of PLINs that cause an excessive retention of lipids in the LD may promote WAT expansion and obesity. This alteration may favor LD expansion in cancer tissues. Pharmacological interventions to prevent this type of imbalance could be applicable to the treatment of obesity-related diseases and cancer. The challenge to develop drugs that target the activity of PLINs may be facilitated by the knowledge that some drugs already used in clinical practice are known to alter body weight by altering PLINs activity. The present review is intended to provide new insights into the coordination of PLINs activity to foster the development of PLINs pharmacology, particularly with new classes of drugs that are able to directly target each PLIN.