Carcinogenic, non-carcinogenic risk, and attributable cases to organochlorine pesticide exposure in women from Northern Mexico.

This study aimed to estimate the carcinogenic and non-carcinogenic risk as well as the attributable cases due to exposure to organochlorine pesticides (OCPs): hexachlorobenzene (HCB), dichlorophenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), heptachlor, and chlordane. From serum concentrations of pesticides of interest in a sample of 908 women from Northern Mexico, the risk for both cancer and non-cancer health effects was evaluated. The population attributable fraction (PAF) was also calculated based on summary association estimates between exposure to OCPs and different health events. Findings revealed that due to their OCP exposure slightly less than half of the women in the sample were at increased risk of developing non-cancerous diseases. Moreover, approximately 25% and 75% of participants were at risk of develop some type of cancer associated with their HCB and DDE concentrations, respectively. In addition, it was estimated that 40.5% of type 2 diabetes, 18.7% of endometriosis, and 23.1% of non-Hodgkin's lymphoma cases could have been prevented if women had not been exposed to these OCPs. Results suggest that the use of OCPs may have contributed to the disease burden in the study area and, based on the time required for these substances to be eliminated from the body, there are probably some women who are still at elevated risk of developing diseases associated to OCPs.

Food groups consumption and urinary metal mixtures in women from Northern Mexico.

OBJECTIVE: We aimed to evaluate the association between food groups and mixtures of urinary metal concentrations in a sample of women; as well as identify the most important metals within each mixture. METHODS: This is a cross-sectional analysis between food groups consumption and mixtures of various metals in urine from 439 women, ≥18 years old, from Northen Mexico. We estimated the dietary intake of 20 food groups through a validated semi-quantitative food frequency questionnaire. Urinary metal concentration of aluminum, antimony, arsenic, barium, cadmium, cesium, chromium, cobalt, copper, lead, manganese, magnesium, molybdenum, nickel, selenium, thallium, tin, vanadium, and zinc, were measured by inductively coupled plasma triple quad. We used weighted quantile sum (WQS) regression with binomial family specification to assess the association of food groups and metal mixtures, as well as to identify the most important ones. RESULTS: We identified tin, lead, and antimony as the most important metals, in the metal mixtures that were positively associated with the consumption of eggs, non-starchy vegetables, fruits, seafood, corn, oil seeds, chicken, soda, legumes, red and/or processed meats, as well as negatively with the consumption of alliums, corn tortillas and/or vegetable oils. CONCLUSION: Our findings suggest that food consumption is related to more than one metal in the study sample, and highlights the presence of some of them. Further research is required to identify the possible sources of metals in food, as well as the chronic adverse health effects attributed to their simultaneous presence.

miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review.

The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. We therefore performed an extensive literature analysis to evaluate the clinical utility of miRNAs with a confirmed direct relationship with treatment response to ICIs. As a result of this systematic review, we have stratified the miRNA landscape into (i) miRNAs whose levels directly modulate response to ICIs, (ii) miRNAs whose expression is modulated by ICIs, and (iii) miRNAs that directly elicit toxic effects or participate in immune-related adverse events (irAEs) caused by ICIs.

A protective maternal nutrient concomitant intake associated with acute leukemia might be modified by sex, in children under 2 years.

Introduction: Maternal dietary consumption during pregnancy has been inconclusively associated with acute leukemia (AL) in infants, probably because epidemiological evidence has emerged mainly from the analysis of one-by-one nutrient, which is not a real-life scenario. Our objective was to evaluate the association between AL in Mexican children under 2 years of age and their mothers' nutrients concomitant intake during pregnancy, as well as to explore whether there are differences between girls and boys. Methods: We conducted a study of 110 cases of AL and 252 hospital-based controls in the Mexico City Metropolitan area from 2010 to 2019. We obtained information on maternal intake of 32 nutrients by a food frequency questionnaire and used weighted quantile sum regression to identify nutrient concomitant intakes. Results: We found a concomitant intake of nutrients negatively associated with AL (OR 0.17; CI95% 0.03,0.88) only among girls; and we did not find a nutrient concomitant intake positively associated with AL. Discussion: This is the first study that suggests nutrients that have been individually associated with AL are not necessarily the same in the presence of other nutrients (concomitant intake); as well as that maternal diet might reduce AL risk only in girls.

Exposure to Organochlorine Pesticides and Female Breast Cancer Risk According to Molecular Receptors Expression: a Systematic Review and Meta-analysis of Epidemiological Evidence.

PURPOSE OF REVIEW: Organochlorine pesticides (OCP) have been proposed as potential mammary carcinogens since they interact with steroid signaling pathways. However, the epidemiological results are not conclusive. Most studies have evaluated breast cancer (BC) as a single entity without considering the different molecular expressions, including estrogen receptor (ER), progesterone receptor (PR), and HER2, that could differ in their association with these contaminants. Hence, we assessed the association between biological concentration of OCP and BC, according to its molecular receptor expression, based on a systematic review and meta-analysis. RECENT FINDINGS: Of the 141 articles eligible for full-text review, nine met the inclusion criteria. The way in which molecular expression was reported was heterogeneous; therefore, the inclusion of studies in the meta-analysis was limited to eight articles. A negative association was identified for ß-hexachlorocyclohexane and trans-nonachlor with ER + tumors and between hexachlorobenzene and ER - tumors. No associations were observed for p,p'-dichlorodiphenyldichloroethylene, cis-nonachlor, and dieldrin, and it was not possible to evaluate the associations between OCP with HER2 expression or triple-negative tumors due to lack of data. The results suggest that some OCP might be associated with BC depending on the expression of ER. However, the evidence is not conclusive due to the scarce data. We identified several methodological aspects to fill the gaps in knowledge and increase the comparability among studies.

Lifestyle Quality Indices and Female Breast Cancer Risk: A Systematic Review and Meta-Analysis.

Breast cancer (BC) poses an important burden of disease, which probably could be reduced by adopting healthy lifestyles like healthy body weight, healthy diet, and physical activity, among others. Many studies have reported that adherence to healthy lifestyles may decrease BC risk. The main objective of this study was to estimate a summary association of studies evaluating a healthy lifestyle index and BC risk. A systematic review and meta-analysis following the Cochrane methodology were carried out. Observational studies, including healthy lifestyle indices and their association with BC, were searched from 4 databases. For the meta-analysis, random-effects model was used to evaluate overall BC risk, BC by molecular subtype and menopausal status. Thirty-one studies were included in the systematic review, and 29 studies in the meta-analysis. When the highest vs. the lowest category to a healthy lifestyle index were compared, the study identified a 20% risk reduction for BC in prospective studies (hazard ratio [HR] 0.80 95% CI: 0.78, 0.83) and an odds ratio (OR) of 0.74 (95% CI: 0.63, 0.86) for retrospective studies. The inverse association remained statistically significant when stratified by menopausal status, except for premenopausal BC in prospective studies. Furthermore, an inverse association was found for molecular subtypes estrogen receptor (ER+)/progesterone receptor (PR+): HR = 0.68 (95%CI: 0.63, 0.73), ER+/PR-: HR = 0.78 (95% CI: 0.67, 0.90) and ER-/PR-: HR = 0.77 (95% CI: 0.64, 0.92). Most studies scored at a low risk of bias and a moderate score for the certainty of the evidence. Adherence to a healthy lifestyle reduces the risk of BC, regardless of its molecular subtypes, which should be considered a priority to generate recommendations for BC prevention at a population level. International prospective register of systematic reviews (PROSPERO) ID: CRD42021267759.

Urinary cadmium concentrations and intake of nutrients, food groups and dietary patterns in women from Northern Mexico.

Cadmium (Cd) is a toxic metal found in some foods. There is limited evidence about the relationship of Cd exposure with nutrient and food groups consumption, and almost no information regarding dietary patterns. The objective was to evaluate the association between diet and urinary Cd, and to explore whether metal concentrations vary according to the intake of some nutrients. Urinary Cd concentrations of 891 female residents of northern Mexico were determined by tandem mass spectrometry. We obtained food consumption through a food frequency questionnaire and we used previously defined food groups and estimated dietary patterns by factor analysis. We found positive associations between Cd and daily consumption of non-starchy vegetables (ß = 0.067, 95% CI 0.030, 0.1023), legumes (ß = 0.139, 95% CI 0.065, 0.213) and processed meats (ß = 0.163, 95% CI 0.035.0.291), as well as the Western (ß = 0.083, 95% CI: 0.027.0.139) and Prudent dietary patterns (ß = 0.035, 95% CI: -0.020, 0.091). In contrast, we observed a negative association with the vegetable oil group (ß = -0.070, 95% CI -0.125, -0.014). In addition, we found higher concentrations of Cd in women under 50 years of age with a lower iron intake than recommended. Food is a source of exposure to this metal and at the same time provides nutrients that modulate its metabolism. It is important to generate dietary guidelines to reduce the health effects of Cd exposure.

Psychosis in Parkinson's Disease: Looking Beyond Dopaminergic Treatments.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. The symptoms of PD are characterized not only by motor alterations but also by a spectrum of nonmotor symptoms. Some of these are psychiatric manifestations such as sleep disorders; depression; cognitive difficulties that can evolve into dementia; and symptoms of psychosis, which include hallucinations, illusions, and delusions. Parkinson's disease psychosis (PDP) occurs in 18-50% of patients with PD. Treating PDP is challenging because antipsychotic drugs tend to be inefficient or may even worsen the disease's motor symptoms. OBJECTIVE: This review aims to summarize the current understanding of the molecular mechanisms involved in PDP and recent innovative alternatives for its treatment. METHODS: This is a narrative review in which an extensive literature search was performed on the Scopus, EMBASE, PubMed, ISI Web of Science, and Google Scholar databases from inception to August 2021. The terms "Parkinson's disease psychosis", "Parkinson psychosis," "neurodegenerative psychosis", and "dopamine psychosis" were among the keywords used in the search. RESULTS: Recently, views on the etiology of hallucinations and illusions have evolved remarkably. PDP has been cemented as a multifactorial entity dependent on extrinsic and novel intrinsic mechanisms, including genetic factors, neurostructural alterations, functional disruptions, visual processing disturbances, and sleep disorders. Consequently, innovative pharmacological and biological treatments have been proposed. Pimavanserin, a selective 5-HT2A inverse agonist, stands out after its approval to treat PDP-associated hallucinations and illusions. CONCLUSION: Future results from upcoming clinical trials should further characterize the role of this drug in the management of PDP as well as other treatment options with novel mechanisms of action, such as saracatinib, SEP-363856, cannabidiol, electroconvulsive therapy, and transcranial magnetic stimulation.

"Western" and "prudent" dietary patterns are associated with breast cancer among Mexican pre- and postmenopausal women.

Breast cancer (BC) is the leading cancer worldwide among women. "Prudent" dietary patterns have been consistently and negatively associated with the risk of BC. However, prospective studies have shown a positive association between "Western" dietary patterns and the risk of BC, but only among postmenopausal women. In this regard, evidence from Latin America is scarce. Our aim was to assess the hypothesis that 2 dietary patterns (Western or prudent) were contrastingly associated with BC in pre- and postmenopausal women from Northern Mexico. We recruited 1045 BC incident cases and 1030 age matched (±5 years) population controls. Sociodemographic, reproductive, and dietary characteristics were obtained by direct interviews. We used a semiquantitative food frequency questionnaire to obtain information about diet 1 year before diagnosis for cases and 1 year before the interview for controls. Dietary patterns were identified through factor analysis. A Western-like pattern, which was mainly determined by positive loads in red and processed meats and foods rich in fats and sugars, was positively associated with BC both in pre- (odds ratio [OR] =23.47; 95% CI, 14.01-36.96) and in postmenopausal women (OR = 18.85; 95% CI, 13.74-25.87). In contrast, a prudent-like pattern, which was characterized by positive loads of vegetables, legumes, and corn, was negatively associated with pre- (OR = 0.35; 95% CI, 0.26-0.49) and postmenopausal BC (OR = 0.25; 95% CI, 0.19-0.32). Our results show the importance of dietary patterns in BC development regardless of menopausal status.

Electroconvulsive Therapy in Psychiatric Disorders: A Narrative Review Exploring Neuroendocrine-Immune Therapeutic Mechanisms and Clinical Implications.

Electroconvulsive therapy (ECT) is based on conducting an electrical current through the brain to stimulate it and trigger generalized convulsion activity with therapeutic ends. Due to the efficient use of ECT during the last years, interest in the molecular bases involved in its mechanism of action has increased. Therefore, different hypotheses have emerged. In this context, the goal of this review is to describe the neurobiological, endocrine, and immune mechanisms involved in ECT and to detail its clinical efficacy in different psychiatric pathologies. This is a narrative review in which an extensive literature search was performed on the Scopus, Embase, PubMed, ISI Web of Science, and Google Scholar databases from inception to February 2022. The terms "electroconvulsive therapy", "neurobiological effects of electroconvulsive therapy", "molecular mechanisms in electroconvulsive therapy", and "psychiatric disorders" were among the keywords used in the search. The mechanisms of action of ECT include neurobiological function modifications and endocrine and immune changes that take place after ECT. Among these, the decrease in neural network hyperconnectivity, neuroinflammation reduction, neurogenesis promotion, modulation of different monoaminergic systems, and hypothalamus-hypophysis-adrenal and hypothalamus-hypophysis-thyroid axes normalization have been described. The majority of these elements are physiopathological components and therapeutic targets in different mental illnesses. Likewise, the use of ECT has recently expanded, with evidence of its use for other pathologies, such as Parkinson's disease psychosis, malignant neuroleptic syndrome, post-traumatic stress disorder, and obsessive-compulsive disorder. In conclusion, there is sufficient evidence to support the efficacy of ECT in the treatment of different psychiatric disorders, potentially through immune, endocrine, and neurobiological systems.

Dietary contribution to total urinary arsenic in Mexican women.

Exposure to inorganic arsenic (iAs) damages health in many ways. The main routes of human exposure are consumption of contaminated water and diet, but evidence regarding the dietary contribution of iAs is limited. The objective of this work was to determine the foods and beverages that contribute to urinary total arsenic levels (TAs). This is a secondary analysis of an original study of breast cancer cases and population controls carried out in northern Mexico during the period 2007-2011, from which 1,462 women without a history of diabetes were selected. We estimated the consumption of the food and beverage groups with a frequency questionnaire. We measured the concentrations of urinary iAs metabolites by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Total arsenic ranged from 0.5 to 2,360 µg/g creatinine. After adjusting for covariates, we observed a positive association between TAs (with arsenobetaine) with non-bottled drinking water intake, as well as the consumption of root vegetables, vegetables and fruits rich in water, eggs, fish and shellfish. Our findings highlight the relevance of water consumption and some foods for TAs exposure. Food quality monitoring deserves attention in high-risk regions of arsenic contamination.

Metal exposure and breast cancer among Northern Mexican women: assessment of genetic susceptibility.

This study aims to assess breast cancer (BC) association with metals and whether polymorphisms in CYP1A1, CYP1B1, GSTM1 and GSTT1 act as confounders or as modifiers of those relationships. We performed a secondary analysis of 499 histologically confirmed BC cases and the same number of age-matched population controls. We measured urinary concentrations of 18 metals with mass spectrometry. We determined the genetic variants of interest by allelic discrimination and multiplex PCR. After adjusting for covariates, we found BC negatively associated with arsenic, barium, cobalt, copper, magnesium, molybdenum and vanadium concentrations and positively with those of caesium, manganese, tin and thallium. Most associations remained after stratifying by the genetic variants. We identified that polymorphisms in CYP1B1, CYP1A1 and GSTM1 genes interacted with some metals on BC: interaction p-values CYP1B1 G119T × antimony= 0.036, CYP1B1 G119T × cobalt <0.001, CYP1B1 G119T × tin= 0.032, CYP1A1 A4889G × aluminium= 0.018, CYP1A1 A4889G × arsenic= 0.031, CYP1A1 A4889G × nickel= 0.036, CYP1A1 A4889G × vanadium= 0.031 and GSTM1 deletion × barium= 0.035. Exposure to various individual metals, along with genetic characteristics may contribute to BC development. Further studies are warranted to confirm our results.

Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches.

The constant changes in cancer cell bioenergetics are widely known as metabolic reprogramming. Reprogramming is a process mediated by multiple factors, including oncogenes, growth factors, hypoxia-induced factors, and the loss of suppressor gene function, which support malignant transformation and tumor development in addition to cell heterogeneity. Consequently, this hallmark promotes resistance to conventional anti-tumor therapies by adapting to the drastic changes in the nutrient microenvironment that these therapies entail. Therefore, it represents a revolutionary landscape during cancer progression that could be useful for developing new and improved therapeutic strategies targeting alterations in cancer cell metabolism, such as the deregulated mTOR and PI3K pathways. Understanding the complex interactions of the underlying mechanisms of metabolic reprogramming during cancer initiation and progression is an active study field. Recently, novel approaches are being used to effectively battle and eliminate malignant cells. These include biguanides, mTOR inhibitors, glutaminase inhibition, and ion channels as drug targets. This review aims to provide a general overview of metabolic reprogramming, summarise recent progress in this field, and emphasize its use as an effective therapeutic target against cancer.

Psycho-Neuro-Endocrine-Immunological Basis of the Placebo Effect: Potential Applications beyond Pain Therapy.

The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations regarding its effects. During recent years, it has been discovered that the placebo response not only has neurobiological functions on analgesia, but that it is also capable of generating effects on the immune and endocrine systems. The possible integration of changes in different systems of the organism could favor the well-being of the individuals and go hand in hand with conventional treatment for multiple diseases. In this sense, classic conditioning and setting expectations stand out as psychological mechanisms implicated in the placebo effect. Recent advances in neuroimaging studies suggest a relationship between the placebo response and the opioid, cannabinoid, and monoaminergic systems. Likewise, a possible immune response conditioned by the placebo effect has been reported. There is evidence of immune suppression conditioned through the insular cortex and the amygdala, with noradrenalin as the responsible neurotransmitter. Finally, a conditioned response in the secretion of different hormones has been determined in different studies; however, the molecular mechanisms involved are not entirely known. Beyond studies about its mechanism of action, the placebo effect has proved to be useful in the clinical setting with promising results in the management of neurological, psychiatric, and immunologic disorders. However, more research is needed to better characterize its potential use. This review integrates current knowledge about the psycho-neuro-endocrine-immune basis of the placebo effect and its possible clinical applications.

Breast cancer and urinary metal mixtures in Mexican women.

Humans are environmentally exposed to many metals throughout their lives. Simultaneous exposure to several metals could result in synergistic or antagonistic toxicological effects among them; however, the information on exposure to mixtures of metals and breast cancer (BC) is scarce. The objective of this report was to compare metals considered human carcinogens, individually and as mixtures, in women with and without BC. This is a secondary analysis of a population-based case-control study that was carried out from 2007 to 2011 in Northern Mexico. A total of 499 histologically confirmed BC cases and 499 controls were included. Information about sociodemographic, lifestyle and reproductive characteristics was obtained by in-person interviews. Urinary concentrations of aluminum (Al), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), antimony (Sb), cobalt (Co), molybdenum (Mo), tin (Sn), and vanadium (V) were determined by inductively coupled plasma triple quadrupole. Metal mixtures were identified by principal component analysis with creatinine-corrected metals. Over 90% of subjects had metal measurements above the detection limit except tin (86%) and antimony (78.4%). After adjusting by selected covariables, we observed that the individual urinary concentrations of V, Co, and Mo were lower among cases compared to controls; in contrast to Sn that had higher concentrations. We identified two principal component mixtures with opposite relationships with BC: Cr, Ni, Sb, Al, Pb and Sn (OR = 1.15; CI95% 1.06,1.25) and Mo and Co (OR = 0.56; CI95% 0.49,0.64). This is the first study that identified urinary metal mixtures that differed between women with and without BC. Our results warrant confirmation in further prospective epidemiological studies. In addition, the elucidation of underlying mechanisms of metal interactions on BC risk deserves further research.

Tobacco Smoke Exposure and Urinary Cadmium in Women from Northern Mexico.

Cadmium (Cd), a carcinogenic metal also related to reproductive and cardiovascular diseases, is contained in tobacco and elevated concentrations of it in humans have been consistently associated with first-hand tobacco smoke; however, there is scarce and inconclusive evidence of the relationship between Cd and secondhand smoke (SHS) exposure. Our aim was to evaluate the association between exposure to tobacco, both active and SHS, with urinary Cd concentrations in Mexican women. In a cross-sectional analysis that included 998 women living in northern Mexico, we measured the concentration of creatinine-adjusted urinary Cd (µg-cadmium/g-creatinine) using inductively coupled plasma triple quadrupole (ICP-QQQ) in tandem mass spectrometry mode (MS/MS). We gathered tobacco smoking information through an in-person interview and formed seven groups: non-smokers without SHS exposure; non-smokers with SHS exposure; ex-smokers without SHS exposure <1 year of quitting; ex-smokers without SHS exposure ≥1 year of quitting, ex-smokers with SHS exposure <1 year of quitting; ex-smokers with SHS exposure ≥1 year of quitting and current smokers. The interview also yielded sociodemographic characteristics. We used linear multivariable regression models to estimate the association between Cd concentrations and tobacco smoke exposure. Compared to non-smokers without SHS exposure, we found higher Cd concentrations in ex-smokers with SHS exposure <1 year of quitting and current smokers (adjusted geometric means 0.51 vs. 1.01 and 0.69 µg-cadmium/g-creatinine, respectively). Our results do not support a conclusion that SHS exposure is a source of Cd body burden.

SGLT2i and GLP-1RA in Cardiometabolic and Renal Diseases: From Glycemic Control to Adipose Tissue Inflammation and Senescence.

Background. Over the last few years, the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) has increased substantially in medical practice due to their documented benefits in cardiorenal and metabolic health. In this sense, and in addition to being used for glycemic control in diabetic patients, these drugs also have other favorable effects such as weight loss and lowering blood pressure, and more recently, they have been shown to have cardio and renoprotective effects with anti-inflammatory properties. Concerning the latter, the individual or associated use of these antihyperglycemic agents has been linked with a decrease in proinflammatory cytokines and with an improvement in the inflammatory profile in chronic endocrine-metabolic diseases. Hence, these drugs have been positioned as first-line therapy in the management of diabetes and its multiple comorbidities, such as obesity, which has been associated with persistent inflammatory states that induce dysfunction of the adipose tissue. Moreover, other frequent comorbidities in long-standing diabetic patients are chronic complications such as diabetic kidney disease, whose progression can be slowed by SGLT2i and/or GLP-1RA. The neuroendocrine and immunometabolism mechanisms underlying adipose tissue inflammation in individuals with diabetes and cardiometabolic and renal diseases are complex and not fully understood. Summary. This review intends to expose the probable molecular mechanisms and compile evidence of the synergistic or additive anti-inflammatory effects of SGLT2i and GLP-1RA and their potential impact on the management of patients with obesity and cardiorenal compromise.

Cellular targets in diabetic retinopathy therapy.

Despite the existence of treatment for diabetes, inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy. Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles. Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease. Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia. The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy. Therefore, in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that, potentially, can prevent the development and progression of the disease.

Specialized Pro-Resolving Lipid Mediators: The Future of Chronic Pain Therapy?

Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP.

Lipid Accumulation Product Is More Related to Insulin Resistance than the Visceral Adiposity Index in the Maracaibo City Population, Venezuela.

BACKGROUND: Visceral adiposity is related to insulin resistance (IR), a metabolic state considered as a risk factor for other cardiometabolic diseases. In that matter, mathematical indexes such as the visceral adiposity index (VAI) and the lipid accumulation product (LAP) could indirectly assess IR based on visceral adiposity. OBJECTIVE: To evaluate the association and diagnostic accuracy of VAI and LAP to diagnose IR in the adult population of Maracaibo city. METHODS: This is a cross-sectional descriptive study with multistage sampling. Receiver operating characteristic (ROC) curves were built to determine VAI and LAP cutoff points to predict IR. A set of logistic regression models was constructed according to sociodemographic, psychobiologic, and metabolic variables. RESULTS: 1818 subjects were evaluated (51.4% women). The area under the curve (AUC) values for LAP and VAI were 0.689 (0.665-0.714) and 0.645 (0.619-0.670), respectively. Both indexes showed a higher IR risk in the upper tertile in bivariate analysis. However, in the logistic regression analysis for the IR risk, only the 2nd (OR: 1.91; 95% CI: 1.37-2.65; p < 0.01) and 3rd (OR: 5.40; 95% CI: 3.48-8.39; p < 0.01) LAP tertiles showed a significant increase. This behaviour was also observed after adjusting for hs-C-reactive protein (hs-CPR). CONCLUSION: Although both indexes show a low predictive capacity in individuals with IR in the Maracaibo city population, the LAP index was more strongly associated with IR.