Environmental pesticide exposure and Alzheimer's disease in southern Spain: A cross-sectional study.

The intensive cultivation under plastic in southern Spain has made the agricultural model highly productive. Although strict regulations on pesticide usage exist, exposure to pesticides in the environment has been associated with an increased appearance of neurodegenerative diseases including Alzheimer's disease (AD). A cross-sectional study was performed to examine the prevalence and risk of AD related to pesticide exposure in Andalusia (Spain). We utilized the Odds Ratio statistical test to compare the prevalence rate of AD in the exposed and unexposed areas. 40,044 cases were collected from computerized hospital records between 2000 and 2021. Districts with higher pesticide use showed significantly higher prevalence rates and increased risk of developing AD, compared to those with lower pesticide use. These findings provide further evidence supporting an increased risk of AD following environmental exposure to pesticides at the level of the general population.

A Th2-type immune response and low-grade systemic inflammatory reaction as potential immunotoxic effects in intensive agriculture farmers exposed to pesticides.

Pesticides are chemicals widely used in agriculture to keep crops healthy and prevent them from being destroyed by pests, thus contributing to a sustainable food and feed production. However, long-term exposure to these compounds may be harmful to human health as they can affect the function of various organs systems, including the immune system. There is growing evidence that pesticides may increase the risk of developing immune-based diseases and inflammation. This study assessed whether greenhouse farmers occupationally exposed to pesticides presented alterations in immunoregulatory proteins, used as surrogate biomarkers of immune function. The study population consisted of 175 greenhouse workers occupationally exposed to pesticides and 91 non-exposed controls. Serum levels of 27 cytokines, chemokines and growth factors were measured using a magnetic bead-based immunoassay in a subpopulation of 111 greenhouse workers and 79 non-exposed controls. Since analytical determinations were performed in two periods of the same crop season with different use of pesticides (period of high and low pesticide exposure), linear mixed models for repeated measures were used to optimize statistical inference. The increase in IL-13, IL-4 and IL-6 observed in greenhouse workers compared to controls, and in the period of high exposure to pesticides relative to that of low exposure, suggest an altered Th1/Th2 balance towards the Th2 response. This finding points to a type-2 inflammation commonly presented as allergic inflammation, which has often been reported in farm-workers and in which pesticide exposure is considered a risk factor. Furthermore, the increase in IL-1ß and VEGF, mediators of inflammation and angiogenesis, may suggest a low-grade systemic inflammation that might underlie chronic pathological conditions linked to pesticide exposure.

Exposure to Environmental Pesticides and the Risk of Autism Spectrum Disorders: A Population-Based Case-Control Study.

Background and Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in communication, social interactions, and repetitive behaviors. Although the factors that influence the development of this condition are unknown, certain chemical compounds such as pesticides have been proposed as possible contributors. Due to the lack of an established causal link between pesticide exposure and ASD, this study aimed to evaluate this potential association. Materials and Methods: A case-control study was carried out to ascertain the prevalence and risk associated with ASD in relation to pesticide exposure over a 21-year study period (2000-2021). Results: We included 2821 individuals diagnosed with ASD residing in areas of both high and low pesticide exposure in southern Spain. There was a rise in the ASD prevalence rate in regions with elevated pesticide use when compared to regions with low use [odds ratio (OR): 1.34, 95% confidence interval (CI), (1.24-1.44)]. Notably, men had the highest likelihood, with an OR: 1.42, 95% CI, (1.30-1.55). Furthermore, after performing multiple binary logistic regression adjusted for age, sex, and geographical area, males exhibited a higher likelihood compared to females [OR: 2.41, 95% CI, (2.21-2.62)]. Conclusions: Overall, this research suggests a connection between heightened environmental pesticide exposure due to increased agricultural use and autism.

Renal tubular dysfunction in greenhouse farmers exposed to pesticides unveiled by a panel of molecular biomarkers of kidney injury.

Growing evidence suggests that chronic exposure to pesticides may cause adverse effects on the health of the exposed population leading to organ-specific toxicity, including kidney damage. Traditional markers used to assess renal function (glomerular filtration rate (GFR), and serum creatinine and cystatin C -Cys-C-) are inadequate to evaluate a potential subclinical renal impairment linked to occupational exposure to pesticides, since levels above the upper limit of normal only occur when renal damage is very extensive. The use of more sensitive biomarkers is therefore needed. This study investigated novel urinary biomarkers of kidney function (microalbuminuria, osteopontin (OPN), trefoil factor 3 (TFF3), ß-2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL), and Cys-C), together with the aforementioned traditional serum biomarkers, to assess potential kidney damage in farmers exposed to pesticides in an intensive agriculture setting. The study population consisted of 175 greenhouse workers and 91 healthy control subjects from Almeria (Southeastern Spain), a major hub of greenhouse agriculture. Data were collected at two different time-points of the same crop season: a period with greater pesticide use (high exposure period) and another with lower pesticide use (low exposure period). Significantly higher urinary levels of OPN and TFF3 were found in greenhouse workers than in controls, and in the high pesticide exposure period compared to that of low exposure. These changes suggest a subclinical tubular damage linked to pesticide exposure. In contrast, microalbuminuria, GFR, serum creatinine and Cys-C failed to be associated with pesticide exposure, suggesting that glomerular function was spared. Increased OPN and TFF3 levels over time may suggest a gradual progression from tubular dysfunction to chronic kidney disease in the exposed population.

Intestinal intussusception in adult as an uncommon cause of mechanical obstruction.

A 61-year-old woman admitted for epigastric abdominal pain, three months of evolution, worsens after ingestion, associating abdominal distension and constipation. Physical examination: abdominal pain and distension in the mesogastric zone. Blood tests: slight increase in C-reactive protein; abdominal X-ray: the small bowel dilatation; computed tomography scan: small bowel obstruction due to intussusception. An exploratory laparotomy was performed, confirming a mechanical intestinal occlusion secondary to 5 centimeters jejunal intussusception (image 3); It was execute an intestinal resection with adequate margins and an anisoperistaltic mechanical side-to-side anastomosis. Correct postoperative evolution; hospital discharge on the sixth day. Pathology report: polypoid intussusception, 4.3x3.3 centimeters, superficial ulceration, edema, chronic inflammation; resection margins without alterations.

Occupational exposure to pesticides as a potential risk factor for epilepsy.

Epilepsy is a chronic neurological disorder in which brain activity becomes abnormal, causing seizures. In a previous study we found that environmental exposure to pesticides was associated with a greater risk of epilepsy. The present study examined possible occupational risk factors that may contribute to the occurrence of epilepsy in farmers and pesticide applicators (sprayers). A case-referent study was conducted on 19,704 individuals over a 17-year study period (2000-2016). Epilepsy cases (n = 5091) were collected from Hospital records and referents (non-epilepsy cases, n = 14.613) from the Centre for Prevention of Occupational Risks, both from Almería (South-Eastern Spain). A significant increased risk of having epilepsy was found in farmers working in intensive agriculture (high-yield greenhouse crops) compared to extensive agriculture (open-air crops). The risk was greater for farmers residing in rural areas with high pesticide use (intensive farming crops in plastic greenhouses) and for those not wearing protective gloves. As for sprayers, the greatest risk of epilepsy was observed in those not wearing face mask, and in those living in areas with high pesticide use (greenhouse intensive agriculture). Overall, this study supports previous findings on the association between epilepsy and pesticide exposure in the general population, and extends the risk to farmers occupationally exposed to pesticides, mainly those engaged in intensive agriculture.

Environmental pesticide exposure and the risk of irritable bowel syndrome: A case-control study.

The agricultural model in southern Spain is highly productive, mainly due to the intensive cultivation under plastic. Despite strict pesticide regulation, human exposure to pesticides in the environment has been connected to an increase in diseases such as celiac disease. Certain pesticides have also been associated to the disruption of the intestinal microbiota, which has been tied to the development of irritable bowel syndrome (IBS). A case-control study was conducted in Andalusia, south Spain, to assess the prevalence and risk of IBS related to pesticide exposure. This research found a high prevalence of IBS in Andalusia between 2000 and 2021 in areas with high pesticide exposure using agronomic criteria. Furthermore, the odds ratio for IBS was significantly higher in the population with high pesticide exposure. This study suggests that pesticides may be involved in IBS, whereas more research is needed to determine the role of pesticides in IBS symptomatology.

Game-Based Learning Outcomes Among Physiotherapy Students: Comparative Study.

BACKGROUND: University teaching methods are changing, and in response to a classical teacher-centered approach, new methods continue to strengthen knowledge acquisition by involving students more actively in their learning, thus achieving greater motivation and commitment. OBJECTIVE: This study aimed to analyze the degree of satisfaction of physiotherapy students who used a board game-based approach, as well as to compare the difference between traditional and gamification teaching methods and their influence on the final evaluation of these students. METHODS: A comparative study was conducted. Participants were physiotherapy students who were enrolled in the subject of "physiotherapy in geriatric and adult psychomotricity" (n=59). They were divided into two groups (experimental [n=29] and control [n=30] groups) through convenience sampling. The experimental group received gamification lessons, where the students performed different tests adapted from Party&Co, and the control group received traditional lessons. A total of 16 theoretical lessons were received in both groups. RESULTS: The scores in the final examination of the subject were higher in the experimental group (mean 7.53, SD 0.95) than in the control group (mean 6.24, SD 1.34), showing a statistically significant difference between the two groups (P=.001). CONCLUSIONS: Overall, the "Physiotherapy Party" game not only stimulated learning and motivated students, but also improved learning outcomes among participants, and the improvements were greater than those among students who received traditional teaching.

Evaluation of conventional and non-conventional biomarkers of liver toxicity in greenhouse workers occupationally exposed to pesticides.

The liver plays a prominent role in maintenance of homeostasis and is the major organ for xenobiotic metabolism, including pesticides. Conventional liver function tests are widely used to assess hepatocellular and biliary system dysfunction by measuring serum levels of aminotransferases (ALT, AST) and cholestasis enzymes (alkaline phosphatase -ALP- and γ-glutamyl transferase -GGT-), respectively. Although these tests are not entirely specific for liver damage, their specificity increases when measured concurrently, but still have limited usefulness to predict early liver dysfunction. Hence, non-conventional biomarkers may have a better performance for the early detection of biochemical hepatotoxicity with a greater specificity and sensitivity. A cross-sectional study with a follow-up component was conducted on 175 greenhouse workers regularly exposed to pesticides under integrated production system, and 91 controls living in the same geographical area. All individuals were evaluated for conventional (ALT, AST, ALP, GGT) and non-conventional biomarkers of hepatotoxicity (ornithine transcarbamylase (-OTC-), Arginase-1 -ARG1- and glutathione S-transferase alpha -GSTα-) over two periods of the same crop season, one of high pesticide exposure and other of low exposure. A slight increase in AST was observed in greenhouse workers relative to controls, suggestive of subtle hepatocellular toxicity. Although ALP, ARG1 and GST-α levels were decreased in greenhouse workers, this might be related to a potential homeostatic mechanism that regulates their expression. Altogether, these findings do not represent unambiguous evidence of liver dysfunction (e.g., hepatocellular or biliary system impairment) but may be the result of the low-toxicity pesticides used by greenhouse workers.

Environmental exposure to pesticides and risk of thyroid diseases.

Occupational and environmental exposure to pesticides has been associated with thyroid dysfunction, particularly changes in circulating thyroid hormone levels (T3, T4) and thyroid stimulating hormone (TSH). This study assessed the association between environmental exposure to pesticides and the risk of developing thyroid diseases. A population-based case-control study was carried out among Spanish populations living in areas categorized as of high or low pesticide use according to agronomic criteria, which were used as surrogates for environmental exposure to pesticides. The study population consisted of 79.431 individuals diagnosed with goiter, thyrotoxicosis, hypothyroidism, and thyroiditis (according to the International Classification of Diseases, Ninth Revision) and 1.484.257 controls matched for age, sex and area of residence. Data were collected from computerized hospital records for the period 1998 to 2015. Prevalence rates and risk of having thyroid diseases were significantly higher in areas with higher pesticide use, with a 49% greater risk for hypothyroidism, 45% for thyrotoxicosis, 20% for thyroiditis and 5% for goiter. Overall, this study indicates an association between increased environmental exposure to pesticides as a result of a greater agricultural use and diseases of the thyroid gland, thus supporting and extending previous evidence. This study also provides support to the methodology proposed for real-life risk simulation, thus contributing to a better understanding of the real life threat posed by exposure to multiple pesticides from different sources.

Predictive risk model for the diagnosis of diabetes mellitus type 2 in a follow-up study 15 years on: PRODI2 Study.

Background: The prevalence and mortality related to diabetes mellitus type 2 (DM2) have increased consistently for decades. Identifying adults at high risk of diabetes incidence is important for the execution of intervention. Methods: The participants in the PRODI2 study (n=273), who come from the southeast of Spain and did not have diabetes at the start of the study, were followed for 15 years (1999-2014), and their risk parameters were measured, from which a predictive model was obtained which indicates the level of influence of each factor in the development of DM2. The expected risk of diabetes was calculated by binary logistic regression. Results: Those participants whose father has suffered an acute myocardial infarction are 3.9 times more likely to develop DM2 (confidence interval 95%: 1.498, 10.339); those with at least one parent who has a history of diabetes are 2.7 times more at risk (confidence interval 95%: 1.224, 6.101); the risk of being diabetic was 1.13 times higher for every extra unit on the waist-hip ratio (confidence interval 95%: 1.073, 1.195), and for the hip perimeter an OR of 0.93 was obtained (confidence interval 95%: 0.876, 0.982). Statistically significant differences were observed in all cases (P<0.05). Conclusion: This study shows that the risk of being diabetic rises in patients whose father has suffered an acute myocardial infarction, in those whose mother or father is diabetic and in patients with a high waist perimeter.

Association between environmental exposure to pesticides and epilepsy.

There is increasing evidence of an association between long-term environmental exposure to pesticides and neurodegenerative disorders; however, the relationship with epilepsy has not been addressed thus far. This study was aimed at determining the prevalence and risk of developing epilepsy among people from South-East Spain living in areas of high vs. low exposure to pesticides based on agronomic data. The study population consisted of 4007 subjects with a diagnosis of epilepsy and 580,077 control subjects adjusted for age, sex and geographical area. Data were collected from hospital records of the Spanish health care system (basic minimum dataset) between the years 1998 and 2010. The prevalence of epilepsy was significantly higher in areas of greater pesticide use relative to areas of lesser use. Overall, an increased risk of epilepsy was observed in the population living in areas of high vs. low use of pesticides (OR: 1.65; p < 0.001). Although this study was exploratory in nature, the results suggest that environmental exposure to pesticides might increase the risk of having epilepsy.

Biomarkers of oxidative stress in blood of workers exposed to non-cholinesterase inhibiting pesticides.

In occupational settings workers are often exposed to pesticides at relatively high doses compared to environmental exposures. Long-term exposure to pesticides has been associated with numerous adverse health effects in epidemiological studies, and oxidative stress is often claimed as one of the underlying mechanisms. In fact, different pesticides have been reported to induce oxidative stress due to the generation of free radicals and/or alteration in antioxidant defense enzymes. The present study examined greenhouse workers regularly exposed to diverse pesticides under integrated production system, and a group of controls of the same geographic area without any chemical exposure. Two different periods of the same crop season were assessed, one of high exposure (with greater use of pesticides) and other of low exposure (in which a less use of these compounds was made). Non-specific biomarkers of oxidative stress, e.g. thiobarbituric acid reactive substances (TBARS), ferric reducing ability of serum (FRAS), total thiol groups (SHT), gamma-glutamyl transpeptidase (GGT) and paraoxonase-1 (PON1) were measured in serum samples from all study subjects, alongside erythrocyte acetylcholinesterase (AChE). Results are suggestive of a mild increase in oxidative stress associated with pesticide exposure, which was compensated by an adaptive response to raise the antioxidant defenses and thus counter the detrimental effects of sustained oxidative stress. This response led to significantly increased levels of FRAS, SHT and PON1 in greenhouse workers relative to controls. Furthermore, AChE was decreased likely as a result of oxidative stress as workers did not use organophosphate insecticides.

Observational study of patients in Spain with amyotrophic lateral sclerosis: correlations between clinical status, quality of life, and dignity.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that dramatically affects patients' quality of life (QoL) and dignity of life (DoL). We aimed to study the impact of ALS on QoL and DoL and how these evolve throughout the duration of the disease. METHODS: First, we performed an observational, descriptive study of 43 patients with ALS recruited from the ALS unit at our center and compared them with 20 healthy age- and sex-matched controls. Second, we performed a prospective cohort study, following up 23 patients with ALS over 3 months. All participants completed questionnaires about their functional status, QoL, and DoL. RESULTS: QoL and DoL were significantly worse in the ALS group than in controls (both p < 0.001). During the three-month follow-up in the ALS cohort, statistically significant declines were observed in clinical status and QoL. For clinical status, median scores on the ALS Functional Rating scale changed from 30.95 points at baseline to 27.24 points after 3 months (p = 0.0003). For QoL, median scores on the ALS Assessment Questionnaire changed from 124.19 points at baseline to 131.81 at 3 months (p = 0.0062). However, no significant differences were found between the DoL scores at baseline (48.14 points) and 3 months (45 points) (p-value = 0.12). CONCLUSIONS: ALS is a neurodegenerative disease that affects QoL and DoL alike. We found that clinical status and QoL both deteriorated in patients with ALS as the disease progressed, but that DoL was preserved. However, our findings are limited by small sample sizes. The preservation of DoL may be due to multiple factors, including the therapies provided by the ALS unit. These findings suggest that alongside QoL, DoL may be an important target in the management and care of ALS patients.

Association of reproductive disorders and male congenital anomalies with environmental exposure to endocrine active pesticides.

There is growing evidence that environmental exposure to pesticides may increase the risk of developing reproductive and developmental disorders. This study determined the prevalence and risk of developing gestational disorders and male congenital genitourinary malformations in areas with distinct exposure to pesticides, many of them with potential endocrine disrupting properties. A population-based case-control study was carried out on pregnant women and male children living in ten health districts of Andalusia classified as areas of high and low environmental exposure to pesticides according to agronomic criteria. The study population included 45,050 cases and 950,620 controls matched for age and health district. Data were collected from computerized hospital records between 1998 and 2005. Prevalence rates and risk of miscarriage, low birth weight, hypospadias, cryptorchidism and micropenis were significantly greater in areas with higher use of pesticides in relation to those with lower use, thus supporting and extending previous information.

Activity and determinants of cholinesterases and paraoxonase-1 in blood of workers exposed to non-cholinesterase inhibiting pesticides.

Pesticide exposure has been associated with different adverse health effects which may be modulated to some extent by paraoxonase-1 (PON1) activity and genetic polymorphisms. This study assessed seasonal variations in PON1 activity (using paraoxon -POase-, phenylacetate -AREase-, diazoxon -DZOase- and dihydrocoumarin -DHCase- as substrates), erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (using butyrylthiocholine -BuChE- and benzoylcholine -BeChE- as substrates. The study population consisted of intensive agriculture workers regularly exposed to pesticides other than organophosphates and non-exposed controls from Almería (Southeastern Spain). The effect of common genetic polymorphisms of PON1 and BCHE on paraoxonase-1 and cholinesterase activities toward different substrates was also assessed. Linear mixed models were used to compare esterase activities in agricultural workers and control subjects over the two study periods (high and low exposure to pesticides). The significant decrease in AChE and increase in BuChE and BeChE activities observed in workers with respect to control subjects was attributed to pesticide exposure. Workers also had higher levels of AREase, DZOase and, to a lesser extent, of POase, but showed decreased DHCase activity. While PON1 Q192R and PON1 -108C/T gene polymorphisms were significantly associated with all PON1 activities, PON1 L55M showed a significant association with AREase, DZOase and DHCase. BCHE-K (Karlow variant) was significantly associated with lower BeChE activity (but not with BuChE) and BCHE-A (atypical variant) showed no significant association with any cholinesterase activity. These findings suggest that increased PON1, BuChE and BeChE activities in exposed workers might result from an adaptive response against pesticide exposure to compensate for adverse effects at the biochemical level. This response appears to be modulated by PON1 and BCHE gene polymorphisms.

Occupational pesticide exposure and adverse health effects at the clinical, hematological and biochemical level.

AIMS: Although epidemiological studies have investigated associations between occupational pesticide exposures and different adverse health outcomes, they have rarely assessed individuals at two time-points of a same crop season with different pesticide use. MATERIAL AND METHODS: Clinical symptoms, physical examination signs, hematological and clinical chemistry parameters were measured in 189 intensive agriculture workers and 91 healthy control subjects from Almeria coastline (Southeastern Spain) to evaluate potential effects of pesticide exposure. KEY FINDINGS: Greenhouse workers showed an increased risk of ocular and skin signs relative to controls at the period of high pesticide exposure (OR: 4.80 and 2.87, respectively); however, no differences were observed for clinical symptoms. A greater risk for ECG changes (OR: 3.35) and altered spirometry (OR: 5.02) was found at the period of low exposure. Erythrocyte acetylcholinesterase was significantly decreased in greenhouse workers relative to controls in both periods. Assessment of hematological parameters revealed increased counts of erythrocytes, leukocytes, platelets and hemoglobin in greenhouse workers relative to controls, and also in the period of high versus low pesticide exposure. Changes in clinical chemistry parameters included decreased levels of glucose, creatinine, total cholesterol, triglyceride and alkaline phosphatase in greenhouse workers relative to controls; however, these parameters were raised in the period of high versus low pesticide exposure. SIGNIFICANCE: These findings suggest that chronic occupational exposure to pesticides of lower toxicity than former compounds under integrated production systems elicit mild toxic effects, particularly targeting the skin and eyes, as well as subtle subclinical (biochemical) changes of unknown long-term consequences.

Environmental exposure to pesticides and cancer risk in multiple human organ systems.

There is growing evidence on the association between long-term exposure to pesticides in occupational settings and an elevated rate of chronic diseases, including different types of cancer. However, data on non-occupational exposures are scarce to draw any conclusion. The objective of this study was to investigate the putative associations of environmental pesticide exposures in the general population with several cancer sites and to discuss potential carcinogenic mechanisms by which pesticides develop cancer. A population-based case-control study was conducted among people residing in 10 Health districts from Andalusia (South Spain) to estimate the risk of cancer at different sites. Health districts were categorized into areas of high and low environmental pesticide exposure based on two quantitative criteria: number of hectares devoted to intensive agriculture and pesticide sales per capita. The study population consisted of 34,205 cancer cases and 1,832,969 age and health district matched controls. Data were collected by computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of cancer at most organ sites were significantly higher in districts with greater pesticide use related to those with lower pesticide use. Conditional logistic regression analyses showed that the population living in areas with high pesticide use had an increased risk of cancer at all sites studied (odds ratios between 1.15 and 3.45) with the exception of Hodgkin's disease and non-Hodgkin lymphoma. The results of this study support and extend previous evidence from occupational studies indicating that environmental exposure to pesticides may be a risk factor for different types of cancer at the level of the general population.