Diabetes mellitus type 2 (T2DM) is one of the most common diseases worldwide. Unhealthy dietary habits may lead to T2DM, which is also influenced by the extent of education and knowledge of appropriate diets for this disease.This study aims to highlight the possible association between following different types of diet  and glycemic control among Qatari and long-term resident patients with T2DM.This study is secondary data analysis. Qatar Biobank (QBB) data on 2448 T2DM patients aged 18–60 years were obtained. The first group included participants with HbA1C <7%, while the second included those with HbA1c ≥ 7%.The results of the association of glycemic control with different diets followed by patients with type 2 diabetes were adjusted in four models. In the 4th model , results showed that poor patients with poor glycemic control have higher odds  of following a low-salt diet. The same observation was found in the low-fat diet . However, patients following more than one diet showed lower odds of having poor glycemic control for about 32% .Diet and lifestyle are vital factors that can affect HbA1C levels. The findings of this secondary analysis showed that better glycemic control of the patients was observed in patients following more than diet from the studied diets. Because insulin is an anabolic hormone, a lack of insulin in the target tissues results in abnormal carbohydrate, fat, and protein metabolism (Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia caused by one of two defects: a defect in insulin secretion or a defect in insulin action, or both . Severaltabolism . The efftabolism .n (ADA) describes MNT as a fundamental component that must be integrated into the overall management plan for diabetes. Therefore, MNT is the primary intervention to achieve balanced and controlled blood sugar and avoid complications. Healthcare team members can accomplish these goals by providing evidence-based guidance to help patients with T2DM make healthy food choices and meet their own needs, not to mention that it is crucial to reassess them regularly during their treatment journey  is known to be widespread in adults, the incidence of this type has begun to increase among young adults. The most important reasons are the changes in their lifestyle when they were children, both in terms of life instability and the lower consumption of healthy foods. Obesity has been linked to insulin resistance . DM deve journey . The nut journey .Most of the studies demonstrated that there is an association between glycemic control and the consumption of several nutrients, such as simple carbohydrates, fats, and salt. However, there are few studies on eating patterns and their association with glycemic control (HbA1c <7.0) for Qatari adults (18–60) with diabetes. Therefore, our secondary analysis study aims to identify the possible association between glycemic control and different diets followed by Qatari adults with type 2 diabetes.Participants' data were obtained from Qatar Biobank (QBB) for secondary analysis. QBB is an initiative launched to make vital health research possible by gathering biological samples and information on the health and lifestyle of large numbers of people living in Qatar. The study population included 2,448 adults  Qatari and long-term residents  from 18 to 70 years of age with type 2 diabetes. Pregnant women and patients with terminating illnesses were excluded. Participants were classified into two groups: the first, which included T2DM participants with good glycemic control (HbA1c <7%), while the second group included participants with poor glycemic control (HbA1c ≥7%)] . BiochemFour types of diets were identified among the participants, including a low-fat dieta, low-calorie diet, low-salt diet, and regular diet. Additionally, many participants from the two groups followed more than one diet. The type of diet was determined based on the food choices and the participant's perception of his/her diet as compared to before diagnosis.Glycemic control among patients with T2DM was considered the dependent variable for this study. HbA1c <7 was used as an outcome of the good glycemic control.Anthropometric measurements: body weight and height (sitting and standing) were measured using the Seca stadiometer and balance. Hip and waist circumferences were measured using tape. Body mass index (BMI) was calculated by dividing the weight (kg) by the height (m2) square.n (up to secondary school), medium education , and higher education (university and above). The physical activity levels were assessed in hours per week using the International Physical Activity Questionnaire. Face-to-face interviews with the patients were conducted with the assistance of professional nurses to gather information about their health status, related family medical history, and medication use. Health status (dyslipidemia and hypertension) was recorded from the patients' medical files.Data such as age, education level, smoking status, and physical activity were obtained from participants using a self-administered health and lifestyle questionnaire. Education levels were divided into three categories: lower education (SD) and frequency. Binary regressions were used to assess the association between glycemic control and diet, dietary habits, and sedentary behavior. This association was adjusted for four models. Model 1 is adjusted for gender, age, and comorbidities; model 2 for gender, age, sociodemographic, and comorbidities; model 3 for gender, age, sociodemographic, anthropometric, and comorbidities; and model 4 for gender, age, sociodemographic, anthropometric, dietary habits, and physical activity, comorbidities, and medications. The statistical significance level was set as P-value ≤0.05.Statistical Package for the Social Sciences version 23  was used to analyze the data. Data were presented as mean ± standard divisioOur study aimed to identify a possible association between glycemic control and different diets followed by patients with type 2 diabetes. From the present study results, we found that a higher percentage of participants with poor glycemic control was in the age group between 51and 70 years old in all the followed diets. In one of their studies, Ma et al.  mentioneIn this study, a low-salt diet was associated with poor glycemic control and increased waist circumference. These results, arguably, are the opposite of what is found in the literature and suggest that patients with these poor diabetic markers are motivated to follow a low-salt diet. To reach any conclusion, more research on medical advice and the desire to follow it is required. The following studies contradict our findings.According to a survey that was done in Malaysia on Malaysian citizens aged 18 and above, the authors showed that sodium intake was higher among male participants with a higher waist circumference . AnotherMany studies contradicted our results and showed that a low-fat diet is associated with better glycemic control. However, the results of the present study show that a low-fat diet increases the odds of poor glycemic control. A randomized control trial conducted by Kahleova et al. reported that a low-fat plant-based dietary intervention increased insulin sensitivity . MoreoveA study comparing the effect of a high-unrefined carbohydrate, low-fat diet (HC) on glycemic control with those of a very low-carbohydrate, and high-unsaturated/low-saturated fat diet (LC) found that both energy-reduced LC and HC diets with low-saturated fat content produce significant improvements in glycemic control in adults with T2DM. Glycemic control was greatest with the LC compared with HC . These rThe main limitation is the determination of the diet type, which was based on the food choices and the participant's perception of his/her diet as compared to before diagnosis. Diet alone could not be considered the main reason for poor glycemic control. Other confounders can play a role in glycemic control, such as age, gender, and medication. Additionally, our study is a secondary analysis from a single time point survey and not a pre/post special diet. However, this study has several strengths. First, the sample size is a total of 2,448 participants, which represents a large number of the Qatari population. Additionally, the sample size is homogeneous since all patients are of Qatari nationality or have had a long-term residency in Qatar.The findings of this secondary analysis study suggested that patients with diabetes who stated that they regulated multiple factors of their diet  may have better glycemic control. Longitudinal studies are needed to confirm our results.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Qatar BioBank. The patients/participants provided their written informed consent to participate in this study. The Institutional Review Board (IRB) of QBB approved under the IRB exempted category (Ex-2021-QF-QBB-RES-ACC-00058-180).RT and HB were responsible for the study conception and design and responsible for the development of the methodology. RT and ZS were responsible for the analysis and interpretation of data. RT, ZS, AH, YE, MA-A, KA, and ZA-H were responsible for drafting the manuscript. RT, ZS, AH, and HB were responsible for reviewing and revising the manuscript. All authors contributed to the article and approved the submitted version.This article was supported by Qatar university Internal Grant No. QUEST-1-CHS-2022-280. The findings achieved herein are solely the responsibility of the author[s].The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Due to a production error, there was a mistake in the legend for Figure 1 as published. The legend for Figure 2 was incorrectly used in its place. The correct legend appears below.Flow chart of the enrolment of participants. Number of Chronic Inflammatory Disease patients who were screened, included in the study and included in the analysis. Patients screened for eligibility were not explicitly recorded in the study. For CD, UC, and PsO we estimated a number based on the mean inclusion rate from two clinics that kept a pre-screening log. For RA, axSpA, and PsA, the number is not an estimate but the total number of patients that initiated biologic treatment in the clinic during enrolment. IBD, Inflammatory bowel disease (Crohn's disease and Ulcerative colitis); CD, Crohn's disease; UC, Ulcerative colitis; RA, Rheumatoid arthritis; axSpA, Axial spondyloarthritis; PsA, Psoriatic arthritis; PsO, Psoriasis; FFQ, Food Frequency Questionnaire; HFLM, high fibre/low meat; LFHM, low fibre/high meat; ITT, intention-to-treat; SF-12 PCS + MCS, short form health survey the physical and mental component summary, The short health scale includes four health dimensions ; CRP, C-reactive protein.Due to a production error, there was a mistake in the legend for Figure 2 as published. The legend for Figure 1 was incorrectly used in its place. The correct legend appears below.Meta-analysis (random effects model) of the included Chronic Inflammatory Diseases (CIDs) on the “As Observed” population comparing clinical response to biologics in patients with a high intake of fibre and low intake of red/processed meat (HFLM) vs. patients with a low intake of fibre and high intake of red/processed meat (LFHM). The horizontal lines represent the odds ratio (OR) ± 95% confidence interval. Event = clinical response according to the specified criteria for each CID, i.e., the number shows how many out of the total number of participants in the group, that have had a clinical response. The “As Observed” populations means patients with complete data for clinical response .The publisher apologizes for this mistake. The original version of this article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


On a scale ranging from −10 to +10, the median MPX knowledge score in the study sample was +3 (interquartile range: +1 to +5). Educational level was a determinant of MPX knowledge in multivariate analysis. More than 50% of the participants agreed at least to some extent with 9 out of 12 of the EVI conspiracy items. Multivariate analysis showed that embracing conspiracy beliefs about EVIs was associated with being female, and agreeing with or having no opinion regarding the role of MSM in MPX spread. The current study revealed the high prevalence of belief in conspiracies surrounding EVIs, and its accompanying intervention measures, among the general public in Jordan. In addition, a lower level of MPX knowledge was observed compared to previous studies among university students and health professionals in the country. We recommend evaluating the impact of the widely prevalent conspiracy beliefs on health aspects in future studies. This aim is particularly relevant in the Middle Eastern countries where embracing specific conspiracy ideas is a common occurrence.Conspiracy theories accompany the emergence of infectious diseases and the 2022 multi-country monkeypox (MPX) outbreak is no exception. It is possible that the adoption of conspiracy beliefs negatively impacts health behavior. We aimed to assess the prevalence of conspiratorial attitudes towards emerging virus infections (EVIs) and the response measures aiming to control these infections among the general public in Jordan. In addition, we assessed MPX knowledge and the belief in the role of men who have sex with men (MSM) in virus spread. The online survey data were collected during 24 May 2022–28 June 2022. The survey instrument was based on previously published scales designed to measure MPX knowledge and EVI conspiracies. A total of 611 respondents formed the final study sample, with a mean age of 44 years and a majority of females ( In humans, the emergence and re-emergence of zoonotic infectious diseases via cross-species transmission is a well-described natural phenomenon . SeveralThe direct health effects of zoonotic infections are feared due to the high case-fatality rate reported in some diseases  ,9,10. InThe multi-country monkeypox (MPX) outbreak in 2022 is a clear example of the prompt infodemic emergence accompanying the reporting of a novel infectious disease . CirculaOrthopoxvirus genus together with variola virus, the causative agent of smallpox, which was the first and only infectious disease to be declared eradicated from the human population [Monkeypox is a viral zoonosis that has been endemic in West and Central Africa for more than 50 years, with occasional outbreaks in Europe and the U.S. ,43. The pulation . The clapulation . For exapulation ,43,46. Ipulation ,48.Monkeypox is a self-limited disease with variable presentations, particularly during the current 2022 outbreak ,52,53,54The widespread transmission of MPXV resulted in more than 73,000 cases across 109 countries in the year 2022 alone. Thus, the number of confirmed cases recorded amid 2022 MPX outbreak surpassed the cumulative number of confirmed, probable and suspected cases reported over a period of 50 years . The disPrior to the 2022 MPX outbreak, human-to-human transmission of MPXV was reported, particularly in relation to household contact or healthcare settings ,60. ViruUpon the first encounter of a novel infectious disease, assessment of the baseline level of knowledge among the general population can be beneficial. This is related to previous evidence indicating that inaccurate knowledge can be linked with higher levels of anxiety, worries and potential conspiratorial ideation in response to the perceived threat of novel infectious agents ,73. In aOur previous work showed the discernible gaps in knowledge towards MPX among healthcare workers and university students in health schools in Jordan and Kuwait ,39,77. IThe cross-sectional design was based on a self-administered questionnaire distributed online.The inclusion criteria, as indicated in the introductory section of the survey, were residence in Jordan and age ≥ 18 years.The study questionnaire was distributed online during 25 May 2022–28 June 2022. The questionnaire was created using Google Forms. The anonymous survey was distributed in the Arabic language without monetary incentives for participation. Public posts and direct messages were used to promote participation in the survey using the following social media and instant messaging platforms: Facebook, Twitter and WhatsApp.Study approval was granted by the Scientific Research Committee—School of Medicine—University of Jordan (reference number: 2544/2022/67). The minimum sample size needed in this study was calculated using Epitools—Epidemiological Calculators, based on an estimated prevalence of 50%, a desired precision of estimate at 4% and the population size in Jordan, which was about 10,400,000 in 2022 ,82. AccoThe questionnaire used in the current study was based on the previously published papers addressing MPX knowledge and conspiracy beliefs towards coronavirus disease 2019 (COVID-19) ,39,77,83Second, the following socio-demographic variables were assessed in a separate section: age, sex, the highest educational level attained (high school or less vs. undergraduate degree vs. postgraduate degree), place of residence , and employment status (employed vs. unemployed).Third, MPX knowledge was assessed using a ten-item section, with “yes”, “no” and “I do not know” as the possible responses. The MPX knowledge items were based on a previous study by Harapan et al. in Indonesia, with a slight modification as follows : (1) thrFourth, a single item assessed the view of the study respondents towards the role of male homosexuals in the spread of the current MPX outbreak, measured on a 7-point Likert scale ranging from strongly agree through neutral/no opinion to strongly disagree.Finally, a twelve-item section followed, which comprised the emerging virus infections conspiracy scale (EVICS), based on a previous study by Freeman et al. . This scEach item was measured on a 7-point Likert scale ranging from strongly disagree (+1), to disagree (+2), somewhat disagree (+3), neutral/no opinion (+4), somewhat agree (+5), agree (+6) and strongly agree (+7). Thus, the EVICS possible range was 12–84, with higher scores indicating a higher prevalence of endorsing conspiratorial beliefs regarding emerging virus infections. Data and statistical analysis were conducted using IBM SPSS Statistics for Windows .Level classification for each MPX knowledge item, and for the total MPX K-score, was determined as follows: satisfactory/good knowledge for >70% correct responses; moderate/fair knowledge for 50–70% correct responses; and poor knowledge for <50% correct responses.Based on the mean EVICS score in the entire study sample, the EVICS score was dichotomized into two categories as follows: EVICS ≥ 56 denoting a higher endorsement of conspiracies regarding emerging virus infections vs. EVICS < 46, indicating a lower level of embracing of these conspiracies.U test (M-W), Kruskal—Wallis test (K-W), chi-squared test and logistic regression multivariate analyses were used as appropriate. The statistical significance level was considered to be p < 0.050.The Mann—Whitney n = 433, 70.9%), those with undergraduate degrees as the highest educational level , those residing in the capital, Amman , and employed respondents . Characteristics of the study sample divided by sex is shown in The study sample consisted of 611 respondents. The mean and median age of study respondents was 41 years (interquartile range: 30–50 years), with a majority of females , and for the item which assessed the belief of viruses as bioweapons designed by superpowers for global control  = 16.2, interquartile range (IQR): 44.0 to 67.0, and range: 12 to 84. The highest prevalence of agreement with conspiracy items was found for the item assessing skepticism towards the official explanation of virus emergence , while age (p = 0.433), educational level (p = 0.208), place of residence (p = 0.563), and employment status (p = 0.842) did not show statistically significant differences.Univariate analysis showed a stronger belief in conspiracies towards virus emergence among females compared to males , and a minority knew that vaccination is available to prevent the disease , and, among residents in the capital compared to those residing outside Amman , while age (p = 0.747), sex (p = 0.136), and employment status (p = 0.080) did not show statistically significant differences.Univariate analysis showed a higher MPX K-score among participants with postgraduate degrees compared to undergraduates and those with high school or lower educational attainment . In addition, the agreement category had a higher mean EVICS compared to the neutral and disagreement categories . Moreover, older age was associated with the agreement category compared to the neutral and disagreement categories . Using the chi-squared test, no significant differences were found based on sex (p = 0.401), educational level (p = 0.083), place of residence (p = 0.337), and employment status (p = 0.401).Divided into three categories , the participants in the agreement category had a higher MPX K-score  = 1.8) and with the agreement that male homosexuals had a role in MPX spread as opposed to disagreement (OR = 5.2). In addition, the neutral or lack of opinion towards the role of male homosexuals in MPX spread was associated with higher EVICS compared to disagreement  of the study sample involving the general public in Saudi Arabia . HoweverFrom a global perspective, a recent study among Italian adults by Gallè et al. revealed a low level of MPX knowledge and its prevention measures . SignifiThe current study illustrated a higher level of MPX knowledge based on the educational level attained with the highest level of MPX knowledge among postgraduates. Interestingly, the level of MPX knowledge was not linked to the embracing of conspiracies, in contrast to our previous studies among health professionals and university students in health schools in Jordan ,77. A prDespite the previous evidence of an unsatisfactory level of MPX knowledge among health students and health professionals in Jordan, the current study showed even deeper gaps in knowledge among the general public in the same country. This is understandable if the timing of the survey is taken into account, which was at the beginning of MPX reporting, when the information about the outbreak was sparse. Across the three tested categories in the three contemporaneous projects in relation to survey timing, HCWs displayed the highest level of knowledge, followed by health students and, as expected, the general public had the lowest level of knowledge. Previous and recent studies which were conducted in Indonesia, Italy and several Middle Eastern countries among health professionals in general, and physicians in particular showed that there is room for improving the level of MPX knowledge, which can help improve the outbreak response ,43,83,89Improving knowledge on an emerging virus infection can potentially have a positive effect, as shown previously by Abramson and Piltch-Loeb, during the Zika virus outbreak in the U.S. . RefininTwo interesting results of this study were linked to the agreement with the role of MSM in MPX spread. A majority of the study participants agreed at least to some extent with this statement. The agreement was linked with older age and higher MPX knowledge. Interestingly, the participants who agreed with the role of MSM in MPX spread had higher odds of embracing virus emergence conspiracy beliefs. Although the disproportionately higher occurrence of MPX among MSM networks was evident during the current outbreak, raising awareness that community spread of the virus can occur as well is of utmost importance, especially with cases being recorded in women and children, including neonates ,133,134.The current study should be viewed in light of several limitations that included selection and sampling biases based on the sampling approach, measurement bias based on the need to culturally adapt the scales used to the Arabic language, and the social desirability bias in the context of response to EVICS items. Female predominance should be taken into account, especially based on the finding in this study that a greater number of females embrace conspiracies. In addition, the sample size albeit sufficient was relatively small; therefore, it might not be representative of the entire population residing in Jordan. Future studies are recommended to assess the correlation of conspiracy beliefs towards virus emergence, which is a notable phenomenon in the general public in Jordan, with health behavior including attitude to MPX vaccination. Furthermore, our study was limited by the lack of comprehensive socio-demographic data to elucidate possible factors correlated with embracing of conspiracy beliefs and MPX knowledge. Such data in the context of MPX should include monthly income, exposure to animals or pets, history of prior viral illnesses, and history of chronic illnesses.The results of the current study point to the widespread prevalence of conspiracy beliefs in a sample of the general public in Jordan. The proliferation of conspiracy ideas towards emerging virus infections could be detrimental on health seeking behavior, which should be investigated in future studies. Thus, a special focus should be directed towards providing an explanation of virus emergence that is scientifically accurate and simplified, to remove any skepticism towards the explanation of infectious disease outbreaks. In this study, proper knowledge about MPX, which is an important determinant of engaging in the preventive efforts, was unsatisfactory. Thus, information campaigns directed towards the general public are encouraged to motivate the community engagement in preparedness and response to the MPX outbreak. These educational measures should consider the provision of concise, scientific messages involving information about virus emergence, and the treatment and prevention of MPX. The issues of stigma and discrimination towards groups with a high risk of contracting MPX should also be prioritized.


Cognitive impairment in older adults is a major public concern for Kazakhstan’s aging population. We aimed to (1) administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment in a sample of adults aged 60+ without dementia in Almaty, Kazakhstan; (2) investigate the associations between demographic factors and test performance; and (3) provide information on the distribution of NTB scores as preliminary local normative data relevant for this population. A cross-sectional evaluation of 276 participants aged 60+ in Almaty, Kazakhstan, was conducted using cognitive instruments including tests of memory, attention, language, executive functions, visuospatial abilities, and processing speed. Multiple linear regression analyses were used to examine the association of demographic factors with neuropsychological test performance. The results from the regression analysis showed that those who are younger, have more years of education, are women, and are of Russian ethnicity had significantly better performance. The current study illustrated (1) the feasibility of administering the NTB to older adults in the general population in Kazakhstan; (2) the preliminary local normative neuropsychological measures; and (3) their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan. Kazakhstan is an upper-middle-income country, the second largest of the former Soviet republics in Central Asia, undergoing a rapid epidemiological transition . KazakhsDespite the anticipated rise in cognitive impairment and dementia in Kazakhstan, reports on the prevalence of cognitive impairment and dementia in Kazakhstan are scarce ,8. RecenIn Kazakhstan, many comprehensive neuropsychological tests used in the US  are avaTherefore, the aims of this study were (1) to administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment to a random sample of older adults aged 60 and older without dementia in Almaty, Kazakhstan; (2) to investigate the associations between demographic factors and test performance; and (3) to provide information on the distribution of NTB scores as preliminary local normative data relevant for this population.We conducted a cross-sectional study among older adults of both genders aged 60 years and older who had lived in Almaty for the last 20 years. We recruited participants from an outpatient clinic. An outpatient clinic in Kazakhstan is a primary care facility to receive government-provided medical care. Every citizen in Kazakhstan must register at an outpatient clinic. We used outpatient clinic #32 in the Turksib District of Almaty, Kazakhstan. The Turksib District has historically been known as an older part of Almaty with a population of about 235,000. Migration within and between cities in Kazakhstan is uncommon due to cultural practices resulting in residents living in a certain area for decades. Kazakh and Russian are the major ethnic groups in Kazakhstan. Under the Soviet Union (1936–1991), the Kazakh language in school was banned and children uniformly learned Russian . Thus, oParticipants had to meet the following criteria in addition to the age and residency criteria above: (1) fluency in speaking and writing the Russian language; (2) capacity to provide informed consent; and (3) an MMSE score of 23 or higher. Participants were excluded if they had significant neurological and mental disorders , severe health conditions , history of vascular surgery in the past 6 months (any surgery that used cardiopulmonary bypass), severe sensory  or language impairment which would compromise evaluation of cognitive status, prior history of head trauma with a loss of consciousness, an illness associated with excessive alcohol consumption, and any substance abuse or use of medications for sleep disorders for the last 30 days before the neuropsychological assessment.We recruited participants using the Population Registration Portal, a national electronic patient management database with health information on each registered citizen of Kazakhstan. We built a de-identified list of subjects by age and predetermined health conditions based on the above-described inclusion and exclusion criteria. Using this list, we randomly selected potential participants. These potential participants were invited to the clinic and were screened by administering the MMSE. Written informed consent was obtained before the administration of MMSE. The NTB was administered only to those whose MMSE score was ≥23. We started recruitment in September 2019, and our target recruitment number was 400. However, due to the COVID-19 pandemic, we terminated our recruitment in March 2020 when we had screened 289. Among these 289 subjects, 276 participated in the study, resulting in a rate of participation of 95.5%. During the clinic visit, we collected information on gender, ethnicity , date of birth, and years of education.A US neuropsychologist (BS) trained a Kazakh behavioral neurologist (RT) who is fluent in English, Russian, and Kazakh on neuropsychological assessment with older adults across a spectrum of cognitive status. The training was held in Pittsburgh, US, for three days. Then, these two neuropsychologists trained two fellows at the Kazakh National Medical University, who were fluent in English, Russian, and Kazakh. The behavioral neurologist (RT) and the two fellows administered the NBT.We adopted the NTB used in the Duke–Tomsk PREPARE Study of the Duke University Alzheimer Disease Research Center in the US in conjunction with the Nebbiolo Center for Clinical Trials . RussianAll participants were assessed individually in a quiet room in the outpatient clinic with comfortable settings to avoid distractions. Trained research interviewers administered face-to-face neuropsychological tests to participants, assessing executive functions/working memory, attention/psychomotor speed, verbal episodic memory, and language abilities.MMSE  is a cogParticipants took part in a face-to-face interview with a standardized questionnaire. The first stage consisted of screening out dementia with the MMSE (cutoff point <23) and assessing potential risk factors. When participants passed the MMSE screen, the following tests were administered.Questions on functional status were obtained by the Alzheimer’s Disease Cooperative Study (ADCS) cognitive function screening instrument about difficulties in daily life  . Other qGlobal cognitive status was assessed using the Montreal Cognitive Assessment (MoCA) . The RusAdditionally, participants were assessed by the Consortium to Establish a Registry in Alzheimer’s Disease (CERAD) Word List Learning test, including delayed recall and recognition , phonemiThe CERAD Word List Learning test of verbal episodic memory involves three repeated learning trials of a ten word list, with immediate free recall in each trial, a 30 min delayed free recall, and a recognition condition with the original ten words and ten distractor words.In semantic verbal fluency, participants were asked to say as many words as possible within 60 s from each of two categories: animals and vegetables. The total score was the number of correct words generated, with errors or repetitions subsequently excluded. In phonemic verbal fluency, participants were asked to say as many words as possible within 60 s for each of the letters (/A/), (/Π/), and (/C/), excluding proper nouns and same-word variations.TMT A and B assess attention/psychomotor speed and executive functions, respectively. Participants are asked to connect a series of numbers and letters on a page with a pencil. TMT A is composed of the numbers 1 through 25. TMT B consists of numbers and letters and requires that subjects alternate between numbers and letters sequentially.The multilingual naming test (MINT) is a confrontation naming test designed for bilingual speakers. Participants were shown and asked to name 32 black and white line drawings of objects. The score reflects the number of spontaneously correctly named objects (without cues).The study was approved by the Institutional Review Boards of the Kazakh National Medical University and the University of Pittsburgh. Written informed consent was obtained from each participant.p-value < 0.05 was considered statistically significant.Statistical analysis was performed using SAS version 9.4 . The study subjects were categorized according to age <65 vs. ≥65 and years of education (<12 years vs. ≥12 years). Categorical variables were expressed as frequency and percent. We used the Chi-square and Fisher’s exact tests to assess differences in categorical variables. Scores of NTB were expressed as the median and interquartile range (25th and 75th percentile). The Mann–Whitney U test was used to compare the distribution by age group, gender, and ethnicity. Multiple linear regression analyses were performed to determine the association of age as a continuous variable, gender, ethnicity, and years of education with the neuropsychological test scores. Scores with a skewed distribution  were log-transformed. A two-sided p = 0.289) and education (p = 0.216). However, ethnicity (p = 0.016) differed significantly between age groups (The mean age was 64.7 years (SD = 4.6). The overall and age-group-specific characteristics of the participants are presented in e groups .p = 0.098). In almost all tests, the younger age group (those aged < 65) had significantly better scores than the older age group (those aged ≥ 65) (p = 0.181). Russians and other Europeans had significantly better scores in almost all tests than Kazakhs and Central Asians. Exceptions included CERAD delayed recall (p = 0.728) (ed ≥ 65) . Excepti= 0.728) . In most= 0.728) .Most of the currently used neuropsychological tests were developed and validated in developed countries . EvidencConsistent with the sizeable neuropsychological literature on aging, performance on most NTB tests was negatively associated with age and positively associated with education . Gender n = 276) due to the COVID-19 pandemic, although we intended to recruit 400 participants. Finally, the number of male participants was much smaller than that of females. Thus, the results in males must be interpreted cautiously. Future research will benefit from including individuals from diverse regions and backgrounds and a larger sample size with more balanced proportions of males and females.There are several limitations of this study. First, all the participants were recruited from one outpatient clinic. Thus, the generalizability was limited. Second, the total number of participants was relatively small (There are several strengths in this study. First, we used the NTB widely used in the US, which was translated and validated in Russian . Second,This study in Kazakhstan demonstrated the feasibility of administering the NTB widely used in neuropsychological research in the US and reported preliminary local normative neuropsychological measures and their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan.


This study aims to evaluate the effectiveness of the trial of national multicentric school-based health lifestyles intervention toward childhood obesity on the KBP at individual, family and schools' levels.The national trial was a multi-centered, cluster-controlled trial, which was conducted in seven provinces from September 2013 to February 2014, aiming at preventing childhood overweight and obesity. Integrated intervention strategies focused on changing specific practice related to energy intake and expenditure, such as decreasing the consumption of sweetened fizzy drinks, increasing the consumption of vegetables, ensuring proper protein intake, reducing sedentary practice including screen time, and maintaining at least 1 h of moderate to vigorous physical activity. A total of 27,477 children and adolescents in the control group and 30,997 in the intervention group were recruited with a mean follow-up period of 6.7 months. The binomial response mixed-effects model was used for assessing the effects of the national school-based health lifestyles intervention on obesity-related KBP at students individual, parents' and schools' levels.P < 0.05). In terms of obesity-related belief, individuals in the intervention group was more motivated than the control group, participants in the intervention group had higher correctness of 71.18, 52.94, and 56.60% than the control group of 68.61, 49.86, and 54.43%, (P < 0.05). In addition, healthier habits of eating breakfast and drinking milk every day were observed in the intervention group. For the beliefs toward obesity, parents of the intervention group had higher correctness than the control group. At the same time except for the fruit consumption, other obesity-related practice in the intervention group were healthier than the control group (P < 0.05). Except for some beliefs and practice, the intervention effect at the parent level was not significant in other aspects.Children and adolescents in the intervention group mastered better obesity-related knowledge, and they had higher correct response rates to all questions about obesity-related knowledge compared to the control group (The obesity-related knowledge and beliefs of children and adolescents got improved significantly. However, the effects on the knowledge, beliefs and certain practices of their parents and school administrators failed to reach significance. Obesity of children and adolescents was widely perceived as one of the most important public health challenges now . It was Previous multiple obesity interventions programs for children and adolescents had little or no obvious effect. Most of the studies were from Europe and the United States, and only a small amount were from low–and middle-income countries . Based oThe basic assumptions of the knowledge, belief and practice (KBP) health education model were that people's beliefs about whether or not they were susceptible to disease, and their perceptions of the benefits of trying to avoid it, influenced their readiness to act . The KBPWe used The Health Lifestyles Intervention in Chinese Children and Adolescents (HLI-CCA), which was a multi-centered, cluster-controlled, school-based intervention with family and school participation aiming to prevent overweight and obesity in children and adolescents. It included elements of education around nutrition and physical activity as well as modifications to school environments and engagement of families . For thiThis national trial with a multi-centered, cluster-controlled trial design took place in seven provinces (centers) including Hunan, Ningxia, Tianjin, Chongqing, Liaoning, Shanghai, and Guangdong from September 2013 to February 2014. The full trial protocol has been published previously in detail . A multiBased on the trial protocol, a planned sample size of 7,000 had a 90% ability to detect a 10% difference in the obesity intervention group with a 5% statistical significance (two-sided) . A samplThe HLI-CCA aimed to deliver a general healthy lifestyle message encouraging a healthy energy balance. The intervention consisted of four components: (a) Create supportive school and family environment, (b) Health lifestyles education and related compulsory physical activities, (c) Instruct and promote school physical education, d) Self-monitor obesity related behaviors. In schools assigned to the intervention, the HLI-CCA was delivered to children and adolescents with integrated intervention strategies focused on changing specific practice related to energy intake and expenditure. We used the “52110” method to manage children's daily behavior. ‘5', indicated the daily intake of fruits and vegetables should reach the size of 5 adults' fists. ‘2', suggested refers to watching TV or playing video games for <2 h. ‘1', indicated do more than 1 h of moderate or high-intensity physical activity every day. ‘1', meant another 1 is to eat no more than 1 serving of meat per day. The amount of 1 serving here is equivalent to the size and thickness of an adult's palm (excluding fingers), about 80–110 grams. 0, 0 indicated avoiding sugar-sweetened beverages. We carried out health education for students in the form of health education lectures and theme class meetings, including weekly health education lectures 30 min/week) and two theme class meetings (2 times 60 min). Reducing sedentary practice including screen time, physical exercise time  reached 1 h/day, and the intensity of physical exercise was above medium. Integrating the above intervention elements, the comprehensive intervention strategy of the HLI-CCA includes the following three parts during the whole intervention period , concret min/weekWe targeted the school and family environments through a few strategies for creating a supportive environment of both physical activity and healthier dietary habits. Elements included the provision were published elsewhere , 30. In Information on students' basic characteristics , knowledge and belief, feeding practice, physical activity, etc., was obtained through student and parental questionnaires, and information on obesity-related management of school was also collected through school questionnaires. Both parental and children's questionnaires of children grade 1–3 were reported by parents. We found in the pre-experiment that parents were very aware of their children's behaviors and were able to respond correctly to their children's behaviors. Meanwhile, the questionnaire was filled out according to the children's answers. Therefore, the influence of parents filling in the questionnaire was largely reduced. Children above the fourth grade would fill in children's questionnaire by themselves instructed by the class teacher. The physical examination was carried out according to the operational specifications of the “2010 China Student Physical Fitness and Health Survey Report” . InformaThe type of obesity was determined in combination with the national health industry standard. In accordance with the guideline of screening for overweight and obesity among school-age children and adolescents (WS/T586-2018) , those wInformation of obesity-related KBP was collected using standardized self-administrated questionnaire. The obesity-related knowledge and practice collection of students' questionnaires and the parental questionnaire were the same. Obesity-related knowledge included four questions on dietary habits and physical activities. The responses of all items were: “true,” “false,” or “don't know.” The answers of obesity-related beliefs questions were: “yes,” “no.” Obesity-related practice included 4 questions on dietary lifestyles. As previously published , 36, theFor parental questionnaire, there were four questions on obesity-related beliefs, all of which were answered: “yes,” “no.” In terms of school's questionnaire, there were one questions on knowledge related to obesity with the answers: “true,” “false” or “don't know” and one question on belief related to obesity with the answers: “yes,” “no.” In addition, two practice of schools related to obesity were asked, regarding arranging sports activities in the afternoon and not providing SSBs in the school canteen, with the responses: “yes” and “no.” Arranging sports activities was defined as: schools should provide necessity exercise facilities and ensure at least 1-h exercise time every school day.P-values.Description of baseline information was expressed as mean ± SD for continuous variables and number (%) for categorical variables. Mixed-effects regression model analysis was used to evaluate the impact of the intervention on the categorical variables, and was applied to calculate the odds ratio (OR) and 95% confidence interval (95% CI) after adjusting for age, sex, province, and urban/rural area, with values >1 indicating an increase in the effective effect of the variable following the intervention and values <1 indicating a decrease in the effective effect, with significant A stratified analysis based on baseline urban and rural areas was used to explore which causes were sensitive to the intervention. Considering the age composition of our primary and secondary school levels, in our study, the subgroup analysis method was adopted, and grouping analysis was conducted according to three age groups, 6–10, 11–14, and 15–18 years old, to determine the effective or sensitive subgroups of the intervention.P < 0.05 was considered statistically significant.All analyses were performed with SPSS 25.0  and Stata version14.0. A two-sided P < 0.05). Lower levels of height, weight, BMI, hip circumference, and waist circumference were observed for control groups, compared with the intervention group (P < 0.05). According to the Chinese standard, IOTF standard and WHO standard, the prevalence of overweight/obesity was 23.2/24.0%, 20.0/20.6% and 24.4/25.5% for the intervention and control groups, respectively.Baseline information was presented in P < 0.05). Concerning obesity-related beliefs, participants in the intervention group had higher correctness of 71.18, 52.94, and 56.60% than the control group of 68.61, 49.86, and 54.43%, respectively, with all P levels <0.05. In terms of feeding practice, the practice of having breakfast  and drinking milk every day  improved, with differences being statistically significant (P < 0.001). Children and adolescents in the rural intervention group improved obesity-related knowledge and feeding practice. It was worth noting that in the intervention group, girls were better than boys in terms of obesity-related beliefs. However, 6–10 years children and adolescents, and single-children had better knowledge about obesity, but in practice children and adolescents aged 11–15 and non-only-child children did better As shown in There was no significant difference between the intervention and control groups in terms of knowledge about the obesity toward children among parents , 5.P < 0.05). There was no difference in most practice items between these two groups. However, regarding some items , the intervention group had a higher correct responses rates than the control group (P < 0.05)  . It was  < 0.05) .We found that the intervention effect on obesity-related beliefs was more pronounced for mothers working in administrator, clerk, and professional occupations . At the P < 0.001). In contrast, the practice of not providing SSBs in the school canteen did not get satisfactory improvement after intervention in the intervention group, but was still better than the control group (P < 0.001). But we also found that the practice of not providing SSBs in school cafeterias in the 6–10-year-old age group did not improve after the intervention, but the intervention had a certain effect in the 11–14 and 12–18-year-old age groups (P < 0.001)  . It was < 0.001) –10.Stratified analyses were conducted also using mixed-effects regression model.The results of hierarchical analysis were similar to the main results and did not change essentially when the study sample was divided according to urban or rural areas, different ages and sociodemographic variables –15.To our knowledge, this was the first and the largest school-based, family-involved, comprehensive intervention trial assessing the obesity-centered intervention effectiveness toward Chinese children and adolescents on KBP at individual, parents and schools' levels. We found that the significant improvements in children and adolescents' knowledge and beliefs about obesity were observed after the mean 6-month comprehensive obesity intervention trial, but obesity-related practice were not obvious. However, the effects were not significant enough for their parents and schools' administrators knowledge, beliefs and certain. It was reasonable that practice could not change significantly over a short time, and a longer length of time to observe and more intensive interventions was required , 40.This study highlighted the importance of guiding the construction of multiple environments for childhood obesity intervention and to break the obesity susceptibility environment in the real world. In this study, the significant improvements in children and adolescents' knowledge and beliefs about obesity indicated that this kind of school-based comprehensive obesity intervention was rather effective to a certain extent, but a longer time should be considered to continuously improve the physical health. The intervention study on childhood obesity in 24 schools from three different geographical regions in China showed that the intervention improved obesity-related knowledge , was conChildren and adolescents' poor dietary practice, including skipping breakfast, low consumption of fruits and vegetables, unhealthy snacking practice and decreased activity times, might affect their nutritional status and contribute to overweight and obesity , 48, lowPrevious studies reported a statistically significant decrease in the daily consumption of carbonated drinks in the intervention group compared to control group , 52. HowBecause parents were of major importance regarding their children's nutrition and outdoor activities, parents should be actively involved in school-based obesity prevention efforts. A study showed that parental beliefs toward childhood obesity were the most important determinant of childhood obesity , 53. NotIn addition to family interventions, the school environment was considered as an important intervention site for obesity prevention. In this study, the intervention had little impact on the knowledge and beliefs of the schools' administrators, but there was a significant improvement of school's practice or measures, such as arranging sports activities in the afternoon and sugar-sweetened beverages were not available in the school canteen. The combination of academic stress and competition between schools might have led to the results. A study involving 141 high school students aged 14 to 18 from Holon showed that school education about food and nutrition only amounted to 28.3% of the total . TherefoThe strengths of this study were as follows. Firstly, we obtained data based on the national representative sample from seven provinces in China, and we focused on 6–18-year-old children and adolescents. Secondly, data were obtained on knowledge beliefs and practice among student, family, and school dimensions, allowing for a multifaceted analysis of the program's impact on childhood overweight and obesity. Besides, we included data from multiple districts and schools and conduct regular follow-up studies, allowing us to see the effects of the program over 6 months. In conclusion, this study considered the effects of childhood obesity interventions on individual, family and school environment. Some limitations should also be paid attention. Firstly, a questionnaire-based study cannot fundamentally explain the underlying reasons for the results. Secondly, the questionnaire survey could result in a possible trend of respondents toward compliance, which could favor positive outcomes to some extent. Thirdly, the lifestyle data was derived completed from a questionnaire, the dietary data recall of 7 days might not represent long-term dietary behaviors. The long-term dietary behavior might have other results to our current 7-day dietary data. Therefore, in future studies, the use of food tracking, such as photo tracking, could be used to accurately assess the frequency and intake of fruits and other dietary intakes of individuals. Fourthly, the content of knowledge, belief, and practice at the individual, family, and school levels were not comprehensive, and the information was limited, which cannot effectively and comprehensively reflect the real situation of students. We did not taken into account other possible correlated factors of obesity intervention, such as exposure to social media, social comparison, and psychological factors . Our resIn summary, this multi-center, school-based, 6-month obesity intervention with family and school participation in China significantly improved the obesity-related knowledge and beliefs among children and adolescents aged 6–18 years, but their lifestyle practice did not get satisfactory improvements, which could be an important reason for the limited effect of many international child obesity intervention projects. Besides, limited improvement in knowledge, beliefs, and certain practice were also observed among parents and schools. Further obesity related interventions with longer duration and more intensive interventions should be implemented to verify the conclusion. At the same time, the role of parents and schools' administrators in obesity intervention should still be strengthened to protect children and adolescents from being overweight or obesity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Peking University (IRB0000105213034). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.XW and JL performed the data analysis. XW, JL, DG, QM, YL, TM, MC, and LC interpreted, wrote, and finalized the manuscript. YZ, YD, JY, YS, and JM participate in the reviewing and revising the manuscript. All authors contributed in conceiving, design of this study, read, and approved the final manuscript.This study was granted by the Research Special Fund for Public Welfare Industry of Health (201202010) and the National Natural Science Foundation of China (81673192) awarded to JM. Capital's Funds for Health Improvement and Research (2022-1G-4251 to YS), the Natural Science Foundation of Beijing (Grant No. 7222247 to YS).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The aim of this study was to evaluate the influence of early exposure to agricultural pesticides and their relationship with autism spectrum disorder.This systematic review was registered at PROSPERO as CRD42020204842. The subject was systematically analyzed on PubMed, Scopus, and Web of Science databases until April 2021. Only studies with humans with early exposure to agricultural pesticides and diagnosis of autism were included. Exclusion criteria were studies on pesticides for domestic or veterinary use and late exposure. There were no language and time restriction. The quality analysis of the studies used the Newcastle-Ottawa Scale.Six case-control studies were included; three of them measured the route of exposure by maternal biomarkers and the others by the residence address. The studies had scores between moderate and high in the quality assessment tool. It was found high rates of association between early exposure to agricultural pesticides and autism and detection limit above the quantification for a sample of polychlorinated biphenyls, hexachlorobenzene, and dichlorodiphenyldichloroethylene.There is evidence concerning the exposure to agricultural pesticides in early life and the development of the autism spectrum disorder; however, more studies are required to better understand their possible association. The diagnostic system that is most commonly used is the Diagnostic and Statistical Manual of Mental Disorders — 5th edition (DMS-5), published in 2013 by the American Psychiatric Association e o International Classification of Disease — 11th edition (ICD-11), published in 2019 by the World Health Organization (WHO).The autism spectrum disorder (ASD) is a neurobehavioral condition with a complex neurological development defined by prejudiced interaction and social communication, restricted and repetitive patterns of behavior, interests, or activities. such as low birth weight, preterm birth, advanced age of the parents, gestational diabetes, prior fetal loss, hypertension, proteinuria, pre-eclampsia and maternal edema, multiple births, the Apgar score of <5 min, maternal obesity and family history of mental and neurological disorders, such as more than one child with autism.Its etiology is not well understood; however, studies suggest that a wide exposure or multiple exposures to a broad class of conditions can compromise the perinatal and neonatal, In contrast to the genetic factors that are irreversible, the environmental factors are modifiable. Studies show the increase of the association of early exposure to the environmental toxins with the occurrence of autism, such as air pollution in general and that caused by vehiclesand pesticides.Environmental factors have been identified as risk factors for neurodevelopment disorders, including ASD. although, depending on their class, specific substances can impact negatively on human health acutely or chronically.The pesticides are used to control retention of agricultural plagues,This systematic review aimed to comprehend the influence of premature exposure, from the preconception period until the child's first year of life, especially to agricultural pesticides and their possible relation with ASD. The protocol was registered at the international prospective register of systematic reviews (PROSPERO) database under the registration number CRD42020204842.The systematic review protocol was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) protocol.“Is there an association between premature exposure to agricultural pesticides and the diagnosis of autism spectrum disorder (ASD)?” was the research question of this systematic review, with the following PICOST: Children of both sexes; Premature exposure to agricultural pesticides; Non-exposure to agricultural pesticides; Diagnosis of Autistic Spectrum Disorder; Case-control or cohort studies; At least one measurement.To identify potentially relevant studies to the present review, a systematic literature search of databases  was conducted in July 2020, using MeSH terms and free terms, resulting in the following search: (“autistic disorder” OR “autism spectrum disorder” OR “Asperger syndrome” OR autism OR autistic OR ASD) AND pesticides. All terms were searched in title, abstract, and keyword. No restrictions were applied regarding language or publication date.Our research included only articles dealing with humans, and the inclusion criteria were as follows: (a) case-control or cohort studies; (b) early exposure to agricultural pesticides; (c) diagnosis of ASD; (d) information on correct exposure by at least one biological relative or maternal biomarkers; (e) published articles complete and with results. The exclusion criteria were as follows: (a) pesticides for domestic or veterinary use; (b) late exposure; (c) use of a risk screening tool or autistic traits; (d) knowledge of high risk for ASD development or non-typical development; (e) presence of concomitant intervention; (f) other neurological disorders; (g) animal model; and (h) meta-analyses, editorials, and narrative reviews.The articles were screened in two phases. First, duplicates and triplicates articles were removed. In the first phase, two reviewers (A.B and C.C) independently analyzed titles and abstracts in the electronic database and selected articles to identify potentially eligible articles. In the second phase, three reviewers  independently analyzed and performed the full reading of the articles selected in the first phase, excluding all the articles that did not meet the eligibility criteria. The bibliographic reference of the analyzed articles was also used as a search. At all stages, a third reviewer (I.M) was consulted in the case of any concerns or disagreements among the other investigators, thus resolving all disputes by consensus.Data extraction was completed independently by four authors in a Microsoft Excel spreadsheet, pre-tested, and developed specifically for this systematic review. The data from the articles were extracted: a) Author, year, and country; b) Study population; c) Measurement of exposure and outcome; and d) Results. Disagreements were resolved by consensus in a team meeting. The extraction was done in a table format, allowing comparisons between studies. The higher the score, the greater the methodological quality of the study. The tool was applied by two evaluators independently. Disagreements were subsequently discussed with a third reviewer and assessed until a consensus was reached by all the evaluators.The Newcastle-Ottawa Scale (NOS) Quality Assessment Form for case-control studies was used for assessing the risk of bias. NOS was used because it is a qualitative assessment tool for non-randomized studies that allows assessment in three spheres, namely, the group's selection , the comparability of the group's (one item), and the verification of exposure or outcome of interest (three items). In each item, it is possible to score either a single star or not, but only with comparison, it is possible to score up to two. The maximum score for each study is 9 stars. A flowchart detailing the process of identification, screening, eligibility, and the inclusion of studies is presented in A total of 436 potentially relevant studies were identified from the results of the electronic searches  and another three additional studies were identified from the references of analyzed articles in this systematic review. After removing duplicates and triplicates, 281 records remained for sorting the title and abstract. Of these, 49 complete studies were read in their entirety. After excluding 43 articles that did not meet the inclusion criteria, 6 studies were included. and Finland, were selected. Only two of the included articles were derived from cohort studies, but the methodology used was case and control. The sample of the six studies totalized 46,926 individuals: 2,994 cases and 43,932 controls. The sample size ranged from 75 to 545 children with ASD. The way to assess exposure included assessment by maternal biomarkers and analysis by home address. The main characteristics of the studies included in this systematic review are described in Six case-control studies, with data from California PCB congener: PCB 29, PCB 74, PCB 99, PCB 118, 138, 153, and 156, PCB 158, PCB 170 and 180, PCB 183 and PCB 187, PCB 194, PCB 196/203 and PCB 199, DDT, dichlorodiphenyldichloroethylene (DDE), trans-nonachlor, hexachlorobenzene (HCB), and 2,2’4,4’-tetrabromodiphenyl ether (BDE)-47.The pesticides analyzed by maternal biomarkers were as follows: total polychlorinated biphenyls (PCBs); organophosphates (OPs), bifentrin and trifluralin, carbamates, pyrethroids, Glyphosate, chlorpyrifos (CPF), diazinon, acephate, malathion, permethrin, bifenthrin, methyl bromide, imidacloprid, avermectin, and myclobutanil.Regarding the assessment by place of residence, the following pesticides were found: organochlorines, and was recently replicated in the systematic review by Moura et al. These studies considered the score 0–3 stars as low methodological quality, 4–6 stars as moderate quality, and 7–9 stars as high quality. According to this classification, the studies included in this systematic review obtained moderate and high scores, as shown in The classification score was used according to the meta-analysis by Hu et al. the non-explanation of the selection of control cases derived from the cohort, as well as the lack of similar assessment of individuals were included in the control group.NOS-identified selection bias in the case definition found on previous records from other care services, without reassessment of ASD diagnostic tests, Lyall et al., and Von Ehrenstein et al. included matching factors that were considered extremely important by the authors of this systematic review. The others made less specific adjustments, such as socio-demographic indices, ethnicity, and education.The adjustments made by Cheslack-Postava et al., that was considered a form of self-report. In this same sphere of evaluation, a lack of information on sampling losses was detected.In measuring exposure, three of the articles verified exposure by housing registrationThe results of this systematic review show high rates of association between early exposure to agricultural pesticides and autism, and samples of PCBs, HCB, and DDE had detection limit above the quantification being assessed for maternal biomarkers or home address. demonstrated that the quantity of organochlorines for the cases of ASD was found to be OR=6.1. When comparing the fourth quartile versus no exposure, the risk factor for autism had association with OPs (p=0.042), organochlorines (p=0.025), trifluralin (p=0.046), and bifenthrin (p=0.048) during pregnancy. During the embryogenesis of the central nervous system (CNS) (days 7–49), the results for organochlorines were reduced with an increase in the distance of 250–1,000m  from home to the application of the pesticides.The study by Roberts et al. in which he further suggested the increase in anencephaly associated with organophosphorus pesticides and spina bifida with amides, benzimidazoles, and methyl carbamates. Exposed mothers with combinations of two or more pesticides may be at increased risk of having a baby affected by NTDs.Environmental exposure to certain categories of agricultural pesticides can increase the risk of neural tube defects (NTDs), with effect estimates of less than 1,000m for residential proximity, as demonstrated in the study by Rull et al., reinforces the hypothesis that agricultural pesticides act negatively on neural and behavioral development in children, when exposed during intrauterine or in the first year of life, as the exposure to OP is associated with neurodevelopment in children. Of the 27 articles analyzed, 26 associated negative effects of pesticides on neurobehavioral development.Corroborating the findings, the systematic review by Muñoz-Quezada et al. evaluated the application of agricultural pesticides and OPs, which were the most commonly applied pesticides close to home during pregnancy, which had been identified in the following order: CPF (20.7%), acephate (15.4%), and diazinon (14.5%). The second class of pesticide most commonly applied was pyrethroids, which had been identified in the following proportion: esfenvalerate (24%), lamdacyalothrin (17.3%), permethrin (16.5%), cypermethrin (12.8%), and tau-fluvalinate (10.5%). Of the carbamates, approximately 80% were methomyl or carbaryl, and of the organochlorines, 60% of all applications were dienochlor. With these findings, it was found that the proximity of OPs, at some point during pregnancy, was associated with an increased risk of 60% for ASD, greater for exposures in the third trimester (OR=2.0), and application of CPF in the second trimester (OR=3.3). Children of mothers who live close to pyrethroid insecticide application shortly before conception or during the third trimester had a higher risk of ASD and developmental delay (DD), with ORs ranging from 1.7 to 2.3. The risk of DD increased in the vicinity of carbamate pesticide applications, but no specific vulnerable period was identified. Among those exposed, only one-third were exposed to a single compound over the course of the pregnancy.The study by Shelton et al. CPFs were likely to cause clinically significant tremor in all four dichotomous measures of tremor in boys when analyzed using the chi-square test .According to the study by Rauh et al. where prenatal exposure, mainly by female children, to OP insecticides was more sensitive to negative effects on motor function.In addition to neurodevelopmental problems, CPFs were associated with decreased motor function at 9 months of age, as demonstrated by Silver et al., and major oxidative stress processes.In animals models, De Felice et al. observed that strains of mice with idiopathic autism with prenatal exposure to CPF insecticide indicate significantly delayed motor maturation, the persistence of immature patterns such as pivoting at the expense of coordinated locomotion and a tendency toward enhanced ultrasound vocalization, found that rats’ CPF exposure reflects in behavior and in some possible neuroanatomical differences, especially in those that are highly relevant in neurodevelopmental disorders, including autism spectrum disorder. The effects that were observed in both sexes at multiple time points and that did not inhibit acetylcholinesterase activity in the brain or blood suggest that current regulations regarding safe levels of CPF need to be reconsidered.Berg et al. noted the risk of developing ASD associated with prenatal exposure to glyphosate (OR=1.16), CPF (OR=1.13), diazinon (OR=1.11), malathion (OR=1.11), avermectin (OR=1.12), and permethrin (OR=1.10). In addition, the risk of developing ASD with comorbid intellectual disability (ID) was associated with prenatal exposure to glyphosate (OR=1.33), CPF (OR=1.27), diazinon (OR=1.41), permethrin (OR=1.46), methyl bromide (OR=1.33), and myclobutanil (OR=1.32). In case of exposure in the first year of life, the chance of developing ASD with IDs increased by up to 50% for some pesticide substances, such as glyphosate and diazinon.Von Ehrenstein et al. detected ASD-like behavioral abnormalities in rat pups after maternal exposure to high levels of glyphosate and abnormal composition of the intestinal microbiota and short-chain fatty acids.Pu et al. in his meta-analysis, did not verify the relationship between glyphosate and ASD, but reported evidence from studies on humans, animals, and mechanics of a convincing link between exposure to glyphosate-based herbicides (GBHs) and increased meta-relative risk (meta-RR) of non-Hodgkin lymphoma (NHL) increased by 41% .Zhang et al., observed that in all the participants’ prenatal serum samples, POPs, except for DDE and HCB, were present at levels above the detection limit. Total PCBs at or above the 90th percentile were associated with an OR=1.91 for autism, suggesting that qualitatively higher levels of total PCBs may be associated with ASD risk.As the main results, the study by Cheslack-Postava et al. Most studies reported inverse associations with neurodevelopmental outcomes, which is caused due to exposure not only in the perinatal period but also in adolescence.The effects of PCBs on the results of neurodevelopment are consistent across different studies, as evidenced by the systematic review conducted by Berghuis and Roze. from 12 articles analyzed, 8 of them found associations of developmental PCB exposure with deficits in at least one measure of cognition. It is stated that PCBs modulate the signaling pathways involved not only in the main symptoms of ASD but also in its associated comorbidities. However, it is important to note that not all PCB congeners act in the same way in the development of toxicity, as there is a difference between them and their metabolites.According to the systematic review by Panesar et al. assessed whether prenatal exposure to PCBs and organochlorine pesticides (OCPs) was associated with the development of ASD and ID without autism in the offspring. As a result, in the ASD group, the levels of PCBs and trans-nanochlorines were higher than in the CG (control group). In addition, higher blood levels of PCBs 138/158, 153, 170, and 180 (AOR>1.5) have been associated with the development of ASD.The work conducted by Lyall and collaborators persistent organic pollutants (POPs) are also associated with attention-deficit hyperactivity disorder (ADHD) form. The study realized by Rosenquist et al. investigated the association between prenatal and childhood exposures to PCB-153 and p,p’-DDE and behavior in children aged between 5 and 9 years. A high OR score was observed for hyperactivity, with results for prenatal (OR=1.24) and postnatal (OR=1.08) PCB-153 and for prenatal (OR=1.43) and postnatal (OR=1.27) p,p’-DDE. Therefore, early exposure to p,p’-DDE and PCB-153 was associated with a higher prevalence of abnormal hyperactivity scores in the study population.In addition to neurotoxic properties, concluded an evidence that maternal exposure to insecticides is associated with autism among children, as the chances of autism in the offspring increased significantly when maternal levels of p,p’-DDE were in the upper 75th percentile of the control distribution (OR=1.32). The association between maternal levels of DDE greater than the 75th percentile and the ASD chances was significant between male children (OR=1.35) and among cases of individuals with IDs (OR=2.21), but there was no association between the levels of total PCBs and maternal counterparts with ASD.The study conducted by Brown et al. in which prenatal DDE levels in female children were inversely associated with IQ (p=0.01) and processing speed at the age of 7 years .Evidence that DDE levels may be associated with the cognitive development of these children was found in the study by Gaspar et al., lack of estimated exposure to other potential sources, such as food, use of chemicals, smoking, and other environmental factors, as well as the non-pairing of specific factors in each study were mentioned as limiting factors. We also cited the possible errors in the pesticide application database, as well as the change of address without knowledge.The findings of this review are limited by the small number of articles included. Among the selected studies, in addition to the limited sample size,In addition to the limiting factors of the articles presented, the quality tool used in this systematic review, the Newcastle-Ottawa Scale, does not have a classification of the studies under evaluation, requiring standardization among researchers. In conclusion, the studies provided found high rates of association between early exposure to agricultural pesticides and autism, which are mainly related to organochlorines, OPs, carbamates, and pyrethroids. In addition to the observation that maternal biomarkers for p,p’-DDE were increased in cases of autism and autism with IDs, divergences were found in the case of PCBs. Sample of PCBs, HCB, and DDE had detection limit above the quantification. With this, we conclude that there are studies regarding the premature exposure to agricultural pesticides and the development of ASD. However, these results should be considered with caution, due to these methodological limitations and also lack of evaluation of related genetic and environmental factors. It is hoped that the results collected by this systematic review can contribute to the development of other studies, including genetic and environmental factors. Knowing its limitations, it is necessary to continue and improve future studies for a better understanding and correlation between pesticides and autism spectrum disorder.As stated, an urgent approach strategy is needed to reduce the use of pesticides and encourage the adoption of agroecological practices in order to ensure food and nutritional security population, as well as the reduction of risk to human and environmental health.


Polyhedrons, spheroids and bolas (PSBs) are present in lithic series from the Lower Palaeolithic onwards and are found in several regions of the world. Nevertheless, very little is known about them. We propose here to summarise, illustrate and discuss the current state of our knowledge about these artefacts. Based on the available data in the literature and on our observations of several collections, we set up a database comprising 169 Palaeolithic assemblages with PSBs. Thanks to the statistical analysis of these data, we aim to highlight potential relationships between PSB characteristics  and assemblage composition and context, according to regions and chrono-cultural attributions. We also aim to discuss the question of artefacts from possible independent local histories, especially in Northwest Europe, where these objects are scarce. Our study concludes that hard stones  available locally were generally selected to produce PSBs. Soft sedimentary rocks are suitable for their manufacture, and were selected too, whereas siliceous materials were left aside. We hypothesise that the scarcity of PSBs in Northwest Europe could result from a combination of cultural and environmental factors: it could be part of a regional tradition, influenced by the abundance of siliceous materials in the environment. In this region where the lithic production is widely made of flint, even though other materials were available, objects made from hard stones are scarce, resulting in a toolkit with only rare PSBs and cleavers. Was flint too brittle for the functions of PSBs? Raw materials of PSBs are often similar to those of heavy-duty tools in assemblages, which could provide other clues about their functions . It is possible that their raw materials partly conditioned their final shape. PSBs can comprise a wide variety of artefacts, that for some could have change of status , diffused, adapted but also reinvented over two million years. Palaeolithic polyhedrons, spheroids and bolas (PSBs) are enigmatic spherical stone objects as their functions and manufacture modes are still poorly known. They are present in archaeological assemblages from the Oldowan onwards, and are among the oldest manufactured stone items. The earliest occurrences were discovered in East and North Africa, dated at 2.0–1.9 Ma at Ewass Oldupa, Tanzania ). DifferRounded artefacts are well documented for more recent periods e.g., , 14, 15), 1514, 1This paper presents and analyses a large database of 169 Palaeolithic assemblages with PSBs from the Oldowan, Core-and-Flake-type industries (Mode 1-type), Acheulian, Middle Stone Age and Middle Palaeolithic sites, across Africa, Eurasia and the Levant. Thanks to the statistical study of these data, we aim to highlight potential relationships between the presence and quantities of PSBs in sites, the context and composition of assemblages and regional or chrono-cultural variabilities. This will contribute to the debate on the presence of ‘apparently identical objects’ in archaeological records distant in time and space, issued from independent local histories and made by different hominin species. Particularly, we aim to investigate the possible reason(s)  for their scarcity in Europe and in the later periods of the Palaeolithic. The results will also allow us to discuss potential selection of materials for the manufacture of these objects , which can give clues about their possible functions. Finally, in some cases, we hypothesise a relationship between the degree of roundedness of PSBs and their raw materials, and discuss the question of intentional cubical to rounded final morphologies.hâches celtiques by Boucher de Perthes ), Perthes  when he  Perthes  only con Perthes  describe Perthes  who distcasseurs d’os, presuming that they were used for bison and horse bone breakage to access marrow. In addition to these items, they also described approximately 15 limestone and quartz stones rounded by crushing. They called them bolas  and suggested that they were used to capture animals, in reference to South American ethnographic stone or metal balls attached to ropes, composed of one to three pieces. Bolas were used by Amerindians and gauchos from Argentina, Uruguay and south Brazil as projectiles mainly to capture animals, and were also functional for combat. This hypothesis of PSBs used as projectiles convinced several authors  provide objective data that could support the idea of some Palaeolithic PSBs (and manuports) being missiles ).bola). The aim of the process would be to purposefully obtain a spherical artefact according to reasoned organised final shaping, in order to use it for a predefined (unknown) function  = (H-k+1) / (n-k); where H is the value obtained in the Kruskall-Wallis test; n the total number of observations and k the number of groups. Interpretation of the eta-squared estimate: 0.01–0.06 , 0.06–0.14 (moderate effect), > = 0.14 (large effect). Effsize: Estimate of the effect size. Magnitude: Magnitude of effect size. Empty dark grey cell: No result because the p-value of the Kruskall-Wallis test was >0.05.Method calculation: The effect size for Kruskall-Wallis test is computed as the eta squared based on the H-statistic: eta(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S4 Table(PDF)Click here for additional data file.S5 Table(PDF)Click here for additional data file.S6 Table(PDF)Click here for additional data file.S1 Text(PDF)Click here for additional data file.S2 Text(PDF)Click here for additional data file.