Patients with rheumatoid arthritis (RA), who suffer from impaired physical function and fatigue, may have difficulties with grocery shopping and preparing meals. Also, to improve symptoms, patients often experiment with diets but seldom consult a dietitian. Although this could lead to a nutritiously deprived diet, an up-to-date, thorough description of the nutrient intake in Swedish patients with RA is absent. Here, we investigated the habitual dietary energy and nutrient intake in patients with RA living in southwestern Sweden.Three-day food records performed at two time points during the ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) trial, were used. The intake of energy and nutrients was analyzed using The Swedish Food Composition Database.A total of 62 participants  were included in the study, where 18 participants completed one 3-day food record and 44 participants completed two 3-day food records. Median (IQR) intake of total fat was above or in the upper range of recommendations , and males: 40.3  E%). Median (IQR) intake of saturated fatty acids exceeded recommendations , while median (IQR) carbohydrate and fiber intakes were below recommendations . The reported intake of other macronutrients was in line with recommendations. For several micronutrients, e.g., vitamin A and D, folate, and calcium, median intake was below recommended intake. Vitamin A intake was especially low and did not reach lower intake level (LI) for 14 and 17% of females and males, respectively. For females, about 10% did not reach LI for vitamin D, calcium, and riboflavin.We found that patients with RA residing in southwestern Sweden reported a high intake of saturated fatty acids and low intake of fiber and several micronutrients.https://clinicaltrials.gov/ct2/show/NCT02941055?term=NCT02941055&draw=2&rank=1], identifier [NCT02941055].[ Rheumatoid arthritis (RA) is an autoimmune, chronic disease affecting about 20 million people worldwide and more than 2.3 million in Western Europe . The disImpaired physical function, as well as fatigue and a negatively affected mental health, could affect grocery shopping, cooking, and appetite, and thus impact energy and nutrient intake. Several studies have reported energy and nutrient intake in patients with RA, but the results are somewhat disparate –24. SomeThere is a lack of up-to-date studies using a high-quality dietary assessment method, i.e., weighed food records, investigating and thoroughly describing nutritional intake in Swedish patients with RA. The ADIRA (Anti-inflammatory Diet in Rheumatoid Arthritis) trial was a randomized crossover trial primarily investigating the effect of a proposed anti-inflammatory diet on disease activity in patients with RA . Here, wIn this study, data from the ADIRA trial were used. Details on the study design are described elsewhere , 26. In Shortly after the screening visit, participants completed a 3-day food record. For participants later included in the ADIRA trial, this was scheduled to be done before starting the first diet period, and also at the end of the washout period. A dietitian carefully went through the procedure of performing a food record with each participant. Details on the instructions to the participants have been described previously . In brieAll food records were analyzed by the same dietitian using Dietist Net Pro version 18.12.16 (Kost och Näringsdata AB) and primarily The Swedish Food Composition Database 2017-12-15 . When ceIf the participant had only used household measuring spoons and cups, and the food database did not provide information about weight from these kinds of measures, the following alternatives, in this order, were used instead, namely, (1) the tables in the key to Portionsguide , (2) theWhen choosing which nutrients to include in this study, two requirements were observed, i.e., (1) a recommended intake (RI) for the nutrient in Sweden and (2) reliable data in The Swedish Food Composition Database 2017-12-15 , as wellgretinol+μgβ−carotene/12+othercarotenoids/24, 1 μg vitamin E = 1 μg α-tocopherol, and NE are the sum of niacin in the food and the niacin formed by the body from the conversion of the amino acid tryptophan (60 mg tryptophan = 1 NE) , kilocalories , g, mg, μg, and/or energy percent (E%). In addition, the fiber intake was also reported as g/MJ. Vitamins A and E and niacin intake were reported as retinol equivalents (RE), α-tocopherol equivalents (α-TE), and niacin equivalents (NE), respectively. In The Swedish Food Composition Database, RE are calculated as μ = 1 NE) . N-3 fatNordic nutrition recommendations 2012  were use2. Details on how DAS28  was calculated have been described previously (For body mass index (BMI) calculations, participants were weighed in light clothing and without shoes. Details on height measurement are described elsewhere . BMI waseviously . During eviously . In brieHistograms were used to explore the distribution of the variables. A few variables did not exhibit normal distribution; still, to allow for comparison with the nutrient intake in the Swedish population in general, values are presented both as mean ± standard deviation (SD) and median plus interquartile range (IQR). For categorical variables, number (%) is presented. As males and females tend to have different eating patterns , results are presented stratified by sex. The average daily nutrient intake based on each 3-day food record was calculated. For participants with two 3-day food records, the mean of the daily nutrient intake for those two records was used. When investigating how many of the participants reached RI, AR, and LI, the sex- and age-specific recommendations were used for each individual. The RI for folate is higher for females in reproductive age and both RI and AR for iron are lower for postmenopausal females. As median age for menopause in Swedish females is 52 years old , reproduThis study was conducted according to the Declaration of Helsinki and approved by the regional ethical review board in Gothenburg . Written and informed consent was provided by all participants.n = 12), started an ADIRA diet before initiating their first food and beverage registration (n = 2) or dropped out from the ADIRA trial before the second food record was collected after the ADIRA trial washout period (n = 4). The majority of the study participants were females (81%), had a university degree (53%), and did not use nicotine  MJ for females and 9.02  MJ for males . The medFor both males and females, median reported intake of several micronutrients was below RI, e.g., vitamins A and D, folate, calcium, and selenium . For vitLess than 75% of the study population reached AR for several micronutrients . VitaminIn this study, we found that many patients with RA residing in southwestern Sweden reported an inadequate intake of several nutrients. The majority of participants reported a high intake of total fat and almost all participants reported too high an intake of SFA. The intake of carbohydrates was generally low, and fiber intake was lower than recommended for most participants. For many participants, intake of several micronutrients reached neither RI nor AR. Reported intake was especially low for vitamin A, where about 15% of the participants did not even reach LI. For about 10% of the female study population, intake of vitamin D, riboflavin, and calcium were also below LI.This study is one of very few with the main aim to thoroughly investigate the energy and nutrient intake in Swedish patients with RA. Previous studies reporting nutrient intake in Swedish patients with RA have often focused on other outcomes but have explored dietary intake at baseline, and mainly energy and macronutrient intake –11. In oAs for micronutrient intake, we found that the reported intakes were especially low for vitamin A and, among the female population, also for vitamin D, thiamin, riboflavin, calcium, and potassium. These findings are comparable to those in previous Swedish studies, with some exceptions. Lourdudoss et al.  reportedStudies conducted outside of Sweden mostly display a different macronutrient distribution compared to our study, i.e., more carbohydrates –18 and lAlthough patients with RA reported a slightly higher fat intake and lower carbohydrate intake, the reported intake of energy and micronutrients in our study were similar to that of the general Swedish population, according to the national survey Riksmaten 2010-11 . FurtherIt is well-established that diet has an impact on health and the risk for developing diseases such as cardiovascular disease (CVD) and cancer. CVD is the leading cause of death in patients with RA and occurs more often in this patient group than in the general population . We receIn this study, we reported the percentage of the study population with a reported intake corresponding to the RI, AR, and LI. The RI is determined by taking into account practically all individuals in a population, including those who may have a higher requirement than most individuals . Althougper se) may have occurred (This study has some limitations we want to address. First, we gave participants thorough instructions on how to perform a food record and emphasized the weighing of food items. Nevertheless, this was not always possible for the participants and on such occasions, errors could possibly have occurred, e.g., incorrect portion size quantification by the participant or incorrect conversion to weight by the dietitian . Second,occurred , causingoccurred . Howeveroccurred . FurtherThere are also several strengths. First of all, we used the most precise method to assess nutrient intake, i.e., weighed food records . Second,Patients with RA are a nutritionally vulnerable group, and, in this study, we found that this patient group in southwestern Sweden reported a high intake of SFAs, and low intake of several micronutrients and fiber. Routinely offering a dietitian consultation at the time of diagnosis would likely improve nutritional intake for these patients and possibly lower the risk for comorbidities.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 the Regional Ethical Review Board in Gothenburg, Sweden. The patients/participants provided their written informed consent to participate in this study.AW, HL, LB, and IG designed the study. ATW, LB, HL, AW, and EH conducted the research. ATW analysed the data, wrote the manuscript, and had primary responsibility for the final content. All authors assisted in interpreting the data and have read and approved the final manuscript.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.


Pseudonitzschia, has aroused increasing attention. Aptamers, a new molecular recognition element, provide clarity in the monitoring of DA. In this study, aptamers of DA were successfully screened by Capture-SELEX. Through identification and truncation optimization, aptamer C1-d with a high affinity  and high specificity for DA was obtained. The binding mechanism between DA and the aptamer was explored by molecular docking and molecular dynamics (MD) simulation, revealing the critical sites for DA–aptamer interaction. Meanwhile, a BLI-based aptasensor was constructed by C1-d, which displayed a linear range from 0.625 to 10 μM and a LOD of 13.7 nM. This aptasensor exhibited high specificity, good precision and repeatability, and high recovery rates for real samples; the process of detection could be completed in 7 min. This study is the first to identify and investigate the binding mechanism of DA–aptamer interaction and constructed a BLI-based aptasensor for DA, which lays a theoretical foundation for the detection and prevention of DA.With the incidence of harmful algal blooms (HABs) increasing in recent years, the urgent demand for the detection of domoic acid (DA), an amnesic shellfish toxin mainly produced by red tide algae  In 1987, a serious food poisoning outbreak occurred in Canada. More than 100 residents contracted food poisoning through eating contaminated seafood. Victims showed gastrointestinal symptoms  and chronic nerve damage , and some cases even led to coma and death . Since t15H7NO6, molecular weight 311.33) is a kind of small-molecular excitatory proline derivative and potent neurotoxin, which is mainly produced by the Pseudonitzschia genus. After being ingested by aquatic organisms, DA is enriched through the food chain, thus threatening human health. Importantly, the heat stability of DA makes its toxicity difficult to overcome through ordinary cooking methods. In addition, there is no effective treatment for the poisoning induced by DA. Domoic acid contains three carboxyl groups and a secondary amino group, and its form in solution is easily affected by pH. There are eight isomers of DA (A–H). These isomers may be the reaction products of DA exposed to ultraviolet light, rather than the natural products of algae. The main contaminant of marine and aquatic organisms is DA, which is the most toxic of all these isomers  + 0.01530 (R2 = 0.9951) (2 = 0.9912)  B. Moreov 0.9912) C. After  0.9912) . The rep 0.9912) . There w 0.9912) D. Both tTo evaluate the practicality of aptasensors in real detection, seawater and shellfish samples spiked when different concentrations of DA were prepared. As shown in The HPLC methods for DA detection have some limitations, including complicated and time-consuming operation, extensive use of chemical reagents, and difficulty in the simultaneous detection of multiple samples. ELISA assays sometimes cannot avoid cross-reaction. Additionally, the preparation of DA immune antigen is difficult and costly. CE requires cleanup steps to achieve reliable results and highly trained experimental skills. In addition to the above traditional DA detection methods, a few biosensors of DA have also been reported. An immuno-based screening method was developed to detect DA in extracts of shellfish species using a surface plasmon resonance-based optical biosensor. Its detection limits are in the μg/g range and performed most accurately at the European Union’s official action limit for DA of 20 μg/g . StevensAlthough the LOD (1.066 ng/mL) of this aptasensor in seawater sample detection is higher than some detection methods , the LODKD value of 109 nM was finally obtained. Additionally, it showed high affinity and high specificity for DA, as identified by the BLI assay. The binding mechanism of DA to the aptamer and their key sites of interaction were predicted by molecular docking and MD simulation, which further confirmed the high affinity and high specificity between C1-d and DA. Furthermore, we constructed a BLI-based aptasensor by C1-d, which has high specificity, good precision, good repeatability, and an acceptable recovery rate for DA detection. In brief, a rapid and sensitive BLI-based aptasensor was established in this work, which provides a new horizon for efficient monitoring of DA and lays a foundation for the application of aptasensors in the detection of marine biotoxins.In this research, DA aptamers were successfully selected by Capture-SELEX. Through truncation optimization, an aptamer named C1-d with a Domoic acid is widely distributed almost all over the world. It has become a serious threat to the marine environment and human health because of its high toxicity, fast-acting nature, and lack of a suitable antidote. Aptamers, as a new molecular recognition component, have great potential for the detection and prevention of marine biotoxins worldwide. They have the potential to establish rapid, specific, efficient, and sensitive detection technologies and to provide a clinical basis for the research of targeted drugs and the treatment of marine biological toxins. In future research, the aptamers used in this research will be attempted to be made into other types of kits and biosensors for DA detection. They are also expected to be used in the DA separation and enrichment reagents for eliminating disease-causing biohazards or efficiently adsorbing harmful pollutants in water.


There is an extensive library of language tests, each with excellent psychometric properties; however, many of the tests available take considerable administration time, possibly bearing psychological strain on patients. The Short and Tailored Evaluation of Language Ability (STELA) is a simplified, tablet-based language ability assessment system developed to address this issue, with a reduced number of items and automated testing process.The aim of this paper is to assess the administration time, internal consistency, and validity of the STELA.auditory comprehension and reading comprehension) and 3 expression modalities . Performance in each modality was scored as the correct answer rate (0-100), and overall performance expressed as the sum of modality scores (out of 500 points).The STELA consists of a tablet app, a microphone, and an input keypad for clinician’s use. The system is designed to assess language ability with 52 questions grouped into 2 comprehension modalities (P<.001). The STELA’s total score was strongly correlated with the WAB Aphasia Quotient , supporting the former’s concurrent validity concerning the WAB, which is a gold-standard aphasia assessment. Strong correlations were also observed at the subscale level; STELA auditory comprehension versus WAB auditory comprehension , STELA repetition versus WAB repetition , STELA naming and sentence formation versus WAB naming and word finding , and the sum of STELA reading comprehension or reading aloud versus WAB reading . Cronbach α obtained for each modality was .862 for auditory comprehension, .872 for reading comprehension, .902 for naming and sentence formation, .787 for repetition, and .892 for reading aloud. Global Cronbach α was .961. The average of the values of item-total correlation to each subscale was 0.61 (SD 0.17).The time taken to complete the STELA was significantly less than the time for the WAB (mean 16.2, SD 9.4 vs mean 149.3, SD 64.1 minutes; Our study confirmed significant time reduction in the assessment of language ability and provided evidence for good internal consistency and validity of the STELA tablet-based aphasia assessment system. While people who sustain brain injury from stroke or cranial trauma have higher survival rates today, remaining disabilities caused by brain damage significantly disturb patients’ daily living. Language ability is one of the important cognitive functions in executing social activities that can be impaired by brain injury. Even if individuals regain the physical ability to perform regular activities of daily living, the impairment in language function often makes it difficult for patients to fully reintegrate into their communities. Language function is fundamental to higher brain function, aiding in communication and underpinning logical thinking, social relationships, self-expression, and even dignity. Early detection and prompt and sufficient rehabilitative interventions specific to deficit severity may help such patients regain their independence and ensure reintegration into society. For this to occur, the timely and accurate assessment of language ability is crucial.Many standardized tests are widely used for evaluating language dysfunction, such as the Western Aphasia Battery (WAB) and Boston Diagnostic Aphasia Exam in clinical settings. However, these tests take considerable time to be administered. Lengthy assessments can pose difficulties for patients with stroke or cranial trauma with language impairments, who often have trouble with long-term concentration due to effects such as inattention and limited endurance ,2. LengtSeveral criteria must be met to evaluate language function in a short period of time and in a treatment-oriented manner. The test should be simplified for quicker completion. Conventional language function assessment tests consist of a significant number of questions. For example, the WAB consists of 225 items. Conversely, screening tests performed in shorter amounts of time have also been developed . They usAlthough these screening tools are useful for briefly checking deficits in language ability, they do not provide sufficient information for planning treatment; to apply test findings in therapy, “language” should be deconstructed and analyzed for its components. For example, aphasia is traditionally assessed across several modalities, such as auditory and reading comprehension, word and sentence production, and repetition. Clinicians construct rehabilitation plans for individual segments based on their understanding of patients’ performance in each segment . Thus, eThe Short and Tailored Evaluation of Language Ability (STELA) is a newly developed computer-based Japanese language ability assessment system for patients with aphasia, which is compact in number of tasks while having the capacity to assess language ability across multiple components. The purpose of this study was to evaluate the clinical feasibility of the STELA by investigating the time-reduction effect of the STELA compared to the WAB as the gold-standard paper-and-pencil test and its internal consistency and validity in assessing the language ability of patients with aphasia.This was a prospective methodological study with a repeated-measures design, in which the reliability and validity of the STELA were evaluated. The research was conducted in Fujita Health University Hospital and Nanakuri Memorial Hospital.This study complied with the principles of the Declaration of Helsinki and was approved by the Medical Ethics Committee of Fujita Health University. All the participants provided written informed consent prior to participation (HM20-060). For privacy protection, the data were deidentified in the analysis.Study participants included patients from the Fujita Health University Hospital’s Department of Rehabilitation and Nanakuri Memorial Hospital, who were diagnosed with impaired language functioning between July 1, 2020, and December 13, 2020. Participants were diagnosed with aphasia on the basis of the WAB results. Inclusion criteria included being 20 years or older, in healthy condition, and confirmed or suspected to have impaired language function when the informed consent was obtained. Patients were excluded if they had a severe cognitive disorder or disturbed consciousness that compromised their ability to follow the instructions during testing.Auditory comprehension and Reading comprehension) and 3 expression modalities . The test comprised 52 questions . Consisting of a tablet app, a microphone, and an input keypad (for clinician’s use), the system is designed to assess language ability in 2 comprehension modalities  score and modality  scores as well as WAB-AQ and the subscales of WAB were used for analysis. The time required from start to finish (completion time) for both scales was also measured.Total and group-wise comparisons of the completion time for all the tasks of the WAB and the STELA were conducted using the Wilcoxon signed rank test.The internal consistency and validity of the STELA were evaluated. The STELA’s internal consistency was evaluated for Cronbach α  of each The sample size estimated Cronbach α using the Bonett method , yieldinP=.003), while that of the WAB-AQ was distributed normally . Their primary diseases were cerebral infarction , cerebral hemorrhage , subarachnoid hemorrhage , brain tumor , and cerebral contusion . On average, the STELA was administered 91.5 (SD 128.3) days after the event and 4.5 (SD 3.4) days apart from the WAB. Patients’ global scores were the STELA total score=362.5  versus WAB-AQ=66.9 . The score of the STELA was not normally distributed : this tendency was significant in every WAB category of aphasia severity . The time taken to complete the STELA was significantly less than the time for WAB =189.0, Auditory comprehension=.862, Reading comprehension=.872, Naming and sentence formation=.902, Repetition=.787, and Reading aloud=.892. Global Cronbach α was calculated as .961. The average of the values of item-total correlation (Spearman rho) to each subscale was 0.61 (0.17). Total item correlations were 0.30 or more for all items and were significant for all but the following four items: 2 items from the word comprehension in Auditory comprehension, 1 item from the paragraph comprehension in Auditory comprehension, and 1 from the paragraph comprehension in Reading comprehension. For each item, Cronbach α was recomputed for each subscale without it—none of the resulting alpha-without-the-item values exceeded the original α by ≥.10.The results of the internal consistency evaluation are shown in P<.001; auditory comprehension , repetition , naming and sentence formation , and the sum of reading comprehension and reading aloud . Low variation in the response data may be responsible for these exceptions, as the first item of the word comprehension set is the easiest question within the modality, while the third item of the news text comprehension set is the hardest. Nevertheless, no alpha-without-the-item value in any modality (these items included) exceeded the corresponding Cronbach α with the item included by over .10, reflecting good homogeneity in each subscale’s item set.The STELA’s internal consistency was supported for all modalities and overall, by very high Cronbach α coefficients, measured at .96 for the whole scale and ranging from .79 to .90 for its subscales. Furthermore, all item-total correlations measured in each subscale were .30 or more, and statistically significant except three of them; significance level of correlations for the exceptions were marginal . Additionally, test-retest reliability was not investigated in this study, as our participants were primarily in the subacute phase after their cerebrovascular event, a period wherein aphasia symptoms can fluctuate significantly in a short period. To evaluate the STELA’s test-retest reliability, a study with a patient population in the chronic phase of illness should be further considered.In this study, clinical feasibility of the STELA tablet-based aphasia assessment system was investigated. The results showed the significantly shorter administration time of the STELA compared with that of the WAB as a gold-standard paper-and-pencil test, and the data also supported the internal consistency and the concurrent validity with WAB. These results support the potential usefulness of the STELA in daily rehabilitation practice.


Tuberculosis (TB) is a preventable and treatable disease but it is the leading cause of death among people living with HIV (PLHIV). In addition, the emergence of the HIV pandemic has also had a major impact on TB incidence rates. There are studies in spatial patterns of TB and HIV separately in Ethiopia; there is, however, no information on spatial patterns of TB-HIV coinfection in the country at the districts level at least using yearly data. This paper, therefore, aimed at determining the spatial clustering of TB-HIV coinfection prevalence rates in the country at the districts level on an annual basis over a four-year period, 2015–2018. Gi∗ local statistic, a chi-square test, and a modified t-test statistic for Spearman's correlation coefficient were used to evaluate the spatial clustering and spatial heterogeneity of TB among PLHIV and HIV among TB patients prevalence rates.  District-level aggregated data on the number of TB-HIV infections were obtained from the Ethiopian Federal Ministry of Health for 2015 to 2018. The univariate and bivariate global Moran's index, Getis-Ord I values range between 0.021 and 0.134 ; however, the prevalence of TB among PLHIV was significant only for 2015 and 2017 . Spearman's correlation also shows there was a strong positive association between the two prevalence rates over the study period. The local indicators of spatial analysis using the Getis–Ord statistic revealed that hot-spots for TB among PLHIV and HIV among TB patients have appeared in districts of various regions and the two city administrations in the country over the study period; however, the geographical distribution of hotspots varies over the study period. Similar trends were also observed for the cold-spots except for 2017 and 2018 where there were no cold-spots for TB among PLHIV.  The district-level prevalence rate of HIV among TB patients was positively and significantly spatially autocorrelated with global Moran's  The study presents detailed knowledge about the spatial clustering of TB-HIV coinfection in Ethiopia at the districts level, and the results could provide information for planning coordinated district-specific interventions to jointly control both diseases in Ethiopia. Tuberculosis (TB) and human immunodeficiency virus (HIV) are two of the most severe public health problems worldwide. Prior to the global coronavirus COVID-19) pandemic, TB was the single infectious disease that claimed more lives each year than HIV 9 pandemi. The twoTuberculosis is a preventable and treatable disease; however, it is the leading cause of death among people living with HIV (PLHIV) claiming millions of lives each year . The emeTB claimed the lives of 1.3 million individuals in 2017 and an extra 300,000 PLHIV died due to TB-related illness . In 2017In Ethiopia, an estimated 16,000 PLHIV contracted TB in 2016. During this year, a routine National Tuberculosis Program (NTP) report indicates that 8,625 (about 54%) have been receiving cotreatment. Narrowing this gap will be made possible by programmes for HIV and TB that are better at locating HIV and TB cases. According to studies conducted in Ethiopia, TB incidence is higher in areas with high HIV prevalence , 14. TheHowever, in Ethiopia, the distribution and prevalence of TB vary across regions and across districts within a region –16. FurtFew studies have reported the epidemiology of TB-HIV coinfection at the Hospital level , 24 in EIdentifying districts where the burden of TB-HIV coinfection is concentrated and its spatial distribution at the district level may help to identify populations at higher risk of coinfection. For effective surveillance programs and resource allocation , includiThe remainder of the paper is structured as follows. The data are first described. The statistical techniques employed in this investigation are then described in detail. The Results section contains the outcomes of using these techniques on the study's data. Finally, the Discussion and Conclusion sections, respectively, provide a discussion on the study's findings and limitations, as well as conclusions and suggestions for additional research.Ethiopia is located in the North Eastern part of Africa. It shares borders with Eritrea to the North, Sudan in the west, Djibouti in the Northeast, Somalia in the east and Southeast, and Kenya in the south. The area of the country is roughly 1,127,127 square kilometres. Before 2020, the Federal Democratic Republic of Ethiopia has divided administratively into nine regional states , Gambella, and Harari) and two city administrations (Addis Ababa and Dire Dawa). The map in The Ethiopian Federal Ministry of Health provided district-level aggregate data from 2015 to 2018 on the number of TB patients enrolled in the national TB program, the number of TB cases tested for HIV, the number of TB patients with HIV-positive test results, the number of HIV patients who were screened for TB during their visit, the number of HIV patients with active TB and geographic coordinates (shape-files) of the country. The Federal Ministry of Health receives quarterly reports of these illnesses from the district health office via the Health Management Information System (HMIS) , 27. In This study used spatial analysis to determine where HIV prevalence among TB patients clustered geographically. This was carried out by dividing the number of TB cases with HIV-positive test results in a district by the total number of TB cases who were tested for HIV in that same district to determine the prevalence. The ratio of the number of TB cases with HIV-positive test results to the total number of HIV patients in the same district enrolled in HIV care facilities who were screened for TB during their visit was used to compute the prevalence of TB among PLHIV . These aθi(hiv) and θi(tb) are the true but unknown prevalence of HIV among TB patients and TB among people living with HIV, respectively, in district i, i=1,…, n=804, in Ethiopia, there are 804 districts at the time of data collection. The null hypothesis need to be tested that all districts have the same level of prevalence, say, prevalence of HIV among TB patients, i.e., H0 : θ(hiv)1=…=θn(hiv) against an alternative hypothesis that there is at least one district with a different risk level, i.e., H1 : θk(hiv) ≠ θl(hiv) for some k ≠ l. This test can be performed using a chi-square test [Oi be the number of HIV cases among TB patients reported in district i and ni be the number of TB patients in the same district. The maximum likelihood estimate of θi(hiv) is given by Oi/ni. Then, the chi-square test statistic has the following form:Ei=ni × (∑Oi/∑Ei) is the expected number of HIV cases among TB patients in district i assuming that HIV cases among TB patients arise at random across the country so that any district's share of the total number of HIV cases observed is proportional to the size of its own population at risk, i.e., number of TB patients. This assumption implies a constant prevalence or risk across the country. The test statistic measures an overall deviation from the constant prevalence. If the observed numbers for some of the districts are much different from the expected, then the test statistic C would become large, suggesting a departure from the constant prevalence assumption, which implies the presence of spatial heterogeneity in the number of HIV among TB patients. To assess statistical significance, when the number of districts n is large, which is the case for this study, the test statistic C follows a χ2 distribution with n − 1 degrees of freedom under the null hypothesis of a constant prevalence across the country. Therefore, we reject the null hypothesis H0 if C > χn−12 or if p value is less than 5% significance level.Suppose are test . Let Oi t0 and hence the distribution of t0 under the null hypothesis H0 : ρ=0; for example, positive spatially autocorrelation increases the variance of t0 due to information loss wij=1wij=wji and wii=0, which implies no self-correlation of an element with itself, hence the resulting spatial proximity matrix is necessarily symmetric.Following this definition, since I becomes close to 0 when some pairs of neighbors have the same direction of deviation and others have deviations in the opposite direction  or for local Moran's om spdep  R packagtialPack  R packagThe School of Science Ethics Committee at the University of South Africa granted permission for the study (ERC Reference Number: 2021/CSET/SOS/045). In addition, the Ethiopian Ministry of Health Office gave its consent for the study's data to be used. Because we used aggregated district-level data in this investigation, informed consent from the study participants was not obtained.The total number of TB patients enrolled in the national TB program, the total number of TB cases tested for HIV, the total number of TB patients with HIV-positive test results, the total number of HIV patients who were screened for TB during their visit, and the total number of HIV patients with active TB in Ethiopia stratified by gender and year are presented in n=49,949) were male. Similarly, in 2016, 2017, and 2018, a higher proportion of TB cases enrolled to DOTS and who were tested for HIV were male, about 54.31% , 55.26% , and 55.32% , respectively. However, in the years 2015, 2016, 2017, and 2018, consistently higher proportions of patients enrolled in HIV care who were screened for TB were female 61.67% , 61.95% , 62.58% , and 62.91% , respectively  and 623,927 HIV patients who were screened for TB during their visit were enrolled in HIV care. These numbers in 2016 were 91,692 and 914,987, in 2017 were 93,317 and 1,041,330, and in 2018 they were 52,402 and 719,651. All these reported cases were considered in this study. Except for those districts where their TB or HIV data had not available, the data used to cover all regions, zones, and districts of Ethiopia. From a total number of 91,382 TB cases enrolled to DOTS and who were tested for HIV in Ethiopia in 2015, about 54.66% , and the prevalence of TB among HIV patients, denoted by TB(HIV), in Ethiopia by year in all regions and two city administrations for the study period are given in However, Figures In the case of TB among people living with HIV , the higp values that are very close to 0, suggesting strong evidence against the null hypothesis of a constant prevalence of HIV among TB patients and TB among people living with HIV across Ethiopia, which agrees with the findings in the previous section. However, this test does not account for spatial data features, such as spatial autocorrelation of HIV cases among TB patients and TB cases among people living with HIV, this is discussed in the following section.The chi-square tests on spatial heterogeneity in the number of HIV cases among TB patients had large test statistics of 9224.158, 8150.445, 7972.045, and 3964.088 for years 2015, 2016, 2017, and 2018, respectively. The same test for TB cases among people living with HIV had large test statistics of 67018.41, 30388.34, 22000.47, and 26112.08 for years 2015, 2016, 2017, and 2018, respectively. These large test statistics result in I statistics of both data, i.e., HIV cases among TB patients and TB cases among people living with HIV, and Clifford & Richardson [t-test for spatial association of the two data sets for the study period. The modified t-test incorporates the spatial arrangement of the districts using the coordinates of the centroids.chardson  modifiedI = 0.069  and 0.037  for the prevalence of TB among people living with HIV (PLHIV), respectively. Whereas for the HIV prevalence among TB patients Global Moran's I for 2015, 2016, 2017, and 2018 were 0.118, 0.134, 0.021, and 0.067, respectively, all with p value <0.001. The positive Global Moran's I values in I value for the prevalence of TB among PLHIV was a small negative number close to zero (−0.001) with associated p value of 0.93 > 0.05, suggesting neighboring districts inclined to have spatially dispersed prevalence in the opposite directions. However, the dispersion was statistically nonsignificant.The results in I is consistently positive across the years for the prevalence of HIV among TB patients, indicating that over the study period of 2015–2018, any two spatially adjacent districts tend to have a similar prevalence of HIV among TB patients. Observe from t-test for spatial association show that TB among PLHIV and HIV among TB patients were significantly spatial associated (p < 0.001). The correlation varied with time, where the highest correlation was observed in year 2016 (r=0.692) and the lowest was in year 2018 (r=0.517). The global bivariate Moran's I was also consistently positive across the years suggesting that the district-level prevalence rates of TB among PLHIV were positively influenced by the prevalence of HIV among TB patients in the neighborhood districts and vice versa.The global Moran's (1) Spatial Clustering of TB-HIV Coinfections. To further investigate the spatial heterogeneity, i.e., to identify the hot-spots and cold-spots districts for the prevalence of HIV among TB patients and for the prevalence of TB among PLHIV, we applied the Getis–Ord Gi∗ statistic. Maps showing the distribution of spatial clusters of the prevalence of HIV among TB patients and the prevalence of TB among PLHIV are presented in Figures Gi∗ statistics in The Getis–Ord Despite improvements in TB and HIV eradication due to WHO-coordinated efforts, these illnesses nevertheless have alarming mortality and morbidity statistics , 42. ForThe prevalence of HIV among TB patients and the prevalence of TB among PLHIV varied between regions and between districts in Ethiopia over the study period. The chi-square tests on spatial heterogeneity in the number of HIV cases among TB patients have also supported these findings where the tests rejected the null hypothesis of a constant prevalence of HIV among TB patients and TB among PLHIV across Ethiopia.Gi∗ statistics show that the prevalence of TB among PLHIV was spatially clustered; i.e., there are hot-spots in districts of Gambela, Oromiya , SNNP, and Somalli (in Liben and Deghabour zones) regions in 2015. However, unlike in 2015, in the other years, relatively few hot-spot districts were observed. This may be because of the wide implementation of the TB-HIV collaborative activities at the health facilities [The current study's results also demonstrate that over time, there were geographical differences in the prevalence of TB-HIV coinfection. These findings agree with those of Alene et al. , who foucilities . In 2015In this study, we have noticed that the hot-spots for the prevalence of TB among PLHIV have appeared in the country over the study period more in urbanized areas such as Awassa, Bahir Dar, Gondar, Jimma, and Shashemene. This may be connected to population movement within a district or between districts that are adjacent in search of employment or better living conditions. Studies conducted in Ethiopia have shown that spatial clustering of TB related to migration –49 and oWhereas in 2015 hot-spots for the prevalence of HIV among tuberculosis patients were observed in some districts of Afar, Amhara, Gambela, Oromiya, Somali regions, and Addis Ababa city administration. In addition, to those regions which had hot-spot districts in 2015, in 2016, hot-spots were also observed in districts of the Tigray region. However, in 2017 except in Gambella region and Addis Ababa city administration those regions which had hot-spots for the prevalence of TB among PLHIV also had hot-spot districts for the prevalence of HIV among TB patients. Hot-spots were also observed for HIV among TB patients in districts of Afar, Amhara, Oromiya, Somali, Tigray regions and districts of Addis Ababa city administration in 2018. However, more districts in the Oromiya region in 2015, Benishangul-Gumuz and Oromiya regions in 2016, Benishangul-Gumuz, Gambela, Oromiya, and SNNP regions in 2017, and Benishangul-Gumuz, Harer, Oromiya and SNNP regions, and in Dire Dawa city administration in 2018 were identified as cold-spots, respectively.Hot-spot areas for the prevalence of HIV among TB patients were also observed at the border of Nuer and Anuak zones in Gambella region with South Sudan, Jarar zone of Somalia region with Somali-land, Shabelle and Afder zones of Somalia region with Somalia, Eastern Tigray with Eritrea, and Awsi Rasu zone of Afar with Djibouti. There are refugee camps close to the border of Gambella and Tigray regions and in some areas which are the border of Oromiya and Somalia regions and Kenya. Generally, refugees are often in situations where they do not have a proper job access to generate additional income. As a result, women and young girls in refugee camps often enter commercial sex work to earn income, food, and to gain access to other resources ; this exI statistics for TB among PLHIV, except in 2018, and HIV among TB patients were positive suggesting that neighboring districts tend to possess similar characteristics in the prevalence of TB/HIV coinfection. The global bivariate Moran's I statistic was also positive for the study period, implying that neighboring districts had an effect on the two types of TB-HIV coinfection. Spearman's correlation coefficients were positive and statistically significant, they are in agreement with Moran's I statistic values. These coefficients are more than 0.5 for each year and they are consistent with results reported in [According to the findings of the current study, over the majority of the study period in Ethiopia, the prevalence of HIV among TB patients was more geographically associated than the prevalence of TB among PLHIV. This finding agrees with Aturinde et al.  where thorted in , 55.Despite the fact that there are a limited number of studies that have examined the spatial clustering of HIV and TB separately at the national level in Ethiopia  and TB-HI statistic, Getis–Ord Gi∗ statistic with LISA cluster maps and Spearman correlation coefficient with its modified t-test. According to the findings of our study, between the years of 2015 and 2018, there was strong spatial clustering in Ethiopia of both the prevalence of HIV among TB patients and the prevalence of TB among PLHIV at the districts level. The LISA detected districts which were hot-spots and cold-spots for the prevalence of TB among PLHIV and the prevalence of HIV among TB patients in various regions and the two city administrations. In some cases, these spots were unstable over the study period except for some of the districts in the Afar and Amhara regions and Addis Ababa city administration which were consistently identified as hot-spots for the prevalence of HIV among TB patients. The study presents detailed knowledge about the spatial clustering of TB-HIV coinfection in Ethiopia at the districts level and the findings could provide information for planning coordinated district-specific interventions to jointly control both diseases in Ethiopia.In this study, we evaluated the spatial clustering of two types of TB-HIV coinfection prevalence by applying the global Moran's


Furthermore, we did not find a significant causal effect of RA on bipolar disorder in the reverse MR analysis (p > 0.05). In addition, our study found no evidence of a bidirectional causal relationship between genetically predicted broad depression, major depression, anxiety, and RA (p > 0.05). The genetically proxied bipolar disorder population has a lower RA risk, which may indicate that there is a hidden mechanism for inhibiting the pathogenesis of RA in bipolar disorder. However, results do not support a causal connection between depression, anxiety, and RA.A correlation between mental illness and systemic rheumatoid arthritis (RA) has been observed in several prior investigations. However, little is known about the causative relationship between them. The present study aimed to systematically investigate the potential association between genetically determined mental illness and RA. Two-sample bidirectional Mendelian randomization (MR) analysis was performed using publicly released genome-wide association studies (GWAS). We selected independent genetic variants associated with four mental illnesses  as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between mental illness and RA. Results of the IVW analysis suggested that genetic predisposition to bipolar disorder was associated with a decreased risk of RA (odds ratio [OR] = 0.825, 95% CI = 0.716 to 0.95,  Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, which mainly accumulates in hand and foot joints, resulting in cartilage and bone damage and disability . The preMental illness, including bipolar disorder, depression, and anxiety ,4, is onHowever, the occurrence rate of bipolar disorder in patients with RA remains controversial. Several studies support that the prevalence of bipolar disorder in RA patients is higher than that in non-RA patients ,13. The Mental illness leads to increased disease activity, further deterioration of dysfunction, and decreased quality of life, and may reduce susceptibility to first-line antirheumatic drugs in patients with RA ,17,18. THowever, correlation does not imply causation. Correlation is only expressed as the statistical association between two variables, referring to quantifiable relationships in the data . CorrelaMendelian randomization (MR) is a statistical method that uses genetic variation  as an instrumental variable (IV) to determine causal associations between risk factors and outcome variables . Since tAn overview of the study design is shown in The IVs used in MR analysis need to satisfy 3 assumptions: (1) there is a strong correlation between IVs and risk factors; (2) there is no relationship between IVs and confounders and they are independent of each other; (3) there is no direct relationship between IVs and outcome variables .p < 5 × 10−8) as IVs. There are 64 genomic loci associated with bipolar disorder   . The F-vSummary statistics on broad depression, bipolar disorder, major depression, anxiety, and RA were obtained from the largest publicly available GWASs. There are clear screening criteria for the determination of each phenotype . The summary statistics for bipolar disorder involved 41,917 cases and 371,549 controls from 57 cohorts . The broad depression GWAS summary statistics were extracted from the UK Biobank, which analyzed 322,580 subjects . Genetic variants associated with major depression were obtained from the 3 largest genome-wide depression association studies with 807,553 individuals, including personal genetics company 23 andMe, Inc., UK Biobank, and a meta-analysis of 35 cohorts . Genetic variants associated with anxiety came from 9 samples of European ancestry from 7 large independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated, DSM-based anxiety disorders, 2 phenotypic approaches were applied: case-control (CC) comparisons and quantitative factor scores (FS). The results showed that the FS phenotype identified a larger number of associated SNPs than the CC model. Therefore, we finally used the results from the FS model as the GWAS needed in this study. The summary statistics for RA were obtained from assessments of more than 50,000 subjects, including 14,361 RA cases and 43,923 controls from 18 studies of Europeans.The dataset used in our study was publicly available and each GWAS involved was ethically approved by the respective institutions. In addition, we checked the populations of the exposure and the outcome sample to exclude possible bias in the study results caused by sample overlap.p value [MR analyses were conducted in the R statistical computing environment using the “TwoSampleMR” package. The software package can harmonize exposure and outcome data sets, including information on SNPs, effect size, standard error (se), effect allele frequency, and p value . The Harp > 0.05), a random effects model will be used to combine the effects, otherwise, a fixed effects model will be used [We used the inverse variance–weighted (IVW) method as the main causal evaluation method, which uses asymptotic estimates of the standard error of the causal (ratio) estimate of each variable. Its main characteristic is that the existence of the intercept term is not considered and the reciprocal of the local variance (the quadratic power of se) was used as the weight for fitting . Accordi be used .However, this method does not take into account the uncertainty of genetic association and risk factors, and there may be a risk of underestimating the real changes in the estimates, especially when the IV is weak ,43. TherWe also used Cochrane Q statistic and MR-Egger regression analysis to evaluate the bias caused by gene polymorphism. If an SNP works not only through the hypothetical approach but also through other means, it represents the existence of horizontal pleiotropy between the 2. The existence of horizontal multiplicity violates the assumption that instrumental variables are satisfied . The assp-value < 0.0125 meets the Bonferroni threshold of statistical significance (0.05/4 = 0.0125). Results with p-values greater than 0.0125 but less than 0.05 were considered suggestive evidence. Otherwise, the results were not considered statistically significant.The “leave-one-out” method was used to evaluate the stability of the results, that is, each SNP was omitted to determine whether a single SNP supports causal correlation. We also applied MR-PRESSO  to detect and correct outliers that could contribute to pleiotropic bias . Since o2 > 0.80). The 2-sample MR study was re-evaluated after removing SNPs that may control for confounding traits to support the stability of the results.Finally, we retrieved potential secondary phenotypes for each SNP used as IVs from PhenoScanner , random-effects inverse variance weighted; MR-PRESSO, MR-pleiotropy residual sum, and outlier.p = 0.03, p < 0.05). Corrected results did not change after removing one outlier using MR-PRESSO . In the p = 0.22, p = 0.35; p = 0.35; p > 0.05; In the IVW analysis, we did not find any significant causal relations between broad depression , broad depression , major depression , and anxiety  by the primary method of IVW -6/IL-8/matrix metalloproteinase (MMP)-3 production of RA synovial fibroblasts (RASF) [The MR result allowed us to consider whether there is some kind of related pathological mechanism between bipolar disorder and RA and whether this pathological mechanism has the opposite effect on each other. Research shows that there is a rare mutation in the calcium channel gene in bipolar disorder, resulting in the genetic damage of voltage-gated calcium channels and the increase in calcium signals . At pres damaged . Increass (RASF) , increass (RASF) , and reds (RASF) . TherefoThe dopamine hypothesis has always been a key theory in the pathophysiology of manic and depressive phases of bipolar disorder. The animal model, the autopsy results of the expression of the dopaminergic gene, and the imaging examinations all proved that bipolar disorder patients had excessive secretion of dopamine, which may be associated with the increase in the density of dopamine transporters and the upregulation of D2/3 receptor levels . ClinicaChristensenellaceae was thought a highly heritable taxon in the human gut microbiome [Christensenellaceae could not be detected in patients with bipolar disorder [Christensenellaceae in patients with RA was higher than that of healthy people [Christensenellaceae remain undefined. The change in Christensenellaceae abundance may be one of the mechanisms underlying the role of bipolar disorder in reducing the risk of RA, but the underlying pathological mechanisms still need further study and in-depth research.In addition, the imbalance of gut microbiota may be a potential mechanism of RA and bipolar disorder. The crobiome . Currentdisorder , but they people . The proThe “inflammatory hypothesis” is considered to be one of the mechanisms leading to the pathogenesis of bipolar disorder . HoweverAt present, epidemiology mainly supports the increased prevalence of bipolar disorder in patients with RA. The reason for the contradiction between our results and epidemiological findings may be that traditional observational studies were confused by smoking status. The MR analysis showed that smoking was a causal risk factor for bipolar disorder  as well A large number of epidemiological studies have shown that there was comorbidity between RA, depression, and anxiety ,23. Howe2+ signaling pathway and the dopamine concentrations on the pathogenesis of RA, which may open new lines of exciting research.There are several advantages to this study. First of all, based on the associated research, this study takes the genetic variable as the design variable, ruled out the interference of residual confounding, and explores the causal relationship between bipolar disorder, depression, anxiety, and RA. Secondly, so far, the incidence of RA in patients with bipolar disorder has not been studied in epidemiology. The analysis results of the protective effect of bipolar disorder on RA obtained in our study may provide a reference for epidemiology in the future. Finally, we found the protective effect of bipolar disorder on RA and speculated that there may be a reverse pathological mechanism between bipolar disorder and RA, especially the effect of the CaThe study also has its limitations. The conclusion of the causal correlation between anxiety and RA is unstable and increasing the sample size of IVs may lead to more stable results. However, due to the lack of significant loci on anxiety disorders in the literature, we cannot obtain more IVs for research. In addition, most of the genetic variations in this study were heterogeneity in MR analysis. Although we have uniformly used the European population sample to prevent the heterogeneity caused by population stratification, there are many differences among different populations, such as gender, age, social status, and so on, which may still cause differences. Finally, fewer IVs can be used as broad depression after the screening, which may lead to the breadth of the 95% CI. Thus, the results of the causal effect of broad depression on RA may not be accurate.


Conclusions: Newborns from MCBA pregnancies with sIUGR appear to have similar overall neurological development to IUGR. Notably, IUGR seems to have the most moderate neurobehavioral disorder (fine motor) as a consequence of impaired antenatal brain development due to placenta insufficiency leading to chronic hypoxia.Background: There are few data concerning the neonatal and long-term prognosis of monochorionic biamniotic twin pregnancies (MCBA) complicated by selective intrauterine growth restriction (sIUGR). The aim of the study is to assess the neurological outcomes at two years of age of these newborns and compares these outcomes to those of newborns resulting from intrauterine growth restriction (IUGR) pregnancies. Methods: The study focuses on a cross-sectional prospective cohort of patients treated between 2012 and 2019 in Marseille, France. The primary endpoint is the overall score of the Ages and Stages questionnaires (ASQ) at two years, which assesses the global neurodevelopment. The secondary endpoint is the assessment of neonatal morbi-mortality for both groups (composite endpoint). Results: In total, 251 patients were included in the analysis: 67 in the sIUGR group and 184 in the IUGR group. There was no statistically significant difference in the overall ASQ score at two years but there was the finest motor skills impairment in the IUGR group. The areas most often impaired were communication and fine motor skills. There were no significant differences between the neonatal morbi-mortality of the two groups (adjusted OR = 0.95,  In total, 10–15% of monochorionic biamniotic twin pregnancies (MCBA) are affected by selective intrauterine growth restriction (sIURG) ), sepsis and intensive care unit admission rate).The composite criterion of interest for neonatal morbi-mortality is the occurrence of one or more of the following events: (1) neonatal death; (2) grade III or IV intraventricular hemorrhage; (3) white matter lesions, a type of cystic periventricular leukomalacia; (4) bronchopulmonary dysplasia defined as the need for oxygen supplementation for at least 28 days, associated with the use of oxygen greater than or equal to 30% and/or ventilatory support  at 36 weeks of age-corrected amenorrhea ; or (5) The sIUGR sample size was limited by the earliest date computer access to our center’s patient records was permitted.All pregnancies meeting the criteria for sIUGR were followed. The estimated number of twin pregnancies that could be included in this study, given the usual follow-up in our department, was 80. It is difficult to calculate the necessary number of subjects, as we did not find a comparable population in the literature with an evaluation according to the ASQ questionnaire. Moreover, as the study was observational, there were no additional constraints or changes in the management and follow-up of pregnancies and newborns.For each sIUGR included, at least two “controls” were also included, i.e., two IUGR. Given there was a greater number of IUGR cases than the number of sIUGR cases followed, we stopped recruitment in 2015 to obtain at least twice the number of sIUGR examples. An additional margin of 50% was considered given the estimated loss to follow-up (LFU) at two years.p-value was less than 0.05. This statistical analysis was performed with the 20.0 edition of the SPSS software for the infant data and with the 20.0 edition of the IBM SPSS Statistics software  for the obstetrical and neonatal data.All tests were bilateral. Results were considered statistically significant if the Regarding the primary endpoint, the two groups (sIUGR and IUGR) were compared with respect to the overall ASQ score at 2 years of age. Pearson’s chi-squared test was used, and scores from each of the five ASQ domains were assessed.Subgroups, according to gestational age, were created to compare data at two years for the same gestational age.According to the newborn’s gestational age, sex, birth weight, and socioeconomic conditions ), a multivariate analysis was performed.The two-year analysis began in January 2021, thus children who were not at least two years old at that time were excluded.t-test (or Mann–Whitney U test if it was necessary) was used for the quantitative variable. Levene’s test was used to check the normal distribution. We used the chi-squared test for categorical variables.Regarding the secondary endpoint, the perinatal data and the composite criterion of morbi-mortality were compared between the two groups (sIUGR and IUGR). Student’s A multivariate analysis was performed in order to compare the neonatal outcome without the differences between the two groups. We made a statistical adjustment on the birth weight, the gestational age at birth, the gender, and indications of birth according to five main causes: spontaneous or planned, fetal rhythm anomalies (FRA), Doppler abnormalities , growth arrest, or another cause. Results were shown as odds ratios (OR) with a confidence interval of 95% (95% CI).Since the number of patients lost to follow-up was significant, the perinatal data of the final populations (followed at two years) and the initially included populations were compared with each other to check for attrition bias .Initial characteristics of the population184 patients were followed for sIUGR at our center between January 2012 and December 2019. In total, 67 of these were included for neonatal analysis.There were 264 IUGR patients followed, with 184 being included in the IUGR neonatal analysis group.The two populations are comparable. The median age at diagnosis was 25–26 weeks GA for sIUGR and IUGR, respectively, with more than 90% of early-onset IUGR in both groups.p = 0.001).There are, however, more severe abnormalities on the umbilical diastole in the sIUGR group: positive in 52.2% of the fetuses of the sIUGR group vs. 73.4% for the IUGR group, null or negative intermittently, respectively, for 17.9% vs. 15.8 %, and null or negative permanently for 29.9% vs. 10.9% .The different birth indications are statistically dissimilar between the groups with more induced births for sIUGR  were followed up to the age of two years. Among the 184 IUGR assessed at birth, 75 were followed up to two years of age (41%) . We founp = 0.84). In the sIUGR group, there were 12 children (32.4%) with an ASQ below the threshold as compared to 18 children in the IUGR group (24%), (p = 0.82).The median of the global ASQ was not significantly different in either group   .Nine sIUGR children (33%) still showed growth retardation below the third percentile at two years as compared to 40 children from the IUGR cohort group (47%) .p = 0.5). There was also no statistically significant difference in the neonatal criteria taken separately: pH at birth, mortality rate, resuscitation admission rate, respiratory distress, brain abnormalities, ulcerative colitis, and sepsis (p > 0.05).In the multivariate analysis , we adjup = 0.06). In all results, there is no significant difference, even with morbidity and the composite criteria of morbi-mortality: p = 0.92 , but it is not statistically significant (p = 0.92  in the mp = 0.07) with a tendency for communication impairment (0.07) for the sIUGR group.There is no significant difference except for a trend in the number of altered domains  of children followed either for sIUGR in MCBA twin pregnancies or for IUGR in a single pregnancy.The results of our study show that the long-term neurobehavioral evolution at 2 years on the overall ASQ is similar between the sIUGR group and the IUGR group, except for the more pathological fine motor domain in the IUGR group. The two most impaired ASQ domains in the total population are in relation to communication (13%) and fine motor skills (8%).Neonatal morbidity is similar between the two groups; the sIUGR group seems to have a difference in mortality but it is not statistically significant.In the literature, there are further studies concerning IUGR neurobehavioral outcomes. Based on those studies, we can hypothesize that growth discrepancy in monochorionic pregnancies is a separate clinical entity whose consequences begin in the antenatal period, which is reinforced by Gratacos’ Doppler studies . The useThe retrospective nature of our study, the small number of children included in the sIUGR group and the high ratio of those lost to follow-up  are limitations to the interpretation of our study. We assess infants until 24 months on their neurodevelopment, but we have no data on the longer-term prognosis during childhood (it would be interesting to continue the follow-up).We did not define a gestational age limit for inclusion, and therefore included both very preterm and full-term newborns in order to obtain a sufficient number of data . Pregnancies with in utero death were excluded from the analysis to focus on the neonatal and long-term prognosis of the sIUGR twin. Therefore, the most severe clinical situations were not assessed in the analysis . We madep < 0.01. MCBA discordant twins had a six times higher risk of cerebral palsy as compared to DC twins . Note that in our work, we do not study cerebral palsy because of the relatively high gestational age of our population, but we have a greater tendency to death, signifying great antenatal severity. The finest motor impairment in the IUGR population is consistent because fine motor impairment is predictive of a more globally associated neurobehavioral impairment at school age, as described in the IUGR population [p < 0.0001). The verbal IQ score is lower in the smaller twin versus the larger twin (0.5 SD less). There is the same trend, but not significantly, for ASQ in the communication domain in our study. Sierakowski et al. [p = 0.02), lower developmental test scores (up to 2.2 points) [A review of the recent literature in 2019 , whose opulation . In addipulation  and invopulation . Indeed,pulation ,44. Thespulation . Edmondspulation  describei et al.  show tha points)  and lowe points)  comparedAll these results suggest that monochorionic (MC) twins with sIUGR have a higher risk of long-term neurodevelopmental impairment as compared to concordant dichorionic or monochorionic twins, and the smaller twin seems to be more affected than his co-eutrophic twin. Despite all these data, the overall level of evidence seems insufficient and needs further exploration.Boghossian et al.  evaluateHowever, other studies find different long-term outcome results. Monset-Couchard et al.  evaluateHowever, in the literature, there is no study, to our knowledge, comparing MCBA twin pregnancies with sIUGR and single pregnancies with vascular IUGR. If we assume that the IUGR pregnancies have more frequent neurodevelopmental problems centered on attentional abilities and academic performance, our results confirm greater fine motor impairment in IUGR pregnancies and suggest that the growth discrepancy in monochorionic pregnancies appears to play a role antenatally in death, but hypotrophy correlates to neurodevelopment at two years of age ,50,51. APre-linguistic sensorimotor skills are necessary for the child’s language development. Impairment of sensorimotor functions  is noted in children with language disorders . Our finAll in all, few studies examine sIUGR in monochorionic pregnancies. Those assessments are heterogeneous, with limited numbers, and the comparison populations are varied between co-twin, dichorionic pregnancy, and concordant MC pregnancy. However, our study seems to confirm the findings of other studies indicating the tendency for a more adverse outcome for the discordant twin, favored by monochorionicity. This is confirmed by a recent study finding a higher risk of adverse outcomes in MC twins but no differences in the neurodevelopmental follow-up at 2 years between MC and DC twins .Thus, one hypothesis suggests that neurobehavioral disorders in premature IUGR infants are due to cerebral hypoconnectivity secondary to an encephalopathy of prematurity. This begins prenatally because of placental vascular disturbances. Monochorionicity with sIUGR could lead to more deaths and/or to more diffuse disturbances and cerebral structural abnormalities at an early stage .MCBA twin pregnancies with sIUGR require regular monitoring, including umbilical diastole Doppler assessment, to assess the risk of a poor prognosis and to estimate the optimal threshold for an induced delivery ,21. To e


Anticancer treatment gives rise to adverse effects such as increased pain and changes to body weight and menstrual cycles, with negative effects on activities of daily living. To analyze the effect of food orientation combined with supervised  versus home-based (HB) aerobic training on lifestyle  levels), body composition, metabolic profile and cardiorespiratory fitness, among breast cancer survivors. Clinical trial study (six months) conducted at a public university in Presidente Prudente, Brazil. Twenty-three female breast cancer survivors (40-75 years old) were allocated to aerobic training groups, either FF or HB. Both groups were trained and received food orientation. They were evaluated through a dietary record, ergometric treadmill test and blood test and the Baecke questionnaire. After six months, both groups had reduced their lipid levels, total energy consumption and polyunsaturated fat intake, and had increased their PA levels and treadmill test durations. However, only the HB showed reduced carbohydrate percentage and increased folic acid; and only the FF showed reduced lipid, saturated fat and sodium levels, along with increased carbohydrate and protein levels. No differences in body composition or metabolic profile were found. These results demonstrated the feasibility of HB aerobic training. In isolation, HB showed greater regulation of carbohydrate percentage and increased folic acid levels. Moreover, these breast cancer survivors presented improvements in food consumption, PA levels and cardiorespiratory fitness, while also maintaining their body composition and metabolic profile after the intervention, independent of the group. Hormone therapy is an adjuvant treatment used by breast cancer patients to reduce the risk of tumor recurrence through hormonal blocking, among those with positive hormonal receptors.On the other hand, food orientation allied with physical activity (PA) has been demonstrated to improve quality of life among breast cancer survivors.,Home-based interventions can be developed in different areas and places, such as public squares and patients’ homes. Hence, this approach has also been used to increase adherence.Aerobic training has been the form of exercise most recommended for breast cancer patients, due to its safety.Conversely, some studies are still showing controversial results. In one such study, 22 overweight or obese black breast cancer survivors who underwent an aerobic intervention combined with nutritional counseling for 12 weeks did not show any body weight reduction.The aim of this study was to analyze the effect of food orientation combined with face-to-face versus home-based aerobic training on lifestyle , body composition, metabolic profile and cardiorespiratory fitness among women undergoing hormone therapy for breast cancer.Twenty-three women without current aerobic training who were undergoing hormone therapy (either still in treatment or with treatment concluded) for breast cancer, consisting of use of either tamoxifen or aromatase inhibitors, volunteered to participate in this study. The women who had concluded their treatment had had at least five years of hormone therapy. To be included, the participants needed to have not had any aerobic training for at least three months before the intervention. Potential participants were excluded if they presented any mental disorder or physical condition that would not allow them to perform the aerobic training. In addition, any women who were incapable of verbal communication or had physical impairments or were pregnant or breastfeeding at that time were also excluded. Participants were also excluded if they withdrew from the training or suffered any physical injuries. The women were allocated either to a face-to-face training group (FF) (n = 10) or to a home-based training group (HB) (n = 13).This study was approved by the Research Ethics Committee of the School of Science and Technology, São Paulo State University , in Presidente Prudente, Brazil, under protocol number 78971417.9.0000.5402 , and was registered at clinicaltrials.gov under the number NCT03494400 . All the procedures were conducted in accordance with the Declaration of Helsinki. Thus, potential participants were informed of the aim and procedures of the study, with a complete explanation, and those who agreed to participate signed a written informed consent statement.To recruit potential participants, phone numbers of female breast cancer patients who were undergoing hormone therapy were obtained from cancer hospitals. Social media were also used to publicize the study, in order to facilitate inclusion of women living in nearby municipalities or who were not on the phone lists. All the participants were blindly coded and allocated 1:1 with sequence boundaries in the random sequence generator random.org.The participants’ clinical characteristics were verified at the baseline through an anamnesis. All evaluations were carried out before and after the 24-week intervention.The participants’ nutritional status was determined through a dietary record, which was applied on three occasions: on two workdays and on one weekend day. This dietary record, which consisted of recording all food consumed throughout the day, was collected at the baseline and after the 24 weeks of the intervention.,In order to evaluate the daily physical activity (PA) level, the Baecke questionnaire was applied. This questionnaire has been validated for the Brazilian adult population.Anthropometric measurements were made on a mechanical scale (Filizola) to the nearest 0.1 kg; and on a fixed stadiometer (Sanny) to the nearest 0.1 cm or with a measuring tape (Sanny) to the nearest 0.1 cm. The body mass index was also calculated.,A bioelectrical impedance device  was used to obtain resistance and reactance data. The participants received recommendations regarding clothing, food and drug use, to be evaluated.The participants’ metabolic profile was analyzed by assaying their glycemia, insulin, triglyceride, total cholesterol and cholesterol fraction levels. For this, blood samples were collected in vacuum tubes with gel without anticoagulant. An enzymatic colorimetric kit was used and the samples were processed in an Autohumalyzer A5 device .The modified Naughton test was performed on an ergometric treadmill , with a maximum capacity of 180 kg, inclination of 26% and velocity of 24 km/h, in a climate-controlled laboratory. This ramp test involved incremental increases in velocity and inclination, and each stage was maintained for two minutes.The aerobic intervention combined with food orientation lasted for 24 weeks. The aerobic training followed a recommended duration of 150 minutes per week.max), according to age (220-age).,The aerobic training protocol for the FF was undertaken on an ergometric treadmill  in an air-conditioned laboratory. The participants trained three times a week on non-consecutive days . The intensity of the training was controlled using a heart rate monitor  and was adjusted for the maximum heart rate .,,Both FF and HB received dietary recommendations for breast cancer survivors,Descriptive statistics were calculated: means, confidence intervals and absolute and relative frequencies. Data normality and variance homogeneity were verified through the Shapiro-Wilk and Levene tests, respectively. The participants’ characteristics were analyzed using Student’s t test for body mass index and Fisher’s exact test for menopause status, medications, chemotherapy and/or radiotherapy utilization, cancer recurrence and/or metastases, time and type of hormone therapy used, with comparisons between FF and HB.2. The SPSS 21.0 software  was applied to perform the statistical analysis. A statistical difference was considered to be present when P < 0.05.Repeated ANOVA measurements (within-between interactions) were calculated to assess food consumption, daily PA level, body composition and metabolic profile. Subsequently, the Bonferroni post-hoc test was used to verify any statistical differences. The chi-square test and Fisher’s exact test were used to verify body composition and metabolic profile classification at the baseline and after the 24 weeks of the intervention. The chi-square test was used to analyze total cholesterol, low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), triglycerides and glycemia; while Fisher’s exact test was used to analyze HDL-C and insulin. The effect size was calculated by means of ηpTwenty-eight women undergoing hormone therapy for breast cancer participated in this study, and 23 of them completed the 24-week intervention . It was 2 = 0.419) and difference in the time analysis , with increased levels in FF (P = 0.007). The groups differed at the baseline (P = 0.022) (We observed that the participants’ lipid consumption (g) presented reductions, as shown in the post-hoc test: for FF, P = 0.001; and for HB, P = 0.008. The percentage of lipid consumption decreased only for FF (P = 0.002). The carbohydrate percentage presented interaction  .2 = 0.602), with a reduction for FF (P = 0.010), such that there was a difference between the groups at the end of the 24-week intervention (P = 0.027). Conversely, the carbohydrate percentage (P = 0.029) presented a reduction and folic acid (mg) presented an increase (P = 0.018) in HB  and polyunsaturated fat (g) showed reductions in the FF group , as also did HB , in the post-hoc test. The FF group presented an increase in protein (%) (P = 0.005) and a reduction in saturated fat (g) (P = 0.016). The sodium level (mg) was influenced over time  in HB .2 = 0,519), with different increases in FF (P = 0.010) and in HB (P = 0.038)  and the HB group  . The dur= 0.038) .Body composition and metabolic profile did not present significant differences . NonetheIn this study, the nutritionist’s recommendations were given in person and online via smartphones. It is worth mentioning that in the literature, it has been established that informative interventions combined with aerobic training seem to be more efficient with regard to improving quality of life, compared with interventions alone.Hence, food orientation seems to be a means for changing habits. On the other hand, changes in dietary habits might also be due to alterations related to physical exercise, which generate improvements in the anti-inflammatory process. Consequently, leptin and insulin signaling in conjunction with the central nervous system improve the signaling of the satiety command in the hypothalamus.Our results showed that total energy consumption  decreased, both in FF and in HB. This finding corroborated the data in the literature. A feasibility study among 22 overweight and obese black female breast cancer survivors who participated in an aerobic intervention for 12 weeks found that reductions in energy intake and fat consumption occurred.Another noteworthy finding in this study was the decreases in macronutrient intake, such as lipid (g) and polyunsaturated fat (g) consumption. These data indicate that our intervention enabled adjustment of fat consumption in both groups and adjustment of lipid consumption in FF.We observe broader alterations in the FF group, which included simultaneously increased protein (%) and carbohydrate (g) intake, along with reduced lipid (%) and saturated fat (%) levels. However only HB showed a carbohydrate reduction (%). Especially for FF, these results indicated that the balance in macronutrient consumption was enhanced. This was possibly because the adjustments that macronutrients were able to provide to the liver and muscle fat became better. In this regard, overfeeding on sucrose and fat, combined with low protein content, has been seen to increase storage of intrahepatocellular and intramyocellular lipids, consequently increasing fat accumulation in the liver and muscles.The sodium (mg) consumption was also reduced in both groups, which seems to be a prevention factor against breast cancer recurrence. A cohort study carried out among South African women showed that there was an association between salty foods and the risk of breast cancer development during the post-menopause period.We observed that in the HB group, the amount of folic acid intake was enhanced. In both groups, folic acid patterns were within normality after the intervention. Folic acid is composed of vitamin B, which is essential for biological reactions since folates provide carbon for deoxyribonucleic acid (DNA) biosynthesis and thus assist in maintaining the gene balance. Furthermore, folate deficiency is associated with cardiovascular and brain diseases, and also cancer.In the literature, it has been proposed that changes to food habits through aerobic home-based training interventions may be a differential in clinical research. This may be due to changes in consumption of fiber and processed meat, along with better choice of purchases, such that vegetables, whole grains, proteins and legumes are bought instead of sweets and processed snacks.In the present study, similar results for FF and HB were observed regarding increases in PA levels and maintenance of body composition and metabolic profile. These results are in accordance with those from a study in which 100 women with breast cancer were assessed. The sample was separated into three groups: one of them received counselling via telephone, another received on-site recommendations and the third was a control group. The two intervention groups received counselling aimed at decreasing their energy intake, and underwent regular aerobic PA combined with behavioral therapy, for six months.Our data indicated that changes in lifestyle occurred, along with increased PA levels and improved food consumption. However, these improvements did not provide body weight loss. The results from this study are in agreement with data in the literature, in which no significant improvements in body composition were found after six months of aerobic intervention and nutritional counselling, among 61 breast cancer women undergoing chemotherapy.Regarding the effects of hormone therapy on body weight gain, no significant differences between aromatase inhibitors and tamoxifen were observed in comparison with a placebo.In this study, most of the participants were within the recommended range of metabolic profile.Clinically, cancer survivors show metabolic alterations, as well as dysfunction or increased cardiac overload, in comparison with individuals of a similar age without a diagnosis of cancer.Some limitations of the present study need to be acknowledged. These include prescription of training on the basis of HRmax, which may present variability between participants of a mean of 12 heartbeats/minute.We suggest that multicenter studies should be conducted on this population, with analysis on inflammatory cytokines, in order to better comprehend the nutritional alterations caused by the relationships of body composition and metabolic profile with the central nervous system.The aerobic intervention combined with food orientation was a feasible strategy for promoting improvements in food consumption, daily PA and cardiorespiratory fitness, and for maintaining body composition and metabolic profile, among women undergoing hormone therapy for breast cancer.The groups also stood out individually, such that in the FF group, there was greater regulation of macronutrients and, in the HB group, the folic acid level increased and the percentage of carbohydrates decreased. These results demonstrated the feasibility of HB aerobic training, as a complementary treatment for breast cancer survivors.