Their performance further deteriorated after surgery and by the day of discharge. They most often required long-lasting postoperative rehabilitation and had the longest LOS (35 days). Operation was most often required for CH tumors (77.7%), and all metrics and LOS parameters were better in these patients (p < 0.001). Patients with CPA tumors had the best outcomes (p < 0.001). Most patients (83.4%) with brain tumors did not require specialized rehabilitation, and LOS after surgery in the control group was on average 5.1 days after surgery. VS tumor patients represent a rehabilitation challenge. Postoperative rehabilitation planning must take the tumor site and preoperative condition into account.Brain tumor location is an important factor determining the functional state after brain tumor surgery. We assessed the functional state and course of rehabilitation of patients undergoing surgery for brain tumors and assessed the location-dependent risk of loss of basic motor skills and the time needed for improvement after surgery. There were 835 patients who underwent operations, and 139 (16.6%) required rehabilitation during the inpatient stay. Karnofsky Performance Scale, Barthel Index, and the modified Rankin scale were used to assess functional status, whereas Gait Index was used to assess gait efficiency. Motor skills, overall length of stay (LOS) in hospital, and LOS after surgery were recorded. Patients were classified into four groups: cerebral hemisphere (CH), ventricular system (VS), and cerebellopontine angle (CPA) tumors; and a control group not requiring rehabilitation. VS tumor patients had the lowest scores in all domains compared with the other groups before surgery ( Rehabilitation after brain tumor surgery is complex due to the diverse symptoms and neurological sequelae seen in these patients. Outcomes for brain tumor patients are influenced by many factors, including disease growth rate and duration, tumor size, grade of malignancy, and patient age. Tumor location has a particularly important impact on outcomes ,4,5,6,7.As survival after brain tumor surgery increases ,19,20,21We therefore specifically addressed these knowledge gaps in the current study. Our primary aim was to assess the functional status, motor skills, and gait efficiency of patients undergoing brain tumor surgery. An additional aim was to assess the incidence of complications affecting the rehabilitation course and time parameters such as the overall LOS, LOS after surgery, LOS in the Intensive Care Unit (ICU), the time needed for rehabilitation, and the time needed to improve any loss in basic motor skills after surgery.n = 96), ventricular system , and cerebellopontine angle . Surgery for all CPA tumors was via retrosigmoid access. Access to the remaining locations was selected individually to minimize damage to brain tissues. Head MRI with tractography was used to select access, and functional MRI was used in selected cases.The inclusion criteria were as follows: patients after brain tumor surgery; neurological deficits found; functional state worsened by surgery; and need for prolonged rehabilitation. The Bioethics Committee at the Military Medical Chamber approved the study protocol (no. 164/18). This was a single-center prospective, observational case-control study (three intervention groups and a control group) with follow-up time from the day of admission to the clinic to the day of discharge. There were 835 patients undergoing operations for brain tumors from August 2018 to February 2020 (18 months), 139 (16.6%) of whom required rehabilitation during their inpatient stay at the Neurosurgery Clinic. Three patients refused to participate in the study, and three died. The study therefore included 133 patients who underwent rehabilitation after brain tumor surgery. One-hundred and twenty-seven patients (95.5%) had tumors in the three most common locations: cerebral hemispheres , motor skills , and gait efficiency (Gait Index—GI). Activities of daily living (ADL) were assessed with the Barthel Index (BI), which assesses self-reliance in eating, self-transferring , maintaining personal hygiene, using the toilet, washing, moving on flat surfaces and stairs, dressing, and controlling urine and bowel motions. Each activity is scored 5, 10, or 15 up to a total of 100 points: 0–20 means a severe condition, 20–80 indicates that the patient requires help of various degrees, and >80 denotes an independent patient. The validity, reliability, and responsiveness of this scale have previously been reported, with its Pearson product moment correlation coefficient (PCC) ≥ 0.80 and Cronbach’s α coefficient or intraclass correlation (ICC) ≥ 0.70 denoting high test–retest and inter-rater reliability, respectively . The BI General condition and performance living with cancer was assessed with the Karnofsky Performance Status Scale . This scale assesses the impact of cancer on patients’ activity, taking into account their care and medical needs. A KPS score > 70 means that the patient can continue with normal activities and work with no special care needed; a KPS of 40–70 denotes that the patient is unable to work, can live at home, can care for most personal needs, but that a varying degree of assistance is needed; a KPS < 40 denotes that the patient is unable to care for self and requires the equivalent of institutional or hospital care, and the disease may be progressing rapidly . In a stThe degree of dependence was assessed with amodified Rankin scale . This scale assesses to what extent and in what time dimension the patient requires care. The MRS has been shown to have strong test–retest and inter-rater reliability in different studies . With respect to validity, moderate to strong correlations (Pearson r = 0.60 to 0.86) have also been reported ,31.Impossible to achieve an upright vertical position;Possible to stand with the assistance of the therapist who secures the knees, hips, and trunk;Independent standing, the possibility of supporting with equipment;Gait while learning to walk with a therapist, no the possibility of practical use;Gait with the assistance of another person, but only within a room, accessing the wheelchair, toilet;Gait with the assistance of another person, distance of several dozen meters ;Independent gait with a walking frame;Independent gait with crutches or walking stick;Incorrect independent gait;Correct independent gait.Gait efficiency was assessed with the 10-point scale (Gait Index—GI), graded in 1-point increments:The Bioethics Committee at the Military Medical Chamber approved this scale. This is a simple and easy-to-use scale used by us in the Neurosurgery Clinic to assess gait disorders in everyday practice. This scale has not yet been validated in patients with brain tumors.Secondary variables included the overall LOS, the LOS after surgery, the LOS in the ICU, the number of rehabilitation days, and the incidence of complications affecting the rehabilitation course. The Landriel Ibañez four-grade classification was used to assess the severity and type of complications affecting the course of rehabilitation, where Grade I refers to non-life-threatening complications treated without invasive procedures; Grade II refers to complications requiring invasive management; Grade III refers to complications requiring treatment in the ICU; and Grade IV refers to death due to complications.Assessments were performed by completing an assessment sheet. Each participant was given an individual sheet with an assigned number. In the first part of the assessment, data on hospital stay and surgery, medical record number, date of admission and discharge, date of surgery, number of days in the ICU, number of days of rehabilitation, tumor location, gender, and age were entered. This part was completed on the day of inclusion and was completed on upon discharge (endpoint). The discharge time was 2–90 days in the CH, VS, and CPA groups and 3–8 days after surgery in the control group. The second part of the assessment was about individual motor skills: passive sitting (the patient can spend time in a wheelchair), active sitting , independent standing, and independent gait with or without orthopedic equipment. The results were recorded before the operation on the day of inclusion and the day after surgery on which the patient was able to perform each of them. The third part of the assessment was completed three times: on the day of inclusion, immediately after surgery (day 2–3), and upon discharge. All ten skills assessed by the BI scale and the overall BI, KPS, MRS, and GI scores were noted based on observing and testing the patient according to each instrument. The final part of the assessment was concerned with the complications of the course of rehabilitation: the ability to independently walk with or without orthopedic equipment; which day after surgery the complication appeared; and for how many days it resulted in limiting exercise, verticalization, and leaving the bed. These data in part four were entered on a regular basis. The tests were performed directly by staff working with the patients in the neurosurgery clinic. Researchers had access to all medical records, including the results of specialist consultations, but the most important data were our own based on the performed tests and scales.p-value < 0.05 was considered statistically significant. All calculations were carried out using the Statistica 13.0 PL statistical package .Normal distributions of the study variables were verified with the Shapiro–Wilk test. All data are presented as mean ± SD or number (percentage) participants. Multiple groups were compared by analysis of variance (ANOVA) followed by Tukey’s HSD test or by the Kruskal–Wallis rank-sum test. Differences in quantitative variables were determined with the use of a parametric t-test or a nonparametric Mann–Whitney test. Relationships between categorical variables were determined with Pearson’s chi-squared test. To investigate group and time effects in functional activity, we used a multiple repeated measures analysis of variance (ANOVA) between groups  and with time (before surgery/after surgery/at discharge). A Of 835 patients with brain tumors, the majority  had CH surgery, 96 of whom (14.8%) required rehabilitation; 53 patients (6.3%) had VS tumors, 16 (30.2%) of whom needed postoperative rehabilitation; and 52 (6.2%) patients had CPA tumors, 15 (28.8%) of whom required rehabilitated. There were 81 patients (9.8%) who had tumors at other locations that were not included due to the small sample sizes at each tumor location.Eighty patients after CH tumor surgery (12.3%) required rehabilitation due to limb paresis or paralysis compared with 26.4% patients after VS tumor surgery, and only one patient after CPA tumor surgery. Thirteen patients (25.0%) after CPA tumor surgery, five patients (0.8%) with CH tumors, and one patient with a VS tumor (1.8%) received rehabilitation for facial nerve palsy. Other reasons for rehabilitation included balance and coordination disturbances, general weakness disallowing independent functioning, and apraxia .p < 0.001). Similarly, the VS group spent longer in ICU after surgery compared with the CH group (Six hundred and eighty-five patients (82%) had received first surgery: 518 for CH tumors, 49 for VS tumors, 46 for CPA tumors, and 72 for tumors at other locations. One hundred and fifty patients had received reoperations (18%): 131 for CH tumors, 4 for VS tumors, 6 for CPA tumors, and 9 at other locations. The proportion of first operation and reoperations was similar for all patients  and rehaCH group .Complications affected the course of rehabilitation in 35 patients. Twenty-eight patients had a single complication, four had two complications, and three had three complications. The most common complications were bleeding into the VS and hydrocephalus (seven patients); hematoma, cerebrospinal fluid leakage from the surgical wound, and cardiorespiratory failure in six people; and edema in four people. These complications occurred in 21/96 (21.9%) patients in the CH group ; 13/16 (81.3%) patients in the VS group ; and 1/15 (6.7%) patients in the CPA group . Patients in the VS group had a particularly high complication rate, especially Grade II and III complications, and a higher proportion of surgical complications than medical complications .p < 0.001). There was a significant interaction between group and timepoint, indicating that the effects of time were different for the four groups (p < 0.001). The control group had comparable scores for each instrument, and no significant differences were observed .Two-way repeated ANOVA revealed a difference between groups at different timepoints  for BI, KPS, MRS, and GI , while the patients in the VS group required help (BI = 77.5). After surgery, patients in the CH and CPA groups required help to various degrees , with VS group patients classified as “severe” (BI = 20). Patients in the CPA group returned to pre-surgery levels (independent) at discharge, while patients in the CH and VS groups required help to varying degrees. The control patients in all three assessments were independent according to the BI scale .The mean KPS score before surgery in the CH, VS, and CPA groups classified patients as able to carry on normal activity and work, with no special care needed (KPS > 70). The mean KPS decreased after surgery and the CH and CPA patients were classified as unable to work, able to live at home, care for most personal needs, with a varying degree of assistance needed (KPS 40–70), while the VS patients were unable to care for self (KPS = 35). KPS values at discharge for the CH and VS groups were between 40 and 70, and CPA patients returned to a score > 70. The control patients in all three assessments were classified as able to carry on with normal activities (KPS > 70) .The mean MRS score in the CH and VS groups classified patients as slightly disabled: unable to perform all previous activities but able to look after their own affairs without assistance. Patients in the CPA group were not significantly disabled (MRS = 0.7). After surgery, patients in the VS group had the highest score (MRS = 4.5), denoting severe disability: bedridden, incontinent, and requiring constant nursing care and attention. The scores in CH and CPA patients  meant moderate disability. Patients in the CPA group returned to pre-surgery levels (no significant disability) at discharge, while patients in the CH and VS groups were classified as moderately disabled. In all three assessments, the control patients were not significantly disabled and, despite symptoms, were able to carry out all usual duties and activities .The mean GI score in the CH and VS groups classified patients as independently walking with orthopedic equipment before surgery (GI 7–8), while patients in the CPA group walked independently (GI = 9.5). After surgery, patients in the CH and VS groups could not walk (GI < 5), while CPA patients could walk with the assistance of another person but only within a room and with access to a wheelchair (GI = 5.2). Patients in the CPA group returned to pre-surgery levels (independent gait) at discharge, patients in the CH group could walk with orthopedic equipment, and VS group patients walked with the assistance of another person, but only within a room. The control patients were independent in gait in all three assessments .p < 0.05; The CH and VS groups had significantly lower BI, KPS, and GI scores and higher MRS scores than the control group before surgery. After surgery and at discharge, the CPA group was characterized by higher BI, KPS, and GI scores and lower MRS scores compared to the CH group, respectively (n = 205).The proportion of patients walking independently (GI > 6) decreased by 24% in the CH group and by 31.3% in the VS group on the day of discharge compared with before surgery. The percentage of self-walking patients increased by 6.7% in the CPA group and by 2.5% in the control group . Table 5p > 0.05). The control group was characterized by significantly shorter times for all conditions . VS, CPA, and CH groups were comparable with respect to independent standing and gait  according to all metrics. Patients with VS tumors had a higher proportion of surgical complications, most often required postoperative rehabilitation, and their rehabilitation lasted the longest, resulting in the longest hospital stay.Despite continuous progress in diagnosis and treatment ,33, patiPerioperative complications also impact the results and course of rehabilitation and are reported in anywhere between nine and 40% of patients ,43,44,45Previous studies analyzing the impact of a complication on LOS have usually either focused on a specific tumor type or specific surgical method ,49,50. OEach scale used here assessed a different aspect of activity: KPS, the performance status in the context of cancer; MRS, the degree of dependence on other people; and BI, independence in ADL. These scales have been used by some authors to predict postoperative function and hospital discharge time ,58,59. OOur results are unequivocal due to several factors. First, VS tumors can disrupt the functions of brain regions important to the whole organism . Second, an intraventricular location is always a deep site. When a tumor cannot be removed endoscopically, access to it often poses a risk of greater damage to the brain tissue located in the access path compared to other locations. Different surgical approaches to the ventricles can be used, namelythe telovelar approach, the transvermian trajectory, and the tonsillobiventral fissure approach. The selection of the surgical approach for intraventricular tumor resection fundamentally depends on the surgeon’s experience and preference. Third, hemostasis during VS tumor surgery is difficult as some agents cannot be used in the ventricular system and due to reduced blood clotting in the CSF environment. Fourth, patients receiving surgery at this site frequently need a postoperative ventricular drain, which increases the risk of CNS infection and prolongs the ban on verticalization and delays the start of intensive rehabilitation. Finally, these tumors often result in hydrocephalus, which may require further surgical intervention ,17,63,64Our study has some limitations. First, the group sizes were very different (reflecting the incidence of tumors at these locations); thus, despite the clear differences between groups, there may be bias. Our study was single-center and, although covering 1.5 years and involving 835 patients, represents a relatively small number of patients, since only 16.6% required postoperative rehabilitation. The tumor size, histology, type, and precise location were unknown, and these parameters would be interesting to study with respect to function. The surgical approach was another important factor to consider, but we did not analyze this on the assumption that in each individual case, the choice was optimal. Finally, we did not use information on some important neurological parameters such as the degree of paresis before and after surgery, which was beyond the scope of this article. Future studies should also assess the impact of complications arising from first surgery or re-operation, a subgroup we excluded due to a lack of statistical power.Patients receiving operations for VS tumors had the worst motor function and independence in daily activities before surgery, and this group deteriorated both immediately after operation and at discharge according to all metrics. Postoperative complications were also most common in this group. Patients with VS tumors most often required postoperative rehabilitation, and their rehabilitation lasted the longest, which resulted in the longest hospital stay. VS tumor patients represent a rehabilitation challenge in a neurosurgical unit, and postoperative rehabilitation planning must take the tumor site and preoperative condition into account.


Excluding persons from magnetic resonance imaging (MRI) research studies based on their medical history or because they have tattoos, can create bias and compromise the validity and generalizability of study results. In the population-based Rhineland Study, we limited exclusion criteria for MRI and allowed participants with passive medical implants, tattoos or permanent make-up to undergo MRI. Thereby, we could include 16.6% more people than would have been possible based on common recommendations. We observed no adverse events or artifacts. This supports that most passive medical implants, tattoos and permanent make-up are MRI suitable and can be scanned in research settings. Millions of MRI scans are acquired every year in the US and adverse reactions of medical implants for MRI are rare. The U.S. Food and Drug Administration (FDA) receives only 300 reports on adverse events yearly . Most oformation . Howevern = 330) showed that there is only a low risk for adverse reactions in persons with tattoos, this study still excluded persons with larger or neck or head tattoos , tattoos and permanent make-up to undergo 3 T MRI.The study is based on the first 5,000 participants of the Rhineland Study, a prospective, single-center, community-based cohort study. We invite all inhabitants aged above 30 years from two geographically defined areas in Bonn, Germany, to participate in the study. The sole exclusion criteria was inability to provide informed consent.Approval to undertake the study was obtained from the ethics committee of the University of Bonn, Medical Faculty. The study is carried out in accordance with the recommendations of the International Council for Harmonization Good Clinical Practice standards. We obtain written informed consent from all participants in accordance with the Declaration of Helsinki.We established an MRI expert committee that developed the procedure for clarification of MRI suitability. This committee included scientists from Population Health Sciences  and MR Physics (TS) from the DZNE, Bonn, and the Clinic for Neuroradiology , University Hospital Bonn. Depending on the nature of the implants, other experts were consulted .Our procedure was as follows : Active One year after the introduction of this procedure, the MRI expert committee evaluated it. During this period, 169 participants with medical implants had been discussed by the expert committee and subsequently been scanned without any problems. Based on these experiences, the MRI expert committee made a list of medical implants that from then on could be considered as MRI suitable by the study technicians without further consulting the MRI expert committee. This list included the following medical devices, if implanted after 2005, with or without relevant medical documentation: hip and knee replacements, stents, bypass, clips, breast implants filled with silicone, and screws, plates and stiffening of the spinal cord < 13 cm. The 2005 cut-off was chosen because in recent years such implants are typically made of titanium. A medical implant had to be implanted at least 6 weeks before the MRI examination.All eligible participants underwent a one-hour MRI examination of brain structure and function on 3 T MRI scanners . The scanners were equipped with an 80 mT/m gradient system and a 64-channel phased-array head-neck coil. All MRI sequences and protocols were either developed in-house for the purpose of the Rhineland Study or based on Siemens product sequences. The MRI protocol included the following sequences: a 3D T1-weighted Multi-Echo Magnetization Prepared RApid Gradient-Echo sequence  , 15, a 3Before the MRI examination, we verbally informed all participants with medical implants, non-removable jewelry, tattoos and/or permanent make-up about the possibility of adverse events, including tingling sensations, (slight) heating, and burning. They were instructed to squeeze the alarm ball during the MRI examination as soon as they would feel any tingling sensation. In case of an adverse reaction, we would ask about their symptoms and document these as well, and provide first aid if needed.For participants with head implants or permanent make-up, we checked all scouts for possible artifacts which would require immediate stopping of MRI data acquisition. For permanent make-up, this would include any artifacts on the scouts, for head implants any artifact that would make the scan of the brain unreadable. Additionally, all T1-weighted, T2-weighted, and FLAIR scans have been visually inspected for quality during the initial quality assessment of the Rhineland Study, where two raters independently checked for artifacts that might affect the quality of automated brain segmentations.n = 305 and n = 544, respectively)  .In total, 4,259 (85.2%) participants were considered eligible for MRI, of whom 3,639 (85.4%) were actually scanned . Of thoParticipants had up to six medical implants, mostly plates, screws, stents, clips, or hip- or knee-replacement , which w2 (IQR: 30–450 cm2), ranging up to 7,960 cm2, with 72 (17.7%) tattoos being larger than 20 cm in dimension  per person ranged from one to eight, at in total 532 individual body locations. Most frequent locations were on the torso (33.8%), arms (20.5%), or legs  . The majimension . We scanimension . Most taNone of the participants reported adverse events nor was the quality of any of the MR scout images reduced by any implants or permanent make-up. There were no artifacts seen during the initial quality assessment due to permanent make-up or medical implants in the head which made the brain images unreadable.n = 108, neck: n = 15, genital area: n = 2), tattoos covering more than 5% of the total body area (n = 28), tattoos bigger than 20 cm in diameter (n = 60), or tattoos <20 cm apart from each other (n = 21) (multiple reasons possible)  .If we had followed most recent recommendations by the FDA that require an MRI safety certificate , we woulThus, compared to these established practices and FDA guidelines we classified an additional 830 participants with tattoos or medical implants (45 had both) as MRI eligible (16.6% of our source population). Of these, 703 participants underwent MRI.Of note, the FDA guidelines can be interpreted more loosely, allowing for an implant to be identified as MRI suitable based on other medical documentation. Had we used those criteria, we still would have had to exclude 589 of our 810 participants with passive medical implants.With our given sample size for tattoos and medical implants, we would be able to detect with 90% confidence adverse reactions in 0.8 and 0.4%, respectively, and with 80% confidence in 0.5 and 0.3%, respectively.In this large population-based study, we allowed participants with passive medical implants without MRI safety certificates, tattoos, or permanent make-up to undergo 3 Tesla MRI. We did not observe any adverse events or artifacts that notably reduced quality of the brain scans. Through our relaxed MRI eligibility criteria, we could include 16.6% more people than would have been possible based on FDA guidelines .Older case reports described adverse reactions in people with tattoos undergoing MRI –11, yet www.mrisafety.com. Nevertheless, it is essential to be able to identify medical implants in order to confirm eligibility. We found that <0.5% of those with a passive medical implant had an MRI safety certificate. Most of our participants had no relevant documentation to identify the medical implant, and would therefore have been excluded had we strictly followed the FDA recommendations. We were able to classify two thirds of these participants as MRI eligible, based on information the participant provided verbally. In the excluded cases, participants could not tell us what exact procedures they underwent nor when. Therefore, we could not out rule any potential risks for the participant to undergo MRI.The FDA recommends to exclude people from MRI for research purposes if their medical implant cannot be identified as MRI eligible . Of courwww.mrisafety.com  research studies establish MRI expert panels to determine MRI safety of passive devices, incorporating recent advances in the scientific communities [e.g., ISMRM , tattoos, and permanent make-up are eligible for 3 Tesla MRI research studies. Our procedure could guide new research studies in the clarification of MRI suitability. This is crucial to reduce selection bias in, and thereby increase generalizability and validity of, MRI research studies.RS-DUAC@dzne.de.The datasets presented in this article are not readily available because of data protection regulations. Access to data can be provided to scientists in accordance with the Rhineland Study's Data Use and Access Policy. Requests to access the datasets should be directed to Rhineland Study's Data Use and Access Committee, The studies involving human participants were reviewed and approved by University of Bonn, Medical Faculty. The participants provided their written informed consent to participate in this study.VL, EH, TS, and MB contributed to conception and design of the study. VL performed the statistical analysis and wrote the first draft of the manuscript. All authors contributed to data acquisition and analysis, manuscript revision, and read and approved the submitted version.The Rhineland Study at the DZNE is predominantly funded by the Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine-Westphalia.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.


Background: The high levels of serum calcium and cholesterol are the important risk factors of cardiovascular disease (CVD), which frequently influence each other during the development of CVD. However, few studies have examined their temporal relationship to confirm the precursor, and it is still largely unknown whether and how their temporal relationship would influence the development of CVD. This study aimed to establish the temporal relationship between the changes in serum calcium and cholesterol using the longitudinal cohort data, and examine whether this temporal relationship influenced the arterial elasticity indicated by brachial-ankle pulse wave velocity (baPWV).Methods: This is a cohort study with a sample of 3,292 Chinese participants (aged 20–74 years) with 5.7 years follow-up. Serum calcium and cholesterol were measured at baseline and follow-up survey. The cross-lagged path analysis was used to examine their temporal relationship, and mediation analysis was performed to evaluate the potential mediating effect.Results: The cross-lagged path coefficients  from baseline serum calcium to follow-up cholesterol was significantly greater than the path coefficients  from baseline cholesterol to follow-up serum calcium  after adjusting for the multiple covariates. The path coefficients from baseline serum calcium to follow-up cholesterol in the participants with high baPWV was significantly greater than the participants with low baPWV . Moreover, cholesterol partially mediated the association between the higher serum calcium and greater subsequent baPWV values, the percentage of the total effect mediated by cholesterol was estimated at 21.7%.Conclusion: Our findings indicate that increased serum calcium precedes increased in serum cholesterol, and this temporal relationship may contribute to the development of higher baPWV levels. A few pathway , whereas pathway , indicatThe cross-lagged path analysis is a statistical method that is frequently used to dissect the temporal relationship among the closely related variables. A series of recent studies have successful used this method to establish the temporal relationship between the two closely related biochemical indicators for confirming the priority therapeutic targets for the prevention of diabetes, hypertension, or CVD –10. TherData were drawn from the Harbin Cohort Study on Diet, Nutrition, and Chronic Non-communicable Disease Study (HDNNCDS) , carried out in 2010 with a follow-up in 2015–2016 . The HDNData on the dietary habits and lifestyles, physical activity level, smoking, and drinking status were collected using the face-to-face questionnaires answered by the participants. Regular exercise was defined as any type of recreational or sports other than walking performed 3 or more days per week for at least 30 min. The current smokers were defined as those who smoked at least 100 cigarettes in a lifetime or smoked every day. The current drinkers were defined as those who consumed ≥1 alcoholic drink each month in the past 1 year before the survey.2). The blood samples were collected from all the participants at both the baseline and follow-up surveys. The blood samples were collected and immediately centrifuged at 2,500 g for 15 min to obtain serum and were then cooled. After collection, the plasma samples were kept in a portable, insulated bag with ice packs (at about 0–4°C) and were processed within 6 h for long-term storage at −80°C. The blood sample repositories for the study are equipped with the appropriate alarm systems and emergency electricity backup to prevent the accidental thawing. Serum calcium, total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automatic biochemistry analyzer . The chemical reagents of analytical grade were used . All the analytical methods were controlled according to the instructions from the manufacturer by preventive maintenance, function checks, calibration, and quality control.The height and weight were measured with the participants wearing light, thin clothing, and no shoes. The height and weight were measured to the nearest 0.1 cm and 0.1 kg, respectively. Body mass index (BMI) was calculated as weight (kg) divided by the square of the height in meters . The technicians from our center were all similarly trained and accredited. The subjects were instructed not to take any medications, alcohol, or caffeine on the day of the examination. After rest in supine position for 10 min, the subjects remained in supine position while the cuff is attached to the plethysmographic and oscillometric sensors placed around both the arms and ankles. The baPWV was measured two times automatically and the mean of the right and left PWVs was calculated as the representative baPWV .The serum calcium and cholesterol were measured at two time points, which is a typically cross-lagged panel design. To improve the normality of the distribution serum calcium and cholesterol were log transformed at the baseline and follow-up. The generalized linear models were performed to test differences in the continuous variables between the high baPWV group and low baPWV group.CI with adjustment for age, sex, BMI, smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of cardiovascular disease, TG, HDL-C, LDL-C, and drug use for hypertension or dyslipidemia.The baseline serum calcium and cholesterol were grouped by quintiles, and the differences between the follow-up serum calcium or cholesterol and the baseline serum calcium or cholesterol were calculated , which were then grouped by the median values. The logistic regression models were performed to calculate the relative ratio (RR) and 95% Z transformation . The theoretical model of cross-lagged path analysis assumes that if the relationship between the changes in serum calcium and cholesterol was bidirectional, then they can predict each other, and their cross-lagged path coefficients will not be significantly different. However, if the changes in serum calcium and cholesterol have an underlying causal relationship, then the causal variable can predict the consequent variable, and the cross-lagged path coefficient of the causal variable will be significantly greater than that of the consequent variable. The path coefficients for β1 represented the baseline cholesterol on subsequent serum calcium, and the path coefficients for β2 represented the baseline serum calcium on subsequent cholesterol. Fisher's Z test was used to test the difference between β1 and β2 derived from the standardized variables. The root mean square residual (RMR) for which values < 0.05 and comparative fitness index (CFI) for which values >0.90 reflect a good fit  and LISREL 8.52. A two-sided p-value < 0.05 was considered statistically significant.After determining the temporal relationship between serum calcium and cholesterol, a causal mediation model was constructed to examine whether the association of serum calcium with value of baPWV was mediated by cholesterol after adjusting for age, sex, BMI, smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of CVD, TG, HDL-C, LDL-C, and drug use for hypertension or dyslipidemia. The baseline serum calcium was the predictor variable (X); follow-up cholesterol was mediator (M); follow-up value of baPWV was the outcome variable (Y). A mediation analysis was performed using the R package Lavaan . The anaP < 0.001), and have greater BMI , energy intake , the serum calcium levels ,cholesterol level , TG , LDL-C , higher smoking rate , exercise frequency , drug use for hypertension , and dyslipidemia  rate at the baseline. The high baPWV group have greater serum calcium levels and cholesterol levels than the low baPWV group at follow-up.This analysis consists of 3,292 participants who measured serum calcium and cholesterol at the baseline and follow-up. The characteristics of the studied population by the high baPWV group and low baPWV group are presented in RR = 2.11, 95% CI: 1.74–2.55). Similarly, compared with the participants in the lowest quintile of serum cholesterol, the participants in the highest quintile are more likely to have greater increased in serum calcium . These results suggested that the conventional analysis models could not dissect the temporal relationship between the changes in serum calcium and cholesterol. The cross-lagged path analysis of serum calcium and cholesterol is shown in 2 = 0.110, 95% CI: 0.077–0.156, P < 0.001) is significantly greater than the path coefficient from the baseline cholesterol to the follow-up serum calcium  after adjusting for age, sex, BMI, smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of CVD, TG, HDL-C, LDL-C, and drug use for hypertension or dyslipidemia with P < 0.001 for difference between β1 and β2. The models are relatively well fitted in our analysis, RMR and CFI were 0.017 and 0.989, respectively. The variance of follow-up serum calcium and cholesterol (R2) explained by the baseline serum calcium and cholesterol are estimated at 0.10 and 0.25, respectively.Compared with the participants in the lowest quintile of serum calcium, the participants in the highest quintile are more likely to have greater increased in the serum cholesterol with adjustment for the potential confounders such as the baseline serum cholesterol (CI: 0.724–0.754).2 = 0.155, P < 0.001) from the baseline serum calcium to follow-up cholesterol in the high baPWV group are greater than that  in the low baPWV group, but not significant . The model fitting parameters are RMR = 0.013 and CFI = 0.977 in the high baPWV group, and RMR = 0.018 and CFI = 0.971 in the low baPWV group.Tot = 0.060; P < 0.001) is estimated without cholesterol in the model. The overall indirect effect of cholesterol was calculated by β1 and β2 . The percentage of the total effect mediated by cholesterol is estimated at 21.7%.After adjusting for age, sex, BMI, smoking, alcohol consumption, regular exercise, marriage, caloric intake, family history of CVD, TG, HDL-C, LDL-C, and drug use for hypertension or dyslipidemia, the mediation effects of follow-up cholesterol on the association between the baseline serum calcium and follow-up value of baPWV is shown in P < 0.001). The overall indirect effect for cholesterol is 0.008 (P < 0.001). The percentage of the total effect mediated by cholesterol is estimated at 29.6%. The third sensitivity shows that after excluding the participants who took antihypertensive or cholesterol-lowering drugs, the unidirectional relationship from the increased in serum calcium to cholesterol is still observed  directly affect the function of vascular endothelial cells; (2) promoting the proliferation of the smooth muscle cells –31. In vferation . Other sadhesion .Further, the results of mediation analysis also indicated that cholesterol partially mediated the correlation between the serum calcium and further increased the arterial elasticity or incidence of CVD, providing some evidence for the pathogenesis of CVD. These results are consistent with a previous study, which suggested that the accumulation of cholesterol in the smooth muscle cells is an important contributor to the early stimulus initiating atherogenesis in the vessel wall, calcium channel blockers would have protective effect on atherosclerosis . Based oIn this study, we established the temporal relationship between the serum calcium and cholesterol by the cross-lagged path analysis, and further performed the mediation analysis, suggesting that the unidirectional relationship from calcium to cholesterol was linked to incident CVD. However, we also recognized that this study has several limitations. First, this study only included the Asian subjects, which is likely to limit the generalizability of our findings to other ethnic populations. Second, finding from the other studies prove that the genetic variants related to the serum calcium levels is associated with coronary artery disease and myocardial infarction . The futIn summary, this longitudinal cohort study confirms the unidirectional relationship between the serum calcium and cholesterol, and that the higher serum cholesterol levels partially mediated the association between increased in serum calcium and increased in arterial elasticity or incidence of CVD. These findings add evidence for understanding the potential pathophysiological mechanisms for the serum calcium-CVD association. Also, this study highlights serum calcium as a possible therapeutic target for the prevention of hypercholesterolemia and CVD. Management of the serum calcium levels may be an effective strategy for reducing the risk for CVD, and cholesterol is likely a reasonable therapeutic target of CVD induced by the high serum calcium levels.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Institutional Review Boards of Harbin Medical University. The patients/participants provided their written informed consent to participate in this study.HS, WW, and YY conceived and designed the experiments. XM and TH performed the experiments. WJ and FD analyzed the data. XM wrote the paper. HS was involved in designing the experiments. All authors have read and approved the final manuscript.This work was supported by the funds from the Harbin Medical University Innovation Research Fund (2020-KYYWF-1443).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.


Fatigue is a common and disabling non-motor symptom (NMS) of Parkinson’s disease (PD); however, it has been poorly understood in patients with progressive supranuclear palsy (PSP). We investigated the association between fatigue, clinical features, and other NMS in patients with probable PSP. In 72 probable PSP patients, fatigue was investigated using the Parkinson Fatigue Scale (PFS). Further, all patients were evaluated using the PSP rating scale (PSPRS), Beck Depression Inventory (BDI), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), PD Sleep Scale (PDSS), NMS scale (NMSS), PD Questionnaire-39 summary index (PDQ-39 SI), and Scale for outcomes in PD-Autonomic (SCOPA-AUT). The prevalence of fatigue assessed by PFS was 38.9% (28/72) in patients with PSP. The secondary fatigue was defined as fatigued patients with depression and/or sleep disturbances. We divided the patients into primary (n = 15), secondary (n = 13), and non-fatigue groups. There were no differences in age, sex, disease duration, and PSPRS, PDSS, MMSE, and FAB scores among the three groups. The primary fatigue group had higher scores in PDQ-39 SI compared to the non-fatigue group. The secondary fatigue group showed higher scores in NMSS, PDQ-39 SI, and SCOPA-AUT compared to the non-fatigue group. PFS was positively correlated with NMSS and PDQ-39 SI and SCOPA-AUT. Fatigue is common in patients with PSP and is associated with the NMS and the quality of life in these patients. The present study provides meaningful insight into fatigue in patients with PSP. Patients with PSP not only have motor symptoms but also exhibit various non-motor symptoms (NMS), such as cognitive decline, urinary symptoms, emotional problems, and fatigue2. Fatigue is a disabling symptom in various movement disorders including Parkinson’s disease (PD), and studies showed that fatigue significantly affects the patients’ quality of life (QoL)5. Several studies have investigated NMS including fatigue in patients with PSP and reported that sleep/fatigue problems are common in these patients, with a prevalence of 82.9–100%9. However, none of the previous studies used the specialized scale to assess fatigue, and their results were based on the non-motor symptoms scale for PD (NMSS). The NMSS contains a subdomain for evaluating sleep/fatigue; however, it is difficult to precisely measure fatigue and its severity because only one of the four questions included in this domain is related to fatigue (does fatigue or lack of energy limit the patients’ daytime activities?)10. Generally, fatigue is described as an overwhelming feeling of tiredness and exhaustion occurring in the context of various neurological diseases3. Fatigue has been inconsistently used in previous studies, and it is difficult to define fatigue because it is subjective and various factors such as mood disorders, sleep disorders, orthostatic hypotension, and anemia can affect fatigue5.Progressive supranuclear palsy (PSP) is a rapidly progressive neurodegenerative disease characterized by supranuclear gaze palsy, frequent falling, and parkinsonism5. Moreover, we also investigated the associated clinical features, including other NMSs.Thus, fatigue is a common NMS in patients with PSP. Specialized studies focused on fatigue and investigation of its clinical impact are needed to improve the understanding and management of this disabling symptom. Herein, we investigated fatigue in patients with probable PSP using the Parkinson Fatigue Scale (PFS), which is a specialized scale for assessing fatigue13. Fifteen patients  were included in the primary fatigue group and thirteen patients  were included in the secondary fatigue group . The demographic characteristics of the enrolled patients are shown in Table There were no significant differences among the primary, secondary, and non-fatigue groups in terms of age, sex, disease duration, PSP subtype and PSPRS. The BDI of the secondary fatigue group was higher than that of the other groups. The proportion of the patients who taking antidepressants were not differ among the three groups. The MMSE, FAB, and PDSS scores were not different among the three groups. The NMSS of the secondary fatigue group was higher than the primary and non-fatigue group, but there was no difference between the primary and non-fatigue group. In terms of the PDQ-39 summary index (PDQ-39 SI), the secondary fatigue group showed the highest score, followed by the primary and non-fatigue group. Regarding the SCOPA-AUT, differences were only observed between the secondary fatigue and non-fatigue groups Table .p = 0.001) was significantly associated with fatigue, but other factors did not show a significant association   based on the presence of depression, and thereby, we were able to minimize the confounding effects of depressive mood.9. Chaithra et al. investigated the NMS in patients with PSP using NMSS and reported that sleep/fatigue was the most common NMS in these patients, with a prevalence of 82.9%7. Ou et al. also investigated the NMS in patients with PSP using NMSS and reported that 100% of these patients (27/27) had sleep/fatigue symptoms6. However, none of these five studies used the specialized scale for assessing fatigue. Four out of the five studies used sleep/fatigue domains of NMSS8 and the other study used a simple question to investigate fatigue9. Although the sleep/fatigue domain of NMSS consists of questions about sleep and fatigue, it might not be sufficient to assess fatigue. Our result, which showed a much lower prevalence of fatigue in patients with PSP, supports this contention. Interestingly, there were no differences in the sleep/fatigue domain of NMSS between the primary and non-fatigue groups, and the sleep/fatigue scale was not correlated with PFS. Only the secondary fatigue group, in which patients had fatigue and depression simultaneously, showed a higher NMSS sleep/fatigue domain score than the primary and non-fatigue groups , but the prevalence of fatigue was much lower than that reported in previous studies (from 82.9 to 100%)4. In PD, fatigue is believed to be an intrinsic symptom rather than a secondary or reactive symptom, because it may precede the motor symptoms and did not correlate with disease duration or motor disability14. Previous studies investigating fatigue in PD suggest that fatigue is not simply related to the striatal dopaminergic system but is also associated with the imbalance between different neurotransmitters. Studies on PD suggest that the serotonergic system may contribute to the development of fatigue; however, further investigation is needed to explain the pathophysiology15. As with PD, the present study showed that fatigue in patients with PSP is not associated with disease duration and disease severity (PSPRS). Instead, fatigue in patients with PSP showed a positive correlation with NMSS. Furthermore, a previous study investigating prodromal symptoms of PSP showed that 10% of patients with PSP had fatigue before the diagnosis of PSP, similar to that observed in PD16. These results suggest that fatigue in PSP might not only be related to the dopaminergic system but also to the non-dopaminergic system, as in PD. However, there is a paucity of evidence regarding fatigue in PSP; therefore, further studies are required to understand the pathophysiology of fatigue in PSP.The pathophysiology of fatigue in neurological diseases, including PD, has not been well studied18. Therefore, it is unclear whether all the patients who taking antidepressants had depression or not.The logistic regression model of the present study showed that BDI play a crucial role in fatigue. Nevertheless, there was no difference in the use of antidepressants among the groups. The results suggest that the effect of taking antidepressants on NMS is minimal, and fatigue and depression may be more important on NMS of PSP. Total of 72 patients, 22 of whom had depression and only 8 of them (36.4%) was taking antidepressant. It suggests that depression in PSP might be undertreated because of the side effects, or the lack of awareness. There are few other possibilities associated with the using the antidepressants. Last, the antidepressants can be used for the behavior control in PSP, not just for the depression as used in frontotemporal lobe dementia in clinical practice4. Several medications such as methylphenidate, dopaminergic medications, and antidepressants have been suggested for the treatment of PD-associated fatigue4. Generally, patients with PSP exhibit a poor response to dopaminergic replacement therapy, and this therapy has a limited effect on these patients19. Given that secondary fatigue patients with depression have worse QoL than non-fatigue patients, antidepressants would be worth trying. The other possibility is that the secondary fatigue patients likely to represent the PSP patients who had higher non-motor burden, not just simply ‘depressive fatigued patients’. However, it needs more investigations to reveal the association between the depression, fatigue, and other NMS in PSP.Both the primary fatigue and secondary fatigue groups had worse QoL (PDQ-39 SI) than the non-fatigue group, despite the lack of differences in PSP-related symptoms (PSPRS). Our results suggest that primary and secondary fatigue can worsen the QoL of patients with PSP. Thus, improving fatigue can help to improve the QoL of patients with PSP. Unfortunately, fatigue in parkinsonism is poorly understood, and its treatment is limited20. However, not all scales, including PFS, have been validated for patients with PSP. We believe that PFS is the most reliable scale for assessing fatigue in patients with PSP, considering the clinical similarity between PSP and PD. Moreover, several scales have been suggested as an assessment tool for PSP in patients with PD, although these scales have not been validated in PSP21.Several scales have been introduced for the assessment of fatigue. The PFS is a specialized scale for measuring fatigue in PD patientsIn conclusion, fatigue is a common NMS in patients with PSP and is correlated with other NMS and QoL in these patients. The pathophysiology and clinical impact of fatigue in patients with PSP are largely unknown. The first step in the treatment of fatigue is the identification of symptoms and investigation of the associated factors. In this aspect, the present study provides meaningful insight into fatigue in patients with PSP. Further studies are needed to reveal the pathophysiology of fatigue in patients with PSP and to develop novel treatment modalities.1. The inclusion criteria were: (1) age 40 to 80 years, (2) decreased DAT uptake in the striatal dopaminergic depletion determined using 18F-radiolabeled N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane PET, and (3) Mini-Mental State Examination (MMSE) score ≥ 2123. Patients who had any of the following conditions were excluded: (1) cancer, hypo- or hyperthyroidism, liver cirrhosis, chronic kidney disease, and (2) history of relevant head injury, cerebrovascular diseases, or musculoskeletal diseases. This study was approved by the Institutional Review Board of the Samsung Medical Center, and all subjects provided written informed consent. All methods were performed in accordance with the relevant guidelines and regulations.Patients with PSP who visited the Movement Disorders Clinic of the Samsung Medical Center between January 2018 and December 2020 were recruited. PSP was diagnosed based on the Movement Disorders Society criteria, and patients with probable PSP were included in the study24. Parkinson Fatigue Scale (PFS) was used to assess fatigue20. We also assessed the patients using the Beck Depression Inventory (BDI)11, MMSE23, Frontal Assessment Battery (FAB)25, PD sleep scale (PDSS)26, non-motor symptom scale (NMSS), PD questionnaire-39 (PDQ-39)27, and scale for outcomes in PD-autonomic (SCOPA-AUT)28. Fatigue was considered when the mean PFS was ≥ 3.320. The patients were divided into the primary fatigue and secondary fatigue group, referred to the previous study12. The fatigued patients who without depression (BDI < 16)29 and without sleep disturbance (PDSS > 82)30 classified as primary fatigue, and who had any one of two-condition classified as secondary fatigue.Patient demographics including age and sex, and information on disease duration, diagnosis, and comorbidities were collected. The PSP-rating scale (PSPRS) was used to assess all enrolled patients by movement disorder specialists13. Demographic and clinical features were compared using the analysis of variance (ANOVA) test, chi-square test, or Fisher’s exact test, depending on the variable. We also performed the logistic regression analysis to determine the factors associated with fatigue. The association between PFS and other investigated scales was analyzed using Pearson partial correlation analysis, adjusting for potential confounders . Bonferroni’s correction was performed to correct for multiple comparisons. All tests were two-tailed, and the α level was set to p < 0.05. Statistical analyses were performed using IBM SPSS for Windows .The normality of the data was evaluated using the Shapiro–Wilk test. We included the following covariates in the logistic model: age, sex, disease duration, PSPRS, BDI, MMSE, FAB, and daytime sleepiness (item 15 score of the PDSS)Supplementary Information.


In this pilot comparative study, we investigated and compared the effects of existing vector control tools on sandfly densities and mortality to inform and support the National Kala-azar Elimination Program (NKEP). The interventions included insecticidal wall painting (IWP), reduced-coverage insecticidal durable wall lining (DWL), insecticide-impregnated bednets (ITN), and indoor residual spraying with deltamethrin (IRS). Sakhua union with seven villages was the study area, which was the most highly endemic visceral leishmaniasis union in Trishal upazila, Bangladesh. Each cluster containing the different interventions included approximately 50 households. Study methods included random selection of clusters, collection of sandfly by CDC light trap and manual aspirator to determine sandfly density, and sandfly mortality determined by WHO cone bioassay test. Trained field research assistants interviewed household heads using structured questionnaires for sociodemographic information, as well as safety and acceptability of the interventions. Descriptive and analytical statistical methods measured interventions’ effect and its duration on sandfly density reduction and mortality. We measured the relative efficacy of IWP on sandfly control against DWL, ITN, and IRS by the difference-in-difference regression model. We found that existing interventions were effective and safe for sandfly control with different duration of effect and acceptability. The relative efficacy of IWP for sandfly reduction varied by –59% to –91%, –75% to –81%, and –30% to –104% compared with DWL, ITN, and IRS, respectively, at different time points during the 12-month follow-up. These study results will guide the NKEP for selection of sandfly control tool(s) in its subsequent consolidation and maintenance phases. Leishmania donovani and is transmitted by female Phlebotomus argentipes sandflies. In the Indian subcontinent, the disease is endemic, and its presence has been documented since the 19th century where the first reported VL outbreak was in 1824 in the territory of current Bangladesh. During this period, VL caused the deaths of 75,000 people over 3 years.Visceral leishmaniasis (VL) or kala-azar (KA) is a vectorborne disease caused by Nevertheless, the ongoing National KA elimination program (NKEP) demonstrates that the VL incidence can be reduced using existing tools for diagnosis, treatment, and vector control with the government’s commitment and support from development partners.,,,,Early detection and management of VL cases, vector control, disease surveillance, community participation and partnership and operational research were the key elements of the attack phase. Although the strategies for subsequent phases are yet to be defined, effective sandfly control is required for the success of the subsequent phases. During the malaria eradication era from 1960 to 1970, VL disappeared from Bangladesh.In this study, we compared the performance of IWP against existing sandfly control tools including DWL, ITN, and IRS.The trial ID is ClinicalTrials.gov ID: NCT03269006.The study was a comparative study carried out from November 2015 to January 2017 in the Trishal upazila of Mymensingh. Trishal has 12 unions  in which five were VL endemic. We selected seven villages the Sakua union for this study because it had the highest VL burden based on the previous 12 months hospital  reports. We divided each village into clusters, each cluster with approximately 50 households (HHs). One cluster from each village was randomly selected, from which we randomly selected 36 HHs for conducting entomological activities. Baseline sandfly measurements (sandfly density) were determined in all seven clusters 2 to 4 weeks before the interventions. Of these seven clusters, four were selected randomly, and interventions were also allocated in the selected four clusters randomly (one intervention for each cluster) where IWP was the intervention of interest for comparison with DWL, ITN, and IRS . Trained2. The formulation is vinyl paint with an aqueous base, with the active ingredients CaCO3 and resin microcapsules, allowing a gradual release of active ingredients. Microcapsules range from one to several hundred micrometers in size. Once painted, the expected concentration of insecticide per square meter surface area of the wall should be 1.225, 1.75, and 0.11 g/m2, respectively, for alphacypermethrin, D-allethin, and pyriproxyphen.Experts from Inesfly, Valencia, Spain, trained field research assistants (FRAs) in painting of different type of HH walls following manufacturer’s standard operating procedures. FRAs painted 56 HHs under the IWP study arm with Inesfly 5AIGRNG TM containing alphacypermethrin 0.7%, D-allethin 1.0%, and pyriproxyphen (0.063%) with a coverage of 2.43 m2.Trained FRAs installed DWL up to 1-m height from floor  in the indoor walls of the main room in 55 HHs in this arm. The commercial DWL is deltamethrin-impregnated DWL containing deltamethrin at 170 mg a.i./mNinety-five existing bednets in 52 HHs in the ITN arm were impregnated following manufacturer’s instruction .54 HHs received IRS by the deltamethrin 5 WP  and sprayed up to 6 feet (180 cm) of the indoor walls by the research team at month zero.The NKEP conducted routine IRS approximately 6 months after the start of the study in the study villages except the houses covered by the study interventions.Entomological activities included sandfly collection and sandfly density measurements at baseline (2–4 weeks) before intervention, and after interventions at 1, 3, 6, 9, and 12 months in 36 HHs in each arm. Sandfly mortality assays were performed by the WHO Cone bioassay test in 12 HHs in each arm after intervention at 1, 3, 6, 9, and 12 months.pm to 6 am, 2 inches away from the wall with a distance of 6 inches between the floor and the bottom of the sac. We defined sandfly density in a HH by the number of P. argentipes per HH for 2 nights and cluster female P. argentipes sandfly densities (FPAD) by the mean of the FPAD per HH in the cluster. The study entomologist performed sandfly identification following taxonomic keys by Lewis ,Study entotechnicians collected sandflies on two consecutive nights with CDC light traps with guidance from a member of the study team. Light traps were placed in a corner of the house from 6 Study entotechnicians conducted the WHO cone bioassay test under supervision of the study entomologist using the cone method (WHOPES 2005.11)The efficacy of IWP was determined by 1) the percent reduction of sandfly density by IWP compared with DWL, ITN, and IRS; 2) percent sandfly mortality by IWP, DWL, ITN, and IRS assessed by the WHO cone bioassay test.We calculated sample size assuming 55% of sandfly density reduction compared with that by DWL, ITN, and IRS, anticipating a study power of 80% with 5% level of significance. The required number of HH was 32 per intervention. We included 36 HHs per intervention in alignment, with the sample size calculation.The data management assistants entered data into Epi Info Version 3.5. Before data analysis, variables related to HHs’ socioeconomic demographics, presence of domestic animals, and protection practice from sandfly and mosquito bites were dichotomized. Household asset scores were generated by principal component analysis (PCA) using the following variables: electricity, television, khat/choki, mattress, bednet, motorcycle, bicycle, rickshaw, shallow machine, dheki, crushing mill, fishing net, store, chair/table, mobile phone, clock, almirah, researve shari, sewing machine, and fishing hatchery. Initially, we categorized PCA assets score into tertile: low, medium, and high. Then we merged medium and high into one category as “medium/high.” A data analyst checked the nature of the data by descriptive analysis, used parametric and nonparametric methods where applicable for comparing between means and performed a chi-square test to compare between proportions.We investigated the association of the cluster FPAD with baseline characteristics of HHs in each cluster. Baseline and follow-up FPAD of the cluster were plotted to investigate the trend of the FPAD in the cluster. The FPAD of the cluster at each time point during follow-up was compared with its baseline FPAD to calculate percent reduction in FPAD in the cluster during follow-ups.We found that baseline sandfly density of IWP cluster significantly varied from other clusters. Some of the covariates also significantly varied between IWP and other clusters. Hence, we used the difference-in-difference (DID) regression model to account the baseline differences of sandfly density as well as the variation in the covariates between IWP and other clusters during measurement of the efficacy of the IWP relative to other intervention clusters. An interaction term for the intervention arm at follow-up was included in this model to estimate the effect of the intervention. Technically the simple regression model had the following structure:Intervention effect was measured using DID in the average FPAD generated from the c-coefficient in the model. A negative c-coefficient means the sandfly density has decreased and hence the IWP was more effective than the comparator, and vice versa. The c-coefficient should be zero if there is no difference in the effect on sandfly density between IWP and the comparator intervention. Percentage reduction of FPAD by IWP relative to DWL, ITN, and IRS is calculated and given with 95% confidence interval (CI):We considered an intervention effective for killing sandflies if the Abbot’s corrected sandfly mortality remained ≥ 80%. We performed all analysis by STATA version 13.0.P = 0.001) and ITN (P = 0.002) clusters.The study included 217 HHs with 56, 55, 52, and 54 in the IWP, DWL, ITN, and IRS clusters, respectively, with a total population of 1,020 people. The baseline mean (95% CI) FPAD in IWP, DWL, ITN, and IRS was 1.64 (1.01–2.27), 0.56 (0.19–0.92), 0.58 (0.22–0.95), and 1.03 (0.48–1.57), respectively. The IWP FPAD differed significantly with that of DWL , IWP, and IRS are effective for sandfly control; however, the strength and duration of efficacy differed considerably, and the IWP had superior performance compared with ITN, DWL, and IRS interventions.,,The conventional method for sandfly control is IRS, which has been used by the NKEP in Bangladesh since 2012. Its efficacy has been demonstrated by many previous studies.,Studies in the past on the Indian subcontinent including Bangladesh demonstrated the high efficacy of DWL (for both full- and reduced-surface coverage) for controlling sandflies.–In a previous study, we found that ITN was effective for controlling sandflies for up to18 months,Anopheles, the malaria vector, a finding that encouraged us to investigate its efficacy on sandflies.,IWP containing three insecticides is a new tool for vector control and was the intervention of interest in this study. Although it was developed and had been used for pest control, studies in Africa have demonstrated its usefulness for controlling The safety of IWP, DWL, ITN, and IRS were excellent because no serious adverse events or adverse reactions were reported, and no inconveniences were reported except transient unpleasant smell in 12% of the HHs where ITN were deployed. IRS acceptability, however, is a concern, as it decreased to 54%. This underlines the need of sandfly control tool(s) that can be acceptable and taken up by the community people by themselves. Potential options are IWP, ITN, and DWL. Currently, manufacturers have stopped production of the KO TAB 1-2-3 and DWL, and therefore IWP remains the only available option at present.The main limitation of the study is that it was not possible to investigate the impact of the interventions on VL cases because the current disease burden in Bangladesh is fortunately low. We also could not measure the concentration of the insecticides and their decay over time in ITN, DWL, and IWP because we did not have the appropriate technology. We also could not include an untreated control cluster because the control program rolled out the routine IRS cycle during follow-up phase of this study. Theoretically, this could have cointervention effects. However, the differences found in the effects of the different interventions on FPAD and its varying trends in different clusters over time indicate that the potential spatial effect, cointervention effect, and contamination of the routine IRS did not compromise our study results and conclusions.We now have evidence for a range of effective sandfly control tools. On the basis of our study, we consider IWP and DWL superior to IRS in terms of strength and duration of efficacy and long-term sustainability for sandfly control. Of the two, IWP is available and can be taken up by communities. A study is underway to investigate the efficacy of IWP for sandfly control deployed by the community under supervision of public health workers.The current price of IWP (30 USD per HH) and DWL (50 USD per HH) for full coverage is comparatively high for communities and national programs. The partial coverage with DWL makes its cost closer to that of IWP. The IWP and DWL interventions may offer options for local entrepreneurship for producing and applying the materials. Transfer of production to local manufacturers that can meet quality standards will reduce their price. This process has already started in Bangladesh where the IWP is now produced locally under supervision of the original manufacturer. Future studies are needed with locally produced IWP for investigation of its cost-effectiveness for sandfly and other vectors control. It would also be useful to have data in the longer term to show how the efficacy for sandfly control evolves over time beyond 12 months. For this reason, we have an ongoing study for long-term sustainability.In summary, IWP is a new effective tool for VL vector control. On the basis of our study evidence and the current sandfly control method by the NKEP (IRS in 50–60 HHs around a VL index case), the NKEP may consider IWP for sandfly control for subsequent phases of the program where a longer duration of efficacy is required.


Migrant women may have a higher risk for gestational diabetes mellitus (GDM) and the related adverse outcomes. We studied the prevalence of GDM among migrant-origin women in Finland.N = 379 634) was included. Women were classified into nine regional categories based on the country of origin. Finnish origin women were the reference group. Generalized linear models adjusted for maternal age, parity, socioeconomic position, pre-pregnancy body mass index and year of delivery were used to study the association between region/country of origin and GDM.This study used data from the nationwide Medical Birth Register. Information on the most recent singleton births of women delivering between 2004 and 2014  to 18.4% (South Asian origin), compared to 8.7% in the Finnish reference group. When adjusted for confounders, women of South Asian, East Asian, Middle Eastern/North African and Russian/former USSR origin had a higher risk for GDM than Finnish origin women. By country of origin, women originating from Pakistan, Bangladesh, Sri Lanka, India, Afghanistan, Nepal, China, Philippines, Vietnam, Thailand, Morocco, Turkey, Iran, Iraq and former USSR had a higher risk for GDM than Finnish origin women.There is substantial variation in the prevalence of GDM by country of origin. Women of South Asian, East Asian and Middle Eastern/North African origin had the highest risk for GDM and may warrant special attention. These include maternal overweight and obesity,,,Ethnicity or the country of origin has been identified as one of the risk factors for GDM.There is very little information on the prevalence of GDM in migrant or ethnic minority populations in Finland. One previous study found that women of Kurdish origin had a higher risk of GDM compared to the general Finnish population.n = 389 758). After excluding multiple births (n = 7525) and women with preexisting diabetes , the final study sample was 379 634. Data on the country of origin and socioeconomic position were obtained from national statistical authority Statistics Finland and linked to study data by using the personal identification code for each woman.This study utilized the data from the national Medical Birth Register (MBR) of Finland. The MBR collects data on the mother’s sociodemographic characteristics, previous pregnancies and deliveries, present pregnancy and its monitoring, delivery and complications, and information on the newborn health.a priori based on the United Nations’ geographical classification of countries. Country of origin was defined as the country of birth of the pregnant woman's parents. If both parents were born abroad, the country of birth of the woman's biological mother was considered to be the primary country of origin. If at least one of the parents was born in Finland, the country of origin was defined as Finland. Women were classified into nine regional categories according to their country of origin: (i) Finland; (ii) Western Europe/North America/Oceania (i.e. Western Europe); (iii) Eastern Europe; (iv) Russia and the former Union of Soviet Socialist Republics (USSR); (v) South Asia; (vi) East Asia; (vii) Sub-Saharan Africa; (viii) Middle East/North Africa; and (ix) Latin America/Caribbean. Women with an unknown country of origin  were excluded. A list of countries and numbers of women in each group are presented in The migrant groups were categorized The presence of GDM was extracted from the MBR based on the ICD-10 codes. We included ICD-10 codes O24.4 , O24.9 , and P70.0 or P70.1 (child of a diabetic mother) to identify the presence of GDM. All these ICD-10 codes were compiled together and finally dichotomized (yes/no).2), and do not have a family history of T2DM.In Finland, GDM is diagnosed when fasting plasma glucose value is ≥5.3 mmol/l, the 1-h value is ≥10.0 mmol/l or the 2-h value is ≥ 8.6 mmol/l.2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥30 kg/m2). The delivery year was categorized as 2004–2007, 2008–2011 and 2012–2014 and used in adjustments to account for changes in the screening strategy for GDM in Finland from 2008 onwards and changes in the proportion of deliveries of migrant women of all deliveries during the study period.Mother's age at delivery was categorized into four categories: <25, 25–29, 30–34, and ≥35 years. Socioeconomic position was categorized into five categories: upper-level employees , lower-level employees , manual workers, other (including pensioners/homemakers/students), and unknown. Parity (number of previous births) was categorized as 0, 1, and ≥2. Pre-pregnancy BMI was categorized as underweight . Generalized linear models with the log-link function were used to obtain relative risk (RR) estimates with 95% confidence intervals (CIs). Finnish origin women were the reference group. Model I was an unadjusted model whereas Model II was adjusted for age, socioeconomic position, pre-pregnancy BMI, parity, and delivery year. Age, BMI, parity and delivery year were used as continuous variables in the adjusted model. Furthermore, after identifying the migrant groups at a higher risk for GDM, we run respective, additional analyses for GDM risk by individual countries among the high-risk migrant groups, using Finnish origin women as the reference category. In the individual country analyses, countries with more than 10 GDM cases were included to ensure statistical power and data protection. All analyses were performed in Statistical Package for the Social Sciences .The permission to use the data was obtained from the respective registries from the Finnish Institute of Health and Welfare (THL) and Statistics Finland. We analyzed and stored the anonymized data at THL, following THL’s data safety regulations.n = 31 321) of women were of migrant origin. Very few women  of all women were second-generation women of migrant origin. Women of Russian/former USSR origin constituted the largest (n = 11 961), whereas women of Latin American/Caribbean origin (n = 736) were the smallest migrant origin group  or unknown. Women from Sub-Saharan African and Middle Eastern/North African origin had the higher percentages of two or more parity than any other group. Sub-Saharan African and Middle Eastern/North African women had a higher, whereas and East Asian women had a lower prevalence of overweight and obesity compared with Finnish origin women.n = 349, 18.4%) and lowest among women of Latin American/Caribbean origin  (n = 30 454) among Finnish origin women. In addition, The prevalence of GDM was the highest among women of South Asian origin  . The preThis nationwide, register-based study demonstrated substantial variation in the prevalence of GDM by region and country of origin among women giving birth in Finland during a period of eleven years. After adjusting for confounders, women originating from Pakistan, Bangladesh, Sri Lanka, India, Afghanistan and Nepal (South Asia), China, Philippines, Vietnam, Thailand (East Asia), Morocco, Turkey, Iran and Iraq (the Middle East/North Africa) and the former USSR had a higher risk for GDM than Finnish origin women.Adjustment for the main risk factors of GDM, such as older age and BMI, explains some differences in the RRs in our study. The South Asian and Russian/USSR origin women were younger than Finnish origin women on average. Respectively, the Sub-Saharan origin women had a higher BMI and the East Asian and Russian/USSR origin women had a lower BMI than the Finnish origin women on average.,Although obesity is strongly associated with the risk of developing GDM, Makgoba et al. demonstrated that women with a normal BMI from African and South Asian origin had an odds ratio of 2.62 (95% CI 1.83–3.74) and 3.00 (95% CI 2.51–3.57), respectively, to develop GDM compared with the general population of women in the European countries.,Two large studies from the USA have demonstrated that women who migrated from their country of birth to the USA had a higher rate of GDM compared to women of the same origin but who were born in the USA, except for women of Japanese and South Korean origin.2, age ≥40 years, fetal macrosomia in current or previous pregnancy, GDM in a previous pregnancy, or family history of T2DM.In this study, the prevalence of GDM was about 9% among the Finnish origin, which is almost half of the current national prevalence.,Our findings are in accordance with, the findings of recent studies from Denmark and Norway.Yuen et al. reviewed studies on the prevalence of GDM by ethnicity in 2018, including studies conducted mainly in the Australia and the USA but also one study from Italy and one from the UK.This study contributed to the limited literature on GDM among migrant origin women in Finland and identified the high-risk migrant origin groups for GDM. The outcome measure (GDM) was based on standard ICD-10 codes extracted from the MBR. Furthermore, the data in the nationwide MBR have a high degree of completenessAs our data were based on routinely collected information, we had no information on several important migration indicators, such as migration status, length of stay, and language skills, which might have contributed to the differences between the groups. Although we have adjusted for some known confounders, we could not adjust for unhealthy diet and low physical activity which are well-known risk factors for GDM and could differ between women of migrant origin and Finnish women. Our variable on the socioeconomic position was based on employment and occupation, which was unknown for almost 30% of women from Sub-Saharan Africa and the Middle East/North Africa. Better indicators of socioeconomic position, such as the highest educational attainment and family income, should be used in future studies whenever possible.Future studies could explore possible reasons for the higher GDM risk in certain migrant origin groups. Possible differences in the adverse outcomes of GDM and treatment of GDM could also be compared between the migrant origin groups and the reference group. Women originating from the high-risk countries should be offered culturally tailored care to manage GDM during pregnancy. More research is needed on how to prevent the development of GDM among women of migrant origin. The interventions carried out among pregnant women in Western countries have had limited effects on prevention of GDM.In conclusions, this study provided evidence on a higher risk of GDM among women of South Asian, East Asian and Middle Eastern/North African origin in Finland. GDM is a serious pregnancy complication and causes various short- and long-term effects on the health of both mother and the newborn. Therefore, women from these high-risk groups should be given special attention and help in the maternity care.EURPUB online.We would like to acknowledge the Finnish Cultural Foundation, grant number 50201295 for funding this study.Conflicts of interest: None declared.Women originating from South Asian, East Asian and Middle Eastern/North African countries have a higher risk for developing GDM compared to Finnish origin women in Finland.When analyzed by individual country of origin, women originating from Pakistan, Bangladesh, Sri Lanka, India, Nepal, Afghanistan, China, Philippines, Vietnam, Thailand, Morocco, Turkey, Iran and Iraq and the former USSR countries had a higher risk for GDM than Finnish origin women.Women originating from Western Europe, Eastern Europe, Sub-Saharan African and Latin America/Caribbean countries did not differ from Finnish origin women for the risk of GDM.ckab078_Supplementary_DataClick here for additional data file.


The present study aimed to evaluate the lipid profile and atherogenic indexes in HIV-positive women with and without coinfection with human papillomavirus.  Preliminary study was conducted with HIV-positive women. Laboratory tests  and detection of human papillomavirus  were performed. For the analysis of the results, the data were categorized into two groups: with coinfection (HIV+/HPV+) and without coinfection (HIV+/HPV–). p=0.04), LDL cholesterol (p=0.03), and non-HDL cholesterol (p=0.04), as well as for the Castelli I index, Castelli II index, and atherogenic coefficient .  Eighty-two HIV-positive women, aged between 35 and 49 years, participated in this study among whom 50% had HPV coinfection (HIV+/HPV+). Regarding comorbidities, there was a predominance of dyslipidemia (46.3%). The analysis of laboratory determinations and atherogenic indexes showed statistical relevance in the serum concentrations of total cholesterol ( The present study demonstrated a correlation between the lipid profile and atherogenic indexes with HIV/HPV coinfection, demonstrating a possible synergy between these viruses. However, further studies in this area must be carried out. The human immunodeficiency virus (HIV) remains a major public health problem worldwide. It is estimated that 37.9 million people were living with HIV in 2019 and that approximately 1.7 million new cases are expected to arise worldwide [After the discovery of HIV, the search for treatment began, and with the advent of combined antiretroviral therapy , significant successes were achieved . HoweverBefore the introduction of HAART, there were reports of hypertriglyceridemia; however, after its use, new changes in lipid metabolism started to be observed, and although its etiology is not completely elucidated, dyslipidemia in people living with HIV is highly prevalent , 7. In aAlthough atherogenesis is a multifactorial process, abnormalities in lipid metabolism are one of the main factors for its development. In general, the assessment of coronary risk is based on the determination of serum concentrations of the lipid profile, more precisely of LDL cholesterol, but scientific data have shown that this assessment is not sufficient to estimate cardiovascular risk , 12.In this context, atherogenic indexes  have been shown to be better predictors for the risk of cardiovascular disease when compared to the absolute levels of lipids or lipoproteins , 12. KanCurrently, the potential risk of developing cardiovascular disease in people with human papillomavirus (HPV) is also emphasized, due to the increased incidence of CVD in DNA-HPV-positive women. The mechanism involved in this rate is still unclear, but it has been observed that the formation of atheromatous plaque occurs earlier in these people, probably due to the constant stimulation of the immune system and systemic inflammatory process –18.The study by Kuo and Fujise  found thTherefore, coinfection between HIV and HPV viruses are linked, in addition to immunosuppression caused by HIV, with chronic systemic inflammation, which plays an important role in the development of cancer, atheroma plaque, and cardiovascular disease. In this context, knowing that it is of paramount importance to understand the biological interactions between HIV and HPV, the present study aimed to evaluate the lipid profile and atherogenic indexes in HIV-positive women with coinfection with human papillomavirus.This research was approved by the Ethics and Research Committee of the University Hospital of the Federal University of Maranhão (HU-UFMA), São Luís/MA . Written informed consent was obtained from all women.This is a preliminary study (nonprobabilistic sample) carried out in the period between August 2018 and December 2019; a cross-sectional study was carried out in which 82 HIV-positive women, voluntarily accepted to participate in the present study; the participants were attended at two reference centers for HIV treatment . Inclusion criteria were as follows: (1) age ≥18 years, (2) previous HIV diagnosis, and (3) being on antiretroviral therapy. Pregnant women, women with contraindications for Pap smears , and women with hysterectomies were not included.All participants answered the questionnaire about their sociodemographic data , current history of the disease, continuous use of drug treatment, and life habits .Samples of cervical swabs were collected for the detection of human papillomavirus and blood samples for the realization of the participants' glycid and lipid profiles. Conventional cytological smears were obtained with Ayre's spatula  and endocervical brush , extended in a glass slide, fixed with ethanol, and stained using the Pap technique. Cytological examinations of Pap smear were reported using the 2001 Bethesda Reporting System. Venous blood samples were obtained from volunteers after a 12-hour fasting period. After collection into tubes without anticoagulant, plasma and serum were separated by centrifugation and stored in freezer at -20 degree Celsius until further analysis.The cobas® 6000 equipment, in the cobas c 501 modules, was used for the determination of fasting blood glucose (GL), total cholesterol (TC), HDL cholesterol (HDLc), and triglycerides (TG), and cobas c module was used for the measurement of serum insulin. With the data of the lipid profile, it was possible to perform the calculations of LDL cholesterol {(CT – HDLc) – (TG/5)}, non-HDL cholesterol (CT – HDLc), and atherogenic indexes: Castelli I index: CI/I (CT/HDLc ratio), Castelli II index: CI/II (LDLc/HDLc ratio), plasma atherogenic index: AIP {(logTG)/HDLc}, and atherogenic coefficient: AC { and the HOMA-IR index (fasting glycemia x 0.0555 x fasting insulin/22.5). The HOMA and TyG indexes were used to verify possible insulin resistance (IR).DNA extraction was performed using a cervical swab using the Biopur Mini Spin Plus Extraction Kit , following the protocol described in the manufacturer's user manual. For DNA-HPV detection, the Nested Polymerase Chain Reaction technique was used in a Gene Amp PCR system 9700 thermocycler , with the PGMY 09 and 11 primers  and GP+5 and GP+6  . The prot-test was used to verify the differences between the means of the groups evaluated. The results obtained provided their distribution in two groups: with coinfection (HIV+/HPV+) and without coinfection (HIV+/HPV–). A 95% confidence interval and a significance level of p ≤ 0.05 were adopted for the analysis performed. All tests were applied using IBM SPSS® Statistics software version 24.0.The data considered categorical were presented in proportion, using the Chi-square test and Fisher's exact test. The normality of the distribution of numerical variables was assessed by the Kolmogorov–Smirnov test. For the numerical variables, Student's p = 0.045) when comparing the groups  were positive for DNA-HPV. Regarding the sociodemographic data, in both groups, 68.3% have up to 9 years of study, the average family income was up to one minimum wage and no condom use . The group without coinfection had more women without fixed partners (56.1%); reported that their first relationship was between >15 years old (51.2%); that they had already become pregnant several times (73.2%) and who do not use oral contraceptives (97.5). In comparison, the coinfected group had more women with married/stable relationship (51.2%) and reported that their first relationship was between 12 and 15 years old (48.8%) and that they had already become pregnant several times (78%). There are no statistically significant results in these parameters . The groe groups .p=0.04), LDL cholesterol (p=0.03), and non-HDL cholesterol (p=0.04) when comparing the two groups. In addition, there were statistically significant values in the calculations of the Castelli I index, Castelli II index, and atherogenic coefficient .The laboratory determinations are described in p=0.36, insulin: p=0.85, HOMA index: p=0.09, and TyG: p=0.41) present a higher concentration in the group with coinfection, this result was not sufficiently different between the groups to generate statistically significant values , including cardiovascular disease (CVD), diabetes and other metabolic conditions, renal disease, liver disease, cancers, and mental illness , 6. ReceThe pathomechanisms of these relations are not yet fully understood and may significantly affect the health of a large part of the population. Accelerated atherosclerosis is assumed to play a key role in the pathophysiology of these relationships. In this context, the present study aimed to evaluate the lipid profile and atherogenic indexes in HIV-positive women with coinfection with human papillomavirus.Although it is not a representative sample of people living with HIV from the Legal Amazon region, Maranhão/Brazil, the data are preliminary and are similar to the general epidemiological data available from people living with HIV and to other studies carried in Brazil.With regard to socioeconomic issues, the two groups were very homogeneous, with no statistically significant differences between them; however, there are similarities with previously published research as in Ng'adwe et al. , where mRegarding comorbidities, in the present study, it can be observed that only the consumption of alcoholic beverages alone showed statistically significant values between the groups; however, for the diagnosis of comorbidity, not only isolated factors are observed, but several factors are also predisposing for CVD. Thus, dyslipidemia was present in 45.12% of the participants' results, which is an important cardiovascular risk factor.Although HIV infection and its therapies have been associated with changes in adipose tissue and disorders of glucose and lipid metabolism that may prematurely increase the risk of cardiovascular disease , 6, morep=0.04), LDL cholesterol (p=0.03), and non-HDL cholesterol (p=0.04) when compared to the group of HIV-positive women with and without HPV coinfection. In addition, there were statistically significant values in the calculations of the Castelli I index, Castelli II index, and atherogenic coefficient. With these data, it is possible to raise the hypothesis of a possible synergy between the HIV and HPV viruses in lipid disorders and risk for cardiovascular diseases [Dyslipidemia has several origins and can have the most varied types of implications, such as cardiovascular diseases. From a physiological and clinical point of view, total cholesterol and triglycerides are among the most biologically relevant lipids for health since cholesterol is a precursor to steroid hormones, bile acids, and vitamin D . It was diseases .The pathophysiological mechanisms that could potentially determine the associations between HIV and HPV infection and CVD are not yet convincingly defined. In general, proatherosclerotic mechanisms related to infections may be local or systemic and direct or indirect.The longer use of HAART and greater exposure to HIV can generate a chronic inflammatory process, which, in the long term, causes changes in the patterns of cellular behavior and metabolism of lipids and glycids . And so,Suppressing viral replication with HAART significantly reduces immune activation for HIV seropositive individuals, but it does not eliminate it. These people have persistently higher levels of systemic inflammation when compared with HIV-negative controls both before and while receiving HAART. This is reflected by higher levels of serum biomarkers  observed in HIV seropositive individuals compared with negative seronegative controls , 31, 32.Between 2003 and 2006, one of the first large studies in the United States was conducted demonstrating the association between HPV, especially high-risk HPV types and an increased prevalence of self-reported diagnosis of myocardial infarction and stroke among HIV-positive women . Brito eβ, IL-6, IL-17, and IL-18 and decreased anti-inflammatory properties of high-density lipoprotein (HDL), reactive oxygen species formation, and procoagulant activity [The systemic effects of these viruses include immune activation is both specific and non-specific, involving several mechanisms. The increased release of cytokines, activation, and proliferation of T-helper cells elevated the interferon-alpha, interferon-gamma, tumor necrosis factor-alpha, interleukins IL-1The present study corroborates with such CVD risk findings in women with human papillomavirus when the groups are analyzed through the lipid profile and atherogenic indices, such as Castelli I, Castelli II index, and atherogenic coefficient. The resulting effects of immune activation and chronic inflammation on the cardiovascular system are far reaching and likely explain the increased risk for cardiovascular events noted in this population. To our knowledge, this is the first study to investigate the lipid profile and atherogenic indexes in HIV-positive women with coinfection with human papillomavirus, and these results propose the hypothesis that a possible synergy between the HIV and HPV viruses into immune activation and risk factors for cardiovascular disease, although more studies are needed to investigate the mechanisms involved.We encountered a limitation in this study that even presenting statistically significant data, it does not have a large sample size when compared to people living with HIV in the state of Maranhão. Since women living with HIV self-describe themselves and are afraid of exposure, this makes it difficult to make an estimated sample calculation. The prejudice itself is also counted as a limitation, as many women refused to sign the consent form for fear of exposure, and others gave up for fear of having to present themselves to a different group from the multiprofessional team that lives with them daily or monthly; these are the reasons for a lost sample number. However, our study analyzes the lipid profile in HIV people with HPV coinfection, a ratio that has not been carried out in previous studies, which emphasizes the importance of this. This work has practical evidence that highlights the need for studies aimed at better understanding the mechanisms of CVD in HIV and HPV infections, defining clear intervention targets, and identifying clinically relevant markers to measure response.The present study demonstrated a high prevalence of HIV/HPV coinfection. The lipid profile  and the atherogenic indexes  showed a correlation with HIV/HPV coinfection, demonstrating a possible synergy, in lipid disorders and cardiovascular risk, between the two viruses. However, further studies in this area must be carried out.