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Background: Members of vulnerable populations are underrepresented in Parkinson's disease (PD) research. A complex web of research barriers perpetuates this gap. Community-based research methods are one approach to addressing this issue. The present PD study was designed to examine the effectiveness of community-based interventions to overcome barriers and increase research participation among underrepresented groups (URGs)., Methods: Eight study sites across the US were selected and paired based on proposed interventions with specific URGs. Surveys assessed knowledge and attitudes toward PD research. Finally, researchers examined whether the present study affected recruitment to Fox Insight, an online PD research study also recruiting at each site., Results: In total, 474 participants were recruited. At post-intervention for the FIRE-UP PD Study, recruitment increased significantly in intervention compared to control sites among Black and African American non-Hispanic/Latino populations (p = 0.003), White Hispanic/Latino (p = 0.003) populations, and Not Listed Hispanic/Latino populations (p < 0.001) as well as those with an educational attainment of a high school diploma/General Education Diploma (GED) (p = 0.009), and an income <$20,000 (p = 0.005) or between $20,000-$34,999 (p < 0.001). Study surveys measuring changes in awareness and attitudes toward PD research had mixed results. In Fox Insight, 181 participants were passively recruited with a shift toward more diverse participant demographics., Conclusion: Research participation demographics reflective of the general population are critical to PD investigation and treatment. The FIRE-UP PD Study showed the effectiveness of localized community engagement strategies in increasing URG recruitment to PD research. Therefore, further PD research employing community-based methods to improve diverse participant recruitment is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite federal regulations mandating the inclusion of underrepresented groups in research, recruiting diverse participants remains challenging. Identifying and implementing solutions to recruitment barriers in real time might increase the participation of underrepresented groups. Hence, the present study created a comprehensive dashboard of barriers to research participation. Barriers to participation were recorded in real time for prospective participants. Overall, 230 prospective participants expressed interest in the study but were unable to join due to one or more barriers. Awareness of the most common obstacles to research in real time will give researchers valuable data to meaningfully modify recruitment methods., Competing Interests: None., (© The Author(s) 2024.)

Latinx trans and non-binary individuals (LTNB) face increased cancer-related health disparities. Studies evidence how barriers at the individual, provider and organizational levels drive cancer disparities among LTNB individuals. These barriers increase the emotional discomfort associated with testing and disengagement from cancer prevention efforts. Moreover, there are no guidelines or interventions that address cancer prevention specifically among LTNB individuals. There is a need to develop interventions informed by the LTNB communities to promote cancer prevention and screening. The study aims to describe the recommendations provided by LTNB individuals to foster cancer screening and prevention in the communities residing in Puerto Rico and Florida. We conducted two online focus groups with a total of 15 LTNB participants. Participants were recruited using non-probabilistic purposive sampling. We used rapid-qualitative analysis for data interpretation. Findings are gathered in three main themes: (1) recommendations for promoting cancer prevention screening among providers; (2) specific recommendations to promote cancer screening among LTBN individuals; and (3) recommendations on delivery formats to foster cancer prevention. These results evidence the need and feasibility of developing community informed tailored interventions targeting cancer screening and preventative care to reduce cancer-related health disparities among the LTNB population.

Purpose: The aim of this study was to perform a quantitative quality assurance of diffusion-weighted MRI to assess the variability of the mean apparent diffusion coefficient (ADC) and other radiomic features across the scanners involved in the REGINA trial., Materials and Methods: The NIST/QIBA diffusion phantom was acquired on six 3 T scanners from five centres with a rectum-specific diffusion protocol. All sequences were repeated in each scan session without moving the phantom from the table. Linear interpolation to two isotropic voxel spacing (0.9 and 4 mm) was performed as well as the ComBat feature harmonisation method between scanners. The absolute accuracy error was evaluated for the mean ADC. Repeatability and reproducibility within-subject coefficients of variation (wCV) were computed for 142 radiomic features., Results: For the mean ADC, accuracy error ranged between 0.1 % and 8.5 %, repeatability was <1 % and reproducibility was <3 % for diffusivity range between 0.4 and 1.1x10 -3 mm 2 /s. For the other radiomic features, wCV was below 10 % for 24 % and 15 % features for repeatability with resampling 0.9 mm and 4 mm, respectively, and 13 % and 11 % feature for reproducibility. ComBat method could improve significantly the wCV compared to reproducibility without ComBat (p-value < 0.001) but variation was still high for most of the features., Conclusion: Our study provided the first investigation of feature selection for development of robust predictive models in the REGINA trial, demonstrating the added value of such a quality assurance process to select conventional and radiomic features in prospective multicentre trials., Competing Interests: Declaration of Competing Interest The radiology and medical physics departments of Institut Jules Bordet has a research agreement with Siemens. The authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Ortho -boronoaldehydes react with amine-based nucleophiles with dramatically increased rates and product stabilities, relative to unfunctionalised benzaldehydes, leading to exciting applications across biological and material chemistry. We have developed a novel Förster resonance energy transfer (FRET)-based assay to provide key new insights into the reactivity of these boronoaldehydes, allowing us to track conjugation with unprecedented sensitivity and accuracy under standardised conditions. Our results highlight the key role played by reaction pH, buffer additives, and boronoaldehyde structure in controlling conjugation speed and stability, providing design criteria for further innovations and applications in the field., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Population reflective research enrollment improves study generalizability and disease knowledge. Nevertheless, the proportion of underrepresented groups (URGs) in Parkinson's disease (PD) research remains low. Hence, the current manuscript describes the process of designing a study to analyze the effectiveness of strategies to overcome barriers to URG recruitment in PD research., Methods: The Fostering Inclusivity in Research Engagement for Underrepresented Populations in Parkinson's Disease (FIRE-UP PD) study asked participating sites to identify a URG or geographical region to target to assess knowledge and attitudes toward PD research as well as increase Fox Insight (an online study with The Michael J. Fox Foundation) participation across eight months. URGs were defined as racial and ethnic minorities, women, rural populations, and low socioeconomic status groups. Participating sites were paired based on their proposed interventions and were randomly assigned to either the intervention or control condition., Results: The FIRE-UP PD study was divided into pre-intervention, intervention, and post-intervention periods to measure changes in awareness and trust in PD research along with engagement and interest in PD protocols through the use of several surveys. Interventions included developing educational tools to engage local communities, building partnerships within local PD communities, and recruiting stakeholders to reimagine medical and research information for the community., Conclusion: Improving representation in research is a crucial step toward improving access to PD diagnoses and treatments. This is one of the first multi-site PD research studies to include community engagement to address barriers to research participation and improve research recruitment of URGs., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction:  Reconstructive techniques for cloaca, anorectal malformations (ARM), and Hirschsprung disease (HD) may require intestinal flaps on vascular pedicles for vaginal reconstruction and/or colonic pull-throughs. Visual assessment of tissue perfusion is typically the only modality used. We investigated the utility of intraoperative indocyanine green fluorescence angiography (ICG-FA) and hypothesized that it would be more accurate than the surgeon's eye., Materials and Methods:  Thirteen consecutive patients undergoing cloacal reconstruction (9), HD (3), and ARM repair (1) underwent ICG-FA laser SPY imaging to assess colonic, rectal, vaginal, and neovaginal tissue perfusion following intraoperative visual clinical assessment. Operative findings were correlated with healing at 6 weeks, 3 months, and 1 year postoperatively., Results:  ICG-FA resulted in a change in the operative plan in 4 of the 13 (31%) cases. In three cases, ICG-FA resulted in the distal bowel being transected at a level (>10 cm) higher than originally planned, and in one case the distal bowel was discarded, and the colostomy used for pull-through., Conclusion:  ICG-FA correctly identified patients who might have developed a complication from poor tissue perfusion. Employing this technology to assess rectal or neovaginal pull-throughs in cloacal reconstructions, complex HD, and ARM cases may be a valuable technology., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: Acute orbital inflammation can lead to irreversible vision loss in serious cases. Treatment thus far has been limited to systemic steroids or surgical decompression of the orbit. An animal model that mimics the characteristic features of acute orbital inflammation as found in thyroid eye disease can be used to explore novel treatment modalities., Methods: We developed a murine model of orbital inflammation by injecting oxazolone into the mouse orbit. The mice underwent magnetic resonance imaging (MRI) and were euthanized at various time points for histologic examination. Immunofluorescence studies of specific inflammatory cells and cytokine arrays were performed., Results: We found clinical and radiographic congruity between the murine model and human disease. After 72 hours, sensitized mice exhibited periorbital dermatitis and inflammation in the eyelids of the injected side. By one week, increased proptosis in the injected eye with significant eyelid edema was appreciated. By four weeks, inflammation and proptosis were decreased. At all three time points, the mice demonstrated exophthalmos and periorbital edema. Histopathologically, populations of inflammatory cells including T cells, macrophages, and neutrophils shared similarities with patient samples in thyroid eye disease. Proteomic changes in the levels of inflammatory and angiogenic markers correlated to the expected angiogenic, inflammatory, and fibrotic responses observed in patients with thyroid eye disease., Conclusions: A murine model of orbital inflammation created using oxazolone recapitulates some of the clinical features of thyroid eye disease and potentially other nonspecific orbital inflammation, typified by inflammatory cell infiltration, orbital tissue expansion and remodeling, and subsequent fibrosis., Translational Relevance: This animal model could serve as a viable platform with which to understand the underlying mechanisms of acute orbital inflammation and to investigate potential new, targeted treatments., Competing Interests: Disclosure: D. Amarnani, None; A.V. Sanchez, None; L.L. Wong, None; B.V. Duffy, None; L. Ramos, None; S.K. Freitag, None; D.R. Bielenberg, None; L.A. Kim, None; N.G. Lee, None, (Copyright 2020 The Authors.)

Introduction: Gastrointestinal (GI) operations represent a significant proportion of the surgical site infection (SSI) burden in pediatric patients, resulting in significant morbidity. We have previously demonstrated that a GI bundle decreases SSI rates, length of stay (LOS), and hospital charges. Following this success, we hypothesized that by targeting the preoperative antibiotics for stoma closures based on organisms found in infected wounds, we could further decrease SSI rates., Methods: As part of a broad quality improvement effort to reduce SSI rates, we reviewed the responsible pathogens and their sensitivities as well as the preoperative antibiotic used, and found that 15% of wound infections were caused by enterococcus. Based on this information, starting in April 2017, we changed the prior preoperative antibiotic cefoxitin to ampicillin-sulbactam, which more accurately targeted the prevalent pathogens from April 2017 to October 2018., Results: The baseline SSI rate for all stoma takedown patients was 21.4% (25 of 119). After bundle implementation, this decreased to 7.9% (17 of 221; p = 0.03) over a period of 2.5 years. Then, after changing the preoperative antibiotics, our rate of SSI decreased further to 2.2% (1 of 44; p = 0.039) over a period of 1.5 years., Conclusion: Significant reduction of SSI in GI surgery can be accomplished with several prevention strategies (our GI bundle). Then a change of the preoperative antibiotic choice, chosen based on causative wound infection organisms, may further decrease SSI rates. We recommend an institution specific analysis of wound infections and modification of preoperative antibiotics if the responsible organisms are resistant to the original antibiotic choice., Type of Study: Retrospective cohort study., Level of Evidence: Level III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction:  Previous research in children with Hirschsprung's disease (HD) and Down's syndrome (DS) has focused on colorectal outcomes. We set out to review urinary outcomes in this patient group., Materials and Methods:  The medical records of all patients aged five years and older with HD were reviewed, and patients and caregivers filled out the Vancouver Symptom Score at intake, which is designed and validated to diagnose dysfunctional elimination syndrome., Results:  A total of 104 patients with HD were included in this study. Of these, 16 (15%) patients had DS. There were no significant differences in the prevalence of enterocolitis or colorectal symptoms between patients with or without DS. Five of 88 (6%) patients without DS and 7 of 16 (44%) ( p  = 0.00001) with DS reported having urinary accidents. Patients with HD and DS scored higher on the Vancouver score (9 vs. 17.5; p  = 0.007), indicating more severe urinary symptoms. Patients who also reported fecal accidents scored significantly higher on the Vancouver (12 vs. 9; n  = 61; p  = 0.016), indicating more problems., Conclusion:  Patients with DS appear to be a unique subset of HD patients who have a higher prevalence of urinary symptoms after surgery. In the postoperative care of patients with HD and DS, a strong focus should be placed on postoperative urinary care in addition to their bowel care. This could significantly ease care and contribute to the quality of life of the parents and the patient., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction:  Repair of anorectal malformations (ARMs), primarily or with a reoperation, may be performed in certain circumstances without a diverting stoma. Postoperatively, the passage of bulky stool can cause wound dehiscence and anastomotic disruption. To avoid this, some surgeons keep patients NPO (nothing by mouth) for a prolonged period. Here, we report the results of a change to our routine from NPO for 7 days to clear fluids or breast milk., Materials and Methods:  After primary or redo ARM surgery, patients given clear liquids were compared to those who were kept strictly NPO. Age, indication for surgery, incision type, use of a peripherally inserted central catheter (PICC) line, and wound complications were recorded., Results:  There were 52 patients, including 15 primary and 37 redo cases. Group 1 comprised 11 female and 15 male patients. The mean age at surgery was 4.9 years (standard deviation [SD]: 2.3). There were 8 primary cases and 18 redo cases. Twelve (46.6%) received a PICC line. The average start of clear liquids was on day 5.3 (SD: 2.2) after examination of the wound, and the diet advanced as tolerated. The first stool passage was recorded on average on day 2.3 (SD: 1.3). Four minor wound complications and no major wound complications occurred.Group 2 comprised 14 females and 12 male patients. The mean age at surgery was 3.5 (SD: 2.4) years. There were 7 primary and 19 redo cases. One (3.8%) patient required a PICC line. A clear liquid diet was started within 24 hours after surgery. A regular diet was started on average on day 5.8 (SD: 1.3). The first stool passage was recorded on an average of day 1.6 (SD: 0.9). Three minor wound complications occurred; however, there was no significant difference between the two groups (SD: 0.71). One major wound complication occurred. However, there was no significant difference in major wound complications between the groups (SD: 0.33)., Conclusion:  No increase in wound problems was noted in children receiving clear liquids or breast milk compared with the strict NPO group, and PICC line use was reduced. We believe this change in practice simplifies postoperative care without increasing the risk of wound complications., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Acquired skin-level strictures following posterior sagittal anorectoplasty (PSARP) and some rare cases of congenital anal stenosis can be managed using a Heineke-Mikulicz like anoplasty (HMA). We hypothesized that this procedure was an effective, safe, and durable outpatient procedure in select patients., Methods: We retrospectively reviewed all patients who underwent HMA for skin level strictures following PSARP or for certain congenital anal stenoses from 2014 to 2017., Results: Twenty-eight patients (19 males, 9 females) with a mean age of 5.8 years (range 0.5-24.4) underwent HMA. Twenty-six had a prior PSARP, of which 18 were redo, and 8 were primary procedures. Two patients had congenital skin level anal stenosis. The mean follow up was 1.0 years (range 0.4-2.9). The average preprocedure anal size was Hegar 8, which after HMA increased 8 Hegar sizes to 16 (95% CI 7-9, p < 0.001). There were no operative complications. One patient restenosed and required a secondary procedure., Conclusion: HMA is a safe procedure for skin-level anal strictures following PSARP (primary and redo) and can also be used in some rare cases of congenital anal stenosis. Long-term follow up to determine the restricture rate is ongoing. A plan to do an HMA if a stricture develops may offer an alternative to routine anal dilations, particularly after a redo PSARP in an older child., Type of Study: Case series., Level of Evidence: Level IV., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Studying the reproductive ecology of aggregate broadcast spawning fishes is difficult because it generally is not feasible to sample all potential parents and unambiguously assign their offspring. We used molecular-based parentage analysis to gain insights into the reproductive ecology of the endangered Bonytail, and to evaluate whether protected off-channel habitats could be used as an alternative to hatchery production. By genotyping adults and offspring stocked (n = 4130) into two experimental backwaters across three years, we determined that most adults (82-97%) contributed to progeny production across years and backwaters, with one exception. Both sexes mated multiply and the number of mates and family size were positively correlated. There was also a positive correlation between adult size and metrics of reproductive success. There were strong interactions between sample years and backwaters suggesting that environmental factors are the primary driver of variance in reproductive success. Knowledge of mating systems and sources of variance in reproductive success is important for management of endangered fish because high variance in reproductive success leads to substantial losses of genetic variation when few individuals reproduce successfully. Although variance in reproductive success was observed, most adults contributed to genetically diverse progeny in experimental backwaters. These results support the use of predator-free, but otherwise natural, backwaters as an effective conservation tool for reintroducing Bonytail to its native habitat.

Parabens have been widely used as antimicrobial agents, mainly in food products, pharmaceuticals, and cosmetics. Although they are known as safe preservatives, they also cause some harm to human health, which has been discussed lately. Therefore, the aim of this study was to evaluate the occurrence of nine parabens (including isomers) in mineral and drinking waters, besides in drinking water treatment sludge (DWTS) samples with determination by liquid chromatography tandem mass spectrometry (LC-MS/MS). Both methods solid phase extraction (SPE) and QuEChERS were validated. Calibration curves showed a correlation coefficient of 0.99 for all compounds. LOQ values ranged from 0.04 to 4 μg L -1 in aqueous matrices and from 5 to 500 ng g -1 in DWTS. Recoveries between 70 and 115% were reached with RSD below 20% for all compounds in SPE whereas recoveries between 62 and 119% were found with RSD below 20% for almost all compounds in QuEChERS. Matrix effect had low values (< 20%); it was only above 20% for methylparaben in the SPE and for pentylparaben in the QuEChERS. Using a quick and simple extraction procedures with SPE, QuEChERS, and LC-MS/MS analyses, these methods proved to be selective and sensitive. They were successfully applied to real samples (treated water, mineral water, and sludge), and methylparaben was detected at concentration levels below 0.242 μg L -1 in mineral and treated water samples and 10 ng g -1 in DWTS samples.

Rare or novel gene variants in patients with proliferative diabetic retinopathy may contribute to disease development. We performed whole exome sequencing (WES) on patients at the phenotypic extremes of diabetic retinal complications: 57 patients diagnosed with proliferative diabetic retinopathy (PDR) as cases and 13 patients with no diabetic retinopathy despite at least 10years of type 2 diabetes as controls. Thirty-one out of the 57 cases and all 13 controls were from the African American Proliferative Diabetic Retinopathy Study (AA). The rest of the cases were of mixed ethnicities (ME). WES identified 721 candidate genes with rare or novel non-synonymous variants found in at least one case with PDR and not present in any controls. After filtering for genes with null alleles in greater than two cases, 28 candidate genes were identified in our ME cases and 16 genes were identified in our AA cases. Our analysis showed rare and novel variants within these genes that could contribute to the development of PDR, including rare non-synonymous variants in FAM132A, SLC5A9, ZNF600, and TMEM217. We also found previously unidentified variants in VEGFB and APOB. We found that VEGFB, VPS13B, PHF21A, NAT1, ZNF600, PKHD1L1 expression was reduced in human retinal endothelial cells (HRECs) cultured under high glucose conditions. In an exome sequence analysis of patients with PDR, we identified variants in genes that could contribute to pathogenesis. Six of these genes were further validated and found to have reduced expression in HRECs under high glucose conditions, suggestive of an important role in the development of PDR., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a neurological syndrome characterized by small vessel disease (SVD), stroke, and vascular cognitive impairment and dementia caused by mutations in NOTCH3 No therapies are available for this condition. Loss of mural cells, which encompass pericytes and vascular smooth muscle cells, is a hallmark of CADASIL and other SVDs, including diabetic retinopathy, resulting in vascular instability. Here, we showed that Notch3 signaling is both necessary and sufficient to support mural cell coverage in arteries using genetic rescue in Notch3 knockout mice. Furthermore, we show that systemic administration of an agonist Notch3 antibody prevents mural cell loss and modifies plasma proteins associated with Notch3 activity, including endostatin/collagen 18α1 and Notch3 extracellular domain in mice with the C455R mutation, a CADASIL variant associated with Notch3 loss of function. These findings open opportunities for the treatment of CADASIL and other SVDs by modulating Notch3 signaling., (© 2017 Machuca-Parra et al.)

Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world's working adult population and affects those with type 1 and type 2 diabetes. We identified Runt-related transcription factor 1 (RUNX1) as a gene upregulated in CD31 + vascular endothelial cells obtained from human PDR fibrovascular membranes (FVMs) via transcriptomic analysis. In vitro studies using human retinal microvascular endothelial cells (HRMECs) showed increased RUNX1 RNA and protein expression in response to high glucose, whereas RUNX1 inhibition reduced HRMEC migration, proliferation, and tube formation. Immunohistochemical staining for RUNX1 showed reactivity in vessels of patient-derived FVMs and angiogenic tufts in the retina of mice with oxygen-induced retinopathy, suggesting that RUNX1 upregulation is a hallmark of aberrant retinal angiogenesis. Inhibition of RUNX1 activity with the Ro5-3335 small molecule resulted in a significant reduction of neovascular tufts in oxygen-induced retinopathy, supporting the feasibility of targeting RUNX1 in aberrant retinal angiogenesis., (© 2017 by the American Diabetes Association.)

The paper is focused on elaboration of ZrO2 films on pure zirconium via anodizing in phosphoric acid with and without fluoride at constant potentials of 30 V and 60 V. The structure and composition of the films were investigated using scanning electronic microscopy, Raman spectroscopy and X-ray photoelectron spectroscopy. The composition of the oxides formed at both potentials can be identified as monoclinic ZrO2. In addition to Zr and O, the layers formed in phosphoric acid contain phosphorus originating from the phosphoric acid. When the phosphoric acid solution contains NaF, fluorine is also incorporated into the oxide layer. The oxides formed at a higher voltage have greater roughness than those formed at 30 V. Anodized samples exhibit smaller current densities during anodic polarization compared to the as-received zirconium covered with native oxide., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Acute pancreatitis is one of the main causes of intra-abdominal hypertension, which may lead to multiple physiologic alterations. The aim of this study was to determine the relationship between acute pancreatitis and intra-abdominal hypertension, and to evaluate the utility of intra-abdominal pressure (IAP) as a marker of severity in acute pancreatitis., Methods: From July 2002 to July 2004, 45 patients admitted for acute pancreatitis were included in this prospective, observational study. The diagnostic criteria for acute pancreatitis were compatible clinical manifestations and a 3-fold increase in serum amylase levels. Severe pancreatitis was defined as Apache II score >or=8. IAP was determined every 12 hours, and the maximum and the mean values were used for analysis and correlated with prognostic factors of acute pancreatitis., Results: A statistical relationship was observed between maximum IAP and the typical prognostic factors of acute pancreatitis. Maximum IAP had a significant relationship with the computed tomography severity index and the number of complementary tests required. The maximum IAP was significantly greater in patients who died and in patients requiring vasoactive drugs, total parenteral nutrition, or operative treatment related to complications. The maximum IAP was also greater in patients who developed systemic inflammatory response syndrome, multiorgan failure, increase in number and/or volume of intra-abdominal collections, those who required aspiration of the necrosis for suspected infection, those who demonstrated the presence of microorganisms, and those with positive blood cultures., Conclusion: The maximum IAP is a useful, inexpensive, and easy method to measure prognostic marker of the evolution and complications of acute pancreatitis.