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Purpose: This study reviewed the literature examining type and frequency of gesture use in children diagnosed with autism spectrum disorder (ASD) in comparison to other populations. The findings can inform future studies and programs targeting the use of gestures as an early indicator of ASD.Methods: A six step search procedure was utilized to identify all articles exploring gesture use in children with ASD in comparison to other populations. Articles meeting inclusion criteria were double coded by the investigators with 97% agreement. Results examining type and frequency of gesture were synthesized and three common themes were identified: comparison group(s), age of participants with ASD, and gesture terminology.Results: A total of 32 studies met inclusion criteria for this study. Of these studies, nine exclusively measured type of gesture, 17 exclusively measured frequency, and 6 measured both type and frequency. Results indicate that children with ASD used different types and frequency of gesture in comparison to other populations. The most studied age range was 4-5 years and most studies used typically developing children as the comparison group. Gesture terminology and definition were extremely variable.Conclusions: Children with ASD are using different types and frequencies of gesture when compared to other populations. More research including younger and more diverse populations is needed to translate these findings into clinical practice. Additionally, there is a need for more consistent use of gesture terminology and definition.

Purpose: The purpose of this pilot study is to begin exploring the diversity, equity, and inclusion (DEI) initiatives being implemented by communication sciences and disorders (CSD) programs at various universities across the United States with the intent to guide and support future research studies. Method: Publicly available data of DEI initiatives used by CSD programs across the United States were utilized for this study. A three-step procedure was used to explore reported initiatives. First, responses were reviewed to determine whether the reported initiatives were focusing on diversity, equity, and/or inclusion. Second, each independent initiative was reviewed, and common themes were identified. Third, the reported impact of DEI initiatives on CSD programs was explored. Results: This study produced four major findings related to DEI initiatives in CSD programs: (a) The majority of CSD programs included in this study reported use of DEI initiatives focusing on inclusion; (b) CSD programs included in this study reported implementation of DEI initiatives that fall into seven themes; (c) CSD programs included in this study reported DEI initiative impact on students and a reduced number of programs reported impact on faculty, staff, and the community; and (d) the DEI initiatives of CSD programs included in this study appeared to vary according to university-level factors. Conclusions: There is a dearth of information relating to the use of DEI initiatives being implemented by CSD programs. The results of this pilot study can be used to implement future studies and programs with the ultimate goal of improving DEI in the fields of speech-language pathology and audiology.

Attributed to Romeyn de Hooghe, Allegory of Coinage envisions the global horizons of Dutch monetary governance. The central female personification, Moneta of Holland, receives tributaries from Africa, America, and Asia. Bearing sacks of silver and gold, these male laborers appear within a hybrid landscape that visually relates the technologies for mining and refining precious metals to the crafts of minting and assaying specie. Likely made to decorate the offices of the Masters-General of the Mints, who supervised mints in the Dutch Republic, Allegory of Coinage encouraged these officials to perceive how their governance of the material production of coins was embedded in a global division of labour for sourcing and distributing precious metals.

The objective of this study was to adapt the National Diabetes Prevention Program (N-DPP) into a pragmatic tool for primary care settings by using daily text messaging to deliver all N-DPP content, supplemented by Fitbit technology to provide behavioral strategies typically delivered by personnel in traditional programs. Test the mobile health (mHealth), technology-based N-DPP adaptation (DPPFit) in primary care patients with prediabetes using a remote intervention based on the traditional 16 core sessions of the DPP.A pilot study with pre/post survey analysis of aggregate data were used to determine changes in weight, physical activity, sedentary behavior, and associated diabetes risk outcomes among study participants (n = 33). In this study, participants were issued Fitbit devices and provided the remote intervention over 16 weeks via automated text messaging technology, which followed the content of the DPP core education sessions.Data analysis from baseline to 6-month follow-up demonstrate mean weight loss of 3.3 kg (95% CI: -6.2 to -0.5;The remote DPPFit intervention demonstrates a promising and practical approach to the management of prediabetes in a primary care setting. The results support the use of the DPPFit program and application to achieve meaningful outcomes in a population with prediabetes. A randomized controlled trial with a larger sample is warranted.

Inflammatory conditions, including allergic asthma and conditions in which chronic low-grade inflammation is a risk factor, such as stress-related psychiatric disorders, are prevalent and are a significant cause of disability worldwide. Novel approaches for the prevention and treatment of these disorders are needed. One approach is the use of immunoregulatory microorganisms, such as Mycobacterium vaccae NCTC 11659, which have anti-inflammatory, immunoregulatory, and stress-resilience properties. However, little is known about how M. vaccae NCTC 11659 affects specific immune cell targets, including monocytes, which can traffic to peripheral organs and the central nervous system and differentiate into monocyte-derived macrophages that, in turn, can drive inflammation and neuroinflammation. In this study, we investigated the effects of M. vaccae NCTC 11659 and subsequent lipopolysaccharide (LPS) challenge on gene expression in human monocyte-derived macrophages. THP-1 monocytes were differentiated into macrophages, exposed to M. vaccae NCTC 11659 (0, 10, 30, 100, 300 µg/mL), then, 24 h later, challenged with LPS (0, 0.5, 2.5, 250 ng/mL), and assessed for gene expression 24 h following challenge with LPS. Exposure to M. vaccae NCTC 11659 prior to challenge with higher concentrations of LPS (250 ng/mL) polarized human monocyte-derived macrophages with decreased IL12A, IL12B, and IL23A expression relative to IL10 and TGFB1 mRNA expression. These data identify human monocyte-derived macrophages as a direct target of M. vaccae NCTC 11659 and support the development of M. vaccae NCTC 11659 as a potential intervention to prevent stress-induced inflammation and neuroinflammation implicated in the etiology and pathophysiology of inflammatory conditions and stress-related psychiatric disorders.

Purpose: The purpose of this study was to explore screening practices for autism spectrum disorder (ASD) in Mexico and the United States (U.S.). Methods: Data from a larger study exploring the knowledge, screening, and diagnostic practices of healthcare practitioners from Mexico and the U.S. was used for the current study. The original survey was created by experts in ASD and consisted of 63 questions: 15 demographic questions, 20 questions relating to knowledge of ASD, 11 questions relating to screening practices, and 17 questions relating to diagnostic practices. All surveys were completed by professionals engaging in the screening and diagnosis of ASD. For this study, a total of thirty- five survey responses for the screening portion of the survey (30 from the U.S. and 5 from Mexico) were explored. Qualitative data and descriptive statistics were utilized. Results: Many of the responses relating to screening practices from professionals practicing in Mexico and the U.S. were consistent with best practice guidelines from the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics (AAP), and the Mexican Public Health Guide. Furthermore, many similarities were found in the screening practices of professionals from both countries. Differences in screening practices reported by professionals from Mexico and the U.S. were found in the type of professional involved in the screening process and professional referrals after a failed ASD screening. Additionally, some professionals from both the U.S. and Mexico reported the use of inappropriate screening tools, and the average age reportedly screened was much higher than the current recommendations of the American Academy of Pediatrics (Hyman et al., 2020). Conclusion: An understanding of the screening practices currently being used in Mexico and the U.S. provides both researchers and clinicians with a better understanding of what is being implemented by different professionals. This study identified areas of strength and areas of weaknesses in the screening process for ASD in both countries. These results can now be used in future studies and programs targeting improved screening processes in Mexico in the U.S. Improved screening processes are important because of the potential to result in an earlier age of diagnosis of ASD and provision of services at a younger age. The latter of which is associated with better outcomes for children with ASD. Keywords: autism spectrum disorder, screening, Mexico, United States.

Activation-induced cytidine deaminase (AID) catalyses the deamination of deoxycytidines to deoxyuracils within immunoglobulin genes to induce somatic hypermutation and class-switch recombination1,2. AID-generated deoxyuracils are recognized and processed by subverted base-excision and mismatch repair pathways that ensure a mutagenic outcome in B cells3–6. However, why these DNA repair pathways do not accurately repair AID-induced lesions remains unknown. Here, using a genome-wide CRISPR screen, we show that FAM72A is a major determinant for the error-prone processing of deoxyuracils. Fam72a-deficient CH12F3-2 B cells and primary B cells from Fam72a−/− mice exhibit reduced class-switch recombination and somatic hypermutation frequencies at immunoglobulin and Bcl6 genes, and reduced genome-wide deoxyuracils. The somatic hypermutation spectrum in B cells from Fam72a−/− mice is opposite to that observed in mice deficient in uracil DNA glycosylase 2 (UNG2)7, which suggests that UNG2 is hyperactive in FAM72A-deficient cells. Indeed, FAM72A binds to UNG2, resulting in reduced levels of UNG2 protein in the G1 phase of the cell cycle, coinciding with peak AID activity. FAM72A therefore causes U·G mispairs to persist into S phase, leading to error-prone processing by mismatch repair. By disabling the DNA repair pathways that normally efficiently remove deoxyuracils from DNA, FAM72A enables AID to exert its full effects on antibody maturation. This work has implications in cancer, as the overexpression of FAM72A that is observed in many cancers8 could promote mutagenesis. FAM72A differentially controls mutation rates by regulating uracil processing at different stages of the cell cycle, thereby regulating somatic hypermutation and class-switch recombination in B cells.

Purpose The purpose of this study was to develop a novel swine model of recurrent gastrointestinal bleeding that could potentially be utilized for the study of provocative mesenteric angiography. Methods Animal experiments were approved by the Institutional Animal Care and Use Committee. The superior mesenteric artery was catheterized via percutaneous transfemoral access. Via laparotomy, multiple small incisions were created in the small bowel wall of four swine. After hemostasis was achieved, varying amounts of thrombolytics were infused into the superior mesenteric artery via a 5 french catheter. The number of incisions with observable rebleeding and interval until rebleeding were ascertained. Results In a test animal, active extravasation was confirmed to be detectable on digital subtraction angiography at a small bowel incision site. After tissue plasminogen activator (tPA) administration into the superior mesenteric artery, rebleeding from the incisions was visually observed in 11 of 30 small bowel incisions (37%). Provoked bleeding occurred at a median of 6 minutes (mean: 5 minutes and 52 seconds) after completion of tPA injection with a range of approximately 1 to 10 minutes. Conclusion This pilot study proposes a feasible model for provocative mesenteric angiography in swine.

Mycobacteria have a distinctive glycolipid-rich outer membrane, the mycomembrane, which is a critical target for tuberculosis drug development. However, proteins that associate with the mycomembrane, or that are involved in its metabolism and host interactions, are not well-characterized. To facilitate the study of mycomembrane-related proteins, we developed photoactivatable trehalose monomycolate analogues that metabolically incorporate into the mycomembrane in live mycobacteria, enabling in vivo photo-cross-linking and click-chemistry-mediated analysis of mycolate-interacting proteins. When deployed in Mycobacterium smegmatis with quantitative proteomics, this strategy enriched over 100 proteins, including the mycomembrane porin (MspA), several proteins with known mycomembrane synthesis or remodeling functions (CmrA, MmpL3, Ag85, Tdmh), and numerous candidate mycolate-interacting proteins. Our approach is highly versatile, as it (i) enlists click chemistry for flexible protein functionalization; (ii) in principle can be applied to any mycobacterial species to identify endogenous bacterial proteins or host proteins that interact with mycolates; and (iii) can potentially be expanded to investigate protein interactions with other mycobacterial lipids. This tool is expected to help elucidate fundamental physiological and pathological processes related to the mycomembrane and may reveal novel diagnostic and therapeutic targets.

Recent studies have examined social needs (social determinants of health) among cancer survivors, but studies have not specifically focused on patients with leukemia or lymphoma. We examined food insecurity and other social needs among hematologic cancer survivors, including individuals who had completed primary therapy for leukemia, lymphoma, or multiple myeloma. A particular focus of the study was on the relationship between social needs and health-related quality of life.We conducted a postal survey of a multiethnic cohort of hematologic cancer survivors who reside in Augusta, GA, or the surrounding area and who had been treated at the Georgia Cancer Center.A total of 53 patients with a history of hematologic cancer (leukemia, lymphoma, or multiple myeloma) completed the survey (10.6% response rate). The mean age was 62.6 years. The participants were diverse according to annual household income and employment status. About two-thirds were white and almost one-third were African American. Five of 52 participants (9.6%) experienced food insecurity. Patients with food insecurity had poorer HRQOL compared with those who were food secure (63.3 vs. 87.33, p = 0.0308). A similar pattern was seen for those who had difficulty paying utility bills, those who had housing insecurity, and those who had to go without health care because of a lack of transportation. Overall, there was a statistically significant inverse association between HRQOL and number of social needs (p = 0.004).When caring for cancer survivors, social needs such as food insecurity and housing insecurity are important considerations for oncologists and primary care providers, especially when caring for patients with lower socioeconomic status and racial/ethnic minorities.

The purpose of this study was to determine whether fallopian tube embolization with n-butyl-2-cyanoacrylate (NBCA) administered via a microcatheter in a rabbit model was technically feasible and resulted in short-term tubal occlusion.In 10 female New Zealand white rabbits, the two cervices were cannulated using a 5 Fr catheter and hydrophilic guidewire transvaginally. Salpingography confirmed tubal patency bilaterally. A 2.4 Fr microcatheter was advanced to the distal fallopian tube, and NBCA/ethiodized oil was administered as the microcatheter was withdrawn to fill the length of the tube. A metallic coil was deployed prior to NBCA administration in half of the fallopian tubes. Rabbits were evaluated for tubal occlusion with salpingography at 1 month, followed by euthanasia and histopathologic analysis. Inflammation and fibrosis were graded from 0 (normal) to 3 (severe).Fallopian tube embolization was technically successful in 17/20 fallopian tubes (85%). 13/17 (76%) embolized fallopian tubes were occluded at 1 month on salpingography (7/9 NBCA only, 6/8 NBCA and coil). On histopathologic analysis, direct or indirect evidence of occlusion was observed in 14/17 fallopian tubes (82%). Mild or early fibrosis was observed in 65% of the tubes. The mean inflammation and fibrosis scores for the embolized tubes were 0.62 and 0.94, respectively.This pilot study found that embolization of the fallopian tubes using NBCA administered via a microcatheter is technically feasible and results in occlusion of most fallopian tubes in the short term with minimal inflammation. Investigation of efficacy in preventing pregnancy over the long term is warranted.

Uterine artery arteriovenous malformations (AVMs) are rare anomalies that may result in uterine hemorrhage. A 40-year-old G8P5126 woman presented with severe vaginal bleeding and an estimated 2000 mL of blood loss at home. Three weeks prior, she had a vaginal delivery of a term infant resulting in post-partum hemorrhage, with 2700 mL of blood loss. The patient had a history of ectopic pregnancy, placenta previa, and dilatation and curettage. Interventional radiology was consulted, and the patient underwent angiography of the internal iliac and uterine arteries revealing the presence of a uterine AVM, which was successfully embolized using a thick mixture of n-butyl cyanoacrylate and lipiodol. The patient experienced no further episodes of bleeding and was discharged within 24 hours. Recognition of typical symptoms and risk factors for uterine arteriovenous malformations can facilitate early diagnosis and appropriate treatment.

Ureteroarterial fistula is a rare condition wherein a communication develops between a ureter and the common, internal, or external iliac artery. Localizing the fistula can be difficult, as cystoscopy, CT angiography, and conventional angiography have low sensitivity in identifying the fistula. Provocative maneuvers within the ureter, however, can aid in the visualization of fistulae on angiography. Prior reports of endovascular repair have utilized transfemoral access, which makes performing concurrent provocative maneuvers in the ureter challenging. We present a case of successful endovascular ureteroarterial fistula localization and embolization in an 80-year-old woman with recurrent gross hematuria by the transradial approach, aided by concurrent provocative maneuvers performed via cystoscopy. The transradial endovascular approach facilitated a multi-disciplinary joint procedure that resulted in effective treatment of the patient.

The present study examined the frequency of gesture use and the relationship between frequency of gesture use and developmental abilities in typically developing 9- to 15-month-old, prelinguistic Hispanic and non-Hispanic White children. Data was collected through parent questionnaires, the Mullen Scales of Early Learning (MSEL), and two, 15-min video samples for each participant (semi-structured and structured settings). All video samples were coded for the frequency of the following gestures: total frequency, behavior regulation, social interaction, and joint attention. Results showed that children from both ethnicities used fewer gestures in a semi-structured setting in comparison to a structured setting and non-Hispanic White children produced higher frequencies of behavior regulation gestures and joint attention gestures, but lower frequencies of social interaction gestures. When controlling for ethnicity, gender, and age total frequency of gesture and frequencies of behavior regulation and social interaction were predictive of various developmental abilities. Furthermore, participant gender, age, and ethnicity were significantly related to various developmental abilities explored. These relationships were dependent upon setting. An understanding of the use of gesture and the relationship between gesture use and developmental abilities in prelinguistic children from different ethnic backgrounds has implication for early identification of delays and differences and is important to consider when exploring the connection between gesture and language and whether there are gesture-language, gesture-motor, and/or gesture-cognition integrated systems.

The disaccharide trehalose is essential for viability of Mycobacterium tuberculosis, which synthesizes trehalose de novo but can also utilize exogenous trehalose. The mycobacterial cell wall encompasses two permeability barriers, the cytoplasmic membrane and the outer mycolic acid-containing mycomembrane. The ABC transporter LpqY–SugA–SugB–SugC has previously been demonstrated to mediate the specific uptake of trehalose across the cytoplasmic membrane. However, it is still unclear how the transport of trehalose molecules across the mycomembrane is mediated. In this study, we harnessed the antimycobacterial activity of the analogue 6-azido trehalose to select for spontaneous resistant M. tuberculosis mutants in a merodiploid strain harbouring two LpqY–SugA–SugB–SugC copies. Mutations mediating resistance to 6-azido trehalose mapped to the proline–proline–glutamate (PPE) family member PPE51 (Rv3136), which has recently been shown to be an integral mycomembrane protein involved in uptake of low-molecular weight compounds. A site-specific ppe51 gene deletion mutant of M. tuberculosis was unable to grow on trehalose as the sole carbon source. Furthermore, bioorthogonal labelling of the M. tuberculosis Δppe51 mutant incubated with 6-azido trehalose corroborated the impaired internalization. Taken together, the results indicate that the transport of trehalose and trehalose analogues across the mycomembrane of M. tuberculosis is exclusively mediated by PPE51.

APOBEC3 family of DNA-cytosine deaminases inactivate and mutate several human viruses. We constructed a human cell line that is inducible for EGFP-tagged APOBEC3A and found A3A predominantly in the nuclei. When these cells were infected with Herpes Simplex Virus-1, virus titer was unaffected by A3A expression despite nuclear virus replication. When A3A expression and virus infection were monitored, A3A was found predominantly to be nuclear in infected cells up to 3 hours post-infection, but was predominantly cytoplasmic by 12 hours. This effect did not require the whole virus, and could be reproduced using the UL39 gene of the virus which codes for a subunit of the viral ribonucleotide reductase. These results are similar to the reported exclusion of APOBEC3B by Epstein Barr virus ortholog of UL39, BORF2, but HSV1 UL39 gene product appears better at excluding A3A than A3B from nuclei.

Activation-induced deaminase (AID) and apolipoprotein B mRNA-editing enzyme catalytic subunit (APOBEC) enzymes convert cytosines to uracils, creating signature mutations that have been used to predict sites targeted by these enzymes. Mutation-based targeting maps are distorted by the error-prone or error-free repair of these uracils and by selection pressures. To directly map uracils created by AID/APOBEC enzymes, here we used uracil-DNA glycosylase and an alkoxyamine to covalently tag and sequence uracil-containing DNA fragments (UPD-Seq). We applied this technique to the genome of repair-defective, APOBEC3A-expressing bacterial cells and created a uracilation genome map, i.e. uracilome. The peak uracilated regions were in the 5′-ends of genes and operons mainly containing tRNA genes and a few protein-coding genes. We validated these findings through deep sequencing of pulldown regions and whole-genome sequencing of independent clones. The peaks were not correlated with high transcription rates or stable RNA:DNA hybrid formation. We defined the uracilation index (UI) as the frequency of occurrence of TT in UPD-Seq reads at different original TC dinucleotides. Genome-wide UI calculation confirmed that APOBEC3A modifies cytosines in the lagging-strand template during replication and in short hairpin loops. APOBEC3A's preference for tRNA genes was observed previously in yeast, and an analysis of human tumor sequences revealed that in tumors with a high percentage of APOBEC3 signature mutations, the frequency of tRNA gene mutations was much higher than in the rest of the genome. These results identify multiple causes underlying selection of cytosines by APOBEC3A for deamination, and demonstrate the utility of UPD-Seq.

As breast cancer relative survival continues to increase, many breast cancer patients face many issues, including recurrence of cancer and cancer-related side effects that impact several aspects of their quality of life. With breast cancer patients living longer, there is more of a concern for negative breast cancer outcomes. Although physical activity is an affordable and relatively convenient way to improve breast cancer outcomes, only about one-third of breast cancer survivors engage in the recommended level of physical activity. This article reviews articles published to date to examine whether home-based physical activity interventions are effective in improving physical activity and other outcomes among breast cancer survivors who have completed primary therapy for the disease. The present review is based upon bibliographic searches in PubMed and CINAHL and relevant search terms. Articles published in English from 1980 through February 28, 2019 were identified. A total of 360 article citations were identified in PubMed and non-duplicates in CINAHL. After screening the abstracts or full texts of these articles and reviewing the references of previous review articles, 20 studies that met the eligibility criteria. Three of the studies were pre-/post-test trials and 17 were randomized controlled trials. home-based exercise programs are effective in improving physical activity among breast cancer survivors who have completed primary therapy for the disease. Home-based exercise programs such as walking programs offer a convenient and affordable option for women who wish to increase their physical activity and maintain a healthy lifestyle.

The world’s protected area network is constantly changing, and the dynamics of this network are tracked using the World Database on Protected Areas (WDPA). This database evolved from a list of protected areas first mandated by the United Nations in 1959, and it now informs the key indicators that track progress toward area-based conservation targets. In this capacity, the WDPA illuminates the role of protected areas in advancing a range of international objectives and agreements, including the Convention on Biological Diversity and the Sustainable Development Goals. Despite ongoing challenges in maintaining such a complex global dataset, the WDPA is continuously improving and taking advantage of new technology, making it widely applicable to diverse users, including those in sectors far from its original intended audience. In the future, the WDPA will expand to include areas that contribute to conservation and sustainable use outside of formal protected areas, and will increasingly link to other key global datasets. These innovations in the way the WDPA is managed and used will deliver vital knowledge to support a sustainable future for biodiversity and people globally. The World Database on Protected Areas has evolved since 1959 to become an essential resource for monitoring global progress in terrestrial and marine habitat protection. This Review illustrates the users and uses of the WDPA, its history of quality improvements and challenges for future development.

Murine FAM72A, mFAM72A, binds the nuclear form of uracil-DNA glycosylase, mUNG2, inhibits its activity and causes its degradation. In immunoprecipitation assays the human paralog, hFAM72A, binds hUNG2 and is a potential anti-cancer drug target because of its high expression in many cancers. Using purified mFAM72A, and mUNG2 proteins we show that mFAM72A binds mUNG2, and the N-terminal 25 amino acids of mUNG2 bind mFAM72A at a nanomolar dissociation constant. We also show that mFAM72A is present throughout the cells, and mUNG2 helps localize it to nuclei. Based on in silico models of mFAM72A-mUNG2 interactions, we constructed several mutants of mFAM72A and found that while they have reduced ability to deplete mUNG2, the mutations also destabilized the former protein. We confirmed that Withaferin A, a predicted lead molecule for the design of FAM72A inhibitors, binds mFAM72A with micromolar affinity but has little affinity to mUNG2. We identified two potential metal-binding sites in mFAM72A and show that one of the sites contains an Fe-S cluster. This redox-sensitive cluster is involved in the mFAM72A-mUNG2 interaction and modulates mFAM72A activity. Hydrogen peroxide treatment of cells increases mUNG2 depletion in a FAM72A-dependent fashion suggesting that mFAM72A activity is redox-sensitive.

Background Uterine Artery Embolization (UAE) is a minimally invasive procedure used to treat symptomatic uterine fibroids. The HydroPearl Microsphere (Terumo Interventional Systems) is an embolic agent approved for UAE and other embolization procedures. The purpose of this article is to describe our initial experience with HydroPearl for UAE in patients with symptomatic uterine fibroids. Twenty-one patients who underwent UAE using HydroPearl Microspheres at a single institution from May 1, 2018 to December 31, 2019 were included in the study. The electronic medical record (EMR) was reviewed for documentation of short- and long-term complications, as well as improvements in menorrhagia and bulk-type symptoms. We also describe unique attributes of the HydroPearl Microsphere that should be considered when utilizing this embolization particle for UAE. Results Of the 21 patients, 18 had a 3-month or later post-procedure follow-up documented in the EMR and were included in the analysis. The average time between the UAE procedure and the most recent clinical note was 145 days. Sixteen patients reported symptoms of menorrhagia and 13 reported bulk symptoms prior to the UAE procedure. On follow-up, 13/16 patients (81%) and 12/13 patients (92%) experienced improvement in menorrhagia and bulk symptoms, respectively. The only recorded complication was amenorrhea in 4 patients (22%) who had an average age of 51 years. Conclusions Several characteristics of HydroPearl Microsphere may prove helpful when considering these embolic particles for use in UAE. Our initial experience with this embolic agent suggest that the reatment response for menorrhagia and bulk symptoms are largely similar to success rates reported in the literature for other embolic agents. Larger studies are needed to evaluate the safety and efficacy of this embolic particle for this indication.

Background Deep learning-based radiological image analysis could facilitate use of chest x-rays as a triaging tool for COVID-19 diagnosis in resource-limited settings. This study sought to determine whether a modified commercially available deep learning algorithm (M-qXR) could risk stratify patients with suspected COVID-19 infections. Methods A dual track clinical validation study was designed to assess the clinical accuracy of M-qXR. The algorithm evaluated all Chest-X-rays (CXRs) performed during the study period for abnormal findings and assigned a COVID-19 risk score. Four independent radiologists served as radiological ground truth. The M-qXR algorithm output was compared against radiological ground truth and summary statistics for prediction accuracy were calculated. In addition, patients who underwent both PCR testing and CXR for suspected COVID-19 infection were included in a co-occurrence matrix to assess the sensitivity and specificity of the M-qXR algorithm. Results 625 CXRs were included in the clinical validation study. 98% of total interpretations made by M-qXR agreed with ground truth (p = 0.25). M-qXR correctly identified the presence or absence of pulmonary opacities in 94% of CXR interpretations. M-qXR's sensitivity, specificity, PPV, and NPV for detecting pulmonary opacities were 94%, 95%, 99%, and 88% respectively. M-qXR correctly identified the presence or absence of pulmonary consolidation in 88% of CXR interpretations (p = 0.48). M-qXR's sensitivity, specificity, PPV, and NPV for detecting pulmonary consolidation were 91%, 84%, 89%, and 86% respectively. Furthermore, 113 PCR-confirmed COVID-19 cases were used to create a co-occurrence matrix between M-qXR's COVID-19 risk score and COVID-19 PCR test results. The PPV and NPV of a medium to high COVID-19 risk score assigned by M-qXR yielding a positive COVID-19 PCR test result was estimated to be 89.7% and 80.4% respectively. Conclusion M-qXR was found to have comparable accuracy to radiological ground truth in detecting radiographic abnormalities on CXR suggestive of COVID-19.

Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a “two hit” stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day –28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days –21, –14, –7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0–56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days –1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.

Activation-induced cytidine deaminase (AID) catalyzes the deamination of deoxycytidines within Immunoglobulin (Ig) genes to induce somatic hypermutation (SHM) and class switch recombination (CSR) 1,2. AID-induced deoxyuracils within Ig loci are recognized and processed by subverted base excision and mismatch repair pathways that ensure a mutagenic outcome in B lymphocytes 3–8. However, it is unclear why DNA repair pathways that remove deoxyuracil from DNA are not efficient at faithfully repairing AID-induced lesions. Here, we identified through a genome-wide CRISPR screen that FAM72A, a protein with no ascribed function, is a major determinant for the error-prone processing of deoxyuracil. Fam72a-deficient CH12F3-2 B cells and primary B cells from Fam72a−/− mice have reduced CSR and SHM frequencies. The SHM spectrum in B cells from Fam72a−/− mice is opposite to that observed in Ung2−/− mice 9, suggesting that UNG2 is hyperactive in FAM72A-deficient cells. Indeed, FAM72A binds to UNG2 resulting in reduced UNG2 activity, and significantly reduced protein levels in the G1 phase, coinciding with peak AID activity. This effect leads to increased genome-wide deoxyuracils in B cells. By antagonizing UNG2, FAM72A therefore increases U•G mispairs that engage mutagenic mismatch repair promoting error-prone processing of AID-induced deoxyuracils. This work shows that FAM72A bridges base-excision repair and mismatch repair to modulate antibody maturation.

Almost half of breast cancer survivors are aged ≥ 65 years and the proportion is likely to increase due to the aging of the population. The objectives of this article were to review studies of health outcomes among older breast cancer survivors ≥ 65 years to identify gaps in the published literature and offer suggestions for future research. The present review is based upon bibliographic searches in PubMed and CINAHL and relevant search terms. Articles published in English from January 1, 1970 through October 1, 2018 were identified using the following MeSH search terms and Boolean algebra commands. This review has revealed that older breast cancer survivors cope with health issues related to cancer treatment and the aging process, including comorbidities, osteoporosis, symptoms, physical functioning, cognitive functioning, nutrition, and physical activity. Additional research is needed to examine therapeutic interventions to address the health conditions older breast cancer survivors are coping with. Particular focus of further research should be on the nutritional status and physical activity levels of older breast cancer survivors. Individualized nutrition plans and tailored physical activity programs for older survivors are needed that meet people where they are and that form habits.

Little research exists on how partners of sex offenders are perceived. Using attachment theory, we hypothesised that one's attachment would generalise to perceptions of sexual offenders and their partners. One hundred and six British adults’ attachment styles were assessed, as well as perceptions of sex offenders and their partners. Generally, perceivers’ attachment avoidance was associated with positive perceptions of both partners and offenders, while attachment anxiety was associated with negative perceptions of partners but positive perceptions of sex offenders. Perceptions of sex offenders and their partners were highly correlated and negative in nature, and sex offenders were more negatively perceived.

Superior hypogastric nerve block (SHNB) decreases pain and use of narcotic pain medication following uterine artery embolization (UAE). The purpose of this retrospective study was to evaluate the effect of the addition of a corticosteroid (triamcinolone) to SHNB on analgesia following UAE. Records of 16 patients were reviewed for when pain occurred or acutely worsened after the procedure. No major complications were identified. Patients reported that pain began or worsened an average of 33.8 hours after the procedure, when their average pain increased from 0.6/10 to 5.9/10 (P < .001). This suggests that addition of triamcinolone to SHNB could result in prolonged analgesia following UAE.

Although they have been widely studied, important questions remain about the impact of breast cancer survivorship care plans on improving health outcomes. The goal of this article was to review published studies on the impact of cancer survivorship care plans on health outcomes and health care delivery among breast cancer survivors. A total of 111 article citations were identified in PubMed and non-duplicates in CINAHL. After screening the abstracts or full texts of these articles and reviewing the references of previous review articles, 7 studies met the eligibility criteria. All of the studies had a randomized controlled design. Early trials of the efficacy of breast cancer survivorship care plans generally showed little or no improvement in health outcomes. The positive findings of recent studies suggest that survivorship care interventions that empower and activate patients to self-manage their follow-up care and improve patient-provider communication may be especially promising.

Uterine artery embolization (UAE) has been shown to be a safe and effective treatment for symptomatic uterine fibroids, with over 25 years of supporting data. Although UAE is a well-established treatment option, several misperceptions exist that may limit the number of patients who are considered candidates for UAE. There are also challenges that may affect the ability of interventional radiologists to effectively treat some patients and offer the best possible experience. This article will discuss these misperceptions and challenges, which represent opportunities for further growth and innovation that will allow interventional radiologists to better serve this patient population.

Purpose The aim of this study was to examine the relationship between frequency of gesture use and language with a consideration for the effect of age and setting on frequency of gesture use in prelinguistic typically developing children. Method Participants included a total of 54 typically developing infants and toddlers between the ages of 9 months and 15 months separated into two age ranges, 9-12 months and 12-15 months. All participants were administered the Mullen’s Scale of Early Learning and two gesture samples were obtained: one sample in a structured setting and the other in an unstructured setting. Gesture samples were coded by research assistants blind to the purpose of the research study and total frequency and frequencies for the following gesture types were calculated: behavior regulation, social interaction, and joint attention ( Bruner, 1983 ). Results Results indicated that both age and setting have a significant effect on frequency of gesture use and frequency of gesture is correlated to receptive and expressive language abilities; however, these relationships are dependent upon the gesture type examined. Conclusions These findings further our understanding of the relationship between gesture use and language and support the concept that frequency of gesture is related to language abilities. This is meaningful because gestures are one of the first forms of intentional communication, allowing for early identification of language abilities at a young age.

The AID/APOBEC enzymes deaminate cytosines in single-stranded DNA (ssDNA) and play key roles in innate and adaptive immunity. The resulting uracils cause mutations and strand breaks that inactivate viruses and diversify antibody repertoire. Mutational evidence suggests that two members of this family, APOBEC3A (A3A) and APOBEC3B, deaminate cytosines in the lagging-strand template during replication. To obtain direct evidence for the presence of these uracils, we engineered a protein that covalently links to DNA at uracils, UdgX, for mammalian expression and immunohistochemistry. We show that UdgX strongly prefers uracils in ssDNA over those in U•G or U:A pairs, and localizes to nuclei in a dispersed form. When A3A is expressed in these cells, UdgX tends to form foci. The treatment of cells with cisplatin, which blocks replication, causes a significant increase in UdgX foci. Furthermore, this protein- and hence the uracils created by A3A- colocalize with replication protein A (RPA), but not with A3A. Using purified proteins, we confirm that RPA inhibits A3A by binding ssDNA, but despite its overexpression following cisplatin treatment, RPA is unable to fully protect ssDNA created by cisplatin adducts. This suggests that cisplatin treatment of cells expressing APOBEC3A should cause accumulation of APOBEC signature mutations.

Patients with chronic lymphocytic leukemia and unmutated immunoglobulin heavy-chain variable region gene (IGHV) have inferior survival from time of treatment in clinical studies. We assessed real-world outcomes based on mutational status and treatment regimen in a nationwide population-based cohort, comprising all 4,135 patients from the Danish chronic lymphocytic leukemia registry diagnosed between 2008 and 2017. In total, 850 patients with known mutational status received treatment: 42% of patients received intensive chemoimmunotherapy consisting of fludarabine, cyclophosphamide plus rituximab, or bendamustine plus rituximab; 27% received chlorambucil in combination with anti-CD20 antibodies or as monotherapy, and 31% received other, less common treatments. No difference in overall survival from time of first treatment according to mutational status was observed, while treatment-free survival from start of first treatment was inferior for patients with unmutated IGHV. The median treatment-free survival was 2.5 years for patients treated with chlorambucil plus anti-CD20, and 1 year for those who received chlorambucil monotherapy. The 3-year treatment-free survival rates for patients treated with fludarabine, cyclophosphamide plus rituximab, and bendamustine plus rituximab were 90% and 91% for those with mutated IGHV, and 76% and 53% for those with unmutated IGHV, respectively, and the 3-year overall survival rates were similar for the two regimens (86-88%). Thus, it appears that, in the real-world setting, patients progressing after intensive chemoimmunotherapy as first-line therapy can be rescued by subsequent treatment, without jeopardizing their long overall survival. Intensive chemoimmunotherapy remains a legitimate option alongside targeted agents, and part of a personalized treatment landscape in chronic lymphocytic leukemia, while improved supportive care and treatment options are warranted for unfit patients.

The world's protected area network is constantly changing, and the dynamics of this network are tracked using the World Database on Protected Areas (WDPA). This database evolved from a list of protected areas first mandated by the United Nations in 1959, and it now informs the key indicators that track progress toward area-based conservation targets. In this capacity, the WDPA illuminates the role of protected areas in advancing a range of international objectives and agreements, including the Convention on Biological Diversity and the Sustainable Development Goals. Despite ongoing challenges in maintaining such a complex global dataset, the WDPA is continuously improving and taking advantage of new technology, making it widely applicable to diverse users, including those in sectors far from its original intended audience. In the future, the WDPA will expand to include areas that contribute to conservation and sustainable use outside of formal protected areas, and will increasingly link to other key global datasets. These innovations in the way the WDPA is managed and used will deliver vital knowledge to support a sustainable future for biodiversity and people globally.

This chapter argues that gentrification's effects on African Americans vary by region. Regional socioeconomic context, primarily patterns of urban organization, population concentration, and African American home-buying power shape the effects of neighborhood change. It reviews pertinent literature related to gentrification. The chapter outlines a theoretical framework for understanding the nuances of gentrification from a regional political economy perspective and detailed research design. It presents the findings from a quantitative and spatial analysis, and highlights interregional differences in Black home-buying power. The chapter discusses the broader impact of regional effects on racialized neighborhood change. It also provides a brief background on the intersection of race and place. The chapter suggests that there are regional, subregional, and local variation in the potential for and possible effects of gentrification, the optimal method for a systematic analysis of contextual effects at any geographic level is a mixed methods approach; the exact causal mechanism underlying the causes and effects of gentrification require additional exploration.

Phorbol 12-myristate 13-acetate (PMA) promotes skin cancer in rodents. The mutations found in murine tumors are similar to those found in human skin cancers, and PMA promotes proliferation of human skin cells. PMA treatment of human keratinocytes increases the synthesis of APOBEC3A, an enzyme that converts cytosines in single-stranded DNA to uracil, and mutations in a variety of human cancers are attributed to APOBEC3A or APOBEC3B expression. We tested here the possibility that induction of APOBEC3A by PMA causes genomic accumulation of uracils that may lead to such mutations. When a human keratinocyte cell line was treated with PMA, both APOBEC3A and APOBEC3B gene expression increased, anti-APOBEC3A/APOBEC3B antibody bound a protein(s) in the nucleus, and nuclear extracts displayed cytosine deamination activity. Surprisingly, there was little increase in genomic uracils in PMA-treated wild-type or uracil repair-defective cells. In contrast, cells transfected with a plasmid expressing APOBEC3A acquired more genomic uracils. Unexpectedly, PMA treatment, but not APOBEC3A plasmid transfection, caused a cessation in cell growth. Hence, a reduction in single-stranded DNA at replication forks may explain the inability of PMA-induced APOBEC3A/APOBEC3B to increase genomic uracils. These results suggest that the proinflammatory PMA is unlikely to promote extensive APOBEC3A/APOBEC3B-mediated cytosine deaminations in human keratinocytes.

Computed tomographic (CT) fluoroscopy-guided percutaneous cryoablation is an effective therapeutic method used to treat focal renal masses. The purpose of this study is to quantify the radiation dose to the patient and interventional radiologist during percutaneous cryoablation of renal masses using CT fluoroscopic guidance. Over a 1-year period, the CT fluoroscopy time during percutaneous cryoablation of renal masses was recorded in 41 patients. The level of complexity of each procedure was designated as simple, intermediate, or complex. Patient organ radiation doses were estimated using an anthropomorphic model. Dose to the interventional radiologist was estimated using ion chamber survey meters. The average CT fluoroscopy time for technically simple cases was 47 s, 126 s for intermediate cases, and 264 s for complex cases. The relative risk of hematologic stomach and liver malignancy in patients undergoing this procedure was 1.003–1.074. The lifetime attributable risk of cancer ranged from 2 to 58, with the highest risk in younger patients for developing leukemia. The estimated radiation dose to the interventionalist without lead shielding was 390 mR (3.9 mGy) per year of cases. The radiation risk to the patient during CT fluoroscopy-guided percutaneous renal mass cryoablation is, as expected, related to procedure complexity. Quantification of patient organ radiation dose was estimated using an anthropomorphic model. This information, along with the associated relative risk of malignancy, may assist in evaluating risks of the procedure, particularly in younger patients. The radiation dose to the interventionist is low regardless of procedure complexity, but highlights the importance of lead shielding.

Background Previous observational studies and systematic reviews have suggested that adherence to the Mediterranean diet is associated with a reduced risk of breast cancer, but have not examined associations with molecular subtypes of breast cancer. The current review examines the association with adherence to the Mediterranean diet and risk of breast cancer according to molecular subtypes. Methods Bibliographic searches were conducted in PubMed and CINAHL using relevant MeSH search terms and Boolean algebra commands. Results Six cohort studies and one case-control study have examined adherence with the Mediterranean diet and risk of breast cancer according to estrogen-receptor (ER) and progesterone-receptor (PR) status and human epidermal growth factor 2 (HER2) oncogene expression. Taken overall, studies suggest that the Mediterranean dietary pattern is inversely associated with breast cancer risk in postmenopausal women, and that the inverse association is somewhat stronger among ER- tumors. Although there is a suggestion that the Mediterranean diet is inversely associated with PR- tumors and with ER-/PR-/HER2- ("triple negative" tumors), results to date have been mixed and the number of studies that have examined associations with this dietary pattern among tumors characterized by multiple molecular subtypes remains small. Conclusions The results of this systematic review suggest that consumption of a Mediterranean diet pattern is associated with a reduced risk of postmenopausal breast cancer, particularly among ER- tumors. Additional cohort studies that have sufficient sample sizes and long-term follow-up are warranted to identify sizeable numbers of invasive breast cancer cases, thereby allowing for characterization of the tumors by molecular subtype.

Objectives There is limited evidence about the association between health literacy and use of patient web portals in patients with chronic illnesses. The objective of this review was to learn more about health literacy and use of patient web portals. Methods Bibliographic searches were conducted in PubMed and CINAHL using relevant MeSH search terms and Boolean algebra commands. Results Qualitative studies and studies with a cross-sectional, cohort, or pre-/post-test design have shown that persons with limited health literacy are less likely to use patient web portals, although there is inconsistency in the association across studies. Conclusions The conflicting findings may be partially due to racial and ethnic differences in health literacy or level of comfort in sharing private health information using mobile technologies. Several opportunities exist to improve the usability and acceptability of web portals for patients with limited health literacy including enhancements in the design of the portals, patient and provider education and training, and engagement of proxies such as caregivers and close family members.