Rare confounder: benign multicystic peritoneal mesothelioma in a patient with mucinous colon adenocarcinoma.

Benign multicystic peritoneal mesothelioma (BMPM) is a rare condition, in which patients have multiple cystic lesions of the peritoneum. BMPM can mimic mucinous carcinomatosis and can thus create a diagnostic dilemma. We present the case of a 76-year-old woman who was referred for management of ascending colon adenocarcinoma and was noted to have several nonspecific cystic lesions in the abdomen and pelvis on preoperative computed tomography and diagnostic laparoscopy. Frozen section analysis suggested the lesions contained 'mucin'. Due to concern for metastases, right colectomy was aborted. Final histologic analysis of the laparoscopic biopsies revealed mesothelial cysts, consistent with BMPM, unrelated to her colon adenocarcinoma. Laparoscopic right colectomy was performed 2 weeks later. BMPM can create diagnostic and therapeutic uncertainty in patients with known visceral malignancies when discovered incidentally. Frozen section analysis may not be accurate in differentiating the two, and final histologic confirmation should be sought prior to definitive treatment.

Glia maturation factor-γ regulates amyloid-ß42 phagocytosis through scavenger receptor AI in murine macrophages.

Dysfunctional phagocytic clearance of ß-amyloid (Aß) in microglia and peripheral macrophages/monocytes has been implicated in Alzheimer's disease (AD), but the mechanisms underlying this dysfunction are not yet well understood. In this study, we examined the role of glia maturation factor-γ (GMFG), an actin-disassembly protein that is highly expressed in immune cells, in macrophage Aß phagocytosis and in regulating scavenger receptor AI (SR-AI), a cell-surface receptor that has previously been implicated in Aß clearance. GMFG knockdown increased phagocytosis of Aß42 in BMDMs and RAW264.7 murine macrophages, while GMFG overexpression reduced Aß42 uptake in these cells. Blocking with anti-SR-AI antibodies inhibited Aß42 uptake in GMFG-knockdown cells, establishing a role for SR-AI in Aß42 phagocytosis. GMFG knockdown increased SR-AI protein expression under both basal conditions and in response to Aß42 treatment via both the transcriptional and post-transcriptional level in RAW264.7 macrophages. GMFG knockdown modulated Aß42-induced K48-linked and K63-polyubiquitination of SR-AI, the phosphorylation of SR-AI and JNK, suggesting that GMFG plays a role for intracellular signaling in the SR-AI-mediated uptake of Aß. Further, GMFG-knockdown cells displayed increased levels of the transcriptional factor MafB, and silencing of MafB in these cells reduced their SR-AI expression. Finally, GMFG was found to interact with the nuclear pore complex component RanBP2, and silencing of RanBP2 in GMFG-knockdown cells reduced their SR-AI expression. Collectively, these data support the role of GMFG as a novel regulator of SR-AI in macrophage Aß phagocytosis, and may provide insight into therapeutic approaches to potentially slow or prevent the progression of AD.

Interventional Radiology Management of Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a clinically severe and devastating complication of decompensated liver disease affecting mortality, quality of life for patients and families, hospital admission rates, and overall health-care costs globally. Depending on the cause of HE, several medical treatment options have been developed and become available. In some refractory HE, such as spontaneous portosystemic shunt-related HE (SPSS-HE) or posttransjugular intrahepatic portosystemic shunt HE (post-TIPS HE), advanced interventional radiology (IR) procedures have been used, and shown to be effective in these conditions. This review presents 2 effective IR procedures for managing SPSS-HE and post-TIPS HE.

The Influence of Strength and Sport Exposure on Psychological Readiness After ACL Reconstruction.

BACKGROUND: Among young athletes returning to sport after anterior cruciate ligament reconstruction (ACLR), the extent to which psychological readiness is influenced by factors beyond the psychological domain is largely unknown. HYPOTHESIS: Young athletes with recent sport exposure and higher quadriceps strength will demonstrate higher psychological readiness within 8 weeks of medical clearance to return to sport (RTS) after ACLR. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 38 young athletes after primary ACLR completed testing within 8 weeks of medical clearance to RTS. All participants completed isometric knee extension strength testing, in addition to the ACL Return to Sport after Injury (ACL-RSI) questionnaire. Athletes who participated in sport between time of medical clearance to RTS and date of study enrollment were categorized as SPORT-YES. Those who had not yet participated in sports were categorized as SPORT-NO. Multiple linear regression analyses were used to determine differences in ACL-RSI scores based on quadriceps strength and sport exposure status, while adjusting for age and sex. RESULTS: Of the 38 participants, 20 (52.6%) were categorized as SPORT-YES. The regression model estimating overall ACL-RSI score (P < 0.01, adjusted R2 = 0.389) included significant independent contributions from age, sex, and sport exposure variables (age: P = 0.01, ß [95% CI] = -2.01 [-3.54, -0.48]; sex (male): P = 0.02, ß [95% CI] = 12.50 [2.36, 22.64]; strength: P = 0.51, ß [95% CI] = -2.47 [-10.07,5.13]; sport exposure: P < 0.01, ß [95% CI] = 12.89 [3.58, 22.19]). CONCLUSION: In partial accordance with our hypothesis, recent sport exposure was significantly associated with higher ACL-RSI scores among young athletes in the weeks after medical clearance to RTS after ACLR, while quadriceps strength was not. CLINICAL RELEVANCE: Future prospective work is needed to determine the existence and direction of causal relationships between exposure to sport environment and psychological readiness among young athletes after ACLR.

A cold-atom Ramsey clock with a low volume physics package.

We demonstrate a Ramsey-type microwave clock interrogating the 6.835 GHz ground-state transition in cold [Formula: see text]Rb atoms loaded from a grating magneto-optical trap (GMOT) enclosed in an additively manufactured loop-gap resonator microwave cavity. A short-term stability of [Formula: see text] is demonstrated, in reasonable agreement with predictions from the signal-to-noise ratio of the measured Ramsey fringes. The cavity-grating package has a volume of [Formula: see text]67 cm[Formula: see text], ensuring an inherently compact system while the use of a GMOT drastically simplifies the optical requirements for laser cooled atoms. This work is another step towards the realisation of highly compact portable cold-atom frequency standards.

SH2 domain protein E and ABL signaling regulate blood vessel size.

Blood vessels in different vascular beds vary in size, which is essential for their function and fluid flow along the vascular network. Molecular mechanisms involved in the formation of a vascular lumen of appropriate size, or tubulogenesis, are still only partially understood. Src homology 2 domain containing E (She) protein was previously identified in a screen for proteins that interact with Abelson (Abl)-kinase. However, its biological role has remained unknown. Here we demonstrate that She and Abl signaling regulate vessel size in zebrafish embryos and human endothelial cell culture. Zebrafish she mutants displayed increased endothelial cell number and enlarged lumen size of the dorsal aorta (DA) and defects in blood flow, eventually leading to the DA collapse. Vascular endothelial specific overexpression of she resulted in a reduced diameter of the DA, which correlated with the reduced arterial cell number and lower endothelial cell proliferation. Chemical inhibition of Abl signaling in zebrafish embryos caused a similar reduction in the DA diameter and alleviated the she mutant phenotype, suggesting that She acts as a negative regulator of Abl signaling. Enlargement of the DA size in she mutants correlated with an increased endothelial expression of claudin 5a (cldn5a), which encodes a protein enriched in tight junctions. Inhibition of cldn5a expression partially rescued the enlarged DA in she mutants, suggesting that She regulates DA size, in part, by promoting cldn5a expression. SHE knockdown in human endothelial umbilical vein cells resulted in a similar increase in the diameter of vascular tubes, and also increased phosphorylation of a known ABL downstream effector CRKL. These results argue that SHE functions as an evolutionarily conserved inhibitor of ABL signaling and regulates vessel and lumen size during vascular tubulogenesis.

Illuminating the druggable genome: Pathways to progress.

There are ∼4500 genes within the 'druggable genome', the subset of the human genome that expresses proteins able to bind drug-like molecules, yet existing drugs only target a few hundred. A substantial subset of druggable proteins are largely uncharacterized or understudied, with many falling within G protein-coupled receptor (GPCR), ion channel, and kinase protein families. To improve scientific understanding of these three understudied protein families, the US National Institutes of Health launched the Illuminating the Druggable Genome Program. Now, as the program draws to a close, this review will lay out resources developed by the program that are intended to equip the scientific community with the tools necessary to explore previously understudied biology with the potential to rapidly impact human health.

The Community Engaged Digital Alzheimer's Research (CEDAR) Study: A Digital Intervention to Increase Research Participation of Black American Participants in the Brain Health Registry.

BACKGROUND: Although Black/African American older adults bear significant inequities in prevalence, incidence, and outcomes of Alzheimer's disease and related dementias, they are profoundly under-included in Alzheimer's Disease research. Community-Engaged Research (e.g., equitable community/science partnerships) is an evidence-based approach for improving engagement of underrepresented populations into Alzheimer's Disease research, but has lacked scalability to the national level. As internet use among older adults from underrepresented populations continues to grow, internet-based research shows promise as a feasible, valid approach to engagement and longitudinal assessment. The Community Engaged Digital Alzheimer's Research (CEDAR) study utilizes a community-engaged research approach to increase the engagement and research participation of Black/African American adults in the Brain Health Registry (BHR) and Alzheimer Disease clinical research. OBJECTIVES: To describe the methods and evaluate the feasibility of the CEDAR culturally-informed digital platform within BHR. DESIGN: All Black/African American participants in BHR were invited to enroll in CEDAR and to consider serving on a newly convened Community-Scientific Partnership Board to guide the study. The community board guided the development a culturally-informed cadre of engagement materials and strategies to increase research participation. Engagement strategies included incentives for study task completion, culturally-informed communications (e.g., landing page, emails and social media), resources about brain health, and video and written testimonials by CEDAR participants. SETTING: BHR, an Internet-based registry and cohort. PARTICIPANTS: BHR participants self-identifying as Black/African American were invited to enroll. All participants who signed an online informed consent document were enrolled. MEASUREMENTS: We report the number of participants invited, enrolled, completed tasks, and volunteered to join the community board. We compared the demographics, cognitive profile, and baseline BHR task completion rates between CEDAR participants and all those invited to join the study. RESULTS: Of 3738 invited, 349 (9.34%) enrolled in CEDAR. 134 (37% of CEDAR participants) volunteered to join the community board, of which 19 were selected for the community board. Compared to those invited, the CEDAR cohort had a higher percentage of female participants (84.5%) and a lower percentage of participants who identify as belonging to more than one ethnocultural group (21.8%). Compared to those did not enroll in CEDAR, those enrolled in CEDAR had a higher percentage of participants completing all BHR tasks (22%) and a higher percentage of participants completing at least one cognitive test (76%). Those enrolled in CEDAR also had a higher percentage of participants having an enrolled study partner (18%). CONCLUSIONS: A culturally-informed Community-Engaged Research approach, including a remotely-convened community board, to engagement of Black/African American participants in an online research registry is feasible. This approach can be adapted for use in various clinical studies and other settings. Future studies will evaluate the effectiveness of the engagement strategies.

A New Measure of Posterior Morphology in Sagittal Craniosynostosis: The Occipital Bullet Index.

INTRODUCTION: Sagittal craniosynostosis (SC) is associated with scaphocephaly, an elongated narrow head shape. Assessment of regional severity in the scaphocephalic head is limited by the use of serial computed tomographic (CT) imaging or complex computer programing. Three-dimensional measurements of cranial surface morphology provide a radiation-free alternative for assessing cranial shape. This study describes the creation of an occipital bulleting index (OBI), a novel tool using surface morphology to assess the regional severity in patients with SC. METHODS: Surface imaging from CT scans or 3D photographs of 360 individuals with SC and 221 normocephalic individuals were compared to identify differences in morphology. Cartesian grids were created on each individual's surface mesh using equidistant axial and sagittal planes. Area under the curve (AUC) analyses were performed to identify trends in regional morphology and create measures capturing population differences. RESULTS: The largest differences were located in the medial regions posteriorly. Using these population trends, a measure was created to maximize AUC. The OBI has an AUC of 0.72 with a sensitivity of 74% and a specificity of 61%. When the frontal bossing index is applied in tandem, the two have a sensitivity of 94.7% and a specificity of 93.1%. Correlation between the two scores in individuals with SC was found to be negligible with an intraclass correlation coefficient of 0.018. Severity was found to be independent of age under 24 months, sex, and imaging modality. CONCLUSIONS: This index creates a tool for differentiating control head shapes from those with SC and has the potential to allow for objective evaluation of the regional severity, outcomes of different surgical techniques, and tracking shape changes in individuals over time, without the need for radiation.

SH2 domain protein E (SHE) and ABL signaling regulate blood vessel size.

Blood vessels in different vascular beds vary in lumen diameter, which is essential for their function and fluid flow along the vascular network. Molecular mechanisms involved in the formation of a vascular lumen of appropriate size, or tubulogenesis, are still only partially understood. Src homology 2 domain containing E (She) protein was previously identified in a screen for proteins that interact with Abelson (Abl)-kinase. However, its biological role has remained unknown. Here we demonstrate that She and Abl signaling regulate vascular lumen size in zebrafish embryos and human endothelial cell culture. Zebrafish she mutants displayed increased endothelial cell number and enlarged lumen size of the dorsal aorta (DA) and defects in blood flow. Vascular endothelial specific overexpression of she resulted in a reduced diameter of the DA lumen, which correlated with the reduced arterial cell number and lower endothelial cell proliferation. Chemical inhibition of Abl signaling in zebrafish embryos caused a similar reduction in the DA diameter and alleviated the she mutant phenotype, suggesting that She acts as a negative regulator of Abl signaling. Enlargement of the DA lumen in she mutants correlated with an increased endothelial expression of claudin 5a and 5b (cldn5a / cldn5b), which encode proteins enriched in tight junctions. Inhibition of cldn5a expression partially rescued the enlarged DA in she mutants, suggesting that She regulates DA lumen size, in part, by promoting cldn5a expression. SHE knockdown in human endothelial umbilical vein cells resulted in a similar increase in the diameter of vascular tubes, and also increased phosphorylation of a known ABL downstream effector CRKL. These results argue that SHE functions as an evolutionarily conserved inhibitor of ABL signaling and regulates lumen size during vascular tubulogenesis.

Transfacial Two-pin External Mandibular Distraction Osteogenesis: A Technique for Neonatal Airway Obstruction from Robin Sequence.

Surgical management in those with moderate-to-severe airway obstruction includes tongue-lip adhesion, tracheostomy, and/or mandibular distraction osteogenesis. This article describes a transfacial two-pin external device technique for mandibular distraction osteogenesis, utilizing minimal dissection. Methods: The first percutaneous pin is transcutaneously placed just inferior to the sigmoid notch parallel to the interpupillary line. The pin is then advanced through the pterygoid musculature at the base of the pterygoid plates, toward the contralateral ramus, and exits the skin. A second parallel pin is placed spanning the bilateral mandibular parasymphysis distal to the region of the future canine. With the pins in place, bilateral high ramus transverse corticotomies are performed. Using univector distractor devices, the length of activation varies, with the goal of overdistraction to achieve a class III relationship of the alveolar ridges. Consolidation is limited to a 1:1 period with the activation phase, and removal is performed by cutting and pulling the pins out of the face. Results: To guide optimal transcutaneous pin placement, transfacial pins were then placed through twenty segmented mandibles. Mean upper pin (UP) distance was 20.7 ± 1.1 mm from the tragus. The distance between the cutaneous entry of the UP and lower pin was 23.5 ± 0.9 mm, and the tragion-UP-lower pin angle was 118.7 ± 2.9°. Conclusions: The two-pin technique has potential advantages regarding nerve injury and mandibular growth, given an intraoral approach with limited dissection. It may safely be performed on neonates whose small size may preclude the use of internal distractor devices.

"Creation of the Scaphocephalic Index: Measurement of Global and Regional Severity in Scaphocephaly".

INTRODUCTION: The recently described frontal bossing index (FBI) and occipital bullet index (OBI) allow for quantification of scaphocephaly. A similar index examining biparietal narrowing has not been described. Addition of such an index measuring width would allow for direct evaluation of the primary growth restriction in sagittal craniosynostosis (SC) and the formation of an optimized global Width/Length measure. METHODS: CT scans and 3D photos were used to recreate scalp surface anatomy. Equidistant axial, sagittal, and coronal planes were overlaid creating a Cartesian grid. Points of intersection were analyzed for population trends in biparietal width. Using the most descriptive point coupled with the sellion's protrusion to control for head size, the vertex narrowing index (VNI) is formed. By combining this index with the FBI and OBI, the Scaphocephalic Index (SCI) is created as a tailored W/L measure. RESULTS: Using 221 control and 360 individuals with sagittal craniosynostosis, the greatest difference occurred superiorly and posteriorly at a point 70% of the head's height and 60% of the head's length. This point had an area under the curve (AUC) of 0.97 and sensitivity and specificity of 91.2% and 92.2% respectively. The SCI has an AUC of 0.9997, sensitivity and specificity >99%, and interrater reliability of 0.995. The correlation coefficients between the CT imaging and 3D photography was 0.96. CONCLUSION: The VNI, FBI, and OBI evaluate regional severity while the SCI is able to describe global morphology in patients with sagittal craniosynostosis. These allow for superior diagnosis, surgical planning, and outcome assessment, independent of radiation.

Characterization of olfactomedin 4+ cells in prostate and urethral-tube epithelium during murine postnatal development and in adult mice.

Olfactomedin4 (Olfm4) is expressed in normal mouse prostate. However, Olfm4+ cells in the murine prostate have not been well characterized. In this study, we generated an Olfm4eGFP reporter mouse line with C57BL/6 mice and investigated the distribution of Olfm4/eGFP-expressing cells during postnatal development from P1, P7, P14, P20, P42, P56 to adult male mouse prostate and urethral tube. We observed Olfm4/eGFP expression in urogenital and prostatic epithelial cells during early postnatal development, which persisted into adulthood in urethral-tube and anterior-prostate (AP) epithelium. We found Olfm4+ cells are E-cadherin+/CD44+/Foxa1+ and some of subpopulation are Ck8+/Ck5+/Sca-1-/Ck4-/Syn- in the adult mouse AP epithelium. Functional studies of single-cell preparations of Olfm4/eGFP-expressing cells isolated from adult Olfm4eGFP mouse prostate demonstrated that Olfm4+ cells can grow and form colonies, spheres, or organoids in culture. Bioinformatic analysis of Olfm4+ cells using single-cell RNA sequencing meta data in adult mouse urethra (GSE145865) identified upregulation of genes related to cell and tissue migration and development, as well as upregulation of xenobiotic metabolism signaling pathways. In conclusion, Olfm4eGFP mouse is a novel model to further study Olfm4's biological functions and Olfm4+ cells may contribute importantly to cellular processes supporting development and homeostasis of the epithelium in murine prostate and urethral tube.

Understanding Online Registry Facilitators and Barriers Experienced by Black Brain Health Registry Participants: The Community Engaged Digital Alzheimer's Research (CEDAR) Study.

BACKGROUND: Failure of Alzheimer's disease and related diseases (ADRD) research studies to include and engage Black participants is a major issue, which limits the impact and generalizability of research findings. Little is known about participation of Black adults in online ADRD-related research registries. OBJECTIVES: As part of the Community Engaged Digital Alzheimer's Research (CEDAR) Study, this study aims to increase our understanding of facilitators and barriers of Black adults to participating in ADRD-related online registries, as well as to understand their preferences for communication channels. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: We invited all Black participants enrolled in the Brain Health Registry (BHR) to complete a cross-sectional online survey. The survey consisted of rating scales and open-text questions asking about their attitudes towards brain health research, reasons for joining and continuing to participate in BHR, difficulties with participating, and preferences for modes of contact and website usage. RESULTS: Of all invited Black BHR participants (N=3,636), 198 (5.5%) completed the survey. The mean age was 58.4 (SD=11.3), mean years of education were 16.3 (SD=2.4), and 85.5% identified as female. Reported facilitators for joining and continuing to participate in BHR were personal interest (e.g., learning more about own brain health) and altruism (e.g., helping research). Among additional registry features which could encourage return, receiving feedback or scores about BHR tasks was rated the highest. Of those who found BHR participation difficult (21%), the most frequent reason was time burden. The most preferred way of receiving study information was via email. Participants reported that the websites that they used the most were YouTube and Facebook. DISCUSSION: The results of our study can inform the development of culturally-responsive registry features and engagement efforts to improve inclusion and participation of Black adults in online ADRD research. Providing participants with feedback about their registry performance and reducing the number of registry tasks are among the recommended strategies.

The Need for Additional Surgery after Passive versus Active Approaches to Syndromic Craniosynostosis: A Meta-analysis.

Endoscopically assisted craniofacial surgery (EACS) has numerous advantages over traditional, open approaches, such as fronto-orbital advancement in treating nonsyndromic craniosynostosis. However, several articles report high reoperation rates in syndromic patients treated with EACS. This meta-analysis and review examines undesirable outcome rates (UORs), defined as reoperation or Whitaker category III/IV, in syndromic patients undergoing primary EACS compared with procedures that actively expand the cranial vault. Methods: PubMed and Embase were searched in June 2022 to identify all articles reporting primary reoperation or Whitaker outcomes for syndromic patients undergoing cranial vault expanding surgery or suturectomy. A meta-analysis of proportions was performed comparing UORs, and a trim-and-fill adjustment method was used to validate sensitivity and assess publication bias. Results: A total of 721 articles were screened. Five EACS articles (83 patients) and 22 active approach articles (478 patients) met inclusion criteria. Average UORs for EACS and active approaches were 26% (14%-38%) and 20% (13%-28%), respectively (P = 0.18). Reoperation occurred earlier in EACS patients (13.7 months postprimary surgery versus 37.1 months for active approaches, P = 0.003). Relapse presentations and reason for reoperation were also reviewed. Subjectively, EACS UORs were higher in all syndromes except Apert, and Saethre-Chotzen patients had the highest UOR for both approaches. Conclusions: There was no statistically significant increase in UORs among syndromic patients treated with EACS compared with traditional approaches, although EACS patients required revision significantly sooner. Uncertainties regarding the long-term efficacy of EACS in children with syndromic craniosynostosis should be revisited as more data become available.

Ultra-low noise, bi-polar, programmable current sources.

We present the design process and implementation of fully open-source, ultra-low noise programmable current source systems in two configurations. Although originally designed as coil drivers for Optically Pumped Magnetometers (OPMs), the device specifications make them potentially useful in a range of applications. The devices feature a bi-directional current range of ±10 and ±250 mA on three independent channels with 16-bit resolution. Both devices feature a narrow 1/f noise bandwidth of 1 Hz, enabling magnetic field manipulation for high-performance OPMs. They exhibit a low noise of 146 pA/Hz and 4.1 nA/Hz, which translates to 15 and 16 ppb/Hz noise relative to full scale.