U(1)' solution to the mu-problem and the proton decay problem in supersymmetry without R-parity

The Minimal Supersymmetric Standard Model (MSSM) is plagued by two major fine-tuning problems: the mu-problem and the proton decay problem. We present a simultaneous solution to both problems within the framework of a U(1)'-extended MSSM (UMSSM), without requiring R-parity conservation. We identify several classes of phenomenologically viable models and provide specific examples of U(1)' charge assignments. Our models generically contain either lepton number violating or baryon number violating renormalizable interactions, whose coexistence is nevertheless automatically forbidden by the new U(1)' gauge symmetry. The U(1)' symmetry also prohibits the potentially dangerous and often ignored higher-dimensional proton decay operators such as QQQL and UUDE which are still allowed by R-parity. Thus, under minimal assumptions, we show that once the mu-problem is solved, the proton is sufficiently stable, even in the presence of a minimum set of exotics fields, as required for anomaly cancellation. Our models provide impetus for pursuing the collider phenomenology of R-parity violation within the UMSSM framework.Comment: Version published in Phys. Rev.

Comparative effectiveness of acupuncture in sham-controlled trials for knee osteoarthritis: A systematic review and network meta-analysis

Objectives: Although many trials have assessed the effect of acupuncture on knee osteoarthritis (KOA), its efficacy remains controversial. Sham acupuncture techniques are regarded as representative control interventions in acupuncture trials and sometimes incorporate the use of sham devices (base units) to support a non-penetrating needle. To achieve successful blinding, these trials also use acupuncture base units in the verum acupuncture group. Base units are not used in real-world clinical settings. We aimed to assess the effect sizes of verum and sham acupuncture for KOA in sham-controlled trials with or without base units. Methods: A total of 10 electronic databases for randomized controlled trials (RCTs) comparing the efficacy of verum manual acupuncture and sham acupuncture for the treatment of KOA were searched for articles published before April 12, 2022. The primary outcome was pain intensity, and the secondary outcomes included physical function. The first assessment after the end of treatment was chosen for analysis. Effect sizes are reported as standardized mean differences (SMDs) with 95% confidence intervals (95% CIs). The risk of bias was assessed using the Cochrane risk of bias tool, and publication bias was evaluated using a funnel plot and Egger’s test. The quality of evidence for estimates was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results: Fifteen RCTs were included. There was generally a low risk of bias except for the difficulty in blinding acupuncture therapists (performance bias). Compared to verum acupuncture in sham-controlled trials using base units, verum acupuncture in sham-controlled trials without base units was more effective for improving pain (SMD −0.56, 95% CI −1.09 to −0.03) and function (SMD −0.73, 95% CI −1.36 to −0.10) in KOA. The quality of evidence for network estimates was moderate to low due to the risk of bias and imprecision. Conclusion: These findings suggest that verum acupuncture in different types of sham-controlled trials has different effect sizes for KOA. Because base units are not used in clinical settings, the results of verum acupuncture in sham-controlled trials with base units need to be interpreted carefully

Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants.

Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau). Recently, we further showed that these specialized neurons show preferential aggregation of TDP-43 in FTLD-TDP. Whether VENs and fork cells are prone to tau accumulation in FTLD-tau remains unclear, and no previous studies of these neurons have focused on patients with pathogenic variants in the gene encoding microtubule-associated protein tau (FTLD-tau/MAPT). Here, we examined regional profiles of tau aggregation and neurodegeneration in 40 brain regions in 8 patients with FTLD-tau/MAPT and 7 with Pick's disease (PiD), a sporadic form of FTLD-tau that often presents with bvFTD. We further qualitatively assessed the cellular patterns of frontoinsular tau aggregation in FTLD-tau/MAPT using antibodies specific for tau hyperphosphorylation, acetylation, or conformational change. ACC and mid-insula were among the regions most affected by neurodegeneration and tau aggregation in FTLD-tau/MAPT and PiD. In these two forms of FTLD-tau, severity of regional neurodegeneration and tau protein aggregation were highly correlated across regions. In FTLD-tau/MAPT, VENs and fork cells showed disproportionate tau protein aggregation in patients with V337 M, A152T, and IVS10 + 16 variants, but not in patients with the P301L variant. As seen in FTLD-TDP, our data suggest that VENs and fork cells represent preferentially vulnerable neuron types in most, but not all of the MAPT variants we studied

Parent Prevention Communication Profiles and Adolescent Substance Use: A Latent Profile Analysis and Growth Curve Model

This current study identifies distinct parent prevention communication profiles and examines whether youth with different parental communication profiles have varying substance use trajectories over time. Eleven schools in two rural school districts in the Midwestern United States were selected, and 784 students were surveyed at three time points from the beginning of 7th grade to the end of 8th grade. A series of latent profile analyses were performed to identify discrete profiles/subgroups of substance-specific prevention communication (SSPC). The results revealed a 4-profile model of SSPC: Active-Open, Passive-Open, Active-Silent, and Passive-Silent. A growth curve model revealed different rates of lifetime substance use depending on the youth’s SSPC profile. These findings have implications for parenting interventions and tailoring messages for parents to fit specific SSPC profiles

In vitro and in vivo assessments of an optimal polyblend composition of polycaprolactone/gelatin nanofibrous scaffolds for Achilles tendon tissue engineering

In this study, we manufactured various ratios of polycaprolactone (PCL)/gelatin (GE) highly aligned electrospun nanofibrous scaffolds (ENs) to investigate the effects of polymer ratio on tenogenic differentiation activity. For biological assessments, the cell proliferation rate was optimal in the PCL/GE (9:1) group. Interestingly, however, the tenogenic differentiation rate was best for the PCL/GE (7:3) group. From our outcomes, we established that a poly-blending mix of PCL/GE (7:3) is a promising ratio for tenogenic differentiation. Thus, our findings may provide for an effective mesh to promote tenogenic differentiation of ENs in future tendon tissue engineering applications.This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean government (MSIP&MOHW) (No. 2017M3A9E4048170)

Case Report Sarcoidosis Associated with Oxaliplatin-Based Chemotherapy for Colorectal Cancer

Acute lung injury occasionally occurs after chemotherapy, but pulmonary toxicities by oxaliplatin-based chemotherapy have rarely been identified. A 76-year-old female with rectosigmoid colon cancer presented with ongoing dyspnea after the eighth cycle of standard chemotherapy (5-fluorouracil, sodium folinic acid, and oxaliplatin: FOLFOX). Nodular consolidation progressed despite antibiotics and BAL fluid analysis was compatible with the diagnosis of sarcoidosis. Corticosteroid therapy rapidly improved the symptoms and radiographic findings. We report this first case of secondary sarcoidosis related to FOLFOX therapy with review of references

Insulin Sensitivity Is Retained in Mice with Endothelial Loss of Carcinoembryonic Antigen Cell Adhesion Molecule 1

CEACAM1 regulates endothelial barrier integrity. Because insulin signaling in extrahepatic target tissues is regulated by insulin transport through the endothelium, we aimed at investigating the metabolic role of endothelial CEACAM1. To this end, we generated endothelial cell-specific Ceacam1 null mice (VECadCre+Cc1(fl/fl)) and carried out their metabolic phenotyping and mechanistic analysis by comparison to littermate controls. Hyperinsulinemic-euglycemic clamp analysis showed intact insulin sensitivity in VECadCre+Cc1(fl/fl) mice. This was associated with the absence of visceral obesity and lipolysis and normal levels of circulating non-esterified fatty acids, leptin, and adiponectin. Whereas the loss of endothelial Ceacam1 did not affect insulin-stimulated receptor phosphorylation, it reduced IRS-1/Akt/eNOS activation to lower nitric oxide production resulting from limited SHP2 sequestration. It also reduced Shc sequestration to activate NF-kappaB and increase the transcription of matrix metalloproteases, ultimately inducing plasma IL-6 and TNFalpha levels. Loss of endothelial Ceacam1 also induced the expression of the anti-inflammatory CEACAM1-4L variant in M2 macrophages in white adipose tissue. Together, this could cause endothelial barrier dysfunction and facilitate insulin transport, sustaining normal glucose homeostasis and retaining fat accumulation in adipocytes. The data assign a significant role for endothelial cell CEACAM1 in maintaining insulin sensitivity in peripheral extrahepatic target tissues

Center on Disability Studies eNewsletter, September 2023

Welcome to the September 2023 CDS Quarterly eNewsletter. Special highlights in this issue include: Maui Response Director’s Message Featured Artist Alexandra McClurg, MACL Educators Scholarship, Spark Aloha! H-PEP Inclusive First Aid/CPR/AED Upcoming Classes Nā Hōkū Newsletter Release, Project Hoʻokuʻi V Mia Ives-Rublee and Justice Shorter #PacRim 2024 Keynotes Hōkūlani Insider Newsletter Release, Project Hōkūlani Swim Safe: ASD Program Upcoming Classes Scholarships Opportunities, #PacRim2024 Sponsor and Exhibitor Invitations, #PacRim2024 Hawaiʻi Inclusive Early Childhood Professional Prep Project Soccer Classes, Wellness Matters Program Webinar with Dr. Jun Yaeda, University of Tsukuba, Japan September Events, Access to Independence Featured Film Release on KHON, The Power of Hoʻokuʻ

Developmental delay in Rett syndrome: data from the natural history study

Background: Early development appears normal in Rett syndrome (OMIM #312750) and may be more apparent than real. A major purpose of the Rett Syndrome (RTT) Natural History Study (NHS) was to examine achievement of developmental skills or abilities in classic and atypical RTT and assess phenotype-genotype relations in classic RTT. Methods: Developmental skills in four realms, gross and fine motor, and receptive and expressive communication from initial enrollment and longitudinal assessments for up to 7 years, were assessed from 542 females meeting criteria for classic RTT and 96 females with atypical RTT divided into two groups: 50 with better and 46 with poorer functional scores. Data were analyzed for age at acquisition and loss of developmental features and for phenotype-genotype effects. Acquired, lost, and retained skills were compared between classic RTT and atypical RTT with better or poorer functional scores using Fisher's Exact test. To examine if the mean total score from the Motor Behavioral Assessment during follow-up differed for acquiring a skill, we used a generalized estimating equation assuming compound symmetry correlation structure within a subject. A general linear model was used to examine whether the mean age of acquisition or loss of a developmental skill differed by mutation type. P values <0.05 were considered significant and were two-sided without adjustment for multiple testing. Statistical analyses utilized SAS 9.3 (SAS Institute, Cary, NC, USA). Results: Early developmental skills or abilities were often acquired albeit later than normal. More complex motor and communication acquisitions were delayed or absent. Clinical severity was less in those achieving the respective skill. Individuals with R133C, R294X, and R306C point mutations and 3′ truncations tended to have better developmental outcomes. Conclusions: Early developmental skills were acquired by many, but clear differences from normal emerged, particularly in skills expected after age 6 months. When comparing clinical severity, greater acquisition of specific skills was associated with specific mutations, confirming the impression that these mutations confer milder developmental abnormalities. These data may serve for planning and interpretation of early intervention studies in RTT. Trial registration This NHS study, clinicaltrials.gov (NCT00296764), represents the largest group of RTT participants assessed repeatedly by direct examination