To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19
  B cells approximates 40%-50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity.
 
  In this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50-150 mg/m
  ), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy.
 
  Five patients received at least 1 IV infusion of low-dose rituximab, following alemtuzumab therapy, with a mean follow-up of 41 months. None of the 5 patients developed secondary autoimmune disorders. An additional 5 patients with follow-up over less than 24 months received at least 1 infusion of low-dose rituximab treatment following alemtuzumab treatment. No secondary autoimmune diseases were observed.
 
  An anti-CD20 "whack-a-mole" B-cell depletion strategy may serve to mitigate alemtuzumab-associated secondary autoimmunity in MS by reducing the imbalance in B- and T-cell regulatory networks during immune reconstitution. We believe that these observations warrant further investigation.
 
  This study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases.
 This study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases.Fluid flow is a powerful morphogenic force during embryonic development. The physical forces created by flowing fluids can either create morphogen gradients or be translated by mechanosensitive cells into biological changes in gene expression. In this Primer, we describe how fluid flow is created in different systems and highlight the important mechanosensitive signalling pathways involved for sensing and transducing flow during embryogenesis. Specifically, we describe how fluid flow helps establish left-right asymmetry in the early embryo and discuss the role of flow of blood, lymph and cerebrospinal fluid in sculpting the embryonic cardiovascular and nervous system.
  Multiple early childhood screenings are recommended, but gaps persist in implementation. Our aim for this project was to improve screening, discussion, referral, and follow-up of development, autism spectrum disorder (ASD), maternal depression, and social determinants of health (SDoH) to 90% by July 2018.
 
  This 1-year national quality improvement collaborative involved 19 pediatric primary care practices. Supported by virtual and in-person learning opportunities, practice teams implemented changes to early childhood screening. Monthly chart reviews were used to assess screening, discussion, referral, and follow-up for development, ASD, maternal depression, and SDoH. Parent surveys were used to assess parent-reported screening and referral and/or resource provision. Practice self-ratings and team surveys were used to assess practice-level changes.
 
  Participating practices included independent, academic, hospital-affiliated, and multispecialty group practices and community health centers in 12 states. The cps. Continued advocacy for adequate resources to support referral and follow-up is needed to translate increased screening into improved health outcomes.
  An updated synthesis of research on substance abuse prevention programs can promote enhanced uptake of programs with proven effectiveness, particularly when paired with information relevant to practitioners and policy makers.
 
  To assess the strength of the scientific evidence for psychoactive substance abuse prevention programs for school-aged children and youth.
 
  A systematic review was conducted of studies published up until March 31, 2020.
 
  Articles on substance abuse prevention programs for school-aged children and youth were independently screened and included if they met eligibility criteria (1) the program was designed for a general population of children and youth (ie, not designed for particular target groups), (2) the program was delivered to a general population, (3) the program only targeted children and youth, and (4) the study included a control group.
 
  Two reviewers independently evaluated study quality and extracted outcome data.
 
  Ninety studies met eligibility criteria, representing 16 programs. Programs evaluated with the largest combined sample sizes were Drug Abuse Resistance Education, Project Adolescent Learning Experiences Resistance Training, Life Skills Training (LST), the Adolescent Alcohol Prevention Trial, and Project Choice.
 
  Given the heterogeneity of outcomes measured in the included studies, it was not possible to conduct a statistical meta-analysis of program effectiveness.
 
  The most research has been conducted on the LST program.  https://www.selleckchem.com/products/BIBW2992.html  However, as with other programs included in this review, studies of LST effectiveness varied in quality. With this review, we provide an updated summary of evidence for primary prevention program effectiveness.
 The most research has been conducted on the LST program. However, as with other programs included in this review, studies of LST effectiveness varied in quality. With this review, we provide an updated summary of evidence for primary prevention program effectiveness.Thermomyces dupontii, a widely distributed thermophilic fungus, is an ideal organism for investigating the mechanism of thermophilic fungal adaptation to diverse environments. However, genetic analysis of this fungus is hindered by a lack of available and efficient gene-manipulating tools. In this study, two different Cas9 proteins from mesophilic and thermophilic bacteria, with in vivo expression of a single guide RNA (sgRNA) under the control of tRNAGly, were successfully adapted for genome editing in T. dupontii We demonstrated the feasibility of applying these two gene editing systems to edit one or two genes in T. dupontii The mesophilic CRISPR/Cas9 system displayed higher editing efficiency (50 to 86%) than the thermophilic CRISPR/Cas9 system (40 to 67%). However, the thermophilic CRISPR/Cas9 system was much less time-consuming than the mesophilic CRISPR/Cas9 system. Combining the CRISPR/Cas9 systems with homologous recombination, a constitutive promoter was precisely knocked in to activate a silent polyketide synthase-nonribosomal peptide synthase (PKS-NRPS) biosynthetic gene, leading to the production of extra metabolites that did not exist in the parental strains.