Low-frequency, therapeutic ultrasound treatment for congenital ectodermal dysplasia in toddlers

Hay-Wells Syndrome is a rare genetic disorder characterized by ankyloblepharon, ectodermal dysplasia, and cleft palate. Recalcitrant scalp wounds with secondary infections are common. This case series describes the use of acoustic pressure wound therapy in 3-year-old fraternal twins (male and female) with HWS-associated scalp wounds. Present since infancy, the wounds were severe and extensive at presentation to the authors' wound clinic. Previous management consisted of standard topical treatments, including foam; oxidized, regenerated-cellulose/collagen with silver; calcium alginate; silver sulfadiazine cream; and biologic tissue matrix. Following admission to the authors' wound clinic, acoustic pressure wound therapy was administered one to three times weekly for 3 to 10 minutes for 7 months in addition to standard topical treatments to provide nonsurgical debridement and reduce wound bioburden without inflicting additional pain. Substantial improvements occurred during the first 5 weeks of consistent treatment. When treatments became sporadic due to health and family issues, wound deterioration occurred. After 7 months, wound sizes decreased by 31.3% in the boy and 1.1% in the girl, 70% of the wound surface in both children was covered with granulation tissue, and no clinical signs of infection were evident. The treatments were well tolerated. So far, the twins each received a total of 37 treatments. Consistent, long-term acoustic pressure wound therapy improved the status of severe, recalcitrant, Hay-Wells Syndrome-associated scalp wounds.     

Sulindac derivatives that activate the peroxisome proliferator-activated receptor gamma but lack cyclooxygenase inhibition

A series of novel derivatives of the nonsteroidal anti-inflammatory drug (NSAID) sulindac sulfide were synthesized as potential agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma). Nonpolar and aromatic substitutions on the benzylidene ring as well as retention of the carboxylic acid side chain were required for optimal activity. Compound 24 was as potent a compound as any other in the series with an EC50 of 0.1 microM for the induction of peroxisome proliferator response element (PPRE)-luciferase activity. Direct binding of compound 24 to PPARgamma was demonstrated by the displacement of [(3)H]troglitazone, a PPARgamma agonist, in a scintillation proximity assay. Compound 24 also stimulated the binding of PPARgamma to a PPRE-containing oligonucleotide and induced expression of liver fatty-acid binding protein (L-FABP) and adipocyte fatty acid-binding protein (aP2), two established PPARgamma target genes. Taken together, these compounds represent potential leads in the development of novel PPARgamma agonists.     

Public education materials about Vascular Composite Allotransplantation and donation in the United States: Current scope and limitations

As the field of Vascular Composite Allotransplantation (VCA) grows, demand for VCA donations will increase. The public should be made aware of this treatment option to support patients' informed decision-making and authorization for deceased donation. We assessed the availability and quality of existing VCA public education materials from organ procurement organizations (OPOs), transplant centers, the Organ Procurement and Transplant Network, Veterans Affairs, and the Department of Defense. A content analysis was performed to identify topics covered and important gaps. In total, 1314 public education materials were analyzed, including OPO Facebook posts (61.6%), OPO Twitter posts (29.9%), websites (6.4%), and written documents (eg, fact sheets, research reports) (2.1%). Upper extremity (34.7%) and face (34.5%) transplants were more commonly covered than reproductive (6.4%) or other VCA types (2.8%). Most materials (76.6%) referenced a specific VCA story. However, few materials described which patient population could benefit from VCA (eg, Veterans, amputees, burn victims, 16.4%), the authorization requirements for VCA donation (6.6%), or the appearance of transplanted VCA organs (1.2%). Current VCA public education materials do not adequately educate the public. More comprehensive education materials are needed to prepare the public to authorize VCA donation, become potential donors, or learn about transplant options.     

Assessing disorganized attachment representations: a systematic psychometric review and meta-analysis of the Manchester Child Attachment Story Task

Narrative story stem measures are increasingly popular for the assessment of attachment representations among early school-age children. Given their clinical and theoretical importance, disorganized representations are typically a focus of assessment procedures. The Manchester Child Attachment Story Task (MCAST) is one such measure. A systematic literature review and meta-analysis was conducted to evaluate the documented reliability and validity of the MCAST with a focus on assessing disorganized representations. Twenty-five studies were included in the review encompassing 1,876 children from nine countries. Results suggest that inter-rater reliability for the MCAST is acceptable and the prevalence of disorganization identified on the MCAST among various subgroups (e.g. community, clinical, adopted/maltreated) is comparable to prevalence estimates from other developmental periods using other assessment methods. In addition, prevalence of disorganization on the MCAST differed in hypothesized ways between the various subgroups. However, MCAST disorganization did not correlate in predictable ways with many constructs when relationships were examined within samples. Few studies examined the relationship of disorganization on the MCAST with parenting variables, aspects of adoption and maltreatment, and emotion regulation skills. Recommendations for further study of the MCAST and for how the tool might be integrated into clinical and developmental research are provided.     

Physical therapy management of pediatric and adolescent neck pain: a call to action

Abstract

Background: Neck pain is reported to be as high as 40% in adolescents and can be a precursor to developing adult persistent neck pain.

Objectives: To identify and review literature on physical therapy management of pediatric and adolescent neck pain.

Methods: A sensitive search strategy adhered to PRISMA guidelines. Our systematic review used the databases PubMed, CINAHL, and Embase including articles published from inception to May 2019. For the article to be included, it had to meet the following criteria: (a) age under 18?years old; (b) musculoskeletal neck pain; (c) any intervention or treatment provided by physical therapists; (d) English language; (e) any outcome measure that reported disability, function, or pain; (f) any and all published literature: randomized controlled trials (RCTs), systematic reviews, cohort studies, case reports, editorials, and commentaries.

Results: Our comprehensive search yielded 5,115 articles and two studies met eligibility. Both articles were written by the same author group. The articles investigated the effect of pain neuroscience education (PNE) plus deep neck muscle strengthening in twenty-one students ages 15-18?years old with chronic idiopathic neck pain. The results concluded there may be some benefit to PNE plus deep neck flexor and extensor strength.

Conclusions: The main finding of this systematic review is the paucity of published research on physical therapy management of pediatric and adolescent neck pain. Our systematic review serves as a call to action for physical therapists to perform further research in order to provide the best evidence-based care for this population.     

A centromere satellite concomitant with extensive karyotypic diversity across the Peromyscus genus defies predictions of molecular drive

A common feature of eukaryotic centromeres is the presence of large tracts of tandemly arranged repeats, known as satellite DNA. However, these centromeric repeats appear to experience rapid evolution under forces such as molecular drive and centromere drive, seemingly without consequence to the integrity of the centromere. Moreover, blocks of heterochromatin within the karyotype, including the centromere, are hotspots for chromosome rearrangements that may drive speciation events by contributing to reproductive isolation. However, the relationship between the evolution of heterochromatic sequences and the karyotypic dynamics of these regions remains largely unknown. Here, we show that a single conserved satellite DNA sequence in the order Rodentia of the genus Peromyscus localizes to recurrent sites of chromosome rearrangements and heterochromatic amplifications. Peromyscine species display several unique features of chromosome evolution compared to other Rodentia, including stable maintenance of a strict chromosome number of 48 among all known species in the absence of any detectable interchromosomal rearrangements. Rather, the diverse karyotypes of Peromyscine species are due to intrachromosomal variation in blocks of repeated DNA content. Despite wide variation in the copy number and location of repeat blocks among different species, we find that a single satellite monomer maintains a conserved sequence and homogenized tandem repeat structure, defying predictions of molecular drive. The conservation of this satellite monomer results in common, abundant, and large blocks of chromatin that are homologous among chromosomes within one species and among diverged species. Thus, such a conserved repeat may have facilitated the retention of polymorphic chromosome variants within individuals and intrachromosomal rearrangements between species—both factors that have previously been hypothesized to contribute towards the extremely wide range of ecological adaptations that this genus exhibits.

     

An innovative advance to increase the use of the vaccine information statement

Because many physicians do not use the Vaccine Information Statement (VIS), we created a revised statement that would alert the physician to the need to use the VIS. Even though the Centers for Disease Control (CDC) coordinated this evaluation, both the CDC and most of the State Board of Medical Examiners did not support this revision of the VIS. Despite the disinterest of the vast majority of the State Board of Medical Examiners, we would recommend that this updated VIS be implemented immediately to educate our society on the information in the VIS.     

Wild-type and A315T mutant TDP-43 exert differential neurotoxicity in a Drosophila model of ALS

The RNA-binding protein TDP-43 has been linked to amyotrophic lateral sclerosis (ALS) both as a causative locus and as a marker of pathology. With several missense mutations being identified within TDP-43, efforts have been directed towards generating animal models of ALS in mouse, zebrafish, Drosophila and worms. Previous loss of function and overexpression studies have shown that alterations in TDP-43 dosage recapitulate hallmark features of ALS pathology, including neuronal loss and locomotor dysfunction. Here we report a direct in vivo comparison between wild-type and A315T mutant TDP-43 overexpression in Drosophila neurons. We found that when expressed at comparable levels, wild-type TDP-43 exerts more severe effects on neuromuscular junction architecture, viability and motor neuron loss compared with the A315T allele. A subset of these differences can be compensated by higher levels of A315T expression, indicating a direct correlation between dosage and neurotoxic phenotypes. Interestingly, larval locomotion is the sole parameter that is more affected by the A315T allele than wild-type TDP-43. RNA interference and genetic interaction experiments indicate that TDP-43 overexpression mimics a loss-of-function phenotype and suggest a dominant-negative effect. Furthermore, we show that neuronal apoptosis does not require the cytoplasmic localization of TDP-43 and that its neurotoxicity is modulated by the proteasome, the HSP70 chaperone and the apoptosis pathway. Taken together, our findings provide novel insights into the phenotypic consequences of the A315T TDP-43 missense mutation and suggest that studies of individual mutations are critical for elucidating the molecular mechanisms of ALS and related neurodegenerative disorders.