Development of a hospital-academic collaboration to implement an interprofessional telehealth breastfeeding support group.

Accessible lactation support for breastfeeding parents, even in well-resourced areas, is often insufficient. At the same time, opportunities for real-life, sustainable interprofessional learning experiences for health professions students are scarce. Delivery of lactation support via telehealth allows for greater accessibility for both consumers and students. This study describes the development of an interprofessionally-facilitated telehealth breastfeeding support group, a partnership between a health professions graduate school and a teaching hospital in Boston, MA. Program conceptualization, theoretical basis, and development are reviewed. Occupational therapy and nursing students were involved in the group at various points of entry and with different degrees of engagement. Students developed skills in group facilitation, lactation support, and program evaluation. The group had consistent participation, ranging from 2 to more than 10 participants per session, serving parents across urban and rural areas. The group format and development could be replicated to provide needs for local communities of parents and interprofessional students.

Interventions for Caregivers of People Who Have Had a Stroke: A Systematic Review.

IMPORTANCE: It is vital that occupational therapy practitioners address caregivers' needs to enable them to maintain participation in caregiving for people poststroke. OBJECTIVE: To explore the evidence for the effectiveness of interventions within the scope of occupational therapy practice for caregivers of people poststroke that facilitate maintaining participation in the caregiver role. DATA SOURCES: We conducted a narrative synthesis systematic review of the literature published in the MEDLINE, PsycINFO, CINAHL, OTseeker, and Cochrane databases between January 1, 1999, and December 31, 2019. Article reference lists were also hand searched. STUDY SELECTION AND DATA COLLECTION: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines were used, and articles were included if they were within the date range and scope of occupational therapy practice and included caregivers of someone poststroke. Two independent reviewers used Cochrane methodology to perform the systematic review. FINDINGS: Twenty-nine studies met the inclusion criteria and were divided into five intervention themes: cognitive-behavioral therapy (CBT) techniques, caregiver education only, caregiver support only, caregiver education and support, and multimodal interventions. Both the CBT technique of problem-solving combined with stroke education and one-on-one caregiver education and support interventions had strong strength of evidence. Multimodal interventions had moderate strength of evidence, and caregiver education only and caregiver support only had low strength of evidence. CONCLUSIONS AND RELEVANCE: Addressing caregiver needs with problem-solving and caregiver support in addition to typical education and training is essential. More research is needed that uses consistent doses, interventions, treatment settings, and outcomes. What This Article Adds: Although more research is needed, occupational therapy practitioners should provide combinations of interventions such as problem-solving techniques, customized support for each caregiver, and individualized education in the care of the stroke survivor.

Interventions Using Cognitive-Behavioral Therapy Techniques for Caregivers of People With Stroke (January 1, 1999- December 31, 2019).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Project. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from the systematic review on stroke and interventions using cognitive-behavioral therapy techniques for caregivers of people with stroke.

Education and Training Interventions for Caregivers of People With Stroke (January 1, 1999-December 31, 2019).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from a systematic review on interventions providing only education and training for caregivers of people with stroke.

Virtual Faculty and Peer Mentoring to Promote Social Belonging among Minoritized Physical Therapist and Nursing Students.

Minoritized health sciences students report experiencing social isolation and discrimination, and cite the lack of faculty representation as barriers to their success. While virtual mentoring can increase sense of belonging and connectedness, these effects have not been examined in minoritized health sciences students. The purpose of this study was to investigate whether virtual mentoring from faculty and peers could decrease social isolation and promote social belonging among minoritized first-year physical therapy and nursing students. Using a mixed methods explanatory sequential design, racial and ethnic minority physical therapy and nursing students (n = 8) received virtual mentoring and attended virtual networking events while students from across the health profession programs served as a comparison group (n = 16). While virtual mentoring relationships took longer to establish, there was an increase in satisfaction with mentoring for the intervention group compared with no improvement for the comparison group who received traditional academic advising. Qualitative data analysis revealed that mentors served as role models who had overcome barriers and persevered, decreasing feelings of isolation, and bolstering mentee confidence. A virtual multiple-mentor model can decrease isolation and promote social belonging for minoritized students and offer support for students even after the pandemic.

Multimodal Interventions for Caregivers of People With Stroke (January 1, 1999- December 31, 2019).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from the systematic review on stroke and multimodal interventions for caregivers of people with stroke.

Education and Support Interventions for Caregivers of Persons With Stroke (January 1, 1999-December 31, 2019).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from a systematic review on stroke and education and support interventions for caregivers of people with stroke.

Fatigue and functional outcomes in cancer rehabilitation.

PURPOSE: Cancer-related fatigue (CRF) is one of the most common symptoms experienced by oncology patients, though its impact on functional outcomes during inpatient rehabilitation is relatively unknown. The purpose of this study is to determine whether CRF severity on admission is related to functional gains following standard rehabilitation care in an inpatient oncology rehabilitation population. METHODS: A retrospective cohort study was conducted within an inpatient oncology unit at a long-term acute care hospital. Seventy-six patients admitted to the hospital between April and December 2015 with an oncology diagnosis, planned discharge, and completed standardized assessments of CRF and functional ability were included in this study. Patients received standard interdisciplinary rehabilitation services including physical and occupational therapy. CRF was assessed on admission using the Brief Fatigue Inventory, and functional abilities were assessed on admission and discharge using the basic mobility and daily activity domains of the Activity Measure for Post-Acute Care inpatient short forms (AM-PAC). RESULTS: Ninety-seven percent of patients reported CRF, and 57% reported severe CRF upon admission. Patients demonstrated on average a 30% and 14% reduction in functional impairment in basic mobility and daily activity respectively during their admission. There was no significant correlation found between CRF on admission and change in functional impairment. CONCLUSION: This study contributes to existing literature in that it found patients who received inpatient rehabilitation services demonstrate significant improvement in their functional status despite reporting CRF upon admission to a long-term acute care hospital oncology unit.

Quality control guidelines for clinical-grade human induced pluripotent stem cell lines.

Use of clinical-grade human induced pluripotent stem cell (iPSC) lines as a starting material for the generation of cellular therapeutics requires demonstration of comparability of lines derived from different individuals and in different facilities. This requires agreement on the critical quality attributes of such lines and the assays that should be used. Working from established recommendations and guidance from the International Stem Cell Banking Initiative for human embryonic stem cell banking, and concentrating on those issues more relevant to iPSCs, a series of consensus workshops has made initial recommendations on the minimum dataset required to consider an iPSC line of clinical grade, which are outlined in this report. Continued evolution of this field will likely lead to revision of these guidelines on a regular basis.

Good Cell Culture Practice for stem cells and stem-cell-derived models.

The first guidance on Good Cell Culture Practice (GCCP) dates back to 2005. This document expands this to include aspects of quality assurance for in vitro cell culture focusing on the increasingly diverse cell types and culture formats used in research, product development, testing and manufacture of biotechnology products and cell-based medicines. It provides a set of basic principles of best practice that can be used in training new personnel, reviewing and improving local procedures, and helping to assure standard practices and conditions for the comparison of data between laboratories and experimentation performed at different times. This includes recommendations for the documentation and reporting of culture conditions. It is intended as guidance to facilitate the generation of reliable data from cell culture systems, and is not intended to conflict with local or higher level legislation or regulatory requirements. It may not be possible to meet all recommendations in this guidance for practical, legal or other reasons. However, when it is necessary to divert from the principles of GCCP, the risk of decreasing the quality of work and the safety of laboratory staff should be addressed and any conclusions or alternative approaches justified. This workshop report is considered a first step toward a revised GCCP 2.0.

Higher activity of the inducible nitric oxide synthase contributes to very early onset inflammatory bowel disease.

OBJECTIVES: The NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD). METHODS: Seventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant. RESULTS: The NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10(-6), OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02-5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage. CONCLUSIONS: These studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production.

Generation of induced pluripotent stem cells from CD34+ cells across blood drawn from multiple donors with non-integrating episomal vectors.

The methodology to create induced pluripotent stem cells (iPSCs) affords the opportunity to generate cells specific to the individual providing the host tissue. However, existing methods of reprogramming as well as the types of source tissue have significant limitations that preclude the ability to generate iPSCs in a scalable manner from a readily available tissue source. We present the first study whereby iPSCs are derived in parallel from multiple donors using episomal, non-integrating, oriP/EBNA1-based plasmids from freshly drawn blood. Specifically, successful reprogramming was demonstrated from a single vial of blood or less using cells expressing the early lineage marker CD34 as well as from unpurified peripheral blood mononuclear cells. From these experiments, we also show that proliferation and cell identity play a role in the number of iPSCs per input cell number. Resulting iPSCs were further characterized and deemed free of transfected DNA, integrated transgene DNA, and lack detectable gene rearrangements such as those within the immunoglobulin heavy chain and T cell receptor loci of more differentiated cell types. Furthermore, additional improvements were made to incorporate completely defined media and matrices in an effort to facilitate a scalable transition for the production of clinic-grade iPSCs.

Active-site models for the nickel-iron hydrogenases: effects of ligands on reactivity and catalytic properties.

Described are new derivatives of the type [HNiFe(SR)(2)(diphosphine)(CO)(3)](+), which feature a Ni(diphosphine) group linked to a Fe(CO)(3) group by two bridging thiolate ligands. Previous work had described [HNiFe(pdt)(dppe)(CO)(3)](+) ([1H](+)) and its activity as a catalyst for the reduction of protons (J. Am. Chem. Soc. 2010, 132, 14877). Work described in this paper focuses on the effects on properties of NiFe model complexes of the diphosphine attached to nickel as well as the dithiolate bridge, 1,3-propanedithiolate (pdt) vs 1,2-ethanedithiolate (edt). A new synthetic route to these Ni-Fe dithiolates is described, involving reaction of Ni(SR)(2)(diphosphine) with FeI(2)(CO)(4) followed by in situ reduction with cobaltocene. Evidence is presented that this route proceeds via a metastable µ-iodo derivative. Attempted isolation of such species led to the crystallization of NiFe(Me(2)pdt)(dppe)I(2), which features tetrahedral Fe(II) and square planar Ni(II) centers (H(2)Me(2)pdt = 2,2-dimethylpropanedithiol). The new tricarbonyls prepared in this work are NiFe(pdt)(dcpe)(CO)(3) (2, dcpe = 1,2-bis(dicyclohexylphosphino)ethane), NiFe(edt)(dppe)(CO)(3) (3), and NiFe(edt)(dcpe)(CO)(3) (4). Attempted preparation of a phenylthiolate-bridged complex via the FeI(2)(CO)(4) + Ni(SPh)(2)(dppe) route gave the tetrametallic species [(CO)(2)Fe(SPh)(2)Ni(CO)](2)(µ-dppe)(2). Crystallographic analysis of the edt-dcpe compund [2H]BF(4) and the edt-dppe compound [3H]BF(4) verified their close resemblance. Each features pseudo-octahedral Fe and square pyramidal Ni centers. Starting from [3H]BF(4) we prepared the PPh(3) derivative [HNiFe(edt)(dppe)(PPh(3))(CO)(2)]BF(4) ([5H]BF(4)), which was obtained as a ∼2:1 mixture of unsymmetrical and symmetrical isomers. Acid-base measurements indicate that changing from Ni(dppe) (dppe = Ph(2)PCH(2)CH(2)PPh(2)) to Ni(dcpe) decreases the acidity of the cationic hydride complexes by 2.5 pK(a)(PhCN) units, from ∼11 to ∼13.5 (previous work showed that substitution at Fe leads to more dramatic effects). The redox potentials are more strongly affected by the change from dppe to dcpe, for example the [2](0/+) couple occurs at E(1/2) = -820 for [2](0/+) vs -574 mV (vs Fc(+/0)) for [1](0/+). Changes in the dithiolate do not affect the acidity or the reduction potentials of the hydrides. The acid-independent rate of reduction of CH(2)ClCO(2)H by [2H](+) is about 50 s(-1) (25 °C), twice that of [1H](+). The edt-dppe complex [2H](+) proved to be the most active catalyst, with an acid-independent rate of 300 s(-1).

Short-course ondansetron for the prevention of methotrexate-induced nausea in children with Crohn disease.

OBJECTIVES: Methotrexate (MTX) is an effective treatment for Crohn disease (CD); however, its application may be limited by the occurrence of nausea. We assessed whether a short course of ondansetron minimized this adverse event. PATIENTS AND METHODS: A retrospective case-control study of patients with CD who received MTX at the Children's Hospital of Eastern Ontario between 2001 and 2009 was conducted. RESULTS: Sixty-four patients received MTX during this time period. The mean age of diagnosis was 12.0 ± 3.0 years (± standard deviation), and the mean age when MTX was initiated was 13.6 ± 2.6 years. Those receiving only 1 or 2 doses of MTX (N = 4) and stopped for reasons other than development of nausea were not included in the analysis. Fifty patients received ondansetron premedication using a 4- to 8-week tapering schedule with MTX, and only 1 patient (2.0%) developed nausea within the first 3 months of MTX. In contrast, 6 of 10 patients (60.0%, P < 0.001) not premedicated with ondansetron reported nausea following MTX within 3 months. Four of these 6 patients subsequently received ondansetron and had no further complaints. Following ondansetron discontinuation, 5 of 50 (10%) patients developed nausea with subsequent MTX injections, but responded to reinstitution of ondansetron. Some children developed anticipatory nausea (6/60, 10%) and 3 experienced nausea relief after initiating premedication with ondansetron. CONCLUSIONS: Nausea following MTX is a common complaint in patients with CD. For most, this adverse effect may be prevented through the use of a short-course ondansetron as premedication. Ondansetron to treat MTX-induced nausea also can be successfully used but a proactive preventive strategy can be achieved.

Derivation of induced pluripotent stem cells from human peripheral blood T lymphocytes.

Induced pluripotent stem cells (iPSCs) hold enormous potential for the development of personalized in vitro disease models, genomic health analyses, and autologous cell therapy. Here we describe the generation of T lymphocyte-derived iPSCs from small, clinically advantageous volumes of non-mobilized peripheral blood. These T-cell derived iPSCs ("TiPS") retain a normal karyotype and genetic identity to the donor. They share common characteristics with human embryonic stem cells (hESCs) with respect to morphology, pluripotency-associated marker expression and capacity to generate neurons, cardiomyocytes, and hematopoietic progenitor cells. Additionally, they retain their characteristic T-cell receptor (TCR) gene rearrangements, a property which could be exploited for iPSC clone tracking and T-cell development studies. Reprogramming T-cells procured in a minimally invasive manner can be used to characterize and expand donor specific iPSCs, and control their differentiation into specific lineages.

EBV is necessary for proliferation of dually infected primary effusion lymphoma cells.

Epstein Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are found together in approximately 80% of primary effusion lymphomas (PEL), but their contribution to these cancers is unclear. We found that dominant-negative derivatives of EBNA1 inhibited EBV-positive PEL cells from forming colonies. Those rare PEL cells that proliferated after expression of the dominant-negative derivatives usually expressed these derivatives at low or undetectable levels and continued to maintain their EBV genomes. Those proliferating cells expressing higher levels of the derivatives expressed mutant derivatives that could not bind DNA. These findings indicate that EBV is required to sustain proliferation, as measured by colony formation of dually infected PEL cells. The dominant-negative derivatives of EBNA1 had no effect on the colony-forming ability of five EBV-negative, KSHV-negative hematopoietic cell lines. Surprisingly, they did inhibit the colony-forming ability of EBV-negative, KSHV-positive PEL cells. The small fraction of cells that continued to proliferate expressed only mutants of the EBNA1 derivatives that could no longer bind DNA. These findings indicate that the site-specific DNA-binding activity of EBNA1 or its derivatives when expressed efficiently in EBV-negative, KSHV-positive PEL cells inhibits their colony formation possibly through their binding to the KSHV genome.

Antagonistic control of oxidative stress-induced cell death in Arabidopsis by two related, plant-specific zinc finger proteins.

The most familiar form of plant programmed cell death is the hypersensitive response (HR) associated with successful plant immune responses. HR is preceded by an oxidative burst and the generation of both reactive oxygen intermediates (ROI) and NO. The Arabidopsis LSD1 gene encodes a negative regulator of plant programmed cell death that meets several criteria for a regulator of processes relevant to ROI management during pathogen responses. Here we demonstrate that a highly conserved LSD1 paralogue, LOL1, acts as a positive regulator of cell death. Manipulation of LOL1 expression alters both the superoxide-dependent, runaway cell death phenotype of lsd1 plants and the normal HR. We also show that LSD1 and LOL1 have antagonistic effects on copper-zinc superoxide dismutase accumulation, consistent with functions in cell death control via maintenance of ROI homeostasis.

A secondary structure that contains the 5' and 3' splice sites suppresses splicing of duck hepatitis B virus pregenomic RNA.

Pregenomic RNA (pgRNA) plays two major roles in the hepadnavirus life cycle. It is the mRNA for two proteins required for DNA replication, C and P, and it is the template for reverse transcription. pgRNA is a terminally redundant transcript whose synthesis does not involve RNA splicing. For duck hepatitis B virus (DHBV), a spliced RNA is derived from pgRNA by removal of a single intron. The mechanism for the simultaneous cytoplasmic accumulation of unspliced (pgRNA) and spliced RNA was not known. We found that mutations within two regions of the DHBV genome reduced the level of pgRNA while increasing the level of spliced RNA. One region is near the 5' end of pgRNA (region A), while the second is near the middle of pgRNA (region B). Inspection of the DHBV nucleotide sequence indicated that region A could base pair with region B. The 5' and 3' splice sites of the intron of the spliced RNA are within regions A and B, respectively. Substitutions that disrupted the predicted base pairing reduced the accumulation of pgRNA and increased the accumulation of spliced RNA. Restoration of base pairing, albeit mutant in sequence, resulted in restoration of pgRNA accumulation with a decrease in the level of spliced RNA. Our data are consistent with a model in which splicing of the pgRNA is suppressed by a secondary structure between regions A and B that occludes the splicing machinery from modifying pgRNA.