A systematic review of change in symptoms, well-being and quality of life with group singing in people with cancer and their caregivers.

PURPOSE: This systematic review aimed to assess the impact of group singing on physical function, cancer-related symptoms, well-being (emotional, physical, social, spiritual), and health-related quality of life in individuals with cancer and their caregivers. METHODS: A search was performed using Ovid MEDLINE, Embase, Scopus and Web of Science from inception to April 2023; key words included cancer, choir, and group singing. Observational cohort, prospective or retrospective studies, randomized controlled studies, and crossover studies were included. Two teams of independent reviewers extracted data and assessed the risk of bias using the Downs and Black Tool. RESULTS: A total of 6 studies (6 reports) met the inclusion criteria for this review, with a mix of study designs. The overall quality of the studies was poor. Group singing significantly reduced anxiety levels in those with cancer and their caregivers, while the effects on depression were variable and there was no impact on fatigue. Caregivers reported improved well-being, self-efficacy and self-esteem. Both those with cancer and their caregivers had reductions in fear, anger, confusion; and reported improvement in energy, relaxation and connectedness at longer term follow-up compared to no treatment. Those with cancer reported improvements in health-related quality of life domains of bodily pain, vitality and mental health with group singing, though the effects on caregivers were mixed. CONCLUSIONS: Group singing may have favourable effects on selected symptoms, aspects of well-being, and domains of health-related quality of life specific to vitality, bodily pain, and mental health in individuals with cancer and their caregivers.

Barriers and facilitators to implementing self-directed therapy activities in inpatient rehabilitation settings.

BACKGROUND: Self-directed therapy activities are not currently part of routine care during inpatient rehabilitation. Understanding patient and clinician perspectives on self-directed therapy is key to increasing implementation. The aim of this study was to investigate barriers and facilitators to implementing a self-directed therapy programme ("My Therapy") in adult inpatient rehabilitation settings. METHODS: My Therapy was recommended by physiotherapists and occupational therapists and completed by rehabilitation inpatients independently, outside of supervised therapy sessions. Physiotherapists, occupational therapists, and patients were invited to complete an online questionnaire comprising open-ended questions on barriers and facilitators to prescribing and participating in My Therapy. A directed content analysis of free-text responses was undertaken, with data coded using categories of the Capability, Opportunity, and Motivation Model of Behaviour (COM-B model). RESULTS: Eleven patients and 20 clinicians completed the questionnaire. Patient capability was reported to be facilitated by comprehensive education by clinicians, with mixed attitudes towards the format of the programme booklet. Clinician capability was facilitated by staff collaboration. One benefit was the better use of downtime between the supervised therapy sessions, but opportunities for patients to engage in self-directed therapy were compromised by the lack of space to complete the programme. Clinician opportunity was reported to be provided via organisational support but workload was a reported barrier. Patient motivation to engage in self-directed therapy was reported to be fostered by feeling empowered, engaged, and encouraged to participate. Clinician motivation was associated with belief in the value of the programme. CONCLUSION: Despite some barriers to rehabilitation patients independently practicing therapeutic exercises and activities outside of supervised sessions, both clinicians and patients agreed it should be considered as routine practice. To do this, patient time, ward space, and staff collaboration are required. Further research is needed to scale-up the implementation of the My Therapy programme and evaluate its effectiveness.

Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens.

Despite the identification of the high-incidence red cell antigen Era nearly 40 years ago, the molecular background of this antigen, together with the other 2 members of the Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing of individuals with serologically defined Er alloantibodies identified several missense mutations within the PIEZO1 gene, encoding amino acid substitutions within the extracellular domain of the Piezo1 mechanosensor ion channel. Confirmation of Piezo1 as the carrier molecule for the Er blood group antigens was demonstrated using immunoprecipitation, CRISPR/Cas9-mediated gene knockout, and expression studies in an erythroblast cell line. We report the molecular bases of 5 Er blood group antigens: the recognized Era, Erb, and Er3 antigens and 2 novel high-incidence Er antigens, described here as Er4 and Er5, establishing a new blood group system. Anti-Er4 and anti-Er5 are implicated in severe hemolytic disease of the fetus and newborn. Demonstration of Piezo1, present at just a few hundred copies on the surface of the red blood cell, as the site of a new blood group system highlights the potential antigenicity of even low-abundance membrane proteins and contributes to our understanding of the in vivo characteristics of this important and widely studied protein in transfusion biology and beyond.

The Perceptions of Telehealth Physiotherapy for People with Bronchiectasis during a Global Pandemic-A Qualitative Study.

Physiotherapy is a core component of management for people with bronchiectasis and has predominantly been delivered in an in-person consultative format. With the global pandemic, a telehealth physiotherapy model of service evolved, but the perceptions and experiences from the consumer perspective of this service have not been evaluated. Participants who had a diagnosis of bronchiectasis and received a minimum of two telehealth physiotherapy sessions during the months of March 2020 to December 2020 at a private hospital were invited to take part in a semistructured interview. Interview transcripts were coded independently, with themes established by consensus from two researchers. In total, nine participants completed interviews (age range 44 to 83 years, 67% male), with four themes identified. Themes were initial mixed opinions and acceptance of telehealth physiotherapy as an alternate model, ease of use and limitations to the telehealth platform, enablers and barriers to physiotherapy service provision, and preferences for future models of telehealth physiotherapy beyond a pandemic. In the event of the continuation of telehealth physiotherapy services for people with bronchiectasis, the perceptions and experiences outlined by consumers could be applied to inform future modification of this model of service.

Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype.

The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44.

Feasibility of increasing the dosage of inpatient occupational therapy and physiotherapy rehabilitation via independent tasks and exercises: 'My Therapy'.

INTRODUCTION: The dosage of occupational therapy and physiotherapy positively correlates with rehabilitation patient and health service outcomes. Nevertheless, increasing the dosage during inpatient rehabilitation without additional resources can be challenging. This study aimed to determine feasibility of increasing the dosage of inpatient occupational therapy and physiotherapy rehabilitation with independent tasks and exercises outside of supervised sessions, the 'My Therapy' programme. METHODS: A two-group, quasi-experimental, pre-post-design examined feasibility of delivering My Therapy in addition to usual care, compared to usual care alone, for hospitalised musculoskeletal and frail older rehabilitation patients. My Therapy was prescribed by the occupational therapist and physiotherapist. A booklet was provided with an individually tailored set of tasks and exercises that were a sub-set of routine therapy, to be practised safely, effectively and independently outside of supervised sessions. The primary outcome was feasibility of My Therapy implementation to achieve at least 70% adherence. Secondary outcomes were self-reported daily My Therapy participation (minutes), total daily rehabilitation participation (minutes), adverse events, length of stay, 10-metre walk speed, FIM scores and discharge destination. RESULTS: Participation in My Therapy was achieved by 72% (83/116) of the My Therapy group, who averaged 14 min (SD 14) of daily practice outside of supervised sessions. Total daily rehabilitation participation was 177 min (SD 47) for My Therapy participants (n = 116) and 148 min (SD 88) for usual care participants (n = 89); mean difference 30 min (p = .00). A minimal clinically important difference in FIM was achieved for a significantly higher portion of the My Therapy group (22%, n = 26) compared to usual care (10%, n = 9; p = .02). There were no adverse events, safety concerns or group differences for other secondary outcomes. CONCLUSION: My Therapy was a feasible and safe way to increase the dosage of inpatient occupational therapy and physiotherapy rehabilitation via independent practice. Clinical Trial Registry: ACTRN12616000691448.

Resistance to malaria through structural variation of red blood cell invasion receptors.

The malaria parasite Plasmodium falciparum invades human red blood cells by a series of interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy-number variants affecting the host invasion receptor genes GYPA and GYPB We find that a nearby association with severe malaria is explained by a complex structural rearrangement involving the loss of GYPB and gain of two GYPB-A hybrid genes, which encode a serologically distinct blood group antigen known as Dantu. This variant reduces the risk of severe malaria by 40% and has recently increased in frequency in parts of Kenya, yet it appears to be absent from west Africa. These findings link structural variation of red blood cell invasion receptors with natural resistance to severe malaria.

The RHD(1227G>A) DEL-associated allele is the most prevalent DEL allele in Australian D- blood donors with C+ and/or E+ phenotypes.

BACKGROUND: Red blood cells (RBCs) with D antigen levels only detected by anti-D adsorption-elution and an antiglobulin test express a DEL phenotype. For two DEL types, including RHD(1227G>A), immunization of D- recipients has been reported. This study's aim was to measure the prevalence of DEL-associated RHD alleles in a cohort of Australian D- donors to develop a model to estimate alloimmunization risk. STUDY DESIGN AND METHODS: D-, C+ and/or E+ blood donors were screened for RHD exons using quantitative polymerase chain reaction. Donors with RHD signals were DEL phenotyped with MCAD6 anti-D. RHD alleles were characterized via single-nucleotide polymorphism array or sequencing. Extended DEL phenotyping was performed with an anti-D panel. RESULTS: Among 2027 donors, 39 carried RHD alleles that have been previously reported to associate with either the DEL or the weak D phenotype. An additional five donors carried previously unreported RHD alleles and exhibited the DEL phenotype: RHD(IVS2-2delA), RHD(IVS1+5G>C), RHD(ex9:del/CE), and RHD(ex8:del/CE) represented twice. In total, DEL/weak D-associated RHD alleles were detected in 44 of 2027 donors or 2.17% (95% confidence interval, 1.54%-2.81%). The RHD(1227G>A) DEL allele was the most frequent (n = 16). The risk of transfusing D- females not more than 40 years of age with an RHD(1227G>A) DEL RBC unit (when managed as D-) is estimated to be one in 149,109 transfusions (range, 100,680-294,490). CONCLUSION: DEL/weak D-associated RHD alleles were found in 2.17% of Australian D-, C+ and/or E+ blood donors. This differs from previous European reports in that the clinically significant RHD(1227G>A) DEL allele is the most prevalent.

Is Next Generation Sequencing the future of blood group testing?

Blood group genotyping has many advantages over conventional phenotyping for both blood donors and patients, and a number of high-throughput methods have now been developed. However, these are limited by a requirement for existing knowledge of the relevant blood group gene polymorphisms, and rare or novel mutations will not be detected. These mutations could be successfully identified by DNA sequencing of the blood group genes, and such an approach has been made feasible by the introduction of Next Generation Sequencing (NGS) technology. NGS enables many genes from multiple samples to be sequenced in parallel, resulting in sequencing information that could be used to obtain accurate blood group phenotype predictions in both blood donors and patients.

RhD variant caused by an in-frame triplet duplication in the RHD gene.

BACKGROUND: The RHD gene is highly polymorphic and a large number of D variants have already been detected. Several mechanisms are involved in the origin of D variants. In-frame deletions, resulting in a single-amino-acid deletion, have been described associated with RhD and RhCE variants. No in-frame duplications and/or insertions have been reported in the RH genes to date. STUDY DESIGN AND METHODS: Blood samples from a Brazilian blood donor and his sister were serologically tested with routine anti-D reagents and anti-D panels (ALBAclone advanced partial D typing kit, Alba Bioscience Limited; and D-Screen, Diagast), followed by molecular biology techniques, RHD polymerase chain reaction with sequence-specific priming and sequencing. RESULTS: Samples tested negative with routine immunoglobulin M (IgM) anti-D reagents and positive with IgG anti-D, which detect weak D cells. The pattern of results with anti-D panels did not correspond to any described before. A 3-bp in-frame duplication within Exon 1 (c.75_77dupTCT), resulting in the duplication of leucine 26 (p.Leu26dup), was identified in the two samples. CONCLUSION: We report the first RhD variant associated with a 3-bp in-frame duplication in the RHD gene, predicted to be located within the RhD protein transmembrane domain that might be expected to result in a weak-D-like phenotype, concordant with serologic findings.

The McLeod syndrome without acanthocytes.

A 45-year-old man developed chorea, behavioural changes, moderate amyotrophy and polyneuropathy. Hypertrophic cardiomyopathy and increased serum lactate dehydrogenase and creatine kinase (CK) were found. Acanthocytes were not detected. The absence of XK protein and faintly expressed Kell antigens on erythrocytes were found. Genetic test revealed a R133X mutation of the XK gene, confirming the McLeod syndrome. After 7 years he suddenly developed delirium followed by severe hypoglycaemia, hyperthermia, rhabdomyolysis, hepatic and renal failure. Malignant arrhythmia caused death.

Two missense mutations in the CD44 gene encode two new antigens of the Indian blood group system.

BACKGROUND: Blood samples were referred over a 10-year period from five patients whose serum samples contained antibodies to unidentified high-incidence antigens. Three patients (A, B, C) were of Moroccan origin and their antibodies and red blood cells (RBCs) were mutually compatible, but incompatible with those of the other two patients (D, E), who were of Pakistani origin. The antibodies and RBCs of D and E were mutually compatible, but incompatible with those of Patients A, B, and C. All the antibodies were detected during pregnancy. STUDY DESIGN AND METHODS: Serologic tests, including the use of enzyme-treated and chemically modified RBCs, suggested a relationship to CD44 (Indian blood group system). The monoclonal antibody immobilization of erythrocyte antigens (MAIEA) assay with monoclonal CD44 antibodies, immunoblotting of RBC membranes, and CD44 gene sequencing were carried out. RESULTS: Positive reactions in the MAIEA assay confirmed that the patients' antibodies are directed at CD44. Immunoblotting with two of the antibodies gave positive reactions of identical size to monoclonal anti-CD44 and failed to react with the RBCs of a CD44-deficient patient. One of the antibodies reacted with purified CD44. Sequencing of Exons 1 to 5 of CD44 revealed 255C>G in Exon 3 for A, B, and C encoding H85Q and 488C>A in Exon 5 for D and E encoding T163K [corrected] CONCLUSION: Two novel CD44 antigens of high incidence have been identified: IN3 (INFI) and IN4 (INJA) in the IN (Indian) blood group system. Lack of IN3 and IN4 results from homozygosity for mutations encoding H85Q and T163R in CD44, respectively.

McLeod syndrome: life-long neuropsychiatric disorder due to a novel mutation of the XK gene.

A 50-year-old man presented with worsening, virtually lifelong, chorea and progressive behavioural disturbance, involving disinhibition and hoarding, over 10 years. Clinical assessment revealed chorea, dysarthria, areflexia, an inappropriately jovial, impulsive manner and neuropsychological evidence of frontosubcortical dysfunction. Investigation results included an elevated creatine kinase, caudate atrophy and hypoperfusion, acanthocytes in the peripheral blood and the McLeod phenotype. DNA studies demonstrated a single-base deletion at position 172 in exon 1 of the XK gene, giving rise to a premature stop codon at position 129 in exon 2.

Patient interleukin-18 GCG haplotype associates with improved survival and decreased transplant-related mortality after unrelated-donor bone marrow transplantation.

Interleukin-18 (IL-18), a proinflammatory cytokine, is elevated in patients with acute graft-versus-host disease (aGVHD). IL-18 induces Th1 differentiation and cytotoxic T-lymphocyte function, both of which have been implicated in the pathogenesis of aGVHD. However, recent studies have shown that neutralization of IL-18 by antibodies leads to an increased risk of aGVHD-related mortality while administration of IL-18 significantly improved survival. We have genotyped a cohort of 157 patient/donor pairs undergoing unrelated donor bone marrow transplantation (BMT) for three polymorphisms recently identified in the promoter of the IL-18 gene: G-137C, C-607A and G-656T. Using phase software, three main haplotypes were reconstructed: GCG, CAT and GAT. We found no association between the occurrence of aGVHD and patient/donor haplotypes. The presence of the GCG haplotype in patients was associated with significantly decreased risk of transplant-related mortality at 100 d (23% in patients with GCG vs. 48% in patients without GCG, P < 0.01) and at 1 year (36% vs. 65%, P < 0.01). The presence of the GCG haplotype in patients was also associated with improved survival (57% vs. 32%, P < 0.01). Cox regression analysis showed that the presence of the GCG haplotype was associated with a twofold increased probability of survival. These data suggest that the IL-18 promoter GCG haplotype may influence survival after unrelated donor BMT without altering the risk of aGVHD.