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BACKGROUND: A patient survey highlighted that patients treated with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) at one NHS trust lacked confidence with the transition of care between teams. A personalised folder of treatment information was designed and given to patients prior to discharge. AIMS: To obtain patient feedback on the implementation and content of the folder. METHODS: 30 consecutive patients were given the folder at discharge. Participants completed an online questionnaire to determine whether the information in the folder was appropriate, given at the right time in the pathway and enhanced confidence on discharge. FINDINGS: 90% response rate was achieved. Of the respondents, 96% strongly agreed/agreed that the folder was helpful, 4% disagreed; 92% strongly agreed/agreed that the amount of information was right, 8% preferred more information, none less; 74% agreed/strongly agreed that the folder was provided at the right time; 96% said that the content met their expectations. CONCLUSION: Patients treated with CRS and HIPEC have specific needs related to their treatment. Implementation of the patient information folder at discharge increases patient confidence.
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Procedimentos Cirúrgicos de Citorredução , Alta do Paciente , Humanos , PacientesRESUMO
Collagen multifilament bundles comprised of thousands of monofilaments are prepared by multipin contact drawing of an entangled polymer solution consisting of collagen and poly(ethylene oxide) (PEO). The multifilament bundles are hydrated in graded concentrations of PEO and phosphate buffered saline (PBS) to promote assembly of collagen fibrils within each monofilament while preserving the structure of the multifilament bundle. Multiscale structural characterization reveals that the hydrated multifilament bundle contains properly folded collagen molecules packed in collagen fibrils containing microfibrils, staggered by exactly one-sixth of the microfibril D-band spacing to produce a periodicity of 11 nm. Sequence analysis predicts that in this structure, phenylalanine residues are close enough within and between microfibrils to become ultraviolet C (UVC) crosslinked. In agreement with this analysis, the ultimate tensile strength (UTS) and Young's modulus of the hydrated collagen multifilament bundles crosslinked by UVC radiation increase nonlinearly with total UVC energy to reach values in the range of native tendons without damage to the collagen molecules. This fabrication method recapitulates the structure of a tendon across multiple length scales and offers tunability in tensile properties using only collagen molecules and no other chemical additives in addition to PEO, which is almost entirely removed during the hydration process.
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Colágeno , Tendões , Colágeno/análise , Colágeno/química , Tendões/química , Módulo de Elasticidade , Resistência à Tração , Polímeros/análise , Fenômenos BiomecânicosRESUMO
BACKGROUND AND PURPOSE: The prevalence of Huntington disease (HD) has increased over time; however, there is a lack of up-to-date evidence documenting the economic burden of HD by disease stage. This study provides an estimate of the annual direct medical, nonmedical, and indirect costs associated with HD from participants in the Huntington's Disease Burden of Illness (HDBOI) study in five European countries and the USA. METHODS: The HDBOI is a retrospective, cross-sectional study. Data collection was conducted between September 2020 and May 2021. Participants were recruited by their HD-treating physicians and categorized as early stage (ES), mid stage (MS), or advanced stage (AS) HD. Data were collected via three questionnaires: a case report form, completed by physicians who collected health care resource use associated with HD to compute direct medical cost, and optional patient and caregiver questionnaires, which included information used to compute nondirect medical and indirect costs. Country-specific unit cost sources were used. RESULTS: HDBOI cost estimates were 12,663 (n = 2094) for direct medical costs, 2984 (n = 359) for nondirect medical costs, and 47,576 (n = 436) for indirect costs. Costs are higher in patients who are at later stages of disease; for example, direct medical costs estimates were 9220 (n = 846), 11,885 (n = 701), and 18,985 (n = 547) for ES, MS, and AS, respectively. Similar trends were observed for nondirect and indirect costs. Costs show large variations between patients and countries. CONCLUSIONS: Cost estimates from the HDBOI study show that people with HD and their caregivers bear a large economic burden that increases as disease progresses.
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Doença de Huntington , Humanos , Estudos Retrospectivos , Estudos Transversais , Estresse Financeiro , Custos de Cuidados de Saúde , Europa (Continente)/epidemiologia , Efeitos Psicossociais da DoençaRESUMO
This study investigates the feasibility of 3D printing continuous stainless steel fibre-reinforced polymer composites. The printing study was carried out using 316L stainless steel fibre (SSF) bundles with an approximate diameter of 0.15 mm. This bundle was composed of 90 fibres with a 14 µm diameter. This fibre bundle was first coated with polylactic acid (PLA) in order to produce a polymer-coated continuous stainless steel filament, with diameters tailored in the range from 0.5 to 0.9 mm. These filaments were then used to print composite parts using the material extrusion (MEX) technique. The SSF's volume fraction (Vf) was controlled in the printed composite structures in the range from 4 to 30 Vf%. This was facilitated by incorporating a novel polymer pressure vent into the printer nozzle, which allowed the removal of excess polymer. This thus enabled the control of the metal fibre content within the printed composites as the print layer height was varied in the range from 0.22 to 0.48 mm. It was demonstrated that a lower layer height yielded a more homogeneous distribution of steel fibres within the PLA polymer matrix. The PLA-SSF composites were assessed to evaluate their mechanical performance, volume fraction, morphology and porosity. Composite porosities in the range of 2-21% were obtained. Mechanical testing demonstrated that the stainless steel composites exhibited a twofold increase in interlaminar shear strength (ILSS) and a fourfold increase in its tensile strength compared with the PLA-only polymer prints. When comparing the 4 and 30 Vf% composites, the latter exhibited a significant increase in both the tensile strength and modulus. The ILSS values obtained for the steel composites were up to 28.5 MPa, which is significantly higher than the approximately 13.8 MPa reported for glass fibre-reinforced PLA composites.
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Three Web-based calculators, and three analogous spreadsheets, have been generated that predict in vivo metal occupancies of proteins based on known metal affinities. The calculations exploit estimates of the availabilities of the labile buffered pools of different metals inside a cell. Here, metal availabilities have been estimated for a strain of Escherichia coli that is commonly used in molecular biology and biochemistry research, e.g. in the production of recombinant proteins. Metal availabilities have been examined for cells grown in Luria-Bertani (LB) medium aerobically, anaerobically, and in response to H2O2 by monitoring the abundance of a selected set of metal-responsive transcripts by quantitative polymerase chain reaction (qPCR). The selected genes are regulated by DNA-binding metal sensors that have been thermodynamically characterized in related bacterial cells enabling gene expression to be read out as a function of intracellular metal availabilities expressed as free energies for forming metal complexes. The calculators compare these values with the free energies for forming complexes with the protein of interest, derived from metal affinities, to estimate how effectively the protein can compete with exchangeable binding sites in the intracellular milieu. The calculators then inter-compete the different metals, limiting total occupancy of the site to a maximum stoichiometry of 1, to output percentage occupancies with each metal. In addition to making these new and conditional calculators available, an original purpose of this article was to provide a tutorial that discusses constraints of this approach and presents ways in which such calculators might be exploited in basic and applied research, and in next-generation manufacturing.
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Escherichia coli , Peróxido de Hidrogênio , Anaerobiose , Escherichia coli/genética , Escherichia coli/metabolismo , Peróxido de Hidrogênio/metabolismo , Metais/metabolismo , Proteínas Recombinantes/metabolismoRESUMO
Gastrointestinal dysfunction in neuromuscular disease is associated with significant morbidity and mortality. It is often underreported despite its prevalence in this cohort. There are a number of issues reported, with gastrointestinal dysmotility and intestinal pseudo-obstruction carrying a poor outcome. We present a case-series of six patients attending a single-centre specialist muscle clinic with a confirmed diagnosis of a neuromuscular disorder (Duchenne muscular dystrophy, mitochondrial disorders, and desmin-related myopathy) and problematic gastrointestinal dysfunction. We advocate prompt recognition and early management, as part of the multi-disciplinary team, to prevent clinical deterioration.
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Doenças Mitocondriais , Distrofia Muscular de Duchenne , Doenças Neuromusculares , Humanos , Morbidade , Doenças Neuromusculares/complicações , Doenças Neuromusculares/epidemiologiaRESUMO
The gatekeeper training of parents is a promising approach for suicide prevention in young people, but little research has addressed the effectiveness of such training, especially using online delivery. This study aimed to evaluate the efficacy and acceptability of the delivery of an online suicide prevention training program, LivingWorks Start, to improve the capacity of parents to support young people at risk of suicide. The participants were 127 parents of young people aged 12-25 who completed the LivingWorks Start training and consented to participate in the evaluation. The participants completed online surveys before, after, and 3 months after training. The participants showed increases in perceived self-efficacy and formal help-seeking intentions, and reductions in suicide stigma, although stigma returned to the baseline three months post-training. Suicide literacy also increased, but only at the three-month follow-up. Most parents found the training acceptable, and did not find it upsetting. Prior mental health, suicide-related experiences, and pre-participation vulnerability were not predictive of finding the training distressing. Overall, the findings show that online gatekeeper training for parents can be beneficial, and is rarely associated with distress.
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Ideação Suicida , Prevenção do Suicídio , Suicídio , Adolescente , Austrália , Humanos , Saúde Mental , Avaliação de Programas e Projetos de Saúde , Suicídio/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: As people with cystic fibrosis (CF) are living longer, men with CF increasingly face both general and disease-specific sexual and reproductive health (SRH) concerns. This study explored the SRH experiences and preferences of men with CF in health care in the era of widespread use of highly effective CF modulator therapies. METHODS: We recruited men with CF aged 18 years and older to participate in a qualitative descriptive study using semi-structured telephone interviews to explore experiences and preferences related to CF SRH care. Two independent researchers coded interview transcripts and conducted content and thematic analysis using an inductive approach. FINDINGS: We interviewed 24 participants (mean age 33.7 ± 11.8 years, range 19-60) and identified five major themes: 1) CF SRH concerns, specifically infertility, can have negative impacts on men's perceptions of masculinity, relationships, and mental health; 2) As life expectancy increases, addressing male SRH is increasingly important in CF care; 3) Men with CF experience lack of SRH counseling and care; 4) Conversations about SRH should begin in early adolescence and be addressed regularly by CF providers in a stepwise fashion; 5) Men with CF value peer support and SRH information featuring the experiences of other men with CF. CONCLUSIONS: Men with CF acknowledge the need for comprehensive CF care that includes SRH and value early, stepwise, provider-initiated SRH conversations. Future work should seek a broader understanding of the impact of SRH on the mental health of men with CF as these concerns can have significant effects on the lives and self-identities of men with CF.
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Fibrose Cística , Serviços de Saúde Reprodutiva , Saúde Sexual , Adolescente , Adulto , Fibrose Cística/psicologia , Fibrose Cística/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Reprodutiva , Comportamento Sexual/psicologia , Adulto JovemRESUMO
BACKGROUND: New modulator therapies have markedly improved the health of people with cystic fibrosis (CF), allowing an increased focus on quality-of-life improvements for men with CF, including those related to sexual and reproductive health (SRH). This study explored CF providers' attitudes and experiences with addressing men's health in CF. METHODS: We interviewed geographically diverse adult and pediatric United States (U.S.) CF program directors via semi-structured telephone interviews exploring their perspectives and practices related to men's SRH in CF. Two coders analyzed transcribed interviews and created a codebook to identify key themes. RESULTS: We interviewed 20 providers and identified the following themes: 1) Men's SRH is important to address within CF care, but there is no standardization around this aspect of care; 2) There is no consensus about the recommendation or utilization of semen analysis to assess men's infertility; 3) There are many barriers to men's SRH care provision in CF centers, including the low priority of SRH concerns and provider discomfort and lack of expertise in SRH; 4) Providers desire clear evidence-based guidelines and patient resources related to men's SRH in CF; and 5) Providers believe future research should focus on testosterone and the impact of modulators on men's SRH. CONCLUSIONS: CF center directors acknowledge the importance of addressing SRH with men with CF, but there is a lack of standardization and research in this aspect of care. Existing barriers to optimal SRH care and identified facilitators in this study can serve as targets for interventions in the CF care model.
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Fibrose Cística , Saúde Sexual , Adulto , Criança , Fibrose Cística/terapia , Humanos , Masculino , Saúde do Homem , Saúde Reprodutiva , Comportamento Sexual , Estados Unidos/epidemiologiaRESUMO
The mounting global cancer burden has generated an increasing demand for oncologists to join the workforce. Yet, students report limited oncology exposure in undergraduate medical curricula, while undergraduate oncology mentorships remain underutilised. We established an undergraduate oncology society-led mentorship programme aimed at medical students across several UK universities to increase medical student oncology exposure. We electronically recruited and paired oncologist mentors and medical student mentees and distributed a dedicated questionnaire (pre- and post-mentorship) to compare mentees' self-reported cancer specialty knowledge and oncology career motivation after undertaking a 6-week mentorship. We also determined students' interest across specialties and subspecialties and measured mentor availability via percentage programme uptake. Statistical analysis included univariate inferential tests on SPSS software. Twentynine (23.4%) of 124 oncology specialists agreed to become mentors. The mentorship was completed by 30 students across three medical schools: 16 (53.3%) Barts, 10 (33.3%) Birmingham, and 4 (13.3%) King's; 11 (36.7%) mentored by medical oncologists, 10 (33.3%) by clinical/radiation oncologists, and 9 (30%) by surgical oncologists. The mentorship generated a statically significant increase in students' knowledge of the multidisciplinary team and all oncology-related specialties including academia/research but not interest towards a career in oncology. Undergraduate oncology mentoring is an effective educational, networking and motivational tool for medical students. Student societies are a valuable asset in cultivating medical student oncology interest by connecting students to faculty and increasing mentor accessibility. Further research should focus on developing an optimal mentorship structure and evaluating long-term outcomes of such educational initiatives.
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Tutoria , Estudantes de Medicina , Humanos , Oncologia , Mentores , Faculdades de MedicinaRESUMO
BACKGROUND: Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on clinical outcomes after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. OBJECTIVE: To evaluate the long-term quality-adjusted life years (QALYs) gained of endovascular coiling compare to neurosurgical clipping in the UK cohort of ISAT. METHODS: Between September 12, 1994 and May 1, 2002, patients with ruptured intracranial aneurysms who were assumed treatment equipoise were randomly allocated to either neurosurgical clipping or endovascular coiling. We followed-up 1644 patients in 22 UK neurosurgical centers for a minimum of 10 yr. Health-related quality of life (HRQoL) was collected through yearly questionnaires, measured by utilities calculated from the EQ-5D-3L. We compared HRQoL between the 2 treatment groups over a period of 10 yr. In all, 1-yr, 5-yr, and 10-yr QALYs were estimated by combining utility and survival information. RESULTS: Higher average utility values were found in the endovascular group throughout the follow-up period, with mean differences between groups statistically significant in most years. The 10-yr QALYs were estimated to be 6.68 (95% CI: 6.45-6.90) in the coiling group and 6.32 (95% CI: 6.10-6.55) in the clipping group, respectively, a significant mean difference of 0.36 (95% CI: 0.04-0.66). A third of this mean QALYs gain was estimated to derive solely from HRQoL differences. CONCLUSION: HRQoL after treatment of a ruptured intracranial aneurysm was better after endovascular coiling compared to neurosurgical clipping, which contributed significantly to the QALYs gained over a 10-yr period.
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Aneurisma Roto/cirurgia , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/instrumentação , Inquéritos e Questionários , Resultado do Tratamento , Reino Unido , Adulto JovemRESUMO
BACKGROUND: Exposure to suicidal behavior may be associated with increased risk of suicide, suicide attempt, and suicidal ideation and is a significant public health problem. However, evidence to date has not reliably distinguished between exposure to suicide versus suicide attempt, nor whether the risk differs across suicide-related outcomes, which have markedly different public health implications. Our aim therefore was to quantitatively assess the independent risk associated with exposure to suicide and suicide attempt on suicide, suicide attempt, and suicidal ideation outcomes and to identify moderators of this risk using multilevel meta-analysis. METHODS AND FINDINGS: We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, ASSIA, Sociological Abstracts, IBSS, and Social Services Abstracts from inception to 19 November 2019. Eligible studies included comparative data on prior exposure to suicide, suicide attempt, or suicidal behavior (composite measure-suicide or suicide attempt) and the outcomes of suicide, suicide attempt, and suicidal ideation in relatives, friends, and acquaintances. Dichotomous events or odds ratios (ORs) of suicide, suicide attempt, and suicidal ideation were analyzed using multilevel meta-analyses to accommodate the non-independence of effect sizes. We assessed study quality using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. Thirty-four independent studies that presented 71 effect sizes (exposure to suicide: k = 42, from 22 independent studies; exposure to suicide attempt: k = 19, from 13 independent studies; exposure to suicidal behavior (composite): k = 10, from 5 independent studies) encompassing 13,923,029 individuals were eligible. Exposure to suicide was associated with increased odds of suicide (11 studies, N = 13,464,582; OR = 3.23, 95% CI = 2.32 to 4.51, P < 0.001) and suicide attempt (10 studies, N = 121,836; OR = 2.91, 95% CI = 2.01 to 4.23, P < 0.001). However, no evidence of an association was observed for suicidal ideation outcomes (2 studies, N = 43,354; OR = 1.85, 95% CI = 0.97 to 3.51, P = 0.06). Exposure to suicide attempt was associated with increased odds of suicide attempt (10 studies, N = 341,793; OR = 3.53, 95% CI = 2.63 to 4.73, P < 0.001), but not suicide death (3 studies, N = 723; OR = 1.64, 95% CI = 0.90 to 2.98, P = 0.11). By contrast, exposure to suicidal behavior (composite) was associated with increased odds of suicide (4 studies, N = 1,479; OR = 3.83, 95% CI = 2.38 to 6.17, P < 0.001) but not suicide attempt (1 study, N = 666; OR = 1.10, 95% CI = 0.69 to 1.76, P = 0.90), a finding that was inconsistent with the separate analyses of exposure to suicide and suicide attempt. Key limitations of this study include fair study quality and the possibility of unmeasured confounders influencing the findings. The review has been prospectively registered with PROSPERO (CRD42018104629). CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that prior exposure to suicide and prior exposure to suicide attempt in the general population are associated with increased odds of subsequent suicidal behavior, but these exposures do not incur uniform risk across the full range of suicide-related outcomes. Therefore, future studies should refrain from combining these exposures into single composite measures of exposure to suicidal behavior. Finally, future studies should consider designing interventions that target suicide-related outcomes in those exposed to suicide and that include efforts to mitigate the adverse effects of exposure to suicide attempt on subsequent suicide attempt outcomes.
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Ideação Suicida , Tentativa de Suicídio/estatística & dados numéricos , Humanos , Análise Multinível , Fatores de RiscoRESUMO
Background and Purpose- ISAT (International Subarachnoid Aneurysm Trial) demonstrated that 1 year after aneurysmal subarachnoid hemorrhage, coiling resulted in a significantly better clinical outcome than clipping. After 5 years, this difference did not reach statistical significance, but mortality was still higher in the clipping group. Here, we present additional analyses, reporting outcome after excluding pretreatment deaths. Methods- Outcome measures were death with or without dependency at 1 and 5 years after treatment, after exclusion of all pretreatment deaths. Treatment differences were assessed using relative risks (RRs). With sensitivity and exploratory analyses, the relation between treatment delay and outcome was analyzed. Results- After exclusion of pretreatment deaths, at 1-year follow-up coiling was favorable over clipping for death or dependency (RR, 0.77 [95% CI, 0.67-0.89]) but not for death alone (RR, 0.88 [95% CI, 0.66-1.19]). After 5 years, no significant differences were observed, neither for death or dependency (RR, 0.88 [95% CI, 0.77-1.02]) nor for death alone (RR, 0.82 [95% CI, 0.64-1.05]). Sensitivity analyses showed a similar picture. In good-grade patients, coiling remained favorable over clipping in the long-term. Time between randomization and treatment was significantly longer in the clipping arm (mean 1.7 versus 1.1 days; P<0.0001), during which 17 patients died because of rebleeding versus 6 pretreatment deaths in the endovascular arm (RR, 2.81 [95% CI, 1.11-7.11]). Conclusions- These additional analyses support the conclusion of ISAT that at 1-year follow-up after aneurysmal subarachnoid hemorrhage coiling has a better outcome than clipping. After 5 years, with pretreatment mortality excluded, the difference between coiling and clipping is not significant. The high number of pretreatment deaths in the clipping group highlights the importance of urgent aneurysm treatment to prevent early rebleeding.
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Aneurisma Roto/cirurgia , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Hemorragia Subaracnóidea/cirurgia , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Instrumentos Cirúrgicos , Resultado do TratamentoRESUMO
BACKGROUND/OBJECTIVE: Spasticity is a complex and common condition but there is a lack of 'real-world' data on goal setting and spasticity treatment, as well as identifying those features that might be associated with goal achievement. Our aim was to provide such data. METHODS: Prospective attenders at a multi-disciplinary spasticity clinic over 2 years followed for consecutive appointments. Patient demographics and doses of botulinum toxin injected were documented. Main outcome was achievement of a primary goal but secondary goals were also recorded. Independent variables were examined for association to the outcome. RESULTS: A total of 606 goals were set in 224 patients. The majority (75.2%) were achieved with similar levels across active (72.5%), passive (75.7%) and pain (78.6%) goals. However, in terms of the primary goal, active primary goals were achieved less frequently (59.7%) than non-active primary goal (74.2%). A logistic regression confirmed that this was the only independent variable associated with primary goal achievement. The majority of patients (61.6%) required changes to their treatment between appointments, irrespective of time since diagnosis, age or aetiology. CONCLUSIONS: Most goals set in spasticity clinic can be achieved irrespective of type of goal. However, active goals may be harder to accomplish when they are set as a primary goal. This may reflect the desire of individuals to prioritise a desirable goal rather than one that is achievable. While goal setting is important in the management of spasticity patients, very few patient or treatment factors are associated with outcome prediction. Further work needs to identify features that may predict successful outcome.
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Stroke is a leading cause of death and disability worldwide and an increasing number of ischemic stroke patients are undergoing pharmacological and mechanical reperfusion. Both human and experimental models of reperfused ischemic stroke have implicated the complement cascade in secondary tissue injury. Most data point to the lectin and alternative pathways as key to activation, and C3a and C5a binding of their receptors as critical effectors of injury. During periods of thrombolysis use to treat stroke, acute experimental complement cascade blockade has been found to rescue tissue and improves functional outcome. Blockade of the complement cascade during the period of tissue reorganization, repair, and recovery is by contrast not helpful and in fact is likely to be deleterious with emerging data suggesting downstream upregulation of the cascade might even facilitate recovery. Successful clinical translation will require the right clinical setting and pharmacologic strategies that are capable of targeting the key effectors early while not inhibiting delayed repair. Early reports in a variety of disease states suggest that such pharmacologic strategies appear to have a favorable risk profile and offer substantial hope for patients.
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Ativação do Complemento , Complemento C3a/imunologia , Complemento C5a/imunologia , Acidente Vascular Cerebral , Terapia Trombolítica , Humanos , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapiaRESUMO
Self-harm (SH) continues to be a worldwide concern among adolescents and there is a great need for programming aimed at reducing SH in adolescents. Evans and colleagues discuss the opinions of school staff from a representative sample of secondary schools across England and Wales regarding their school's current prevention and intervention practices in responding to self-harm and how this should be addressed in future practice. The most salient points include the high prevalence of SH internationally, the existing barriers to SH prevention and intervention and possible solutions to these barriers. There is clearly an urgent need for high quality, evidence-based interventions that can be embedded in school settings, and have the capacity to overcome both the individual and structural barriers to supporting these vulnerable young people.
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BACKGROUND: Human bone marrow-derived mesenchymal stem/stromal cells (hBM MSCs) have multiple functions, critical for skeletal formation and function. Their functional heterogeneity, however, represents a major challenge for their isolation and in developing potency and release assays to predict their functionality prior to transplantation. Additionally, potency, biomarker profiles and defining mechanisms of action in a particular clinical setting are increasing requirements of Regulatory Agencies for release of hBM MSCs as Advanced Therapy Medicinal Products for cellular therapies. Since the healing of bone fractures depends on the coupling of new blood vessel formation with osteogenesis, we hypothesised that a correlation between the osteogenic and vascular supportive potential of individual hBM MSC-derived CFU-F (colony forming unit-fibroblastoid) clones might exist. METHODS: We tested this by assessing the lineage (i.e. adipogenic (A), osteogenic (O) and/or chondrogenic (C)) potential of individual hBM MSC-derived CFU-F clones and determining if their osteogenic (O) potential correlated with their vascular supportive profile in vitro using lineage differentiation assays, endothelial-hBM MSC vascular co-culture assays and transcriptomic (RNAseq) analyses. RESULTS: Our results demonstrate that the majority of CFU-F (95%) possessed tri-lineage, bi-lineage or uni-lineage osteogenic capacity, with 64% of the CFU-F exhibiting tri-lineage AOC potential. We found a correlation between the osteogenic and vascular tubule supportive activity of CFU-F clones, with the strength of this association being donor dependent. RNAseq of individual clones defined gene fingerprints relevant to this correlation. CONCLUSIONS: This study identified a donor-dependent correlation between osteogenic and vascular supportive potential of hBM MSCs and important gene signatures that support these functions that are relevant to their bone regenerative properties.
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Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , Adulto , Proliferação de Células , Células Cultivadas , Humanos , Adulto JovemRESUMO
Increasingly, human activities, including those aimed at conserving species and ecosystems (conservation activities) influence not only the survival and fitness but also the welfare of wild animals. Animal welfare relates to how an animal is experiencing its life and encompasses both its physical and mental states. While conservation biology and animal welfare science are both multi-disciplinary fields that use scientific methods to address concerns about animals, their focus and objectives sometimes appear to conflict. However, activities impacting detrimentally on the welfare of individual animals also hamper achievement of some conservation goals, and societal acceptance is imperative to the continuation of conservation activities. Thus, the best outcomes for both disciplines will be achieved through collaboration and knowledge-sharing. Despite this recognition, cross-disciplinary information-sharing and collaborative research and practice in conservation are still rare, with the exception of the zoo context. This paper summarizes key points developed by a group of conservation and animal welfare scientists discussing scientific assessment of wild animal welfare and barriers to progress. The dominant theme emerging was the need for a common language to facilitate cross-disciplinary progress in understanding and safeguarding the welfare of animals of wild species. Current conceptions of welfare implicit in conservation science, based mainly on "fitness" (physical states), need to be aligned with contemporary animal welfare science concepts which emphasize the dynamic integration of "fitness" and "feelings" (mental experiences) to holistically understand animals' welfare states. The way in which animal welfare is characterized influences the way it is evaluated and the emphasis put on different features of welfare, as well as, the importance placed on the outcomes of such evaluations and how that information is used, for example in policy development and decision-making. Salient examples from the New Zealand and Australian context are presented to illustrate. To genuinely progress our understanding and evaluation of wild animal welfare and optimize the aims of both scientific disciplines, conservation and animal welfare scientists should work together to evolve and apply a common understanding of welfare. To facilitate this, we propose the formal development of a new discipline, Conservation Welfare, integrating the expertise of scientists from both fields.
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BACKGROUND: Wearable sensors offer the potential to bring new knowledge to inform interventions in patients affected by multiple sclerosis (MS) by thoroughly quantifying gait characteristics and gait deficits from prolonged daily living measurements. The aim of this study was to characterise gait in both laboratory and daily life conditions for a group of patients with moderate to severe ambulatory impairment due to MS. To this purpose, algorithms to detect and characterise gait from wearable inertial sensors data were also validated. METHODS: Fourteen patients with MS were divided into two groups according to their disability level (EDSS 6.5-6.0 and EDSS 5.5-5.0, respectively). They performed both intermittent and continuous walking bouts (WBs) in a gait laboratory wearing waist and shank mounted inertial sensors. An algorithm (W-CWT) to estimate gait events and temporal parameters (mean and variability values) using data recorded from the waist mounted sensor (Dynaport, Mc Roberts) was tested against a reference algorithm (S-REF) based on the shank-worn sensors (OPAL, APDM). Subsequently, the accuracy of another algorithm (W-PAM) to detect and classify WBs was also tested. The validated algorithms were then used to quantify gait characteristics during short (sWB, 5-50 steps), intermediate (iWB, 51-100 steps) and long (lWB, >100 steps) daily living WBs and laboratory walking. Group means were compared using a two-way ANOVA. RESULTS: W-CWT compared to S-REF showed good gait event accuracy (0.05-0.10 s absolute error) and was not influenced by disability level. It slightly overestimated stride time in intermittent walking (0.012 s) and overestimated highly variability of temporal parameters in both intermittent (17.5%-58.2%) and continuous walking (11.2%-76.7%). The accuracy of W-PAM was speed-dependent and decreased with increasing disability. The ANOVA analysis showed that patients walked at a slower pace in daily living than in the laboratory. In daily living gait, all mean temporal parameters decreased as the WB duration increased. In the sWB, the patients with a lower disability score showed, on average, lower values of the temporal parameters. Variability decreased as the WB duration increased. CONCLUSIONS: This study validated a method to quantify walking in real life in people with MS and showed how gait characteristics estimated from short walking bouts during daily living may be the most informative to quantify level of disability and effects of interventions in patients moderately affected by MS. The study provides a robust approach for the quantification of recognised clinically relevant outcomes and an innovative perspective in the study of real life walking.