RESUMO
AIMS: Sexual activity and intimacy improve quality of life for heart attack survivors. After a heart attack, patients frequently experience sexual dysfunction and anxiety about resuming sexual activity. However, most health professionals do not discuss sex or intimacy with their patients. The aim of this research was to explore the perceptions and practices of Australian health professionals in discussing sexual activity and intimacy with heart attack survivors and the barriers to achieving this. METHODS AND RESULTS: This study employed a cross-sectional study design and online self-administered survey questionnaire. Study participants were a convenience sample of Australian health professionals working with cardiac patients, including general practitioners, cardiologists, cardiac rehabilitation specialists, registered nurses, and allied health professionals. Data were analysed using descriptive statistics and cross-tabulations to understand the different perspectives of health professional groups and the overall sample. Of 252 respondents, almost all believed discussing sex and intimacy with heart attack survivors was important, yet less than a quarter reported regularly doing so. About three-quarters reported feeling comfortable discussing sex and intimacy with either men or women, with half comfortable to do so with patients from diverse cultures. Barriers included lack of time, privacy, consumer resources, and protocols to guide discussions. CONCLUSION: This research supports the need for structural changes such as a clinical protocol, longer and more private consultations, staff training, and culturally appropriate patient-oriented resources to support health professionals to guide discussions about sexual activity and intimacy with patients who have had a heart attack.
Assuntos
Infarto do Miocárdio , Comportamento Sexual , Humanos , Estudos Transversais , Feminino , Masculino , Austrália , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Comportamento Sexual/psicologia , Infarto do Miocárdio/psicologia , Atitude do Pessoal de Saúde , Pessoal de Saúde/psicologia , Pessoal de Saúde/estatística & dados numéricos , Qualidade de Vida/psicologia , Comunicação , Idoso , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricosRESUMO
BACKGROUND: Sexual activity and intimacy contribute to wellbeing throughout adult life, including after a heart attack. Providing support and information about sexual activity and intimacy after a heart attack is recognised as part of a comprehensive approach to cardiac rehabilitation. Previous research shows that patients expect health professionals to initiate discussions about sexual activity and intimacy, but that this seldom occurs. METHODS: Drawing on qualitative survey responses from a range of Australian health professionals working in cardiac care and rehabilitation, this research examined their perspectives on discussing sexual activity and intimacy with their patients, and patients' partners. Using a social constructionist approach, thematic analysis was used to identify themes expressed by participants. RESULTS: Discussions about sexual activity and intimacy after heart attack were perceived as nebulous and taboo. The predominance of an illness - rather than wellness - framing of these discussions and a tendency for health professionals to make judgement calls contributed to discussions not occurring. Health professionals also identified a range of intrapersonal, interpersonal and structural obstacles to discussions, including embarrassment, fear of patients' embarrassment, a lack of role clarity, the absence of a clear protocol or training to guide practice, and a lack of time, privacy and patient resources. CONCLUSIONS: Such discussions require normalisation, careful timing, sufficient time and adequate privacy. Staff training, a protocol and appropriate patient resources are needed to support health professionals to initiate discussions. Further research is required that investigates the impact of specific resources and training on health professionals' practice and patient outcomes.
Assuntos
Infarto do Miocárdio , Sexualidade , Adulto , Humanos , Sexualidade/fisiologia , Austrália , Comportamento Sexual , Parceiros Sexuais , Pesquisa QualitativaRESUMO
On a therapeutic landscape unchanged since the 1980's, oocyte donation with IVF still stands as the solitary medical answer to diminished reserve and premature ovarian insufficiency. In 2016, intraovarian platelet-rich plasma (PRP) crossed the horizon as a hopeful reply to these intertwined problems. The once remote mirage of platelet cytokine effects on gene regulation or telomere stabilization has been brought into sharper focus, with current work clarifying how PRP corrects oxidative stress, rectifies tissue hypoxia, downregulates apoptosis, and enhances cellular metabolism. Not yet ready for routine use, this innovative treatment has already offered at least one point of early consensus: How intraovarian PRP results should be classified-Patients are either responders or non-responders. From this it is intriguing that no published PRP protocol has ever reported a supranormal ovarian rebound or hyperstimulation effect. This might be explained by baseline age-related ovarian conditions prevalent among poor responders, but since dysregulated or malignant transformations are also missing in other tissue contexts following autologous PRP treatment, the contribution of some platelet product which intrinsically delimits regenerative action cannot be discounted. Here we summarize results with recent experimental and clinical platelet research, framing those most likely to help advance reproductive endocrinology practice.
Assuntos
Citocinas , Infertilidade , Feminino , Humanos , Infertilidade/patologia , Ovário/patologia , MenopausaRESUMO
Covid-19 in adolescence with multisystem inflammatory injury (MIS-C) is a newly described condition sharing key features with Kawasaki disease and toxic shock syndrome. A May 2020 United Nations WHO brief covering findings from North America and Europe drew notice to this acute post-viral illness characterized by severe, diffuse hyperinflammation leading to multiorgan failure. While females diagnosed with Covid-19 generally have more favorable outcomes than males, this protection is negated by a low estrogen state. This case reports on acute kidney injury/MIS-C with amenorrhea from ovarian insufficiency in childhood, itself an uncommon presentation of idiopathic hypogonadism. Three exon variants were previously identified in a healthy, phenotypically normal 46,XX adolescent who subsequently underwent whole genome sequencing (WGS). She had only two spontaneous menses with a provisional diagnosis of premature ovarian insufficiency made by age 15. Against this background, Covid-19 infection necessitated hospital admission where progressively reduced renal function was a prime component of MIS-C. Combined angiotensin-converting enzyme inhibitor plus transdermal estrogen replacement therapy resulted in normalized estimated glomerular filtration rate (eGFR) from baseline 43 to 68 ml/min/1.73 m2, post-treatment. Serum cystatin-C also improved during this interval from 1.69 to 1.19 mg/L. Among 7 Covid-19 high risk intron variants identified was rs3131294 (6p21), near NOTCH4. Another finding at rs8068318 (17q23) was associated with creatine level and eGFR. This is the first work to explore Covid-19 and associated kidney injury as a component of MIS-C at the intersection of rare multigene variants and functional ovarian loss. The context of transition from adolescence to adulthood is also considered, where successful recovery of renal function was achieved with combined enalapril and supplemental estrogen.
RESUMO
Breast with supraclavicular fossa (Br+SCF) radiotherapy treatments can utilise a monoisocentric technique to concurrently treat the breast area (tangent fields) and supraclavicular area (opposing fields). The region where these treatment areas adjoin is known as the junction region, field junction, or match line. Dose variations that may occur about the junction region, due to geometrical inaccuracies, are typically feathered out in patient free-breathing treatments. However, there is limited information on how dose at the junction is influenced in deep inspiration breath hold (DIBH) treatments. This study aims to investigate dose variation at the field junction for a patient population undertaking a DIBH Br+SCF treatment course. GAFChromic EBT3 film was used to record the dose across the junction at skin surface for approximately one third of the 25 fraction treatment course for 11 patients undergoing DIBH Br+SCF treatment. Single fraction and summated fraction profiles for each patient were compared to profiles in the treatment planning system and assessed the: (1) local dose variations, (2) position of the 50% dose gradient, and (3) relative dose at the nominal junction. Local dose variations of 10% or greater, position displacement of the junction greater than 5 mm, and relative dose differences at the match line greater than 10% can be found within single fraction dose profiles. When these single fractions are summed over the treatment course, the position variations reduce to 2 mm and dose variations reduced to within 10% for 10 of the 11 patients. Only one of 11 patients recorded a summed dose difference greater than ±10% over their treatment, recording 76% ± 8% of the planned dose in this region. This was due to a small overall position displacement of 1.8 ± 1.6 mm from the nominal junction. A feathering of the dose at the junction is present for DIBH Br+SCF patient treatments. The feathering effect is sufficient, in the majority of cases studied, to reduce any differences in dose and displacement present in single fractions. This work also demonstrates that there may be exceptions from this observed behavior that should be considered. Further study in this area using a larger patient cohort is recommended.
Assuntos
Neoplasias da Mama , Neoplasias Unilaterais da Mama , Mama , Neoplasias da Mama/radioterapia , Suspensão da Respiração , Clavícula , Feminino , Coração , Humanos , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Unilaterais da Mama/radioterapiaRESUMO
To evaluate the new Varian, graphical processing unit (GPU)-enabled, volumetric-modulated arc therapy (VMAT) multi-criteria optimisation (MCO) tool for both its dosimetric accuracy and calculation time. This is a new capability within V16.0 and greater of the Varian Eclipse treatment planning system that allows VMAT optimisation and dose calculation using the GPU (termed GPU-VMAT). In versions prior to V16.0 VMAT multi-criteria optimisation calculations were only possible using central processing unit (CPU) (termed CPU-VMAT) and Hybrid-VMAT (H-VMAT). The H-VMAT method breaks down the VMAT plan into IMRT fields which utilised GPU calculations. The study consisted of a cohort of 50 patients representing a range of anatomical treatment sites; bladder (5), brain (5), gynae (5), head & neck (5), lung (7), mediastinum (7) prostate (4), oesophagus (7) and rectum (5). Each case was planned to that of a clinical standard (Base) which was compared to a CPU-VMAT, GPU-VMAT and H-VMAT approaches. The study analysed dose to organ at risk (OAR) and target coverage, plan calculation time data and plan complexity through monitor unit (MU) for each approach. Negligible dosimetric differences were found between the CPU-VMAT, GPU-VMAT and H-VMAT approaches for the cohort of patients evaluated. The largest dosimetric change were observed in the lacrimal gland for a head and neck case, where the GPU-VMAT and H-VMAT achieved a max dose of +2.8 ± 0.0 Gy and -4.6 ± 0.0 Gy, respectively, when compared to CPU-VMAT. The majority of organ at risk's (OAR) provided indistinguishable dosimetric outcomes, namely: heart, kidneys, femur, lens, oral cavity and oesophagus. Large time savings were found using the GPU-VMAT technique compared to CPU-VMAT, a mean decrease in calculation time across all sites of 60.2% ± 15.6%. Negligible dosimetric change between the 2 techniques and large time saving were observed with the GPU-VMAT and H-VMAT approaches when compared to the CPU-VMAT. We have shown that the GPU-VMAT technique has been safely implemented with minimal differences from CPU-VMAT, but with significant optimisation and calculation times savings.
Assuntos
Radioterapia de Intensidade Modulada , Algoritmos , Humanos , Masculino , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
BACKGROUND: Aperture shape controller (ASC) is a recently introduced leaf sequencer that controls the complexity of multileaf collimator apertures in the Photon Optimizer algorithm of the Eclipse treatment planning system. The aim of this study is to determine if the ASC can reduce plan complexity and improve verification results, without compromising plan quality. METHODS: Thirteen plans grouped into cohorts of head and neck/brain, breast/chest and pelvis were reoptimised using the same optimization as the non-ASC setting for low, moderate and high ASC settings. These plans were analyzed using plan quality indices such as the conformity index and homogeneity index in addition to dose-volume histogram based analysis on PTVs and organ at risks. Complexity assessments were performed using metrics such as average leaf pair opening, modulation complexity scores, relative monitor units (MU) and treatment time. Monitor unit per gantry angle variations were also analyzed. A third-party algorithm was also used to assess 3D dose distributions produced using the new leaf sequencer tool. Deliverability for the final multileaf collimator distribution was quantified using portal dose image prediction based gamma analysis. RESULTS: Plan conformality assessments showed comparable results and no significant plan degradation for plans reoptimised using ASC. Reduction in overall MU distributions were seen in some cases using higher ASC however, no overall trends were observed. In general, treatment deliverability, assessed using gamma analysis did not improve drastically however MU per degree distribution in 1 case improved when reoptimised using ASC. Treatment MUs generally reduced when ASC settings were used whilst in 1 case an increase in the treatment time factor > 1.8 was observed. The third-party algorithm assessment showed an underestimation of dose calculations for all cohorts used in this study when a higher ASC setting is used. CONCLUSIONS: The impact of using ASC in treatment plans was characterised in this study. Although plan complexity marginally improved when using higher ASC settings, no consensus could be reached based on metrics analyzed in this study. A reduction in MU distribution was observed with increasing ASC settings in most cases. This study recommends that ASC to be used as an additional tool only to test its suitability to reduce plan complexity.
Assuntos
Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Algoritmos , Estudos de Coortes , Feminino , Humanos , Masculino , Dosagem RadioterapêuticaRESUMO
To evaluate the Varian 'Fast hybrid multi-criteria optimization (MCO) volumetric modulated arc therapy (VMAT)' (H-VMAT) tool for both its dosimetric accuracy and calculation time. This is a new function within V15.6 of the Varian Eclipse treatment planning system that allows VMAT optimization and dose calculation using the graphical processing unit (GPU). In versions prior to V15.6 VMAT MCO calculations were only possible using central processing unit (CPU) not GPU. We termed this approach as native VMAT (N-VMAT). The study consisted of a cohort of 53 patients representing a range of anatomical treatment sites; bladder (5), brain (6), gynaecological (5), head & neck (5), lung (7), mediastinum (7) prostate (6), oesophagus (7), and rectum (5). Each case was planned to that of a clinical standard (Base) which was compared to a H-VMAT and N-VMAT approach. The study analyzed plan calculation time data, dose to organ at risk (OAR) and target coverage for each approach. Negligible dosimetric differences were found between the H-VMAT and N-VMAT approach for the cohort of patients evaluated. The largest dosimetric changes where observed in the optic chiasm and lacrimal gland where the H-VMAT achieved a max dose of 50.9 ± 7.7 Gy and 8.0 ± 0.5 Gy in comparison to the N-VMAT 53.1 ± 6.3 Gy and 10.2 ± 2.9 Gy, respectively. Several OAR's provided indistinguishable dose outcomes, namely; brainstem, heart, kidney's, lens, parotid, and spinal cord. Large time savings were found using the H-VMAT technique when compared to N-VMAT, being 5 to 40 times faster or up to 75 minutes time saving (average of 25 minutes). Negligible dosimetric change between the 2 techniques and large time savings were observed with the GPU enabled H-VMAT approach. We have shown that the H-VMAT technique has been safely implemented and is ready for clinical use.
Assuntos
Algoritmos , Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Órgãos em Risco , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversosRESUMO
Anhydrouridines react with aliphatic amines to give N-alkyl isocytosines, but reported procedures often demand very long reaction times and can be low yielding, with narrow scope. A modified procedure for such reactions has been developed, using microwave irradiation, significantly reducing reaction time and allowing facile access to a diverse range of novel nucleosides on the gram scale. The method has been used to prepare a precursor to a novel analogue of lysidine, a naturally occurring iminonucleoside found in tRNA.
Assuntos
Aminas/química , Citosina/análogos & derivados , Lisina/análogos & derivados , Nucleosídeos/síntese química , Nucleosídeos de Pirimidina/síntese química , RNA de Transferência/química , Citosina/química , Lisina/síntese química , Lisina/química , Estrutura Molecular , Nucleosídeos/química , Nucleosídeos de Pirimidina/química , RNA de Transferência/metabolismoRESUMO
To evaluate, in terms of dosimetric accuracy and calculation efficiency, the implementation of a graphic processing unit (GPU)-based Acuros XB dose calculation engine within version 15.5 of the Varian Eclipse treatment planning system. Initial phantom based calculations and a range of 101 clinical cases were analyzed on a dedicated test system. Dosimetric differences, based on dose-volume histrogram parameters and plan comparison, were compared between central processing unit (CPU) and GPU based calculation. Calculation times were also compared between CPU and GPU, as well as PLAN and FIELD modes. No dosimetric differences were found between CPU and GPU. CPU based calculations ranged from 25 to 533 seconds per plan, reducing to 13 to 70 seconds for GPU. GPU was 4.4 times more efficient than CPU. FIELD mode was up to 1.3 times more efficient than PLAN mode. For the clinical cases and version of Eclipse used, no dosimetric differences were found between CPU and GPU. Based on this, GPU architecture has been safely implemented and is ready for clinical use. GPU based calculation times were superior to CPU, being on average, 4.4 times faster.
Assuntos
Gráficos por Computador , Planejamento da Radioterapia Assistida por Computador/métodos , Feminino , Humanos , Masculino , Dosagem RadioterapêuticaRESUMO
A coherent optical packet transceiver based on doubly differential star 16-ary quadrature amplitude modulation (DD-star-16-QAM) is presented for spectrally and energy efficient reconfigurable networks. The coding and decoding processes for this new modulation format are presented, simulations and experiments are then performed to investigate the performance of the DD-star-16-QAM in static and dynamic scenarios. The static results show that the influence of frequency offset (FO) can be cancelled out by doubly differential (DD) coding and the correction range is only limited by the electronic bandwidth of the receivers. In the dynamic scenario with a time-varying FO and linewidth, the DD-star-16-QAM can overcome the time-varying FO, and the switching time of around 70 ns is determined by the time it takes the dynamic linewidth to reach the requisite level. This format can thus achieve a shorter waiting time after switching tunable lasers than the commonly used square-16-QAM, in which the transmission performance is limited by the frequency transients after the wavelength switch.
RESUMO
Compared with chronological age, criminologists have paid less attention to the biological sense of age typically expressed by pubertal development. Studies that have examined pubertal timing's effects on delinquency have almost exclusively been conducted in Western countries using mostly White samples. To our knowledge, no study has ever examined this issue in the Asian context. The current study is the first attempt to bridge this research gap by examining the association among menarcheal timing, the sex composition of schools, and delinquency in a representative sample of 1,108 ninth-grade girls in South Korea. The results show that significant association between early menarche and delinquency exists only in mixed-sex schools but not in all-girls schools. In addition, the significant linkage between early menarche and delinquency in mixed-sex schools is mediated by delinquent peer associations.
Assuntos
Povo Asiático/psicologia , Comparação Transcultural , Delinquência Juvenil/etnologia , Delinquência Juvenil/psicologia , Puberdade Precoce/etnologia , Puberdade Precoce/psicologia , Instituições Acadêmicas , Meio Social , Adolescente , Caráter , Criança , Feminino , Humanos , Menarca/etnologia , Menarca/psicologia , República da CoreiaRESUMO
We study and experimentally validate the vector theory of four-wave mixing (FWM) in semiconductor optical amplifiers (SOA). We use the vector theory of FWM to design a polarization insensitive all-optical wavelength converter, suitable for advanced modulation formats, using non-degenerate FWM in SOAs and parallelly polarized pumps. We demonstrate the wavelength conversion of polarization-multiplexed (PM)-QPSK, PM-16QAM and a Nyquist WDM super-channel modulated with PM-QPSK signals at a baud rate of 12.5 GBaud, with total data rates of 50 Gbps, 100 Gbps and 200 Gbps respectively.
RESUMO
General theory attributes criminal behavior primarily to low self-control, whereas evolutionary neuroandrogenic (ENA) theory envisions criminality as being a crude form of status-striving promoted by high brain exposure to androgens. General theory predicts that self-control will be negatively correlated with risk-taking, while ENA theory implies that these two variables should actually be positively correlated. According to ENA theory, traits such as pain tolerance and muscularity will be positively associated with risk-taking and criminality while general theory makes no predictions concerning these relationships. Data from Malaysia and the United States are used to test 10 hypotheses derived from one or both of these theories. As predicted by both theories, risk-taking was positively correlated with criminality in both countries. However, contrary to general theory and consistent with ENA theory, the correlation between self-control and risk-taking was positive in both countries. General theory's prediction of an inverse correlation between low self-control and criminality was largely supported by the U.S. data but only weakly supported by the Malaysian data. ENA theory's predictions of positive correlations between pain tolerance, muscularity, and offending were largely confirmed. For the 10 hypotheses tested, ENA theory surpassed general theory in predictive scope and accuracy.
Assuntos
Androgênios/fisiologia , Comportamento Criminoso , Teoria Psicológica , Autocontrole , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIM: To investigate systematic changes in dose arising when treatment plans optimised using the Anisotropic Analytical Algorithm (AAA) are recalculated using Acuros XB (AXB) in patients treated with definitive chemoradiotherapy (dCRT) for locally advanced oesophageal cancers. BACKGROUND: We have compared treatment plans created using AAA with those recalculated using AXB. Although the Anisotropic Analytical Algorithm (AAA) is currently more widely used in clinical routine, Acuros XB (AXB) has been shown to more accurately calculate the dose distribution, particularly in heterogeneous regions. Studies to predict clinical outcome should be based on modelling the dose delivered to the patient as accurately as possible. METHODS: CT datasets from ten patients were selected for this retrospective study. VMAT (Volumetric modulated arc therapy) plans with 2 arcs, collimator rotation ± 5-10° and dose prescription 50 Gy / 25 fractions were created using Varian Eclipse (v10.0). The initial dose calculation was performed with AAA, and AXB plans were created by re-calculating the dose distribution using the same number of monitor units (MU) and multileaf collimator (MLC) files as the original plan. The difference in calculated dose to organs at risk (OAR) was compared using dose-volume histogram (DVH) statistics and p values were calculated using the Wilcoxon signed rank test. The potential clinical effect of dosimetric differences in the gross tumour volume (GTV) was evaluated using three different TCP models from the literature. RESULTS: PTV Median dose was apparently 0.9 Gy lower (range: 0.5 Gy - 1.3 Gy; p < 0.05) for VMAT AAA plans re-calculated with AXB and GTV mean dose was reduced by on average 1.0 Gy (0.3 Gy -1.5 Gy; p < 0.05). An apparent difference in TCP of between 1.2% and 3.1% was found depending on the choice of TCP model. OAR mean dose was lower in the AXB recalculated plan than the AAA plan (on average, dose reduction: lung 1.7%, heart 2.4%). Similar trends were seen for CRT plans. CONCLUSIONS: Differences in dose distribution are observed with VMAT and CRT plans recalculated with AXB particularly within soft tissue at the tumour/lung interface, where AXB has been shown to more accurately represent the true dose distribution. AAA apparently overestimates dose, particularly the PTV median dose and GTV mean dose, which could result in a difference in TCP model parameters that reaches clinical significance.
Assuntos
Algoritmos , Neoplasias Esofágicas/radioterapia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Esofágicas/diagnóstico por imagem , Humanos , Órgãos em Risco/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Probabilidade , Dosagem Radioterapêutica/normas , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Drawing upon a recent study on the association between low self-control and differential responses from the criminal justice system, this study examined whether academic performance, a construct linked to self-control, was also associated with the probability of police arrest. The result indicated that academic performance did have a statistically significant inverse association with the likelihood of police arrest, net of low self-control and delinquency.
Assuntos
Delinquência Juvenil/legislação & jurisprudência , Delinquência Juvenil/psicologia , Polícia , Prisioneiros/legislação & jurisprudência , Prisioneiros/psicologia , Logro , Adolescente , Adulto , Desvalorização pelo Atraso , Função Executiva , Feminino , Humanos , Inteligência , Controle Interno-Externo , Masculino , National Longitudinal Study of Adolescent Health , Probabilidade , Estados Unidos , Adulto JovemRESUMO
We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was investigated. Four additional chimeric peptide-PMO conjugates including newly identified peptide 9 (B-9-PMO and 9-B-PMO) and control peptide 3 (B-3-PMO and 3-B-PMO) were tested in mdx mice. Immunohistochemical staining, RT-PCR and western blot results indicated that B-9-PMO induced significantly higher level of exon skipping and dystrophin restoration than its counterpart (9-B-PMO), further corroborating the notion that the activity of chimeric peptide-PMO conjugates is dependent on relative position of the tissue-targeting peptide motif within the chimeric peptide with respect to PMOs. Subsequent mechanistic studies showed that enhanced cellular uptake of B-MSP-PMO into muscle cells leads to increased exon-skipping activity in comparison with MSP-B-PMO. Surprisingly, further evidence showed that the uptake of chimeric peptide-PMO conjugates of both orientations (B-MSP-PMO and MSP-B-PMO) was ATP- and temperature-dependent and also partially mediated by heparan sulfate proteoglycans (HSPG), indicating that endocytosis is likely the main uptake pathway for both chimeric peptide-PMO conjugates. Collectively, our data demonstrate that peptide orientation in chimeric peptides is an important parameter that determines cellular uptake and activity when conjugated directly to oligonucleotides. These observations provide insight into the design of improved cell targeting compounds for future therapeutics studies.Molecular Therapy-Nucleic Acids (2013) 2, e124; doi:10.1038/mtna.2013.51; published online 24 September 2013.
RESUMO
OBJECTIVE: To measure Irish opinion on a range of assisted human reproduction (AHR) treatments. METHODS: A nationally representative sample of Irish adults (n=1,003) were anonymously sampled by telephone survey. RESULTS: Most participants (77%) agreed that any fertility services offered internationally should also be available in Ireland, although only a small minority of the general Irish population had personal familiarity with AHR or infertility. This sample finds substantial agreement (63%) that the Government of Ireland should introduce legislation covering AHR. The range of support for gamete donation in Ireland ranged from 53% to 83%, depending on how donor privacy and disclosure policies are presented. For example, donation where the donor agrees to be contacted by the child born following donation, and anonymous donation where donor privacy is completely protected by law were supported by 68% and 66%, respectively. The least popular (53%) donor gamete treatment type appeared to be donation where the donor consents to be involved in the future life of any child born as a result of donor fertility treatment. Respondents in social class ABC1 (58%), age 18 to 24 (62%), age 25 to 34 (60%), or without children (61%) were more likely to favour this donor treatment policy in our sample. CONCLUSION: This is the first nationwide assessment of Irish public opinion on the advanced reproductive technologies since 2005. Access to a wide range of AHR treatment was supported by all subgroups studied. Public opinion concerning specific types of AHR treatment varied, yet general support for the need for national AHR legislation was reported by 63% of this national sample. Contemporary views on AHR remain largely consistent with the Commission for Assisted Human Reproduction recommendations from 2005, although further research is needed to clarify exactly how popular opinion on these issues has changed. It appears that legislation allowing for the full range of donation options (and not mandating disclosure of donor identity at a stipulated age) would better align with current Irish public opinion.