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BACKGROUND: Cancer immunotherapy approaches that elicit immune cell responses, including T and NK cells, have revolutionized the field of oncology. However, immunosuppressive mechanisms restrain immune cell activation within solid tumors so additional strategies to augment activity are required. METHODS: We identified the co-stimulatory receptor NKG2D as a target based on its expression on a large proportion of CD8+ tumor infiltrating lymphocytes (TILs) from breast cancer patient samples. Human and murine surrogate NKG2D co-stimulatory receptor-bispecifics (CRB) that bind NKG2D on NK and CD8+ T cells as well as HER2 on breast cancer cells (HER2-CRB) were developed as a proof of concept for targeting this signaling axis in vitro and in vivo. RESULTS: HER2-CRB enhanced NK cell activation and cytokine production when co-cultured with HER2 expressing breast cancer cell lines. HER2-CRB when combined with a T cell-dependent-bispecific (TDB) antibody that synthetically activates T cells by crosslinking CD3 to HER2 (HER2-TDB), enhanced T cell cytotoxicity, cytokine production and in vivo antitumor activity. A mouse surrogate HER2-CRB (mHER2-CRB) improved in vivo efficacy of HER2-TDB and augmented NK as well as T cell activation, cytokine production and effector CD8+ T cell differentiation. CONCLUSION: We demonstrate that targeting NKG2D with bispecific antibodies (BsAbs) is an effective approach to augment NK and CD8+ T cell antitumor immune responses. Given the large number of ongoing clinical trials leveraging NK and T cells for cancer immunotherapy, NKG2D-bispecifics have broad combinatorial potential.
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Neoplasias de la Mama , Linfocitos T CD8-positivos , Células Asesinas Naturales , Subfamilia K de Receptores Similares a Lectina de Células NK , Humanos , Animales , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/inmunología , Ratones , Linfocitos T CD8-positivos/inmunología , Células Asesinas Naturales/inmunología , Femenino , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/terapia , Receptor ErbB-2/inmunología , Línea Celular Tumoral , Inmunoterapia/métodos , Activación de Linfocitos/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismoRESUMEN
We present the cases of 2 children diagnosed with extrahepatic portosystemic shunts, a very rare vascular anomaly, on investigation of cardiac symptomatology. Poorly developed portal venous systems necessitated staged shunt occlusion. This was achieved using atrial flow regulator devices positioned in an inferior vena cava stent platform performed in the cardiac catheterization laboratory.
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Background: Bilothorax is defined as the presence of bile in the pleural space. It is a rare condition, and diagnosis is confirmed with a pleural fluid-to-serum bilirubin ratio of >1. Methods: The PubMed, Embase, Google Scholar, and CINAHL databases were searched using predetermined Boolean parameters. The systematic literature review was done per PRISMA guidelines. Retrospective studies, case series, case reports, and conference abstracts were included. The patients with reported pleural fluid analyses were pooled for fluid parameter data analysis. Results: Of 838 articles identified through the inclusion criteria and removing 105 duplicates, 732 articles were screened with abstracts, and 285 were screened for full article review. After this, 123 studies qualified for further detailed review, and of these, 115 were pooled for data analysis. The mean pleural fluid and serum bilirubin levels were 72 mg/dL and 61 mg/dL, respectively, with a mean pleural fluid-to-serum bilirubin ratio of 3.47. In most cases, the bilothorax was reported as a subacute or remote complication of hepatobiliary surgery or procedure, and traumatic injury to the chest or abdomen was the second most common cause. Tube thoracostomy was the main treatment modality (73.83%), followed by serial thoracentesis. Fifty-two patients (51.30%) had associated bronchopleural fistulas. The mortality was considerable, with 18/115 (15.65%) reported death. Most of the patients with mortality had advanced hepatobiliary cancer and were noted to die of complications not related to bilothorax. Conclusion: Bilothorax should be suspected in patients presenting with pleural effusion following surgical manipulation of hepatobiliary structures or a traumatic injury to the chest. This review is registered with CRD42023438426.
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Bilirrubina , Derrame Pleural , Femenino , Humanos , Bilis , Bilirrubina/sangre , Derrame Pleural/etiología , Toracocentesis , Toracostomía , AncianoRESUMEN
Images collected during NASA's Double Asteroid Redirection Test (DART) mission provide the first resolved views of the Didymos binary asteroid system. These images reveal that the primary asteroid, Didymos, is flattened and has plausible undulations along its equatorial perimeter. At high elevations, its surface is rough and contains large boulders and craters; at low elevations its surface is smooth and possesses fewer large boulders and craters. Didymos' moon, Dimorphos, possesses an intimate mixture of boulders, several asteroid-wide lineaments, and a handful of craters. The surfaces of both asteroids include boulders that are large relative to their host body, suggesting that both asteroids are rubble piles. Based on these observations, our models indicate that Didymos has a surface cohesion ≤ 1 Pa and an interior cohesion of â¼10 Pa, while Dimorphos has a surface cohesion of <0.9 Pa. Crater size-frequency analyzes indicate the surface age of Didymos is 40-130 times older than Dimorphos, with likely absolute ages of ~ 12.5 Myr and <0.3 Myr, respectively. Solar radiation could have increased Didymos' spin rate leading to internal deformation and surface mass shedding, which likely created Dimorphos.
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Children hospitalised with severe malnutrition have high mortality and readmission rates post-discharge. Current milk-based formulations target restoring ponderal growth but not the modification of gut barrier integrity or microbiome which increases the risk of gram-negative sepsis and poor outcomes. We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes. We conducted an open-label phase II trial at Mbale and Soroti Regional Referral Hospitals, Uganda, involving 160 children aged 6 months to 5 years with severe malnutrition (mid-upper arm circumference (MUAC) < 11·5 cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) (n 80) v. WHO standard F75/F100 feeds (n 80). Co-primary outcomes were change in MUAC and mortality to day 90. Secondary outcomes included weight gain (> 5 g/kg/d), de novo development of diarrhoea, time to diarrhoea and oedema resolution. Day 90 MUAC increase was marginally lower in LF v. WHO arm (1·1 cm (interquartile range (IQR) 1·1) v. 1·4 cm (IQR 1·40), P = 0·09); day 90 mortality was similar (11/80 (13·8 %) v. 12/80 (15 %), respectively, OR 0·91 (95 % CI 0·40, 2·07), P = 0·83). There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the LF, ten children switched to WHO feeds. Per-protocol analysis indicated a trend to lower day 90 mortality and readmission rates in the LF (6/60 (10 %) and 2/60(3 %)) v. WHO feeds (12/71(17·5 %) and 4/71(6 %)). Further refinement of LF and clinical trials are warranted, given the poor outcomes in children with severe malnutrition.
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The giant planets of the Solar System formed on initially compact orbits, which transitioned to the current wider configuration by means of an orbital instability. The timing of that instability is poorly constrained. In this work, we use dynamical simulations to demonstrate that the instability implanted planetesimal fragments from the terrestrial planet region into the asteroid main belt. We use meteorite data to show that the implantation occurred >60 million years (Myr) after the Solar System began to form. Combining this constraint with a previous upper limit derived from Jupiter's trojan asteroids, we conclude that the orbital instability occurred 60 to 100 Myr after the beginning of Solar System formation. The giant impact that formed the Moon occurred within this range, so it might be related to the giant planet instability.
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When observers have prior knowledge about the likely outcome of their perceptual decisions, they exhibit robust behavioural biases in reaction time and choice accuracy. Computational modelling typically attributes these effects to strategic adjustments in the criterion amount of evidence required to commit to a choice alternative - usually implemented by a starting point shift - but recent work suggests that expectations may also fundamentally bias the encoding of the sensory evidence itself. Here, we recorded neural activity with EEG while participants performed a contrast discrimination task with valid, invalid, or neutral probabilistic cues across multiple testing sessions. We measured sensory evidence encoding via contrast-dependent steady-state visual-evoked potentials (SSVEP), while a read-out of criterion adjustments was provided by effector-selective mu-beta band activity over motor cortex. In keeping with prior modelling and neural recording studies, cues evoked substantial biases in motor preparation consistent with criterion adjustments, but we additionally found that the cues produced a significant modulation of the SSVEP during evidence presentation. While motor preparation adjustments were observed in the earliest trials, the sensory-level effects only emerged with extended task exposure. Our results suggest that, in addition to strategic adjustments to the decision process, probabilistic information can also induce subtle biases in the encoding of the evidence itself.
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Señales (Psicología) , Potenciales Evocados Visuales , Humanos , Sesgo , Simulación por Computador , ProbabilidadRESUMEN
The aim of this study was to determine the rate of aspirin responsiveness in a cohort of pediatric patients with in situ xenograft valved right ventricle to pulmonary artery (RV-PA) conduits and/or transcatheter valve replacements (TVR). Aspirin is routinely prescribed to these patients. Optimizing anti-platelet therapy could promote valve longevity and reduce the risk of infective endocarditis in this at-risk group. This was a prospective, observational study. Patients were recruited from both ward and outpatient settings. Patients were eligible if under 18 years and taking aspirin. Non-response to aspirin was defined as > 20% platelet aggregation using light transmission platelet aggregometry (LTA) and < 50% platelet inhibition by thromboelastography with platelet mapping (TEGPM). Participants were invited to provide a confirmatory sample in cases of aspirin resistance and dose adjustments were made. Thirty patients participated. Median age was 9 years (2 months to 18 years). The majority (93%) had complex right ventricular outflow tract pathology. 13 (43%) had an RV-PA conduit and 24 (80%) had a TVR, with valve situated in conduit in 7 (23%) cases. Rate of aspirin non-response on initial testing was 23% (n = 7/30) with median LTA 74.55% (60-76%) and TEG 13.25% (0-44%) in non-responders. Non-responders were more likely to be under 1 year. Two patients required dose increases and one patient non-adherence to dose was identified. Four patients on repeat testing were responsive to aspirin by laboratory tests. The rate of aspirin non-response on laboratory testing in this cohort of patients was 23% and resulted in therapeutic intervention in 10%.
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We report a case of an alternative transcatheter use of the modified Medtronic microvascular plug to modify fenestration stent flow in a patient with a rapidly deteriorating clinical condition. This four-year-old boy developed severe cyanosis following fenestration stent insertion, initially placed due to prolonged drainage post-Fontan with extra-cardiac conduit. In April 2023, he underwent urgent cardiac catheterisation and had partial occlusion of fenestration stent with a modified 9Q microvascular plug. His oxygen saturations improved from 50 to 89% in room air with no re-emergence of raised cavopulmonary pressures.
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Procedimiento de Fontan , Masculino , Humanos , Preescolar , Cateterismo Cardíaco , StentsRESUMEN
BACKGROUND: Hepatitis C virus infection is often asymptomatic, and many patients may be unaware they are infected. Community-based, birth cohort screening has been advocated to identify these patients. It has been estimated that 0.7-1% of individuals born between 1965 and 1985 in Ireland are infected. The cost-effectiveness of screening is critically dependent on the population prevalence. AIMS: The aim is to determine the community prevalence of hepatitis C virus infection in the birth cohort 1965-1985. METHODS: Residual serum samples from blood tests ordered by community general practitioners were anonymised and analysed for the presence of hepatitis C antibody ± antigen. Twelve large general hospitals throughout the country participated. RESULTS: A total of 14,320 samples were tested, 9347 of which were from the birth cohort 1965-1985. Seventy-two samples were positive for hepatitis C antibody of which 12 were positive for hepatitis C antigen (17%). The overall prevalence of hepatitis C antigen in the birth cohort was 0.09%. A higher prevalence (0.39%) was identified in males in two urban areas of Dublin. CONCLUSIONS: Hepatitis C virus seroprevalence was much lower than previously estimated. The proportion of antibody positive patients with hepatitis C antigen was also lower than expected suggesting the effects of treatment and/or high spontaneous viral clearance. Universal birth cohort screening is unlikely to be cost-effective. Targeted birth cohort screening in high prevalence areas could be considered.
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Hepatitis C , Humanos , Hepatitis C/epidemiología , Hepatitis C/diagnóstico , Irlanda/epidemiología , Masculino , Femenino , Prevalencia , Estudios Prospectivos , Persona de Mediana Edad , Cohorte de Nacimiento , Anticuerpos contra la Hepatitis C/sangre , Adulto , Estudios Seroepidemiológicos , Antígenos de la Hepatitis C/sangre , Anciano , Estudios de CohortesRESUMEN
The paper uses inverted glancing angle deposition (I-GLAD) for creating antibacterial surfaces. Antibacterial surfaces are found in nature, such as on insect wings, eyes, and plant leaves. Since the bactericidal mechanism is purely physical for these surfaces, the antimicrobial resistance of bacteria to traditional chemical antibiotics can be overcome. The technical problem is how to mimic, synthesize, and scale up the naturally occurring antibacterial surfaces for practical applications, given the fact that most of those surfaces are composed of three-dimensional hierarchical micro-nano structures. This paper proposes to use I-GLAD as a novel bottom-up nanofabrication technique to scale up bio-inspired nano-structured antibacterial surfaces. Our innovative I-GLAD nanofabrication technique includes traditional GLAD deposition processes alongside the crucial inverting process. Following fabrication, we explore the antibacterial efficacy of I-GLAD surfaces using two types of bacteria: Escherichia coli (E. coli), a gram-negative bacterium, and Staphylococcus aureus (S. aureus), a gram-positive bacterium. Scanning electron microscopy (SEM) shows the small tips and flexible D/P (feature size over period) ratio of I-GLAD nanoneedles, which is required to achieve the desired bactericidal mechanism. Antibacterial properties of the I-GLAD samples are validated by achieving flat growth curves of E. coli and S. aureus, and direct observation under SEM. The paper bridges the knowledge gaps of seeding techniques for GLAD, and the control/optimization of the I-GLAD process to tune the morphologies of the nano-protrusions. I-GLAD surfaces are effective against both gram-negative and gram-positive bacteria, and they have tremendous potentials in hospital settings and daily surfaces.
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OBJECTIVES: This study aimed to determine the status of training of adult congenital heart disease (ACHD) cardiologists in Europe. METHODS: A questionnaire was sent to ACHD cardiologists from 34 European countries. RESULTS: Representatives from 31 of 34 countries (91%) responded. ACHD cardiology was recognised by the respective ministry of Health in two countries (7%) as a subspecialty. Two countries (7%) have formally recognised ACHD training programmes, 15 (48%) have informal (neither accredited nor certified) training and 14 (45%) have very limited or no programme. Twenty-five countries (81%) described training ACHD doctors 'on the job'. The median number of ACHD centres per country was 4 (range 0-28), median number of ACHD surgical centres was 3 (0-26) and the median number of ACHD training centres was 2 (range 0-28). An established exit examination in ACHD was conducted in only one country (3%) and formal certification provided by two countries (7%). ACHD cardiologist number versus gross domestic product Pearson correlation coefficient=0.789 (p<0.001). CONCLUSION: Formal or accredited training in ACHD is rare among European countries. Many countries have very limited or no training and resort to 'train people on the job'. Few countries provide either an exit examination or certification. Efforts to harmonise training and establish standards in exit examination and certification may improve training and consequently promote the alignment of high-quality patient care.
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Cardiólogos , Cardiología , Cardiopatías Congénitas , Humanos , Adulto , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/terapia , Cardiología/educación , Calidad de la Atención de Salud , Europa (Continente)/epidemiologíaRESUMEN
The intensity of tropical cyclones (TCs) is expected to increase in response to greenhouse warming. However, how future climate change will affect TC frequencies and tracks is still under debate. Here, to further elucidate the underlying sensitivities and mechanisms, we study TCs response to different past and future climate forcings. Using a high-resolution TC-resolving global Earth system model with 1/4° atmosphere and 1/10° ocean resolution, we conducted a series of paleo-time-slice and future greenhouse warming simulations targeting the last interglacial (Marine Isotope Stage (MIS) 5e, 125 ka), glacial sub-stage MIS5d (115 ka), present-day (PD), and CO2 doubling (2×CO2) conditions. Our analysis reveals that precessional forcing created an interhemispheric difference in simulated TC densities, whereas future CO2 forcing impacts both hemispheres in the same direction. In both cases, we find that TC genesis frequency, density, and intensity are primarily controlled by changes in tropospheric thermal and moisture structure, exhibiting a clear reduction in TC genesis density in warmer hemispheres.
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BACKGROUND: Isolated left ventricular apical hypoplasia (ILVAH), also known as truncated left ventricle (LV), is a very unusual cardiomyopathy. It is characterised by a truncated, spherical, and non-apex forming LV. The true apex is occupied by the right ventricle. Due to the rarity of the disease, just a few case reports and limited case series have been published in the field. AIM: To analysing the so far 37 reported ILVAH cases worldwide. METHODS: The electronic databases PubMed and Scopus were investigated from their establishment up to December 13, 2022. RESULTS: The majority of cases reported occurred in males (52.7%). Mean age at diagnosis was 26.1 ± 19.6 years. More than a third of the patients were asymptomatic (35.1%). The most usual clinical presentation was breathlessness (40.5%). The most commonly detected electrocardiogram changes were T wave abnormalities (29.7%) and right axis deviation with poor R wave progression (24.3%). Atrial fibrillation/flutter was detected in 24.3%. Echocardiography was performed in 97.3% of cases and cardiac MRI in 91.9% of cases. Ejection fraction was reduced in more than a half of patients (56.7%). An associated congenital heart disease was found in 16.2%. Heart failure therapy was administered in 35.1% of patients. The outcome was favorable in the vast majority of patients, with just one death. CONCLUSION: ILVAH is a multifaceted entity with a so far unpredictable course, ranging from benign until the elderly to sudden death during adolescence.
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BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy is a novel therapy demonstrating durable remissions in patients with refractory or relapsing non-Hodgkin's B-cell lymphoma. Maintaining a patient's nutritional status has been demonstrated to improve outcomes in cancer treatment. However, no studies have investigated how CAR-T therapy affects nutritional status, nor compared its impact with other cancer treatments for this patient group. The primary aim of the present study was to investigate the effect of CAR-T therapy on the prevalence of nutrition impact symptoms (NIS) and nutritional status within 30 days post-treatment of patients with lymphoma compared to a conditioning regimen for autologous haematopoetic stem cell transplant (carmustine/BCNU, Etoposide, cytarabine/Ara-C, Melphalan [BEAM] auto-haematopoetic stem cell transplant [HSCT]). METHODS: Clinical notes of patients with lymphoma who underwent either CAR-T therapy or BEAM auto-HSCT between 2018 and 2021 were reviewed. Data extracted included body weight measurements and NIS, including decreased appetite, nausea, vomiting, diarrhoea, constipation, mucositis, cytokine release syndrome (CRS) and neurotoxicity at baseline and 30 ± 7 days post-treatment. RESULTS: In total, 129 adults with lymphoma (n = 88 CAR-T vs. n = 41 BEAM) were included. Nutritional status was assessed in both groups at baseline prior to treatment. Mean absolute weight change was significantly different between groups (3.05 kg in CAR-T, -5.9 kg in BEAM, p ≤ 0.001). This was also significant when weight loss was categorised into percentage weight loss (p = 0.01). CAR-T patients experienced a significantly lower prevalence of decreased appetite (52.3% vs. 97.6%) nausea (25% vs. 78%,) vomiting (10.2% vs. 53.7%), diarrhoea (43.2% vs. 96.7%) and mucositis (5.7% vs. 75.6%) combined across all levels of severity compared to BEAM chemotherapy (all p ≤ 0.01). CRS and neurotoxicity, which are specific side effects of CAR-T therapy, were moderately positively associated with weight loss. CONCLUSIONS: Weight loss, percentage weight loss and NIS were significantly reduced in CAR-T compared to BEAM treatment. However, patients who experienced neurotoxicity during treatment did have significant weight loss.
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Linfoma , Mucositis , Receptores Quiméricos de Antígenos , Adulto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carmustina/efectos adversos , Citarabina/efectos adversos , Linfoma/tratamiento farmacológico , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptores Quiméricos de Antígenos/uso terapéutico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Pérdida de Peso , Inmunoterapia Adoptiva/efectos adversos , Antígenos CD19/inmunología , Antígenos CD19/uso terapéuticoRESUMEN
INTRODUCTION: Sexting among adolescents continues to garner interest across disciplines due to its prevalence in the lives of young people and the potential for extremely negative outcomes associated with the behavior. The present review aimed to integrate the existing qualitative research on adolescent sexting experiences, to provide empirically-supported recommendations for professionals working with adolescents. METHODS: A search of four databases relating to adolescent experiences of sexting was conducted, resulting in the inclusion of 28 studies in the review. Quality appraisal of these studies was completed in line with the Critical Appraisal Skills Profile qualitative checklist. RESULTS: Major themes in the qualitative studies were synthesized to generate recommendations for professionals. These recommendations are categorized as (a) "proactive" (enhancing positive and contextualized education and attempting to mitigate the likelihood of young people having negative experiences with sexting), (b) "responsive" (management of disclosures of distressing experiences with sexting, including image-based sexual abuse [IBSA]), and (iii) "clinical" (increasing awareness among clinicians of pertinent issues concerning intervention with young people who are engaging in sexting, or who have been victimized by IBSA). CONCLUSIONS: The qualitative literature was found to provide rich insight into adolescent experiences of sexting, thus allowing for the generation of evidence-based recommendations which are consistent with young peoples' own interests and preferences. Limitations in the existing literature base were discussed (e.g., lack of specificity in methodological reporting), and suggestions were given for future research (including the need to explore sexting experiences of LGBTQ + adolescents in more depth).
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Conducta del Adolescente , Envío de Mensajes de Texto , Humanos , Adolescente , Conducta Sexual , Revelación , Investigación Cualitativa , PrevalenciaRESUMEN
The management of atrial septal defects (ASDs) has been revolutionized by the advent of percutaneous transvenous occlusion devices. This case series describes techniques required to perform a transeptal puncture safely and effectively in patients postimplantation of an atrial septal defect occluder to facilitate catheter ablation of atrial arrhythmias. (Level of Difficulty: Intermediate.).
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The majority of patients born with congenital heart disease (CHD) need lifelong surveillance with serial clinical attendance and examinations. However, loss of follow-up (namely no documented follow-up for 3 years or more) is a recognised common problem since it is often related to remarkable worsening in the health of CHD patients with increased morbidity and mortality. Transitioning from paediatric to adult care has proven to be the most vulnerable point in the care of these subjects. As such, a systematic review was carried out to ask the following questions: What is the percentage of loss of follow-up worldwide? Are there regional fluctuations in the percentage? Is there a link between loss of follow-up and the complexity of CHD? What strategies should be employed to lower the risk of discontinuity in care? The most recent worldwide averaged loss of follow-up is 26.1%, with significant fluctuations across continents and countries. This percentage is even higher (31.9%) when one includes all untraceable patients, presuming that they are not having any cardiac follow-up. The highest discontinuity of care was reported in the USA and in patients with simple CHD. Planning the rules of transition seems to be one of the most reliable tools to minimise the number of CHD patients who are lost in transition. Recalling patients, with general practitioners who are crucial in readdressing half of the lost to follow-up CHD patients to adult CHD specialists, and a good relationship between paediatric cardiologists and the adult CHD team are two other valuable strategies in aiding successful transition.
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INTRODUCTION: Paediatric pulmonary hypertension (PH) represents a heterogeneous illness that is responsible for high morbidity and mortality if left without treatment. Idiopathic pulmonary arterial hypertension (IPAH) is a subtype of PAH rarely seen in paediatrics. Limited long-term data are available. METHODS: Over a period of 20 years, 10 paediatric patients were enrolled at two tertiary centres. Their clinical, echocardiographic, and right heart catheterisation (RHC) features and outcome were evaluated. RESULTS: The mean age at first diagnosis was 5.7 ± 5.7 years. The age at the last follow-up was 12.4 ± 6.1 years. The average follow-up was 6.6 ± 0.8 years. There was a female prevalence of 60% (p < 0.05) in this case series. Regarding the NYHA functional class, 80% of IPAH subjects were in class III or IV. The mean saturation was 91 ± 5%. In this regard, 70% of the patients were on a combination of three drugs, with sildenafil (90%) included. On echocardiography, longitudinal right ventricular contractility (TAPSE) was slightly reduced (13.4 ± 2.6 mm), whilst RVSP was severely elevated (101 ± 19 mmHg). The RHC data showed that mPAP was 61.8 ± 23.1 mmHg (p = 0.0017 with RVSP on echocardiography), mRAP was 10.7 ± 3.8 mmHg, CI was 2.6 ± 1 L·min-1·m-2, PVRi was 16.8 ± 12.6 WU·m2, and SVO2 was 63.6 ± 14.8%. Regarding the outcome, two male IPAH patients (20%) died, and 50% underwent lung transplant or were on transplant assessment or already on the waiting list for lung transplantation. One patient underwent a ductus arteriosus stenting (reverse Potts shunt) and another underwent atrial septostomy and stenting. CONCLUSIONS: Notwithstanding the progress in medical therapy, IPAH continues to represent a serious challenge, particularly in the paediatric population, with the need for lung transplantation and significant mortality.
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This paper describes the fabrication of cicada-wing-inspired antimicrobial surfaces using Glancing Angle Deposition (GLAD). From the study of an annual cicada (Neotibicen Canicularis, also known as dog-day cicada) in North America, it is found that the cicada wing surfaces are composed of unique three-dimensional (3D) nanofeature arrays, which grant them extraordinary properties including antimicrobial (antifouling) and antireflective. However, the morphology of these 3D nanostructures imposes challenges in artificially synthesizing the structures by utilizing and scaling up the template area from nature. From the perspective of circumventing the difficulties of creating 3D nanofeature arrays with top-down nanofabrication techniques, this paper introduces a nanofabrication process that combines bottom-up steps: self-assembled nanospheres are used as the bases of the features, while sub-100 nm pillars are grown on top of the bases by GLAD. Scanning electron micrographs show the resemblance of the synthesized cicada wing mimicry samples to the actual cicada wings, both quantitatively and qualitatively. The synthetic mimicry samples are hydrophobic with a water contact angle of 125Ë. Finally, the antimicrobial properties of the mimicries are validated by showing flat growth curves of Escherichia coli (E. coli) and by direct observation under scanning electron microscopy (SEM). The process is potentially suitable for large-area antimicrobial applications in food and biomedical industries.