Experiences of UK and Irish family carers of people with profound and multiple intellectual disabilities during the COVID-19 pandemic.

BACKGROUND: People with profound and multiple intellectual disabilities (PMID) have high and intensive support needs that ordinarily place significant strain on family carers. This was further heightened by the removal of many external supports during the COVID-19 pandemic. We sought to explore the experiences of family carers of people with PMID during the COVID-19 pandemic and understand what the longer-term impact might be on their lives. METHODS: Focus group interviews (n = 32) were conducted with family carers (n = 126) from the four countries of the UK and the Republic of Ireland. Participants were asked questions relating to their experiences of the COVID-19 pandemic, coping strategies, and challenges faced. All focus groups were conducted using the online platform, Zoom. These were audio recorded, transcribed verbatim and analysed employing inductive thematic analysis. FINDINGS: Three main themes were generated from the data including (1.0) COVID-19 as a double-edged sword (2.0), The struggle for support (3.0), Constant nature of caring. These included 11 subthemes. (1.1) 'COVID-19 as a catalyst for change', (1.2) 'Challenges during COVID-19: dealing with change', (1.3) 'Challenges during COVID-19: fear of COVID-19', (1.4); 'The online environment: the new normal' (2.1) 'Invisibility of male carers', (2.2) 'Carers supporting carers', (2.3) 'The only service you get is lip service: non-existent services', (2.4); 'Knowing your rights' (3.1) 'Emotional response to the caring role: Feeling devalued', (3.2) 'Emotional response to the caring role: Desperation of caring', (3.3) 'Multiple demands of the caring role.' CONCLUSIONS: The COVID-19 pandemic presented immense challenges to family carers of people with PMID but also provided some opportunities. Families had already struggled to receive many of the supports and services to which they were entitled to only to have these removed at the onset of the pandemic. The experiences of male carers have been largely absent from the literature with this research showing they want to be included in decision making and require tailored support services. Service providers should see the end of the COVID-19 pandemic as providing opportunity to re-examine current provision and design services with family carers. As the direct threat from COVID-19 diminishes and the experiences of those who lived through this period come to the fore, there is a need to re-examine current models and provision of support to family carers to better meet their needs.

Impact of the COVID-19 pandemic on family carers of those with profound and multiple intellectual disabilities: perspectives from UK and Irish Non-Governmental Organisations.

BACKGROUND: Family carers of people with profound and multiple intellectual disabilities (PMID) experienced a reduction in healthcare services due to the COVID-19 pandemic. Many subsequently turned to Non-Governmental Organisations who worked to support families. However, little research has sought to capture the experiences of family carers or identify effective interventions which might support them. To address these concerns we explored the views of Non-Governmental sector workers across the UK and Ireland who supported families people with PMID during the COVID-19 pandemic. We also sought to explore their views on the characteristics of online support programmes for family carers.  METHODS: This study employed a qualitative design using focus groups with participants (n = 24) from five Non-Governmental Organisations across the UK and Ireland. A focus group guide included questions on challenges, supports, coping and resources which helped during lockdown restrictions. Focus groups were held online, were audio recorded and transcribed verbatim. The resulting transcripts were pseudonymised and subjected to thematic analysis. FINDINGS: Four themes were identified (i) 'mental and emotional health', (ii) 'they who shout the loudest' (fighting for services), (iii) 'lack of trust in statutory services' and (iv) 'creating an online support programme'. Mental and emotional health emerged as the most prominent theme and included three subthemes named as 'isolation', 'fear of COVID-19' and 'the exhaustion of caring'. CONCLUSIONS: The COVID-19 pandemic has increased the vulnerability of family carers who were already experiencing difficulties in accessing services and supports for their families. While Non-Governmental Organisations have been a crucial lifeline there is urgent need to design services, including online support programmes, in partnership with family carers which adequately address their needs.

Is It Time to Create Training Pathways Allowing Earlier Subspecialization within the "House of Orthopaedics"?: AOA Critical Issues.

ABSTRACT: The ability to train an orthopaedic resident in all aspects of orthopaedics in 5 years has become increasingly difficult due to the growth in knowledge and techniques, work-hour restrictions, and reduced resident autonomy. It has become nearly universal for our residents to complete at least 1 subspecialty fellowship prior to entering practice. In some subspecialties, the skills necessary to practice competently have become difficult to master. Simply adding to the current length of training may not address these issues effectively and would add to the economic cost of residency training. Novel training pathways that allow residents to focus earlier and in greater depth on their intended subspecialty while maintaining general orthopaedic competencies can be created without lengthening training. It is time to initiate discussions about these possibilities.

Enhanced Perinatal Programs for People in Prisons: A Summary of Six States' Programs.

Purpose: The purpose of this study was to examine enhanced perinatal support programs for pregnant and postpartum people in six state prisons, describe the service components offered by each program, and discuss similarities and differences of services offered between programs. Methods: In-depth, semi-structured interviews were conducted with each program's site lead(s) in order to collect information regarding each program's historical context, conception, and key aspects of the implementation of service components offered at each site. Results: Program components fell into five broad categories: group-based education and support, one-on-one support, labor and birth support, lactation facilitation and support, and other support services. Results highlight similarities and differences within and across programs and common themes that govern program success. Conclusions: This study provides an initial understanding of the variation in enhanced perinatal programming in six state prisons and offers insights for other states interested in establishing these types of programs. These programs implemented individual components piecemeal to fit site-specific context and needs, instead of adopting the entirety of another program model. Programs' success was largely dependent upon collaboration between program facilitators and partnering prison sites.

Long-term cognitive and psychiatric outcomes of acute respiratory distress syndrome managed with Extracorporeal Membrane Oxygenation.

BACKGROUND: Cognitive dysfunction is often reported in patients who have experienced acute respiratory distress syndrome (ARDS). Extra Corporeal Membrane Oxygenation (ECMO) therapy is increasingly used to manage ARDS patients in ICU, transforming survival rates. However, few studies have examined cognitive outcomes. METHODS: We examined self-reported cognitive complaints, psychiatric outcomes and neuropsychological test performance in survivors of severe hypoxaemia managed with VV-ECMO, at 18-24 month follow-up, compared with a group of healthy controls. RESULTS: Over 70% of ECMO-treated patients (N = 46) complained of difficulty in at least one aspect of cognition on self-report measures (study 1). However, a much lower frequency of cognitive impairment was found on formal neuropsychological testing (study 2). Mean neuropsychological test scores of the ECMO group (N = 24) did not significantly differ from healthy controls (N = 23) after controlling for depression. Less than 30% of ECMO-treated patients showed impairments in anterograde memory, and deficits on general IQ or executive function were seen in <17% of patients. However, we observed high levels of self-reported anxiety and depression in the ECMO-treated patients. CONCLUSIONS: Cognitive outcomes in ECMO-treated patients were generally good, with preserved neuropsychological function in the majority of patients, despite severe hypoxaemia and high rates of self-reported difficulties. However, we saw high levels of mental health symptoms in these patients, highlighting a need for psychological support.

Treatment of metastatic placental site trophoblastic tumor with surgery, chemotherapy, immunotherapy and coil embolization of multiple pulmonary arteriovenous fistulate.

Placental Site Trophoblastic Tumor (PSTT) is a rare malignancy that often presents with extensive disease and can be resistant to traditional treatments. We present the case of a woman with stage IV PSTT who was initially managed with neoadjuvant chemotherapy followed by tumor debulking. Adjuvant therapy was guided by further pathologic analysis that revealed high levels of staining for PD-L1 as well as the presence of tumor infiltrating lymphocytes (TILs). Subsequently, the patient was treated with traditional chemotherapy with the EP/EMA regimen with the addition of pembrolizumab. The patient's treatment course was complicated by the development of pulmonary arteriovenous malformations, autoimmune thyroiditis thought to be secondary to immunotherapy, and significant tinnitus secondary to platinum agents. Currently the patient is in follow up and remains in a complete remission.

Intimate partner violence among HIV-positive women in Nairobi, Kenya.

PURPOSE: This study was conducted to identify the prevalence and sociodemographic factors associated with four forms of intimate partner violence (IPV) among HIV-positive women attending the Comprehensive Care Centre at the Kenyatta National Hospital in Nairobi, Kenya. METHODS: A cross-sectional study was conducted among 600 sexually active HIV-positive women aged 18-69 years from May to August of 2012. A structured questionnaire including questions pertaining to sociodemographic characteristics, health care decisions, and forms of IPV (controlling behavior, emotional abuse, physical violence, and sexual violence) was administered to each woman. RESULTS: All women reported experiencing emotional abuse; 20%, 17%, and 15% experienced controlling behavior, physical violence, and sexual violence, respectively. Women who reported low/below average socioeconomic status (SES) had a greater likelihood of experiencing controlling behavior than women with high/average SES (adjusted odds ratio [aOR] =1.62, 95% CI 1.05-2.51). Women who were unemployed had greater odds of experiencing physical violence than those who were employed (aOR =2.35, 95% CI 1.31-4.23). Non-Christian women had higher odds of experiencing controlling behavior, physical violence, and sexual violence than Christian women (aOR =4.41, 95% CI 1.81-10.76 and aOR =3.33, 95% CI 1.43-7.80). CONCLUSION: Based on the prevalence of IPV and the sociodemographic factors identified to be associated with IPV among women in this study it may be beneficial to include IPV screening as part of routine clinic visits for HIV-positive and other women. Furthermore, women who report emotional abuse or controlling behavior from spouse should not be overlooked, as these two forms of IPV may precede or accompany physical and sexual IPV. Women who report experiencing IPV during clinic visits may be referred to organizations and resources available to battered women in Kenya. Increased funding for anti-IPV programs and changes in policy may also contribute to a reduction in IPV among HIV-positive and other women in Kenya.

Transcription factor Fra-2 and its emerging role in matrix deposition, proliferation and inflammation in chronic lung diseases.

Fos-related antigen-2 (Fra-2) belongs to the activator protein 1 (AP-1) family of transcription factors and is involved in a broad variety of cellular processes, such as proliferation or differentiation. Aberrant expression of Fra-2 or regulation can lead to severe growth defects or diverse pathologies. Elevated Fra-2 expression has been described in several chronic lung diseases, such as pulmonary fibrosis, chronic obstructive pulmonary disease and asthma. However, the pathomechanisms behind the Fra-2-induced pulmonary remodelling are still not fully elucidated. Fra-2 overexpressing mice were initially described as a model of systemic sclerosis associated organ fibrosis, with predominant alterations in the lung. High levels of Fra-2 expression give rise to profound inflammation with severe remodelling of the parenchyma and the vasculature, resulting in fibrosis and pulmonary hypertension, respectively, but also alters bronchial function. In this review we discuss the central role of Fra-2 connecting inflammation, cellular proliferation and extracellular matrix deposition underlying chronic lung diseases and what we can learn for future therapeutic options.

Positivity bias in past and future episodic thinking: Relationship with anxiety, depression, and retrieval-induced forgetting.

Positivity biases in autobiographical memory and episodic future thinking are considered important in mental wellbeing and are reduced in anxiety and depression. The inhibitory processes underlying retrieval-induced forgetting (RIF) have been proposed to contribute to these biases. This investigation found reduced positivity in past and future thinking to be associated with reduced memory specificity alongside greater levels of anxiety, depression, and rumination. Most notably, however, RIF was found to significantly predict memory valence. This indicates that RIF may be important in maintaining such biases, facilitating the forgetting of negative memories when a positive item is actively retrieved.

Changes in awareness of cancer risk factors among adult New Zealanders (CAANZ): 2001 to 2015.

Behaviour change, specifically that which decreases cancer risk, is an essential element of cancer control. Little information is available about how awareness of risk factors may be changing over time. This study describes the awareness of cancer risk behaviours among adult New Zealanders in two cross-sectional studies conducted in 2001 and 2014/5.Telephone interviews were conducted in 2001 (n = 436) and 2014/5 (n = 1064). Participants were asked to recall things they can do to reduce their risk of cancer. They were then presented with a list of potential risk behaviours and asked if these could increase or decrease cancer risk.Most New Zealand adults could identify at least one action they could take to reduce their risk of cancer. However, when asked to provide specific examples, less than a third (in the 2014/5 sample) recalled key cancer risk reduction behaviours such as adequate sun protection, physical activity, healthy weight, limiting alcohol and a diet high in fruit. There had been some promising changes since the 2001 survey, however, with significant increases in awareness that adequate sun protection, avoiding sunbeds/solaria, healthy weight, limiting red meat and alcohol, and diets high in fruit and vegetables decrease the risk of developing cancer.

Meprin ß contributes to collagen deposition in lung fibrosis.

Lung fibrosis is a severe disease characterized by epithelial cell injury, inflammation and collagen deposition. The metalloproteases meprinα and meprinß have been shown to enhance collagen maturation and inflammatory cell infiltration via cleavage of cell-cell contact molecules; therefore we hypothesized that meprins could play a role in lung fibrosis. An exhaustive characterization of bleomycin-treated meprinα, meprinß and the double meprinsαß knock-out (KO) with respective wt-littermates was performed by using several different methods. We observed no difference in lung function parameters and no change in inflammatory cells infiltrating the lung between wt and all meprins KO mice after 14 days bleomycin. No difference in epithelial integrity as assessed by e-cadherin protein level was detected in bleomycin-treated lungs. However, morphological analysis in the bleomycin-treated mice revealed decrease collagen deposition and tissue density in meprinß KO, but not in meprinα and meprinαß KO mice. This finding was accompanied by localization of meprinß to epithelial cells in regions with immature collagen in mice. Similarly, in human IPF lungs meprinß was mostly localized in epithelium. These findings suggest that local environment triggers meprinß expression to support collagen maturation. In conclusion, our data demonstrate the in vivo relevance of meprinß in collagen deposition in lung fibrosis.

Chemoradiotherapy with Brachytherapy or Electron Therapy Boost for Locally Advanced Squamous Cell Carcinoma of the Anus-Reducing the Colostomy Rate.

PURPOSE: The aim of this study is to determine overall survival, disease-specific survival and stoma-free survival after treatment of squamous cell carcinoma of the anus with chemoradiotherapy followed by brachytherapy or electron boost in a recent cohort of patients. METHODS: Fifty-two patients (median age 62 years) were treated with radical chemoradiotherapy (mitomycin C, infusional 5-fluorouracil concurrently with conformal radical radiotherapy 45 Gy in 25 fractions over 5 weeks) followed by a radiotherapy boost between 1 December 2000 and 30 April 2011. Follow-up was to 30 November 2014. Thirty-six patients received a boost (15-20 Gy) over 2 days with 192Ir needle brachytherapy for anal canal tumours, and 16 patients received electron beam therapy (20 Gy in 10 fractions in 2 weeks) for anal margin tumours. A defunctioning stoma was only created prior to chemoradiotherapy for fistula or severe anal pain. RESULTS: The overall survival for the 36 patients treated with chemoradiotherapy followed by brachytherapy was 75 % (95 % CI, 61-89) at 5 years, the disease-specific survival was 91 % (95 % CI, 81-101 %), and the stoma-free survival was 97 % (95 % CI, 91-103 %) all at 5 years. For the 16 patients treated with an electron boost for anal margin tumours, the 5-year overall survival, disease-specific survival and stoma-free survival were 68 % (95 % CI, 44-92 %), 78 % (95 % CI, 56-100 %) and 80 % (95 % CI, 60-100 %), respectively. CONCLUSIONS: A very low stoma formation rate can be obtained with radical chemoradiotherapy followed by a brachytherapy boost for squamous cell carcinoma of the anal canal but not with an electron boost for anal margin tumours.

Ecology and biogeography of megafauna and macrofauna at the first known deep-sea hydrothermal vents on the ultraslow-spreading Southwest Indian Ridge.

The Southwest Indian Ridge is the longest section of very slow to ultraslow-spreading seafloor in the global mid-ocean ridge system, but the biogeography and ecology of its hydrothermal vent fauna are previously unknown. We collected 21 macro- and megafaunal taxa during the first Remotely Operated Vehicle dives to the Longqi vent field at 37° 47'S 49° 39'E, depth 2800 m. Six species are not yet known from other vents, while six other species are known from the Central Indian Ridge, and morphological and molecular analyses show that two further polychaete species are shared with vents beyond the Indian Ocean. Multivariate analysis of vent fauna across three oceans places Longqi in an Indian Ocean province of vent biogeography. Faunal zonation with increasing distance from vents is dominated by the gastropods Chrysomallon squamiferum and Gigantopelta aegis, mussel Bathymodiolus marisindicus, and Neolepas sp. stalked barnacle. Other taxa occur at lower abundance, in some cases contrasting with abundances at other vent fields, and δ13C and δ15N isotope values of species analysed from Longqi are similar to those of shared or related species elsewhere. This study provides baseline ecological observations prior to mineral exploration activities licensed at Longqi by the United Nations.

A novel approach to antibiofilm susceptibility testing using a thermo-reversible matrix.

OBJECTIVE: Biofilm microorganisms are known to have a much higher tolerance to antimicrobials compared to their planktonic equivalents. Therefore, traditional antimicrobial susceptibility testing may not extrapolate to clinical treatment of infections of biofilm origin, and as a result, there is a need to not only develop antimicrobials with antibiofilm activity, but also suitable in vitro testing methods for their evaluation. In this study, we report on a novel method of antibiofilm testing using a thermo-reversible matrix (poloxamer 407), coupled with live/dead staining of bacteria cultured from the matrix. METHOD: Pseudomonas aeruginosa (NCIMB 8626) was cultured in medium containing poloxamer 407 at 37°C for 24 hours to generate biofilms. The preparation was cooled to liquefy the poloxamer and allow recovery of the biofilm cells, which were then stained with SYTO9 to determine viability following exposure to four antimicrobials: polyhexanide, octenadine dihydrochloride, povidone-iodine and silver carbonate. Over an 8-minute time period, fluorescence levels were spectrophotometrically measured and compared with bacterial controls, cultured in the absence of poloxamer and without antimicrobial. RESULTS: Untreated cells showed no reduction in viability over this period. Importantly, planktonic cells were more susceptible to test agents compared with those of a 'biofilm' phenotype cultured in poloxamer. Antibiofilm activity was evident for all of the test agents, with highest relative activity seen with octenadine dihydrochloride. CONCLUSION: In summary, a novel and relatively rapid approach to screen compounds for antibiofilm activity has been described. The method uses standard laboratory equipment and can be readily adapted to test a wide range of microorganisms and other antibiofilm compounds. DECLARATION OF INTEREST: This research was, in part, supported by Advanced Medical Solutions in the form of a Knowledge Transfer Project. Mr J. Nosworthy was employed by Advanced Medical Solutions. There are no other conflicts of interests to declare.

Activation of EP4 receptors prevents endotoxin-induced neutrophil infiltration into the airways and enhances microvascular barrier function.

BACKGROUND AND PURPOSE: Pulmonary vascular dysfunction is a key event in acute lung injury. We recently demonstrated that PGE2 , via activation of E-prostanoid (EP)4 receptors, strongly enhances microvascular barrier function in vitro. The aim of this study was to investigate the beneficial effects of concomitant EP4 receptor activation in murine models of acute pulmonary inflammation. EXPERIMENTAL APPROACH: Pulmonary inflammation in male BALB/c mice was induced by LPS (20 µg per mouse intranasally) or oleic acid (0.15 µL·g-1 , i.v. ). In-vitro, endothelial barrier function was determined by measuring electrical impedance. KEY RESULTS: PGE2 activation of EP4 receptors reduced neutrophil infiltration, pulmonary vascular leakage and TNF-α concentration in bronchoalveolar lavage fluid from LPS-induced pulmonary inflammation. Similarly, pulmonary vascular hyperpermeability induced by oleic acid was counteracted by EP4 receptor activation. In lung function assays, the EP4 agonist ONO AE1-329 restored the increased resistance and reduced compliance upon methacholine challenge in mice treated with LPS or oleic acid. In agreement with these findings, EP4 receptor activation increased the in vitro vascular barrier function of human and mouse pulmonary microvascular endothelial cells and diminished the barrier disruption induced by LPS. The EP2 agonist ONO AE1-259 likewise reversed LPS-induced lung dysfunction without enhancing vascular barrier function. CONCLUSION AND IMPLICATIONS: Our results show that activation of the EP4 receptor strengthens the microvascular barrier function and thereby ameliorates the pathology of acute lung inflammation, including neutrophil infiltration, vascular oedema formation and airway dysfunction. This suggests a potential benefit for EP4 agonists in acute pulmonary inflammation.

Smoke-free policies in New Zealand public tertiary education institutions.

The Framework Convention on Tobacco Control mandates the creation of smoke-free environments to protect non-smokers from second-hand smoke and reduce demand for tobacco. We aimed to examine the extent and nature of smoke-free campus policies at tertiary education institutions throughout New Zealand, and examine the policy development process. Stage one comprised an audit and content analysis of smoke-free policies. In stage two, semi-structured telephone interviews were conducted to investigate the process of developing and implementing policies. Qualitative content analysis was undertaken on interview notes. Policies were identified for most institutions (n = 26/29), though varied widely in nature. Only nine mandated 100% smoke-free campuses without exceptions and few prohibited the sale of tobacco on campus, or connections with the tobacco industry. During interviews (n = 22/29), cited barriers to developing a 100% smoke-free policy included enforcement challenges and anticipated opposition from staff and students. However, participants from institutions with 100% smoke-free policies reported having encountered few challenges. Varying levels of compliance with 100% smoke-free policies were reported yet, overall, these policies were viewed as being effective. Smoke-free campus policies could be strengthened to better reflect a completely tobacco-free organization. Other institutions and workplaces could use these findings to develop 100% smoke-free policies.

Predictive gaze during observation of irrational actions in adults with autism spectrum conditions.

Understanding irrational actions may require the observer to make mental state inferences about why an action was performed. Individuals with autism spectrum conditions (ASC) have well documented difficulties with mentalizing; however, the degree to which rationality understanding is impaired in autism is not yet clear. The present study uses eye-tracking to measure online understanding of action rationality in individuals with ASC. Twenty adults with ASC and 20 typically developing controls, matched for age and IQ watched movies of rational and irrational actions while their eye movements were recorded. Measures of looking time, scan path and saccade latency were calculated. Results from looking time and scan path analyses demonstrate that participants with ASC have reduced visual attention to salient action features such as the action goal and the hand performing the action, regardless of action rationality. However, when participants with ASC do attend to these features, they are able to make anticipatory goal saccades as quickly as typically developing controls. Taken together these results indicate that individuals with autism have reduced attention to observed actions, but when attention is maintained, goal prediction is typical. We conclude that the basic mechanisms of action understanding are intact in individuals with ASC although there may be impairment in the top-down, social modulation of eye movements.

Factor analysis of the Hamilton Depression Rating Scale in Parkinson's disease.

INTRODUCTION: Several studies have validated the Hamilton Depression Rating Scale (HAMD) in patients with Parkinson's disease (PD), and reported adequate reliability and construct validity. However, the factorial validity of the HAMD has not yet been investigated. The aim of our analysis was to explore the factor structure of the HAMD in a large sample of PD patients. METHODS: A principal component analysis of the 17-item HAMD was performed on data of 341 PD patients, available from a previous cross sectional study on anxiety. An eigenvalue ≥1 was used to determine the number of factors. Factor loadings ≥0.4 in combination with oblique rotations were used to identify which variables made up the factors. Kaiser-Meyer-Olkin measure (KMO), Cronbach's alpha, Bartlett's test, communality, percentage of non-redundant residuals and the component correlation matrix were computed to assess factor validity. RESULTS: KMO verified the sample's adequacy for factor analysis and Cronbach's alpha indicated a good internal consistency of the total scale. Six factors had eigenvalues ≥1 and together explained 59.19% of the variance. The number of items per factor varied from 1 to 6. Inter-item correlations within each component were low. There was a high percentage of non-redundant residuals and low communality. CONCLUSION: This analysis demonstrates that the factorial validity of the HAMD in PD is unsatisfactory. This implies that the scale is not appropriate for studying specific symptom domains of depression based on factorial structure in a PD population.

NPY/Y1 receptor-mediated vasoconstrictory and proliferative effects in pulmonary hypertension.

BACKGROUND AND PURPOSE: Pulmonary arteries (PAs) are innervated, but little is known about the role of neuronal axis in pulmonary hypertension (PH). Here, we have examined the role of the neuropeptide Y (NPY) and its Y1 receptor in PH pathogenesis. EXPERIMENTAL APPROACH: NPY was localized by immunofluorescence. Expression of NPY and Y1 receptor were determined by quantitative PCR. Cellular response to NPY stimulation was assessed by Western blotting, thymidine incorporation and calcium imaging. Wire myography and isolated perfused mouse lung were applied to study pulmonary vasoactive effects of NPY. Selective receptor antagonists were used to assess the contribution of receptor subtypes in mediating NPY effects. KEY RESULTS: Samples from PH patients showed increased NPYergic innervation within the PA wall and higher Y1 receptor expression, compared with donors. However, NPY levels were unchanged in both PA and serum. In the chronic hypoxic mouse model, Y1 receptor were up-regulated, while expression of both NPY and Y1 receptor was increased in the lungs of monocrotaline and SU5416-hypoxia rats. On a functional level, NPY acutely increased intracellular calcium levels and enhanced vasoconstriction of lung vessels preconstricted with adrenaline. Furthermore, NPY stimulated proliferation of human pulmonary arterial smooth muscle cells and activated p38 and PKD pathways. Correspondingly, higher phosphorylation of PKD was observed in remodelled vessels from PH patients. The selective Y1 receptor antagonist, BIBO 3304, concentration-dependently inhibited vasoconstrictive and proliferative effects of NPY. CONCLUSIONS AND IMPLICATIONS: NPY and Y1 receptor are possible mediators of both vasoconstriction and pulmonary vascular remodelling in PH.