Acoustic characteristics of fricatives, amplitude of formants and clarity of speech produced without and with a medical mask.

BACKGROUND: Previous research has found that high-frequency energy of speech signals decreased while wearing face masks. However, no study has examined the specific spectral characteristics of fricative consonants and vowels and the perception of clarity of speech in mask wearing. AIMS: To investigate acoustic-phonetic characteristics of fricative consonants and vowels and auditory perceptual rating of clarity of speech produced with and without wearing a face mask. METHODS & PROCEDURES: A total of 16 healthcare workers read the Rainbow Passage using modal phonation in three conditions: without a face mask, with a standard surgical mask and with a KN95 mask (China GB2626-2006, a medical respirator with higher barrier level than the standard surgical mask). Speech samples were acoustically analysed for root mean square (RMS) amplitude (ARMS ) and spectral moments of four fricatives /f/, /s/, /ʃ/ and /z/; and amplitude of the first three formants (A1, A2 and A3) measured from the reading passage and extracted vowels. Auditory perception of speech clarity was performed. Data were compared across mask and non-mask conditions using linear mixed models. OUTCOMES & RESULTS: The ARMS of all included fricatives was significantly lower in surgical mask and KN95 mask compared with non-mask condition. Centre of gravity of /f/ decreased in both surgical and KN95 mask while other spectral moments did not show systematic significant linear trends across mask conditions. None of the formant amplitude measures was statistically different across conditions. Speech clarity was significantly poorer in both surgical and KN95 mask conditions. CONCLUSIONS & IMPLICATIONS: Speech produced while wearing either a surgical mask or KN95 mask was associated with decreased fricative amplitude and poorer speech clarity. WHAT THIS PAPER ADDS: What is already known on the subject Previous studies have shown that the overall spectral levels in high frequency ranges and intelligibility are decreased for speech produced with a face mask. It is unclear how different types of the speech signals that is, fricatives and vowels are presented in speech produced with wearing either a medical surgical or KN95 mask. It is also unclear whether ratings of speech clarity are similar for speech produced with these face masks. What this paper adds to existing knowledge Speech data collected using a real-world, clinical and non-laboratory-controlled settings showed differences in the amplitude of fricatives and speech clarity ratings between non-mask and mask-wearing conditions. Formant amplitude did not show significant differences in mask-wearing conditions compared with non-mask. What are the potential or actual clinical implications of this work? Wearing a surgical mask or a KN95 mask had different effects on consonants and vowels. It appeared from the findings in this study that these masks only affected fricative consonants and did not affect vowel production. The poorer speech clarity in these mask-wearing conditions has important implications for speech perception in communication between clinical staff and between medical officers and patients in clinics, and between people in everyday situations. The impact of these masks on speech perception may be more pronounced in people with hearing impairment and communication disorders. In voice evaluation and/or therapy sessions, the effects of wearing a medical mask can occur bidirectionally for both the clinician and the patient. The patient may find it more challenging to understand the speech conveyed by the clinician while the clinician may not perceptually assess patient's speech and voice accurately. Given the significant correlation between clarity ratings and fricative amplitude, improving fricative signals would be useful to improve speech clarity while wearing these medical face masks.

Children's understanding of epilepsy: A qualitative study.

PURPOSE: To use a qualitative research approach to determine children's understandings of epilepsy and their epilepsy treatment. METHODS: Children aged 7-16 years with physician-confirmed active epilepsy (i.e., having had an epileptic seizure in the past year and or currently taking antiepileptic drugs (AEDs), and not known to have an intellectual disability, were invited to participate. Children had semi-structured interviews separately on two occasions. Between the first and second interviews, an observation of a routine epilepsy clinic appointment of individual children was conducted, and was then discussed during the second interview. Participatory research tools were used in both child interviews to facilitate discussions. Interviews were audio recorded and transcribed, pseudonymized and entered into NVivo (version 12, QSR International). Data were analyzed using a thematic approach. RESULTS: Twenty-three children of mean age 10.1 years (range 8-14), mean duration of epilepsy of 4.6 years (range 2-10) were enrolled. Twelve were 12 female; 7 had focal, 14 had generalized, and 2 had combined epilepsy; 20 were on monotherapy; and 16 had tried previous AEDs. All had an initial (first) interview; 20 were observed during a clinic appointment and had a second interview. Five broad themes emerged: understanding of epilepsy; understanding of seizures; understanding of medication; understanding of children's role in clinical appointments; influences on children's understanding. Children spoke about what epilepsy meant by describing the physical sensations of having a seizure or through the act of taking medication. Children described the role they had, or felt they should have, but reported challenges in being meaningfully involved in clinical appointments. While healthcare professionals were initial information nodes, epilepsy information from parents appeared to be more significant for children. CONCLUSIONS: The perspectives of children with epilepsy are valuable for clinicians to understand; assumptions should not be made that children's views can be accessed via parents. Clinicians need to be constantly aware of children's views and ways of understanding and communicating about their epilepsy. To support this, the research - drawing on children's words, meanings, and stories - was used to inform an easily accessible, gender-neutral, animation about epilepsy that provides information about the condition, seizures, and medication (https://youtu.be/MO7xXL2ZXP8).

Assessing research gaps and unmet needs in endometriosis.

Endometriosis, a systemic disease that is often painful and chronic, affects ∼10% of reproductive-age women. The disease can have a negative impact on a patient's physical and emotional well-being, quality of life, and productivity. Endometriosis also places significant economic and social burden on patients, their families, and society as a whole. Despite its high prevalence and cost, endometriosis remains underfunded and underresearched, greatly limiting our understanding of the disease and slowing much-needed innovation in diagnostic and treatment options. Due in part to the societal normalization of women's pain and stigma around menstrual issues, there is also a lack of disease awareness among patients, health care providers, and the public. The Society for Women's Health Research convened an interdisciplinary group of expert researchers, clinicians, and patients for a roundtable meeting to review the current state of the science on endometriosis and identify areas of need to improve a woman's diagnosis, treatment, and access to quality care. Comprehensive and interdisciplinary approaches to disease management and increased education and disease awareness for patients, health care providers, and the public are needed to remove stigma, increase timely and accurate diagnosis and treatment, and allow for new advancements.

Clinical predictors for oropharyngeal dysphagia and laryngeal dysfunction after lung and heart transplantation.

BACKGROUND: Oropharyngeal dysphagia and laryngeal dysfunction are two lesser known complications after lung and heart transplantation. The presence of these features places this immunocompromised population at high risk of pulmonary complications and subsequent medical deterioration. Early identification of swallowing and voice dysfunction would be beneficial to optimize management. AIMS: To examine the association between patient risk factors and postoperative outcomes with referral to speech pathology (SP) following signs of swallowing and voice dysfunction. METHODS & PROCEDURES: A retrospective review was conducted on demographic data, patient risk factors and postoperative course in 284 patients following lung and/or heart transplantation between 2010 and 2013. Variables were analysed for any association between pre- and postoperative factors and SP referral. OUTCOMES & RESULTS: A total of 24% were referred to SP with a mean age of 47 years. Binary logistic regression identified a statistically significant association between the number of intubations (odds ratio (OR) = 2.066, p = 0.028), intubation duration (OR = 1.004, p < 0.01), length of stay in the intensive care unit (ICU) (OR = 1.068, p < 0.01), and number of ICU admissions (OR = 1.384, p = 0.046) and SP referral. Intubation time and the total days in ICU were greater for patients referred to SP. Mortality also increased for these variables and for the numbers of reintubations and readmissions. Analysis of pre-operative risk factors revealed cerebrovascular disease to be a significant predictor of SP referral (OR = 6.747, p = 0.032). CONCLUSIONS & IMPLICATIONS: This study demonstrates significant clinical indicators for referral to SP for the management of oropharyngeal dysphagia and laryngeal dysfunction in patients after lung or heart transplantation. Further studies are needed to investigate the most efficacious intervention approaches to manage swallowing and voice dysfunction in these patients.

Shame, Dissociation, and Complex PTSD Symptoms in Traumatized Psychiatric and Control Groups: Direct and Indirect Associations With Relationship Distress.

OBJECTIVES: Elevated shame and dissociation are common in dissociative identity disorder (DID) and chronic posttraumatic stress disorder (PTSD) and are part of the constellation of symptoms defined as complex PTSD. Previous work examined the relationship between shame, dissociation, and complex PTSD and whether they are associated with intimate relationship anxiety, relationship depression, and fear of relationships. This study investigated these variables in traumatized clinical samples and a nonclinical community group. METHOD: Participants were drawn from the DID (n = 20), conflict-related chronic PTSD (n = 65), and nonclinical (n = 125) populations and completed questionnaires assessing the variables of interest. A model examining the direct impact of shame and dissociation on relationship functioning, and their indirect effect via complex PTSD symptoms, was tested through path analysis. RESULTS: The DID sample reported significantly higher dissociation, shame, complex PTSD symptom severity, relationship anxiety, relationship depression, and fear of relationships than the other two samples. Support was found for the proposed model, with shame directly affecting relationship anxiety and fear of relationships, and pathological dissociation directly affecting relationship anxiety and relationship depression. The indirect effect of shame and dissociation via complex PTSD symptom severity was evident on all relationship variables. CONCLUSION: Shame and pathological dissociation are important for not only the effect they have on the development of other complex PTSD symptoms, but also their direct and indirect effects on distress associated with relationships.

Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells.

OBJECTIVE: In diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer 3-dimensional (3D) vascular networks in synthetic hydrogels from type 1 diabetes mellitus (T1D) patient-derived human-induced pluripotent stem cells (hiPSCs), to serve as a transformative autologous vascular therapy for diabetic patients. APPROACH AND RESULTS: We validated and optimized an adherent, feeder-free differentiation procedure to derive early vascular cells (EVCs) with high portions of vascular endothelial cadherin-positive cells from hiPSCs. We demonstrate similar differentiation efficiency from hiPSCs derived from healthy donor and patients with T1D. T1D-hiPSC-derived vascular endothelial cadherin-positive cells can mature to functional endothelial cells-expressing mature markers: von Willebrand factor and endothelial nitric oxide synthase are capable of lectin binding and acetylated low-density lipoprotein uptake, form cords in Matrigel and respond to tumor necrosis factor-α. When embedded in engineered hyaluronic acid hydrogels, T1D-EVCs undergo morphogenesis and assemble into 3D networks. When encapsulated in a novel hypoxia-inducible hydrogel, T1D-EVCs respond to low oxygen and form 3D networks. As xenografts, T1D-EVCs incorporate into developing zebrafish vasculature. CONCLUSIONS: Using our robust protocol, we can direct efficient differentiation of T1D-hiPSC to EVCs. Early endothelial cells derived from T1D-hiPSC are functional when mature. T1D-EVCs self-assembled into 3D networks when embedded in hyaluronic acid and hypoxia-inducible hydrogels. The capability of T1D-EVCs to assemble into 3D networks in engineered matrices and to respond to a hypoxic microenvironment is a significant advancement for autologous vascular therapy in diabetic patients and has broad importance for tissue engineering.

Families' experiences of living with pediatric epilepsy: A qualitative systematic review.

Living with epilepsy in childhood has implications for the child and their family beyond the physical effects associated with epileptic seizures. Qualitative research has emerged, aiming to deliver a greater depth of understanding of the experiences of living with epilepsy from the perspectives of children with epilepsy, their parents, and their siblings. This review of qualitative research had three aims: first, to synthesize the demographic and epilepsy profiles of research participants in eligible studies in order to provide a clear picture of who are included and excluded when studying families' experiences; second, to present and discuss the methodological concerns and implications of research involving children with epilepsy; and third, to synthesize the findings arising from qualitative research with families in order to identify common themes across all relevant studies to date. Papers published in the English language prior to January 2016 were identified following a search of eight electronic databases: Embase, Psychinfo, Medline, CINAHL, Web of Knowledge, ASSIA, Web of Science, and SCOPUS. Studies were included if they involved a sample of children with epilepsy (up to 18years of age), parents, or siblings of children with epilepsy and used qualitative methods. Twenty-one studies were identified as eligible for inclusion in the review. Findings in relation to the three aims were the following: 1) Researchers were seeking an understanding of children's experiences directly from children rather than by parental proxy. However, children with learning disabilities were often excluded from research, meaning that their views are not being heard. Parental research was predominantly with mothers, and father experiences were not often accessed. There was very little research with siblings. 2) The rationale for and ethical implications of the choice of research methods adopted were not always clear, and not all studies gave adequate attention to the development of appropriate methods for research involving children. 3) Two dominant themes emerged across the studies: normalcy and children's agency. Cutting across many of the challenges that living with epilepsy presented was the desire (by parents and children) for a 'normal' childhood. The studies also highlighted that children have knowledge about their own condition and epilepsy more generally and that they are involved in managing the ways in which they cope with epilepsy, both in terms of seizure prevention and managing their relations with others, particularly peers. Future research should ensure that appropriate design, data collection, and analytic strategies are adopted to facilitate the participation of all family members. Enhancing the quality of the research will, in turn, optimize validity and opportunities for the translation of findings into better health, education, and social practices to improve care for children and their families affected by epilepsy.

The carbon emissions of writing and illustrating are lower for AI than for humans.

As AI systems proliferate, their greenhouse gas emissions are an increasingly important concern for human societies. In this article, we present a comparative analysis of the carbon emissions associated with AI systems (ChatGPT, BLOOM, DALL-E2, Midjourney) and human individuals performing equivalent writing and illustrating tasks. Our findings reveal that AI systems emit between 130 and 1500 times less CO2e per page of text generated compared to human writers, while AI illustration systems emit between 310 and 2900 times less CO2e per image than their human counterparts. Emissions analyses do not account for social impacts such as professional displacement, legality, and rebound effects. In addition, AI is not a substitute for all human tasks. Nevertheless, at present, the use of AI holds the potential to carry out several major activities at much lower emission levels than can humans.

Dermatosparaxis (Ehlers-Danlos type VIIC): prenatal diagnosis following a previous pregnancy with unexpected skull fractures at delivery.

Dermatosparaxis Ehlers-Danlos syndrome (or EDS VIIC), a rare autosomal recessive connective tissue disorder, is characterized by extreme skin fragility, premature rupture of membranes in pregnancy, and spontaneous rupture of internal organs. Here we report a second patient with EDS VIIC presenting with congenital skull fractures and skin lacerations at birth, complications which may occur more frequently than previously thought in this condition. We also discuss the role of prenatal diagnosis in the management of a subsequent normal pregnancy.

The impact of shame on the therapeutic alliance and intimate relationships.

OBJECTIVES: This study examined the role of shame coping styles and state shame in predicting the therapeutic alliance and intimate relationship functioning in individuals with mental health problems. METHOD: A sample of 50 treatment-receiving adults aged 21 to 67 years with a mix of common mental health difficulties was recruited from a clinical psychology service. Participants were given questionnaire measures of shame states, shame coping styles, intimate relationship functioning, and the therapeutic alliance. RESULTS: Regression analyses indicated that the shame coping strategy of physical and psychological withdrawal was the primary risk factor for development of a less effective therapeutic alliance. Both withdrawal and attack self coping styles were significant predictors of impaired intimate relationship functioning. CONCLUSIONS: These findings have implications for the theoretical role of shame in mental health presentations as well as the potential for internalizing shame coping styles (i.e., withdrawal, attack self) to act as a barrier to successful therapy and interpersonal relationships. The inclusion of shame-focused assessments and interventions in the initial stages of treatment with clients exhibiting these strategies could improve prognosis.

Patient satisfaction with general surgery telephone consultations during the COVID-19 pandemic: a single surgeon experience.

BACKGROUND: COVID-19 pandemic accelerated the development and use of telemedicine in surgical practice. Here we set out to understand patient satisfaction with the use of telephone consultation in the general surgical clinic and preference over face-to-face consultation. METHODS: A prospective cohort study was carried out for consecutive patients seen in a general surgery telephone clinic by a single surgeon in a district general hospital in the UK from 1st September 2021 to 10th March 2022. Demographic data was collected from electronic patient records. At the end of the consultation patients were asked to: 1) score their satisfaction with the telephone consultation on a 5-point Likert Scale; and 2) whether they preferred telephone consultations to face-to-face appointments. It was noted if a patient required a further face-to-face consultation in addition to the telephone consultation. RESULTS: The study included 245 patients who were reviewed by telephone consultation. Most patients (59.6%; N.=146) gave the telephone consultation the highest satisfaction score with a further 31% (N.=76) scoring it as a 4 out of 5. Only 2.8% of patients said they would have preferred a face-to-face consultation and gave a median satisfaction score of 2 (IQR 2-3) compared to 5 (IQR 4-5) in those who preferred telephone consultations (P<0.001). CONCLUSIONS: Telemedicine is associated with high levels of patient satisfaction regardless of patient age or gender. Lower rates of satisfaction are associated with the need for further face-to-face follow-up. If telemedicine is to remain a permanent part of surgical practice, disease specific protocols for its use are required.

Tissue catabolism and donor-specific dexamethasone response in a human osteochondral model of post-traumatic osteoarthritis.

BACKGROUND: Post-traumatic osteoarthritis (PTOA) does not currently have clinical prognostic biomarkers or disease-modifying drugs, though promising candidates such as dexamethasone (Dex) exist. Many challenges in studying and treating this disease stem from tissue interactions that complicate understanding of drug effects. We present an ex vivo human osteochondral model of PTOA to investigate disease effects on cartilage and bone homeostasis and discover biomarkers for disease progression and drug efficacy. METHODS: Human osteochondral explants were harvested from normal (Collins grade 0-1) ankle talocrural joints of human donors (2 female, 5 male, ages 23-70). After pre-equilibration, osteochondral explants were treated with a single-impact mechanical injury and TNF-α, IL-6, and sIL-6R ± 100 nM Dex for 21 days and media collected every 2-3 days. Chondrocyte viability, tissue DNA content, and glycosaminoglycan (sGAG) percent loss to the media were assayed and compared to untreated controls using a linear mixed effects model. Mass spectrometry analysis was performed for both cartilage tissue and pooled culture medium, and the statistical significance of protein abundance changes was determined with the R package limma and empirical Bayes statistics. Partial least squares regression analyses of sGAG loss and Dex attenuation of sGAG loss against proteomic data were performed. RESULTS: Injury and cytokine treatment caused an increase in the release of matrix components, proteases, pro-inflammatory factors, and intracellular proteins, while tissue lost intracellular metabolic proteins, which was mitigated with the addition of Dex. Dex maintained chondrocyte viability and reduced sGAG loss caused by injury and cytokine treatment by 2/3 overall, with donor-specific differences in the sGAG attenuation effect. Biomarkers of bone metabolism had mixed effects, and collagen II synthesis was suppressed with both disease and Dex treatment by 2- to 5-fold. Semitryptic peptides associated with increased sGAG loss were identified. Pro-inflammatory humoral proteins and apolipoproteins were associated with lower Dex responses. CONCLUSIONS: Catabolic effects on cartilage tissue caused by injury and cytokine treatment were reduced with the addition of Dex in this osteochondral PTOA model. This study presents potential peptide biomarkers of early PTOA progression and Dex efficacy that can help identify and treat patients at risk of PTOA.

KMT5B is required for early motor development.

Disruptive variants in lysine methyl transferase 5B (KMT5B/SUV4-20H1) have been identified as likely-pathogenic among humans with neurodevelopmental phenotypes including motor deficits (i.e., hypotonia and motor delay). However, the role that this enzyme plays in early motor development is largely unknown. Using a Kmt5b gene trap mouse model, we assessed neuromuscular strength, skeletal muscle weight (i.e., muscle mass), neuromuscular junction (NMJ) structure, and myofiber type, size, and distribution. Tests were performed over developmental time (postnatal days 17 and 44) to represent postnatal versus adult structures in slow- and fast-twitch muscle types. Prior to the onset of puberty, slow-twitch muscle weight was significantly reduced in heterozygous compared to wild-type males but not females. At the young adult stage, we identified decreased neuromuscular strength, decreased skeletal muscle weights (both slow- and fast-twitch), increased NMJ fragmentation (in slow-twitch muscle), and smaller myofibers in both sexes. We conclude that Kmt5b haploinsufficiency results in a skeletal muscle developmental deficit causing reduced muscle mass and body weight.

Swallowing and laryngeal complications in lung and heart transplantation: Etiologies and diagnosis.

Despite continued surgical advancements in the field of cardiothoracic transplantation, post-operative complications remain a burden for the patient and the multidisciplinary team. Lesser-known complications including swallowing disorders (dysphagia), and voice disorders (dysphonia), are now being reported. Such disorders are known to be associated with increased morbidity and mortality in other medical populations, however their etiology amongst the heart and lung transplant populations has received little attention in the literature. This paper explores the potential mechanisms of oropharyngeal dysphagia and dysphonia following transplantation and discusses optimal modalities of diagnostic evaluation and management. A greater understanding of the implications of swallowing and laryngeal dysfunction in the heart and lung transplant populations is important to expedite early diagnosis and management in order to optimize patient outcomes, minimize allograft injury and improve quality of life.

Proteomic Clustering Reveals the Kinetics of Disease Biomarkers in Bovine and Human Models of Post-Traumatic Osteoarthritis.

Objectives: In this study, we apply a clustering method to proteomic data sets from bovine and human models of post-traumatic osteoarthritis (PTOA) to distinguish clusters of proteins based on their kinetics of release from cartilage and examined these groups for PTOA biomarker candidates. We then quantified the effects of dexamethasone (Dex) on the kinetics of release of the cartilage media proteome. Design: Mass spectrometry was performed on sample medium collected from two separate experiments using juvenile bovine and human cartilage explants (3 samples/treatment condition) during 20- or 21-day treatment with inflammatory cytokines (TNF-α, IL-6, sIL-6R) with or without a single compressive mechanical injury. All samples were incubated with or without 100 nM Dex. Clustering was performed on the correlation between normalized averaged release vectors for each protein. Results: Our proteomic method identified the presence of distinct clusters of proteins based on the kinetics of their release over three weeks of culture. Clusters of proteins with peak release after one to two weeks had biomarker candidates with increased release compared to control. Dex rescued some of the changes in protein release kinetics the level of control, and in all conditions except control, there was late release of immune-related proteins. Conclusions: We demonstrate a clustering method applied to proteomic data sets to identify and validate biomarkers of early PTOA progression and explore the relationships between the release of spatially related matrix components. Dex restored the kinetics of release to many matrix components, but not all factors that contribute to cartilage homeostasis.

HIF2A gain-of-function mutation modulates the stiffness of smooth muscle cells and compromises vascular mechanics.

Heterozygous gain-of-function (GOF) mutations of hypoxia-inducible factor 2α (HIF2A), a key hypoxia-sensing regulator, are associated with erythrocytosis, thrombosis, and vascular complications that account for morbidity and mortality of patients. We demonstrated that the vascular pathology of HIF2A GOF mutations is independent of erythrocytosis. We generated HIF2A GOF-induced pluripotent stem cells (iPSCs) and differentiated them into endothelial cells (ECs) and smooth muscle cells (SMCs). Unexpectedly, HIF2A-SMCs, but not HIF2A-ECs, were phenotypically aberrant, more contractile, stiffer, and overexpressed endothelin 1 (EDN1), myosin heavy chain, elastin, and fibrillin. EDN1 inhibition and knockdown of EDN1-receptors both reduced HIF2-SMC stiffness. Hif2A GOF heterozygous mice displayed pulmonary hypertension, had SMCs with more disorganized stress fibers and higher stiffness in their pulmonary arterial smooth muscle cells, and had more deformable pulmonary arteries compared with wild-type mice. Our findings suggest that targeting these vascular aberrations could benefit patients with HIF2A GOF and conditions of augmented hypoxia signaling.

Oropharyngeal dysphagia and laryngeal dysfunction after lung and heart transplantation: A systematic review.

Purpose: Oropharyngeal dysphagia and laryngeal dysfunction are known to impact on health outcomes of patients with critical illness. The incidence in patients after heart and/or lung transplantation is unknown. This paper investigates the frequency, characteristics and risk factors for these complications following such transplantation.Method: Eight databases were systematically searched. Inclusion criteria were (a) adults who underwent heart and/or lung transplantation as their primary surgery, (b) new onset of oropharyngeal dysphagia and/or laryngeal dysfunction and dysphonia identified in the acute hospital phase (c) original studies (d) in English.Results: Two thousand six hundred and sixteen articles were identified. Five met the inclusion criteria. Studies were few and heterogeneous in design and sample size, therefore meta-analysis was not performed. All included studies were of relatively low quality. However, rates of oropharyngeal dysphagia up to 70.5% were reported, with 25% of these patients presenting with vocal cord palsy.Conclusions: Limited conclusions can be drawn from the available evidence regarding the frequency, characteristics and risk factors for the development of oropharyngeal dysphagia and/or laryngeal dysfunction after heart and/or lung transplantation due to limited evidence and low quality of the included studies. This highlights the need for high quality studies in this population.Implications for rehabilitationOropharyngeal dysphagia and dysphonia are known to impact on mortality and quality of lifeThere is a paucity of literature describing these complications after lung and/or heart transplantation, however the data available indicates high rates of swallowing and voice disorders in this immunosuppressed populationEarly identification and management of oropharyngeal dysphagia and dysphonia is vital to aid rehabilitation and improve mortality and quality of life in patients following lung and/or heart transplantation.

Proteomic analysis reveals dexamethasone rescues matrix breakdown but not anabolic dysregulation in a cartilage injury model.

OBJECTIVES: In this exploratory study, we used discovery proteomics to follow the release of proteins from bovine knee articular cartilage in response to mechanical injury and cytokine treatment. We also studied the effect of the glucocorticoid Dexamethasone (Dex) on these responses. DESIGN: Bovine cartilage explants were treated with either cytokines alone (10 ng/ml TNFα, 20 ng/ml IL-6, 100 ng/ml sIL-6R), a single compressive mechanical injury, cytokines and injury, or no treatment, and cultured in serum-free DMEM supplemented with 1% ITS for 22 days. All samples were incubated with or without addition of 100 nM Dex. Mass spectrometry and western blot analyses were performed on medium samples for the identification and quantification of released proteins. RESULTS: We identified 500 unique proteins present in all three biological replicates. Many proteins involved in the catabolic response of cartilage degradation had increased release after inflammatory stress. Dex rescued many of these catabolic effects. The release of some proteins involved in anabolic and chondroprotective processes was inconsistent, indicating differential effects on processes that may protect cartilage from injury. Dex restored only a small fraction of these to the control state, while others had their effects exacerbated by Dex exposure. CONCLUSIONS: We identified proteins that were released upon cytokine treatment which could be potential biomarkers of the inflammatory contribution to cartilage degradation. We also demonstrated the imperfect rescue of Dex on the effects of cartilage degradation, with many catabolic factors being reduced, while other anabolic or chondroprotective processes were not.

Randomized Interventional Study on Prediction of Preeclampsia/Eclampsia in Women With Suspected Preeclampsia: INSPIRE.

The ratio of maternal serum sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) has been used retrospectively to rule out the occurrence of preeclampsia, a pregnancy hypertensive disorder, within 7 days in women presenting with clinical suspicion of preeclampsia. A prospective, interventional, parallel-group, randomized clinical trial evaluated the use of sFlt-1/PlGF ratio in women presenting with suspected preeclampsia. Women were assigned to reveal (sFlt-1/PlGF result known to clinicians) or nonreveal (result unknown) arms. A ratio cutoff of 38 was used to define low (≤38) and elevated risk (>38) of developing the condition in the subsequent week. The primary end point was hospitalization within 24 hours of the test. Secondary end points were development of preeclampsia and other adverse maternal-fetal outcomes. We recruited 370 women (186 reveal versus 184 nonreveal). Preeclampsia occurred in 85 women (23%). The number of admissions was not significantly different between groups (n=48 nonreveal versus n=60 reveal; P=0.192). The reveal trial arm admitted 100% of the cases that developed preeclampsia within 7 days, whereas the nonreveal admitted 83% (P=0.038). Use of the test yielded a sensitivity of 100% (95% CI, 85.8-100) and a negative predictive value of 100% (95% CI, 97.1-100) compared with a sensitivity of 83.3 (95% CI, 58.6-96.4) and negative predictive value of 97.8 (95% CI, 93.7-99.5) with clinical practice alone. Use of the sFlt-1/PlGF ratio significantly improved clinical precision without changing the admission rate. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN87470468.