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Continuous positive airway pressure (CPAP) ventilation may be used as a potential bridge to invasive mechanical ventilation (IMV), or as a ceiling-of-care for persistent hypoxaemia despite standard oxygen therapy, according to UK guidelines. We examined the association of mode of respiratory support and ceiling-of-care on mortality. We conducted a retrospective cohort analysis of routinely collected de-identified data of adults with nasal/throat SARs-CoV-2 swab-positive results, at the Calderdale and Huddersfield NHS Foundation Trust between 10th March-19th April 2020 (outcomes determined on 22nd May). Of 347 patients with SARs-CoV-2 swab-positive results, 294 (84.7%) patients admitted for Covid-19 were included in the study. Sixty-nine patients were trialled on CPAP, mostly delivered by face mask, either as an early ceiling of care instituted within 24 hours of admission (N = 19), or as a potential bridge to IMV (N = 44). Patients receiving a ceiling of care more than 24 hours after admission (N = 6) were excluded from the analysis. Two hundred and fifteen patients (73.1%) maximally received air/standard oxygen therapy, and 45 (15.3%) patients maximally received CPAP. Thirty-four patients (11.6%) required IMV, of which 24 had received prior CPAP. There were 138 patients with an early ceiling-of-care plan (pre-admission/within 24h). Overall, 103(35.0%) patients died and 191(65.0%) were alive at study end. Among all patients trialled on CPAP either as a potential bridge to IMV (N = 44) or as a ceiling-of-care (N = 19) mortality was 25% and 84%, respectively. Overall, there was strong evidence for higher mortality among patients who required CPAP or IMV, compared to those who required only air/oxygen (aOR 5.24 95%CI: 1.38, 19.81 and aOR 46.47 95%CI: 7.52, 287.08, respectively; p<0.001), and among patients with early ceiling-of-care compared to those without a ceiling (aOR 41.81 95%CI: 8.28, 211.17; p<0.001). Among patients without a ceiling of care (N = 137), 10 patients required prompt intubation following failed oxygen therapy, but 44 patients received CPAP. CPAP failure, defined as death (N = 1) or intubation (N = 24), occurred in 57% (N = 25) of patients. But in total, 75% (N = 33) of those started on CPAP with no ceiling of care recovered to discharge-19 without the need for IMV, and 14 following IMV. Our data suggest that among patients with no ceiling-of-care, an initial trial of CPAP as a potential bridge to IMV offers a favourable therapeutic alternative to early intubation. In contrast, among patients with a ceiling-of care, CPAP seems to offer little additional survival benefit beyond oxygen therapy alone. Information on ceilings of respiratory support is vital to interpreting mortality from Covid-19. Sample size relatively small.Study sample representative of hospitalised Covid-19 patients in UK.Previously unreported data on role of ceilings-of-care in hospitalised Covid-19 patients.Novel data on use of CPAP separated by indication.

During his lifetime, Nikolai Rimsky-Korsakov (1844-1908) was a composer whose work had great influence not only in his native Russia but also internationally. While he remains well-known in Russia--where many of his fifteen operas and various orchestral pieces are still in the standard repertoire--very little of his work is performed in the West today beyond Scheherezade and arrangements of The Flight of the Bumblebee. In Western writings, he appears mainly in the context of the Mighty Handful, a group of five Russian composers to which he belonged at the outset of his career. Rimsky-Korsakov and His World finally gives the composer center stage and due attention. In this collection, Rimsky-Korsakov's major operas, The Snow Maiden, Mozart and Salieri, and The Golden Cockerel, receive multifaceted exploration and are carefully contextualized within the wider Russian culture of the era. The discussion of these operas is accompanied and enriched by the composer's letters to Nadezhda Zabela, the distinguished soprano for whom he wrote several leading roles. Other essays look at more general aspects of Rimsky-Korsakov's work and examine his far-reaching legacy as a professor of composition and orchestration, including his impact on his most famous pupil Igor Stravinsky.

Paracrine signaling via gamma-aminobutyric acid (GABA) and GABA(A) receptors (GABA(A)Rs) has been documented in rodent islets. Here we have studied the importance of GABAergic signaling in human pancreatic islets. Expression of GABA(A)Rs in islet cells was investigated by quantitative PCR, immunohistochemistry, and patch-clamp experiments. Hormone release was measured from intact islets. GABA release was monitored by whole-cell patch-clamp measurements after adenoviral expression of alpha(1)beta(1) GABA(A)R subunits. The subcellular localization of GABA was explored by electron microscopy. The effects of GABA on electrical activity were determined by perforated patch whole-cell recordings. PCR analysis detected relatively high levels of the mRNAs encoding GABA(A)R alpha(2), beta(3,) gamma(2), and pi subunits in human islets. Patch-clamp experiments revealed expression of GABA(A)R Cl(-) channels in 52% of beta-cells (current density 9 pA/pF), 91% of delta-cells (current density 148 pA/pF), and 6% of alpha-cells (current density 2 pA/pF). Expression of GABA(A)R subunits in islet cells was confirmed by immunohistochemistry. beta-Cells secreted GABA both by glucose-dependent exocytosis of insulin-containing granules and by a glucose-independent mechanism. The GABA(A)R antagonist SR95531 inhibited insulin secretion elicited by 6 mmol/l glucose. Application of GABA depolarized beta-cells and stimulated action potential firing in beta-cells exposed to glucose. Signaling via GABA and GABA(A)R constitutes an autocrine positive feedback loop in human beta-cells. The presence of GABA(A)R in non-beta-cells suggests that GABA may also be involved in the regulation of somatostatin and glucagon secretion.

Objectives With increasing use of prospective scanning techniques for cardiac computed tomography (CT), meaningful evaluation of chamber volumes is no longer possible due to lack of normal values. We aimed to define normal values for mid-diastolic (MD) chamber volumes and to determine their significance in comparison to maximum volumes. Methods Normal ranges at MD for left ventricular (LV) volume and mass and left atrial (LA) volume were determined from 101 normal controls. Thereafter, 109 consecutive CT scans, as well as 21 post-myocardial infarction patients, were analysed to determine the relationship between MD and maximum volumes. Results MD volumes correlated closely with maximal volumes (r = 0.99) for both LV and LA, and could estimate maximum volumes accurately. LV mass, measured at ED or MD, were very similar (r = 0.99). Abnormal MD volumes had excellent sensitivity and specificity to detect chamber enlargement based on maximal volumes (LV 86 %, 100 %, respectively; LA 100 %, 92 %, respectively). Conclusion A single MD phase can identify patients with cardiomegaly or LV hypertrophy with a high degree of accuracy and MD volumes can give an accurate estimate of maximum LV and LA volumes. Key points • Traditionally , helical cardiac CT provided clinically important information from chamber volume analysis . • Mid - diastolic left atrial and ventricular volumes correlate closely with maximal volumes . • We derive normal values for mid - diastolic left atrial and ventricular volumes and mass . • A single mid - diastolic phase can be used to identify chamber enlargement and hypertrophy .

\"When Harry Colebourn saw a baby bear at a train station, he knew he could care for it. Harry was a veterinarian. But he was also a soldier in training during World War I. Harry named the bear Winnie, short for Winnipeg, his company's home town, and he brought her along to the military camp in England. Winnie followed Harry everywhere and slept under his cot every night. Before long, she became the regiment's much-loved mascot. But who could care for the bear when Harry went to battle? Harry found just the right place for Winnie--the London Zoo. There a boy named Christopher Robin played with Winnie--he could care for this bear too!\"-- Provided by publisher.

Overcoming gender inequities is a global priority recognized as essential for improved health and human development. Gender-based violence (GBV) is an extreme manifestation of gender inequities enacted in real-world and internet-based environments. In Nigeria, GBV has come to the forefront of attention since 2020, when a state of emergency was declared due to increased reporting of sexual violence. Understanding GBV-related social narratives is important to design public health interventions. We explore how gender-related internet-based conversations in Nigeria specifically related to sexual consent (actively agreeing to sexual behavior), lack of consent, and slut-shaming (stigmatization in the form of insults based on actual or perceived sexuality and behaviors) manifest themselves and whether they changed between 2017 and 2022. Additionally, we explore what role events or social movements have in shaping gender-related narratives in Nigeria. Social listening was carried out on 12,031 social media posts (Twitter, Facebook, forums, and blogs) and almost 2 million public searches (Google and Yahoo search engines) between April 2017 and May 2022. The data were analyzed using natural language processing to determine the most salient conversation thematic clusters, qualitatively analyze time trends in discourse, and compare data against selected key events. Between 2017 and 2022, internet-based conversation about sexual consent increased 72,633%, from an average 3 to 2182 posts per month, while slut-shaming conversation (perpetrating or condemning) shrunk by 9%, from an average 3560 to 3253 posts per month. Thematic analysis shows conversation revolves around the objectification of women, poor comprehension of elements of sexual consent, and advocacy for public education about sexual consent. Additionally, posters created space for sexual empowerment and expressions of sex positivity, pushing back against others who weaponize posts in support of slut-shaming narrative. Time trend analysis shows a greater sense of empowerment in advocating for education around the legal age of consent for sexual activity, calling out double standards, and rejecting slut-shaming. However, analysis of emotions in social media posts shows anger was most prominent in sexual consent (n=1213, 73%) and slut-shaming (n=226, 64%) posts. Organic social movements and key events (#ArewaMeToo and #ChurchToo, the #SexforGrades scandal, and the #BBNaija television program) played a notable role in sparking discourse related to sexual consent and slut-shaming. Social media narratives are significantly impacted by popular culture events, mass media programs, social movements, and micro influencers speaking out against GBV. Hashtags, media clips, and other content can be leveraged effectively to spread awareness and spark conversation around evolving gender norms. Public health practitioners and other stakeholders including policymakers, researchers, and social advocates should be prepared to capitalize on social media events and discourse to help shape the conversation in support of a normative environment that rejects GBV in all its forms.

To document the properties of the voltage-gated ion channels in human pancreatic alpha-cells and their role in glucagon release. Glucagon release was measured from intact islets. [Ca(2+)](i) was recorded in cells showing spontaneous activity at 1 mmol/l glucose. Membrane currents and potential were measured by whole-cell patch-clamping in isolated alpha-cells identified by immunocytochemistry. Glucose inhibited glucagon secretion from human islets; maximal inhibition was observed at 6 mmol/l glucose. Glucagon secretion at 1 mmol/l glucose was inhibited by insulin but not by ZnCl(2). Glucose remained inhibitory in the presence of ZnCl(2) and after blockade of type-2 somatostatin receptors. Human alpha-cells are electrically active at 1 mmol/l glucose. Inhibition of K(ATP)-channels with tolbutamide depolarized alpha-cells by 10 mV and reduced the action potential amplitude. Human alpha-cells contain heteropodatoxin-sensitive A-type K(+)-channels, stromatoxin-sensitive delayed rectifying K(+)-channels, tetrodotoxin-sensitive Na(+)-currents, and low-threshold T-type, isradipine-sensitive L-type, and omega-agatoxin-sensitive P/Q-type Ca(2+)-channels. Glucagon secretion at 1 mmol/l glucose was inhibited by 40-70% by tetrodotoxin, heteropodatoxin-2, stromatoxin, omega-agatoxin, and isradipine. The [Ca(2+)](i) oscillations depend principally on Ca(2+)-influx via L-type Ca(2+)-channels. Capacitance measurements revealed a rapid (<50 ms) component of exocytosis. Exocytosis was negligible at voltages below -20 mV and peaked at 0 mV. Blocking P/Q-type Ca(2+)-currents abolished depolarization-evoked exocytosis. Human alpha-cells are electrically excitable, and blockade of any ion channel involved in action potential depolarization or repolarization results in inhibition of glucagon secretion. We propose that voltage-dependent inactivation of these channels underlies the inhibition of glucagon secretion by tolbutamide and glucose.