BACKGROUND:The threshold of the lower limit of the normal range of lung function has been suggested to be more accurate than the 0.7 fixed ratio (FEV1/FVC < 0.7) for a diagnosis of COPD. We aimed to explore the health status and risk factors of patients overdiagnosed with COPD when using the lower limit of the normal range as a diagnostic reference.METHODS:Subjects with COPD diagnosed by a pulmonologist according to guidelines of the Global Initiative for Chronic Obstructive Lung Disease were recruited from October 2016 to April 2018. Overdiagnosed COPD was defined as FEV1/FVC that meets the criterion of the 0.7 fixed ratio but not the the lower limit of the normal range criterion. Spirometry and questionnaires were performed by eligible subjects.RESULTS:Of the 513 subjects included in the final analysis, 20 (3.9%) were overdiagnosed when using the lower limit of the normal range as the diagnostic reference. The subjects who were overdiagnosed were older, weighed more, had better lung function, lower modified Medical British Research Council scores, and higher St. George's Respiratory Questionnaire and 36-item Short Form Survey scores than the subjects who were correctly diagnosed. Older age, heavier weight, exposure to cooking oil fumes, or a new-built or newly renovated home were associated with an increased risk of overdiagnosis of COPD (age adjusted odds ratio (OR) 1.17, 95% CI 1.09–1.26; weight adjusted OR 1.08, 95% CI 1.03–1.13; exposure to cooking oil fumes adjusted OR 3.00, 95% CI, 1.04–8.68; exposure to new-built or newly renovated home adjusted OR 10.88, 95% CI 1.46–80.87.CONCLUSIONS:The subjects with overdiagnosed COPD had a better health status and lung function than the subjects who were correctly diagnosed. Older age, heavier weight, and exposure to cooking oil fumes or a new-built or newly renovated home were factors associated with the overdiagnosis of COPD. These findings may help reduce overdiagnosis of COPD.

Recent studies have strived to find an association between rapid antidepressant effects and a specific subset of pharmacological targets and molecular pathways. Here, we propose a broader hypothesis of encoding, consolidation, and renormalization in depression (ENCORE-D), which suggests that, fundamentally, rapid and sustained antidepressant effects rely on intrinsic homeostatic mechanisms evoked as a response to the acute pharmacological or physiologic effects triggered by the treatment. We review evidence that supports the notion that various treatments with a rapid onset of action, such as ketamine, electroconvulsive therapy, and sleep deprivation, share the ability to acutely excite cortical networks, which increases synaptic potentiation, alters patterns of functional connectivity, and ameliorates depressive symptoms. We proceed to examine how the initial effects are short-lived and, as such, require both consolidation during wake and maintenance throughout sleep to remain sustained. Here, we incorporate elements from the synaptic homeostasis hypothesis and theorize that the fundamental mechanisms of synaptic plasticity and sleep, particularly the homeostatic emergence of slow-wave electroencephalogram activity and the renormalization of synaptic strength, are at the center of sustained antidepressant effects. We conclude by discussing the various implications of the ENCORE-D hypothesis and offer several considerations for future experimental and clinical research.

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

Impaired insulin secretion from the pancreatic β-cells is central in the pathogenesis of type 2 diabetes (T2D), and microRNAs (miRNAs) are fundamental regulatory factors in this process. Differential expression of miRNAs contributes to β-cell adaptation to compensate for increased insulin resistance, but deregulation of miRNA expression can also directly cause β-cell impairment during the development of T2D. miRNAs are small noncoding RNAs that posttranscriptionally reduce gene expression through translational inhibition or mRNA destabilization. The nature of miRNA targeting implies the presence of complex and large miRNA–mRNA regulatory networks in every cell, including the insulin-secreting β-cell. Here we exemplify one such network using our own data on differential miRNA expression in the islets of T2D Goto-Kakizaki rat model. Several biological processes are influenced by multiple miRNAs in the β-cell, but so far most studies have focused on dissecting the mechanism of action of individual miRNAs. In this Perspective we present key islet miRNA families involved in T2D pathogenesis including miR-200, miR-7, miR-184, miR-212/miR-132, and miR-130a/b/miR-152. Finally, we highlight four challenges and opportunities within islet miRNA research, ending with a discussion on how miRNAs can be utilized as therapeutic targets contributing to personalized T2D treatment strategies.

Nayeli G. Reyes-Nava, Hung-Chun Yu, Curtis R. Coughlin II, Tamim H. Shaikh, and Anita M. Quintana

We used whole-exome sequencing (WES) to determine the genetic etiology of a patient with a multi-system disorder characterized by a seizure phenotype. WES identified a heterozygous de novo missense mutation in the GABRA1 gene (c.875C>T). GABRA1 encodes the alpha subunit of the gamma-aminobutyric acid receptor A (GABA_AR). The GABA_AR is a ligand gated ion channel that mediates the fast inhibitory signals of the nervous system, and mutations in the subunits that compose the GABA_AR have been previously associated with human disease. To understand the mechanisms by which GABRA1 regulates brain development, we developed a zebrafish model of gabra1 deficiency. gabra1 expression is restricted to the nervous system and behavioral analysis of morpholino injected larvae suggests that the knockdown of gabra1 results in hypoactivity and defects in the expression of other subunits of the GABA_AR. Expression of the human GABRA1 protein in morphants partially restored the hypomotility phenotype. In contrast, the expression of the c.875C>T variant did not restore these behavioral deficits. Collectively, these results represent a functional approach to understand the mechanisms by which loss-of-function alleles cause disease.

BACKGROUND AND PURPOSE:

Anoxic brain injury is a result of prolonged hypoxia. We sought to describe the nonquantitative arterial spin-labeling perfusion imaging patterns of anoxic brain injury, characterize the relationship of arterial spin-labeling and DWI, and evaluate the normalized diffusion-to-perfusion ratio to differentiate patients with anoxic brain injury from healthy controls.

Exhaust fumes and cold KFC?

New Zealand is on track to eliminate covid-19 altogether, but keeping the virus out for good will be a challenge, and the economic impacts are likely to hurt

Kiren Rijiju said coronavirus has changed everything and sports need to be conducted in a new way

Kiren Rijiju said coronavirus has changed everything and sports need to be conducted in a new way

"But as I hope we have started to set out today, if we keep doing the right things and if we consider all of the options carefully and with the right objectives in mind, I do believe there will be a way through and we will find that way through."

It comes after headteachers warned the earliest date they could reopen is June 1, and planning would need to begin "very soon" to achieve it.

Brits may have to accept a "new normal" with social distancing measures remaining in place until a vaccine is available, Michael Gove has suggested.

Dominic Raab has said the UK must adjust to "a new normal" in the second phase of the coronavirus response, which he insisted "will not be easy".

The travel industry has sifted through the BBC show’s many sex scenes to showcase shots of Ireland’s landscape

Promoting Ireland as a tourism destination used to be straightforward – just showcase the bucolic landscape and put a slogan on the end – but that was before Normal People turned a chunk of the Atlantic coast into Fifty Shades of Sligo.

The television adaptation of Sally Rooney’s novel features beautiful shots of Sligo’s beaches and mountains, plus Trinity College Dublin, but there is also sex. Lots of sex.

Rev. Dr. William J. Barber II, Rev. Dr. Liz Theoharis

The post ‘Normalcy—Never Again!’ appeared first on The Nation.

If Sally Rooney is the first great millennial novelist, then Marianne Sheridan is the first great millennial TV style icon

Would it make a person really shallow if their favourite thing about the TV adaptation of Normal People was Marianne’s wardrobe? Asking for a friend.

The COVID-19 pandemic has already affected the lives of every American. And while politicians and experts disagree on how best to confront the disease and mitigate its economic ramifications, there is a broad understanding that we are entering a “new normal” — an upending of our lives that will continue at least until a vaccine is developed — and perhaps well beyond that.

A silver chain has taken center stage in Hulu's adaptation of Sally Rooney's "Normal People"

New clip gives viewers a sense of what the much-anticipated series will be like

While plenty of young drama is played for shock or laughs, the anticipated BBC3 adaptation of Sally Rooney's best-selling book lingers on what goes unsaid between its adolescent lovebirds. And there is lots of humping, says arts columnist Fiona Sturges

Daisy Edgar-Jones and Paul Mescal inhabit lovers Marianne and Connell so utterly that it is instantly impossible to imagine them being played by anyone else

The TV adaptation of Sally Rooney's endlessly talked-about novel promises a modern take on romance, and lots of sex, but its heartbreaking tale of love divided by class is only too real, most of us have lived it, says Annie Lord

Adaptation of Sally Rooney's love story stars Paul Mescal and Daisy Edgar-Jones

Show has been praised for its representation of consensual sex

BBC series has been widely praised for its depiction of consensual sex between main characters Marianne and Connell

The actor bringing Sally Rooney's smash-hit novel to life talks to Ellie Harrison about experiencing tragedy at a young age, how Normal People's depiction of sex is the antidote to porn and Hollywood, and what it's like to promote the biggest role of his life in lockdown

'We worked very hard to make it feel like it was a real, accurate and truthful representation of sex amongst young people today,' said the actor

21.8 million people requested the show on BBC iPlayer in its opening week

The 'Normal People' star played an Irish teenager whose sausage inspires him to travel the world

The long-awaited television adaptation of Sally Rooney's millennial love story has arrived

Paul Mescal stars in the BBC's adaptation of Sally Rooney's acclaimed novel

Countries across Europe are gradually easing lockdown measures

The new BBC show tackles male mental health in a carefully nuanced way. Laura Hampson explains why it's compulsory viewing

As Normal People makes its BBC debut, we pick our favourite books with Rooney-esque themes

The ES team pick our favourite, well-thumbed love stories

Passengers may have to collect sealed "grab and go" meal bags before they board planes to reduce their contact with cabin crew on flights under a range of options for the post lockdown era being considered by aviation bosses.

Vodafone's new thermal detection cameras will help businesses scan the temperature of people entering the building

*Spoilers ahead* Don't go any further if you haven't finished Normal People yet...

The number of high intensity "heavy breathing" work-out machines such as treadmills and cross trainers will be hugely reduced in gyms to help make them safe when the lockdown ends.

Hers is a style so good that it's far from normal

Don't pretend you didn't notice it: that whisper-thin necklace glinting against Connell's chest

And it's just £35 per night

In a story about the challenges of communication, the characters in Normal People often find solace in reading

Listen to Patrice Evra for just a few moments and it's clear what Manchester United lost when he walked away from the club.