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Worldwide Increase in Diagnosis of Hypertension in Children




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RNA sequencing profiles and diagnostic signatures linked with response to ramucirumab in gastric cancer [RESEARCH REPORT]

Gastric cancer (GC) is the fifth-ranked cancer type by associated mortality. The proportion of early diagnosis is low, and most patients are diagnosed at the advanced stages. First-line therapy standardly includes fluoropyrimidines and platinum compounds with trastuzumab for HER2-positive cases. For recurrent disease, there are several alternative options including ramucirumab, a monoclonal therapeutic antibody that inhibits VEGF-mediated tumor angiogenesis by binding with VEGFR2, alone or in combination with other cancer drugs. However, overall response rate following ramucirumab or its combinations is 30%–80% of the patients, suggesting that personalization of drug prescription is needed to increase efficacy of treatment. We report here original tumor RNA sequencing profiles for 15 advanced GC patients linked with data on clinical response to ramucirumab or its combinations. Three genes showed differential expression in the tumors for responders versus nonresponders: CHRM3, LRFN1, and TEX15. Of them, CHRM3 was up-regulated in the responders. Using the bioinformatic platform Oncobox we simulated ramucirumab efficiency and compared output model results with actual tumor response data. An agreement was observed between predicted and real clinical outcomes (AUC ≥ 0.7). These results suggest that RNA sequencing may be used to personalize the prescription of ramucirumab for GC and indicate potential molecular mechanisms underlying ramucirumab resistance. The RNA sequencing profiles obtained here are fully compatible with the previously published Oncobox Atlas of Normal Tissue Expression (ANTE) data.




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The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia [RESEARCH REPORT]

We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. (2019) at the genomic level using a different sequencing technology platform. The configuration of this gene fusion predicts the production of a kinase-activating JAK2 fusion protein, which would normally lead to a diagnosis of Philadelphia chromosome–like B-ALL (Ph-like B-ALL). However, the unusual presentation of eosinophilia led us to demonstrate the presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence in situ hybridization (FISH) studies with morphologic correlation. Therefore, we believe this disease, in fact, represents blast crisis arising from an underlying myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty in differentiating Ph-like B-ALL and myeloid/lymphoid neoplasm with eosinophilia and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the diagnosis of MLN-EGR relies on the hematologic presentations and the identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also define Ph-like B-ALL. Yet, our case does not conform to either condition. Therefore, the assessment for lineage restriction of gene rearrangements to reflect the pathophysiologic difference between B-ALL and MLN-EGR in blast crisis is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR with novel gene fusions.




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Prediagnostic Circulating Levels of Sex Steroid Hormones and SHBG in Relation to Risk of Ductal Carcinoma In Situ of the Breast among UK Women

Background:

Sex steroid hormones and sex hormone–binding globulin (SHBG) have been implicated in the etiology of invasive breast cancer, but their associations with risk of the precursor lesion, ductal carcinoma in situ (DCIS) of the breast, remain unclear.

Methods:

We used Cox proportional hazards regression models to estimate the associations of serum levels of estradiol (premenopausal women only), testosterone, and/or SHBG with DCIS risk among 182,935 women. After a median follow-up of 7.1 years, 186 and 531 DCIS cases were ascertained in premenopausal and postmenopausal women, respectively.

Results:

Total and free estradiol were positively associated with risk of DCIS among premenopausal women. The HRs for the highest versus the lowest tertiles were 1.54 (1.06–2.23) and 1.72 [95% confidence interval (CI), 1.15–2.57], respectively. Among postmenopausal women, elevated levels of free testosterone (FT), and to a lesser extent, total testosterone, were positively associated with DCIS risk. The HRs for the highest versus the lowest quartiles were 1.42 (95% CI, 1.09–1.85) and 1.16 (95% CI, 0.91–1.48), respectively. Serum SHBG levels were inversely associated with risk of DCIS among postmenopausal women (HRq4 vs. q1: 0.75; 95% CI, 0.56–0.99).

Conclusions:

This study suggests that elevated levels of estradiol are associated with increased risk of DCIS among premenopausal women, and that among postmenopausal women, elevated levels of testosterone, and particularly those of FT, are associated with increased DCIS risk, while elevated levels of SHBG are associated with reduced risk.

Impact:

These findings may be helpful in developing prevention strategies aimed at reducing breast cancer risk among premenopausal and postmenopausal women.




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Age at Diagnosis and Patient Preferences for Treatment Outcomes in AML: A Discrete Choice Experiment to Explore Meaningful Benefits

Background:

The recent expansion of treatment options in acute myeloid leukemia (AML) has necessitated a greater understanding of patient preferences for treatment benefits, about which little is known.

Methods:

We sought to quantify and assess heterogeneity of the preferences of AML patients for treatment outcomes. An AML-specific discrete choice experiment (DCE) was developed involving multiple stakeholders. Attributes included in the DCE were event-free survival (EFS), complete remission (CR), time in the hospital, short-term side effects, and long-term side effects. Continuously coded conditional, stratified, and latent-class logistic regressions were used to model preferences of 294 patients with AML.

Results:

Most patients were white (89.4%) and in remission (95.0%). A 10% improvement in the chance of CR was the most meaningful offered benefit (P < 0.001). Patients were willing to trade up to 22 months of EFS or endure 8.7 months in the hospital or a two-step increase in long-term side effects to gain a 10% increase in chance of CR. Patients diagnosed at 60 years or older (21.6%) more strongly preferred to avoid short-term side effects (P = 0.03). Latent class analysis showed significant differences of preferences across gender and insurance status.

Conclusions:

In this national sample of mostly AML survivors, patients preferred treatments that maximized chance at remission; however, significant preference heterogeneity for outcomes was identified. Age and gender may affect patients' preferences.

Impact:

Survivor preferences for outcomes can inform patient-focused drug development and shared decision-making. Further studies are necessary to investigate the use of DCEs to guide treatment for individual patients.




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Projected Reductions in Absolute Cancer-Related Deaths from Diagnosing Cancers Before Metastasis, 2006-2015

Background:

New technologies are being developed for early detection of multiple types of cancer simultaneously. To quantify the potential benefit, we estimated reductions in absolute cancer–related deaths that could occur if cancers diagnosed after metastasis (stage IV) were instead diagnosed at earlier stages.

Methods:

We obtained stage-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for 17 cancer types for all persons diagnosed ages 50 to 79 years in 18 geographic regions between 2006 and 2015. For a hypothetical cohort of 100,000 persons, we estimated cancer-related deaths under assumptions that cancers diagnosed at stage IV were diagnosed at earlier stages.

Results:

Stage IV cancers represented 18% of all estimated diagnoses but 48% of all estimated cancer-related deaths within 5 years. Assuming all stage IV cancers were diagnosed at stage III, 51 fewer cancer-related deaths would be expected per 100,000, a reduction of 15% of all cancer-related deaths. Assuming one third of metastatic cancers were diagnosed at stage III, one third diagnosed at stage II, and one third diagnosed at stage I, 81 fewer cancer-related deaths would be expected per 100,000, a reduction of 24% of all cancer-related deaths, corresponding to a reduction in all-cause mortality comparable in magnitude to eliminating deaths due to cerebrovascular disease.

Conclusions:

Detection of multiple cancer types earlier than stage IV could reduce at least 15% of cancer-related deaths within 5 years, affecting not only cancer-specific but all-cause mortality.

Impact:

Detecting cancer before stage IV, including modest shifts to stage III, could offer substantial population benefit.




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[PERSPECTIVES] Toward Systems Pathology for PTEN Diagnostics

Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. Studies have shown an increase in the risk of developing specific cancer types in the presence of a germline PTEN mutation. Furthermore, outside of the familial setting, somatic variants of PTEN occur in numerous malignancies. Here we introduce and discuss the prospect of moving toward a systems pathology approach for PTEN diagnostics, incorporating clinical and molecular pathology data with the goal of improving the clinical management of patients with a PTEN mutation. Detection of a germline PTEN mutation can inform cancer surveillance and in the case of somatic mutation, have value in predicting disease course. Given that PTEN functions in the PI3K/AKT/mTOR pathway, identification of a PTEN mutation may highlight new therapeutic opportunities and/or inform therapeutic choices.




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Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma.

MATERIALS AND METHODS:

A clinical trial using the poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor veliparib concurrently with radiation therapy, followed by maintenance therapy with veliparib + temozolomide, in children with diffuse intrinsic pontine glioma was conducted by the Pediatric Brain Tumor Consortium. Standard MR imaging, DWI, dynamic contrast-enhanced perfusion, and DSC perfusion were performed at baseline and approximately every 2 months throughout treatment. ADC histogram metrics of T2-weighted FLAIR and enhancing tumor volume, dynamic contrast-enhanced permeability metrics for enhancing tumors, and tumor relative CBV from DSC perfusion MR imaging were calculated. Baseline values, post-radiation therapy changes, and longitudinal trends for all metrics were evaluated for associations with survival and pseudoprogression.

RESULTS:

Fifty children were evaluable for survival analyses. Higher baseline relative CBV was associated with shorter progression-free survival (P = .02, Q = 0.089) and overall survival (P = .006, Q = 0.055). Associations of higher baseline mean transfer constant from the blood plasma into the extravascular extracellular space with shorter progression-free survival (P = .03, Q = 0.105) and overall survival (P = .03, Q = 0.102) trended toward significance. An increase in relative CBV with time was associated with shorter progression-free survival (P < .001, Q < 0.001) and overall survival (P = .004, Q = 0.043). Associations of longitudinal mean extravascular extracellular volume fraction with progression-free survival (P = .03, Q = 0.104) and overall survival (P = .03, Q = 0.105) and maximum transfer constant from the blood plasma into the extravascular extracellular space with progression-free survival (P = .03, Q = 0.102) trended toward significance. Greater increases with time were associated with worse outcomes. True radiologic progression showed greater post-radiation therapy decreases in mode_ADC_FLAIR compared with pseudoprogression (means, –268.15 versus –26.11, P = .01.)

CONCLUSIONS:

ADC histogram, perfusion, and permeability MR imaging metrics in diffuse intrinsic pontine glioma are useful in predicting survival and pseudoprogression.




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CT Angiography in Evaluating Large-Vessel Occlusion in Acute Anterior Circulation Ischemic Stroke: Factors Associated with Diagnostic Error in Clinical Practice [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

It is currently not completely clear how well radiologists perform in evaluating large-vessel occlusion on CTA in acute ischemic stroke. The purpose of this study was to investigate potential factors associated with diagnostic error.

MATERIALS AND METHODS:

Five hundred twenty consecutive patients with a clinical diagnosis of acute ischemic stroke (49.4% men; mean age, 72 years) who underwent CTA to evaluate large-vessel occlusion of the proximal anterior circulation were included. CTA scans were retrospectively reviewed by a consensus panel of 2 neuroradiologists. Logistic regression analysis was performed to investigate the association between several variables and missed large-vessel occlusion at the initial CTA interpretation.

RESULTS:

The prevalence of large-vessel occlusion was 16% (84/520 patients); 20% (17/84) of large-vessel occlusions were missed at the initial CTA evaluation. In multivariate analysis, non-neuroradiologists were more likely to miss large-vessel occlusion compared with neuroradiologists (OR = 5.62; 95% CI, 1.06–29.85; P = .04), and occlusions of the M2 segment were more likely to be missed compared with occlusions of the distal internal carotid artery and/or M1 segment (OR = 5.69; 95% CI, 1.44–22.57; P = .01). There were no calcified emboli in initially correctly identified large-vessel occlusions. However, calcified emboli were present in 4 of 17 (24%) initially missed or misinterpreted large-vessel occlusions.

CONCLUSIONS:

Several factors may have an association with missing a large-vessel occlusion on CTA, including the CTA interpreter (non-neuroradiologists versus neuroradiologists), large-vessel occlusion location (M2 segment versus the distal internal carotid artery and/or M1 segment), and large-vessel occlusion caused by calcified emboli. Awareness of these factors may improve the accuracy in interpreting CTA and eventually improve stroke outcome.




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Weird magnetic threads in sun's corona seen for the first time

New images reveal threads of ultra-hot gas woven throughout the sun's corona, in the most detailed look at previously unseen parts of the atmosphere of our closest star




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A Champagne Bottle Sized 'My Personal Bottomless Mimosa' Glass

Just in time for Mother's Day/continued at-home quarantine comes this 750mL 'My Personal Bottomless Mimosa' glass from BigMouth, Inc and available on Amazons. The surprisingly all-glass drinkware (but still hand-wash only on account of the decorations) combines the shape of a champagne bottle with a mimosa glass to holds 8 (read: 2-3) servings, and is perfect for letting the rest of your family know you're not to be bothered for the rest of the day because it may still be early here but, dammit, it's 5 o'clock somewhere that's nine and half hours ahead. Thanks to Tracey H, who informed me she can't count the number of times she's been asked to leave a bottomless brunch for really putting its bottomlessness to the test. Heck yeah, that's called doing God's work.




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Magnificent moms

Kevin Durant said it best when he received the NBA’s Most Valuable Player Award for the 2013-14 season. He was the one on the court scoring more than 30 points per ......




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Pence spokeswoman, married to top Trump adviser, diagnosed with coronavirus

U.S. Vice President Mike Pence's press secretary, the wife of one of President Donald Trump's senior advisers, has tested positive for the coronavirus, raising alarm about the virus' potential spread within the White House's inner most circle.




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Prince William says he was &apos;concerned&apos; about Charles after coronavirus diagnosis as he and Kate launch NHS mental health campaign

The heir to the throne, 71, spent seven days self isolating at his Scottish home Birkhall, when he was told he had contracted the disease late last month.




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Captain Tom Moore praises &apos;magnificent&apos; NHS as he opens Nightingale hospital in Yorkshire

Fundraising hero Captain Tom Moore praised the NHS for doing a "magnificent job" as he opened Yorkshire's new Nightingale hospital via video link today.




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&apos;Bubbly&apos; nurse, 55, dies after coronavirus diagnosis

A nurse who came from South Africa to the UK to bring her "passion for care" to the NHS has died after contracting coronavirus.




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Twins, 37, who both worked as nurses die after both being diagnosed with coronavirus

Twin sisters who had both worked as nurses have died after both testing positive for coronavirus.




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Pug becomes first dog to be diagnosed with Covid-19 in US, animal rights group says

A pug has become the first dog to be diagnosed with coronavirus in the US, an animal rights organisation has reported.




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People knocked out of bed as 5.5 magnitude earthquake hits Puerto Rico

A 5.5-magnitude earthquake has hit near southern Puerto Rico, jolting many people from their beds and causing damage across the island.




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Earthquake with preliminary 6.6 magnitude hits Crete

An earthquake with a reported magnitude of 6.6 has taken place south of the Greek island of Crete.




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Antibody tests at 98% accuracy would lead to 27% of immunity diagnoses being incorrect, government advisers warn

Antibody tests at 98 per cent accuracy would put up to a quarter of population at risk of infection, government advisers have warned.




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Uzbekistan's magnificent cities: where Soviet style meets Islamic heritage

From Tashkent to Samarkand and Bukhara, travel writer Caroline Eden believes Uzbekistan offers a dazzling mix of traditional style and a modern outlook

Twenty five years after the fall of the USSR, it’s interesting how the Soviet-era hangover lingers in Uzbekistan. Hulking apartment blocks are gradually being upgraded, and while you won’t spot statues of Lenin (they’ve been replaced by the nomadic conqueror Tamerlane and celebrated medic Ibn-Sina) you will see plenty of samovars (Russian kettles) and Soviet military medals for sale in the markets. But you will also see master ikat weavers reviving weaving traditions, and many musicians and artists are now turning to their Islamic heritage for influence. This mix of Soviet legacy and Uzbek Islam is one of the things that makes the country so fascinating.

Continue reading...




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Scientists explain magnetic pole&#39;s wanderings

The North Magnetic Pole has been racing across the top of the world, from Canada towards Siberia.





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&apos;Tug of war&apos; effect could explain why North Magnetic Pole has moved from Canada towards Siberia, scientists say

Researchers suggest unusual rapid shift is due to competing patches of magnetic field




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Mike Pence spokeswoman, married to top Trump adviser, diagnosed with coronavirus

Pence spokeswoman Katie Miller, who tested positive Friday, had been in recent contact with Pence but not with the president. She is married to Stephen Miller, a top Trump adviser




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We have a new Gerber baby. Magnolia Earl is this year's spokesbaby, winner of a $25,000 cash prize.

Magnolia, from Ross, California, was chosen among 327,000 contestants who submitted their photos, videos and stories through Gerber's contest website.

      




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Blake Lively to Star in Netflix Thriller ‘Dark Days at the Magna Carta’

Blake Lively will star in "Dark Days at the Magna Carta," a post-apocalyptic thriller that's being developed at Netflix as a possible trilogy. Michael Paisley will write the screenplay for "Dark Days at the Magna Carta," set amid a catastrophic event and centering on a woman going to extreme lengths to survive and save her […]




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Peter MacKay suggests Magnitsky Act should be used against China for COVID-19

Conservative leadership hopeful Peter MacKay is calling for use of the Magnitsky Act if specific individuals in China can be identified as having suppressed information related to COVID-19.




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Boris Johnson discharged from hospital as fiancee Carrie Symonds hails &apos;magnificent&apos; NHS and reveals &apos;dark times&apos; during PM&apos;s treatment

Follow our live coronavirus updates HERE Fiancee Carrie Symonds said: "There were times last week that were very dark indeed"




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Robert Webb &apos;predicted&apos; his near-death experience in novel about man with undiagnosed condition

'I thought at the time it was a work of fiction,' author says




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Dynamo says he&apos;s &apos;definitely through the worst&apos; after coronavirus diagnosis

Coronavirus: the symptoms




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How to nab a free &apos;Make My Magnum&apos; kit this Friday

A sweet way to quell any Friday night boredom




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Suffering from a UTI? You can now diagnose it and receive treatment at home using your smartphone

Receive a test and treatment in the same day




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Blake Lively to star in thriller Dark Days at the Magna Carta

Blake Lively is producing with Shawn Levy, her husband Ryan Reynolds's frequent collaborator.




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Jurgen Klopp reveals Liverpool squad shock at Kenny Dalglish coronavirus diagnosis – &apos;One of us has it&apos;

Liverpool manager Jurgen Klopp has revealed the impact that club legend Sir Kenny Dalglish being diagnosed with coronavirus had on him and his players.




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Norman Hunter: Leeds legend remains &apos;severely unwell&apos; in hospital after Covid-19 diagnosis

Leeds United great Norman Hunter remains "severely unwell" in hospital almost a week after being admitted with coronavirus.




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Mikel Arteta coronavirus diagnosis may have saved lives, says epidemiologist

Suspending professional football in England ahead of the government's decision to formally ban mass gatherings due to the coronavirus pandemic may have saved a number of lives, according to experts.




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Paul Pogba to leave Manchester United? Conditions are right for Real Madrid move, says Willy Sagnol

Former France defender Willy Sagnol believes all the conditions are in place for Paul Pogba to leave Manchester United and sign for Real Madrid this summer.




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Former Liverpool defender Dominic Matteo reveals how eyesight concerns led to brain tumour diagnosis

Dominic Matteo has opened up on the frightening moment that he was hit with a shock brain tumour diagnosis after seeking out an eye test.




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Selma Blair reveals she cried with relief at MS diagnosis after being &#39;not taken seriously&#39; by doctors

The 46-year-old actress is now revealing the agony she went through before receiving a diagnosis of multiple sclerosis (MS) last August."Ever since my son was born, I was in an MS flare-up and didn't know, and I was giving it everything to seem normal," Blair told Robin Roberts in an interview that aired Tuesday on "Good Morning America." "And I was self-medicating when he wasn't with me. Blair recalled that she would get so fatigued prior to her diagnosis that she would need to pull over to take a nap after dropping her son, now 7, off at his school one mile away from their home. During her interview with "GMA" at her Los Angeles home, Blair was in an "exacerbation" of MS, or an attack that causes new symptoms or the worsening of existing symptoms.





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Big B reveals the 'Bhoothnath' connect in 'Agneepath'




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Coronation Street tragedy as Leanne and Steve's son diagnosed with grim disease

Coronation Street is set to tackle another hard-hitting storyline as Steve McDonald and Leanne Battersby's son Oliver is diagnosed with mitochondrial disorder




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A devastating diagnosis for Oliver Battersby on Coronation Street

Leanne and Steve are told their son has a life-threatening illness on Corrie




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NIH-funded study links early sleep problems to autism diagnosis among at-risk children

A small study funded by the National Institutes of Health suggests that sleep problems among children who have a sibling with autism spectrum disorder (ASD) may further raise the likelihood of an ASD diagnosis, compared to at-risk children who do not have difficulty sleeping. Previous research has shown that young children who have a sibling with ASD are at a higher risk for also being diagnosed with the condition.




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Official COVID-19 figures underestimate spread by 'order of magnitude'

A senior epidemiologist says official government modelling underestimates the true spread of COVID-19 in Australia.




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Official COVID-19 figures underestimate spread by 'order of magnitude'

A senior epidemiologist says official government modelling underestimates the true spread of COVID-19 in Australia.




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Magnification on Headsets Challenges Visually Impaired

First-generation headsets helped magnify objects for people with impaired vision, but they also prompted motion sickness. A redesign is aimed at fixing this, but problems persist as patients adjust.
Medscape Medical News




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Official COVID-19 figures underestimate spread by 'order of magnitude'

A senior epidemiologist says official government modelling underestimates the true spread of COVID-19 in Australia.




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Peter MacKay suggests Magnitsky Act should be used against China

Conservative leadership hopeful Peter MacKay is calling for use of the Magnitsky Act if specific individuals in China can be identified as having suppressed information related to COVID-19.




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Five years of horrific pain made Monique question her own sanity, until she was finally diagnosed

This swimmer spent years battling endometriosis, an insidious enemy within her own body that consumed her with crippling pain. The fact that most coaches in women's sport are men also didn't help, she says.