NEW YORK (AP) — New York Gov. Andrew Cuomo, who has won bipartisan praise for rallying supplies for his ravaged hospitals and helping slow the coronavirus, is coming under increasing criticism for not bringing that same level of commitment to a problem that has so far stymied him: nursing homes. In part-lecture, part-cheerleading briefings that have made him a Democratic counter to President Donald Trump, Cuomo has often seemed dismissive and resigned to defeat when asked about his state leading the nation in nursing home deaths. “We’ve tried everything to keep it out of a nursing home, but it’s virtually impossible,” Cuomo told reporters. “Now is not the best time to put your mother in a...

WASHINGTON — Truth can be a casualty when President Donald Trump talks about deaths from the coronavirus in the United States. He’s claimed that the United States is on par with Germany in keeping down COVID-19 deaths, which is not the case in mortality reports. He’s brushed off projections that deaths in his country will double from earlier forecasts, misrepresenting how the numbers were calculated. These distortions emerged over the past week alongside his relentless bragging about the U.S. testing system, which failed in the crucial early weeks and remains globally subpar. Pushing to get the country back to normal, Trump also suggested that children are safe from the coronavirus. ignoring...

New York Gov. Andrew Cuomo, who has won bipartisan praise for rallying supplies for his ravaged hospitals and helping slow the coronavirus, is coming under increasing criticism for not bringing ......

It was widely observed, following a certain event in a Connecticut elementary school on Dec. 14, 2012, that if America would tolerate the slaughter by gunfire of 20 children aged 6 and 7, it would tolerate anything. Nothing proves the truth of that observation more than our response to the coronavirus pandemic. At this moment of maximum peril, we’re tolerating the turning of workers in meatpacking plants and grocery stores, seniors in nursing homes and heedless churchgoers into sacrificial offerings to the gods of “freedom” and “choice.” Grandparents are being counseled to give up their lives “in exchange for keeping the America that all Americans love for your children and grandchildren.”...

The Konya Tropical Butterfly Garden is the only place in Turkey where one can observe every phase of metamorphosis, from small larvae to colorful butterflies.

Anatolia is home to a rich array of natural attractions, including unique geography, climate, location and biodiversity, to explore. Here are nine natural wonders to add to your Turkey must-see bucket list

Turkey's confirmed cases of the coronavirus increased by 2,253 in the past 24 hours, and 64 more people have died, taking the death toll to 3,584, Health Minister Fahrettin Koca said on May 6.

Spain's daily death toll due to Covid-19 today fell to its second lowest since mid-March, as half the country prepares to move to the next phase of its rolling back of lockdown measures.

Follow all the latest developments regarding Covid-19, around the world and at home, as they happen.

The daily death toll from Covid-19 in the United States could have been more than halved if authorities had acted more swiftly in recommending self-isolation and the wearing of face masks, according to a new study.Several US states began issuing stay-at-home orders in late March, while federal health authorities began recommending the use of face masks for all in early April. However, had such measures been implemented just four days earlier, the roughly 2,000 Covid-19 deaths currently being…

Two police officers have been arrested for possessing more than HK$12 million (US$1.9 million) worth of drugs, which the force believes were stolen from the record haul of crystal meth seized last week.One of the two policemen detained, a 41-year-old station sergeant, who is attached to the Kowloon West anti-triad squad, was caught with 2kg of Ice in the Royal Garden Hotel in Tsim Sha Tsui East on Thursday, police said, just days after being part of a team that seized 296kg of the drug in a…

A Hong Kong police officer arrested in connection with the seizure of 25kg of drugs worth HK$12 million is believed to have orchestrated its theft from the scene of a bust he was personally in charge of last week, according to police sources.If true, it would mean the announced record seizure of 296kg of Ice, a form of methamphetamine, actually involved 321kg.Sources said the station sergeant, who was arrested along with a constable in connection with the missing drugs, was in charge of the…

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ISLAMABAD: At least 274,625 people have died of the novel coronavirus since the epidemic surfaced in China late last year, according to international media reports.There have been more than 3,984,488...

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Russell Crowe reveals his Hollywood friend told him 'Gladiator' was going to fail at box office

Truth can be a casualty when President Donald Trump talks about deaths from the coronavirus in the United States.

ISLAMABAD: At least 274,625 people have died of the novel coronavirus since the epidemic surfaced in China late last year, according to international media reports.There have been more than 3,984,488 officially recorded cases spanning 195 countries and territories.The United States is the...

ISLAMABAD: At least 274,625 people have died of the novel coronavirus since the epidemic surfaced in China late last year, according to international media reports.There have been more than 3,984,488 officially recorded cases spanning 195 countries and territories. The United States is the...

Microchip’s Low-Power Radiation-Tolerant (RT) PolarFire FPGA Enables High-Bandwidth Space Systems with Lower Total System Cost

Microchip Announces Industry’s First Space-Qualified COTS-Based Radiation-Tolerant Ethernet Transceiver and Embedded Microcontroller

It certainly wasn’t big, and probably didn’t bang – and the surprises in the conventional story of the universe's origins don’t end there

Megafloods, broken backstops and retreating ice sheets combine in a geological epic: the dramatic story of Britain's protracted original exit from Europe

It certainly wasn’t big, and probably didn’t bang – and the surprises in the conventional story of the universe's origins don’t end there

One of civilisation’s most revolutionary inventions was long thought to be the brainchild of ancient Egyptian scribes. But its true creators may have been far less glamorous

A marble head of the Roman Emperor Octavian Augustus, stolen in Italy in the 1970s, has been returned to Italy by a museum in Belgium. Sharon Reich reports.

Half a million people taking part in the UK Biobank, which gathers genetic information for researchers to study, won't be told if they turn out to be genetically vulnerable to the coronavirus

Title: Hypertension Takes Huge Toll in Developing Countries
Category: Health News
Created: 5/2/2008 2:00:00 AM
Last Editorial Review: 5/2/2008 12:00:00 AM

Title: Bullying May Take Bigger Toll Than Child Abuse, Neglect
Category: Health News
Created: 4/28/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM

Title: 'You've Got Cancer' Can Take Devastating Mental Toll
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM

Title: Just a 'Social Smoker'? Toll on Your Health Still High
Category: Health News
Created: 5/5/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM

Title: Drinking Takes Toll on Bones of People With HIV: Study
Category: Health News
Created: 3/6/2020 12:00:00 AM
Last Editorial Review: 3/9/2020 12:00:00 AM

Title: Xiaflex (collagenase clostridium histolyticum)
Category: Medications
Created: 3/3/2020 12:00:00 AM
Last Editorial Review: 3/3/2020 12:00:00 AM

ABSTRACT

Streptococcus pneumoniae (or pneumococcus) is a highly prevalent human pathogen. Toll-like receptors (TLRs) function as immune sensors that can trigger host defenses against this bacterium. Defects in TLR-activated signaling pathways, including deficiency in the adaptor protein myeloid differentiation factor 88 (MyD88), are associated with markedly increased susceptibility to infection. However, the individual MyD88-dependent TLRs predominantly involved in antipneumococcal defenses have not been identified yet. Here we find that triple knockout mice simultaneously lacking TLR7, TLR9, and TLR13, which sense the presence of bacterial DNA (TLR9) and RNA (TLR7 and TLR13) in the phagolysosomes of phagocytic cells, display a phenotype that largely resembles that of MyD88-deficient mice and rapidly succumb to pneumococcal pneumonitis due to defective neutrophil influx into the lung. Accordingly, TLR7/9/13 triple knockout resident alveolar macrophages were largely unable to respond to pneumococci with the production of neutrophil-attracting chemokines and cytokines. Mice with single deficiencies of TLR7, TLR9, or TLR13 showed unaltered ability to control lung infection but were moderately more susceptible to encephalitis, in association with a decreased ability of microglia to mount cytokine responses in vitro. Our data point to a dominant, tissue-specific role of nucleic acid-sensing pathways in innate immune recognition of S. pneumoniae and also show that endosomal TLRs are largely capable of compensating for the absence of each other, which seems crucial to prevent pneumococci from escaping immune recognition. These results may be useful to develop novel strategies to treat infections by antibiotic-resistant pneumococci based on stimulation of the innate immune system.

IMPORTANCE The pneumococcus is a bacterium that frequently causes infections in the lungs, ears, sinus cavities, and meninges. During these infections, body defenses are triggered by tissue-resident cells that use specialized receptors, such as Toll-like receptors (TLRs), to sense the presence of bacteria. We show here that pneumococci are predominantly detected by TLRs that are located inside intracellular vacuoles, including endosomes, where these receptors can sense the presence of nucleic acids released from ingested bacteria. Mice that simultaneously lacked three of these receptors (specifically, TLR7, TLR9, and TLR13) were extremely susceptible to lung infection and rapidly died after inhalation of pneumococci. Moreover, tissue-resident macrophages from these mice were impaired in their ability to respond to the presence of pneumococci by producing inflammatory mediators capable of recruiting polymorphonuclear leucocytes to infection sites. This information may be useful to develop drugs to treat pneumococcal infections, particularly those caused by antibiotic-resistant strains.

Hydrogen sulfide (H₂S), a plant gasotransmitter, functions in the plant response to cadmium (Cd) stress, implying a role for cysteine desulfhydrase in producing H₂S in this process. Whether d-CYSTEINE DESULFHYDRASE (DCD) acts in the plant Cd response remains to be identified, and if it does, how DCD is regulated in this process is also unknown. Here, we report that DCD-mediated H₂S production enhances plant Cd tolerance in Arabidopsis (Arabidopsis thaliana). When subjected to Cd stress, a dcd mutant accumulated more Cd and reactive oxygen species and showed increased Cd sensitivity, whereas transgenic lines overexpressing DCD had decreased Cd and reactive oxygen species levels and were more tolerant to Cd stress compared with wild-type plants. Furthermore, the expression of DCD was stimulated by Cd stress, and this up-regulation was mediated by a Cd-induced transcription factor, WRKY13, which bound to the DCD promoter. Consistently, the higher Cd sensitivity of the wrky13-3 mutant was rescued by the overexpression of DCD. Together, our results demonstrate that Cd-induced WRKY13 activates DCD expression to increase the production of H₂S, leading to higher Cd tolerance in plants.

Heat stress (HS) has serious effects on plant development, resulting in heavy agricultural losses. A critical transcription factor network is involved in plant adaptation to high temperature. DEHYDRATION RESPONSIVE ELEMENT-BINDING PROTEIN2A (DREB2A) is a key transcription factor that functions in plant thermotolerance. The DREB2A protein is unstable under normal temperature and is degraded by the 26S proteasome; however, the mechanism by which DREB2A protein stability dramatically increases in response to HS remains poorly understood. In this study, we found that the DREB2A protein of Arabidopsis (Arabidopsis thaliana) is stabilized under high temperature by the posttranslational modification SUMOylation. Biochemical data indicated that DREB2A is SUMOylated at K163, a conserved residue adjacent to the negative regulatory domain during HS. SUMOylation of DREB2A suppresses its interaction with BPM2, a ubiquitin ligase component, consequently increasing DREB2A protein stability under high temperature. In addition, analysis of plant heat tolerance and marker gene expression indicated that DREB2A SUMOylation is essential for its function in the HS response. Collectively, our data reveal a role for SUMOylation in the maintenance of DREB2A stability under high temperature, thus improving our understanding of the regulatory mechanisms underlying HS response in plant cells.

Grasses are among the most resilient plants, and some can survive prolonged desiccation in semiarid regions with seasonal rainfall. However, the genetic elements that distinguish grasses that are sensitive versus tolerant to extreme drying are largely unknown. Here, we leveraged comparative genomic approaches with the desiccation-tolerant grass Eragrostis nindensis and...

Isocitrate dehydrogenase (IDH) mutation is a common genetic abnormality in human malignancies characterized by remarkable metabolic reprogramming. Our present study demonstrated that IDH1-mutated cells showed elevated levels of reactive oxygen species and higher demands on Nrf2-guided glutathione de novo synthesis. Our findings showed that triptolide, a diterpenoid epoxide from Tripterygium...

Aerosol–radiation interaction (ARI) plays a significant role in the accumulation of fine particulate matter (PM2.5) by stabilizing the planetary boundary layer and thus deteriorating air quality during haze events. However, modification of photolysis by aerosol scattering or absorbing solar radiation (aerosol–photolysis interaction or API) alters the atmospheric oxidizing capacity, decreases...

Gabriela Montejo-Kovacevich, Simon H. Martin, Joana I. Meier, Caroline N. Bacquet, Monica Monllor, Chris D. Jiggins, and Nicola J. Nadeau

Microclimatic variability in tropical forests plays a key role in shaping species distributions and their ability to cope with environmental change, especially for ectotherms. Nonetheless, currently available climatic datasets lack data from the forest interior and, furthermore, our knowledge of thermal tolerance among tropical ectotherms is limited. We therefore studied natural variation in the microclimate experienced by tropical butterflies in the genus Heliconius across their Andean range in a single year. We found that the forest strongly buffers temperature and humidity in the understorey, especially in the lowlands, where temperatures are more extreme. There were systematic differences between our yearly records and macroclimate databases (WorldClim2), with lower interpolated minimum temperatures and maximum temperatures higher than expected. We then assessed thermal tolerance of 10 Heliconius butterfly species in the wild and found that populations at high elevations had significantly lower heat tolerance than those at lower elevations. However, when we reared populations of the widespread H. erato from high and low elevations in a common-garden environment, the difference in heat tolerance across elevations was reduced, indicating plasticity in this trait. Microclimate buffering is not currently captured in publicly available datasets, but could be crucial for enabling upland shifting of species sensitive to heat such as highland Heliconius. Plasticity in thermal tolerance may alleviate the effects of global warming on some widespread ectotherm species, but more research is needed to understand the long-term consequences of plasticity on populations and species.

Microscopy and rapid diagnostic tests (RDTs) are the main diagnostic tools for malaria but fail to detect low-density parasitemias that are important for maintaining malaria transmission. To complement existing diagnostic methods, an isothermal reverse transcription-recombinase polymerase amplification and lateral flow assay (RT-RPA) was developed. We compared the performance with that of ultrasensitive reverse transcription-quantitative PCR (uRT-qPCR) using nucleic acid extracts from blood samples (n = 114) obtained after standardized controlled human malaria infection (CHMI) with Plasmodium falciparum sporozoites. As a preliminary investigation, we also sampled asymptomatic individuals (n = 28) in an area of malaria endemicity (Lambaréné, Gabon) to validate RT-RPA and assess its performance with unprocessed blood samples (dbRT-RPA). In 114 samples analyzed from CHMI trials, the positive percent agreement to uRT-qPCR was 90% (95% confidence interval [CI], 80 to 96). The negative percent agreement was 100% (95% CI, 92 to 100). The lower limit of detection was 64 parasites/ml. In Gabon, RT-RPA was 100% accurate with asymptomatic volunteers (n = 28), while simplified dbRT-RPA showed 89% accuracy. In a subgroup analysis, RT-RPA detected 9/10 RT-qPCR-positive samples, while loop-mediated isothermal amplification (LAMP) detected 2/10. RT-RPA is a reliable diagnostic test for asymptomatic low-density infections. It is particularly useful in settings where uRT-qPCR is difficult to implement.

¹⁸F-rhPSMA-7 (radiohybrid prostate-specific membrane antigen [PSMA]) is a novel ligand for PET imaging. Here, we present data from a retrospective analysis using PET/CT and PET/MRI examinations to investigate the efficacy of ¹⁸F-rhPSMA-7 PET for primary N-staging of patients with prostate cancer (PC) compared with morphologic imaging (CT or MRI) and validated by histopathology. Methods: Data from 58 patients with high-risk PC (according to the D’Amico criteria) who were staged with ¹⁸F-rhPSMA-7 PET/CT or PET/MRI at our institution between July 2017 and June 2018 were reviewed. The patients had a median prescan prostate-specific antigen value of 12.2 ng/mL (range, 1.2–81.6 ng/mL). The median injected activity of ¹⁸F-rhPSMA-7 was 327 MBq (range, 132–410 MBq), with a median uptake time of 79.5 min (range, 60–153 min). All patients underwent subsequent radical prostatectomy and extended pelvic lymph node dissection. The presence of lymph node metastases was determined by an experienced reader independently for both the PET and the morphologic datasets using a template-based analysis on a 5-point scale. Patient-level and template-based results were both compared with histopathologic findings. Results: Lymph node metastases were present in 18 patients (31.0%) and were located in 52 of 375 templates (13.9%). Receiver-operating-characteristic analyses showed ¹⁸F-rhPSMA-7 PET to perform significantly better than morphologic imaging on both patient-based and template-based analyses (areas under curve, 0.858 vs. 0.649 [P = 0.012] and 0.765 vs. 0.589 [P < 0.001], respectively). On patient-based analyses, the sensitivity, specificity, and accuracy of ¹⁸F-rhPSMA-7 PET were 72.2%, 92.5%, and 86.2%, respectively, and those of morphologic imaging were 50.0%, 72.5%, and 65.5%, respectively. On template-based analyses, the sensitivity, specificity, and accuracy of ¹⁸F-rhPSMA-7 PET were 53.8%, 96.9%, and 90.9%, respectively, and those of morphologic imaging were 9.6%, 95.0%, and 83.2%, respectively. Conclusion: ¹⁸F-rhPSMA-7 PET is superior to morphologic imaging for N-staging of high-risk primary PC. The efficacy of ¹⁸F-rhPSMA-7 is similar to published data for ⁶⁸Ga-PSMA-11.

Background and objectives

Tolvaptan is approved to slow kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. Because in vitro studies indicated that the tolvaptan oxobutyric acid metabolite inhibits organic anion–transporting polypeptide (OATP)1B1 and OATP1B3, United States prescribing information advises avoiding concurrent use with OATP1B1/1B3 substrates, including hepatic hydroxymethyl glutaryl–CoA reductase inhibitors (statins). This post hoc analysis of the pivotal phase 3 tolvaptan trials (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes [TEMPO] 3:4 trial [NCT00428948] and Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD [REPRISE] trial [NCT02160145]) examined the safety of concurrent tolvaptan/statin use.

Caseum, the central necrotic material of tuberculous lesions, is a reservoir of drug-recalcitrant persisting mycobacteria. Caseum is found in closed nodules and in open cavities connecting with an airway. Several commonly accepted characteristics of caseum were established during the preantibiotic era, when autopsies of deceased tuberculosis (TB) patients were common but methodologies were limited. These pioneering studies generated concepts such as acidic pH, low oxygen tension, and paucity of nutrients being the drivers of nonreplication and persistence in caseum. Here we review widely accepted beliefs about the caseum-specific stress factors thought to trigger the shift of Mycobacterium tuberculosis to drug tolerance. Our current state of knowledge reveals that M. tuberculosis is faced with a lipid-rich diet rather than nutrient deprivation in caseum. Variable caseum pH is seen across lesions, possibly transiently acidic in young lesions but overall near neutral in most mature lesions. Oxygen tension is low in the avascular caseum of closed nodules and high at the cavity surface, and a gradient of decreasing oxygen tension likely forms toward the cavity wall. Since caseum is largely made of infected and necrotized macrophages filled with lipid droplets, the microenvironmental conditions encountered by M. tuberculosis in foamy macrophages and in caseum bear many similarities. While there remain a few knowledge gaps, these findings constitute a solid starting point to develop high-throughput drug discovery assays that combine the right balance of oxygen tension, pH, lipid abundance, and lipid species to model the profound drug tolerance of M. tuberculosis in caseum.

Nine hundred Haemophilus influenzae clinical isolates from 83 U.S. and European medical centers were tested for susceptibility by reference broth microdilution methods against ceftolozane-tazobactam and comparators. Results were stratified by β-lactamase production and infection type. Overall, ceftolozane-tazobactam MIC_50/90 values were 0.12/0.25 mg/liter, and 99.0% of isolates were inhibited at the susceptible breakpoint of ≤0.5 mg/liter; the highest MIC value was only 2 mg/liter. Our results support using ceftolozane-tazobactam to treat H. influenzae infections.

BACKGROUND AND PURPOSE:

Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results.