Title: Vegan? Weightlifting May Protect Your Bones
Category: Health News
Created: 8/5/2022 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM

Title: CDC Investigating E. coli Outbreak in Ohio, Michigan
Category: Health News
Created: 8/18/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM

Title: Organ From Live Donor Best When Child Needs New Kidney
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/18/2022 12:00:00 AM

Caenorhabditis elegans is an important model organism for human health and disease, with foundational contributions to the understanding of gene expression and tissue patterning in animals. An invaluable tool in modern gene expression research is the presence of a high-resolution ribosome structure, though no such structure exists for C. elegans. Here, we present a high-resolution single-particle cryogenic electron microscopy (cryo-EM) reconstruction and molecular model of a C. elegans ribosome, revealing a significantly streamlined animal ribosome. Many facets of ribosome structure are conserved in C. elegans, including overall ribosomal architecture and the mechanism of cycloheximide, whereas other facets, such as expansion segments and eL28, are rapidly evolving. We identify uL5 and uL23 as two instances of tissue-specific ribosomal protein paralog expression conserved in Caenorhabditis, suggesting that C. elegans ribosomes vary across tissues. The C. elegans ribosome structure will provide a basis for future structural, biochemical, and genetic studies of translation in this important animal system.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are important hepatic transporters. We previously identified OATP1B3 being critically implicated in the disposition of abiraterone. We aimed to further investigate the effects of abiraterone on the activities of OATP1B1 and OATP1B3 utilizing a validated endogenous biomarker coproporphyrin I (CP-I). We used OATP1B-transfected cells to characterize the inhibitory potential of abiraterone against OATP1B-mediated uptake of CP-I. Inhibition constant (K_i) was incorporated into our physiologically based pharmacokinetic (PBPK) modeling to simulate the systemic exposures of CP-I among cancer populations receiving either our model-informed 500 mg or clinically approved 1000 mg abiraterone acetate (AA) dosage. Simulated data were compared with clinical CP-I concentrations determined among our nine metastatic prostate cancer patients receiving 500 mg AA treatment. Abiraterone inhibited OATP1B3-mediated, but not OATP1B1-mediated, uptake of CP-I in vitro, with an estimated K_i of 3.93 μM. Baseline CP-I concentrations were simulated to be 0.81 ± 0.26 ng/ml and determined to be 0.72 ± 0.16 ng/ml among metastatic prostate cancer patients, both of which were higher than those observed for healthy subjects. PBPK simulations revealed an absence of OATP1B3-mediated interaction between abiraterone and CP-I. Our clinical observations confirmed that CP-I concentrations remained comparable to baseline levels up to 12 weeks post 500 mg AA treatment. Using CP-I as an endogenous biomarker, we identified the inhibition of abiraterone on OATP1B3 but not OATP1B1 in vitro, which was predicted and observed to be clinically insignificant. We concluded that the interaction risk between AA and substrates of OATP1Bs is low.

Human organic anion transporting polypeptide (OATP) 1B1 and 1B3 are two highly homologous liver-specific uptake transporters. However, 2’,7’-dichlorofluorescein (DCF) is preferably transported by OATP1B1. In the present study, the molecular mechanisms for the selective transport of DCF by OATP1B1 were investigated by constructing and characterizing an array of OATP1B1/1B3 chimeras and site-directed mutagenesis. Our results show that transmembrane domain (TM) 10 is crucial for the surface expression and function of OATP1B1, in which Q541 and L545 play the most important roles in DCF transport. Replacement of TM10 in OATP1B1 with its OATP1B3 counterpart led to OATP1B1’s complete intracellular retention. Q541 and L545 may interact with DCF directly via hydrogen bonding and hydrophobic interactions. The decrease of DCF uptake by Q541A and L545S was due to their reduced binding affinity for DCF as compared with OATP1B1. In addition, Q541 and L545 are also crucial for the transport of estradiol-17β-glucuronide (E17βG) but not for the transport of estrone-3-sulfate (E3S), indicating different interaction modes between DCF/E17βG and E3S in OATP1B1. Taken together, Q541 and L545 in TM10 are critical for OATP1B1-mediated DCF uptake, but their effect is substrate-dependent.

The organic cation transporter (OCT)-1 mediates hepatic uptake of cationic endogenous compounds and xenobiotics. To date, limited information exists on how Oct1/OCT1 functionally develops with age in rat and human livers and how this would affect the pharmacokinetics of OCT substrates in children or juvenile animals. The functional ontogeny of rOct/hOCT was profiled in suspended rat (2–57 days old) and human hepatocytes (pediatric liver tissue donors: age 2–12 months) by determining uptake clearance of 4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide (ASP+) as a known rOct/hOCT probe substrate. mRNA expression was determined in rat liver tissue corresponding to rat ages used in the functional studies, while hOCT1 mRNA expressions were determined in the same hepatocyte batches as those used for uptake studies. Maturation of rOct/hOCT activity and expression were evaluated by comparing values obtained at the various ages to the adult values. Relative to adult values (at 8 weeks), ASP⁺ uptake clearance in suspended rat hepatocytes aged 0, 1, 2, 3, 4, 5, and 6 weeks reached 26%, 29%, 33%, 37%, 72%, 63%, and 71%, respectively. Hepatic Oct1 mRNA expression was consistent with Oct activity (correlation coefficient of 0.92). In human hepatocytes, OCT1 activity was age dependent and also correlated with mRNA levels (correlation coefficient of 0.88). These data show that Oct1/OCT1 activities and expression mature gradually in rat/human liver, thereby mirroring the expression pattern of organic anion transporting polypeptide in rat. These high-resolution transporter ontogeny profiles will allow for more accurate prediction of the pharmacokinetics of OCT1/Oct1 substrates in pediatric populations and juvenile animals.

Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2.

ABSTRACTTraining health workers is one of the biggest challenges and cost drivers when introducing a new contraceptive method or service delivery innovation. PATH developed a digital training curriculum for family planning providers who are learning to offer subcutaneous DMPA (DMPA-SC), including through self-injection, as an option among a range of contraceptive methods. The DMPA-SC eLearning course for health workers includes 10 lessons with an emphasis on informed choice counseling and training clients to self-inject. In partnership with Ministries of Health in Senegal and Uganda, the course was rolled out in select areas in 2019–2020, including during the COVID-19 pandemic when physical distancing requirements restricted in-person training. We conducted evaluations in both countries to assess the practical application of this digital training approach for contraceptive introduction. The evaluation consisted of a post-training survey, an observational assessment conducted during post-training supportive supervision, and an estimation of training costs.In both countries, a majority (88.6% in Uganda and 64.3% in Senegal) scored above 80% on a DMPA-SC knowledge test following the training. In Senegal, where there was a comparison group of providers trained in person, those providers scored similar on the post-test to eLearners. Providers in both groups and in both countries felt more prepared to administer DMPA-SC or offer self-injection to clients after receiving a supervision visit (93%–98% of eLearners felt very prepared after supervision as compared to 45%–72% prior). The evaluation results suggest that digital approaches offer a number of benefits, can be cost-effective, and are most optimal when blended with in-person training and/or supportive supervision.

BACKGROUND AND PURPOSE:

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection.

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

Chris suffers from "The Curse of the Steam Deck." Kelley can't pickpocket, so she mugs people at night. And Ryan likes practical grave robbers. Curl up in your clothmap quilt and enjoy our cozy '60s demon world.

The post RPG Cast – Episode 681: “Ganon Is Afraid of Homemade Apple Pie” appeared first on RPGamer.

THE Federal Bureau of Investigation is probing a possible computer hacking attack on J.P. Morgan Chase & Co.

Online interactions are based on trust, since there are few definitive ways to certify the identity of the person with whom one is communicating. Naturally, this situation can lead to deception and manipulation, as it has—to tormenting effect—for Tegan and Sara, the popular indie rock duo whose lives have been turned upside down by a mysterious bad faith actor who, for more than a decade, has impersonated Tegan with fans, friends, and business partners.

Fanatical: The Catfishing of Tegan and Sara is an investigation into the myriad means by which the internet can be wielded to nefarious ends. More than that, though, it’s an anatomy of a crime and the complicated wreckage wrought by it, not just for the famous artists but also for the innocent admirers who were tricked into believing that fiction was reality.

Premiering on Hulu on Oct. 18, following its premiere at the Toronto International Film Festival, Erin Lee Carr’s documentary is a chilling snapshot of the unholy marriage of corrosive fandom and online duplicity. At its center are Tegan and Sara, the identical twin songstresses who began making a name for themselves in the early 2000s both for their talent and for being openly gay. This earned them a loyal fanbase of queer women and men who saw themselves reflected in Tegan and Sara, and that bond was strengthened by the siblings’ active interest in interacting with fans in person—Tegan would chat with show attendees in line and at the merch table—and on LiveJournal and other budding message-board platforms that afforded a previously unavailable degree of contact.

Read more at The Daily Beast.

Disaster was averted at a Kentucky hospital when an ostensibly deceased organ donor began “thrashing” around in the operating theater, a preservationist tells NPR.

“He was moving around,” Natasha Miller recalled of the patient, whom NPR identified as Anthony Thomas “TJ” Hoover II. “He was crying visibly.”

The two surgeons assigned to the transplant naturally refused to go through with the procedure, which was reportedly scheduled to take place at Baptist Health Richmond Hospital in October 2021. But when her colleague called Kentucky Organ Donor Affiliates, which coordinated the harvest, Miller said the supervisor told them they “were going to do the case” and needed to “find another doctor.”

Read more at The Daily Beast.

The mystery surrounding Deadlock, Valve’s work-in-progress MOBA shooter, has largely evaporated. Its freely extendable invite system is about as effective at controlling player headcount as a disinterested football steward, meaning pretty much anyone with a clued-in Steam friend can get in and start poking around its secrets. And yet, being a lane-pushing wizard fighter in the Dota 2 vein, it’s already a vast tangle of interplaying abilities, items, strats, and often unspoken rules, of the kind that even experienced gankists will take hundreds of hours to learn. It’s been too much for poor Brendy, at any rate.

Still, Brendy is but one man. What if we had but four men, working in tandem to crush lanes and flatten Patrons just as Gabe intended? To find out if Deadlock is indeed more comprehensible as a team sport, Graham, Ed, Ollie, and James joined forces, promptly getting fucked up yet emerging from the warlock hospital with a deeper understanding of its workings. Or, at least, if anyone would keep playing.

Read more

Astronomer Jo Dunkley is planning to use the Simons Observatory to snare evidence for inflation, the theory that the universe expanded at incredible speed after its birth

One day, doctors might be able to 3D print copies of your organs in order to test a variety of drugs, thanks to a new technique that uses light and sound for rapid printing

Kurt "CyberGuy" Knutsson shares tips and suggestions for how to get the best use out of the updated Calendar app available with the latest iOS update.

The ongoing saga of the BlackCat/AlphV ransomware gang continues, with a news report that the crew has shut down its servers after a controversial hack of an American healthcare services provider. Bleeping Computer says the gang’s data leak blog shut on Friday and the sites it uses to negotiate ransom payments closed today. This comes […]

Rubbing a common yellow food dye onto a mouse's skin turns it temporarily transparent, so we can monitor its insides without harming the animal

Blood tests have shown that about 7 per cent of workers on dairy farms that had H5N1 outbreaks had antibodies against the disease

A collaboration between a space company and a fashion company yields something elegant.

1. Bypolls LIVE: Voting begins for Wayanad LS seat and 31 Assembly seats in 10 States; Priyanka Gandhi makes debut  The Hindu
2. Priyanka Gandhi's Debut, Bypolls In 31 Assembly Seats: All You Need To Know  NDTV
3. Watch: Rahul Gandhi tries Kerala's longest zipline in bid to promote tourism after landslides  The Times of India
4. Let's ensure resounding victory together: Rahul to Wayanad voters  The Hindu
5. Hope people of Wayanad give me chance to represent them, says Priyanka Gandhi  Telegraph India

A prolific figure in Tamil cinema, the versatile actor appeared in over 400 films across Tamil, Telugu, and Malayalam languages

The launch event will see the YouTubers partnering with Ajey Nagar, known as CarryMinati, for a special fan interaction in Mumbai

The veteran actor, who passed away recently, never lost his creative generosity, constantly working in the movies or short films of up and coming directors, for a fraction of his market rate.

Megan Fox has announced pregnancy with Machine Gun Kelly after experiencing a pregnancy loss in 2023

After tackling the best party games on Switch in 2024, the recent release of Emio – The Smiling Man: Famicom …

Continue reading "The Best Switch Visual Novels and Adventure Games in 2024 – From Fata Morgana and VA-11 Hall-A to Famicom Detective Club and Gnosia"

The shootings were part of a wave of violence that erupted as the country plagued by gang violence swore in its new prime minister after a politically tumultuous process.

L’ex-premier ministre de la Colombie-Britannique John Horgan est décédé à l’âge de 65 ans après une bataille contre le cancer.

Former B.C. premier John Horgan has died at the age of 65, CBC News has confirmed. In June this year, Horgan told CBC that he had been diagnosed with cancer for the third time during a routine followup appointment for his previous throat cancer.

Megan Fox et son petit ami Machine Gun Kelly seront bientôt parents.

La ville de Québec pourra compter sur des prestations du groupe La Bottine Souriante et de la DJ belge MATTN pour l’amener en 2025.

The office of the Additional Director General of Foreign Trade (CLA DGFT) has announced an Export Obligation Discharge Certificate (EODC) Camp scheduled from November 11 to 22, 2024. The camp is

As part of the National Pharmacy Week (NPW) celebration, the Kerala Private Pharmacist Association (KPPA) is organizing a high─impact webinar series from November 17th to 23rd, connected by the common

Finding regulatory violations in two private hospitals operating in the twin cities of Hyderabad and Secunderabad, the Telangana drugs control administration (DCA) has issued advisories to all the private hospitals in the state mandating strict obtainment of NDPS licence (NDPS Form II) from the DCA to purchase and sell NDPS drugs.

Dalam dunia perjudian online yang terus berkembang, pencarian para pemain untuk menemukan peluang terbaik dalam meraih kemenangan mengarah pada fenomena populer: kumpulan game slot gacor dengan persentase RTP tertinggi hari…

The post Kumpulan Game Slot Gacor Dengan Persentase RTP Tertinggi Hari Ini appeared first on Biosimilarnews.

The teachings of Mahatma Gandhi were arguably India’s greatest contribution to the 20th century. Raghunath Anant Mashelkar has borrowed some of that wisdom to devise a frugal new form of innovation he calls “Gandhian engineering.” Coming from humble beginnings, Mashelkar is driven to ensure that the benefits of science and technology are shared more equally. He sums up his philosophy with the epigram “more from less for more.” This engineer has led India’s preeminent R&D organization, the Council of Scientific and Industrial Research, and he has advised successive governments.

What was the inspiration for Gandhian engineering?

Raghunath Anant Mashelkar: There are two quotes of Gandhi’s that were influential. The first was, “The world has enough for everyone’s need, but not enough for everyone’s greed.” He was saying that when resources are exhaustible, you should get more from less. He also said the benefits of science must reach all, even the poor. If you put them together, it becomes “more from less for more.”

My own life experience inspired me, too. I was born to a very poor family, and my father died when I was six. My mother was illiterate and brought me to Mumbai in search of a job. Two meals a day was a challenge, and I walked barefoot until I was 12 and studied under streetlights. So it also came from my personal experience of suffering because of a lack of resources.

How does Gandhian engineering differ from existing models of innovation?

Mashelkar: Conventional engineering is market or curiosity driven, but Gandhian engineering is application and impact driven. We look at the end user and what we want to achieve for the betterment of humanity.

Most engineering is about getting more from more. Take an iPhone: They keep creating better models and charging higher prices. For the poor it is less from less: Conventional engineering looks at removing features as the only way to reduce costs.

In Gandhian engineering, the idea is not to create affordable [second-rate] products, but to make high technology work for the poor. So we reinvent the product from the ground up. While the standard approach aims for premium price and high margins, Gandhian engineering will always look at affordable price, but high volumes.

The Jaipur foot is a light, durable, and affordable prosthetic.Gurinder Osan/AP

What is your favorite example of Gandhian engineering?

Mashelkar: My favorite is the Jaipur foot. Normally, a sophisticated prosthetic foot costs a few thousand dollars, but the Jaipur foot does it for [US] $20. And it’s very good technology; there is a video of a person wearing a Jaipur foot climbing a tree, and you can see the flexibility is like a normal foot. Then he runs one kilometer in 4 minutes, 30 seconds.

What is required for Gandhian engineering to become more widespread?

Mashelkar: In our young people, we see innovation and we see passion, but compassion is the key. We also need more soft funding [grants or zero-interest loans], because venture capital companies often turn out to be “vulture capital” in a way, because they want immediate returns.

We need a shift in the mindset of businesses—they can make money not just from premium products for those at the top of the pyramid, but also products with affordable excellence designed for large numbers of people.

This article appears in the November 2024 print issue as “The Gandhi Inspired Inventor.”

Access to care isn’t enough. Healthcare organizations need to build trust in order to reach underserved communities, experts said on a recent panel.

The post How Can Healthcare Organizations Earn Trust with Marginalized Communities? appeared first on MedCity News.

As radiopharmaceuticals enter a new phase, industry leaders must rethink external services and internal capabilities to master the complexities of delivering advanced therapies.

The post Unlocking the Future of Radioligand Therapy: From Discovery to Delivering at Scale appeared first on MedCity News.

The Pew Charitable Trusts today commended Michigan Governor Gretchen Whitmer (D), state Senate Majority Leader Mike Shirkey (R), and Lee Chatfield (R)—whose term as state House Speaker ended last month—for passing and signing a bipartisan package of bills aimed at protecting public safety while reducing the number of people in county jails.

Yesterday’s conference sessions surfaced interesting questions and approaches regarding the post-acute sector, bundled payment, emergency medicine and anesthesia. Post-Acute Focus: With more and more focus on the need to rationalize and re-organize the post-acute sector, we have seen multiple industry leaders start to evolve their strategies.  I blogged yesterday about AccentCare’s interesting strategy in the...… Continue Reading

A large amount of wind, much discussion about the U.S healthcare, and the public getting soaked again – if you were thinking about Washington, DC and the new Congress, you’re 3,000 miles away from the action. This is the week of the annual JP Morgan Healthcare conference in San Francisco, with many thousands of healthcare...… Continue Reading

Addressing the Social Determinants of Health:  Is the healthcare industry pushing a rock up a hill?  We collectively are trying to provide healthcare with improved quality and reduced cost, but the structure of the nation’s healthcare system remains heavily siloed with the social determinants of health often falling wholly or partly outside the mandate and...… Continue Reading

Day 3 of the JPMorgan healthcare conference was one of striking contrasts between the old and the new. (And, by the way, the rain finally stopped for a day, but it will be back tomorrow to finish off the last day of the conference). The Old:  Sitting in the Community Health Systems (CHS) presentation and...… Continue Reading

Some interesting presentations on the last day of the JPMorgan Healthcare Conference that concentrated on common themes – the increasing importance of ancillary business line to bolster core business revenue and of filling in holes to achieve scale and full-service offerings. Genesis Healthcare – The largest U.S. skilled nursing facility (SNF) provider, which also is...… Continue Reading

Megan Fox is pregnant. The 38-year-old actress — who has Noah, 12, Bodhi, ten, and Journey, eight, with her ex-husband Brian Austin Green — has confirmed via social media that she's expecting her first child with Machine Gun Kelly.

Revelation contained in Kissinger-era documents obtained by WikiLeaks