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Category: Health News
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Category: Health and Living
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A prefilled syringe (PFS) should be able to be adequately and consistently extruded during injection for optimal safe drug delivery and accurate dosing. To facilitate appropriate break-loose and gliding forces (BLGFs) required during injection, certain primary packaging materials (PPMs) such as the syringe barrel and plunger are usually coated with silicone oil, which acts as a lubricant. Due to its direct contact with drug, silicone oil can increase the number of particles in the syringe, which could lead to adverse interactions. Compliance with regulatory-defined silicone oil quantities in certain drug products, such as ophthalmics, presents a trade-off with the necessity for desirable low and consistent BLGF. In addition to its siliconization, the dimensional accuracy of the PPM has an important role in controlling the BLGF. The dimensions of the PPM are individualized depending on the product and its design and have certain tolerances that must be met during manufacturing. Most studies on ophthalmics focused on the adverse interactions between silicone oil and the drug. To the authors' knowledge, there have been no public studies so far that have investigated the impact of the dimensional variability of the PPM on the BLGF in ophthalmic PFSs. In this study, we applied advanced optical shaft and tactile measuring technologies to investigate this impact. The syringes investigated were first sampled during aseptic production and tested for the BLGF. Subsequently, defined dimensions of the PPM were measured individually. The results showed that the dimensional variability of the PPM can have a negative impact on the BLGF, despite their conformity to specifications, which indicates that the currently available market quality of PPMs is improvable for critical drug products such as ophthalmics. This study could serve as an approach to define product-specific requirements for primary packaging combinations and thus appropriate specifications based on data during the development stage of drug products.

Oxidative stress, fibrosis, and inflammasome activation from advanced glycation end product (AGE)–receptor of advanced glycation end product (RAGE) interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of β-caryophyllene (BCP) on activating cannabinoid type 2 receptors (CB2Rs) against diabetic complication, mainly cardiomyopathy and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding a high-fat diet with streptozotocin injections. After the development of diabetes, the animals received a 12-week oral BCP treatment at a dose of 50 mg/kg/body weight. BCP treatment showed significant improvement in glucose tolerance and insulin resistance and enhanced serum insulin levels in diabetic animals. BCP treatment effectively reversed the heart remodeling and restored the phosphorylated troponin I and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a expression. Ultrastructural examination showed reduced myocardial cell injury in DCM mice treated with BCP. The preserved myocytes were found to be associated with reduced expression of AGE/RAGE in DCM mice hearts. BCP treatment mitigated oxidative stress by inhibiting expression of NADPH oxidase 4 and activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2–related factor 2 (Nrf2) signaling. Also, BCP suppressed cardiac fibrosis and endothelial-to-mesenchymal transition in DCM mice by inhibiting transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) signaling. Further, BCP treatment suppressed nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation in DCM mice and alleviated cellular injury to the pancreatic tissues evidenced by significant elevation of the number of insulin-positive cells. To demonstrate a CB2R-dependent mechanism of BCP, another group of DCM mice were pretreated with AM630, a CB2R antagonist. AM630 was observed to abrogate the beneficial effects of BCP in DCM mice. Taken together, BCP demonstrated the potential to protect the myocardium and pancreas of DCM mice mediating CB2R-dependent mechanisms.

The diagnosis of maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus caused by a mutation in a single gene, is often uncertain until genetic testing is performed. We report a 13-yr-old Korean boy who was initially diagnosed with type 2 diabetes (T2DM). MODY was suspected because of his nonobese body habitus and family history of multiple affected members. Targeted panel sequencing of all MODY-related genes was performed using the NextSeq 550Dx platform (Illumina). Sanger sequencing was performed using blood samples from the parents, siblings, and other relatives. A frameshift variant in the 3' region of the last exon of PDX1 was detected in the patient and his family members with diabetes. PP1_Moderate criterion was applied and this variant was confirmed to be the genetic cause of diabetes in the family and classified as likely pathogenic. The study highlights the importance of genetic testing for nonobese, early-onset diabetic patients with multiple affected family members. Increased awareness and aggressive genetic testing for MODY are needed.

BackgroundCOVID-19 pandemic restrictions may have influenced behaviours related to weight.AimTo describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic.Design and settingAn observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP.MethodClinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m2/year) were investigated using multivariable logistic regression.ResultsData were extracted on adults with T2D (n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension (n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = −0.1 kg/m2/year [interquartile range {IQR} −0.7–0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60–69 years versus 18–29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m2/year [IQR −0.6–0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D.ConclusionAmong adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions.

BackgroundOrlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM).AimTo explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes.Design and settingCohort study using anonymised health records from a UK database of general practice.MethodThe UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat’s associations with weight loss in those who had not been prescribed second-line antidiabetic medications.ResultsOut of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09).ConclusionOrlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss.

BackgroundMost people with type 2 diabetes receive treatment in primary care by GPs who are not specialised in diabetes. Thus, it is important to uncover the most essential information needs regarding type 2 diabetes in general practice.AimTo identify information needs related to type 2 diabetes for GPs.Design and settingSystematic review focused on literature relating to Western countries.MethodMEDLINE, Embase, PsycInfo and CINAHL were searched from inception to January 2024. Two researchers conducted the selection process, and citation searches were performed to identify any relevant articles missed by the database search. Quality appraisal was conducted with the Mixed Methods Appraisal Tool. Meaning units were coded individually, grouped into categories, and then studies were summarised within the context of these categories using narrative synthesis. An evidence map was created to highlight research gaps.ResultsThirty-nine included studies revealed eight main categories and 36 subcategories of information needs. Categories were organised into a comprehensive hierarchical model of information needs, suggesting ‘Knowledge of guidelines’ and ‘Reasons for referral’ as general information needs alongside more specific needs on ‘Medication’, ‘Management’, ‘Complications’, ‘Diagnosis’, ‘Risk factors’, and ‘Screening for diabetes’. The evidence map provides readers with the opportunity to explore the characteristics of the included studies in detail.ConclusionThis systematic review provides GPs, policymakers, and researchers with a hierarchical model of information and educational needs for GPs, and an evidence map showing gaps in the current literature. Information needs about clinical guidelines and reasons for referral to specialised care overlapped with needs for more specific information.

This week we learn not to disturb Kelley's special demon slaying time, get too attached to dogs in games, or disturb the Harvest Moon plushie announcement. We also get your suggestions for series that need to be resurrected. Enjoy Action RPG August!

The post RPG Cast – Episode 552: “Aw ***t, She’s Playing Diablo!” appeared first on RPGamer.

Josh uses a cat carrier as an impromptu shield. Kelley learns that her husband's Steamdeck RNG is improved if she's not around. Meanwhile, Chris's turtles are always having mating season.

The post RPG Cast – Episode 631: “God of Diablo” appeared first on RPGamer.

While we're getting a Gears Of War prequel in Gears Of War: E-Day, this does mean that Gears Of War 6 is yet to be a thing. In a recent episode of IGN's Podcast Unlocked, former Gears Of War director and current Diablo 4 lead Rod Fergusson revealed what his plans were for Gears 6 when he left. In short, he was going to take the game to space. Righto.

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JUDY WOODRUFF: It’s been almost a month since Hurricane Maria destroyed much of Puerto Rico and killed at least 48 people. The island and its residents are still coming to grips with the scale of the devastation.

William Brangham brings us the latest.

WILLIAM BRANGHAM: Many Puerto Ricans are still in the dark, without electrical power. Hundreds of thousands still have no access to running water, and the rebuilding of the countless damaged homes, roads and facilities is just beginning.

The Associated Press reported yesterday that almost half the sewage treatment plants on the island are still out of service, increasing the risk of contamination and disease.

I’m joined now by David Begnaud. He’s a correspondent from CBS News who’s been doing some very strong reporting there from since when the storm hit, and is just back from his latest trip to the island.

David, welcome to the NewsHour.

I wonder. We saw many of your reports and others of people still three weeks out from the storm who are still drinking from streams and creeks. You heard — I mentioned this AP report about fears of contamination.

Can you just tell us what is going on there? How are people getting water now?

DAVID BEGNAUD, CBS News: Well, let me tell you this.

The governor of Puerto Rico said this morning that he’s aware of those reports and that they’re looking into it. What’s concerning, William, is that three weeks after the storm and at least a week after the allegations first surfaced that people might be trying to drink from toxic wells at what’s known as Superfund sites, the governor of Puerto Rico is still saying, we’re looking into it and telling people to stay out of rivers where sewage may be spilling into the river.

And, he said, we want them to stay away from the coastal areas.

How are people doing? They’re still desperate to get water. No one seems to be able to figure out how to get enough water to every single person on that island who needs it. And as long as people need water, it’s still an emergency phase.

Nearly four weeks later, no one seems to be able to move from the emergency to the recovery.

WILLIAM BRANGHAM: So, people who are — we see them drinking out of these PVC pipes that they have kind of rigged and sort of poked into the side of a creek.

People are just drinking that water straight, without purification, without boiling it; is that right?

DAVID BEGNAUD: Absolutely.

Look, they have got the PVC pipes tapped into the mountains so that it’s coming out of the stream that way. And they literally are — I saw a woman walk up to a potable water tank that the military had brought in, and she had a Clorox bottle.

And I said, “Ma’am, you’re putting drinkable water in a Clorox bottle?”

And she said, “It’s all I have got.”

Now, that was a good scenario. The other scenarios are people right now who are drinking from streams and creeks and rivers who have no water filters, who have nothing, right? They’re just taking this water.

Now, listen, the government got a million water-purifying tablets within the last week. It took almost three weeks to get those. Now there’s a large push to bring in water filters.

I have got to tell you, most of the water filters I’m seeing brought in are coming from the private sector, and civilian samaritans who are getting 1,000 or more from the mainland and flying them over to Puerto Rico and personally hand-delivering them.

WILLIAM BRANGHAM: That’s really incredible.

Medical facilities were another big — just a huge devastation on the island. I know you have been doing a lot of reporting on the USS Comfort.

DAVID BEGNAUD: Yes.

WILLIAM BRANGHAM: This is the huge Naval hospital that is now just offshore Puerto Rico.

But I understand it hasn’t been fully utilized. Can you tell us what your reporting has found there?

DAVID BEGNAUD: The two men running the ship told us that nearly 87 percent of the ship is empty. Sounds alarming, right? They have 200 beds, and 87 percent are empty.

Now, here’s what they said: We stand ready for whatever the government wants to do. We are waiting to be told by the government.

So, I went to the governor, and said exactly what’s happening. And he said: “Look, I’m not satisfied with what the protocol was from the beginning.”

He said, initially, they were prioritizing only the most critically ill patients go to the Comfort. And he said there was a layered process that was complicating things.

So, the governor, Ricardo Rossello, said: “I started to take out some of those layers, and I, said, listen, take people on the ship who may not be critically ill, but need good medical care and can’t get it at the hospital, where the lights are flickering and the A.C. is not running.”

That’s what the governor said.

Within a matter of hours, I got a tweet from a third-year medical student who said: “Let me tell you what a nightmare it has been to reach the Comfort.”

He said: “We have got a pediatric patient who desperately needs to get off this island, either to a hospital on the mainland or to the Comfort.”

And he said: “I went through Google and the local newspaper to find the number. I couldn’t find it.”

Now, here is how things work. Within about 30 minutes of that tweet going out and that medical student’s story being posted, the governor’s spokesperson responded with numbers that should be able to help.

The bottom line here, William, is that asking relentless questions and the good work of journalism is what’s making a difference there. It’s no one person. There’s no heroic work that’s being done by any journalist, other than people who are going back to the same officials and asking some of the same questions, relentlessly seeking the right answer that will make a difference.

WILLIAM BRANGHAM: One of the other pieces of reporting that you did that was very early in the story was this backlog of supplies trapped in container ships on the ports in Puerto Rico.

I understand some of that — some of those supplies are now moving. Can you tell us, are they getting to where they need to be throughout the island?

DAVID BEGNAUD: So, the shipping containers you’re talking about, about 3,000 sitting in the Port of San Juan, have been moved out, not all of them, but a majority of them.

And they were intended for grocery stores around the island. Right? So, those were private companies that had brought in these shipping containers, paid for the supplies, but couldn’t move them because their truck drivers were either at home, because the home had been destroyed, or the road was impassable.

More and more supplies are getting out. But let me tell you, the grocery stores around the island, they have a lot of nonperishables, Pringles, candy, cookies, all on the shelf.

But when you go to the meat section, it’s nearly 75 percent empty at the stores we have been to, the produce section 90 percent empty. And finding bottled water there is almost like playing a game.

WILLIAM BRANGHAM: David Begnaud, CBS News, thank you so much for your reporting. Thanks for your time.

DAVID BEGNAUD: You bet.

The post Puerto Ricans still don’t have reliable drinking water, and fears of contamination are rising appeared first on PBS NewsHour.

Roads with variable speed limits, designed to manage traffic flow, are normally adjusted according to simple rules, but a 27-kilometre section of the I-24 freeway near Nashville, Tennessee, is now overseen by an artificial intelligence

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