ABSTRACTToxicological emergencies present a significant health challenge in Nepal. Despite the high burden, the country has inadequate formal toxicology training, medical toxicology expertise, and adequate poison control infrastructure. In recognition of this need, the Nepal Poison Information Center (PIC) was established as a collaborative effort involving local and international partners. Through a comprehensive partnership framework, the Nepal PIC provides 24 hours a day, 7 days a week expert guidance to health care workers, conducts educational webinars, and engages in research. Initial data from the pilot phase indicate successful consultation delivery. Challenges include bureaucratic hurdles and the need for sustainable funding. Despite these challenges, the Nepal PIC demonstrates early feasibility and potential for expansion into a comprehensive toxicology center, contributing to the advancement of clinical toxicology in Nepal. Long-term sustainability relies on governmental support and continued advocacy efforts.

ABSTRACTIntroduction:Emergency contraceptive pills (ECPs) are effective and can be used safely at any age repeatedly within the same cycle. They are often favored by youth yet are underutilized. Private facilities can increase ECP access but present barriers including cost. Identifying effective public-sector ECP distribution models can help ensure equitable access. The Malawi Ministry of Health developed a strategy to improve ECP access in 2020. We documented ECP provision through select public, youth-serving channels recommended by the strategy: general and youth-specific outreach, paid and unpaid community health workers (CHWs), and youth clubs.Methods:We conducted this mixed methods study from November 2022–March 2023 in 2 rural districts (Mchinji and Phalombe) implementing the strategy. We conducted qualitative interviews with 10 national stakeholders, 46 providers, and 24 clients aged 15–24 years about ECP service delivery. Additionally, 25 providers collected quantitative tally data about clients seeking ECPs. We analyzed qualitative data using grounded theory and quantitative data descriptively.Results:Stakeholders and providers reported ECP uptake increased in geographies where the strategy was implemented, especially among youth. Providers documented 3,988 client visits for ECPs over 3 months. Of these visits, 26% were from male clients, 36% were from clients aged younger than 20 years, and 64% received ECPs for the first time. Across channels, youth club leaders and unpaid CHWs reported the most client visits per provider and served the youngest clients. However, no ECPs were dispensed during 29% of visits due to stock-outs. While many providers were supportive of youth accessing ECPs, most held unfavorable attitudes toward repeat use.Conclusion:ECP access should be expanded through provision in the studied channels, especially youth clubs and CHWs. However, to meet demand, the supply chain must be strengthened. We recommend addressing providers’ attitudes about repeat use to ensure informed method choice.

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.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy treatment, routinely manifesting as increased pain sensitivity (allodynia) in distal extremities. Despite its prevalence, effective treatment options are limited. Cannabinoids are increasingly being evaluated for their ability to treat chronic pain conditions, including CIPN. While previous studies have revealed sex differences in cannabinoid-mediated antinociception in acute and chronic pain models, there is a paucity of studies addressing potential sex differences in the response of CIPN to cannabinoid treatment. Therefore, we evaluated the long-term antiallodynic efficacy of cannabinoid receptor type 1 (CB₁)-selective, cannabinoid receptor type 2 (CB₂)-selective, and CB₁/CB₂ mixed agonists in the cisplatin CIPN model, using both male and female mice. CB₁ selective agonism was observed to have sex differences in the development of tolerance to antiallodynic effects, with females developing tolerance more rapidly than males, while the antiallodynic effects of selective CB₂ agonism lacked tolerance development. Compound-specific changes to the female estrous cycle and female plasma estradiol levels were noted, with CB₁ selective agonism decreasing plasma estradiol while CB₂ selective agonism increased plasma estradiol. Chronic administration of a mixed CB₁/CB₂ agonist resulted in increased mRNA expression of proinflammatory cytokines and endocannabinoid regulatory enzymes in female spinal cord tissue. Ovarian tissue was noted to have proinflammatory cytokine mRNA expression following administration of a CB₂ acting compound while selective CB₁ agonism resulted in decreased proinflammatory cytokines and endocannabinoid regulatory enzymes in testes. These results support the need for further investigation into the role of sex and sex hormones signaling in pain and cannabinoid-mediated antinociceptive effects.

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.

Patients with arthritis report using cannabis for pain management, and the major cannabinoid delta-9-tetrahydrocannabinol (⁹-THC) has anti-inflammatory properties, yet the effects of minor cannabinoids on arthritis are largely unknown. The goal of the present study was to determine the antiarthritic potential of the minor cannabinoid delta-8-tetrahydrocannabinol (⁸-THC) using the collagen-induced arthritis (CIA) mouse model. Adult male DBA/1J mice were immunized and boosted 21 days later with an emulsion of collagen and complete Freund’s adjuvant. Beginning on the day of the booster, mice were administered twice-daily injections of ⁸-THC (3 or 30 mg/kg), the steroid dexamethasone (2 mg/kg), or vehicle for two weeks. Dorsal-ventral paw thickness and qualitative measures of arthritis were recorded daily, and latency to fall from an inverted grid was measured on alternating days, to determine arthritis severity and functional impairment. On the final day of testing, spontaneous wire-climbing behavior and temperature preference in a thermal gradient ring were measured to assess CIA-depressed behavior. The ⁸-THC treatment (30 mg/kg) reduced paw swelling and qualitative signs of arthritis. ⁸-THC also blocked CIA-depressed climbing and CIA-induced preference for a heated floor without producing locomotor effects but did not affect latency to fall from a wire grid. In alignment with the morphologic and behavioral assessments in vivo, histology revealed that ⁸-THC reduced synovial inflammation, proteoglycan loss and cartilage and bone erosion in the foot joints in a dose-dependent manner. Together, these findings suggest that ⁸-THC not only blocked morphologic changes but also prevented functional loss caused by collagen-induced arthritis.

Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between laboratories or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), 8-tetrahydrocannabinol (8-THC), and 9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high-dose 8-THC evoked some tetrad behaviors in both sexes, while THCV and low-dose 8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential.

There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa. The two most abundant cannabinoids (⁹-tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). Although the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials. In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. We will also discuss the therapeutic areas that have been examined for this cannabinoid, notably antinociceptive, antibacterial, and anti-seizure activities. Finally, we will discuss areas where new research is needed and potential novel medicinal applications for CBC.

Our knowledge of the roles of individual cytochrome P450 (P450) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for "phenotyping" metabolism reactions with new drug candidates. Endogenous biomarkers are being used for noninvasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining "orphan" P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating interspecies differences in drug metabolism, particularly in the context of "metabolism in safety testing" regulatory issues ["disproportionate (human) metabolites"].

BACKGROUND AND PURPOSE:

Mechanical thrombectomy is a fundamental intervention for acute ischemic stroke treatment. While conventional techniques are effective, cyclic aspiration (CyA) shows potential for better recanalization rates. We aim to investigate factors affecting CyA and compare them with static aspiration (StA).

BACKGROUND AND PURPOSE:

Reocclusion after treatment is a concern in endovascular therapy for isolated intracranial atherothrombotic stroke-related large-vessel occlusion (AT-LVO). However, the optimal endovascular therapy technique for AT-LVO has not yet been investigated. This study evaluated the optimal endovascular therapy technique for AT-LVO in a real-world setting.

The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.

Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the HPGD gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in HPGD was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for HPGD, all provide sufficient evidence to reclassify the HPGD c.38C > A, p.Ala13Glu variant as likely pathogenic.

T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.

PURPOSE

The impact of digital health on medically underserved patients is unclear. This study aimed to determine the early impact of a digital innovation to grow quality care through an interprofessional care team (DIG IT) on the blood pressure (BP) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of medically underserved patients.

Chronic pulmonary aspergillosis has a range of manifestations from indolent nodules to semi-invasive infection. Patients may be asymptomatic or have chronic symptoms such as cough and weight loss or present with life-threatening haemoptysis. The physician can choose from a range of available therapies including medical therapy with antifungals, minimally invasive therapy with intracavitary antifungal therapy and surgery involving open thoracotomy or video-assisted thoracoscopic surgery. The patients with the most severe forms of pulmonary infection may not be surgical candidates due to their underlying pulmonary condition. The management of haemoptysis can include tranexamic acid, bronchial artery embolisation, antifungals or surgery. There are few controlled studies to inform clinicians managing complex cases, so a multidisciplinary approach may be helpful.

RADIO shock jock fan Alan Jones unleashed on both sides of politics on Q&A last night — and came out in defence of Brexit.

3D Scotland are an innovative, Glasgow-based company who specialise in the design and manufacture of unique chess sets. Their sets have proved extremely popular as Christmas gifts, graduation gifts, fathers’ day gifts and everything in between.

The plane is hailed as 'one of the most advanced aircraft available on the market'

It’s an extra large podcast this week. Alex, Kelley, Nathan, Chris, and Anna Marie break down all they’ve been playing. A huge news week is covered with colourful commentary. And we go off on more than one tangent. Help us, we’re incorrigible.

The post RPG Cast – Episode 556: “Chris Is Right for Once!” appeared first on RPGamer.

Kelley watches DVDs like a caveman. Josh chews on all the expensive things. Meanwhile, Chris stands by some barrels.

The post RPG Cast – Episode 609: “Throwing Corpses at the Door Till You Let Me In” appeared first on RPGamer.

Matt makes twenty slices of toast. Josh is still fighting sewer rat six. Kelley's dog is NOT a baby. And Chris saves E3 with the power of...no...he can't do it. No GEX allowed.

The post RPG Cast – Episode 684: “Remember What I Said at the Fazoli’s Drive Thru?” appeared first on RPGamer.

Robert finds out what Godzilla sushi tastes like. Josh pimps his Segway. Phil has a pictomancer at home. The awards all Chris's fault, because he didn't vote. Also, PoE is to Chris, as CoH is to Phil.

The post RPG Cast – Episode 710: “Xenoblade Chronicles X Doesn’t Love You Back” appeared first on RPGamer.

Here we see data representing the sales through to consumers and change in sales performance of the three current platforms (PlayStation 5, Xbox Series X|S, and Nintendo Switch) and two legacy platforms (PlayStation 4 and Xbox One) over comparable periods for 2021, 2022, 2023, and 2024. Also shown is the market share for each of the consoles over the same periods.

Year to Date Sales Comparison (Same Periods Covered)

Market Share (Same Periods Covered)

2021 – (January 2021 to October 2021)

2022 – (January 2022 to October 2022)

2023 – (January 2023 to October 2023)

2024 – (January 2024 to October 2024)

"Year to date" sales for 2021, 2022, 2023, and 2024 sales are shown in series at the top of the table and then just below a comparison of 2024 versus 2023 and 2024 versus 2022 is displayed.  This provides an easy-to-view summary of all the data.

Total Sales and Market Share for Each Year

Microsoft

• Xbox Series X|S
• 0.09 million units sold year-to-date
• Down year-on-year 0.03 million units (-23.2%)

Nintendo

• Nintendo Switch
• 2.47 million units sold year-to-date
• Down year-on-year 0.75 million units (-23.4%)

Sony

• PlayStation 5
• 1.16 million units sold year-to-date
• Down year-on-year 0.94 million units (-44.9%)
• PlayStation 4
• 0.01 million units sold year-to-date
• Down year-on-year 0.05 million (-77.2%)

Note: VGChartz 2024 estimates through October includes 44 weeks, while 2023, 2022, and 2021 estimates includes 43 weeks.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463009/ps5-vs-xbox-series-xs-vs-switch-2024-japan-sales-comparison-charts-through-october/

MSNBC’s Chris Hayes called out Fox News for not showing the full context of Donald Trump’s “enemy within” comments during Vice President Kamala Harris’ interview on the network earlier Wednesday.

The anchor of All In opened his broadcast by calling attention to something that Harris herself did in the sit-down with Fox’s Bret Baier. The clip that the right-wing network showed to Harris as part of Baier’s question was of Trump during his all-female town hall event in Georgia—the one where Trump bizarrely argued he was the “father of IVF.”

In the clip that Fox aired directly to Harris during her interview, Trump wasn’t heard talking about how former House Speaker Nancy Pelosi or Rep. Adam Schiff are the “enemy within.” Instead, Fox made it so Harris had to react to him talking more mildly about “phony investigations.” The network omitted Trump’s line about “the enemy within.”

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.

Enshrouded has received what developers Keen Games are calling the survival game's "most sizable" update yet, sizable being an appropriate word for mountains. Expect a new playable area, the Alabaneve Summits, with its own enemies, resources, non-threatening wildlife and quests. The maximum character level has risen to 35! There are new townsfolk to find and place in your poorly built houses! You can tame animals, and make them live in poorly built houses too! You can get hypothermia!

Read more

October marked the "biggest" sales month for supermarkets in the UK so far despite food price hikes.

To transport our planet across the universe, we would need to bring the whole solar system to sustain life on Earth – on this episode of Dead Planets Society, our hosts contemplate how to shepherd all that baggage on this scenic journey

The books, TV, games and more that New Scientist staff have enjoyed this week

In between two spacecraft visiting Jupiter’s moon Io, a volcano spreading material over hundreds of kilometres has appeared

Exoplanets in binary star systems usually orbit both stars, but astronomers have now spotted three planets orbiting one or the other star in a pair

The first 18 satellites of a planned Chinese mega constellation are brighter than all but 500 stars in the sky, raising fears of a huge impact on astronomy

The ion tail of C/2023 A3 (Tsuchinshan-ATLAS) could appear as a blue streak across the northern hemisphere sky during October, in a rare event thought to happen only every few decades

AI companies hope that feeding ever more data to their models will continue to boost performance, eventually leading to human-level intelligence. Behind this hope is the "transformer", a key breakthrough in AI, but what happens if it fails to deliver?

Computer code dating back to the 1960s is still vital to banks, airlines and governments, but programmers familiar with the language are in short supply. Now AI models are being trained to fill the skills gap

Google has built a quantum computer that makes fewer errors as it is scaled up, and this may pave the way for machines that could solve useful real-world problems for the first time

Thanks to artificial intelligence, understanding animals may be closer than we think. But we may not like what they are going to tell us, says RSPCA chief executive Chris Sherwood

After seven years of voicing Elena Ferrante’s ambitious heroine, the Italian actress brings Lenù Greco home.

In Canada, your IP address has the right to remain silent. Elon Musk is suing OpenAI for not being Open. Apple faces a class action not allowing competitive access to backup services and the World Server Throwing Competition in March 2024 is accused of being too violent towards servers.   All this and more on the […]

The Orionids meteor shower peaks on Monday, but will continue to light up the sky through Nov. 22, as debris from Halley's Comet enters Earth's atmosphere.

Three people have been taken to hospital after a car mounted the pavement and smashed into a restaurant in Piccadilly Circus, the Metropolitan Police have said.

Its latest roadmap suggests that if you want white fans, you should wait for an announcement in Q1 2022.

Archaeologists say they have discovered the oldest known evidence for intensive ochre mining worldwide, at least 48,000 years ago, in Lion Cavern at Ngwenya in Eswatini, a landlocked country in southern Africa.

The post Lion Cavern in Eswatini is World’s Oldest Ochre Mine, Archaeologists Say appeared first on Sci.News: Breaking Science News.

Stem cells made in the lab may one day aid cancer treatment by reducing our reliance on donors

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