If God is still speaking to His people today—particularly through mental impressions and premonitions—how can believers exercise discernment when it comes to interpreting and applying these divine messages? Put simply, how is following the private, subjective “leading” of the Lord any more reliable than gazing into a crystal ball?

Half of the participants in the Taxing Times survey still find compliance with tax obligations difficult

Princess Diana's former chauffeur raises eyebrows with shocking revelationPrince William and Prince Harry's mother Princess Diana's former chauffeur has finally broken his silence for the first time in 30 years about his service to the royals.In chat with The Mail on Sunday, Steve Davies revealed...

A male fourth-year business administration student of PHINMA Cagayan de Oro College stressed that the delay [of allowances] could affect students’ academic performance, especially those who do not have parents to rely on like him.

The judge overseeing Donald Trump’s criminal hush money case has put off ruling on whether the president-elect’s conviction should be thrown out on immunity grounds, enabling prosecutors to weigh next steps following his November 5 election victory.

Justice Juan Merchan had been due to rule on Tuesday on Trump’s argument that the US Supreme Court’s decision in July that presidents are immune from prosecution involving their official acts meant the New York state case should be dismissed.

Instead, Merchan granted a request by Manhattan District Attorney Alvin Bragg’s office to have until Nov 19 to consider how to approach the case in light of Trump’s looming inauguration in January 2025, email correspondence made public on Tuesday showed.

Trump’s scheduled Nov 26 sentencing is now widely expected to be postponed.

Trump in May became the first US president — former or sitting — convicted of a crime when a jury in Manhattan found him guilty on 34 felony counts of falsifying business records to cover up a potential sex scandal shortly before his first election win in 2016. Trump, who pleaded not guilty, has vowed to appeal the verdict after sentencing.

Prosecutor Matthew Colangelo wrote there were “competing interests” between ensuring a criminal case proceeds as usual and protecting the office of the president.

“The People agree that these are unprecedented circumstances,” Colangelo wrote.

Trump is set to be the first felon inaugurated as president after his victory over Vice President Kamala Harris.

At issue in the six-week Manhattan trial was a $130,000 payment made by Trump’s then-lawyer Michael Cohen to adult film actress Stormy Daniels to keep quiet about a sexual encounter she said she had with him in 2006 but which he has denied.

Trump’s defense lawyer Emil Bove wrote that the case ultimately needed to be dismissed to avoid interfering with Trump’s presidential duties.

“The stay, and dismissal, are necessary to avoid unconstitutional impediments to President Trump’s ability to govern,” Bove wrote.

Trump faced four criminal cases

Trump, 78, is hoping to enter office unencumbered by any of four criminal cases he has faced and which once were thought to have threatened to derail his 2024 candidacy to return to the White House after having served from 2017 to 2021.

The Republican Trump has portrayed the hush money case brought by Bragg, a Democrat, and the three other state and federal criminal indictments brought in 2023 as politically motivated attempts to harm his presidential campaign. He pleaded not guilty in all four cases.

“It is now abundantly clear that Americans want an immediate end to the weaponization of our justice system,” Trump campaign spokesperson Steven Cheung said in a statement on Tuesday.

Special Counsel Jack Smith brought two of the cases against Trump, one involving classified documents he kept after leaving office and the other involving his efforts to overturn his 2020 election loss. A Florida-based federal judge in July dismissed the documents case. The Justice Department is now evaluating how to wind down Smith’s election-related case.

Trump also faces state criminal charges in Georgia over his bid to reverse his 2020 loss in that state, but the case remains in limbo.

The Supreme Court, in a decision arising from one of Smith’s two cases against Trump, decided that presidents are immune from prosecution involving their official acts and that juries cannot be presented evidence of official acts in trials over personal conduct. It marked the first time that the court recognized any degree of presidential immunity from prosecution.

In making the case for immunity, Trump’s lawyers said the jury that convicted Trump in the hush money case was shown evidence by prosecutors of his social media posts as president and heard testimony from his former aides about conversations that occurred in the White House during his 2017-2021 term.

Bragg’s office countered that the Supreme Court’s ruling has no bearing on the case, which they said concerned “wholly unofficial conduct.” The Supreme Court in its ruling found no immunity for a president’s unofficial acts.

to wire a relay for headlights

These photos showcase some of the intricately created birds' nests found in the Natural History Museum in Tring, UK, home to one of the world's largest ornithological collections

We instinctively know that relaxing feels good, but we are now figuring out what it does to the brain and uncovering the best ways to unwind to maximise its benefits

Friends who blow hot and cold put more strain on your physical and mental health than enemies. Here's how to spot them and handle them

A super-stretchy hydrogel can stretch to 15 times its original length and return to its initial shape, and could be used to make soft inflatable robots

ITER, a €20 billion nuclear fusion reactor under construction in France, will now not switch on until 2035 - a delay of 10 years. With smaller commercial fusion efforts on the rise, is it worth continuing with this gargantuan project?

A 15-kilometre-long mass of lava has formed underneath the Reykjanes peninsula in Iceland and could erupt at any time

Iceland is bracing for a volcanic eruption, as thousands of small earthquakes have shaken the southern part of the Reykjanes peninsula since October

Iceland’s Fagradalsfjall volcano, located on the country’s south-west Reykjanes peninsula, has erupted after weeks of earthquake activity

As a 15-kilometre crack formed ahead of the recent eruptions, magma flowed into it at the highest rate observed anywhere in the world

A huge plume of sulphur dioxide from the latest eruption in Iceland is drifting across Europe, but it isn't expected to cause any significant harm

The Renaissance artist Michelangelo had carried out human dissections, which may have led him to include women with breast cancer in some of his pieces

Reaching net-zero emissions is essential for halting climate change - but even after we achieve this goal, parts of the planet will continue to warm. Delaying net zero will worsen these effects

Pictograms and petroglyphs depicting abstract lines and shapes offer a rare glimpse into the culture of people who lived in South America thousands of years ago

Title: How Does Melatonin Make You Feel, and Are There Side Effects?
Category: Health and Living
Created: 7/15/2022 12:00:00 AM
Last Editorial Review: 7/15/2022 12:00:00 AM

Title: Whiplash May Result in Delayed Jaw Pain
Category: Health News
Created: 8/31/2007 12:00:00 AM
Last Editorial Review: 8/31/2007 12:00:00 AM

Title: Computer-Related Eye Strain Not Just for Adults
Category: Health News
Created: 8/31/2007 12:00:00 AM
Last Editorial Review: 8/31/2007 12:00:00 AM

Title: Soothe Back-to-School Anxiety, Teach Kids to Relax
Category: Health News
Created: 8/23/2009 8:10:00 AM
Last Editorial Review: 8/24/2009 12:00:00 AM

Title: In Early Trial, Targeted Therapy Fights Advanced Melanoma
Category: Health News
Created: 8/25/2010 6:10:00 PM
Last Editorial Review: 8/26/2010 12:00:00 AM

Title: New Drug May Treat Advanced Melanoma
Category: Health News
Created: 8/26/2010 11:04:00 AM
Last Editorial Review: 8/26/2010 11:04:24 AM

Title: Survival More Likely With Exercise-Related Cardiac Arrest: Study
Category: Health News
Created: 8/30/2012 6:05:00 PM
Last Editorial Review: 8/31/2012 12:00:00 AM

Title: VA Hospital Delays Didn't Cause Deaths, Investigators Say
Category: Health News
Created: 8/26/2014 12:35:00 PM
Last Editorial Review: 8/27/2014 12:00:00 AM

Title: Could a Laser Skin Test Someday Replace Biopsy to Spot Melanoma?
Category: Health News
Created: 8/21/2015 12:00:00 AM
Last Editorial Review: 8/24/2015 12:00:00 AM

Title: Blood Test May One Day Predict Breast Cancer Relapse
Category: Health News
Created: 8/26/2015 12:00:00 AM
Last Editorial Review: 8/27/2015 12:00:00 AM

Title: Moles Not Most Likely Spot for Melanomas
Category: Health News
Created: 8/29/2017 12:00:00 AM
Last Editorial Review: 8/29/2017 12:00:00 AM

Title: Spotting the Signs of Deadly Melanoma Skin Cancers
Category: Health News
Created: 8/22/2021 12:00:00 AM
Last Editorial Review: 8/23/2021 12:00:00 AM

Title: Unrelated Folks Who Look Alike Share Similar DNA
Category: Health News
Created: 8/23/2022 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM

BACKGROUND:Post–COVID-19 syndrome has affected millions of people, with rehabilitation being at the center of non-pharmacologic care. However, numerous published studies show conflicting results due to, among other factors, considerable variation in subject characteristics. Currently, the effects of age, sex, time of implementation, and prior disease severity on the outcomes of a supervised rehabilitation program after COVID-19 remain unknown.METHODS:This was a non-randomized case-control study. Subjects with post–COVID-19 sequelae were enrolled. Among study participants, those who could attend an 8-week, supervised rehabilitation program composed the intervention group, whereas those who couldn’t the control group. Measurements were collected at baseline and 8 weeks thereafter.RESULTS:Study groups (N = 119) had similar baseline measurements. Participation in rehabilitation (n = 47) was associated with clinically important improvements in the 6-min walk test (6MWT) distance, adjusted (for potential confounders) odds ratio (AOR) 4.56 (95% CI 1.95–10.66); 1-min sit-to-stand test, AOR 4.64 (1.88-11.48); Short Physical Performance Battery, AOR 7.93 (2.82–22.26); health-related quality of life (HRQOL) 5-level EuroQol-5D (Visual Analog Scale), AOR 3.12 (1.37–7.08); Montreal Cognitive Assessment, AOR 6.25 (2.16–18.04); International Physical Activity Questionnaire, AOR 3.63 (1.53–8.59); Fatigue Severity Scale, AOR 4.07 (1.51–10.98); Chalder Fatigue Scale (bimodal score), AOR 3.33 (1.45–7.67); Modified Medical Research Council dyspnea scale (mMRC), AOR 4.43 (1.83–10.74); Post–COVID-19 Functional Scale (PCFS), AOR 3.46 (1.51–7.95); and COPD Assessment Test, AOR 7.40 (2.92–18.75). Time from disease onset was marginally associated only with 6MWT distance, AOR 0.99 (0.99–1.00). Prior hospitalization was associated with clinically important improvements in the mMRC dyspnea scale, AOR 3.50 (1.06–11.51); and PCFS, AOR 3.42 (1.16–10.06). Age, sex, and ICU admission were not associated with the results of any of the aforementioned tests/grading scales.CONCLUSIONS:In this non-randomized, case-control study, post–COVID-19 rehabilitation was associated with improvements in physical function, activity, HRQOL, respiratory symptoms, fatigue, and cognitive impairment. These associations were observed independently of timing of rehabilitation, age, sex, prior hospitalization, and ICU admission.

The brain's capacity to predict and anticipate changes in internal and external environments is fundamental to initiating efficient adaptive responses, behaviors, and reflexes that minimize disruptions to physiology. In the context of feeding control, the brain predicts and anticipates responses to the consumption of dietary substances, thus driving adaptive behaviors in the form of food choices, physiological preparation for meals, and engagement of defensive mechanisms. Here, we provide an integrative perspective on the multisensory computation between exteroceptive and interoceptive cues that guides feeding strategy and may result in food-related disorders.

Binding of arbitrary information into distinct memory representations that can be used to guide behavior is a hallmark of relational memory. What is and is not bound into a memory representation and how those things influence the organization of that representation remain topics of interest. While some information is intentionally and effortfully bound—often the information that is consistent with task goals or expectations about what information may be required later—other information appears to be bound automatically. The present set of experiments sought to investigate whether spatial memory would be systematically influenced by the presence and absence of distinct categories of stimuli on a spatial reconstruction task. In this task, participants must learn multiple item-location bindings and place each item back in its studied location after a short delay. Across three experiments, participants made significantly more within-category errors (i.e., misassigning one item to the location of a different item from the same category) than between-category errors (i.e., misassigning one item to the location of an item from a different category) when categories were perceptually or semantically distinct. These data reveal that category information contributed to the organization of the memory representation and influenced spatial reconstruction performance. Together, these results suggest that categorical information can influence memory organization, and not always to the benefit of overall task performance.

Hepatocyte nuclear factor 4 alpha antisense 1 (HNF4A-AS1) is a long noncoding RNA (lncRNA) gene physically located next to the transcription factor HNF4A gene in the human genome. Its transcription products have been reported to inhibit the progression of hepatocellular carcinoma (HCC) and negatively regulate the expression of cytochrome P450s (CYPs), including CYP1A2, 2B6, 2C9, 2C19, 2E1, and 3A4. By altering CYP expression, lncRNA HNF4A-AS1 also contributes to the susceptibility of drug-induced liver injury. Thus, HNF4A-AS1 lncRNA is a promising target for controlling HCC and modulating drug metabolism. However, HNF4A-AS1 has four annotated alternative transcripts in the human genome browsers, and it is unclear which transcripts the small interfering RNAs or small hairpin RNAs used in the previous studies are silenced and which transcripts should be used as the target. In this study, four annotated and two newly identified transcripts were confirmed. These six transcripts showed different expression levels in different liver disease conditions, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and obesity. The expression patterns of all HNF4A-AS1 transcripts were further investigated in liver cell growth from human embryonic stem cells to matured hepatocyte-like cells, HepaRG differentiation, and exposure to rifampicin treatment. Several HNF4A-AS1 transcripts highly displayed correlations with these situations. In addition, some of the HNF4A-AS1 transcripts also showed a strong correlation with CYP3A4 during HepaRG maturation and rifampicin exposure. Our findings provide valuable insights into the specific roles of HNF4A-AS1 transcripts, paving the way for more targeted therapeutic strategies for liver diseases and drug metabolism.

Early detection of drug-drug interactions (DDIs) can facilitate timely drug development decisions, prevent unnecessary restrictions on patient enrollment, resulting in clinical study populations that are not representative of the indicated study population, and allow for appropriate dose adjustments to ensure safety in clinical trials. All of these factors contribute to a streamlined drug approval process and enhanced patient safety. Here we describe a new approach for early prediction of the magnitude of change in exposure for cytochrome P450 (P450) CYP3A4-related DDIs of small-molecule anticancer drugs based on the model-based extrapolation of human-CYP3A4-transgenic mice pharmacokinetics to humans. Victim drugs brigatinib and lorlatinib were evaluated with the new approach in combination with the perpetrator drugs itraconazole and rifampicin. Predictions of the magnitude of change in exposure deviated at most 0.99- to 1.31-fold from clinical trial results for inhibition with itraconazole, whereas exposure predictions for the induction with rifampicin were less accurate, with deviations of 0.22- to 0.48-fold. Results for the early prediction of DDIs and their clinical impact appear promising for CYP3A4 inhibition, but validation with more victim and perpetrator drugs is essential to evaluate the performance of the new method.

Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited.

⁹-Tetrahydrocannabinol (THC) is a psychoactive phytocannabinoid found in the Cannabis sativa plant. THC is primarily metabolized into 11-hydroxy-⁹-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-⁹-tetrahydrocannabinol (COOH-THC), which may themselves be psychoactive. There is very little research-based evidence concerning the pharmacokinetics and pharmacodynamics of 11-OH-THC as an individual compound. Male C57BL/6 mice were treated with THC or 11-OH-THC via intraperitoneal injection, tail vein intravenous injection, or oral gavage, and whole-blood compound levels were measured to determine pharmacokinetic parameters [C_max, time to C_max (T_max), elimination half-life, area under the curve, apparent volume of distribution, systemic clearance, terminal rate constant, and absolute bioavailability] while also monitoring changes in catalepsy, body temperature, and nociception. 11-OH-THC achieved a T_max at 30 minutes for all routes of administration. The maximum concentration at 30 minutes was not different between intravenous and intraperitoneal routes, but the oral gavage C_max was significantly lower. THC had a 10-minute time to the maximum concentration, which was the first blood collection time point, for intravenous and intraperitoneal and 60 minutes for oral gavage, with a lower C_max for intraperitoneal and oral gavage compared with intravenous. When accounting for circulating compound levels and ED₅₀ responses, these data suggest that 11-OH-THC was 153% as active as THC in the tail-flick test of nociception and 78% as active as THC for catalepsy. Therefore, 11-OH-THC displayed equal or greater activity than the parent compound THC, even when accounting for pharmacokinetic differences. Thus, the THC metabolite 11-OH-THC likely plays a critical role in the bioactivity of cannabis; understanding its activity when administered directly will aid in the interpretation of future animal and human studies.

Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of ⁶⁸Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis–associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUV_max and SUV_mean showed a positive correlation with the immunohistochemical FAP expression score (SUV_max: r = 0.57, P = 0.001; SUV_mean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.

Intrapatient intermetastatic heterogeneity (IIH) has been demonstrated in metastatic castration-resistant prostate cancer (mCRPC) patients and is of the utmost importance for radiopharmaceutical therapy (RPT) eligibility. This study was designed to determine the prevalence of IIH and RPT eligibility in mCRPC patients through a triple-tracer PET imaging strategy. Methods: This was a multisite prospective observational study in which mCRPC patients underwent both ¹⁸F-FDG and ⁶⁸Ga-prostate-specific membrane antigen (PSMA)–617 PET/CT scans. A third scan with ⁶⁸Ga-DOTATATE, a potential biomarker of neuroendocrine differentiation, was performed if an ¹⁸F-FDG–positive/⁶⁸Ga-PSMA–negative lesion was found. Per-tracer lesion positivity was defined as having an uptake at least 50% above that of the liver. IIH prevalence was defined as the percentage of participants having at least 2 lesions with discordant features on multitracer PET. Results: IIH was observed in 81 patients (82.7%), and at least 1 ¹⁸F-FDG–positive/⁶⁸Ga-PSMA–negative lesion was found in 45 patients (45.9%). Of the 37 participants who also underwent ⁶⁸Ga-DOTATATE PET/CT, 6 (16.2%) had at least 1 ⁶⁸Ga-DOTATATE–positive lesion. In total, 12 different combinations of lesion imaging phenotypes were observed. On the basis of our prespecified criteria, 52 (53.1%) participants were determined to be eligible for PSMA RPT, but none for DOTATATE RPT. Patients with IIH had a significantly shorter median overall survival than patients without IIH (9.5 mo vs. not reached; log-rank P = 0.03; hazard ratio, 2.7; 95% CI, 1.1–6.8). Conclusion: Most mCRPC patients showed IIH, which was associated with shorter overall survival. On the basis of a triple-tracer PET approach, multiple phenotypic combinations were found. Correlation of these imaging phenotypes with genomics and treatment response will be relevant for precision medicine.

BACKGROUND AND PURPOSE:

Preoperative assessment of meningioma consistency is beneficial for optimizing surgical strategy and prognosis of patients. We aim to develop a noninvasive prediction model for meningioma consistency utilizing MR elastography and DTI.

BACKGROUND AND PURPOSE:

Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD.

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.

BACKGROUND AND PURPOSE:

Alterations of the basilar artery (BA) anatomy have been suggested as a possible MRA feature of Fabry disease (FD). Nonetheless, no information about their clinical or pathophysiologic correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).