Deception and Fraud in the Justification of "Pediatric Drug Development": A Challenge at the Interface of Medicine and Law.

United States and European Union laws demand separate clinical studies in children as a condition for drugs' marketing approval. Justified by carefully framed pseudo-scientific wordings, more so the European Medicines Agency than the United States Food and Drug Administration, "Pediatric Drug Development" is probably the largest abuse in medical research in history. Preterm newborns are immature and vulnerable, but they grow.

Medical Termination of Pregnancy: Law and Controversies in the United States and Australia.

This editorial reviews the changes over two decades in the United States and Australia in relation to the law governing access to drugs enabling medical termination of pregnancy. It also scrutinises three contentious decisions by the United States Supreme Court between 2022 and 2024 in relation to abortion. It argues that the receptive environment in the United States Supreme Court, as it is currently constituted, to challenges to the lawfulness of terminations of pregnancy and abortion medications is likely to inspire comparable challenges as part of the "Abortion Wars" in other countries, including Australia.

Objective study validity diagnostics: a framework requiring pre-specified, empirical verification to increase trust in the reliability of real-world evidence.

Objective: Propose a framework to empirically evaluate and report validity of findings from observational studies using pre-specified objective diagnostics, increasing trust in real-world evidence (RWE).

Materials And Methods: The framework employs objective diagnostic measures to assess the appropriateness of study designs, analytic assumptions, and threats to validity in generating reliable evidence addressing causal questions. Diagnostic evaluations should be interpreted before the unblinding of study results or, alternatively, only unblind results from analyses that pass pre-specified thresholds.

Imagining Coat-Hangers and Pills: A Qualitative Exploration of Abortion Beliefs and Attitudes in Hostile Policy Contexts in the United States.

Objective: We explored awareness of and attitudes about the safety of various methods people use to attempt to end a pregnancy without medical assistance, which we refer to in this study collectively as self-managed abortion (SMA).

Methods: In 2020, we invited individuals living in eight United States (US) states considered "hostile" to abortion rights or with a history of criminalizing abortions performed outside the formal healthcare system to participate in semi-structured telephone interviews regarding their attitudes toward these practices. We analyzed coded transcripts for content and themes.

Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer's disease ligands.

TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer's disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry.

Effect of daily alcohol intake on sex hormone levels among postmenopausal breast cancer survivors on aromatase inhibitor therapy: a randomized controlled crossover pilot study.

Background: Alcohol intake is associated with a higher risk of estrogen receptor-positive (ER+) breast cancer (BC), presumably through its confirmed ability to increase sex hormone levels. Whether consuming alcohol within the recommended limit of one serving per day increases sex hormone levels among postmenopausal women taking aromatase inhibitors (AI) to inhibit estrogen production remains unknown. Therefore, we compared sex hormone levels following white wine to levels following white grape juice among ER + BC survivors taking AIs.

SMAC-armed oncolytic virotherapy enhances the anticancer activity of PD1 blockade by modulating PANoptosis.

Background: Oncolytic viruses (OVs) are increasingly recognized as promising tools for cancer therapy, as they selectively infect and destroy tumor cells while leaving healthy cells unharmed. Despite considerable progress, the limited therapeutic efficacy of OV-based virotherapy continues to be a significant challenge in cancer treatment.

Methods: The SMAC/DIABLO gene was inserted into the genome of vesicular stomatitis virus (VSV) to generate VSV-S.

Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer's disease.

Background: Blood-brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.

Methods: We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who had come to autopsy from the University of Kentucky AD Research Center (UK-ADRC) community-based cohort; all cases with dementia had confirmed severe ADNC.

Understanding barriers and facilitators to implementation of a patient safety bundle for pregnancy-related severe hypertension in 3 North Carolina outpatient clinics: a qualitative study.

Background: Pregnancy related hypertension is a leading cause of preventable maternal morbidity and mortality in the US, with consistently higher rates affecting racial minorities. Many complications are preventable with timely treatment, in alignment with the Alliance for Innovation on Maternal Health's Patient Safety Bundle ("Bundle"). The Bundle has been implemented successfully in inpatient settings, but 30% of preeclampsia-related morbidity occurs in outpatient settings in North Carolina.

Predicting loss of independence among geriatric patients following gastrointestinal surgery.

Background: While existing risk calculators focus on mortality and complications, elderly patients are concerned with how operations will affect their quality of life, especially their independence. We sought to develop a novel clinically relevant and easy-to-use score to predict elderly patients' loss of independence after gastrointestinal surgery.

Methods: This retrospective cohort study included patients age ≥ 65 years enrolled in the American College of Surgeons National Surgical Quality Improvement Program database and Geriatric Pilot Project who underwent pancreatic, colorectal, or hepatic surgery (January 1, 2014- December 31, 2018).

Changes to muscle and fascia tissue after eighteen days of ankle immobilization post-ankle sprain injury: an MRI case study.

Background: Ankle sprains often result in muscle atrophy and reduced range of motion, which can cause long-term ankle instabilities. Understanding the changes to muscle-such as atrophy-and concomitant changes to deep fascia-which may thicken alongside muscle loss-after ankle sprain injury is important to understanding structural changes about the joint and how they might contribute to longer-term impairments. Here, we employ advanced MRI to investigate skeletal muscle and fascial structural changes during the recovery period of one patient undergoing immobilization after ankle sprains.

Cancer-related health behaviors during the COVID 19 pandemic in geographically diverse samples across the US.

Background: The COVID-19 pandemic involved business closures (e.g., gyms), social distancing policies, and prolonged stressful situations that may have impacted engagement in health behaviors.

Changes in muscle performance among older adults with myeloid malignancies engaging in a mobile health (mHealth) exercise intervention: a single arm pilot study.

Background: Older adults with cancer are vulnerable to declines in muscle performance (e.g., strength, speed, duration of muscular contraction), which are associated with worse cancer-related outcomes.

Simulated retail food environments: A literature review of systems science approaches to advance equity in access to healthy diets.

As researchers increasingly utilize systems science simulation modeling (SSSM), little is known about how and by whom SSSMs are being leveraged to address inequities in access to healthy diets. We evaluated the extent to which studies (n = 66) employing SSSM to examine retail food environments (RFEs): included three pillars of equity (social position, human capital, socioeconomic and political context) that shape RFEs and access to healthy diets; grounded model design and development in theory; engaged with diverse stakeholders and lived experiences related to RFEs; and translated model findings towards addressing inequities in RFEs. Most studies (n = 58) included some model characteristics related to social position (e.

Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling.

In mice engineered to express enhanced green fluorescent protein (eGFP) under the control of the entire glutamate transporter 1 (GLT1) gene, eGFP is found in all 'adult' cortical astrocytes. However, when 8.3 kilobases of the human GLT1/EAAT2 promoter is used to control expression of tdTomato (tdT), tdT is only found in a subpopulation of these eGFP-expressing astrocytes.

Differences in anxiety, depression and pain experience among adults with chronic low back pain as a function of nicotine product use.

The landscape of nicotine use in the United States (US) has continued to evolve, with electronic cigarette use (hereafter e-cigarette) becoming more evident in recent years. Patterns of dual nicotine use, or using combustible nicotine in conjunction with e-cigarettes, may increase dependence on nicotine, continued exposure to toxins, and corresponding health risks. One of the most prevalent health problems related to nicotine use is the experience of chronic pain.

Minority stress in relation to biological outcomes among sexual and gender minority people: a systematic review and update.

Here we present an updated systematic review identifying studies published 2019-2024, since our prior systematic review in 2020, that examine the association between minority stress and a biological outcome among sexual and gender minority (SGM) people. Pubmed, Web of Science, and Embase were queried to identify studies that examined an association between minority stress (including prejudice events and conditions, anticipation of rejection and discrimination, concealment or disclosure of SGM identity(ies), internalized stigma, or structural stigma) and a biological health outcome among SGM people. Included studies were coded for methodological approaches, study population, minority stress measure, biological outcomes, count of overall analyses, and count of analyses where an association was detected.

Impact of COVID-19 Public Health Measures on Antiretroviral Therapy Use Among Ugandans Living with HIV in Sero-Different Couples.

Antiretroviral therapy (ART) use and HIV suppression among people living with HIV (PLHIV) are critical for HIV control and prevention. Extreme restrictions on movement early during the COVID-19 pandemic in Uganda may have impeded the ability to initiate and sustain access to and use of ART. From our stepped-wedge cluster-randomized trial of an integrated PrEP and ART intervention for HIV-serodifferent couples at 12 ART clinics in Uganda, we identified participants who enrolled and had a 6-month post-ART initiation viral load measured before the beginning of the first COVID-19 lockdown (Period 1), participants whose enrollment and 6-month viral load measurement straddled pre-COVID and COVID lockdown times (Period 2), and participants whose enrollment and 6-month viral load were quantified entirely during COVID-19 (Period 3).

Commutability assessment of new standard reference materials (SRMs) for determining serum total 25-hydroxyvitamin D using ligand binding and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays.

Commutability is where the measurement response for a reference material (RM) is the same as for an individual patient sample with the same concentration of analyte measured using two or more measurement systems. Assessment of commutability is essential when the RM is used in a calibration hierarchy or to ensure that clinical measurements are comparable across different measurement procedures and at different times. The commutability of three new Standard Reference Materials (SRMs) for determining serum total 25-hydroxyvitamin D [25(OH)D], defined as the sum of 25-hydroxyvitamin D [25(OH)D] and 25-hydroxyvitamin D [25(OH)D], was assessed through an interlaboratory study.

IRE1α-XBP1 safeguards hematopoietic stem and progenitor cells by restricting pro-leukemogenic gene programs.

Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.

Tibial Skeletal Adaptations in Male and Female Marine Corps Officer Candidates Undergoing 10 Weeks of Military Training.

Military training improves tibial density, structure, and estimated strength; however, men and women may adapt differently. Most work performed in military populations has assessed changes in bone health during initial entry programs, a timeframe at the beginning of a service member's career when bones may be more adaptable to a novel mechanical stimulus. The purpose of this investigation was to examine changes in tibial volumetric bone mineral density (vBMD), structure, and estimated strength, and biomarkers of bone metabolism (P1NP, osteocalcin, TRAP5b, sclerostin) between male and female candidates measured at the start and end of United States Marine Corps Officer Candidates School (OCS), a 10-week military training program attended by older service members (~ 25 y/o) who may have previous military experience.

Conditional Deletion of Gremlin-1 in Cathepsin K-expressing Mature Osteoclasts Altered the Skeletal Response to Calcium Depletion in Sex-Dependent Manner.

This study assessed the novel concept that osteoclast-derived Grem1 has regulatory functions in the skeletal response to calcium stress using an osteoclastic Grem1 conditional knockout (cKO) mouse model. The calcium stress was initiated by feeding cKO mutants and wildtype (WT) littermates a calcium-deficient diet for 2 weeks. Deletion of Grem1 in mature osteoclasts did not affect developmental bone growth nor basal bone turnover.

A real-world drug safety surveillance study from the FAERS database of hepatocellular carcinoma patients receiving pembrolizumab alone and plus lenvatinib.

Pembrolizumab plus Lenvatinib is regarded as a significant treatment option for advanced unresectable hepatocellular carcinoma (HCC). This study aims to meticulously monitor and identify adverse events (AEs) related to this combined therapy, enhance patient safety, and offer evidence-based recommendations for the appropriate use of these drugs. We gathered adverse drug reactions (ADRs)-related data from the FAERS database for HCC patients who received Pembrolizumab, both alone and in combination with Lenvatinib from the first quarter of 2014 to the fourth quarter of 2023.

Exploratory disproportionality analysis of potentially drug-induced eosinophilic pneumonia using United States Food and Drug Administration adverse event reporting system.

Drug-induced eosinophilic pneumonia (EP) is an uncommon adverse drug reaction. Many drugs have been reported to cause EP, the evidence mainly being in the form of case reports/case series. This study aims to conduct an exploratory analysis of the United States Food and Drug Administration adverse event reporting system (FAERS) database to identify previously unknown drugs that can cause EP and supplement the available evidence for known culprit drugs.

Surgical Margins and Oncologic Outcomes Following Wedge Resection of Pulmonary Metastases in Pediatric and Young Adult Patients with Sarcoma.

Introduction: Children and young adults diagnosed with sarcoma often present with pulmonary metastases requiring wedge resection. It is important to balance the risk of pulmonary recurrence against the desire to limit resection of benign parenchyma. This study aims to determine the impact of resection margins on survival and recurrence among pediatric and young adult sarcoma patients.