True lateral imaging during lumbar medial branch radiofrequency neurotomy: Interobserver reliability.

Background: True lateral imaging (TLI), obtained by superimposing bilateral lumbar spine structures and aligning superior endplate cortical bone, requires deliberate rotational adjustments of the laterally positioned fluoroscope in both the axial and longitudinal planes. True lateral segmental imaging is necessary to depict true and accurate radiofrequency (RF) cannula positioning relative to bony anatomy during lumbar medial branch radiofrequency neurotomy (LMBRFN).

Objective: To determine the interobserver reliability of TLI during LMBRFN.

Inpatient pain alleviation after orthopaedic trauma surgery-are we doing a good job?

Purpose: Poor pain alleviation (PPA) after orthopaedic surgery is known to increase recovery time, readmissions, patient dissatisfaction, and lead to chronic postsurgical pain. This study's goal was to identify the magnitude of PPA and its risk factors in the orthopaedic trauma patient population.

Methods: A single-institution's electronic medical records from 2015 to 2018 were available for retrospective analysis.

2',3',4'-Trihydroxychalcone changes estrogen receptor α regulation of genes and breast cancer cell proliferation by a reprogramming mechanism.

Background: Menopausal hormone therapy (MHT) is recommended for only five years to treat vasomotor symptoms and vulvovaginal atrophy because of safety concerns with long-term treatment. We investigated the ability of 2',3',4'-trihydroxychalcone (2',3',4'-THC) to modulate estrogen receptor (ER)-mediated responses in order to find drug candidates that could potentially prevent the adverse effects of long-term MHT treatment.

Methods: Transfection assays, real time-polymerase chain reaction, and microarrays were used to evaluate the effects of 2',3',4'-THC on gene regulation.

Delayed diagnosis and subsequently increased severity of acute appendicitis (compatible with clinical-pathologic grounds) during the COVID-19 pandemic: an observational case-control study.

Background: During a global crisis like the current COVID-19 pandemic, delayed admission to hospital in cases of emergent medical illness may lead to serious adverse consequences. We aimed to determine whether such delayed admission affected the severity of an inflammatory process regarding acute appendicitis, and its convalescence.

Methods: In a retrospective observational cohort case-control study, we analyzed the medical data of 60 patients who were emergently and consecutively admitted to our hospital due to acute appendicitis as established by clinical presentation and imaging modalities, during the period of the COVID-19 pandemic (our study group).

Three regulatory compliant test systems show no signs of MDMA-related genotoxicity.

3,4 Methylenedioxymethamphetamine (MDMA)-assisted therapy has been recently found to be highly effective for treatment of posttraumatic stress disorder (PTSD). Previous studies have been inconclusive in elucidating potential MDMA genotoxicity. We performed three regulatory compliant studies to investigate the potential of genotoxic effects of MDMA treatment in humans: (1) an bacterial reverse mutation (Ames) assay, (2) an chromosome aberration test in Chinese hamster ovary cells, and (3) an micronucleus study in male Sprague Dawley rats.

Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data.

Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient's own immune system to target immune response evading cancer cells. However, this unique mechanism of action may cause immune-related adverse events, irAEs.

Mucus Release and Airway Constriction by TMEM16A May Worsen Pathology in Inflammatory Lung Disease.

Activation of the Ca activated Cl channel TMEM16A is proposed as a treatment in inflammatory airway disease. It is assumed that activation of TMEM16A will induce electrolyte secretion, and thus reduce airway mucus plugging and improve mucociliary clearance. A benefit of activation of TMEM16A was shown in vitro and in studies in sheep, but others reported an increase in mucus production and airway contraction by activation of TMEM16A.

Concomitant drugs associated with increased mortality for MDMA users reported in a drug safety surveillance database.

3,4-Methylenedioxymethamphetamine (MDMA) is currently being evaluated by the Food and Drug Administration (FDA) for the treatment of post-traumatic stress disorder (PTSD). If MDMA is FDA-approved it will be important to understand what medications may pose a risk of drug-drug interactions. The goal of this study was to evaluate the risks due to MDMA ingestion alone or in combination with other common medications and drugs of abuse using the FDA drug safety surveillance data.

Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization's List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications.

An unsupervised learning approach to identify novel signatures of health and disease from multimodal data.

Background: Modern medicine is rapidly moving towards a data-driven paradigm based on comprehensive multimodal health assessments. Integrated analysis of data from different modalities has the potential of uncovering novel biomarkers and disease signatures.

Methods: We collected 1385 data features from diverse modalities, including metabolome, microbiome, genetics, and advanced imaging, from 1253 individuals and from a longitudinal validation cohort of 1083 individuals.

Analysis of postmarketing safety data for proton-pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis.

Proton pump inhibitors, PPIs, are widely prescribed and sold globally. Although initially intended for time-limited treatment of acute disorders, such as gastric ulcers and esophagitis, PPIs are now commonly used for prolonged durations and are considered safe for over the counter access. Recent studies have raised concern over associations between PPI use and acute kidney injury, chronic kidney disease, end-stage renal disease, and electrolyte abnormalities.

Population scale retrospective analysis reveals distinctive antidepressant and anxiolytic effects of diclofenac, ketoprofen and naproxen in patients with pain.

Currently approved monoamine modulating antidepressant and anxiolytic pharmaceutics fail in over one third of patients due to delayed and variable therapeutic effect, adverse reactions preceding the therapeutic action, and adherence issues. Even with adequate adherence to the regimen and tolerability, one third of the patients do not respond to any class of antidepressants. There is a strong correlation between treatment resistant depression and increase in inflammatory cytokines in plasma and cerebrospinal fluid.

Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones.

Background: Acetaminophen (paracetamol) is one of the most common medications used for management of pain in the world. There is lack of consensus about the mechanism of action, and concern about the possibility of adverse effects on reproductive health.

Methods: We first established the metabolome profile that characterizes use of acetaminophen, and we subsequently trained and tested a model that identified metabolomic differences across samples from 455 individuals with and without acetaminophen use.

Publisher Correction: Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications.

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.

Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications.

Current therapeutic approaches to depression fail for millions of patients due to lag in clinical response and non-adherence. Here we provide new support for the antidepressant effect of an anesthetic drug, ketamine, by Inverse-Frequency Analysis of eight million reports from the FDA Adverse Effect Reporting System. The results of the examination of population scale data revealed that patients who received ketamine had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain.

Uterine rotation: a cause of intestinal obstruction.

Intestinal obstruction is an uncommon surgical emergency during pregnancy that affects seriously the prognosis of gestation. The underlying cause can be identified in the majority of cases and usually consists of adhesions secondary to previous abdominal or pelvic surgery, followed in order of frequency by intestinal volvuli. In recent years there have been no reports in which the gravid uterus has been the cause of intestinal obstruction.

Unfavorable course in pregnancy-associated thrombotic thrombocytopenic purpura necessitating a perimortem Cesarean section: a case report.

Introduction: Thrombotic thrombocytopenic purpura is a type of occlusive thrombotic microangiopathy that is not specific to pregnancy but occurs with an increased frequency during it. Prognosis of thrombotic thrombocytopenic purpura greatly depends on early diagnosis and treatment. As delivery does not generally cause resolution of thrombotic thrombocytopenic purpura, pregnancy termination is not initially considered, especially under 34 weeks, although it may be required under some conditions such as preeclampsia.

Bezielle selectively targets mitochondria of cancer cells to inhibit glycolysis and OXPHOS.

Bezielle (BZL101) is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. Bezielle is an aqueous extract from the herb Scutellaria barbata. We have reported previously that Bezielle was selectively cytotoxic to cancer cells while sparing non-transformed cells.

Identification and analysis of the active phytochemicals from the anti-cancer botanical extract Bezielle.

Bezielle is a botanical extract that has selective anti-tumor activity, and has shown a promising efficacy in the early phases of clinical testing. Bezielle inhibits mitochondrial respiration and induces reactive oxygen species (ROS) in mitochondria of tumor cells but not in non-transformed cells. The generation of high ROS in tumor cells leads to heavy DNA damage and hyper-activation of PARP, followed by the inhibition of glycolysis.

Tissue-specific regulation of genes by estrogen receptors.

Estrogens are frequently used in reproductive medicine. The Women's Health Initiative trial found that the risks of menopausal hormone therapy (MHT) exceed the benefits. The estrogens in MHT, however, were introduced prior to our understanding of the mechanism of action of estrogens.

Estrogenic plant extracts reverse weight gain and fat accumulation without causing mammary gland or uterine proliferation.

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα).

Bezielle (BZL101)-induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: a combined proteomic and metabolomic study.

Bezielle is an orally administered aqueous extract of Scutellaria barbata for treatment of advanced and metastatic breast cancer. Phase I trials showed promising tolerability and efficacy. In our study, we used a combined proteomic-metabolomic approach to investigate the molecular pathways affected by Bezielle in ER-positive BT474 and ER-negative SKBR3 cell lines.

Estrogen receptor β causes a G2 cell cycle arrest by inhibiting CDK1 activity through the regulation of cyclin B1, GADD45A, and BTG2.

The role of estrogen receptor beta (ERβ) in breast cancer is unclear. ERβ is considered to have a protective role in breast cancer development based on findings demonstrating that ERβ expression inhibits ERα-mediated proliferation of breast cancer cells. We previously demonstrated that ERβ causes a ligand independent G2 cell cycle arrest in MCF-7 cells.