INhaled Sedation versus Propofol in REspiratory failure in the Intensive Care Unit (INSPiRE-ICU1): protocol for a randomised, controlled trial.

Introduction: Sedation in mechanically ventilated adults in the intensive care unit (ICU) is commonly achieved with intravenous infusions of propofol, dexmedetomidine or benzodiazepines. Significant limitations associated with each can impact their usage. Inhaled isoflurane has potential benefit for ICU sedation due to its safety record, sedation profile, lack of metabolism and accumulation, and fast wake-up time.

The Effect of Nursing Moral Distress on Intent to Leave Employment.

Objective: This study explored the impact of moral distress (MD) and respondent characteristics on intent to leave employment.

Background: Managing patient care, within organizational constraints, may create physical discomfort or mental peace disturbances such as MD, negatively impacting RN retention.

Methods: Responses from 948 RNs were collected using an anonymous online survey.

Secondary oral squamous cell carcinoma following haematopoietic stem cell transplantation.

We report the cases of 10 patients with oral squamous cell carcinoma (SCC) post-haematopoietic stem cell transplant (HSCT). Median latency from HSCT to oral SCC diagnosis was 10 years (range: 4-17 years), with 90% (9/10) reporting a history of chronic graft-versus-host disease (cGVHD) and 40% (4/10) exhibiting active severe manifestations of oral GvHD. Clinical findings at diagnosis included induration, ulceration, tenderness, bleeding, hyperkeratosis, speckling and lymphadenopathy.

Evolution and variation in amide aminoacyl-tRNA synthesis.

The amide proteogenic amino acids, asparagine and glutamine, are two of the twenty amino acids used in translation by all known life. The aminoacyl-tRNA synthetases for asparagine and glutamine, asparaginyl-tRNA synthetase and glutaminyl tRNA synthetase, evolved after the split in the last universal common ancestor of modern organisms. Before that split, life used two-step indirect pathways to synthesize asparagine and glutamine on their cognate tRNAs to form the aminoacyl-tRNA used in translation.

CD, or not CD, that is the question: a digital interobserver agreement study in coeliac disease.

Objective: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis.

PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma.

Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream component of the CDK4/6 pathway. However, the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 has not been established.

Modifiable in-hospital factors for 12-month global cognition, post-traumatic stress disorder symptoms, and depression symptoms in adults hospitalized with COVID-19.

Background: We sought to identify potentially modifiable in-hospital factors associated with global cognition, post-traumatic stress disorder (PTSD) symptoms, and depression symptoms at 12 months.

Methods: This was a multi-center prospective cohort study in adult hospitalized patients with acute COVID-19. The following in-hospital factors were assessed: delirium; frequency of in-person and virtual visits by friends and family; and hydroxychloroquine, corticosteroid, and remdesivir administration.

Oral mucosal melanoma in situ: a case report and review of the literature.

Oral mucosal melanoma is a rare presentation of malignant melanoma with a 5-year survival rate of only 15%. Oral mucosal melanoma in situ (OMMIS) is its assumed precursor. This report describes one of only 20 documented cases of OMMIS and outlines how early clinical recognition resulted in prompt histopathological diagnosis and subsequent complete surgical excision.

A Multidisciplinary Approach for the Management of Portal Vein Thrombosis.

Portal venous thrombosis (PVT) is an uncommon disease associated with highly morbid conditions such as intestinal ischemia and portal hypertension. Patients at higher risk of developing PVT include those with cirrhosis, malignancy, or prothrombotic states. The mainstay of treatment is early initiation of anticoagulation.

The therapeutic potential of targeting minimal residual disease in melanoma.

Background: Cutaneous melanoma is a lethal form of skin cancer with morbidity and mortality rates highest amongst European, North American and Australasian populations. The developments of targeted therapies (TTs) directed at the oncogene BRAF and its downstream mediator MEK, and immune checkpoint inhibitors (ICI), have revolutionized the treatment of metastatic melanoma, improving patient outcomes. However, both TT and ICI have their limitations.

From crime scene to courtroom: A review of the current bioanalytical evidence workflows used in rape and sexual assault investigations in the United Kingdom.

Sexual assault casework requires the collaboration of multiple agency staff to formalise an investigative pipeline running from crime scene to court. While the same could be said of many other forensic investigations, few require the additional support of health care staff and the combined forensic involvement of body-fluid examiners, DNA experts and analytical chemists. The sheer amount of collaborative effort between agencies is laid out through a detailed examination of the investigative workflow from crime scene to courtroom with each step in the pipelines detailed and discussed.

Inhibition of the MNK1/2-eIF4E Axis Augments Palbociclib-Mediated Antitumor Activity in Melanoma and Breast Cancer.

Aberrant cell-cycle progression is characteristic of melanoma, and CDK4/6 inhibitors, such as palbociclib, are currently being tested for efficacy in this disease. Despite the promising nature of CDK4/6 inhibitors, their use as single agents in melanoma has shown limited clinical benefit. Herein, we discovered that treatment of tumor cells with palbociclib induces the phosphorylation of the mRNA translation initiation factor eIF4E.

Control of the Nanopore Architecture of Anodic Alumina via Stepwise Anodization with Voltage Modulation and Pore Widening.

Control of the morphology and hierarchy of the nanopore structures of anodic alumina is investigated by employing stepwise anodizing processes, alternating the two different anodizing modes, including mild anodization (MA) and hard anodization (HA), which are further mediated by a pore-widening (PW) step in between. For the experiment, the MA and HA are applied at the anodizing voltages of 40 and 100 V, respectively, in 0.3 M oxalic acid, at 1 °C, for fixed durations (30 min for MA and 0.

Transnasal Humidified Rapid-Insufflation Ventilatory Exchange for Difficult Airway Management in Adults With Recessive Dystrophic Epidermolysis Bullosa: A Case Series.

Airway management of adult patients with recessive dystrophic epidermolysis bullosa presents significant challenges associated with tissue fragility and distortion of airway anatomy. This retrospective case series describes 11 adult patients with recessive dystrophic epidermolysis bullosa and difficult airways undergoing 24 general anesthetics in which transnasal humidified rapid-insufflation ventilatory exchange was used for preoxygenation and apneic oxygenation. Despite an average time to intubation of over 6 minutes, transnasal humidified rapid-insufflation ventilatory exchange provided oxygenation before endotracheal intubation without the need for bag-mask ventilation or supraglottic airway ventilation, facilitating smooth and atraumatic flexible scope intubation.

Six-month intervention with wild blueberries improved speed of processing in mild cognitive decline: a double-blind, placebo-controlled, randomized clinical trial.

Background: As the sector of the population over 65y increases, cognitive decline and dementia become a public health issue. Interventions to improve brain health and thus, quality of life for older adults are needed.

Objective: It was hypothesized that those consuming a flavonoid-rich, lyophilized wild blueberry powder would evidence improvements in cognitive performance as measured behaviorally and electrophysiologically compared to those consuming a placebo powder across a 6-month intervention period.

Standardization of Pediatric Noncardiac Operating Room to Intensive Care Unit Handoffs Improves Communication and Patient Care.

Objectives: Handoffs are critical points in transitioning care between multidisciplinary teams, yet data regarding intensive care unit (ICU) handoffs in pediatric noncardiac surgical patients are lacking. We hypothesized that standardized handoffs from the pediatric operating room (OR) to the ICU would improve physician presence, communication, and patient care parameters.

Methods: This quality improvement initiative was performed at a tertiary children's hospital.

Harnessing the immunotherapeutic potential of CDK4/6 inhibitors in melanoma: is timing everything?

CDK4/6 inhibitors (CDK4/6i) were developed as a cancer therapeutic on the basis of their tumor-intrinsic cytostatic potential, but have since demonstrated profound activity as immunomodulatory agents. While currently approved to treat hormone receptor-positive breast cancer, these inhibitors are under investigation in clinical trials as treatments for a range of cancer types, including melanoma. Melanoma is a highly immunogenic cancer, and has always been situated at the forefront of cancer immunotherapy development.

Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAF melanoma.

Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling.

Stride-level analysis of mouse open field behavior using deep-learning-based pose estimation.

Gait and posture are often perturbed in many neurological, neuromuscular, and neuropsychiatric conditions. Rodents provide a tractable model for elucidating disease mechanisms and interventions. Here, we develop a neural-network-based assay that adopts the commonly used open field apparatus for mouse gait and posture analysis.

Enhancing Adoptive Cell Transfer with Combination BRAF-MEK and CDK4/6 Inhibitors in Melanoma.

Despite the success of immune checkpoint inhibitors that target cytotoxic lymphocyte antigen-4 (CTLA-4) and programmed-cell-death-1 (PD-1) in the treatment of metastatic melanoma, there is still great need to develop robust options for patients who are refractory to first line immunotherapy. As such there has been a resurgence in interest of adoptive cell transfer (ACT) particularly derived from tumor infiltrating lymphocytes. Moreover, the addition of cyclin dependent kinase 4/6 inhibitors (CDK4/6i) have been shown to greatly extend duration of response in combination with BRAF-MEK inhibitors (BRAF-MEKi) in pre-clinical models of melanoma.

Incidental Findings of Appendiceal Diverticulitis Presenting as Acute Appendicitis.

Diverticulosis of the appendix (DA) is a rare pathological finding that clinically imitates acute appendicitis and is most commonly found in adult males with chronic abdominal pain. It has a higher rate of perforation compared to acute appendicitis (84% vs 12%, P<0.01), and is consequently associated with a higher rate of mortality.

Behavioral and Cognitive Differences in Early Childhood related to Prenatal Marijuana Exposure.

Prenatal marijuana exposure (PME) negatively impacts child development and behavior; however, few studies have examined these associations at early ages among children exposed to today's highly potent marijuana. Using a prospective prenatal cohort (Columbus, Ohio, USA), PME was determined from maternal self-report, medical chart abstraction, and urine toxicology from prenatal visits and delivery. At age 3.