Pulmonary-delivered Anticalin Jagged-1 antagonists reduce experimental airway mucus hyperproduction and obstruction.

Mucus hypersecretion and mucus obstruction are pathogenic features in many chronic lung diseases directly linked to disease severity, exacerbation, progression, and mortality. The Jagged-1/Notch pathway is a promising therapeutic target that regulates secretory and ciliated cell trans-differentiation in the lung. However, the Notch pathway is also required in various other organs.

Elarekibep (PRS-060/AZD1402), a new class of inhaled Anticalin medicine targeting IL-4Ra for type 2 endotype asthma.

Background: Type 2 endotype asthma is driven by IL-4 and IL-13 signaling via IL-4Ra, which is highly expressed on airway epithelium, airway smooth muscle, and immunocytes in the respiratory mucosa, suggesting potential advantages of an inhalable antagonist. Lipocalin 1 (Lcn1), a 16 kDa protein abundant in human periciliary fluid, has a robust drug-like structure well suited to protein engineering, but it has never been used to make an inhaled Anticalin protein therapeutic.

Objectives: We sought to reengineer Lcn1 into an inhalable IL-4Ra antagonist and assess its pharmacodynamic/kinetic profile.

Design, Synthesis, and Biological Characterization of Inhaled p38α/β MAPK Inhibitors for the Treatment of Lung Inflammatory Diseases.

The identification of novel inhaled p38α/β mitogen-activated protein kinases (MAPK) (MAPK14/11) inhibitors suitable for the treatment of pulmonary inflammatory conditions has been described. A rational drug design approach started from the identification of a novel tetrahydronaphthalene series, characterized by nanomolar inhibition of p38α with selectivity over p38γ and p38δ isoforms. SAR optimization of is outlined, where improvements in potency against p38α and ligand-enzyme dissociation kinetics led to several compounds showing pronounced anti-inflammatory effects (inhibition of TNFα release).

Framework for creating an incident command center during crises.

The Hospital Incident Command System (HICS) is an incident management system specific to hospitals based on the principles of Incident Command System (ICS), and it includes prevention, protection, mitigation, response, and recovery. It plays a crucial role in effective and timely response during the periods of disasters, mass casualties, and public health emergencies. In recent times, hospitals have used a customized HICS structure to coordinate effective responses to public health problems such as the Ebola outbreak in the US and SARS epidemic in Taiwan.

Lamotrigine and Stevens-Johnson Syndrome Prevention.

Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs.

A phase 2 study to evaluate the safety, efficacy and pharmacokinetics of DP2 antagonist GB001 and to explore biomarkers of airway inflammation in mild-to-moderate asthma.

Background: GB001 is an oral antagonist of the prostaglandin D2 receptor that may inhibit recruitment and activation of airway eosinophils, reducing airway inflammation.

Objective: To assess GB001 safety, efficacy and pharmacokinetics from a Phase 2 study and explore the association between type 2 biomarkers (fractional exhaled nitric oxide and blood eosinophils) and asthma control markers following GB001 administration.

Methods: A randomized, placebo-controlled, double-blind study evaluating 36 patients with mild-to-moderate atopic asthma.

Rehabilitation of emergent awareness of errors post traumatic brain injury: A pilot intervention.

Impaired awareness of errors is common following traumatic brain injury (TBI) and can be a barrier to successful rehabilitation. The objective of this study was to develop and evaluate a computer-based intervention programme aimed at improving error awareness in individuals with TBI. A further aim was to explore its effects on metacognitive awareness and variability of performance.

Retroperitoneal Laparoscopic Radical Nephrectomy Allows Continuation of Peritoneal Dialysis in Patients with End-Stage Renal Disease.

Patient outcomes for retroperitoneal laparoscopic radical nephrectomy (RLRN) in adults on peritoneal dialysis (PD) have not been described in the literature. This is the first series on the successful application of RLRN for renal cell carcinoma (RCC) among adults with end-stage renal disease (ESRD) on PD. In our series of 5 patients, all were able to promptly resume PD, no wound complications were noted at postoperative visits, and no evidence of recurrence was identified on surveillance imaging at follow-up.

Reconsidering Olanzapine as a Possible Culprit for Drug Fever, defying "Incomplete Neuromalignant Syndrome".

This case is important because it is the first time Olanzapine-induced fever has been described in the absence of neuroleptic malignant syndrome. In the context of the available antipsychotics with the atypical agents dominating the pool, only few of those are known to be well tolerated among the patients. Fever may be looked at by the physicians as a minor problem yet, it can be disabling to the large set of patients.

Dual behavior of N-acetylcysteine during ethanol-induced oxidative stress in embryonic chick brains.

Objectives: Ethanol (EtOH) causes oxidative stress in embryos. Because N-acetylcysteine (NAC) failures and successes in ameliorating EtOH-induced oxidative stress have been reported, the objective was to determine if exogenous NAC ameliorated EtOH-induced oxidative stress within embryonic chick brains.

Methods: Control eggs were injected with approximately 25 µl of water on day 0, 1, and 2 of development (E).

Strengthening nursing and midwifery capacity in rural New South Wales, Australia.

A small rural health service and two university schools of nursing joined forces to establish a rural clinical school to advance clinical education and research. The collaboration, while in its infancy, has given rise to outcomes that strength the capacity of nursing and midwifery services in the community.

Connecting Self-Awareness and Error-Awareness in Patients with Traumatic Brain Injury.

Impaired self-awareness after traumatic brain injury (TBI) is often seen in stark contrast to the observations of significant-others, who are acutely aware of the difficulties experienced by patients. Our objective was to investigate the relationship between metacognitive knowledge in daily life and emergent awareness of errors during laboratory tasks, since the breakdown of error detection mechanisms may impose limitations on the recovery of metacognitive knowledge after TBI. We also examined the extent to which these measures of awareness can predict dysexecutive behaviors.

Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases.

Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), bronchiectasis (BE), and pulmonary hypertension (PH).

Updates in Psychosomatic Medicine: 2014.

Background: The amount of literature published annually related to psychosomatic medicine is vast; this poses a challenge for practitioners to keep up-to-date in all but a small area of expertise.

Objectives: To introduce how a group process using volunteer experts can be harnessed to provide clinicians with a manageable selection of important publications in psychosomatic medicine, organized by specialty area, for 2014.

Methods: We used quarterly annotated abstracts selected by experts from the Academy of Psychosomatic Medicine and the European Association of Psychosomatic Medicine in 15 subspecialties to create a list of important articles.

Delirium: the lived experience of older people who are delirious post-orthopaedic surgery.

Delirium is a common, potentially preventable and reversible cause of postoperative functional disability, morbidity, and mortality. It can lead to increased health-care use and also poses a substantial challenge for nurses caring for patients who experience delirium after surgery. Predominantly, the published work concentrates on diagnosis, reduction of the modifiable risk factors, and treatments.

Key influences identified by first year undergraduate nursing students as impacting on the quality of clinical placement: A qualitative study.

Background: Despite the fact that high quality clinical placement is an integral component of pre-registration nursing education for the development of the future nursing workforce, the literature identifies an ongoing struggle to 'get it right'.

Objective: To examine qualitative data gathered through the Quality Clinical Placements Evaluation project to identify what pre-registration nursing students deemed helpful and not helpful influences on their first year Professional Experience Placement.

Design: A total of 553 first year undergraduate nursing students from 2010 to 2012 were enrolled in the programme and all were invited to complete a validated survey to measure the quality of their first clinical placement.

Development and reliability testing of the quality clinical placement evaluation tool.

Aims And Objectives: To develop and test the content and face validity, and reliability of the quality clinical placement evaluation tool.

Background: The importance of clinical experience during undergraduate nursing degrees is undisputed. To date, tools available to measure quality of clinical placements have focused on single perspectives, that of the undergraduate or that of the supervising nurse.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

Purpose: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes.

Materials And Methods: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each.

Efficacy and safety of flexible dose fesoterodine in men and women with overactive bladder symptoms including nocturnal urinary urgency.

Purpose: Awakening from sleep to urinate is the hallmark of nocturia, a condition that impacts several facets of health related quality of life and for which current therapy is suboptimal. Given the paucity of prospective data on antimuscarinics for the management of nocturia, we investigated the efficacy and safety of flexible dose fesoterodine for the treatment of nocturnal urgency in subjects with nocturia and overactive bladder.

Materials And Methods: Subjects with 2 to 8 nocturnal urgency episodes per 24 hours began a 2-week, single-blind, placebo run-in followed by 1:1 randomization to 12 weeks of double-blind treatment with fesoterodine (4 mg daily for 4 weeks with an optional increase to 8 mg) or placebo using predefined criteria for nocturnal urgency episodes, nocturnal urine volume voided and total 24-hour urine volume voided.

Post-discharge experiences of children and their families following children's surgery.

Increasing rates of day surgery and decreasing length of hospital stay mean children's recovery from surgery extends beyond hospital and into the home. The objective of this study is to improve the understanding of experiences of children and their families during recovery at home post surgery. This is an exploratory, interpretive study using diaries and semi-structured interviews with children and parents.

Perioperative bowel habits of women undergoing gynecologic surgery: a pilot study.

Objectives: To describe perioperative bowel habits of women undergoing gynecologic surgery.

Methods: This prospective cohort study included women undergoing gynecologic surgery. Before surgery, participants completed the Bristol Stool Form Scale (BSFS), a validated instrument describing stool characteristics consistent with transit categories: slow (BSFS 1-2), normal (BSFS 3-5), and fast (BSFS 6-7).

Severe acidosis during laparoscopic repair of pelvic organ prolapse and incontinence.

The creation and maintenance of a carbon dioxide pneumoperitoneum to allow a laparoscopic approach to surgery for pelvic organ prolapse has been associated with hypercapnea and respiratory acidosis. We present a case report of a 68-year-old patient who developed severe acidosis during a robotic-assisted laparoscopic sacrocolpopexy and discuss a practical approach to surgical and anesthetic decision making.

Patient expectations did not predict outcome of drug and behavioral treatment of urgency urinary incontinence.

Objectives: : This study aimed to determine whether expectations of treatment outcomes in women participating in a drug and behavioral treatment trial for urge urinary incontinence are related to patient factors, demographics, health-related locus of control, and treatment outcomes.

Methods: : Baseline assessments included expectations (improvement in bladder condition, time to improvement in bladder condition, and duration of improvement) and the Medical Health Locus of Control (MHLC) scale. Outcomes were measured by the Patient Global Impression of Improvement scale (PGI-I) at the end of active treatment (10 weeks) and 8 months after trial start.