Respiratory insufficiency in neuronopathic and neuropathic disorders

Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barre syndrome (GBS) who required long-term ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed (1). None have been weaned from support after a period of ventilation ranging from one month to 10 years. Eight patients have subsequently died.      

Impact of a concept map teaching approach on nursing students’ critical thinking skills

Nurses confront complex problems and decisions that require critical thinking in order to identify patient needs and implement best practices. An active strategy for teaching students the skills to think critically is the concept map. This study explores the development of critical thinking among nursing students in a required pathophysiology and pharmacology course during the first year of a Bachelor of Science in Nursing in response to concept mapping as an interventional strategy, using the Health Education Systems, Incorporated critical thinking test. A two‐group experimental study with a pretest and posttest design was used. Participants were randomly divided into a control group (n = 42) taught by traditional didactic lecturing alone, and an intervention group (n = 41), taught by traditional didactic lecturing with concept mapping. Students in the concept mapping group performed much better on the Health Education Systems, Incorporated than students in the control group. It is recommended that deans, program directors, and nursing faculties evaluate their curricula to integrate concept map teaching strategies in courses in order to develop critical thinking abilities in their students.     

Identification and Management of Women at High Risk for Hereditary Breast/Ovarian Cancer Syndrome

Abstract:  Despite advances in identifying genetic markers of high risk patients and the availability of genetic testing, it remains challenging to efficiently identify women who are at hereditary risk and to manage their care appropriately. HughesRiskApps, an open-source family history collection, risk assessment, and Clinical Decision Support (CDS) software package, was developed to address the shortcomings in our ability to identify and treat the high risk population. This system is designed for use in primary care clinics, breast centers, and cancer risk clinics to collect family history and risk information and provide the necessary CDS to increase quality of care and efficiency. This paper reports on the first implementation of HughesRiskApps in the community hospital setting. HughesRiskApps was implemented at the Newton-Wellesley Hospital. Between April 1, 2007 and March 31, 2008, 32,966 analyses were performed on 25,763 individuals. Within this population, 915 (3.6%) individuals were found to be eligible for risk assessment and possible genetic testing based on the 10% risk of mutation threshold. During the first year of implementation, physicians and patients have fully accepted the system, and 3.6% of patients assessed have been referred to risk assessment and consideration of genetic testing. These early results indicate that the number of patients identified for risk assessment has increased dramatically and that the care of these patients is more efficient and likely more effective.     

叔丁基醚的制备

醇或酚与2当量叔丁基溴在0．1当量碳酸铅催化下,35～45℃搅拌1～2．25h,得相应的叔丁基醚,14例收率75％～96％。     

Rapid interrogation of cancer cell of origin through CRISPR editing

The increasing complexity of different cell types revealed by single-cell analysis of tissues presents challenges in efficiently elucidating their functions. Here we show, using prostate as a model tissue, that primary organoids and freshly isolated epithelial cells can be CRISPR edited ex vivo using Cas9–sgRNA (guide RNA) ribotnucleoprotein complex technology, then orthotopically transferred in vivo into immunocompetent or immunodeficient mice to generate cancer models with phenotypes resembling those seen in traditional genetically engineered mouse models. Large intrachromosomal (∼2 Mb) or multigenic deletions can be engineered efficiently without the need for selection, including in isolated subpopulations to address cell-of-origin questions.

Models to study the earliest stages in cancer progression must, by definition, start with normal cells to assess the consequences of a suspected oncogenic perturbation. Inbred mouse strains and genetically engineered mouse models (GEMMs) have, for decades, served as gold standards for such studies but require significant time (years) to generate, breed, and age mice. CRISPR technology has greatly accelerated the pace of generating GEMMs through delivery of sgRNAs (guide RNAs) and/or Cas9 to tissues such as lung and liver (1–3). The ability to grow primary tissues ex vivo as organoids and introduce precise genetic changes into these cultures provides an alternative platform to model genomic alterations with speed and efficiency, as reported for intestine and prostate (4–7). Here we demonstrate highly efficient (50 to 90%) editing of primary prostate epithelial organoid cultures, including multigenic or intrachromosomal (>2 Mb) deletions, through transient electroporation of Cas9–sgRNA ribonucleoprotein (cRNP) complexes. We also show cRNP-based CRISPR editing can be performed on freshly isolated prostate epithelial cells and then transplanted orthotopically into the prostates of recipient mice in a single day, enabling extremely rapid generation of in vivo cancer models in immunodeficient as well as immunocompetent settings. Finally, we show that this approach can be used to address cancer cell-of-origin questions by multigenic editing selectively in luminal versus basal epithelial cells.     

Medication-related osteonecrosis of the jaw: A disease of significant importance for older patients

Background

Medication-related osteonecrosis of the jaw (MRONJ) is clinically defined as a non-healing jawbone ulcerative-necrotic lesion appearing after dental therapy or minor trauma in patients treated previously with anti-resorptive, anti-angiogenic or immunomodulators. Older patients with osteoporosis and cancer receive these pharmacological agents regularly. As these patients are long-term survivors, efficient treatment is of paramount importance for their quality of life.

Methods

Literature searches via PubMed were conducted to identify relevant MRONJ studies. Basic information on MRONJ classification, clinical features, and pathosphysiology is presented herein as well as various clinical studies dealing with MRONJ in patients with osteoporosis and cancer. Lastly, we discuss current managment of patients and new trends in treatment of MRONJ.

Results

Although close follow-up and local hygiene have been advocated by some authors, severe forms of MRONJ are not responsive to conservative therapy. At present, there is no “gold standard” therapy for this condition. However, as the physiopathological basis of MRONJ is represented by the anti-angiogenic action of various pharmacological agents, new methods to increase and promote local angiogenesis and vascularization have recently been successfully tested in vitro, limited preclinical studies, and in a pilot clinical study.

Conclusions

It appears that the best method implies application on the lesion of endothelial progenitor cells as well as pro-angiogenic factors such as Vascular Endothelial Growth Factor (VEGF) and other related molecules. More recently, scaffolds in which these factors have been incorporated have shown positive results in limited trials. However, these studies must be replicated to include a large number of cases before any official therapeutic protocol is adopted.