Inspiratory muscle training in adults with chronic obstructive pulmonary disease: an update of a systematic review

The purpose was to update an original systematic review to determine the effect of inspiratory muscle training (IMT) on inspiratory muscle strength and endurance, exercise capacity, dyspnea and quality of life for adults with chronic obstructive pulmonary disease (COPD). The original MEDLINE and CINAHL search to August 2003 was updated to January 2007 and EMBASE was searched from inception to January 2007. Randomized controlled trials, published in English, with adults with stable COPD, comparing IMT to sham IMT or no intervention, low versus high intensity IMT, and different modes of IMT were included. Nineteen of 274 articles in the original search met the inclusion criteria. The updated search revealed 17 additional articles; 6 met the inclusion criteria, all of which compared targeted, threshold or normocapneic hyperventilation IMT to sham IMT. An update of the sub-group analysis comparing IMT versus sham IMT was performed with 10 studies from original review and 6 from the update. Sixteen meta-analyses are reported. Results demonstrated significant improvements in inspiratory muscle strength (PI(max), PI(max) % predicted, peak inspiratory flow rate), inspiratory muscle endurance (RMET, inspiratory threshold loading, MVV), exercise capacity (Ve(max), Borg Score for Respiratory Effort, 6MWT), Transitional Dyspnea Index (focal score, functional impairment, magnitude of task, magnitude of effort), and the Chronic Respiratory Disease Questionnaire (quality of life). Results suggest that targeted, threshold or normocapneic hyperventilation IMT significantly increases inspiratory muscle strength and endurance, improves outcomes of exercise capacity and one measure of quality of life, and decreases dyspnea for adults with stable COPD.     

Pulmonary Aspergillus fumigatus infection in rats affects gastrointestinal homeostasis

Microbiota inhabiting mucosal tissues is involved in maintenance of their immune homeostasis. Growing body of evidence indicate that dysbiosis in gut influence immune responses at distal sites including lungs. There are also reports concerning gut involvement with pulmonary injury/inflammation in settings of respiratory viral and bacterial infections. The impact of infections with other microorganisms on gut homeostasis is not explored. In this study, the rat model of sublethal pulmonary infection with Aspergillus fumigatus was used to investigate the effect of fungal respiratory infection on gut immune-mediated homeostasis. Signs of intestinal damage, intestinal and gut-draining lymphoid tissue cytokine responses and gut bacterial microbiota diversity were examined. Intestinal injury, inflammatory cell infiltration, as well as increased levels of intestinal interferon-γ (IFN-γ) and interleukin-17 (IL-17) (as opposed to unchanged levels of anti-inflammatory cytokine IL-10) during the two-week period depict intestinal inflammation in rats with pulmonary A. fumigatus infection. It could not be ascribed to the fungus as it was not detected in the intestine of infected rats. Increased production of pro-inflammatory cytokines by major gut-draining mesenteric lymph nodes point to these lymphoid organs as places of generation of cytokine-producing cells. No changes in spleen or systemic cytokine responses was observed, showing lack of the effects of pulmonary A. fumigatus infection outside mucosal immune system. Drop of intestinal bacterial microbiota diversity (disappearance of several bacterial bands) was noted early in infection with normalization starting from day seven. From day three, appearance of new bacterial bands (unique to infected individuals, not present in controls) was seen, and some of them are pathogens. Alterations in intestinal bacterial community might have affected intestinal immune tolerance contributing to inflammation. Disruption of gut homeostasis during pulmonary infection might render gastrointestinal tract more susceptible to variety of physiological and pathological stimuli. Data which showed for the first time gut involvement with pulmonary infection with A. fumigatus provide the baseline for future studies of the impact of fungal lung infections to gut homeostasis, particularly in individuals susceptible to these infections.     

A host cell membrane protein, golgin-97, is essential for poxvirus morphogenesis

Acquisition of the membrane and genome encapsidation is an important step in the replication of enveloped viruses. The biogenesis of the poxviral primary membrane and the core as well as the mechanisms of their maturation are poorly understood. Using RNA interference approach, we demonstrate that a cellular trans-Golgi network membrane protein, golgin-97, is essential for virus replication. Analysis of the virion morphology in the cells depleted of golgin-97 shows that the protein is required for the virus morphogenesis and, in particular, for the formation of the first infectious virus form, mature virus, but not its precursor, immature virus. This suggests that golgin-97 may be involved in the maturation of the virus core and, potentially, the virus membrane.     

Virion tails of Beet yellows virus: Coordinated assembly by three structural proteins

Filamentous virions of Beet yellows virus contain a long body formed by a major capsid protein and a short tail that is assembled by a minor capsid protein (CPm), an Hsp70-homolog (Hsp70h), a 64-kDa protein (p64), and a 20-kDa protein (p20). Using mutation analysis and newly developed in planta assays, here we investigate the genetic requirements for the tail assembly. We show that the inactivation of CPm dramatically reduces incorporation of both Hsp70h and p64. Furthermore, inactivation of Hsp70h prevents incorporation of p64 into virions and vice versa. Hsp70h and p64 are each required for efficient incorporation of CPm. We also show that the tails possessing normal relative amounts of CPm, Hsp70h, and p64 can be formed in the absence of the major capsid protein and p20. Similar to the tails isolated from the wild-type virions, these mutant tails encapsidate the approximately 700 nt-long, 5'-terminal segments of the viral RNA. Taken together, our results imply that CPm, Hsp70h and p64 act cooperatively to encapsidate a defined region of the closterovirus genome.     

Evaluation of MicroRNA92, MicroRNA638 in Acute Lymphoblastic Leukemia of Egyptian Children

Objective: miRNA considers a small non-coding RNA molecule that has tumor suppressor or oncogenic functions and regulates gene expression. miRNA may be involved in the pathogenesis of acute lymphoblastic leukemia (ALL).  miRNA was evaluated in patients with ALL to correlate their importance in the clinical prediction and the response to chemotherapy. Subject and methods: The study population included 30 healthy control and 71 children with ALL is divided into 4 groups: healthy, newly diagnosed, remitted, and relapsed groups. We quantify miRNA 92a, miRNA 638 expression using real-time PCR in childhood ALL. Results: plasma miRNA 92a and miRNA 638 expressions were elevated in ALL cases at the time of diagnosis (2.51 and 2.19 folds), and relapsed (2.1 and 1.61 folds) than that of patients with remitted ALL. There was a positive correlation between miRNA 92a and miRNA 638 patients with ALL. Also, total leukocyte and blast correlated with miRNA 92a and miRNA 638 unlike hemoglobin, and platelets didn’t correlate with miRNA 92a and miRNA 638. The sensitivity of miRNA 92a and miRNA 638 were 41.5% and 54.7% respectively while the specificity was 100 % of miRNA 92a and miRNA 638. Conclusion: miRNA 92a and miRNA 638 are recommended to be used as potential predictive and follow-up markers in children with ALL remitted and relapsed cases.     

Attitude and Knowledge of Physicians and Nurses About Ionizing Radiation

The purpose of this study was to describe physicians' and nurses' knowledge and attitude about the potential dangers of imaging tests. The study comprised 144 participants; 68 physicians, and 76 nurses. Over 70% of the physicians reported that to complete their diagnosis, they always sent patients for ionized testing. Most of the physicians and nurses indicated that they knew that these tests could cause cancer and genetic changes. Over 80% of the medical staff did not know the amount of environmental radiation that was equal to an x-ray test or computed tomography scan. Thirty percent of the respondents noted that they did not protect the patient's sensitive organs during radiation procedures. As for the physicians and nurses in the invasive unit, they did not follow precise instructions for self-protection from exposure to radiation while working. There is a necessity to follow up on quantity of exposure to x-ray and computed tomography scan radiation for all patients and to promote physicians' and nurses' knowledge about protection from exposure to radiation.     

Modified High-Dose Melphalan and Autologous Stem Cell Transplantation for Immunoglobulin Light Chain Amyloidosis

High-dose melphalan and autologous stem cell transplantation (HDM/SCT) have been used in patients with immunoglobulin light chain (AL) amyloidosis for over 2 decades now with durable responses, prolonged survival, and decreasing treatment-related mortality. Historically, patients with poorer baseline functional status, advanced age, renal compromise, and cardiac involvement have been treated with a risk-adapted modified conditioning dose of melphalan (mHDM) of 100 to 140 mg/m² before SCT. In part because of these baseline characteristics, patients receiving mHDM/SCT have had poorer outcomes compared with patients receiving full-dose melphalan at 200 mg/m². With the advent of novel therapeutic agents such as proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies for the treatment of AL amyloidosis, it is imperative to understand the long-term effects of mHDM/SCT. Here we report the long-term outcomes of 334 patients with AL amyloidosis treated with mHDM/SCT. Median overall survival was 6.1 years and median event-free survival 4.3 years, with median overall survival reaching 13.4 years for patients who had achieved a hematologic complete response (CR). Overall hematologic response rate was 69%, and treatment-related mortality was 3% after 2010. Thus, mHDM/SCT leads to prolonged survival and favorable outcomes, especially if a hematologic CR is achieved.     

Quantitative evaluation of prostatectomy for benign prostatic hypertrophy under a national health insurance law: a multi-centre study

Assessing regional variation between various medical centres in diagnostic and surgical processes is an approach aimed at evaluating the quality of care. This study analyses the differences between eight medical centres in Israel, where all citizens are covered by medical insurance, through the National Health Insurance Law (NHIL). The analysis refers to the diagnostic process, type of surgery and immediate post-surgical complications associated with prostatectomy for benign prostatic hypertrophy (BPH), which is the most frequent surgical procedure performed on men aged 50+. The study sample was comprised of 261 consecutive prostatectomy patients operated on in eight Israeli medical centres (MC), located in various parts of the country, between November 1996 and April 1997. Co-operation with participating directors of surgical wards was obtained after confidentiality of information had been assured. Surgeons in selected departments abstracted data routinely recorded in the patient's file and filled-out a standard one-page questionnaire. The following items were included: age, the presence of accompanying chronic diseases, preoperative tests, type of operation, and post-surgical complications. In the various MCs 32.6% of the patients underwent more than five preoperative tests ranging from 8.9% to 88.9% (<0.01). Assessment of kidney and bladder normality ranged from 75% to 100% (P < 0.01). The rate of patients whose prostatic symptoms (I-PSS) were assessed ranged from 0% to 79% (P < 0.01). There were also differences in severity of prostatism between the MCs, with severe symptoms ranging from 54.0% to 89.3% (P < 0.05), for type of operation performed (for 'open' prostatectomies, 35.4% to 68.0%, P < 0.01) and post-operative complications (19.0% to 41.6%, P = 0.07). After controlling for case-mix, type of operation was the most important predictor for post-surgical complications. MCs with low volume of surgeries had a higher rate of postoperative complications. We conclude that diagnostic and type of operation and post-surgical complications differed between various MCs. Participating surgeons were willing to fill out a one-page standard questionnaire from data routinely recorded in patients' files.     

Neuropsychological predictors of conversion from mild cognitive impairment to Alzheimer’s disease: a feature selection ensemble combining stability and predictability

Background

Predicting progression from Mild Cognitive Impairment (MCI) to Alzheimer’s Disease (AD) is an utmost open issue in AD-related research. Neuropsychological assessment has proven to be useful in identifying MCI patients who are likely to convert to dementia. However, the large battery of neuropsychological tests (NPTs) performed in clinical practice and the limited number of training examples are challenge to machine learning when learning prognostic models. In this context, it is paramount to pursue approaches that effectively seek for reduced sets of relevant features. Subsets of NPTs from which prognostic models can be learnt should not only be good predictors, but also stable, promoting generalizable and explainable models.

Methods

We propose a feature selection (FS) ensemble combining stability and predictability to choose the most relevant NPTs for prognostic prediction in AD. First, we combine the outcome of multiple (filter and embedded) FS methods. Then, we use a wrapper-based approach optimizing both stability and predictability to compute the number of selected features. We use two large prospective studies (ADNI and the Portuguese Cognitive Complaints Cohort, CCC) to evaluate the approach and assess the predictive value of a large number of NPTs.

Results

The best subsets of features include approximately 30 and 20 (from the original 79 and 40) features, for ADNI and CCC data, respectively, yielding stability above 0.89 and 0.95, and AUC above 0.87 and 0.82. Most NPTs learnt using the proposed feature selection ensemble have been identified in the literature as strong predictors of conversion from MCI to AD.

Conclusions

The FS ensemble approach was able to 1) identify subsets of stable and relevant predictors from a consensus of multiple FS methods using baseline NPTs and 2) learn reliable prognostic models of conversion from MCI to AD using these subsets of features. The machine learning models learnt from these features outperformed the models trained without FS and achieved competitive results when compared to commonly used FS algorithms. Furthermore, the selected features are derived from a consensus of methods thus being more robust, while releasing users from choosing the most appropriate FS method to be used in their classification task.