The Outcome of Infantile Onset Pompe Disease in South of Iran

Background: Infantile Onset Pompe Disease (IOPD) is a rare autosomal recessive neuromuscular disorder. It is associated with cardiomegaly, hypotonia, paresis, and death in the first year of life. Since 2006, following the use of Alglucosidase alfa as Enzyme Replacement Therapy (ERT), the patients’ survival is improved to a noticeable extent. Objectives: The purpose of this study is to examine the outcome of IOPD patients in South of Iran and the degree of responsiveness to ERT. Patients and Methods: All patients who were diagnosed with IOPD on the bases of clinical symptoms, and enzyme assay on dried blood spot, were included in the study; and were followed up regarding cardiac function, locomotor activity, and cognition. Results: Six patients with IOPD were identified. All these six patients suffered from Hypertrophic Cardiomyopathy (HCM). Four (67%) of them also had generalized hypotonia. Three patients expired during the first weeks due to severe respiratory infection. One of them also got involved with Acute Cardiopulmonary Failure while receiving the fifth dose of ERT; and expired. However, the remaining two patients had a significant improvement after the maximum of 117 weeks of following up both cardiac and locomotor findings. These two patients were the same patients who showed cardiac symptoms from the beginning but did not have generalized hypotonia. Conclusions: Although ERT has a significant effect on enhancing the survival of IOPD patients, it should be associated with meticulous heart-respiratory cares during the first months of treatment and preventing infection especially nosocomial infections.

Characteristics of microRNAs and their potential relevance for the diagnosis and therapy of the acute respiratory distress syndrome: from bench to bedside

Acute respiratory distress syndrome (ARDS) is a complex disease associated with high morbidity and mortality. Biomarkers and specific pharmacologic treatment of the syndrome are lacking. MicroRNAs (miRNAs) are small (∼19–22 nucleotides) noncoding RNA molecules whose function is the regulation of gene expression. Their uncommon biochemical characteristics (eg, their resistance to degradation because of extreme temperature and pH fluctuations, freeze-thaw cycles, long storage times in frozen conditions, and RNAse digestion) and their presence in a wide range of different biological fluids and the relatively low number of individual miRNAs make these molecules good biomarkers in different clinical conditions. In addition, miRNAs are suitable therapeutic targets as their expression can be modulated by different available strategies. The aim of the present review is to offer clinicians a global perspective of miRNA, covering their structure and nomenclature, biogenesis, effects on gene expression, regulation of expression, and features as disease biomarkers and therapeutic targets, with special attention to ARDS. Because of the early stage of research on miRNAs applied to ARDS, attention has been focused on how knowledge sourced from basic and translational research could inspire future clinical studies.

Assessment of interstitial lung disease in Sjögren’s syndrome by lung ultrasound: a pilot study of correlation with high-resolution chest tomography

The background of this study is to assess the accuracy of lung ultrasound (LUS) to diagnose interstitial lung disease (ILD) in Sjögren’s syndrome (Sjs), in patients who have any alterations in pulmonary function tests (PFT) or respiratory symptoms. LUS was correlated with chest tomography (hrCT), considering it as the imaging gold standard technique to diagnose ILD. This is a pilot, multicenter, cross-sectional, and consecutive-case study. The inclusion criteria are ≥18 years old, Signs and symptoms: according to ACEG 2002 criteria, respiratory symptoms (dyspnea, cough), or any alterations in PFR. LUS was done following the International Consensus Conference on Lung Ultrasound protocol for interstitial syndrome (B pattern). Of the 50 patients in follow-up, 13 (26%) met the inclusion criteria. All were women with age 63.62 years (range 39–88). 78.6% of the cases had primary Sjs (SLE, RA, n = 2). The intra-rater reliability k is 1, according to Gwet’s Ac1 and GI index (probability to concordance—e(K)—, by Cohen, of 0.52). LUS has a sensitivity of 1 (95% CI 0.398–1.0), specificity of 0.89 (95% CI 0.518–0.997), and a positive probability reason of 9.00 (95% CI 7.1–11.3) to detect ILD. The correlation of Pearson is r = 0.84 (p < 0.001). To check the accuracy of LUS to diagnose ILD, a completely bilateral criterion of yes/no for interstitial pattern was chosen, AUC reaches significance, 0.94 (0.07) (95% CI 0.81–1.0, p = 0.014). LUS reaches an excellent correlation to hrCT in Sjs affected with ILD, and might be a useful technique in daily clinical practice for the assessment of pulmonary disease in the sicca syndrome. © 2016 SIMI

The impact of denture related disease on the oral microbiome of denture wearers

Advances in healthcare over the last 100 years has resulted in an ever increasing elderly population. This presents greater challenges for adequate systemic and oral healthcare delivery. With increasing age there is a natural decline in oral health, leading to the loss of teeth and ultimately for some having to wear denture prosthesis. It is currently estimated that approximately one fifth of the UK and US populations have some form of removable prosthesis. The microbiology of denture induced mucosal inflammation is a pivotal factor to consider in denture care management, similar to many other oral diseases of microbial influence, such as caries, gingivitis and periodontitis. Dentures support the growth of microbial biofilms, structures commonly known as denture plaque. Microbiologically, denture stomatitis (DS) is a disease primarily considered to be of yeast aetiology, with the literature disproportionately focussed on Candida spp. However, the denture surface is capable of carrying up to 1011 microbes per milligram, the majority of which are bacteria. Thus it is apparent that denture plaque is more diverse than we assume. There is a fundamental gap in our understanding of the bacterial composition of denture plaque and the role that they may play in denture related disease such as DS. This is categorised as inflammation of the oral mucosa, a disease affecting around half of all denture wearers. It has been proposed that bacteria and fungi interact on the denture surface and that these polymicrobial interactions lead to synergism and increased DS pathogenesis. Therefore, understanding the denture microbiome composition is the key step to beginning to understand disease pathogenesis, and ultimately help improve treatments and identify novel targets for therapeutic and preventative strategies. A group of 131 patients were included within this study in which they provided samples from their dentures, palatal mucosa, saliva and dental plaque. Microbes residing on the denture surface were quantified using standard Miles and Misra culture technique which investigated the presence of Candida, aerobes and anaerobes. These clinical samples also underwent next generation sequencing using the Miseq Illumina platform to give a more global representation of the microbes present at each of these sites in the oral cavity of these denture wearers. This data was then used to compare the composition and diversity of denture, mucosal and dental plaque between one another, as well as between healthy and diseased individuals. Additional comparisons included denture type and the presence or absence of natural teeth. Furthermore, microbiome data was used to assess differences between patients with varying levels of oral hygiene. The host response to the denture microbiome was investigated by screening the patients saliva for the presence and quantification of a range of antimicrobial peptides that are associated with the oral cavity. Based on the microbiome data an in vitro biofilm model was developed that reflected the composition of denture plaque. These biofilms were then used to assess quantitative and compositional changes over time and in response to denture cleansing treatments. Finally, the systemic implications of denture plaque were assessed by screening denture plaque samples for the presence of nine well known respiratory pathogens using quantitative PCR. The results from this study have shown that the bacterial microbiome composition of denture wearers is not consistent throughout the mouth and varies depending on sample site. Moreover, the presence of natural dentition has a significant impact on the microbiome composition. As for healthy and diseased patients the data suggests that compositional changes responsible for disease progression are occurring at the mucosa, and that dentures may in fact be a reservoir for these microbes. In terms of denture hygiene practices, sleeping with a denture in situ was found to be a common occurrence. Furthermore, significant shifts in denture microbiome composition were found in these individuals when compared to the denture microbiome of those that removed their denture at night. As for the host response, some antimicrobial peptides were found to be significantly reduced in the absence of natural dentition, indicating that the oral immune response is gradually impaired with the loss of teeth. This study also identified potentially serious systemic implications in terms of respiratory infection, as 64.6% of patients carried respiratory pathogens on their denture. In conclusion, this is the first study to provide a detailed understanding of the oral microbiome of denture wearers, and has provided evidence that DS development is more complex than simply a candidal infection. Both fungal and bacterial kingdoms clearly play a role in defining the progression of DS. The biofilm model created in this study demonstrated its potential as a platform to test novel actives. Future use of this model will aid in greater understanding of host: biofilm interactions. Such findings are applicable to oral health and beyond, and may help to identify novel therapeutic targets for the treatment of DS and other biofilm associated diseases.

Physiological and symptomatic responses to cycling and walking in intermittent claudication

To shed light on the potential efficacy of cycling as a testing modality in the treatment of intermittent claudication (IC), this study compared physiological and symptomatic responses to graded walking and cycling tests in claudicants. Sixteen subjects with peripheral arterial disease (resting ankle: brachial index (ABI) < 0.9) and IC completed a maximal graded treadmill walking (T) and cycle (C) test after three familiarization tests on each mode. During each test, symptoms, oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (RER) and heart rate (HR) were measured, and for 10 min after each test the brachial and ankle systolic pressures were recorded. All but one subject experienced calf pain as the primary limiting symptom during T; whereas the symptoms were more varied during C and included thigh pain, calf pain and dyspnoea. Although maximal exercise time was significantly longer on C than T (690 +/- 67 vs. 495 +/- 57 s), peak VO2, peak VE and peak heart rate during C and T were not different; whereas peak RER was higher during C. These responses during C and T were also positively correlated (P < 0.05) with each other, with the exception of RER. The postexercise systolic pressures were also not different between C and T. However, the peak decline in ankle pressures from resting values after C and T were not correlated with each other. These data demonstrate that cycling and walking induce a similar level of metabolic and cardiovascular strain, but that the primary limiting symptoms and haemodynamic response in an individual's extremity, measured after exercise, can differ substantially between these two modes.

Weather variability, tides, and Barmah Forest Virus Disease in the Gladstone region, Australia

In this study we examined the impact of weather variability and tides on the transmission of Barmah Forest virus (BFV) disease and developed a weather-based forecasting model for BFV disease in the Gladstone region, Australia. We used seasonal autoregressive integrated moving-average (SARIMA) models to determine the contribution of weather variables to BFV transmission after the time-series data of response and explanatory variables were made stationary through seasonal differencing. We obtained data on the monthly counts of BFV cases, weather variables (e.g., mean minimum and maximum temperature, total rainfall, and mean relative humidity), high and low tides, and the population size in the Gladstone region between January 1992 and December 2001 from the Queensland Department of Health, Australian Bureau of Meteorology, Queensland Department of Transport, and Australian Bureau of Statistics, respectively. The SARIMA model shows that the 5-month moving average of minimum temperature (β = 0.15, p-value < 0.001) was statistically significantly and positively associated with BFV disease, whereas high tide in the current month (β = −1.03, p-value = 0.04) was statistically significantly and inversely associated with it. However, no significant association was found for other variables. These results may be applied to forecast the occurrence of BFV disease and to use public health resources in BFV control and prevention.

Correcting for bias when estimating the cost of hospital-acquired infection : an analysis of lower respiratory tract infections in non-surgical patients

Hospital acquired infections (HAI) are costly but many are avoidable. Evaluating prevention programmes requires data on their costs and benefits. Estimating the actual costs of HAI (a measure of the cost savings due to prevention) is difficult as HAI changes cost by extending patient length of stay, yet, length of stay is a major risk factor for HAI. This endogeneity bias can confound attempts to measure accurately the cost of HAI. We propose a two-stage instrumental variables estimation strategy that explicitly controls for the endogeneity between risk of HAI and length of stay. We find that a 10% reduction in ex ante risk of HAI results in an expected savings of £693 ($US 984).