Evaluation of an accelerated protocol for detection of extended-spectrum beta-lactamase-producing gram-negative bacilli from positive blood cultures

We evaluated a protocol for the accelerated detection of extended-spectrum beta-lactamases (ESBLs) in gram-negative bloodstream pathogens. Two hundred eighty-three blood culture bottles were subjected to direct ESBL testing by inoculating samples directly from blood culture bottles onto agar plates containing cefotaxime and ceftazidime disks, with and without clavulanate. Standard ESBL testing in accordance with the NCCLS guidelines after subculturing on agar plates was performed in parallel. Results of the direct ESBL testing were reported 2.3 days sooner and were comparable to those of the standard NCCLS method with sensitivity, specificity, and positive and negative predictive values of 100, 98, 94, and 100%, respectively.     

Percutaneous absorption of physostigmine: optimization of delivery from a binary solvent by thermodynamic control

A series of binary vehicles was used to deliver physostigmine across dermatomed human skin. The vehicles consisted of isopropyl myristate (IPM) and isopropyl alcohol (IPA) mixed in various volume fractions. The kinetics of penetration is conveniently considered as the sum total of two contributing effects: a "push" process resulting from the excess free energy (delta EG) of the penetrant in the donor vehicle, and a "pull" process resulting from the effect of IPA and IPM on the skin barrier. The inverse ratio of the solubility of the drug in a given vehicle to that in pure IPA was used to estimate the relative delta EG, hence the relative "push" effect. The solubility of physostigmine was highest in pure IPA (delta = 11.5), lowest in pure IPM (delta = 8.5), and intermediate in their various mixtures. But the permeability coefficient (Kp) of physostigmine was highest when delivered from a 1:9 (v/v) solution of IPA:IPM and a calculated delta y = 8.8. A further increase in the volume fraction of IPA caused an opposite decrease in the Kp values of physostigmine. The "steady-state" flux (Jss) of IPA from the same vehicle was lowest at a volume fraction of 1:9 and highest at one of 1:1 IPA:IPM. Thus, the maximal physostigmine penetration enhancing effect of IPA occurs at the lowest flux of IPA found in the present series. This indicates that the "pull" process ascribed to the presence of IPA in the barrier membrane is not important enough to outweigh the decrease in delta EG of physostigmine following an increase in the volume fraction of IPA in the donor vehicle, or that an excess of IPA in the barrier is not conducive to further enhancement of physostigmine diffusivity across the barrier. Optimized percutaneous delivery of physostigmine is possible by thermodynamic control of the penetration process.     

In vitro-derived insulin-producing cells modulate Th1 immune responses and induce IL-10 in streptozotocin-induced mouse model of pancreatic insulitis

Background: Insulitis is defined by the presence of immune cells infiltrating in the pancreatic islets that might progress into the complete β-cell loss. The immunomodulatory properties of bone marrow-derived mesenchymal stem cells(BM-MSCs) have attracted much attention. This study aimed to evaluate the possible immunomodulatory effects of rat BM-MSCs and MSCs-derived insulin-producing cells(IPCs) in a mouse model of pancreatic insulitis. Methods: Insulitis was induced in BALB/c mice using five consecuti ve doses of streptozotocin. MSCs or IPCs were directly injected into the pancreas of mice and their effects on the expression of Th subsetsrelated genes were evaluated. Results: Both BM-MSCs and IPCs significantly reduced the expression of pancreatic Th1-related IFN-γ( P 0.001 and P 0.05, respectively) and T-bet genes(both P 0.001). Moreover, the expression of IL-10 gene was significantly increased in IPC-treated compared to BM-MSC-or PBS-treated mice( P 0.001 both comparisons). Conclusions: BM-MSCs and IPCs could successfully suppress pathologic Th1 immune responses in the mouse model of insulitis. However, the marked increase in IL-10 gene expression by IPCs compared to BM-MSCs suggests that their simultaneous use at the initial phase of autoimmune diabetes might be a better option to reduce inflammation but these results need to be verified by further experiments.     

Robust-Deep: A Method for Increasing Brain Imaging Datasets to Improve Deep Learning Models’ Performance and Robustness

A small dataset commonly affects generalization, robustness, and overall performance of deep neural networks (DNNs) in medical imaging research. Since gathering large clinical databases is always difficult, we proposed an analytical method for producing a large realistic/diverse dataset. Clinical brain PET/CT/MR images including full-dose (FD), low-dose (LD) corresponding to only 5 % of events acquired in the FD scan, non-attenuated correction (NAC) and CT-based measured attenuation correction (MAC) PET images, CT images and T1 and T2 MR sequences of 35 patients were included. All images were registered to the Montreal Neurological Institute (MNI) template. Laplacian blending was used to make a natural presentation using information in the frequency domain of images from two separate patients, as well as the blending mask. This classical technique from the computer vision and image processing communities is still widely used and unlike modern DNNs, does not require the availability of training data. A modified ResNet DNN was implemented to evaluate four image-to-image translation tasks, including LD to FD, LD+MR to FD, NAC to MAC, and MRI to CT, with and without using the synthesized images. Quantitative analysis using established metrics, including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), and joint histogram analysis was performed for quantitative evaluation. The quantitative comparison between the registered small dataset containing 35 patients and the large dataset containing 350 synthesized plus 35 real dataset demonstrated improvement of the RMSE and SSIM by 29% and 8% for LD to FD, 40% and 7% for LD+MRI to FD, 16% and 8% for NAC to MAC, and 24% and 11% for MRI to CT mapping task, respectively. The qualitative/quantitative analysis demonstrated that the proposed model improved the performance of all four DNN models through producing images of higher quality and lower quantitative bias and variance compared to reference images.     

Neonatal hyperthyrotropinemia: population characteristics,diagnosis, management and outcome after cessation of therapy

Introduction Neonatal hyperthyrotropinaemia (HT), defined by elevated TSH and normal T₄, is either transient or persistent. The eventual outcome of neonatal HT is unpredictable and the management of HT patients is controversial. We assessed perinatal parameters and diagnostic measures that may distinguish between transient and persistent HT, compared with congenital hypothyroidism (CH). We also aimed to recommend optimal treatment in these forms of thyroid impairment. Design and patients A multi‐centre, retrospective study was conducted in six paediatric endocrinology units. Forty‐three HT patients and 83 CH patients were included in the study. Measurements We evaluated differences in birth weight (BW), gestational age (GA), modes of diagnosis, screening and confirmatory T₄ and TSH levels, thyroid imaging results and optimal thyroxine doses between HT and CH and between the two forms of HT. Results Newborns with HT had lower BW and GA than those with CH. Transient (n = 18) and persistent HT (n = 25) patients were indistinguishable by most parameters, but those with persistent HT had a higher prevalence of abnormal thyroid imaging (69%vs 8%; P = 0·005). During treatment, 79% and 55% of transient and persistent HT patients respectively experienced elevated levels of free T_4. Although most HT patients were reevaluated after 2·5 years, six transient HT patients stopped therapy and showed full recovery within the first year of life. Conclusions We recommend obtaining thyroid imaging to distinguish between the two forms of HT. Adherence to recommended doses of thyroxine and probably early cessation of therapy in transient HT can prevent iatrogenic hyperthyroidism in these patients.     

Determination of heavy metals in albumen of hen eggs from the Markazi Province (Iran) using ICP-OES technique

Increase of distribution of environmental contaminants such as heavy metals have been caused the knowledge of the safety and hygiene of food is very important, especially eggs, because of its role in the daily diet. There are very few studies about the investigation of the heavy metal contents in egg-white. In this study, six heavy metals include Aluminium (Al), Arsenic (As), Lead (Pb), Cadmium (Cd), Mercury (Hg), Antimony (Sb) in egg-white from 32 industrial poultry farms were investigated, by ICP-OES. All the samples were collected in all area of Markazi Province, Iran in autumn 2013. The mean concentrations of heavy metals in egg-white as follows: 0.119 for Al, 0.785 for As, 0.750 for Pb, 0.249 for Cd, 0.270 for Hg and 0.186?mg/kg for Sb. Also, the concentration of the some heavy metals were higher than maximum allowable concentration that probably it is associated to use pesticides and activities of industrial factories around the poultry farms.     

Gastrointestinal colonization by KPC-producing Klebsiella pneumoniae following hospital discharge: duration of carriage and risk factors for persistent carriage

The natural history of KPC-producing Klebsiella pneumoniae (KPC KP) carriage is unknown. We aimed to examine the duration of KPC KP carriage following hospital discharge and to study the risk factors for persistent carriage. A cohort of 125 KPC KP carriers was followed monthly for between 3 and 6 months after discharge from an acute-care hospital. Rectal swabs and data were collected at baseline and at each visit. KPC KP was detected by culture and direct bla_KPC PCR. Acquisition time was regarded as the earliest date of KPC KP isolation. Resolution of carriage was defined as a negative KPC KP test in at least two consecutive samples. Analyses were separated for recent (<4 months) (REC, 75 patients) and remote (≥4 months) (REM, 50 patients) acquisition groups. Risk factors for persistent carriage were examined by survival analyses for the REC group and by prevalence methods for the REM group. The mean age of patients was 67.5 years and 49.6% were male. Forty-six (61%) patients in the REC group and 14 (28%) in the REM group were persistent carriers (p < 0.001). A significant risk factor for persistent carriage identified in both the REC and REM groups was the presence of any catheter (p < 0.05). Unique risk factor groups included long-term care facility (LTCF) residence (p < 0.01) and a low functional status as measured by the Barthel’s index (p < 0.05) in the REC group and high Charlson’s score in the REM group (p < 0.05). Out of the entire 100 patients who had at least one negative sample, only 65 remained negative on subsequent cultures. In conclusion, persistent carriage of KPC KP is associated with catheter use and a low functional status; it is more common in patients with recent acquisition and is related to LTCF stay. A single negative KPC KP test is insufficient to exclude persistent carriage.     

Lysosomal cholesterol accumulation: driver on the road to inflammation during atherosclerosis and non‐alcoholic steatohepatitis

Many studies show an association between the accumulation of cholesterol inside lysosomes and the progression towards inflammatory disease states that are closely related to obesity. While in the past, the knowledge regarding lysosomal cholesterol accumulation was limited to its association with plaque severity during atherosclerosis, recently, a growing body of evidence indicates a causal link between lysosomal cholesterol accumulation and inflammation. These findings make lysosomal cholesterol accumulation an important target for intervention in metabolic diseases that are characterized by the presence of an inflammatory response. In this review, we aim to show the importance of cholesterol trapping inside lysosomes to the development of inflammation by focusing upon cardiovascular disease and non‐alcoholic steatohepatitis (NASH) in particular. We summarize current data supporting the hypothesis that lysosomal cholesterol accumulation plays a key role in the development of inflammation during atherosclerosis and NASH. In addition, potential mechanisms by which disturbed lysosomal function can trigger the inflammatory response, the challenges in improving cholesterol trafficking in macrophages and recent successful research directions will be discussed.