Mobile resistome of human gut and pathogen drives anthropogenic bloom of antibiotic resistance

BACKGROUND:The impact of human activities on the environmental resistome has been documented in many studies, but there remains the controversial question of whether the increased antibiotic resistance observed in anthropogenically impacted environments is just a result of contamination by resistant fecal microbes or is mediated by indigenous environmental organisms. Here, to determine exactly how anthropogenic influences shape the environmental resistome, we resolved the microbiome, resistome, and mobilome of the planktonic microbial communities along a single river, the Han, which spans a gradient of human activities. RESULTS:The bloom of antibiotic resistance genes (ARGs) was evident in the downstream regions and distinct successional dynamics of the river resistome occurred across the spatial continuum. We identified a number of widespread ARG sequences shared between the river, human gut, and pathogenic bacteria. These human-related ARGs were largely associated with mobile genetic elements rather than particular gut taxa and mainly responsible for anthropogenically driven bloom of the downstream river resistome. Furthermore, both sequence- and phenotype-based analyses revealed environmental relatives of clinically important proteobacteria as major carriers of these ARGs. CONCLUSIONS:Our results demonstrate a more nuanced view of the impact of anthropogenic activities on the river resistome: fecal contamination is present and allows the transmission of ARGs to the environmental resistome, but these mobile genes rather than resistant fecal bacteria proliferate in environmental relatives of their original hosts. Video abstract

A Novel Magnetic Resonance Quality Assurance Phantom (KMRP-4): Multi-Site Comparison With the American College of Radiology Phantom

Purpose: To propose a novel standard magnetic resonance imaging (MRI) phantom, hereafter called the Korea Magnetic Resonance Phantom-4th edition (KMRP-4). Its related quality control (QC) assessment protocols and its comparison with the American College of Radiology (ACR) phantom and its QC assessment protocols. / Materials and Methods: Internally, the KMRP-4 phantom is composed of cubic and triangular vessels, brain tissue structures, and a uniform region designed to facilitate a variety of QC protocols. Using magnetic resonance (MR) images of these structures, we quantitatively evaluated a total of 10 parameters, seven from those of existing ACR protocols (i.e., geometric accuracy, high-contrast spatial resolution, slice thickness accuracy, slice position accuracy, image intensity uniformity, percent signal ghosting, and low-contrast object detectability) and three additional parameters for evaluating vessel conspicuity, brain tissue contrast, and signal-to-noise ratio (SNR) introduced in the KMRP-4 protocols. Twentyt-wo MRI systems of 0.32–3.0 T static magnetic field strength were tested using both ACR and KMRP-4 phantoms. Mann–Whitney U-tests were performed on the seven evaluation items of the ACR method to compare KMRP-4 and ACR methods. / Results: The results of Mann–Whitney U-test demonstrated that p-values were more than 0.05 for all seven items that could be assessed with both ACR and KMRP-4, indicating similar results between the two methods. Additionally, assessments of vessel conspicuity, brain tissue contrast, and SNR using the KMRP-4 method demonstrated utility of the KMRP-4 phantom. / Conclusion: A novel standard phantom and related QC methods were developed to perform objective, observer-independent, and semi-automatic QC tests. Quantitative comparisons of MR images with KMPR-4 and ACR phantoms were performed. Results demonstrated the utility of the newly proposed KMRP-4 phantom and its related QC methods

Mesenchymal Stem Cell-Extracellular Vesicle Therapy for Stroke: Scalable Production and Imaging Biomarker Studies

A major clinical hurdle to translate MSC-derived extracellular vesicles (EVs) is the lack of a method to scale-up the production of EVs with customized therapeutic properties. In this study, we tested whether EV production by a scalable 3D-bioprocessing method is feasible and improves neuroplasticity in animal models of stroke using MRI study. MSCs were cultured in a 3D-spheroid using a micro-patterned well. The EVs were isolated with filter and tangential flow filtration and characterized using electron microscopy, nanoparticle tracking analysis, and small RNA sequencing. Compared to conventional 2D culture, the production-reproduction of EVs (the number/size of particles and EV purity) obtained from 3D platform were more consistent among different lots from the same donor and among different donors. Several microRNAs with molecular functions associated with neurogenesis were upregulated in EVs obtained from 3D platform. EVs induced both neurogenesis and neuritogenesis via microRNAs (especially, miR-27a-3p and miR-132-3p)-mediated actions. EV therapy improved functional recovery on behavioral tests and reduced infarct volume on MRI in stroke models. The dose of MSC-EVs of 1/30 cell dose had similar therapeutic effects. In addition, the EV group had better anatomical and functional connectivity on diffusion tensor imaging and resting-state functional MRI in a mouse stroke model. This study shows that clinical-scale MSC-EV therapeutics are feasible, cost-effective, and improve functional recovery following experimental stroke, with a likely contribution from enhanced neurogenesis and neuroplasticity

Successful management of heterotopic cornual pregnancy with laparoscopic cornual resection

AbstractObjectiveTo examine the feasibility of laparoscopic cornual resection for the treatment of heterotopic cornual pregnancy.Study designWomen who underwent laparoscopic cornual resection for heterotopic cornual pregnancy at our hospital between January 2003 and March 2015 were retrospectively analyzed. We evaluated significant parameters such as operative complications and postoperative pregnancy outcomes of concomitant pregnancy.ResultsThirteen patients with heterotopic cornual pregnancy were included in the study. All were pregnant through assisted reproductive technology, and the diagnosis was made at a median of 6+6 weeks (range 5+4–10+0). They were successfully treated with laparoscopic cornual resection and admitted for a median of 4 days (range, 2–7) postoperatively. The median operative time was 65min (range, 35–145min) and estimated blood loss was 200mL (range, 10–3000mL). There was a spontaneous abortion at 7+6 gestational weeks in a patient who received bilateral cornual resection. Seven patients delivered babies at term and 3 at preterm. All 10 women delivered without any maternal or neonatal complications. Two were lost to follow-up.ConclusionsLaparoscopic cornual resection is a feasible primary approach for the management of heterotopic cornual pregnancy

Wireless thin film transistor based on micro magnetic induction coupling antenna

A wireless thin film transistor (TFT) structure in which a source/drain or a gate is connected directly to a micro antenna to receive or transmit signals or power can be an important building block, acting as an electrical switch, a rectifier or an amplifier, for various electronics as well as microelectronics, since it allows simple connection with other devices, unlike conventional wire connections. An amorphous indium gallium zinc oxide (α-IGZO) TFT with magnetic antenna structure was fabricated and studied for this purpose. To enhance the induction coupling efficiency while maintaining the same small antenna size, a magnetic core structure consisting of Ni and nanowires was formed under the antenna. With the micro-antenna connected to a source/drain or a gate of the TFT, working electrical signals were well controlled. The results demonstrated the device as an alternative solution to existing wire connections which cause a number of problems in various fields such as flexible/wearable devices, body implanted devices, micro/nano robots, and sensors for the 'internet of things' (IoT).1

Combining SGLT2 Inhibition With a Thiazolidinedione Additively Attenuate the Very Early Phase of Diabetic Nephropathy Progression in Type 2 Diabetes Mellitus

Although both sodium glucose co-transporter 2 inhibition by dapagliflozin and thiazolidinedione, pioglitazone have glucose-lowering and anti-inflammatory effects, the therapeutic efficacy of their combination on diabetic nephropathy has not been investigated. 9-week-old male db/db mice were randomly assigned to 4 groups and administrated with (1) vehicle, (2) dapagliflozin, (3) pioglitazone, or (4) dapagliflozin and pioglitazone combination. Human proximal tubule (HK-2) cells were treated with glucose or palmitate acid in the presence of medium, dapagliflozin, pioglitazone, or both. Glomerular tuft area and mesangial expansion of the kidney more reduced in the combination group compared to control and single therapy groups. Podocyte foot process width and glomerular basement membrane thickness decreased regardless of treatment, while the combination group showed the slowest renal hypertrophy progression (P < 0.05). The combination treatment decreased MCP-1, type I and IV collagen expression in the renal cortex. Only the combination treatment decreased the expression of angiotensinogen, IL-6, and TGF-β while it enhanced HK-2 cell survival (all P < 0.05). In conclusion, dapagliflozin and pioglitazone preserved renal function, and combination therapy showed the greatest benefit. These findings suggest that the combination therapy of dapagliflozin with pioglitazone is more effective than the single therapy for preventing the progression of nephropathy in patients with type 2 diabetes

Risk of Incident Dementia According to Metabolic Health and Obesity Status in Late Life: A Population-Based Cohort Study.

CONTEXT: The risk for dementia among subjects who are obese with normal metabolic profiles, or called metabolically healthy obese (MHO), remains uninvestigated. OBJECTIVE: To determine the association between late-life metabolic health and obesity status and risk of incident dementia. DESIGN: Retrospective cohort study. SETTING: The National Health Insurance System, Republic of Korea. PATIENTS: A total of 12,296,863 adults >50 years old who underwent health examinations from 2009 to 2012 without baseline history of dementia. MAIN OUTCOME MEASURE: Incident overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: Among subjects ≥60 years old, 363,932 (6.4%) developed dementia during a median follow-up of 65 months (interquartile range 51 to 74 months). The MHO group showed the lowest incidence of overall dementia [hazard ratio (HR) 0.85; 95% CI, 0.84 to 0.86] and AD (HR 0.87; 95% CI, 0.86 to 0.88), but not VaD, compared with the metabolically healthy nonobese group. All components of metabolic syndrome except obesity significantly elevated the risk of dementia, and these associations were more pronounced in VaD. In particular, being underweight dramatically increased the risk of dementia. CONCLUSIONS: The MHO phenotype in late life demonstrated lower risk of overall dementia and AD but not VaD. Additional studies in other populations are warranted to elucidate current results and may predict individuals most at risk for developing dementia

Case report: A novel occurrence of persistent left cranial vena cava coexisting with polycystic kidney disease in a cat

A 7-year-old castrated male Munchkin cat was presented with anorexia. This cat had been diagnosed with chronic kidney disease due to polycystic kidney disease. Tachycardia with a systolic murmur (grade III/VI) was auscultated and for further diagnosis, echocardiography was performed. Based on echocardiography, persistent left cranial vena cava (PLCVC) was suspected due to enlargement of the coronary sinus and confirmed by saline contrast echocardiography. The dilated coronary sinus compressed the left atrium, and left ventricular hypertrophy with the systolic anterior motion of the mitral valve, aortic regurgitation, and mitral regurgitation were identified. After medical management using atenolol, left atrial function and other hemodynamics of the heart were improved, including the disappearance of regurgitation and normalization of left ventricular wall thickness. This case report describes the echocardiographic characteristics, diagnostic procedures, and disease progression in a cat with PLCVC after medical management using atenolol. Additionally, this is the first report of a cat with PLCVC, coexisting with polycystic kidney disease