Neuromodulation and ablation with focused ultrasound-toward the future of noninvasive brain therapy

<正>With an aging patient population and an increased burden of neurological disease, the demand for noninvasive alternatives to open neurosurgical procedures is imperative. Noninvasive or minimally invasive approaches to targeting brain regions include transcranial magnetic stimulation(TMS), transcranial direct current stimulation, temporally interfering electric fields, and focused ultrasound(FUS). Among these modalities, FUS offers a unique combination     

Rethinking the uncertainty of African swine fever virus contamination in feed ingredients and risk of introduction into the United States

Economically relevant pathogens, such as African swine fever virus (ASFV), have been shown to survive when experimentally inoculated in some feed ingredients under the environmental conditions in transoceanic transport models. However, these models did not characterize the likelihood of virus survival under various time and temperature processes that feed ingredients undergo before they are added to swine diets. Here, we developed a quantitative risk assessment model to estimate the probability that one or more corn or soybean meal ocean vessels (25,000 tonnes) contaminated with ASFV would be imported into the United States annually. This final probability estimate was conditionally based on five likelihoods: the probability of initial ASFV contamination (p0), ASFV inactivation during processing (p1) and transport (p2), recontamination (pR), and ASFV inactivation while awaiting customs clearance at United States entry (p3). The probability of ASFV inactivation was modelled using corn and soybean (extruded or solvent extracted) processing conditions (times and temperatures), D-values (time to reduce 90% or 1-log) estimated from studies of ASFV thermal inactivation in pork serum (p1), and survival in feed ingredients during transoceanic transport (p2 and p3). ‘What-if’ scenarios using deterministic values for p0 and pR (1%, 10%, 25%, 50%, 75%, and 100%) were used to explore their impact on risk. The model estimated complete inactivation of ASFV after extrusion or solvent extraction processes regardless of the initial ASFV contamination probability assumed. The value of recontamination (ranging from 1% to 75%) was highly influential on the risk of one ASFV-contaminated soybean meal vessel entering the United States. Median risk estimates ranged from 0.064% [0.006%–0.60%; 95% probability interval (PI)], assuming a pR of 1.0%, up to 4.67% (0.45%–36.50% 95% PI) assuming a pR of 75.0%. This means that at least one vessel with ASFV-contaminated soybean meal would be imported once every 1563–21 years, respectively. When all raw corn was assumed to be contaminated (p0 = 100%), and no recontamination was assumed to occur (pR = 0%), the median probability of one vessel with ASFV-contaminated corn entering the United States was 2.02% (0.28%–9.43% 95% PI) or once every 50 years. Values of recontamination between 1% and 75% did not substantially change the risk of corn. Days of transport, virus survival during transport (D-value), and number of vessels shipped were the parameters most influential for increased likelihood of a vessel with ASFV-contaminated soybean meal or corn entering the United States. The model helped to identify knowledge gaps that are most influential on output values and serves as a framework that could be updated and parameterized as new scientific information becomes available. We propose that the quantitative risk assessment model developed in this study can be used as a framework for estimating the risk of ASFV entry into the United States and other ASFV-free countries through other types of imported feed ingredients that may potentially become contaminated. Ultimately, this model can be used to develop risk mitigation strategies and critical control points for inactivating ASFV during feed ingredient processing, storage, and transport, and contribute to the design and implementation of biosecurity measures to prevent the introduction of ASFV into the United States and other ASFV-free countries.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

Mycobacterium abscessus Complex Identification with Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

We determined that the Vitek MS Plus matrix-assisted laser desorption ionization–time of flight mass spectrometry using research-use-only (RUO) v.4.12 and in vitro-diagnostic (IVD) v.3.0 databases accurately identified 41 Mycobacterium abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates identified by whole-genome sequencing to the species but not the subspecies level, from Middlebrook 7H11 and Burkholderia cepacia selective agars. Peak analysis revealed three peaks potentially able to differentiate between subspecies.     

An Optimized Mouse Thigh Infection Model for Enterococci and Its Impact on Antimicrobial Pharmacodynamics

Negligible in vivo growth of enterococci and high-level dispersion of data have led to inaccurate estimations of antibiotic pharmacodynamics (PD). Here we improved an in vivo model apt for PD studies by optimizing the in vitro culture conditions for enterococci. The PD of vancomycin (VAN), ampicillin-sulbactam (SAM), and piperacillin-tazobactam (TZP) against enterococci were determined in vivo, comparing the following different conditions of inoculum preparation: aerobiosis, aerobiosis plus mucin, and anaerobiosis plus mucin. Drug exposure was expressed as the ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC) (VAN) or the time in a 24-h period that the drug concentration for the free, unbound fraction exceeded the MIC under steady-state pharmacokinetic conditions (fT_>MIC) (SAM and TZP) and linked to the change in log₁₀ CFU/thigh. Only anaerobiosis plus mucin enhanced the in vivo growth, yielding significant PD parameters with all antibiotics. In conclusion, robust in vivo growth of enterococci was crucial for better determining the PD of tested antibacterial agents, and this was achieved by optimizing the procedure for preparing the inoculum.