Dosimetry Analysis in Non-brain Tissues During TMS Exposure of Broca's and M1 Areas.

For human protection, the internal electric field is used as a dosimetric quantity for electromagnetic fields lower than 5-10 MHz. According to international standards, in this frequency range, electrostimulation is the main adverse effect against which protection is needed. One of the topics to be investigated is the quantification of the internal electric field threshold levels of perception and pain. Pain has been reported as a side effect during transcranial magnetic stimulation (TMS), especially during stimulation of the Broca's (speech) area of the brain. In this study, we designed an experiment to conduct a dosimetry analysis to quantify the internal electric field corresponding to perception and pain thresholds when targeting the Broca's and M1 areas from magnetic stimulator exposure. Dosimetry analysis was conducted using a multi-scale analysis in an individualized head model to investigate electrostimulation in an axonal model. The main finding is that the stimulation on the primary motor cortex has higher perception and pain thresholds when compared to Broca's area. Also, TMS-induced electric field applied to Broca's area exhibited dependence on the coil orientation at lower electric field threshold which was found to be related to the location and thickness of pain fibers. The derived dosimetry quantities provide a scientific rationale for the development of human protection guidelines and the estimation of possible side effects of magnetic stimulation in clinical applications.

Factors associated with falls in Japanese polio survivors.

Purpose: To identify factors associated with falls in Japanese polio survivors and assess the extent of their impact.Materials and methods: Subjects were 128 polio survivors. Fall history and fear of falling, lower limb muscle strength, gait ability (determined by walking speed and number of steps per day), post-polio syndrome incidence, and orthosis or walking aid use were assessed, and factors associated with falls were identified using logistic regression analysis.Results: The fall rate was 64%. Fallers (subjects with one or more falls in the preceding 12 months) had low lower limb muscle strength, slow walking speed, high total scores on the Fall Efficacy Scale-International, which assesses fear of falling, and a high orthosis use rate. Knee extension muscle strength on the weaker side was identified as a main factor influencing risk of falls (odds ratio: 0.72, 95% confidence interval: 0.56-0.96). Receiver operating characteristic curve analysis gave a cutoff value for knee extension muscle strength on the weaker side of 0.42 N/kg or lower.Conclusion: Low knee extension muscle strength on the weaker side was associated with falls, but predictive ability using a single internal factor might be poor. It appears that a comprehensive examination, including other factors, is required.Implications for rehabilitationAs polio survivors age, their risk of falling increases.To identify polio survivors who are at risk of falls, it is important to determine the factors associated with falls and their influence on fall risk.The results of this study showed that reduced knee extension muscle strength on the weaker side was a risk factor for falls in polio survivors.To precisely predict the risk of falls in polio survivors, a comprehensive evaluation of both internal and external factors is required.

Breeding of a new potato variety 'Nagasaki Kogane' with high eating quality, high carotenoid content, and resistance to diseases and pests.

'Nagasaki Kogane' is a new potato variety bred from a cross between 'Saikai 35' as a female parent and 'Saikai 33' as a male. 'Saikai 35' is resistant to bacterial wilt, contains the H1 and Rychc genes for resistance to the potato cyst nematode (PCN) and potato virus Y (PVY), respectively, and has high carotenoid content, while 'Saikai 33' has large and high-yielding tubers and is resistant to both bacterial wilt and PCN. The carotenoid content of 'Nagasaki Kogane' is higher than that of 'Dejima', a common double cropping variety. The taste quality of steamed 'Nagasaki Kogane' is comparable to that of 'Inca-no-mezame' tubers, which has high levels of carotenoid, and superior to 'Nishiyutaka', another popular double cropping variety. 'Nagasaki Kogane' is suitable for French fries, because its tuber has high starch content. The marketable yield of 'Nagasaki Kogane' was higher than that of 'Inca-no-mezame' in spring cropping, although it was lower than that of 'Nishiyutaka' in double cropping regions. 'Nagasaki Kogane' tubers are larger on average than 'Inca-no-mezame' tubers in spring cropping. Moreover, the 'Nagasaki Kogane' variety is resistant to PCN and PVY, and exhibits a high level of resistance to bacterial wilt.

Randomized controlled comparative study on effect of training to improve lower limb motor paralysis in convalescent patients with post-stroke hemiplegia.

[Purpose] The motor paralysis-improving effect on the hemiplegic lower limb was compared among mirror therapy, integrated volitional-control electrical stimulation, therapeutic electrical stimulation, repetitive facilitative exercises, and the standard training method in post-stroke hemiplegia patients. [Subjects and Methods] Eighty one stroke patients admitted to a convalescent rehabilitation ward were randomly allocated to the above 5 treatment groups. Each patient performed functional training of the paralytic lower limb for 20 minutes a day for 4 weeks, and changes in the lower limb function were investigated using the Stroke Impairment Assessment Set. [Results] The hip and knee joint functions did not significantly improve in the standard training control group, but significant improvements were observed after 4 weeks in the other intervention groups. Significant improvement was noted in the ankle joint function in all groups. [Conclusion] Although the results were influenced by spontaneous recovery and the standard training in the control group, the hip and knee joints were more markedly improved by the interventions in the other 4 groups of patients with moderate paralysis, compared to the control group.

In vitro and in vivo antibacterial activity of T-3912, a novel non-fluorinated topical quinolone.

The in vitro and in vivo activity of T-3912, a novel non-fluorinated topical quinolone, was compared with that of nadifloxacin, ofloxacin, levofloxacin, clindamycin, erythromycin and gentamicin. The in vitro activity of T-3912 against methicillin-susceptible Staphylococcus aureus, ofloxacin-resistant and methicillin-resistant S. aureus, Staphylococcus epidermidis, ofloxacin-resistant S. epidermidis, penicillin-resistant Streptococcus pneumoniae and Propionibacterium acnes was four-fold to 16 000-fold greater than that of other agents at the MIC90 for the clinical isolates. The activity of T-3912 was not influenced by grlA mutation in S. aureus, and the degree of MIC increase of T-3912 for grlA-gyrA double and triple mutants was lowest among the quinolones tested (nadifloxacin, levofloxacin and ofloxacin). The inhibitory activity of T-3912 was compared with other quinolones for DNA gyrase and topoisomerase IV of S. aureus SA113. T-3912 showed the greatest inhibitory activity for both enzymes among the quinolones tested. The isolation frequency of spontaneous mutants resistant to T-3912 was < 1.7 x 10(-9) and < 2.0 x 10(-9) for S. aureus SA113 and P. acnes JCM 6425, respectively. Furthermore, resistance to T-3912 could not be clearly detected in the 28th transfer by the serial passage method. T-3912 exhibited more potent bactericidal activity against S. aureus and P. acnes than nadifloxacin and clindamycin in a short time period. T-3912 in a 1% gel formulation showed good therapeutic activity against a burn infection model caused by S. aureus SA113, P. acnes JCM6425 and multidrug-resistant S. aureus F-2161. These results indicate that T-3912 is potentially a useful quinolone for the treatment of skin and soft-tissue infections and that its potent bactericidal activity might be able to shorten the treatment period.

Synthesis, antibacterial activity, and toxicity of 7-(isoindolin-5-yl)-4-oxoquinoline-3-carboxylic acids. Discovery of the novel des-F(6)-quinolone antibacterial agent garenoxacin (T-3811 or BMS-284756).

The palladium-catalyzed cross-coupling reaction of 5-(tributylstannyl)isoindoline and its 1- and 3-methyl derivatives with 6-fluoro or 6-unsubstituted 7-bromo-1-cyclopropyl-8-methoxy (or difluoromethoxy)-4-oxoquinoline-3-carboxylate afforded the corresponding 1-cyclopropyl-7-(5-isoindolinyl)-4-oxoquinoline-3- carboxylic acids: 6-fluoro, 1a-7a and 6-nonfluoro, 1b-7b. The in vitro antibacterial spectra of the newly synthesized quinolones were mostly characterized by excellent Gram-positive activity against Staphylococcus aureus and Streptococcus pneumoniae including quinolone-resistant strains, and also by significant Gram-negative activity comparable to 7-(1-piperazinyl)fluoroquinolones. Comparative examinations of the in vitro antibacterial profiles and the in vivo toxicity in terms of intravenous lethality, micronuclei-inducing potential and convulsive activity provided 6-nonfluorinated 1-cyclopropyl-8-(difluoromethoxy)-7-(1-methylisoindolin-5-yl)-4- oxoquinoline-3-carboxylic acid [(+/-)-5b] as the candidate for evaluation of the stereoisomers. The enantiomers (R)-5b and (S)-5b were synthesized via the Suzuki coupling reaction of (R)- and (S)-1-methyl derivatives of 2-(triphenylmethyl)isoindolin-5-boronic acid with the corresponding 7-bromo-8-(difluoromethoxy)-4- oxoquinoline-3-carboxylate. The (R)-5b stereoisomer proved to be 2- to 4-fold more active than the (S)-5b stereoisomer against the organisms tested, with the exception of an equal potency observed with S. pneumoniae IID553 and Haemophilus influenzae ATCC49247. A noticeable in vitro antibacterial profile of (R)-5b was that it is 16- and 64-fold more active than levofloxacin (CAS 100986-85-4) and ciprofloxacin (CAS 86393-32-0), respectively, against Mycoplasma pneumoniae IID813 (MIC of 0.0313 microgram/ml), and 4-fold more active than ciprofloxacin and levofloxacin against Mycobacterium tuberculosis M-4 (MIC of 0.0313 microgram/ml). Additional studies indicate that (R)-5b (T-3811, CAS 194804-75-6) exhibits excellent antibacterial activity against a wide range of organisms including anaerobes and common respiratory pathogens, while demonstrating a high selectivity against the mammalian homolog topoisomerases. The methane-sulfonate of (R)-5b (T-3811ME, CAS 223652-90-2) is now undergoing clinical testings.