[Writing Medical Papers in Comfortable English to be Accepted by Internationally High Class Journals].

A Japanese medical paper grammatically translated into English may not be accepted by elite international journals. The problem lies not with the language, but the title and structure of the Japanese papers. Indicative titles must be changed to informative titles. The introduction should consist of current knowledge, unknowns, and problems of the subject discussed. The discussion section may end with words stressing the value of the conclusion. In Japanese, medical terms comprise nouns, whereas in English, nouns and verbs are used in medical terms. The right usage of medical verbs, omission of unnecessary words and phrases common in Japanese papers, and "simple and clear statements" would improve the flow of English. For example, "Complete removal of the tumor of the patient was performed" may be rephrased as "The tumor was completely removed;" omitting the unnecessary word "patient," improved the flow of the English.

[Effective Education of Foreign Languages Based on the Brain Mechanism].

Wernicke's receptive speech area in a multilingual has separately located areas, each specific for a respective language. Such specific areas will not be established by learning respective languages through grammatical literal translation. Effective foreign language education is to establish a restricted area within the receptive speech area specific to the language to be learned by listening and conversation training.

Determination of 3-hydroxypropylmercapturic acid in urine by three column-switching high-performance liquid chromatography with electrochemical detection using a diamond electrode.

A three column-switching high-performance liquid chromatography (HPLC) using an electrochemical detector (ECD) equipped with a diamond electrode was established to determine 3-hydroxypropylmercapturic acid (3-HPMA) in urine. An extracted urine sample was consecutively fractionated using a strong anion-exchange column (first column) and a C8 column (second column) via a switching valve before application on an Octa Decyl Silyl (ODS) column (third column), followed by ECD analysis. The% recovery of 3-HPMA standard throughout the three-column process and limit of detection (LOD) were 94±1% and 0.1pmol, respectively. A solid phase extraction step is required for the sensitive analysis of 3-HPMA in urine by column-switching HPLC-ECD despite a decreased% recovery (55%) of urine sample spiked with 100pmol of 3-HPMA. To test the utility of our column-switching HPLC-ECD method, 3-HPMA levels of 27 urine samples were determined, and the correlation between HPLC-ECD and LC-Electrospray ionization (ESI)-MS/MS method was examined. As a result, the median values of µmol 3-HPMA/g Creatinine (Cre) in urine obtained by column-switching HPLC-ECD and LC-MS/MS were 2.19±2.12µmol/g Cre and 2.13±3.38µmol/g Cre, respectively, and the calibration curve (y=1.5171x-1.007) exhibited good linearity within a defined range (r2=0.907). These results indicate that the combination of column-switching HPLC and ECD is a powerful tool for the specific, reliable detection of 3-HPMA in urine.

Distinguishing mild cognitive impairment from Alzheimer's disease with acrolein metabolites and creatinine in urine.

BACKGROUND: We previously reported that the level of urinary 3-hydroxypropyl mercapturic acid (3-HPMA)/creatinine (Cre) was reduced following stroke. The aim of this study was to determine whether the level of 3-HPMA/Cre in urine was reduced in subjects with dementia. METHODS: The level of 3-HPMA was measured by LC-MS/MS, and that of amino acid conjugated acrolein (AC-Acro) was by ELISA. The study included 128 elderly subjects divided into 74 non-demented (control), 22 mild cognitive impairment (MCI) and 32 Alzheimer's disease (AD) subjects. RESULTS: The urinary 3-HPMA/Cre and AC-Acro/Cre in MCI plus AD subjects were significantly lower than those in control subjects. In addition, urinary Cre in AD subjects was significantly higher than that in MCI subjects, and 3-HPMA/Cre and AC-Acro/Cre in AD subjects were significantly lower than that in MCI subjects. Among these three markers, the lower 3-HPMA/Cre ratio was most strongly correlated with the decline of MMSE (Mini-Mental State Examination) and the increase in CDRsob (Clinical Dementia Rating Scale Sum of Boxes Scores). Furthermore, reduction in 3-HPMA/Cre in urine was well correlated with increase in Aß40/42 in plasma in demented subjects. CONCLUSION: The results indicate that 3-HPMA/Cre in urine is the most reliable biochemical marker to distinguish AD subjects from MCI subjects among three markers.

Utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy as adjunct techniques for screening and predicting dementia due to Alzheimer's disease in clinical practice.

We validated the utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy (1H MRS) as an adjunct screening technique for dementia due to Alzheimer's disease (AD). We examined the posterior cingulate gyri of 228 subjects using VSRAD and 1H MRS in addition to conventional cerebrospinal fluid biomarkers at baseline. At the 3-year follow-up, the 228 subject were classified as follows: 93 healthy subjects, 42 MCI-non-converters (MCI-NC), 25 MCI-converters to AD (MCI-C), 44 AD, 8 dementia with Lewy bodies (DLB), 5 normal pressure hydrocephalus, and 11 patients with other neurological diseases. Our results demonstrated that subjects with increased medial temporal atrophy (MTA) severity on VSRAD, increased Cho/Cr, MI/Cr ratio, and decreased NAA/Cr and NAA/MI ratio on 1H MRS at baseline were at risk of dementia due to AD. Receiver operating characteristic analysis showed that severity of MTA and the NAA/MI ratio distinguished patients with AD and MCI-C from controls. Furthermore, the 118 subjects without dementia and MTA showing only a decreased NAA/MI ratio at baseline developed to MCI-C, AD, and DLB 3 years later. 1H MRS detected biochemical abnormalities preceding brain atrophy and cognitive decline. VSRAD combined with 1H MRS may be routinely applied to screen for MCI/AD and prodromal AD in clinical practice.

Distinction between mild cognitive impairment and Alzheimer's disease by CSF amyloid ß40 and ß42, and protein-conjugated acrolein.

BACKGROUND: We found previously that the amyloid ß40/42 (Aß40/42) ratio and the level of protein-conjugated acrolein (PC-Acro) in plasma were increased in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects. We determined whether MCI and AD subjects can be differentiated based on the levels of Aß40, Aß42, and PC-Acro in cerebrospinal fluid (CSF). METHODS: Aß40, Aß42, PC-Acro, Tau and phosphorylated Tau in CSF were measured by ELISA. RESULTS: Median values of Aß40, Aß40/PC-Acro and Aß40/42 in CSF were significantly lower in 54 AD subjects than those in 40 MCI subjects. Severity of VOI (volume of interest) atrophy was most intensely correlated with the decrease in Aß40/PC-Acro and then that in Aß40 and Aß42/PC-Acro. MMSE was most intensely correlated with the decrease in Aß42 and Aß40, and then that in Aß42/PC-Acro and Aß40/PC-Acro. CONCLUSION: A decrease in Aß40/PC-Acro in CSF is well correlated with brain damage, and a decrease in Aß42 and Aß40 is well correlated with cognitive ability. Measurement of PC-Acro together with Aß40 and Aß42 provides a more precise evaluation of severity of AD subjects.

Increased protein-conjugated acrolein and amyloid-ß40/42 ratio in plasma of patients with mild cognitive impairment and Alzheimer's disease.

The objective of this study was to determine whether plasma levels of acrolein, a compound that causes cell damage, and amyloid-ß (Aß) are useful biochemical markers for Alzheimer's disease (AD). The study included 221 elderly subjects divided into 101 non-demented [33 healthy control and 68 non-demented subjects with white matter hyperintensity (nd-WMH)], 50 mild cognitive impairment (MCI), and 70 AD. Increases in both protein-conjugated acrolein (PC-Acro) and Aß40/42 ratio were observed in MCI and AD patients compared with values in control subjects. When the combined measurements of PC-Acro and Aß40/42 ratio were evaluated using the median value of the relative risk value for dementia, they were in the order AD (0.98) ≥ MCI (0.97) > nd-WMH (0.83) > control (0.35). The results indicate that measurements of PC-Acro and Aß40/42 ratio not only detect MCI and AD patients but also nd-WMH subjects. Furthermore, both PC-Acro and Aß40/42 ratio in plasma for 120 MCI and AD patients were significantly higher than those for 101 control and nd-WMH subjects, indicating that both values become useful biochemical markers for MCI and AD subjects.

A revised clinical assessment of motor and memory disturbances.

For clinical assessment of motor disturbances, the motor system is better classified into the voluntary versus automatic motor systems than into the pyramidal versus extrapyramidal motor systems. The voluntary motor system is related to externally guided movements initiated by the premotor area while the automatic motor system is related to memory guided automatic movements initiated by the supplementary motor area and supported by an appropriate posture and associated movements. Among the pyramidal tract signs, muscle weakness alone is related to involvement of the corticospinal fibers of Betz cell origin while hyperreflexia and spasticity is related to involvement of the reticulospinal fibers running medial to the corticospinal fibers in the spinal cord. The earliest clinical manifestation of cervical myelopathy due to cervical spondylosis is always hyperreflexia and spasticity without any muscle weakness. The memory depends upon the 3 processes of encoding, retention, and recall, and must be classified into the immediate memory or recall lasting for only several seconds tested by the digit span test, the intermediate memory lasting for up to 2 years at maximum at the hippocampus whose disturbance can best be tested by the digit learning test, and the long-term memory which can last as long as one lives which can be tested by asking one's experience before more than 2 years. The classical dichotic concept of recent (short-term) versus remote (long-term) memories must be abandoned.

Whole-surface analysis of semiconductor wafers by accumulating short-time mapping data of total-reflection X-ray fluorescence spectrometry.

Total-reflection X-ray fluorescence (TXRF) spectrometry with no chemical preconcentration, often called "straight-TXRF", is now widely used in the semiconductor industry. The small detection area of TXRF enablesmapping measurement of contamination of the semiconductor surface, which is very useful in process characterization. However, the small detection area had been believed to limit rapid whole-surface analysis. Contrary to this general understanding, in this study we demonstrated that a new method, called "sweeping-TXRF", which is essentially short-time multipoint mapping by straight-TXRF, can rapidly provide an average concentration. A considerable problem of this method is the contribution of errors in glancing angle and areal element distribution to the fluorescence. Using statistics, we examined the errors and demonstrated that most of them are canceled and are not significant in actual semiconductor applications. The results of an experiment that measured localized 6 x 10(10) atoms cm(-2) nickel contamination supported the above conclusion. Applying sweeping-TXRF to existing TXRF instruments is easy-the only requirement is a small software modification. We believe that sweeping-TXRF will be utilized for rapid whole-surface analysis in many fields, especially in the semiconductor industry.