Novel Screening Tool Using Non-linguistic Voice Features Derived from Simple Phrases to Detect Mild Cognitive Impairment and Dementia.

Appropriate intervention and care in detecting cognitive impairment early are essential to effectively prevent the progression of cognitive deterioration. Diagnostic voice analysis is a noninvasive and inexpensive screening method that could be useful for detecting cognitive deterioration at earlier stages such as mild cognitive impairment. We aimed to distinguish between patients with dementia or mild cognitive impairment and healthy controls by using purely acoustic features (i.e., nonlinguistic features) extracted from two simple phrases. Voice was analyzed on 195 recordings from 150 patients (age, 45-95 years). We applied a machine learning algorithm (LightGBM; Microsoft, Redmond, WA, USA) to test whether the healthy control, mild cognitive impairment, and dementia groups could be accurately classified, based on acoustic features. Our algorithm performed well: area under the curve was 0.81 and accuracy, 66.7% for the 3-class classification. Thus, our vocal biomarker is useful for automated assistance in diagnosing early cognitive deterioration.

Nanoscale defect evaluation framework combining real-time transmission electron microscopy and integrated machine learning-particle filter estimation.

Observation of dynamic processes by transmission electron microscopy (TEM) is an attractive technique to experimentally analyze materials' nanoscale phenomena and understand the microstructure-properties relationships in nanoscale. Even if spatial and temporal resolutions of real-time TEM increase significantly, it is still difficult to say that the researchers quantitatively evaluate the dynamic behavior of defects. Images in TEM video are a two-dimensional projection of three-dimensional space phenomena, thus missing information must be existed that makes image's uniquely accurate interpretation challenging. Therefore, even though they are still a clustering high-dimensional data and can be compressed to two-dimensional, conventional statistical methods for analyzing images may not be powerful enough to track nanoscale behavior by removing various artifacts associated with experiment; and automated and unbiased processing tools for such big-data are becoming mission-critical to discover knowledge about unforeseen behavior. We have developed a method to quantitative image analysis framework to resolve these problems, in which machine learning and particle filter estimation are uniquely combined. The quantitative and automated measurement of the dislocation velocity in an Fe-31Mn-3Al-3Si autunitic steel subjected to the tensile deformation was performed to validate the framework, and an intermittent motion of the dislocations was quantitatively analyzed. The framework is successfully classifying, identifying and tracking nanoscale objects; these are not able to be accurately implemented by the conventional mean-path based analysis.

Partial anomalous pulmonary venous connection with portosystemic shunt in a cat.

A nine-month-old castrated male domestic shorthair presented for evaluation with a three-month history of hematuria. Portosystemic shunts and calculi within the bladder were suspected, and computed tomography angiography was performed. Computed tomography angiography identified an extrahepatic portosystemic shunt and a partial anomalous pulmonary venous connection, with the lobar vein of the right caudal lobe draining into the caudal vena cava. After anesthesia was administered to the cat, tachypnea and wheezing respiratory sounds were observed, and thoracic radiography revealed the right middle lung lobe atelectasis and an unstructured interstitial pattern in the left cranial lobe. Echocardiography showed left and right atrial enlargement and slight interventricular septal flattening in diastole. Based on these findings, cardiogenic pulmonary edema was suspected, and the cat was treated with furosemide. The clinical symptoms were resolved the next day. Closure of the extrahepatic portosystemic shunt was performed on days 47 and 157. Left atrial enlargement and interventricular septal flattening were attenuated after the procedure. At the time of writing this report (seventeen months after diagnosis), the cat exhibited no clinical signs, but subjective right atrial enlargement remained at approximately the same level. This report represents the first case of a partial anomalous pulmonary venous connection and a portosystemic shunt in a cat.

APOBEC3A associates with human papillomavirus genome integration in oropharyngeal cancers.

The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has been increasing in developed countries. We recently demonstrated that members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16 genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA denaturation PCR and next-generation sequencing. A3s were more abundantly expressed in HPV16-positive OPCs than in HPV-negative, as assessed using immunohistochemistry and reverse transcription quantitative PCR. In addition, interferons upregulated A3s in an HPV16-positive OPC cell line. Furthermore, quantitative PCR analysis of HPV DNA suggests that APOBEC3A (A3A) expression is strongly correlated with the integration of HPV DNA. These results suggest that HPV16 infection may upregulate A3A expression, thereby increasing the chance of viral DNA integration. The role of A3A in HPV-induced carcinogenesis is discussed.

Autoimmune arthritis deteriorates bone quantity and quality of periarticular bone in a mouse model of rheumatoid arthritis.

This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA. INTRODUCTION: Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA. METHODS: Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing. RESULTS: SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice. CONCLUSIONS: Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.

Washing of platelets can be fully automated using a closed-system cell processor and BRS-A platelet additive solution.

This study evaluated the in vitro properties of platelets (PLTs) washed with BRS-A additive solution in the Haemonetics ACP215 automated processing system. Two washing modes, 'manually/automatically adding ACD-A to BRS before/during the washing process', represented the control and test groups, respectively. Outcomes were compared over 7 days of storage (n = 7, for both). PLT recovery following washing processing (26-27 min) was 86·2 ± 1·7% and 86·0 ± 2·2% and plasma protein removal was 98·8 ± 0·3% and 99·0 ± 0·2% in the control and test groups, respectively (not significant). Both groups exhibited comparable in vitro properties.

Relationship among cervical, thoracic, and lumbopelvic sagittal alignment in healthy adults.

PURPOSE: To evaluate the association between cervical sagittal alignment and thoracic/lumbopelvic sagittal alignment in healthy Japanese adults. METHODS: 30 male and 22 female healthy adults aged 22 to 50 years were recruited. Spinal parameters were measured on radiographs, including the cervical sagittal vertical axis, sagittal vertical axis, C7 tilt angle, Ishihara index for cervical lordosis, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence. RESULTS: The C7 tilt angle positively correlated with the Ishihara index (r=0.52, p<0.0001) and thoracic kyphosis (r=0.53, p<0.0001). The Ishihara index positively correlated with thoracic kyphosis (r=0.34, p=0.01) and C7 tilt angle (r=0.52, p<0.0001). Pelvic incidence positively correlated with sacral slope (r=0.45, p=0.001), lumbar lordosis (r=0.26, p=0.07), and pelvic tilt (r=0.29, p=0.03). Compared with men, women had a smaller Ishihara index (0.07 vs. 0.001, p=0.03), thoracic kyphosis (30.5º vs 24.1º, p=0.02), and C7 tilt angle (23.1º vs. 16.8º, p=0.02). Women had less cervical lordosis and thoracic kyphosis, that is, a straighter cervico-thoracic sagittal alignment. CONCLUSION: In healthy Japanese adults, cervical sagittal alignment is associated with thoracic sagittal alignment but not with lumbopelvic alignment.

In vitro analysis of volume-reduced washed platelet concentrates stored in bicarbonated Ringer's solution containing less than 5% residual plasma.

BACKGROUND AND OBJECTIVES: Volume-reduced washed platelet (PLT) concentrates (PCs) can prevent circulatory overload and allergic reactions in patients undergoing PLT transfusions. For these reasons, they are in demand for paediatric settings and for patients at risk of circulatory overload. Here, we evaluated the quality of volume-reduced washed PCs stored for 5 days in a novel acetate-free PLT additive solution (PAS) containing glucose and bicarbonate (BRS-A) with <5% residual plasma protein. MATERIALS AND METHODS: PCs from two apheresis donations were mixed and divided equally into control and test units. For the test unit (volume-reduced washed PCs), PLTs were washed and stored in 90 ml BRS-A with <5% plasma protein. PLTs in the control unit were stored in 200 ml 100% plasma without any washing manipulations. The in vitro properties of PLTs in both units were compared over a 5-day storage period. RESULTS: The procedure for volume-reduced washed PCs effectively removed >98% plasma protein in 100% plasma PCs and yielded an approximately twofold lower mean volume (91 ml) compared to that observed with the control units. Immediately after washing, the mean PLT concentration of the test units was 20·5 × 10(11) /l, twofold higher than that of the control units. The pH (37°C) levels in the test unit remained above 7·0 for 5 days. Glucose consumption and lactate production rates of the test units on days 1-3 were higher than those of the control units, leading to glucose exhaustion in the test unit by Day 3. Hypotonic shock responses and CD62P and CD42b expression levels in both units were comparable during 5-day storage. CONCLUSION: Considering the pH buffering capacity of BRS-A, a 90-ml volume may be acceptable for maintaining the in vitro quality of washed PLTs for at least 2 days.

Measurement and comparison of individual external doses of high-school students living in Japan, France, Poland and Belarus-the 'D-shuttle' project.

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter 'D-shuttle' for two weeks, and kept a journal of his/her whereabouts and activities. The distributions of annual external doses estimated for each region overlap with each other, demonstrating that the personal external individual doses in locations where residence is currently allowed in Fukushima Prefecture and in Belarus are well within the range of estimated annual doses due to the terrestrial background radiation level of other regions/countries.

NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD.

The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype (P=3.82 × 10(-16), odds ratio=212). The association of R139C with early (<8 weeks) leukopenia (white blood cells<3000 mm(-3)), which was previously reported in Korean patients, was replicated in our Japanese IBD cohort (P=1.92 × 10(-16), odds ratio=28.4). However, we could not confirm the association with late leukopenia in the Japanese subjects. Patients with the C/T genotype discontinued treatment or required thiopurine dose reduction significantly earlier than patients with the C/C genotype (P=1.45 × 10(-4)); however, on manipulating the doses, there was no significant difference in the thiopurine continuation rates between the groups. In the maintenance period, the frequencies of 6MP usage were higher, and the doses of thiopurines were significantly lower in patients with the C/T genotype than in those with the C/C genotype (0.574±0.316 mg kg(-1) per day vs 1.03±0.425 mg kg(-1) per day, P=6.21 × 10(-4)). NUDT R139C was significantly associated with early severe hair loss in Japanese patients with IBD. We also verified the previously reported association of R139C with early leukopenia in a different East Asian population. It is recommended that treatment with thiopurines should be avoided for patients with the T/T genotype. Low-dose 6MP (0.2-0.3 mg kg(-1) per day) could be used rather than AZA for the patients with C/T genotype to continue thiopurine treatments. However, late leukopenia and other several adverse events could not be completely predicted by R139C genotypes.

STAT3 integrates cooperative Ras and TGF-ß signals that induce Snail expression.

The epithelial-mesenchymal transition (EMT) is a crucial morphological event that occurs during the progression of epithelial tumors. EMT can be induced by transforming growth factor ß (TGF-ß) in certain kinds of cancer cells through the induction of Snail, a key regulator of EMT. We have previously found that TGF-ß remarkably induces Snail expression in cooperation with Ras signals; however, the underlying mechanism of this synergism has not yet been determined. Here, we demonstrate that signal transducer and activator of transcription 3 (STAT3) acts as a mediator that synergizes TGF-ß and Ras signals. The overexpression of STAT3 enhanced Snail induction, whereas siRNA-mediated knockdown of STAT3 inhibited it. The STAT3-YF mutant, which has Tyr 705 substituted with Phe, did not enhance Snail induction. Several STAT3 mutants lacking transcriptional activity also failed to enhance it; however, the putative STAT3-binding elements in the Snail promoter regions were not required for STAT3-mediated Snail induction. Protein inhibitor of activated STAT3 (PIAS3) inhibited the enhanced Snail promoter activity induced by TGF-ß and Ras. The interaction between PIAS3 and STAT3 was reduced by TGF-ß in cells harboring oncogenic Ras, whereas TGF-ß promoted the binding of PIAS3 to Smad3, a crucial mediator of TGF-ß signaling. Therefore, these findings suggest that STAT3 enhances Snail induction when it is dissociated from PIAS3 by TGF-ß in cooperation with Ras signals.

Lessons learned from Fukushima Daiichi nuclear power plant accident: efficient education items of radiation safety for general public.

The Fukushima Daiichi nuclear power plant (FNP-1) accident, while as tragic as the tsunami, was a man-made disaster created by the ignorance of the effects of radiation and radioactive materials. Therefore, it is important that all specialists in radiation protection in medicine sympathize with the anxiety of the general public regarding the harmful effects of radiation and advise people accordingly. All questions and answers were collected related to inquiries from the general public that were posted to reliable websites, including those of the government and radiation-related organizations, from March 2011 to November 2012. The questions were summarized and classified by similarity of content. (1) The total number of questions is 372. The content was broadly classified into three categories: inquiries for radiation-related knowledge and about health effects and foods. The questions asked to obtain radiation-related knowledge were the most common, accounting for 38 %. Thirty-six percentage of the questions were related to health effects, and 26 % involved foods, whereas 18 % of the questions were related to children and pregnancy. (2) The change over time was investigated in 290 questions for which the time of inquiry was known. Directly after the earthquake, the questions were primarily from people seeking radiation-related knowledge. Later, questions related to health effects increased. The anxiety experienced by residents following the nuclear accident was caused primarily by insufficient knowledge related to radiation, concerns about health effects and uncertainties about food and water safety. The development of educational materials focusing on such content will be important for risk communication with the general public in countries with nuclear power plants. Physicians and medical physicist should possess the ability to respond to questions such as these and should continue with medical examinations and treatments in a safe and appropriate manner.

Effects of washing of the face with a mild facial cleanser formulated with sodium laureth carboxylate and alkyl carboxylates on acne in Japanese adult males.

BACKGROUND/PURPOSE: Washing the face with a mild cleanser is generally recommended for acne care. Occasionally, the general public has the misconception that acne is exacerbated by cleansers and furthermore it has concerns about inducing skin irritation and xerosis by intensive washing. Recently, we developed a new cleanser based on sodium laureth carboxylate and alkyl carboxylates (AEC/soap) that cleans sebum well without penetrating the stratum corneum. METHODS: We designed a controlled clinical trial conducted on adult Japanese males with moderate or less acne. Twenty subjects washed their faces with AEC/soap base cleanser twice a day for 4 weeks. Assessment of the efficacy was conducted prior to the start of the study, and at the end of weeks 2 and 4. RESULTS: Significant improvement of the acne was observed within 2 weeks, and acne lesions were not detectable in 25% of the subjects at week 4. Sebum secretion levels on the skin significantly increased on the forehead, but significantly decreased on the cheek which correlated with the improvement. No complaints of dryness or irritation occurred during the study. CONCLUSION: Washing the face twice a day with facial cleanser based on AEC/soap is an effective care for moderate or less grade facial acne.

Three-dimensional surface figure measurement of high-accuracy spherical mirror with nanoprofiler using normal vector tracing method.

Processing technology using an extreme ultraviolet light source, e.g., next-generation lithography, requires next-generation high-accuracy mirrors. As it will be difficult to attain the degree of precision required by next-generation high-accuracy mirrors such as aspherical mirrors through conventional processing methods, rapid progress in nanomeasurement technologies will be needed to produce such mirrors. Because the measuring methods used for the surface figure measurement of next-generation mirrors will require high precision, we have developed a novel nanoprofiler that can measure the figures of high-accuracy mirrors without the use of a reference surface. Because the accuracy of the proposed method is not limited by the accuracy of a reference surface, the measurement of free-form mirrors is expected to be realized. By using an algorithm to process normal vectors and their coordinate values at the measurement point obtained by a nanoprofiler, our measurement method can reconstruct three-dimensional shapes. First, we measured the surface of a concave spherical mirror with a 1000-mm radius of curvature using the proposed method, and the measurement repeatability is evaluated as 0.6 nm. Sub-nanometer repeatability is realized, and an increase in the repeatability would be expected by improving the dynamic stiffness of the nanoprofiler. The uncertainty of the measurement using the present apparatus is estimated to be approximately 10 nm by numerical simulation. Further, the uncertainty of a Fizeau interferometer is also approximately 10 nm. The results obtained using the proposed method are compared with those obtained using a Fizeau interferometer. The resulting profiles are consistent within the range of each uncertainty over the middle portions of the mirror.

Optimal timeline for emergency surgery in patients with strangulated groin hernias.

PURPOSE: This retrospective study evaluates the clinical course and outcomes of patients who underwent surgery for strangulated hernias. METHODS: Among 520 groin hernias from 2001 to 2012, 51 inguinal and 42 femoral hernias were strangulated and operated emergently at a tertiary referral center. Perioperative factors, patient profiles, and time interval to surgery (T total = time from onset to surgery, T 1 = time from onset to initial evaluation, T 2 = time from the first hospital to the tertiary center, T 3 = time from admission at the tertiary center to surgery, T total = T 1 + T 2 + T 3) were analyzed in patients with strangulation, then compared between two groups, the bowel resection (BR) group and the non-bowel resection (NBR) group. RESULTS: T 1, T 2 and T total in the bowel resection group were significantly longer than those in the non-bowel resection group (P < 0.05). Patients who presented initially to the tertiary center (T 2 = 0) had a significantly lower resection rate than patients transported from other hospitals (24 vs. 44 %, P = 0.048). There was no significant difference in morbidity between the BR and NBR groups (35 vs. 24 %, P = 0.231). CONCLUSIONS: The elapsed time from onset to surgery, especially T 1 and T 2, is the most important prognostic factor in patients with strangulated groin hernias. Early diagnosis and transportation are essential for good outcomes.

Hyperspectroscopic imager for baby fibers.

Hyperspectral imaging system for diagnosing digestive diseases was newly developed in order to obtain information on pathology beyond morphology of lesions. In order to guide light reflected from a lesion, a baby fiber, which can be inserted in a forceps channel of the electronic endoscope, was also developed. The performance of the system was evaluated by animal experiment. Obtained hyperspectral data were found to have sufficient quality endurable to practical use. Harmful phenomena to a living body were not observed within the experiment. It was considered from the animal experiment that the present system could be practically used for humans.