Clinical features and outcomes of Merkel cell carcinoma in 20 cats.

The biological behaviour and prognostic factors of Merkel cell carcinoma (MCC) in 20 cats were studied. The tumours were surgically removed and histopathologically examined. The animals were 8 to 20 years old (median age: 14 years), and the tumours were predominantly located in the neck and head. Follow-up data were available in 17 cases, and 12 cats died within a year of surgery. The overall median survival time after resection was 243 days (range 16-360 days). Recurrence occurred in 11 cases, although 6 of them (55%) were found to be margin-negative. Possible metastasis occurred after the surgery in 10 cases, although 6 of them (60%) were found to be margin-negative. The histopathological features of MCC included tumour necrosis in 16 cases (80%), vascular invasion in 6 cases (38%) and high mitotic counts (median: 28.5 per high-power field). Irregular acanthosis was noted adjacent to the tumours in 9 cases (60%). Immunohistochemically, the tumour cells were positive for cytokeratin (CK) 20 and p63 in all cases, synaptophysin in 19 (95%) cases, and CK18 in 16 cases (80%). The study shows that feline MCC is associated with a poor prognosis and exhibited a strong tendency towards local recurrence, regional lymph node metastasis and distant spread.

Association between meteorological factors and reported cases of hand, foot, and mouth disease from 2000 to 2015 in Japan.

The purpose of this study was to clarify the association between hand, foot, and mouth disease (HFMD) epidemics and meteorological conditions. We used HFMD surveillance data of all 47 prefectures in Japan from January 2000 to December 2015. Spectral analysis was performed using the maximum entropy method (MEM) for temperature-, relative humidity-, and total rainfall-dependent incidence data. Using MEM-estimated periods, long-term oscillatory trends were calculated using the least squares fitting (LSF) method. The temperature and relative humidity thresholds of HFMD data were estimated from the LSF curves. The average temperature data indicated a lower threshold at 12 °C and a higher threshold at 30 °C for risk of HFMD infection. Maximum and minimum temperature data indicated a lower threshold at 6 °C and a higher threshold at 35 °C, suggesting a need for HFMD control measures at temperatures between 6 and 35 °C. Based on our findings, we recommend the use of maximum and minimum temperatures rather than the average temperature, to estimate the temperature threshold of HFMD infections. The results obtained might aid in the prediction of epidemics and preparation for the effect of climatic changes on HFMD epidemiology.

Effect of temperature, relative humidity and rainfall on dengue fever and leptospirosis infections in Manila, the Philippines.

Dengue fever (DF) and leptospirosis are serious public problems in tropical regions, especially in Manila, the Philippines. In attempting to understand the causes of DF and leptospirosis seasonality, meteorological factors have been suspected, but quantitative correlation between seasonality and meteorological factors has not been fully investigated. In this study, we investigated correlation of temporal patterns of reported numbers of laboratory-confirmed cases of both DF and leptospirosis with meteorological conditions (temperature, relative humidity, rainfall) in Manila. We used time-series analysis combined with spectral analysis and the least squares method. A 1-year cycle explained underlying variations of DF, leptospirosis and meteorological data. There was a peak of the 1-year cycle in temperature during May, followed by maxima in rainfall, relative humidity and number of laboratory-confirmed DF and leptospirosis cases. This result suggests that DF and leptospirosis epidemics are correlated not only with rainfall but also relative humidity and temperature in the Philippines. Quantifying the correlation of DF and leptospirosis infections with meteorological conditions may prove useful in predicting DF and leptospirosis epidemics, and health services should plan accordingly.

Drug resistance and genetic characteristics of clinical isolates of staphylococci in Myanmar: high prevalence of PVL among methicillin-susceptible Staphylococcus aureus belonging to various sequence types.

Prevalence, drug resistance and genetic characteristics were analysed for a total of 128 clinical isolates of staphylococci obtained from a tertiary hospital in Myanmar. The dominant species were S. aureus (39%) and S. haemolyticus (35%), followed by S. epidermidis (6%) and S. saprophyticus (5%). The majority of S. haemolyticus isolates (71.1%) harboured mecA, showing high resistance rates to ampicillin, cephalosporins, erythromycin and levofloxacin, while methicillin-resistant S. aureus (MRSA) was only 8% (four isolates) among S. aureus with type IV SCCmec. Panton-Valentine leukocidin (PVL) genes were detected in 20 isolates of S. aureus (40%), among which only one isolate was MRSA belonging to sequence type (ST) 88/agr-III/coa-IIIa, and the other 19 methicillin-susceptible S. aureus (MSSA) isolates were classified into six STs (ST88, ST121, ST1153, ST1155, ST1930, ST3206). An ST1153 MSSA isolate with PVL was revealed to belong to a novel coa type, XIIIa. ST121 S. aureus was the most common in the PVL-positive MSSA (47%, 9/19), harbouring genes of bone sialoprotein and variant of elastin binding protein as a distinctive feature. Although PVL-positive MSSA was susceptible to most of the antimicrobial agents examined, ST1930 isolates were resistant to erythromycin and levofloxacin. ST59 PVL-negative MRSA and MSSA had more resistance genes than other MRSA and PVL-positive MSSA, showing resistance to more antimicrobial agents. This study indicated higher prevalence of mecA associated with multiple drug resistance in S. haemolyticus than in S. aureus, and dissemination of PVL genes to multiple clones of MSSA, with ST121 being dominant, among hospital isolates in Myanmar.

Time-series analysis of monthly age-specific numbers of newly registered cases of active tuberculosis in Japan from 1998 to 2013.

We investigated the seasonality of age-specific tuberculosis (TB) in Japan. To allow the development of TB control strategies for different age groups we used a time-series analysis, including a spectral analysis and least squares method, to analyse the monthly age-specific numbers of newly registered cases of all forms of active TB in Japan from January 1998 to December 2013. The time-series data are reported in 10-year age groups: 0-9, 10-19, …, 70-79, and ⩾80 years. We defined the contribution ratio of the 1-year cycle, Q 1, as the contribution of the amplitude of a 1-year cycle to the whole amplitude of the time-series data. The Q 1 values in the age groups corresponding to adolescence and middle life (10-39 years) and old age (⩾70 years) were high. The peaks in the active TB epidemics for the ⩾70 years age group occurred in August and September, 1-2 months behind the peaks for the 10-39 years age group (June and July). An active TB epidemic might be attributable to travel by public transport and irregular employment in the 10-39 years age group and immune system suppression by low winter temperatures in the ⩾70 years age group.

Emerging non-PCV13 serotypes of noninvasive Streptococcus pneumoniae with macrolide resistance genes in northern Japan.

In Japan, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to the nation's routine immunization program in April 2013 and was replaced by the 13-valent pneumococcal conjugate vaccine (PCV13) in November 2013. Distribution of serotypes and macrolide resistance genotypes was investigated for a total of 1097 (975 children, 122 adults) and 960 (873 children, 87 adults) clinical isolates of Streptococcus pneumoniae from noninvasive infections in Hokkaido (northern main island of Japan) in the routine immunization periods for PCV7 and PCV13 (April-October 2013 and November 2013-November 2014, respectively). Serotype was determined by sequential multiplex PCR and additional genetic analyses. Macrolide resistance genes erm(B) and mef(A/E) were detected by multiplex PCR. Although the most prevalent serotypes in children were 23A and 6C in the PCV7 period, after replacement with PCV13, 19A became the most common, followed by 6C, 15A and 23A. Among adults, serotype 3 was consistently the most frequent throughout the study periods. Compared with values from the pre-PCV7 routine immunization period, PCV7 serotypes decreased from 48.3 to 3.3% in the PCV13 period among children, while the rates of non-PCV13 serotypes (particularly 15A, 23A, 11A, 10A and 35B) increased from 39.7 to 75.1% (p < 0.001). In the PCV13 period, erm(B), mef(A/E) and both of these genes were detected in 75.8, 31.6 and 11.3% of all isolates, respectively. Serotype 19A accounted for 76.9% of the isolates with both the macrolide resistance genes, and emerging non-PCV13 serotypes 15A, 15C and 23A mostly harboured erm(B).

The role of temperature in reported chickenpox cases from 2000 to 2011 in Japan.

Annual periodicities of reported chickenpox cases have been observed in several countries. Of these, Japan has reported a two-peaked, bimodal annual cycle of reported chickenpox cases. This study investigated the possible underlying association of the bimodal cycle observed in the surveillance data of reported chickenpox cases with the meteorological factors of temperature, relative humidity and rainfall. A time-series analysis consisting of the maximum entropy method spectral analysis and the least squares method was applied to the chickenpox data and meteorological data of 47 prefectures in Japan. In all of the power spectral densities for the 47 prefectures, the spectral lines were observed at the frequency positions corresponding to the 1-year and 6-month cycles. The optimum least squares fitting (LSF) curves calculated with the 1-year and 6-month cycles explained the underlying variation of the chickenpox data. The LSF curves reproduced the bimodal and unimodal cycles that were clearly observed in northern and southern Japan, respectively. The data suggest that the second peaks in the bimodal cycles in the reported chickenpox cases in Japan occurred at a temperature of approximately 8·5 °C.

Seasonality of reported tuberculosis cases from 2006 to 2010 in Wuhan, China.

We investigated the seasonality of tuberculosis (TB) in Wuhan, China, to evaluate the increased risk of disease transmission during each season and to develop an effective TB control strategy. We applied spectral analysis to the weekly prevalence data of sputum smear positive (SSP) and sputum smear negative (SSN) pulmonary TB reported from 2006 to 2010. Cases of both SSP and SSN feature 1·0- and 0·5-year periodic modes. The least squares method was used to fit curves to the two periodic modes for SSP and SSN data. The curves demonstrated dominant peaks in spring similar to cases reported previously for other locations. Notably for SSP, dominant peaks were also observed in summer. The spring peaks of SSP and SSN were explained in terms of poorly ventilated and humid rooms and vitamin D deficiency. For the summer peaks of SSP, summer influenza epidemics in Wuhan may contribute to the increase in TB prevalence.

Effect of temperature, relative humidity and rainfall on rotavirus infections in Kolkata, India.

Rotavirus is a common viral cause of severe diarrhoea. For the underlying cause of rotavirus seasonality, the meteorological factor has been suspected, whereas quantitative correlation between seasonality and meteorological factor has not been fully investigated. In this study, we investigated the correlation of temporal patterns of the isolation rate of rotavirus with meteorological condition (temperature, relative humidity, rainfall) in Kolkata, India. We used time-series analysis combined with spectral analysis and least squares method. A 1-year cycle explained underlying variations of rotavirus and meteorological data. The 1-year cycle for rotavirus data was correlated with an opposite phase to that for meteorological data. Relatively high temperature could be associated with a low value of isolation rate of rotavirus in the monsoon season. Quantifying a correlation of rotavirus infections with meteorological conditions might prove useful in predicting rotavirus epidemics and health services could plan accordingly.

Time-series analysis of hepatitis A, B, C and E infections in a large Chinese city: application to prediction analysis.

Viral hepatitis is recognized as one of the most frequently reported diseases, and especially in China, acute and chronic liver disease due to viral hepatitis has been a major public health problem. The present study aimed to analyse and predict surveillance data of infections of hepatitis A, B, C and E in Wuhan, China, by the method of time-series analysis (MemCalc, Suwa-Trast, Japan). On the basis of spectral analysis, fundamental modes explaining the underlying variation of the data for the years 2004-2008 were assigned. The model was calculated using the fundamental modes and the underlying variation of the data reproduced well. An extension of the model to the year 2009 could predict the data quantitatively. Our study suggests that the present method will allow us to model the temporal pattern of epidemics of viral hepatitis much more effectively than using the artificial neural network, which has been used previously.

Effects of partially replacing skimmed milk powder with dairy ingredients on rheology, sensory profiling, and microstructure of probiotic stirred-type yogurt during cold storage.

This study aimed to evaluate the quality of stirred-type skim milk probiotic yogurt fortified by partially replacing skim milk powder (SMP) with whey protein concentrate (WPC) and sodium caseinate (Na-CN) during cold storage for 28 d compared with nonfortified yogurt. The rheological properties (as measured using dynamic oscillation) and sensory profiles of probiotic yogurts were greatly enhanced when SMP (i.e., 45%) was replaced with WPC and Na-CN. Higher values of mechanical parameters related to storage and loss modulus and consistent microstructure were found in the fortified yogurts. The acidification profile was not affected by supplementation of the solids in the milk base, and the viable counts of probiotic microbiota were high and satisfactory. These positive characteristics of probiotic yogurts were maintained until the end of the storage period. The microstructure of the fortified yogurt showed some differences compared with the nonfortified product, which were due to changes in chemical composition of the milk base in addition to the colloidal characteristics of the product.

Influence of relative humidity in Vibrio cholerae infection: a time series model.

BACKGROUND & OBJECTIVES: Spread of cholera in West Bengal is known to be related to its ecosystem which favours Vibrio cholerae. Incidence of cholera has not been correlated with temperature, relative humidity and rainfall, which may act as favourable factors. The aim of this study was to investigate the relational impact of climate changes on cholera. METHODS: Monthly V. cholerae infection data for of the past 13 years (1996-2008), average relative humidity (RH), temperature and rainfall in Kolkata were considered for the time series analysis of Seasonal Auto-Regressive Integrated Moving Average (SARIMA) model to investigate relational impact of climatic association of V. cholerae infection and General Linear Model (GLM) for point estimation. RESULTS: The SARIMA (1,0,0)(0,1,1) model revealed that monthly average RH was consistently linear related to V. cholerae infection during monsoon season as well as temperature and rainfall were non-stationary, AR(1), SMA(1) and SI(1) (P<0.001) were highly significant with seasonal difference. The GLM has identified that consistent (<10%) range of RH (86.78 ± 4.13, CV=5.0, P <0.001) with moderate to highest (>7 cm) rainfall (10.1 ± 5.1, CV=50.1, P <0.001) and wide (>5-10ºC) range of temperature (29.00 ± 1.64, CV=5.6, P <0.001) collectively acted as an ideal climatic condition for V. cholerae infection. Increase of RH to 21 per cent influenced an unusual V. cholerae infection in December 2008 compared to previous years. INTERPRETATION & CONCLUSIONS: V. cholerae infection was associated higher RH (>80%) with 29°C temperature with intermittent average (10 cm) rainfall. This model also identified periodicity and seasonal patterns of cholera in Kolkata. Heavy rainfall indirectly influenced the V. cholerae infection, whereas no correlation was found with high temperature.

Prenatal diagnosis of anterior sacral meningocele.

Anterior sacral meningocele is an extremely rare condition and there has been only one previous report of a prenatal diagnosis. We report the case of a 36-year-old primigravida who was referred following detection of a huge fetal pelvic cyst on routine ultrasound examination at 19 + 4 weeks' gestation. Neither fetal ultrasound nor magnetic resonance imaging (MRI) at 20 + 5 weeks' gestation could detect communication between the cyst and the spinal cord. Because extension of the pear-shaped cyst through the pelvic diaphragm down to the perineum was reminiscent of dilated vagina and uterine cervix, a tentative diagnosis of hydrometrocolpos secondary to imperforate hymen was considered. On follow-up MRI at 33 + 5 weeks' gestation, a narrow stalk connecting the pelvic cyst and the spinal canal through the anterior sacral foramen was clearly delineated, allowing us to reach the prenatal diagnosis of anterior sacral meningocele.

Study on the effect of measles control programmes on periodic structures of disease epidemics in a large Chinese city.

Measles is regarded as a disease that can be eliminated by vaccination; however, disease epidemics still occur in Wuhan, China. This study explored the effect of measles control programmes on the periodic structure of disease epidemics in Wuhan. The monthly reported measles incidence from 1953 to 2008 was divided into pre-vaccine range (1953-1965) and post-vaccine range (1966-2008). For the incidence in each range, spectral analysis was conducted and power spectral density (PSD) was obtained. In PSD for the pre-vaccine range, the most dominant spectral line was observed at a 2·0-year period, as in the case of Japan. It was confirmed that spectral lines of periodic modes longer than a 1-year cycle of the incidence rates behave in response to the introduction of measles control programmes. The investigation of periodic structures of measles epidemics will contribute to effective measles control programmes in Wuhan.

Relationship of cholera incidence to El Niño and solar activity elucidated by time-series analysis.

Using time-series analysis, we investigated the monthly cholera incidence in Dhaka, Bangladesh during an 18-year period for its relationship to the sea surface temperature (SST) linked to El Niño, and to the sunspot number. Dominant periodic modes identified for cholera incidence were 11.0, 4.8, 3.5, 2.9, 1.6, 1.0 and 0.5 years. The majority of these modes, e.g. the 11.0-, 4.8-, 3.5-, 1.6- and 1.0-year modes, were essentially consistent with those obtained for the SST data (dominant modes: 5.1, 3.7, 2.5, 2.1, 1.5, 1.0 years) and the sunspot number data (dominant modes: 22.1, 11.1, 7.3, 4.8, 3.1 years). We confirmed that the variations of cholera incidence were synchronous with SSTs, and were inversely correlated to the sunspot numbers. These results suggest that the cholera incidence in Bangladesh may have been influenced by the occurrence of El Niño and also by the periodic change of solar activity.

Dimensionality-controlled insulator-metal transition and correlated metallic state in 5d transition metal oxides Sr n+1Ir nO3n+1 (n=1, 2, and infinity).

We investigated the electronic structures of the 5d Ruddlesden-Popper series Sr n+1Ir nO3n+1 (n=1, 2, and infinity) using optical spectroscopy and first-principles calculations. As 5d orbitals are spatially more extended than 3d or 4d orbitals, it has been widely accepted that correlation effects are minimal in 5d compounds. However, we observed a Mott insulator-metal transition with a change of bandwidth as we increased n. In addition, the artificially synthesized perovskite SrIrO3 showed a very large mass enhancement of about 6, indicating that it was in a correlated metallic state.

Malignant ameloblastic fibro-odontoma in a dog.

An 11-year-old male Collie was presented with a swelling of the face caused by tumor masses arising from the gingiva. Postmortem examination revealed metastases to the lymph nodes, lung, liver, and orbital cavity. Histologically, the tumor represented a combination of fibrosarcomatous proliferation, pulpal mesenchyme, and undifferentiated odontogenic epithelium, with a follicular or plexiform growth pattern. In addition, the follicular areas of the tumor showed a biphasic character, and there were numerous apoptotic cells in plexiform areas. Furthermore, acidophilic material resembling dysplastic dentine or enamel matrix was observed in the metastatic lesion in the lung. Based on the histological characters, the present case was diagnosed as malignant ameloblastic fibro-odontoma. This study is the first known description of a possible malignant ameloblastic fibro-odontoma in a dog with metastasis to distant organs.

Purification of recombinant human serum albumin efficient purification using STREAMLINE.

Two inter-related challenges must be overcome to develop a recombinant human serum albumin process. One is purity; the other is cost. Regarding cost, our goal is to produce recombinant human serum albumin at least as economically as plasma derived human serum albumin. To control production costs, maximum quantities of albumin must be produced from minimum volumes of cell culture, followed by high efficiency, high-yield purification methods. By introducing STREAMLINE technology, we have improved productivity by roughly 50% in terms of processing time and 45% in terms of yield. Furthermore, the life time of the gel and column are very long. After more than 1000 process cycles, performance remained unchanged.

Time series analysis of surveillance data of infectious diseases in Japan.

Temporal variational structures of long-term trends, recursive variations and seasonal variations were investigated, as to the incidence data of infectious diseases obtained from Infectious Diseases Surveillance Program in Japan by a newly devised procedure of time series analysis. In this procedure, three-dimensional spectral array indicates temporal variations of periodic structures of the incidence data, and is useful for investigating the long-term trend of the incidence data. Dominant spectral lines of the whole incidence data for each disease were assigned as the linear combinations of the fundamental modes. The optimum least squares fitting curve calculated with the fundamental modes essentially reproduces the recursive variation of the incidence data and an extension of the curve could be used to predict the incidence of the disease. Seasonal periodic modes of the incidences were estimated. The infectious diseases were classified into three basic groups (measles-, chickenpox- and mumps-patterns) and others, according to the resemblance of temporal variational structures of the incidence data.

Analysis of Pichia pastoris components in recombinant human serum albumin by immunological assays and by HPLC with pulsed amperometric detection.

We have developed a recombinant human serum albumin (rHSA) from Pichia pastoris which expresses high levels of heterologous proteins. rHSA is used clinically in high concentration (approximately 250 mg/ml in a 50 mL vial). We had to consider not only proteins from host cells as impurities but also mannan, which exhibits harmful effects on humans. However, the analysis of mannan in biopharmaceuticals produced from yeast has not been reported. Contaminating mannans in the final product were one important index to assess the clinical safety of rHSA. We have developed a highly sensitive enzyme immunoassay (EIA), utilizing an avidin-biotin system, for the detection of either the protein or mannan polysaccharide components from P. pastoris components (PPC) in rHSA. In addition, we used anion exchange chromatography with pulsed amperometric detection (AE-PAD) for monosaccharide analysis of glycoconjugates for the detection of mannan from PPC in rHSA. The detection limits of the EIA for PPC (PPC EIA) and the AE-PAD were 1 ng of protein/250 mg of rHSA and 180 ng of mannose/mg of rHSA, respectively. The mannan content in partially purified rHSA as determined by the AE-PAD was about same as the PPC content as determined by the PPC EIA. We showed that the PPC EIA and the AE-PAD are useful methods for the purity analysis of biopharmaceuticals produced from yeast.