Temporal and spatial association of Streptococcus suis infection in humans and porcine reproductive and respiratory syndrome outbreaks in pigs in northern Vietnam.

Porcine reproductive and respiratory syndrome (PRRS) outbreaks in pigs are associated with increased susceptibility of pigs to secondary bacterial infections, including Streptococcus suis - an important zoonotic pathogen causing bacterial meningitis in humans. This case-control study examined the association between human S. suis infection and PRRS outbreaks in pigs in northern Vietnam. We included 90 S. suis case-patients and 183 non-S. suis sepsis controls from a referral hospital in Hanoi in 2010, a period of major PRRS epizootics in Vietnam. PRRS exposure was determined using data from the National Centre of Veterinary Diagnosis. By univariate analysis, significantly more S. suis patients were reported residing in or adjacent to a PRRS district compared to controls [odds ratio (OR) 2·82, 95% confidence interval (CI) 1·35-5·89 and OR 3·15, 95% CI 1·62-6·15, respectively]. Only residency in adjacent districts remained significantly associated with risk of S. suis infection after adjusting for sex, occupation, and eating practices. SaTScan analysis showed a possible cluster of S. suis infection in humans around PRRS confirmed locations during the March-August period. The findings indicate an epidemiological association between PRRS in pigs and S. suis infections in humans. Effective strategies to strengthen control of PRRS in pigs may help reduce transmission of S. suis infection to humans.

Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis-results from the TOMORROW study.

UNLABELLED: Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism. INTRODUCTION: Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA. METHODS: We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis. RESULTS: Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (-0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (ß = -0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage. CONCLUSIONS: Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence levels of bone metabolic markers. Decreasing glucocorticoid dosage appears important for improving bone metabolic marker profiles in patients with RA.

Real-time RT-PCR assay to differentiate clades of H5N1 avian influenza viruses circulating in Vietnam.

Continued circulation and geographical expansion of highly pathogenic avian influenza H5N1 virus have led to the emergence of numerous clades in Vietnam. Although viral RNA sequencing and phylogenetic analysis are the gold standard for H5N1 HA clade designation, limited sequencing capacity in many laboratories precludes rapid H5N1 clade identification and detection of novel viruses. Therefore, a Taqman real-time RT-PCR assay for rapid differentiation of the four major H5N1 clades detected in Vietnam was developed. Using HA sequence alignments of clades 1.1, 2.3.2.1, 2.3.4, and 7 viruses, primers and FAM-labeled probes were designed to target conserved regions characteristic of each clade. The assay was optimized and evaluated using circulating clades of H5N1 collected in Vietnam from 2007 to 2012 and shown to be both sensitive and specific for the differentiation of the four H5N1 clades. The assay provides a useful tool for screening of large specimen collections for HA gene sequencing and phylogenetic analysis and for the rapid identification of molecular clade signatures to support outbreak investigations and surveillance activities. Finally, this assay may be useful to monitor for the emergence of novel or variant clades of H5N1 in Vietnam in the future or in other countries where these particular clades may circulate.

Detection of HPAI H5N1 viruses in ducks sampled from live bird markets in Vietnam.

In Vietnam, highly pathogenic avian influenza (HPAI) H5N1 infections in poultry often occur without concomitant clinical signs and outbreaks are not consistently reported. Live bird markets represent a convenient site for surveillance that does not rely on farmers' notifications. Two H5N1 surveys were conducted at live bird markets/slaughter points in 39 districts (five provinces) in the Red River, Mekong delta, and central Vietnam during January and May 2011. Oropharyngeal and rectal swab samples from 12 480 ducks were tested for H5N1 by reverse transcription-polymerase chain reaction in pools of five. Traders and stallholders were interviewed using standardized questionnaires; 3·3% of pools tested positive. The highest prevalence (6·6%) corresponded to the Mekong delta, and no H5N1 was detected in the two Red River provinces. The surveys identified key risk behaviours of traders and stallholders. It is recommended that market surveys are implemented over time as a tool to evaluate progress in HPAI control in Vietnam.

Effects of acute nicotine on somatosensory change-related cortical responses.

Nicotine is known to have enhancing effects on some aspects of attention and cognition. As for the pre-attentive processes of detecting sensory changes, nicotine has significant effects on the auditory and visual systems implying that its pre-attentive effect is common among sensory modalities. The purpose of the present study was to elucidate whether acute nicotine administration has enhancing effects in the somatosensory system. Change-related cortical activity in response to an abrupt increase in stimulus intensity was recorded using magnetoencephalography. The test stimulus consisted of standard electrical pulses at 100 Hz for 500 ms applied to the dorsum of the left hand followed by 0.7-mA stronger pulses for 300 ms. Nicotine was administered in a gum (4 mg of nicotine). Eleven healthy nonsmokers were tested with a double-blind and placebo-controlled design. Effects of nicotine on the cortical response in the primary (S1) and secondary (S2) somatosensory cortices were investigated. Results showed that nicotine failed to affect the S1 response while it significantly increased the amplitude of S2 activity in the hemisphere ipsilateral to the stimulation, and shortened the peak latency of S2 activity in both hemispheres. Since cortical responses in the present study represent a pre-attentive automatic process to encode new somatosensory events, the results suggest that nicotine can exert beneficial cognitive effects without a direct impact on attention and that the effect of nicotine on the automatic change-detecting system is common across sensory modalities.

Lung cancer associated with an azygos lobe successfully treated with video-assisted thoracoscopic surgery.

Primary lung cancer associated with an azygos lobe is extremely rare. Herein, we report the case of a 64-year-old woman with lung adenocarcinoma arising in the right upper lobe with an azygos lobe. The patient underwent a right upper lobectomy and lymph node dissection with video-assisted thoracoscopic surgery. Video-assisted thoracoscopic surgery lobectomy for lung cancer of this variant has yet to be reported. We demonstrate the intraoperative findings and the resected pulmonary lobe. This is the first case of primary lung cancer associated with the azygos lobe treated by lobectomy with video-assisted thoracoscopic surgery.

Loss of multidrug and toxin extrusion 1 (MATE1) is associated with metformin-induced lactic acidosis.

BACKGROUNDS AND PURPOSE: Lactic acidosis is a fatal adverse effect of metformin, but the risk factor remains unclear. Multidrug and toxin extrusion 1 (MATE1) is expressed in the luminal membrane of the kidney and liver. MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin. Therefore, some MATE polymorphisms, that cause it to function abnormally, are hypothesized to induce lactic acidosis. The purpose of this study is to clarify the association between MATE dysfunction and metformin-induced lactic acidosis. EXPERIMENTAL APPROACH: Blood lactate, pH and bicarbonate ion (HCO(3) (-) ) levels were evaluated during continuous administration of 3 mg·mL(-1) metformin in drinking water using Mate1 knockout (-/-), heterozygous (+/-) and wild-type (+/+) mice. To determine the tissue accumulation of metformin, mice were given 400 mg·kg(-1) metformin orally. Furthermore, blood lactate data were obtained from diabetic patients given metformin. KEY RESULTS: Seven days after metformin administration in drinking water, significantly higher blood lactate, lower pH and HCO(3) (-) levels were observed in Mate1(-/-) mice, but not in Mate1(+/-) mice. The blood lactate levels were not affected in patients with the heterozygous MATE variant (MATE1-L125F, MATE1-G64D, MATE2-K-G211V). Sixty minutes after metformin administration (400 mg·kg(-1) , p.o.) the hepatic concentration of metformin was markedly higher in Mate1(-/-) mice than in Mate1(+/+) mice. CONCLUSION AND IMPLICATIONS: MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.

Effects of prior sustained tactile stimulation on the somatosensory response to the sudden change of intensity in humans: an magnetoencephalography study.

The rapid detection of sensory changes is important to survival. The change-detection system should relate closely to memory since it requires the brain to separate a new stimulus from past sensory status. To clarify effects of past sensory status on processing in the human somatosensory cortex, brain responses to an abrupt change of intensity in a train of electrical pulses applied to the hand were recorded by magnetoencephalography (MEG). In Experiment 1, effects of the magnitude of deviance (1.0, 0.5, 0.3, 0.2, and 0.1 mA) between conditioning and test stimuli were examined. In Experiment 2, effects of the duration of the conditioning stimulus (3, 1.5, 1.0, and 0.5 s) were examined. The abrupt change in stimulus intensity activated the contralateral primary (cSI) and secondary somatosensory cortex (cSII). The amplitude of the cSI and cSII activity was dependent on not only the magnitude of the change in intensity but also the length of the conditioning stimulus prior to the change, suggesting that storage of prior tactile information was involved in generating these responses. The possibility that an activity of onset (with no conditioning stimulus) would be involved in the change-related activity was also discussed.

[Metastatic ectopic cervical thymoma with prolonged survival; report of a case].

A 60-year-old woman presented with a palpable and painful nodule of her neck. Physical examination revealed that the anterior neck mass was enlarged without other positive findings. The tumor was not diagnosed with a fine needle aspiration biopsy, so that the excision of the tumor was underwent. The diagnosis at permanent section analysis revealed a non-invasive thymoma. The patient did not receive adjunctive postoperative therapy. For the duration of 6.5-year follow-up, metastasis of the left lobe of thyroid and right upper lobe of lung in twice have been sequentially detected and resected, and now she has been healthy with no known recurrence of the tumor. The recurrence of a non-invasive cervical ectopic thymoma has been reported as extremely rare, and this case indicates that the surgical control for recurrence lesion of cervical ectopic thymoma is effective when the tumor is resectable.

Repeated recurrence of gastric mucosal lesions in rats after a single treatment with compound 48/80, a mast cell degranulator.

We examined the recurrence of gastric mucosal lesions in rats after a single treatment with compound 48/80 (C48/80), a mast cell degranulator. During the period of 0.5 h to 24 h after treatment with C 48/80 (0.75 mg/kg, i.p.), an apparent recurrence of gastric mucosal lesions was found 18 and 24 h after the lesion formation, progression, and recovery occurred during the period of 12 h. Gastric mucosal blood flow showed the maximum reduction at 0.5, 16, and 22 h after treatment followed by the maximum recovery of the decrease at 12, 20, and 24 h, respectively. Gastric mucosal myeloperoxide and xanthine oxidase activities and lipid peroxide content showed the maximum increase at 3, 18, and 24 h after treatment. Gastric mucosal superoxide dismutase activity unchanged after treatment and gastric mucosal catalase activity decreased only at 24 h. Gastric mucosal Se-glutathione peroxidase activity and vitamin E, ascorbic acid, and hexosamine contents showed their maximum decrease at 3, 18, and 24 h after treatment. Gastric mucosal non-protein SH content showed the maximum decrease at 0.5, 16, and 22 h after treatment. Serum histamine and serotonin concentrations increased rapidly after treatment but the increases in serum histamine and serotonin concentrations diminished completely until 12 and 14 h, respectively. These results indicate that lesions recur repeatedly accompanied with an ischemia-reperfusion-like change in blood flow, inflammation, and disruption of antioxidant defense systems in the gastric mucosa of rats in no relation to released histamine and serotonin after a single C48/80 treatment.

Long-term effect of tacrolimus therapy in patients with refractory ulcerative colitis.

BACKGROUND: Little is known about long-term outcome of tacrolimus therapy for ulcerative colitis. Aim To evaluate long-term efficacy and safety of tacrolimus in Japanese patients with refractory ulcerative colitis. METHODS: Twenty-seven patients with UC refractory to conventional therapy were administered tacrolimus with trough whole-blood levels of 10-15 ng/mL to induce remission and 5-10 ng/mL to maintain remission. Median treatment duration was 11 months (1-39 months) and median follow-up duration was 17 months (2-65 months). Evaluation of the clinical response was based on a modified Truelove-Witts severity index (MTWSI). RESULTS: Tacrolimus produced a clinical response in 21 patients (77.8%), and remission was achieved in 19 of these 21 (70.4%) within 30 days. Overall cumulative colectomy-free survival was estimated as 62.3% at 65 months. In 18 of 19 patients treated with corticosteroids at the initiation of tacrolimus therapy, corticosteroids were discontinued or tapered. Adverse events were tremor (25.9%), renal function impairment (18.5%), infectious disease (14.8%), hot flashes (11.1%), hyperkalaemia (7.4%), headache (7.4%), epigastralgia (7.4%) and nausea (3.7%). No mortality occurred. CONCLUSION: Long-term administration of tacrolimus appears to be an effective and well-tolerated treatment for Japanese patients with refractory ulcerative colitis.

Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced acute [corrected] renal failure.

The effect of acute renal failure (ARF) induced by ischemia/reperfusion (I/R) of rat kidney on the expression of organic anion transporters (OATs) was examined. The level of serum indoxyl sulfate (IS), a uremic toxin and substrate of OATs in renal tubules, shows a marked increase with the progression of ARF. However, this increase was significantly attenuated by ingestion of cobalt. The level of mRNA and protein of both rOAT1 and rOAT3 were markedly depressed in the ischemic kidney. The uptake of p-aminohippuric acid (PAH) and estrone sulfate (ES) by renal slices of ischemic rats was significantly reduced compared to control rats. Renal slices taken from ischemic rats treated with cobalt displayed significantly elevated levels of ES uptake. Cobalt intake did not affect PAH uptake, indicating the functional restoration of rOAT3 but not rOAT1. The expression of Na(+)/K(+)-ATPase was markedly depressed in the ischemic kidney, suggesting that the inward Na(+) gradient in renal tubular cells had collapsed, thereby reducing the outward gradient of alpha-ketoglutarate, a driving force of both rOATs. The decreased expression of Na(+)/K(+)-ATPase was significantly restored by cobalt treatment. Our results suggest that the downregulation of renal rOAT1 and rOAT3 could be responsible for the increase in serum IS level of ischemic rats. Cobalt treatment has a significant protective effect on ischemia-induced ARF, being accompanied by the restoration of rOAT3 and/or Na(+)/K(+)-ATPase function.

Immunohistochemical analyses on serum proteins in nephrons of protein-overload mice by "in vivo cryotechnique".

Immunohistochemical analyses on local distributions of serum proteins in living mouse kidneys are usually difficult to examine with conventional preparation methods. By using our "in vivo cryotechnique" combined with freeze-substitution, we have checked immunolocalizations of the serum proteins in nephrons of bovine serum albumin (BSA)-overload mice, and compared them with those obtained by the conventional preparation methods. In two days of daily BSA-injected mice, the immunolocalization of BSA could be observed in Bowman's space and urinary tubules with their overt proteinuria, where another endogenous mouse albumin was similarly immunolocalized. The leakage of BSA and mouse albumin in Bowman's space and their reabsorption into proximal tubules were detected in 55% of nephrons, where no leakage of immunoglobulin G1 (IgG1) was detected. However, the leakage of IgG1, in addition to BSA and mouse albumin, was detected in the other nephrons. By carefully examining immunolocalizations of BSA and IgG1, they were obviously different from those obtained by the conventional preparation methods without normal blood circulation into the kidneys. The immunolocalizations of both BSA and mouse serum proteins could be directly analyzed with the "in vivo cryotechnique", suggesting that functional damage to glomerular filtration barriers are different at early stages of the BSA-overload mouse model, depending on each nephron of living mice.

Transcription-reverse transcription concerted reaction and minimal residual disease in axillary sentinel nodes of breast cancer.

AIMS: To investigate the use of transcription-reverse transcription concerted reaction (TRC) to detect axillary lymph node metastases. METHODS: Metastases in 423 lymph nodes obtained from 50 breast cancer patients were investigated by routine pathological hematoxylin and eosin (H and E) staining and quantitative analysis of carcinoembryonic antigen (CEA) mRNA by TRC. Enhanced pathological studies, serial sectioning and immunohistochemistry were conducted for cases which were negative by routine pathology, but positive by TRC. RESULTS: Pathological examination identified metastatic disease in 67 lymph nodes. TRC CEA mRNA results were concordant with 89.8% of these cases at a threshold of 100 copies. TRC identified 30 false negative nodes, which was reduced to 15 by excluding node biopsies yielding less than 40 microg total RNA. Twelve nodes were histologically negative for cancer, but positive according to TRC. Serial sectioning and immunohistochemical analysis of these nodes revealed macrometastatic lesions in three, micrometastasis in one, and isolated tumor cells in two. CONCLUSION: TRC for the detection of CEA mRNA may complement routine pathological examination by sentinel lymph node biopsy (SNB) in early breast cancer. We have started an enhanced pathological examination with serial sectioning on all excised sentinel nodes to set the best threshold for the TRC method.

Atrophy and hypertrophy of skeletal muscles: structural and functional aspects.

This review summarizes current information on structural and functional changes that occur during muscle atrophy and hypertrophy. Most published studies consider an increase in total mass of a muscle as hypertrophy, whereas a decrease in total mass of a muscle is referred to as atrophy. In hypertrophy, the rate of synthesis is much higher than the rate of degradation of muscle contractile proteins, leading to an increase in the size or volume of an organ due to enlargement of existing cells. When a muscle remains in disuse for a long period, the rate of degradation of contractile proteins becomes greater than the rate of replacement, resulting in muscle atrophy. This defect may occur as a result of lack of nutrition, loss of nerve supply, micro-gravity, ageing, systemic disease, prolonged immobilization or disuse. An understanding of the specific modifications that occur during muscle atrophy and hypertrophy may facilitate the development of novel techniques, as well as new therapies for affected muscles.

The PDZ domain protein PDZK1 interacts with human peptide transporter PEPT2 and enhances its transport activity.

The proton-coupled peptide transporter PEPT2 (SLC15A2) mediates the high-affinity low-capacity transport of small peptides as well as various oral peptide-like drugs in the kidney. In contrast to its well-characterized transport properties, there is less information available on its regulatory mechanism, although the interaction of PEPT2 to the PDZ (PSD-95, DglA, and ZO-1)-domain protein PDZK1 has been preliminarily reported. To examine whether PDZK1 is a physiological partner of PEPT2 in kidneys, we started from a yeast two-hybrid screen of a human kidney cDNA library with the C-terminus of PEPT2 (PEPT2 C-terminus (PEPT2-CT)) as bait. We could identify PDZK1 as one of the positive clones. This interaction requires the PDZ motif of PEPT2-CT detected by a yeast two-hybrid assay, in vitro binding assay and co-immunoprecipitation. The binding affinities of second and third PDZ domains of PDZK1 to PEPT2-CT were measured by surface plasmon resonance. Co-immunoprecipitation using human kidney membrane fraction and localization of PEPT2 in renal apical proximal tubules revealed the physiological meaning of this interaction in kidneys. Furthermore, we clarified the mechanism of enhanced glycylsarcosine (Gly-Sar) transport activity in PEPT2-expressing HEK293 cells after the PDZK1 coexpression. This augmentation was accompanied by a significant increase in the V(max) of Gly-Sar transport via PEPT2 and it was also associated with the increased surface expression level of PEPT2. These results indicate that the PEPT2-PDZK1 interaction thus plays a physiologically important role in both oligopeptide handling as well as peptide-like drug transport in the human kidney.

A longitudinal study to identify constraints to dairy cattle health and production in rural smallholder communities in Northern Vietnam.

The objective of the study was to investigate constraints to dairy cattle health and production in rural smallholder communities in northern Vietnam, one of the target areas of the Vietnam government's dairy development programme. A total of 99 dairy farms (11 per commune) were recruited from 9 of 32 communes in Ba Vi District, using random two-stage cluster sampling. After the initial questionnaire interviews were conducted, farms were visited at three monthly intervals over a period of 1 year. Information on several health and production parameters relating to the study cattle was collected. Using multiple indicator modelling, it was found that Fasciola infestation, farmers who had been involved in dairying for longer (not indicative of better management skills), larger herd size, and cattle being kept in a shed were linked to reduced reproductive performances.

Backward-masking: the effect of the duration of the second stimulus on recognition of the first stimulus.

OBJECTIVE: We recorded event-related magnetic fields following a target stimulus followed by a masking stimulus to investigate the visual backward masking effect using a helmet-type magnetoencephalography system in humans. METHODS: In the target stimulus with masking stimulus conditions, duration of the target stimulus was constant at 16 ms, and duration of the masking stimulus was altered (16, 48 and 144 ms). The target stimulus was masked by the 144-ms masking stimulus, but not by the 16-ms masking stimulus, and was obscured by the 48-ms masking stimulus. For control conditions (Single-condition), event-related magnetic fields were recorded following the sole presentation of the masking stimulus for 32, 64 or 160 ms. RESULTS: One major response was obtained at 180 ms after the onset of the stimulation in each condition. The equivalent current dipole of one major response was estimated to lie in the occipital lobe, but there was a relatively large inter-individual difference. There was no significant difference in latency between the target stimulus with masking stimulus conditions and Single-conditions. In the target stimulus with masking stimulus conditions with the 48- and 144-ms masking stimulus, the root mean square value did not differ from that in the respective Single-condition, while the root mean square value for the target stimulus with masking stimulus conditions with the 16-ms masking stimulus was significantly smaller than that in the Single-condition with the 32-ms masking stimulus, but not different from that in the Single-condition with the 16-ms masking stimulus. CONCLUSIONS: The peak latency of one major response depended on the onset of the first stimulus for both the target stimulus with masking stimulus conditions and Single-condition, but the root mean square value depended on the duration of the masking stimulus. We concluded that the temporal information for the target stimulus was preserved during the masking effect, while the figural information was interrupted by the masking stimulus. Our results suggested that temporal factors for the stimulus were processed differently from those responsible for the object's recognition during backward masking.