Pulmonary abscess caused by Cladosporium cladosporioides after receiving outpatient chemotherapy.

Cladosporium cladosporioides is one of the most ubiquitous dematiaceous fungi that seldomly occur human infection. Here, we demonstrate a rare case of pulmonary phaeohyphomycosis with a distinctive pulmonary lesion during the nadir period of outpatient chemotherapy against endometrial cancer. In addition to severe neutropenia, excessive exposure to C. cladosporioides at patient's residence was considered as dominant causative factor. More caution is considered necessary for pulmonary phaeohyphomycosis in patients who receive outpatient chemotherapy and are homebound during neutropenic status.

Identification of ABCG2 as an Exporter of Uremic Toxin Indoxyl Sulfate in Mice and as a Crucial Factor Influencing CKD Progression.

Chronic kidney disease (CKD) patients accumulate uremic toxins in the body, potentially require dialysis, and can eventually develop cardiovascular disease. CKD incidence has increased worldwide, and preventing CKD progression is one of the most important goals in clinical treatment. In this study, we conducted a series of in vitro and in vivo experiments and employed a metabolomics approach to investigate CKD. Our results demonstrated that ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a major transporter of the uremic toxin indoxyl sulfate. ABCG2 regulates the pathophysiological excretion of indoxyl sulfate and strongly affects CKD survival rates. Our study is the first to report ABCG2 as a physiological exporter of indoxyl sulfate and identify ABCG2 as a crucial factor influencing CKD progression, consistent with the observed association between ABCG2 function and age of dialysis onset in humans. The above findings provided valuable knowledge on the complex regulatory mechanisms that regulate the transport of uremic toxins in our body and serve as a basis for preventive and individualized treatment of CKD.

Evaluation of a TB infection control implementation initiative in out-patient HIV clinics in Zambia and Botswana.

SETTING: Out-patient human immunodeficiency virus (HIV) care and treatment clinics in Zambia and Botswana, countries with a high burden of HIV and TB infection. OBJECTIVE: To develop a tuberculosis infection control (TB IC) training and implementation package and evaluate the implementation of TB IC activities in facilities implementing the package. DESIGN: Prospective program evaluation of a TB IC training and implementation package using a standardized facility risk assessment tool, qualitative interviews with facility health care workers and measures of pre- and post-test performance. RESULTS: A composite measure of facility performance in TB IC improved from 32% at baseline to 50% at 1 year among eight facilities in Zambia, and from 27% to 80% at 6 months among 10 facilities in Botswana. Although there was marked improvement in indicators of managerial, administrative and environmental controls, key ongoing challenges remained in ensuring access to personal protective equipment and implementing TB screening in health care workers. CONCLUSION: TB IC activities at out-patient HIV clinics in Zambia and Botswana improved after training using the implementation package. Continued infrastructure support, as well as monitoring and evaluation, are needed to support the scale-up and sustainability of TB IC programs in facilities in low-resource countries.

Temperature seasonality during fry out-migration influences the survival of hatchery-reared chum salmon Oncorhynchus keta.

Among years, fry-to-adult survival of hatchery-reared chum salmon Oncorhynchus keta was positively correlated with the length (in days) of the fry out-migration period with temperatures suitable for migration. Furthermore, survival decreased with increasing difference in mean temperature between May and June. Thus, prolonged out-migration periods increased the probability of survival from fry to adult, lending support to the hypothesis that long migration periods decrease the risk of mortality (bet-hedging), and increase the probability of migration when environmental conditions in fresh water and the ocean are suitable (match-mismatch).

Working memory training is associated with lower prefrontal cortex activation in a divergent thinking task.

Working memory (WM) training has been shown to lead to improvements in WM capacity and fluid intelligence. Given that divergent thinking loads on WM and fluid intelligence, we tested the hypothesis that WM training would improve performance and moderate neural function in the Alternate Uses Task (AUT)-a classic test of divergent thinking. We tested this hypothesis by administering the AUT in the functional magnetic resonance imaging scanner following a short regimen of WM training (experimental condition), or engagement in a choice reaction time task not expected to engage WM (active control condition). Participants in the experimental group exhibited significant improvement in performance in the WM task as a function of training, as well as a significant gain in fluid intelligence. Although the two groups did not differ in their performance on the AUT, activation was significantly lower in the experimental group in ventrolateral prefrontal and dorsolateral prefrontal cortices-two brain regions known to play dissociable and critical roles in divergent thinking. Furthermore, gain in fluid intelligence mediated the effect of training on brain activation in ventrolateral prefrontal cortex. These results indicate that a short regimen of WM training is associated with lower prefrontal activation-a marker of neural efficiency-in divergent thinking.

Review: The role of autophagy in extravillous trophoblast function under hypoxia.

Autophagy, a process for cellular cleaning through the removal of intracellular components in lysosomes, is a well conserved mechanism from yeast to mammalian cells, and also contributes to the maintenance of cellular homeostasis and of the energetic balance, in cellular and tissue remodeling, and cellular defense against extracellular insults and pathogens. The role of autophagy in placentation has been clarified. Autophagy is induced in trophoblasts under physiological hypoxia during early pregnancy and seems to have a role in placentation. Recent findings suggest that impaired autophagy might induce poor placentation in preeclamptic cases. In this review, we discuss the role of autophagy and summarize the role of autophagy-related genes in placentas.

Antiretroviral therapy uptake among adult tuberculosis patients newly diagnosed with HIV in Nyanza Province, Kenya.

SETTING: In 2008, the Kenya tuberculosis (TB) program reported low (31%) antiretroviral therapy (ART) uptake among human immunodeficiency virus (HIV) infected TB patients. OBJECTIVE: To confirm ART coverage and identify factors associated with HIV clinic enrollment and ART initiation among TB patients. DESIGN: Retrospective chart abstraction of adult TB patients newly diagnosed with HIV and eligible for ART at 58 Nyanza Province TB clinics between October 2006 and April 2008. TB data were linked to HIV clinic data at 50 facilities that provided ART. Associations with HIV clinic enrollment and ART were evaluated. RESULTS: Among 1137 ART-eligible TB patient records sampled, 32% documented HIV clinic enrollment and 29% ART. Date fields were largely incomplete; 11% of the patient records included HIV testing dates and ≤1% had dates for cotrimoxazole prophylaxis, HIV clinic enrollment and ART initiation. Adding HIV clinic data increased HIV clinic enrollment and ART documentation to respectively 62% and 44%. Among TB patients in HIV care, female sex, older age group and baseline CD4 documentation were associated with ART initiation. CONCLUSION: Linking data increased documentation of HIV clinic enrollment and ART uptake. Continued efforts are required to improve the documentation of HIV service delivery, especially in TB clinics. Interventions to increase ART uptake are needed for younger patients and men.

Preferential Fas-mediated apoptotic execution at G1 phase: the resistance of mitotic cells to the cell death.

Apoptosis is induced by various stresses generated from the extracellular and intracellular environments. The fidelity of the cell cycle is monitored by surveillance mechanisms that arrest its further progression if any crucial process has not been completed or damages are sustained, and then the cells with problems undergo apoptosis. Although the molecular mechanisms involved in the regulation of the cell cycle and that of apoptosis have been elucidated, the links between them are not clear, especially that between cell cycle and death receptor-mediated apoptosis. By using the HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, we investigated the relationship between the cell cycle progression and apoptotic execution. To monitor apoptotic execution during cell cycle progression, we observed the cells after induction of apoptosis with time-lapse fluorescent microscopy. About 70% of Fas-mediated apoptotic cells were present at G(1) phase and about 20% of cells died immediately after cytokinesis, whereas more than 60% of etoposide-induced apoptotic cells were at S/G(2) phases in random culture of the cells. These results were confirmed by using synchronized culture of the cells. Furthermore, mitotic cells showed the resistance to Fas-mediated apoptosis. In conclusion, these findings suggest that apoptotic execution is dependent on cell cycle phase and Fas-mediated apoptosis preferentially occurs at G(1) phase.

Efficacy of diffusion-weighted magnetic resonance imaging in detecting infected cysts in a case of polycystic kidney disease.

Hepatic and/or renal cyst infection is a major complication in patients with polycystic kidney disease. In many cases, drainage of infected cysts is necessary, although accurate detection of infected cysts from among the numerous hepatic or renal cysts present is often difficult, because the findings of infected cysts on computed tomography and T1- and T2-weighted magnetic resonance imaging resemble those of normal cysts. We describe here a case of polycystic kidney disease complicated by hepatic cyst infection. On diffusion-weighted magnetic resonance imaging (DWMRI), which is occasionally used in the diagnosis of cerebral abscesses, infected hepatic cysts showed higher signal intensity than other cysts, facilitating differentiation of the cysts requiring drainage from numerous other cysts. Infected cysts showed a marked decrease of the apparent diffusion coefficient (ADC) values compared with those of normal cysts. DWMRI was very effective in detecting infected cysts in our patient and may be of value in other such cases with polycystic kidney disease.

Prevalence of abdominal obesity in adolescents: a systematic review.

The objectives of this study were to (i) review extant literature on the prevalence of abdominal obesity (AO) in adolescents of both sex (10-19 years old); (ii) analyse the cut-off points used for the diagnosis of AO and (iii) compare its prevalence between developed and developing countries. The search was carried out using online databases (MEDLINE, Web of Science, EMBASE, SPORTDiscus, SCIELO and BioMed Central), references cited by retrieved articles and by contact with the authors, considering articles published from the establishment of the databanks until 19 October 2009. Only original articles and those using waist circumference in the diagnosis were considered. Twenty-nine studies met the inclusion criteria. Fourteen of these studies were performed in developed countries. The prevalence of AO varied from 3.8% to 51.7% in adolescents from developing countries. The range of results was smaller among developed countries; with values from 8.7% to 33.2%. Eighteen different cut-off points were used. It was concluded the AO prevalence is high among adolescents, but is not clear what sex has a higher proportion and it is greater in adolescents from developing countries; however, there is no consensus in the literature about the criteria to be used.

Plasma osteoprotegerin, arterial stiffness, and mortality in normoalbuminemic Japanese hemodialysis patients.

UNLABELLED: A high circulating osteoprotegerin (OPG) level may be a risk factor for vascular calcification and mortality in hemodialysis patients. OPG and pulse wave velocity (PWV) were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients who were prospectively followed for 6 years. In long-term normoalbuminemic Japanese hemodialysis patients, OPG levels were strongly linked with both arterial stiffness and worse outcome. INTRODUCTION: A high circulating OPG level is reported to be a risk factor for vascular calcification and mortality in Western chronic kidney disease (CKD) patients but it is not known if this is true for Japanese CKD patients, where a different risk profile may operate. METHODS: OPG and PWV were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients (median age 62 years) who were prospectively followed for 6 years. RESULTS: OPG levels were associated in multivariate analysis with age, dialysis vintage, history of cardiovascular disease (CVD) and parathyroid hormone levels. C-reactive protein levels did not correlate with OPG. Patients with clinical history of CVD had significantly higher OPG levels and OPG levels were positively correlated to PWV, an index of arterial stiffness. These associations were independent of age, sex, dialysis vintage, and diabetes. During the follow-up period, 40 deaths, including 25 cardiovascular deaths, were recorded. In crude analysis, each unit of increase in OPG was associated with increased all-cause (hazard ratios 1.14, 95% confidence interval 1.08-1.20) and CVD mortality (1.14 [1.07-1.21]), which persisted after adjustment for age, sex, dialysis vintage, diabetes, and baseline CVD (1.12 [1.05-1.19] and 1.11 [1.02-1.19], all-cause and CVD mortality, respectively). CONCLUSIONS: In long-term normoalbuminemic Japanese hemodialysis patients, with low prevalence of inflammation, OPG levels were strongly linked with both arterial stiffness and worse outcome.

Inflammatory pseudotumor of the liver in association with spilled gallstones 3 years after laparoscopic cholecystectomy: report of a case.

We report on a case of a female patient diagnosed with inflammatory pseudotumor of the liver in association with spilled gallstones 3 years after laparoscopic cholecystectomy for calculous acute cholecystitis. She was asymptomatic, but CT revealed an intrahepatic mass and two other extrahepatic masses between the liver and the diaphragm. Furthermore, diffusion-weighted MRI and PET suggested all three lesions could be malignant tumors. As the preoperative diagnosis was intrahepatic cholangiocellular carcinoma with peritoneal disseminations, we performed a posterior segmentectomy of the liver combined with partial resection of the diaphragm. Histological examination showed the intrahepatic tumor was an inflammatory granuloma with abscess formations. There were bilirubin stones between the liver and the diaphragm. Therefore, the tumor was diagnosed as inflammatory pseudotumor of the liver in association with spilled gallstones. In conclusion, the liver tumor emerged after laparoscopic cholecystectomy and may involve inflammatory pseudotumor of the liver in association with spilled gallstones.

Endogenous estrogen may prevent bone loss in postmenopausal hemodialysis patients throughout life.

SUMMARY: Postmenopausal hemodialysis patients are at risk of complications related to renal mineral and bone disorder, and postmenopausal osteoporosis. In 112 postmenopausal hemodialysis patients, free estrogen index was positively correlated with bone mineral density (BMD) Z-score and the annual percent change of BMD in multiple regression analysis. Endogenous estrogen may prevent bone loss in postmenopausal hemodialysis patients throughout life. INTRODUCTION: Women on dialysis are not only at risk of developing mineral and bone disorder, but also suffer from postmenopausal osteoporosis. We assessed the effect of sex hormones on bone metabolism in postmenopausal hemodialysis patients. METHODS: We enrolled 112 postmenopausal hemodialysis patients with a mean age of 68.4 ± 10.4 years. We measured the serum levels of estradiol, testosterone, sex hormone-binding globulin (SHBG), and intact parathyroid hormone (intact-PTH), as well as bone metabolism parameters and radial bone mineral density (BMD). The free estrogen index (FEI) was calculated from the estradiol and SHBG values. After conventional dialysis was performed for 12 months, BMD was measured again and the annual percent change was calculated. Estradiol and SHBG were also measured in 25 postmenopausal women without chronic kidney disease. RESULTS: Estradiol levels were higher in the hemodialysis patients than in the postmenopausal women without chronic kidney disease. In patients with relatively normal bone turnover (intact-PTH: from 150 to 300 pg/ml), the FEI showed a positive correlation with the BMD Z-score. The annual percent change of BMD showed a positive correlation with the FEI according to multiple regression analysis. CONCLUSIONS: Endogenous estrogen may prevent bone loss in postmenopausal hemodialysis patients throughout life.

Piloting the use of personal digital assistants for tuberculosis and human immunodeficiency virus surveillance, Kenya, 2007.

SETTING: Improved documentation of human immunodeficiency virus (HIV) testing and care among tuberculosis (TB) patients is needed to strengthen TB-HIV programs. In 2007, Kenya piloted the use of personal digital assistants (PDAs) instead of paper registers to collect TB-HIV surveillance data from TB clinics. OBJECTIVE: To evaluate the acceptability, data quality and usefulness of PDAs. DESIGN: We interviewed four of 31 district coordinators who collected data in PDAs for patients initiating TB treatment from April to June 2007. In 10 of 93 clinics, we randomly selected patient records for comparison with corresponding records in paper registers or PDAs. Using Cochran-Mantel-Haenszel tests, we compared missing data proportions in paper registers with PDAs. We evaluated PDA usefulness by analyzing PDA data from all 93 clinics. RESULTS: PDAs were well accepted. Patient records were more frequently missing (28/97 vs. 1/112, P < 0.001) and data fields more frequently incomplete (148/1449 vs. 167/2331, P = 0.03) in PDAs compared with paper registers. PDAs, however, facilitated clinic-level analyses: 48/93 (52%) clinics were not reaching the targets of testing >or=80% of TB patients for HIV, and 8 (9%) clinics were providing <80% of TB-HIV co-infected patients with cotrimoxazole (CTX). CONCLUSION: PDAs had high rates of missing data but helped identify clinics that were undertesting for HIV or underprescribing CTX.

Dynamic, experience-dependent modulation of synaptic zinc within the excitatory synapses of the mouse barrel cortex.

Increasing evidence suggests that synaptic zinc, found within the axon terminals of a subset of glutamatergic neurons in the cerebral cortex, is intricately involved in cortical plasticity. Using the vibrissae/barrel cortex model of cortical plasticity, we have previously shown manipulations of sensory input leads to rapid changes in synaptic zinc levels within the corresponding regions of the somatotopic map in the cortex. Here, using electron microscopy, we show how some of these changes are mediated at the synaptic level. We found that the density of zincergic synapses increased significantly in layers II/III, IV, and V. In layers IV and V, this change occurred in the absence of a significant increase in excitatory synapse density, which seems to indicate that excitatory synapses, which previously did not contain synaptic zinc, begin to newly house zinc within its synaptic vesicles. Our results show that excitatory neurons can dynamically change the phenotype of the vesicular content of their synapses in response to changes in sensory input. Given the range of modulatory effects zinc can have on neurotransmission, such a change in the complement of vesicular contents presumably allow these neurons to utilize synaptic zinc to facilitate plasticity. Thus, our results further support the role of zinc as an active participant in the processes contributing to experience-dependent cortical plasticity.

Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer.

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy. In a variety of cancer cells, overactivation of mTOR has been reported. In addition, mTOR inhibitors, such as rapamycin and its derivatives, are being evaluated in clinical trials as anticancer drugs. However, no active mutants of mTOR have been identified in human cancer. Here, we report that two different point mutations, S2215Y and R2505P, identified in human cancer genome database confer constitutive activation of mTOR signaling even under nutrient starvation conditions. S2215Y was identified in large intestine adenocarcinoma whereas R2505P was identified in renal cell carcinoma. mTOR complex 1 prepared from cells expressing the mutant mTOR after nutrient starvation still retains the activity to phosphorylate 4E-BP1 in vitro. The cells expressing the mTOR mutant show increased percentage of S-phase cells and exhibit resistance to cell size decrease by amino-acid starvation. The activated mutants are still sensitive to rapamycin. However, they show increased resistance to 1-butanol. Our study points to the idea that mTOR activating mutations can be identified in a wide range of human cancer.

Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines.

Tyrosine hydroxylase (TH) catalyzes the conversion of L: -tyrosine to L: -dopa, which is the initial and rate-limiting step in the biosynthesis of catecholamines [CA; dopamine (DA), noradrenaline, and adrenaline], and plays a central role in the neurotransmission and hormonal actions of CA. Thus, TH is related to various neuro-psychiatric diseases such as TH deficiency, Parkinson's disease (PD), and schizophrenia. Four isoforms of human TH (hTH1-hTH4) are produced from a single gene by alternative mRNA splicing in the N-terminal region, whereas two isoforms exist in monkeys and only a single protein exist in all non-primate mammals. A catalytic domain is located within the C-terminal two-thirds of molecule, whereas the part of the enzyme controlling enzyme activity is assigned to the N-terminal end as the regulatory domain. The catalytic activity of TH is end product inhibited by CA, and the phosphorylation of Ser residues (Ser(19), Ser(31), and especially Ser(40) of hTH1) in the N-terminus relieves the CA-mediated inhibition. Ota and Nakashima et al. have investigated the role of the N-terminus of TH enzyme in the regulation of both the catalytic activity and the intracellular stability by producing various mutants of the N-terminus of hTH1. The expression of the following three enzymes, TH, GTP cyclohydrolase I, which synthesizes the tetrahydrobiopterin cofactor of TH, and aromatic-L: -amino acid decarboxylase, which produces DA from L: -dopa, were induced in the monkey striatum using harmless adeno-associated virus vectors, resulting in a remarkable improvement in the symptoms affecting PD model monkeys Muramatsu (Hum Gene Ther 13:345-354, 2002). Increased knowledge concerning the amino acid sequences of the N-terminus of TH that control enzyme activity and stability will extend the spectrum of the gene-therapy approach for PD.

[Intralobar sequestration in elderly patient; report of a case].

A 71-year-old woman who had been treated as bronchitis was diagnosed as intralobar sequestration by a computed tomography scan. She had 2 episodes of hemosputum in recent 30 years but the amounts were small and they spontaneously stopped in a day. She had an abnormal vessel from thoracic descending aorta of which diameter was 1 cm draining to the basal segment of the left lung. She was operated on a left lower lobectomy with ligation of the vessel via a thoracotomy. Postoperative course was uneventful, and she discharged home on the 9th postoperative day.

[Resected case of pulmonary arteriovenous malformation diagnosed with a brain abscess as a clinical manifestation; report of a case].

A 63-year-old female with Rendu-Osler-Weber disease had general fatigue and right hemiparesis. A computed tomography (CT) scan of her head demonstrated an enhancing cystic mass in the left frontal lobe, and it was diagnosed as a brain abscess and then drainaged. Thereafter, a pulmonary arteriovenous malformation (PAVM) identified in the left lingular segment by chest CT scan and the PAVM was resected by partial resection of the lung.

Glycolytic enzyme Pgk1 is strongly expressed in the developing tooth germ of the mouse lower first molar.

This study examined detailed in situ expression patterns and possible functional roles of phosphoglycerate kinase 1 (Pgk1) gene in the developing tooth germ of the mouse lower first molar. The strong expression of Pgk1 mRNA was seen in the odontogenic epithelial cells and surrounding mesenchymal cells of the tooth germ from embryonic day 10.5 (E10.5) to E18.0. Western blotting analysis demonstrated that Pgk1 protein formed 84-kDa protein complex in these embryonic organs. The results of immunoprecipitation-western blotting also suggested this complex to be formed with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Moreover, the immunofluorescence expression of those proteins was shown to overlap each other in the tooth germ at E15.0. A strong immunofluorescence expression of both Pgk1 and GAPDH also corresponded to the in situ expression of those mRNAs. These results suggested that Pgk1 plays some functional roles in the development of tooth germ and other embryonic organs by forming protein complex with GAPDH.