C-reactive protein (CRP) is a marker of inflammation and a risk predictor of cardiovascular disease. Current CRP assays are focused on the quantification of the CRP levels as pentamers. However, CRP can be present as other multimeric forms. There will be a market need to measure the CRP multimeric structure in addition to the levels in human populations. To meet this need, we investigated whether the long-term archived samples could be used instead of freshly collected samples.
The specimens of serum, plasma and tissues were collected from transgenic rats expressing the human CRP. These samples were stored at 4°C, −20°C and −80°C for different periods. Non-denaturing Western blot analysis was used to observe the influence of storage conditions to multimeric structures of human CRP. Our results showed that there was no difference on multimeric structures of human CRP between samples stored at 4°C, −20°C and −80°C, between samples stored at −80°C for twenty-four hours and three months, and between plasma and serum.
This study implicated that archived samples stored at these conditions in those large longitudinal studies could be used for investigating the multimeric structures of CRP. Our report may speed up these researches and save labors and budget by enabling them to use currently available archived samples rather than freshly collected samples.
Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.
We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.
The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.
ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.
MscL, the highly conserved bacterial mechanosensitive channel of large conductance, functionally serves as an osmotic “emergency release valve”, is among the best studied mechanosensors and a paradigm of how a channel senses and responds to membrane tension. While all homologues tested thus far encode channel activity, many show functional differences. Here we tested E. coli and S aureus chimeras and find that the periplasmic region of the protein, particularly E. coli I49 and the equivalent S aureus F47 at the periplasmic lipid-aqueous interface of the first transmembrane domain, drastically influences both the open dwell time and threshold of channel opening. One mutant shows a severe hysteresis, confirming the importance of this residue in determining the energy barriers for channel gating. We propose that this site acts similar to a spring for a clasp knife, adjusting the resistance for obtaining and stabilizing an open or closed channel structure.
mechanosensitive channel; channel kinetics; osmoregulation; protein-lipid interactions
Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare aggressive form of NK-cell neoplasm. We report an uncommon case of 36-year-old male who showed jaundice and spontaneous splenic rupture. The diagnosis was established by the biopsy of liver and spleen. The monomorphous medium-size neoplastic cells infiltrated into portal areas and sinus of liver as well as the cords and sinus of the spleen. Necrosis, mitotic figures and significant apoptosis could be seen easily. These neoplastic cells demonstrated a typical immunophenotype of CD3ε+, CD56+, CD16+, Granzyme B+, TIA-1+. T-cell receptor γ (TCR-γ) gene rearrangement analysis showed germline configuration and the result of in situ hybridization for Epstein-Barr virus-encoded RNA (EBER-ISH) was positive. The patient has undergone an aggressive clinical course and died of multi-organ function failure 14 days later after admission. To the best of our knowledge, this is the first case of ANKL with spontaneous splenic rupture, and we should pay more attention to recognize it.
The virtual slide(s) for this article can be found here:
Aggressive natural killer-cell leukemia; Jaundice; Spontaneous splenic rupture
Acupuncture regulates autonomic function. Our previous studies have shown that electroacupuncture (EA) at the Jianshi–Neiguan acupoints (P5–P6, underlying the median nerve) inhibits central sympathetic outflow and attenuates excitatory cardiovascular reflexes, in part, through an opioid mechanism. It is unknown if EA at these acupoints influences the parasympathetic system. Thus, using c-Fos expression, we examined activation of nucleus ambiguus (NAmb) neurons by EA, their relation to cholinergic (preganglionic parasympathetic) neurons and those containing enkephalin. To enhance detection of cell bodies containing enkephalin, colchicine (90–100 μg/kg) was administered into the subarachnoid space of cats 30 hr prior to EA or sham-operated controls for EA. Following bilateral barodenervation and cervical vagotomy, either EA for 30 min at P5–P6 acupoints or control stimulation (needle placement at P5–P6 without stimulation) was applied. While perikarya containing enkephalin were observed in some medullary nuclei (e.g., râphe), only enkephalin-containing neuronal processes were found in the NAmb. Compared to controls (n=4), more c-Fos immunoreactivity, located principally in close proximity to fibers containing enkephalin was noted in the NAmb of EA-treated cats (n=5; P<0.01). Moreover, neurons double-labeled with c-Fos and choline acetyltransferase in the NAmb were identified in EA-treated, but not the control animals. These data demonstrate for the first time that EA activates preganglionic parasympathetic neurons in the NAmb. Because of their close proximity, these EA-activated neurons likely interact with nerve fibers containing enkephalin. These results suggest that EA at the P5–P6 acupoints has the potential to influence parasympathetic outflow and cardiovascular function, likely through an enkephalinergic mechanism.
Acupuncture; nucleus ambiguus; acetylcholine; enkephalin; c-Fos
To evaluate whether the location of moist desquamation matches high dose area for breast cancer patients receiving adjuvant radiotherapy (RT) after breast conservative surgery.
One hundred and nine breast cancer patients were enrolled to this study. Their highest skin dose area (the hot spot) was estimated from the treatment planning. We divided the irradiated field into breast; sternal/parasternal; axillary; and inframammary fold areas. The location for moist desquamation was recorded to see if it matches the hot spot. We also analyzed other possible risk factors which may be related to the moist desquamation.
Forty-eight patients with 65 locations developed moist desquamation during the RT course. Patients with larger breast sizes and easy to sweat are two independent risk factors for moist desquamation. The distribution of moist desquamation occurred most in the axillary area. All nine patients with the hot spots located at the axillary area developed moist desquamation at the axillary area, and six out of seven patients with the hot spots located at the inframammary fold developed moist desquamation there. The majority of patients with moist desquamation over the breast or sternal/parasternal areas had the hot spots located at these areas.
For a patient with moist desquamation, if a hot spot is located at the axillary or inframammary fold areas, it is very likely to have moist desquamation occur there. On the other hand, if moist desquamation occurs over the breast or sternal/parasternal areas, we can highly expect these two areas are also the hot spot locations.
Breast cancer; Radiotherapy; Radiation dermatitis; High dose area
Endometriosis is a common gynecological condition with complex etiology defined by the presence of endometrial glands and stroma outside the womb. Endometriosis is a common cause of both cyclic and chronic pelvic pain, reduced fertility, and reduced quality-of-life. Diagnosis and treatment of endometriosis is, on average, delayed by 7–10 years from the onset of symptoms. Absence of a timely and non-invasive diagnostic tool is presently the greatest barrier to the identification and treatment of endometriosis. Twin and family studies have documented an increased relative risk in families. To identify genetic factors that contribute to endometriosis we conducted a two-stage genome-wide association study (GWAS) of a European cohort including 2,019 surgically confirmed endometriosis cases and 14,471 controls. Three of the SNPs we identify associated at P<5×10−8 in our combined analysis belong to two loci: LINC00339-WNT4 on 1p36.12 (rs2235529; P = 8.65×10−9, OR = 1.29, CI = 1.18–1.40) and RND3-RBM43 on 2q23.3 (rs1519761; P = 4.70×10−8, OR = 1.20, Cl = 1.13–1.29, and rs6757804; P = 4.05×10−8, OR = 1.20, Cl = 1.13–1.29). Using an adjusted Bonferoni significance threshold of 4.51×10−7 we identify two additional loci in our meta-analysis that associate with endometriosis:, RNF144B-ID4 on 6p22.3 (rs6907340; P = 2.19×10−7, OR = 1.20, Cl = 1.12–1.28), and HNRNPA3P1-LOC100130539 on 10q11.21 (rs10508881; P = 4.08×10−7, OR = 1.19, Cl = 1.11–1.27). Consistent with previously suggested associations to WNT4 our study implicate a 150 kb region around WNT4 that also include LINC00339 and CDC42. A univariate analysis of documented infertility, age at menarche, and family history did not show allelic association with these SNP markers. Clinical data from patients in our study reveal an average delay in diagnosis of 8.4 years and confirm a strong correlation between endometriosis severity and infertility (n = 1182, P<0.001, OR = 2.18). This GWAS of endometriosis was conducted with high diagnostic certainty in cases, and with stringent handling of population substructure. Our findings broaden the understanding of the genetic factors that play a role in endometriosis.
Monoclonal antibodies (McAbs) against chloramphenicol (CAP) were produced to detect CAP residues, which could be toxic and possesses a potential threat to human health. The CAP-BSA conjugate was obtained by bovine serum albumin (BSA) coupled with CAP, and used to immunize the mice. The splenocytes from the immunized mice were fused with mouse myeloma cells SP2/0 to form hybridoma, which may secrete McAbs against CAP. Hybridomas 1D1 and 3G12 secreting McAbs against CAP were obtained by screening. Ascites containing McAbs were prepared by injecting 1 x 106 cells of hybridoma 1D1 and 3G12 into the abdomen of mice. Protein A affinity chromatography was used to purify McAbs against CAP in a single chromatographic step with recovery yield above 80% and purity above 95% and full recovery of antibody activity. Experiments showed that McAb 3G12 was highly specific for CAP and had no cross-reactivity with analogues which have a structure similar to CAP. The IC50 value was 50.8 ng/mL.
Chloramphenicol; McAbs; Preparation; Purification
MscL is a bacterial mechanosensitive channel that protects cells from lysis upon acute decrease in external osmotic environment. It is one of the best characterized mechanosensors known, thus serving as a paradigm of how such molecules sense and respond to stimuli. In addition, the fact that it can be genetically modified, expressed, isolated, and manipulated has led to its proposed use as a triggered nanovalve for various functions including sensors within microelectronic array chips, as well as vesicular-based targeted drug release. X-ray crystallography reveals a homo-pentameric complex with each subunit containing two transmembrane α-helices (TM1 and TM2) and a single carboxyl terminal α-helix arranging within the complex to form a five-fold cytoplasmic bundle (CB), whose function and stability remain unclear. In this study, we show three routes that throttle the open channel conductance. When the linker between the TM2 and CB domain is shortened by deletions or constrained by either cross linking or heavy metal coordination, the conductance of the channel is reduced; in later two cases, even reversibly. While having implications for the stability of the CB, these data also provide routes for engineering MscL sensors that are more versatile for potential nanotech devices.
Osmoregulation; Conductance; Nanopore; Biosensor; Drug-release device
In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.
The study of eukaryotic cell division has overwhelmingly focused on cells from two branches of evolution, fungal and metazoan, with more distant eukaryotes rarely studied. One exception is apicomplexan pathogens where in the last two decades development of genetic models has been rapid. While not a perfect solution to fill the missing evolutionary diversity, Apicomplexans represent one of the oldest eukaryotic lineages possibly pre-dating the divergence of plant and animal kingdoms. A key to uncovering novel and conserved cell cycle mechanisms in these protists was the development of forward genetic approaches that permit unbiased discovery of essential growth factors. The apicomplexan, Toxoplasma has provided the best resource so far with ∼60,000 chemical mutants yielding a collection of 165 temperature-sensitive isolates that arrest in all phases of the parasite cell cycle. Efforts to identify the defective genes in this model are providing insights into the regulatory factors possibly active in the original eukaryote cell cycle, like the mRNA splicing factor discovered in this study.
In the title HoIII–erythritol complex, [Ho(NO3)3(C4H10O4)(C2H5OH)], the HoIII cation is chelated by a tridentate erythritol ligand and three bidentate nitrate anions. An ethanol molecule further coordinates the HoIII cation, completing the irregular O10 coordination geometry. In the crystal, an extensive O—H⋯O hydrogen-bond network links the molecules into a three-dimensional supramolecular structure.
A β-turn is a secondary protein structure type that plays a significant role in protein configuration and function. On average 25% of amino acids in protein structures are
located in β-turns. It is very important to develope an accurate and efficient method for β-turns prediction. Most of the current successful β-turns prediction methods use support vector
machines (SVMs) or neural networks (NNs). The kernel logistic regression (KLR) is a powerful classification technique that has been applied successfully in many classification problems. However, it is often not found in β-turns classification, mainly because it is computationally expensive. In this paper, we used KLR to obtain sparse β-turns prediction in short evolution time. Secondary structure information and position-specific scoring matrices (PSSMs) are utilized as input features. We achieved Qtotal of 80.7% and MCC of 50% on BT426 dataset. These results show that KLR method with the right algorithm can yield
performance equivalent to or even better than NNs and SVMs in β-turns prediction. In addition, KLR yields probabilistic outcome and has a well-defined extension to multiclass case.
There are many discussions about dyslexia based on studies conducted in western countries, and some risk factors to dyslexia, such as gender and home literacy environment, have been widely accepted based on these studies. However, to our knowledge, there are few studies focusing on the risk factors of dyslexia in China. Therefore, the aim of our study was to investigate the prevalence of dyslexia and its potential risk factors.
A cross-sectional study was conducted in Qianjiang, a city in Hubei province, China. Two stages sampling strategy was applied to randomly selected 5 districts and 9 primary schools in Qianjiang. In total, 6,350 students participated in this study and there were 5,063 valid student questionnaires obtained for the final analyses. Additional questionnaires (such as Dyslexia Checklist for Chinese Children and Pupil Rating Scale) were used to identify dyslexic children. The chi-square test and multivariate logistic regression were employed to reveal the potential risk factors to dyslexia.
Our study revealed that the prevalence of dyslexia was 3.9% in Qianjiang city, which is a middle-sized city in China. Among dyslexic children, the gender ratio (boys to girls) was nearly 3∶1. According to the P-value in the multivariate logistic regression, the gender (P<0.01), mother's education level (P<0.01), and learning habits (P<0.01) (active learning, scheduled reading time) were associated with dyslexia.
The prevalence rate of dyslexic children in middle-sized cities is 3.9%. The potential risk factors of dyslexic children revealed in this study will have a great impact on detecting and treating dyslexic children in China as early as possible, although more studies are still needed to further investigate the risk factors of dyslexic children in China.
Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are complications causing weakness of respiratory and limb muscles in critically ill patients. As an important differential diagnosis of Guillain-Barré syndrome (GBS), CIP and CIM should be diagnosed with caution, after a complete clinical and laboratory examination. Although not uncommon in ICU, CIP and CIM as severe complications of percutaneous nephrostolithotomy (PNL) have not been documented in literature.
A 48-year-old Chinese woman was referred to our hospital, complaining of occasional pain in the right lower back for one month. Lithiasis was diagnosed by ultrasonographical and radiological examinations on the urinary system. PNL was indicated and performed. The patient developed CIP and CIM on the fourth day after PNL. Early recognition and treatment of the severe complications contributed to a satisfactory recovery of the patient.
This case expands our understanding of the complications of PNL and underscores the importance of differentiating CIP/CIM from GBS in case of such patients developing weakness after the treatment. Clinical characteristics and examination results should be carefully evaluated to make the diagnosis of CIP or CIM. Both anti-septic prophylaxis and control of hyperglycemia might be effective for the prevention of CIP or CIM; aggressive treatment on sepsis and multiple organ failure is considered to be the most effective measure to reduce the incidence of CIP/CIM.
Critical illness polyneuropathy; Critical illness myopathy; Percutaneous nephrostolithotomy; Sepsis; Guillain-Barré syndrome
We investigated serological correlates of protection against Neisseria meningitidis serogroup A (NmA) in Burkina Faso before the introduction of NmA conjugate vaccine.
We collected blood from a representative sample (N = 1022) of Bobo-Dioulasso residents. Sera were evaluated for serum bactericidal antibody (SBA) activity against NmA strains of immunotype L11 (F8238) and L10 (3125) and NmA-specific IgG. Seroprevalence was compared to the age-specific NmA meningitis incidence in Bobo-Dioulasso during March 2007–February 2008. Meningococcal carriage was evaluated in a subset (N = 538). Geometric mean titres (GMT)/concentrations (GMC) of SBA and NmA-specific IgG increased with age, peaking around age 20 years. Overall, 70% of our sample had NmA-specific IgG ≥2 ug/mL. Meningitis incidence was highest in those aged <6 months and 5–19 years. No NmA carriers were found. Compared to the reference strain SBA, GMTs were higher against a locally isolated strain and around 40-fold lower against Dutch strain 3125.
This study provides estimates of natural immunity to NmA, according to a variety of antibody measures, which will be helpful in ascertaining antibody persistence after MenAfriVac™ introduction. Age-specific seroprevalence of reference strain SBA titres most likely reflects exposure to meningococci and consecutive reactive immunity. We could not define any serological correlate of protection.
To explore the feasibility of using Internet outreach to encourage men who have sex with men (MSM) to get tested for HIV at voluntary counseling and testing (VCT) clinics in Beijing and Urumqi, China.
From June to August 2007, two volunteers contacted MSM using instant messaging, online chat rooms, mobile phone, and e-mail (active recruitment). Banners with study information were put at the front pages of three major Chinese gay websites (passive recruitment). Those contacted were offered a modest financial incentive to seek HIV testing at existing VCT clinics. Those who subsequently sought HIV testing services at VCT clinics and provided informed consent completed a questionnaire and a blood draw to test for HIV and syphilis.
A total of 3,332 MSM were contacted and 429 attended VCT clinics. One out of every 4 men that were recruited through instant messaging actually went for HIV testing, while the recruitment yields for online gay chat rooms, mobile phone contact, and email were 1∶6, 1∶10, and 1∶140, respectively. The majority of participants (80%, 317/399) reported being motivated to seek HIV testing out of concern for their health, and only 3% (11/399) reported being motivated by the financial incentive. Active recruitment tend to recruit MSM who are younger (X2 = 11.400, P = 0.001), never tested for HIV (X2 = 4.281, P = 0.039), tested less often (X2 = 5.638, P = 0.018).
Internet outreach is a promising way to encourage MSM to seek HIV testing at existing VCT clinics. Active recruitment can target MSM who are younger, never tested for HIV and tested less often.
Most of previous empirical studies with genome-wide prediction were focused on within-environment prediction based on a single-environment (SE) model. In this study, we evaluated accuracy improvements of across-environment prediction by using genetic and residual covariance across correlated environments. Predictions with a multienvironment (ME) model were evaluated for two corn polygenic leaf structure traits, leaf length and leaf width, based on within-population (WP) and across-population (AP) experiments using a large maize nested association mapping data set consisting of 25 populations of recombinant inbred-lines. To make our study more applicable to plant breeding, two cross-validation schemes were used by evaluating accuracies of (CV1) predicting unobserved phenotypes of untested lines and (CV2) predicting unobserved phenotypes of lines that have been evaluated in some environments but not others. We concluded that (1) genome-wide prediction provided greater prediction accuracies than traditional quantitative trait loci-based prediction in both WP and AP and provided more advantages over quantitative trait loci -based prediction for WP than for AP. (2) Prediction accuracy with ME was significantly greater than that attained by SE in CV1 and CV2, and gains with ME over SE were greater in CV2 than in CV1. These gains were also greater in WP than in AP in both CV1 and CV2. (3) Gains with ME over SE attributed to genetic correlation between environments, with little effect from residual correlation. Impacts of marker density on predictions also were investigated in this study.
best linear unbiased prediction; GenPred; genetic correlation; maize; ridge regression; shared data resources
Newly synthesized protein kinase C (PKC) undergoes a series of phosphorylation to render a mature form of the enzyme. It is this mature PKC that possesses the catalytic competence to respond to second messengers for activation and downstream signaling. The first and rate-limiting phosphorylation occurs at a threonine residue in the activation loop (AL), which triggers the rest maturation processing of PKC and regulates PKC activity in response to cellular stimulation. Given the fact that PKC is enriched in striatal neurons, we investigated the regulation of PKC phosphorylation at the AL site in the rat striatum by the psychostimulant cocaine in vivo. We found that PKC was phosphorylated at the AL site at a moderate level in the normal rat brain. Acute systemic injection of cocaine increased the PKC-AL phosphorylation in the two striatal structures (caudate putamen and nucleus accumbens). Cocaine also elevated the PKC-AL phosphorylation in the medial prefrontal cortex. The cocaine-stimulated PKC phosphorylation in the striatum is rapid and transient. A reliable increase in PKC phosphorylation was seen 7 min after drug injection, which declined to the normal level by 1 h. This kinetics corresponds to that seen for another striatum-enriched protein kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase, in response to cocaine. This study suggests a new model for exploring the impact of cocaine on protein kinases in striatal neurons. By modifying PKC phosphorylation at the AL site, cocaine is believed to possess the ability to alter the maturation processing of the kinase in striatal neurons in vivo.
protein kinase C; ERK; dopamine; stimulant; caudate; nucleus accumbens; prefrontal cortex; addiction
Coxsackievirus A9 (CA9) was one of the most prevalent serotype of enteroviral infections in Taiwan in 2011. After several patient series were reported in the 1960s and 1970s, few studies have focused on the clinical manifestations of CA9 infections. Our study explores and deepens the current understanding of CA9.
We analyzed the clinical presentations of 100 culture-proven CA9-infected patients in 2011 by reviewing their medical records and depicted the CA9 phylogenetic tree.
Of the 100 patients with culture-proven CA9 infections, the mean (SD) age was 4.6 (3.4) years and the male to female ratio was 1.9. For clinical manifestations, 96 patients (96%) had fever and the mean (SD) duration of fever was 5.9 (3.4) days. Sixty one patients (61%) developed a skin rash, and the predominant pattern was a generalized non-itchy maculopapular rash without vesicular changes. While most patients showed injected throat, oral ulcers were found in only 19 cases (19%), among whom, 6 were diagnosed as herpangina. Complicated cases included: aseptic meningitis (n=8), bronchopneumonia (n=6), acute cerebellitis (n=1), and polio-like syndrome (n=1). Phylogenetic analysis for current CA9 strains is closest to the CA9 isolate 27-YN-2008 from the border area of mainland China and Myanmar.
The most common feature of CA9 during the 2011 epidemic in Taiwan is generalized febrile exanthema rather than herpangina or hand, foot, and mouth disease. Given that prolonged fever and some complications are possible, caution should be advised in assessing patients as well as in predicting the clinical course.
Coxsackievirus A9; Enterovirus; Viral exanthema; Phylogenetic tree
Objective. To explore the urinary biochemistry features of syndromes of traditional Chinese medicine (TCM) such as syndrome of stagnation of liver Qi, spleen deficiency, liver Qi stagnation, and spleen deficiency (LSSDS) in sub-optimal health status (SHS). Methods. 12 cases for each syndrome group in SHS were selected, 12 subjects were used as a normal control group, and 1H NMR detection was, respectively, carried out, and the data was corrected by the orthogonal signal correction (OSC) and then adopted a partial least squares (PLS) method for discriminate analysis. Results. The OSC-PLS (ctr) analysis results of the nuclear overhauser enhancement spectroscopy (NOESY) detection indicated that the syndromes in SHS could be differentiated, and there were significant differences in the levels of metabolites of the urine samples of the four groups; the biomarkers of LSSDS in SHS were found out. The contents of citric acid (2.54 and 2.66), trimethylamineoxide (3.26), and hippuric acid (3.98, 7.54, 7.58, 7.62, 7.66, 7.82, and 7.86) in the urine samples of LSSDS group were lower than that of the normal control group. Conclusion. There are differences in the 1H-NMR metabolic spectrum of the urine samples of the four groups, and the specific metabolic products of the LSSDS in SHS can be identified from metabonomics analysis.
NT-proBNP has been widely regarded as a useful tool for diagnosis or exclusion of heart failure (HF) in many settings. However, in patients with acute exacerbation of chronic bronchitis (AECB), its roles have not been well described. The objective of this study was to evaluate the diagnostic performance of NT-proBNP for identifying left ventricular (LV) failure in such patients.
Methods and Results
311 AECB patients and 102 stable chronic bronchitis patients with no history of HF were enrolled. Plasma NT-proBNP concentrations were measured using Roche Elecsys. The European Society of Cardiology (ESC) diagnostic principles were adopted to identify HF and the diagnostic performance of NT-proBNP was evaluated by ROC. Our results showed, the median NT-proBNP level in patients with LV failure [4828.4 (2044.4–9203.6) ng/L] was significantly higher than that in those without LV failure [519.2 (179.1–1409.8) ng/L, p<0.001] and stable controls [207.5 (186.5–318.2) ng/L, p<0.001]. LV failure, renal function, atrial fibrillation and systolic pulmonary artery pressure were independent predictors of NT-proBNP levels (all p<0.05). The area under ROC curve (AUC) of NT-proBNP for identifying LV failure was 0.884, significantly superior to clinical judgment alone (AUC 0.835, p = 0.0294). At the optimal cutoff value of 935.0 ng/L, NT-proBNP yielded sensitivity 94.4%, specificity 68.2%, accuracy 74.3% and negative predictive value 97.6%. Adding the results of NT-proBNP to those of clinical judgment improved the diagnostic accuracy for LV failure.
As a tool for diagnosis or exclusion of HF, NT-proBNP can help physicians identify LV failure in patients with AECB.
Increased incidence of adenovirus infection in children was noticed since September 2010 in Taiwan and severe cases requiring intensive care were noted later. We did this study to find the clinical characteristics and risk factors associated with severe adenovirus infection.
Patients and Methods
We collected cases of severe adenovirus infection between November 2010 and June 2011 to analyze their clinical characteristics in two medical centers in northern Taiwan. Severe adenovirus infection was defined as laboratory-confirmed adenovirus cases with required intensive care. Hexon gene sequencing was performed for molecular genotyping.
45 patients were included, 22 cases (49%) were infected with serotype 7, 19 (42%) with serotype 3, and 4 with serotype 2. The median age (range) was 2.75 years (0.08–15.43 years); 87% were below 5 years. Male to female ratio was 1.65 (28 to 17). Of these patients, 56% had underlying neurological diseases, 50% experienced fever higher than 40°C and 69% suffered fever longer than one week. The clinical diagnosis included pneumonia in 40 (89%) patients, bronchopneumonia in 5 (11%), and encephalitis in 7 (16%). At least 22 patients had pleural effusion. They had complications of respiratory failure (53%), acute respiratory distress syndrome (24%), hypotension (40%), and 6 (13%) patients needed extracorporeal membranous oxygenation. Ten (22%) patients died, all with underlying major systemic diseases and 7 (70%) infected with serotype 7.
Adenovirus serotype 7 and 3 can cause severe disease–even death–in children, especially those with underlying neurological diseases. Patients infected with adenovirus serotype 7 tended to have a higher case-fatality rate.
Ionotropic glutamate receptors, especially the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtype, undergo dynamic trafficking between the surface membrane and intracellular organelles. This trafficking activity determines the efficacy and strength of excitatory synapses and is subject to modulation by changing synaptic inputs. Given the possibility that glutamate receptors in the central nervous system might be a sensitive target of anesthetic agents, this study investigated the possible impact of anesthesia on trafficking and subcellular expression of AMPA receptors in adult mouse brain neurons in vivo. We found that anesthesia induced by a systemic injection of pentobarbital did not alter total protein levels of three AMPA receptor subunits (GluR1–3) in cortical neurons. However, an anesthetic dose of pentobarbital reduced GluR1 and GluR3 proteins in the surface pool and elevated these proteins in the intracellular pool of cortical neurons. The similar redistribution of GluR1/3 was observed in mouse striatal neurons. Pentobarbital did not significantly alter GluR2 expression in the two pools. Chloral hydrate at an anesthetic dose also reduced surface GluR1/3 expression and increased intracellular levels of these proteins. The effect of pentobarbital on subcellular distribution of AMPA receptors was reversible. Altered subcellular distribution of GluR1/3 returned to normal levels after the anesthesia subsided. These data indicate that anesthesia induced by pentobarbital and chloral hydrate can alter AMPA receptor trafficking in both cortical and striatal neurons. This alteration is characterized by the concurrent loss and addition of GluR1/3 subunits in the respective surface and intracellular pools.
pentobarbital; chloral hydrate; glutamate; GluR1; GluR3; trafficking
Emerging evidence supports an important role of posterior parasylvian areas in both pain and touch processing. Whether there are separate or shared networks for these sensations remains controversial. The present study compared spatial patterns of brain activation in response to unilateral nociceptive heat (47.5° C) or innocuous tactile stimulation (8 Hz vibration) to digits through high-resolution fMRI in squirrel monkeys. In addition, the temporal profile of heat stimulus evoked fMRI BOLD signal changes was characterized. By examining high-resolution fMRI and histological measures at both the individual and group levels, we found that both nociceptive heat and tactile stimuli elicited activation in bilateral secondary somatosensory and ventral parietal areas (S2/PV) and in ipsilateral ventral somatosensory area (VS) and retroinsula (Ri). Bilateral posterior insular cortex (pIns) and area 7b responded preferentially to nociceptive heat stimulation. Single voxels within each activation cluster showed robust BOLD signal changes during each block of nociceptive stimulation. Across animals (n = 11), nociceptive response magnitudes of contralateral VS and pIns, and ipsilateral Ri were significantly greater than corresponding areas in the opposite hemisphere. In sum, both distinct and shared areas in regions surrounding the posterior sylvian fissure were activated in response to nociceptive and tactile inputs in non-human primates.
nociception; hand; primates; cortex; touch; fMRI
Mitochondrial catastrophe can be the cause or consequence of apoptosis and is associated with a number of pathophysiological conditions. The exact relationship between mitochondrial catastrophe and caspase activation is not completely understood. Here we addressed the underlying mechanism, explaining how activated caspase could feedback to attack mitochondria to amplify further cytochrome c (cyto.c) release. We discovered that cytochrome c1 (cyto.c1) in the bc1 complex of the mitochondrial respiration chain was a novel substrate of caspase 3 (casp.3). We found that cyto.c1 was cleaved at the site of D106, which is critical for binding with cyto.c, following apoptotic stresses or targeted expression of casp.3 into the mitochondrial intermembrane space. We demonstrated that this cleavage was closely linked with further cyto.c release and mitochondrial catastrophe. These mitochondrial events could be effectively blocked by expressing non-cleavable cyto.c1 (D106A) or by caspase inhibitor z-VAD-fmk. Our results demonstrate that the cleavage of cyto.c1 represents a critical step for the feedback amplification of cyto.c release by caspases and subsequent mitochondrial catastrophe.
cytochrome c1 cleavage; mitochondrial catastrophe; caspase; apoptosis