Infantile intracardiac thrombus in severe encephalo-myocarditis.

Myocarditis is an uncommon disease in childhood and has a wide range of clinical presentations, from subtle to devastating and thus requires a high index of suspicion. Intracardiac thrombus formation following myocarditis is rare and thus its management remains challenging and not well defined. We report a child whom presented with a viral prodrome, rapidly deteriorated into multi organ failure and developed fulminant viral myocarditis with encephalitis that was complicated with an intracardiac thrombus formation. We describe the challenges faced, the successful medical treatment offered and propose factors that can help guide appropriate treatment.

Comparison of image quality of abdominopelvic CT in paediatric patients: low osmolar contrast media versus less iodine-containing iso-osmolar contrast media at different peak kilovoltages.

AIM: To evaluate the effect of iso-osmolar contrast media (IOCM) at different tube voltages on image quality for abdominal computed tomography (CT) in paediatric patients. MATERIALS AND METHODS: The low osmolar contrast media (LOCM) group and IOCM group consisted of 101 and 102 CT examinations, respectively, in patients <18 years old. Images were reviewed retrospectively. Objective measurement of the contrast enhancement and noise were analysed and contrast-to-noise ratios (CNRs) of the abdominal aorta, portal vein, and liver were calculated. Four radiologists participated in subjective analysis using a four-point scale system to evaluate degrees of contrast enhancement, image noise, beam-hardening artefact, and overall image quality. Reader performance for correctly differentiating the two kinds of contrast media was evaluated. RESULTS: Regarding the objective measurement, contrast enhancement was significantly higher in the LOCM group (p<0.05). In subjective analysis, only CT using 120 kVp showed significantly stronger enhancement in the LOCM group (p=0.002), and sensitivity to differentiate the IOCM was 80.6%. Overall sensitivity and specificity for correctly differentiating IOCM were 57.1%, and 56.9%, respectively. CONCLUSION: The application of IOCM was found to be feasible for performing paediatric abdominopelvic CT with a low tube voltage protocol. Although objective measurements of contrast enhancement were significantly lower in the IOCM group, subjective contrast enhancement and image quality assessments were not statistically different between groups.

In vitro adhesion and invasion by Cladosporium sphaerospermum in human bronchial epithelial cells (BEAS-2B) and human pulmonary alveolar epithelial cells (HPAEpiC).

Cladosporium spores are ubiquitous in indoor and outdoor environment and may potentially trigger allergic responses upon inhalation. To date, there is limited investigation on the fate of Cladosporium spores after being inhaled into the respiratory tract. This study was conducted to investigate the interaction of Cladosporium sphaerospermum with Human Bronchial Epithelial Cells (BEAS-2B) and Human Pulmonary Alveolar Epithelial Cells (HPAEpiC). C. sphaerospermum conidia were harvested and co-cultured with BEAS-2B or HPAEpiC cells for 72 hours. At each time point (30 minutes, 2, 4, 24, 48 and 72 hours), adherence and invasion of the cells by C. sphaerospermum conidia (and hyphae) were investigated by immunofluorescence staining. This study demonstrated the adherence and internalization of C. sphaerospermum conidia within these epithelial cells. In addition, the conidia were able to germinate and invade the epithelial cells. The ability of the fungal conidia to adhere, internalize, germinate and invade both the bronchial and alveolar epithelial cells of the respiratory tract in vitro might contribute to the understanding of the pathogenesis of Cladosporium in respiratory infection and allergy in vivo.

In vitro adhesion and invasion by Cladosporium sphaerospermum in human bronchial epithelial cells (BEAS-2B) and human pulmonary alveolar epithelial cells (HPAEpiC)

@#Cladosporium spores are ubiquitous in indoor and outdoor environment and may potentially trigger allergic responses upon inhalation. To date, there is limited investigation on the fate of Cladosporium spores after being inhaled into the respiratory tract. This study was conducted to investigate the interaction of Cladosporium sphaerospermum with Human Bronchial Epithelial Cells (BEAS-2B) and Human Pulmonary Alveolar Epithelial Cells (HPAEpiC). C. sphaerospermum conidia were harvested and co-cultured with BEAS-2B or HPAEpiC cells for 72 hours. At each time point (30 minutes, 2, 4, 24, 48 and 72 hours), adherence and invasion of the cells by C. sphaerospermum conidia (and hyphae) were investigated by immunofluorescence staining. This study demonstrated the adherence and internalization of C. sphaerospermum conidia within these epithelial cells. In addition, the conidia were able to germinate and invade the epithelial cells. The ability of the fungal conidia to adhere, internalize, germinate and invade both the bronchial and alveolar epithelial cells of the respiratory tract in vitro might contribute to the understanding of the pathogenesis of Cladosporium in respiratory infection and allergy in vivo. INTRODUCTION Cladosporium species is a member of the phylum Ascomycota. The common species include C. herbarum, C. cladosporioides and C. sphaerospermum. This genus has worldwide distribution. Aerobiological studies reported that majority of fungal spores in outdoor air is from the phyla Ascomycota and Basidiomycota, while Cladosporium is one of the most studied allergenic Ascomycetes fungi (Knutsen et al., 2012). Cladosporium spores are found abundantly in indoors and outdoors at approximately 18/m3 and 141/m3 respectively (Codina et al., 2008). As an imperfect dematiaceous fungus, Cladosporium species causes opportunistic infections such

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women.

Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal. INTRODUCTION: We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation. METHOD: One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity - 1) used to identify the optimal MOF and HF ITs. RESULTS: The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis. CONCLUSION: The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.

A 2.2 NEF Neural-Recording Amplifier Using Discrete-Time Parametric Amplification.

This paper proposes a 2.2 noise efficiency factor (NEF) instrumentation amplifier for neural recording applications. A parametric amplifier based on the MOS C-V characteristic is designed as a pre-amplifier stage, lowering the input referred noise of the following stages by 3.4×. Sampling noise is minimized by oversampling the input signal and switching power is reduced by adopting an 8-phase soft-charging technique.

Image quality of CT angiography in young children with congenital heart disease: a comparison between the sinogram-affirmed iterative reconstruction (SAFIRE) and advanced modelled iterative reconstruction (ADMIRE) algorithms.

AIM: To compare the image quality of computed tomography angiography (CTA) reconstructed by sinogram-affirmed iterative reconstruction (SAFIRE) with that of advanced modelled iterative reconstruction (ADMIRE) in children with congenital heart disease (CHD). MATERIAL AND METHODS: Thirty-one children (8.23±13.92 months) with CHD who underwent CTA were enrolled. Images were reconstructed using SAFIRE (strength 5) and ADMIRE (strength 5). Objective image qualities (attenuation, noise) were measured in the great vessels and heart chambers. Two radiologists independently calculated the contrast-to-noise ratio (CNR) by measuring the intensity and noise of the myocardial walls. Subjective noise, diagnostic confidence, and sharpness at the level prior to the first branch of the main pulmonary artery were also graded by the two radiologists independently. RESULTS: The objective image noise of ADMIRE was significantly lower than that of SAFIRE in the right atrium, right ventricle, and myocardial wall (p<0.05); however, there were no significant differences observed in the attenuations among the four chambers and great vessels, except in the pulmonary arteries (p>0.05). The mean CNR values were 21.56±10.80 for ADMIRE and 18.21±6.98 for SAFIRE, which were significantly different (p<0.05). In addition, the diagnostic confidence of ADMIRE was significantly lower than that of SAFIRE (p<0.05), while the subjective image noise and sharpness of ADMIRE were not significantly different (p>0.05). CONCLUSION: CTA using ADMIRE was superior to SAFIRE when comparing the objective and subjective image quality in children with CHD.

Pseudoepitheliomatous keratotic and micaceous balanitis treated with topical 5-fluorouracil and liquid nitrogen.

Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is an uncommon premalignant condition involving the glans penis. We report the case of an 86-year-old man who presented with phimosis and pain on retracting his foreskin. He had previously undergone circumcision, which revealed a hyperkeratotic plaque with thin mica-like scales involving his glans penis. Histology of the lesion showed hyperkeratosis, parakeratosis, epidermal acanthosis and papillomatosis with no evidence of dysplasia. Immunohistochemistry for human papillomavirus was negative. The patient was treated with topical 5-fluorouracil and liquid nitrogen with clinical improvement. He is now under long-term surveillance for verrucous carcinoma and squamous cell carcinoma.

The role of host microfilaments and microtubules during opsonin-independent interactions of Cryptococcus neoformans with mammalian lung cells.

The purpose of this investigation was to characterise the interactions of Cryptococcus neoformans with mammalian host alveolar epithelial cells and alveolar macrophages, with emphasis on the roles of the cryptococcal capsule and the host cell cytoskeletons. The adherence and internalisation of C. neoformans into mammalian lung cells and the roles of host cell cytoskeletons in host-pathogen interactions were studied using in vitro models coupled with a differential fluorescence assay, fluorescence staining, immunofluorescence and drug inhibition of actin and microtubule polymerisation. Under conditions devoid of opsonin and macrophage activation, C. neoformans has a high affinity towards MH-S alveolar macrophages, yet associated poorly to A549 alveolar epithelial cells. Acapsular C. neoformans adhered to and internalised into the mammalian cells more effectively compared to encapsulated cryptococci. Acapsular C. neoformans induced prominent actin reorganisation at the host-pathogen interface in MH-S alveolar macrophages, but minimally affected actin reorganisation in A549 alveolar epithelial cells. Acapsular C. neoformans also induced localisation of microtubules to internalised cryptococci in MH-S cells. Drug inhibition of actin and microtubule polymerisation both reduced the association of acapsular C. neoformans to alveolar macrophages. The current study visualises and confirms the interactions of C. neoformans with mammalian alveolar cells during the establishment of infection in the lungs. The acapsular form of C. neoformans effectively adhered to and internalised into alveolar macrophages by inducing localised actin reorganisation, relying on the host's actin and microtubule activities.

Knockdown of c-MET induced apoptosis in ABCB1-overexpressed multidrug-resistance cancer cell lines.

Inappropriate c-MET signaling in cancer can enhance tumor cell proliferation, survival, motility, and invasion. Inhibition of c-MET signaling induces apoptosis in a variety of cancers. It has also been recognized as a novel anticancer therapy approach. Furthermore, reports have also indicated that constitutive expression of P-glycoprotein (ABCB1) is involved in the HGF/c-MET-related pathway of multidrug resistance ABCB1-positive human hepatocellular carcinoma cell lines. We previously reported that elevated expression levels of PKCδ and AP-1 downstream genes, and HGF receptor (c-MET) and ABCB1, in the drug-resistant MES-SA/Dx5 cells. Moreover, leukemia cell lines overexpressing ABCB1 have also been shown to be more resistant to the tyrosine kinase inhibitor imatinib mesylate. These findings suggest that chemoresistant cancer cells may also develop a similar mechanism against chemotherapy agents. To circumvent clinical complications arising from drug resistance during cancer therapy, the present study was designed to investigate apoptosis induction in ABCB1-overexpressed cancer cells using c-MET-targeted RNA interference technology in vitro and in vivo. The results showed that cell viability decreased and apoptosis rate increased in c-MET shRNA-transfected HGF/c-MET pathway-positive MES-SA/Dx5 and MCF-7/ADR2 cell lines in a dose-dependent manner. In vivo reduction of tumor volume in mice harboring c-MET shRNA-knockdown MES-SA/Dx5 cells was clearly demonstrated. Our study demonstrated that downregulation of c-MET by shRNA-induced apoptosis in a multidrug resistance cell line.

The architecture and evolution of cancer neochromosomes.

We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation.

Barium aspiration in an infant: a case report and review of management.

We describe a case of bilateral inhalation of barium in an infant following a barium swallow for investigation of dusky spells associated with feeds. A bronchoscopy subsequently revealed the presence of a mid-tracheal tracheo-esophageal cleft. To date, little has been reported on barium aspiration in children and there is no consensus for management. We review the literature on barium aspiration, its consequences, and make recommendations for management.

An individualized contrast material injection protocol with respect to patient-related factors for dual-source CT coronary angiography.

AIM: To optimize contrast media (CM) injection protocols by individually tailoring the dose to the patient's body weight (BW), body mass index (BMI) and heart rate (HR) at dual-source computed tomography coronary angiography (DSCT-CA). MATERIALS AND METHODS: A total of 423 patients were prospectively enrolled and were randomly assigned to four groups. The control group received 80 ml CM at 5 ml/s. For the HR-optimized group, the injection duration was the same as the scan duration plus 8 s. In the Body-optimized group, the dose of CM was tailored to BW and BMI. In the HR + Body-optimized group, CM protocols tailored to body size and scan duration were applied. Individual variability of arterial attenuation and incidence of arterial over-opacification (attenuation >500 HU) in the four groups were compared. Correlations between BW, BMI, HR, and arterial attenuations were evaluated in the four groups, respectively. RESULTS: Reduced individual variability of arterial attenuation and a significantly lower incidence of arterial over-opacification were found in the Body-optimized group and HR + Body-optimized group. Arterial attenuation was inversely correlated with BW, BMI, and HR in the control group, inversely correlated with BW and BMI in the HR-optimized group, and inversely correlated with HR in the Body-optimized group. In the HR + Body-optimized group, arterial attenuation was not significantly correlated with BW, BMI, or HR respectively. CONCLUSION: CM protocols individually tailored to BW, BMI, and HR can lead to reduced individual variability and a lower incidence of over-opacification of arterial attenuation, but also can reduce the influence of BW, BMI, and HR on arterial attenuations at DSCT-CA.

Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

PML bodies provide an important platform for the maintenance of telomeric chromatin integrity in embryonic stem cells.

We have previously shown that α-thalassemia mental retardation X-linked (ATRX) and histone H3.3 are key regulators of telomeric chromatin in mouse embryonic stem cells. The function of ATRX and H3.3 in the maintenance of telomere chromatin integrity is further demonstrated by recent studies that show the strong association of ATRX/H3.3 mutations with alternative lengthening of telomeres in telomerase-negative human cancer cells. Here, we demonstrate that ATRX and H3.3 co-localize with the telomeric DNA and associated proteins within the promyelocytic leukemia (PML) bodies in mouse ES cells. The assembly of these telomere-associated PML bodies is most prominent at S phase. RNA interference (RNAi)-mediated knockdown of PML expression induces the disassembly of these nuclear bodies and a telomere dysfunction phenotype in mouse ES cells. Loss of function of PML bodies in mouse ES cells also disrupts binding of ATRX/H3.3 and proper establishment of histone methylation pattern at the telomere. Our study demonstrates that PML bodies act as epigenetic regulators by serving as platforms for the assembly of the telomeric chromatin to ensure a faithful inheritance of epigenetic information at the telomere.

Functional hand proportion is approximated by the Fibonacci series.

The debatable relationship of functional human hand proportion with the Fibonacci series has remained an obscure scientific enigma short of clinical interest. The main difficulty of proving such a relationship lies in defining what should constitute true functional proportion. In this study, we re-evaluate this unique relationship using hand flexion creases as anatomical surrogates for the functional axes of joint rotation. Standardised desktop photocopies of palmar views of both hands in full digital extension and abduction were obtained from 100 healthy male volunteers of Chinese ethnicity. The functional axes were represented by the distal digital crease (distal interphalangeal joint, DIPJ), proximal digital crease (proximal interphalangeal joint, PIPJ), as well as the midpoint between the palmar digital and transverse palmar creases (metacarpophalangeal joint, MCPJ). The ratio of DIPJ-Fingertip:PIPJ-DIPJ:MCPJ-PIPJ (p3:p2:p1) was measured by two independent observers and represented as standard deviation about the mean, and then compared to the theoretical ratio of 1:1:2. Our results showed that, for the 2nd to 5th digits, the p2:p3 ratios were 0.97 ± ± 0.09, 1.10 ± 0.10, 1.04 ± 0.12, and 0.80 ± 0.08, respectively; whilst the p1:p2 ratios were 1.91 ± 0.17, 1.98 ± 0.14, 1.89 ± 0.16, and 2.09 ± 0.24, respectively. When the data were analysed for all digits, they showed a combined p3:p2:p1 ratio of 1:0.98:2.01. In conclusion, our results suggest that functional human hand proportion, as defined by flexion creases, is approximated by the Fibonacci series.

Normal DNA methylation dynamics in DICER1-deficient mouse embryonic stem cells.

Reduced DNA methylation has been reported in DICER1-deficient mouse ES cells. Reductions seen at pericentric satellite repeats have suggested that siRNAs are required for the proper assembly of heterochromatin. More recent studies have postulated that the reduced methylation is an indirect effect: the loss of Mir290 cluster miRNAs leads to upregulation of the transcriptional repressor RBL2 that targets the downregulation of DNA methyltransferase (Dnmt) genes. However, the observations have been inconsistent. We surmised that the inconsistency could be related to cell line "age," given that DNA methylation is lost progressively with passage in DNMT-deficient ES cells. We therefore subjected Dicer1(-/-) ES cells to two experimental regimes to rigorously test the level of functional DNMT activity. First, we cultured them for a prolonged period. If DNMT activity was reduced, further losses of methylation would occur. Second, we measured their DNMT activity in a rebound DNA methylation assay: DNA methylation was stripped from Cre/loxP conditionally mutant Dicer1 ES cells using a shRNA targeting Dnmt1 mRNA. Cre expression then converted these cells to Dicer1(-/-), allowing for DNMT1 recovery and forcing the cells to remethylate in the absence of RNAi. In both cases, we found functional DNMT activity to be normal. Finally, we also show that the level of RBL2 protein is not at excess levels in Dicer1(-/-) ES cells as has been assumed. These studies reveal that reduced functional DNMT activity is not a salient feature of DICER1-deficient ES cells. We suggest that the reduced DNA methylation sometimes observed in these cells could be due to stochastic alterations in DNA methylation patterns that could offer growth or survival advantages in culture, or to the dysregulation of pathways acting in opposition to the DNMT pathway.

Tropical distal renal tubular acidosis: clinical and epidemiological studies in 78 patients.

BACKGROUND: Distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene encoding the erythroid and kidney isoforms of anion exchanger 1 (AE1 or band 3) has a high prevalence in some tropical countries, particularly Thailand, Malaysia, the Philippines and Papua New Guinea (PNG). Here the disease is almost invariably recessive and can result from either homozygous or compound heterozygous SLC4A1 mutations. METHODS: We have collected and reviewed our own and published data on tropical dRTA to provide a comprehensive series of clinical and epidemiological studies in 78 patients. RESULTS: Eight responsible SLC4A1 mutations have been described so far, four of them affecting multiple unrelated families. With the exception of the mutation causing South-East Asian ovalocytosis (SAO), none of these mutations has been reported outside the tropics, where dRTA caused by SLC4A1 mutations is much rarer and almost always dominant, resulting from mutations that are quite different from those found in the tropics. SLC4A1 mutations, including those causing dRTA, may cause morphological red cell changes, often with excess haemolysis. In dRTA, these red cell changes are usually clinically recessive and not present in heterozygotes. The high tropical prevalence of dRTA caused by SLC4A1 mutations is currently unexplained. CONCLUSION: A hypothesis suggesting that changes in red cell metabolism caused by these mutations might protect against malaria is put forward to explain the phenomenon, and a possible mechanism for this effect is proposed.

Epigenetic changes in response to tai chi practice: a pilot investigation of DNA methylation marks.

Tai chi exercise has been shown to improve physiological and psychosocial functions, well-being, quality of life, and disease conditions. The biological mechanisms by which tai chi exerts its holistic effects remain unknown. We investigated whether tai chi practice results in positive epigenetic changes at the molecular level. Design. The DNA methylation profiles of sixty CpG-dinucleotide marks in female tai chi practitioners (N = 237; 45-88 years old) who have been practising tai chi for three or more years were compared with those of age-matched control females (N = 263) who have never practised tai chi. Results. Six CpG marks originating from three different chromosomes reveal a significant difference (P < 0.05) between the two cohorts. Four marks show losses while two marks show gains in DNA methylation with age in the controls. In the tai chi cohort all six marks demonstrate significant slowing (by 5-70%) of the age-related methylation losses or gains observed in the controls, suggesting that tai chi practice may be associated with measurable beneficial epigenetic changes. Conclusions. The results implicate the potential use of DNA methylation as an epigenetic biomarker to better understand the biological mechanisms and the health and therapeutic efficacies of tai chi.