Can one hear the shape of the Universe?

It is shown that the recent observations of NASA's explorer mission "Wilkinson Microwave Anisotropy Probe" (WMAP) hint that our Universe may possess a non-trivial topology. As an example we discuss the Picard space which is stretched out into an infinitely long horn but with finite volume.Comment: 4 page

Enhanced five-port ring circuit reflectometer for synthetic breast tissue dielectric determination

In this study,a Six-port Reflectometer (SPR) with dielectric probe sensor is used to predict relative dielectric,εr of normal and tumorous breast tissue in frequency range from 2.34GHz to 3.0GHz. Other than that,a superstrate with an exterior copper layer is overlaid on the surface of a primitive Five-port Ring Circuit (FPRC),which is also a denominated,enhanced superstrate FPRC. It is the main component of the SPR and is presented in this paper as well. The enhanced superstrate FPRC is capable of improving its operating bandwidth by 26% and shifting the operating centre frequency to a lower value without increasing circuit physical size. The detailed design and characteristics of the FPRC are described here. In addition,the enhanced superstrate FPRC is integrated into the SPR for one-port reflection coefficient measurement. The measurement using the SPR is benchmarked with Agilent’s E5071C Vector Network Analyzer (VNA) for one-port reflection coefficient. Maximum absolute mean error of the linear magnitude and phase measurements are recorded to be 0.03 and 5.50°,respectively. In addition,maximum absolute error of the predicted dielectric and loss factor are 1.77 and 0.61,respectively

Schwarzinicine A inhibits transient receptor potential canonical channels and exhibits overt vasorelaxation effects

This study investigated the vasorelaxant effects of schwarzinicine A, an alkaloid recently reported from Ficus schwarzii Koord. Regulation of calcium homeostasis in vascular smooth muscle cells (VSMC) is viewed as one of the main mechanisms for controlling blood pressure. L-type voltage-gated calcium channel (VGCC) blockers are commonly used for controlling hypertension. Recently, the transient receptor potential canonical (TRPC) channels were found in blood vessels of different animal species with evidence of their roles in the regulation of vascular contractility. In this study, we studied the mechanism of actions of schwarzinicine A focusing on its regulation of L-type VGCC and TRPC channels. Schwarzinicine A exhibited the highest vasorelaxant effect (123.1%) compared to other calcium channel blockers. It also overtly attenuated calcium-induced contractions of the rat isolated aortae in a calcium-free environment showing its mechanism to inhibit calcium influx. Fluorometric intracellular calcium recordings confirmed its inhibition of hTRPC3-, hTRPC4-, hTRPC5- and hTRPC6-mediated calcium influx into HEK cells with IC50 values of 3, 17, 19 and 7 μM, respectively. The evidence gathered in this study suggests that schwarzinicine A blocks multiple TRPC channels and L-type VGCC to exert a significant vascular relaxation response

S100A4 downregulates filopodia formation through increased dynamic instability

Cell migration requires the initial formation of cell protrusions, lamellipodia and/or filopodia, the attachment of the leading lamella to extracellular cues and the formation and efficient recycling of focal contacts at the leading edge. The small calcium binding EF-hand protein S100A4 has been shown to promote cell motility but the direct molecular mechanisms responsible remain to be elucidated. In this work, we provide new evidences indicating that elevated levels of S100A4 affect the stability of filopodia and prevent the maturation of focal complexes. Increasing the levels of S100A4 in a rat mammary benign tumor derived cell line results in acquired cellular migration on the wound healing scratch assay. At the cellular levels, we found that high levels of S100A4 induce the formation of many nascent filopodia, but that only a very small and limited number of those can stably adhere and mature, as opposed to control cells, which generate fewer protrusions but are able to maintain these into more mature projections. This observation was paralleled by the fact that S100A4 overexpressing cells were unable to establish stable focal adhesions. Using different truncated forms of the S100A4 proteins that are unable to bind to myosin IIA, our data suggests that this newly identified functions of S100A4 is myosin-dependent, providing new understanding on the regulatory functions of S100A4 on cellular migration

Coronary artery calcification – distribution, extent and 1-year outcomes in patients with low to intermediate pre-test probability of coronary artery disease.

Background: Coronary artery calcium (CAC) is an established marker to predict major cardiovascular events (MACE), and has incremental value over traditional risk factors (CVRF). CAC is widely available, easily reproducible, and used in nearly all coronary computed tomography angiography (CCTA) assessment protocols for coronary artery disease (CAD). The distribution and extent of CAC, and its prognostic implications in local Malaysian patients with low to intermediate pre-test probability (LI-PTP) of CAD had not been established. Objectives: We aimed to establish the distribution, extent and prognostic implications of CAC in patients without known CAD, but with LI-PTP of CAD, undergoing CCTA for chest pain evaluation. Methods: Clinical information was obtained from consecutive patients who underwent CAC and CCTA examination from January 2020 to January 2021 at a single public access tertiary referral centre. The primary outcomes were the distribution and extent of CAC, and its relationship with MACE at 1 year. Results: Of 499 consecutive patients, 7 were excluded due to high PTP. CAC was present in 172/492 (35%). Within this group, 74/172 (41.3%) had CAC score of 1-100 (mild), 75/172 (42.4%) had a CAC of 101- 400 (moderate), 23/172 (13.4%) had CAC of >400 (high). 136 had suspected significant CAD and was offered conventional coronary angiography (CCA). 91/492 underwent CCA, and 38 were found to have significant CAD. Of those found to have significant CAD, 7/38 (18.4%) had CAC of zero, 8/38 (21.1%) had mild CAC, 12/38 (31.6%) moderate, and 11/38 (30%) high CAC. Severe CAC was associated with a higher rate of revascularization 11/23 (47.8%), compared to those with zero 7/320 (2.2%), mild 8/74 (10.8%) and moderate 12/75 (16%) CAC. Predictors of high CAC were age, male gender, and presence of cardiovascular disease risk factors. Of the 492 patients, 230 patients completed 1 year follow-up, and from this, 1 patient had a MACE. Conclusion In patients with LI-PTP risk of CAD, CAC was seen in approximately one third of our cohort. In the group with high CAC, a higher proportion required coronary revascularization, but MACE remained low at 1 year

Coronary Computed Tomography Angiography as part of initial strategy, in assessment of patients with chest pain – clinical experience and 1 year prognosis.

Background: Coronary computed tomography angiography (CCTA) has been showed to have high specificity and sensitivity for detecting coronary artery disease (CAD). In Malaysia, national guidelines state that CCTA may be used in low- to intermediate pre-test probability (LI-PTP) of CAD, who have an equivocal functional test result, and who are asymptomatic or mildly symptomatic with good exercise capacity. Recent evidence suggested a ‘CCTA-first’ strategy in the evaluation of a patient with chest pain could provide prognostic benefits. Prognostic benefits of adopting this strategy in Malaysia has not been well studied. Objectives: We aimed to evaluate 12-month clinical outcomes of patients with LI-PTP, using the CCTA as an initial strategy, or as part of the work-up for, chest pain assessment. Methods: Consecutive patients who underwent CCTA examination from January 2020 to January 2021 were enrolled. Clinical information was then extracted. Primary outcome was defined as presence of stenosis of >50% in a major epicardial coronary artery; and secondary outcome defined as a composite of all-cause mortality, non-fatal myocardial infarction (MI) and coronary revascularisation. Results: Among the initial 499 patients, 7 were excluded as they were high in PTP. The mean PTP was 47.1±26.3. Baseline characteristics were available in 300 patients. The mean age was 53.5±11.4 years, 59.3% were male, 18.6% were diabetic, 71.2% had hypertension, and 50.8% had hypercholestrolaemia. 1.9% had an equivocal functional test for ischaemia. Of the 492 LI-PTP patients who underwent CCTA, 136 patients were suspected to have significant CAD, and recommended conventional coronary angiography (CCA). Of these, 91 patients underwent CCA. From this group 38 were found to have significant CAD which warranted revascularisation – 32 by percutaneous coronary intervention (PCI) and 6 referred for coronary artery bypass surgery (CABG). Therefore, utilising this strategy, 7.7% (38/492) of patients met the primary outcome. Of the original cohort of 492 LI-PTP patients, only 230 completed 1 year follow up, and from this, one patient met the secondary outcome. Conclusion Incorporation of CCTA into contemporary chest pain evaluation identified significant number of patients with significant CAD and was also associated with a low cardiac event rate at 1 year follow-up

Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy

Background: Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of lysosomal acid alpha-glucosidase (GAA) activity, leading to the progressive accumulation of glycogen in lysosomes of the skeletal and cardiac muscles. An alpha-glucosidase (GAA) pseudodeficiency allele is a change in the GAA gene sequence that results in GAA enzyme activity reduction, but does not cause Pompe disease. In Japan and Taiwan, there is high prevalence of pseudodeficiency allele (c.1725G>A and c.2065G>A) detected from their newborn screening. We observed similar prevalence of pseudodeficiency allele among our patients who had genetic test performed for suspected hereditary cardiomyopathy. Objectives: To report the prevalence of GAA pseudodeficiency allele, and to ascertain its clinical significance among patients with cardiomyopathy. Methods: The clinical data of the patients with GAA mutations were retrieved. Patients were called back for neurological examination, lung function test, measurement of creatine kinase (CK) level and dried-blood-spot for GAA enzymatic activity. Results: From January to December 2021, 33 patients underwent genetic testing. 23 out of the 33 genetic analyses included GAA mutation. 9 (39.13%) out of 23 were tested positive for pseudodeficiency allele. Their median age was 53 years (range 29-82), 44.4% were males with equal ethnic distribution (33.3% Malay, 33.3% Chinese, 33.3% Dayaks). All were heterozygous for the pseudodeficiency allele: 5 (55.6%) with c.[1726A; 2065A] allele, the other 4 (44.4%) c.2065G>A. The underlying cardiomyopathy phenotypes were hypertrophic (44.4%), transthyretin amyloid (22.2%), hypertensive (22.2%) and Fabry (11.1%). 1 patient (11.1%) with transthyretin amyloid cardiomyopathy died of advanced heart failure at age 79 years. 1 patient had mild motor weakness of the limbs attributable to thyrotoxicosis, while the other 7 patients had normal skeletal motor function. Their median predicted forced vital capacity was 87.5% (range 76-103), median CK level was 103 U/L (range 39-297) and median GAA activity was 4.8 micromol/l/h (range 3.2-9.2) [normal > 2.0]. Conclusion: The prevalence of GAA pseudodeficiency allele among patients with cardiomyopathy is 39.13%. None of the patients exhibit significant muscle weakness or respiratory insufficiency despite low normal enzymatic activity. Whether the presence of pseudodeficiency allele affects the prognosis of the underlying cardiomyopathy remains uncertain

Utility of Dutch Lipid Clinic Network Score to Estimate Prevalence of Familial Hypercholestrolemia in Patients with ST-Elevation Myocardial Infarction

Background Hypercholesterolaemia is prevalent in the Malaysian population, and its treatment control rates remain suboptimal1. Familial hypercholesterolemia (FH) is an autosomal dominant condition that leads to accelerated arteriosclerotic cardiovascular disease (ASCVD). The prevalence of FH in the general population worldwide has been postulated to be 1:3132 and 1:100 in the Malaysian community3. It has been proposed that lipid lowering treatment prevents further increase in total cardiovascular risk of FH patients, and this recommendation is extensible for FH patients plus atherosclerotic CAD (coronary artery disease). However, despite its implication in CAD, FH is still an underdiagnosed and undertreated condition2-4. To date, the prevalence of FH in the STEMI (ST-elevation myocardial infarction) population in Malaysia is not studied. Establishing the prevalence of FH among patients with CAD and comparing this with the general population would help future efforts at identifying subjects with FH. Objective We aim to estimate the prevalence of FH in patients with STEMI in Sarawak using Dutch Lipid Clinic Network (DLCN) score. Materials and Methods Patients who were admitted for type-1 STEMI from April 2021 until July 2021 to Pusat Jantung Sarawak were recruited. History taking and physical examination were carried out on-site. FH was screened clinically using DLCN score. Results Out of the recruited patients, 45% of the cohort was clinically categorized into probable/ possible FH without genetic testing. Mean age and low density lipoprotein (LDL) were 52.7 and 3.38mmol/l respectively. Prevalence of premature CAD was 63%. Male gender, smoking, high BMI was the most frequent risk factor observed. Conclusions Prevalence of probable/possible familial hypercholesterolemia in a STEMI cohort using DLCN score is 45%. DLCN score in the STEMI cohort is not related to LDL levels

Safety and efficacy of human Wharton's Jelly-derived mesenchymal stem cells therapy for retinal degeneration

Purpose To investigate the safety and efficacy of subretinal injection of human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. Methods RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. Results No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. Conclusions Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies

Some doubts on the validity of the foreground Galactic contribution subtraction from microwave anisotropies

The Galactic foreground contamination in CMBR anisotropies, especially from the dust component, is not easily separable from the cosmological or extragalactic component. In this paper, some doubts will be raised concerning the validity of the methods used to date to remove Galactic dust emission in order to show that none of them achieves its goal. First, I review the recent bibliography on the topic and discuss critically the methods of foreground subtraction: the cross-correlation with templates, analysis assuming the spectral shape of the Galactic components, the "maximum entropy method", "internal linear combination", and "wavelet-based high resolution fitting of internal templates". Second, I analyse the galactic latitude dependence from WMAP data. The frequency dependence is discussed with the data in the available literature. The result is that all methods of subtracting the Galactic contamination are inaccurate. The galactic latitude dependence analysis or the frequency dependence of the anisotropies in the range 50-250 GHz put a constraint on the maximum Galactic contribution in the power spectrum to be less than a ~10% (68% C. L.) for a ~1 degree scale, and possibly higher for larger scales. The origin of most of the signal in the CMBR anisotropies is not Galactic. In any case, the subtraction of the Galaxy is not accurate enough to allow a "precision Cosmology"; other sources of contamination (extragalactic, solar system) are also present.Comment: 24 pages, 1 figure, accepted to be published in J. Astrophys. Ast