No causal effects between rosiglitazone and cardiovascular disease or risk factors: a Mendelian randomization study.

OBJECTIVE: Although many observational studies have shown an association between rosiglitazone and cardiovascular disease (CVD) or risk factors, controversy remains. We conducted a Mendelian randomized (MR) study to explore whether rosiglitazone is causally related to CVDs and risk factors. PATIENTS AND METHODS: Single-nucleotide polymorphisms associated with rosiglitazone at genome-wide significance were identified from a genome-wide association study of 337,159 European-ancestry individuals. Four treatments with rosiglitazone-associated single-nucleotide polymorphisms associated with a higher risk of CVDs were used as an instrumental variable (IV). Summary-level data for 7 CVDs and 7 risk factors were obtained from UK Biobank and consortia. RESULTS: We found no causal effects of rosiglitazone, either on CVDs or risk factors. The results were consistent in sensitivity analyses using Cochran's Q test, MR-PRESSO method, leave-one-out analysis and Mendelian randomization-Egger method (MR-Egger), and no directional pleiotropy was observed. Sensitivity analyses confirmed that rosiglitazone was not significantly associated with CVDs and risk factors. CONCLUSIONS: The findings from this MR study indicate no causal relationship between rosiglitazone and CVDs or risk factors. Hence, previous observational studies may have been biased.

Species diversity, systematic revision and molecular phylogeny of Ganodermataceae (Polyporales, Basidiomycota) with an emphasis on Chinese collections.

Ganodermataceae is one of the main families of macrofungi since species in the family are both ecologically and economically important. The double-walled basidiospores with ornamented endospore walls are the characteristic features of Ganodermataceae. It is a large and complex family; although many studies have focused on Ganodermataceae, the global diversity, geographic distribution, taxonomy and molecular phylogeny of Ganodermataceae still remained incompletely understood. In this work, taxonomic and phylogenetic studies on worldwide species of Ganodermataceae were carried out by morphological examination and molecular phylogenetic analyses inferred from six gene loci including the internal transcribed spacer regions (ITS), the large subunit of nuclear ribosomal RNA gene (nLSU), the second largest subunit of RNA polymerase II gene (rpb2), the translation elongation factor 1-α gene (tef1), the small subunit mitochondrial rRNA gene (mtSSU) and the small subunit nuclear ribosomal RNA gene (nSSU). A total of 1 382 sequences were used in the phylogenetic analyses, of which 817 were newly generated, including 132 sequences of ITS, 139 sequences of nLSU, 83 sequences of rpb2, 124 sequences of tef1, 150 sequences of mtSSU and 189 sequences of nSSU. The combined six-gene dataset included sequences from 391 specimens representing 146 taxa from Ganodermataceae. Based on morphological and phylogenetic analyses, 14 genera were confirmed in Ganodermataceae: Amauroderma, Amaurodermellus, Cristataspora, Foraminispora, Furtadoella, Ganoderma, Haddowia, Humphreya, Magoderna, Neoganoderma, Sanguinoderma, Sinoganoderma, Tomophagus and Trachydermella. Among these genera, Neoganoderma gen. nov. is proposed for Ganoderma neurosporum; Sinoganoderma gen. nov. is proposed for Ganoderma shandongense; Furtadoella gen. nov. is proposed to include taxa previously belonging to Furtadoa since Furtadoa is a homonym of a plant genus in the Araceae; Trachydermella gen. nov. is proposed to include Trachyderma tsunodae since Trachyderma is a homonym of a lichen genus in the Pannariaceae. Twenty-three new species, viz., Ganoderma acaciicola, G. acontextum, G. alpinum, G. bubalinomarginatum, G. castaneum, G. chuxiongense, G. cocoicola, G. fallax, G. guangxiense, G. puerense, G. subangustisporum, G. subellipsoideum, G. subflexipes, G. sublobatum, G. tongshanense, G. yunlingense, Haddowia macropora, Sanguinoderma guangdongense, Sa. infundibulare, Sa. longistipitum, Sa. melanocarpum, Sa. microsporum and Sa. tricolor are described. In addition, another 33 known species are also described in detail for comparison. Scanning electron micrographs of basidiospores of 10 genera in Ganodermataceae are provided. A key to the accepted genera of Ganodermataceae and keys to the accepted species of Ganoderma, Haddowia, Humphreya, Magoderna, Sanguinoderma and Tomophagus are also provided. In total, 278 species are accepted as members of Ganodermataceae including 59 species distributed in China. Taxonomic novelties: New genera: Furtadoella B.K. Cui & Y.F. Sun, Neoganoderma B.K. Cui & Y.F. Sun, Sinoganoderma B.K. Cui, J.H. Xing & Y.F. Sun and Trachydermella B.K. Cui & Y.F. Sun; New species: Ganoderma acaciicola B.K. Cui, J.H. Xing & Y.F. Sun, G. acontextum B.K. Cui, J.H. Xing & Vlasák, G. alpinum B.K. Cui, J.H. Xing & Y.F. Sun, G. bubalinomarginatum B.K. Cui, J.H. Xing & Y.F. Sun, G. castaneum B.K. Cui, J.H. Xing & Y.F. Sun, G. chuxiongense B.K. Cui, J.H. Xing & Y.F. Sun, G. cocoicola B.K. Cui, J.H. Xing & Y.F. Sun, G. fallax B.K. Cui, J.H. Xing & Vlasák, G. guangxiense B.K. Cui, J.H. Xing & Y.F. Sun, G. puerense B.K. Cui, J.H. Xing & Y.F. Sun, G. subangustisporum B.K. Cui, J.H. Xing & Y.F. Sun, G. subellipsoideum B.K. Cui, J.H. Xing & Y.F. Sun, G. subflexipes B.K. Cui, J.H. Xing & Y.F. Sun, G. sublobatum B.K. Cui, J.H. Xing & Y.F. Sun, G. tongshanense B.K. Cui, J.H. Xing & Y.F. Sun, G. yunlingense B.K. Cui, J.H. Xing & Y.F. Sun, Haddowia macropora B.K. Cui, Vlasák & Y.F. Sun, Sanguinoderma guangdongense B.K. Cui & Y.F. Sun, Sa. infundibulare B.K. Cui & Y.F. Sun, Sa. longistipitum B.K. Cui & Y.F. Sun, Sa. melanocarpum B.K. Cui & Y.F. Sun, Sa. microsporum B.K. Cui & Y.F. Sun and Sa. tricolor B.K. Cui & Y.F. Sun; New combinations: Furtadoella biseptata (Costa-Rezende et al.) B.K. Cui & Y.F. Sun, Fu. brasiliensis (Singer) B.K. Cui & Y.F. Sun, Fu. corneri (Gulaid & Ryvarden) B.K. Cui & Y.F. Sun, Neoganoderma neurosporum (J.S. Furtado) B.K. Cui & Y.F. Sun, Sinoganoderma shandongense (J.D. Zhao & L.W. Xu) B.K. Cui, J.H. Xing & Y.F. Sun and Trachydermella tsunodae (Yasuda ex Lloyd) B.K. Cui & Y.F. Sun. Citation: Sun Y-F, Xing J-H, He X-L, Wu D-M, Song C-G, Liu S, Vlasák J, Gates G, Gibertoni TB, Cui B-K (2022). Species diversity, systematic revision and molecular phylogeny of Ganodermataceae (Polyporales, Basidiomycota) with an emphasis on Chinese collections. Studies in Mycology 101: 287-415. doi: 10.3114/sim.2022.101.05.

In vivo effects of bumetanide at brain concentrations incompatible with NKCC1 inhibition on newborn DGC structure and spontaneous EEG seizures following hypoxia-induced neonatal seizures.

Neonatal seizures caused by perinatal asphyxia and hypoxic-ischemic encephalopathy can be refractory to conventional anticonvulsants. This may be due to the depolarizing effects of gamma-aminobutyric acid (GABA) achieved by the activity of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1). The aim of this study is to evaluate the long-term effects of bumetanide, a NKCC1 inhibitor, on hippocampal neurogenesis and seizure susceptibility in hypoxia-induced neonatal seizure model. Wistar rats were subjected to hypoxia-induced neonatal seizures at postnatal day 10 (P10). Following acute seizures, the rats were treated with intraperitoneal injection (i.p.) of bumetanide at a dose of 0.5mg/kg for 3 weeks. In later adulthood, hypoxia-induced seizures increased the number of newborn dentate gyrus cells (DGCs), promoted mossy fiber sprouting (MFS) and reduced the apical dendritic complexity of newborn DGCs 1 month after the insults. In addition, these seizures resulted in long-lasting consequences, such as spontaneous electroencephalography (EEG) seizures, though spatial learning impairments were not seen. Bumetanide treatments significantly enhanced cell proliferation and dendritic development of newborn DGCs after neonatal seizures, accompanied by the decreased seizure activity. However, systemic administration of bumetanide resulted in much lower brain concentrations, and was incompatible with NKCC1 inhibition in blood-brain barrier (BBB)-protected brain tissue. Our results suggested that bumetanide might have long-term effects in suppressing seizure activity, and altering the neurogenesis after neonatal seizures. These effects of bumetanide may be mediated by the targets outside the BBB-protected central nerve system (CNS) or CNS-located target(s) other than NKCC1.

Forced limb-use enhanced neurogenesis and behavioral recovery after stroke in the aged rats.

Constraint-induced movement therapy (CIMT) after stroke enhances not only functional reorganization but also structural plasticity of the brain in the adult rats. We examined whether forced limb-use which mimicked CIMT could influence ischemia-induced neurogenesis, apoptosis and behavioral recovery in the aged rats. Aged rats were divided into a sham group, an ischemia group, and an ischemia group with forced limb-use. Focal cerebral ischemia was induced by injection of endothelin-1. Forced limb-use began on post-stroke day 7 by fitting a plaster cast around the unimpaired upper limbs of rats for 3 weeks. Behavioral recovery was evaluated by tapered/ledged beam-walking test on postoperative day 32. The expression of doublecortin, neuronal nuclei, glial fibrillary acidic protein and Iba-1 were measured by single or double immunohistochemistry, and apoptosis was measured by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. The production of neuroblasts in the subventricular zone (SVZ) was significantly increased after stroke. Forced limb-use enhanced the proliferation of newborn neurons in the SVZ, as well as increased the long-term survival of newborn neurons. Furthermore, forced limb-use suppressed apoptosis and improved the motor functions after stroke in the aged rats. Forced limb-use exerted few effects on inflammation. Neither the number nor dendritic complexity of newborn granule cells in the hippocampus was affected by forced limb-use. Forced limb-use is effective in enhancing neurogenesis and behavioral recovery after stroke even in the aged rats.

Short-term changes of intraocular pressure after cervical interlaminar epidural injection: a pilot study.

BACKGROUND: Cervical epidural injection (CEI) is widely performed on patients with intervertebral disc herniation. The aim of the present study was to investigate the short-term effects of CEI on non-invasive intraocular pressure (IOP) measurements in subjects with normal eyes. METHODS: This prospective study enrolled 15 patients who were undergoing CEI at the C5/6 level with an interlaminar approach in the left lateral decubitus position. IOP was measured in both eyes by a rebound tonometer (Icare-PRO, Icare Finland Oy, Helsinki, Finland). A total volume of 14 ml (4 ml non-ionic contrast, a mixture of 0.2% lidocaine 1 ml and normal saline 4 ml for irrigation and a mixture of normal saline 4.5 ml with non-particulate betamethasone 2 mg) was injected with 1.0 ml s(-1). IOP was measured 5 min after the lateral decubitus position (T0, baseline), immediately after CEI (T1), and 1 min intervals for 5 min (T2-T6). RESULTS: The values of left and right baseline IOP (T0) were 18.9 (2.0) and 15.6 (2.6) mm Hg, respectively. IOP of left and right eyes at T1 [26.6 (4.2) and 21.2 (2.5) mm Hg, respectively] and T2 [26.2 (4.5) and 21.0 (2.8) mm Hg, respectively] were significantly higher compared with T0. These values immediately decreased at T3 and returned to baseline levels within 5 min after CEI. CONCLUSIONS: CEI resulted in an elevation of IOP of both eyes. However, the effects were transient only lasting a few minutes.

Reduction of gate leakage current on AlGaN/GaN high electron mobility transistors by electron-beam irradiation.

This study examined the effect of electron-beam (E-beam) irradiation on the AIGaN/GaN HEMTs for the reduction of gate leakage. After E-beam irradiation, the gate leakage current significantly decreased from 2.68 x 10(-8) A to 4.69 x 10(-9) A at a drain voltage of 10 V. The maximum drain current density of the AIGaN/GaN HEMTs with E-beam irradiation increased 14%, and the threshold voltage exhibited a negative shift, when compared to that of the AIGaN/GaN HEMTs before E-beam irradiation. These results strongly suggest that the reduction of gate leakage current resulted from neutralization nitrogen vacancies and removing of oxygen impurities.

Investigation of gold-coated bare fiber probe for in situ intra-vitreous coherence domain optical imaging and sensing.

We have investigated the usage of gold-plated bare fiber probes for in situ imaging of retinal layers and surrounding ocular tissues using time-domain common-path optical coherence tomography. The fabricated intra-vitreous gold-plated micro-fiber probe can be fully integrated with surgical tools working in close proximity to the tissue to provide subsurface images having a self-contained reference plane independent to the Fresnel reflection between the distal end of the probe and the following medium for achieving reference in typical common-path optical coherence tomography. We have fully characterized the probe in an aqueous medium equivalent to the vitreous humor in the eye and were able to differentiate various functional retinal tissue layers whose thickness is larger than the system's resolution.

Common path optical coherence tomography with fibre bundle probe.

A simple common path optical coherence tomography using a fibre optic bundle as a probe is demonstrated experimentally. The mechanical lateral scans are accomplished outside the specimen, proximal entrance of the fibre bundle, which eliminated the need for moving parts in the distal end of the probe. This feature allows the probe to be made submillimetre in size and easily integrated into surgical tools for intraoperative imaging. The axial and lateral resolutions of the system, and preliminary images of phantom samples, are reported.

Performance evaluation of stereo endoscopic imaging system incorporating TFT-LCD.

This paper presents a 3D endoscopic video system designed to improve visualization and enhance the ability of the surgeon to perform delicate endoscopic surgery. In a comparison of the polarized and electric shutter-type stereo imaging systems, the former was found to be superior in terms of both accuracy and speed for knot-tying and for the loop pass test. The results of our experiments show that the proposed 3D endoscopic system has a sufficiently wide viewing angle and zone for multi-viewing, and that it provides better image quality and more stable optical performance compared with the electric shutter-type.

Automatic stimulus breaker for electric dental pulp tester using pain response.

The pulp test provides a means of examining the vitality of dental pulp using physical or chemical stimulation. During electrical pulp testing, an electrical current stimulates the intradental nerve, which may be painful and stressful to patients. The study involved measurement of the electromyogram (EMG) from the anterior belly of the digastric muscle, finger movement and voice response during electrical pulp testing. The excessive stimulus time from the onset time of response (EMG, voice and finger movement) to the end of the stimulation was obtained. The results indicated that the responses occurred in the order: EMG, finger and voice. Based on these results, an automatic stimulus shut-off circuit was developed using the above-mentioned responses to stimulus during electric pulp testing. Excessive stimulus time was reduced by prompt switching-off of the pulp tester output, 64 ms on average after the first detected response (EMG). Consequently, excessive stimulus times were reduced by 284 and 152 ms on average for the subject and examiner disconnection, respectively, using the developed automatic shut-off circuit. Therefore it was possible to minimise pain and stress by reducing excessive pulp stimulation.

A new approach for detection of leg movement using segmental electrical impedance changes.

The purpose of this paper is to provide a new approach for detection using bio-impedance. This impedance is measured by the four-electrode method. As the impedance changes resulting from ankle, knee, and hip movements depend on electrode placement, we determined the optimal electrode configurations for these movements by searching for high correlation coefficients, large impedance changes, and minimum interference in ten subjects (age: 20 +/- 4). Our optimal electrode configurations showed very strong relationships between the ankle joint angle and ankle impedance (gamma = - 0.913 +/- 0.03), between the knee joint angle and knee impedance (gamma = 0.944 +/- 0.02), and between the hip joint angle and hip impedance (gamma = 0.823 +/- 0.08). This study showed that lower leg movement could be easily measured by the impedance measurement system with two pairs of skin electrodes.

Over expression of aromatase protein is highly related to MMPs levels in human breast carcinomas.

Estrogens can play a critical role in the development of breast cancer. Aromatase which catalyzes the formation of aromatic C18 estrogens from C19 androgens is regarded to be responsible for the cancer local production of estrogen. Studies not only from aromatase transfected breast cancer cells, but also transgenic mouse, which overexpressed aromatase, demonstrated that in situ produced estrogen plays more important roles than circulating estrogens in breast tumor promotion and progression. Matrix-metalloproteinases (MMPs) have been implicated in the proeolytic process, which play important roles in the aggressiveness of cancer cells including invasion of adjacent tissue and metastasis to distant sites. Expression of MMP2 and 9 may be stimulated by estrogens in hormonal dependent breast cancers, since tumor aromatase can stimulate breast cancer growth and progression in both an autocrine and a paracrine manner. Theoretically aromatase overexpression, that causes relatively high estrogen concentration in situ, may be positively related to MMP2 and 9 expression, indicate worse prognosis in breast cancers, and maybe insensitive to tamoxifen therapy. In the present study, we studied the expression of aromatase activity and MMPs in human breast carcinoma both in vitro and in vivo. In human breast carcinoma cell lines including MCF-7, MDA-MB-231 and MDA-MB-435, the expression of aromatase levels both in mRNA and protein activity was related to MMP2 and MMP9. In humam breast cancer samples, we demonstrated that aromatase expressions were strongly associated with MMP2 and MMP9 levels. It was interesting to observe that the positive relationship was only present in the ER and/or PR positive patients. This may indicate that both MMP2 and MMP9 were up regulated by estrogen produced by aromatase through ER. So in endocrine therapy, either blocking the ER by tamoxifen or inhibiting the aromatase by aromatase inhibitors for example letrozole, may both inhibit tumor growth and lower the metastatic potential especially in ER positive breast cancer patients by means of down-regulation of MMP2/9.

An improved approach for measurement of stroke volume during treadmill exercise.

In this study, a new ensemble averaging technique was developed to measure cardiac output during treadmill exercise. Each dz/dt peak is used as a starting point for ensemble averaging, instead of the conventionally used R point of ECG, in order to prevent the peak dz/dt waveform (C point) to be smoothed, which results in increased dz/dtmax. When using the R point as a reference, time interval from the R point to the peak dz/dt varies for each heart beat. Signal to noise ratios (SNR) of the five subjects with the new technique were 12.9, 16. 4, 10.6, 14.0, and 4.6% higher than those with the conventional one at rest and during four levels of exercise, respectively. Power density spectra of the averaged dz/dt waveforms by the peak dz/dt and R point referencing were also analyzed. Stroke volumes of the five subjects averaged by the peak dz/dt were 4.9, 6.8, 7.6, 7.4, and 9.8% higher than those by the R point at rest and during four levels of exercise, respectively.

A new ensemble averaging technique in impedance cardiography for estimation of stroke volume during treadmill exercise.

In this study, a new ensemble average technique is developed to measure cardiac output during treadmill exercise. Each dz/dt peak is used as a starting point for ensemble averaging, instead of the conventionally used R point of the ECG, in order to prevent the peak dz/dt waveform (C point) from smoothing, which results in increased dz/dtmax. The R-Z interval from the R point of the ECG to the peak dz/dt varies for each heart beat especially during strenuous exercise. Signal-to-noise ratios of five subjects obtained with the new technique are 0-32.6% higher than those obtained with the conventional technique at rest and during four levels of treadmill exercise. Power spectral densities of the averaged dz/dt waveforms by the peak dz/dt and R point references are also analyzed. Stroke volumes of the five subjects averaged by the peak dz/dt are 0-23.5% higher than those obtained by the R point at rest and during four levels of exercise.