A Study of the Dynamics of Cardiac Ischemia using Experimental and Modeling Approaches

The dynamics of cardiac ischemia was investigated using experimental studies and computer simulations. An experimental model consisting of an isolated and perfused canine heart with full control over blood flow rate to a targeted coronary artery was used in the experimental study and a realistically shaped computer model of a canine heart, incorporating anisotropic conductivity and realistic fiber orientation, was used in the simulation study. The phenomena investigated were: (1) the influence of fiber rotation on the epicardial potentials during ischemia and (2) the effect of conductivity changes during a period of sustained ischemia. Comparison of preliminary experimental and computer simulation results suggest that as the ischemic region grows from the endocardium towards the epicardium, the epicardial potential patterns follow the rotating fiber orientation in the myocardium. Secondly, in the experimental studies it was observed that prolonged ischemia caused a subsequent reduction in the magnitude of epicardial potentials. Similar results were obtained from the computer model when the conductivity of the tissue in the ischemic region was reduce

Haplotype Structure of FSHB, the Beta-Subunit Gene for Fertility-Associated Follicle-Stimulating Hormone: Possible Influence of Balancing Selection

Follicle-stimulating hormone (FSH) is essential for human reproduction. The unique functions of this hormone are provided by the FSH receptor-binding beta-subunit encoded by the FSHB gene. Resequencing and genotyping of FSHB in three European, two Asian and one African population, as well as in the great apes (chimpanzee, gorilla, orangutan), revealed low diversity and significant excess of polymorphisms with intermediate frequency alleles. Statistical tests for FSHB showed deviations from neutrality in all populations suggesting a possible effect of balancing selection. Two core haplotypes were identified (carried by 76-96.6% of each population's sample), the sequences of which are clearly separated from each other. As fertility most directly affects an organism's fitness, the carriers of these haplotypes have apparently had more success in human history to contribute to the next generation. There is a preliminary observation suggesting that the second most frequent FSHB haplotype may be associated with rapid conception success in females. Interestingly, the same haplotype is related to an ancestral FSHB variant shared with the ancestor of the great apes. The determination of the functional consequence of the two core FSHB variants may have implications for understanding and regulating human fertility, as well as in assisting infertility treatments

Renal cell carcinoma metastasis to the ciliary body responds to proton beam radiotherapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report an unexpected presentation of metastatic renal cell carcinoma (RCC) to the ciliary body and an interesting response to proton beam radiotherapy.</p> <p>Case presentation</p> <p>We encountered a case of angle-closure glaucoma as the initial presentation of ocular metastasis to the ciliary body in a 65-year-old Caucasian man who had undergone right radical nephrectomy for RCC 15 years earlier. He underwent YAG (yttrium aluminium garnet) laser peripheral iridotomy while further metastatic workup took place. His condition was eventually diagnosed as stage IV metastatic RCC of the clear cell type and involved multiple sites, including the ciliary body, brain, lungs, liver, and pancreas. The progression of RCC metastasis to the ciliary body was studied for 16 months. The ciliary body mass continued to grow despite systemic treatment with temsirolimus and interleukin-2 and intravitreal injections of bevacizumab. The tumor size peaked at 6.11 × 6.06 mm before the start of proton therapy, which reduced the tumor size to 5.07 × 4.39 mm.</p> <p>Conclusions</p> <p>RCC can produce metastases involving unusual sites many years after resection of the primary tumor. Proton therapy was found to be effective in treating RCC metastasis to the ciliary body in settings in which other treatment modalities failed.</p

The Vissannapeta eucrite

A wholly encrusted single stone that fell in Vissannapeta, Andhra Pradesh, India has been identified as a cumulate eucrite based on its primary texture and mineral composition: anorthite (An92.4-94.6), orthopyroxene (En49.1-51.8Fs44.2-49.7Wo1.2-4.0), and clinopyroxene (En38.8-46.8Fs14.8-33.6Wo19.6-46.4). The stone is pyramidal in shape, and the crust shows rib-like flow features indicating that it had an oriented passage through the atmosphere towards the terminal stage of its flight. Conditions of its fall, mineralogical characteristics, and results of measurements of cosmogenic radioactivity (26Al, 22Na, and 54Mn) and track density are described. Aluminum-26 and 22Na in Vissannapeta are &#8764; 75% of the expected values and also lower by a similar factor compared to the activities measured in Piplia Kalan, another eucrite, which fell &#8764; 18 months before Vissannapeta. Because higher activity of 22Na and 54Mn would be expected from solar cycle modulation of galactic cosmic rays, these results, as well as the track density gradient, indicate that Vissannapeta was a small body (&#8804; 120 kg) in the interplanetary space wherein the nuclear cascade due to galactic cosmic rays did not develop fully. Tracks, surface morphology, and crustal features indicate at least two fragmentation events in the atmosphere

Fall, classification and cosmogenic records of the Sabrum (LL6) chondrite

The petrographic and chemical characteristics of a fresh Indian meteorite fall at Sabrum are described. Its mean mineral composition is defined by olivine (Fa31.4), orthopyroxene (Fs25.1,Wo2.0), clinopyroxene (Wo45En45.6Fs9.4) and plagioclase (An10.6Ab83.6Or5.8). The meteorite shows moderate shock features, which indicate that it belongs to the S4 category. Based on mineralogical and chemical criteria the meteorite is classified as an LL6 brecciated veined chondrite. Several cosmogenic radioisotopes (46Sc, 7Be, 54Mn, 22Na and 26Al), noble gas (He, Ne, Ar, Kr and Xe), nitrogen isotopes, and particle tracks density have been measured. Concentrations of cosmogenic 21Ne and 38Ar indicate that its cosmic-ray exposure age is 24.8 Ma. Small amounts of trapped Kr and Xe, consistent with petrologic class 5/6, are present. The track density in olivines is found to be (1.3 &#177; 0.3) &#215; 106/cm2. Activities of most of the short-lived isotopes are lower than those expected from solar cycle variation. 22Na/26Al (1.12 &#177; 0.02) is found to be significantly anomalous, being ~25% lower than expected from the Climax neutron monitor data. These results indicate that the cosmic-ray flux during the terminal segment of the meteoroid orbit was low. The activities of 26Al and 60Co and the track density indicate small meteoroid size with a radius ~15 cm

Predictors of 1- and 12-month mortality in bifurcation coronary intervention: a contemporary perspective

Aim: Bifurcation-PCI is performed frequently, although without extensive evidence to back up a definitive solution for its complexity. We set out to identify factors associated with 1- and 12-month mortality after bifurcation-PCI between 2017 and 2021 in our tertiary centre in Wales, UK. Results: Of 732 bifurcation PCI cases (mean age 69; 25% female), 67% were in ACS, 42% were left main PCI and 25.3% involved two-stent strategy. 30-day and 12-month mortality were 1.9% and 8.2%, respectively. Age, diabetes, smoking and renal failure are associated with mortality after bifurcation-PCI, while the choice between provisional and 2-stent strategies did not impact mortality/TLR. Conclusion: Awareness of ‘real-world’ outcomes of bifurcation-PCI should be used for appropriate patient selection, technique planning and procedural consent

Dopamine Regulates Mobilization of Mesenchymal Stem Cells during Wound Angiogenesis

Angiogenesis is an important step in the complex biological and molecular events leading to successful healing of dermal wounds. Among the different cellular effectors of wound angiogenesis, the role of mesenchymal stem cells (MSCs) is of current interest due to their transdifferentiation and proangiogenic potentials. Skin is richly innervated by sympathetic nerves which secrete dopamine (DA) and we have recently shown that concentration of DA present in synaptic cleft can significantly inhibit wound tissue neovascularization. As recent reports indicate that MSCs by mobilizing into wound bed play an important role in promoting wound angiogenesis, we therefore investigated the effect of DA on the migration of MSCs in wound tissues. DA acted through its D2 receptors present in the MSCs to inhibit their mobilization to the wound beds by suppressing Akt phosphorylation and actin polymerization. In contrast, this inhibitory effect of DA was reversed after treatment with specific DA D2 receptor antagonist. Increased mobilization of MSCs was demonstrated in the wound site following blockade of DA D2 receptor mediated actions, and this in turn was associated with significantly more angiogenesis in wound tissues. This study is of translational value and indicates use of DA D2 receptor antagonists to stimulate mobilization of these stem cells for faster regeneration of damaged tissues

Communicating climate change: conduits, content, and consensus

Climate change has been the subject of increasing efforts by scientists to understand its causes and implications; it has been of growing interest to policymakers, international bodies, and a variety of nongovernment organizations; and it has attracted varied amounts of attention from traditional and, increasingly, online media. These developments have been aligned with shifts in the nature of climate change communication, with changes in how researchers study it and how a variety of actors try to influence it. This article situates the theory and practice of climate change communication within developments that have taken place since we first reviewed the field in 2009. These include the rise of new social media conduits for communication, research, and practice aimed at fine tuning communication content, and the rise to prominence of scientific consensus as part of that content. We focus in particular on continuing tensions between a focus on the part of communicators to inform the public and more dialogic strategies of public engagement. We also consider the tension between efforts to promote consensus and certainty in climate science and approaches that attempt to engage with uncertainty more fully. We explore the lessons to be learnt from climate communication since 2009, highlighting how the field remains haunted by the deficit model of science communication. Finally, we point to more fruitful future directions for climate change communication, including more participatory models that acknowledge, rather than ignore, residual uncertainties in climate science in order to stimulate debate and deliberation

Acute appendicitis caused by endometriosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Endometriosis is a well-recognized gynecological condition in the reproductive age group. Surgical texts present the gynecological aspects of the disease in detail, but the published literature on unexpected manifestations, such as appendiceal disease, is inadequate. The presentation to general surgeons may be atypical and pose diagnostic difficulty. Thus, a definitive diagnosis is likely to be established only by the histological examination of a specimen.</p> <p>Case presentation</p> <p>We report a case of endometriosis of the appendix in a 25-year-old Caucasian woman who presented with symptoms of acute appendicitis and was treated by appendectomy, which resulted in a good outcome.</p> <p>Conclusions</p> <p>We discuss special aspects of acute appendicitis caused by endometriosis to elucidate the pathologic entity of this variant of acute appendicitis.</p

Dopamine Regulates Angiogenesis in Normal Dermal Wound Tissues

Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA) is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities