Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice

Background: Carbamazepine is an antiepileptic drug used widely for the treatment of epileptic seizures and neuropathic pain. Several malformations in humans, mainly neural tube defects, have been reported as a consequence of its use during pregnancy. The association between maternal use of carbamazepine and congenital eye malformations is not very well understood. Objective: The purpose of this study was to examine this association after intraperitoneal injection of carbamazepine during the period of organogenesis in mice. Methods: Balb/c timed-pregnant mice were divided into 4 experimental and control groups. Two experimental groups received daily intraperitoneal injections of 15mg/kg (group I) or 30mg/kg (group II) of carbamazepine on gestational days 6 to 15. Two control groups received normal saline or Tween 20 (polysorbate 20). Dams underwent Cesarean section on gestational day 18 and embryos were harvested. External examination for eye malformations, routine histological processing of malformed fetuses to study eye morphology, and skeletal staining were performed. Results: The mean weight and crown-rump of the fetuses in both experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, calvarial deformity, vertebral deformity, short tail, and brachydactyly. Premature opening of one or both eyes with mild to severe exophthalmos occurred in the 2 experimental groups. Deformed lens, retinal folds with undeveloped layers, and corneal folds with absence of surface epithelium were detected in both experimental groups. Conclusions: This study, to the best of our knowledge, showed for the first time that intraperitoneal administration of carbamazepine at clinically comparable doses during organogenesis can induce several eye malformations in mice. The implication of these results needs to be considered when carbamazepine is administered during human pregnancy. © 2010 Informa UK Ltd

SUq(2)SU_q(2) Lattice Gauge Theory

We reformulate the Hamiltonian approach to lattice gauge theories such that, at the classical level, the gauge group does not act canonically, but instead as a Poisson-Lie group. At the quantum level, it then gets promoted to a quantum group gauge symmetry. The theory depends on two parameters - the deformation parameter $\lambda$ and the lattice spacing $a$. We show that the system of Kogut and Susskind is recovered when $\lambda \rightarrow 0$, while QCD is recovered in the continuum limit (for any $\lambda$). We thus have the possibility of having a two parameter regularization of QCD.Comment: 26 pages, LATEX fil

Hypoxia mimetic agents for ischemic stroke

Every year stroke claims more than 6 million lives worldwide. The majority of them are ischemic stroke. Small molecule-based therapeutics for ischemic stroke has attracted a lot of attention, but none has been shown to be clinically useful so far. Hypoxia-inducible factor-1 (HIF-1) plays a crucial role in the transcriptional adaptation of cells to hypoxia. Small molecule-based hypoxia-mimetic agents either stabilize HIF-1α via HIF-prolyl hydroxylases (PHDs) inhibition or through other mechanisms. In both the cases, these agents have been shown to confer ischemic neuroprotection in vitro and in vivo. The agents which act via PHD inhibition are mainly classified into iron chelators, iron competitors, and 2 oxoglutarate (2OG) analogs. This review discusses HIF structure and key players in the HIF-1 degradation pathway as well as the genes, proteins and chemical molecules that are connected to HIF-1 and how they affect cell survival following ischemic injury. Furthermore, this review gives a summary of studies that used PHD inhibitors and other HIF-1α stabilizers as hypoxia-mimetic agents for the treatment of ischemic injury

Restoration of heart function using transplantation of human umbilical cord matrix-derived cardiomyocytes and vascular endothelial growth factor

Objectives: In the previous study, although it has been shown that intramyocardial injection of human umbilical cord matrix stem cell (hUCM) improved cardiac function 4 weeks post MI, but angiogenesis has not been observed. Angiogenesis and replacing lost cardiomyocytes with new, live cardiomyocytes are considered as two key agents in cardiac repair. To achieve the above two factors we examined the effects of combination of stem cell and angiogenic therapy approaches by simultaneously injection of hUCM-derived cardiomyocytes with vascular endothelial growth factor (VEGF) in cardiac repair. Methods: MI-induced animals(by ligation of LAD) received 50 μl PBS, 5 � 106 differentiated hUCM cells (dhUCM), 5μg VEGF in normal saline and 5 � 106 dhUCM cells combined with 5μg VEGF in normal saline, intramyocardialy. MI group, with no other intervention, served as a control group. We were assessed survival, migration and integration of dhUCM cells, as well as angiogenesis eight weeks post MI induction. Results: Eight weeks post MI, although dhUCM and VEGF groups have shown that LVEF and LVFS improved significantly, but animals in dhUCM+VEGF group have the highest rise in LVEF and LVFS in comparison to the other MI-induced groups (p<0.05). Histological and morphological analysis have revealed that myocardium of animals in dhUCM+VEGF group have the highest vascular density and the lowest fibrosis tissue in comparison to the other MI-induced groups (p<0.05). Immunohistological assessments revealed that transplanted dhUCM cells have survived, migrated to infarcted area and integrated with recipient cardiac tissue. Conclusion: we have found that intramyocardial administration of dhUCM cells combined with VEGF improved cardiac function, enhanced angiogenesis and reduced fibrosis tissue formation after MI, eight weeks post MI. © Kaveh et al

LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke

Stroke is one of the commonest causes of death with limited treatment options. L-Carnosine has shown great promise as a neuroprotective agent in experimental stroke, but translation to the clinic is impeded by the large doses needed. We developed and evaluated the therapeutic potential of a novel delivery vehicle which encapsulated carnosine in lipoprotein receptor related protein-1 (LRP-1)-targeted functionalized polymersomes in experimental ischemic stroke. We found that following ischemic stroke, polymersomes encapsulating carnosine exhibited remarkable neuroprotective effects with a dose of carnosine 3 orders of magnitude lower than free carnosine. The LRP-1-targeted functionalization was essential for delivery of carnosine to the brain, as non-targeted carnosine polymersomes did not exhibit neuroprotection. Using Cy3 fluorescence in vivo imaging, we showed that unlike non-targeted carnosine polymersomes, LRP-1-targeted carriers accumulated in brain in a time dependent manner. Our findings suggest that these novel carriers have the ability to deliver neuroprotective cargo effectively to the brain

Hopf algebras and Markov chains: Two examples and a theory

The operation of squaring (coproduct followed by product) in a combinatorial Hopf algebra is shown to induce a Markov chain in natural bases. Chains constructed in this way include widely studied methods of card shuffling, a natural "rock-breaking" process, and Markov chains on simplicial complexes. Many of these chains can be explictly diagonalized using the primitive elements of the algebra and the combinatorics of the free Lie algebra. For card shuffling, this gives an explicit description of the eigenvectors. For rock-breaking, an explicit description of the quasi-stationary distribution and sharp rates to absorption follow.Comment: 51 pages, 17 figures. (Typographical errors corrected. Further fixes will only appear on the version on Amy Pang's website, the arXiv version will not be updated.

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial

Background Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke. Objective We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury. Methods Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS treatment by sex, age (≥62 years), time from stroke (>2 years), severity (baseline FMA-UE score >34), paretic side of body, country of enrollment (USA vs UK) and presence of cortical involvement of the index infarction. We assessed whether there was any interaction with treatment. Findings The primary outcome increased by 5.0 points (SD 4.4) in the VNS group and by 2.4 points (SD 3.8) in the Control group (P=.001, between group difference 2.6, 95% CI 1.03-4.2). The between group difference was similar across all subgroups and there were no significant treatment interactions. There was no important difference in rates of adverse events across subgroups. Conclusion The response was similar across subgroups examined. The findings suggest that the effects of paired VNS observed in the VNS-REHAB trial are likely to be consistent in wide range of stroke survivors with moderate to severe upper extremity impairment

Personalized peptide-based vaccination for treatment of colorectal cancer: rational and progress

Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high rate of morbidity and mortality. A large proportion of patients with early stage CRC who undergo conventional treatments develop local recurrence or distant metastasis and in this group of advanced disease, the survival rate is low. Furthermore there is often a poor response and/or toxicity associated with chemotherapy and chemo-resistance may limit continuing conventional treatment alone. Choosing novel and targeted therapeutic approaches based on clinicopathological and molecular features of tumors in combination with conventional therapeutic approach could be used to eradicate residual micrometastasis and therefore improve patient prognosis and also be used preventively. Peptide-based vaccination therapy is one class of cancer treatment that could be used to induce tumor-specific immune responses, through the recognition of specific antigen-derived peptides in tumor cells, and this has emerged as a promising anti-cancer therapeutic strategy. The aim of this review was to summarize the main findings of recent studies in exciting field of peptide-based vaccination therapy in CRC patients as a novel therapeutic approach in treatment of CRC

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Tempo-spatial behavior of Surface Urban Heat Island of Isfahan Metropolitan Area

The population of Isfahan has increased ten times over the past six decades. The rapid urbanization of the historical city of Isfahan has had a great environmental impact. At the same time, drying of Zayandeh Rood, increasing the air temperature, decreasing rain has brought the city to a critical environmental situation. The emergence of the urban heat island is only one of the consequences of the environmental changes of the past decades. Urban heat island has consequences for the health of citizens and it affects the consumption of water and energy. In this study, MODIS Aqua/LST data was used for night and day from 1379 to 1395. By using this data, the background climate of the metropolis of Isfahan was identified with the distance-azimuth (DA) charts. Then the representative pixel within the city and the representative pixel of the background climate were identified. Based on the time series of LST over these two pixels SUHI index of Isfahan metropolis was calculated. Studies show that the Isfahan metropolitan area is colder than the suburbs during the day and it is warmer than its surroundings during the night. The magnitude of the SUHI is maximal in January and is weaker in the summer. Regarding the temporal and spatial behavior of the SUHI, it seems that the changes made by the city in humidity, albedo, and composition of the atmosphere have played an important role in the emergence of the SUHI. Zayandeh Rood has played a major role in modulating the land surface temperature in the metropolitan area of Isfahan, and its drying has had environmental consequences