Coronary artery microfistulae, Thebesian veins, or vessels of Wearn?

We present the case of a 73-year-old woman with coronary artery-left ventricular multiple microfistulae, who was admitted with symptoms and ECG suggestive of coronary artery disease. Coronary angiography revealed tortuous coronary arteries with multiple microfistulae between the left coronary artery and the left ventricle, as well as between the right coronary artery and the left ventricle. Transthoracic echocardiography (TTE) was also able to clearly demonstrate the presence of the microfistulae with their direction of blood flow towards the left ventricle.

Contact angle hysteresis on nonwetting microstructured surfaces: Effect of randomly distributed pillars or holes.

We present a numerical study of the advancing and receding apparent contact angles for a liquid meniscus in contact with an ultrahydrophobic surface with randomly distributed microsized pillars or holes in the Cassie's wetting regime. We study the Wilhelmy plate system in the framework of the full capillary model to obtain these angles using the heterogeneous surface approximation model for a broad interval of values of pillar or hole concentration and for both square and circular shapes of the pillars or holes cross-section. Three types of random placing of defects on the plate are investigated, i.

The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging.

While primarily produced in the pineal gland, melatonin's influence goes beyond its well-known role in regulating sleep, nighttime metabolism, and circadian rhythms, in the field of chronobiology. A plethora of new data demonstrates melatonin to be a very powerful molecule, being a potent ROS/RNS scavenger with anti-inflammatory, immunoregulatory, and oncostatic properties. Melatonin and its metabolites exert multiple beneficial effects in cutaneous and systemic aging.

Type II & III inhibitors of tropomyosin receptor kinase (Trk): a 2020-2022 patent update.

Introduction: The Trk family proteins are membrane-bound kinases predominantly expressed in neuronal tissues. Activated by neurotrophins, they regulate critical cellular processes through downstream signaling pathways. Dysregulation of Trk signaling can drive a range of diseases, making the design and study of Trk inhibitors a vital area of research.

Efficacy of eprinomectin 5 mg/mL topical solution administered pour on at 1 mg per kg body weight against Oestrus ovis myiasis in sheep and goats.

The larvae of the nasal bot, Oestrus ovis, mainly parasitize sheep and goats and some species of wild Caprinae but other mammals and humans are also vulnerable to infestation. Eprinomectin 5 mg/mL topical solution (EPRINEX® Multi, Boehringer Ingelheim) administered at 1 mg eprinomectin per kg body weight pour on was recently authorized as an anthelmintic for sheep and goats with zero hours milk withdrawal in several countries in Europe. As the product in cattle has claims against a broad range of parasites including insect parasites and activity against O.

Investigating the anti-cancer potential of pyrimethamine analogues through a modern chemical biology lens.

Pharmacological inhibition of dihydrofolate reductase (DHFR) is an established approach for treating a variety of human diseases, including foreign infections and cancer. However, treatment with classic DHFR inhibitors, such as methotrexate (MTX), are associated with negative side-effects and resistance mechanisms that have prompted the search for alternatives. The DHFR inhibitor pyrimethamine (Pyr) has compelling anti-cancer activity in in vivo models, but lacks potency compared to MTX, thereby requiring higher concentrations to induce therapeutic responses.

Type I inhibitors of tropomyosin receptor kinase (Trk): a 2020-2022 patent update.

Introduction: Trk inhibitors are significant in the realm of personalized medicine as they target specific genetic alterations, such as gene fusions, leading to improved treatment outcomes for cancer patients. By tailoring the treatment to the genetic characteristics of the tumor rather than the tumor type, Trk inhibitors offer the potential for more effective and precise therapies, resulting in enhanced response rates and prolonged survival for patients with fusion-positive cancers.

Areas Covered: Patents covering type I inhibitors targeting the Trk family are discussed, building upon our prior review series on Trk inhibitors.

Contact angle hysteresis on random self-affine rough surfaces in Wenzel's wetting regime: Numerical study.

We present a numerical study of the advancing and receding apparent contact angles for a liquid meniscus in contact with random self-affine rough surfaces in Wenzel's wetting regime. Within the framework of the Wilhelmy plate geometry, we use the full capillary model to obtain these global angles for a wide range of local equilibrium contact angles and for different parameters that determine the self-affine solid surfaces: Hurst exponent, wave vector domain, and root-mean-square roughness. We find that the advancing and receding contact angles are single-valued functions that depend only on the roughness factor determined by the set of values of the parameters of the self-affine solid surface.

Attenuation of Hypothyroidism-Induced Cognitive Impairment by Modulating Serotonin Mediation.

Thyroid hormones play an important role in the modeling of neural networks in the brain. Besides its metabolic effects, thyroid dysfunction, and hypothyroidism in particular, is frequently associated with cognitive decline and depressive-like behavior. The current study aimed to examine the changes in behavior, cognition, and memory in rats with propylthiouracil-induced overt hypothyroidism.

Cycloguanil and Analogues Potently Target DHFR in Cancer Cells to Elicit Anti-Cancer Activity.

Dihydrofolate reductase (DHFR) is an established anti-cancer drug target whose inhibition disrupts folate metabolism and STAT3-dependent gene expression. Cycloguanil was proposed as a DHFR inhibitor in the 1950s and is the active metabolite of clinically approved DHFR inhibitor Proguanil. The Cycloguanil scaffold was explored to generate potential cancer therapies in the 1970s.

Dependence of the contact line roughness exponent on the contact angle on substrates with dilute mesa defects: numerical study.

We compute the roughness exponent of the averaged contact line width of a liquid on heterogeneous substrates with randomly distributed dilute defects in statics. We study the case of circular "mesa"-type defects placed on homogeneous base. The shape of the liquid meniscus and the contact line are obtained numerically, using the full capillary model when a vertical solid plate, partially dipped in a tank of liquid, is slowly withdrawing from the liquid.

STAT Protein Thermal Shift Assays to Monitor Protein-Inhibitor Interactions.

STAT3 protein is a sought-after drug target as it plays a key role in the progression of cancer. Many STAT3 inhibitors (STAT3i) have been reported, but accumulating evidence suggests many of these act as off-target/indirect inhibitors of STAT signaling. Herein, we describe the STAT protein thermal shift assay (PTSA) as a novel target engagement tool, which we used to test the binding of known STAT3i to STAT3 and STAT1.

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells.

Inversion of force lines in fiber-reinforced jammed granular material.

Freestanding columns, built out of nothing but loose gravel and continuous strings can be stable even at several meters in height and withstand vertical loads high enough to severely fragment grains of the column core. We explain this counter-intuitive behavior through dynamic simulations with polyhedral rigid particles and elastic wire chains. We evaluate the fine structure of the particle contact networks, as well as confining forces and reveal fundamental intrinsic differences to the well-studied case of confining silos.

Clinical Case of Life-threatening Co-infection Due to and in a Cat: First Report of Feline Heartworm Disease in Bulgaria.

The present report describes the first clinically manifested and serologically proven case of infection in a cat in Bulgaria. A 10-year-old intact male cat was referred to the Small Animal Clinic, Trakia University with a history of anorexia, weight loss, intermittent coughing and itching skin lesions on the head and neck. Physical examination revealed abnormal heart sounds and respiration, cyanosis of the mucous membranes, and generalized enlargement of the lymph nodes.

Depinning regimes and contact angle hysteresis of a drop on doubly periodic microtextured surfaces.

We investigate numerically the drop shape evolution under quasistatic drop volume change on doubly periodic microtextured surfaces in the framework of the capillary model. Taking into account the symmetries of the periodic lattice of defects, we study the drop contact line (CL) motion along all lines of symmetry, allowing us to get a more complete view of the CL behavior. Four CL depinning regimes for a liquid drop are distinguished related to the stick, slip, and jump motion of the CL.

Preliminary Study on the Prevalence of Endoparasite Infections and Vector-borne Diseases in Outdoor Dogs in Bulgaria.

The present work was designed to evaluate the prevalence of gastrointestinal parasites and some vector-borne pathogens in dogs in Bulgaria. A total of 172 owned dogs, keeping outside, were included in the study. Fecal samples were examined using standard flotation and sedimentation methods.

Evolution of fragment size distributions from the crushing of granular materials.

We study fragment size distributions after crushing single and many particles under uniaxial compression inside a cylindrical container by means of numerical simulations. Under the assumption that breaking goes through the bulk of the particle we obtain the size distributions of fragments for both cases after large displacements. For the single-particle crushing, this fragmentation mechanism produces a log-normal size distribution, which deviates from the power-law distribution of fragment sizes for the packed bed.

A randomized, blinded, controlled, multi-centered field study assessing the treatment of gastrointestinal nematode infections in cats with fluralaner plus moxidectin spot-on solution (Bravecto® Plus).

Background: A spot-on formulation containing fluralaner (280 mg/ml) plus moxidectin (14 mg/ml) (Bravecto® Plus) was developed for the treatment of nematode infections as well as providing 12 weeks of protection against insect and acarine parasites in cats. The effectiveness and safety of this product against feline gastrointestinal nematodes was assessed in naturally-infested, client-owned cats under field conditions in Albania, Bulgaria, Germany and Hungary.

Methods: To be eligible for enrollment in this investigator-blinded study cats had to be at least 10 weeks-old, weigh at least 1.

Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation.

The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because -deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice.

Contact angle hysteresis on doubly periodic smooth rough surfaces in Wenzel's regime: The role of the contact line depinning mechanism.

We report here on the contact angle hysteresis, appearing when a liquid meniscus is in contact with doubly sinusoidal wavelike patterned surfaces in Wenzel's wetting regime. Using the full capillary model we obtain numerically the contact angle hysteresis as a function of the surface roughness factor and the equilibrium contact angle for a block case and a kink case contact line depinning mechanism. We find that the dependencies of the contact angle hysteresis on the surface roughness factor are different for the different contact line depinning mechanisms.

A comparison of the hourly output between the Ambu® Smart-Infuser™ Pain Pump and the On-Q Pump® with Select-A-Flow™ Variable Rate Controller with standard and overfill volumes.

Background: The Ambu Smart-Infuser Pain Pump and the On-Q Pump with Select-a-Flow Variable Rate Controller are elastomeric devices with a flow regulator that controls the rate of infusion of a local anesthetic agent through a peripheral catheter. As a safety evaluation, we evaluated the infusion characteristics of these two devices when filled with manufacturer recommended standard volumes and when overfilled with a volume 50% in excess of that which is recommended.

Methods: Nineteen disposable devices from the two manufacturers were used in this study.

Continuous chloroprocaine infusion for thoracic and caudal epidurals as a postoperative analgesia modality in neonates, infants, and children.

Background: Neonates and infants have decreased metabolic capacity for amide local anesthetics and increased risk of local anesthetic toxicity compared to the general population. Chloroprocaine is an ester local anesthetic that has an extremely short plasma half-life in infants as well as adults. Existing reports support the safety and efficacy of continuous chloroprocaine epidural infusions in neonates and young infants during the intraoperative period.

Nanoparticles formed from PNIPAM-g-PEO copolymers in the presence of indomethacin.

Biocompatible double-hydrophilic PNIPAM-g-PEO copolymers containing 0.3-3.2 mol% PEO grafts were synthesized and utilized to prepare indomethacin (IMC)-loaded core-shell nanoparticles by dialysis and nanoprecipitation methods.

Phospholipids as implant coatings.

Bio-interfaces such as bio-membranes are of outmost importance for a variety of live processes. Among them are cell-interactions which take place in, on or through cell membranes. Therefore we propose to cover metallic surfaces with phospholipids to facilitate cell-material interaction.