Ultrasonic vocalization of pup and adult fat-tailed gerbils (Pachyuromys duprasi).

Ultrasonic vocalizations (USVs) of laboratory rodents indicate animal emotional arousal and may serve as models of human disorders. We analysed spectrographically USV calls of pup and adult fat-tailed gerbils Pachyuromys duprasi during 420-s tests, including isolation, touch and handling. Based on combination of six different USV syllable contour shapes and six different note compositions, we classified 782 USV syllables of 24 pups aged 5-10 days to 18 types and 232 syllables of 7 adults to 24 types. Pups and adults shared 16 of these 26 USV types. Percentages of USV syllables with certain contour shapes differed between pups and adults. The contour shape and note composition significantly affected most acoustic variables of USV syllables in either pups or adults. The 1-note USV syllables were most common in either pups or adults. Pup USV syllables were overall longer and higher-frequency than adult ones, reminiscent of the USV ontogenetic pathway of bats and distinctive to rats and mice. We discuss that the USV syllable types of fat-tailed gerbils were generally similar in contour shapes and note compositions with USV syllable types of mice and rats, what means that software developed for automated classifying of mice ultrasound might be easily adapted or re-tuned to gerbil USV calls. However, using fat-tailed gerbils as model for biomedical research including control of USV vocalization is only possible since 6th day of pup life, because of the delayed emergence of USV calls in ontogeny of this species

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells

Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention : the RENo study

Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA <sub>2</sub> DS <sub>2</sub> -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA <sub>2</sub> DS <sub>2</sub> -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA <sub>2</sub> DS <sub>2</sub> -VASc score were associated with increased risk of cerebrovascular events