Background Prenatal alcohol exposure (PAE) enhances the risk for alcoholism by increasing the propensity to consume alcohol and altering neurophysiological response to alcohol challenge. Transgenerationally transmittable genetic alterations have been implicated in these behavioral changes. To date, transgenerational transmission of PAE-induced behavioral responses to alcohol has never been experimentally investigated. Therefore, we explored the transgenerational transmission of PAE-induced behavioral effects across 3 generations. Methods Pregnant Sprague Dawley dams received 1 g/kg ethanol (EtOH) or water daily on gestational days 17 through 20 via gavage, or remained untreated in their home cages. To produce second filial (F2) or F3 generations, similarly treated adult F1 or F2 offspring were mated and left undisturbed through gestation. On postnatal day (PND) 14, male and female F1, F2, and F3 offspring were tested for consumption of 5% (w/v) EtOH (in water), or water. Using the loss of righting reflex (LORR) paradigm on PND 42, F1 and F2 adolescent male offspring were tested for sensitivity to acute EtOH-induced sedation–hypnosis at 3.5 or 4.5 g/kg dose. F3 male adolescents were similarly tested at 3.5 g/kg dose. Blood EtOH concentration (BEC) was measured at waking. Results EtOH exposure increased EtOH consumption compared to both water and untreated control groups in all generations. EtOH-treated group F1 and F2 adolescents displayed attenuated LORR duration compared to the water group. No attenuated LORR was observed in the F3 generation. BEC at waking corroborated with the significant LORR duration differences while also revealing differences between untreated control and water groups in F1 and F2 generations. Conclusions Our results provide novel behavioral evidence attesting that late gestational moderate EtOH exposure increases EtOH intake across 3 generations and may alter sensitivity to EtOH-induced sedation–hypnosis across 2 generations.

Chronic oral methylphenidate (MP) exposure in rats is associated with numerous developmental and behavioral consequences. The present study investigated the persistence of the effects of chronic oral MP exposure after abstinence from MP use. Male and female rats were exposed to daily orally self-administered water, low dose MP (LD), or high dose (HD) MP for 13 weeks, followed by a 4-week abstinence period. Fluid, food consumption and bodyweights were monitored and animals were tested for locomotor activity, anxiety- and depressive-like symptoms, learning and memory, and social behavior during both the treatment and abstinence phases of the experiment. During treatment, MP attenuated bodyweight regardless of sex, but increased food and fluid consumption in females and males by 20.7% and 30.1%, respectively. MP also increased locomotor activity in both males and females observed as increased distance travelled in an open field. (59.1% and 95.9%, respectively) and increased locomotor activity in the home cage over a 24-hour circadian cycle (45.5% and 63.0%). Additionally, MP exerted an anxiolytic effect observed as increased time spent in the open arms of an elevated plus maze (31.1% in HD males, 59.2% in HD females), and an increased latency to immobility in a forced swim test (330% in HD males, 418% in HD females). The effects of MP (bodyweight, consumption, locomotion, anxiolytic, and anti-depressive) were, almost without exception, eliminated during the abstinence period. MP had no impact on learning and memory performance as measured by a T-maze, or social behavior during treatment. These findings suggest that the behavioral consequences of chronic oral MP treatment in our preclinical model are reversible in rats following an abstinence period from use of the drug.

Methylphenidate (MP) is a commonly prescribed psychostimulant for Attention Deficit Hyperactivity Disorder (ADHD). We recently reported behavioral and developmental effects of chronic MP use in healthy rats. The current study investigated how interrupting chronic MP treatment with weekend abstinence altered the behavioral and physiological consequences of chronic MP treatment, and if prolonged abstinence would reverse the observed effects. Male Sprague Dawley rats were assigned to one of three treatment groups: water (W); low dose (LD) MP; and high dose (HD) MP. For 13 weeks, rats had access to drink from a bottle containing 4 mg/kg MP (LD), 30 mg/kg MP (HD) or water (W) for 1 hour, and 10 mg/kg MP (LD), 60 mg/kg MP (HD) or water (W) for the next 7 hours, each week day. During weekends, all animals received only water as well as throughout the 5-week-long abstinence phase, which immediately followed the treatment phase. Throughout the treatment phase, regardless of weekend abstinence, chronic MP resulted in significant decreased food and fluid intake and body weight. Also, HD MP exposure resulted in the following behavioral effects: increased open field and circadian locomotor activity; increased latency to immobility and decreased time spent immobile in the forced swim test; increased center activity in the open field and percent of time spent in an open arm of the elevated-plus-maze; and increased social affiliation and memory in the Crawley’s three chamber sociability test. During the prolonged (5-week) abstinence phase, all these effects were reversed while HD treated rats increased their fluid intake. These results indicated that intermittent brief abstinence periods (weekend’s off-treatment) produced the same behavioral and developmental effects as those previously reported with chronic (7 days/week) MP treatment, but were reversible following a prolonged abstinence period (5 weeks).

Gestational alcohol use is well documented as detrimental to both maternal and fetal health, producing increased offspring’s tendency for alcoholism, as well as behavioral and neuropsychological disorders. In both rodents and in humans, parental care can influence the development of offspring physiology and behavior. Animal studies that have investigated gestational alcohol use on parental care and/or their interaction mostly employ heavy alcohol use and single strains. This study aimed at investigating the effects of low gestational ethanol dose on parental behavior and its transgenerational transmission, with comparison between two rat strains. Pregnant Sprague Dawley (SD) and Long Evans (LE) progenitor dams (F0) received 1g/kg ethanol or water through gestational days 17– 20 via gavage, or remained untreated in their home cages. At maturity, F1 female offspring were mated with same strain and treatment males and were left undisturbed through gestation. Maternal behavior was scored in both generations during the first six postnatal days. Arched-back nursing (ABN) was categorized as: 1, when the dam demonstrated minimal kyphosis; 2, when the dam demonstrated moderate kyphosis; and 3, when the dam displayed maximal kyphosis. Overall, SD showed greater amounts of ABN than LE dams and spend more time in contact with their pups. In the F0 generation, water and ethanol gavage increased ABN1 and contact with pups in SD, behaviors which decreased in treated LE. For ABN2, ethanol-treated SD dams showed more ABN2 than water-treated dams, with no effect of treatment on LE animals. In the F1 generation, prenatal exposure affected retrieval. Transgenerational transmission of LG was observed only in the untreated LE group. Strain-specific differences in maternal behavior were also observed. This study provides evidence that gestational gavage can influence maternal behavior in a strain-specific manner. Our results also suggest that the experimental procedure during gestation and genetic variations between strains may play an important role in the behavioral effects of prenatal manipulations.

BackgroundFew studies have explored the association between stroke thrombectomy (ST) volume and hospital accreditation with clinical outcomes.ObjectiveTo assess the association of ST case volume and accreditation status with in-hospital mortality and home discharge disposition using the national Medicare Provider Analysis and Review (MEDPAR) database.MethodsRates of hospital mortality, home discharge disposition, and hospital stay were compared between accredited and non-accredited hospitals using 2017–2018 MEDPAR data. The association of annual ST case volume with mortality and home disposition was determined using Pearson’s correlation. Median rate of mortality and number of ST cases at hospitals within the central quartiles were estimated.ResultsA total of 29 355 cases were performed over 2 years at 847 US centers. Of these, 354 were accredited. There were no significant differences between accredited and non-accredited centers for hospital mortality (14.8% vs 14.5%, p=0.34) and home discharge (12.1% vs 12.0%, p=0.78). A significant positive correlation was observed between thrombectomy volume and home discharge (r=0.88; 95% CI 0.58 to 0.97, p=0.001). A significant negative relationship was found between thrombectomy volume and mortality (r=−0.86; 95% CI −0.97 to −0.49, p=0.002). Within the central quartiles, the median number of ST cases at hospitals with mortality was 24/year, and the median number of ST cases at hospitals with home discharge rate was 23/year.ConclusionA higher volume of ST cases was associated with lower mortality and higher home discharge rate. No significant differences in mortality and discharge disposition were found between accredited and non-accredited hospitals.

Methylphenidate (MP) is a commonly prescribed psychostimulant to individuals with Attention Deficit Hyperactivity Disorder, and is often used illicitly among healthy individuals with intermittent breaks to coincide with breaks from school. This study examined how intermittent abstinence periods impact the physiological and behavioral effects of chronic oral MP self‐administration in rats, and whether these effects persist following prolonged abstinence from the drug. Rats were treated orally with water, low‐dose (LD), or high‐dose (HD) MP, beginning at PND 28. This daily access continued for three consecutive weeks followed by a 1‐week abstinence; after three repeats of this cycle, there was a 5‐week abstinence period. Throughout the study, we examined body weight, food intake, locomotor activity, and anxiety‐ and depressive‐like behaviors. During the treatment phase, HD MP decreased body weight, food intake, and depressive‐ and anxiety‐like behaviors, while it increased locomotor activity. During intermittent abstinence, the effects of MP on locomotor activity were eliminated. During prolonged abstinence, most of the effects of HD MP were ameliorated to control levels, with the exception of weight loss and anxiolytic effects. These findings suggest that intermittent exposure to chronic MP causes physiological and behavioral effects that are mostly reversible following prolonged abstinence.

Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanism. This study investigated the intergenerational consequences of prenatal exposure to low ethanol dose (1g/kg) during gestational days 17–20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long Evans and Sprague Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at 3.5g/kg or 4.5g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague Dawley rats. Lastly, we investigated PAE related changes in expression of GABAA receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA receptor subunits’ expression in the F1 and F2 PAE groups compared to control animals. GABAA receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE didn’t alter cerebral cortical GABAA receptor subunit expressions in the F1 generation, but it decreased GABAA receptor α4 and δ subunits’ expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring.

BACKGROUND: The use of modern transfemoral balloon guide catheters (BGC) for flow reversal during carotid artery stenting is scarcely described in the literature but represents a promising and efficient technique for embolic protection. OBJECTIVE: To describe a flow-reversal technique using the Walrus BGC (Q'Apel Medical Inc.) and report our center's experience. METHODS: We performed a retrospective analysis of data for consecutive patients aged 18 years or older who underwent elective carotid artery stenting with the use of flow reversal through the Walrus BGC between July 2020 and September 2021. Patient characteristics, procedural details, and clinical follow-up were evaluated. RESULTS: One hundred and five patients were included. Mean age was 69.8 ± 9.4 years, and 36 (34.3%) were women. The most common comorbidities were hyperlipidemia (76.2%) and hypertension (57.1%). Fifty-nine (56.2%) patients were symptomatic. Ninety-nine (94.3%) patients had stenosis ≥70%. Contralateral stenosis ≥50% was present in 44 patients (41.9%). Distal filters were used after flow reversal was established in 90 patients (85.7%). Angioplasty was performed in 85 patients (80.9%). Stenting was successful in 100% of cases. No periprocedural transient ischemic attacks (TIAs) or strokes occurred. Stroke occurred in 2 patients (1.9%) during the 30-day follow-up period, resulting in 1 (0.9%) death. CONCLUSION: In our experience, this technique was safe, feasible, and efficient, with 100% technical success and no periprocedural thromboembolic complications. More extensive studies are needed to establish the role of proximal protection with flow reversal using modern BGCs.