Therapeutic Ultrasound for Enhanced Corneal Permeability to Macromolecules.

OBJECTIVES: Topically applied macromolecules have the potential to provide vision-saving treatments for many of the leading causes of blindness in the United States. The aim of this study was to determine if ultrasound can be applied to increase transcorneal drug delivery of macromolecules without dangerously overheating surrounding ocular tissues. METHODS: Dissected corneas of adult rabbits were placed in a diffusion cell between a donor compartment filled with a solution of macromolecules (40, 70 kDa, or 150 kDa) and a receiver compartment. Each cornea was exposed to the drug solution for 60 minutes, with the experimental group receiving 5 minutes of continuous ultrasound or 10 minutes of pulsed ultrasound at a 50% duty cycle (pulse repetition frequency of 500 ms on, 500 ms off) at the beginning of treatment. Unfocused circular ultrasound transducers were operated at 0.5 to 1 W/cm2 intensity and at 600 kHz frequency. RESULTS: The greatest increase in transcorneal drug delivery seen was 1.2 times (P < .05) with the application of pulsed ultrasound at 0.5 W/cm2 and 600 kHz for 10 minutes with 40 kDa macromolecules. Histological analysis revealed structural damage mostly in the corneal epithelium, with most damage occurring at the epithelial surface. CONCLUSIONS: This study suggests that ultrasound may be used for enhancing transcorneal delivery of macromolecules of lower molecular weights. Further research is needed on the long-term effects of ultrasound parameters used in this study on human ocular tissues.

Ultrasound-Enhanced Transcorneal Drug Delivery for Treatment of Fungal Keratitis.

PURPOSE: Transcorneal drug delivery is hindered by ocular physical and biochemical properties, such as tear production, the epithelial layer of the cornea, and blinking. The aim of this study was to determine whether ultrasound can be applied to increase the transcorneal drug delivery of natamycin used in the treatment of fungal keratitis without dangerously overheating the surrounding ocular tissues. METHODS: To verify the safety of various sets of ultrasound parameters, modeling studies were conducted using OnScale, an ultrasonic wave modeling software. Ultrasound parameters determined optimal for ocular tissue safety were used in a laboratory setting in a jacketed Franz diffusion cell setup. Histological images of the cross-section of the corneas used in experiments were examined for cell damage under a microscope. RESULTS: Increases in transcorneal drug delivery were seen in every treatment parameter combination when compared with the sham treatment. The highest increase was 4.0 times for 5 minutes of pulsed ultrasound at a 25% duty cycle and a frequency of 400 kHz and an intensity of 0.5 W/cm 2 with statistical significance ( P < 0.001). Histological analysis revealed structural damage only in the corneal epithelium, with most damage being at the epithelial surface. CONCLUSIONS: This study suggests that ultrasound is a safe, effective, and minimally invasive treatment method for enhancing the transcorneal drug delivery of natamycin. Further research is needed into the long-term effects of ultrasound parameters used in this study on human ocular tissues.

Assessing Preparedness of Labor and Delivery Personnel in Transferring to a New Unit.

OBJECTIVES: This case study intends to examine how staff characteristics, training methods, and duration of training impact overall staff preparedness and comfortability when transitioning to a new Labor and Delivery. BACKGROUND: A new medical facility offers an opportunity for greater capacity and expanding services, but it also poses new challenges for staff. Success in this transition depends on how quickly the staff can adapt to their new environment and how prepared they are to deliver high-quality care to patients. METHODS: An optional survey was conducted to determine the staff's confidence in their training using a 5-point Likert-type scale. RESULTS: After responses were collected, a paired samples two-sided t test revealed that there was no statistically significant change in the confidence and preparedness for staff. CONCLUSIONS: With this overall outcome, medical facilities will have more discernment on ways to improve their employees' trust and confidence in performing their tasks and providing care while in a new environment. This will then be reflected in the care given toward patients in the future.

Evaluation of Sodium Bisulfate on Reducing Salmonella Heidelberg Biofilm and Colonization in Broiler Crops and Ceca.

Salmonella Heidelberg (SH) on contaminated poultry causes economic and health risks to producers and consumers. We hypothesized that sodium bisulfate (SBS) would decrease SH biofilm on polyvinyl chloride (PVC) coupons and decrease the horizontal transfer of SH in broilers. Experiment 1: Salmonella Heidelberg biofilm was cultured with PVC coupons, which were treated with SBS at a pH of 3.5 for 10 min, 8 h, and 24 h. Experiment 2: Nine replicate pens per treatment were divided between two rooms. A seeder contact model was used to mimic a natural infection environment. Treatments consisted of tap water or sodium bisulfate in water at a pH of 3.5. Salmonella Heidelberg incidence and enumeration were measured in crops and ceca. Sodium bisulfate significantly reduced biofilm by 2.16 and 1.04 logs when treated for 8 and 24 h, respectively. Crop colonization was significantly decreased in trials 1 and 2 by 0.29 and 0.23 logs, respectively. Crop pH was significantly decreased in trial 2. Ceca colonization was significantly decreased in trial 1 by 0.39 logs. The results from the present study suggest that SBS may be administered to drinking water to decrease SH gut colonization and to reduce biofilm.

A Novel UHPLC-MS/MS Method for Measuring 8-iso-Prostaglandin F2α in Bronchoalveolar Lavage Fluid.

In August 2019, the Centers for Disease Control and Prevention (CDC) received the first reports of lung injuries that were eventually termed e-cigarette, or vaping, product use-associated lung injury (EVALI). As part of the investigation, CDC laboratories rapidly developed assays for analyzing substances in bronchoalveolar lavage (BAL) fluid collected from EVALI case patients. This report describes the development and validation of a high-throughput isotope dilution UHPLC-MS/MS method for measuring a major oxidative stress biomarker, 8-iso-prostaglandin F2α (8-isoprostane), in BAL fluid samples. The method showed good sensitivity, 17.6 pg/ml LOD, and requires only 50 µl of sample volume. The method had high throughput with an analytical run time of 11 min. The within-day and between-day coefficient of variation (CV) were below 2%. Accuracy, calculated from spiked recovery, at three spiking levels, ranged from 95.5-101.8%. This novel UHPLC-MS/MS method characterizes oxidative stress in lung epithelial tissue and thus helps to elucidate potential pathologic processes.

Racial differences in the risk of second primary bladder cancer following radiation therapy among localized prostate cancer patients.

OBJECTIVES: To investigate the race-specific second primary bladder cancer (SPBC) risk following prostatic irradiation. METHODS: Louisiana residents who were diagnosed with localized prostate cancer (PCa) in 1996-2013 and received surgery or radiation were included. Patients were followed until SPBC diagnosis, death, or Dec. 2018. The exposure variable was type of treatment (radiation only vs. surgery only). The outcome was time from PCa diagnosis to SPBC diagnosis, stratified by race. Fine and Gray's competing risk model was applied with death as a competing event and adjustment of sociodemographic and tumor characteristics. We used 5 years and 10 years as lag time in the analyses. RESULTS: A total of 26,277 PCa patients with a median follow-up of 10.7 years were analyzed, including 18,598 white and 7679 black patients. About 42.9 % of whites and 45.7 % of blacks received radiation. SPBC counted for 1.84 % in the radiation group and 0.90 % in the surgery group among white patients and for 0.91 % and 0.58 %, respectively, among black patients. The adjusted subdistribution hazard ratio of SPBC was 1.80 (95 % CI: 1.30-2.48) for radiation recipients compared to surgery recipients among white patients; 1.93 (95 % CI: 1.36-2.74) if restricted to external beam radiation therapy (EBRT). The SPBC risk was not significantly different between irradiated and surgically treated among blacks. CONCLUSIONS: The SPBC risk is almost two-fold among white irradiated PCa patients compared to their counterparts treated surgically. Our findings highlight the need for enhanced surveillance for white PCa survivors receiving radiotherapy, especially those received EBRT.

The impact of an autonomy-supportive yoga intervention on self-determination in adults with intellectual and developmental disabilities.

The aim of this study was to examine the impact of an autonomy-supportive yoga intervention on the self-determination of adults with intellectual and developmental disabilities. Research supports the use of autonomy-supportive interventions to increase positive health outcomes with this population. The present study utilized a qualitative approach with eight subjects participating in semi-structured qualitative interviews. Content analysis identified support for three themes related to the impact of yoga: autonomy, relatedness, competence. The results suggested that the yoga intervention may support self-determination for adults with IDD, as the participants' responses demonstrated increased feelings of autonomy, competence, and relatedness. The results also indicated that an autonomy-supportive yoga intervention can be achieved with adults with intellectual and developmental disabilities by targeting the key constructs of autonomy, relatedness, and competence.

Yoga for Functional Fitness in Adults with Intellectual and Developmental Disabilities.

BACKGROUND: Yoga is an effective intervention to improve functional fitness in adults with and without disabilities, but little research exists regarding yoga's impact on functional fitness for individuals with intellectual and developmental disabilities (IDDs). AIMS: The purpose of this study was to examine the benefits of a group yoga intervention on the functional fitness of adults with IDDs. METHODS AND MATERIALS: This yoga intervention included 12 sessions of yoga over 7 weeks (60-min sessions twice a week) at a special population recreation and leisure program. The functional fitness test was used to examine physical functioning before and after the yoga intervention. RESULTS AND CONCLUSIONS: Eight adults completed the baseline and posttest measures (age mean = 31; standard deviation = 6.55; 50% male). There were significant improvements in lower-body strength (9.00 ± 4.63 vs. 11.50 ± 3.16, P = 0.04, 28% improvement), upper-body strength (11.25 ± 3.54 vs. 14.25 ± 3.37, P = 0.018, 27% improvement), and agility and balance (9.29 ± 4.1 vs. 6.60 ± 1.54, P = 0.036, 29% improvement). Functional fitness often declines for people with IDD at a faster rate than the general population; thus, these significant changes indicate that a yoga intervention may enhance functional fitness for people with IDD. Clinicians or other healthcare providers might consider yoga as a means to improve functional fitness in adults with IDDs.

Subtype-selective nicotinic acetylcholine receptor agonists can improve cognitive flexibility in an attentional set shifting task.

Nicotinic acetylcholine receptors (nAChRs) are considered to be viable targets to enhance cognition in patients diagnosed with schizophrenia. Activation of nAChRs with selective nicotinic receptor agonists may provide effective means to pharmacologically treat cognitive deficits observed in schizophrenia. Cognitive flexibility is one aspect of cognition, which can be assessed in a rodent model of the attentional set-shifting task (ASST). The aim of the present study was two-fold, firstly, to evaluate the efficacy of a series of subtype selective nAChR agonists, such as those that target α7 and α4ß2 nAChR subtypes in non-compromised rodents. Secondly, nicotine as a prototypic agonist was evaluated for its effects to restore attentional deficits produced by sub-chronic ketamine exposure in the ASST. Male hooded Lister rats underwent habituation, consisting of a simple odour and medium discrimination with subsequent assessment 24 h later. In experimentally naïve rats, α7 subtype selective agonists, compound-A and SSR180711 along with PNU-120596, an α7 positive allosteric modulator (PAM), were compared against the ß2* selective agonist, 5IA-85380. All compounds except for PNU-120596 were observed to significantly improve extra-dimensional (ED) shift performance, nicotine, 5IA-85380 and SSR180711 further enhanced the final reversal (REV3) stage of the task. In another experiment, sub-chronic ketamine treatment produced robust deficits during the ED and the REV3 stages of the discriminations; rodents required significantly more trials to reach criterion during these discriminations. These deficits were attenuated in rodents treated acutely with nicotine (0.1 mg/kg SC) 10 min prior to the ED shift. These results highlight the potential utility of targeting nAChRs to enhance cognitive flexibility, particularly the α7 and ß2* receptor subtypes. The improvement with nicotine was much greater in rodents that were impaired following the sub-chronic ketamine exposure suggesting a greater therapeutic opportunity to target nicotinic receptors for patients diagnosed with schizophrenia.

Nicotine improves performance in an attentional set shifting task in rats.

A large number of studies in both humans and experimental animals have demonstrated nicotine-induced improvements in various aspects of cognitive function, including attention and memory. The prefrontal cortex (PFC) is thought to be critically involved in the modulation of executive function and these attentional processes are enhanced by nicotine acting at nicotinic acetylcholine receptors. The involvement of nicotinic processes on cognitive flexibility in particular has not been specifically investigated. The effects of nicotine on attentional flexibility were therefore evaluated using the rodent attentional set shifting task in rats. Nicotine injected both acutely and following repeated pre-exposure significantly improved both intradimensional and extradimensional set shifting performance in the task. Further investigation of the acute effects of nicotine demonstrated this improvement in attentional flexibility to be dose-dependent. These results implicate the nicotinic receptor system in the mediation of processes underlying cognitive flexibility and suggest that nicotine improves attentional flexibility in rats, both within and between perceptual dimensions of a compound stimulus. Nicotine-induced alterations in prefrontal circuitry may underlie these effects on cognitive flexibility. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Subtype-selective nicotinic agonists enhance olfactory working memory in normal rats: a novel use of the odour span task.

Nicotinic agonists have been shown to enhance performance in cognitive tasks based on attention and memory. The aim of this study was to use a test of olfactory working memory; the odour span task (OST) in rodents, to investigate the effects of subtype-specific nicotinic agonists on working memory in normal rats. Rats were trained in a non-matching to sample (NMTS) rule and then the full OST, which involved identifying a novel odour from an increasing number of presented odours. Male hooded Lister rats were treated with nicotine, selective nicotinic agonists or vehicle (saline). In order to validate the task, muscarinic and nicotinic receptor antagonists were also examined. Nicotine at both 0.05 and 0.1mg/kg significantly increased mean span length in the OST. The selective alpha 4 beta 2 nicotinic receptor agonist metanicotine (0.1mg/kg s.c.) and the selective alpha 7 nicotinic receptor agonist (R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide) (compound A, 10mg/kg i.p.) also improved performance. In contrast, mecamylamine and scopolamine significantly decreased mean span length. These findings suggest a role for the activation of both alpha 4 beta 2 and alpha 7 subtypes of neuronal nicotinic receptor in mediating enhancements of olfactory working memory capacity in normal, non-compromised rats. These nicotinic receptor subtypes may therefore prove to be useful targets for the development of novel treatments for neuropsychiatric disorders that involve cognitive dysfunction.

Cannabinoids and prefrontal cortical function: insights from preclinical studies.

Marijuana use has been associated with disordered cognition across several domains influenced by the prefrontal cortex (PFC). Here, we review the contribution of preclinical research to understanding the effects of cannabinoids on cognitive ability, and the mechanisms by which cannabinoids may affect the neurochemical processes in the PFC that are associated with these impairments. In rodents, acute administration of cannabinoid agonists produces deficits in working memory, attentional function and reversal learning. These effects appear to be largely dependent on CB1 cannabinoid receptor activation. Preclinical studies also indicate that the endogenous cannabinoid system may tonically regulate some mnemonic processes. Effects of cannabinoids on cognition may be mediated via interaction with neurochemical processes in the PFC and hippocampus. In the PFC, cannabinoids may alter dopaminergic, cholinergic and serotonergic transmission. These mechanisms may underlie cognitive impairments observed following marijuana intake in humans, and may also be relevant to other disorders of cognition. Preclinical research will further enhance our understanding of the interactions between the cannabinoid system and cognitive functioning.

Differential effects of two chronic diazepam treatment regimes on withdrawal anxiety and AMPA receptor characteristics.

Withdrawal from chronic benzodiazepines is associated with increased anxiety and seizure susceptibility. Neuroadaptive changes in neural activity occur in limbo-cortical structures although changes at the level of the GABA(A) receptor do not provide an adequate explanation for these functional changes. We have employed two diazepam treatment regimes known to produce differing effects on withdrawal aversion in the rat and examined whether withdrawal-induced anxiety was accompanied by changes in AMPA receptor characteristics. Rats were given 28 days treatment with diazepam by the intraperitoneal (i.p.) route (5 mg/kg) and the subcutaneous (s.c.) route (15 mg/kg). Withdrawal anxiety in the elevated plus maze was evident in the group withdrawn from chronic s.c. diazepam (relatively more stable plasma levels) but not from the chronic i.p. group (fluctuating daily plasma levels). In the brains of these rats, withdrawal anxiety was accompanied by increased [3H]Ro48 8587 binding in the hippocampus and thalamus, and decreased GluR1 and GluR2 subunit mRNA expression in the amygdala (GluR1 and GluR2) and cortex (GluR1). The pattern of changes was different in the chronic i.p. group where in contrast to the chronic s.c. group, there was reduced [3H]Ro48 8587 binding in the hippocampus and no alterations in GluR1 and GluR2 subunit expression in the amygdala. While both groups showed reduced GluR1 mRNA subunit expression in the cortex overall, only the agranular insular cortex exhibited marked reductions following chronic i.p. diazepam. Striatal GluR2 mRNA expression was increased in the i.p. group but not the s.c. group. Taken together, these data are consistent with differential neuroadaptive processes in AMPA receptor plasticity being important in withdrawal from chronic benzodiazepines. Moreover, these processes may differ both at a regional and receptor function level according to the behavioral manifestations of withdrawal.