Confocal Laser Scanning Microscopic Visualization of the Transport of Dextrans After Nasal Administration to Rats: Effects of Absorption Enhancers

Purpose. To visualize the transport pathway(s) of high molecular weight model compounds across rat nasal epithelium in vivousing confocal laser scanning microscopy. Furthermore, the influence of nasal absorption enhancers (randomly methylated -cyclodextrin and sodium taurodihydrofusidate) on this transport was studied. Methods. Fluorescein isothiocyanate (FITC)-labelled dextrans with a molecular weight of 3,000 or 10,000 Da were administered intranasally to rats. Fifteen minutes after administration the tissue was fixed with Bouin. The nasal septum was surgically removed and stained with Evans Blue protein stain or DiIC18(5) lipid stain prior to visualization with the confocal laser scanning microscope. Results. Transport of FITC-dextran 3,000 across nasal epithelium occurred via the paracellular pathway. Endocytosis of FITC-dextran 3,000 was also shown. In the presence of randomly methylated -cyclodextrin 2% (w/v) similar transport pathways for FITC-dextran 3,000 were observed. With sodium taurodihydrofusidate 1% (w/v) the transport route was also paracellular with endocytosis, but cells were swollen and mucus was extruded into the nasal cavity. For FITC-dextran 10,000 hardly any transport was observed without enhancer, or after co-administration with randomly methylated -cyclodextrin 2% (w/v). Co-administration with sodium taurodihydrofusidate 1% (w/v) resulted in paracellular transport of FITC-dextran 10,000, but morphological changes, i.e. swelling of cells and mucus extrusion, were observed. Conclusions. Confocal laser scanning microscopy is a suitable approach to visualize the transport pathways of high molecular weight hydrophilic compounds across nasal epithelium, and to study the effects of absorption enhancers on drug transport and cell morphology.     

Association of exceptional parental longevity and physical function in aging

Offspring of parents with exceptional longevity (OPEL), who are more likely to carry longevity-associated genotypes, may age more successfully than offspring of parents with usual survival (OPUS). Maintenance of physical function is a key attribute of successful aging. While many genetic and non-genetic factors interact to determine physical phenotype in aging, examination of the contribution of exceptional parental longevity to physical function in aging is limited. The LonGenity study recruited a relatively genetically homogenous cohort of Ashkenazi Jewish (AJ) adults age 65 and older, who were defined as either OPEL (having at least one parent who lived to age 95 or older) or OPUS (neither parent survived to age 95). Subjective and objective measures of physical function were compared between the two groups, accounting for potential confounders. Of the 893 LonGenity subjects, 365 were OPEL and 528 were OPUS. OPEL had better objective and subjective measures of physical function than OPUS, especially on unipedal stance (p = 0.009) and gait speed (p = 0.002). Results support the protective role of exceptional parental longevity in preventing decline in physical function, possibly via genetic mechanisms that should be further explored.     

The Effect of Pain on Major Cognitive Impairment in Older Adults

Older adults frequently report pain; cross-sectional studies have shown that pain is associated with worse cognitive function. However, longitudinal studies are lacking. We prospectively studied 441 participants without dementia, including 285 with pain, aged 65 years and older, enrolled in the Central Control of Mobility in Aging study, a prospective cohort study. We analyzed the longitudinal association between pain (measured with the Medical Outcomes Study pain severity scale) and major cognitive impairment (measured with the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test Delta) using Cox regression analysis adjusted for age, gender, ethnicity, and education. Over a mean follow-up of 2.75 years (standard deviation?=?1.94), there was no difference in the risk of developing cognitive impairment between participants with pain and participants without pain. However, among those with pain, risk for developing major memory impairment was higher among those with high levels of pain than those with low levels of pain (adjusted hazard ratio?=?3.47, 95% confidence interval?=?1.42–8.46). The association with pain and incident impairments in attention or executive function was not significant. We did not find that pain is associated with incident cognitive impairment in general, but among older adults with pain, a high level of pain is associated with increased risk of developing incident memory impairment.

Mental Health Service Users’ Perceptions of Stigma,From the General Population and From Mental Health Professionals in Mexico: A Qualitative Study

Community Mental Health Journal - Negative attitudes towards people with mental health disorders have been widely studied and identified in the general population, and even within health care...     

Development and evaluation of a simulator-based laparoscopic training program for surgical novices

Background

The use of simulation to train novice surgeons in laparoscopic skills is becoming increasingly popular. To maximize benefit from simulation, training needs to be delivered and assessed in a structured manner. This study aimed to define performance goals, demonstrate construct validity of the training program, and evaluate whether novice surgeons could reach the preset performance goals.

Methods

Nine expert laparoscopic surgeons established performance goals for three basic modules of an augmented-reality laparoscopic simulator. The three laparoscopic modules were used by 40 novice surgeons and 40 surgical trainees (postgraduate years [PGYs] 1–4). The performance outcomes were analyzed across the different groups (novice, PGYs 1 and 2, PGYs 3 and 4, expert) to determine construct validity. Then 26 recruited novices trained on the three modules with the aim of reaching the performance goals.

Results

The results demonstrated a significant difference in performance between all levels of experience for time (p < 0.001), motion analysis (p < 0.001), and error score (p < 0.001), thus demonstrating construct validity. All 26 novice surgeons significantly improved in performance with repetition for the metrics of time (p < 0.001) and motion analysis (p < 0.001). For two of the modules, the proficiency goals were reached in fewer than 10 trials by 80 % of the study participants.

Conclusion

Basic skills in laparoscopic surgery can be learned and improved using proficiency-based simulation training. It is possible for novice surgeons to achieve predefined performance goals in a reasonable time frame.     

Trajectories of Substance Use among Child Welfare-Involved Youth: Longitudinal Associations with Child Maltreatment History and Emotional/Behavior Problems

Background: Maltreated children experience a variety of adverse outcomes including substance use problems. Although previous research indicated that there may be distinct trajectories of substance use among these youth, studies have examined them as if they were a single homogeneous group. Objectives: The goals of this study were to explore substance use trajectories among child welfare-involved youth and to identify characteristics that distinguish substance use trajectories. Methods: Data from the National Survey of Child and Adolescent Well-Being (NSCAW II) were used. Multilevel latent growth mixture modeling (MLGMM) was performed using a subsample of 625 youth from ages 11–17 years investigated for maltreatment in 2008–2009. Measures included self-reported use of substance use during the previous 30 days, demographic characteristics, maltreatment history, placement in out-of-home care, and behavioral health problems. Results: MLGMM identified two distinct substance use trajectory classes including High Stable Substance Use and Rapid Progression Use. Findings suggest that the experience of physical abuse is the key factor that distinguishes the two groups. When the effects of class-specific covariates were examined, results suggest that involvement in substance use behavior and its escalation vary between groups and are affected by youth’s different previous experiences. Conclusions/Importance: The results have important implications for understanding individual differences in substance use behavior over time and how these differences were shaped by youth’s experiences of family adversity. Study findings may be helpful for developing and enhancing the effectiveness of interventions targeted at decreasing substance use behaviors in child welfare-involved youth.     

Rectal cancer surgery: volume–outcome analysis

Purpose  

There is strong evidence supporting the importance of the volume–outcome relationship with respect to lung and pancreatic cancers. This relationship for rectal cancer surgery however remains unclear. We review the currently available literature to assess the evidence base for volume outcome in relation to rectal cancer surgery.     

Posterior urethral valves causing urinomas: Two case reports

The cases of two male babies with posterior urethral valves complicated by the formation of urinomas are reported. Early diagnosis and treatment of this condition is important, as morbidity and mortality from resultant renal failure can be significant if it is unrecognized.     

An open-label trial of quetiapine for antipsychotic-induced sexual dysfunction

This study evaluated the effect of switching outpatients with schizophrenia and antipsychotic-induced sexual dysfunction to open-label quetiapine treatment. Secondary objectives were to compare the antipsychotic and prolactin-related effects of quetiapine versus prestudy antipsychotic treatment. Eight patients with at least moderately severe antipsychotic-induced sexual dysfunction (N = 7 taking risperidone, 4-6 mg/d; N = 1 taking haloperidol, 10 mg/d) were evaluated prospectively after they switched to 6 weeks of quetiapine treatment. The assessments that we used included evaluations of sexual functioning (Arizona Sexual Experience Scale [ASEX]; McGahuey et al., 2000), psychopathology (Positive and Negative Syndrome Scale [PANSS]; Kay, Fiszbeinm, & Opler, 1997), adverse events, and plasma prolactin levels. Quetiapine was associated with clinically and statistically significant improvement in ASEX total scores (p = 0.008) and significantly decreased PANSS total scores (p = 0.03). Plasma prolactin levels tended to decrease after the transition to quetiapine (p = 0.09). Quetiapine appears to offer an option to reduce antipsychotic-induced sexual dysfunction for outpatients with schizophrenia.