Electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD): A modified study protocol.

OBJECTIVE: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented. METHODS: Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants. RESULTS: Study is ongoing and open to enrollment. CONCLUSION: The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.

Best practices in managing child and adolescent behavioral health emergencies.

Behavioral health emergencies most commonly present as depression, suicidal behavior, aggression, and severe disorganization. Emergency clinicians should avoid relying solely on past medical history or previous psychiatric diagnoses that might prematurely rule out medical pathologies. Treatments for behavioral health emergencies consist of de-escalation interventions aimed at preventing agitation, aggression, and harm. This issue reviews medical pathologies and underlying causes that can result in psychiatric presentations and summarizes evidence-based practices to evaluate, manage, and refer patients with behavioral health emergencies.

Perioperative morbidity associated with bariatric surgery: an academic center experience.

HYPOTHESIS: As the demand for bariatric surgery increases, it becomes increasingly important to define predictors of morbidity and mortality. We hypothesize that specific clinical variables predict postoperative morbidity after bariatric surgery. DESIGN, SETTING, AND PATIENTS: This is a retrospective review of 452 patients undergoing inpatient bariatric surgery at an academic tertiary care institution. INTERVENTIONS: Patients underwent open or laparoscopic gastric bypass or biliopancreatic diversion with duodenal switch at Oregon Health & Science University, Portland, from 2000 to 2003. Patient data were prospectively entered into a database. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality were analyzed among all patients, and logistic regression was used to identify clinical predictors of morbidity. RESULTS: Major and minor morbidity rates were 10% and 13%, respectively; mortality was 0.9%. Age was associated with postoperative complications (odds ratio = 1.056 for each additional year). Duodenal switch was also associated with higher morbidity than gastric bypass (odds ratio = 2.149). Body mass index, sex, diabetes, surgical approach, and surgeon experience did not predict complications. CONCLUSIONS: Increased age is a predictor of complications after bariatric surgery. Duodenal switch is also associated with a higher morbidity rate than gastric bypass. Surgeons should caution older patients (>/=60 years) of a higher risk of postoperative complications, and a higher risk associated with duodenal switch. Large multicenter studies will be necessary to accurately define other clinical predictors of morbidity and mortality after bariatric surgery.

Human epithelial-specific response to pathogenic Campylobacter jejuni.

The gastrointestinal epithelia of mammals are tolerant of their resident gut microbiota but are usually highly responsive to entero-pathogens; the host-specific responses have not been well characterized. To this end, the transcriptional responses of cultured human (Caco-2) and murine (CT-26) colonic epithelial cells were compared after exposure with the microfloral bacterium Lactobacillus reuteri or the human gastrointestinal pathogen Campylobacter jejuni. When in bacterial broth, both species elicit a stronger differential gene expression response in human colonic cells compared with mouse colonic cells. However, when these data are adjusted to remove bacterial broth effects, only human colonic epithelia exposed to C. jejuni show altered gene expression, suggesting that the human pathogen C. jejuni induces a host-specific response. The genes with altered expression are involved in growth, transcription, and steroid biosynthesis. Interestingly, human genes involved in cell polarity and water transport were significantly changed in response to C. jejuni exposure, linking infection with gastrointestinal disease. This study demonstrates that mouse and human colonic epithelia remain relatively unresponsive to commensal bacterial challenge, while the human pathogen C. jejuni elicits a host-specific response.

Demographic and clinical characteristics of adolescents in Hawaii with obsessive-compulsive disorder.

BACKGROUND: A high prevalence rate of obsessive-compulsive disorder (OCD) among Hawaiian adolescents, particularly Native Hawaiians, has been reported. Because Native Hawaiian and other Polynesian youth are at an increased risk for rheumatic fever, caused by an autoimmune response to group A beta-hemolytic streptococci, we hypothesized that the genetic and environmental risk factors for streptococcal infections and their autoimmune sequelae potentially may be associated with the presence of OCD and may partially explain this high OCD prevalence. OBJECTIVE: To describe, among the adolescents in Hawaii diagnosed as having OCD through a previous study, OCD prevalence by ethnicity, household crowding and other measures of socioeconomic status, various measures of physical health and health-seeking behavior, and comorbid psychopathologic features. DESIGN: Six hundred nineteen adolescents from 5 high schools in the state of Hawaii were interviewed from April 15, 1993, to May 7, 1996. Interview instruments included the Diagnostic Interview Schedule for Children and other measurements of psychopathology. Obsessive-compulsive disorder diagnoses, based on current and past 6-month symptoms elicited via structured interview of the adolescents, were reported. RESULTS: Relative to other ethnicities, Native Hawaiians had a 2-fold higher risk (odds ratio = 2.03) for OCD. Degree of Polynesian ancestry correlated positively with OCD prevalence. Obsessive-compulsive disorder prevalence also correlated positively with crowding in the household; measures of physical illness; and measures of depression, anxiety, aggression, and illicit substance use. CONCLUSIONS: The characteristics of OCD in this sample suggest the need to consider the possibility of a streptococcal origin and the need for further studies to clarify the genetic and environmental risk factors for OCD in Hawaiian and other Polynesian youth.

Binocular capture: the role of non-linear position mechanisms.

When monocular Vernier targets are presented with binocular disparate elements, an increase in vertical separation elevates alignment thresholds and also shifts its perceived visual direction towards the visual direction of the binocular disparate surround. This observation has been termed binocular capture. There is increasing evidence that this shift in the visual direction of the monocular target may be related to the type of position encoding mechanism involved in processing the relative position signal. This study investigated the interaction between capture magnitude and vertical separation for stimulus conditions that favored the recruitment of linear or non-linear position encoding mechanisms. Relative alignment thresholds and bias were measured for a pair of vertically separated (8', 30', 60', 120') monocular Gabor gratings (1, 2, 4 and 8 cpd). Grating stimuli were constructed to constrain relative alignment judgments to the carrier grating (CO) or to the envelope (EO). Relative alignment thresholds and bias were also measured for a pair of vertically separated monocular Gabor gratings comprising a 1 cpd vertical square wave grating (SQ) or a 1 cpd missing fundamental grating (MF). Capture magnitudes were significantly larger across vertical separation and varied proportionally with relative alignment threshold for the EO and MF conditions. This was not evident with the CO and SQ conditions. The stark difference in capture magnitudes between the stimuli conditions suggest that the increase in capture magnitude observed with increasing vertical separation is intimately related to the transition from a "capture-immune" first-order spatial filter mechanism to a "capture-vulnerable" non-linear/feature-based position encoding mechanism.

Common Cervical and Cerebral Vascular Variants.

Successful open and endovascular carotid artery intervention depends on a thorough foundational knowledge of cervical and intracranial vascular anatomy. It is essential for the carotid interventionist to be familiar with the common and rare variants of the cervical and intracranial vasculature, and to understand the implications of these variants for the performance of carotid intervention with protection of the distal circulation. This article provides interventionists with a basic description of the normal and relevant variant vascular anatomy from the aortic arch to the circle of Willis, and outlines the potential difficulties that specific variants may present for endovascular therapy.

Quality of life and parental adjustment in pediatric pulmonary hypertension.

BACKGROUND: This study examines the impact of pulmonary hypertension (PH) on the quality of life (QoL) of affected youth, as well as the relationships among PH disease severity, parental adjustment variables, and family relational functioning. METHODS: Subjects were 47 eligible parents of children with PH aged 2 to 18 years who were evaluated at Boston Children's Hospital. Measures of patient QoL and of parental stress, coping, and adjustment were administered to the caregivers. Clinicians rated illness severity and family relational functioning. RESULTS: Youth with PH scored significantly lower than healthy norms on a measure of parent-reported QoL (total, psychosocial, and physical QoL, each P < .0001). The parents reported encountering stressful events more frequently than published norms of parents of children with cancer (P < .0001). Thirty-four percent of parents of children with PH met criteria for presumed psychiatric diagnosis, and they reported using psychologic coping strategies significantly more often than a normative sample. A summary parental stress measure correlated inversely with child QoL, an effect that held true even after controlling for disease severity (P = .03). CONCLUSIONS: PH takes a major toll on children and their families. Decreased QoL among youth with PH was significantly associated with high levels of parental stress, over and above the effect of illness severity. These findings suggest that interventions to better support the caretakers of affected children and adolescents should accompany medical treatment advances so as to improve QoL for patients facing pediatric PH.

Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis.

Emerging evidence has implicated reactive oxygen species (ROS) in the pathogenesis of inflammatory bowel disease (IBD). Although intestinal epithelial cells produce the ROS-neutralizing enzyme superoxide dismutase (SOD), the protein and activity levels of copper/zinc (Cu/Zn) and manganese (Mn) SOD are perturbed in inflamed tissues of IBD patients. Thus we investigated the ability of MnSOD from Streptococcus thermophilus to reduce colitis symptoms in interleukin (IL) 10-deficient mice using Lactobacillus gasseri as a delivery vehicle. Cohorts of 13-15 IL-10-deficient mice were left untreated or supplemented with native L. gasseri or L. gasseri expressing MnSOD for 4 wk. Colonic tissue was collected and inflammation was histologically scored. The presence of innate immune cells was investigated by immunohistochemistry and the host antioxidant response was determined by quantitative PCR. It was demonstrated that L. gasseri was stably maintained in mice for at least 3 days. L. gasseri producing MnSOD significantly reduced inflammation in IL-10-deficient mice compared with untreated controls (P < 0.05), whereas the anti-inflammatory effects of both native and MnSOD producing L. gasseri were more pronounced in males. The anti-inflammatory effects of L. gasseri were associated with a reduction in the infiltration of neutrophils and macrophages. Transcripts of antioxidant genes were equivalent in colonic tissues obtained from control and probiotic-treated IL-10-deficient mice. This study demonstrates that L. gasseri producing MnSOD has significant anti-inflammatory activity that reduces the severity of colitis in the IL-10-deficient mouse.

Molecular characterization and functional analysis of the manganese-containing superoxide dismutase gene (sodA) from Streptococcus thermophilus AO54.

This report describes the isolation, sequencing, and functional analysis of the sodA gene, encoding Mn-superoxide dismutase, from Streptococcus thermophilus AO54. The gene was found to encode a 201 amino acid polypeptide with 88 and 83% identity to SodA from Streptococcus mutans and Streptococcus agalacticae, respectively. Primer extension analysis revealed a transcriptional start site 27 nucleotides upstream of initiation codon. The gene was expressed in Escherichia coli and was able to rescue the growth of a sodAsodB mutant in a minimal-medium containing 10(-6)M paraquat. A sodA mutant of S. thermophilus was constructed and found to be more sensitive to aerobic growth than its parent strain. Supplementing the medium with MnCl(2) improved the growth of the mutant, only under microaerophilic conditions. The results suggest that sodA is essential for the aerobic growth of S. thermophilus. In the absence of functional SodA, manganese ions may provide partial protection against oxygen toxicity.

Expression of a heterologous manganese superoxide dismutase gene in intestinal lactobacilli provides protection against hydrogen peroxide toxicity.

In living organisms, exposure to oxygen provokes oxidative stress. A widespread mechanism for protection against oxidative stress is provided by the antioxidant enzymes: superoxide dismutases (SODs) and hydroperoxidases. Generally, these enzymes are not present in Lactobacillus spp. In this study, we examined the potential advantages of providing a heterologous SOD to some of the intestinal lactobacilli. Thus, the gene encoding the manganese-containing SOD (sodA) was cloned from Streptococcus thermophilus AO54 and expressed in four intestinal lactobacilli. A 1.2-kb PCR product containing the sodA gene was cloned into the shuttle vector pTRK563, to yield pSodA, which was functionally expressed and complemented an Escherichia coli strain deficient in Mn and FeSODs. The plasmid, pSodA, was subsequently introduced and expressed in Lactobacillus gasseri NCK334, Lactobacillus johnsonii NCK89, Lactobacillus acidophilus NCK56, and Lactobacillus reuteri NCK932. Molecular and biochemical analyses confirmed the presence of the gene (sodA) and the expression of an active gene product (MnSOD) in these strains of lactobacilli. The specific activities of MnSOD were 6.7, 3.8, 5.8, and 60.7 U/mg of protein for L. gasseri, L. johnsonii, L. acidophilus, and L. reuteri, respectively. The expression of S. thermophilus MnSOD in L. gasseri and L. acidophilus provided protection against hydrogen peroxide stress. The data show that MnSOD protects cells against hydrogen peroxide by removing O(2)(.-) and preventing the redox cycling of iron. To our best knowledge, this is the first report of a sodA from S. thermophilus being expressed in other lactic acid bacteria.