Initiatives for promoting educator wellbeing: a Delphi study.

BACKGROUND: Growing demands on educators have resulted in increased levels of burnout and stress and decreasing wellbeing. This study aimed to establish expert consensus on the key characteristics required in prospective educator wellbeing initiatives. METHODS: The Delphi approach is a process of forecasting that is based on the aggregated opinion of panel members (or experts) within a field of study. Using a Delphi approach, academic and practitioner expertise were sought over a two-rounds, with 17 and 14 participants in each round respectively. The study aimed to identify how systemic factors (e.g., leadership) could be utilised to promote educator wellbeing. The study also sought expert consensus on enablers and barriers for engagement in educator wellbeing initiatives. RESULTS: Findings highlighted the importance of fostering positive relationships with colleagues, communities and families, and the active role of wellbeing teams to promote wellbeing initiatives. The need for leaders to address their own wellbeing and build trust within teams was also identified. Panel members identified the need for prospective funding to prioritise wellbeing initiatives. There was also a preference for ongoing initiatives rather than stand-alone wellbeing events that conveyed the ongoing importance of managing one's wellbeing. CONCLUSIONS: This paper presents practical recommendations that can be used to inform the development and evaluation of future initiatives and policy. Applying the consensus derived from this study is likely to make wellbeing initiatives more viable and facilitate uptake amongst educators.

Psychological resilience, emotional symptoms, and recovery duration in adolescent sport-related concussion.

OBJECTIVE: This study aimed to explore the relation between resilience, emotional changes following injury, and recovery duration in sport-related concussion. METHODS: Thirty-one high school student-athletes (ages 14-18) with sports-related injuries (concussion, n = 17 orthopedic injury, n = 14) were recruited from a pediatric sports medicine clinic. Participants completed self-report resilience ratings and self- and parent-reported post-concussion symptoms as part of a neuropsychological test battery. Hierarchical regression analyses examined predictors of recovery duration, including: (1) injury group and sex, (2) self- and parent-reported emotional symptom changes, and (3) resilience score. RESULTS: Injury group and sex alone were not predictors of recovery duration (p = .60). When parent and patient reported emotional response to injury were added to the analysis, 35% of the variance in length of recovery was explained, making the model statistically significant (F (2.26) = 3.57, p = .019). Including resilience did not reach statistical significance (p = .443). Post hoc analysis revealed parent-report of emotional changes was significantly associated with recovery duration t(31) = 3.16, p < .01), while self-report was not (p = .54). CONCLUSIONS: Parent-reported emotional change plays a pivotal role in predicting recovery length among adolescents recovering from sport-related concussion and orthopedic injury. These pilot findings highlight the significance of caregiver input in the clinical exam and emphasize the potential for acute interventions supporting psychological resources to enhance recovery outcomes across adolescent sport-related injuries.

Effects of Cumulative Head Impact Exposure in Adolescent Male Contact and Collision Sport Student Athletes.

OBJECTIVE: This prospective cohort study aimed to investigate the association between head impact exposure (HIE) and neuropsychological sequelae in high school football and ice hockey players over 1 year. SETTING: Community sample. PARTICIPANTS: A cohort of 52 adolescent American football and ice hockey players were enrolled in the study, with a final study sample of 35 included in analyses. DESIGN: The study followed a prospective cohort design, with participants undergoing neuropsychological screening and accelerometer-based measurement of HIE over 1 season. MAIN MEASURES: Changes in cognition, emotions, behavior, and reported symptoms were assessed using standardized neuropsychological tests and self-reported questionnaires. RESULTS: Cumulative HIE was not consistently associated with changes in cognition, emotions, behavior, or reported symptoms. However, it was linked to an isolated measure of processing speed, showing inconsistent results based on the type of HIE. History of previous concussion was associated with worsened verbal memory recognition (ImPACT Verbal Memory) but not on a more robust measure of verbal memory (California Verbal Learning Test [CVLT]). Reported attention-deficit/hyperactivity disorder history predicted improved neurocognitive change scores. No associations were found between reported history of anxiety/depression or headaches/migraines and neuropsychological change scores. CONCLUSION: Overall, our findings do not support the hypothesis that greater HIE is associated with an increase in neuropsychological sequelae over time in adolescent football and ice hockey players. The results align with the existing literature, indicating that HIE over 1 season of youth sports is not consistently associated with significant neuropsychological changes. However, the study is limited by a small sample size, attrition over time, and the absence of performance validity testing for neurocognitive measures. Future studies with larger and more diverse samples, longer follow-up, and integration of advanced imaging and biomarkers are needed to comprehensively understand the relationship between HIE and neurobehavioral outcomes. Findings can inform guidelines for safe youth participation in contact sports while promoting the associated health and psychosocial benefits.

Longitudinal Outcomes of Cumulative Impact Exposure on Oculomotor Functioning in Professional Motorsport Drivers.

Importance: Professional motorsport drivers are regularly exposed to biomechanical forces comparable with those experienced by contact and collision sport athletes, and little is known about the potential short-term and long-term neurologic sequelae. Objective: To determine whether cumulative impact exposure is associated with oculomotor functioning in motorsport drivers from the INDYCAR professional open-wheel automobile racing series. Design, Setting, and Participants: This is a longitudinal retrospective cohort study conducted across 3 racing seasons (2017-2019). Statistical analyses were conducted in November 2021. Data were retrieved from a secondary care setting associated with the INDYCAR series. INDYCAR series drivers who participated in 3 professional level racing seasons and were involved in at least 1 contact incident (ie, crash) in 2 of the 3 seasons were included in the study. Exposure: Cumulative acceleration and deceleration forces and total contact incidents (ie, crashes) measured via accident data recorder third generation chassis and ear accelerometers. Main Outcomes and Measures: Postseries oculomotor performance, including predictive saccades, vergence smooth pursuit, and optokinetic nystagmus, was measured annually with a head-mounted, clinical eye tracking system (Neurolign Dx 100). Results: Thirteen drivers (mean [SD] age, 29.36 [7.82] years; all men) sustained median resultant acceleration forces of 38.15 g (observed range, 12.01-93.05 g; 95% CI, 30.62-65.81 g) across 81 crashes. A 2-way multivariate analysis of variance did not reveal a statistically significant association between ear and chassis average resultant g forces, total number of contact incidents, and racing season assessed (F9,12 = 0.955; P = .54; Wilks Λ = 0.44). Conclusions and Relevance: In this cohort study of professional drivers from the INDYCAR series, there were no statistically significant associations among cumulative impact exposure, racing season assessed, and oculomotor performance. Longitudinal studies across racing seasons using multidimensional examination modalities (eg, neurocognitive testing, advanced imaging, biomarkers, and physical examination) are critical to understand potential neurological and neurobehavioral sequelae and long-term consequences of cumulative impact exposure.

Assessing Preseason Baseline Cognitive Functioning in High School Student Athletes: A "Hybrid" Approach.

OBJECTIVE: International consensus statements highlight the value of neuropsychological testing for sport-related concussion. Computerized measures are the most frequently administered assessments of pre-injury baseline and post-injury cognitive functioning, despite known measurement limitations. To our knowledge, no studies have explored the convergent validity of computerized Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and traditional, well-validated paper and pencil (P&P) neuropsychological tests in high school student athletes. This study aimed to assess a "hybrid" adolescent test battery composed of ImPACT and P&P measures to determine the extent of shared variance among ImPACT and P&P tests to inform comprehensive yet streamlined assessment. METHOD: Participants included male and female high school student athletes in the Southeastern United States participating in American football, hockey, and soccer who completed a battery of ImPACT and P&P tests (N = 69). RESULTS: We performed principal component analysis with ProMax rotation to determine components of the hybrid battery that maximally accounted for observed variance of the data (Kaiser-Meyer-Olkin factor adequacy = 0.71). Our analysis revealed four independent factors (Verbal Learning and Memory, ImPACT Memory and Speed, Verbal Processing Speed/Executive Functions, and Nonverbal Processing Speed/Executive Functions) explaining 75% of the variance. CONCLUSIONS: Findings of this study in adolescent student athletes support those from the adult literature demonstrating the independence of ImPACT and P&P tests. Providers should be aware of limitations in using standalone ImPACT or P&P measures to evaluate cognitive functioning after concussion. If confirmed in a larger, clinical sample, our findings suggest that a hybrid battery of computerized and P&P measures provides a broad scope of adolescent cognitive functioning to better inform recovery decisions, including return to play after concussion.

Intracellular Invasion by Streptococcus pyogenes: Invasins, Host Receptors, and Relevance to Human Disease.

The human oral-nasal mucosa is the primary reservoir for Streptococcus pyogenes infections. Although the most common infection of consequence in temperate climates is pharyngitis, the past 25 years have witnessed a dramatic increase in invasive disease in many regions of the world. Historically, S. pyogenes has been associated with sepsis and fulminate systemic infections, but the mechanism by which these streptococci traverse mucosal or epidermal barriers is not understood. The discovery that S. pyogenes can be internalized by mammalian epithelial cells at high frequencies (1-3) and/or open tight junctions to pass between cells (4) provides potential explanations for changes in epidemiology and the ability of this species to breach such barriers. In this article, the invasins and pathways that S. pyogenes uses to reach the intracellular state are reviewed, and the relationship between intracellular invasion and human disease is discussed.

Quality of life predicts outcome of deep brain stimulation in early Parkinson disease.

OBJECTIVE: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications. METHODS: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI. RESULTS: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group. CONCLUSION: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS. CLINICALTRIALSGOV IDENTIFIER: NCT00354133.

Dr. Edward Hacskaylo: a memoir and tribute.

Edward Hacskaylo was a pioneer in many aspects of mycorrhiza research and significantly influenced our understanding of the physiology and ecology of mycorrhizas. This memoir highlights Dr. Hacskaylo's many contributions and his impact on mycorrhiza research, especially through his encouragement and mentoring of young scientists.

A Functional Return-to-Play Progression After Exertional Heat Stroke in a High School Football Player.

OBJECTIVE: To present a functional return-to-play (RTP) progression after exertional heat stroke (EHS) in a 17-year-old high school football defensive end (height = 185 cm, mass = 145.5 kg). BACKGROUND: The patient had no pertinent medical history but moved to a warm climate several days before the EHS occurred. After completing an off-season conditioning test (14- × 110-yd [12.6- × 99.0-m] sprints) on a warm afternoon (temperature = approximately 34°C [93°F], relative humidity = 53%), the patient collapsed. An athletic trainer (AT) was called to the field, where he found the patient conscious but exhibiting central nervous system dysfunction. Emergency medical services were summoned and immediately transported the patient to the hospital. DIFFERENTIAL DIAGNOSIS: Exertional heat stroke, heat exhaustion, exertional sickling, rhabdomyolysis, and cardiac arrhythmia. TREATMENT: The patient was immediately transported to a hospital, where his oral temperature was 39.6°C (103.3°F). He was transferred to a children's hospital and treated for rhabdomyolysis, transaminitis, and renal failure. He was hospitalized for 11 days. After a physician's clearance once the laboratory results normalized, an RTP progression was completed. The protocol began with light activity and progressed over 3 weeks to full football practice. During activity, an AT monitored the patient's gastrointestinal temperature, heart rate, rating of perceived exertion, fluid consumption, and sweat losses. UNIQUENESS: Documentation of RTP guidelines for young athletes is lacking. We used a protocol intended for the football setting to ensure the athlete was heat tolerant, had adequate physical fitness, and could safely RTP. Despite his EHS, he recovered fully, with no lasting effects, and successfully returned to compete in the final 5 games of the season. CONCLUSIONS: Using a gradual RTP progression and close monitoring, a high school defensive end successfully returned to football practice and games after EHS. This case demonstrates the feasibility of implementing a safe RTP protocol after EHS and may serve as a guide to ATs working in the high school setting. This case also highlights the need for more research in this area.

Prospective Longitudinal Analysis of Immune Responses in Pediatric Subjects After Pharyngeal Acquisition of Group A Streptococci.

BACKGROUND.: Despite the significant burden of disease associated with infection by group A streptococcus (GAS), little is known about the human immune response to GAS antigens after natural infection. METHODS.: We evaluated 195 serum samples obtained prospectively over a consecutive 24-month period from 41 pediatric subjects who experienced a new pharyngeal GAS acquisition. An enzyme-linked immunoassay was used to determine the kinetics and antigen specificity of antibodies against 13 shared GAS antigens and 18 type-specific M peptides. The majority of the antigens tested are currently being considered as vaccine candidates. RESULTS.: Twelve M types of GAS were recovered from 41 subjects who experienced 51 new GAS acquisitions that elicited antibody responses against at least 1 of the 31 antigens tested (immunologically significant new GAS acquisitions). The immune responses to the 13 shared antigens were highly variable. Increases in antibody levels were detected against a mean of 3.5 shared antigens (range, 1-8). Antibody responses to the homologous M peptide were observed in 32 (63%) of the 51 episodes. Seven subjects acquired more than 1 M type of GAS. There were no new immunologically significant acquisitions of an M type against which the subject had preexisting antibodies to the homologous M peptide. Of the subjects with new GAS acquisition, 65% were asymptomatic, yet immune responses were detected against 1 or more GAS antigens. Immune responses to streptolysin O and/or deoxyribonuclease B were observed after 67% of the new GAS acquisitions. Persistently positive (>12 weeks) throat culture results were returned for 20% of the 41 subjects despite immune responses to homologous M peptides and/or shared antigens. CONCLUSIONS.: The availability of throat culture results, GAS isolates, and serial serum samples collected prospectively over a 2-year period of observation provided a unique opportunity for us to assess the serologic status of pediatric subjects before and after new pharyngeal acquisitions of GAS. With the exception of antibody responses to the homologous M peptides, no clear pattern of immune responses against the remaining GAS antigens was seen. There were no new immunologically significant acquisitions of emm types of GAS against which the subjects had preexisting elevated levels of antibodies against the homologous M peptide. The observation that 65% of new GAS acquisitions caused no symptoms yet were immunologically significant suggests that the majority of infections are not detected, which would result in missed opportunities for primary prevention of rheumatic fever and rheumatic heart disease with appropriate antimicrobial therapy.

The policy and politics of the 2015 long-term care reform in the Netherlands.

As of 2015 a major reform in LTC is taking place in the Netherlands. An important objective of the reform is to reign in expenditure growth to safeguard the fiscal sustainability of LTC. Other objectives are to improve the quality of LTC by making it more client-tailored. The reform consists of four interrelated pillars: a normative reorientation, a shift from residential to non-residential care, decentralization of non-residential care and expenditure cuts. The article gives a brief overview of these pillars and their underlying assumptions. Furthermore, attention is paid to the political decision-making process and the politics of implementation and evaluation. Perceptions of the effects of the reform so far widely differ: positive views alternate with critical views. Though the reform is radical in various aspects, LTC care will remain a largely publicly funded provision. A statutory health insurance scheme will remain in place to cover residential care. The role of municipalities in publicly funded non-residential care is significantly upgraded. The final section contains a few policy lessons.

Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells.

Group A streptococcal (GAS) infection induces the production of Abs that cross-react with host neuronal proteins, and these anti-GAS mimetic Abs are associated with autoimmune diseases of the CNS. However, the mechanisms that allow these Abs to cross the blood-brain barrier (BBB) and induce neuropathology remain unresolved. We have previously shown that GAS infection in mouse models induces a robust Th17 response in nasal-associated lymphoid tissue (NALT). Here, we identified GAS-specific Th17 cells in tonsils of humans naturally exposed to GAS, prompting us to explore whether GAS-specific CD4+ T cells home to mouse brains following i.n. infection. Intranasal challenge of repeatedly GAS-inoculated mice promoted migration of GAS-specific Th17 cells from NALT into the brain, BBB breakdown, serum IgG deposition, microglial activation, and loss of excitatory synaptic proteins under conditions in which no viable bacteria were detected in CNS tissue. CD4+ T cells were predominantly located in the olfactory bulb (OB) and in other brain regions that receive direct input from the OB. Together, these findings provide insight into the immunopathology of neuropsychiatric complications that are associated with GAS infections and suggest that crosstalk between the CNS and cellular immunity may be a general mechanism by which infectious agents exacerbate symptoms associated with other CNS autoimmune disorders.

Clinical and Neurologic Manifestation of Minimal Hepatic Encephalopathy and Overt Hepatic Encephalopathy.

Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric manifestations. A combined effort with neuropsychological and psychometric evaluation has to be performed to recognize the syndrome, whereas minimal HE (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed through specialized neuropsychiatric testing. Early diagnosis and treatment may drastically improve the quality of life for many cirrhotic patients. Further research to gain better insight into the pathophysiology and diagnostic accuracy of HE will help determine future management strategies.

In Situ Peptide-MHC-II Tetramer Staining of Antigen-Specific CD4+ T Cells in Tissues.

The invention of peptide-MHC-tetramer technology to label antigen-specific T cells has led to an enhanced understanding of T lymphocyte biology. Here we describe the development of an in situ pMHC-II tetramer staining method to visualize antigen-specific CD4+ T cells in tissues. This method complements other methods developed that similarly use MHC class II reagents to stain antigen-specific CD4+ T cells in situ. In this study, we used group A streptococcus (GAS) expressing a surrogate peptide (2W) to inoculate C57BL/6 mice, and used fresh nasal-associated lymphoid tissues (NALT) in optimizing the in situ staining of 2W:I-Ab specific CD4+ T cells. The results showed 2W:I-Ab tetramer-binding CD4+ T cells in GAS-2W but not GAS infected mice. This method holds promise to be broadly applicable to study the localization, abundance, and phenotype of antigen-specific CD4+ T cells in undisrupted tissues.

Neutral sphingomyelinase-2 is a redox sensitive enzyme: role of catalytic cysteine residues in regulation of enzymatic activity through changes in oligomeric state.

Neutral sphingomyelinase-2 (nSMase-2) is the major sphingomyelinase activated in response to pro-inflammatory cytokines and during oxidative stress. It is a membrane-bound 655 amino acid protein containing 22 cysteine residues. In this study, we expressed recombinant mouse nSMase-2 protein in Escherichia coli, and investigated whether nSMase-2 is a redox sensitive enzyme. Our results demonstrate that nSMase-2 exists as both monomers and multimers that are associated with high and low enzymatic activity respectively. Mutational analysis of nSMase-2 identified within its C-terminal catalytic domain several oxidant-sensitive cysteine residues that were shown to be involved in enzyme oligomerization. Changing Cys(617) to Ser for example is a gain-of-function mutation associated with a decreased propensity for oligomerization. Alternatively, nSMase-2 expression in a bacterial strain that lacks endogenous thioredoxin, Rosetta-gami2, results in increased oligomer formation and lower enzyme activity. Phenotypic rescue was accomplished by treating nSMase-2 lysates with recombinant human thioredoxin. This indicates that nSMase-2 may be a novel substrate for thioredoxin. FRET analysis confirmed the presence of nSMase-2 multimers in mammalian HEK cells and their localization to the plasma membrane. In conclusion, our results identify nSMase-2 as a redox-sensitive enzyme, whose basal activity is influenced by thioredoxin-mediated changes in its oligomeric state.

Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.

Sports medicine in children: sports-related concussion.

Concussion is a commonly encountered consequence of participation in sports. The symptoms of youth concussion are subtle and vary from athlete to athlete. Much attention has been paid recently to the diagnosis of concussion, and the understanding of this condition has increased significantly in the past 10 years. Legislative initiatives have focused on the diagnosis and management of concussion to keep children and adolescents with concussion away from the field of play until their symptoms have resolved fully. Family physicians need to be aware of evolving knowledge regarding concussion and the resulting changes in the definition, diagnosis, and management of this condition.

Effects of triple-drug therapy with nitazoxanide, high-dose ribavirin and peginterferon-α-2a in patients with chronic hepatitis C.

AIM: The historical standard of care for patients with chronic hepatitis C virus (HCV) was peginterferon (PEG IFN) and ribavirin combination therapy, yielding sustained virological response (SVR) rates of 38-52% in HCV genotype 1 patients. This study evaluated a novel three-drug regimen of nitazoxanide and high-dose ribavirin as lead-in therapy, followed by PEG IFN-α-2a in triple therapy. METHODS: A prospective, open-label pilot study was conducted in treatment-naive patients with HCV genotype 1. Patients received nitazoxanide 500 mg twice a day for 2 weeks, then nitazoxanide plus ribavirin 1400 mg/day for 2 weeks, then nitazoxanide plus ribavirin plus PEG IFN-α-2a 180 µg weekly for 12 weeks, followed by ribavirin plus PEG IFN-α-2a for 12 weeks (48 weeks if HCV RNA negative after week 24). Primary outcome was SVR. Other outcomes included very rapid virological response (VRVR), rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and safety and tolerability. RESULTS: Thirty-three patients with a mean age of 46 years, detectable HCV RNA (64% with <600 000 IU/mL), and METAVIR fibrosis scores (F1:F2:F3) of 15%:49%:36% were enrolled. Outcomes were as follows: SVR, 67% (22/33); VRVR, 39% (13/33); RVR, 48% (16/33); EVR, 70% (23/33); and ETR, 67% (22/33). Most patients required at least one growth factor. Two patients discontinued because of adverse events. CONCLUSION: This three-drug regimen was effective in achieving SVR in patients with HCV genotype 1. No patients relapsed, and the toxicity profile was favorable. Further studies on the role of nitazoxanide in the treatment of chronic HCV are warranted.

Novel endoscopic delivery modality of infrared coagulation therapy for internal hemorrhoids.

BACKGROUND: A novel endoscopic delivery system for infrared coagulation therapy (IRC) has been designed recently. IRC is a well-established treatment for symptomatic internal hemorrhoids. Patients frequently undergo lower endoscopy before hemorrhoid treatment to eliminate other sources of bleeding. Current treatment options are difficult to perform without an anal retractor, adequate lighting, and specialized instruments. Endoscopic IRC is an attractive alternative to standard IRC, because it can be performed during the lower endoscopy. TECHNIQUE: Endoscopic IRC utilizes infrared radiation generated by a control box, which is applied to the tissue through a flexible, fiber optic light guide (Precision Endoscopic Infrared Coagulator™). The light guide is placed through the colonoscope or flexible sigmoidoscope in the same chamber as other endoscopic instruments. METHODS: A retrospective review was performed using a prospectively collected database. A standardized protocol was utilized in all patients. Patients graded their symptoms before and after therapy by using the visual analog symptom severity scoring system (range, 0-10). These results were analyzed by using the nonparametric Wilcoxon signed-rank test. Exact P values were computed by using the R function wilcox.exact. RESULTS: A total of 55 patients underwent endoscopic IRC for predominately grade II and grade III symptomatic internal hemorrhoids (71 %). There were 22 (40 %) female patients. Posttherapy results indicated a significant improvement in global symptoms (pretreatment average global score = 2.24 vs. posttreatment average global score = 0.28; P < 0.0001). There have been no adverse events reported to date. CONCLUSIONS: Endoscopic IRC provides improved visibility and efficiency, allowing simultaneous treatment of symptomatic internal hemorrhoids at the time of lower endoscopy. Patients experienced significant improvement in their symptoms after a single session of endoscopic IRC. There are a variety of additional endoscopic IRC therapeutic utilities: endoscopic management of angiodysplasia, inflammation, hemostasis, and NOTES applications.

Ribozyme-mediated trans insertion-splicing into target RNAs.

The trans insertion-splicing (TIS) reaction is a technique that can be used to site-specifically insert an RNA donor substrate into a separate RNA acceptor substrate. The TIS reaction, which is catalyzed by a group I intron-derived ribozyme from Pneumocystis carinii, is described with regards to system design, ribozyme preparation, and the overall protocol for conducting the TIS reaction.