Common Data Element Collection in Underserved School Communities: Challenges and Recommendations.

OBJECTIVES: To provide recommendations for future common data element (CDE) development and collection that increases community partnership, harmonizes data interpretation, and continues to reduce barriers of mistrust between researchers and underserved communities. METHODS: We conducted a cross-sectional qualitative and quantitative evaluation of mandatory CDE collection among Rapid Acceleration of Diagnostics-Underserved Populations Return to School project teams with various priority populations and geographic locations in the United States to: (1) compare racial and ethnic representativeness of participants completing CDE questions relative to participants enrolled in project-level testing initiatives and (2) identify the amount of missing CDE data by CDE domain. Additionally, we conducted analyses stratified by aim-level variables characterizing CDE collection strategies. RESULTS: There were 15 study aims reported across the 13 participating Return to School projects, of which 7 (47%) were structured so that CDEs were fully uncoupled from the testing initiative, 4 (27%) were fully coupled, and 4 (27%) were partially coupled. In 9 (60%) study aims, participant incentives were provided in the form of monetary compensation. Most project teams modified CDE questions (8/13; 62%) to fit their population. Across all 13 projects, there was minimal variation in the racial and ethnic distribution of CDE survey participants from those who participated in testing; however, fully uncoupling CDE questions from testing increased the proportion of Black and Hispanic individuals participating in both initiatives. CONCLUSIONS: Collaboration with underrepresented populations from the early study design process may improve interest and participation in CDE collection efforts.

Test-to-Stay in Kindergarten Through 12th Grade Schools After Household Exposure to Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Test-to-stay (TTS) is a strategy to limit school exclusion following an exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the use of TTS within universally masked kindergarten through 12th grade (K-12) school settings following household SARS-CoV-2 exposure. METHODS: Three hundred twenty-two participants were enrolled. Serial rapid antigen testing was performed up to 15 days post-exposure. Analysis-eligible participants completed the 15-day testing protocol, tested positive any time during the testing window, or received a negative test on or after day 9. Primary outcomes included within-school tertiary attack rate (TAR) (test positivity among close contacts of positive TTS participants), and school days saved among TTS participants. RESULTS: Seventy-three of 265 analysis-eligible participants tested positive for SARS-CoV-2 (secondary attack rate of 28% [95% CI: 16-63%]). Among 77 within-school close contacts, 2 were positive (TAR = 3% [95% CI: 1-5%]). Participant absences were limited to 338 days, resulting in 82% of 1849 school days saved. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: TTS facilitates continued in-person learning and can greatly reduce the number of missed school days. CONCLUSIONS: Within universally masked K-12 schools, TTS is a safe alternative to school exclusion following household SARS-CoV-2 exposure.

SARS-CoV-2 Screening Testing Programs for Safe In-person Learning in K-12 Schools.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening testing is a recommended mitigation strategy for schools, although few descriptions of program implementation are available. METHODS: Kindergarten through 12th grade (K-12) students and staff practicing universal masking during the delta and omicron variant waves from five schools in Durham, North Carolina and eight schools in Kansas City, Missouri participated; Durham's program was structured as a public health initiative facilitated by school staff, and Kansas City's as a research study facilitated by a research team. Tests included school-based rapid antigen or polymerase chain reaction testing, at-home rapid antigen testing, and off-site nucleic acid amplification testing. RESULTS: We performed nearly 5700 screening tests on more than 1600 K-12 school students and staff members. The total cost for the Durham testing program in 5 public charter K-12 schools, each with 500-1000 students, was $246 587 and approximately 752 h per semester; cost per test was $70 and cost per positive result was $7076. The total cost for the Kansas City program in eight public K-12 schools was $292 591 and required approximately 537 h in personnel time for school-based testing; cost per test was $132 and cost per positive result was $4818. SARS-CoV-2 positivity rates were generally lower (0-16.16%) than rates in the community (2.7-36.47%) throughout all testing weeks. CONCLUSIONS AND RELEVANCE: Voluntary screening testing programs in K-12 schools are costly and rarely detect asymptomatic positive persons, particularly in universally masked settings. CLINICAL TRIAL REGISTRATION: NCT04831866.

Assessing Depressive Symptoms in Patients With Cancer Treated With Interleukin-2: A Comparison of 2 Measures.

BACKGROUND: High-dose interleukin-2 is a therapy available for individuals with renal cell carcinoma; however, it can produce adverse effects, specifically depressive symptoms. There is limited information regarding the trajectory of depressive symptoms and measurement-based care assessment of depressive symptoms. OBJECTIVE: The purpose was to describe the trajectory of depressive symptoms and compare 2 depression measures. METHODS: A descriptive, mixed-method case study approach was used to describe the longitudinal trajectory of depressive symptoms The qualitative assessment included a journal entry and an interview. The quantitative depression symptom severity measures included the 8-item self-report Patient-Reported Outcomes Measurement Information System Depression and the 30-item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C). RESULTS: Ten cases were enrolled. The maximum number of interleukin-2 doses that any patient received within a single hospitalization ranged from 4 to 12. Mean scores on the 8-item Patient-Reported Outcomes Measurement Information System Depression showed no changes in depressive symptoms from pretreatment to posttreatment, nor across hospitalizations. Mean total scores on the IDS-C increased from "normal" to "mild severity" depressive symptom range across all treatment cycles, suggesting transient depressive symptoms within hospitalizations. Qualitative data from the case supported the IDS-C increase, suggesting that the patient developed depressive symptoms pretreatment to posttreatment. CONCLUSIONS: Understanding the trajectory of depressive symptoms allows for the identification of critical time points when depressive symptoms present and change across treatment. It is critical to use measurement-based care using validated measures to assess for the presence and changes in depressive symptoms. IMPLICATIONS FOR PRACTICE: Validated self-report or clinician-rated depression symptom measures should be used to document the presence or absence of depressive symptoms in this population.

Test-to-Stay After SARS-CoV-2 Exposure: A Mitigation Strategy for Optionally Masked K-12 Schools.

OBJECTIVES: We evaluated the impact of a test-to-stay (TTS) program on within-school transmission and missed school days in optionally masked kindergarten through 12th grade schools during a period of high community severe acute respiratory syndrome coronavirus 2 transmission. METHODS: Close contacts of those with confirmed severe acute respiratory syndrome coronavirus 2 infection were eligible for enrollment in the TTS program if exposure to a nonhousehold contact occurred between November 11, 2021 and January 28, 2022. Consented participants avoided school exclusion if they remained asymptomatic and rapid antigen testing at prespecified intervals remained negative. Primary outcomes included within-school tertiary attack rate (test positivity among close contacts of positive TTS participants) and school days saved among TTS participants. We estimated the number of additional school-acquired cases resulting from TTS and eliminating school exclusion. RESULTS: A total of 1675 participants tested positive or received at least 1 negative test between days 5 and 7 and completed follow-up; 92% were students and 91% were exposed to an unmasked primary case. We identified 201 positive cases. We observed a tertiary attack rate of 10% (95% confidence interval: 6%-19%), and 7272 (89%) of potentially missed days were saved through TTS implementation. We estimated 1 additional school-acquired case for every 21 TTS participants remaining in school buildings during the entire study period. CONCLUSIONS: Even in the setting of high community transmission, a TTS strategy resulted in substantial reduction in missed school days in optionally masked schools.

Tapping into the minds and hearts of the local public health workforce during the COVID-19 pandemic.

SETTING: Ottawa Public Health (OPH) provides public health programming and services in the Ottawa region. At the onset of the COVID-19 pandemic in March 2020, the OPH COVID-19 Case and Contact Management Team was established to help manage the spread of COVID-19 and support individuals who test positive, and their close contacts. INTERVENTION: In order to guide and support the COVID-19 Case and Contact Management Team, the COVID-19 Strategic Support Team implemented an anonymous internal communication tool called the COVID-19 Case Management Forum. Case and Contact Management employees were invited to submit their questions, concerns, and words of encouragement on the forum, and the COVID-19 Strategic Support Team routinely replied to forum submissions via team email. OUTCOMES: Qualitative analyses of employee forum submissions revealed 6 main themes and 31 unique sub-themes related to questions, concerns, and feelings that arose throughout this pandemic response. Recurrent themes emerged relating to process questions, communication challenges, solution generation, and feelings of frustration. Summative content analyses of the COVID-19 Strategic Support team's replies demonstrated 6 main answer types: explaining procedures, identifying resources, explaining rationales, human resource explanations, sharing employee feedback with relevant parties, and creating practice tools. IMPLICATIONS: The online forum tool was developed and implemented early in the pandemic response to provide key insights into OPH's public health workforce needs and well-being throughout the COVID-19 response. The forum encouraged open dialogue and provided opportunities to establish clarity in a time of rapid situational change.

RéSUMé: CONTEXTE: Santé publique Ottawa (SPO) offre des programmes et services de soins de santé publique dans la région d'Ottawa. Dès le début de la pandémie de COVID-19 en mars 2020, l'équipe chargée de la gestion des cas et des contacts de la COVID-19 de SPO a été créée pour faciliter la gestion de la propagation de la COVID-19 et soutenir les personnes qui ont obtenu un test positif. INTERVENTION: Afin de guider et de soutenir l'équipe de gestion des cas et des contacts de la COVID-19, l'équipe de soutien stratégique en gestion de la COVID-19 a mis en place un forum de communication interne anonyme appelé Forum de gestion des cas de la COVID-19. Les employés de la gestion des cas et des contacts ont été invités à soumettre leurs questions, préoccupations et mots d'encouragement sur le forum, et l'équipe de soutien stratégique en gestion de la COVID-19 a régulièrement répondu aux commentaires du forum par courrier électronique. RéSULTATS: Les analyses qualitatives des commentaires du forum envoyés par les employés ont révélé 6 thèmes principaux et 31 sous-thèmes liés aux questions, aux préoccupations et aux sentiments qui ont surgi tout au long de la lutte contre la pandémie. Les thèmes récurrents se rapportent aux questions de processus, aux défis liés à la communication, à la recherche de solutions et aux sentiments de frustration. Les analyses de contenu sommatives des réponses de l'équipe de soutien stratégique en gestion de la COVID-19 ont révélé 6 principaux types de réponses : expliquer les procédures, identifier les ressources, expliquer les justifications, expliquer les ressources humaines, partager les commentaires des employés avec les parties concernées et créer des outils pratiques. IMPLICATIONS: L'outil de forum en ligne a été élaboré et mis en oeuvre au début de l'intervention face à la pandémie pour fournir des informations clés sur les besoins et le bien-être du personnel de SPO tout au long de la lutte contre la COVID-19. Le forum encourageait un dialogue ouvert et a permis d'apporter plusieurs précisions dans un milieu en évolution constante et rapide.

Test-to-Stay After Exposure to SARS-CoV-2 in K-12 Schools.

OBJECTIVES: We evaluated the safety and efficacy of a test-to-stay program for unvaccinated students and staff who experienced an unmasked, in-school exposure to someone with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serial testing instead of quarantine was offered to asymptomatic contacts. We measured secondary and tertiary transmission rates within participating schools and in-school days preserved for participants. METHODS: Participating staff or students from universally masked districts in North Carolina underwent rapid antigen testing at set intervals up to 7 days after known exposure. Collected data included location or setting of exposure, participant symptoms, and school absences up to 14 days after enrollment. Outcomes included tertiary transmission, secondary transmission, and school days saved among test-to-stay participants. A prespecified interim safety analysis occurred after 1 month of enrollment. RESULTS: We enrolled 367 participants and completed 14-day follow-up on all participants for this analysis. Nearly all (215 of 238, 90%) exposure encounters involved an unmasked index case and an unmasked close contact, with most (353 of 366, 96%) occurring indoors, during lunch (137 of 357, 39%) or athletics (45 of 357, 13%). Secondary attack rate was 1.7% (95% confidence interval: 0.6%-4.7%) based on 883 SARS-CoV-2 serial rapid antigen tests with results from 357 participants; no tertiary cases were identified, and 1628 (92%) school days were saved through test-to-stay program implementation out of 1764 days potentially missed. CONCLUSION: After unmasked in-school exposure to SARS-CoV-2, even in a mostly unvaccinated population, a test-to-stay strategy is a safe alternative to quarantine.

A School-Based SARS-CoV-2 Testing Program: Testing Uptake and Quarantine Length After In-School Exposures.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related quarantines, which are required after close contact with infected individuals, have substantially disrupted in-person education for kindergarten through 12th grade (K-12) students. In recent recommendations, shortened durations of quarantine are allowed if a negative SARS-CoV-2 test result is obtained at 5 to 7 days postexposure, but access to testing remains limited. We hypothesized that providing access to in-school SARS-CoV-2 testing postexposure would increase testing and reduce missed school days. METHODS: This prospective cohort study was conducted in one large public K-12 school district in North Carolina and included 2 periods: preimplementation (March 15, 2021, to April 21, 2021) and postimplementation (April 22, 2021, to June 4, 2021), defined around initiation of an in-school SARS-CoV-2 testing program in which on-site access to testing is provided. Number of quarantined students and staff, testing uptake, test results, and number of missed school days were analyzed and compared between the preimplementation and postimplementation periods. RESULTS: Twenty-four schools, including 12 251 in-person learners, participated in the study. During preimplementation, 446 close contacts were quarantined for school-related exposures; 708 close contacts were quarantined postimplementation. Testing uptake after school-related exposures increased from 6% to 40% (95% confidence interval: 23% to 45%) after implementation, and 89% of tests were conducted in-school. After in-school testing implementation, close contacts missed ∼1.5 fewer days of school (95% confidence interval: -2 to -1). CONCLUSIONS: Providing access to in-school testing may be a worthwhile mechanism to increase testing uptake after in-school exposures and minimize missed days of in-person learning, thereby mitigating the pandemic's ongoing impact on children.

Masking Adherence in K-12 Schools and SARS-CoV-2 Secondary Transmission.

OBJECTIVES: Masking is an essential coronavirus 2019 mitigation tool assisting in the safe return of kindergarten through 12th grade children and staff to in-person instruction; however, masking adherence, compliance evaluation methods, and potential consequences of surveillance are currently unknown. We describe 2 school districts' approaches to promote in-school masking and the consequent impact on severe acute respiratory syndrome coronavirus 2 secondary transmission. METHODS: Two North Carolina school districts developed surveillance programs with daily versus weekly interventions to monitor in-school masking adherence. Safety teams recorded the proportion of students and staff appropriately wearing masks and provided real-time education after observation of improper masking. Primary infections, within-school transmission, and county-level severe acute respiratory syndrome coronavirus 2 infection rates were assessed. RESULTS: Proper mask use was high in both intervention groups and districts. There were variations by grade level, with lower rates in elementary schools, and proper adherence being higher in the weekly surveillance group. Rates of secondary transmission were low in both districts with surveillance programs, regardless of intervention frequency. CONCLUSIONS: Masking surveillance interventions are effective at ensuring appropriate masking at all school levels. Creating a culture of safety within schools led by local leadership is important and a feasible opportunity for school districts with return to in-person school. In our study of schools with high masking adherence, secondary transmission was low.

Predictors of farther mobilization on day of surgery and shorter length of stay after total joint arthroplasty.

BACKGROUND: Mobilization on the day of total joint arthroplasty (TJA) is associated with shorter length of stay. The question of whether incrementally farther mobilization on the day of surgery (POD0) contributes to shorter length of stay has not been widely studied. The purpose of this study was to determine if farther mobilization on POD0 led to shorter length of stay and to identify the predictors of farther mobilization and length of stay. METHODS: A retrospective chart review was undertaken using data for patients who had a primary TJA and mobilized on POD0. Patients were categorized into the following 4 mobilization groups: sat on the bedside (Sat), stood by the bed or walked in place (Stood), walked in the room (Room) and walked in the hall (Hall). The primary outcome was length of stay. Predictors of farther mobilization on POD0 and length of stay were identified using regression analyses. RESULTS: The sample comprised 283 patients. The Hall group had significantly shorter length of stay than all other groups. There were sex differences across the mobilization groups. Simultaneous regression analysis showed that farther mobilization was predicted by younger age, male sex, lower body mass index, spinal anesthesia and fewer symptoms limiting mobilization. Hierarchical regression showed that shorter length of stay was predicted by male sex, lower body mass index, lower American Society of Anaesthesiologists physical status classification score, less pain/stiffness and farther mobilization on POD0. CONCLUSION: Understanding the modifiable and nonmodifiable predictors of mobilization after TJA and length of stay can help identify patients more likely to mobilize farther on the day of surgery, which would contribute to better resource allocation and discharge planning. Focusing on symptom management could increase opportunities for farther mobilization on POD0 and thereby decrease length of stay.

CONTEXTE: La mobilisation le jour même d'une arthroplastie totale (AT) est associée à une durée d'hospitalisation réduite. Or, le lien entre l'ampleur de la mobilisation le jour de la chirurgie (jour postopératoire 0 [JPO0]) et la réduction de la durée d'hospitalisation n'a pas été largement étudié. La présente étude visait à déterminer si une mobilisation plus importante au JPO0 réduit la durée d'hospitalisation, de même qu'à repérer les facteurs prédictifs de mobilisation importante et de durée d'hospitalisation. MÉTHODES: Une analyse rétrospective a été menée à l'aide des dossiers de patients ayant subi une AT primaire et ayant été mobilisés au JPO0. Les patients ont été classés en 4 groupes en fonction de l'ampleur de leur mobilisation : assis au bord du lit (assis), debout à côté du lit ou marche sur place (debout), marche dans la chambre (chambre) et marche dans le couloir (couloir). Le principal résultat à l'étude était la durée d'hospitalisation. Les facteurs prédictifs de mobilisation importante au JPO0 et de durée d'hospitalisation ont été dégagés au moyen d'analyses de régression. RÉSULTATS: L'échantillon comprenait 283 patients. Le groupe couloir présentait une durée d'hospitalisation significativement plus courte que les autres. Des différences entre les sexes ont été observées dans tous les groupes. Selon une analyse de régression simultanée, les facteurs prédictifs de mobilisation importante étaient un jeune âge, le sexe masculin, un faible indice de masse corporelle, une anesthésie rachidienne et un nombre limité de symptômes nuisant à la mobilisation. Une analyse de régression hiérarchique a quant à elle montré que les facteurs prédictifs de durée hospitalisation réduite étaient le sexe masculin, un faible indice de masse corporelle, un faible score à la classification de l'état de santé physique de l'American Society of Anesthesiologists, une douleur ou des raideurs moindres, et une mobilisation importante au JPO0. CONCLUSION: La mise en évidence des facteurs prédictifs modifiables et non modifiables de mobilisation et de durée d'hospitalisation après une AT peut faciliter le repérage des patients susceptibles d'être davantage mobilisés, ce qui contribuerait à une meilleure allocation des ressources et faciliterait la planification des congés. Accorder une attention particulière au soulagement des symptômes pourrait accroître les occasions de mobilisation importante au JPO0 et, par conséquent, réduire la durée d'hospitalisation.

Partnership for development: A peer mentorship model for PhD students.

Formal mentoring relationships socialize Doctor of Philosophy (PhD) students to their current and future roles as nursing scholars. Despite formal mentoring, some students may desire or benefit from additional mentoring in an informal setting. Informal mentoring complements the one-to-one relationship students develop with a primary faculty mentor or dissertation chair. This manuscript describes the development, implementation, and evaluation of a student-driven, peer mentorship model, titled Partnership for Development. This small group, peer mentorship model was implemented in a PhD program at a School of Nursing during an academic year. Five student peer facilitators organized a total of 32 PhD students, 2 post-doctoral associates, and invited 5 faculty to participate. Data includes pre- and post-implementation surveys completed by the students and peer facilitator field notes. Student reported post-participation benefits included: getting to know faculty in an informal setting (n=6), socializing with students from other cohorts (n=6), and obtaining a sense of camaraderie with other PhD students (n=5). We recommend peer mentorship for other PhD programs as a way to socialize PhD students into the role of nurse scientist and assist students during their tenure as a PhD student.

Cognitive and Affective Symptoms Experienced by Cancer Patients Receiving High-Dose Intravenous Interleukin 2 Therapy: An Integrative Literature Review.

BACKGROUND: Alterations in cognitive/affective functioning are among the most challenging adverse effects experienced by 80% of patients with metastatic melanoma and metastatic renal cell carcinoma undergoing high-dose interleukin 2 (IL-2) therapy. OBJECTIVE: The purpose of this literature review is to describe what is known about IL-2-induced cognitive/affective symptoms, their prevalence, and level of severity and synthesize findings to determine areas for future research to address symptom management challenges. This review describes the IL-2 patient experience and the pathophysiology leading to these changes. METHODS: An online electronic search using PubMed was performed to identify relevant literature published between 1992 and 2015. Of the original 113 articles, information was extracted from 9 articles regarding cognitive symptoms, affective symptoms, sample size, research design, reliability, and validity. RESULTS: Our review suggests that the trajectories, breadth, and depth of cognitive/affective symptoms have yet to be described. Despite intervention studies designed to address the psychosocial complications of IL-2, an understanding of the level of altered cognitive/affective symptoms experienced by IL-2 patients remains unclear. CONCLUSION: Our literature review reveals a lack of standardization when assessing, reporting, and managing cognitive/affective symptoms. Patients/family members have reported cognitive/affective symptoms to be the most alarming and difficult symptoms, yet these symptoms are not adequately screened for, and patients were not informed about potential changes. IMPLICATIONS FOR PRACTICE: Assessing patients for cognitive/affective alterations is important to reduce anxiety while improving outcomes. Education about the illness trajectory (what to expect during/after treatment) can help care partners/patients set realistic shared expectations and increase coping.

Get Tested Why Not? A novel approach to internet-based chlamydia and gonorrhea testing in Canada.

OBJECTIVE: The objective of the Get Tested Why Not campaign is to increase access to chlamydia and gonorrhea testing and sexual health information, with specific focus on youth. PARTICIPANTS: Individuals between the ages of 15-29 are most affected by chlamydia and gonorrhea infections in Ottawa and were identified as the target population. Youth from the target population were engaged in the development and launch of the campaign. SETTING: Development of the campaign began in 2009 and led to a launch on March 21, 2011. Social media promotion as well as traditional advertising approaches developed awareness of the campaign within the target population. INTERVENTION: The campaign consists of a bilingual, youth-friendly website and texting service. After assessing appropriateness of testing, clients can download a requisition form for urine-based chlamydia and gonorrhea testing and submit a sample at one of 26 laboratories across Ottawa. OUTCOMES: During year 1 of the campaign, there were 13,385 website hits and 104 specimens submitted for chlamydia and gonorrhea testing. The majority (57.6%, n=60) of requisitions were submitted by members of the target population (age 15-29). Of the requisitions submitted, 95 (91.3%) were negative, 4 (3.9%) were positive and 5 (4.8%) were cancelled due to lab errors. CONCLUSION: The campaign is reaching the target population and has demonstrated a positive impact on knowledge and intended behaviours of users. The use of technology has expanded testing options, thereby potentially broadening Ottawa Public Health's reach to clients who may be less likely to test through traditional testing approaches.

The impact of escitalopram on IL-2-induced neuroendocrine, immune, and behavioral changes in patients with malignant melanoma: preliminary findings.

Interleukin (IL)-2, a T-cell cytokine used to treat malignant melanoma, can induce profound depression. To determine whether pretreatment with the antidepressant escitalopram could reduce IL-2-induced neuroendocrine, immune, and neurobehavioral changes, 20 patients with Stage IV melanoma were randomized to either placebo or the serotonin reuptake inhibitor, escitalopram (ESC) 10-20 mg/day, 2 weeks before, and during IL-2 treatment (720 000 units/kg Q8 h × 5 days (1 cycle) every 3 weeks × 4 cycles). Generalized estimation equations were used to examine HPA axis activity (plasma ACTH and cortisol), immune activation (plasma IL-6), and depressive symptoms (Hamilton Depression Rating Scale (HDRS) score). Tolerance of IL-2 treatment (concomitant medications required) and adherence (number of IL-2 doses received) were also assessed. Both the groups (ESC (n=9), placebo (n=11)) exhibited significant IL-2-induced increases in plasma cortisol, IL-6, and depressive symptoms (p<0.05), as well as a temporal trend for increases in plasma ACTH (p=0.054); the effects of age and treatment were not significant. Higher plasma ACTH concentrations were associated with higher depressive symptoms during cycles 1-3 of IL-2 therapy (p<0.01). Although ESC had no significant effects on ACTH, cortisol, IL-6, tolerance of, or adherence to IL-2, ESC treatment was associated with lower depressive symptoms, ie, a maximal difference of ∼3 points on the HDRS, which, though not statistically significant (in part, due to small sample size), represents a clinically significant difference according to the National Institute for Health and Clinical Excellence guidelines. A larger sample size will establish whether antidepressant pretreatment can prevent IL-2-induced neurobehavioral changes.

Identification of the membrane receptor of a class XIV myosin in Toxoplasma gondii.

Apicomplexan parasites exhibit a unique form of substrate-dependent motility, gliding motility, which is essential during their invasion of host cells and during their spread between host cells. This process is dependent on actin filaments and myosin that are both located between the plasma membrane and two underlying membranes of the inner membrane complex. We have identified a protein complex in the apicomplexan parasite Toxoplasma gondii that contains the class XIV myosin required for gliding motility, TgMyoA, its associated light chain, TgMLC1, and two novel proteins, TgGAP45 and TgGAP50. We have localized this complex to the inner membrane complex of Toxoplasma, where it is anchored in the membrane by TgGAP50, an integral membrane glycoprotein. Assembly of the protein complex is spatially controlled and occurs in two stages. These results provide the first molecular description of an integral membrane protein as a specific receptor for a myosin motor, and further our understanding of the motile apparatus underlying gliding motility in apicomplexan parasites.

Proteolytic processing of TgIMC1 during maturation of the membrane skeleton of Toxoplasma gondii.

Membrane skeletons play an important role in the maintenance of cell shape and integrity in many cell types. In the protozoan parasite Toxoplasma gondii this function is performed by the subpellicular network, a resilient structure composed of tightly interwoven 10-nm filaments. We report here that this network is assembled at an early stage in the development of daughter parasites. The networks of immature and mature parasites differ dramatically with respect to their stability. Although in immature parasites the network is completely solubilized by detergent, the network in mature parasites is entirely detergent-resistant. Conversion of the detergent-labile to the detergent-resistant network occurs late in daughter cell development and appears to be coupled to proteolytic processing of the carboxyl terminus of TgIMC1, the major subunit of the network filaments. A single cysteine residue in the TgIMC1 carboxyl terminus was found to be essential for this processing event. The dramatic change in resistance to detergent extraction probably reflects an overall change in structural stability of the subpellicular network that accompanies maturation of daughter parasites and allows a switch from an assembly-competent but loose structure to one that is rigid and offers mechanical strength to the mature parasite.

Daughter cell assembly in the protozoan parasite Toxoplasma gondii.

The phylum Apicomplexa includes thousands of species of obligate intracellular parasites, many of which are significant human and/or animal pathogens. Parasites in this phylum replicate by assembling daughters within the mother, using a cytoskeletal and membranous scaffolding termed the inner membrane complex. Most apicomplexan parasites, including Plasmodium sp. (which cause malaria), package many daughters within a single mother during mitosis, whereas Toxoplasma gondii typically packages only two. The comparatively simple pattern of T. gondii cell division, combined with its molecular genetic and cell biological accessibility, makes this an ideal system to study parasite cell division. A recombinant fusion between the fluorescent protein reporter YFP and the inner membrane complex protein IMC1 has been exploited to examine daughter scaffold formation in T. gondii. Time-lapse video microscopy permits the entire cell cycle of these parasites to be visualized in vivo. In addition to replication via endodyogeny (packaging two parasites at a time), T. gondii is also capable of forming multiple daughters, suggesting fundamental similarities between cell division in T. gondii and other apicomplexan parasites.