Prior Exposure Research Articles

Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60

BackgroundOngoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher...

Palliative care in the older adult Veteran.

The United States military Veteran population is aging, thus leading to a group of Veterans who have functional disabilities, sensory impairments, and geriatric syndromes such as frailty and dementia. As they age, Veterans are also at risk of being diagnosed with a variety of serious illnesses, such as neurologic conditions and cancers, some of which are a consequence of prior military service or toxic exposures. In addition to frailty and multicomplexity, Veterans have higher rates of mental health disorders than civilians. All of these factors lead to a population of older Veterans who can benefit from palliative care involvement. Major tenets of palliative care focus on enhancing quality of life and provision of goal-concordant care, which are also aims of the services provided by the Veterans Health Administration (VHA) to all enrolled Veterans. Palliative care involvement in the holistic care of Veterans can deliver expert pain and symptom management, promote Veteran-centric plans of care, and provide crucial support of complex medical decision making often required for those Veterans with serious illness. In this review article, we discuss the unique palliative care needs of Veterans as they age, while also sharing information about relevant resources and services provided by the VHA.

Low Temperature Tolerance of Peach Flower Buds and Shoot Tissues Is Differentially Influenced by Freezing and High Temperature Exposure

In northern temperate zones, peach trees are vulnerable to cold temperature injury in the fall, particularly as climate change prolongs warm weather in the fall and potentially delays the onset of cold acclimation. Four experiments evaluated how cold acclimation of flower buds and shoot phloem, cambium, and xylem is affected by exposure to varying temperatures in the fall. One-year-old peach shoots from trees grown in Maine, USA, were collected from October through November, exposed to 1, 3, or 6 days of low, high, and freezing temperatures, and subjected to stepwise controlled freezing to about −30 °C. Injury was visually quantified as oxidative browning of flower buds and shoot tissues. High temperature exposure, even of a single day, decreased cold tolerance of flower buds and shoot tissues until late November, when high temperatures only minimally decreased cold hardiness. In mid-November, increasing the duration of high temperature exposure from 1 to 3 days decreased cambium and phloem hardiness, but hardiness in flower buds was not further decreased by the longer duration of 3 days. By late November, hardiness in flower buds, cambium, and phloem was less responsive to high temperature, and was increased by prior exposure to 6 days of freezing. After high temperature, xylem lost hardiness to a small degree in mid-October and late November, but in mid-November this occurred in only one experiment. In this study, deacclimation during high temperature in the fall was greater in cambium and phloem than in flower buds and at times greater than in xylem.

The effects of exposure and explicit stereotypes on veracity judgments of Polish-accented English speech: A preregistered close replication and extension of Boduch-Grabka & Lev-Ari (2021)

Abstract Boduch-Grabka and Lev-Ari (2021) showed that so-called “native” British-English speakers judged statements produced by Polish-accented English speakers as less likely to be true than statements produced by “native” speakers and that prior exposure to Polish-accented English speech modulates this effect. Given the real-world consequences of this study, as well as our commitment to assessing and mitigating linguistic biases, we conducted a close replication, extending the work by collecting additional information about participants’ explicit biases towards Polish migrants in the UK. We did not reproduce the original pattern of results, observing no effect of speaker accent or exposure on comprehension or veracity. In addition, the measure of explicit bias did not predict differential veracity ratings for Polish- and British-accented speech. Although the current pattern of results differs from that of the original study, our finding that neither comprehension nor veracity were impacted by accent or exposure condition is not inconsistent with the Boduch-Grabka and Lev-Ari (2021) processing difficulty account of the accent-based veracity judgment effect. We explore possible explanations for the lack of replication and future directions for this work.

Knowledge, protective behaviours, and perception of Lyme disease in an area of emerging risk: results from a cross-sectional survey of adults in Ottawa, Ontario

BackgroundThe number of Lyme disease risk areas in Canada is growing. In regions with emerging tick populations, it is important to emphasize peridomestic risk and the importance of protective behaviours in local public health communication. This study aims to identify characteristics associated with high levels of Lyme disease knowledge and adoption of protective behaviours among residents in the Ottawa, Ontario region.MethodsA geographically stratified web survey was conducted in November 2020 (n = 2018) to determine knowledge, attitudes, and practices regarding Lyme disease among adult residents. Responses were used to calculate: (i) composite scores for knowledge and adoption of protective practices; and (ii) an exposure risk index based on reported activity in woodlands during the spring-to-fall tick exposure risk period.Results60% of respondents had a high knowledge of Lyme disease, yet only 14% indicated they often use five or more measures to protect themselves. Factors strongly associated with a high level of Lyme disease knowledge included being 55 or older (Odds Ratio (OR) = 2.04), living on a property with a yard (OR = 3.22), having a high exposure index (OR = 1.59), and knowing someone previously infected with Lyme disease (OR = 2.05). Strong associations with the adoption of a high number of protective behaviours were observed with membership in a non-Indigenous racialized group (OR = 1.70), living on a property with a yard (OR = 2.37), previous infection with Lyme disease (OR = 2.13), prior tick bite exposure (OR = 1.62), and primarily occupational activity in wooded areas (OR = 2.31).ConclusionsThis study highlights the dynamics between Lyme disease knowledge, patterns of exposure risk awareness, and vigilance of personal protection in a Canadian region with emerging Lyme disease risk. Notably, this study identified gaps between perceived local risk and protective behaviours, presenting opportunities for targeted enhanced communication efforts in areas of Lyme disease emergence.

Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study.

Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA. Adults with RA who initiated treatment with once daily UPA (15mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events. A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4-71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month3) and sustained improvements up to 6months were observed for all PROs. The safety profile was consistent with previous reports. Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit-risk profile. NCT04574492.

Converging Effects of Chronic Pain and Binge Alcohol Consumption on Anterior Insular Cortex Neurons Projecting to the Dorsolateral Striatum in Male Mice.

Chronic pain and alcohol use disorder (AUD) are highly comorbid, and patients with chronic pain are more likely to meet the criteria for AUD. Evidence suggests that both conditions alter similar brain pathways, yet this relationship remains poorly understood. Prior work shows that the anterior insular cortex (AIC) is involved in both chronic pain and AUD. However, circuit-specific changes elicited by the combination of pain and alcohol use remain understudied. The goal of this work was to elucidate the converging effects of binge alcohol consumption and chronic pain on AIC neurons that send projections to the dorsolateral striatum (DLS). Here, we used the Drinking-in-the-Dark (DID) paradigm to model binge-like alcohol drinking in mice that underwent spared nerve injury (SNI), after which whole-cell patch-clamp electrophysiological recordings were performed in acute brain slices to measure intrinsic and synaptic properties of AIC→DLS neurons. In male, but not female, mice, we found that SNI mice with no prior alcohol exposure consumed less alcohol compared with sham mice. Electrophysiological analyses showed that AIC→DLS neurons from SNI-alcohol male mice displayed increased neuronal excitability and increased frequency of miniature excitatory postsynaptic currents. However, mice exposed to alcohol prior to SNI consumed similar amounts of alcohol compared with sham mice following SNI. Together, our data suggest that the interaction of chronic pain and alcohol drinking have a direct effect on both intrinsic excitability and synaptic transmission onto AIC→DLS neurons in mice, which may be critical in understanding how chronic pain alters motivated behaviors associated with alcohol.

Abstract A051: Prior chlamydial infection and ovarian cancer risk by tumor p53 expression

Abstract A051: Prior chlamydial infection and ovarian cancer risk by tumor p53 expression

Model biological systems demonstrate the inducibility of pathways that strongly reduce cryoprotectant toxicity

Cryoprotectant toxicity is a limiting factor for the cryopreservation of many living systems. We were moved to address this problem by the potential of organ vitrification to relieve the severe shortage of viable donor organs available for human transplantation. The M22 vitrification solution is presently the only solution that has enabled the vitrification and subsequent transplantation with survival of large mammalian organs, but its toxicity remains an obstacle to organ stockpiling for transplantation. We therefore undertook a series of exploratory studies to identify potential pretreatment interventions that might reduce the toxic effects of M22. Hormesis, in which a living system becomes more resistant to toxic stress after prior subtoxic exposure to a related stress, was investigated as a potential remedy for M22 toxicity in yeast, in the nematode worm C. elegans, and in mouse kidney slices. In yeast, heat shock pretreatment increased survival by 18-fold after exposure to formamide and by over 9-fold after exposure to M22 at 30 °C; at 0 °C and with two-step addition, treatment with 90% M22 resulted in 100% yeast survival. In nematodes, surveying a panel of pretreatment interventions revealed 3 that conferred nearly total protection from acute whole-worm M22-induced damage. One of these protective pretreatments (exposure to hydrogen peroxide) was applied to mouse kidney slices in vitro and was found to strongly protect nuclear and plasma membrane integrity in both cortical and medullary renal cells exposed to 75–100% M22 at room temperature for 40 min. These studies demonstrate for the first time that endogenous cellular defenses, conserved from yeast to mammals, can be marshalled to substantially ameliorate the toxic effects of one of the most toxic single cryoprotectants and the toxicity of the most concentrated vitrification solution so far described for whole organs.

Bees display limited acclimation capacity for heat tolerance.

Bees are essential pollinators and understanding their ability to cope with extreme temperature changes is crucial for predicting their resilience to climate change, but studies are limited. We measured the response of the critical thermal maximum (CTMax) to short-term acclimation in foragers of six bee species from the Greek island of Lesvos, which differ in body size, nesting habit, and level of sociality. We calculated the acclimation response ratio as a metric to assess acclimation capacity and tested whether bees' acclimation capacity was influenced by body size and/or CTMax. We also assessed whether CTMax increases following acute heat exposure simulating a heat wave. Average estimate of CTMax varied among species and increased with body size but did not significantly shift in response to acclimation treatment except in the sweat bee Lasioglossum malachurum. Acclimation capacity averaged 9% among species and it was not significantly associated with body size or CTMax. Similarly, the average CTMax did not increase following acute heat exposure. These results indicate that bees might have limited capacity to enhance heat tolerance via acclimation or in response to prior heat exposure, rendering them physiologically sensitive to rapid temperature changes during extreme weather events. These findings reinforce the idea that insects, like other ectotherms, generally express weak plasticity in CTMax, underscoring the critical role of behavioral thermoregulation for avoidance of extreme temperatures. Conserving and restoring native vegetation can provide bees temporary thermal refuges during extreme weather events.

Severe Intraocular Inflammation Following Intravitreal Faricimab

Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

Inherited terrestrial cosmogenic nuclides in landscapes of selective glacial erosion: lessons from Lochnagar, Eastern Grampian Mountains, Scotland

ABSTRACTInheritance from prior exposure often complicates the interpretation of terrestrial cosmogenic nuclide (TCN) inventories in glaciated terrain. Lochnagar, a mountain in eastern Scotland, holds a clear geomorphological record of corrie glaciation and the thinning of the last Scottish ice sheet over the last ~15 ka. Yet attempts to date the main stages in deglaciation after sampling of 21 granite boulders for 10Be, 26Al and 14C from corrie moraines, an ice sheet lateral moraine and boulder spreads revealed widespread, but variable, TCN inheritance. Only the youngest boulder ages fit within the range of expected deglaciation ages. To identify the sources of geological uncertainty, we provide simple models of ice cover duration and erosion histories for plateau, corrie and strath landscape domains, identify the variable nuclide inheritance that derives from different sources for boulders in these domains, and outline the effects of rotation, splitting and erosion of boulders during glacial transport. The combined effects increase clustering around arbitrary mean TCN values that exceed deglaciation ages. A further implication is that boulders have survived beneath overriding ice sheets. Such boulder trapping at Lochnagar may have resulted from topographic controls on katabatic winds and surface ablation acting on a thinning, cold‐based ice sheet.

A Review of Hepatitis B Reactivation Risk on Immunosuppressants with a Focus on Newer Immunomodulators

Abstract Purpose of Review Hepatitis B virus reactivation (HBVr) can complicate the use of immunosuppressive, antiviral, and chemotherapeutic medications in individuals with a history of prior exposure to HBV or chronic infection. Timely management is crucial to prevent fatalities. This review focuses on the various classes of biologics linked to the risk of HBVr, with emphasis on newer immunosuppressive and immunomodulator therapies. Recent Findings Immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, and chimeric antigen receptor T-cell immunotherapies are associated with a high risk of hepatitis B virus reactivation (HBVr) in patients who are hepatitis B surface antigen-positive (HbsAg-positive). This risk decreases significantly when patients start nucleoside analogue (NA) prophylaxis. It is recommended to use NA prophylaxis alongside these medications and closely monitor for reactivation upon discontinuation of NA prophylaxis. Summary To minimize the risk of reactivation when starting immunosuppressive, antiviral, and chemotherapeutic agents in individuals at high, intermediate, and low risk for hepatitis B virus reactivation (HBVr), it is crucial to employ specific strategies for risk assessment, monitoring, and management.

Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response

BackgroundThe inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard chemotherapies.MethodsWe optimized drug screen methods on 5–11 PDOs per condition of the complete set of 23 PDOs from patients treated for metastatic colorectal cancer (mCRC). PDOs were exposed to 5-fluorouracil (5-FU), irinotecan- and oxaliplatin-based chemotherapy. We compared medium with and without N-acetylcysteine (NAC), different readouts and different combination treatment set-ups to capture the strongest association with patient response. We expanded the screens using the optimized methods for all PDOs. Organoid sensitivity was correlated to the patient’s response, determined by % change in the size of target lesions. We assessed organoid sensitivity in relation to prior exposure to chemotherapy, mutational status and sidedness.ResultsDrug screen optimization involved excluding N-acetylcysteine from the medium and biphasic curve fitting for 5-FU & oxaliplatin combination screens. CellTiter-Glo measurements were comparable with CyQUANT and did not affect the correlation with patient response. Furthermore, the correlation improved with application of growth rate metrics, when 5-FU & oxaliplatin was screened in a ratio, and 5-FU & SN-38 using a fixed dose of SN-38. Area under the curve was the most robust drug response curve metric. After optimization, organoid and patient response showed a correlation coefficient of 0.58 for 5-FU (n = 6, 95% CI -0.44,0.95), 0.61 for irinotecan- (n = 10, 95% CI -0.03,0.90) and 0.60 for oxaliplatin-based chemotherapy (n = 11, 95% CI -0.01,0.88). Median progression-free survival of patients with resistant PDOs to oxaliplatin-based chemotherapy was significantly shorter than sensitive PDOs (3.3 vs 10.9 months, p = 0.007). Increased resistance to 5-FU in patients with prior exposure to 5-FU/capecitabine was adequately reflected in PDOs (p = 0.003).ConclusionsOur study emphasizes the critical impact of the screening methods for determining correlation between PDO drug screens and mCRC patient outcomes. Our 5-step optimization strategy provides a basis for future research on the clinical utility of PDO screens.

Infective complications in the renal transplant recipients

Infections remain a common complication of solid-organ transplantation and are a major factor of morbidity and mortality in renal transplant recipients. The incidence of infection in renal transplant patients is directly related to the net immunosuppressive effect achieved and the duration of the administration of immunosuppressive therapy. The major types of infections can be categorized according to the time post-transplant during which they occur: in the first month after transplantation post-surgical bacterial infections and in the period from one to four months post-transplant opportunistic infections, overall cytomegalovirus; late infections, beyond 6-12 months, are community-acquired infections. Opportunistic infections (like Pneumocystis carini, Listeria monocytogenes, and Aspergillus fumigatus) most frequently occur in the first 12 months post-transplant and can be modulated by prior exposures and the use of prophylaxis.

Posttraumatic stress and probable post traumatic stress disorder as it relates to smoking behavior and beliefs among trauma exposed hispanic persons who smoke.

There has been little scientific effort to evaluate the associations between cigarette smoking and cessation-related constructs and exposure to traumatic events, posttraumatic stress, and Posttraumatic Stress Disorder (PTSD) symptoms among Hispanic persons who smoke in the United States (US). Such trauma-related factors may pose unique difficulties for Hispanic persons who smoke and possess a desire to quit. As such, the present investigation sought to fill this gap in the literature and examine posttraumatic stress and probable PTSD in terms of their relations with several clinically significant smoking constructs among trauma-exposed Hispanic persons who smoke from the United States. Participants included 228 Spanish-speaking Hispanic persons who endorsed prior traumatic event exposure and smoked combustible cigarettes daily (58.3% female, Mage= 32.1 years, SD = 9.65). Results indicated that posttraumatic stress symptoms were related to increased cigarette dependence, perceived barriers for smoking cessation, and more severe problems when trying to quit with effect sizes ranging from small to moderate in adjusted models. Additionally, Hispanic persons who smoke with probable PTSD compared to those without probable PTSD showcased a statistically effect for perceived barriers for cessation (p < .008) and a severity of problems when trying to quit (p < .001). No effect was evident for cigarette dependence after alpha correction. Overall, the present study offers novel empirical evidence related to the role of posttraumatic stress symptoms and PTSD among Hispanic persons who smoke in the US. Such findings highlight the need to expand this line of research to better understand the role of posttraumatic stress and PTSD among Hispanic persons who smoke which can inform smoking cessation treatments for Hispanic persons who smoke experiencing trauma-related symptomology.

Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection

The yellow fever 17D vaccine (YF17D) is highly effective but is frequently administered to individuals with pre-existing cross-reactive immunity, potentially impacting their immune responses. Here, we investigate the impact of pre-existing flavivirus immunity induced by the tick-borne encephalitis virus (TBEV) vaccine on the response to YF17D vaccination in 250 individuals up to 28 days post-vaccination (pv) and 22 individuals sampled one-year pv. Our findings indicate that previous TBEV vaccination does not affect the early IgM-driven neutralizing response to YF17D. However, pre-vaccination sera enhance YF17D virus infection in vitro via antibody-dependent enhancement (ADE). Following YF17D vaccination, TBEV-pre-vaccinated individuals develop high amounts of cross-reactive IgG antibodies with poor neutralizing capacity. In contrast, TBEV-unvaccinated individuals elicit a non-cross-reacting neutralizing response. Using YF17D envelope protein mutants displaying different epitopes, we identify quaternary dimeric epitopes as the primary target of neutralizing antibodies. Additionally, TBEV-pre-vaccination skews the IgG response towards the pan-flavivirus fusion loop epitope (FLE), capable of mediating ADE of dengue and Zika virus infections in vitro. Together, we propose that YF17D vaccination conceals the FLE in individuals without prior flavivirus exposure but favors a cross-reactive IgG response in TBEV-pre-vaccinated recipients directed to the FLE with potential to enhance dengue virus infection.

Cholera toxin and O-specific polysaccharide immune responses after oral cholera vaccination with Dukoral in different age groups of Bangladeshi participants.

Vaccination is important to prevent cholera. There are limited data comparing anti-O-specific polysaccharide (OSP) and anti-cholera toxin-specific immune responses following oral whole-cell with cholera toxin B-subunit (WC-rBS) vaccine (Dukoral, Valneva) administration in different age groups. An understanding of the differences is relevant because young children are less well protected by oral cholera vaccines than older children and adults. We compared responses in 50 adults and 49 children (ages 2 to <18) who were administered two doses of WC-rBS at a standard 14-day interval. All age groups had significant IgA and IgG plasma-blast responses to the OSP and cholera toxin B-subunit (CtxB) antigens that peaked 7 days after vaccination. However, in adults and older children (ages 5 to <18), antibody responses directed at the OSP antigen were largely IgA and IgG, with a minimal IgM response, while younger children (ages 2 to <5) mounted significant increases in IgM with minimal increases in IgA and IgG antibody responses 30 days after vaccination. In adults, anti-OSP and CtxB memory B-cell responses were detected after completion of the vaccination series, while children only mounted CtxB-specific IgG memory B-cell responses and no OSP-memory B-cell responses. In summary, children and adults living in a cholera endemic area mounted different responses to the WC-rBS vaccine, which may be a result of more prior exposure to Vibrio cholerae in older participants. The absence of class-switched antibody responses and memory B-cell responses to OSP may explain why protection wanes more rapidly after vaccination in young children compared to older vaccinees.IMPORTANCEVaccination is an important strategy to prevent cholera. Though immune responses targeting the OSP of V. cholerae are believed to mediate protection against cholera, there are limited data on anti-OSP responses after vaccination in different age groups, which is important as young children are not well protected by current oral cholera vaccines. In this study, we found that adults mounted memory B-cell responses to OSP, which were not seen in children. Adults and older children mounted class-switched (IgG and IgA) serum antibody responses to OSP, which were not seen in young children who had only IgM responses to OSP. The lack of class-switched antibody responses and memory B-cell responses to OSP in younger participants may be due to lack of prior exposure to V. cholerae and could explain why protection wanes more rapidly after vaccination in young children.

Predictors of early adulthood insomnia following exposure to a single mass violence attack during adolescence: 7–13 year follow-up from the Utøya and HUNT studies

ABSTRACT Background: The long-term impact of mass violence attacks is practically unknown, especially in children and adolescents. In a previous study, we found that 8.5 years after a terror attack targeting mainly adolescents, nearly half of the survivors met diagnostic criteria for insomnia. Objectives: The aims of this study were to investigate: (1) whether exposure to a single mass violence event during adolescence increases the risk of insomnia almost a decade later above that expected for a non-exposed population; and (2) whether prior interpersonal violence exposure and early post-traumatic reactions predict later insomnia. Method: Participants were survivors of the 2011 Utøya Island terrorist attack (n = 279) and controls from the HUNT Norwegian general population study (n = 35,664). Early adulthood insomnia was assessed using four items from the Karolinska Sleep Questionnaire 8.5 years after the attack. Participants who had also completed earlier data collection waves for both studies (n = 116 and 2382, respectively) were included in logistic regression models testing the associations between predictors during adolescence and later insomnia. Results: Nearly a decade after the Utøya attack, 38.4% (n = 56) of the survivors reported symptoms of insomnia indicative of probable insomnia compared to 20.5% (n = 5771) of controls. Terror exposure during adolescence was a significant predictor of later insomnia [odds ratio (OR) = 3.18, 95% confidence interval (CI) = 2.05–4.87, p < .001]. Early post-trauma symptoms of anxiety and depression (OR = 1.34, 95% CI = 1.02–1.76, p = .033) and weekly headaches (OR = 1.64, 95% CI = 1.08–2.47, p = .018) were also significant predictors while controlling for background factors and other predictors. Conclusion: Long-term assessment and treatment are needed for survivors of mass violence to improve resilience and recovery.

Allergic Contact Dermatitis to Octyl Cyanoacrylate Skin Glue After Surgical Wound Closure: A Systematic Review.

The rising incidence of allergic contact dermatitis (ACD) after cyanoacrylate adhesive use necessitates a comprehensive understanding of its clinical presentations, risk factors, and management. In this systematic review, we conducted an exhaustive search following PRISMA guidelines within Medline and PubMed databases to identify studies reporting cases of ACD resulting from cyanoacrylate adhesive application in wound closure. A total of 47 studies, covering 193 ACD cases, were included in our analysis. These cases involved 35 male, 120 female patients, and 38 cases without gender information (M:F ratio = 1:3.43), with ages ranging from 7 to 92 years (mean age 43.9 years). The majority of cases (n = 140) were part of 6 orthopedic studies, focusing on joint replacements (n = 68), orthopedic surgeries (n = 38), and breast surgeries (n = 29). The remaining 58 cases encompassed various surgical procedures. Common clinical manifestations included swelling, pruritic rash, erythema, vesicles, and itching around the surgical sites, typically appearing around 10 days post-adhesive application (within a range of 6 hours to 6 weeks). Patients with prior exposure to 2-octyl cyanoacrylate tended to exhibit earlier symptoms. Similar rates of dermatitis were observed across different adhesive brands, suggesting brand independence. Treatment strategies involved adhesive removal, administration of steroids and antihistamines, meticulous wound care, and, in some cases, surgical intervention. Notably, 3.1% of the 193 cases required surgical intervention. Risk factors, including a history of atopic dermatitis, high body mass index, diabetes, prior adhesive exposure, and surgical history, were identified in the studies. Patch tests confirmed 2-octyl cyanoacrylate as the allergen in 21 studies. Our review aims to enhance health care professionals' understanding of ACD resulting from the use of cyanoacrylate adhesive, facilitating improved postsurgical management and prevention strategies. Recognizing diverse risk factors, understanding varying clinical presentations, distinguishing ACD from infection, and employing appropriate treatment approaches are essential for achieving optimal outcomes in such cases.