Ambient solid-state triplet-triplet annihilation upconversion in ureasil organic-inorganic hybrid hosts.

Triplet-triplet-annihilation upconversion (TTA-UC) has attracted significant attention as an approach to harvest low energy solar photons that cannot be captured by conventional photovoltaic devices. However, device integration requires the design of solid-state TTA-UC materials that combine high upconversion efficiency with long term stability. Herein, we report an efficient solid-state TTA-UC system based on organic-inorganic hybrid polymers known as ureasils as hosts for the archetypal sensitiser/emitter pair of palladium(ii) octaethylporphyrin and diphenylanthracene. The role of the ureasil structure on the TTA-UC performance was probed by varying the branching and molecular weight of the organic precursor to tune the structural, mechanical, and thermal properties. Solid-state green-to-blue UC quantum yields of up to 1.86% were observed under ambient conditions. Notably, depending on the ureasil structure, UC emission could be retained for >70 days without any special treatment, including deoxygenation. Detailed analysis of the structure-function trends revealed that while a low glass transition temperature is required to promote TTA-UC molecular collisions, a higher inorganic content is the primary factor that determines the UC efficiency and stability, due to the inherent oxygen barrier provided by the silica nanodomains.

Ultra-Small Air-Stable Triplet-Triplet Annihilation Upconversion Nanoparticles for Anti-Stokes Time-Resolved Imaging.

Image contrast is often limited by background autofluorescence in steady-state bioimaging microscopy. Upconversion bioimaging can overcome this by shifting the emission lifetime and wavelength beyond the autofluorescence window. Here we demonstrate the first example of triplet-triplet annihilation upconversion (TTA-UC) based lifetime imaging microscopy. A new class of ultra-small nanoparticle (NP) probes based on TTA-UC chromophores encapsulated in an organic-inorganic host has been synthesised. The NPs exhibit bright UC emission (400-500 nm) in aerated aqueous media with a UC lifetime of ≈1 µs, excellent colloidal stability and little cytotoxicity. Proof-of-concept demonstration of TTA-UC lifetime imaging using these NPs shows that the long-lived anti-Stokes emission is easily discriminable from typical autofluorescence. Moreover, fluctuations in the UC lifetime can be used to map local oxygen diffusion across the subcellular structure. Our TTA-UC NPs are highly promising stains for lifetime imaging microscopy, affording excellent image contrast and potential for oxygen mapping that is ripe for further exploitation.

A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder.

Objective: Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD. Methods: Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures. Results: The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events. Conclusions: This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.Reprinted from Am J Psychiatry 2021; 178:193-202, with permission from American Psychiatric Association Publishing. Copyright © 2021.

Limited transmission of SARS-CoV-2 in schools in Ireland during the 2020-2021 school year.

BackgroundThe role of schools in SARS-CoV-2 transmission has been a debated topic since the beginning of the COVID-19 pandemic.AimTo examine SARS-CoV-2 transmission in all schools in Ireland during the 2020-21 school year.MethodsIn a national descriptive cross-sectional study, we investigated PCR-confirmed cases of COVID-19 among students (aged < 20 years) and staff (aged ≥ 20 years) who attended school during their infectious period to identify school close contacts. SARS-CoV-2 PCR test results of all school close contacts were pooled to obtain an overall positivity rate and to stratify positivity rate by school setting and role (i.e. student or staff).ResultsIn total, 100,474 individuals were tested as close contacts in 1,771 schools during the 2020-21 school year. An overall close contact positivity rate of 2.4% was observed across all schools (n = 2,373 secondary cases). The highest positivity rate was seen in special schools (3.4%), followed by primary (2.5%) and post-primary schools (1.8%) (p < 0.001). Of the close contacts identified, 90.5% (n = 90,953) were students and 9.5% (n = 9,521) were staff. Overall, students had a significantly higher positivity rate than staff (2.4% vs 1.8%, p < 0.001).ConclusionThis study demonstrated that a low level of SARS-CoV-2 transmission occurred in Irish schools during the 2020-21 academic year. In the event of future pandemics, and as the COVID-19 pandemic continues, there is a need to carefully weigh up the harms and benefits associated with disrupted education to mitigate infectious disease transmission before reflexively closing classes or schools.

Multisystem inflammatory syndrome in the context of paediatric COVID-19 infection in the Republic of Ireland April 2020 to April 2021.

AIM: Our aim was to describe the epidemiology of multisystem inflammatory syndrome in children (MIS-C) in the Republic of Ireland, in the context of all cases of COVID-19 in children, during the first year of the SARS-CoV-2 pandemic. METHODS: Cases of MIS-C were identified by prospective surveillance in Irish hospitals from April 2020 to April 2021. Paediatric COVID-19 cases and outbreaks in schools or childcare facilities were notified to and routinely investigated by Public Health. Univariate and bivariate analyses were carried out in Excel, Stata and JMP statistical package. RESULTS: Fifty-four MIS-C cases (median age 7.58 years; males 57%) were identified over the study period. MIS-C incidence was higher in certain ethnicities ('black' 21.3/100,000 [95% CI 4.3-38.4]; and 'Irish Traveller' 14.7/100,000 [95% CI -5.7-35.1]) than those of 'white' ethnicity (3.4 /100,000). MIS-C cases occurred in three temporal clusters, which followed three distinct waves of community COVID-19 infection, irrespective of school closures. Formal contact tracing identified an epidemiological link with a COVID-19-infected family member in the majority of MIS-C cases (77%). In contrast, investigation of COVID-19 school outbreaks demonstrated no epidemiological link with MIS-C cases during the study period. CONCLUSION: Efforts at controlling SARS-CoV-2 transmission in the community may be a more effective means to reduce MIS-C incidence than school closures. Establishing a mandatory reporting structure for MIS-C will help delineate the role of risk factors such as ethnicity and obesity and the effect of vaccination on MIS-C incidence.

Exaggerated amygdala response to threat and association with immune hyperactivity in depression.

BACKGROUND: Depression is characterized by altered neurobiological responses to threat and inflammation may be involved in the development and maintenance of symptoms. However, the mechanistic pathways underlying the relationship between the neural underpinnings of threat, inflammation and depressive symptoms remain unknown. METHODS: Twenty participants with major depressive disorder (MDD) and 17 healthy controls (HCs) completed this study. Peripheral blood mononuclear cells (PBMCs) were collected and stimulated ex vivo with lipopolysaccharide (LPS). We then measured a broad array of secreted proteins and performed principal component analysis to compute an aggregated immune reactivity score. Subjects completed a well-validated emotional face processing task during functional magnetic resonance imaging (fMRI). Amygdala activation was measured during perception of threat for the main contrast of interest: fear > happy face. Participants completed the Mood and Anxiety Symptom Questionnaire (MASQ) and the Perceived Stress Scale (PSS). Correlation analyses between amygdala activation, the aggregate immune score, and symptom were computed across groups. A mediation analysis was also performed across groups to further explore the relationship between these three variables. RESULTS: In line with our hypotheses and with prior work, the MDD group showed greater amygdala activation in response to threat compared to the HC group [t35 = -2.038, p = 0.049]. Internal consistency of amygdala activation to threat was found to be moderate. Response to an ex vivo immune challenge was greater in MDD than HC based on the computed immune reactivity score (PC1; t35 = 2.674, p = 0.011). Amygdala activation was positively correlated with the immune score (r = 0.331, p = 0.045). Moreover, higher amygdala activation was associated with greater anxious arousal measured by the MASQ (r = 0.390, p = 0.017). Exploring the role of stress, we found that higher perceived stress was positively associated with both inflammatory response (r = 0.367, p = 0.026) and amygdala response to threat (r = 0.325, p = 0.050). Mediation analyses showed that perceived stress predicted anxious arousal, but neither inflammation nor amygdala activation fully accounted for the effect of perceived stress on anxious arousal. CONCLUSION: These data highlight the potential importance of threat circuitry hyperactivation in MDD, consistent with prior reports. We found that higher levels of inflammatory biomarkers were associated with higher amygdala activation, which in turn was associated with anxious arousal. Future research utilizing larger sample sizes are needed to replicate these preliminary results.

A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome.

OBJECTIVE: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS). METHODS: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52. RESULTS: The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction in overall seizure frequency was observed in the triheptanoin arm relative to baseline, and a 13.5% difference was observed relative to placebo (p = .58). In patients with absence seizures only (n = 9), a median 62.2% reduction in seizure frequency was observed in the triheptanoin arm relative to baseline. Only one patient with absence seizures only was present in the control group, preventing comparison. No statistically significant differences in seizure frequency were observed. Common treatment-emergent adverse events included diarrhea, vomiting, abdominal pain, and nausea, mostly mild or moderate in severity. No serious adverse events were considered to be treatment related. One patient discontinued due to status epilepticus. SIGNIFICANCE: Triheptanoin did not significantly reduce seizure frequency in patients with Glut1DS not on the ketogenic diet. Treatment was associated with mild to moderate gastrointestinal treatment-related events; most resolved following dose reduction or interruption and/or medication for treatment. Triheptanoin was not associated with any long-term safety concerns when administered at dose levels up to 35% of total daily caloric intake for up to 1 year.

Public Health Messaging and Strategies to Promote "SWIFT" Lung Cancer Detection: a Qualitative Study Among High-Risk Individuals.

Lung cancer (LC) is the most common cancer and the leading cause of cancer mortality globally. A positive association between LC incidence and socioeconomic deprivation exists. High-risk individuals are less likely to be aware of LC and to correctly appraise LC symptoms and seek medical help accordingly. This qualitative study explored strategies to promote early detection of LC among at-risk individuals living in high-incidence areas in Ireland. Five semi-structured focus groups were conducted with 46 individuals. Data were collected face-to-face in community centres and organisations in high-incidence areas in two Irish counties and analysed using inductive qualitative content analysis. Participants believed that there was insufficient information regarding LC and recommended promoting LC awareness at a young rather than old age. They favoured public health messages that are Simple, clear, and honest; Worded positively; Incorporating a shock element; Featuring a celebrity, healthcare professional, or survivor; and Targeted (SWIFT). Most participants reported becoming immune to messages on cigarette packaging and recommended using a combination of broadcast and print media within national government-run campaigns to promote LC awareness and early detection. Study findings suggest that promoting LC awareness, help-seeking, early presentation, and diagnosis can be achieved by developing and testing targeted interventions. Promoting LC awareness requires a multi-sectoral policy network, or a whole systems approach. Such approaches ought to consider the multifactorial drivers of LC risk behaviours; involve coordinated, collective actions across various stakeholders; operate across multiple agencies; and take a life course perspective.

Lessons from inter-disciplinary collaboration to mitigate SARS-CoV-2 transmission in schools, Ireland, 2020/2021, to inform health systems and multisectoral recovery.

Introduction: School closures associated with the COVID-19 pandemic resulted in the loss of educational and social supports for up to 1,000,000 students in Ireland and disproportionately affected students from lower socio-economic backgrounds. For the 2020/2021 school year, multisectoral and interdisciplinary "Schools Teams" were established within Public Health departments to maintain in-person education by minimizing transmission of SARS-CoV-2 in schools. This study aimed to describe this model and explore the experiences of Schools Team members in the East of Ireland to identify factors that influenced effective working that can be sustained in the context of health systems and multisectoral recovery. Methods: Schools Teams were comprised of multidisciplinary staff from regional Public Health departments and redeployed staff from the Education sector. Governance rested with Public Health departments. All staff operated to nationally agreed protocols following training. The experiences of the East Schools Team members were explored through an online survey and semi-structured interviews. Results: The survey response rate was 53/70 (75.7%). Participants reported clear channels of communication within the team (44, 83.0%), feeling comfortable in their role following training (43, 82.7%) and a positive team culture (51, 96.2%) as key facilitators of effective inter-disciplinary working. Insufficient administrative support and mixed messaging to schools were identified as barriers to efficient team collaboration. Discussion: The Schools Team model illustrates the potential for multisectoral partnerships to effectively address complex public health priorities and contribute toward health system resilience to health threats. By recognizing and leveraging the ability of allied sectors such as the education sector, to contribute to public health goals, countries can move toward the kind of whole-of-government approach to health recognized as key to health system resilience. The strong links between the education and public health sectors developed through this collaboration could be extended and strengthened to more effectively pursue public health priorities in school settings. More broadly, mechanisms to support multisectoral working should be developed, expanding beyond reactive interventions to proactively address key health priorities and build resilience across health systems and communities. Such collaborations would promote healthier populations by promoting and encouraging a public health perspective among other sectors and embedding "health in all policies".

Peripheral immune cell reactivity and neural response to reward in patients with depression and anhedonia.

Increased levels of peripheral cytokines have been previously associated with depression in preclinical and clinical research. Although the precise nature of peripheral immune dysfunction in depression remains unclear, evidence from animal studies points towards a dysregulated response of peripheral leukocytes as a risk factor for stress susceptibility. This study examined dynamic release of inflammatory blood factors from peripheral blood mononuclear cells (PBMC) in depressed patients and associations with neural and behavioral measures of reward processing. Thirty unmedicated patients meeting criteria for unipolar depressive disorder and 21 healthy control volunteers were enrolled. PBMCs were isolated from whole blood and stimulated ex vivo with lipopolysaccharide (LPS). Olink multiplex assay was used to analyze a large panel of inflammatory proteins. Participants completed functional magnetic resonance imaging with an incentive flanker task to probe neural responses to reward anticipation, as well as clinical measures of anhedonia and pleasure including the Temporal Experience of Pleasure Scale (TEPS) and the Snaith-Hamilton Pleasure Scale (SHAPS). LPS stimulation revealed larger increases in immune factors in depressed compared to healthy subjects using an aggregate immune score (t49 = 2.83, p = 0.007). Higher peripheral immune score was associated with reduced neural responses to reward anticipation within the ventral striatum (VS) (r = -0.39, p = 0.01), and with reduced anticipation of pleasure as measured with the TEPS anticipatory sub-score (r = -0.318, p = 0.023). Our study provides new evidence suggesting that dynamic hyper-reactivity of peripheral leukocytes in depressed patients is associated with blunted activation of the brain reward system and lower subjective anticipation of pleasure.

Elucidating the nomenclature and taxonomy of Phalaena euphemia Stoll, 1781, the type species of the genus Heraclia Hbner, [1820] (Lepidoptera, Noctuidae, Agaristinae).

The genus Heraclia (Lepidoptera, Noctuidae, Agaristinae) and the species involved in the confused nomenclature and taxonomy of the type species, Phalaena euphemia Stoll, 1781 are investigated. The rediscovery of the type specimen of Noctua geryon Fabricius, 1781, a taxon that had previously been treated as the senior synonym of euphemia, justified the revival of the latter from synonymy with the former. The type material of euphemia could not be traced and a neotype is designated to fix the published name to a physical specimen. In addition to detailed diagnoses and re-descriptions, the revised taxonomy of Heraclia euphemia and Heraclia geryon is provided and the following new synonymies are proposed: Eusemia pallida Walker, 1854 and Eusemia niveosparsa Westwood, 1881 are synonymised with H. geryon and Eusemia nugatrix Westwood, 1881 is synonymised with H. euphemia. Distributional data for each of the species are presented.

Neuroimaging correlates and predictors of response to repeated-dose intravenous ketamine in PTSD: preliminary evidence.

Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants of a randomized clinical trial of repeated-dose intravenous ketamine vs midazolam (total N = 21). In a pre-registered analysis, we tested whether changes in an a priori set of imaging measures from a target neural circuit were predictive of improvement in PTSD symptoms, using leave-one-out cross-validated elastic-net regression models (regions of interest in the target circuit consisted of the dorsal and rostral anterior cingulate cortex, ventromedial prefrontal cortex, anterior hippocampus, anterior insula, and amygdala). Improvements in PTSD severity were associated with increased functional connectivity between the ventromedial prefrontal cortex (vmPFC) and amygdala during emotional face-viewing (change score retained in model with minimum predictive error in left-out subjects, standardized regression coefficient [ß] = 2.90). This effect was stronger in participants who received ketamine compared to midazolam (interaction ß = 0.86), and persisted following inclusion of concomitant change in depressive symptoms in the analysis model (ß = 0.69). Improvement following ketamine was also predicted by decreased dorsal anterior cingulate activity during emotional conflict regulation, and increased task-free connectivity between the vmPFC and anterior insula (ßs = -2.82, 0.60). Exploratory follow-up analysis via dynamic causal modelling revealed that whilst improvement in PTSD symptoms following either drug was associated with decreased excitatory modulation of amygdala→vmPFC connectivity during emotional face-viewing, increased top-down inhibition of the amygdala by the vmPFC was only observed in participants who improved under ketamine. Individuals with low prefrontal inhibition of amygdala responses to faces at baseline also showed greater improvements following ketamine treatment. These preliminary findings suggest that, specifically under ketamine, improvements in PTSD symptoms are accompanied by normalization of hypofrontal control over amygdala responses to social signals of threat.

Organic Polymer Hosts for Triplet-Triplet Annihilation Upconversion Systems.

Triplet-triplet annihilation upconversion (TTA-UC) is a process by which a lower energy photon can be upconverted to a higher energy state. The incorporation of TTA-UC materials into solid-state hosts has enabled advances in solar energy and many other applications. The choice of host system is, however, far from trivial and often calls for a careful compromise between characteristics such as high molecular mobility, low oxygen diffusion, and high material stability, factors that often contradict one another. Here, we evaluate these challenges in the context of the state-of-the-art of primarily polymer hosts and the advantages they hold in terms of material selection and tunability of their diffusion or mechanical or thermal properties. We encourage more collaborative research between polymer scientists and photophysicists in order to further optimize the current systems and outline our thoughts for the future direction of the field.

Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder.

GEMIN5, an RNA-binding protein is essential for assembly of the survival motor neuron (SMN) protein complex and facilitates the formation of small nuclear ribonucleoproteins (snRNPs), the building blocks of spliceosomes. Here, we have identified 30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, and cerebellar ataxia harboring biallelic variants in the GEMIN5 gene. Mutations in GEMIN5 perturb the subcellular distribution, stability, and expression of GEMIN5 protein and its interacting partners in patient iPSC-derived neurons, suggesting a potential loss-of-function mechanism. GEMIN5 mutations result in disruption of snRNP complex assembly formation in patient iPSC neurons. Furthermore, knock down of rigor mortis, the fly homolog of human GEMIN5, leads to developmental defects, motor dysfunction, and a reduced lifespan. Interestingly, we observed that GEMIN5 variants disrupt a distinct set of transcripts and pathways as compared to SMA patient neurons, suggesting different molecular pathomechanisms. These findings collectively provide evidence that pathogenic variants in GEMIN5 perturb physiological functions and result in a neurodevelopmental delay and ataxia syndrome.

Promoting lung cancer awareness, help-seeking and early detection: a systematic review of interventions.

Lung cancer (LC) is the leading cause of cancer death. Barriers to the early presentation for LC include lack of symptom awareness, symptom misappraisal, poor relationship with doctors and lack of access to healthcare services. Addressing such barriers can help detect LC early. This systematic review describes the effect of recent interventions to improve LC awareness, help-seeking and early detection. This review was guided by the Cochrane Handbook for Systematic Reviews of Interventions. Electronic databases MEDLINE, CINAHL, ERIC, APA PsycARTICLES, APA PsycInfo and Psychology and Behavioral Sciences Collection were searched. Sixteen studies were included. Knowledge of LC was successfully promoted in most studies using educational sessions and campaigns. LC screening uptake varied with most studies successfully reducing decision conflicts using decision aids. Large campaigns, including UK-based campaign 'Be Clear on Cancer', were instrumental in enhancing LC awareness, promoting help-seeking and yielding an increase in chest X-rays and a decrease in the number of individuals diagnosed with advanced LC. Multimodal public health interventions, such as educational campaigns are best suited to raise awareness, reduce barriers to help-seeking and help detect LC early. Future interventions ought to incorporate targeted information using educational resources, face-to-face counselling and video- and web-based decision aids.

A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD. METHODS: Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures. RESULTS: The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events. CONCLUSIONS: This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.

Awareness and help-seeking for early signs and symptoms of lung cancer: A qualitative study with high-risk individuals.

PURPOSE: Lung cancer is the most common malignancy and the leading cause of cancer death globally. Lung cancer incidence and mortality are highest among socioeconomically deprived individuals. This study explored awareness and help-seeking for early signs and symptoms of lung cancer among high-risk individuals. METHODS: Participation was sought from multiple community centres and organisations in high-incidence and socioeconomically deprived areas in Ireland. Semi-structured focus groups were conducted with individuals at risk for lung cancer. Data were analysed using thematic analysis. RESULTS: Five focus groups were conducted with 46 participants. Two themes were identified: (i) lung cancer awareness, beliefs, and experiences and (ii) help-seeking for early signs and symptoms of lung cancer. Participants had fragmented knowledge of lung cancer and associated this malignancy with death. Symptom change, persistence, seriousness, and family history of lung cancer served as triggers to help-seeking. General practitioners were identified as the first point of contact for symptoms of concern, yet their presumed negative attitudes towards smokers served as barriers to help-seeking. Other barriers included symptom misappraisal, fear, denial, use of self-help measures, being inherently a non-help seeker, and machoism and stoicism among men. CONCLUSION: Study findings offer guidance regarding lung cancer knowledge gaps and barriers to help-seeking that ought to be considered in public health interventions aimed to promote lung cancer awareness and early detection. CLINICAL IMPLICATIONS: This study highlights the need for healthcare professionals to adopt a non-judgmental approach during consults for symptoms indicative of lung cancer. This can potentially help detect lung cancer early.

Unusual Neuroimaging in a Case of Rapidly Progressive Juvenile-Onset Krabbe Disease.

Krabbe disease is a progressive neurologic disorder caused by deficiency of the lysosomal enzyme galactocerebrosidase. The disease commonly has an early-infantile onset, but can have late-infantile, juvenile, or adult-onset phenotypes. Classic computed tomography (CT) and magnetic resonance imaging (MRI) findings in Krabbe have been well described. We report a patient, ultimately diagnosed with juvenile-onset Krabbe, who presented with atypical CT imaging and rapid disease progression. Our patient was a previously healthy and developmentally appropriate female who presented at 3 years 4 months of age with ataxia and motor regression that had progressed over the course of 6 weeks without an identifiable catalyst. CT, performed in the emergency setting, demonstrated extensive white matter hyperdensity. Subsequent MRI showed T2 hyperintensity of the white matter corresponding to the areas of hyperdensity on the CT, as well as enhancement of multiple cranial nerves bilaterally, suggestive of Krabbe disease. Enzymatic testing demonstrated low galactocerebrosidase activity and molecular testing of GALC revealed compound heterozygosity for 2 known pathogenic mutations, consistent with a diagnosis of Krabbe Disease. This included the common 30-kb deletion and a known pathogenic mutation associated with juvenile/adult-onset disease. Our patient's diffuse hyperdensity on CT offers a new radiographic finding to include in the repertoire of Krabbe imaging, and thus aide in the diagnostic evaluation. The rapidity of progression our patient demonstrated is additionally unique and should be considered in the identification of juvenile Krabbe as well as the complicated decision-making process regarding potential treatments.