Distinguishing viral versus bacterial lower respiratory tract infection (LRTI) is challenging. We previously developed a rapid, host response-based test (Biomeme HR-B/V assay) using peripheral blood samples to identify viral versus bacterial infection. We assessed the performance of this assay when using nasopharyngeal (NP) samples.

Patients with LRTI were enrolled, and a NP swab sample was run using the HR-B/V assay (assessing 24 gene targets) on the FranklinTM platform. The performance of the prior classifier at identifying viral versus bacterial infection was assessed. A novel predictive model was generated for NP samples using the same 24 targets. Results were validated using external datasets with nasal/NP RNA sequence data.

Nineteen patients (median age 62 years, 52.1% male) were included. When using the prior HR-B/V classifier on NP samples of 19 patients with LRTI (12 viral, 7 bacterial), the area under the receiver operator curve (AUC) for viral versus bacterial infection was 0.786 (0.524–1), with accuracy 0.79 (95% CI 0.57–0.91), positive percent agreement (PPA) 0.43 (95% CI 0.16–0.75), and negative percent agreement (NPA) 1.00 (95% CI 0.76–1). The novel model had AUC 0.881 (95% CI 0.726–1), accuracy 0.84 (95% CI 0.62–0.94), PPA 0.86 (95% CI 0.49–0.97), and NPA 0.83 (95% CI 0.55–0.95) for bacterial infection. Validation in two external datasets showed AUC of 0.932 (95% CI 0.90–0.96) and 0.915 (95% CI 0.88–0.95).

We show that host response in the nasopharynx can distinguish viral versus bacterial LRTI. These findings need to be replicated in larger cohorts with diverse LRTI etiologies.

Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

Adverse childhood experiences (ACEs) are associated with physical and mental health difficulties in adulthood. This study examines the associations of ACEs with functional impairment and life stress among military personnel, a population disproportionately affected by ACEs. We also evaluate the extent to which the associations of ACEs with functional outcomes are mediated through internalizing and externalizing disorders.

The sample included 4,666 STARRS Longitudinal Study (STARRS-LS) participants who provided information about ACEs upon enlistment in the US Army (2011–2012). Mental disorders were assessed in wave 1 (LS1; 2016–2018), and functional impairment and life stress were evaluated in wave 2 (LS2; 2018–2019) of STARRS-LS. Mediation analyses estimated the indirect associations of ACEs with physical health-related impairment, emotional health-related impairment, financial stress, and overall life stress at LS2 through internalizing and externalizing disorders at LS1.

ACEs had significant indirect effects via mental disorders on all functional impairment and life stress outcomes, with internalizing disorders displaying stronger mediating effects than externalizing disorders (explaining 31–92% vs 5–15% of the total effects of ACEs, respectively). Additionally, ACEs exhibited significant direct effects on emotional health-related impairment, financial stress, and overall life stress, implying ACEs are also associated with these longer-term outcomes via alternative pathways.

This study indicates ACEs are linked to functional impairment and life stress among military personnel in part because of associated risks of mental disorders, particularly internalizing disorders. Consideration of ACEs should be incorporated into interventions to promote psychosocial functioning and resilience among military personnel.

Adult medulloblastoma is a rare entity with a predilection for the development of radiation-induced malignant glioma (RIMG). Management of RIMG in the setting of prior craniospinal irradiation is a challenging scenario.

We report a case of a 51-year-old male with short-interval development of multicentric malignant glioma with MET mutation who previously underwent craniospinal radiation for adult medulloblastoma. Due to radiographic findings, linear accelerator (LINAC)-based fractionated stereotactic/IMRT was delivered to the right temporal lesion alongside systemic therapy. The patient had interval development of an IDH wildtype, high-grade left cerebellar glioma and underwent surgical resection and subsequent gamma knife stereotactic radiosurgery (GKRS) to the cavity.

GKRS targeting the surgical cavity was delivered with a fractionated regimen of 27 Gy in 3 fractions to the margin. One year after completion of GKRS, the patient had not developed any symptomatic radiation necrosis or neuroimaging changes reflective of treatment toxicity. In this patient, GKRS to minimise the integral dose exposure of normal tissues surrounding the target volume proved to be particularly advantageous in the setting of prior craniospinal irradiation.

RIMG poses significant challenges for radiation oncologists, particularly in the reirradiation setting. Decision-making involving multidisciplinary input balanced the necessity of dose escalation achieved by GKRS, while minimising the cumulative dose in the setting of prior craniospinal irradiation.

Targeting the glutamatergic system is posited as a potentially novel therapeutic strategy for psychotic disorders. While studies in subjects indicate that antipsychotic medication reduces brain glutamatergic measures, they were unable to disambiguate clinical changes from drug effects.

To address this, we investigated the effects of a dopamine D2 receptor partial agonist (aripiprazole) and a dopamine D2 receptor antagonist (amisulpride) on glutamatergic metabolites in the anterior cingulate cortex (ACC), striatum and thalamus in healthy controls.

A double-blind, within-subject, cross-over, placebo-controlled study design with two arms (n = 25 per arm) was conducted. Healthy volunteers received either aripiprazole (up to 10 mg/day) for 7 days or amisulpride (up to 400 mg/day) and a corresponding period of placebo treatment in a pseudo-randomised order. Magnetic resonance spectroscopy (1H-MRS) was used to measure glutamatergic metabolite levels and was carried out at three different time points: baseline, after 1 week of drug and after 1 week of placebo. Values were analysed as a combined measure across the ACC, striatum and thalamus.

Aripiprazole significantly increased glutamate + glutamine (Glx) levels compared with placebo (β = 0.55, 95% CI [0.15, 0.95], P = 0.007). At baseline, the mean Glx level was 8.14 institutional units (s.d. = 2.15); following aripiprazole treatment, the mean Glx level was 8.16 institutional units (s.d. = 2.40) compared with 7.61 institutional units (s.d. = 2.36) for placebo. This effect remained significant after adjusting for plasma parent and active metabolite drug levels. There was an observed increase with amisulpride that did not reach statistical significance.

One week of aripiprazole administration in healthy participants altered brain Glx levels as compared with placebo administration. These findings provide novel insights into the relationship between antipsychotic treatment and brain metabolites in a healthy participant cohort.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Diagnosing HIV-Associated Neurocognitive Disorders (HAND) requires attributing neurocognitive impairment and functional decline at least partly to HIV-related brain effects. Depressive symptom severity, whether attributable to HIV or not, may influence self-reported functioning. We examined longitudinal relationships among objective global cognition, depressive symptom severity, and self-reported everyday functioning in people with HIV (PWH).

Longitudinal data from 894 PWH were collected at a university-based research center (2002–2016). Participants completed self-report measures of everyday functioning to assess both dependence in instrumental activities of daily living (IADL) and subjective cognitive difficulties at each visit, along with depressive symptom severity (BDI-II). Multilevel modeling examined within- and between-person predictors of self-reported everyday functioning outcomes.

Participants averaged 6 visits over 5 years. Multilevel regression showed a significant interaction between visit-specific global cognitive performance and mean depression symptom severity on likelihood of dependence in IADL (p = 0.04), such that within-person association between worse cognition and greater likelihood of IADL dependence was strongest among individuals with lower mean depressive symptom severity. In contrast, participants with higher mean depressive symptom severity had higher likelihoods of IADL dependence regardless of cognition. Multilevel modelling of subjective cognitive difficulties showed no significant interaction between global cognition and mean depressive symptom severity (p > 0.05).

The findings indicate a link between cognitive abilities and IADL dependence in PWH with low to moderate depressive symptoms. However, those with higher depressive symptoms severity report IADL dependence regardless of cognitive status. This is clinically significant because everyday functioning is measured through self-report rather than performance-based assessments.

Historically, it has been proposed that functional neurological symptoms occur more frequently on the left side of the body due to a distinct body representation and emotional processing of the right hemisphere, yet objective imaging data to support this are lacking. We aimed to investigate whether patients with acute left-sided symptoms (right hemisphere) suspected of having a minor stroke are more likely to show negative diffusion-weighted imaging (DWI) compared to those with right-sided symptoms.

Data are from the SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment) multicenter prospective cohort study conducted between 2013 and 2017. Patients with mild persistent unilateral hemiparesis and/or hemisensory symptoms (National Institute of Health Stroke Scale ≤ 3) and available DWI were included. The primary outcome was the proportion of patients with a negative DWI.

Of 1731 patients, 584 (30.8%) were included. Of these, 310 (53.1%) patients presented with left-sided symptoms and 274 (46.9%) with right-sided symptoms. Overall, 214 (36.6%) patients had a negative DWI, 126 (58.9%) with left-sided symptoms and 88 (41.1%) with right-sided symptoms: risk ratio (RR) 1.27 (95% CI = 1.02–1.57). Left-sided hemiparesis was associated with negative DWI (RR 1.42 [95% CI = 1.08–1.87]), while left-sided hemisensory symptoms were not (RR 1.11 [95% CI = 0.87–1.41]). There was no effect modification by age or sex on this association (Pinteraction 0.787 and 0.057, respectively).

Unilateral left-sided neurological symptoms were more frequently associated with negative DWI compared to right-sided symptoms in suspected minor stroke patients. This observation is exploratory, as the final diagnosis in DWI-negative cases was not established.