Long-term benefits of targeted micronutrition with the holoBLG lozenge in house dust mite allergic patients

Summary Purpose The long-term effects of targeted micronutrition with the holoBLG lozenge in house dust mite (HDM) allergic rhinoconjunctivitis (ARC) patients were evaluated at a follow-up visit in an allergen exposure chamber (AEC). Methods Patients who were supplemented for 3‑months with the holoBLG lozenge in a previous study with two controlled HDM-AEC challenges [visits: V1, V3] were recruited for a third AEC challenge (V5) 7–8 months after cessation of supplementation. Symptoms (nose, conjunctival, bronchial, others), well-being, and lung function parameters were recorded exactly as in the previous study. Primary endpoint was change in median Total Nasal Symptom Score (TNSS) at V5 compared to V1. Secondary endpoints included e.g. change in median Total Symptom Score (TSS) and the exploratory analysis of temporal evolution of symptom scores using linear mixed effects models. Results Of the 32 patients included in the original study, 27 could be recruited for the follow-up visit with a third AEC challenge. An improvement of 20% (p = 0.15) in the primary endpoint TNSS [V1: 2.5 (interquartile range [IQR]: 1–4), V5: 2.0 (IQR: 1–3)] was observed; 40% (p = 0.04) improvement was seen for the TSS [V1: 5.0 (IQR: 3–9), V5: 3.0 (IQR: 2–5.5)]. Analysis of temporal evolution of all symptom scores, and the personal well-being revealed sustained, clinically meaningful improvement at V5 compared to V1. No relevant lung function parameter differences were observed. Conclusions Sustained long-term reduction of TNSS (primary endpoint) and sustained long-term improvement of secondary endpoints (temporal evolution of all symptom scores and well-being) were demonstrated 7–8 months after cessation of holoBLG supplementation, indicative of a long-lasting nature of immune resilience induced by holoBLG. Trial registration The study was registered at clinicaltrials.gov (NCT04872868).

Baseline Quality of Life of Physical Function Is Highly Relevant for Overall Survival in Advanced Rectal Cancer

In advanced rectal cancer, neoadjuvant radiochemotherapy and total mesorectal excision lead to long overall survival. The quality of life (QOL) of the patients is clearly related to the prognosis. Our question was whether the prognosis can be represented with only one question or one score from the QOL questionnaires. 360 consecutively recruited patients diagnosed with advanced rectal cancer were questioned during radiochemotherapy and a follow-up of 8 years. The questionnaires QLQ-C30 and QLQ-CR38 were used; 10 functional and 17 symptom scores were calculated. The functional score “physical function” and the symptom scores “fatigue”, “nausea and vomiting”, “pain” and “appetite loss” were highly prognostic (p < 0.001) for overall survival. “Physical function” was highly prognostic at all time points up to 1 year after starting therapy (p ≤ 0.001). The baseline “physical function” score divided the cohort into a favorable group with an 8-year overall survival rate of 70.4% versus an unfavorable group with 47.5%. In the multivariable analysis, baseline “physical function”, age and distant metastases were independent predictors of overall survival. The score “physical function” is a powerful unrelated risk factor for overall survival in patients with rectal cancer. Future analyses should study whether increased “physical function” after diagnosis could improve survival.

Exploring the causal role of intimate partner violence and abuse on depressive symptoms in young adults: a population-based cohort study

Background Previous studies have shown an association between experience of intimate partner violence and abuse (IPVA) and depression. Whether this is a causal relationship or explained by prior vulnerability that influences the risk of both IPVA and depression is not known. Methods We analysed data from the Avon Longitudinal Study of Parents and Children prospective cohort (N = 1764 women, 1028 men). To assess the causal association between IPVA at 18–21 years old and logged depressive symptom scores at age 23, we used (i) multivariable linear regression, (ii) inverse probability of treatment weighting (IPTW), and (iii) difference-in-difference (DiD) analysis, which compared the mean change in logged depressive symptom scores between ages 16 and 23 between those who experienced IPVA and those who did not. Results Women who experienced IPVA had on average 26% higher depressive symptom scores after adjustment for measured confounders (ratio of geometric means 1.26, 95% CI 1.13 to 1.40). In men, the difference was 5% (ratio of geometric means 1.05, 95% CI 0.92 to 1.21). Results from IPTW analysis were similar. In the DiD analysis, there was no evidence that being exposed to IPVA affected the change in depressive symptom scores over time compared to being in the non-exposed group for either women (difference-in-differences 1%, −12 to 16%) or men (−1%, −19 to 20%). Conclusions Multivariable linear regression and IPTW suggested an association between IPVA and higher depressive symptom score in women but not men, but DiD analysis indicated a null effect in both women and men. This suggests the causal origins of higher depressive symptoms in this young adult population are likely to reflect prior vulnerability that leads to both higher depressive symptoms and increased risk of IPVA exposure.

Negative Symptom Domains Are Associated With Verbal Learning in Adolescents With Early Onset Psychosis

Background: Early-onset psychosis (EOP) is among the leading causes of disease burden in adolescents. Negative symptoms and cognitive deficits predicts poorer functional outcome. A better understanding of the association between negative symptoms and cognitive impairment may inform theories on underlying mechanisms and elucidate targets for development of new treatments. Two domains of negative symptoms have been described in adult patients with schizophrenia: apathy and diminished expression, however, the factorial structure of negative symptoms has not been investigated in EOP. We aimed to explore the factorial structure of negative symptoms and investigate associations between cognitive performance and negative symptom domains in adolescents with EOP. We hypothesized that (1) two negative symptom factors would be identifiable, and that (2) diminished expression would be more strongly associated with cognitive performance, similar to adult psychosis patients.Methods: Adolescent patients with non-affective EOP (n = 169) were included from three cohorts: Youth-TOP, Norway (n = 45), Early-Onset Study, Norway (n = 27) and Adolescent Schizophrenia Study, Mexico (n = 97). An exploratory factor analysis was performed to investigate the underlying structure of negative symptoms (measured with the Positive and Negative Syndrome Scale (PANSS)). Factor-models were further assessed using confirmatory factor analyses. Associations between negative symptom domains and six cognitive domains were assessed using multiple linear regression models controlling for age, sex and cohort. The neurocognitive domains from the MATRICS Consensus Cognitive Battery included: speed of processing, attention, working memory, verbal learning, visual learning, and reasoning and problem solving.Results: The exploratory factor analysis of PANSS negative symptoms suggested retaining only a single factor, but a forced two factor solution corroborated previously described factors of apathy and diminished expression in adult-onset schizophrenia. Results from confirmatory factor analysis indicated a better fit for the two-factor model than for the one-factor model. For both negative symptom domains, negative symptom scores were inversely associated with verbal learning scores.Conclusion: The results support the presence of two domains of negative symptoms in EOP; apathy and diminished expression. Future studies on negative symptoms in EOP should examine putative differential effects of these symptom domains. For both domains, negative symptom scores were significantly inversely associated with verbal learning.

Biomarkers to aid the return to play decision following sports-related concussion: a systematic review

Premature return to play (RTP) following sports-related concussion (SRC) is associated with significant morbidity including risk of neurological and non-neurological injury, persistent post-concussion symptoms and chronic neurological deficits. Assessing athletes for RTP is critical but these decisions are currently based on clinical assessments that are subject to bias and symptomatic reporting that rely on compliance. An objective and easily obtained biomarker that can indicate recovery following SRC would aid clinicians to make safer RTP decisions. We performed a systematic review to identify potential biomarkers from saliva, urine and blood sources that could inform the clinical RTP decision. The MEDLINE database was searched. Inclusion criteria were studies focusing on adults diagnosed with SRC, fluid biomarkers from blood, saliva or urine and clinical recovery from SRC or at RTP. We assessed each biomarker for their time course post SRC and relationship to clinical recovery. Secondary outcomes included correlation with symptom scores and predictive value for prolonged RTP. We identified 8 studies all investigating blood-based markers of diffuse axonal injury (tau, NFL, SNTF), neuroglial injury (NSE, VLP-1, UCH-L1, S100B, GFAP), inflammation and hormonal disturbances. Tau, SNTF, UCH-1, GFAP, S100B and the inflammatory cytokine MCP-4 are raised post SRC and return to baseline by RTP. Changes in tau, NFL, SNTF, GFAP and MCP-4 post SRC correlate with severity of concussion as measured by symptom severity or RTP duration. There is only preliminary case-reporting for hormonal biomarkers. The evidence is limited by a lack of highly powered studies, variation in use of athletic and Contact sport controls (CSC) and a lack of consistent sampling and assessment protocols. There is promise for biomarkers to aid RTP decisions following SRC, most notably in use alongside clinical assessment in RTP criteria to allow greater precision in identifying mild and severe concussion.

Role of periostin in evaluating the responsiveness of allergic patients to allergen-specific immunotherapy

Objectives: Allergen-specific immunotherapy (AIT) has been considered the most effective treatment for IgE mediated allergies, especially respiratory allergies. Several biomarkers have been developed to evaluate the clinical efficacy of AIT, yet none of them have been thoroughly validated. So our objective here is to investigate the usefulness of periostin as a biomaker for monitoring the efficacy of allergen immunotherapy. Materials and methods: This study included 46 healthy non-atopic volunteers and 46 patients with allergic rhinitis (AR). They were sensitized only to date palm pollen. The participants were tested by skin prick test and total serum IgE levels were measured. Serum samples were collected from healthy subjects and allergic patients before and after the one-year AIT. Serum levels of periostin, eotaxin, and sIL-2R were estimated by ELISA. Symptom scores in the allergic patients were also evaluated before and after completing one year AIT. Results: There is a significant increase in serum levels of IgE, periostin, sIL-2R, and eotaxin in allergic patients as compared to healthy controls. Symptom scores, sIL-2R and serum periostin levels were significantly decreased after one-year AIT in AR patients. Conclusion: Periostin can be used as a biomarker to evaluate AIT efficacy in AR patients. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 184-190

Cholinergic relevant functional reactivity is associated with dopamine responsiveness of tremor in Parkinson’s disease

Tremor in Parkinson’s disease (PD) has distinct responsiveness to dopamine, which is supposed not be exclusively related to dopamine deficiency but has a close relationship with cholinergic system. This phenomenon indicates that cholinergic system may be an important regulatory for distinct dopamine responsiveness of parkinsonian tremor. Through investigating the alterations of cholinergic and dopaminergic network during levodopa administration, we aimed at exploring the mechanisms of differed dopamine responsiveness of parkinsonian tremor. Fifty-two PD patients with tremor were enrolled. MRI scanning, UPDRS III and its sub-symptom scores were collected in OFF and ON status (dopaminergic challenge test). Then, patients were divided into two groups (dopamine-resistant tremor and dopamine-responsive tremor) according to the tremor change rate median score. Dopaminergic and cholinergic network were obtained. LASSO regression was conducted to identify functional connectivity with distinct reactivity during levodopa administration between groups. Afterwards, detailed group comparisons, interaction and correlation analyses were performed. The reactivity of cholinergic connectivity showed the highest possibility to distinguish two groups, especially connectivity of right basal forebrain 123 to right parietal operculum cortex (R.BF123-R.PO). After levodopa administration, connectivity of R.BF123-R.PO was decreased for dopamine-responsive tremor while which remained unchanged for dopamine-resistant tremor. The reactivity of R.BF123-R.PO was negatively correlated with tremor change rate. Reduced cholinergic connectivity to parietal operculum may be an underlying mechanism for the responsive tremor in PD and the distinct cholinergic reactivity of parietal operculum to levodopa may be a core pathophysiology for the differed DA responsiveness of tremor in PD.

Gut Microbiota and Depressive Symptoms at the End of CRT for Rectal Cancer: A Cross-Sectional Pilot Study

Background. The role of alterations in gut microbiota composition (termed dysbiosis) has been implicated in the pathobiology of depressive symptoms; however, evidence remains limited. This cross-sectional pilot study is aimed at exploring whether depressive symptom scores changed during neoadjuvant chemotherapy and radiation therapy to treat rectal cancer, and if gut microbial taxa abundances and predicted functional pathways correlate with depressive symptoms at the end of chemotherapy and radiation therapy. Methods. 40 newly diagnosed rectal cancer patients (ages 28-81; 23 males) were assessed for depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and provided stool samples for 16S rRNA sequencing. Gut microbiome data were analyzed using QIIME2, and correlations and regression analyses were performed in R. Results. Participants had significantly higher depressive symptoms at the end as compared to before CRT. The relative abundances of Gemella, Bacillales Family XI, Actinomyces, Streptococcus, Lactococcus, Weissella, and Leuconostocaceae were positively correlated (Spearman’s rho = 0.42 to 0.32), while Coprobacter, Intestinibacter, Intestimonas, Lachnospiraceae, Phascolarctobacterium, Ruminiclostridium, Ruminococcaceae (UCG-005 and uncultured), Tyzzerella, and Parasutterella (Spearman’s rho = − 0.43 to − 0.31 ) were negatively correlated with HAM-D scores. Of the 14 predicted MetaCyc pathways that correlated with depressive symptom scores at the end of CRT, 11 (79%) were associated with biosynthetic pathways. Conclusions. Significant bacterial taxa and predicted functional pathways correlated with depressive symptoms at the end of chemotherapy and radiation therapy for rectal cancer which warrants further examination and replication of our findings.

Concussion Subtyping in Patients With Persistent Post-Concussive Symptoms Using a New Concussion Clinical Profile Screen Tool (CP Screen)

ObjectiveTo identify the prevalence of subtypes in Persistent Post Concussion Symptoms (PPCS) and investigate their potential relationships.BackgroundThe CP-Screen is designed to evaluate 5 clinical profiles and 2 modifiers that are predominant within concussion patients. The CP screen includes 29 items that are expressed as weighted outcome scores for each of the 7 concussion subtypes.Design/MethodsThis was a retrospective-chart review of 1,136 visits for 362 patients with PPCS at a concussion center. Age range was 12–81 and average age was 32, 65.7% were female and 34.3% male. 360 visits were in the 12–21 pediatric age range. Each patient completed an electronic CP-Screen prior to each visit, which was uploaded to the EHR. All patients were seen between October 2020 and April 2021.ResultsOverall, the most common subtypes were cognitive (34.0%), neck (17.8%), and mood (16.8%). The highest overall observed subtype average CP symptom score was mood (32.8/89) and the lowest was visual (23.6/89). For pediatric the most common phenotypes were cognitive (36.7%), mood (17.9%), and visual (15.4%). The highest observed pediatric average CP symptom score was mood (30.8/89) and the lowest was sleep (20.1/89). For those with cognitive primary profile, neck and ocular were the most common secondary and tertiary profiles in both groups. Females presented with cognitive, mood, neck as their most common profiles compared to cognitive, neck, ocular in males in both groups. Neck, mood, and visual primary profiles all presented with cognitive fatigue as their secondary profile.ConclusionsCP screen was overall a useful tool in helping identify clinical profiles in PPCS. Cognitive fatigue was a predominant profile in PPCS across all ages and sexes. Those with predominant mood profiles presented with the highest symptom scores. Mood profile was more predominant in females. Cognitive primary profile was found to be most linked to cervical, mood, and visual profiles.

P300 Evoked Response Potentials Patterns in Different Complex Concussion Phenotypes

ObjectiveDetermine the utility of P300 Evoked Response Potentials (ERP) voltage patterns in predicting phenotypical sequelae of patients with complex concussions or Persistent Post Concussive Symptoms (PPCS).BackgroundERPs have been used to aid in the diagnosis of multiple neurologic disorders. They have also been recently used in the evaluation of concussions.Design/MethodsA retrospective study of 54 patients, 10–71 year (mean age 29.6 yrs), with PPCS were tested between 6 and 12 weeks post-injury using the standard oddball audio P300 ERP protocol with measures extracted including best central parietal P300 ERP. PPCS Phenotyping was completed in each patient using a standardized post-concussive questionnaire and Rivermead method for 5 primary phenotypes and mixed type.ResultsP300 average Voltage for the entire group was 11.6 mV. Overall, these were significantly lower than age-matched non concussed controls whose average voltage was 16.3 mV (p < 0.0001). Average P300 voltages for each phenotype: Cognition- 14.1 mV, Vestibular- 8.6 mV, Headache- 11.1 mV, Mood- 13.6 mV, Neck Pain- 9.6 mV, Visual- 9.8 mV, Mixed- 6.9 mV, Mixed and Vestibular phenotypes demonstrated the lowest average voltage potentials (6.9 mV and 8.6 mV respectively) which coincided with higher average symptom scores (70.5 and 54.5 respectively). Cognition and Mood demonstrated the highest average voltage potentials (14.1 mV and 13.6 nV respectively), which coincided with lower average symptom scores (40.3 and 48.7, respectively). Mood (13.6 mV) was the lowest average symptom score in the group at 40.3 and Mixed (6.9 mV) was highest at 70.5. Comparing phenotypes against one other, mixed vs mood (p = 0.03), cognition vs vestibular (p = 0.02), and cognition vs mixed (p = 0.009) showed statistical significance.ConclusionsP300 ERPs may help identify persistent abnormal complex concussion neurophysiology. ERPs can also potentially exhibit phenotype specific patterns and be a useful tool in helping differentiate more somatic/physiologic vs mood-based phenotypes. This can ultimately lead in the aid in diagnosis, prognosis, subtyping, and targeted phenotype management.