Severe Symptoms Research Articles

Examining Erythrocytes as Potential Blood Biomarkers for Autism Spectrum Disorder: Their Relationship to Symptom Severity and Adaptive Behavior.

Multiple research teams have documented various abnormalities in erythrocyte properties in children with autism spectrum disorder (ASD) compared with neurotypical individuals. Reduced erythrocyte deformability, a crucial factor for microcirculation and oxygen delivery, may affect brain function. Other key factors like nitric oxide (NO) and Na,K-ATPase-regulated cation transport also play roles in both erythrocyte deformability and ASD, suggesting a possible relationship between erythrocyte parameters and autism severity. Thus, this study aims to describe these associations, exploring erythrocyte properties as potential biomarkers in ASD. A total of 179 ASD children were enrolled in this study. Diagnosis was confirmed by the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Autism Diagnostic Interview-Revised. The Vineland Adaptive Behavior Scales, Third Edition (VABS-3), was used to assess adaptive behavior. RBC deformability was measured using a filtration technique, while NO production by RBCs was assessed via DAF-2DA fluorescence. Na,K-ATPase kinetics and RBC osmotic resistance were evaluated spectrophotometrically. Children with more severe ASD symptoms had more impaired deformability and osmotic resistance than children with mild symptoms. Higher RBC NO production was linked to better scores in some VABS-3 subdomains, and in the social affect domain of ADOS-2. Higher affinity of Na,K-ATPase for sodium negatively correlated with the occurrence of repetitive and restricted behavior-one of the core ASD symptoms. This study identified potential links between ASD severity and RBC properties. While erythrocyte quality can influence ASD symptomatology, the observed relationships-such as those involving RBC deformability, NO production, Na,K-ATPase kinetics, and osmotic resistance-were not strong or consistent enough to be considered reliable diagnostic or prognostic biomarkers.

Depression in patients with chronic otolaryngology symptoms – A vicious cycle

BackgroundDepression is a common comorbidity among individuals with otolaryngologic disorders, particularly those with longstanding conditions. This study aims at analysing the sociodemographic profile of depressive disorders in patients with chronic otolaryngology symptoms or conditions, and the correlation with PHQ-9 score.MethodsA cross-sectional study was conducted on a hundred patients presenting to the outpatient department with chronic otolaryngology symptoms or conditions. They were requested to fill in the PHQ-9 questionnaire, containing questions based on the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for major depressive disorder (MDD).ResultsMedian age was 39, male: female ratio was 1.17. Nasal obstruction (29%), ear discharge (25%), and headache (17%) were the common presenting complaints. Mean and median PHQ-9 scores were 5.03 and 4 respectively. Seven patients (7%) had MDD, while eleven (11%) had other depressive disorder; 9% of cases were found to have no significant otolaryngologic problem despite presenting with symptoms, two of which were found to have depressive disorder. Thirty-five (35%) and thirty-six (36%) patients had minimal and mild depressive symptoms respectively, while one (1%) had severe depressive symptoms. Statistical significance was noted for the duration of symptoms (p-value 0.005); high statistical significance was found for occupation and otolaryngology diagnosis (p-value < 0.001 each). PHQ-9 score showed statistical significance in comparison with gender and duration of symptoms (p-value 0.046 and 0.005 respectively). Correlation of severity of depressive disorder revealed statistical significance with gender (p-value 0.049) and high statistical significance with duration of symptoms (p-value < 0.001).ConclusionChronic otolaryngology conditions are associated with significant morbidity, attributable to longstanding disturbing symptoms and prolonged treatment protocols, leading to depression. Nevertheless, depression in chronic otolaryngology disorders may aggravate or overlap the clinical symptoms or may go undetected. Hence it may be worthwhile to evaluate for depressive disorders in chronic patients presenting to otolaryngology.

Baseline gut microbiome alpha diversity predicts chemotherapy-induced gastrointestinal symptoms in patients with breast cancer

Chemotherapy frequently causes debilitating gastrointestinal symptoms, which are inadequately managed by current treatments. Recent research indicates the gut microbiome plays a role in the pathogenesis of these symptoms. The current study aimed to identify pre-chemotherapy microbiome markers that predict gastrointestinal symptom severity after breast cancer chemotherapy. Fecal samples, blood, and gastrointestinal symptom scores were collected from 59 breast cancer patients before, during, and after chemotherapy. Lower pre-chemotherapy microbiome alpha diversity and abundance of specific microbes (e.g., Faecalibacterium) predicted greater chemotherapy-induced gastrointestinal symptoms. Notably, tumor and diet characteristics were associated with lower pre-chemotherapy alpha diversity. Lower baseline alpha diversity also predicted higher chemotherapy-induced microbiome disruption, which was positively associated with diarrhea symptoms. The results indicate certain cancer patients have lower microbiome diversity before chemotherapy, which is predictive of greater chemotherapy-induced gastrointestinal symptoms and a less resilient microbiome. These patients may be strong candidates for pre-chemotherapy microbiome-directed preventative interventions (e.g., diet change).

Deep learning-based algorithm for automatic quantification of nigrosome-1 and Parkinsonism classification using susceptibility map-weighted MRI.

To develop and validate a deep learning-based automatic quantification for nigral hyperintensity and a classification algorithm for neurodegenerative parkinsonism using susceptibility map-weighted imaging (SMwI). We retrospectively collected 450 participants (210 with idiopathic Parkinson's disease [IPD] and 240 individuals in the control group) for training data between November 2022 and May 2023, and 237 participants (168 with IPD, 58 with essential tremor, and 11 with drug-induced Parkinsonism) for validation data between July 2021 and January 2022. SMwI data were reconstructed from multi-echo GRE. Diagnostic performance for diagnosing IPD was assessed using deep learning-based automatic quantification (Heuron NI) and classification (Heuron IPD) model. Reference standard for IPD was based on 18F-FP-CIT PET finding. Additionally, the correlation between the H&Y stage and volume of nigral hyperintensity in patients with IPD was assessed. Quantification of nigral hyperintensity using Heuron NI showed AUC of 0.915 (95% CI, 0.872-0.947) and 0.928 (95% CI, 0.887-0.957) on the left and right, respectively. Classification of nigral hyperintensity abnormality using Heuron IPD showed AUC of 0.967 (95% CI, 0.881-0.991) and 0.976 (95% CI, 0.948-0.992) on the left and right, respectively. H&Y score ≥ 3 showed significant smaller nigral hyperintensity volume (1.43 ± 1.19 mm3) compared to H&Y score 1-2.5 (1.98 ± 1.63 mm3; p = 0.008). Our deep learning-based model proves rapid, accurate automatic quantification of nigral hyperintensity, facilitating IPD diagnosis, symptom severity prediction, and patient stratification for personalized therapy. Further study is warranted to validate the findings across various clinical settings. IPD = Idiopathic Parkinson's disease; SN = substantia nigra; SMwI = susceptibility map weighted imaging; QSM = quantitative susceptibility mapping; CNN = convolutional neural network; ICV = intracranial volume.

Manipulating levels of uncertainty in a decision making task for obsessive-compulsive disorder.

The study aims to investigate whether manipulating levels of uncertainty would influence performance in a decision-making task in obsessive-compulsive disorder (OCD). This case-control study compares the performance in beads task (measuring reflection/decisional impulsivity) performance and trait impulsivity (Short Urgency-Premeditation-Perseverance-Sensation Seeking-Positive Urgency (UPPS-P)) in patients with OCD (n=65) and non-clinical controls (n=45). Mann Whitney U test was carried out to assess between-group differences. The OCD group had significantly lesser draws to decision (U=1845 , p=.019) and subjective decisional-certainty (U=1518, p=0.00) in the low-uncertainty (85:15) condition , higher scores of negative urgency (U= 2163, p=<0.001) and lower scores on sensation-seeking (U= 907.5, p=.001) in the UPPS-P. However, the comparison of beads task performance does not survive correction for multiple comparisons. Patients with OCD engage in impulsive decision-making in the lower-uncertainty condition in comparison to healthy controls, despite low subjective certainty of the decision. They also had increased scores on the trait impulsivity factor of negative urgency. Future studies may explore the relationship between trait impulsivity as well as the contributions of symptom severity, anxiety and decisional certainty to impulsivity in OCD.

Mitigating Cybersickness in Virtual Reality: Impact of Eye–Hand Coordination Tasks, Immersion, and Gaming Skills

Cybersickness remains a significant challenge for virtual reality (VR) applications, particularly in highly immersive environments. This study examined the effects of immersion, task performance, and individual differences on cybersickness symptoms across multiple stages of VR exposure. Forty-seven participants aged 18–45 completed a within-subjects design that involved the Cybersickness in Virtual Reality Questionnaire (CSQ-VR) and the Deary–Liewald Reaction Time (DLRT) task. Cybersickness symptoms were assessed across four stages: before and after VR immersion, and before and after a 12 min rollercoaster ride designed to induce cybersickness. The results showed significant increases in symptoms following the rollercoaster ride, with partial recovery during the post-ride tasks. Eye–hand coordination tasks, performed after the ride and VR immersion, mitigated nausea, as well as vestibular, and oculomotor symptoms, suggesting that task engagement plays a key role in alleviating cybersickness. The key predictors of symptom severity included a susceptibility to motion sickness and gaming experience, particularly proficiency in first-person shooter (FPS) games, which was associated with a reduced cybersickness intensity. While task engagement reduced symptoms in the later stages, particularly nausea and vestibular discomfort, overall cybersickness levels remained elevated post-immersion. These findings underscore the importance of task timing, individual differences, and immersive experience design in developing strategies to mitigate cybersickness and enhance user experiences in VR environments.

Evaluating the efficacy of curcumin in the management of oral potentially malignant disorders: a systematic review and meta-analysis.

Oral potentially malignant disorders (OPMDs) not only harbour the risk of malignant transformation but can also affect patients' quality of life owing to severe symptoms. Therefore, there is an urgent need for therapeutic strategies to improve patients' quality of life. The objective of this meta-analysis was to comprehensively assess the efficacy of curcumin in the management of OPMDs. PubMed, Embase, the Cochrane Library, and Web of Science were searched for clinical trials evaluating the efficacy of curcumin in the treatment of OPMDs from inception until March 2024. RevMan 5.4 software was used to perform statistical and subgroup analyses. Sixteen randomised controlled trials (1,089 patients) were selected. Curcumin exhibited comparable efficacy to conventional controls in alleviating pain (I2 = 98%, P = 0.49) and improving tongue protrusion (I2 = 94%, P = 0.51) in oral submucous fibrosis (OSF). Additionally, topical use of curcumin had an efficacy equivalent to that of conventional therapy in reducing pain (I2 = 83%, P = 0.31) and facilitating clinical remission (I2 = 67%, P = 0.38) of oral lichen planus (OLP). The topical use of curcumin may palliate pain and promote clinical healing in OLP patients. Systemic curcumin can ameliorate the degree of pain and tongue protrusion in OSF. Therefore, our study suggests that curcumin could serve as an alternative treatment for managing OPMDs with lower medical toxicity than steroids, especially when steroids are not suitable. Further studies with larger sample sizes and adequate follow-up periods are required to validate our results.

Identification and transfer to stepped care of depressed and psychosocially stressed parents during peri- and postpartum—UPlusE: study protocol for cluster randomized trial of a screening intervention

BackgroundPerinatal depression affects 10–15% of mothers and approximately 5% of fathers. However, only a small number of affected individuals seek treatment. If left unrecognized and untreated, it can have negative long-term consequences for the family’s health, leading to subsequent high costs. Early treatment is crucial, yet there is a notable underdiagnosis and undertreatment. Affected individuals are often seen during this time, e.g. in paediatric practices, but not by specialists in mental health. Consequently, this study aims to increase detection and treatment rates of affected individuals by implementing a screening for depression and psychosocial stress in perinatal and postpartum parents within routine obstetric and paediatric care with subsequent advice and—if necessary—further referral to a mental health specialist.MethodsUPlusE is a prospective, cluster-randomized controlled trial conducted in an outpatient setting. Obstetric and paediatric practices will be randomized into an intervention and control group (1:1 ratio). Practices and enrolling patients will be required to use specific smartphone apps (practice apps) for interaction. The screening will occur with the apps at each paediatric checkup up to the child’s age of 12 months, using the Edinburgh Postnatal Depression Scale (EPDS), KID-PROTEKT questionnaire, and the scale 1 (impaired bonding) of the Postpartum Bonding Questionnaire (PBQ-1). The goal is to screen 10,000 patients across Germany. Gynaecologists and paediatricians will receive certified training on peripartum depression. Participants in the intervention group with scores above cut-offs (EPDS ≥ 10, KID-PROTEKT ≥ 1, PBQ-1 ≥ 12) will receive counselling through their treating gynaecologists/paediatricians and will be provided with regional addresses for psychiatrists, psychotherapists, and “Frühe Hilfen” (early prevention) as well as family counselling centres, depending on symptom severity. At each screening, participants will be asked whether they sought support, where, and with whom (utilization). Utilization is the primary outcome.DiscussionThe screening is designed to reduce underdiagnosis to enable suitable support at an early stage (especially for those often overlooked, such as individuals with “high-functioning depression”) and hence to avoid manifestation of mental health problems in the whole family, especially infants who are exceptionally dependent on their parents and their well-being will benefit from this program.Trial registrationGerman Clinical Trials Register, DRKS00033385. Registered on 15 January 2024.

Pain and Fertility Outcomes in Patients Undergoing Cyst Excision Versus Cyst Aspiration in Moderate to Severe Endometriosis: A Case Series

Background: Endometriosis and ovarian cysts are prevalent gynecological disorders characterized by the presence of abnormal tissue growth in the pelvic cavity. Objective: To document the pain and fertility outcomes in patients undergoing cyst excision versus cyst aspiration in moderate to severe endometriosis presenting to a tertiary healthcare facility. Methods: This was a case series conducted in the Department of Obstetrics and Gynecology, Vinayaka Missions Medical College &amp; Hospital, Vinayaka Missions Research Foundation (VMRF, Deemed to be University), Karaikal, Puducherry, India between June 2021 and May 2023 (n=14). Results: The study included 14 patients, divided evenly with 7 undergoing cyst excision and 7 undergoing cyst aspiration. Before surgery, both groups had comparable baseline characteristics in terms of age, symptom severity, and the nature of the ovarian cysts. After surgery, patients who underwent cyst excision showed a higher rate of pain relief compared to those who underwent cyst aspiration (61% versus 26%, respectively). In terms of fertility outcomes, 55% of patients in the cyst excision group achieved improved clinical pregnancy outcomes after surgery, whereas 35% of those in the cyst aspiration group had comparable results. Conclusion: Cyst excision appears to be associated with superior pain relief and faster recovery compared to cyst aspiration in patients with endometriosis or ovarian cysts.

Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson’s disease

Mitochondrial dysfunction plays an important role in Parkinson’s disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for mitochondrial health. We investigated the links between blood mtDNA-CN and PD severity and risk using the Accelerating Medicines Partnership program for Parkinson’s Disease dataset, replicating our results in the UK Biobank. Our findings reveal that reduced blood mtDNA-CN levels are associated with heightened PD risk and increased severity of motor symptoms and olfactory dysfunction. We estimated blood cell composition using complete blood cell profile when available or RNA-sequencing data as a surrogate. After adjusting for blood cell composition, the associations between mtDNA-CN and PD risk and clinical symptoms became non-significant. Bidirectional Mendelian randomization analysis also found no evidence of a direct causal relationship between blood mtDNA-CN and PD susceptibility. Hence peripheral inflammatory immune responses rather than mitochondrial dysfunction underpin these previously identified associations in PD.

Dilodia sapinea as the pathogen causing trunk canker on Pinus bungeana trees in China

Pinus bungeana belonging to the genus Pinus is a pine tree species endemic to China. It plays vital roles in afforestation, forest regeneration, landscaping, forest ecosystems, and environmental protection. However, P. bungeana has been listed as a rare and endangered species in recent years due to population fragmentation. The occurrence of lethal diseases on the trees has made the situation even worse. This study aimed to identify the pathogen causing the trunk canker on P. bungeana trees in Qingdao, China. The morphological identification of the pathogen relied primarily on the morphology of conidia. Molecular identification was performed using the combined sequences of ITS, Tef and Tub2 genes. The eight isolates were all identified as Diplodia sapinea. The pathogenicity of the eight isolates was examined both in vitro and in vivo. The results showed that all the fungal isolates caused severe canker symptoms on the inoculated P. bungeana branches. Moreover, D. sapinea was re-isolated from the inoculated branches. This study is novel in reporting D. sapinea causing trunk canker on P. bungeana trees in China.

Identifying thresholds for meaningful improvements in NTDT-PRO scores to support conclusions about treatment benefit in clinical studies of patients with non-transfusion-dependent beta-thalassaemia: analysis of pooled data from a phase 2, double-blind, placebo-controlled, randomised trial

ObjectivesTo estimate thresholds for defining meaningful within-patient improvement from baseline to weeks 13–24 and interpreting meaningfulness of between-group difference for the non-transfusion-dependent beta-thalassaemia patient-reported outcome (NTDT-PRO) tiredness/weakness (T/W) and shortness...

Missing outcome data in randomised clinical trials of psychological interventions: a review of published trial reports in major psychiatry journals

BackgroundMissing outcome data can pose a serious threat to the validity of randomised clinical trial results. We aimed to study the extent of missing outcome data in randomised clinical trials of psychological interventions.MethodsWe performed a retrospective study of randomised clinical trial reports of psychological interventions published in World Psychiatry, JAMA Psychiatry, Lancet Psychiatry, American Journal of Psychiatry, British Journal of Psychiatry, or Psychotherapy and Psychosomatics from 2017 to 2022. We assessed the proportion of missing outcome data, whether missing data patterns differed between types of outcomes, participants, intervention lengths, and psychological intervention types, how missing outcome data were handled in the statistical analyses, and whether trialists discussed missing outcome data in the discussion section of the manuscript.ResultsWe identified 182 randomised clinical trials (233 primary outcomes), of which 206 outcomes (88.4%) were assessed at high risk of bias due to missing data. The overall mean percentage of missing outcome data was 18.3% (95% confidence interval (CI): 16.7–20%) for all outcomes. The percentages of missing data were 18.9% (95% CI: 17.1–20.6%; 180 outcomes) for symptom severity scales and 1.8% (95% CI: 2.3–3.3%; 6 outcomes) for ‘hard’ binary outcomes. Trials including participants with borderline personality disorder had the highest percentage of missing outcome data (33.1%; 95% CI: 22.3–43.9%) compared with other psychiatric disorders. Fisher’s exact test showed that intervention lengths and psychological intervention types were associated with the proportion of missing outcome data (p < 0.001), but there were no clear patterns.ConclusionMissing outcome data is a considerable problem in randomised clinical trials of psychological interventions, and trialists should consider the corresponding methodological limitations in the design and analysis to reduce the risk of bias due to missing outcome data.Clinical trial registration numberNot applicable.

Musculoskeletal pain is associated with poor sleep quality and increased daytime sleepiness in dental students: a cross-sectional pilot study.

While a bidirectional relationship between sleep health and musculoskeletal (MSK)-pain have been established among chronic pain patients, few studies explored it among dental students. This cross-sectional study assessed the relationship of self-report MSK-pain with sleep health and psychological outcomes among dental students, and whether differences existed as a function of number and location of painful body-sites. Validated questionnaires were sent through REDCap to dental students at a predoctoral dental school, assessing presence, location (head, shoulder/neck, jaw, back, body), and intensity of MSK-pain, sleep health (risk of sleep apnea, insomnia severity symptoms, sleep quality, daytime sleepiness, and chronotype), and psychological outcomes (anxiety/depression). Differences between those with and without MSK-pain, and across participants with different number and location of painful sites were tested with t-tests and ANOVA, adjusting for age/gender. Out of 80 participants (82.5% females), 76.3% reported MSK-pain (68.9% in neck/shoulders). Those with MSK-pain scored significantly worse in sleep quality (7.7±3.7 vs. 4.8±2.1, p<.001), daytime sleepiness (6.1±4.2 vs. 3.3±2.7, p<.001). Those with >3 painful body-sites reported worse sleep quality (p=.006) and daytime sleepiness (p=.003) than pain-free controls. There were no differences on sleep and psychological outcomes as a function of number of painful body-sites. Those reporting back pain scored worse in insomnia (p=.037), daytime sleepiness (p=.002), and sleep quality (p=.006) than those without back pain. MSK-pain is prevalent among dental students and associated with worse sleep health. While number of painful sites may not influence sleep/psychological health, specific locations (e.g., back pain) were associated with worse sleep functioning.

The Association Between Change in Symptom Severity and Personal Recovery in Patients With Severe Mental Illness

Abstract This study examined the relationship between change in symptom severity and personal recovery in patients with severe mental illness (SMI). Forty-nine outpatients at Mentrum/Arkin, Amsterdam, the Netherlands, were assessed at baseline and 3 years later, using the Brief Psychiatric Rating Scale and the Mental Health Recovery Measure. Correlation coefficients and linear regression analyses were used. Further, the impact of severity of symptoms at baseline on change in personal recovery was evaluated. Results show that change in symptom severity explained 31.8% of the variance of change in personal recovery. Change in depression/anxiety explained 27.3% of the variance of change in personal recovery. Higher affective symptom severity at baseline significantly predicted positive change in personal recovery. In conclusion, besides change in symptom severity, other potential determinants of personal recovery should be addressed in treatment of patients with SMI, for example, self-esteem and social functioning. Treatment of depression/anxiety symptoms may increase personal recovery.

Electrocortical Profiles in Relation to Childhood Adversity and Depression Severity: A Preliminary Report.

Objective: Assessment of electroencephalographic (EEG) activity in depression has provided insights into neural profiles of the illness. However, there is limited understanding on how symptom severity and risk factors, such as childhood adversity, influence EEG features. Methods: Eyes-closed EEG was acquired in N = 28 depressed individuals being treated in a tertiary psychiatric setting. Absolute alpha, beta, theta, and delta power and inter-/intra-hemispheric coherence were examined. Relations between the Montgomery-Åsberg Depression Scale (MADRS) and Adverse Childhood Experience (ACE) Questionnaire and EEG features were assessed. Results: Individuals in the high (MADRS≥30) versus lower (MADRS ≤ 29) symptom severity group exhibited greater overall beta power, and lower Fp1-Fp2 delta and theta coherence. Those with high (≥3) versus lower (≤2) ACE scores exhibited greater T7-T8 beta coherence. Lowest F3-F4 beta coherence was observed in those with high ACE/high depression severity. A negative correlation existed between F8-P8 alpha coherence and symptom severity. Conclusions: Those with higher depression severity exhibit increased beta power, possibly reflecting a hyper-vigilant state. Depression severity and ACE history may produce subtle alterations in frontal delta/theta and temporal/frontal beta coherence regions. Significance: This is the first study to examine the neural impact of depression severity and ACE-assessed childhood trauma in depressed individuals receiving treatment in a tertiary setting, accounting for the clinical reality of the prevalence of their co-occurrence.

Evaluation of Suppressor of Cytokine Signaling 1, Interleukin-29 and Lysosomal Trafficking Regulator in Severe COVID-19

Background: The pathogenesis of Severe SARS-CoV-2 is closely linked to severe immune responses and inflammation caused by the SARS-CoV-2 virus. In this context, the suppressor of cytokine signaling 1 (SOCS1) has a crucial role in inhibiting cytokine-induced immune responses. On the other hand, interleukin-29 (IL-29) and lysosomal trafficking regulator (LYST) are important molecules involved in inducing immune responses. Objectives: This study aimed to assess the mRNA levels of SOCS1, IL-29, and LYST in the SARS-CoV-2-infected patients with severe symptoms. Methods: In this cross-sectional study, 70 SARS-CoV-2 infected patients with severe symptoms and 70 healthy controls were evaluated. RNA was extracted from peripheral blood and after cDNA synthesis, the mRNA levels of SOCS1, IL-29, and LYST were assessed by Real-Time PCR technique Results: The study revealed that severe COVID-19 patients exhibited a significant increase in mRNA levels of IL-29 compared to healthy individuals. However, there were no observed alterations in the mRNA levels of SOCS1 and LYST in the patient group. Conclusions: The results emphasize the importance of IL-29 as a potential biomarker or therapeutic target for severe COVID-19 cases. Further research is needed to investigate the specific mechanisms through which IL-29 influences immune responses and contributes to the development of severe disease. Additionally, exploring other factors that may regulate SOCS1 and LYST expression could provide a more comprehensive understanding of their roles in COVID-19 pathogenesis.

EDI&amp;S SO06 Do All Patients with Biliary Problems Need Surgery? Applying C-Gall Study Results to Long Waiters for Laparoscopic Cholecystectomy

Abstract Background The recent C-GALL study, a multi-centre randomised trial, found no significant difference in quality of life at two years between operative and non-operative management of uncomplicated gallstone disease. This suggests some patients may not benefit from elective laparoscopic cholecystectomy (LC), potentially leading to over-listing for surgery. By identifying patients who may no longer need surgery, we could reduce waiting lists and improve resource allocation. This study aims to reassess patients with an enforced period of observation on an elective waiting list for LC, to determine if they wish to make a different decision about proceeding with surgery. Method Patients listed for an elective LC who had been waiting longer than 11 months from referral were reviewed. Patients were contacted through telephone clinics by a surgeon. Data was collected on type of gallstone disease, history of abdominal surgery, biliary pain since last seen by a clinician, pain radiation to the back, pain reduction with simple analgesia, nausea, and heartburn. Identified patients were contacted and, if exhibiting minimal or no symptoms, were offered the option to be removed from the waiting list with 12 months of patient-initiated follow-up and high priority relisting if their clinical condition worsened. Results We contacted 59 patients awaiting elective LC Most were female (49, 83%), had biliary colic (43, 73%), and were under 60 years old (38, 64%). Seventeen patients (29%) were happy to opt out due to lack of symptoms. Of these, 13 (76%) were female, 11 (65%) had biliary colic, and 7 (41%) were under 60. Chi-squared analysis identified age as the only predictive factor, with those under 60 being less likely to opt out (p=0.038). We will continue to monitor representation and the need for reoperation to ensure safety and the findings remain consistent overtime. Conclusion The study demonstrates that a significant proportion of patients awaiting elective LC can be safely managed without planned cholecystectomy, potentially reducing waiting lists, cost and utilisation of healthcare resources. We would advise considering review of long waiters to re-evaluate their clinical need for cholecystectomy in order to improve sustainability within surgery. These findings support a more personalised approach to managing biliary pain, prioritising patients for surgery based on symptom severity.

Oomycete communities in lowland tropical forest soils vary in species abundance and comprise saprophytes and pathogens of seeds and seedlings of multiple plant species.

The soils in lowland tropics are teeming with microbial life, which can impact plant community structure and diversity through plant-soil feedbacks. While bacteria and fungi have been the focus of most studies in the tropics, oomycetes may have an outsized effect on seed and seedling health and survival, given their affinity for moister, warmer environments. We assessed the diversity and pathogenicity of oomycete species present in a lowland tropical forest in Panama. We used a culture-dependent leaf-baiting assay and culture-independent soil DNA metabarcoding methods to quantify zoospore abundance and species diversity. A subset of the isolates from the baiting assay were used to evaluate pathogenicity and symptom severity on seedlings of three tree species. Oomycetes were ubiquitous and common members of the soil microbial community in lowland tropical forests, and zoospore abundance was far greater compared to similar studies from temperate and mediterranean forests. The various oomycete species also varied in the ability to infect host plants. Species of Pythium were more virulent, while species of Phytopythium caused less severe symptoms but were more diverse and commonly isolated from the soil. Finally, we found that individual hosts accumulated a distinct oomycete community and was the only factor that had an effect on community structure. Collectively, these findings demonstrate that oomycetes are ubiquitous, host-generalist pathogens and saprophytes, that can impact seed and seedling survival in lowland tropical forests.

Aperiodic (1/f) neural activity robustly tracks symptom severity changes in treatment-resistant depression.

A reliable physiological biomarker for Major Depressive Disorder is essential for developing and optimizing neuromodulatory treatment paradigms. This study investigates a passive electrophysiologic biomarker that tracks changes in depressive symptom severity on the order of minutes to hours. We analyze brief recordings from intracranial electrodes implanted deep in the brain during a clinical trial of deep brain stimulation for treatment-resistant depression in 5 human subjects (nfemale= 3, nmale = 2). This surgical setting allows for precise temporal and spatial sensitivity in the ventromedial prefrontal cortex, a challenging area to measure. We focused on the aperiodic slope of the power spectral density, a metric reflecting the balance of activity across all frequency bands and serving as a proxy for excitatory/inhibitory balance in the brain. Our findings demonstrate that shifts in aperiodic slope correlate with depression severity, with flatter (less negative) slopes indicating reduced depression severity. This significant correlation was observed in all N=5 subjects, particularly in the ventromedial prefrontal cortex. This biomarker offers a new way to track patient responses to Major Depressive Disorder treatment, paving the way for individualized therapies in both intracranial and non-invasive monitoring contexts.