Prodromal Research Articles

Association of Acetaminophen (Paracetamol) Use With Severity and Outcomes in Patients With Viral Hepatitis-Associated Acute Liver Failure.

Acute viral hepatitis (AVH) comprises 11% of acute liver failure (ALF) in North America while acetaminophen (APAP) toxicity represents 46%. The use of APAP to treat prodromal hepatitis symptoms is common. It is unknown if concurrent APAP use impacts liver injury in AVH-induced ALF. In this prospective, multicenter cohort study, 356 patients meeting criteria for AVH including hepatitis A, B, Epstein-Barr virus, and herpes simplex virus, all leading to ALF (hepatic encephalopathy after acute illness, international normalized ratio ≥1.5), or acute liver injury (acute liver injury, international normalized ratio >2.0, no hepatic encephalopathy) were reviewed for evidence of APAP use: APAP ingestion history or measurement of serum APAP level or APAP-CYS adducts, a specific biomarker released into blood with APAP injury. Patients were grouped by APAP exposure level, from high (measurable APAP levels or toxic APAP-CYS), medium (therapeutic APAP-CYS), low (history of APAP ingestion only and/or barely detectable APAP-CYS), or no exposure recorded. Two hundred five of 356 patients (57.5%) with AVH-ALF had evidence of APAP use: 87 out of 356 (24%) demonstrated high or medium exposures. The aminotransferase and bilirubin levels of high/medium group resembled a mixed APAP-viral injury. Mortality was the highest (51.6%, 21.4%, 28.8%, and 30.5%), and transplant-free survival was the lowest (22.6%, 44.6%, 41.5%, and 40.4%) in the high exposure group compared with medium, low, and no exposure groups. However, the specific comparisons of mortality and transplant-free survival between the high exposure and no exposure groups were not statistically different even after adjusting for baseline patient characteristics differences. APAP use in AVH-ALF is common and may negatively impact outcomes compared with little or no APAP exposure. Prospective studies of the safest and effective dose of APAP to use in patients with AVH are needed.

Role of Shwasakuthar Rasa and Other Herbomineral Formulations with Yoga in Migraine

Ayurveda is an ancient traditional system of medicine to treat illness and encourage well being by using natural whole body healing techniques. Migraine is a primary headache disorder which is characterized by episodic recurrent attacks. As it affects one billion individuals each year across the worldwide has proven to one of the most common neurological disorders with high prevalence and morbidity among the younger age groups. Migraine can be classified on the basis of presence of Aura which shows prodromal symptoms like irritability, behavioural changes, etc and associated symptoms of photophobia, phonophobia and vomiting that usually lasts for 4 to 72 hours. In Ayurveda, migraine is clinically correlated with Ardhavabhedaka which is described as Tridoshapradhana by Sushruta and Vatakaphapradhana by Vagabhata. The management of migraine is done routinely by reducing the symptoms and the episodic recurrent attacks with Ayurvedic approach as modern medicine cause gastric irritation and drug dependency which further triggers the attack. The present case of 35 years old female diagnosed with migraine has shown symptoms of headache involving left side of head associated with nausea, vomiting and sensitivity to light and sound. The patient was treated with Nasya Karma which act as a gateway to head as said by Acharya Charaka and with oral Ayurvedic herbomineral formulation Shamana Chikitsa was done that alleviates the symptoms of Ardhavabhedaka. A significant relief from all symptoms was observed within a period of 15 days, demonstrating the Ayurveda as the best way to improve the overall well being of mind, body and spirit.

Navigating Doshapaka and Dhatupaka in Health and Disease Across Traditional and Modern Perspectives.

In Ayurvedic classics, Rogapariksha i.e.,Pancha-Nidana which has encompasses five aspects of clinical diagnosis viz.,Hetu (etiological considerations), Poorva-rupa (prodromal symptoms), Rupa (clinical features), Samprapti (patho-physiological processes), and Upashaya-anupashaya (therapeutic diagnostics). Review: Doshapaka is a stage which is favorable for the treatment of diseases. This is because ama is separated from the doshas in this condition. The doshas get digested, the vitiation of doshas get settled down. The doshas which have got dissociated from ama either tend to become normal or start moving towards visceral organs. Dhatupaka is a pathological and unfavorable condition of body, it is a condition in which tissues are severely destructed in quick time. This leads to manifestation of many diseases and loss of immunity and strength. Conclusion: The knowledge of Doshapaka helps a physician in preventing errors while treating the Doshic conditions, administering cleansing. Knowledge of tissue destruction and suppuration would help physician to diagnose this condition as early as possible, support tissues with tissue forming and balancing intervetions and also to save life of patient.

Characterizing drug-induced epidermal necrolysis in a pediatric cohort.

This study aims to characterize the timeline and clinical features of onset, progression, and management of drug-induced epidermal necrolysis in pediatric patients. Sixteen pediatric patients were retrospectively identified and selected if under age 18 years at admission with one identified culprit drug exposure. Culprit drugs were antiepileptics (12/16, 75%) and antibiotics (4/16, 25%). Notably, anti-epileptic drugs (AED) had delayed onset and reported dose escalations that precipitated symptom onset; thus, patients prescribed AED with or without planned dose escalations should be monitored for prodromal symptoms longer than the typical onset window.

Biomarkers of Parkinson's disease in perspective of early diagnosis and translation of neurotrophic therapies.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopamine neurons and aberrant deposits of alpha-synuclein (α-syn) in the brain. The symptomatic treatment is started after the onset of motor manifestations in a late stage of the disease. Preclinical studies with neurotrophic factors (NTFs) show promising results of disease-modifying neuroprotective or even neurorestorative effects. Four NTFs have entered phase I-II clinical trials with inconclusive outcomes. This is not surprising because the preclinical evidence is from acute early-stage disease models, but the clinical trials included advanced PD patients. To conclude the value of NTF therapies, clinical studies should be performed in early-stage patients with prodromal symptoms, that is, before motor manifestations. In this review, we summarize currently available diagnostic and prognostic biomarkers that could help identify at-risk patients benefiting from NTF therapies. Focus is on biochemical and imaging biomarkers, but also other modalities are discussed. Neuroimaging is the most important diagnostic tool today, but α-syn imaging is not yet viable. Modern techniques allow measuring various forms of α-syn in cerebrospinal fluid, blood, saliva, and skin. Digital biomarkers and artificial intelligence offer new means for early diagnosis and longitudinal follow-up of degenerative brain diseases.

Ethical Considerations for Identifying Individuals in the Prodromal/Early Phase of Parkinson's Disease: A Narrative Review.

The ability to identify individuals in the prodromal phase of Parkinson's disease has improved in recent years, raising the question of whether and how those affected should be informed about the risk of future disease. Several studies investigated prognostic counselling for individuals with isolated REM sleep behavior disorder and have shown that most patients want to receive information about prognosis, but autonomy and individual preferences must be respected. However, there are still many unanswered questions about risk disclosure or early diagnosis of PD, including the impact on personal circumstances, cultural preferences and specific challenges associated with different profiles of prodromal symptoms, genetic testing or biomarker assessments. This narrative review aims to summarize the current literature on prognostic counselling and risk disclosure in PD, as well as highlight future perspectives that may emerge with the development of new biomarkers and their anticipated impact on the definition of PD.

Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.

Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis

Objective: To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma. Methods: This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect. Results: Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma (β=-0.092, P=0.039),and had a positive predictive effect on the surgical method (β=0.244,P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma (β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions: The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Effects of attentional deployment training for relieving negative emotion in individuals with subthreshold depression

ObjectiveAs a prodromal stage to major depressive disorder (MDD), subthreshold depression (StD) has a higher prevalence in the population, resulting in a greater healthcare burden. StD individuals’ current negative emotion could be moderated by attentional deployment. However, it remains unclear whether attentional deployment training can mitigate subsequent negative emotion in StD individuals. MethodsBased on 160 participants, we combined decision task (Experiment 1, N = 69), eye-tracking (Experiment 2, N = 40), and EEG (Experiment 3, N = 51) techniques to investigate how one-week attentional deployment (gain-focus, GF) training modulated the emotional processing of negative stimulus and its underlying neural correlates in StD individuals. ResultsAfter one-week GF training, StD individuals significantly reduced the first fixation time and total fixation time on the negative part (missed opportunities) of decision outcome and showed a decrease in emotional sensitivity to missed opportunities. An increase in N1 and decrease in P3 and LPP (late positive potentials) amplitudes, as well as a decrease in alpha oscillation, were observed when StD individuals faced missed opportunities after training. Additionally, the extent of reduction in StD individuals’ emotional sensitivity to missed opportunities could be significantly predicted by the degree of decrease in alpha oscillation. ConclusionOne-week attentional deployment training could modulate negative emotion in StD individuals and the degree of change in alpha oscillation might act as an objective indicator for the effectiveness of training. SignificanceOur study provides a convenient and effective approach to alleviate the negative emotion of StD individuals.

Prodromic Inflammatory-Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer's Disease.

Inflammatory-oxidative stress is known to be pivotal in the pathobiology of Alzheimer's disease (AD), but the involvement of this stress at the peripheral level in the disease's onset has been scarcely studied. This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNFα, INFγ, IL-1β, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer's disease could be a consequence of peripheral alteration in the leukocyte inflammation-oxidation state.

A retrospective study of the MDS criteria for prodromal Parkinson’s disease in the general population

The Movement Disorder Society developed research criteria for the detection of the prodromal phase of Parkinson’s disease (PD). Accurate identification of this phase is essential for early interventions. Therefore, we investigated the diagnostic value of these research criteria in the general population. Lifelines is an ongoing cohort study of 167,000 participants from the general population of the Northern Netherlands. 160 participants self-reported to have developed PD during three rounds of follow-up of five years each. Data were available to infer six out of eleven risk markers, and six out of twelve prodromal markers. We retrospectively compared the criteria in the prodromal stage of a group of 160 ‘converters’ with 320 age- and sex-matched controls. The overall incidence rate of PD was 0.20 per 1.000 person-years (95% CI: 0.049−0.36), increasing with age and rates were higher in men. The median probability for prodromal PD in PD-converters was 1.29% (interquartile range: 0.46−2.9), compared to 0.83% (0.39−1.8) for controls (P = 0.014). The MDS set of criteria for prodromal PD had an ROC-AUC of 0.577, and was therefore not sufficient to adequately predict conversion to PD. We were unable to predict conversion to PD in the general population using a selection of the prodromal PD research criteria. Ancillary investigations are required to improve the diagnostic accuracy of the criteria, but most are precluded from large-scale use. Strategies, including olfactory tests or alpha-synuclein seeding amplification assays may improve the detection of prodromal PD in the general population.

Evidence for female dominance in the Milne-Edwards' sportive lemur (Lepilemur edwardsi).

Female dominance over males is more frequent in Malagasy lemurs than in other primate clades, but patterns of female-male dominance vary among species, and few data are available for one particularly species-rich genus, Lepilemur. We investigated the types, temporal distribution, and outcome of female-male agonistic conflicts in the Milne-Edwards' sportive lemur (Lepilemur edwardsi). Ten L. edwardsi belonging to five social units were equipped with radio collars and observed during 79 focal follows between May and November 1998. We quantified agonistic conflicts, monthly conflict rates, and documented the winner and context for all conflicts. Female-male agonistic conflicts (N = 162) occurred at a mean rate of 0.21 conflicts/hour within groups. Agonistic conflicts peaked during the birth season and occurred mostly in unknown or infant proximity contexts. Females won 96% of all decided agonistic conflicts (N = 154). Other outcomes occurred only when females were with infants during the birth season. In that context, one female sometimes withdrew from her pair partner, and another female withdrew or fled from an extra-group male whose attacks eventually led to infanticide. Our results suggest female dominance in pair-living L. edwardsi. We hypothesize that elevated female aggression may convey fitness benefits to female Lepilemur because it generally allows females to intervene quickly and efficiently on behalf of their infants against nonfather males who may approach the newborn infants when they are parked in vegetation.

Clinical utility of the at-risk for psychosis state beyond transition: A multidimensional network analysis.

To be relevant to healthcare systems, the clinical high risk for psychosis (CHR-P) concept should denote a specific (i.e., unique) clinical population and provide useful information to guide the choice of intervention. The current study applied network analyses to examine the clinical specificities of CHR-P youths compared to general help-seekers and non-CHR-P youth. 146 CHR-P (mean age = 14.32 years) and 103 non-CHR-P (mean age = 12.58 years) help-seeking youth were recruited from a neuropsychiatric unit and assessed using the Structured Interview for Psychosis-Risk Syndromes, Children's Depression Inventory, Multidimensional Anxiety Scale for Children, Global Functioning: Social, Global Functioning: Role, and Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale. The first network structure comprised the entire help-seeking sample (i.e., help-seekers network), the second only CHR-P patients (i.e., CHR-P network), and the third only non-CHR-P patients (i.e., non-CHR-P network). In the help-seekers network, each variable presented at least one edge. In the CHR-P network, two isolated "archipelagos of symptoms" were identified: (a) a subgraph including functioning, anxiety, depressive, negative, disorganization, and general symptoms; and (b) a subgraph including positive symptoms and the intelligence quotient. In the non-CHR-P network, positive symptoms were negatively connected to functioning, disorganization, and negative symptoms. Positive symptoms were less connected in the CHR-P network, indicating a need for specific interventions alongside those treating comorbid disorders. The findings suggest specific clinical characteristics of CHR-P youth to guide the development of tailored interventions, thereby supporting the clinical utility of the CHR-P concept.

Arginine-Vasotocin Neuronal System in Steindachneridion parahybae (Siluriformes: Pimelodidae) and Its Influence on Artificially Induced Spawning in Captivity

This study summarizes new data on induced spawning of Steindachneridion parahybae, focusing on the aggressive behavior of females. This study characterizes the vasotocinergic system using immunohistochemistry, highlighting the potential influence of arginine-vasotocin (AVT) on reproductive physiology. Two experimental groups were proposed: (A) control, with one female in the aquarium, and (B) experimental, with two females in the same aquarium. Dominant (D) females presented a more aggressive behavior and did not show any injury. They apparently had a length and body mass higher than injured nondominant (ND) females. The analysis identified positive AVT immunoreactive (ir) neurons exclusively within the preoptic area, including parvocellular, magnocellular, and gigantocellular subpopulations, containing fibers-ir extending into the pituitary gland. Cellular and nuclear areas were greater in D compared to ND in the magnocellular subpopulation. There were no differences between parvocellular and gigantocellular subpopulations. There was a difference on the steroid plasma profile of cortisol (more in ND than in D) and 17α,20β-dihydroxy-4-pregnen-3-one (more in D than in ND). Furthermore, control and D females presented higher optical densities for AVT-ir, gonadotropin-releasing hormone-ir, and luteinizing hormone-ir than ND. In general, there were no differences in the results of female (control group) with D females. The AVT system is highly complex, possibly counting multiple sites of action during artificial reproduction and acting directly and/or indirectly associated with behavioral and physiological changes in S. parahybae females when induced to spawning.

Cardiovascular risk factors among older persons with cognitive frailty in middle income country

BACKGROUND Cognitive frailty, characterized by the coexistence of cognitive impairment and physical frailty, represents a multifaceted challenge in the aging population. The role of cardiovascular risk factors in this complex interplay is not yet fully understood. AIM To investigate the relationships between cardiovascular risk factors and older persons with cognitive frailty by pooling data from two cohorts of studies in Malaysia. METHODS A comprehensive approach was employed, with a total of 512 community-dwelling older persons aged 60 years and above, involving two cohorts of older persons from previous studies. Datasets related to cardiovascular risks, namely sociodemographic factors, and cardiovascular risk factors, including hypertension, diabetes, hypercholesterolemia, anthropometric characteristics and biochemical profiles, were pooled for analysis. Cognitive frailty was defined based on the Clinical Dementia Rating scale and Fried frailty score. Cardiovascular risk was determined using Framingham risk score. Statistical analyses were conducted using SPSS version 21. RESULTS Of the study participants, 46.3% exhibited cognitive frailty. Cardiovascular risk factors including hypertension (OR:1.60; 95%CI: 1.12-2.30), low fat-free mass (OR:0.96; 95%CI: 0.94-0.98), high percentage body fat (OR:1.04; 95%CI: 1.02-1.06), high waist circumference (OR:1.02; 95%CI: 1.01-1.04), high fasting blood glucose (OR:1.64; 95%CI: 1.11-2.43), high Framingham risk score (OR:1.65; 95%CI: 1.17-2.31), together with sociodemographic factors, i.e. , being single (OR 3.38; 95%CI: 2.26-5.05) and low household income (OR 2.18; 95%CI: 1.44-3.30) were found to be associated with cognitive frailty. CONCLUSION Cardiovascular-risk specific risk factors and sociodemographic factors were associated with risk of cognitive frailty, a prodromal stage of dementia. Early identification and management of cardiovascular risk factors, particularly among specific group of the population might mitigate the risk of cognitive frailty, hence preventing dementia.

Developing disease-modifying interventions in idiopathic REM sleep behavior disorder and early synucleinopathy

Alpha-synucleinopathies are prevalent neurological disorders that cause significant disability, leading to progressive clinical deterioration that is currently managed solely through symptomatic treatment. Efforts to evaluate disease-modifying therapies during the established stage of the disease have not yielded positive outcomes in terms of clinical or imaging efficacy endpoints. However, alpha-synucleinopathies have a long prodromal phase that presents a promising opportunity for intervention with disease-modifying therapies. The presence of polysomnography-confirmed REM sleep behavior disorder (RBD) is the most reliable risk factor for identifying individuals in the prodromal stage of alpha-synucleinopathy. This paper discusses the rationale behind targeting idiopathic/isolated RBD in disease-modifying trials and outlines possible study designs, including strategies for patient stratification, selection of biomarkers to assess disease progression and patient eligibility, as well as the identification of suitable endpoints. Additionally, the potential targets for disease-modifying treatment in alpha-synucleinopathies are summarized.

Interpretable deep clustering survival machines for Alzheimer’s disease subtype discovery

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that has impacted millions of people worldwide. The neuroanatomical heterogeneity of AD has made it challenging to fully understand the disease mechanism. Identifying AD subtypes during the prodromal stage and determining their genetic basis would be immensely valuable for drug discovery and subsequent clinical treatment. Previous studies that clustered subgroups typically used unsupervised learning techniques, neglecting the survival information and potentially limiting the insights gained. To address this problem, we propose an interpretable survival analysis method called Deep Clustering Survival Machines (DCSM), which combines both discriminative and generative mechanisms. Similar to mixture models, we assume that the timing information of survival data can be generatively described by a mixture of parametric distributions, referred to as expert distributions. We learn the weights of these expert distributions for individual instances in a discriminative manner by leveraging their features. This allows us to characterize the survival information of each instance through a weighted combination of the learned expert distributions. We demonstrate the superiority of the DCSM method by applying this approach to cluster patients with mild cognitive impairment (MCI) into subgroups with different risks of converting to AD. Conventional clustering measurements for survival analysis along with genetic association studies successfully validate the effectiveness of the proposed method and characterize our clustering findings.

MODERN VIEW TO OPTIMIZATION OF DIAGNOSTICS OF PARKINSON'S DISEASE

Parkinsonism is one of the most significant problems of clinical neurology, both due to its high prevalence in the world's populations and due to the significant disability of patients. The work analyzes the diagnosis of Parkinson's disease (as well as other neurodegenerative diseases) at the prodromal stage. A review of methods for preclinical and early clinical diagnosis of PD shows that the study of prodromal markers and criteria for the premotor phase of PD will make it possible in the future to significantly change the course of the disease using neuroprotective therapy at the stage preceding the death of a significant number of dopaminergic neurons of the substantia nigra.

Prevalence of autism in first-episode psychosis in two Hong Kong teaching hospitals.

Autistic features are commonly observed in children and adolescents with first-episode psychosis, but they are sometimes overlooked by clinicians and caregivers. By comprehensively examining the clinical profiles of 103 children and adolescents (below 18 years old) with first-episode psychosis and conducting the Autism Diagnostic Interview-Revised (the 'gold standard' autism diagnostic tool) with their primary caregivers, we showed that around 28% of patients with first-episode psychosis had a comorbid autism diagnosis, and boys were 3.57 times more likely to have first-episode psychosis-autism spectrum disorder comorbidity than girls. After administering the Autism Diagnostic Interview-Revised, we also observed that an additional 30% of patients with first-episode psychosis met the autism spectrum disorder diagnostic cut-off; their autism spectrum disorder symptoms were probably overshadowed by prodromal psychotic symptoms and left undetected before this study. The co-occurrence of autism and first-episode psychosis might be more common than we previously thought. Careful autism screening and assessment is highly recommended for clinicians working with patients with psychosis.

Impact of celiac disease in Behçet's syndrome patients: a study based on the database of Türkiye.

Our primary aim was to investigate the effects of concomitant celiac disease (CD) on the clinical characteristics of Behçet's syndrome (BS) patients. The study was a retrospective, nationwide, multicenter study. Turkish Ministry of Health National Electronic Database (e-Nabız) is used under Health Ministry's supervision to extract the subject's data. Statistical analyses were made by the Statistical Package for Social Sciences (SPSS) software version 20 (IBM Corp., Armonk, New York). Continuous variables were presented by mean ± standard derivation (SD) or median (min-max) according to normality and compared by student-t test. A binary logistic regression analysis was performed to further investigating the relation between having a concomitant CD with each BD manifestation and comorbidity, frequencies of which were detected to be significantly different in the student-test. A total of 84,241 patients diagnosed with BS were analyzed, and CD was identified in 175 (0.21 %) patients. The group with CD had a mean age of 41.30 ± 13.69 which was significantly younger. the prevalence of females was significantly higher (71.4%). The mean age of first admission for BS was also significantly younger in the group with CD (36.64 ± 13.28). BS patients with CD had a significantly higher prevalence of inflammatory bowel disease (27.2% vs. 7.3%, p < 0.001). When comorbid conditions were investigated depression (35.4% vs. 23.3%, p < 0.001), migraine (7.4 % vs. 2.6%, p < 0.001), fibromyalgia (10.9% vs. 4.5%, p < 0.001) and osteoporosis (12.6% vs. 6.6%, p = 0.001) were significantly more frequent in BS patients with CD. Our results suggest coexistence of CD in BS patients is related to female dominance and probably to an earlier disease onset. Several CD-related comorbidities as well as inflammatory bowel disease were more frequent in the CD group which implied an increased overall disease burden.