Common Mechanism Research Articles

Smdi: an R package to perform structural missing data investigations on partially observed confounders in real-world evidence studies.

Partially observed confounder data pose a major challenge in statistical analyses aimed to inform causal inference using electronic health records (EHRs). While analytic approaches such as imputation are available, assumptions on underlying missingness patterns and mechanisms must be verified. We aimed to develop a toolkit to streamline missing data diagnostics to guide choice of analytic approaches based on meeting necessary assumptions. We developed the smdi (structural missing data investigations) R package based on results of a previous simulation study which considered structural assumptions of common missing data mechanisms in EHR. smdi enables users to run principled missing data investigations on partially observed confounders and implement functions to visualize, describe, and infer potential missingness patterns and mechanisms based on observed data. The smdi R package is freely available on CRAN and can provide valuable insights into underlying missingness patterns and mechanisms and thereby help improve the robustness of real-world evidence studies.

Pulmonary hypertension and insulin resistance: a mechanistic overview.

Pulmonary arterial hypertension (PAH) is a vascular remodeling disease, characterized by increased blood pressure levels in pulmonary circulation, leading to a restriction in the circulation flow and heart failure. Although the emergence of new PAH therapies has increased survival rates, this disease still has a high mortality and patients that receive diagnosis die within a few years. The pathogenesis of PAH involves multiple pathways, with a complex interaction of local and distant cytokines, hormones, growth factors, and transcription factors, leading to an inflammation that changes the vascular anatomy in PAH patients. These abnormalities involve more than just the lungs, but also other organs, and between these affected organs there are different metabolic dysfunctions implied. Recently, several publications demonstrated in PAH patients a disturbance in glucose metabolism, demonstrated by higher levels of glucose, insulin, and lipids in those patients. It is possible that a common molecular mechanism can have a significant role in this connection. In this regard, this narrative review intends to focus on the recent papers that mainly discuss the molecular determinants between insulin resistance (IR) associated PAH, which included obesity subclinical inflammation induced IR, PPAR gamma and Adiponectin, BMPR2, mitochondrial dysfunction and endoplasmic reticulum stress. Therefore, the following review will summarize some of the existing data for IR associated PAH, focusing on the better understanding of PAH molecular mechanisms, for the development of new translational therapies.

Unwrap RAP1's Mystery at Kinetoplastid Telomeres.

Although located at the chromosome end, telomeres are an essential chromosome component that helps maintain genome integrity and chromosome stability from protozoa to mammals. The role of telomere proteins in chromosome end protection is conserved, where they suppress various DNA damage response machineries and block nucleolytic degradation of the natural chromosome ends, although the detailed underlying mechanisms are not identical. In addition, the specialized telomere structure exerts a repressive epigenetic effect on expression of genes located at subtelomeres in a number of eukaryotic organisms. This so-called telomeric silencing also affects virulence of a number of microbial pathogens that undergo antigenic variation/phenotypic switching. Telomere proteins, particularly the RAP1 homologs, have been shown to be a key player for telomeric silencing. RAP1 homologs also suppress the expression of Telomere Repeat-containing RNA (TERRA), which is linked to their roles in telomere stability maintenance. The functions of RAP1s in suppressing telomere recombination are largely conserved from kinetoplastids to mammals. However, the underlying mechanisms of RAP1-mediated telomeric silencing have many species-specific features. In this review, I will focus on Trypanosoma brucei RAP1's functions in suppressing telomeric/subtelomeric DNA recombination and in the regulation of monoallelic expression of subtelomere-located major surface antigen genes. Common and unique mechanisms will be compared among RAP1 homologs, and their implications will be discussed.

Pharmacological and Psychological Treatment Have Common and Specific Effects on Brain Activity in Obsessive-Compulsive Disorder

Initial treatment for obsessive-compulsive disorder (OCD) consists of pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) and/or psychological treatment with cognitive behavioral therapy (CBT). The assumption is that both treatments have different neural working mechanisms, but empirical evidence is lacking. We investigated whether these treatments induce similar or different functional neural changes in OCD. We conducted a longitudinal nonrandomized controlled trial in which thirty-four OCD patients were treated with sixteen weeks of CBT or SSRIs. Functional magnetic resonance imaging was performed before and after treatment during emotional processing (emotional face matching and symptom provocation tasks) and response inhibition (stop signal task). Twenty matched healthy controls were scanned twice with a similar time interval. Both CBT and SSRIs were successful in reducing OCD symptoms. Compared to healthy controls, treatment led to a reduction of insula activity in OCD patients during symptom provocation. The comparison between treatment groups revealed widespread divergent brain changes in the cerebellum, posterior insula, caudate nucleus, hippocampus, and occipital and prefrontal cortex during all tasks, explained by relative increases of activity following CBT compared to relative decreases of activity following SSRIs. Pharmacological and psychological treatment primarily lead to opposite changes in brain function, with a common reduction of insula activity during symptom provocation. These findings provide insight into common and specific neural mechanisms underlying treatment response, suggesting that CBT and SSRIs support recovery from OCD along partly distinct pathways. This trial is registered with NTR6575.

Defining the Role of Extrachromosomal DNA Amplifications in Medulloblastoma.

Circular extrachromosomal DNA (ecDNA), a common mechanism of oncogene amplification, has been identified as a major contributor to intratumoral heterogeneity and patient outcomes. In a recent publication in Nature Genetics, Chapman and colleagues further explored the role of ecDNA in the context of medulloblastoma. Using whole-genome sequencing, they found that 18% of the patients carry ecDNA amplification across a 468 medulloblastoma patient cohort. The presence of ecDNA was associated with worse survival. Single-cell FISH imaging and multiomic sequencing revealed that ecDNA copy number displayed a cell-to-cell variability within the sample, contributing to tumor heterogeneity. Furthermore, through sequencing and CRISPRi experiments, the authors uncovered frequent enhancer rewiring events on ecDNA that drive proliferation.

Male facial cues to physical strength in Europe: Medium-strength preference and higher aggressiveness attribution to the weakest.

The capacity to assess male physical strength from facial cues may be adaptive given health and fitness-related associations with muscular strength. Our study complements recent research on strength-related face perceptions of male Maasai by applying the protocol to male European faces and assessors. Five distinct facial morphs calibrated for handgrip strength (HGS) were manufactured with geometric morphometrics performing regressions of the Procrustes shape coordinates on HGS in a sample of 26 European men (18-32 years). Young adult men and women (n = 445) rated these morphs on physical strength, attractiveness, and aggressiveness. Facial morphs calibrated to lower HGS were rated as less strong, less attractive, and more aggressive than those calibrated to higher HGS. Medium levels of HGS were associated with the highest attractiveness ratings. The rating patterns of physical strength, attractiveness, and aggressiveness for European male facial morphs exhibit similarity to previous ratings of Maasai male faces. Therefore, the current findings corroborate the suggestion of a common mechanism for social attributions based on facial cues to physical strength, modulated by local ecology and societal context.

Integrated Bioinformatics Analysis and Target Drug Prediction of Inflammatory Bowel Disease Co-existent Diabetes Mellitus.

Inflammatory bowel disease (IBD) has become one of the public problems worldwide and its incidence rate is increasing year by year. Its concomitant disease i.e. diabetes mellitus (DM) has attracted more and more attention due to DM altering the progression of IBD and leading to long periods of intermittent recurrence and deterioration. The common mechanism and potential target drug of IBD with comorbid chronic conditions of DM were explored. Gene expression profile data were downloaded from the Gene Expression Omnibus (GEO) public database. The differentially expressed genes (DEGs) were identified by R software. GO annotation and pathway enrichment were performed, a protein-protein interaction (PPI) network was constructed, associated lncRNAs were predicted and drug prediction targeting key genes was made. Additionally, the regulatory network among core genes, associated pathways, and predicted lncRNA in IBD with coexistent DM were visualized. We identified the critical gene MMP3 with lncRNA CDKN2BAS involved in the PPAR pathway, which uncovered the underlying regulatory mechanism of IBD with coexistent DM. We also predicted the potential therapeutic compound ZINC05905909 acting on MMP3. Our findings revealed the regulatory mechanism chain of critical gene MMP3, lncRNA CDKN2BAS, and PPAR pathway and provided potential therapeutic compound ZINC05905909 for drug therapy to treat comorbid IBD DM.

Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review.

Post-acute sequelae of COVID-19 can present as multi-organ pathology, with neuropsychiatric symptoms being the most common symptom complex, characterizing long COVID as a syndrome with a significant disease burden for affected individuals. Several typical symptoms of long COVID, such as fatigue, depressive symptoms and cognitive impairment, are also key features of other psychiatric disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and major depressive disorder (MDD). However, clinically successful treatment strategies are still lacking and are often inspired by treatment options for diseases with similar clinical presentations, such as ME/CFS. Acetylcarnitine, the shortest metabolite of a class of fatty acid metabolites called acylcarnitines and one of the most abundant blood metabolites in humans can be used as a dietary/nutritional supplement with proven clinical efficacy in the treatment of MDD, ME/CFS and other neuropsychiatric disorders. Basic research in recent decades has established acylcarnitines in general, and acetylcarnitine in particular, as important regulators and indicators of mitochondrial function and other physiological processes such as neuroinflammation and energy production pathways. In this review, we will compare the clinical basis of neuropsychiatric long COVID with other fatigue-associated diseases. We will also review common molecular disease mechanisms associated with altered acetylcarnitine metabolism and the potential of acetylcarnitine to interfere with these as a therapeutic agent. Finally, we will review the current evidence for acetylcarnitine as a supplement in the treatment of fatigue-associated diseases and propose future research strategies to investigate the potential of acetylcarnitine as a treatment option for long COVID.

Migraine Comorbidities.

Novel knowledge about the interrelationships and reciprocal effects of migraine and epilepsy, migraine and mood disorders, or migraine and irritable bowel syndrome has emerged in recent decades. Over time, comorbid pathologies associated with migraine that share common physiopathological mechanisms were studied. Among these studied pathologies is epilepsy, a disorder with common ion channel dysfunctions as well as dysfunctions in glutamatergic transmission. A high degree of neuronal excitement and ion channel abnormalities are associated with epilepsy and migraine and antiepileptic drugs are useful in treating both disorders. The coexistence of epilepsy and migraine may occur independently in the same individual or the two may be causally connected. The relationship between cortical spreading depression (CSD) and epileptic foci has been suggested by basic and clinical neuroscience research. The most relevant psychiatric comorbidities associated with migraine are anxiety and mood disorders, which influence its clinical course, treatment response, and clinical outcome. The association between migraine and major depressive disorder can be explained by a robust molecular genetic background. In addition to its role as a potent vasodilator, CGRP is also involved in the transmission of nociception, a phenomenon inevitably linked with the stress and anxiety caused by frequent migraine attacks. Another aspect is the role of gut microbiome in migraine's pathology and the gut-brain axis involvement. Irritable bowel syndrome patients are more likely to suffer migraines, according to other studies. There is no precise explanation for how the gut microbiota contributes to neurological disorders in general and migraines in particular. This study aims to show that migraines and comorbid conditions, such as epilepsy, microbiota, or mood disorders, can be connected from the bench to the bedside. It is likely that these comorbid migraine conditions with common pathophysiological mechanisms will have a significant impact on best treatment choices and may provide clues for future treatment options.

Disease-associated polyalanine expansion mutations impair UBA6-dependent ubiquitination

Expansion mutations in polyalanine stretches are associated with a growing number of diseases sharing a high degree of genotypic and phenotypic commonality. These similarities prompted us to query the normal function of physiological polyalanine stretches and to investigate whether a common molecular mechanism is involved in these diseases. Here, we show that UBA6, an E1 ubiquitin-activating enzyme, recognizes a polyalanine stretch within its cognate E2 ubiquitin-conjugating enzyme USE1. Aberrations in this polyalanine stretch reduce ubiquitin transfer to USE1 and, subsequently, polyubiquitination and degradation of its target, the ubiquitin ligase E6AP. Furthermore, we identify competition for the UBA6-USE1 interaction by various proteins with polyalanine expansion mutations in the disease state. The deleterious interactions of expanded polyalanine tract proteins with UBA6 in mouse primary neurons alter the levels and ubiquitination-dependent degradation of E6AP, which in turn affects the levels of the synaptic protein Arc. These effects are also observed in induced pluripotent stem cell-derived autonomic neurons from patients with polyalanine expansion mutations, where UBA6 overexpression increases neuronal resilience to cell death. Our results suggest a shared mechanism for such mutations that may contribute to the congenital malformations seen in polyalanine tract diseases.

Physiological and Transcriptomic Analyses Reveal Commonalities and Specificities in Wheat in Response to Aluminum and Manganese.

Aluminum (Al) and manganese (Mn) toxicity are the top two constraints of crop production in acid soil. Crops have evolved common and specific mechanisms to tolerate the two stresses. In the present study, the responses (toxicity and tolerance) of near-isogenic wheat lines (ET8 and ES8) and their parents (Carazinho and Egret) to Al and Mn were compared by determining the physiological parameters and conducting transcriptome profiling of the roots. The results showed the following: (1) Carazinho and ET8 exhibited dual tolerance to Al and Mn compared to Egret and ES8, indicated by higher relative root elongation and SPAD. (2) After entering the roots, Al was mainly distributed in the roots and fixed in the cell wall, while Mn was mainly distributed in the cell sap and then transported to the leaves. Both Al and Mn stresses decreased the contents of Ca, Mg, and Zn; Mn stress also inhibited the accumulation of Fe, while Al showed an opposite effect. (3) A transcriptomic analysis identified 5581 differentially expressed genes (DEGs) under Al stress and 4165 DEGs under Mn stress. Among these, 2774 DEGs were regulated by both Al and Mn stresses, while 2280 and 1957 DEGs were exclusively regulated by Al stress and Mn stress, respectively. GO and KEGG analyses indicated that cell wall metabolism responds exclusively to Al, while nicotianamine synthesis exclusively responds to Mn. Pathways such as signaling, phenylpropanoid metabolism, and metal ion transport showed commonality and specificity to Al and Mn. Transcription factors (TFs), such as MYB, WRKY, and AP2 families, were also regulated by Al and Mn, and a weighted gene co-expression network analysis (WGCNA) identified PODP7, VATB2, and ABCC3 as the hub genes for Al tolerance and NAS for Mn tolerance. The identified genes and pathways can be used as targets for pyramiding genes and breeding multi-tolerant varieties.

Genome-wide identification, characterization, and expression analysis of m6A readers-YTH domain-containing genes in alfalfa

Eukaryotic messenger RNAs (mRNAs) are often modified with methyl groups at the N6 position of adenosine (m6A), and these changes are interpreted by YTH domain-containing proteins to regulate the metabolism of m6A-modified mRNAs. Although alfalfa (Medicago sativa) is an established model organism for forage development, the understanding of YTH proteins in alfalfa is still limited. In the present investigation, 53 putative YTH genes, each encoding a YT521 domain-containing protein, were identified within the alfalfa genome. These genes were categorized into two subfamilies: YTHDF (49 members) and YTHDC (four members). Each subfamily demonstrates analogous motif distributions and domain architectures. Specifically, proteins encoded by MsYTHDF genes incorporate a single domain structure, while those corresponding to MsYTH5, 8, 12, 16 who are identified as members of the MsYTHDC subfamily, exhibit CCCH-type zinc finger repeats at their N-termini. It is also observed that the predicted aromatic cage pocket that binds the m6A residue of MsYTHDC consists of a sequence of two tryptophan residues and one tyrosine residue (WWY). Conversely, in MsYTHDF, the binding pocket comprises two highly conserved tryptophan residues and either one tryptophan residue (WWW) or tyrosine residue (WWY) in MsYTHDF.Through comparative analysis of qRT-PCR data, we observed distinct expression patterns in specific genes under abiotic stress, indicating their potential regulatory roles. Notably, five genes (MsYTH2, 14, 26, 27, 48) consistently exhibit upregulation, and two genes (MsYTH33, 35) are downregulated in response to both cold and salt stress. This suggests a common mechanism among these YTH proteins in response to various abiotic stressors in alfalfa. Further, integrating qRT-PCR with RNA-seq data revealed that MsYTH2, MsYTH14, and MsYTH16 are highly expressed in leaves at various development stages, underscoring their potential roles in regulating the growth of these plant parts. The obtained findings shed further light on the biological functions of MsYTH genes and may aid in the selection of suitable candidate genes for future genetic enhancement endeavors aimed at improving salt and cold tolerance in alfalfa.

Mass Spectrometry-Based Characterization of Protein Aggregates in Tissues and Biofluids.

Protein aggregation is a common mechanism in multiple neurodegenerative and heart diseasesand the accumulation of proteins in aggregates is toxic to cells, causing injury and death. The degree of protein aggregation directly correlates with the severity of the disease. Misfolded proteins present thermodynamic barriers that culminate in the loss of structure and function and the exposure of hydrophobic residues. The exposure of hydrophobic residues is the driving force behind protein aggregation, as it reduces surface free energy and increases the propensity for the formation of large insoluble aggregates. Exploring the protein content of aggregates is fundamental to understanding their formation mechanism and pathophysiological effects. We demonstrate here a method for isolating aggregated protein content in human plasma and mouse brain samples. The samples were characterized by mass spectrometry analysis, transmission electron microscopy, and western blotting. We report the identification of proteins associated with neurodegenerative diseases in the isolated pellets. The western blotting analyses of the isolated pellet showed the positivity for CD89 and CD63, consolidated markers of exosomes, confirming the presence of exosomes within the pellet but not in the supernatant in human plasma. Notably, the concomitant isolation of exosomes together with the protein aggregates was feasible starting from 200 μL of human plasma. Moreover, the presented methodology separated albumin from the aggregated pellet, allowing identification of larger diversity of proteins through mass spectrometry analysis.

Updates on Prognostication of Takotsubo Cardiomyopathy: A Literature Review

Abstract Takotsubo cardiomyopathy (TTC), commonly known as “broken heart syndrome” or “stress cardiomyopathy,” is characterized by transient left ventricular (LV) systolic dysfunction, usually in the absence of significant obstructive coronary artery stenosis. The pathophysiology of TTC remains elusive; however, the three most common plausible mechanisms include catecholamine surge causing myocardial stunning, multivessel coronary spasm, and microvascular dysfunction. Although initially thought to be a benign, reversible, and transient disorder, newer research data demonstrate that TTC may sometimes have severe short-term complications and some long-term residual effects. Several risk factors have been associated with the outcomes of TTC. In this review, we aim to provide a comprehensive review of the prognostication of TTC in the context of different clinical variables presented in multiple research studies. Various clinical factors, including the types of TTC triggers, the patient’s sex, the presence of cardiogenic shock, atrial arrhythmias, LV tract obstruction, and the presence of certain other clinical comorbidities may significantly impact patient outcomes in TTC patients. A thorough understanding of these factors helps clinicians to better prognosticate the outcome of their patients. Furthermore, early institution of aggressive treatment interventions in the presence of these risk factors may improve the subsequent clinical course.

Radiation and Chemical Program Research for Multi-Utility and Repurposed Countermeasures: A US Department of Health and Human Services Agencies Perspective.

Although chemical and radiological agents cause toxicity through different mechanisms, the multiorgan injuries caused by these threats share similarities that convene on the level of basic biological responses. This publication will discuss these areas of convergence and explore "multi-utility" approaches that could be leveraged to address common injury mechanisms underlying actions of chemical and radiological agents in a threat-agnostic manner. In addition, we will provide an overview of the current state of radiological and chemical threat research, discuss the US Government's efforts toward medical preparedness, and identify potential areas for collaboration geared toward enhancing preparedness and response against radiological and chemical threats. We also will discuss previous regulatory experience to provide insight on how to navigate regulatory paths for US Food and Drug Administration (FDA) approval/licensure/clearance for products addressing chemical or radiological/nuclear threats. This publication follows a 2022 trans-agency meeting titled, "Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures," sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). Discussions from this meeting explored the overlapping nature of radiation and chemical injury and spurred increased interest in how preparedness for one threat leads to preparedness for the other. Herein, subject matter experts from the NIAID and the Biomedical Advanced Research and Development Authority (BARDA), a part of the Administration for Strategic Preparedness and Response (ASPR), summarize the knowledge gained from recently funded biomedical research, as well as insights from the 2022 meeting. These topics include identification of common areas for collaboration, potential use of biomarkers of injury to identify injuries caused by both hazards, and common and widely available treatments that could treat damage caused by radiological or chemical threats.

A short guide to recent developments in laser-based gas phase spectroscopy, applications, and tools

This article provides an overview of laser-based absorption spectroscopy applications and discusses the parameter space and requirements of laser systems for each of these applications, with a special emphasis on frequency comb systems. We walk the reader through the basics of laser absorption spectroscopy, review common line-broadening mechanisms as fundamental challenges to precision spectroscopy, look into established solutions, introduce frequency-comb-based absorption spectroscopy, and suggest a novel approach to broadband precision spectroscopy in the mid-infrared spectral region based on a combination of broadband high-power ultra-stable optical frequency combs, crystalline supermirror technology, and an instrumental line-shape-free measurement technique. We conclude after an introduction of noise sources and their implications for precision measurements with an in-depth discussion and overview of the current state-of-the-art laser and optical parametric frequency conversion technologies.

Molecular biomarkers in Electrohypersensitivity and Multiple Chemical Sensitivity: How They Can Help Diagnosis, Follow-Up, and in Etiopathologic Understanding.

Electrohypersensitivty (EHS) and multiple chemical sensitivity (MCS) are new worldwide emerging neurologic disorders in the framework of sensitivity-related environmental pathology. We have recently extended and confirmed our previous observation showing that EHS and MCS share clinically identical symptoms and may co-exist as a unique, common, sensitivity-related neurologic syndrome in 25% of the cases. There is presently no published biological study of these disorders, except the one we have previously published as preliminary. In the present study, we show that EHS and MCS and the combined syndrome share identical biochemical changes. More precisely, by measuring levels of peripheral blood and urine molecular biomarkers in a cohort of 2,018 consecutive cases, we show that both disorders and the combined syndrome can be objectively characterized, in about 90% of the cases, by a decrease in the production of 6-hydroxymelatonin sulfate in urine, while in 30-50% they are characterized by increased levels of histamine and of heat shock proteins (HSP) 27 and/or 70, and of protein S100B and nitrotyrosine in the peripheral blood. Increased levels of histamine and HSP are indicators of low grade inflammation while increased levels of protein S100B and nitrotyrosine are indicators of blood-brain barrier disruption/opening. In addition, we show that in about 15% of the cases anti-myelin autoantibodies can be detected in the peripheral blood, accounting for the occurrence of an autoimmune response. Sensitivity, specificity and reproducibility of the biochemical tests are discussed, as well as the role of these indicators used as biomarkers for the diagnosis and follow-up of patients. We also discuss cases with undetectable biological change for which they can be nevertheless diagnosed by cerebral neurotransmitters analysis in urine and brain imaging. On the basis of these biological data it is suggested that EHS and/or MCS are new brain disorders, generated via a common etiopathogenic mechanism.

Childhood primary stabbing headache: A double center study.

Primary stabbing headache (PSH) is an idiopathic headache disorder characterized by head pain occurring as a transient and localized single stab or a series of stabs. The present study aimed to examine the characteristics of childhood PSH and whether they fit the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria. We also investigated the association with migraine and episodic syndromes. In this retrospective study, we included 60 patients seen at two headache clinics (Rome and Bari) between 2016 and 2022. A headache-focused history was obtained. All patients had normal neurological examination. PSH was defined according to ICHD-3 criteria. Twenty-three patients were male (38%) and median (range) age at disease onset was 8 (3-17) years. Stabs recurred with irregular frequency and their duration varied from a few seconds up to 30 minutes. Stabs were located in different head regions. Twenty-five patients (42%) underwent neuroimaging exams. Five children reported a limitation of daily activities and none had a chronic pattern. Forty-seven patients (78%) reported a family history of primary headache, especially migraine, and forty-three had episodic syndromes (i.e. infantile colic, benign paroxysmal vertigo, motion sickness, recurrent abdominal pain, cyclic vomiting). Twenty patients had an associated primary headache: 16 suffered from migraine and four suffered from tension type-headache. According to ICHD-3 criteria, thirty-one patients had a diagnosis of probable PSH as a result of a duration of stabs longer than a few seconds (>3 seconds). Features of childhood PSH can vary widely. As seen in previous studies, several patients reported a stab duration longer than a few seconds and this might suggest that current ICHD-3 criteria may need adjustments to be suitable for children. High frequency of associated migraine and episodic syndromes could suggest a common pathophysiological mechanism between PSH and migraine. We can hypothesize that PSH and migraine attacks may be part of a spectrum of the same disease, although further evidence is needed. Larger studies with long-term follow-up are needed to improve understanding of this condition.

Impact of lifestyle modification on nonalcoholic fatty liver with prediabetes and type 2 diabetes

Prediabetes is characterized by impaired glucose uptake and insulin sensitivity in the muscle, as well as a significant risk of developing diabetes, chronic renal disease, cardiovascular disease, and death. A definite bidirectional connection exists between pre-diabetes, diabetes, and NAFLD. The presence of NAFLD is associated with the subsequent development of new-onset type 2 diabetes (T2DM). There was a 6-fold rise in new-onset diabetes in people whose fatty liver severity progressed from mild to moderate or severe over 5 years, and a decrease in T2DM incidence comparable to that in those without steatosis. Insulin resistance is a common pathophysiological mechanism across metabolic illnesses, including prediabetes, diabetes, and NAFLD. As a result, better names for metabolically linked metabolic fatty liver disease have been considered. Lifestyle is the cornerstone of treatment for patients with prediabetes, T2DM, and NAFLD. Several significant randomized controlled trials show that a customized low-calorie meal plan and behavioral change are highly effective in preventing or delaying prediabetes, type 2 diabetes, and improving other cardiometabolic markers (such as blood pressure, lipids, and inflammation). Several drugs already approved for the treatment of prediabetes and diabetes are beneficial for NAFLD/NASH.

Understanding Psoriasis as a Biobehavioral Network Disease

Psoriasis is a common immune-mediated inflammatory disease that can often be associated with psychiatric problems such as depression and anxiety. Although psychiatric disorders were initially considered secondary, the high prevalence suggests that common pathophysiological mechanisms may be involved in the development of psoriasis and psychiatric disorders. The shared neuroendocrine and immune mediators weave a web of networks with bidirectional pathways. Biopsychosocial patterns of psoriasis include psychological and behavioral consequences influencing personal social networks, psychological dispositions, and brain-skin psychoimmunological network patterns, which sums in a network of networks. The pathodynamics of other organ diseases like diabetes, liver diseases, internal organ tumors, and latent long-term inflammatory processes (chronic tonsillitis, prostatitis, abscesses and inflammations in the gums, chronic sinusitis) influence psoriasis. Vice versa, psoriasis might cause a pathological impact on other organ systems via networked connections, like arthritis or psychological dispositions. Treatment of psoriasis needs networking through the cooperation of dermatology, rheumatology, and psychiatry and by combining different therapies.