Polysomnographically Defined Restless Sleep Disorder and Periodic Limb Movements during Sleep in Children Born Prematurely.

INTRODUCTION: Children born prematurely (<37 weeks' gestation) are at increased risk of perinatal complications, comorbidities, and iron deficiency. Iron deficiency is associated with restless legs syndrome and periodic limb movement disorder. In this study, we assessed the prevalence of restless sleep disorder (RSD) and elevated periodic limb movements during sleep (PLMS) in children born prematurely who underwent polysomnography. METHODS: A retrospective chart review of sleep studies was conducted in children aged 1-18 years (median age 4 years) with a history of premature birth. Children with genetic syndrome, airway surgery, or tracheostomy were excluded. Three groups were compared: children with PLMS index >5, children with RSD, and children with neither elevated PLMS index nor RSD. RESULTS: During the study, 2577 sleep studies were reviewed. Ninety-two studies fit our criteria and were included in the analysis. The median age at birth was 31 weeks, and the interquartile range (IQR) was 27-34 weeks. A total of 32 (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring. After polysomnography, 18% were found to have a PLMS index >5/h, and 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters among the children with RSD, PLMS, and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p = 0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5) or the non-RSD/non-PLMS (median 2.0, IQR 0.8-4.5) groups. CONCLUSIONS: There was an elevated frequency of RSD and elevated PLMS in our cohort of children born prematurely. Children born prematurely are at higher risk of iron deficiency which can be a contributor factor to sleep -related movement disorders. These results add new knowledge regarding the prevalence of RSD and PLMS in these children.

Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

Unveiling the pathophysiology of restless legs syndrome through transcriptome analysis.

The aim of this study was to analyze signaling pathways associated with differentially expressed messenger RNAs in people with restless legs syndrome (RLS). Seventeen RLS patients and 18 controls were enrolled. Coding RNA expression profiling of 12,857 gene transcripts by next-generation sequencing was performed. Enrichment analysis by pathfindR tool was carried-out, with p-adjusted ≤0.001 and fold-change ≥2.5. Nine main different network groups were significantly dysregulated in RLS: infections, inflammation, immunology, neurodegeneration, cancer, neurotransmission and biological, blood and metabolic mechanisms. Genetic predisposition plays a key role in RLS and evidence indicates its inflammatory nature; the high involvement of mainly neurotropic viruses and the TORCH complex might trigger inflammatory/immune reactions in genetically predisposed subjects and activate a series of biological pathways-especially IL-17, receptor potential channels, nuclear factor kappa-light-chain-enhancer of activated B cells, NOD-like receptor, mitogen-activated protein kinase, p53, mitophagy, and ferroptosis-involved in neurotransmitter mechanisms, synaptic plasticity, axon guidance, neurodegeneration, carcinogenesis, and metabolism.

The association between posterior resting-state EEG alpha rhythms and functional MRI connectivity in older adults with subjective memory complaint.

Resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms are dominant in posterior cortical areas in healthy adults and are abnormal in subjective memory complaint (SMC) persons with Alzheimer's disease amyloidosis. This exploratory study in 161 SMC participants tested the relationships between those rhythms and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) connectivity between thalamus and visual cortical networks as a function of brain amyloid burden, revealed by positron emission tomography and cognitive reserve, measured by educational attainment. The SMC participants were divided into 4 groups according to 2 factors: Education (Edu+ and Edu-) and Amyloid burden (Amy+ and Amy-). There was a statistical interaction (p < 0.05) between the two factors, and the subgroup analysis using estimated marginal means showed a positive association between the mentioned rs-fMRI connectivity and the posterior rsEEG alpha rhythms in the SMC participants with low brain amyloidosis and high CR (Amy-/Edu+). These results suggest that in SMC persons, early Alzheimer's disease amyloidosis may contrast the beneficial effects of cognitive reserve on neurophysiological oscillatory mechanisms at alpha frequencies and connectivity between the thalamus and visual cortical networks.

Biomarkers of neurodegeneration in isolated and antidepressant-related rapid eye movement sleep behavior disorder.

BACKGROUND AND PURPOSE: This study compared the features of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and antidepressant-related REM sleep behaviour disorder (RBD) with the aim of highlighting markers that might distinguish the two entities. METHODS: The observational cohort study included RBD patients with and without antidepressant use (antiD+ and antiD- patients, respectively), without cognitive impairment and parkinsonism. Clinical features of RBD, subtle motor and non-motor symptoms of parkinsonism, sleep architecture, REM atonia index, dopamine transporter-single photon emission computed tomography (DAT-SPECT) and skin biopsies for the intraneuronal alpha-synuclein (α-syn), were evaluated in the baseline work-up. RESULTS: Thirty-nine patients, 10 antiD+ and 29 antiD-, were included. AntiD+ patients (more frequently female) reported more psychiatric symptoms, less violent dream enactment, and less frequent hyposmia. Dermal α-syn was detected in 93.1% of antiD- versus 30% of antiD+ patients (p = 0.00024). No differences appeared in other motor and non-motor symptoms, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III score, DAT-SPECT, or polysomnographic features. CONCLUSIONS: Patients with antidepressant-related RBD have clinical and neuropathological features suggesting a lower risk of evolution than those with iRBD.

Gene Expression Profiling of Post Mortem Midbrain of Parkinson's Disease Patients and Healthy Controls.

Parkinson's disease (PD) stands as the most prevalent degenerative movement disorder, marked by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. In this study, we conducted a transcriptome analysis utilizing post mortem mRNA extracted from the substantia nigra of both PD patients and healthy control (CTRL) individuals. Specifically, we acquired eight samples from individuals with PD and six samples from CTRL individuals, with no discernible pathology detected in the latter group. RNA sequencing was conducted using the TapeStation 4200 system from Agilent Technologies. A total of 16,148 transcripts were identified, with 92 mRNAs displaying differential expression between the PD and control groups. Specifically, 33 mRNAs were significantly up-regulated, while 59 mRNAs were down-regulated in PD compared to the controls. The identification of statistically significant signaling pathways, with an adjusted p-value threshold of 0.05, unveiled noteworthy insights. Specifically, the enriched categories included cardiac muscle contraction (involving genes such as ATPase Na+/K+ transporting subunit beta 2 (ATP1B2), solute carrier family 8 member A1 (SLC8A1), and cytochrome c oxidase subunit II (COX2)), GABAergic synapse (involving GABA type A receptor-associated protein-like 1 (GABARAPL1), G protein subunit beta 5 (GNB5), and solute carrier family 38 member 2 (SLC38A2), autophagy (involving GABARAPL1 and tumor protein p53-inducible nuclear protein 2 (TP53INP2)), and Fc gamma receptor (FcγR) mediated phagocytosis (involving amphiphysin (AMPH)). These findings uncover new pathophysiological dimensions underlying PD, implicating genes associated with heart muscle contraction. This knowledge enhances diagnostic accuracy and contributes to the advancement of targeted therapies.

Sleep and Sleep Complaints in Juvenile Fibromyalgia Syndrome.

OBJECTIVE: To investigate sleep quality in juvenile fibromyalgia syndrome (JFS) and its effect on the global burden of the disease. METHODS: Consecutive patients with JFS who performed full-night polysomnography (PSG) were included in this cross-sectional study. JFS-related symptoms, neuropsychiatric features, and sleep quality were assessed using self-report measures. PSG sleep parameters, including N3 distribution index, were obtained from patients and age-matched healthy controls. RESULTS: We included 25 patients (20 females, median age 15.7 yrs). Nonrestorative sleep was reported by 22 of 25 (88%) patients. Patients with JFS showed significantly longer sleep period time (P = 0.004) and increased wake after sleep onset (P = 0.03) compared to healthy peers. The N3 distribution index was significantly lower in patients than in the control group (P = 0.02). Subjective poor sleep quality was related to Widespread Pain Index (WPI; r s -0.65), Symptom Severity Scale (r s -0.64), depressive symptoms (r s -0.58), fatigue (r s -0.44), and symptom severity upon awakening (r s -0.65). The N3 distribution index was correlated to depressive symptoms (r s 0.41) and irritability (rs 0.40). On multiple regression analysis, WPI was predicted by subjective sleep quality (ß -0.32, P = 0.04), whereas depressive symptoms were predicted by subjective sleep measures (ß -0.32, P = 0.04) and PSG parameters (N3 min: ß -0.07, P = 0.03). CONCLUSION: Sleep complaints are a key hallmark of JFS and have significant effect on relevant clinical domains of the disease, such as pain and depression.

Periodic leg movements during sleep and iron status in infants with prematurity, Down syndrome and Prader-Willi syndrome.

Sleep disturbances including bedtime problems and night awakenings are common during infancy. Polysomnography during the first years of life is performed mainly to rule out sleep-disordered breathing; however, sleep-related movement disorders can constitute a significant contributor to sleep disruption in this age group. Almost no studies have investigated the presence of periodic limb movements during sleep and underlying iron deficiency in infants, especially in those born preterm or with an underlying genetic syndrome. In this retrospective study we included infants 3-24 months referred for polysomnography for snoring or frequent nocturnal awakenings. All children had bloodwork (ferritin and haemoglobin) conducted within 3 months of the overnight sleep study. We studied 79 infants, including 31 (39.2%) full-term without diagnosis, 10 (12.7%) born premature, 16 (20.3%) with Down syndrome, 15 (19.0%) with Prader-Willi syndrome, and the remaining seven (8.9%) had various disorders. Compared with those with Down syndrome, Prader-Willi syndrome and full-term infants, those with prematurity showed a statistically significant elevated periodic limb movement index and lower ferritin levels than the other groups. Both ferritin (r = -0.18) and haemoglobin (r = -0.30) were negatively correlated with periodic limb movement index; however, this correlation reached statistical significance only for haemoglobin. Iron deficiency is associated with increased periodic leg movements during sleep in infants. Infants with prematurity had higher periodic limb movement index and lower ferritin levels than infants with Down syndrome, Prader-Willi syndrome or without diagnosis.

Effects of bupropion and SSRI antidepressants on leg movement activity and chin muscle tone during sleep in adolescents.

STUDY OBJECTIVES: To evaluate the effects of bupropion on periodic limb movements during sleep (PLMS) and chin electromyography tone in children taking it for their mood disorder, compared to the effects of selective serotonin reuptake inhibitors (SSRIs) and of bupropion combined with SSRIs. METHODS: Six adolescents (aged 16.0 ± 0.63 years) taking bupropion alone and 6 adolescents (aged 15.9 ± 1.36 years) taking bupropion in combination with an SSRI antidepressant were recruited, along with 10 adolescents (aged 16.2 ± 0.2 years) taking different SSRIs, and they were also enrolled together with 17 age- and sex-matched control patients (aged 15.5 ± 1.26 years). Polysomnographic studies were obtained, and participants' leg movement activity during sleep and muscle tone were assessed quantitatively (atonia index) during all sleep stages. RESULTS: Participants taking SSRIs showed PLMS indices significantly higher than those of control patients, whereas adolescents taking bupropion showed only slightly increased indexes of nonperiodic leg movements during sleep. No differences in PLMS were observed between adolescents taking bupropion alone or in association with SSRIs. The atonia index showed, within each sleep stage, the lowest values in the 2 groups taking SSRIs and the highest in the control patients; adolescents taking bupropion alone tended to show values slightly smaller than those of the control patients. CONCLUSIONS: We found that similar to adults, in adolescents SSRIs but not bupropion are associated with increased PLMS. Bupropion also seems to counteract the SSRI-induced increase of PLMS, when administered in combination; thus, the dopaminergic effect of bupropion seems to outmatch the antidopaminergic action of SSRIs. Conversely, bupropion does not counteract the effects of SSRIs on chin electromyography tone. CITATION: DelRosso LM, Mogavero MP, Fickensher A, Bruni O, Schenck CH, Ferri R. Effects of bupropion and SSRI antidepressants on leg movement activity and chin muscle tone during sleep in adolescents. J Clin Sleep Med. 2023;19(1):151-161.

Examples of Inverse Comorbidity between Cancer and Neurodegenerative Diseases: A Possible Role for Noncoding RNA.

Cancer is one of the most common causes of death; in parallel, the incidence and prevalence of central nervous system diseases are equally high. Among neurodegenerative diseases, Alzheimer's dementia is the most common, while Parkinson's disease (PD) is the second most frequent neurodegenerative disease. There is a significant amount of evidence on the complex biological connection between cancer and neurodegeneration. Noncoding RNAs (ncRNAs) are defined as transcribed nucleotides that perform a variety of regulatory functions. The mechanisms by which ncRNAs exert their functions are numerous and involve every aspect of cellular life. The same ncRNA can act in multiple ways, leading to different outcomes; in fact, a single ncRNA can participate in the pathogenesis of more than one disease-even if these seem very different, as cancer and neurodegenerative disorders are. The ncRNA activates specific pathways leading to one or the other clinical phenotype, sometimes with obvious mechanisms of inverse comorbidity. We aimed to collect from the existing literature examples of inverse comorbidity in which ncRNAs seem to play a key role. We also investigated the example of mir-519a-3p, and one of its target genes Poly (ADP-ribose) polymerase 1, for the inverse comorbidity mechanism between some cancers and PD. We believe it is very important to study the inverse comorbidity relationship between cancer and neurodegenerative diseases because it will help us to better assess these two major areas of human disease.

Dietary Phytoestrogen Intake and Cognitive Status in Southern Italian Older Adults.

BACKGROUND: Aging society faces significant health challenges, among which cognitive-related disorders are emerging. Diet quality has been recognized among the major contributors to the rising prevalence of cognitive disorders, with increasing evidence of the putative role of plant-based foods and their bioactive components, including polyphenols. Dietary polyphenols, including phytoestrogens, have been hypothesized to exert beneficial effects toward brain health through various molecular mechanisms. However, the evidence on the association between dietary phytoestrogen intake and cognitive function is limited. The aim of this study was to investigate the association between phytoestrogen intake and cognitive status in a cohort of older adults living in Sicily, Southern Italy. METHODS: Dietary information from 883 individuals aged 50 years or older was collected through a validated food frequency questionnaire. Cognitive status was assessed through the Short Portable Mental Status Questionnaire. RESULTS: The highest total isoflavone (including daidzein and genistein) intake was inversely associated with cognitive impairment compared to the lowest (odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.20-0.92). Higher intake of total lignans and, consistently, all individual compounds (with the exception of secoisolariciresinol) were inversely associated with cognitive impairment only in the unadjusted model. CONCLUSIONS: A higher intake of phytoestrogens, especially isoflavones, was associated with a better cognitive status in a cohort of older Italian individuals living in Sicily. Taking into account the very low intake of isoflavones in Italian diets, it is noteworthy to further investigate selected populations with habitual consumption of such compounds to test whether these results may be generalized to the Italian population.

The effect of laboratory-verified smoking on SARS-CoV-2 infection: results from the Troina sero-epidemiological survey.

Previous research yielded conflicting results on the association between cigarette smoking and risk of SARS-CoV-2 infection. Since the prevalence of smoking is high globally, the study of its impact on COVID-19 pandemic may have considerable implications for public health. This study is the first to investigate the association between the SARS-CoV-2 antibody sero-positivity and biochemically verified smoking status, to refine current estimates on this association. SARS-CoV-2-specific IgG and serum cotinine levels (a well-known marker of tobacco exposure) were assessed in a large sero-epidemiological survey conducted in the town of Troina (Sicily, Italy). A propensity score matching was carried out to reduce the effect of possible factors on SARS-CoV-2 infection risk among study participants. Of the 1785 subjects included in our study, one-third was classified as current smokers, based on serum cotinine levels. The overall proportion of subjects with positive serology for SARS-CoV-2 IgG was 5.4%. The prevalence of SARS-CoV-2 antibody positivity and previous COVID-19 diagnosis were reduced in smokers. This reduced prevalence persisted after adjusting for possible confounders (such as sex, age, previous infection, chronic conditions, and risk group) at regression analyses, and the point estimates based on the PS-matched models resulted consistent with those for the unmatched population. This study found a lower proportion of positive SARS-CoV-2 serology among current smokers, using direct laboratory measures of tobacco exposure and thus avoiding possible bias associated with self-reported smoking status. Results may also serve as a reference for future clinical research on potential pharmaceutical role of nicotine or nicotinic-cholinergic agonists against COVID-19.

Daily mocha coffee intake and psycho-cognitive status in non-demented non-smokers subjects with subcortical ischaemic vascular disease.

Coffee intake has been recently associated with better cognition and mood in mild vascular cognitive impairment (mVCI). As tobacco can reduce the caffeine half-life, we excluded smokers from the original sample. Hamilton Depression Rating Scale (HDRS), mini-mental state examination (MMSE), Stroop Colour-Word Interference Test (Stroop), activities of daily living (ADL0) and instrumental ADL were the outcome measures. Significant differences were observed in higher consumption groups (moderate intake for HDRS; high intake for MMSE and Stroop) compared to the other groups, as well as in age and education. With age, education and coffee used as independent predictors, and HDRS, Stroop and MMSE as dependent variables, a correlation was found between age and both MMSE and Stroop, as well as between education and MMSE and between HDRS and Stroop; coffee intake negatively correlated with HDRS and Stroop. Higher coffee consumption was associated with better psycho-cognitive status among non-smokers with mVCI.

Phenolic Acids and Prevention of Cognitive Decline: Polyphenols with a Neuroprotective Role in Cognitive Disorders and Alzheimer's Disease.

Cognitive impairment, also known as cognitive decline, can occur gradually or suddenly and can be temporary or more permanent. It represents an increasingly important public health problem and can depend on normal aging or be linked to different neurodegenerative disorders, including Alzheimer's disease (AD). It is now well-established that lifestyle factors including dietary patterns play an important role in healthy aging as well as in the prevention of cognitive decline in later life. Among the natural compounds, dietary polyphenols including phenolic acids have been recently the focus of major attention, with their supplementation being associated with better cognitive status and prevention of cognitive decline. Despite their therapeutic potential, human studies investigating the relation between phenolic acids intake and cognitive outcomes are rather scarce. In this review, we provide preclinical evidence that different dietary polyphenols such as rosmarinic acid, ellagic acid, and cinnamic aldehyde can exert neuroprotective and pro-cognitive activities through different molecular mechanisms including the modulation of pro-oxidant and antioxidant machinery as well as inflammatory status. Future and more numerous in vivo studies are needed to strengthen the promising results obtained at the preclinical level. Despite the excellent pharmacokinetic properties of phenolic acids, which are able to be accumulated in the brain at pharmacologically relevant levels, future studies should also identify which among the different metabolites produced as a consequence of phenolic acids' consumption may be responsible for the potential neuroprotective effects of this subgroup of polyphenols.

A Transcriptome Analysis of mRNAs and Long Non-Coding RNAs in Patients with Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The number of cases of PD is expected to double by 2030, representing a heavy burden on the healthcare system. Clinical symptoms include the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain, which leads to striatal dopamine deficiency and, subsequently, causes motor dysfunction. Certainly, the study of the transcriptome of the various RNAs plays a crucial role in the study of this neurodegenerative disease. In fact, the aim of this study was to evaluate the transcriptome in a cohort of subjects with PD compared with a control cohort. In particular we focused on mRNAs and long non-coding RNAs (lncRNA), using the Illumina NextSeq 550 DX System. Differential expression analysis revealed 716 transcripts with padj ≤ 0.05; among these, 630 were mRNA (coding protein), lncRNA, and MT_tRNA. Ingenuity pathway analysis (IPA, Qiagen) was used to perform the functional and pathway analysis. The highest statistically significant pathways were: IL-15 signaling, B cell receptor signaling, systemic lupus erythematosus in B cell signaling pathway, communication between innate and adaptive immune cells, and melatonin degradation II. Our findings further reinforce the important roles of mitochondria and lncRNA in PD and, in parallel, further support the concept of inverse comorbidity between PD and some cancers.

Polyphenols and neuroprotection: Therapeutic implications for cognitive decline.

Dietary polyphenols have been the focus of major interest for their potential benefits on human health. Several preclinical studies have been conducted to provide a rationale for their potential use as therapeutic agents in preventing or ameliorating cognitive decline. However, results from human studies are scarce and poorly documented. The aim of this review was to discuss the potential mechanisms involved in age-related cognitive decline or early stage cognitive impairment and current evidence from clinical human studies conducted on polyphenols and the aforementioned outcomes. The evidence published so far is encouraging but contrasting findings are to be taken into account. Most studies on anthocyanins showed a consistent positive effect on various cognitive aspects related to aging or early stages of cognitive impairment. Studies on cocoa flavanols, resveratrol, and isoflavones provided substantial contrasting results and further research is needed to clarify the therapeutic potential of these compounds. Results from other studies on quercetin, green tea flavanols, hydroxycinnamic acids (such as chlorogenic acid), curcumin, and olive oil tyrosol and derivatives are rather promising but still too few to provide any real conclusions. Future translational studies are needed to address issues related to dosage, optimal formulations to improve bioavailability, as well as better control for the overall diet, and correct target population.

Role and Dysregulation of miRNA in Patients with Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative synucleinopathy that has a not yet fully understood molecular pathomechanism behind it. The role of risk genes regulated by small non-coding RNAs, or microRNAs (miRNAs), has also been highlighted in PD, where they may influence disease progression and comorbidities. In this case-control study, we analyzed miRNAs on peripheral blood mononuclear cells by means of RNA-seq in 30 participants, with the aim of identifying miRNAs differentially expressed in PD compared to age-matched healthy controls. Additionally, we investigated the pathways influenced by differentially expressed miRNAs and assessed whether a specific pathway could potentially be associated with PD susceptibility (enrichment analyses performed using the Ingenuity Pathway Analysis tools). Overall, considering that the upregulation of miRNAs might be related with the downregulation of their messenger RNA targets, and vice versa, we found several putative targets of dysregulated miRNAs (i.e., upregulated: hsa-miR-1275, hsa-miR-23a-5p, hsa-miR-432-5p, hsa-miR-4433b-3p, and hsa-miR-4443; downregulated: hsa-miR-142-5p, hsa-miR-143-3p, hsa-miR-374a-3p, hsa-miR-542-3p, and hsa-miR-99a-5p). An inverse connection between cancer and neurodegeneration, called "inverse comorbidity", has also been noted, showing that some genes or miRNAs may be expressed oppositely in neurodegenerative disorders and in some cancers. Therefore, it may be reasonable to consider these miRNAs as potential diagnostic markers and outcome measures.

Restless legs syndrome.

Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by an urge to move that appears during rest or is exacerbated by rest, that occurs in the evening or night and that disappears during movement or is improved by movement. Symptoms vary considerably in age at onset, frequency and severity, with severe forms affecting sleep, quality of life and mood. Patients with RLS often display periodic leg movements during sleep or resting wakefulness. RLS is considered to be a complex condition in which predisposing genetic factors, environmental factors and comorbidities contribute to the expression of the disorder. RLS occurs alone or with comorbidities, for example, iron deficiency and kidney disease, but also with cardiovascular diseases, diabetes mellitus and neurological, rheumatological and respiratory disorders. The pathophysiology is still unclear, with the involvement of brain iron deficiency, dysfunction in the dopaminergic and nociceptive systems and altered adenosine and glutamatergic pathways as hypotheses being investigated. RLS is poorly recognized by physicians and it is accordingly often incorrectly diagnosed and managed. Treatment guidelines recommend initiation of therapy with low doses of dopamine agonists or α2δ ligands in severe forms. Although dopaminergic treatment is initially highly effective, its long-term use can result in a serious worsening of symptoms known as augmentation. Other treatments include opioids and iron preparations.

Seroepidemiological Survey on the Impact of Smoking on SARS-CoV-2 Infection and COVID-19 Outcomes: Protocol for the Troina Study.

BACKGROUND: After the global spread of SARS-CoV-2, research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. However, emerging results on the role of smoking in SARS-CoV-2 infection susceptibility or COVID-19 outcomes are conflicting, and their robustness remains uncertain. OBJECTIVE: In this context, this study aims at quantifying the proportion of SARS-CoV-2 antibody seroprevalence, studying the changes in antibody levels over time, and analyzing the association between the biochemically verified smoking status and SARS-CoV-2 infection. METHODS: The research design involves a 6-month prospective cohort study with a serial sampling of the same individuals. Each participant will be surveyed about their demographics and COVID-19-related information, and blood sampling will be collected upon recruitment and at specified follow-up time points (ie, after 8 and 24 weeks). Blood samples will be screened for the presence of SARS-CoV-2-specific antibodies and serum cotinine, being the latter of the principal metabolite of nicotine, which will be used to assess participants' smoking status. RESULTS: The study is ongoing. It aims to find a higher antibody prevalence in individuals at high risk for viral exposure (ie, health care personnel) and to refine current estimates on the association between smoking status and SARS-CoV-2/COVID-19. CONCLUSIONS: The added value of this research is that the current smoking status of the population to be studied will be biochemically verified to avoid the bias associated with self-reported smoking status. As such, the results from this survey may provide an actionable metric to study the role of smoking in SARS-CoV-2 infection and COVID-19 outcomes, and therefore to implement the most appropriate public health measures to control the pandemic. Results may also serve as a reference for future clinical research, and the methodology could be exploited in public health sectors and policies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32285.

A study of gene expression by RNA-seq in patients with prostate cancer and in patients with Parkinson disease: an example of inverse comorbidity.

BACKGROUND: Prostate cancer (PCa) is one of the leading causes of death in Western countries. Environmental and genetic factors play a pivotal role in PCa etiology. Timely identification of the genetic causes is useful for an early diagnosis. Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder; it is associated with the presence of Lewy bodies and genetic factors are involved in its pathogenesis. Several studies have indicated that the expression of target genes in patients with PD is inversely related to cancer development; this phenomenon has been named "inverse comorbidity". The present study was undertaken to evaluate whether a genetic dysregulation occurs in opposite directions in patients with PD or PCa. METHODS AND RESULTS: In the present study, next-generation sequencing transcriptome analysis was used to assess whether a genetic dysregulation in opposite directions occurs in patients with PD or PCa. The genes SLC30A1, ADO, SRGAP2C, and TBC1D12 resulted up-regulated in patients with PD compared to healthy donors as controls and down-regulated in patients with PCa compared with the same control group. CONCLUSIONS: These results support the hypothesis of the presence of inverse comorbidity between PD and PCa.