Atrial Arrhythmia in Sickle Cell Anemia Adults: A missing link towards understanding and preventing strokes.

Although sickle cell disease (SCD) patients carry both significant left atrial (LA) remodeling and increased risk of stroke, the prevalence of atrial arrhythmia (AA) has never been prospectively evaluated. This study aims to investigate the prevalence and predictors of atrial arrhythmia in homozygous SCD (SCA). From 2019 to 2022, 130 patients with SCA were referred to the physiology department to specifically analyze cardiac function and prospectively included in the DREPACOEUR registry. They underwent a 24-hour electrocardiogram monitoring (24h-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary endpoint was the occurrence of AA, defined by the presence of excessive supraventricular ectopic activity (ESVEA) on ECG-Holter (i.e., >720 premature atrial contractions [PACs] or any run ≥ 20 PACs), recent history of paroxysmal atrial fibrillation (AF), or persistent AF. The mean patient age was 45±12 years and 48% of male. Overall, AA was found in 34 (26%) patients. Age (52±9 vs. 42±12 years, P=0.002), LA dilation (LAVi, 71±24 vs. 52±14 ml/m², P<0.001) and history of stroke without underlying cerebral vasculopathy or other defined cause (26% vs. 5%, P=0.009, OR=6.6 [1.4; 30.3]) were independently associated with AA. Age and LAVi correlated with PAC load per 24 hours on ECG-Holter (R=0.56 and 0.33, P<0.001 respectively) and an age over 47 years or a LAVi >55mL/m² could predict AA with a PPV of 33% and a NPV of 92%. AAs are frequent in SCA patients and increase with age and LA remodeling, leading to a major additional risk factor for ischemic stroke. This study provides arguments and means to early screen for AA potentially preventing cerebral complications.

A finite element analysis study on different angle correction designs for inclined implants in All-On-Four protocol.

BACKGROUND: The aim of this study is to investigate, through finite element analysis (FEA), the biomechanical behavior of the built-in angle corrected dental implant versus implant with angled multiunit abutment used in All-On-Four treatment protocol. METHODS: Two (3D) finite element models of a simplified edentulous mandible were constructed with two different posterior implant designs based on the All-On-Four protocol. Four implants were placed in each model, the two anterior implants were positioned vertically at the lateral incisor/canine sites. Depending on the implant fixture design in posterior area, there are two models created; Model I; the mandible was rehabilitated with four co-axis (4 mm in diameter × 15 mm in length) implants with distally built-in angle corrected implants (24-degree angle correction) .While Model II, the mandible was rehabilitated with four conventional (4 mm in diameter × 14 mm in length) implants with a distally inclined posterior implants (25 degree) and angled multiunit abutments. CAD software (Solidworks© 2017; Dassault Systems Solidworks Corp) was used to model the desired geometry. Axial and inclined Loads were applied on the two models. A Finite element analysis study was done using an efficient software ANSYS© with specified materials. The resultant equivalent Von-Misses stresses (VMS), maximum principal stresses and deformation analysis were calculated for each part (implants and prosthetic components). RESULTS: When applying axial and non-axial forces, model II (angled multiunit model) showed higher deformation on the level of Ti mesh about 13.286 µm and higher VMS 246.68 MPa than model I (angle corrected implant). Model I exhibited higher maximum stresses 107.83 MPa than Model II 94.988 MPa but the difference was not statistically significant. CONCLUSION: Within the limitation of the FEA study, although angle correcting implant design is showing higher values in maximum principle stresses compared with angled multiunit abutments, model deformation and resultant VMS increased with angled multiunit abutments. The angle correcting designs at implant level have more promising results in terms of deformation and VMS distribution than angle correction at abutment level.

Vertical versus angled immediately loaded implants for assisting maxillary overdentures with locator attachments: A preliminary results of one-year randomized clinical trial.

OBJECTIVES: This study aimed to evaluate the clinical outcomes and patient satisfaction of 4-implant-assisted maxillary overdentures using two different designs. MATERIALS AND METHODS: Thirty edentulous participants received four implants in the maxillary ridge. The patients were randomly divided into two equal groups: (1) the control (CG, Vertical) group (n = 15); participants received four vertical implants with straight locator attachments to retain maxillary overdentures, and (2) the study (SG, Angled) group (n = 15); participants received four angled implants with angled locator attachments to retain maxillary overdentures. Peri-implant tissue health [Plaque (PL) and gingival (GI) indices, pocket depth (PD), implant stability (ISQ) and crestal bone loss (CBL)] were evaluated after denture insertion (T0), 6 (T6), and 12 (T12) months after insertion. Patient satisfaction was evaluated using a visual analog scale (VAS) after 12 months. RESULTS: The survival rates were 96.7% and 95% for the control and study groups respectively. PL, GI, and PD increased significantly in both groups with the passage of time. No significant difference in PL, GI, PD, and ISQ was noted between groups at all observation times. CG showed higher CBL than SG at T12. For the VAS results, there was no significant difference between groups. SG recorded significantly higher satisfaction regarding comfort with maxillary and mandibular dentures, retention of mandibular dentures, oral hygiene, the ability to chew hard food, and occlusion than CG. CONCLUSION: Within the limitations of this study, angled implants with angled locator attachments may be recommended to retain maxillary overdentures opposing intact dentition or fixed restoration as it was associated with improvements of several parameters of peri-implant tissue health and patient satisfaction compared to vertical implants with straight locator attachments.

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review.

Repetitive Transcranial Magnetic Stimulation (rTMS) is an invaluable treatment option for neuropsychiatric disorders. Co-occurring recreational and nonmedical substance use can be common in those presenting for rTMS treatment, and it is unknown how it may affect the safety and efficacy of rTMS for the treatment of currently approved neuropsychiatric indications. This scoping review aimed to map the literature on humans receiving rTMS and had a history of any type of substance use. The search identified 274 articles providing information on inclusion/exclusion criteria, withdrawal criteria, safety protocols, type of rTMS and treatment parameters, adverse events and effect on primary outcomes that related to substance use. There are neurophysiological effects of substance use on cortical excitability, although the relevance to clinical rTMS practice is unknown. The current literature supports the safety and feasibility of delivering rTMS to those who have co-occurring neuropsychiatric disorder and substance use. However, specific details on how varying degrees of substance use alters the safety, efficacy, and mechanisms of rTMS remains poorly described.

Efficacy of insula deep repetitive transcranial magnetic stimulation combined with varenicline for smoking cessation: A randomized, double-blind, sham controlled trial.

BACKGROUND: Current smoking cessation treatments are limited in terms of efficacy, particularly with regards to long term abstinence. There is a large amount of evidence implicating the insula in nicotine addiction. OBJECTIVE: To examine the efficacy of bilateral repetitive transcranial magnetic stimulation (rTMS) directed to the insular cortex with the H11 coil, relative to sham stimulation, on smoking abstinence and smoking outcomes in smokers who are receiving standard varenicline treatment. METHODS: This randomized, double-blind, sham controlled trial recruited 42 participants who were randomized to receive either active (n = 24) or sham (n = 18) high frequency rTMS directed to the insula (4 weeks), while receiving varenicline treatment (12 weeks). The primary outcome was 7-day point prevalence abstinence at the end of 12 weeks. RESULTS: Smokers in the active group had significantly higher abstinence rates than those in the sham group (82.4% vs. 30.7%, p = 0.013) at the end of treatment (Week 12). Secondary outcome measures of abstinence rate at the end of rTMS treatment (Week 4), abstinence rate at 6 months, and smoking outcomes (e.g., craving, withdrawal) showed no significant differences between groups. No differences were found in adverse events reported between the groups. CONCLUSION: This study provides evidence of the potential benefit of having a combined treatment for smoking cessation using insula rTMS with the H11 coil and varenicline. Maintenance rTMS sessions and continuation of varenicline for those in abstinence may induce longer-term effects and should be considered in future studies.

Repetitive transcranial magnetic stimulation for smoking cessation: Next steps for translation and implementation into clinical practice.

Tobacco smoking is a significant determinant of preventable morbidity and mortality worldwide. It is now possible to modulate the activity of the neurocircuitry associated with nicotine dependence using repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive neurostimulation approach, which has recently demonstrated efficacy in clinical trials and received regulatory approval in the US and Canada. However there remains a paucity of replication studies and real-world patient effectiveness data as access to this intervention is extremely limited. There are a number of unique challenges related to the delivery of rTMS that need to be addressed prior to widespread adoption and implementation of this treatment modality for smoking cessation. In this paper, we review the accessibility, scientific, technological, economical, and social challenges that remain before this treatment can be translated into clinical practice. By addressing these remaining barriers and scientific challenges with rTMS for smoking cessation and delineating implementation strategies, we can greatly reduce the burden of tobacco-related disease worldwide.

Insula deep rTMS and varenicline for smoking cessation: A randomized control trial study protocol.

Background: Current approved therapies for smoking cessation have modest long-term effects for abstinence. The insular cortex has been identified by preclinical and clinical studies as a critical target for addiction treatment. Insula functions can be modulated non-invasively using brain stimulation. It is unknown if deep repetitive transcranial magnetic stimulation (rTMS) of the insula can improve smoking cessation of smokers trying to quit using varenicline. Methods: This will be a randomized, double-blind, sham-controlled clinical trial with 50 nicotine dependent smokers looking to quit. They will be randomly assigned to receive either active (10 Hz) or sham insula deep rTMS. Deep rTMS will be administered for 4 weeks (5 days/week). All participants will receive open label varenicline for 12 weeks. The primary outcome measure will be the 7-day point prevalence abstinence at the end of 12 weeks. The secondary outcomes will be Fagerström Test of Nicotine Dependence, Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire of Smoking Urges, expired carbon monoxide measurements, cigarettes smoked per day, point prevalence abstinence at end of 4 weeks, prolonged and continuous abstinence at 6 months. The measures will be collected throughout the 3-month treatment period as well as at the 6-month follow up. Discussion: This trial will test for the first time the impact of deep insula rTMS on smoking cessation in smokers treated with varenicline. This trial will use an H-coil specific to the insula, while previous studies have targeted both the insula and prefrontal cortex. This trial will inform on the utility to combine insula deep rTMS with varenicline to improve smoking abstinence rates. Clinical Trial Registration: Trial registered at https://clinicaltrials.gov/ct2/show/NCT04083144 (Identifier: NCT04083144).

Comparing immediate- and delayed-onset posttraumatic stress disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III).

Delayed-onset posttraumatic stress disorder (PTSD) is defined as a period of 6 months or more between trauma exposure and episode onset. Due to the limited research and lack of epidemiological studies on this form of the disorder, we investigated its prevalence, clinical features, and psychiatric comorbidities in a nationally representative sample of U.S. adults. Using National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) data collected from individuals who met the DSM-5 criteria for PTSD (N = 1,980), we compared delayed- and immediate-onset PTSD with regard to demographic and clinical variables, including comorbidity with psychiatric and substance use disorder (SUD) diagnoses. The overall prevalence of delayed-onset PTSD was 11.0%. Respondents with delayed-onset PTSD were more likely than those with immediate-onset PTSD to report active military combat exposure, more physical and emotional difficulties, and higher levels of pain; these individuals were also more likely to be divorced and less likely to meet the diagnostic criteria for select SUDs. After adjusting for confounding variables, we found a decreased risk of delayed-onset PTSD among individuals with hallucinogen use disorder, OR = 0.30; 95% CI [0.11, 0.87], d = 0.5. We found no significant associations between PTSD onset status and any other SUD, including alcohol use disorder, after adjusting for covariates. Further longitudinal research is required to investigate the temporal associations between PTSD onset and its clinical characteristics and comorbidities, as this could have implications on disorder progression and treatment approaches.

Peri-implant tissue health and patient satisfaction of vertical versus inclined posterior implants used to support overdentures with bar attachments. A one-year randomized trial.

INTRODUCTION: This study aimed to evaluate peri-implant tissue health and patient satisfaction of vertical and inclined posterior implants for mandibular bar overdentures. MATERIALS AND METHODS: Thirty edentulous participants received four implants in the interforaminal area of the mandible. The patients were randomly assigned into two equal groups; (1) vertical group (control): all implants were inserted vertically parallel to each other. Inclined group (study): the anterior implants were placed vertically, and the posterior implants were tilted 30° distally. Hader bar attachment with two 7 mm-distal cantilevers (vertical group) and without cantilevers (inclined group) was used to connect the implants to mandibular overdentures. Peri-implant tissue health (Plaque [PL] and gingival [GI] indices, pocket depth [PD], and crestal bone loss [CBL]) were evaluated after denture insertion (T0), 6 (T6), and 12 (T12) months after insertion. Patient satisfaction was evaluated using a visual analog scale after 12 months. RESULTS: At T12, the vertical group showed significantly higher PL, PD, and CBL than the inclined group for anterior (p < 0.037) and posterior (p < 0.017) implants. The vertical group showed significantly higher GI than the inclined group for anterior implants (p = 0.003), and the inclined group showed significantly higher GI than the vertical group for posterior implants (p = 0.016). The inclined group showed significantly higher scores for general satisfaction (p = 0.049), prosthesis as a part of you (p = 0.013), appearance (p < 0.001), stability (p = 0.002), ease of cleaning (p < 0.001), and comfort (p = 0.001) than the vertical group. CONCLUSION: Inclined posterior implants used to support mandibular bar overdentures are recommended than vertical implants, as it was associated with improved patient satisfaction and peri-implant tissue health.

The Effect of Nicotine Dependence on the Risk of Developing Post-traumatic Stress Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions.

INTRODUCTION: It is evident that an association between smoking and post-traumatic stress disorder (PTSD) exists, but research is lacking in establishing the directionality of the relationship. AIMS AND METHODS: We used longitudinal data from waves I (2001-2002) and II (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Individuals with nicotine dependence (ND) were matched to individuals without ND using propensity score matching to estimate the risk of developing PTSD after trauma. We also matched smokers (with or without ND) to lifetime nonsmokers to estimate their risk of developing PTSD after trauma. Lastly, we conducted a mediation analysis on the effect of ND severity on PTSD symptoms. RESULTS: Individuals with ND (n = 1514) were more likely to develop PTSD (odds ratio: 1.59; 95% confidence interval: 1.09-2.32; p = .017) compared with individuals without ND (n = 6047). Smokers (regardless of ND status) (n = 2335) compared with nonsmokers (n = 5226) had no significant effect on risk of PTSD (p = .26). Withdrawal was found to be a mediator of the effect of ND severity on PTSD symptoms. CONCLUSIONS: ND, but not smoking status, increases a smoker's risk of developing PTSD. This provides information that could aid in preventive strategies for individuals with ND who are exposed to trauma. IMPLICATIONS: This study provides evidence in a national representative sample of adults in the United States that ND may increase one's risk of developing PTSD after exposure to trauma. It also shows the directionality of the association between smoking and PTSD. Lastly, it demonstrates that withdrawal may be the link to the association between ND and PTSD. We hope that with these findings, preventative strategies are put in place for smokers who are dependent and are exposed to trauma, such that they do not develop PTSD.

Addressing the Importance of Stem Cell-Based Therapy: A Perspective in the Treatment of COVID-19.

Severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) is an extremely pathogenic virus belonging to the family of Coronaviridae. First identified in Wuhan, China in December 2019 after an epidemiological investigation of an emerging cluster of pneumonia of unknown etiology, SARS-CoV-2 was declared the cause of a pandemic on March 11 by the World Health Organization (WHO), pointing to the over 118000 cases of Coronavirus disease 2019 (COVID-19) in over 110 countries. Despite the promising results of drug repositioning studies in the treatment of COVID-19, the evidence of their safety and efficacy remains inconclusive. Cell based therapy has been proven safe and possibly effective in treating multiple lung injuries and diseases, but its potential use in the treatment of COVID-19 has not been yet elucidated. Our aim in this review is to provide an overview of the immunomodulatory effect and the regenerative capacity of stem cells and their secretome in the treatment of many diseases including lung injuries. Those findings may contribute to a better understanding of the potential of stem cell therapy in SARS-CoV-2 infection and its potential use in order to find a solution for this healthcare crisis.

Precuneus stimulation alters the neural dynamics of autobiographical memory retrieval.

Autobiographical memory (AM) unfolds over time, but little is known about the dynamics of its retrieval. Space-based models of memory implicate the hippocampus, retrosplenial cortex, and precuneus in early memory computations. Here we used transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to investigate the causal role of the precuneus in the dynamics of AM retrieval. During early memory search and construction, precuneus stimulation compared to vertex stimulation led to delayed evoked neural activity within 1000 â€‹ms after cue presentation. During later memory elaboration, stimulation led to decreased sustained positivity. We further identified a parietal late positive component during memory elaboration, the amplitude of which was associated with spatial perspective during recollection. This association was disrupted following precuneus stimulation, suggesting that this region plays an important role in the neural representation of spatial perspective during AM. These findings demonstrate a causal role for the precuneus in early AM retrieval, during memory search before a specific memory is accessed, and in spatial context reinstatement during the initial stages of memory elaboration and re-experiencing. By utilizing the high temporal resolution of MEG and the causality of TMS, this study helps clarify the neural correlates of early naturalistic memory retrieval.

Randomized Clinical Trials Investigating Innovative Interventions for Smoking Cessation in the Last Decade.

Every year, billions of dollars are spent treating smoking and related conditions, yet smoking-related morbidity and mortality continue to rise. There are currently only three FDA-approved medications for smoking cessation: nicotine replacement therapy, bupropion, and varenicline. Although these medications increase abstinence rates, most individuals relapse following treatment. This chapter reviews clinical trials published within the past 10 years investigating novel smoking cessation pharmacotherapies. Among these pharmacotherapies, some showed promising results, such as cytisine and endocannabinoid modulators, whereas others failed to produce significant effects. More research is needed to develop drugs that produce higher rates of long-term abstinence and to determine which subgroups of patients benefit from a given treatment.

Transcriptomic Characterization of the Human Insular Cortex and Claustrum.

The insular cortex has been linked to a multitude of functions. In contrast, the nearby claustrum is a densely connected subcortical region with unclear function. To view the insula-claustrum region from the molecular perspective we analyzed the transcriptomic profile of these areas in six adult and four fetal human brains. We identified marker genes with specific expression and performed transcriptome-wide tests for enrichment of biological processes, molecular functions, and cellular components. In addition, specific insular and claustral expression of genes pertaining to diseases, addiction, and depression was tested. At the anatomical level, we used brain-wide analyses to determine the specificity of our results and to determine the transcriptomic similarity of the insula-claustrum region. We found UCMA to be the most significantly enriched gene in the insular cortex and confirmed specific expression of NR4A2, NTNG2, and LXN in the claustrum. Furthermore, the insula was found to have enriched expression of genes associated with mood disorders, learning, cardiac muscle contraction, oxygen transport, glutamate and dopamine signaling. Specific expression in the claustrum was enriched for genes pertaining to human immunodeficiency virus (HIV), severe intellectual disability, epileptic encephalopathy, intracellular transport, spine development, and macroautophagy. We tested for enrichment of genes related to addiction and depression, but they were generally not highly specific to the insula-claustrum region. Exceptions include high insular expression of genes linked to cocaine abuse and genes associated with ever smoking in the claustrum. Brain-wide, we find that markers of the adult claustrum are most specifically expressed in the fetal and adult insula. Altogether, our results provide a novel molecular perspective on the unique properties of the insula and claustrum.

The Insula: A Brain Stimulation Target for the Treatment of Addiction.

Substance use disorders (SUDs) are a growing public health concern with only a limited number of approved treatments. However, even approved treatments are subject to limited efficacy with high long-term relapse rates. Current treatment approaches are typically a combination of pharmacotherapies and behavioral counselling. Growing evidence and technological advances suggest the potential of brain stimulation techniques for the treatment of SUDs. There are three main brain stimulation techniques that are outlined in this review: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). The insula, a region of the cerebral cortex, is known to be involved in critical aspects underlying SUDs, such as interoception, decision making, anxiety, pain perception, cognition, mood, threat recognition, and conscious urges. This review focuses on both the preclinical and clinical evidence demonstrating the role of the insula in addiction, thereby demonstrating its promise as a target for brain stimulation. Future research should evaluate the optimal parameters for brain stimulation of the insula, through the use of relevant biomarkers and clinical outcomes for SUDs.

A retrospective study of the clinical benefit from acetylsalicylic acid desensitization in patients with nasal polyposis and asthma.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD), also known as Samter's triad, is a clinical syndrome which consists of aspirin (ASA) intolerance, chronic rhinosinusitis with nasal polyposis, and intrinsic bronchial asthma (Press Med 119:48-51, 1922). ASA challenge is the gold standard for diagnosing AERD (Curr Allergy Asthma 9:155-163, 2009). The practice of ASA challenge and desensitization in Canada is infrequently utilized, which may explain its omission as a viable therapeutic option in the latest Canadian clinical practice guidelines for acute and chronic rhinosinusitis (AACI 7:1-38, 2011). METHODS: This retrospective study assessed 111 patients who underwent ASA desensitization in the Allergy and Immunology clinic at St. Joseph's Healthcare (SJHC) in London, Ontario. The mean age was 50.7 years, and 52.5% (n = 58) were male. Sixty-one percent (n = 68) claimed prior, significant reactions to ASA, and all patients had features of AERD. RESULTS: Seventy-three percent (n = 81) claimed symptom improvement after achieving maintenance dosing on the desensitization protocol. Of this population, 21.6% (n = 24) improved in all 3 areas of interest (sense of taste or smell, upper respiratory symptoms and lower respiratory symptoms). Twenty-six percent (n = 29) had adverse effects, mostly in the way of gastrointestinal upset, but no severe adverse events were seen. CONCLUSIONS: ASA desensitization helps improve symptoms in patients with AERD. Further, it allows patients to tolerate additional ASA and other non-steroidal anti-inflammatories (NSAIDs) when needed for supplemental analgesia or for cardio-protection. This is of particular benefit in those who require these medications for improved quality of life, and for reduced morbidity and mortality, such as those with cardiovascular disease or chronic pain. There should be further studies conducted in Canada as well as consideration for ASA desensitization to be included in the next clinical practice guidelines.

The effect of infrequent low-dose rosuvastatin on the lipid profile.

We retrospectively studied 21 patients who had difficulty tolerating daily or alternating-day statins. Patients received rosuvastatin at a mean frequency of 1.7 doses per week, and a mean dose of 11.7 mg per week. We assessed lipid profiles at baseline and after at least 3 months of therapy. We found that total and low-density lipoprotein cholesterol were reduced by 2.03 ± 2.04 and 1.31 ± 0.83 mmol/L (27.9% and 31.5%), respectively, from baseline (both P < 0.001). Thus, in patients with statin intolerance, infrequent low-dose rosuvastatin significantly improved low-density lipoprotein cholesterol and was well tolerated over the long term.