Accelerated Stability Assessment of Extemporaneously Compounded Amiloride Nasal Spray.

Amiloride is a U.S. Food and Drug Administration-approved diuretic agent used to treat hypertension and congestive heart failure. Recent human and animal studies have suggested that amiloride may also have a role in treating anxiety through its acid-sensing ion channel antagonism. Intranasal administration of amiloride nasal spray via an extemporaneously compounded preparation has the potential for rapid delivery to the site of action to achieve therapeutic outcomes in individual patients with anxiety disorders. However, these patient-specific preparations do not have the pre-formulation characterization, including chemical stability, that conventional manufactured dosage forms have. The objective of this study was to assess the estimated chemical stability of compounded amiloride nasal spray over 6 months and 12 months utilizing accelerated degradation with high heat and the Arrhenius equation. A stability-indicating highperformance liquid chromatography analytical method was employed at appropriate intervals over a 12-month period to reveal that amiloride remained chemically stable over the period tested and by extrapolation. Physical stability and compatibility with the preservative benzyl alcohol were also confirmed via visual inspection, pH monitoring, and measurement of turbidity.

The Toronto Adolescent and Youth Cohort Study: Study Design and Early Data Related to Psychosis Spectrum Symptoms, Functioning, and Suicidality.

BACKGROUND: Psychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality. METHODS: The TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11-24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data. RESULTS: A total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs. CONCLUSIONS: Initial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality.

Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride.

Early-life adversities are associated with altered defensive responses. Here, we demonstrate that the repeated cross-fostering (RCF) paradigm of early maternal separation is associated with enhancements of distinct homeostatic reactions: hyperventilation in response to hypercapnia and nociceptive sensitivity, among the first generation of RCF-exposed animals, as well as among two successive generations of their normally reared offspring, through matrilineal transmission. Parallel enhancements of acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 messenger RNA transcripts were detected transgenerationally in central neurons, in the medulla oblongata, and in periaqueductal gray matter of RCF-lineage animals. A single, nebulized dose of the ASIC-antagonist amiloride renormalized respiratory and nociceptive responsiveness across the entire RCF lineage. These findings reveal how, following an early-life adversity, a biological memory reducible to a molecular sensor unfolds, shaping adaptation mechanisms over three generations. Our findings are entwined with multiple correlates of human anxiety and pain conditions and suggest nebulized amiloride as a therapeutic avenue.

Pain, mental health and healthcare utilization: Impact of the COVID-19 pandemic on youth with chronic pain, parents and siblings.

BACKGROUND: Paediatric chronic pain was a public health emergency before the novel coronavirus (COVID-19) pandemic, and this problem is predicted to escalate. Pain tends to occur intergenerationally in families, and youth with chronic pain and their parents have high rates of mental health issues, which can further exacerbate pain. Siblings of youth with chronic pain have been largely overlooked in research, as well as the impact of the pandemic on posttraumatic stress disorder (PTSD) symptoms and healthcare utilization. METHODS: This cross-sectional study examined pain, mental health and healthcare utilization in three groups: youth with chronic pain (n = 357), parents of youth with chronic pain (n = 233) and siblings of youth with chronic pain (n = 156) during the COVID-19 pandemic in Canada. RESULTS: More so than with pain symptoms, the results revealed high levels of mental health symptoms (i.e. anxiety, depressive, and PTSD), particularly in individuals more personally impacted by the pandemic. The largest effect was seen on PTSD symptoms for all groups. For parents with chronic pain, greater personal COVID-19 impact was related to worse pain interference. Reported rates of healthcare utilization were strikingly high, with youth with chronic pain, parents (reporting on behalf of their children with chronic pain), and siblings of youth with chronic pain reporting that most consultations were due to pain. CONCLUSIONS: Longitudinal research assessing these outcomes across continued waves of the pandemic is needed to ensure timely, tailored and equitable access to pain and mental health assessment and treatment. SIGNIFICANCE: This study examined pain, mental health, substance use and healthcare utilization in youth with chronic pain, siblings and parents during the COVID-19 pandemic. Greater personal impact of the pandemic was not largely associated with poorer pain outcomes; however, it was associated with mental health, with the largest effect on PTSD symptoms. The high rates and significant association of COVID-19 impact with PTSD symptoms underscore the importance of including PTSD assessment as part of routine screening practices in pain clinics.

Adolescent anxiety and pain problems: A joint, genome-wide investigation and pathway-based analysis.

Both common pain and anxiety problems are widespread, debilitating and often begin in childhood-adolescence. Twin studies indicate that this co-occurrence is likely due to shared elements of risk, rather than reciprocal causation. A joint genome-wide investigation and pathway/network-based analysis of adolescent anxiety and pain problems can identify genetic pathways that subserve shared etiopathogenetic mechanisms. Pathway-based analyses were performed in the independent samples of: The Quebec Newborn Twin Study (QNTS; 246 twin pairs and 321 parents), the Longitudinal Study of Child Development in Quebec (QLSCD; n = 754), and in the combined QNTS and QLSCD sample. Multiple suggestive associations (p<1×10-5), and several enriched pathways were found after FDR correction for both phenotypes in the QNTS; many nominally-significant enriched pathways overlapped between pain problems and anxiety symptoms (uncorrected p<0.05) and yielded results consistent with previous studies of pain or anxiety. The QLSCD and the combined QNTS and QLSCD sample yielded similar findings. We replicated an association between the pathway involved in the regulation of myotube differentiation (GO:0010830) and both pain and anxiety problems in the QLSDC and the combined QNTS and QLSCD sample. Although limited by sample size and thus power, these data provide an initial support to conjoint molecular investigations of adolescent pain and anxiety problems. Understanding the etiology underlying pain and anxiety co-occurrence in this age range is relevant to address the nature of comorbidity and its developmental pathways, and shape intervention. The replication across samples implies that these effects are reliable and possess external validity.

We need to talk: The urgent conversation on chronic pain, mental health, prescribing patterns and the opioid crisis.

The opioid crisis' pathways from first exposure onwards to eventual illnesses and fatalities are multiple, intertwined and difficult to dissect. Here, we offer a multidisciplinary appraisal of the relationships among mental health, chronic pain, prescribing patterns worldwide and the opioid crisis. Because the opioid crisis' toll is especially harsh on young people, emphasis is given on data regarding the younger strata of the population. Because analgesic opioid prescription constitute a recognised entry point towards misuse, opioid use disorder, and ultimately overdose, prescribing patterns across different countries are examined as a modifiable hazard factor along these pathways of risk. Psychiatrists are called to play a more compelling role in this urgent conversation, as they are uniquely placed to provide synthesis and lead action among the different fields of knowledge and care that lie at the crossroads of the opioid crisis. Psychiatrists are also ideally positioned to gauge and disseminate the foundations for diagnosis and clinical management of mental conditions associated with chronic pain, including the identification of hazardous and protective factors. It is our hope to spark more interdisciplinary exchanges and encourage psychiatrists worldwide to become leaders in an urgent conversation with interlocutors from the clinical and basic sciences, policy makers and stakeholders including clients and their families.

Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study.

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs. Clinical trial identifier: NCT04673240.

Individual- and family-level associations between child psychopathology and parenting.

Parenting can protect against the development of, or increase risk for, child psychopathology; however, it is unclear if parenting is related to psychopathology symptoms in a specific domain, or to broad liability for psychopathology. Parenting differs between and within families, and both overall family-level parenting and the child-specific parenting a child receives may be important in estimating transdiagnostic associations with psychopathology. Data come from a cross-sectional epidemiological sample (N = 10,605 children ages 4-17, 6434 households). Parents rated child internalizing and externalizing symptoms and their parenting toward each child. General and specific (internalizing, externalizing) psychopathology factors, derived with bifactor modeling, were regressed on parenting using multilevel modeling. Less warmth and more aversive/inconsistent parenting in the family, and toward an individual child relative to family average, were associated with higher general psychopathology and specific externalizing problems. Unexpectedly, more warmth in the family, and toward an individual child relative to family average, was associated with higher specific internalizing problems in 4-11 (not 12-17) year-olds. Less warmth and more aversive/inconsistent parenting are broad correlates of child psychopathology. Aversive/inconsistent parenting, is also related to specific externalizing problems. Parents may behave more warmly when their younger children have specific internalizing problems, net of overall psychopathology.

Pharmacokinetics of intranasal amiloride in healthy volunteers.

Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid-sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models. An intranasal formulation of amiloride will be highly beneficial to treat acute panic attacks due to advantages such as the rapid onset of action and patient compliance. The aim of this single-center, open-label trial was to evaluate the basic pharmacokinetics (PKs) and safety of amiloride after intranasal administration in healthy human volunteers at three doses (0.2, 0.4, and 0.6 mg). Amiloride was detected in plasma within 10 min of intranasal administration and showed a biphasic PK profile with an initial peak within 10 min of administration followed by a second peak between 4 and 8 h of administration. The biphasic PKs indicate an initial rapid absorption via the nasal pathway and later slower absorption by non-nasal pathways. Intranasal amiloride exhibited a dose-proportional increase in the area under the curve and did not exhibit any systemic toxicity. These data indicate that intranasal amiloride is rapidly absorbed and safe at the doses evaluated and can be further considered for clinical development as a portable, rapid, noninvasive, and nonaddictive anxiolytic agent to treat acute panic attacks.

"We survived the pandemic together": The impact of the COVID-19 pandemic on Canadian families living with chronic pain.

Introduction: Pediatric chronic pain is a significant problem in Canada, affecting one in five youth. This study describes the impact of the pandemic on the experiences of Canadian families living with chronic pain through interviews with youth living with chronic pain, parents, and siblings. Methods: Employing a qualitative descriptive design, in-depth semistructured interviews were completed with Canadian youth living with pain, as well as parents and siblings. Participants were not required to be related. Interviews were analyzed using a reflexive thematic analysis approach. Results: Forty-four interviews were completed with 14 parents, 19 youth with chronic pain, and 11 siblings from across the country. Three key themes were developed: (1) absorbing and shifting: the toll of the pandemic on the family system (e.g., loss of coping mechanisms, shifting roles to respond to the pandemic), (2) social ambiguity and abandonment (e.g., social sacrifice and abandonment by the health care system), and (3) building community resilience: familial adaptation to the pandemic (e.g., family cohesion, confidence, and self-management). Discussion/Conclusions: Youth, parents, and siblings reported that the pandemic impacted coping strategies across the family system. These results outline the challenges youth experienced managing their pain and overall health throughout the pandemic and the resilience built within families during this time. Going forward, it would be relevant to examine how racialized and structurally marginalized youth with chronic pain and their families experienced the pandemic. Future research should examine how unexpected benefits of the pandemic (e.g., increased confidence and self-management) may be sustained into the future.

Introduction: La douleur chronique pédiatrique est un problème important au Canada, qui touche un jeune sur cinq. Cette étude décrit les répercussions de la pandémie sur les expériences des familles canadiennes vivant avec la douleur chronique par des entrevues avec des jeunes vivant avec une douleur chronique, des parents et des frères et sœurs.Méthodes: À l'aide d'un devis descriptif qualitatif, des entretiens semi-structurés approfondis ont été réalisés auprès de jeunes Canadiens vivant avec la douleur, leurs parents, et leurs frères et sœurs. Il n'était pas nécessaire que les participants aient un lien familial. Les entretiens ont été analysés à l'aide d'une approche d'analyse thématique réflexive.Résultats: Quarante-quatre entretiens ont été réalisés auprès de 14 parents, 19 jeunes souffrant de douleur chronique et 11 frères et sœurs de tout le pays. Trois thèmes clés ont été abordés : (1) l'absorption et le changement : le coût de la pandémie pour le système familial (p. ex., perte de mécanismes d'adaptation, changement de rôles pour réagir à la pandémie), (2) l'ambiguïté sociale et l'abandon (p. ex., le sacrifice social et l'abandon par le système de soins de santé), et (3) le renforcement de la résilience communautaire : adaptation familiale à la pandémie (p. ex., cohésion familiale, confiance et auto-prise en charge).Discussion/Conclusions: Les jeunes, les parents et les frères et sœurs ont signalé que la pandémie avait eu des répercussions sur les stratégies d'adaptation dans l'ensemble du système familial. Ces résultats décrivent les défis rencontrés par les jeunes pour prendre en charge leur douleur et leur santé globale tout au long de la pandémie, ainsi que la résilience démontrée par les familles pendant cette période. À l'avenir, il serait pertinent d'examiner comment les personnes racialisées et les jeunes structurellement marginalisés souffrant de douleur chronique et leurs familles ont vécu la pandémie.Les recherches futures devraient examiner comment les avantages inattendus de la pandémie (par exemple, une confiance accrue et l'auto-prise en charge) peuvent être maintenus à l'avenir.

A Twin Study of the Relationships between Cognitive Disengagement Syndrome and Anxiety Phenotypes in Childhood and Adolescence.

Data on the etiological factors underlying the co-occurrence of Cognitive Disengagement Syndrome (CDS) with anxiety symptoms are very limited. The present study investigated the nature of latent shared etiological elements in 400 Italian twin pairs aged 8-18, explaining the covariation between CDS and anxiety symptoms. Preliminary analysis demonstrated significant correlations between Child Behaviour Checklist/6-18 Sluggish Cognitive Tempo Scale and two (Somatic Anxiety, Generalized Anxiety) out of five Screen for Child Anxiety Related Disorders anxiety subscales. Results from causal analysis seem to exclude the hypothesis that co-occurrence between CDS and Anxiety Symptoms could be due to a direct phenotypic effect of one trait upon the other. Model fitting-analysis indicated that the aforementioned associations were partially explained by shared genetic and environmental factors influencing a common liability factor. A latent variable capturing the covariation between CDS and anxiety problems can be considered as a unifying (patho)physiological mechanism/system common to these constructs. Our results support the adoption of a broader view of the relationships between CDS and anxiety phenotypes in childhood and adolescence for both clinicians and educators.

Mediating effect of genome-wide DNA methylation on suicidal ideation induced by stressful events.

OBJECTIVE: Schizophrenia is a debilitating disease that is associated with higher rates of death by unnatural causes including suicide. Exposure to stressful events is an important risk factor for suicidal ideation (SI); however, the mechanisms that link stress, SI, and suicide remain unclear. Epigenetic processes are involved in both vulnerability to suicidal behavior and stress. Therefore, we sought to study the relationship between epigenetic modifications and suicidal behavior and stress. METHODS: This pilot study was conducted on 39 patients diagnosed with schizophrenia (54% men and age 45.5 ± 12.7). We analyzed the effects of (a) stress exposure and (b) the mediation of DNA methylation [via an epigenetic wide association study (EWAS) of more than 450 000 CpG sites across the genome] on SI severity. RESULTS: The top CpG site mediating the effect of global stress exposure on SI was cg27660192 located in an intergenic region on chromosome 11, exerting a facilitating effect on worsening SI through DNA hypomethylation. CONCLUSION: These preliminary results indicate that DNA methylation in peripheral tissues can shed light on the complex relationship between stress and SI in schizophrenia.

Balance Rehabilitation through Robot-Assisted Gait Training in Post-Stroke Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. METHODS: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. RESULTS: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of -0.62 (95%CI - 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (ß = -1.019, 95% CI - 1.827; -0.210, p-value = 0.0135). CONCLUSIONS: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy.

Tolerability, Safety and Efficacy of a Specific Rehabilitation Treatment Protocol for Axillary Web Syndrome: An Observational Retrospective Study.

Axillary web syndrome (AWS) is a highly prevalent surgical complication affecting BC survivors. It presents as a subcutaneous cording that limits the upper limb range of motion (ROM) and causes pain. Its etiology is still debated, and its treatment is not well defined. Therefore, we aimed to investigate the safety, tolerability and efficacy of our specific AWS rehabilitative treatment protocol. We conducted an observational retrospective study on a cohort of 92 AWS patients referred to the oncological outpatient service of a university hospital. We collected data from medical records before (T0) and after (T1) the treatment. The studied protocol was composed of 60-min sessions, carried out 3 times/week by specialized physiotherapists, until the clinical resolution of AWS. We found that a mean of 8.74 ± 2.12 rehabilitative sessions were needed, and only one patient stopped early. At T1, shoulder ROM was complete in both abduction and flexion in 98% of patients; AWS was no longer detectable in 64% of them, and pain significantly decreased compared to T0. In conclusion, our protocol proved to be safe, well-tolerated and seemed to be effective in treating AWS.

Monthly correlates of longitudinal child mental health during the COVID-19 pandemic according to children and caregivers.

Multiple reviews identify the broad, pervasive initial impact of the global COVID-19 pandemic on the mental health of children, who may be particularly vulnerable to long-term psychiatric sequelae of the ongoing pandemic. However, limited longitudinal research examines persistence of, or change in, children's distress or psychiatric symptomatology. From June 2020 through December 2021, we enrolled two cohorts of families of children aged 8-13 from Southwestern Ontario into a staggered baseline, longitudinal design that leveraged multi-informant report (N = 317 families). In each family, one child and one parent/guardian completed a baseline assessment, 6 monthly follow-up assessments, and one final follow-up assessment 9 months post-baseline. At each assessment, the child and parent/guardian completed the CoRonavIruS health Impact Survey and measures of child anxiety, depressive, irritability, and posttraumatic stress syndromes. Children's mental health, indexed by the severity of multiple syndromes, fluctuated over the study period. Elevated local monthly COVID-19 prevalence, hospitalization, and death rates were associated with monthly elevations in children's reported worry about contracting COVID-19 and stress related to stay-at-home orders. In turn, both elevated monthly worry about contracting COVID-19 and stress related to stay-at-home orders were associated with monthly elevations in child- and parent-/guardian-report of children's emotional distress and psychiatric syndromes. This study illustrates the importance of, and informs the potential design of, longitudinal research to track the mental health of children, who may be particularly vulnerable to broad psychosocial sequelae of health crises such as the COVID-19 pandemic.

Review: Impact of urgent youth outpatient mental health care on patient and health system outcomes - a scoping review.

BACKGROUND: Young people often face barriers to psychiatric care and are increasingly seeking crisis services for mental health issues through the emergency department (ED). Urgent psychiatric care models provide youth in crisis with rapid access to time-limited mental health care on an outpatient basis. This scoping review aims to evaluate the impact of such urgent psychiatric services for youth aged 13-25 on patient and health system outcomes. METHODS: We conducted a literature search on PubMed, EMBASE, MEDLINE, PsycINFO, and the Cochrane Database of Systematic Reviews for studies published from inception to November 20, 2020. We included studies that described outpatient psychiatric services designed for youth aged 13 to 25, took place in a clinical setting, and offered any combination of assessment, treatment, and referral. We excluded studies describing suicide intervention programmes. RESULTS: Our search yielded six studies, four of which were descriptive studies and two of which were randomized controlled trials. Most studies found that access to urgent psychiatric care for youth was associated with reduced ED volumes, fewer health system costs, and fewer hospitalizations. None of the studies presented evidence that urgent psychiatric services are associated with improved patient symptomatology or functioning. CONCLUSIONS: The results of this scoping review highlight the scarcity of robust evidence evaluating the effectiveness of urgent care for youth mental health. Further experimental studies and a set of standardized quality measures for evaluating these services are needed to bridge this critical gap in mental health care for youth in crisis.

Reasons and Determinants of BoNT-A Treatment Discontinuation in Patients Living with Spasticity: A 10-Year Retrospective Analysis.

BACKGROUND: The present study aimed to evaluate the reasons and determinants of BoNT-A discontinuation in patients with stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. METHODS: It is a retrospective study of 56 discontinuer patients treated with botulinum toxin between January 2011 and December 2021. Discontinuation rates and their predictors were estimated using Kaplan-Meier, Log rank test, and Cox's regression method of analyses. RESULTS: The mean age was 56.54 years, 53.57% were affected by post-stroke spasticity, 17.86% by spinal cord injury, 12.5% and 16.07% by traumatic brain injury and multiple sclerosis, respectively. The median discontinuation time was 5 months. The main reason for discontinuation were logistic problems (37%) and orthopedic surgeries or intrathecal baclofen (27%). Discontinuers were more likely to have severe spasticity (R = 1.785), have no pain (HR = 1.320), no access to rehabilitation services (HR = 1.402), and have cognitive impairment (HR = 1.403). CONCLUSIONS: The main reasons for discontinuation are related to logistic issues (due to distance or the absence of an adequate caregiver) and surgical interventions for spasticity, including intrathecal baclofen. It is crucial to identify possible predictors of discontinuation to improve the effectiveness of a multidisciplinary management. The study confirms the crucial role of rehabilitation and caregivers in achieving better long-term outcomes.

The Lack of Systemic and Subclinical Side Effects of Botulinum Neurotoxin Type-A in Patients Affected by Post-Stroke Spasticity: A Longitudinal Cohort Study.

Botulinum Neurotoxin type-A (BoNT-A) is the treatment of choice for focal post-stroke spasticity (PSS). Due to its mechanism of action and the administration method, some authors raised concern about its possible systemic diffusion leading to contralateral muscle weakness and autonomic nervous system (ANS) alterations. Stroke itself is a cause of motor disability and ANS impairment; therefore, it is mandatory to prevent any source of additional loss of strength and adjunctive ANS disturbance. We enrolled 15 hemiparetic stroke survivors affected by PSS already addressed to BoNT-A treatment. Contralateral handgrip strength and ANS parameters, such as heart rate variability, impedance cardiography values, and respiratory sinus arrythmia, were measured 24 h before (T0) and 10 days after (T1) the ultrasound (US)-guided BoNT-A injection. At T1, neither strength loss nor modification of the basal ANS patterns were found. These findings support recent literature about the safety profile of BoNT-A, endorsing the importance of the US guide for a precise targeting and the sparing of "critical" structures as vessels and nerves.

Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis.

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life.