Whooping Cough Cases Increase in Central Italy after COVID-19 Pandemic.

Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. pertussis prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for B. pertussis were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of B. pertussis, which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate B. pertussis DNA levels (Ct mean: 26). Only one child, with very high B. pertussis DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status.

Use of an Orthodontic and Otolaryngological Approach in an Infant with Holoprosencephaly.

Holoprosencephaly is a complex human brain malformation resulting from incomplete cleavage of the prosencephalon into both hemispheres. Congenital nasal pyriform aperture stenosis (CNPAS) is sometimes found in patients with mild forms of holoprosencephaly. Surgical treatment is required. Low-invasive surgical approaches involve balloon dilation of the pyriform opening. We present the case of an 8-day-old girl diagnosed with holoprosencephaly, CNPAS, and the presence of a solitary median maxillary central incisor. Once examined by neonatologist, geneticist, pneumologist, otolaryngologist, and pediatric dentist, a combined otolaryngological-orthodontic approach was used. The obstruction of the right nasal cavity was treated by widening the nasal cavities and stabilizing them with a balloon dilation technique. After surgery, the respiratory space was increased by applying a neonatal palatal expander plate (NPEP) considering the palatal deformity: ogival shaped, anterior vertex growth direction, reduction of transverse diameters. The NPEP promoted distraction of the median palatine suture and assisted the nasal dilation. Therefore, after the insertion of NPEP, the physiological sucking-swallowing mechanism was activated. In infants with CNPAS, NPEP can be useful to ensure the safe stability of nasal dilation. A multidisciplinary approach is fundamental. In our experience, the close collaboration between an otolaryngologist and orthodontist is essential for the management of the patient with CNPAS.

Management of respiratory issues in patients with Rett syndrome: Italian experts' consensus using a delphi approach.

BACKGROUND: Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems. OBJECTIVE: Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients. MATERIALS AND METHODS: Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1-5 scale. The cut-off level for consensus was 75%, obtained through multiple rounds. RESULTS: The panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome, and in selected cases with other RS types. Noninvasive ventilation should be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP-mask, AMBU bag, or cough machine), more appropriate and tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomy in patients at increased risk of ab ingestis pneumonia. CONCLUSIONS: This consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.

Combining Mini-Mental State Examination and Montreal Cognitive Assessment for assessing the clinical efficacy of cholinesterase inhibitors in mild Alzheimer's disease: a pilot study.

Current drugs for Alzheimer's Disease (AD), such as cholinesterase inhibitors (ChEIs), exert only symptomatic activity. Different psychometric tools are needed to assess cognitive and non-cognitive dimensions during pharmacological treatment. In this pilot study, we monitored 33 mild-AD patients treated with ChEIs. Specifically, we evaluated the effects of 6 months (Group 1 = 17 patients) and 9 months (Group 2 = 16 patients) of ChEIs administration on cognition with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Frontal Assessment Battery (FAB), while depressive symptoms were measured with the Hamilton Depression Rating Scale (HDRS). After 6 months (Group 1), a significant decrease in MoCA performance was detected. After 9 months (Group 2), a significant decrease in MMSE, MoCA, and FAB performance was observed. ChEIs did not modify depressive symptoms. Overall, our data suggest MoCA is a potentially useful tool for evaluating the effectiveness of ChEIs.

Joint trajectories of bullying victimization and sexual harassment victimization as predictors of adolescent alcohol use.

OBJECTIVE: The present study examined the independent and joint effects of bullying victimization and sexual harassment victimization on adolescent alcohol use over time within a community sample of adolescents. METHOD: Adolescents aged 13-15 years old at baseline (N = 800, Mage = 14.42, SD = 0.83; 57.5% female) recruited from Western New York State made five online survey reports of peer victimization and alcohol use over a 2-year period. Latent class growth analysis was used to identify trajectory classes of victimization from bullying and sexual harassment over time, and regression modeling was used to examine the associations with later alcohol use. RESULTS: Three developmental courses were identified for bullying victimization (moderate/decreasing, high/decreasing, never or low) and for sexual harassment victimization (moderate/decreasing, moderate/increasing, never or low). Adolescents in the moderate/decreasing group of bullying victimization subsequently consumed more alcoholic drinks when they drank. Belonging to the moderate/increasing group of sexual harassment was associated with increased later alcohol intoxication and number of drinks. Bullying victimization and sexual harassment victimization were concurrently correlated over time. Adolescents who followed the joint trajectory group of moderately decreasing bullying and increasing sexual harassment were more likely to report increased later alcohol intoxication and number of drinks. CONCLUSIONS: Moderate levels of bullying victimization along with increasing sexual harassment victimization are associated prospectively with greater alcohol use in adolescence. Findings highlight the importance of considering the cumulative, joint effects of multiple types of peer victimization on adolescent health outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Precollege Risk Markers for College Rape and Verbal Sexual Coercion: Same or Different?

Verbal sexual coercion (VSC) and rape are common experiences among college women. Although they have been theorized to involve different risk markers, few prospective studies have examined predictors of VSC and rape separately. The present prospective study was designed to identify precollege risk markers for VSC and rape in first-year college women, with the goal of considering the degree to which they overlap or differ. Women (N = 449) recruited from the community just prior to high school graduation completed measures of sexual victimization (SV) since age 14 but prior to college, sexual refusal assertiveness, high school heavy episodic drinking (HED), college drinking intentions, and sociosexuality. Follow-up surveys at the end of the first and second college semesters assessed VSC and rape. Using the Sexual Experiences Survey's severity scoring method, women were classified into one of three groups according to the most severe type of SV reported in the first year of college: neither VSC nor rape (71%), VSC (16%), and rape (13%). Most women who experienced rape (73%) also experienced VSC. Precollege SV and college drinking intentions predicted both rape and VSC. Sexual refusal assertiveness and high school HED did not independently predict either form of victimization. Sociosexuality predicted rape but not VSC. Findings suggest a substantial overlap in the predictors of VSC and rape and support the severity continuum underlying many conceptualizations of SV.

Do Risk Factors for Incapacitated and Other Sexual Assault Differ for Black and White College Women? A Preliminary Investigation.

Heavy episodic drinking (HED) and hookups are risk factors for college women's sexual assault (SA). Black women engage in these behaviors less frequently than White women. We prospectively examined HED and hookups as mechanisms of incapacitated SA (ISA) and other SA (OSA) risks for Black and White first-year college women and sociocontextual factors that may contribute differentially to risk. In mediation analyses, Black women's less frequent HED predicted lower ISA. SA characteristics (e.g., setting) also differed by race. Mechanisms and types of assault risk may not be the same for all college women, an important consideration for intervention efforts.

Care Issues in Patients with Rett Syndrome: A Parental Perspective.

BACKGROUND: The purpose of this study is to better understand the way caregivers of patients with Rett syndrome perceive the quality of the health care services they receive and identify its main shortcomings. METHODS: A survey was distributed to all caregivers who are part of AIRETT (the Italian Association of Relatives of Patients with RS). The survey gathered information on the management of relatives of patients with Rett syndrome. RESULTS: The data refers to 52 patients, all females, with a median age of 15 years at the time of the survey. Concerning RS specificity, our data confirm the high complexity of this chronic, multifaceted condition, mainly characterized by the presence of epilepsy, apnea, severe scoliosis, and gastrointestinal symptoms. The specialists more frequently involved in the care of patients were general practitioners or family pediatricians (98%) and neurologists (92%), and more rarely physiatrists (71%). Only 15% of patients were followed by a pulmonologist, despite the fact that respiratory problems were frequent (apneas were present in 81% of patients, and 2% had a tracheostomy). Although 63.5% of patients presented with gastrointestinal symptoms and 2% had a gastrostomy, only 33% were followed by a gastroenterologist. Moreover, although orthopedic issues were present in 78.8% of patients, including severe scoliosis in 22% of them, only 25% were followed by an orthopedist. Furthermore, despite the fact that RS patients are fragile, about one quarter of them were not vaccinated. As far as organizational issues are concerned, several specialized centers are located in various regions throughout the country. As a consequence, the high mobility rate from one center to another resulted in non-homogeneous assistance. CONCLUSIONS: The study shows that caregivers of RS patients take over most obligations and burdens by increasing their perceived level of stress. For the majority of patients, the most frequent complications were not followed by the reference subspecialist, with the only exception of epilepsy. Moreover, improving vaccination strategies for these patients is necessary.

Batch and Flow Green Microwave-Assisted Catalytic Conversion Of Levulinic Acid to Pyrrolidones.

This paper reports a new sustainable protocol for the microwave-assisted catalytic conversion of levulinic acid into N-substituted pyrrolidones over tailor-made mono (Pd, Au) or bimetallic (PdAu) catalysts supported on either highly mesoporous silica (HMS) or titania-doped HMS, exploiting the advantages of dielectric heating. MW-assisted reductive aminations of levulinic acid with several amines were first optimized in batch mode under hydrogen pressure (5 bar) in solvent-free conditions. Good-to-excellent yields were recorded at 150 °C in 90 min over the PdTiHMS and PdAuTiHMS, that proved recyclable and almost completely stable after six reaction cycles. Aiming to scale-up this protocol, a MW-assisted flow reactor was used in combination with different green solvents. Cyclopentyl methyl ether (CPME) provided a 99 % yield of N-(4-methoxyphenyl) pyrrolidin-2-one at 150 °C over PdTiHMS. The described MW-assisted flow synthesis proves to be a safe procedure suitable for further industrial applications, while averting the use of toxic organic solvents.

Sleep architecture and Nusinersen therapy in children with Spinal Muscular Atrophy type 1.

BACKGROUND: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder, the phenotype of the disease is caused by the mutation of the SMN1 (survival motor neuron 1) gene which encodes for the SMN protein. Innovative treatments for SMA have become available and the first molecule approved is Nusinersen, an antisense oligonucleotide that increases the production of SMN protein. Nusinersen has been shown to be associated with a significant motor improvement and an increase of the event-free survival. For these reasons the aim of the present study is to assess if Nusinersen is able modify sleep architecture and microstructure and to improve sleep structure in these patients. METHODS: Sixteen patients affected by SMA1 were enrolled in the study (4 boys, 12 girls; median age 72.5 months, intelligence quotient range 24-84). All patients underwent complete nocturnal PSG before the start of the treatment trough intrathecal injections with Nusinersen (T0) and after the fifth infusion (day 180, T180). PSG recordings were visually scored and interpreted according to the indications of the American Academy of Sleep Medicine (AASM) and and microstructure by means of the Cyclic Alternating Pattern (CAP). RESULTS: After 6 months therapy we found a significantly reduced sleep latency and a significantly increased sleep efficiency. Regarding sleep microstructure parameters (CAP), we did not find any significant change after therapy however, it is worth mentioning that a moderate effect size was observed for the increase in CAP A3 index. CONCLUSIONS: We observed short-term effects of Nusinersen on sleep with an improvement in sleep efficiency and reduction in sleep onset latency; regarding sleep microstructure, a moderate effect size was found for the number of CAP A3 subtypes that slightly increased, possibly indicating a slightly higher arousability. This finding points at a probably overall better sleep pattern organization associated with the treatment, but they need to be confirmed by larger studies with patients treated earlier in life and for a longer period.

Interesterification of Glyceryl Trioctanoate Catalyzed by Sulfonic Silica-Based Materials: Insight into the Role of Catalysts on the Reaction Mechanism.

In the present work, the acid-catalyzed interesterification of glyceryl trioctanoate (GTO) with ethyl acetate was investigated as a model reaction for the one-step production of biofuel and its additives. The activity of heterogeneous acid catalysts, such as silica-based propyl-sulfonic ones, was evaluated. Propyl-sulfonic groups were grafted on both amorphous and mesoporous silica oxide (SBA-15, KIT-6) using different functionalization processes and characterized by N2 adsorpion-desorption isotherm (BET), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and potentiometric titration. During the optimization of the reaction conditions with the most active catalyst (Am-Pr-SO3H), it was shown that the addition of ethanol allowed a total conversion of GTO together with 89% and 56% yield of ethyl octanoate and triacetin, respectively. The catalytic performance is strictly correlated to the catalyst features, in terms of both the acid capacity and the porous structure. Moreover, the catalytic performance is also affected by a synergistic mechanism between silanols and Pr-SO3H groups towards the 'silanolysis' of ethyl acetate. The overall results show that the presence of ethanol, the reaction time, and the amount of catalyst shifts the reaction towards the formation of the biofuel mixture composed by ethyl octanoate and triacetin.

Sexual Victimization in Adolescence: Pathways of Risk from Sexual Harassment via Risky Alcohol Use and Delinquency Among U.S. Adolescents.

Sexual harassment is a common, yet understudied form of peer victimization experienced by adolescents during a critical period in the development of sexual identity. Adverse sexual experiences early in life (e.g., child sexual abuse) can increase risk of future sexual assault victimization; however, it is unclear as to whether sexual harassment victimization is also a risk factor for sexual assault. We examined the prospective association between peer sexual harassment and experiencing sexual victimization in the following year among a community sample of 13-15-year-old adolescents (N = 800, 57% female) from the northeastern USA. We also examined whether risky alcohol use and delinquency mediated the association between sexual harassment and sexual assault victimization, as well as whether the paths differed by gender. Results indicated that sexual harassment victimization prospectively predicted later sexual victimization for both girls and boys. Using a parallel mediation path model, we determined that for girls, sexual harassment victimization predicted both risky alcohol use and delinquency, but only risky alcohol use was predictive of sexual victimization. For boys, sexual harassment victimization predicted delinquency but not risky alcohol use. Risky alcohol use was not associated with sexual victimization for boys. Findings indicate that sexual harassment victimization increases risk of later sexual victimization in adolescence, but the pathways differ by gender.

It's not just drinking, but where you drink: A daily diary study of drinking venue effects on sexual activity with new partners.

It is well established that young adults' drinking is positively associated with sexual activity with new partners. While pharmacologic effects of alcohol (e.g., impaired sexual decision-making) can contribute to sexual activity with new partners, the context in which alcohol is consumed may also be important. We tested the hypothesis that drinking venues such as parties and bars increase the likelihood of sexual activity with new partners beyond any pharmacological effects of drinking quantity. Participants were 427 first-year men (aged 18-19). They reported on their relationship status and sociosexuality (i.e., attitudes/behaviors related to casual sex) at baseline and completed daily diary reports of drinking events (including number of drinks and venue) and sexual activity with new or previous partners over the span of 56 days. Drinking events at parties/bars (but not at home) increased the odds of sexual activity in the next four hours with new partners (but not with previous partners), even after controlling for the number of drinks consumed. Parties/bars are an integral part of facilitating sexual activity with new partners, and have effects independent of pharmacological alcohol effects, which has implications for reducing alcohol-related risky sexual activity. Interventions should not only target alcohol consumption, but where consumption takes place.

Do couple drinking episodes lead to intimate partner aggression? An ecological momentary assessment study of same-sex and mixed-sex couples.

OBJECTIVE: Alcohol use is an established risk factor for intimate partner aggression (IPA); however, few studies have considered whether couple drinking episodes increase the short-term likelihood of IPA episodes. The present ecological momentary assessment study considered the temporal effects of alcohol consumption on IPA perpetration and victimization within a sample of community couples at elevated risk of aggression. METHOD: Mixed-sex (n = 191), same-sex male (n = 31), and same-sex female (n = 27) cohabiting couples (total N = 249; ages 21-35) made three independent, random reports for 30 consecutive days. Dyadic multilevel modeling was used to examine the impact of each partner's drinking episodes on the occurrence of verbal and physical perpetration and victimization events within the next 4 hr, using the actor-partner interdependence model. RESULTS: Actor and partner alcohol use increased the likelihood of conflict and likelihood of conflicts involving verbal perpetration and victimization within the next 4 hr; alcohol effects on physical aggression were weaker. Actor alcohol effects on IPA remained significant after the addition of several control variables; partner effects did not. The absence of Alcohol × Gender interaction effects suggests that alcohol effects on IPA do not depend on actor or partner gender or their combination. CONCLUSIONS: There are robust alcohol effects on the occurrence of verbal aggression perpetration and victimization episodes, with weak effects on physical aggression perpetration. Conflicts that include alcohol are not more likely to include aggression; rather, alcohol increases the likelihood of conflict occurring, with a proportion of those involving verbal aggression. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Elixir of love or venom of violence: When does a drinking event result in couple intimacy or couple conflict?

The short-term consequences of drinking events may be positive or negative. Most studies have considered only one outcome, but people may experience different alcohol outcomes on different occasions, depending on the circumstances. The present study sought to identify predictors of drinking events that resulted in couple intimacy, conflict, or neither outcome using existing data from a 30-day ecological momentary assessment (EMA) study. Participants were a community sample of partnered, moderately drinking adults with a recent history of verbal or physical partner aggression (N = 249 couples). They provided reports of drinking events, intimacy and conflict events, and ratings of relationship harmony and discord in three randomly signaled reports each day. Mixed-effects multinomial analyses were used to compare predictors of drinking events that, within three hours, resulted in intimacy, conflict, or neither outcome. Consistent with previous research, characteristics of the drinker (individual tendencies to experience intimacy or conflict) and characteristics of the drinking event (alcohol quantity, drinking companions) both predicted drinking outcomes. Moreover, the pre-drinking relationship context predicted post-drinking relationship outcomes, consistent with the idea that alcohol focuses attention on salient contextual cues. Specifically, greater pre-drinking relationship harmony predicted greater likelihood of experiencing intimacy after drinking, whereas greater pre-drinking relationship discord predicted greater likelihood of experiencing conflict after drinking. In summary, characteristics of the drinker, the drinking event, and the pre-drinking relationship context contribute to the likelihood that a given drinking event will have short-term positive or negative relationship outcomes.

Children with medical complexity and pediatric palliative care: Data by a respiratory intermediate care unit.

Pediatric palliative care (PPC) is an active and total approach to the care of children with life-limiting conditions and their families. PPC programs provide ongoing treatment for children with medical complexity (CMC), many of whom will reach adulthood. Aim of the study was to describe a population of CMC attendingin six preselected months the Respiratory Intermediate Care Unit of a tertiary referral hospital for southern and central Italy. We enrolled all CMC patients admitted to our unit in six preselected months and registered pathologies and different categories of childhood diseases, devices and needs, hospitalization and home care plan. Among the 275 children admitted to our unit, 130 CMC were included. Median age was 9.9 (0.1-40.0) years. The main pathologies recorded were neuromuscular, neurological, respiratory, metabolic and malformative diseases, genetic syndromes and outcomes of prematurity. Comorbidity due to respiratory, digestive, neurological, cardiac and urological involvement was present in a high percentage of cases. Among our patients, only 46 were not carriers of any medical device. The average length of hospitalization was 7.0 (1.0-270.0) days with 2 (1.0-7.0) admissions per year per patient. Home care activation was not required for 47 out of 130 patients. Children eligible for PPC are increasing and their survival results in a rise of comorbidities and special needs demanding multilevel interventions. Respiratory symptoms are the most recurrent ones observed, thus requiring an expert in PPC with expertise in the respiratory field. Sharing data and knowledge of CMC needs may help improve care coordination.

Translational readthrough at F8 nonsense variants in the factor VIII B domain contributes to residual expression and lowers inhibitor association.

In hemophilia A, F8 nonsense variants, and particularly those affecting the large factor VIII (FVIII) B domain that is dispensable for coagulant activity, display lower association with replacement therapy-related anti-FVIII inhibitory antibodies as retrieved from multiple international databases. Since null genetic conditions favor inhibitor development, we hypothesized that translational readthrough over premature termination codons (PTC) may contribute to immune tolerance by producing full-length proteins through the insertion of amino acid subset(s). To quantitatively evaluate the readthrough output in vitro, we developed a very sensitive luciferase-based system to detect very low full-length FVIII synthesis from a wide panel (n=45; ~60% patients with PTC) of F8 nonsense variants. PTC not associated with inhibitors displayed higher readthrough-driven expression levels than inhibitor-associated PTC, a novel observation. Particularly, higher levels were detected for B-domain variants (n=20) than for variants in other domains (n=25). Studies on plasma from six hemophilia A patients with PTC, integrated by expression of the corresponding nonsense and readthrough-deriving missense variants, consistently revealed higher FVIII levels for B-domain variants. Only one B-domain PTC (Arg814*) was found among the highly represented PTC not sporadically associated with inhibitors, but with the lowest proportion of inhibitor cases (4 out of 57). These original insights into the molecular genetics of hemophilia A, and particularly into genotype-phenotype relationships related with disease treatment, demonstrate that B-domain features favor PTC readthrough output. This provides a potential molecular mechanism contributing to differential PTC-associated inhibitor occurrence, with translational implications for a novel, experimentally based classification of F8 nonsense variants.

Hypoventilation and sleep hypercapnia in a case of congenital variant-like Rett syndrome.

BACKGROUND: Breathing disturbances are often a primary clinical concern especially during wakefulness of the classic form of Rett syndrome, but data for atypical forms are lacking. CASE PRESENTATION: We report the case of a 20-month-old female affected by Rett syndrome with congenital variant-like onset, characterized by severe hypotonia and neurodevelopment impairment. She presented hypoventilation, persistent periodic breathing, and sustained desaturation during sleep, without obstructive or mixed events. Pulse oximetry and capnography during wakefulness were strictly normal. To the best of our knowledge, this is the first case of a patient affected by a congenital variant of Rett syndrome presenting sleep hypercapnia. Hypotonia may play a major role in the genesis of hypoventilation and hypoxemia in our patient. Non-invasive ventilation led to quality-of-life improvements. CONCLUSIONS: Thus, we suggest screening patients with congenital-like Rett syndrome through transcutaneous bedtime carbon dioxide and oxygen monitoring. Moreover, assisted control mode was a breakthrough to achieve adequate ventilation in our case.

Translation termination codons in protein synthesis and disease.

Fidelity of protein synthesis, a process shaped by several mechanisms involving specialized ribosome regions and external factors, ensures the precise reading of sense as well as stop codons (UGA, UAG, UAA), which are usually localized at the 3' of mRNA and drive the release of the polypeptide chain. However, either natural (NTCs) or premature (PTCs) termination codons, the latter arising from nucleotide changes, can undergo a recoding process named ribosome or translational readthrough, which insert specific amino acids (NTCs) or subset(s) depending on the stop codon type (PTCs). This process is particularly relevant for nonsense mutations, a relatively frequent cause of genetic disorders, which impair gene expression at different levels by potentially leading to mRNA degradation and/or synthesis of truncated proteins. As a matter of fact, many efforts have been made to develop efficient and safe readthrough-inducing compounds, which have been challenged in several models of human disease to provide with a therapy. In this view, the dissection of the molecular determinants shaping the outcome of readthrough, namely nucleotide and protein contexts as well as their interplay and impact on protein structure/function, is crucial to identify responsive nonsense mutations resulting in functional full-length proteins. The interpretation of experimental and mechanistic findings is also important to define a possibly clear picture of potential readthrough-favorable features useful to achieve rescue profiles compatible with therapeutic thresholds typical of each targeted disorder, which is of primary importance for the potential translatability of readthrough into a personalized and mutation-specific, and thus patient-oriented, therapeutic strategy.

Peer sexual harassment, affect, and substance use: Daily level associations among adolescents.

INTRODUCTION: Peer sexual harassment is associated with adolescent substance use at the global level; however, it is unknown whether substance use occurs proximal in time to the sexual harassment experience. This study used daily reports to examine the proximal relations between sexual harassment victimization and affect and substance use. Based on theories of self-medication, we hypothesized that negative affect and substance use (cigarettes, electronic cigarettes, alcohol, and marijuana) would be higher than typical on days when sexual harassment occurred relative to nonvictimization days. METHOD: A community sample of 13-16-year-old adolescents (N = 204, 55.4% female) from a metropolitan area in the northeastern United States completed 56 days of online reports assessing experiences with peer sexual harassment, substance use (cigarettes, electronic cigarettes, alcohol, and marijuana), and positive and negative affect. RESULTS: Multilevel modeling revealed that experiencing sexual harassment on a given day was associated with higher than typical negative affect on that day, relative to nonvictimization days. The likelihood of cigarette and alcohol use (but not electronic cigarettes, marijuana, or positive affect) was greater on days when sexual harassment occurred. CONCLUSION: Sexual harassment victimization is proximally associated with negative affect and alcohol and cigarette use, suggesting that adolescents may be using substances to cope with sexual harassment victimization. The co-occurrence of sexual harassment with negative affect and substance use points to the need for prevention efforts that conjointly address sexual harassment victimization, coping, and substance use.