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L-carnosine (Car) is an endogenous dipeptide with significant potential in drug discovery for neurodegenerative diseases, while TAT1, a small arginine-rich peptide derived from the HIV-1 trans-activator protein (TAT), is known to stimulate proteasome activity. In this study, three isomeric peptides were synthesised by incorporating the Car moiety at the N-terminus, C-terminus, or central position of the TAT1 sequence. To differentiate these isomers, high-resolution and energy-resolved CID MS/MS experiments were conducted. The resulting MS/MS spectra showed a high degree of similarity among the peptides, predominantly characterised by fragment ion peaks arising from arginine-specific neutral losses. Energetic analysis was similarly inconclusive in resolving the isomers. However, Principal Component Analysis (PCA) enabled clear differentiation of the three peptides by considering the entire MS/MS spectra rather than focusing solely on precursor ion intensities or major fragment peaks. PCA loadings revealed distinct fragment ions for each peptide, albeit with lower intensities, providing insights into consecutive fragmentation patterns. Some of these specific peaks could also be attributed to scrambling during fragmentation. These results demonstrate the potential of PCA as a simple chemometric tool for semi-automated peak identification in complex MS/MS spectra.

Nutritional supplements are often characterised by unpleasant tastes or aftertastes, primarily due to the presence of vitamins, minerals, and amino acids as active compounds. These taste defects can be masked by sweeteners or specific flavourings. However, the development of such strategies requires a thorough understanding of the sensory characteristics of nutritional supplements. In the present study, the sensory properties of four effervescent nutritional supplements, differing in composition, were evaluated using Quantitative Descriptive Analysis (QDA) across three modalities: orthonasal and retronasal odour perception, as well as aftertaste and aroma persistence. Bitterness, astringency, and metallic sensations were found to be responsible for the negative sensory attributes of the products in solution. The addition of flavouring agents was found to have either a positive or negative effect on the taste characteristics of the supplements. Indeed, certain fruity notes enhanced sweet and sour sensations and were found to mask negative sensory perceptions, although this effect varied depending both on the nature of the nutritional supplement and on the QDA modalities, mainly due to the oral process progressing. A better understanding of these perceptual interactions could provide a solution for masking strategies, potentially reducing the use of additives that can be expensive and detrimental to health.

Background: Clinicians are challenged by the ambiguity and uncertainty in assessing level of consciousness in individuals with disorder of consciousness (DoC). There are numerous challenges to valid and reliable neurobehavioral assessment and classification of DoC due to multiple environmental and patient-related biases including behavioral fluctuation and confounding or co-occurring medical conditions. Addressing these biases could impact accuracy of assessment and is an important aspect of the DoC assessment process. Methods: A pre-assessment checklist was developed by a group of interdisciplinary DoC clinical experts and researchers based on the existing literature, current validated tools, and expert opinions. Once finalized, the checklist was electronically distributed to clinicians with a range of experience in neurobehavioral assessment with DoC. Respondents were asked to use the checklist prior to completing a neurobehavioral assessment. A survey was also provided to respondents to obtain feedback regarding checklist feasibility and utility in optimizing the behavioral assessments. Results: Thirty-three clinicians completed the survey after using the checklist. Over half of the respondents were a combination of physicians, neuropsychologists, and physical therapists. All respondents served the adult DoC population and 42% percent had over ten years of clinical experience. Eighty percent reported they found the format of the checklist useful and easy to use. All respondents reported the checklist was relevant to preparing for behavioral assessment in the DoC population. Eighty-four percent reported they would recommend the use of the tool to other clinicians. Conclusions: The use of a pre-assessment checklist was found to be feasible and efficacious in increasing interdisciplinary clinician’s ability to optimize the patient and environment in preparation for neurobehavioral assessment. Initial results of clinicians’ perception of the utility of a pre-assessment checklist were positive. However, further validation of the tool is needed with larger sample sizes to improve representation of clinical use across disciplines and care settings.

Opioid use disorder involves disruptions to glutamate homeostasis and dendritic spine density in the reward system. PKMζ is an atypical isoform of protein kinase C that is expressed exclusively in neurons and plays a role in postsynaptic glutamate signaling and dendritic spine maturation. As opioid use leads to alterations in glutamate transmission and dendritic spine density, we hypothesized that PKMζ deletion would alter opioid-taking behaviors. The current study examined two doses of oxycodone self-administration in male and female mice with constitutive deletion of PKMζ compared to wildtype controls. At a dose of 0.25 mg/kg/infusion, PKMζ deletion significantly potentiated oxycodone self-administration in both male and female mice. However, increases in motivation for oxycodone, as indicated by increased breakpoint on a progressive ratio schedule, were only seen in male PKMζ knockout mice and not females. When we examined a lower dose of oxycodone, 0.125 mg/kg/infusion, PKMζ knockout led to increases in oxycodone self-administration only in female mice. Additionally, female PKMζ knockout mice exhibited higher breakpoints on a progressive ratio schedule at this dose compared to all other groups. In addition to the self-administration studies, we also examined locomotor sensitization in response to experimenter administered oxycodone. PKMζ KO decreased oxycodone induced locomotion in males and potentiated oxycodone sensitization in females. Together, these results suggest that PKMζ acts to dampen oxycodone taking in both sexes, but females may be more sensitive to its effects.

IntroductionMental health practitioners (MHPs), including occupational therapists (OTs), need support to adopt a truly recovery-oriented practice. Like other practitioners, if OTs often embrace the principles of recovery as a philosophical foundation for their practice, these principles may not always reflect in their attitudes, behaviors or in their interventions. While further research is needed to demonstrate the positive effects of recovery-oriented training programs on MHPs’ attitudes and practice, there is a need to explore novel training programs. The Recovery College (RC) model is one of the interventions that are designed to facilitate these changes in practice, through co-production and co-delivery of recovery-focused courses curriculum. Although the perceived benefits and outcomes of RC courses are widely documented, very few studies focus specifically on what MHPs gain from them or on their global experience. The aim of this article is to describe the experience of MHPs learners in RC courses and the perceived benefits on their practice.MethodsAn exploratory descriptive qualitative study was conducted. Data were collected through semi-structured interviews and analyzed using Miles and Huberman’s stepwise qualitative analysis method.ResultsParticipants were 13 MHPs working in community organizations or healthcare institutions and who participated as learners in a RC, in the province of Quebec, Canada. Ten themes emerged from the qualitative analysis. Participants expressed their perspectives on the format of the courses, their initial expectations and their recommendations. They also identified the types of knowledge they shared during the courses. Participants reported changes in their practice, raised awareness on their clinical and personal issues, improved well-being and recovery. Group composition, interactions within the group, complementarity of the different types of knowledge, and pedagogical design and learning activities were identified as key ingredients of RC.ConclusionsThis study highlighted RCs’ role in enriching MHPs clinically and personally. RC curriculum and courses drive changes in practice and attitudes towards service users. RCs may assist MHPs reflect on practice and improve their clinical reasoning. This study advances understanding of a promising, accessible training program for adopting a recovery-oriented practice amid a paradigm shift among MHPs and OTs.

Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation.

Objective To describe antibiotic prescribing practices using the WHO AWaRe (Access, Watch, Reserve) classification in West African children under 5 years of age attending public primary health centres (PHCs).Design Cross-sectional study.Setting The AIRE project implemented the systematic use of pulse oximetry into integrated management of childhood illness consultations in West African countries (Burkina Faso, Guinea, Mali and Niger). We described antibiotic prescriptions for outpatient children at 16 PHCs and for severe cases referred at district hospitals.Patients Between 14 June 2021 and 19 June 2022, 15 854 outpatients were included: 968 neonates and young infants (0–28 days) and 14 886 children (2–59 months). Among them, 78 (8.1%) neonates and young infants and 385 (2.6%) children were hospitalised. We evaluated 58 hospitalised neonates and young infants and 275 hospitalised children, respectively.Main outcome measures Frequency of antibiotic prescriptions according to the AWaRe classification recommended by WHO.Results At the PHC level, proportions of neonates and young infants with ≥1 antibiotic prescription were 83%, 62%, 71% and 59% in Burkina Faso, Guinea, Mali and Niger, respectively. A total of 805 antibiotics were prescribed (85% Access and 13% Watch). The proportions of children with ≥1 antibiotic prescription reached 71%, 66%, 63% and 36% in Burkina Faso, Guinea, Mali and Niger, respectively. Out of the 9630 antibiotics prescribed, 93% were Access (mainly amoxicillin), and 7% Watch. At the hospital level, Watch antibiotics were mainly prescribed for severe cases referred. No Reserve antibiotics were prescribed.Conclusions High proportions of antibiotics were prescribed to outpatient children included, the appropriateness of which needs further study. Nevertheless, in every country, the proportion prescribed in the Access group reached the minimum threshold of 60% of all antibiotic prescriptions, as recommended by WHO.Trial registration number PACTR202206525204526.

In 2010, the United States Human and Health Services (US HHS) and the European Union's (EU) Directorate General for Communications Networks, Content and Technology signed a memorandum of understanding to stimulate cooperation surrounding health-related information communications technology. The key project that emerged from this agreement is the International Patient Summary (IPS), intended to provide succinct clinically relevant patient summaries, which are generalizable and condition-independent, that can be readily used by all clinicians for the care of patients. Although allergies are included in the main information required by the IPS library and framework, it is misrepresented which leads to underdiagnosis or misdiagnosis of patients suffering from allergic and hypersensitivity conditions (A/H). The French and Montpellier World Health Organization (WHO) Collaborating Centres have provided arguments for supporting representation of A/H in the IPS. These are based on the relevance of the new classification of A/H in the WHO International Classification of Diseases 11th version (ICD-11), and the need for alignment of eHealth tools with harmonized health information. We first present the A/H in the IPS initiative with the mission of producing an international information system that can be used globally in electronic health records to standardize clinical diagnoses and facilitate communication between clinicians caring for patients with A/H diseases. It is believed this initiative will provide a strong voice for the allergy community and an effective process for improving the quality of health data that will optimize medical care for our patients worldwide.

Adolescence is a critical period for brain development in humans and stress exposure during this time can have lasting effects on behavior and brain development. Social isolation and loneliness are particularly salient stressors that lead to detrimental mental health outcomes particularly in females, although most of the preclinical work on social isolation has been done in male animals. Our lab has developed a model of post-weaning adolescent social isolation that leads to increased drug reward sensitivity and altered neuronal structure in limbic brain regions. The current study utilized this model to determine the impact of adolescent social isolation on a three-chamber social interaction task both during adolescence and adulthood. We found that while post-weaning isolation does not alter social interaction during adolescence (PND45), it has sex-specific effects on social interaction in young adulthood (PND60), potentiating social interaction in male mice and decreasing it in female mice. As early life stress can activate microglia leading to alterations in neuronal pruning, we next examined the impact of inhibiting microglial activation with daily minocycline administration during the first 3 weeks of social isolation on these changes in social interaction. During adolescence, minocycline dampened social interaction in male mice, while having no effect in females. In contrast, during young adulthood, minocycline did not alter the impact of adolescent social isolation in males, with socially isolated males exhibiting higher levels of social interaction compared to their group housed counterparts. In females, adolescent minocycline treatment reversed the effect of social isolation leading to increased social interaction in the social isolation group, mimicking what is seen in naïve males. Taken together, adolescent social isolation leads to sex-specific effects on social interaction in young adulthood and adolescent minocycline treatment alters the effects of social isolation in females, but not males.

Regulatory T cells (Treg) play a prominent role in utero tolerating non-inherited maternal antigens and in regulating immune responses against pathogens at birth. This study investigates Treg immunity in newborns in West Africa, where sepsis remains a major public health problem. Treg phenotypes on neonates subgroups with early-onset sepsis (EOS), presumed sepsis, and healthy newborn with and without prenatal risk factors were evaluated. Treg phenotypes varied according to prenatal conditions, with increase in Treg frequency and Foxp3 expression in healthy newborns with prenatal risk factors compared to those with none risk. Compared to healthy newborns with prenatal risk factors, EOS neonates had a significantly reduced frequency of Treg and Foxp3 expression. In the Treg pool, higher frequency of activated Treg was observed in EOS neonates, suggesting an in-utero activation upstream of the sepsis onset. Their migration to the infection site may explain the reduced frequency of circulating Integrin α4β1+ Treg suggestive of homing to the endothelial tissue. EOS neonates show increases expression of CTLA-4, PD-1 and CD39 on Treg, which negatively regulate the activation of effector T cells (Teff) corroborating by the lower frequency of Teff in EOS neonates. The higher frequency of CD39+ Treg and the lower frequency of integrinα4β1+ Treg in EOS non-survivor suggests that Treg exhaustement and endothelial homing are associated with outcome severity. Neonates developing EOS are born with an altered Treg phenotypic profile. Treg expression of CTLA-4, PD-1, CD39, and integrinα4β1 cell markers can be considered as early warning or diagnostic markers of EOS.

The Preparedness and Resilience for Emerging Threats (PRET) initiative takes an innovative mode-of-transmission approach to pandemic planning by advocating for integrated preparedness and response systems and capacities for groups of pathogens with common transmission pathways. The World Health Organization (WHO) launched this initiative in 2023 with the publication of PRET Module 1 addressing respiratory pathogens. Exercise PanPRET-1 is a customizable tabletop simulation exercise (TTX) package developed to complement PRET Module 1. The exercise scenario focuses on strengthening capacities for multisectoral coordination, risk communication and community engagement, and the triggers for operational decision-making. This article reports on the experiences of the first four countries to implement Exercise PanPRET-1: Cook Islands, Costa Rica, Lebanon and Mongolia. Exercise outcomes demonstrated that PanPRET-1 can be an effective tool for testing pandemic plans in a multisectoral forum and identifying opportunities to improve preparedness and response in key domains. In quantitative evaluations in Cook Islands, Costa Rica and Mongolia, high proportions of exercise participants indicated that multiple aspects of the exercise were well-designed and were beneficial for improving health emergency preparedness. Exercise participants in Lebanon provided qualitative feedback indicating that they found the exercise to be beneficial. Conducting a TTX and monitoring the implementation of action plans based on exercise findings facilitates a country-owned whole-of-society vision for pandemic planning. Countries are encouraged to incorporate TTX such as Exercise PanPRET-1 into a continuous cycle of activity to improve pandemic preparedness.

Introduction Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulation (tACS) intervention in subacute brain-injured patients on recovery of consciousness, related brain oscillations and brain network dynamics.Methods and analyses The study is comprised of two phases: a validation phase (n=12) and a randomised controlled trial (n=138). Both phases will be conducted in medically stable brain-injured adult patients (traumatic brain injury and hypoxic-ischaemic encephalopathy), with a Glasgow Coma Scale score ≤12 after continuous sedation withdrawal. Recruitment will occur at the intensive care unit of a Level 1 Trauma Centre in Montreal, Quebec, Canada. The intervention includes a 20 min 10 Hz tACS at 1 mA intensity or a sham session over parieto-occipital cortical sites, repeated over five consecutive days. The current’s frequency targets alpha brain oscillations (8–13 Hz), known to be associated with consciousness. Resting-state electroencephalogram (EEG) will be recorded four times daily for five consecutive days: pre and post-intervention, at 60 and 120 min post-tACS. Two additional recordings will be included: 24 hours and 1-week post-protocol. Multimodal measures (blood samples, pupillometry, behavioural consciousness assessments (Coma Recovery Scale-revised), actigraphy measures) will be acquired from baseline up to 1 week after the stimulation. EEG signal analysis will focus on the alpha bandwidth (8–13 Hz) using spectral and functional network analyses. Phone assessments at 3, 6 and 12 months post-tACS, will measure long-term functional recovery, quality of life and caregivers’ burden.Ethics and dissemination Ethical approval for this study has been granted by the Research Ethics Board of the CIUSSS du Nord-de-l’Île-de-Montréal (Project ID 2021–2279). The findings of this two-phase study will be submitted for publication in a peer-reviewed academic journal and submitted for presentation at conferences. The trial’s results will be published on a public trial registry database (ClinicalTrials.gov).Trial registration number NCT05833568.

Introduction Public health and social measures refer to non-pharmaceutical interventions implemented by individuals, communities and governments at all levels. Public health and social measures are a key strategy to offer [...], The importance of strong coordination for research on public health and social measures was highlighted at the Seventy-fourth World Health Assembly in 2021. This article describes efforts undertaken by the World Health Organization (WHO) to develop a global research agenda on the use of public health and social measures during health emergencies. This work includes a multistep process that started with a global technical consultation convened by WHO in September 2021. The consultation included experts from around the world and from a wide range of disciplines, such as public health, education, tourism, finance and social sciences, and aimed to identify research and implementation approaches based on lessons learnt during the coronavirus disease 2019 pandemic. To prepare for future epidemics and pandemics, it is essential to adopt a more robust, comparable and systematic research approach to public health and social measures. Such comprehensive approach will better inform agile, balanced and context-specific implementation decisions during future emergencies. This article describes the methods used to develop global research priorities for public health and social measures and the next steps needed. La soixante-quatorzieme Assemblee mondiale de la Sante en 2021 a souligne l'importance d'une coordination solide pour la recherche sur la sante publique et les mesures sociales. Le present article decrit les efforts entrepris par ('Organisation mondiale de la sante (OMS) pour elaborer un programme de recherche mondial sur l'utilisation des mesures de sante publique et des mesures sociales lors de situations d'urgence sanitaire. Ce travail comprend un processus en plusieurs etapes qui a commence par une consultation technique mondiale organisee par l'OMS en septembre 2021. La consultation a reuni des experts du monde entier issus d'un large eventail de disciplines telles que la sante publique, l'education, le tourisme, la finance et les sciences sociales. Elle visait a identifier des approches de recherche et de mise en reuvre fondees sur les enseignements tires de la pandemie de maladie a coronavirus de 2019. Pour se preparer aux futures epidemies et pandemies, il est essentiel d'adopter une approche de recherche plus solide, comparable et systematique en matiere de sante publique et de mesures sociales. Cette approche globale permettra de mieux eclairer les decisions de mise en reuvre agiles, equilibrees et adaptees au contexte lors des futures situations d'urgence. Le present article decrit les methodes appliquees pour definir les priorites mondiales de recherche en matiere de sante publique et de mesures sociales, ainsi que les prochaines etapes a franchir. En la 74.a Asamblea Mundial de la Salud, celebrada en 2021, se destaco la importancia de una solida coordinacion en la investigacion sobre salud publica y medidas sociales. Este articulo describe los esfuerzos que ha emprendido la Organizacion Mundial de la Salud (OMS) para desarrollar un programa mundial de investigacion sobre el uso de medidas sociales y de salud publica durante las emergencias sanitarias. Este trabajo incluye un proceso de varios pasos que comenzo con una consulta tecnica mundial que convoco la OMS en septiembre de 2021. La consulta incluyo a expertos de todo el mundo y de una gran variedad de disciplinas, como la salud publica, la educacion, el turismo, las finanzas y las ciencias sociales, y tuvo como objetivo identificar enfoques de investigacion y aplicacion basados en las lecciones aprendidas durante la pandemia de la enfermedad por coronavirus de 2019. Para prepararse ante futuras epidemias y pandemias, es esencial adoptar un enfoque de investigacion mas solido, comparable y sistematico en materia de salud publica y medidas sociales. Este enfoque integral informara mejor las decisiones de aplicacion agiles, equilibradas y adaptadas al contexto durante futuras emergencias. En este articulo se describen los metodos utilizados para elaborar las prioridades mundiales de investigacion sobre salud publica y medidas sociales, asi como los proximos pasos necesarios. [phrase omitted]

Ilhame Anwar,1 Aissatou Faye,1 Jessica Pereira Gonçalves,1 Laélia Briand Madrid,1 Gwenaëlle Maradan,2 Laurence Lalanne,3,4,* Marie Jauffret-Roustide,5– 7,* Marc Auriacombe,8– 10,* Perrine Roux1 1Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l’Information Médicale, ISSPAM, Marseille, France; 2ORS PACA, Observatoire régional de la santé Provence-Alpes-Côte d’Azur, Marseille, France; 3INSERM 1114, Department of Psychiatry and Addictology, University Hospital of Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France; 4Department of Psychiatry and Addictology, University Hospital of Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France; 5CERMES3 (Inserm U988/UMR CNRS 8211/EHESS/Paris Descartes University), Paris, France; 6British Columbia Center on Substance Use, Vancouver, Canada; 7Baldy Center on Law and Social Policy, Buffalo University, New York, NY, USA; 8Univ. Bordeaux, Bordeaux, France; 9Addiction Team (Laboratoire de psychiatrie)/SANPSY, CNRS USR 3413, Bordeaux, France; 10Pôle Addictologie, CH Charles Perrens and CHU de Bordeaux, Bordeaux, France*These authors contributed equally to this workCorrespondence: Ilhame Anwar, Sciences Economiques et Sociales de la Santé et Traitement de l’Information Médicale (SESSTIM), Faculté des sciences médicales et paramédicales, 27 Bd Jean Moulin 13385 Marseille Cedex 5, Marseille, France, Email ilhame.anwar@inserm.frPurpose: Injection drug use is strongly associated with stigmatization by loved ones, healthcare providers, and society in general. This stigmatization can have negative consequences on the health of people who inject drugs (PWID) and limit their access to care. Women who inject drugs face greater stigma than men because of gendered social norms and the intersectional effect between gender and drug use identities. For this analysis, we aimed to study discrimination - which is closely linked to stigmatization - experienced by PWID, considering the intersectionality between drug use discrimination and gender discrimination in the French context.Methods: We used data from the COSINUS cohort study, conducted between June 2016 and May 2019 in four French cities. We selected 427 of the 665 PWID who regularly injected drugs enrolled in COSINUS, at three months of follow-up, and performed multivariable logistic regression to identify factors associated with self-reported drug use discrimination.Results: Women comprised 20.6% of the study sample. Sixty-nine percent of the participants declared drug use discrimination and 15% gender discrimination. In the multivariable regression analysis, PWID who had hurried injection out of fear of being seen were almost twice as likely to have experienced drug use discrimination (OR [95% CI]: 1.77 [1.15, 2.74], p = 0.010). Likewise, women experiencing gender discrimination were almost three times as likely to have experienced drug use discrimination (OR [95% CI]: 2.84 [1.07,7.56], p=0.037).Conclusion: Women who inject drugs experienced gender and drug use intersectional discrimination. This could be a reason for the low attendance rates of women in healthcare settings. In addition, discrimination negatively impacted injection drug use practices (eg, hurried injection), particularly for people with unstable housing who injected in public spaces. We recommend introducing adapted services in healthcare facilities for women who inject drugs, and creating a favorable social and physical environment for all PWID in order to improve their health and access to care.Keywords: gender, injection drug use, intersectionality, discrimination