Microcystin-LR sensitizes the Oncorhynchus mykiss intestinal epithelium and interacts with paralytic shellfish toxins to alter oxidative balance.

In the context of harmful algal blooms, fish can be exposed to the combined effects of more than one toxin. We studied the effects of consecutive exposure to Microcystin-LR (MCLR) in vivo and paralytic shellfish toxins (PST) ex vivo/in vitro (MCLR+PST) in the rainbow trout Oncorhynchus mykiss's middle intestine. We fed juvenile fish with MCLR incorporated in the feed every 12 h and euthanized them 48 h after the first feeding. Immediately, we removed the middle intestine to make ex vivo and in vitro preparations and exposed them to PST for one hour. We analyzed glutathione (GSH) and glutathione disulfide (GSSG) contents, glutathione S-transferase (GST), glutathione reductase (GR), catalase (CAT), and protein phosphatase 1 (PP1) activities in ex vivo intestinal strips; apical and basolateral ATP-biding cassette subfamily C (Abcc)-mediated transport in ex vivo everted and non- everted sacs; and reactive oxygen species (ROS) production in isolated enterocytes in vitro. MCLR+PST treatment decreased the GSH content, GSH/GSSG ratio, GST activity, and increased ROS production. GR activity remained unchanged, while CAT activity only increased in response to PST. MCLR inhibited PP1 activity and activated Abcc-mediated transport only at the basolateral side of the intestine. Our results show a combined effect of MCLR+PST on the oxidative balance in the O. mykiss middle intestine, which is not affected by the two toxins groups when applied individually. Basolateral Abcc transporters activation by MCLR treatment could lead to an increase in the absorption of toxicants (including MCLR) into the organism. Therefore, MCLR makes the O. mykiss middle intestine more sensitive to possibly co-occurring cyanotoxins like PST.

Melatonin and Its Role in the Epithelial-to-Mesenchymal Transition (EMT) in Cancer.

The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, ultimately leading cells to stemness, increased invasiveness, chemo- and radioresistance and the formation of cancer metastasis. Amongst the different existing types of the EMT, type 3 is directly involved in carcinogenesis. A type 3 EMT occurs in neoplastic cells that have previously acquired genetic and epigenetic alterations, specifically affecting genes involved in promoting clonal outgrowth and invasion. Markers such as E-cadherin; N-cadherin; vimentin; and transcription factors (TFs) like Twist, Snail and ZEB are considered key molecules in the transition. The EMT process is also regulated by microRNA expression. Many miRNAs have been reported to repress EMT-TFs. Thus, Snail 1 is repressed by miR-29, miR-30a and miR-34a; miR-200b downregulates Slug; and ZEB1 and ZEB2 are repressed by miR-200 and miR-205, respectively. Occasionally, some microRNA target genes act downstream of the EMT master TFs; thus, Twist1 upregulates the levels of miR-10b. Melatonin is an endogenously produced hormone released mainly by the pineal gland. It is widely accepted that melatonin exerts oncostatic actions in a large variety of tumors, inhibiting the initiation, progression and invasion phases of tumorigenesis. The molecular mechanisms underlying these inhibitory actions are complex and involve a great number of processes. In this review, we will focus our attention on the ability of melatonin to regulate some key EMT-related markers, transcription factors and micro-RNAs, summarizing the multiple ways by which this hormone can regulate the EMT. Since melatonin has no known toxic side effects and is also known to help overcome drug resistance, it is a good candidate to be considered as an adjuvant drug to conventional cancer therapies.

The Effects of Nature Exposure Therapies on Stress, Depression, and Anxiety Levels: A Systematic Review.

BACKGROUND: Mental well-being plays a pivotal role within the broader spectrum of health and illness, encompassing factors such as stress, depression, and anxiety. Nature-based therapeutic interventions have emerged as a promising approach to addressing these mental health challenges. This study seeks to assess the impact of these interventions on stress, depression, and anxiety levels. METHODS: We conducted an extensive search for randomized clinical trials that examined stress, anxiety, and depression levels. The selected studies underwent a rigorous risk-of-bias assessment following the guidelines outlined in the Cochrane Handbook for Systematic Reviews. RESULTS: Our review encompassed findings from eight publications. Among them, two studies measuring cortisol levels revealed significant differences between the pre-test and post-test measurements within the intervention groups. In two studies that employed the Stress Response Inventory, a significant decrease in stress levels was observed within the intervention groups in contrast to the control groups. However, no significant differences were noted in studies that utilized the Restorative Outcome Scale. In the assessment of anxiety and depression levels, three studies employed the Positive and Negative Affect Schedule, while four studies utilized The Profile of Mood States scale; none of these studies demonstrated significant differences. CONCLUSIONS: The current body of evidence offers limited support for advocating nature-based therapeutic interventions as a primary approach to reducing stress, depression, and anxiety.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

Health care-related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease.

BACKGROUND: Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD). METHODS: Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality. RESULTS: Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]. CONCLUSIONS: Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted.

A Novel Heterozygous De Novo MORC2 Missense Variant Causes an Early Onset and Severe Neurodevelopmental Disorder.

Microrchidia CW-type zinc finger protein 2 (MORC2) is an ATPase-containing nuclear protein which regulates transcription through chromatin remodelling and epigenetic silencing. MORC2 may have a role in the development of neurones, and dominant variants in this gene have recently been linked with disorders including Charcot-Marie-Tooth type 2Z disease, spinal muscular atrophy and, more recently, a neurodevelopmental syndrome consisting of developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN), presenting with hypotonia, microcephaly, brain atrophy, intellectual disability, hearing loss, faltering growth, and craniofacial dysmorphism. Notably, variants in MORC2 have shown clinical features overlapping with those of Cockayne and Leigh syndromes. Here, we report a case of MORC2-related DIGFAN syndrome in a female infant caused by a novel heterozygous de novo variant. The condition was early onset and severe, further expanding the range of genotypes associated with this disorder. Clinical features included unilateral hearing loss, developmental delay and regression within the first year of life, microcephaly, severe feeding difficulties, and faltering growth, resulting in death at 13 months of age.

Prefrontal Regulation of Safety Learning during Ethologically Relevant Thermal Threat.

Learning and adaptation during sources of threat and safety are critical mechanisms for survival. The prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) have been broadly implicated in the processing of threat and safety. However, how these regions regulate threat and safety during naturalistic conditions involving thermal challenge still remains elusive. To examine this issue, we developed a novel paradigm in which adult mice learned that a particular zone that was identified with visuospatial cues was associated with either a noxious cold temperature ("threat zone") or a pleasant warm temperature ("safety zone"). This led to the rapid development of avoidance behavior when the zone was paired with cold threat or approach behavior when the zone was paired with warm safety. During a long-term test without further thermal reinforcement, mice continued to exhibit robust avoidance or approach to the zone of interest, indicating that enduring spatial-based memories were formed to represent the thermal threat and thermal safety zones. Optogenetic experiments revealed that neural activity in PL and IL was not essential for establishing the memory for the threat zone. However, PL and IL activity bidirectionally regulated memory formation for the safety zone. While IL activity promoted safety memory during normal conditions, PL activity suppressed safety memory especially after a stress pretreatment. Therefore, a working model is proposed in which balanced activity between PL and IL is favorable for safety memory formation, whereas unbalanced activity between these brain regions is detrimental for safety memory after stress.

Psychometric properties of the parenting belief scale in a multi-country sample of parents from high-income countries.

BACKGROUND: Parents' beliefs about how private/public their parenting role is and their acceptability of the use of corporal punishment as a disciplinary measure have been associated with how parents raise their children and their willingness to seek support. However, there are no reliable and valid instruments measuring these beliefs. OBJECTIVE: This study evaluated the psychometric properties of the Parenting Belief Scale, a self-reported brief measure targeting parents' perception of parenting as a private concern and their attitudes towards the use of corporal punishment. PARTICIPANTS AND SETTING: Participants were 6949 parents from several high-income countries (i.e., Australia, Belgium, Canada, Germany, Hong Kong, Australia, and the UK) who completed the International Parenting Survey, an online cross-sectional survey focused on parents' self-report of their parenting, children, and family. METHODS: This study evaluated the internal consistency, factor structure (i.e., exploratory and confirmatory factor analyses), and convergent and discriminant validity of the Parenting Belief Scale. RESULTS: Findings indicated that this scale was a relatively reliable measure to evaluate parents' perceived privacy in their role and acceptability of corporal punishment. A two-factor structure was confirmed by both exploratory and confirmatory factor analyses. Correlations with scales of parenting practices supported the convergent and discriminant validity of the Parenting Belief Scale. CONCLUSIONS: This study supported the use of the Parenting Belief Scale across high-income countries to evaluate parenting beliefs in influencing parenting practices and parents' help-seeking behaviours.

Implicancias teórico-clínicas de las prácticas psicoterapéuticas feministas o con perspectiva de género en Chile / Theoretical-clinical implications of feminist or gender-sensitive psychotherapeutic practices in Chile

Este artículo tiene como objetivo comprender, mediante el análisis de 16 entrevistas semies-tructuradas, las implicancias teórico-clínicas del posicionamiento con perspectiva de género o feminista en la práctica psicoterapéutica contemporánea en Chile, desde la perspectiva de consultantes y psicoterapeutas. Como resultados, se observa que el valor de esta psicoterapia radica en entregar una lectura sociocultural del malestar generizado. Sin embargo, quienes consultan reproducen estereotipos de género al elegir este enfoque a propósito del género fe-menino de la psicoterapeuta, pues consideran que habría un mayor entendimiento “por ser mu-jer”, lo cual les garantizaría un espacio seguro, libre de juicios y revictimización. Se destaca que las intervenciones de este enfoque tienen un componente político que favorece el trabajo de la desculpabilización de las consultantes. Esto resulta favorable en ciertos casos, pero po-dría obstaculizar el abordaje y reconocimiento de aquellas características singulares del sujeto que inciden en el sufrimiento y trascienden la certeza ideológica. (AU)

This article aims to understand, through 16 semi-structured interviews analysis, the theoreti-cal-clinical implications of the gender or feminist perspective in contemporary psychothera-peutic practice in Chile, from the perspective of consultants and psychotherapists. As a result, it is observed that the value of this psychotherapy lies in providing a sociocultural reading of gendered discomfort. However, those who consult reproduce gender stereotypes by choosing this approach due to the female gender of the psychotherapist, as they consider that there would be a better understanding “because of her being a woman”, which would guarantee them a safe space, free of judgments and revictimization. It should be noted that the inter-ventions of this approach have a political component that favors the work of disempowerment of the consultants. This is favorable in certain cases but could hinder the approach and recog-nition of those unique characteristics that affect particularsuffering in every case and trans-cend ideological certainty. (AU)

Environmental risk management: A participatory diagnosis from a rural school in Colombia.

The rural population is potentially exposed to several environmental risks. Environmental risk management is a recurring challenge in rural educational communities that are far from large urban areas. Assessing and identifying the knowledge on prevention and response to environmental risks and natural disasters is fundamental for planning and designing educational programs for communities to face disasters. This article presented the practical application of a participatory methodology to obtain information about the knowledge and experience in the prevention and attention of environmental threats and natural disasters in the rural school Las Huacas, village of Quintana, municipality of Popayán, in the region of Cauca, Colombia. The diagnosis methodology consisted of three phases: preparatory, fieldwork and analytical. The participatory diagnosis allowed the construction of instruments and tools for social interaction, the conduction of dynamic workshops and the systematisation of the collected information. The results evidenced the lack of knowledge on environmental disasters and how parents and children must face them. The absence of communication facilities implied a high degree of vulnerability, which was compensated with the awareness, commitment and participation in the processes led by the educational community. The next challenge is the participatory construction of a scholar environmental risk-management plan supported on appropriated information and communication technologies. Contribution: This article presents the practical application of a participatory methodology to obtain information about the rural context and the knowledge and experience in the prevention and attention of environmental threats and natural disasters in a rural school in Cauca, Colombia.

Real-world effectiveness and persistence of secukinumab in the treatment of patients with psoriatic arthritis.

Introduction: Psoriatic arthritis (PsA) is a complex and heterogeneous inflammatory disease. Secukinumab, a biologic disease-modifying antirheumatic drug (bDMARD), has extensive clinical evidence of efficacy and safety in the treatment of PsA but data in clinical practice are still limited. This study aims to provide real-world evidence on secukinumab use, effectiveness, and persistence in PsA. Methods: A retrospective, multicenter study was conducted on patients diagnosed with PsA and treated with secukinumab up to June 2021 at 12 centers in the Valencian Community (Spain). Data on DAS28-CRP, DAPSA, Tender and Swollen Joint Counts (TJC, SJC), enthesitis, dactylitis, skin and nail involvement, pain, patient and physician global assessment (ptGA, phGA) using 100-mm visual analog scale (VAS), and persistence for up to 24 months were collected. Results: A total of 178 patients were included (49% men; mean [standard deviation, SD] age: 51.4 [10.5] years; 39% obese). Secukinumab was used as a first-, second-, or ≥ third-line bDMARD in 37, 21, and 42% of patients, respectively. The percentage of patients achieving at least low disease activity (DAS28-CRP ≤ 3.2) increased from 25% at baseline to 66% at month 6 (M6) and was maintained (75%) up to M24. Mean (SD) DAS28-CRP baseline values (3.9 [1.2]) decreased to 2.9 (1.1) (p < 0.001) at M6 and remained low through M24 (2.6 [1.1]) (p < 0.001). Secukinumab also improved peripheral arthritis increasing the percentage of patients with TJC = 0 (20% baseline; 57% M24) and SJC = 0 (37% baseline; 80% M24). Treatment reduced the percentage of patients with enthesitis (25% baseline; 6% M24), dactylitis (20% baseline; 4% M24), and skin (70% baseline; 17% M24), and nail (32% baseline; 2% M24) involvement. Additionally, we observed improvements in the mean pain VAS (-26.4 mm M24), ptGA (-26.2 mm M24), and phGA (-24.8 mm M24). Secukinumab showed an overall 24-month persistence rate of 67% (95% confidence interval [CI]: 60-74%). Patients receiving first-line secukinumab showed the highest 24-month persistence rate (83, 95% CI: 73-92; p = 0.024). Conclusion: Secukinumab showed long-term effectiveness across the six key PsA domains thus reducing disease activity and pain, which are major treatment goals. This was accompanied by high persistence rates, especially in bDMARD naive patients.

Validation of prognostic and predictive value of total tumoral load after primary systemic therapy in breast cancer using OSNA assay.

PURPOSE: This study aimed to validate the classification of breast cancer (BC) patients in progression risk groups based on total tumor load (TTL) value to predict lymph node (LN) affectation after neo-adjuvant systemic therapy (NAST) obtained in the NEOVATTL study. METHODS/PATIENTS: This was an observational, retrospective, international, multicenter study including patients with infiltrating BC who received NAST followed by sentinel lymph node biopsy (SLNB) analyzed with one-step nucleic acid amplification (OSNA) from nine Spanish and two Italian hospitals. Patients were classified into three groups according to the progression risk, measured as disease-free survival (DFS), based on TTL values (> 250, 250-25,000, and > 25,000 copies/µL). The previous (NEOVATTL study) Cox regression model for prognosis was validated using prognostic index (PI) and Log ratio test (LRT) analyses; the value of TTL for axillary non-SLN affectation was assessed using receiver operating characteristic (ROC) curves. RESULTS: We included 263 patients with a mean age of 51.4 (± SD 10.5) years. Patients with TTL > 25,000 copies/µL had a shorter DFS (HR 3.561 [95% CI 1.693-7.489], p = 0.0008 vs. TTL ≤ 25,000). PI and LRT analyses showed no differences between the two cohorts (p = 0.2553 and p = 0.226, respectively). ROC analysis showed concordance between TTL and non-SLN involvement (area under the curve 0.828), with 95.7% sensitivity and 92.9% specificity at a TTL cut-off of > 15,000 copies/µL. CONCLUSIONS: In BC patients who had received NAST and underwent SLNB analysis using OSNA, a TTL value of > 25,000 copies/µL was associated with a higher progression risk and > 15,000 copies/µL was predictive of non-SLN involvement.

Post-parotidectomy facial nerve function: comparison between original and modified Sunnybrook Facial Grading Systems.

BACKGROUND: Facial nerve dysfunction is the principal postoperative complication related to parotidectomy. OBJECTIVE: To test the hypothesis that the modified Sunnybrook Facial Grading System (mS-FGS) is superior to the original S-FGS in the assessment of facial nerve function following parotidectomy. METHODS: Prospective, longitudinal study evaluating patients with primary or metastatic parotid neoplasms undergoing parotidectomy with facial nerve-sparing between 2016 and 2020. The subjects were assessed twice, on the first postoperative day and at the first outpatient evaluation, 20-30 days post-surgery. Facial assessments were performed using the original and modified (plus showing the lower teeth) versions of the Sunnybrook System and documented by pictures and video recordings. Intra- and inter-rater agreements regarding the assessment of the new expression were analyzed. RESULTS: 101 patients were enrolled. In both steps, the results from the mS-FGS were significantly lower (p < 0.001). Subjects with a history of previous parotidectomy and those who underwent neck dissection had more severe facial nerve impairment. The mandibular marginal branch was the most frequently injured, affecting 68.3% of the patients on the first postoperative day and 52.5% on the first outpatient evaluation. Twenty patients (19.8%) presented an exclusive marginal mandibular branch lesion. The inter-rater agreement of the new expression assessment ranged from substantial to almost perfect. The intra-rater agreement was almost perfect (wk = 0.951). CONCLUSION: The adoption of the Modified Sunnybrook System, which includes evaluation of the mandibular marginal branch, increases the accuracy of post-parotidectomy facial nerve dysfunction appraisal.

ANTECEDENTES: A disfunção do nervo facial é a principal complicação pós-operatória relacionada à parotidectomia. OBJETIVO: Testar a hipótese de que o sistema Sunnybrook de graduação facial modificado (mS-FGS) é superior ao S-FGS original na avaliação da função do nervo facial após parotidectomia. MéTODOS:: Estudo longitudinal prospectivo avaliando o pós-operatório de pacientes com neoplasias parotídeas primárias ou metastáticas, submetidos à parotidectomia com preservação do nervo facial, entre 2016 e 2020. Os indivíduos foram avaliados duas vezes, no primeiro dia de pós-operatório e na primeira avaliação ambulatorial, 20-30 dias após a cirurgia. As avaliações faciais foram realizadas usando as versões original e modificada (que incluem mostrar os dentes inferiores) do sistema Sunnybrook e documentadas por fotos e vídeos. Foram adicionalmente analisadas as concordâncias intra e interexaminadoras da avaliação da nova expressão. RESULTADOS: Cento e um pacientes foram incluídos. Em ambas as etapas, os resultados do mS-FGS foram significativamente menores (p < 0,001). Indivíduos com história de parotidectomia prévia e aqueles submetidos ao esvaziamento cervical apresentaram comprometimento mais grave do nervo facial. O ramo marginal mandibular foi o mais afetado, acometendo 68,3% dos pacientes no primeiro dia de pós-operatório e 52,5% na primeira avaliação ambulatorial. Vinte pacientes (19,8%) apresentaram lesão exclusiva do ramo marginal mandibular. A concordância interexaminadores da avaliação da nova expressão variou de substancial a quase perfeita. A concordância intraexaminador foi quase perfeita (wk = 0,951). CONCLUSãO:: A adoção do sistema Sunnybrook modificado, que inclui a análise do ramo marginal mandibular, aumenta a precisão da avaliação da disfunção do nervo facial pós-parotidectomia.

Child maltreatment and resilience in adulthood: a protocol for a systematic review and meta-analysis.

Background: Although child maltreatment (CM) has been linked to health problems and poor psychosocial functioning, not all individuals exposed to CM develop or experience negative consequences later in life. This suggests that some individuals show resilience after being exposed to CM. However, conclusions have been limited by inconsistent findings across different CM subtypes and resilience domains.Objective: To develop a protocol for conducting a systematic review and meta-analysis to quantify associations between CM (overall and its subtypes) and resilience (global and its multiple domains) in adulthood, and to examine moderators and mediators of these associations.Method: PubMed, PsycINFO, Embase, Scopus, and Web of Science will be searched to identify relevant studies on the association between CM (exposure) and resilience (outcome) in adults (≥ 18 years). Data will be screened and extracted by at least two independent reviewers. The methodological quality of the included studies will be independently assessed with a modified version of the Newcastle-Ottawa Scale (NOS). If deemed viable, a meta-analysis will be conducted using a random effects model. Heterogeneity of evidence will be estimated with the I2 statistic, and publication bias will be assessed. The effects of potential moderators (e.g. timing and severity of CM, age, sex, family cohesion, socio-economic status, country/region) will be analysed using meta-regression and subgroup analyses, and meta-analytical structural equation modelling will be employed to synthesise indirect mediation effects. Candidate moderators and mediators (e.g. genetic factors, brain functioning, attachment style, personality traits, physical activity, and social support) will be also examined qualitatively.Conclusions: This protocol will facilitate a systematic review and meta-analysis that has the potential to enhance our knowledge about the association between CM exposure in early life and resilience in adulthood. Understanding associations and underlying mechanisms between CM and resilience is potentially important in informing prevention and interventions to sustain health and improve outcomes among adults with a history of CM.PROSPERO registration: CRD42023394120.

In this study protocol, we propose to quantitatively summarise the existing literature on the relationship between child maltreatment and resilience with regard to mental health consequences and psychosocial functioning later in life.This preregistered systematic review and meta-analysis will establish the procedures to investigate associations between an overall classification of child maltreatment and its different associated subtypes, and a global/trait classification of resilience and its different domains in adults.This protocol will further determine the analytical approach to explore and summarise effect moderators and mediators of the association between child maltreatment and resilience in adulthood.The resulting synthesis, that will be based on this protocol, could enhance our understanding of the strength of the association between child maltreatment and resilience and inform prevention strategies and clinical interventions to improve health and psychosocial functioning in adult survivors.

Post-parotidectomy facial nerve function: comparison between original and modified Sunnybrook Facial Grading Systems / Função do nervo facial pós-parotidectomia: comparação entre os Sistemas Sunnybrook de Graduação Facial original e modificado

Abstract Background: Facial nerve dysfunction is the principal postoperative complication related to parotidectomy. Objective: To test the hypothesis that the modified Sunnybrook Facial Grading System (mS-FGS) is superior to the original S-FGS in the assessment of facial nerve function following parotidectomy. Methods: Prospective, longitudinal study evaluating patients with primary or metastatic parotid neoplasms undergoing parotidectomy with facial nerve-sparing between 2016 and 2020. The subjects were assessed twice, on the first postoperative day and at the first outpatient evaluation, 20-30 days post-surgery. Facial assessments were performed using the original and modified (plus showing the lower teeth) versions of the Sunnybrook System and documented by pictures and video recordings. Intra- and inter-rater agreements regarding the assessment of the new expression were analyzed. Results: 101 patients were enrolled. In both steps, the results from the mS-FGS were significantly lower (p < 0.001). Subjects with a history of previous parotidectomy and those who underwent neck dissection had more severe facial nerve impairment. The mandibular marginal branch was the most frequently injured, affecting 68.3% of the patients on the first postoperative day and 52.5% on the first outpatient evaluation. Twenty patients (19.8%) presented an exclusive marginal mandibular branch lesion. The inter-rater agreement of the new expression assessment ranged from substantial to almost perfect. The intra-rater agreement was almost perfect (wk = 0.951). Conclusion: The adoption of the Modified Sunnybrook System, which includes evaluation of the mandibular marginal branch, increases the accuracy of post-parotidectomy facial nerve dysfunction appraisal.

Resumo Antecedentes: A disfunção do nervo facial é a principal complicação pós-operatória relacionada à parotidectomia. Objetivo: Testar a hipótese de que o sistema Sunnybrook de graduação facial modificado (mS-FGS) é superior ao S-FGS original na avaliação da função do nervo facial após parotidectomia. Métodos: Estudo longitudinal prospectivo avaliando o pós-operatório de pacientes com neoplasias parotídeas primárias ou metastáticas, submetidos à parotidectomia com preservação do nervo facial, entre 2016 e 2020. Os indivíduos foram avaliados duas vezes, no primeiro dia de pós-operatório e na primeira avaliação ambulatorial, 20-30 dias após a cirurgia. As avaliações faciais foram realizadas usando as versões original e modificada (que incluem mostrar os dentes inferiores) do sistema Sunnybrook e documentadas por fotos e vídeos. Foram adicionalmente analisadas as concordâncias intra e interexaminadoras da avaliação da nova expressão. Resultados: Cento e um pacientes foram incluídos. Em ambas as etapas, os resultados do mS-FGS foram significativamente menores (p < 0,001). Indivíduos com história de parotidectomia prévia e aqueles submetidos ao esvaziamento cervical apresentaram comprometimento mais grave do nervo facial. O ramo marginal mandibular foi o mais afetado, acometendo 68,3% dos pacientes no primeiro dia de pós-operatório e 52,5% na primeira avaliação ambulatorial. Vinte pacientes (19,8%) apresentaram lesão exclusiva do ramo marginal mandibular. A concordância interexaminadores da avaliação da nova expressão variou de substancial a quase perfeita. A concordância intraexaminador foi quase perfeita (wk = 0,951). Conclusão: A adoção do sistema Sunnybrook modificado, que inclui a análise do ramo marginal mandibular, aumenta a precisão da avaliação da disfunção do nervo facial pós-parotidectomia.

Surviving Sepsis After Burn Campaign.

INTRODUCTION: The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes. METHODS: The International Society for Burn Injuries (ISBI) reached out to regional or national burn organizations to recommend members to participate in the program. Two members of the ISBI developed specific "patient/population, intervention, comparison and outcome" (PICO) questions that paralleled the 2021 Surviving Sepsis Campaign [1]. SSABC participants were asked to search the current literature and rate its quality for each topic. At the Congress of the ISBI, in Guadalajara, Mexico, August 28, 2022, a majority of the participants met to create "statements" based on the literature. The "summary statements" were then sent to all members for comment with the hope of developing an 80% consensus. After four reviews, a consensus statement for each topic was created or "no consensus" was reported. RESULTS: The committee developed sixty statements within fourteen topics that provide guidance for the early treatment of sepsis in burn patients. These statements should be used to improve the care of sepsis in burn patients. The statements should not be considered as "static" comments but should rather be used as guidelines for future testing of the best treatments for sepsis in burn patients. They should be updated on a regular basis. CONCLUSION: Members of the burn community from the around the world have developed the Surviving Sepsis After Burn Campaign guidelines with the goal of improving the outcome of sepsis in burn patients.

Risk indicators associated with peri-implant diseases: a retrospective cross-sectional study of Colombian patients with 1 to 18 years of follow-up.

PURPOSE: Peri-implant mucositis (PIM) and peri-implantitis (PI) are multicausal conditions with several risk factors contributing to their pathogenesis. In this study, we retrospectively investigated risk variables potentially associated with these peri-implant diseases (PIDs) over a follow-up period of 1 to 18 years. METHODS: The study sample consisted of 379 implants placed in 155 patients. Single-visit clinical and radiographic evaluations were employed to determine the presence or absence of PIDs. Parameters related to the patient, site, surgery, implant, and prosthetic restoration were documented. The relationships between risk variables and the occurrence of PIDs were individually examined and adjusted for confounders using multivariate binary logistic regression models. RESULTS: The prevalence rates of PIM and PI were 28.4% and 36.8% at the patient level and 33.5% and 24.5% at the implant level, respectively. Poor oral hygiene, active gingivitis/periodontitis, preoperative alveolar ridge deficiency, early or delayed implant placement, implant length of 11.0 mm or less, and poor restoration quality were strong and independent risk indicators for both PIDs. Furthermore, a follow-up period of more than 5 years and a loading time of more than 4 years were important indicators for PI. Simultaneously, age and smoking status acted as modifiers of the effect of mesiodistal (MD) and buccolingual (BL) widths of restoration on PI. CONCLUSIONS: In this study population, oral hygiene, periodontal status, preoperative alveolar ridge status, implant placement protocol, implant length, and the quality of coronal restoration appear to be robust risk indicators for both PIM and PI. Additionally, the length of follow-up and functional loading time are robust indicators of PI. Furthermore, the potential modifying relationships of age and smoking status with the MD and BL widths of restoration may be crucial for the development of PI.

Identification of Glaucoma in Diabetics Using the Laguna-ONhE Colourimetric Method and OCT Spectralis.

BACKGROUND: Previous retrospective results are evaluated prospectively and blinded. METHODS: A total of 221 eyes previously classified as normal (G1), 279 as moderate risk of glaucoma (G2) and 217 as high risk (G3) according to the Globin Discriminant Function (GDF) Laguna-ONhE index were examined with OCT Spectralis- Results: In G1, the Bruch's Membrane Opening Minimum Rim Width (BMO-MRW) was 332 ± 55 microns; in G2, it was 252 ± 47 (p < 0.0001); and in G3, 231 ± 44 (p < 0.0001). In G1, the 1% and 5% percentiles were 233 and 248, respectively; in G2, they were lower in 28.80% and 42.29% of cases, respectively; and in G3, in 50.23% and 63.59% of cases, respectively. Most of the cases were normal-tension glaucomas. Laguna-ONhE indices showed a curvilinear correlation with BMO-MRW results. The Retinal Nerve Fibre Layer (RNFL) showed a poor relationship with BMO. Assuming G1 to be truly normal, BMO-MRW would have a Receiver operating characteristic (ROC) curve area of 0.901 for G2 and G3 and 0.651 for RNFL. A significant reduction in pixels corresponding to vessels was found in G2 and G3 vs. G1 (p < 0.0001). CONCLUSIONS: In some cases, these defects appear to be mainly glaucomatous, and in others, they are associated with diabetic microangiopathy. In normal tension glaucoma, RNFL defects may be less severe than those inside the nerve.

Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation.

Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism. PWS is not a known cancer predisposition syndrome, but previous investigations regarding the prevalence of cancer in these patients suggest an increased risk of developing specific cancer types such as myeloid leukemia and testicular cancer. We present the results from a Swedish national population-based cohort study of 360 individuals with PWS and 18,000 matched comparisons. The overall frequency of cancer was not increased in our PWS cohort, but we found a high frequency of pediatric cancers. We also performed whole-genome sequencing of blood- and tumor-derived DNAs from a unilateral dysgerminoma in a 13-year-old girl with PWS who also developed bilateral ovarian sex cord tumors with annular tubules. In germline analysis, there were no additional findings apart from the 15q11.2-q13 deletion of the paternal allele, while a pathogenic activating KIT mutation was identified in the tumor. Additionally, methylation-specific multiplex ligation-dependent probe amplification revealed reduced methylation at the PWS locus in the dysgerminoma but not in the blood. In conclusion, our register-based study suggests an increased risk of cancer at a young age, especially testicular and ovarian tumors. We found no evidence of a general increase in cancer risk in patients with PWS. However, given our limited observational time, further studies with longer follow-up times are needed to clarify the lifetime cancer risk in PWS. We have also described the second case of locus-specific loss-of-imprinting in a germ cell tumor in PWS, suggesting a possible mechanism of carcinogenesis.

Complete genome sequence of Pediococcus acidilactici A40, a bacterium with biocontrol and plant growth-promoting properties.

We report the complete genome assembly of Pediococcus acidilactici A40, a bacterium with biocontrol and plant growth-promoting properties, obtained from Colombia.