Challenges in Treating Pediatric Cancer Patients during the COVID-19 Pandemic: Balancing Risks and Care.

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and PaxlovidTM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2.

Potential Anti-Infectious Activity of Essential Oil Chemotypes of Lippia origanoides Kunth on Antibiotic-Resistant Staphylococcus aureus Strains.

Staphylococcus aureus infections are prevalent in healthcare and community environments. Methicillin-resistant S. aureus is catalogued as a superbug of high priority among the pathogens. This Gram-positive coccus can form biofilms and produce toxins, leading to persistent infection and antibiotic resistance. Limited effective antibiotics have encouraged the development of innovative strategies, with a particular emphasis on resistance mechanisms and/or virulence factors. Medicinal aromatic plants have emerged as promising alternative sources. This study investigated the antimicrobial, antibiofilm, and antihemolysis properties of three different chemotypes of Lippia origanoides essential oil (EO) against susceptible and drug-resistant S. aureus strains. The chemical composition of the EO was analyzed using GC-MS, revealing high monoterpene concentrations, with carvacrol and thymol as the major components in two of the chemotypes. The third chemotype consisted mainly of the sesquiterpene ß-caryophyllene. The MIC values for the two monoterpene chemotypes ranged from 62.5 to 500 µg/mL for all strains, whereas the sesquiterpene chemotype showed activity against seven strains at concentrations of 125-500 µg/mL, which is the first report of its anti-S. aureus activity. The phenolic chemotypes inhibited biofilm formation in seven S. aureus strains, whereas the sesquiterpene chemotype only inhibited biofilm formation in four strains. In addition, phenolic chemotypes displayed antihemolysis activity, with IC50 values ranging from 58.9 ± 3.8 to 128.3 ± 9.2 µg/mL. Our study highlights the importance of L. origanoides EO from the Yucatan Peninsula, which has the potential for the development of anti-S. aureus agents.

Emotional tone in clinical high risk for psychosis: novel insights from a natural language analysis approach.

Background: Individuals at clinical high risk (CHR) for psychosis experience subtle emotional disturbances that are traditionally difficult to assess, but natural language processing (NLP) methods may provide novel insight into these symptoms. We predicted that CHR individuals would express more negative emotionality and less emotional language when compared to controls. We also examined associations with symptomatology. Methods: Participants included 49 CHR individuals and 42 healthy controls who completed a semi-structured narrative interview. Interview transcripts were analyzed using Linguistic Inquiry and Word Count (LIWC) to assess the emotional tone of the language (tone -the ratio of negative to positive language) and count positive/negative words used. Participants also completed clinical symptom assessments to determine CHR status and characterize symptoms (i.e., positive and negative symptom domains). Results: The CHR group had more negative emotional tone compared to healthy controls (t=2.676, p=.009), which related to more severe positive symptoms (r2=.323, p=.013). The percentages of positive and negative words did not differ between groups (p's>.05). Conclusions: Language analyses provided accessible, ecologically valid insight into affective dysfunction and psychosis risk symptoms. Natural language processing analyses unmasked differences in language for CHR that captured language tendencies that were more nuanced than the words that are chosen.

The prevalence and mortality risks of PRISm and COPD in the United States from NHANES 2007-2012.

BACKGROUND: We estimated the prevalence and mortality risks of preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) in the US adult population. METHODS: We linked three waves of pre-bronchodilator spirometry data from the US National Health and Nutritional Examination Survey (2007-2012) with the National Death Index. The analytic sample included adults ages 20 to 79 without missing data on age, sex, height, BMI, race/ethnicity, and smoking status. We defined COPD (GOLD 1, 2, and 3-4) and PRISm using FEV1/FVC cut points by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the prevalence of GOLD stages and PRISm by covariates across the three waves. We estimated adjusted all-cause and cause-specific mortality risks by COPD stage and PRISm using all three waves combined. RESULTS: Prevalence of COPD and PRISm from 2007-2012 ranged from 13.1%-14.3% and 9.6%-10.2%, respectively. We found significant differences in prevalence by sex, age, smoking status, and race/ethnicity. Males had higher rates of COPD regardless of stage, while females had higher rates of PRISm. COPD prevalence increased with age, but not PRISm, which was highest among middle-aged individuals. Compared to current and never smokers, former smokers showed lower rates of PRISm but higher rates of GOLD 1. COPD prevalence was highest among non-Hispanic White individuals, and PRISm was notably higher among non-Hispanic Black individuals (range 31.4%-37.4%). We found associations between PRISm and all-cause mortality (hazard ratio [HR]: 2.3 95% CI: 1.9-2.9) and various cause-specific deaths (HR ranges: 2.0-5.3). We also found associations between GOLD 2 (HR: 2.1, 95% CI: 1.7-2.6) or higher (HR: 4.2, 95% CI: 2.7-6.5) and all-cause mortality. Cause-specific mortality risk varied within COPD stages but typically increased with higher GOLD stage. CONCLUSIONS: The prevalence of COPD and PRISm remained stable from 2007-2012. Greater attention should be paid to the potential impacts of PRISm due to its higher prevalence in minority groups and its associations with mortality across various causes including cancer.

The potential impact of removing a ban on electronic nicotine delivery systems using the Mexico smoking and vaping model (SAVM).

Objective: To develop the Mexico Smoking and Vaping Model (Mexico SAVM) to estimate cigarette and electronic nicotine delivery systems (ENDS) prevalence and the public health impact of legalizing ENDS use. Methods: SAVM, a cohort-based discrete-time simulation model, compares two scenarios. The ENDS-Restricted Scenario estimates smoking prevalence and associated mortality outcomes under the current policy of an ENDS ban, using Mexico-specific population projections, death rates, life expectancy, and smoking and e-cigarette prevalence. The ENDS-Unrestricted Scenario projects smoking and vaping prevalence under a hypothetical scenario where ENDS use is allowed. The impact of legalizing ENDS use is estimated as the difference in smoking- and vaping-attributable deaths (SVADs) and life-years lost (LYLs) between the ENDS-Restricted and Unrestricted scenarios. Results: Compared to a national ENDS ban, The Mexico SAVM projects that legalizing ENDS use could decrease smoking prevalence by 40.1% in males and 30.9% in females by 2049 compared to continuing the national ENDS ban. This reduction in prevalence would save 2.9 (2.5 males and 0.4 females) million life-years and avert almost 106 (91.0 males and 15.5 females) thousand deaths between 2025 and 2049. Public health gains decline by 43% to 59,748 SVADs averted when the switching rate is reduced by half and by 24.3% (92,806 SVADs averted) with a 25% ENDS risk level from that of cigarettes but increased by 24.3% (121,375 SVADs averted) with the 5% ENDS risk. Conclusions: Mexico SAVM suggests that greater access to ENDS and a more permissive ENDS regulation, simultaneous with strong cigarette policies, would reduce smoking prevalence and decrease smoking-related mortality. The unanticipated effects of an ENDS ban merit closer scrutiny, with further consideration of how specific ENDS restrictions may maximize public health benefits.

Perceptions of stigma in youth at clinical high risk for psychosis and depressive symptomatology.

It is unclear what types of stigma youth at clinical high risk for psychosis (CHR) experience, and the relationship between them and symptomatology. 94 CHR youth, and a control group of 45 youth with no psychosis spectrum symptoms (NP) were rated for perceived devaluation (i.e. negative views from others) and internalized mental health stigma (i.e. the extent to which they would agree with said views) as well as positive and mood symptomatology. CHR youth reported stigma more frequently than the NP group (χ2(1) = 53.55, p < .001) and at higher levels (perceived devaluation: t (137) = 8.54, p < .001; internalized stigma: t (137) = 7.48, p < .001). Surprisingly, in the CHR group, positive symptoms held no significant relationship to stigma measures. However, ratings of perceived devaluation stigma were associated with depressive symptomatology (ß = 0.27, t = 2.68, p = .0087) and depression scores were conversely associated with perceived devaluation stigma (ß = 0.30, t = 2.05, p = .043). These findings speak to the relationship between depressive symptomatology and perceived devaluation stigma in CHR youth. Perceived devaluation stigma showed greater clinical significance and could have different mechanisms than internalized stigma in CHR youth. It is also noteworthy that while positive symptoms play a central role in defining the CHR syndrome, they seem less relevant to the experience of stigma than mood symptoms. These findings highlight the importance of interventions aimed at ameliorating youth's exposure to negative views about mental health as those managing depressive symptomatology.

[Mental Health Gap Action Programme: a theoretical model of barriers to implementation by health personnel in Chocó, ColombiaPrograma de Ação para Reduzir as Lacunas em Saúde Mental: modelo teórico das barreiras de implementação por profissionais de saúde de Chocó, Colômbia]. / Programa de acción para superar las brechas en salud mental: un modelo teórico de las barreras de implementación desde el personal de salud en Chocó, Colombia.

Objectives: Mental, neurological, and substance use (MNS) disorders have a high prevalence in Colombia and there is a treatment gap. The World Health Organization (WHO) Mental Health Gap Action Programme (mhGAP) has various components. The mhGAP 2.0 Intervention Guide, aimed at improving primary health care, is a guide for the assessment and management of MNS disorders based on clinical decision-making protocols. The objective of this study was to determine the barriers that may hinder the program implementation process. Methods: A qualitative study with content analysis was conducted in three phases: i) study preparation, organization, and presentation; ii) open coding, categorization, and abstraction of contents; and iii) information analysis. The study included semi-structured interviews with 21 people involved in the provision of mental health services in Chocó (Colombia): five medical doctors, seven nurses, and three psychologists, as well as six professionals working in the administrative area of the department's health secretariats. The perceptions of these stakeholders were explored. Open-ended questions were asked to explore experiences with the process, as well as the barriers identified in practice. Results: Four different thematic categories were identified: intersectoral action, long-standing challenges, opportunities, and suitability of tools. Conclusions: A theoretical model of barriers to implementation of the mhGAP program was constructed, based on stakeholder perceptions. Controlling barriers is perceived as a possible way to contribute significantly to population health.

Objetivo: Os transtornos mentais, neurológicos e por uso de substâncias psicoativas são muito prevalentes, e há uma lacuna na atenção a esses transtornos na Colômbia. O Programa de Ação para Reduzir as Lacunas em Saúde Mental (mhGAP, na sigla em inglês) da Organização Mundial da Saúde (OMS) consta de vários componentes. Um deles é o Manual de Intervenções mhGAP 2.0, elaborado para aprimorar a atenção primária à saúde. O documento contém orientações para avaliação e manejo de transtornos mentais, neurológicos e por uso de substâncias psicoativas e foi elaborado com base em protocolos para a tomada de decisões clínicas. O objetivo do estudo foi determinar as barreiras que podem surgir no processo de implementação do programa. Métodos: Estudo qualitativo com enfoque de análise de conteúdo desenvolvido em três fases: i) preparação, organização e apresentação do estudo; ii) codificação aberta, categorização e abstração do conteúdo; e iii) análise das informações. O estudo incluiu entrevistas semiestruturadas com 21 pessoas envolvidas na prestação de serviços de saúde mental em Chocó (Colômbia): cinco profissionais da medicina, sete de enfermagem e três de psicologia, bem como seis profissionais que trabalham na área administrativa das secretarias de saúde do departamento. As percepções das partes interessadas, ou seja, do pessoal assistencial e administrativo do setor de saúde no departamento de Chocó, foram exploradas. Foram feitas perguntas abertas a fim de investigar suas experiências com o processo de atenção e as barreiras identificadas na prática. Resultados: Foram identificadas quatro categorias temáticas: intersetorialidade, desafios de longa data, possibilidades e adequação das ferramentas. Conclusões: Elaborou-se um modelo teórico sobre as barreiras de implementação do Programa mhGAP com base nas percepções das partes interessadas. O controle das barreiras é visto como uma possível forma de contribuir significativamente para a saúde da população.

NeuroSense: A non-invasive and configurable somatosensory stimulator with OPENVIBE communication.

Understanding the somatosensory system and its abnormalities requires the development of devices that can accurately stimulate the human skin. New methods for assessing the somatosensory system can enhance the diagnosis, treatments, and prognosis for individuals with somatosensory impairments. Therefore, the design of NeuroSense, a tactile stimulator that evokes three types of daily life sensations (touch, air and vibration) is described in this work. The prototype aims to evoke quantitative assessments to evaluate the functionality of the somatosensory system and its abnormal conditions that affect the quality of life. In addition, the device has proven to have varying intensities and onset latencies that produces somatosensory evoked potentials and energy desynchronization on somatosensory cortex.

Comprehensive spatial distribution of patients with first-episode psychosis (FEP) and its relation to socio-economic factors.

BACKGROUND: The functional-cognitive impact of first-episode psychosis (FEP) is extremely relevant and implies dysfunction from early life stages like adolescence and youth. Like other illnesses, FEP incidence is also influenced by environmental factors. It is necessary to attend to this age group with early interventions and to act on the environmental factors that the literature correlates with increased FEP incidence: socio-economic aspects, social adversity, bullying at school or cannabis use. In this context, identifying the areas of cities where FEP patients concentrate is important to perform early interventions. The spatial analysis of patient distribution in a whole city is one way to identify the most vulnerable areas and to propose psycho-social interventions for the possible prevention and/or early detection of FEP by improving urban mental health. METHODS: An epidemiological study of point patterns to determine the areas of a city with a higher incidence of patients with FEP. To do so, the addresses of FEP cases were georeferenced from 1 January 2016 to 31 October 2022, and 109 FEP patients were analysed. Data from a random sample of 383 controls, comprising their addresses, age, and sex, were randomly obtained from the official city council database. By GIS, the areas with higher FEP incidence were analysed to see if they coincided with the zones where inhabitants with lower incomes lived. RESULTS: The risk ratio of the FEP patients was compatible with the constant risk ratio in Albacete (p = 0.22). When performing the process separately with cases and controls only in men and women, the results were not significant for both distributions (p value: 0.12 and 0.57, respectively). Nonetheless, areas within the city had a significantly higher risk. These groups of cases coincided with those who had lower income and more inequality for women, but this pattern was not clear for men. CONCLUSIONS: Classifying city areas per income can help to determine the zones at higher risk of FEP, which would allow early healthcare and preventive measures for these zones.

Evolution of interconsultal activity to endocrinology and nutrition in hospitalization floor in a third level hospital.

INTRODUCTION: Endocrinology and Nutrition (EyN) is an outpatient and hospital medical specialty. This study aims to understand the evolution of the activity of interdepartmental consultation (IC) carried out by EyN in hospitalization floor of a third level hospital, comparing its evolution with other medical specialties, and comparing endocrine IC with nutritional IC. MATERIAL AND METHODS: Longitudinal and retrospective study which analyzes IC notes of EyN and other medical specialties between 01-01-2013 and 31-12-2022. RESULTS: A total of 76093 IC notes (12623 patients) were performed by the EyN service (average age 65.4 years; 59% male) with an average of 4.8 notes per patient. Average annual growth was 7% in notes and 4% in patients (versus 6% and 3% of all other medical services, differences statistically significant). Of all patients hospitalized for 4 or more days, EyN went from attending 7.9% (2013) to 12.3% (2022). 66% of the IC performed by EyN was for nutritional cause and 34% for other pathologies. CONCLUSIONS: The EyN service is the one that most patients attend in hospital IC activity, with growth over the last few years greater than other medical specialties. Nutritional pathology is the main reason for IC.

Psychophysiological evaluation of the Smartick method in children with reading and mathematical difficulties.

Introduction: Assistive technologies for learning are aimed at promoting academic skills, such as reading and mathematics. These technologies mainly embrace mobile and web apps addressed to children with learning difficulties. Nevertheless, most applications lack pedagogical foundation. Additionally, the task of selecting suitable technology for educational purposes becomes challenging. Hence, this protocol posits the psychophysiological assessment of an online method for learning (OML) named Smartick. This platform comprises reading and math activities for learning training. In this protocol, individual monitoring of each child is proposed to determine the progress in learning caused by Smartick. Methods and analysis: One hundred and twelve children aged between 8 and 12 who present reading or math difficulty after a rigorous psychometric evaluation will be recruited. The study comprises four sessions. In sessions 1 and 2, collective and individual psychometric evaluations will be performed, respectively. Reading and mathematical proficiency will be assessed, as well as attentional levels and intellectual quotient. Subsequently, each child will be semi-randomly assigned to either the experimental or control groups. Afterward, a first EEG will be collected for all children in session 3. Then, experimental groups will use Smartick for 3 months, in addition to their traditional learning method. In contrast, control groups will only continue with their traditional learning method. Finally, session 4 will consist of performing a second psychometric evaluation and another EEG, so that psychophysiological parameters can be encountered that indicate learning improvements due to the OML, regardless of the traditional learning method at hand. Discussion: Currently, few studies have validated learning improvement due to assistive technologies for learning. However, this proposal presents a psychophysiological evaluation addressed to children with reading or math difficulties who will be trained with an OML.

IFITM5-related (type V) osteogenesis imperfecta with evidence of perinatal involvement: A case report.

Osteogenesis imperfecta (OI) is a rare hereditary disorder characterized by bone fragility and frequent fractures. While most cases are attributed to variations in collagen-coding genes COL1A1 and COL1A2, other genes such as IFITM5 have also been associated with the disease, accounting for up to 5 % of cases. Here, we report a case of a 3-month-old female with a femur fracture and limb deformity. X-rays revealed evidence of osteopenia and previous fractures in the arms, clavicle, ribs, and left limb, alongside prenatal bone deformities detected by ultrasound. Initial clinical evaluation suggested progressively deforming (Sillence's type III) osteogenesis imperfecta (OI). Molecular testing led to the diagnosis of IFITM5-related OI, identifying the c.-14C>T (rs587776916) variant. Although this variant has been previously reported in patients with IFITM5-related OI, prenatal involvement had not been associated with this variant.

Effect of Trichomonacide 6-Nitro-1H-benzimidazole Derivative Compounds on Expression Level of Metabolic Genes in Trichomonas vaginalis.

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 µM. These results are promising for potential future therapeutic applications.

Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers.

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

Programa de prevención del riesgo de suicidio «RENACE» / [“RENACE” suicide risk prevention program]

A pesar de que en España el suicidio supone la primera causa de muerte externa, no existe a nivel nacional un plan de prevención o intervención protocolizado. Este estudio tiene como objetivo final el diseño, la implementación y la evaluación de un nuevo programa de prevención del riesgo de suicidio en el Complejo Hospitalario Universitario de Albacete, llamado «RENACE». Para ello, se describe el perfil sociodemográfico y clínico de los pacientes con ideación y con conducta suicida. Se obtuvieron los siguientes resultados: la mayoría de pacientes fueron mujeres (59%) y el grupo etario más prevalente fue el de 31 a 65 años. Entre la población infantojuvenil, predominó el rango de edad de 14 a 17 años. En cuanto al perfil clínico, el diagnóstico principal fue trastornos relacionados con traumas y factores de estrés, seguido de trastornos depresivos. (AU)

Despite the fact that suicide is the leading cause of external death in Spain, there is no protocolized prevention or intervention plan at national level. The final aim of this study is the design, implementation and evaluation of a new suicide risk prevention program at the Albacete University Hospital Complex, called "RENACE". For this purpose, the sociodemographic and clinical profile of patients with suicidal ideation and behavior was described. The following results were obtained: the majority of patients were women (59%) and the most prevalent age group was 31 to 65 years old. Among the juvenile population, the predominant age range was 14 to 17 years. Regarding the clinical profile, the main diagnosis was trauma-related disorders and stress factors, followed by depressive disorders. (AU)

Transport-controlled growth decoupling for self-induced protein expression with a glycerol-repressible genetic circuit.

Decoupling cell formation from recombinant protein synthesis is a potent strategy to intensify bioprocesses. Escherichia coli strains with mutations in the glucose uptake components lack catabolite repression, display low growth rate, no overflow metabolism, and high recombinant protein yields. Fast growth rates were promoted by the simultaneous consumption of glucose and glycerol, and this was followed by a phase of slow growth, when only glucose remained in the medium. A glycerol-repressible genetic circuit was designed to autonomously induce recombinant protein expression. The engineered strain bearing the genetic circuit was cultured in 3.9 g L-1 glycerol + 18 g L-1 glucose in microbioreactors with online oxygen transfer rate monitoring. The growth was fast during the simultaneous consumption of both carbon sources (C-sources), while expression of the recombinant protein was low. When glycerol was depleted, the growth rate decreased, and the specific fluorescence reached values 17% higher than those obtained with a strong constitutive promoter. Despite the relatively high amount of C-source used, no oxygen limitation was observed. The proposed approach eliminates the need for the substrate feeding or inducers addition and is set as a simple batch culture while mimicking fed-batch performance.

New Genetic Variants of RUNX2 in Mexican Families Cause Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures with bulging calvaria, hypoplasia, or aplasia of clavicles permitting abnormal opposition of the shoulders; wide public symphysis; short middle phalanx of the fifth fingers; and vertebral, craniofacial, and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The gene responsible for CCD is the Runt-related transcription factor 2 (RUNX2) gene. We characterize the clinical, genetic, and bioinformatic results of four CCD cases: two cases within Mexican families with six affected members, nine asymptomatic individuals, and two sporadic cases with CCD, with one hundred healthy controls. Genomic DNA analyses of the RUNX2 gene were performed for Sanger sequencing. Bioinformatics tools were used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652delTA; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability-related, and structural alterations in the RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. Moreover, the proband 1 presented clinical data not previously reported that could represent an expanded phenotype of severe expression.

Lambda-double-fixation for medial epicanthoplasty in Blepharophimosis - Ptosis - Epicanthus Inversus Syndrome.

PURPOSE: This study aims to describe a novel approach to medial epicanthoplasty in patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and evaluate the surgical outcome of this technique. METHODS: A retrospective, noncomparative, interventional case series involving 22 BPES patients who underwent medial epicanthoplasty using the Lambda-Double-Fixation technique (LDFT) performed by a single surgeon. Pre- and postoperative measurements of inner intercanthal distance (DIC) and horizontal palpebral fissure (HPFL) were recorded. Concurrent or staged ptosis surgery and lateral cantholysis, along with any complications, were documented. RESULTS: The mean age of the patients was 2.9 ± 2.2 years. Preoperatively, the mean DIC measured 34.0 ± 2.7 mm, significantly reducing to 23.7 ± 2.1 mm postoperatively (p < 0.001). A notable increase in mean HPFL was observed in both eyes postoperatively: right eye form 18.4 ± 2.4 mm to 23.7 ± 1.8 mm (p < 0.001) and left eye from 18.3 ± 2.4 mm to 23.8 ± 1.9 mm (p < 0.001). Postoperative scars were barely visible in all patients. CONCLUSION: LDFT is a simple and reproducible technique for medial epicanthoplasty in BPES. Our results affirm that LDFT induces a physiologically concave reshaping of the medial canthal region, optimizing access to the peritarsal zone and ensuring a secure fixation of the new canthus. These benefits lead to a reduction in ICD and an increase in HPFL, leading to a cosmetically appealing postoperative outcome.

Meiotic prophase length modulates Tel1-dependent DNA double-strand break interference.

During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, in S. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance. We have proposed that clustering is caused by a limited number of sub-chromosomal domains becoming primed for DSB formation. Here, we provide evidence that DSB clustering is abolished when meiotic prophase timing is extended via deletion of the NDT80 transcription factor. We propose that extension of meiotic prophase enables most cells, and therefore most chromosomal domains within them, to reach an equilibrium state of similar Spo11-DSB potential, reducing the impact that priming has on estimates of coincident DSB formation. Consistent with this view, when Tel1 is absent but Ndt80 is present and thus cells are able to rapidly exit meiotic prophase, genome-wide maps of Spo11-DSB formation are skewed towards pericentromeric regions and regions that load pro-DSB factors early-revealing regions of preferential priming-but this effect is abolished when NDT80 is deleted. Our work highlights how the stochastic nature of Spo11-DSB formation in individual cells within the limited temporal window of meiotic prophase can cause localised DSB clustering-a phenomenon that is exacerbated in tel1Δ cells due to the dual roles that Tel1 has in DSB interference and meiotic prophase checkpoint control.

Impact of the COVID-19 Pandemic on Prenatal Care Utilization Among Italian and Immigrant Pregnant Women: A Multicenter Survey.

Objectives: To compare the utilization of prenatal services between immigrant and Italian women during the COVID-19 pandemic. Methods: A cross-sectional survey was conducted at 3 maternity care centers in Italy. Results: We included 1,312 women, 1,198 (91.3%) were Italian and 114 (8.7%) were immigrants. A significantly higher proportion of Italians underwent 8 or more prenatal care visits (64.4% vs. 54.4%, p = 0.03) and more immigrants than Italians attended their appointments at hospital settings (45% vs. 18%, p < 0.001). Regarding prenatal course, Italians were more likely than immigrants to attend a non-hospital setting or an online class (49.6% and 30.2% vs. 34.9% and 11.6%, p = 0.008). A higher influenza vaccine uptake among immigrants compared with Italians was observed (39.5% vs. 19.8%, p < 0.001). Among women not receiving certain prenatal services, immigrants were more likely to state COVID-19 pandemic was the main reason for non-compliance. Conclusion: Immigrant pregnant women were more likely to receive prenatal services at a hospital setting than their Italian counterparts. Among women who did not comply with prenatal services, immigrants were more likely to cite the pandemic as their main reason.