Spontaneous Hemoperitoneum Due to Ruptured Uterine Artery: A Rare Complication During Pregnancy.

Spontaneous rupture of the uterine artery is a rare and life-threatening cause of hemoperitoneum in pregnancy, associated with high maternal and perinatal morbidity and mortality. We present a case of a 29-year-old woman, in the 36th week of gestation, with acute abdomen due to hemoperitoneum. Ultrasound revealed free fluid in the abdominal cavity, with no signs of fetal distress, and the patient was mildly hypotensive. Exploratory laparotomy and cesarean section were performed, and extensive blood clots on the upper abdominal quadrants were discovered, as well as a bleeding left uterine artery. We expect that this case raises awareness of the ruptured uterine artery as a possible etiology of hemoperitoneum during pregnancy.

Feasibility and Acceptability of Pediatric Smartphone Lung Auscultation by Parents: Cross-Sectional Study.

Background: The use of a smartphone built-in microphone for auscultation is a feasible alternative to the use of a stethoscope, when applied by physicians. Objective: This cross-sectional study aims to assess the feasibility of this technology when used by parents-the real intended end users. Methods: Physicians recruited 46 children (male: n=33, 72%; age: mean 11.3, SD 3.1 y; children with asthma: n=24, 52%) during medical visits in a pediatric department of a tertiary hospital. Smartphone auscultation using an app was performed at 4 locations (trachea, right anterior chest, and right and left lung bases), first by a physician (recordings: n=297) and later by a parent (recordings: n=344). All recordings (N=641) were classified by 3 annotators for quality and the presence of adventitious sounds. Parents completed a questionnaire to provide feedback on the app, using a Likert scale ranging from 1 ("totally disagree") to 5 ("totally agree"). Results: Most recordings had quality (physicians' recordings: 253/297, 85.2%; parents' recordings: 266/346, 76.9%). The proportions of physicians' recordings (34/253, 13.4%) and parents' recordings (31/266, 11.7%) with adventitious sounds were similar. Parents found the app easy to use (questionnaire: median 5, IQR 5-5) and were willing to use it (questionnaire: median 5, IQR 5-5). Conclusions: Our results show that smartphone auscultation is feasible when performed by parents in the clinical context, but further investigation is needed to test its feasibility in real life.

Silymarin inhibits dermal gelatinolytic activity and reduces cutaneous inflammation.

Milk thistle (Silybum marianum) is well-known for its antioxidant activity due to the presence of silymarin. Albeit some studies show a potential for skin inflammation, its activity against dermal MMP-9 and MMP-2 remains to be studied. Silymarin isolated from an S. marianum herbal extract was tested for gelatinase inhibition in the presence of isolated MMP-9 and in dermal adenocarcinome HaCaT cells. Silymarin was then further tested in vivo, using a cutaneous inflammation mice model mediated by reactive oxygen species. Silymarin was able to significantly inhibit gelatinolytic activity in vitro without impairing cell growth and viability. Furthermore, inhibition was more pronounced in cells than with the isolated gelatinase, suggesting an additional effect upon metabolic pathways. In vivo, silymarin was able to reduce ear edema up to 74% and attenuated histological lesions. Results highlight silymarin potential for application in skin inflammatory disorders via gelatinase inhibition.

The pathogenicity of Plasmopara viticola: a review of evolutionary dynamics, infection strategies and effector molecules.

Oomycetes are filamentous organisms that resemble fungi in terms of morphology and life cycle, primarily due to convergent evolution. The success of pathogenic oomycetes lies in their ability to adapt and overcome host resistance, occasionally transitioning to new hosts. During plant infection, these organisms secrete effector proteins and other compounds during plant infection, as a molecular arsenal that contributes to their pathogenic success. Genomic sequencing, transcriptomic analysis, and proteomic studies have revealed highly diverse effector repertoires among different oomycete pathogens, highlighting their adaptability and evolution potential.The obligate biotrophic oomycete Plasmopara viticola affects grapevine plants (Vitis vinifera L.) causing the downy mildew disease, with significant economic impact. This disease is devastating in Europe, leading to substantial production losses. Even though Plasmopara viticola is a well-known pathogen, to date there are scarce reviews summarising pathogenicity, virulence, the genetics and molecular mechanisms of interaction with grapevine.This review aims to explore the current knowledge of the infection strategy, lifecycle, effector molecules, and pathogenicity of Plasmopara viticola. The recent sequencing of the Plasmopara viticola genome has provided new insights into understanding the infection strategies employed by this pathogen. Additionally, we will highlight the contributions of omics technologies in unravelling the ongoing evolution of this oomycete, including the first in-plant proteome analysis of the pathogen.

Neurological Spectrum of Epstein-Barr Virus Infection: A Rare Clinical Case.

The Epstein-Barr virus (EBV) is a DNA virus that has been infecting humans since ancient times, capable of causing a wide range of pathologies and affecting approximately 90% of the population. A 61-year-old male with no significant medical history presented with a 5-day history of imbalance and difficulty walking. Neurological examination revealed specific findings, including absent reflexes, bilateral asynergy, and gait abnormalities. Contrasting with Guillain-Barré Syndrome, lumbar puncture suggested a central nervous system infection. Serological testing confirmed Epstein-Barr virus (EBV) positivity, and intravenous immunoglobulin led to significant improvement. Electromyogram results suggested inflammatory/ipnfectious polyradiculopathy. Repeat EBV serology, showing strongly positive IgG and negative IgM, confirmed the diagnosis of Polyradiculoneuropathy secondary to EBV. This case underscores the rare neurological complications of EBV and the importance of considering viral infections in such presentations.

Imaging characterization of the fellow eye in patients with unilateral polypoidal choroidal vasculopathy.

INTRODUCTION: New insights on polypoidal choroidal vasculopathy (PCV) have shed light regarding its pathophysiology and associations. However, PCV characterization is still incomplete in Caucasians, which is due to presumed lower prevalence in this population. Features typically associated with AMD such as drusen, retinal pigmentary changes or atrophy are seen in PCV, as precursors and in the fellow eye. Pachychoroid spectrum, predisposing to PCV, also presents with chronic changes in the retinal pigment epithelium (RPE), such as drusen-like deposits (DLD), and in the choroid. The purpose of this study is to perform a multimodal imaging characterization of unaffected fellow eyes in a sample of Caucasian patients with unilateral PCV. METHODS: Multicenter retrospective cohort study with a sample of 55 unaffected fellow eyes from patients diagnosed with unilateral PCV confirmed by indocyanine green angiography. The sample was characterized in the baseline by color fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography and indocyanine green angiography. Morphological characteristics of both the retina and the choroid were evaluated. The SD-OCT of the last follow-up visit was also evaluated in order to exclude evolution to PCV or choroidal neovascularization. All images captured underwent evaluation by two independent graders. Informed consent was obtained from all participants. RESULTS: Fifty-five patients (median age, 74 ± 15 years) were included. After 15.5 ± 6.4 months of follow-up, only one developed disease (1.9%). Soft and/or hard drusen were present in 60% and pachydrusen in 23.6%. Pachychoroid signs were present in 47.2%, the double-layer sign in 36.4%, disruption of the RPE changes in 16.4% and RPE atrophy in 10.9%. ICGA revealed choroidal vascular dilation in 63.6% and punctiform hyperfluorescence in 52.7%. Branching vascular networks were identified in only 1.9% of cases. CONCLUSION: The identification of pachychoroid signs in the OCT and ICGA were present in over half of the cases and the presence of the double-layer sign in more than a third provide crucial insights for enhanced characterization of this pathology and deeper understanding of its pathogenesis. These findings contribute significantly to the current knowledge, offering valuable markers to discern various phases of the pathology's progression.

Preliminary study: cognitive behavioural therapy for insomnia in adolescents with anorexia nervosa.

PURPOSE: Insomnia and anorexia nervosa (AN) are frequently comorbid, negatively affecting the evolution and the prognosis of AN. Within this framework, the management of sleep disorders appears as critical. The aim of this retrospective study is to assess, for the first time, the efficacy of cognitive and behavioural therapy for insomnia (CBT-I) on sleep disturbances in adolescents with AN. To do so, we investigated the impact of CBT-I on sleep disturbances and sleep-related outcomes, in BMI, AN symptoms, anxiety and depressive symptoms, emotionality and quality of life. These features were compared between two groups of patients with AN, one following CBT-I, and the other receiving the regular treatment at the psychiatric unit. METHODS: Data collection occurred between January and May 2022. The study included 42 adolescents in-treatment at the Eating Disorders care specialised unit at Salvator Hospital in Marseille. They were randomly assigned to the CBT-I group (N = 31) or the control group (N = 11). Several clinical elements were assessed using sleep diaries and self-report questionnaires. RESULTS: Participants undergoing CBT-I showed a significant improvement in sleep latency, total wake time and sleep efficacy, as well as in physical well-being. No significant effects were found regarding AN symptoms. CONCLUSION: These preliminary findings provide support for CBT-I effectiveness in adolescents with AN, as shown by significant improvements in several sleep parameters, as well as in physical well-being. These promising results, underline the relevance of this topic and its potential benefits for a more appropriate treatment for adolescents with AN. LEVEL OF EVIDENCE: Level V, retrospective study.

Retinal Metastases as the Initial Presentation of Advanced Lung Adenocarcinoma.

Introduction: Most lung cancers are diagnosed at an advanced stage. Common metastatic sites include the brain, bone, liver and adrenal glands. Ocular metastases, however, are extremely rare. We present a case of advanced lung adenocarcinoma presenting exclusively with photopsias attributable to retinal metastases. Case description: We describe a woman in her fifties, a lifetime non-smoker with an unremarkable medical and family history, who presented to the emergency department with photopsias for a week. Ophthalmology evaluation revealed decreased visual acuity bilaterally, and a fundus examination disclosed lesions suggestive of bilateral retinal metastases. A comprehensive evaluation diagnosed a stage IVb lung adenocarcinoma with exon 19 mutation on epidermal growth factor receptor gene. Subsequently, she developed complaints of headaches and dizziness. She received frontline osimertinib 80 mg daily, preceded by upfront whole-brain radiation therapy with partial orbital inclusion for symptomatic ocular and brain metastases. After ten radiation therapy sessions, her complaints were resolved and an ophthalmology revaluation revealed improvement in visual acuity and resolution of photopsia complaints. The patient is currently on osimertinib and preserves an ECOG score of 0. Conclusion: Retinal metastases usually indicate advanced disease, so presenting with isolated ocular symptoms is exceedingly rare. Especially in cases of uncommon metastases, a multidisciplinary approach is fundamental for a prompt diagnosis and timely treatment, impacting prognosis and quality of life. LEARNING POINTS: Ocular metastases in lung cancer are usually a sign of advanced disease.Advanced lung adenocarcinoma presenting solely with retinal metastases is extremely rare.A multidisciplinary team is essential for the diagnosis and treatment of lung cancer with uncommon metastases.

Epidemiology and genetic diversity of invasive Neisseria meningitidis strains circulating in Portugal from 2003 to 2020.

Invasive meningococcal disease (IMD) continues to be a public health problem due to its epidemic potential, affecting mostly children. We aimed to present a detailed description of the epidemiology of IMD in Portugal, including insights into the genetic diversity of Neisseria meningitidis strains. Epidemiological analysis included data from the Portuguese National Reference Laboratory of Neisseria meningitidis during 2003 to 2020. Since 2012, N. meningitidis isolates have also been assessed for their susceptibility to antibiotics and were characterized by whole genome sequencing. During 2003-2020, 1392 confirmed cases of IMD were analyzed. A decrease in the annual incidence rate was observed, ranging from 1.99 (2003) to 0.39 (2020), with an average case fatality rate of 7.1%. Serogroup B was the most frequent (69.7%), followed by serogroups C (9.7%), Y (5.7%), and W (2.6%). Genomic characterization of 329 isolates identified 20 clonal complexes (cc), with the most prevalent belonging to serogroup B cc41/44 (26.3%) and cc213 (16.3%). Isolates belonging to cc11 were predominantly from serogroups W (77.3%) and C (76.5%), whereas cc23 was dominant from serogroup Y (65.7%). Over the past 4 years (2017-2020), we observed an increasing trend of cases assigned to cc213, cc32, and cc11. Regarding antimicrobial susceptibility, all isolates were susceptible to ceftriaxone and 61.8% were penicillin-nonsusceptible, whereas 1.4% and 1.0% were resistant to ciprofloxacin and rifampicin. This is the first detailed study on the epidemiology and genomics of invasive N. meningitidis infections in Portugal, providing relevant data to public health policy makers for a more effective control of this disease.

Cardiovascular rhythmicity in overweight and obese children / Ritmicidade cardiovascular em crianças com sobrepeso e obesidade

Abstract Introduction: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. Methods: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. Results: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. Discussion: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

Resumo Introdução: Acredita-se que a obesidade desempenhe um papel na desregulação da ritmicidade cardíaca em crianças obesas, mas esse é um campo de investigação ainda pouco explorado. O objetivo deste trabalho foi avaliar o impacto do sobrepeso e da obesidade na ritmicidade cardiovascular circadiana e ultradiana de crianças pré-púberes, em comparação com crianças com peso normal. Métodos: Realizamos um estudo transversal com 316 crianças, acompanhadas na coorte de nascimentos Geração XXI (Portugal). Foram medidos dados antropométricos e a pressão arterial ambulatorial de 24 horas, e os perfis foram examinados com uma análise de Fourier para ritmos circadianos e ultradianos de pressão arterial (PA) e frequência cardíaca (FC). Resultados: Crianças com sobrepeso/obesidade apresentaram mais frequentemente um padrão de PA não-dipper em comparação com crianças com peso normal (31,5% vs. 21,6%; p = 0,047). A prevalência da pressão arterial média (PAM) de 24 horas e da ritmicidade da FC de 8 horas foi significativamente menor em crianças obesas (79,3% vs. 88,0%; p = 0,038 e 33,3% vs. 45,2%; p = 0,031, respectivamente). A prevalência das restantes ritmicidades da PAM e da FC foi semelhante em ambos os grupos. Não foram encontradas diferenças nos valores medianos das amplitudes e acrofases dos ritmos de PAM e FC. Discussão: As alterações encontradas na ritmicidade sugerem que a análise da ritmicidade circadiana e ultradiana pode ser sensível na detecção de desregulações cardiovasculares precoces, mas são necessários novos estudos para reforçar nossos achados e entender melhor suas implicações a longo prazo.

Genomic evidence for West Antarctic Ice Sheet collapse during the Last Interglacial.

The marine-based West Antarctic Ice Sheet (WAIS) is considered vulnerable to irreversible collapse under future climate trajectories, and its tipping point may lie within the mitigated warming scenarios of 1.5° to 2°C of the United Nations Paris Agreement. Knowledge of ice loss during similarly warm past climates could resolve this uncertainty, including the Last Interglacial when global sea levels were 5 to 10 meters higher than today and global average temperatures were 0.5° to 1.5°C warmer than preindustrial levels. Using a panel of genome-wide, single-nucleotide polymorphisms of a circum-Antarctic octopus, we show persistent, historic signals of gene flow only possible with complete WAIS collapse. Our results provide the first empirical evidence that the tipping point of WAIS loss could be reached even under stringent climate mitigation scenarios.

Determination of Antimicrobial Resistance and the Impact of Imipenem + Cilastatin Synergy with Tetracycline in Pseudomonas aeruginosa Isolates from Sepsis.

Pseudomonas aeruginosa is among the most ubiquitous bacteria in the natural world, exhibiting metabolic and physiological versatility, which makes it highly adaptable. Imipenem + cilastatin and tetracycline are antibiotic combinations commonly used to treat infections caused by P. aeruginosa, including serious infections such as sepsis. In the context of bacterial infections, biofilm, formed by bacterial cells surrounded by extracellular substances forming a matrix, plays a pivotal role in the resistance of P. aeruginosa to antibiotics. This study aimed to characterize a representative panel of P. aeruginosa isolates from septicemias, assessing their susceptibility to various antibiotics, specifically, imipenem + cilastatin and tetracycline, and the impact of these treatments on biofilm formation. Results from antibiotic susceptibility tests revealed sensitivity in most isolates to six antibiotics, with four showing near or equal to 100% sensitivity. However, resistance was observed in some antibiotics, albeit at minimal levels. Notably, tetracycline showed a 100% resistance phenotype, while imipenem + cilastatin predominantly displayed an intermediate phenotype (85.72%), with some resistance (38.1%). Microdilution susceptibility testing identified effective combinations against different isolates. Regarding biofilm formation, P. aeruginosa demonstrated the ability to produce biofilms. The staining of microtiter plates confirmed that specific concentrations of imipenem + cilastatin and tetracycline could inhibit biofilm production. A significant proportion of isolates exhibited resistance to aminoglycoside antibiotics because of the presence of modifying genes (aac(3)-II and aac(3)-III), reducing their effectiveness. This study also explored various resistance genes, unveiling diverse resistance mechanisms among P. aeruginosa isolates. Several virulence genes were detected, including the las quorum-sensing system genes (lasI and lasR) in a significant proportion of isolates, contributing to virulence factor activation. However, genes related to the type IV pili (T4P) system (pilB and pilA) were found in limited isolates. In conclusion, this comprehensive study sheds light on the intricate dynamics of P. aeruginosa, a remarkably adaptable bacterium with a widespread presence in the natural world. Our findings provide valuable insights into the ongoing battle against P. aeruginosa infections, highlighting the need for tailored antibiotic therapies and innovative approaches to combat biofilm-related resistance.

Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling.

External beam radiotherapy (RT) is a leading first-line therapy for prostate cancer (PCa), and, in recent years, significant advances have been accomplished. However, RT resistance can arise and result in long-term recurrence or disease progression in the worst-case scenario. Thus, making crucial the discovery of new targets for PCa radiosensitization. Herein, we generated a radioresistant PCa cell line, and found p53 to be highly expressed in radioresistant PCa cells, as well as in PCa patients with recurrent/disease progression submitted to RT. Mechanism dissection revealed that RT could promote p53 expression via epigenetic modulation. Specifically, a decrease of H3K27me3 occupancy at TP53 gene promoter, due to increased KDM6B activity, was observed in radioresistant PCa cells. Furthermore, p53 is essential for efficient DNA damage signaling response and cell recovery upon stress induction by prolonged fractionated irradiation. Remarkably, KDM6B inhibition by GSK-J4 significantly decreased p53 expression, consequently attenuating the radioresistant phenotype of PCa cells and hampering in vivo 3D tumor formation. Overall, this work contributes to improve the understanding of p53 as a mediator of signaling transduction in DNA damage repair, as well as the impact of epigenetic targeting for PCa radiosensitization.

Implementation determinants of physical activity interventions in primary health care settings using the TICD framework: a systematic review.

BACKGROUND: Translation into practice of effective physical activity interventions in primary care is difficult, due to a complex interaction of implementation determinants. We aimed to identify implementation barriers and facilitators of four primary care interventions: physical activity assessment, counselling, prescription, and referral. METHODS: A systematic review of qualitative, quantitative and mixed-methods studies published since 2016 was conducted. The "Tailored Implementation for Chronic Diseases" (TICD) framework was adapted to extract and synthesize barriers and facilitators. RESULTS: Sixty-two studies met the inclusion criteria. Barriers (n = 56) and facilitators (n = 55) were identified across seven domains, related to characteristics of the intervention, individual factors of the implementers and receivers, organizational factors, and political and social determinants. The five most frequently reported determinants were: professionals' knowledge and skills; intervention feasibility/compatibility with primary health care routine; interventions' cost and financial incentives; tools and materials; and professionals' cognitions and attitudes. "Social, political and legal factors" domain was the least reported. Physical activity counselling, prescription, and referral were influenced by determinants belonging to all the seven domains. CONCLUSION: The implementation of physical activity interventions in primary care is influenced by a broader range of determinants. Barriers and facilitators related with health professionals, intervention characteristics, and available resources were the most frequently reported. A deep understanding of the local context, with particularly emphasis on these determinants, should be considered when preparing an intervention implementation, in order to contribute for designing tailored implementation strategies and optimize the interventions' effectiveness.

Adaptive reinforcement learning for task scheduling in aircraft maintenance.

This paper proposes using reinforcement learning (RL) to schedule maintenance tasks, which can significantly reduce direct operating costs for airlines. The approach consists of a static algorithm for long-term scheduling and an adaptive algorithm for rescheduling based on new maintenance information. To assess the performance of both approaches, three key performance indicators (KPIs) are defined: Ground Time, representing the hours an aircraft spends on the ground; Time Slack, measuring the proximity of tasks to their due dates; and Change Score, quantifying the similarity level between initial and adapted maintenance plans when new information surfaces. The results demonstrate the efficacy of RL in producing efficient maintenance plans, with the algorithms complementing each other to form a solid foundation for routine tasks and real-time responsiveness to new information. While the static algorithm performs slightly better in terms of Ground Time and Time Slack, the adaptive algorithm excels overwhelmingly in terms of Change Score, offering greater flexibility in handling new maintenance information. The proposed RL-based approach can improve the efficiency of aircraft maintenance and has the potential for further research in this area.

Interstitial Ectopic Pregnancy: A Rare Diagnosis.

An ectopic pregnancy is located outside the uterus, mostly found in the fallopian tubes. The main predisposing factors are usually related to anatomical and/or functional disturbances of the fallopian tubes. Typically, an ectopic pregnancy presents with vaginal bleeding or abdominal pain in the first trimester of pregnancy, although it may be asymptomatic. The diagnosis of ectopic pregnancy, which is based on transvaginal ultrasound associated with the serum beta fraction of human chorionic gonadotropin values, is of the highest relevance due to the mortality risk involved. We report the case of a 26-year-old woman who presented with a four-week history of amenorrhea and abdominal pain. Initially, the diagnostic hypothesis was a pelvic inflammatory disease, as the patient complained of pain during deep palpation of the lower quadrants of the abdomen, and gynecological observation detected malodorous discharge and cervical tenderness. Antibiotic treatment was initiated. The patient was later diagnosed with ectopic pregnancy, which was discovered during a routine pregnancy ultrasound. She was submitted to urgent laparotomy with intraoperative confirmation of the interstitial location of the gestational sac.

Monitoring Sensors for Urban Air Quality: The Case of the Municipality of Lisbon.

Air pollution is a global issue that impacts environmental inequalities, and air quality sensors can have a decisive role in city policymaking for future cities. Science and society are already aware that during the most challenging times of COVID-19, the levels of air pollution in cities decreased, especially during lockdowns, when road traffic was reduced. Several pollution parameters can be used to analyse cities' environmental challenges, and it is more pressing than ever to have city climate decisions supported by sensor data. We have applied a data science approach to understand the evolution of the levels of carbon monoxide, nitrogen dioxide, particulate matter 2.5, and particulate matter 10 between August 2021 and July 2022. The analysis of the air quality levels, captured for the first time via 80 monitoring stations distributed throughout the municipality of Lisbon, has allowed us to realize that nitrogen dioxide and particulate matter 10 exceed the levels that are recommended by the World Health Organization, thereby increasing the health risk for those who live and work in Lisbon. Supported by these findings, we propose a central role for air quality sensors for policymaking in future cities, taking as a case study the municipality of Lisbon, Portugal, which is among the European cities that recently proposed be climate-neutral and smart city by 2030.