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We analyzed the distribution of seismic moment in Italy, computed from instrumental seismicity recorded by the Italian National Seismic Network in the past 14 years, to map the areas where seismic deformation processes have been active in this time interval. Seismic moment is the most suitable parameter to quantify earthquake size. It is related to the geometric characteristics of faults, to seismic energy and it is a quantity that can be summed and represented in its cumulative value. The maps of seismic moment distribution display more information than epicentral maps, better showing actively deforming regions. They provide further and original evidence for the existence, within the Apenninic belt, of two regions (north and south) characterized by different seismic energy release. The seismic moment is almost continuously and homogeneously distributed all along the belt in the Northern Apennines, whereas in the Southern Apennines it is concentrated in the zones recently activated by mainshock-aftershock seismic sequences. Seismic deformation takes place in a 30 km narrow belt along the Apennines, while in the transition zone between the Northern and Southern Apennines this belt is about 100 km wide. Comparing instrumental seismic moment release with the areas struck by the largest historical earthquakes which have occurred in the past six centuries, we qualitatively extended back to the past the information on where the seismic deformation occurs. In the Southern Apennines background energy release from instrumental seismicity is very low in the several areas hit by large historical earthquakes, suggesting that these seismogenic zones are currently quiescent.

Background. This study was undertaken to test the hypothesis that diabetes and pregnancy detrimentally affect the normal function of urethral striated muscles in rats, providing a model for additional studies related to urinary incontinence. The aim of this study was to evaluate morphological alterations in the urethral striated muscles of diabetic pregnant rats. Design and methods. Twenty female Wistar rats were distributed into four experimental groups of five rats as follows: virgin, pregnant, diabetic virgin, and diabetic pregnant. Diabetes was induced using streptozotocin administration (40 mg/kg i.v.). The rats were lethally anesthetized, and the urethra and vagina were extracted as a unit. Cryostat sections (6 µm thick) were cut and stained with hematoxylin-eosin, and immunohistochemical procedures were performed and subjected to morphological and semi quantitative analysis. Results. The urethral striated muscle from the diabetic pregnant rats presented with the following variations: thinning and atrophy, disorganization and disruption associated with the colocalization of fast and slow fibers and a steady decrease in the proportion of fast vs slow fibers. Conclusion. Diabetes and pregnancy impair the urethral striated muscle and alter its fiber type distribution.

Abstract Background The increasing demand for childbirth care based on physiological principles has led official bodies to encourage health centers to provide evidence-based care aimed at promoting women’s participation in informed decision-making and avoiding excessive medical intervention during childbirth. One of the goals is to reduce pain and find alternative measures to epidural anesthesia to enhance women’s autonomy and well-being during childbirth. Currently, water immersion is used as a non-pharmacological method for pain relief. This review aimed to identify and synthesize evidence on women’s and midwives’ experiences, values, and preferences regarding water immersion during childbirth. Methods A systematic review and thematic synthesis of qualitative evidence were conducted. Databases were searched and references were checked according to specific criteria. Studies that used qualitative data collection and analysis methods to examine the opinions of women or midwives in the hospital setting were included. Non-qualitative studies, mixed-methods studies that did not separately report qualitative results, and studies in languages other than English or Spanish were excluded. The Critical Appraisal Skills Program Qualitative Research Checklist was used to assess study quality, and results were synthesized using thematic synthesis. Results Thirteen studies met the inclusion criteria and were included in this review. The qualitative studies yielded three key themes: 1) reasons identified by women and midwives for choosing a water birth, 2) benefits experienced in water births, and 3) barriers and facilitators of water immersion during childbirth. Conclusions The evidence from qualitative studies indicates that women report benefits associated with water birth. From the perspective of midwives, ensuring safe water births requires adequate resources, midwives training, and rigorous standardized protocols to ensure that all pregnant women can safely opt for water immersion during childbirth with satisfactory results.

Background: Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified., Objective: We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA., Design: We evaluated the expression of PRMT5, its functional partner MEP50 and methylthioadenosine phosphorylase (MTAP)-an enzyme that modulates the sensitivity of PRMT5 to pharmacological inhibitors-in human CCA tissues. PRMT5-targeting drugs, currently tested in clinical trials for other malignancies, were assessed in human CCA cell lines and organoids, as well as in two immunocompetent CCA mouse models. Transcriptomic, proteomic and functional analyses were performed to explore the underlying antitumoural mechanisms., Results: PRMT5 and MEP50 proteins were correlatively overexpressed in most CCA tissues. MTAP was absent in 25% of intrahepatic CCA. PRMT5-targeting drugs markedly inhibited CCA cell proliferation, synergising with cisplatin and gemcitabine and hindered the growth of cholangiocarcinoma organoids. PRMT5 inhibition blunted the expression of oncogenic genes involved in chromatin remodelling and DNA repair, consistently inducing the formation of RNA loops and promoting DNA damage. Treatment with PRMT5-targeting drugs significantly restrained the growth of experimental CCA without adverse effects and concomitantly induced the recruitment of CD4 and CD8 T cells to shrinking tumourous lesions., Conclusion: PRMT5 and MEP50 are frequently upregulated in human CCA, and PRMT5-targeting drugs have significant antitumoural efficacy in clinically relevant CCA models. Our findings support the evaluation of PRMT5 inhibitors in clinical trials, including their combination with cytotoxic and immune therapies., Competing Interests: Competing interests: MAA is editor of Gut. All other authors have no conflict of interest., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Competing Interests: Funding Support and Author Disclosures Dr Ribeiro is supported in part by CNPq (310790/2021-2 and 465518/2014-1) and by FAPEMIG (PPM-00428-17 and RED-00081-16). Dr Nunes is supported in part by CNPq (308288/2020-3). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in the early diagnosis and prediction of CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on 12 November 2023, using the MeSH terms "Children", "CPB", "L-FABP", and "Acute Kidney Injury". Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p < 0.05. Of 508 studies assessed, nine were included, comprising 1658 children, of whom 561 (33.8%) developed CPB-AKI. Significantly higher uL-FABP levels in AKI versus non-AKI patients first manifested at baseline to 6 h post-CPB. At 6 h, uL-FABP correlated with CPB duration (r = 0.498, p = 0.036), postoperative serum creatinine (r = 0.567, p < 0.010), and length of hospital stay (r = 0.722, p < 0.0001). Importantly, uL-FABP at baseline (AUC = 0.77, 95% CI: 0.64-0.89, n = 365), 2 h (AUC = 0.71, 95% CI: 0.52-0.90, n = 509), and 6 h (AUC = 0.76, 95% CI: 0.72-0.80, n = 509) diagnosed CPB-AKI earlier. Hence, higher uL-FABP levels associate with worse clinical parameters and may diagnose and predict CPB-AKI earlier.

We present the first high-quality catalog of early aftershocks of the three mainshocks of the 2016 central Italy Amatrice-Visso-Norcia normal faulting sequence. We located 10,574 manually picked aftershocks with a robust probabilistic, non-linear method achieving a significant improvement in the solution accuracy and magnitude completeness with respect to previous studies. Aftershock distribution and relocated mainshocks give insight into the complex architecture of major causative and subsidiary faults, thus providing crucial constraints on multi-segment rupture models. We document reactivation and kinematic inversion of a WNW-dipping listric structure, referable to the inherited Mts Sibillini Thrust (MST) that controlled segmentation of the causative normal faults. Spatial partitioning of aftershocks evidences that the MST lateral ramp had a dual control on rupture propagation, behaving as a barrier for the Amatrice and Visso mainshocks, and later as an asperity for the Norcia mainshock. We hypothesize that the Visso mainshock re-activated also the deep part of an optimally oriented preexisting thrust. Aftershock patterns reveal that the Amatrice Mw5.4 aftershock and the Norcia mainshock ruptured two distinct antithetic faults 3-4 km apart. Therefore, our results suggest to consider both the MST cross structure and the subsidiary antithetic fault in the finite-fault source modelling of the Norcia earthquake.

This article describes the development of an electronic prototype to organize medications - the Electronic System for Personal and Controlled Use of Medications (Sistema Eletrônico de Uso Personalizado e Controlado de Medicamentos, SUPERMED). The prototype includes a drawer containing 1 month's supply of medicines, sound and visual medication timers, and a memory card for recording the times when the box was opened/closed (scheduled and unscheduled). This information is later transferred to a computer. Evolutionary prototyping was used to develop SUPERMED with the Arduino platform and C programming. To read alarm and box opening/closing data, software was developed in Java. Once the alarms are programmed (ideally by a health care professional), no additional adjustments are required by the patient. The prototype was tested during 31 days by the developers, with satisfactory functioning. The system seems adequate to organize medications and facilitate adherence to treatment. New studies will be carried out to validate and improve the prototype.

Aims of Study: To describe the characteristics of paediatric varicella in patients admitted through the emergency department (ED) of the Armand-Trousseau Children hospital in Paris and the evolution of the causes of admission during the study period., Study Design: Retrospective longitudinal cohort study from March 1990 to February 2001., Results: One hundred and eight children were hospitalized for varicella during these 11 years. Sixty per cent were under 2 years of age and all but one were immunocompetent. The first cause of admission was the presence of at least 1 complication (83,3%) classified as: cutaneous (34%), digestive (19,8,%), respiratory (17,6%), neurological (15,3%) and ENT complications (8,8%). Over 11 years, the rate of overall complications remained stable but there was an important increase in varicella cases admitted through the ED mainly due to increase in cutaneous superinfections., Conclusion: These data confirm the potential severity of varicella and underline the emerging problem of increasing cutaneous complications. Additional studies are necessary to address this phenomenon and to determine optimal prophylactic measures.

Objectives: To describe the different modalities of ambulatory management of acute pyelonephritis in patients older than 3 months of age in paediatric emergency units of the Ile de France region in 2004., Methods: Between October 2003 and April 2004, referents of 39 paediatric emergency units of the Ile de France region were questioned through a written questionnaire concerning the management of acute pyelonephritis: in or outpatient modalities, antibiotic regimen (molecule and route of administration), investigations and follow-up., Results: Thirty-one questionnaires (79.5%) were returned and analysed. A written protocol was available in 60% of the units. Outpatient management was performed in 24/31 centres. Young age, poor clinical tolerance, urological abnormalities and social difficulties were the major contra-indications for such management. Ultrasonic echography at diagnosis (within 24 h) was performed in 50% of the units. Antibiotics were started using IV route in 18/24 units (75%) and ceftriaxone and aminoside were respectively prescribed in 100% and 29.4% of the units for a duration of 1 to 5 days before switching to the oral route. Antibiotherapy was started orally in 6 units and cefixime was chosen by 5 of them. Follow-up consultations were scheduled in 100% of the units but with various delay after initiation of the treatment. The total duration of treatment was mostly 10 days and oral prophylactic antibiotherapy was prescribed by 10/24 centres after completion of the treatment. Cystoureterography was systematically realized by 83.3% of the units., Conclusions: Despite important differences in the management of acute pyelonephritis in Ile-de-France, a majority of the units follows similar therapeutic modalities. In the absence of consensus, new recommendations are necessary concerning the management of pyelonephritis in infants and children in France.

Aim: To determine cognitive performances and affective development of a cohort of very premature babies at the age of 4 years., Population and Methods: Longitudinal case-control study. Newborns less than 33 weeks gestation were included from 1992 to 1994 and were matched with two full-term newborns. At 4 years of age, they have been evaluated for medical status, cognitive functions with the K-ABC test and affective condition with the PSA and Conners' tests., Results: The preterm group was significantly different from the controls for: a smaller height, (P < 0.01), a lower socioeconomic level (P = 0.027), a lower nursery school level (44% versus 27,6%, P = 0.05), the incapacity to draw "a bonhomme" (55,3% versus 93%, P < 0.001), lower performances for the K-ABC and PSA tests, a pathologic Conners score (20.4% versus 2.4%, P < 0.001). Multivariate analysis by logistic regression showed a similar neuropsychological results: a lower score of K-ABC (< 80, P = 0.0006, odds-ratio = 33.2), and a lower social competence score of PSA (< 45, P = 0.004, odds-ratio = 35.9)., Conclusion: Follow-up of premature babies is required, and measures to prevent or minimize cognitive and social disabilities are mandatory.

Sickle-cell disease (SCD) is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumonococcal bacteremia and meningitis due to S. pneumoniae are often lethal and justify the penicillin prophylaxis, which has provided a dramatic decrease in early mortality bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia, because they are often intricated. Osteomyelitis is generally due to Salmonella, most often S. enteritidis. Multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Osteomyelitis is less frequent in developed countries and must been differentiated with bone infarction by use of bone scintigraphy. Parvovirus B19 infection causes acute erythroblastopenias. Malaria does not result in cerebral malaria, but can lead to severe anaemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (osteomyelitis, meningitis), and M. pneumoniae (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at three months of age and no closely-spaced immunizations, most notably against peumococci, hepatitis B virus, S. typhi and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. New conjugated pneumococcal vaccines are effective in protecting very young infants and should therefore be used in sickle cell patients.

Sickle cell anaemia is a chronic disease which evolves on the background of a basal state punctuated by critical periods, often with complications requiring overall treatment. The management of both periods must be well integrated into the treatment programme. In order to treat occlusive crisis, medical staff must be well trained and equipped for the complicated clinical diagnoses involved in drepanocytosis: bone infarction or osteomyelitis, pneumonia or acute chest syndrome, multifocal crisis or severe infectious disease. Neonatal diagnosis is the best way for early treatment by preventing severe pneumococcal diseases, ensuring sufficient hydration and appropriate surveillance, as well as providing family education. Much progress has been made over the last decade in the early treatment of retinitis, biliary lithiasis, and aseptic hip necrosis. It is also important to ensure accurate prescriptions for hydroxyurea. Specialised centres for drepanocytosis treatment are now a growing necessity and should be encouraged in order to provide treatment for dispersed patients against a relatively little known disease.

Objective: To investigate the diagnostic value of the physical examination and electrocardiogram in the evaluation of heart murmur in new patients referred to the pediatric cardiologist., Method: From 1 April to 30 September 1998, all consecutive patients referred to the pediatric cardiology clinic for evaluation of heart murmur were included. They were prospectively categorized with no heart disease, possible heart disease or definite heart disease based on history and physical examination. They then underwent electrocardiogram with which the diagnosis was reevaluated by the pediatric cardiologist. Lastly, a doppler-echocardiography was systematically performed., Results: In 120 children aged four days to 14 years (median: ten months), 72 (60%) showed abnormalities on doppler-echocardiography and 48 (40%) no heart disease. After physical examination, 52 patients were categorized with no heart disease: 45 patients had a normal doppler-echocardiography; in three of them, the diagnosis was incorrectly modified to possible heart disease on the basis of the electrocardiogram. In the other seven children, the electrocardiogram was normal and the doppler-echocardiography revealed minor (n = 5) or moderate (n = 2) heart defects. Nineteen patients were suspected of having possible heart disease, no diagnosis was modified after analysis of the electrocardiogram and six had normal doppler-echocardiography; 49 patients were correctly diagnosed as having definite heart disease. The sensibility of the physical examination was 90.3%, the specificity was 93.8%, the positive predictive value 95.6% and the negative predictive value 86.5%., Conclusion: The electrocardiogram is of no help in the discrimination between heart disease and no heart disease in children referred to the pediatric cardiologist for a cardiac murmur. The physical examination is able to differentiate children with or without heart disease in most of the cases.