An empirical approach to the definition of the target margins in eye radiosurgery.

INTRODUCTION: A system for stabilizing and monitoring eye movements during LINAC-based photon beam one single fraction stereotactic radiotherapy was developed at our Institution. This study aimed to describe the feasibility and the efficacy of our noninvasive optical localization system that was developed, tested, and applied in 20 patients treated for uveal melanoma. METHODS: Our system consisted of a customized thermoplastic mask to immobilize the head, a gaze fixation LED, and a digital micro-camera. The localization procedure, which required the active collaboration of the patient, served to monitor the eye movements during all phases of the treatment, starting from the planning computed tomography up to the administration of radiotherapy, and allowed the operators to suspend the procedure and to interact with the patient in case of large movements of the pupil. RESULTS: Twenty patients were treated with stereotactic radiosurgery (27 Gy in one fraction) for primary uveal melanoma. All patients showed a good tolerance to the treatment; until now, all patients were in local control during the follow up and one died for distant progression 6 months after radiosurgery. CONCLUSIONS: This study showed that this noninvasive technique, based on eye position control, is appropriate and can contribute to the success of LINAC-based stereotactic radiotherapy. A millimetric safety margin to the clinical target volume was adequate to take account for the organ movement. All patients treated till now showed a good local control; failures in the disease control were due to metastatic spread.

Photon-based high-dose single-fraction radiosurgery, an effective treatment modality for recurrent uveal melanoma.

Introduction: To evaluate and report the outcome of a patient with locally recurrent uveal melanoma (UM) previously treated with brachytherapy (BT), using a second personalized globe-sparing radiotherapy approach. Material and methods: In June 2020, a 78-year-old man arrived at our institution with diplopia and suspected uveal melanoma. At the ophthalmological evaluation (B-scan and A-scan ultrasonography) a lesion in the right eye at 6-7 hours of about 5 mm thickness, with internal lacunar areas, approximately 7 mm away from the limbus, was observed. The patient underwent ruthenium plaque BT at a total dose of 110 Gy prescribed to the apex of the tumour. At the follow-up, the lesion was under control until September 2021, but it recurred with a satellite exudative detachment in the lower and temporal sectors 7-10 hours. At the B-scan the lesion had a maximum thickness of 4.6 mm. Subsequently, in a multidisciplinary discussion, one single fraction stereotactic radiosurgery was scheduled. The prescribed dose was 27 Gy in the de-novo lesion and 24 Gy in the previously irradiated site. Stereotactic radiosurgery was performed in October 2021. Results: The time interval between the 2 treatments was 15 months. Twenty months after recurrence, local tumour control was observed, and no metastases were detected on follow-up examinations. No severe acute or late toxicity was observed due to the retreatment. Conclusions: Photon stereotactic radiotherapy is a feasible, acceptably tolerated modality, and it represents an eye-preserving treatment also for patients with recurrent UM unfit for BT.

3D enamel thickness in Neandertal and modern human permanent canines.

Enamel thickness figures prominently in studies of human evolution, particularly for taxonomy, phylogeny, and paleodietary reconstruction. Attention has focused on molar teeth, through the use of advanced imaging technologies and novel protocols. Despite the important results achieved thus far, further work is needed to investigate all tooth classes. We apply a recent approach developed for anterior teeth to investigate the 3D enamel thickness of Neandertal and modern human (MH) canines. In terms of crown size, the values obtained for both upper and lower unworn/slightly worn canines are significantly greater in Neandertals than in Upper Paleolithic and recent MH. The 3D relative enamel thickness (RET) is significantly lower in Neandertals than in MH. Moreover, differences in 3D RET values between the two groups appear to decrease in worn canines beginning from wear stage 3, suggesting that both the pattern and the stage of wear may have important effects on the 3D RET value. Nevertheless, the 3D average enamel thickness (AET) does not differ between the two groups. In both groups, 3D AET and 3D RET indices are greater in upper canines than in lower canines, and overall the enamel is thicker on the occlusal half of the labial aspect of the crown, particularly in MH. By contrast, the few early modern humans investigated show the highest volumes of enamel while for all other components of 3D enamel, thickness this group holds an intermediate position between Neandertals and recent MH. Overall, our study supports the general findings that Neandertals have relatively thinner enamel than MH (as also observed in molars), indicating that unworn/slightly worn canines can be successfully used to discriminate between the two groups. Further studies, however, are needed to understand whether these differences are functionally related or are the result of pleiotropic or genetic drift effects.

Massive Osteochondral Lesion of the Talus in a Skeletally Immature Patient Associated With a Tarsal Coalition and Valgus Hindfoot.

Rarely, osteochondral lesions of the talus occur without a history of trauma. Accurate interpretation of the mechanical load distributions onto the ankle leading to potential atraumatic cartilage damage must always be studied. The published data on the optimal treatment of talar osteochondral lesions in skeletally immature patients are scarce, especially when the lesions are associated with hindfoot malalignment. We describe the case of a pediatric female with an atraumatic osteochondral lesion of the talus associated with a talocalcaneal coalition and a valgus hindfoot, which we consider the first case to be reported. She presented with prolonged bilateral ankle pain and catching during gait of approximately 2 years' duration with a restricted range of motion, with the pain more excruciating in the right ankle. Radiographs revealed a large osteochondral lesion located at the lateral talar dome. The patient underwent partial osteochondral allograft transplantation, together with hindfoot realignment and coalition resection with a fat graft interposition. At the 2-year follow-up examination, the patient was free of pain in her right foot and ankle, with no signs of radiologic failure.

Moral Disengagement Strategies in Sex Offenders.

Sexual abuse is a heterogeneous phenomenon. The literature on sexual offenders considers risk factors in the individual and familial history as well as precursors such as cognitive distortions, defence mechanisms and moral disengagement (MD) mechanisms. This study investigates the MD in sex offenders and non-sex offenders in a sample of 362 males comprising a control group of 268 non-offenders, a group of 42 detained sex offenders and a group of 52 detained non-sex offenders. Participants were administered a semi-structured interview and the Moral Disengagement Scale (MDS). The results show a significant difference between the jailed participants (non-sex offenders and sex offenders) and controls; offenders were found to generally display overall higher levels of MD. Among the jailed participants, sex offenders seem to make more use of MD mechanisms than non-sex offenders.

Piscivory in a Miocene Cetotheriidae of Peru: first record of fossilized stomach content for an extinct baleen-bearing whale.

Instead of teeth, modern mysticetes bear hair-fringed keratinous baleen plates that permit various bulk-filtering predation techniques (from subsurface skimming to lateral benthic suction and engulfment) devoted to various target prey (from small invertebrates to schooling fish). Current knowledge about the feeding ecology of extant cetaceans is revealed by stomach content analyses and observations of behavior. Unfortunately, no fossil stomach contents of ancient mysticetes have been described so far; the investigation of the diet of fossil baleen whales, including the Neogene family Cetotheriidae, remains thus largely speculative. We report on an aggregate of fossil fish remains found within a mysticete skeleton belonging to an undescribed late Miocene (Tortonian) cetotheriid from the Pisco Formation (Peru). Micro-computed tomography allowed us to interpret it as the fossilized content of the forestomach of the host whale and to identify the prey as belonging to the extant clupeiform genus Sardinops. Our discovery represents the first direct evidence of piscivory in an ancient edentulous mysticete. Since among modern mysticetes only Balaenopteridae are known to ordinarily consume fish, this fossil record may indicate that part of the cetotheriids experimented some degree of balaenopterid-like engulfment feeding. Moreover, this report corresponds to one of the geologically oldest records of Sardinops worldwide, occurring near the Tortonian peak of oceanic primary productivity and cooling phase. Therefore, our discovery evokes a link between the rise of Cetotheriidae; the setup of modern coastal upwelling systems; and the radiation of epipelagic, small-sized, schooling clupeiform fish in such highly productive environments.

Three-dimensional parametric mapping in quantitative micro-CT imaging of post-surgery femoral head-neck samples: preliminary results.

Osteoporosis and pathological increased occurrence of fractures are an important public health problem. They may affect patients' quality of life and even increase mortality of osteoporotic patients, and consequently represent a heavy economic burden for national healthcare systems. The adoption of simple and inexpensive methods for mass screening of population at risk may be the key for an effective prevention. The current clinical standards of diagnosing osteoporosis and assessing the risk of an osteoporotic bone fracture include dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) for the measurement of bone mineral density (BMD). Micro-computed tomography (micro-CT) is a tomographic imaging technique with very high resolution allowing direct quantification of cancellous bone microarchitecture. The Authors performed micro-CT analysis of the femoral heads harvested from 8 patients who have undergone surgery for hip replacement for primary and secondary degenerative disease to identify possible new morphometric parameters based on the analysis of the distribution of intra-subject microarchitectural parameters through the creation of parametric images. Our results show that the micro-architectural metrics commonly used may not be sufficient for the realistic assessment of bone microarchitecture of the femoral head in patients with hip osteoarthritis. The innovative micro-CT approach considers the entire femoral head in its physiological shape with all its components like cartilage, cortical layer and trabecular region. The future use of these methods for a more detailed study of the reaction of trabecular bone for the internal fixation or prostheses would be desirable.

[Hybrid imaging: present and future of non-invasive diagnosis]. / Imaging ibrido: presente e futuro della diagnostica non invasiva.

The integration of complementary information from different medical imaging techniques opened, since the 90s, new scenarios and possibilities for non-invasive diagnosis. The anatomo-functional information obtained with the image fusion (i.e., by composing PET and CT or SPECT and CT), is greater than the sum of information given by each modality, and allows quantitative evaluation of functional parameters through the application of specific model-based image processing. Before the introduction of integrated multimodal scanners from most manufacturers (hardware fusion), many software techniques have been used to allow image fusion from different modalities; such methods of software fusion is still important for all modalities that cannot by merged in a single scanner, or whenever the patient movement can introduce inter-modality misalignments within the same exam in an integrated scanner or if each modality is utilized at different times and on separate scanners. This article summarizes the software and hardware evolution of clinical and preclinical hybrid imaging, and discusses the outcome of this technology in the clinical environment with particular emphasis on the cardiovascular application.

Maternal High-Fat Diet Programs White and Brown Adipose Tissues In Vivo in Mice, with Different Metabolic and Microbiota Patterns in Obesity-Susceptible or Obesity-Resistant Offspring.

Maternal obesity causes metabolic dysfunction in the offspring, including dysbiosis, overeating, obesity, and type 2 diabetes. Early-life phases are fundamental for developing subcutaneous (SAT) and brown adipose tissues (BAT), handling energy excesses. Imaging of 18F-fluorodeoxyglucose by positron emission tomography (PET) and radiodensity by computerized tomography (CT) allows assessing adipose tissue (AT) whitening and browning in vivo and the underlying metabolic efficiency. Our aim was to examine these in vivo traits in SAT and BAT concerning gut microbiota composition in 1- and 6-month-old mice born to normal (NDoff) and high-fat diet-fed dams (HFDoff), accounting for body weight responses. We found low radiodensity (high lipids) in HFDoff SAT at 1 month, relating to an increased abundance of Dorea genus in the caecum and activation of the fatty acid biosynthetic pathway. Instead, low BAT radiodensity and glucose uptake were seen in adult HFDoff. Glucose was shifted in favor of BAT at 1 month and SAT at 6 months. In adults, unclassified Enterococcaceae and Rikenellaceae, and Bacillus genera were negatively related to BAT, whereas unclassified Clostridiales genera were related to SAT metabolism. Stratification of HFDoff based on weight-response, namely maternal induced obesity (MIO-HFDoff) or obesity-resistant (MIOR-HFDoff), showed sex dimorphism. Both subgroups were hyperphagic, but only obese mice had hyper-leptinemia and hyper-resistinemia, together with BAT dysfunction, whereas non-obese HFDoff had hyperglycemia and SAT hypermetabolism. In the caecum, unclassified Rikenellaceae (10-fold enrichment in MIO-HFDoff) and Clostridiales genera (4-fold deficiency in MIOR-HFDoff) were important discriminators of these two phenotypes. In conclusion, SAT whitening is an early abnormality in the offspring of HFD dams. In adult life, maternal HFD and the induced excessive food intake translates into a dimorphic phenotype involving SAT, BAT, and microbiota distinctively, reflecting maternal diet*sex interaction. This helps explain inter-individual variability in fetal programming and the higher rates of type 2 diabetes observed in adult women born to obese mothers, supporting personalized risk assessment, prevention, and treatment.

Liver and White/Brown Fat Dystrophy Associates with Gut Microbiota and Metabolomic Alterations in 3xTg Alzheimer's Disease Mouse Model.

Metabolic impairments and liver and adipose depots alterations were reported in subjects with Alzheimer's disease (AD), highlighting the role of the liver-adipose-tissue-brain axis in AD pathophysiology. The gut microbiota might play a modulating role. We investigated the alterations to the liver and white/brown adipose tissues (W/BAT) and their relationships with serum and gut metabolites and gut bacteria in a 3xTg mouse model during AD onset (adulthood) and progression (aging) and the impact of high-fat diet (HFD) and intranasal insulin (INI). Glucose metabolism (18FDG-PET), tissue radiodensity (CT), liver and W/BAT histology, BAT-thermogenic markers were analyzed. 16S-RNA sequencing and mass-spectrometry were performed in adult (8 months) and aged (14 months) 3xTg-AD mice with a high-fat or control diet. Generalized and HFD resistant deficiency of lipid accumulation in both liver and W/BAT, hypermetabolism in WAT (adulthood) and BAT (aging), abnormal cytokine-hormone profiles, and liver inflammation were observed in 3xTg mice; INI could antagonize all these alterations. Specific gut microbiota-metabolome profiles correlated with a significant disruption of the gut-microbiota-liver-adipose axis in AD mice. In conclusion, fat dystrophy in liver and adipose depots contributes to AD progression, and associates with altered profiles of the gut microbiota, which candidates as an appealing early target for preventive intervention.

Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches.

Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While bacteria, particularly Pseudomonas aeruginosa, have a well-established negative effect on CF lung disease, the impact of fungal infections remains unclear. In patients with CF, inhalation of Aspergillus conidia can cause allergic bronchopulmonary aspergillosis (ABPA), a Th2-mediated lung disease that can contribute to disease progression. Clinical features, diagnostic criteria and treatment of ABPA are still a matter of debate. Given the consequences of a late ABPA diagnosis or the risk of ABPA overdiagnosis, it is imperative that the diagnostic criteria guidelines are reviewed and standardized. Along with traditional criteria, radiological features are emerging as tools for further classification as well as novel immunological tests. Corticosteroids, itraconazole and voriconazole continue to be the bedrock of ABPA therapy, but other molecules, such as posaconazole, vitamin D, recombinant INF-γ and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators, have been showing positive results. However, few studies have been conducted recruiting CF patients, and more research is needed to improve the prevention and the classification of clinical manifestations as well as to personalize treatment. Early recognition and early treatment of fungal infections may be fundamental to prevent progression of CF disease. The aim of this narrative review is to give an update on ABPA in children with CF.

[Osteo-articular infections by Kingella kingae in children in a highly complex pediatric hospital: epidemiology and associated factors]. / Infecciones osteo-articulares por Kingella kingae en niños en un hospital pediátrico de alta complejidad: epidemiología y factores asociados.

BACKGROUND: The epidemiology of osteoarticular infections (IOA) has changed in recent years. The incidence of Kingella kingae in Latin America is unknown. AIMS: To describe the epidemiology in patients with IOA in a children hospital. To estimate the incidence of IOA due to K. kingae and compare with other etiologies. METHODS: Prospective cohort. Patients older than 1 month hospitalized between March, 1th 2017 and February, 28th 2019 with suspected IOA and diagnostic procedure (biopsy or arthrocentesis) were included. STATA 13 was used. RESULTS: n: 84 patients. The etiology was identified in 58 patients (69.1%). Staphylococus aureus predominated (n: 44; 52.4%) and K. kingae (n: 9; 10.8%). In the period studied, the incidence of IOA by K. kingae was 10.8 cases per 100 hospitalized IOA. In multivariate analysis, age less than 4 years (OR 13.8, 95% CI 5.5-82.7), recent respiratory symptoms (OR 5.7, 95% CI 3.5-31.6, p 0.04) and normalization before the fifth day of C-reactive protein (CRP) (OR 3.38 95% CI 1.8-16.3, p 0.01) were associated with IOA by K. kingae. CONCLUSIONS: In this cohort of children the incidence of K. kingae was 10.8 cases per 100 IOA. Kingella kingae represented the second documented etiology, after S. aureus. Age under 4 years, recent respiratory symptoms and normalization before the fifth day of quantitative CRP were statistically associated with IOA by K. kingae.

Microbiota signatures relating to reduced memory and exploratory behaviour in the offspring of overweight mothers in a murine model.

An elevated number of women of reproductive age are overweight, predisposing their offspring to metabolic and neuropsychiatric disorders. Gut microbiota is influenced by maternal factors, and has been implicated in the pathogenesis of neurodegenerative diseases. Our aim was to explore the effects of maternal high-fat feeding on the relationship linking gut microbiota and cognitive development in the offspring. Murine offspring born to dams undergoing normal diet (NDm) and high-fat diet (HFDm) were studied at 1 or 6 months of age to assess cognitive function by Y-maze test, cerebral glucose metabolism and insulin sensitivity by Positron Emission Tomography, brain density by Computed Tomography, microbiota profile (colon, caecum) and inferred metabolic pathways (KEGG analysis) by 16S ribosomal RNA sequencing. From 3 weeks post-weaning, mice born to HFDm developed hyperphagia and overweight, showing reduction in memory and exploratory behaviour, and brain insulin resistance in adulthood. We identified a panel of bacteria characterizing offspring born to HFD dams from early life, and correlating with dysfunction in memory and exploratory behaviour in adults (including Proteobacteria phylum, Parabacteroides and unclassified Rikenellaceae genera). Microbiota-derived metabolic pathways involved in fatty acid, essential aminoacid and vitamin processing, sulphur metabolism, glutaminergic activation and Alzheimer's disease were differently present in the HFDm and NDm offspring groups. Our results document tight relationships between gut dysbiosis and memory and behavioural impairment in relation to maternal HFD. Persistent bacterial signatures induced by maternal HFD during infancy can influence cognition during adulthood, opening the possibility of microbiota-targeted strategies to contrast cognitive decline.

Combined Effect of Fatty Diet and Cognitive Decline on Brain Metabolism, Food Intake, Body Weight, and Counteraction by Intranasal Insulin Therapy in 3×Tg Mice.

Obesity and cognitive decline can occur in association. Brain dysmetabolism and insulin resistance might be common underlying traits. We aimed to examine the effect of high-fat diet (HFD) on cognitive decline, and of cognitive impairment on food intake and body-weight, and explore efficacy of chronic intranasal insulin (INI) therapy. We used control (C) and triple transgenic mice (3×Tg, a model of Alzheimer's pathology) to measure cerebral mass, glucose metabolism, and the metabolic response to acute INI administration (cerebral insulin sensitivity). Y-Maze, positron emission-computed tomography, and histology were employed in 8 and 14-month-old mice, receiving normal diet (ND) or HFD. Chronic INI therapy was tested in an additional 3×Tg-HFD group. The 3×Tg groups overate, and had lower body-weight, but similar BMI, than diet-matched controls. Cognitive decline was progressive from HFD to 3×Tg-ND to 3×Tg-HFD. At 8 months, brain fasting glucose uptake (GU) was increased by C-HFD, and this effect was blunted in 3×Tg-HFD mice, also showing brain insulin resistance. Brain mass was reduced in 3×Tg mice at 14 months. Dentate gyrus dimensions paralleled cognitive findings. Chronic INI preserved cognition, dentate gyrus and metabolism, reducing food intake, and body weight in 3×Tg-HFD mice. Peripherally, leptin was suppressed and PAI-1 elevated in 3×Tg mice, correlating inversely with cerebral GU. In conclusion, 3×Tg background and HFD exert additive (genes*lifestyle) detriment to the brain, and cognitive dysfunction is accompanied by increased food intake in 3×Tg mice. PAI-1 levels and leptin deficiency were identified as potential peripheral contributors. Chronic INI improved peripheral and central outcomes.

Radiobiological Effectiveness of Ultrashort Laser-Driven Electron Bunches: Micronucleus Frequency, Telomere Shortening and Cell Viability.

Laser-driven electron accelerators are capable of producing high-energy electron bunches in shorter distances than conventional radiofrequency accelerators. To date, our knowledge of the radiobiological effects in cells exposed to electrons using a laser-plasma accelerator is still very limited. In this study, we compared the dose-response curves for micronucleus (MN) frequency and telomere length in peripheral blood lymphocytes exposed to laser-driven electron pulse and X-ray radiations. Additionally, we evaluated the effects on cell survival of in vitro tumor cells after exposure to laser-driven electron pulse compared to electron beams produced by a conventional radiofrequency accelerator used for intraoperative radiation therapy. Blood samples from two different donors were exposed to six radiation doses ranging from 0 to 2 Gy. Relative biological effectiveness (RBE) for micronucleus induction was calculated from the alpha coefficients for electrons compared to X rays (RBE = alpha laser/alpha X rays). Cell viability was monitored in the OVCAR-3 ovarian cancer cell line using trypan blue exclusion assay at day 3, 5 and 7 postirradiation (2, 4, 6, 8 and 10 Gy). The RBE values obtained by comparing the alpha values were 1.3 and 1.2 for the two donors. Mean telomere length was also found to be reduced in a significant dose-dependent manner after irradiation with both electrons and X rays in both donors studied. Our findings showed a radiobiological response as mirrored by the induction of micronuclei and shortening of telomere as well as by the reduction of cell survival in blood samples and cancer cells exposed in vitro to laser-generated electron bunches. Additional studies are needed to improve preclinical validation of the radiobiological characteristics and efficacy of laser-driven electron accelerators in the future.

Evaluation of the effect of a gamma irradiated DBM-pluronic F127 composite on bone regeneration in Wistar rat.

Demineralized bone matrix (DBM) is widely used for bone regeneration. Since DBM is prepared in powder form its handling properties are not optimal and limit the clinical use of this material. Various synthetic and biological carriers have been used to enhance the DBM handling. In this study we evaluated the effect of gamma irradiation on the physical-chemical properties of Pluronic and on bone morphogenetic proteins (BMPs) amount in DBM samples. In vivo studies were carried out to investigate the effect on bone regeneration of a gamma irradiated DBM-Pluronic F127 (DBM-PF127) composite implanted in the femur of rats. Gamma irradiation effects (25 kGy) on physical-chemical properties of Pluronic F127 were investigated by rheological and infrared analysis. The BMP-2/BMP-7 amount after DBM irradiation was evaluated by ELISA. Bone regeneration capacity of DBM-PF127 containing 40% (w/w) of DBM was investigated in transcortical holes created in the femoral diaphysis of Wistar rat. Bone porosity, repaired bone volume and tissue organization were evaluated at 15, 30 and 90 days by Micro-CT and histological analysis. The results showed that gamma irradiation did not induce significant modification on physical-chemical properties of Pluronic, while a decrease in BMP-2/BMP-7 amount was evidenced in sterilized DBM. Micro-CT and histological evaluation at day 15 post-implantation revealed an interconnected trabeculae network in medullar cavity and cellular infiltration and vascularization of DBM-PF127 residue. In contrast a large rate of not connected trabeculae was observed in Pluronic filled and unfilled defects. At 30 and 90 days the DBM-PF127 samples shown comparable results in term of density and thickness of the new formed tissue respect to unfilled defect. In conclusion a gamma irradiated DBM-PF127 composite, although it may have undergone a significant decrease in the concentration of BMPs, was able to maintains bone regeneration capability.

Effects of long time exposure to simulated micro- and hypergravity on skeletal architecture.

This manuscript reports the structural alterations occurring in mice skeleton as a consequence of the longest-term exposition (90 days) to simulated microgravity (hindlimb unloading) and hypergravity (2g) ever tested. Bone microstructural features were investigated by means of standard Cone Beam X-ray micro-CT, Synchrotron Radiation micro-CT and histology. Morphometric analysis confirmed deleterious bone architectural changes in lack of mechanical loading with a decrease of bone volume and density, while bone structure alterations caused by hypergravity were less evident. In the femurs from hypergravity-exposed mice, the head/neck cortical thickness increment was the main finding. In addition, in these mice the rate of larger trabeculae (60-75 µm) was significantly increased. Interestingly, the metaphyseal plate presented a significant adaptation to gravity changes. Mineralization of cartilage and bone deposition was increased in the 2g mice, whereas an enlargement of the growth plate cartilage was observed in the hindlimb unloaded group. Indeed, the presented data confirm and reinforce the detrimental effects on bone observed in real space microgravity and reveal region-specific effects on long bones. Finally these data could represent the starting point for further long-term experimentations that can deeply investigate the bone adaptation mechanisms to different mechanical force environments.

Infecciones osteo-articulares por Kingella kingae en niños en un hospital pediátrico de alta complejidad: epidemiología y factores asociados / Osteo-articular infections by Kingella kingae in children in a highly complex pediatric hospital: epidemiology and associated factors

Resumen Introducción: La epidemiología de las infecciones osteo-articulares (IOA) se ha modificado en los últimos años. La incidencia de Kingella kingae en Latinoamérica es desconocida. Objetivo: Describir la epidemiología de los niños con IOA. Estimar la incidencia de IOA causadas por K. kingae y compararlas con otras etiologías. Material y Métodos: Cohorte prospectiva. Se incluyeron pacientes mayores de 1 mes de edad, hospitalizados entre el 1 de marzo de 2017 y 28 de febrero de 2019, con sospecha de IOA y procedimiento diagnóstico (biopsia o artrocentesis). Se utilizó STATA 13. Resultados: n: 84 pacientes. Se identificó la etiología en 58 pacientes (69,1%). Predominaron Staphylococcus aureus (n: 44; 52,4%) y K. kingae (n: 9; 10,8%). En el período estudiado, la incidencia de IOA por K. kingae fue de 10,8 casos cada 100 IOA hospitalizadas. En el análisis multivariado, la edad inferior a 4 años (OR 13,8, IC95% 5,5-82,7), el cuadro respiratorio reciente (OR 5,7, IC95% 3,5-31,6, p 0,04) y la normalización antes del quinto día de la proteína C reactiva (PCR) (OR 3,8 IC95% 1,8- 16,3, p 0,01) se asociaron con las IOA por K. kingae. Conclusiones: En esta cohorte de niños, la incidencia de K.kingae fue de 10,8 casos cada 100 IOA. Kingella kingae representó la segunda etiología documentada, luego de S. aureus. La edad inferior a 4 años, el cuadro respiratorio reciente y la normalización antes del quinto día de la PCR cuantitativa se asociaron estadísticamente con IOA por K. kingae.

Abstract Background: The epidemiology of osteoarticular infections (IOA) has changed in recent years. The incidence of Kingella kingae in Latin America is unknown. Aims: To describe the epidemiology in patients with IOA in a children hospital. To estimate the incidence of IOA due to K. kingae and compare with other etiologies. Methods: Prospective cohort. Patients older than 1 month hospitalized between March, 1th 2017 and February, 28th 2019 with suspected IOA and diagnostic procedure (biopsy or arthrocentesis) were included. STATA 13 was used. Results: n: 84 patients. The etiology was identified in 58 patients (69.1%). Staphylococus aureus predominated (n: 44; 52.4%) and K. kingae (n: 9; 10.8%). In the period studied, the incidence of IOA by K. kingae was 10.8 cases per 100 hospitalized IOA. In multivariate analysis, age less than 4 years (OR 13.8, 95% CI 5.5-82.7), recent respiratory symptoms (OR 5.7, 95% CI 3.5-31.6, p 0.04) and normalization before the fifth day of C-reactive protein (CRP) (OR 3.38 95% CI 1.8-16.3, p 0.01) were associated with IOA by K. kingae. Conclusions: In this cohort of children the incidence of K. kingae was 10.8 cases per 100 IOA. Kingella kingae represented the second documented etiology, after S. aureus. Age under 4 years, recent respiratory symptoms and normalization before the fifth day of quantitative CRP were statistically associated with IOA by K. kingae.

Duplication of the transverse colon in an adult: case report and review.

Tubular duplication of the colon is very rare especially in adulthood, because it is frequently symptomatic earlier in newborn life, so only few cases are reported in literature. Several theories are proposed to explain the onset and the evolution of gut malformations as the aberrant lumen recanalization or the diverticular theory, the alteration of the lateral closure of the embryonal disk or finally the dorsal protrusion of the yolk-sac for herniation or adhesion to the ectoderm for an abnormality of the longitudinal line, but none clarifies the exact genesis of duplication. We present a case of "Y-shaped" tubular duplication of the transverse colon in a 21-year-old adult, with a history of chronic pain and constipation, referred to our department for abdominal pain with retrosternal irradiation, treated with the resection of the aberrant bowel.

Istaroxime stimulates SERCA2a and accelerates calcium cycling in heart failure by relieving phospholamban inhibition.

BACKGROUND AND PURPOSE: Calcium handling is known to be deranged in heart failure. Interventions aimed at improving cell Ca(2) (+) cycling may represent a promising approach to heart failure therapy. Istaroxime is a new luso-inotropic compound that stimulates cardiac contractility and relaxation in healthy and failing animal models and in patients with acute heart failure (AHF) syndrome. Istaroxime is a Na-K ATPase inhibitor with the unique property of increasing sarcoplasmic reticulum (SR) SERCA2a activity as shown in heart microsomes from humans and guinea pigs. The present study addressed the molecular mechanism by which istaroxime increases SERCA2a activity. EXPERIMENTAL APPROACH: To study the effect of istaroxime on SERCA2a-phospholamban (PLB) complex, we applied different methodologies in native dog healthy and failing heart preparations and heterologous canine SERCA2a/PLB co-expressed in Spodoptera frugiperda (Sf21) insect cells. KEY RESULTS: We showed that istaroxime enhances SERCA2a activity, Ca(2) (+) uptake and the Ca(2) (+) -dependent charge movements into dog healthy and failing cardiac SR vesicles. Although not directly demonstrated, the most probable explanation of these activities is the displacement of PLB from SERCA2a.E2 conformation, independently from cAMP/PKA. We propose that this displacement may favour the SERCA2a conformational transition from E2 to E1, thus resulting in the acceleration of Ca(2) (+) cycling. CONCLUSIONS AND IMPLICATIONS: Istaroxime represents the first example of a small molecule that exerts a luso-inotropic effect in the failing human heart through the stimulation of SERCA2a ATPase activity and the enhancement of Ca(2) (+) uptake into the SR by relieving the PLB inhibitory effect on SERCA2a in a cAMP/PKA independent way.