The mRNA-Binding Protein RBM3 Regulates Activity Patterns and Local Synaptic Translation in Cultured Hippocampal Neurons.

The activity and the metabolism of the brain change rhythmically during the day/night cycle. Such rhythmicity is also observed in cultured neurons from the suprachiasmatic nucleus, which is a critical center in rhythm maintenance. However, this issue has not been extensively studied in cultures from areas less involved in timekeeping, as the hippocampus. Using neurons cultured from the hippocampi of newborn rats (both male and female), we observed significant time-dependent changes in global activity, in synaptic vesicle dynamics, in synapse size, and in synaptic mRNA amounts. A transcriptome analysis of the neurons, performed at different times over 24 h, revealed significant changes only for RNA-binding motif 3 (Rbm3). RBM3 amounts changed, especially in synapses. RBM3 knockdown altered synaptic vesicle dynamics and changed the neuronal activity patterns. This procedure also altered local translation in synapses, albeit it left the global cellular translation unaffected. We conclude that hippocampal cultured neurons can exhibit strong changes in their activity levels over 24 h, in an RBM3-dependent fashion.SIGNIFICANCE STATEMENT This work is important in several ways. First, the discovery of relatively regular activity patterns in hippocampal cultures implies that future studies using this common model will need to take the time parameter into account, to avoid misinterpretation. Second, our work links these changes in activity strongly to RBM3, in a fashion that is independent of the canonical clock mechanisms, which is a very surprising observation. Third, we describe here probably the first molecule (RBM3) whose manipulation affects translation specifically in synapses, and not at the whole-cell level. This is a key finding for the rapidly growing field of local synaptic translation.

First Phylogenetic Analysis of Malian SARS-CoV-2 Sequences Provides Molecular Insights into the Genomic Diversity of the Sahel Region.

We are currently facing a pandemic of COVID-19, caused by a spillover from an animal-originating coronavirus to humans occurring in the Wuhan region of China in December 2019. From China, the virus has spread to 188 countries and regions worldwide, reaching the Sahel region on March 2, 2020. Since whole genome sequencing (WGS) data is very crucial to understand the spreading dynamics of the ongoing pandemic, but only limited sequencing data is available from the Sahel region to date, we have focused our efforts on generating the first Malian sequencing data available. Screening 217 Malian patient samples for the presence of SARS-CoV-2 resulted in 38 positive isolates, from which 21 whole genome sequences were generated. Our analysis shows that both the early A (19B) and the later observed B (20A/C) clade are present in Mali, indicating multiple and independent introductions of SARS-CoV-2 to the Sahel region.

First phylogenetic analysis of Malian SARS-CoV-2 sequences provide molecular insights into the genomic diversity of the Sahel region

We are currently facing a pandemic of COVID-19, caused by a spillover from an animal-originating coronavirus to humans occuring in the Wuhan region, China, in December 2019. From China the virus has spread to 188 countries and regions worldwide, reaching the Sahel region on the 2nd of March 2020. Since whole genome sequencing (WGS) data is very crucial to understand the spreading dynamics of the ongoing pandemic, but only limited sequence data is available from the Sahel region to date, we have focused our efforts on generating the first Malian sequencing data available. Screening of 217 Malian patient samples for the presence of SARS-CoV-2 resulted in 38 positive isolates from which 21 whole genome sequences were generated. Our analysis shows that both, the early A (19B) and the fast evolving B (20A/C) clade, are present in Mali indicating multiple and independent introductions of the SARS-CoV-2 to the Sahel region.

IGF-1-Overexpressing Mesenchymal Stem/Stromal Cells Promote Immunomodulatory and Proregenerative Effects in Chronic Experimental Chagas Disease.

Mesenchymal stem/stromal cells (MSCs) have been investigated for the treatment of diseases that affect the cardiovascular system, including Chagas disease. MSCs are able to promote their beneficial actions through the secretion of proregenerative and immunomodulatory factors, including insulin-like growth factor-1 (IGF-1), which has proregenerative actions in the heart and skeletal muscle. Here, we evaluated the therapeutic potential of IGF-1-overexpressing MSCs (MSC_IGF-1) in a mouse model of chronic Chagas disease. C57BL/6 mice were infected with Colombian strain Trypanosoma cruzi and treated with MSCs, MSC_IGF-1, or vehicle (saline) six months after infection. RT-qPCR analysis confirmed the presence of transplanted cells in both the heart and skeletal muscle tissues. Transplantation of either MSCs or MSC_IGF-1 reduced the number of inflammatory cells in the heart when compared to saline controls. Moreover, treatment with MSCs or MSC_IGF-1 significantly reduced TNF-α, but only MSC treatment reduced IFN-γ production compared to the saline group. Skeletal muscle sections of both MSC- and MSC_IGF-1-treated mice showed a reduction in fibrosis compared to saline controls. Importantly, the myofiber area was reduced in T. cruzi-infected mice, and this was recovered after treatment with MSC_IGF-1. Gene expression analysis in the skeletal muscle showed a higher expression of pro- and anti-inflammatory molecules in MSC_IGF-1-treated mice compared to MSCs alone, which significantly reduced the expression of TNF-α and IL-1ß. In conclusion, our results indicate the therapeutic potential of MSC_IGF-1, with combined immunomodulatory and proregenerative actions to the cardiac and skeletal muscles.

Characteristics of older at-risk drinkers who drive after drinking and those who do not drive after drinking.

OBJECTIVE: To describe and compare characteristics of older adults who drive after drinking and those who do not, whether an intervention addressing at-risk drinking reduces risk among those reporting driving after drinking, and reasons reported for driving after drinking. METHODS: Secondary data analysis of a randomized trial testing the efficacy of a multifaceted intervention to reduce at-risk drinking among adults with a mean age of 68 years in primary care (N = 631). RESULTS: Almost a quarter of at-risk drinkers reported driving after drinking (N = 154). Compared to those who did not drive after drinking, those who did were more likely to be younger, male, and working. They consumed a higher average number of drinks per week, had more reasons they were considered at-risk drinkers, and were more likely to meet at-risk drinking criteria due to amount of drinking and binge drinking. Those driving after drinking at baseline reduced the frequency of this behavior at 3 and 12 months and there were no statistically significant differences in the proportions of persons still engaging in driving after drinking among those who were assigned to intervention or control groups. Reasons for driving after drinking included not thinking that it was a problem and having to get home. CONCLUSIONS: Driving after drinking is common in this population of older, at-risk drinkers recruited in primary care settings and, like younger adults, men and those reporting binge drinking are more likely to engage in this behavior. Given that this behavior is dangerous and the population of older adults is fast growing, interventions addressing driving after drinking are needed.

Parapharyngeal neuroglial heterotopia in Pierre Robin sequence: MR imaging findings.

Heterotopic neuroglial tissue is a rare lesion, occurring more frequently in the nasal cavities. Other rare locations are the orbit, the scalp, the palate, the pharynx, the parapharyngeal space and the lungs. They are usually detected occasionally because they are often asymptomatic, but sometimes they might present with dyspnoea, feeding difficulty, snorting and nasal flaring. Respiratory symptoms occur when heterotopic neuroglial tissue is located in the parapharyngeal space. We report a case of an infant affected by Pierre Robin sequence (PRS) who was admitted to our Institution for a worsening respiratory distress that was not explainable only by PRS.

[Morphological and functional aspects of the kidney in children]. / Aspetti morfologici e funzionali del rene in età pediatrica.

Ultrasonography is useful and effective in the evaluation of renal diseases in pediatric age. Sonography is well established as a screening tool to evaluate the kidney for the presence of renal obstruction. Distinction of the obstructed from the non obstructed dilated collecting system is a difficult problem. Doppler Ultrasonography offers potential advantages in the evaluation of childhood genitourinary tract abnormalities.

Prenatal ultrasonographic findings of dominant polycystic kidney disease and postnatal renal evolution.

Autosomal dominant polycystic kidney disease (ADPKD) is a relatively common genetic disorder, and its prenatal diagnosis has been reported with increasing frequency. Nevertheless, no data are available on the significance of prenatal ultrasound (US) patterns in predicting postnatal renal function and outcome. We report on one case of ADPKD diagnosed prenatally by US, and on two cases diagnosed immediately after birth, with different prenatal US and renal outcomes. Data on prenatal US findings and postnatal renal evolution are scanty and largely incomplete. Apparently, none of the prenatal findings are consistently different in cases with and without normal postnatal renal function and blood pressure. More complete information on prenatal US findings and postnatal renal evolution is urgently needed.

[Combined heart-kidney transplantation in pediatric age]. / Trapianto combinato cuore-rene in età pediatrica.

A case of simultaneous heart and kidney transplantation is presented in a 12 years old girl. The patient suffered from dilated cardiomyopathy and end-stage kidney disease. Bilateral vesico-renal refluxes were corrected at the same time of the duplex transplantation. A multiorgan harvesting from a pediatric 8 years old donor was utilized. Follow-up is 40 months. Cytomegalovirus (CMV) infection and acute tubular necrosis from haemoglobinuria were transient complications. Hemolysis from bypass and extracorporeal circulation was involved as pathogenetic factor of the acute tubular necrosis. Cardiac and renal function remain excellent and the child is fully recovered and resumed a normal and active life. Combined heart and kidney transplantation may be of benefit in selected patients, also in pediatric age.

[Ultrasonography in hypertrophic stenosis of the pylorus: clinico-therapeutic implications in borderline cases]. / L'ecografia nella stenosi ipertrofica del piloro: implicazioni clinico-terapeutiche nei reperti dubbi.

Previous publications attempted to define normal and abnormal ranges in the measurement of pyloric length (L), breadth (D), muscle thickness (S), volume (V) and muscle index (MI). We examined with US 286 patients with suspected hypertrophic pyloric stenosis and investigated all the above diagnostic criteria. Normal and abnormal ranges were in agreement in all five measurements, though less apparent for pyloric volume and muscle index. The patients with borderline values were 46 (16%) for pyloric muscle thickness, 98 (34%) for breadth, 52 (18%) for length, but only 22 (7.7%) for pyloric volume and muscle index. Borderline patients received medical therapy with the antispasmodic drug metaclopramide hydrochloride and they were examined with US after 15 days. Only 8 of 22 borderline patients (36%) developed a typical hypertrophic pyloric stenosis. In the others, pyloric volume was reduced and the symptoms subsided. Pyloric parameters cannot be always measured accurately, but pyloric volume and muscle index measures better distinguish normal from abnormal findings. The formula for pyloric volume calculation is simpler than that for pyloric muscle index calculation and easier to memorize, also because no correction for body weight is necessary.

Painless scrotal masses in the pediatric population: prevalence and age distribution of different pathological conditions--A 10 year retrospective multicenter study.

PURPOSE: In the pediatric population a broad spectrum of intrascrotal pathology ranging from congenital to neoplastic lesions present as a painless scrotal mass. The aim of our 10-year retrospective study was to review 71 pediatric cases of a painless scrotal mass to determine the overall and age specific prevalence of diseases manifesting as such masses. MATERIALS AND METHODS: From 1980-1991, 71 patients 1 day to 16 years old with a painless scrotal mass underwent evaluation using 7.5 or 10 MHz. ultrasound probes with transverse and longitudinal sections. RESULTS: The painless scrotal mass was testicular in 61 cases (86%, 28 neoplasms, 27 congenital malformations, and 6 posttraumatic/inflammatory lesions) and extratesticular in 10 (14%, 5 neoplasms, 2 hematoceles, 2 pachyvaginitis and 1 sebaceous cyst). Patient age distribution showed 2 peaks at 0 to 1-year and 13 to 14-year intervals. More than a third of the painless scrotal masses (24 cases) were found during the first year of life, predominantly congenital anomalies (in utero torsion) and neoplasia. A total of 45 patients (63%) underwent surgery (orchiectomy in 39 and conservative treatment in 6) and a pathognomonic echo pattern allowed nonsurgical treatment in 26 (37%). CONCLUSIONS: Testicular ultrasound proved to be highly reliable in differentiating intratesticular from extratesticular lesions but it demonstrated poor specificity because of extensive overlap between benign and malignant pathologies. Therefore, testicular ultrasound changed the management of a few select cases of a painless scrotal mass (epididymal cysts/spermatoceles and in utero torsion).

Cranial ultrasonography in maple syrup urine disease.

We performed serial cranial ultrasonography in four newborns affected by maple syrup urine disease. Symmetric increase of echogenicity of periventricular white matter, basal ganglia (mainly pallidi), and thalami was detected in the acute stage. The degree of ultrasonography abnormalities paralleled the clinical course of the disease.

Tricuspid valve vegetation in a child with periarteritis nodosa.

We report a case of a child who was first seen for acute renal failure and periarteritis nodosa. Angiography findings confirmed this diagnosis. Ultrasound scan revealed large tricuspid valve vegetation, as well as minute vegetation on the right ventricular wall. All vegetation disappeared after 12 months of immunosuppressive therapy. Serology findings for lupus were negative. All clinical and laboratory findings strongly support the hypothesis that this previously undescribed heart involvement is caused by PAN.

Renal vein thrombosis and adrenal hemorrhage in the newborn: ultrasound evaluation of 4 cases.

Renal vein thrombosis and adrenal hemorrhage can both be encountered in the neonatal period and they may occur at the same time. Inferior vena cava thrombosis can complicate some cases. These diseases can be easily diagnosed by means of ultrasound. The authors present 4 cases in which newborns were affected by renal vein thrombosis associated with adrenal hemorrhage and caval thrombosis, evaluated by means of ultrasound. The echographic aspect of renal, adrenal and caval involvement is described.

Hemimegalencephaly: early sonographic pattern.

The sonographic changes in a 30-day-old infant with hemimegalencephaly are reported and compared with the CT and MRI findings. Sonography demonstrated the characteristic anomaly of the white matter not shown until later by CT and MRI.

[Renal echography in the diagnosis of malignant hemolymphopathies with early and prevalent kidney involvement]. / L'ecografia renale (US) nella diagnosi di emolinfopatie maligne con precoce e prevalente interessamento renale.

The Authors report their experience dealing with 21 patients affected by lymphoproliferative disorders with renal lesions. In 4 cases renal ultrasound allowed such a diagnosis, previously unsuspected.