Evaluation of Stature Development During Childhood and Adolescence in Individuals with Familial Hypophosphatemic Rickets

This review was conducted to study the diagnosis, treatment, and growth progression in infants and adolescents with familial hypophosphatemic rickets. The bibliographic search was carried out utilizing the electronic databases MEDLINE, OVID, and LILACS and by direct research within the last 15 years using the keywords rickets, familial hypophosphatemia, vitamin D deficiency, stature growth, childhood, and adolescence. Article selection was done by comparing the evaluation of the growth in patients with familial hypophosphatemic rickets, including the variables that might affect them, for possible future therapeutic proposals. It is concluded that the most significant fact in the treatment of familial hypophosphatemic rickets in infancy was the magnitude of the final stature. The use of growth hormone can be helpful in these patients. However, research reporting treatments with the use of the growth hormone for rickets are controversial. The majority of the authors agree that treatment using vitamin D and phosphate enables some statural growth in cases of early diagnosis, reflecting a better prognosis

A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype

AimX-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The main purpose of this study is to identify the presence of a genotype–phenotype correlation in a cohort of XLH patients.MethodsThis is a retrospective study including patients diagnosed with hypophosphatemic rickets, confirmed by clinical, radiological, and laboratory findings. Medical records were reviewed for phenotypic analyses. Genomic DNA was extracted from the peripheral blood lymphocytes, and PHEX sequencing was performed by exomic NGS sequencing. The Wilcoxon rank-sum test and the two-tailed Fisher's exact test were employed for the statistical analyses of this study.ResultsA total of 41 patients were included in this study, and 63.41% (26/41) of the patients were female. The mutation analyses identified 29.27% missense variants and 29.72% nonsense variants, most of them were considered deleterious (66.41%). Six novel deleterious variants in the PHEX gene were detected in seven patients. The median concentrations of pretreatment serum calcium, phosphorus, and parathyroid hormone (PTH) were not significantly different among patients with different genotypes. An orthopedic surgery due to bone deformity was required in 57.69%.ConclusionsOur analysis did not identify any specific genotype as a predictor. No significant genotype–phenotype correlation was found, suggesting that the recognition of subjacent pathogenic mutation in the PHEX gene may have limited prognostic value. Despite this finding, genetic testing may be useful for identifying affected individuals early and providing appropriate treatment

SNAI1 is upregulated during muscle regeneration and represses FGF21 and ATF3 expression by directly binding their promoters

During skeletal myogenesis, the zinc-finger transcription factors SNAI1 and SNAI2, are expressed in proliferating myoblasts and regulate the transition to terminally differentiated myotubes while repressing pro-differentiation genes. Here, we demonstrate that SNAI1 is upregulated in vivo during the early phase of muscle regeneration induced by bupivacaine injury. Using shRNA-mediated gene silencing in C2C12 myoblasts and whole-transcriptome microarray analysis, we identified a collection of genes belonging to the endoplasmic reticulum (ER) stress pathway whose expression, induced by myogenic differentiation, was upregulated in absence of SNAI1. Among these, key ER stress genes, such as Atf3, Ddit3/Chop, Hspa5/Bip, and Fgf21, a myokine involved in muscle differentiation, were strongly upregulated. Furthermore, by promoter mutant analysis and Chromatin immune precipitation assay, we demonstrated that SNAI1 represses Fgf21 and Atf3 in proliferating myoblasts by directly binding to multiple E boxes in their respective promoter regions. Together, these data describe a new regulatory mechanism of myogenic differentiation involving the direct repressive action of SNAI1 on ER stress and Fgf21 expression, ultimately contributing to maintaining the proliferative and undifferentiated state of myoblasts

ICG fluorescence imaging in colorectal surgery: a snapshot from the ICRAL study group

Background: Fluorescence-guided visualization is a recently proposed technology in colorectal surgery. Possible uses include evaluating perfusion, navigating lymph nodes and searching for hepatic metastases and peritoneal spread. Despite the absence of high-level evidence, this technique has gained considerable popularity among colorectal surgeons due to its significant reliability, safety, ease of use and relatively low cost. However, the actual use of this technique in daily clinical practice has not been reported to date. Methods: This survey was conducted on April 2020 among 44 centers dealing with colorectal diseases and participating in the Italian ColoRectal Anastomotic Leakage (iCral) study group. Surgeons were approximately equally divided based on geographical criteria from multiple Italian regions, with a large proportion based in public (89.1%) and nonacademic (75.7%) centers. They were invited to answer an online survey to snapshot their current behaviors regarding the use of fluorescence-guided visualization in colorectal surgery. Questions regarding technological availability, indications and techniques, personal approaches and feelings were collected in a 23-item questionnaire. Results: Questionnaire replies were received from 37 institutions and partially answered by 8, as this latter group of centers do not implement fluorescence technology (21.6%). Out of the remaining 29 centers (78,4%), fluorescence is utilized in all laparoscopic colorectal resections by 72.4% of surgeons and only for selected cases by the remaining 27.6%, while 62.1% of respondents do not use fluorescence in open surgery (unless the perfusion is macroscopically uncertain with the naked eye, in which case 41.4% of them do). The survey also suggests that there is no agreement on dilution, dosing and timing, as many different practices are adopted based on personal judgment. Only approximately half of the surgeons reported a reduced leak rate with fluorescence perfusion assessment, but 65.5% of them strongly believe that this technique will become a minimum requirement for colorectal surgery in the future. Conclusion: The survey confirms that fluorescence is becoming a widely used technique in colorectal surgery. However, both the indications and methods still vary considerably; furthermore, the surgeons' perceptions of the results are insufficient to consider this technology essential. This survey emphasizes the need for further research to reach recommendations based on solid scientific evidence. Keywords: Colon cancer; Fluorescence guided surgery; ICG; Laparoscopy; Rectal cancer

Dynamic Phosphorylation of the Myocyte Enhancer Factor 2C alpha 1 Splice Variant Promotes Skeletal Muscle Regeneration and Hypertrophy

AFM Research. Grant Numbers: 18364, 16252 Optistem (European collaborative project HEALTH-2007-1.4-6) Fondazione Roma, Telethon ASI Division Signaling and Functional Genomics, German Cancer Research Center (DKFZ) Heidelberg University, Heidelberg, Germany Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdo

RNA polymerase III drives alternative splicing of the potassium channel–interacting protein contributing to brain complexity and neurodegeneration

An RNA polymerase III–transcribed noncoding RNA promotes alternative splicing of KCNIP4, altering amyloid precursor protein processing and contributing to neurodegeneration

PixDD: a multi-pixel silicon drift detector for high-throughput spectral-timing studies

The Pixelated silicon Drift Detector (PixDD) is a two-dimensional multi-pixel X-ray sensor based on the technology of Silicon Drift Detectors, designed to solve the dead time and pile-up issues of photon-integrating imaging detectors. Read out by a two-dimensional self-triggering Application-Specific Integrated Circuit named RIGEL, to which the sensor is bump-bonded, it operates in the 0:5 — 15 keV energy range and is designed to achieve single-photon sensitivity and good spectroscopic capabilities even at room temperature or with mild cooling (< 150 eV resolution at 6 keV at 0 °C). The paper reports on the design and performance tests of the 128-pixel prototype of the fully integrated system

Colorectal surgery in Italy during the Covid19 outbreak: a survey from the iCral study group

Background The COVID19 pandemic had a deep impact on healthcare facilities in Italy, with profound reorganization of surgical activities. The Italian ColoRectal Anastomotic Leakage (iCral) study group collecting 43 Italian surgical centers experienced in colorectal surgery from multiple regions performed a quick survey to make a snapshot of the current situation. Methods A 25-items questionnaire was sent to the 43 principal investigators of the iCral study group, with questions regard- ing qualitative and quantitative aspects of the surgical activity before and after the COVID19 outbreak. Results Two-thirds of the centers were involved in the treatment of COVID19 cases. Intensive care units (ICU) beds were partially or totally reallocated for the treatment of COVID19 cases in 72% of the hospitals. Elective colorectal surgery for malignancy was stopped or delayed in nearly 30% of the centers, with less than 20% of them still scheduling elective colo- rectal resections for frail and comorbid patients needing postoperative ICU care. A significant reduction of the number of colorectal resections during the time span from January to March 2020 was recorded, with significant delay in treatment in more than 50% of the centers. Discussion Our survey confirms that COVID19 outbreak is severely affecting the activity of colorectal surgery centers partici- pating to iCral study group. This could impact the activity of surgical centers for many months after the end of the emergency