[Fragility in a Public Health perspective: principles and tools for a "life course" approach prevention- oriented]. / La Fragilità in una prospettiva di Sanità Pubblica: principi e strumenti per un approccio "life course" orientato alla prevenzione.

The Covid-19 pandemic significantly increased the workload for the Italian Health Service. There is few information in the literature on the pediatric population and on the management of pediatric hospitals. The aim of this article is to describe the management of healthcare services during Covid-19 emergency in Regina Margherita Children's Hospital. The Regina Margherita Children's Hospital is specialized in the prevention, diagnosis and treatment of pediatric diseases. About 1000 health worker work in this Hospital and 278 hospitalization places are available.

Outcomes of the calcaneo-stop procedure for the treatment of juvenile flatfoot in young athletes.

PURPOSE: Flexible flatfoot (FFF) is a widespread condition in juvenile patients. If symptomatic, FFF can require surgical treatment. The calcaneo-stop procedure has shown excellent clinical and radiographic outcomes and low rates of complications. The aim of the present study was to assess the sport practice of young athletes affected by FFF having undergone the calcaneo-stop procedure. METHODS: Between 2008 and 2016, 68 sport practitioners were bilaterally treated by the calcaneo-stop procedure, for a total of 136 FFF cases. Clinical evaluation, including the American Orthopedic Foot and Ankle Score (AOFAS), the Yoo et al score and The Foot & Ankle Disability Index (FADI) and FADI Sport scores were assessed. Radiographic evaluation was based on measurement of talar declination, Costa-Bertani's angle and calcaneal pitch. RESULTS: Mean follow-up was 57.6 months (sd 16.8). The AOFAS score mean increased from 79.3 (sd 5.7) to 97.3 (sd 4.5) three years after surgery. The Yoo score improved from 3.1 (sd 1.0) preoperatively to 11.7 (sd 0.6) three years after surgery. The FADI Sport subscale mean improved from 74.1 (sd 10.4) preoperatively to 95.9 (sd 4.9) three years after surgery.Costa-Bertani's angle decreased from 156.1° (sd 4.2°) to 135.8° (sd 7.3°) at three years postoperatively; mean talar declination angle decreased from 44.2° (sd 6.3°) to 30.6° (sd 3.2°) at three years postoperatively and mean calcaneal pitch increased from 12.6° (sd 2.3°) to 16.3° (sd 1.3°) at three years postoperatively. CONCLUSION: Adolescent patients who underwent the calcaneo-stop procedure reported satisfactory outcomes in terms of clinical and radiological evaluations. Moreover, our results showed an improvement of sport activity levels, with patients recovering sports activity within three months of surgery and without limitation in the execution of preferred activities. LEVEL OF EVIDENCE: IV.

Small molecules targeted to the microtubule-Hec1 interaction inhibit cancer cell growth through microtubule stabilization.

Highly expressed in cancer protein 1 (Hec1) is a subunit of the kinetochore (KT)-associated Ndc80 complex, which ensures proper segregation of sister chromatids at mitosis by mediating the interaction between KTs and microtubules (MTs). HEC1 mRNA and protein are highly expressed in many malignancies as part of a signature of chromosome instability. These properties render Hec1 a promising molecular target for developing therapeutic drugs that exert their anticancer activities by producing massive chromosome aneuploidy. A virtual screening study aimed at identifying small molecules able to bind at the Hec1-MT interaction domain identified one positive hit compound and two analogs of the hit with high cytotoxic, pro-apoptotic and anti-mitotic activities. The most cytotoxic analog (SM15) was shown to produce chromosome segregation defects in cancer cells by inhibiting the correction of erroneous KT-MT interactions. Live cell imaging of treated cells demonstrated that mitotic arrest and segregation abnormalities lead to cell death through mitotic catastrophe and that cell death occurred also from interphase. Importantly, SM15 was shown to be more effective in inducing apoptotic cell death in cancer cells as compared to normal ones and effectively reduced tumor growth in a mouse xenograft model. Mechanistically, cold-induced MT depolymerization experiments demonstrated a hyper-stabilization of both mitotic and interphase MTs. Molecular dynamics simulations corroborate this finding by showing that SM15 can bind the MT surface independently from Hec1 and acts as a stabilizer of both MTs and KT-MT interactions. Overall, our studies represent a clear proof of principle that MT-Hec1-interacting compounds may represent novel powerful anticancer agents.

NORMAL NUTRITIONAL COMPONENTS AND EFFECTS ON BONE METABOLISM IN PREVENTION OF OSTEOPOROSIS.

Osteoporosis is the most common bone disease, affecting millions of people and causing a high risk of fractures and a loss of quality of life. It is characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. A primary method of prevention, in order to reduce the risk of fractures, is represented by an appropriate lifestyle and a correct diet. There are potentially numerous nutrients and dietary components that can influence bone health, and these range from macronutrients to micronutrients as well as bioactive food ingredients. The purpose of this review is to overview osteoporosis, including its definition, etiology, and incidence, and then provide some information on possible dietary strategies for optimizing bone health and preventing osteoporosis. A correct diet to prevent osteoporosis should contain adequate amounts of calcium, vitamins D and K, protein, and fatty acids. The effects of these elements are briefly discussed, reporting on their correlation with bone benefits.

Performance of the CLS Spotorno uncemented stem in the third decade after implantation.

In 2012 we reviewed a consecutive series of 92 uncemented THRs performed between 1986 and 1991 at our institution using the CLS Spotorno stem, in order to assess clinical outcome and radiographic data at a minimum of 21 years. The series comprised 92 patients with a mean age at surgery of 59.6 years (39 to 77) (M:F 43;49). At the time of this review, seven (7.6%) patients had died and two (2.2%) were lost to follow-up. The 23-year Kaplan-Meier survival rates were 91.5% (95% confidence intervals (CI) 85.4% to 97.6%; 55 hips at risk) and 80.3% (95% CI, 71.8% to 88.7%; 48 hips at risk) respectively, with revision of the femoral stem or of any component as endpoints. At the time of this review, 76 patients without stem revision were assessed clinically and radiologically (mean follow-up 24.0 years (21.5 to 26.5)). For the 76 unrevised hips the mean Harris hip score was 87.1 (65 to 97). Femoral osteolysis was detected in five hips (6.6%) only in Gruen zone 7. Undersized stems were at higher risk of revision owing to aseptic loosening (p = 0.0003). Patients implanted with the stem in a varus position were at higher risk of femoral cortical hypertrophy and thigh pain (p = 0.0006 and p = 0.0007, respectively). In our study, survival, clinical outcome and radiographic data remained excellent in the third decade after implantation. Nonetheless, undersized stems were at higher risk of revision owing to aseptic loosening.

Steroid injections in the treatment of humeral unicameral bone cysts: long-term follow-up and review of the literature.

BACKGROUND: Retrospective evaluation of long-term effectiveness of the steroid injections treatment in patients with unicameral bone cysts (UBC). METHODS: From January 1993 to April 2005, 23 children affected by proximal humeral UBC were evaluated according to the Neer-Cole classification system and treated with serial methylprednisolone acetate's injections. The patients were followed up at 1, 3, 6 and 12 months and then every year until the adolescence. RESULTS: After treatment, in 15 out of 23 patients (65.2%), the humeral cysts were referred, respectively, as Grade 1 and in four as Grade 2. In 4 patients, a refracture occurred. Statistical analysis showed an overall good response in 82.6% of patients at the end of the follow-up. Minor complication including skin discoloration accounted for 13.04%. CONCLUSIONS: The steroid injections showed to be an alternative excellent treatment for UBC, with complete healing of the lesions in the majority of cases. This procedure is not expensive, mini-invasive, with low surgical risk and short hospitalization.

Congenital idiopathic talipes equinovarus: an evaluation in infants treated by the Ponseti method.

BACKGROUND: Congenital talipes equinovarus (CTEV) is a common but still not fully understood disorder of the lower limb. It is usually defined as a fixation of the foot in adduction, supination, and varus. Different treatment options exist including the Ponseti method. AIM: We report here the results obtained in infants with CTEV treated by the Ponseti method. PATIENTS AND METHODS: Eighty two patients (114 clubfeet) were enrolled at the Orthopaedic Clinic of Catania University during the period of March 2004 to January 2010 and followed prospectively up to February 2011: 56 patients (68.29%) were male, the anomaly was bilateral in 32 (39%) cases, unilateral in 50 (60.9%) in the right side in 28 (56%). The mean age at initiation of treatment was 14 days (range 3-81 days), severity of the club foot deformity by the Pirani Severity score was 5.56 points (range 4.3-6 points). Total numbers of Ponseti casts before tenotomy, details of tenotomy, and compliance with CTEV brace were recorded. Clinical evaluation was performed using the functional Ponseti Scoring System. Mean follow up was 4 years: range 13-83 months. RESULTS: An average of 6.6 casts was necessary before performing the tenotomy. Tenotomy was performed by a single surgeon (V.P.) in a total of 68 patients (82.93%) always in an operating room under general anaesthesia by a percutaneous approach at a mean age of 106 days (range 45-213 days). Compliance with CTEV brace was satisfactory in 79 patients (96.3%). Functional Ponseti Scores were good/excellent in 79 (96.34%) patients (109 clubfeet; 95.61%). Only 3 patients; 3.7% (5 clubfeet; 4.4%) suffered relapse. Poor compliance with the Denis Browne splint was thought to be the main cause of failure. CONCLUSIONS: The Ponseti method provides an excellent outcome at follow up in the treatment of congenital idiopathic clubfoot.

TGF-ß1 exposure induces epithelial to mesenchymal transition both in CSCs and non-CSCs of the A549 cell line, leading to an increase of migration ability in the CD133+ A549 cell fraction.

Metastasis is the leading cause of death by cancer. Non-small-cell lung cancer (NSCLC) represents nearly 85% of primary malignant lung tumours. Recent researches have demonstrated that epithelial-to-mesenchymal transition (EMT) plays a key role in the early process of metastasis of cancer cells. Transforming growth factor-ß1 (TGF-ß1) is the major inductor of EMT. The aim of this study is to investigate TGF-ß1's effect on cancer stem cells (CSCs) identified as cells positive for CD133, side population (SP) and non-cancer stem cells (non-CSCs) identified as cells negative for CD133, and SP in the A549 cell line. We demonstrate that TGF-ß1 induces EMT in both CSC and non-CSC A549 sublines, upregulating the expression of mesenchymal markers such as vimentin and Slug, and downregulating levels of epithelial markers such as e-cadherin and cytokeratins. CSC and non-CSC A549 sublines undergoing EMT show a strong migration and strong levels of MMP9 except for the CD133(-) cell fraction. OCT4 levels are strongly upregulated in all cell fractions except CD133(-) cells. On the contrary, wound size reveals that TGF-ß1 enhances motility in wild-type A549 as well as CD133(+) and SP(+) cells. For CD133(-) and SP(-) cells, TGF-ß1 exposure does not change the motility. Finally, assessment of growth kinetics reveals major colony-forming efficiency in CD133(+) A549 cells. In particular, SP(+) and SP(-) A549 cells show more efficiency to form colonies than untreated corresponding cells, while for CD133(-) cells no change in colony number was observable after TGF-ß1 exposure. We conclude that it is possible to highlight different cell subpopulations with different grades of stemness. Each population seems to be involved in different biological mechanisms such as stemness maintenance, tumorigenicity, invasion and migration.

Plant adaptation to dynamically changing environment: the shade avoidance response.

The success of competitive interactions between plants determines the chance of survival of individuals and eventually of whole plant species. Shade-tolerant plants have adapted their photosynthesis to function optimally under low-light conditions. These plants are therefore capable of long-term survival under a canopy shade. In contrast, shade-avoiding plants adapt their growth to perceive maximum sunlight and therefore rapidly dominate gaps in a canopy. Daylight contains roughly equal proportions of red and far-red light, but within vegetation that ratio is lowered as a result of red absorption by photosynthetic pigments. This light quality change is perceived through the phytochrome system as an unambiguous signal of the proximity of neighbors resulting in a suite of developmental responses (termed the shade avoidance response) that, when successful, result in the overgrowth of those neighbors. Shoot elongation induced by low red/far-red light may confer high relative fitness in natural dense communities. However, since elongation is often achieved at the expense of leaf and root growth, shade avoidance may lead to reduction in crop plant productivity. Over the past decade, major progresses have been achieved in the understanding of the molecular basis of shade avoidance. However, uncovering the mechanisms underpinning plant response and adaptation to changes in the ratio of red to far-red light is key to design new strategies to precise modulate shade avoidance in time and space without impairing the overall crop ability to compete for light.

Colonization and movement of GFP-labeled Clavibacter michiganensis subsp. michiganensis during tomato infection.

The vascular pathogen Clavibacter michiganensis subsp. michiganensis is responsible for bacterial wilt and canker of tomato. Pathogenicity of this bacterium is dependent on plasmid-borne virulence factors and serine proteases located on the chromosomal chp/tomA pathogenicity island (PAI). In this study, colonization patterns and movement of C. michiganensis subsp. michiganensis during tomato infection was examined using a green fluorescent protein (GFP)-labeled strain. A plasmid expressing GFP in C. michiganensis subsp. michiganensis was constructed and found to be stable in planta for at least 1 month. Confocal laser-scanning microscopy (CLSM) of inoculated stems showed that the pathogen extensively colonizes the lumen of xylem vessels and preferentially attaches to spiral secondary wall thickening of the protoxylem. Acropetal movement of the wild-type strain C. michiganensis subsp. michiganensis NCPPB382 (Cmm382) in tomato resulted in an extensive systemic colonization of the whole plant reaching the apical region after 15 days, whereas Cmm100 (lacking the plasmids pCM1 and pCM2) or Cmm27 (lacking the chp/tomA PAI) remained confined to the area surrounding of the inoculation site. Cmm382 formed biofilm-like structures composed of large bacterial aggregates on the interior of xylem walls as observed by CLSM and scanning electron microscopy. These findings suggest that virulence factors located on the chp/tomA PAI or the plasmids are required for effective movement of the pathogen in tomato and for the formation of cellular aggregates.