Assessing the insulating properties of an ultrathin SrTiO3shell grown around GaAs nanowires with molecular beam epitaxy.

We have studied electronic transport in undoped GaAs/SrTiO3core-shell nanowires standing on their Si substrate with two-tip scanning tunneling microscopy in ultrahigh vacuum. The resistance profile along the nanowires is proportional to the tip separation with resistances per unit length of a few GΩ/µm. Examination of the different transport pathways parallel to the nanowire growth axis reveals that the measured resistance is consistent with a conduction along the interfacial states at the GaAs{110} sidewalls, the 2 nm thick SrTiO3shell being as much as resistive, despite oxygen deficient growth conditions. The origin of the shell resistivity is discussed in light of the nanowire analysis with transmission electron microscopy and Raman spectroscopy, providing good grounds for the use of SrTiO3shells as gate insulators.

Fusion of ultrasound and 3D single-photon-emission computed tomography/computed tomography to identify sentinel lymph nodes in vulvar cancer: feasibility study.

OBJECTIVE: To evaluate the feasibility of fusion of ultrasound imaging and three-dimensional (3D) single-photon-emission computed tomography/computed tomography (SPECT/CT) in detecting sentinel lymph nodes in women with vulvar cancer. METHODS: This was a prospective pilot single-center study. Patients with vulvar cancer who were candidates for sentinel lymph-node biopsy were enrolled between December 2018 and February 2019. Fusion imaging virtual navigation using 3D SPECT/CT and ultrasound was performed to investigate the tumor-draining lymph node. All clinical, imaging, surgical and histological information was collected prospectively and entered into a dedicated Excel file. Feasibility and success of fusion imaging virtual navigation and time needed to perform the three steps of fusion imaging were evaluated. RESULTS: Ten lymph-node sites were evaluated in five consecutive women with a histological diagnosis of vulvar cancer. Fusion imaging virtual navigation was feasible and completed successfully for all (10/10) draining sites. Median overall time to perform fusion imaging was 32 (range, 25-40) min and the time decreased from the first to the last examination. CONCLUSIONS: The present study demonstrated that fusion imaging virtual navigation using 3D SPECT/CT and ultrasound is feasible and able to detect sentinel lymph nodes in women with vulvar carcinoma. Fusion imaging using ultrasound for detection of sentinel lymph nodes opens up multiple diagnostic and therapeutic opportunities in gynecological oncology. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

GSTP1 gene methylation and AHR rs2066853 variant predict resistance to first generation somatostatin analogs in patients with acromegaly.

PURPOSE: Biomarkers of clinical and therapeutic outcome in acromegaly are needed. Polymorphisms or epigenetic changes of detoxification genes, such as those coding for the aryl hydrocarbon receptor (AHR) and the glutathione-S-transferase-P1 (GSTP1), could have a role in GH secreting pituitary tumors' pathophysiology and clinical expression. In this study, we assessed the contribution of GSTP1 gene promoter methylation status, per se or in combination with the occurrence of the AHR gene rs2066853 variant, on clinical features and response to somatostatin analogs (SSA) treatment in acromegaly patients. METHODS: This is an observational, retrospective study, carried out in the Endocrine Unit of an Italian University Hospital. We enrolled 77 wild-type AIP gene acromegaly patients, who have been screened for germline AHR rs2066853 variant and GSTP1 gene promoter methylation. Clinical and biochemical parameters were compared after patients' stratification according to GSTP1 methylation status and the presence of AHR rs2066853. We also evaluated the response to SSA treatment in 71 cases. RESULTS: 17 patients carried the AHR rs2066853 variant and 26 had methylated GSTP1 (GSTP1-methyl) gene promoter. GSTP1-methyl patients showed a higher prevalence of diabetes mellitus (p = 0.01), colonic polyps (p = 0.05), and were more resistant to SSA (p = 0.02) as compared to GSTP1 unmethylated patients (GSTP1-unmethyl). Patients GSTP1-unmethyl and AHR wild-type were the most sensitive to SSA treatment, while those with both GSTP1-methyl and AHR rs2066853 variant were all resistant to SSA (p = 0.01). CONCLUSIONS: In acromegaly, GSTP1 gene methylation associates with resistance to SSA treatment, especially in patients carrying also the AHR rs2066853 variant, and with increased prevalence of colonic polyps and diabetes mellitus.

A long-term follow-up in conservative management of unilateral ureteropelvic junction obstruction with poor drainage and good renal function.

The aim of the study was to retrospectively review the outcome of neonatal ureteropelvic junction obstruction with a good renal function and a poor drainage at a first diuretic renal scan, in cases where surgery was recommended on the basis of a loss of renal function, worsening of hydronephrosis or occurrence of clinical symptoms. Hydronephrosis was graded from 1 to 4 or as ureteral tract dilatation (UTD) P1 to UTD P3. During follow-up, 15 out of 38 patients (34.2%) required surgery while 25 out of 38 (65.8%) could have been managed conservatively. In patients with grade 2, 3, and 4 hydronephrosis, the ureteropelvic junction obstruction resolved or improved spontaneously in 100%, 63%, and 33% of cases (in 100% of UTD P1, 67% of UTD P2, and 50% of UTD P3), respectively. The median of follow-up was 14 years. Chi-square test showed a significant relationship between initial grade of hydronephrosis or UTD and the possibility of an efficient conservative management (p = 0.0088 and p = 0.0460).Conclusion: Conservative management can be safely achieved in ureteropelvic junction obstruction with poor drainage. Scheduled controls are needed for early discovery of functional renal deterioration. High-grade hydronephrosis is unlikely to resolve spontaneously and is often accompanied by a loss of renal function during the first years of life. What is Known: • There is controversy about which management should be adopted in infants with unilateral ureteropelvic junction obstruction with poor drainage but good differential renal function. What is New: • Long-term follow-up suggests that conservative management can be safely achieved also in unilateral ureteropelvic junction obstruction with poor drainage in more than 60% of cases, even if high-grade hydronephrosis is unlikely to resolve spontaneously and it is often accompanied by a loss of renal function during the first years of life. In our experience, surgical intervention was required in more than 50% of cases before 1 year of life and in all cases before 3 years of life.

Extracorporeal shockwaves as regenerative therapy in orthopedic traumatology: a narrative review from basic research to clinical practice.

Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non–invasive therapy, in many cases it can represent a first–line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle–skeletal field will grow, not only for standard indications, but also in post–traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses.

Appropriateness of knee MRI prescriptions: clinical, economic and technical issues.

OBJECTIVES: Many studies show that a large portion of medical prescriptions for diagnostic examinations may be not useful for patient's management or unnecessary. Rapid technological advancement has made it possible for magnetic resonance imaging (MRI) to be increasingly used all over the world, particularly for musculoskeletal disorders. The aim of this study was to assess the appropriateness of the knee MRI prescriptions. MATERIALS AND METHODS: A panel of experts found standard clinical practice guidelines in the management of knee disorders. Secondly, the finalized set of guidelines chosen was compared with the data of 400 patients who underwent previous knee MRIs, which were then reported in a specific questionnaire prepared by the authors. The rate of appropriateness of knee MRI prescriptions was then calculated. RESULTS: Almost 21% of prescriptions were totally inappropriate, 18.8% were uncertain, and 60.2% could be considered totally appropriate. The most frequent prescription indication was for meniscal disorders that account for 26.8% of the total indications. CONCLUSIONS: Our results demonstrate that approximately 40% of the total prescriptions were totally inappropriate or uncertain and that most of these were made by general practitioners. In light of these results, the economic impact of inappropriate prescriptions on the Italian healthcare system has to be seriously considered.

Increased frequency of the rs2066853 variant of aryl hydrocarbon receptor gene in patients with acromegaly.

CONTEXT: Aryl hydrocarbon receptor (AHR) pathway has a key role in cellular detoxification mechanisms and seems implicated in tumorigenesis. Moreover, polymorphisms and mutations of AHR gene have been associated with several human and animal tumours. Although AHR has been found differently expressed in pituitary adenomas, AHR gene mutation status has never been investigated in acromegalic patients. DESIGN: In this study, we evaluated patients with apparently sporadic GH-secreting pituitary adenoma for AHR gene variants. PATIENTS AND METHODS: Seventy patients with sporadic GH-secreting pituitary adenoma (M = 27, age 59.1 ± 1.6 years) and 157 sex- and age-matched controls were enrolled in the study. In all patients and controls, the exons 1, 2, 3, 5 and 10 of AHR gene were evaluated for nucleotide variants by sequencing analysis. RESULTS: The rs2066853 polymorphism was identified in the exon 10 of 18/70 acromegalic patients and 9/157 healthy subjects (25.7 vs. 5.7%, χ(2) = 18.98 P < 0.0001), in homozygosis in one patient and in heterozygosis in the other 17 and in the 9 healthy subjects. Moreover, a heterozygous rs4986826 variant in exon 10 was identified in a patient with heterozygous rs2066853 polymorphism, and in the patient with homozygous rs2066853 variant. This second polymorphism was not detected in the control group. Patients with rs2066853 polymorphism showed increased IGF-1 ULN (P < 0.05) and prevalence of cavernous sinus invasion (P = 0.05), thyroid (P = 0.02), bladder (P = 0.0001) or lymphohematopoietic (P < 0.05) tumours. CONCLUSIONS: AHR gene rs2066853 polymorphism is significantly more frequent in acromegalic patients than in healthy subjects and is associated with increased disease aggressivity. Moreover, the rs4986826 variant was detected in few patients with rs2066853 polymorphism, but its role is to be cleared.

Multicentric data analysis of the learning curve for laparoscopic Shull's repair of pelvic floor defects.

Introduction: Pelvic organs prolapse remains a significant health concern affecting millions of women worldwide. The use of native tissues to suspend the apex has acquired relevance in urogynecologic surgery. One of the most commonly used procedures performed without mesh is the technique described by Shull, consisting of suturing the vaginal apex to the uterosacral ligaments. The objective of the study is to evaluate the learning curve of laparoscopic Shull's repair for the correction of pelvic floor defects, including the surgery time and surgical outcomes. Materials and methods: This is a retrospective study conducted at the Policlinico G. Martino, University of Messina, Messina, Italy, and Policlinico Vanvitelli, Vanvitelli University, Naples, Italy. All patients affected by grade I-IV POP, consisting of apical prolapse with or without cystocele, and who underwent laparoscopic Shull's technique for prolapse correction were enrolled. The endpoints to estimate the learning curve for the procedure were the percentage of laparoscopic procedures completed, operative time, and the early complication rate. Results: A total of 31 laparoscopic Shull repairs were collected for the study. To evaluate the learning curve of the technique, we divided the 31 cases into three different groups: Procedures 0-10; 11-20; 21-31. The parameter for evaluating technique learning was the operative time. Group 21-31 demonstrated an operative time of 97 min (SD 20), compared with 121 min (SD 23) in group 0-10 and 120 min (SD 13) in group 11-20. A comparison of these means through ANOVA showed a p-value of 0.01 for the entire system, and 0.95 for the comparison between 0 and 10 and 11-20, 0.04 for 0-10 vs. 21-31, and 0.02 between 11 and 20 and 21-31. Conclusions: The rate of surgical improvement in terms of time became effective after an average of 20 procedures. However, the improvement seems to be effective case by case for surgeons skilled in basic endoscopy.

Early angiogenic response to shock waves in a three-dimensional model of human microvascular endothelial cell culture (HMEC-1).

The exact nature of shock wave (SW) action is not, as yet, fully understood, although a possible hypothesis may be that shock waves induce neoangiogenesis. To test this hypothesis, a three-dimensional (3D) culture model on Matrigel was developed employing a human microvascular endothelial cell line (HMEC-1) which was stimulated with low energy soft- focused SW generated by an SW lithotripter. After 12 hours we observed a statistically significant increase in capillary connections subsequent to shock-wave treatment in respect to the control group and a marked 3-hour down-regulation in genes involved in the apoptotic processes (BAX, BCL2LI, GADD45A, PRKCA), in cell cycle (CDKN2C, CEBPB, HK2, IRF1, PRKCA), oncogenes (JUN, WNT1), cell adhesion (ICAM-1), and proteolytic systems (CTSD, KLK2, MMP10). Our preliminary results indicate that microvascular endothelial cells in vitro quickly respond to SW, proliferating and forming vessel-like structures, depending on the energy level employed and the number of shocks released. The early decreased expression in the analysed genes could be interpreted as the first reactive response of the endothelial cells to the external stimuli and the prelude to the events characterizing the neo-angiogenic sequence.

A Mini-Review Regarding the Modalities to Study Neurodevelopmental Disorders-Like Impairments in Zebrafish-Focussing on Neurobehavioural and Psychological Responses.

Neurodevelopmental disorders (NDDs) are complex disorders which can be associated with many comorbidities and exhibit multifactorial-dependent phenotypes. An important characteristic is represented by the early onset of the symptoms, during childhood or young adulthood, with a great impact on the socio-cognitive functioning of the affected individuals. Thus, the aim of our review is to describe and to argue the necessity of early developmental stages zebrafish models, focusing on NDDs, especially autism spectrum disorders (ASD) and also on schizophrenia. The utility of the animal models in NDDs or schizophrenia research remains quite controversial. Relevant discussions can be opened regarding the specific characteristics of the animal models and the relationship with the etiologies, physiopathology, and development of these disorders. The zebrafish models behaviors displayed as early as during the pre-hatching embryo stage (locomotor activity prone to repetitive behavior), and post-hatching embryo stage, such as memory, perception, affective-like, and social behaviors can be relevant in ASD and schizophrenia research. The neurophysiological processes impaired in both ASD and schizophrenia are generally highly conserved across all vertebrates. However, the relatively late individual development and conscious social behavior exhibited later in the larval stage are some of the most important limitations of these model animal species.

Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma.

Omalizumab is a humanized monoclonal anti-IgE antibody approved in 2005 by the European Medicine Agency (EMA) for the treatment of severe persistent allergic asthma, which remains inadequately controlled despite optimal therapy with high doses of inhaled corticosteroids and long-acting ß2-adrenergic agonists. Within this context, the present observational study refers to 16 patients currently treated with omalizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy, whose anti- IgE therapy was started in the period included between March 2007 and February 2010, thus lasting at least 10 months. After 40 weeks of add-on treatment with omalizumab, very relevant decreases were detected, in comparison with pre-treatment mean (± standard deviation) values, in monthly exacerbation numbers (from 1.1 ± 0.6 to 0.2 ± 0.4; p < 0.01) and oral corticosteroid consumption (from 22.6 ± 5.0 to 1.2 ± 2.9 mg/day of prednisone; p < 0.01). These changes were associated with stable improvements in lung function, expressed as increases of both FEV1 (from 53.6 ± 14.6% to 77.0 ± 14.9% of predicted values; p < 0.01) and FEV1/FVC ratio (from 56.3 ± 9.5% to 65.8 ± 9.2%; p < 0.01). Moreover, in 5 patients who persistently had increased numbers of eosinophils (mean ± SD: 15.9 ± 8.0% of total WBC count; absolute number: 1,588.0 ± 956.9/µl) despite a long-lasting therapy with inhaled and systemic corticosteroids, the peripheral counts of these cells decreased down to near normal levels (mean ± SD: 6.3 ± 2.3% of total WBC count; absolute number: 462.0 ± 262.3/µl) after 16 weeks of treatment with omalizumab. Therefore, this descriptive evaluation confirms the efficacy of add-on omalizumab therapy in selected patients with exacerbation-prone, chronic allergic uncontrolled asthma, requiring a continuous intake of oral corticosteroids.

Transcription factor SCL is required for c-kit expression and c-Kit function in hemopoietic cells.

In normal hemopoietic cells that are dependent on specific growth factors for cell survival, the expression of the basic helix-loop-helix transcription factor SCL/Tal1 correlates with that of c-Kit, the receptor for Steel factor (SF) or stem cell factor. To address the possibility that SCL may function upstream of c-kit, we sought to modulate endogenous SCL function in the CD34(+) hemopoietic cell line TF-1, which requires SF, granulocyte/macrophage colony-stimulating factor, or interleukin 3 for survival. Ectopic expression of an antisense SCL cDNA (as-SCL) or a dominant negative SCL (dn-SCL) in these cells impaired SCL DNA binding activity, and prevented the suppression of apoptosis by SF only, indicating that SCL is required for c-Kit-dependent cell survival. Consistent with the lack of response to SF, the level of c-kit mRNA and c-Kit protein was significantly and specifically reduced in as-SCL- or dn-SCL- expressing cells. c-kit mRNA, c-kit promoter activity, and the response to SF were rescued by SCL overexpression in the antisense or dn-SCL transfectants. Furthermore, ectopic c-kit expression in as-SCL transfectants is sufficient to restore cell survival in response to SF. Finally, enforced SCL in the pro-B cell line Ba/F3, which is both SCL and c-kit negative is sufficient to induce c-Kit and SF responsiveness. Together, these results indicate that c-kit, a gene that is essential for the survival of primitive hemopoietic cells, is a downstream target of the transcription factor SCL.

3D integration of photonic crystal devices: vertical coupling with a silicon waveguide.

Two integrated devices based on the vertical coupling between a photonic crystal microcavity and a silicon (Si) ridge waveguide are presented in this paper. When the resonator is coupled to a single waveguide, light can be spectrally extracted from the waveguide to free space through the far field emission of the resonator. When the resonator is vertically coupled to two waveguides, a vertical add-drop filter can be realized. The dropping efficiency of these devices relies on a careful design of the resonator. In this paper, we use a Fabry-Perot (FP) microcavity composed of two photonic crystal (PhC) slab mirrors. Thanks to the unique dispersion properties of slow Bloch modes (SBM) at the flat extreme of the dispersion curve, it is possible to design a FP cavity exhibiting two quasi-degenerate modes. This specific configuration allows for a coupling efficiency that can theoretically achieve 100%. Using 3D FDTD calculations, we discuss the design of such devices and show that high dropping efficiency can be achieved between the Si waveguides and the PhC microcavity.

Compact modulated and tunable microdisk laser using vertical coupling and a feedback loop.

A study of vertical coupling conditions between microdisk based resonators and waveguides is presented using an analytical model. The coupling efficiency optimization is investigated and compared to 3D FDTD computations. We also demonstrate that coupling losses can be exploited to favor high quality factor modes in circular resonators. In addition, we propose to modify the shape of the coupled waveguide to enhance mode selectivity and obtain a very compact structure with mode hoping capacities. Lower thresholds and modulation are also expected.

[RadioTransNet, the French network for preclinical research in oncological radiotherapy]. / RadioTransNet, le réseau national de radiothérapie oncologique préclinique.

The ambition of the RADIOTRANSNET network, launched by the INCa at the end of 2018, is to create a French research consortium dedicated to preclinical radiotherapy to foster scientific and clinical interactions at the interface of radiotherapy and radiobiology, and to identify research priorities dedicated to innovation in radiotherapy. The activities of the network are organized around four major axes that are target definition, normal tissue, combined treatments and dose modelling. Under the supervision of the Scientific Council, headed by a coordinator designated by the SFRO and a co-coordinator designated by the SFPM, three leaders coordinate each axis: a radiation-oncologist, a medical physicist and a biologist, who are responsible for organizing a scientific meeting based on the consensus conference methodology to identify priority issues. The selected themes will be the basis for the establishment of a strategic research agenda and a roadmap to help coordinate national basic and translational research efforts in oncological radiotherapy. This work will be published and will be transmitted to the funding institutions and bodies with the aim of opening dedicated calls to finance the necessary human and technical resources. Structuration of a preclinical research network will allow coordinating the efforts of all the actors in the field and thus promoting innovation in radiotherapy.

Slow Bloch mode confinement in 2D photonic crystals for surface operating devices.

2D photonic crystal (2DPC) structures consisting in 2D silicon nanopillar arrays in silica are investigated. The main motivation of this work lies in that 2D rod arrays should be easily combined with refractive structures (e. g. micro-wire waveguides), unlike 2DPC consisting in hole lattices. Such an association is expected to lead to both new functionalities and larger scale integration. In this paper, we study the loss mechanism for non degenerated Bloch modes located at Gamma-point in a 2DPC slab constituted by a square lattice of silicon rods in silica. For such modes, we show that the quality factor is mainly governed by the lateral losses. To further inhibit the lateral losses, a photonic heterostructure is used. 3D FDTD calculations show that quality factors of 4000 are achieved. To reduce the vertical losses, the 2DPC heterostructure is associated with a vertical Bragg mirror, thus resulting in very high quality factors (>40000).

Molecular analysis of uroporphyrinogen decarboxylase deficiency in a family with two cases of hepatoerythropoietic porphyria.

In order to determine the molecular basis of uroporphyrinogen (URO) decarboxylase deficiency responsible for hepatoerythropoietic porphyria (HEP) and familial porphyria cutanea tarda, we used a human URO decarboxylase cDNA to analyze the organization and expression of the URO decarboxylase gene in lymphoblastoid cells from normal individuals and from two patients with HEP. We could detect neither deletions nor rearrangements in the URO decarboxylase gene. Synthesis, processing, and cell-free translation of the specific transcripts appeared to be normal. The half-life of the abnormal protein was 12 times shorter than that of the normal enzyme. The results indicate that the enzyme defect is due to a rapid degradation of the protein in vivo. This study is the first to provide information regarding the molecular mechanism responsible for the URO decarboxylase deficiency in HEP.

Electrically pumped InP-based microdisk lasers integrated with a nanophotonic silicon-on-insulator waveguide circuit.

A compact, electrically driven light source integrated on silicon is a key component for large-scale integration of electronic and photonic integrated circuits. Here we demonstrate electrically injected continuous-wave lasing in InP-based microdisk lasers coupled to a sub-micron silicon wire waveguide, fabricated through heterogeneous integration of InP on silicon-on-insulator (SOI). The InP-based microdisk has a diameter of 7.5 mum and a thickness of 1 mum. A tunnel junction was incorporated to efficiently contact the p-side of the pn-junction. The laser emits at 1.6 mum, with a threshold current as low as 0.5 mA under continuous-wave operation at room temperature, and a threshold voltage of 1.65 V. The SOI-coupled laser slope efficiency was estimated to be 30 muW/mA, with a maximum unidirectional output power of 10 muW.