In vivo imaging of CNS microglial activation/macrophage infiltration with combined [18F]DPA-714-PET and SPIO-MRI in a mouse model of relapsing remitting experimental autoimmune encephalomyelitis.

PURPOSE: To evaluate the feasibility and sensitivity of multimodality PET/CT and MRI imaging for non-invasive characterization of brain microglial/macrophage activation occurring during the acute phase in a mouse model of relapsing remitting multiple sclerosis (RR-MS) using [18F]DPA-714, a selective radioligand for the 18-kDa translocator protein (TSPO), superparamagnetic iron oxide particles (SPIO), and ex vivo immunohistochemistry. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in female SJL/J mice by immunization with PLP139-151. Seven symptomatic EAE mice and five controls underwent both PET/CT and MRI studies between 11 and 14 days post-immunization. SPIO was injected i.v. in the same animals immediately after [18F]DPA-714 and MRI acquisition was performed after 24 h. Regional brain volumes were defined according to a mouse brain atlas on co-registered PET and SPIO-MRI images. [18F]DPA-714 standardized uptake value (SUV) ratios (SUVR), with unaffected neocortex as reference, and SPIO fractional volumes (SPIO-Vol) were generated. Both SUVR and SPIO-Vol values were correlated with the clinical score (CS) and among them. Five EAE and four control mice underwent immunohistochemical analysis with the aim of identifying activated microglia/macrophage and TSPO expressions. RESULTS: SUVR and SPIO-Vol values were significantly increased in EAE compared with controls in the hippocampus (p < 0.01; p < 0.02, respectively), thalamus (p < 0.02; p < 0.05, respectively), and cerebellum and brainstem (p < 0.02), while only SPIO-Vol was significantly increased in the caudate/putamen (p < 0.05). Both SUVR and SPIO-Vol values were positively significantly correlated with CS and among them in the same regions. TSPO/Iba1 and F4/80/Prussian blue staining immunohistochemistry suggests that increased activated microglia/macrophages underlay TSPO expression and SPIO uptake in symptomatic EAE mice. CONCLUSIONS: These preliminary results suggest that both activated microglia and infiltrated macrophages are present in vulnerable brain regions during the acute phase of PLP-EAE and contribute to disease severity. Both [18F]DPA-714-PET and SPIO-MRI appear suitable modalities for preclinical study of neuroinflammation in MS mice models.

[Gender Diversity and Impact on Work and Life Expectancy in Health Care. Results of a Survey Conducted in the Tuscany Region]. / Diversità di genere e impatto sulle aspettative di lavoro e di vita in ambito sanitario. Risultati di una survey in Regione Toscana.

The percentage of female doctors employed in the health sector is constantly increasing both in Europe and in Italy with repercussions on organizational and socio-family models, currently not conceived in terms of equal opportunities, career and quality of life. The published studies have mainly taken into consideration economic and career disparities, (1) however, to date no study combined with surveys has highlighted criteria for evaluating the quality of work through the direct and sincere experience of workers. This reflection gave rise to the idea of a survey organized by the ANAAO Medical Women Group with the patronage of the Tuscan Medical Orders Federation organized on a homogeneous sample, i.e. female doctors from a single Region, Tuscany, in order to evaluate and new approaches in the management of human resources that take into account the delicate balance between the real possibilities available to the doctor and the complexities of experiential work that arise over the course of a lifetime. Empirical evidence deriving from specific investigations conducted at trade union and ordinistic level still document the existence of a gender gap between male and female doctors with respect to the reference parameters of quality work, such as the economic and ergonomic dimension, in relation to the physical and psychological aspects of people.

[Gender composition in the medical profession in Europe. Social implications and criticalities.] / Composizione di genere nella professione medica in Europa. Implicazioni sociali e criticità.

In the last twenty years there has been an increase in the proportion of women practicing the medical profession which has occurred in parallel with the increase in participation of women in the scientific professions. Italy has a stable percentage of women at 40% in 2016 compared to 60% in the Baltic countries, Romania and Croatia (1). This increase in the total number obtained did not automatically guarantee women doctors the right to access the roles of leaders and fair economic consideration in all the European countries analyzed. All this affects the quality of life of women and the authority of the knowledge expressed by them, with consequent implications on the economic and social context.

A multisensor approach coupled with multivariate statistics and geostatistics for assessing the status of land degradation: The case of soils contaminated in a former outdoor shooting range.

Soil contamination in outdoor shooting ranges (OSRs) is a major threat for human health, particularly when, after the end of activities, the land is used for recreational areas or agricultural production. The status of land degradation of an OSR in southern Italy was assessed using a multisensor approach. It was based on: i) proximal sensors, including electromagnetic induction (EMI) for measuring soil electrical conductivity (ECa) and magnetic susceptibility (MSa), γ-ray spectrometry for K, eU and eTh analyses and ultrasonic penetrometry detecting cone index (CI) data representative of soil's strength, ii) field surveys on soil thickness (ST), and iii) laboratory analyses of potentially-toxic-elements (PTEs) by portable X-ray fluorescence spectrometry and polycyclic aromatic hydrocarbons (PAHs) by gas-chromatography. Spatial variability of measurements was modelled and mapped using geostatistical methods. The most densely measured covariate (i.e., the ECa of the topsoil) was used within kriging with external drift to improve the PTEs predictions. The PTEs maps were complemented by maps of spatial uncertainty. A robust multivariate principal component analysis (rPCA) was applied to proximal sensor and laboratory data and allowed to identify associations of PAHs, lead, CI with the topsoil ECa along the first component (PC1), highlighting the correlation between land anthropogenic effects and EMI measures; while the association between the ST (estimating the depth of underground travertine hard-layers) and the bottom soil ECa and MSa along the second component (PC2) evidenced the influence of soil stratigraphy on the EMI measures. This study demonstrates that the simultaneous use of different proximal sensors associated with laboratory analysis can allow to assess and model the spatial variability of the land degradation status of an OSR, including soil compaction, organic and inorganic contamination. The correlation between EMI data with the PTEs content highlights the potential of this technique in the field of soil contamination.

XY1Y2 chromosome system in Salinomys delicatus (Rodentia, Cricetidae).

Salinomys delicatus is considered a rare species due to its restricted and patchy distribution, poor records and low abundances. It is also the phyllotine with the lowest known diploid chromosome number (2n = 18), however its sex chromosome system has never been described. Here, we studied the chromosomes of six females and three males with bands G, C, DAPI/CMA(3) and meiosis. In males, the chromosome number was 2n = 19, with one large metacentric X-chromosome and two medium-sized acrocentrics absent in females. The karyotype of females was the same as previously described (2n = 18, FN = 32), with X-chromosomes being metacentric and the largest elements of the complement. In males, the two acrocentrics and the large metacentric form a trivalent in meiotic prophase. This indicates that S. delicatus has XY(1)Y(2) sex chromosomes, which is confirmed by G and DAPI bands. Constitutive heterochromatin (CH) is restricted to small pericentromeric blocks in all chromosomes. The X-chromosome shows the largest block of centromeric CH, which could favor the establishment of this X-autosome translocation. This sex chromosome system is rare in mammals and, compared with other phyllotine rodents, S. delicatus seems to have undergone a major chromosome restructuring during its karyotypic evolution.

Fentanyl pectin nasal spray for painful mucositis in head and neck cancers during intensity-modulated radiation therapy with or without chemotherapy.

PURPOSE: The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent. METHODS: A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT. RESULTS: Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use. CONCLUSIONS: FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use.

Bidirectional cavopulmonary anastomosis in patients under two years of age.

Between December 1986 and December 1990, a bidirectional cavopulmonary anastomosis was performed in 27 patients younger than 2 years of age, including 12 with heterotaxia syndrome. Age and weight of patients averaged 14.2 +/- 6.6 months and 8.1 +/- 2.2 kg, respectively. Eleven had pulmonary atresia and 16 had pulmonary stenosis. The main pulmonary artery was ligated in seven patients in the latter group (subsequently reopened in one) and left open in nine (subsequently ligated in two). There were four hospital deaths (15%). All patients were discharged with anticoagulant/antithrombotic therapy to be continued for 6 months. There were two late deaths before further operations (8.7%). Two patients, one with acquired massive pulmonary arteriovenous fistulas and one with progressive common atrioventricular valve regurgitation, subsequently underwent definitive repair (biventricular in one), and both died. Heterotaxia syndrome (p = 0.087) and preoperative mean pulmonary artery pressure higher than 15 mm Hg (p = 0.09) were the only risk factors for overall mortality.

Extracorporeal right to left atrial bypass to treat right ventricular failure.

Graft right ventricular failure after heart transplantation, secondary to preoperative functional pulmonary hypertension, was successfully managed in a 49-year-old patient using an extracorporeal right to left atrial bypass. We comment on the case and discuss the type of mechanical assistance used.

Transposition with absent pulmonary valve syndrome: early repair of a rare case.

The congenital absence of the pulmonary valve cusps can occur either isolated or in association with other heart lesions. We report a very rare case of a 40-day-old infant with transposition of the great arteries, ventricular septal defect, pulmonary annular stenosis, absent pulmonary valve and aneurysmal dilation of the central pulmonary arteries, who received surgical treatment at our institution.

Aortic coarctation with hypoplastic arch in neonates: a spectrum of anatomic lesions requiring different surgical options.

Hypoplasia of the transverse aortic arch is frequently associated with isthmic coarctation in many patients referred for operation in early infancy, and the surgical technique should be adjusted to suit each type of anatomic lesion. Referring to the anatomic description of hypoplastic aortic arch reported by Moulaert and associates, between January 1988 and July 1991 we operated on 32 consecutive infants (< or = 3 months old) using a surgical approach based on the echocardiographic and angiographic findings; 20 patients (62%) were younger than 2 weeks of age and 20 patients (62%) had associated intracardiac lesions. According to the location, extension, and size of the hypoplasia of the aortic arch, we had three groups of patients: in group 1 (21 patients) we performed resection and extended end-to-end anastomosis, as previously described in 1985; in group 2 (5 patients) we performed resection, posterior end-to-end anastomosis, and anterior subclavian flap enlargement; and in group 3 (6 patients) we performed direct side-to-end anastomosis between ascending and descending aorta through a median sternotomy. One patient died during the postoperative course in group 3. With a mean follow-up time of 26 months we had 4 cases (13%) of "residual" or "recurrent" coarctation in group 1, successfully repaired at 2 months of age by an anterior approach in 2 patients and by percutaneous angioplasty in the others. In conclusion, hypoplastic aortic arch in neonates represents a common difficulty, and optimal reconstruction of the entire aortic arch is mandatory to reduce operative mortality and incidence of recoarctation, especially when there are complex associated intracardiac lesions or left ventricular dysfunction.

Interrupted aortic arch and aortopulmonary window: one-stage repair in the first week of life.

Aortic arch interruption associated with an aortopulmonary window is a rare congenital malformation that needs an early diagnosis and surgical treatment to avoid irreversible pulmonary lesions. Here we describe a case of a successful one-stage surgical repair in a 3-day-old neonate, without the use of prosthetic material, for the correction of the aortic arch interruption.

Pediatric cardiac transplantation for congenital heart defects: surgical considerations and results.

Among 54 children who underwent 55 heart transplantations, 24 (44%) (mean age, 4.9 +/- 4.8 years; range, 9 days to 18 years) had congenital defects with the following diagnoses: single-ventricle variants (6), hypoplastic left heart syndrome variants (5), transposition complex (6), and miscellaneous defects (7). Twenty patients (83%) had undergone 43 prior operations. Additional surgical procedures included repositioning of transposed great arteries (11), reconstruction of the aortic pathway (4), reconstruction of the pulmonary pathway (8), correction of situs inversus (1), and correction of anomalous pulmonary (1) or systemic (1) venous drainage. Reconstructive procedures were performed using donor or recipient tissue or both. There were six early deaths (hyperacute rejection, 1 patient; pulmonary hypertension, 1; graft failure, 2 patients; infection, 2) and six late deaths (sudden death, 2; chronic rejection, 2; nonspecific graft dysfunction, 1; lymphoproliferative disease, 1). The survival rate was 43% +/- 12% at 3 years. No deaths were related to surgical technique. Survival was not significantly different in pediatric recipients with cardiomyopathy (67% +/- 9%; p = 0.22). Accelerated coronary artery disease was noted in 4 operative survivors (22%; 70% confidence limits, 12% to 36%). All late survivors were free from cardiac symptoms after a mean follow-up of 34 +/- 24 months (range, 6 to 71 months). Based on this study, we reached three conclusions. (1) Careful planning of both harvesting and transplantation procedures allows heart transplantation in recipients with congenital heart diseases. (2) The surgical technique may be demanding, but the early risk is not increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Electromagnetic effects on bone formation at implants in the medullary canal in rabbits.

This experiment was aimed at illuminating the relationship between electromagnetic and mechanical stimuli of bone formation when present simultaneously. Movable and stationary intramedullary wire implants were studied in rabbits treated with a pulsing electromagnetic field (PEMF) 4 h/day for 3 weeks, and were compared with identical control animals without PEMF. Trabecular bone formed routinely at spontaneously movable implants, but not at stationary ones. On average, PEMF-treated movable implants in the femur induced 44% more bone than untreated movable implants. Also, in the PEMF-treated femora, a 22% enlargement of the area of the medullary canal was observed compared with no-field controls. In the tibia, these effects were weak or nonexistent. The PEMF used did not induce bone at stationary implants, suggesting that under these conditions it is not a primary trigger in vivo.

Bone formation near direct current electrodes with and without motion.

The osteogenesis induced in the medullary canal of rabbits by the implantation of moving and stationary wire electrodes was studied with and without the simultaneous application of 20-microA constant direct cathodic current. After 3 weeks, the formation of new trabecular bone in the canal was studied and measured microscopically. Electrically stimulated osteogenesis was not observed at stationary electrodes. As in previous studies with this model, a movable electrode alone stimulated new bone formation whose area was 7-10% of the canal area. The amount of this bone was not statistically increased by the addition of cathode current. Movable, electrically active cathodes were associated, however, with fluid-filled spaces incorporated within the new trabecular bone. When mechanical stimuli were controlled, we were not able to demonstrate that the direct current stainless steel cathode acts either as an inducer or a substantial enhancer of medullary osteogenesis.

Bone growth after osteotomy and internal fixation in young rabbits.

The factors leading to overgrowth following fixation of long-bone fractures in children have never been clearly understood. The amount of trauma and the type of fixation may play a role. A rabbit model was used to investigate the influence of a femoral osteotomy and plate fixation on subsequent growth. Unilateral midshaft femoral osteotomy was performed in 6-week-old rabbits, and the bone was fixed internally with a plate and screws. End-to-end reduction was performed either at full length or with a segment removed. Bone length measurements at the end of growth revealed no significant difference in growth between the control femur and the femur that had undergone osteotomy and plate fixation. Shortened plated femora also showed no tendency to grow longer or faster than full-length fixed femora or controls. Interestingly, in the ipsilateral tibia a small but statistically significant length increase, equivalent to about 2% increase in additional growth, was observed, whereas technetium-99 methylene diphosphonate uptake was reduced in the tibial physes. In the context of the rabbit experimental model chosen, these results suggest that significant femoral over-growth does not occur following femoral osteotomy and plate fixation.

Arterial switch operation: a new technique of coronary transfer.

A successful outcome after arterial switch operation (ASO) for transposition of the great arteries (TGA) depends in large part on the adequacy of transfer of the coronary arteries to the neoaorta. The present paper describes a new technique of coronary transfer which was used in 43 patients: 28 neonates with TGA and intact septum (with coarctation in one), 10 neonates with TGA and ventricular septal defect (with coarctation in one), 2 children undergoing ASO after failed Senning operation and 3 patients with complex TGA. A standardized uniform technique of coronary transfer was used; this technique involved reimplantation of the two coronary ostia side by side after excision of a single button of neoaortic wall. Most coronary patterns were encountered: the usual pattern in 30, circumflex from right coronary artery in 7, inverted coronary arteries in 3, inverted circumflex and right coronary arteries in 3. There was no early coronary-related mortality or morbidity. One late death (3 months) was probably coronary-related. The overall coronary risk was 2.3% (70% confidence limits = 0.3%-7.5%). The proposed technique of coronary transfer can be used in most patients with TGA (all patients without coronary arteries running between the great arteries) and entails a low coronary risk.

Application of low-intensity ultrasound to growing bone in rats.

Low-intensity pulsed ultrasound recently has been shown to accelerate long bone fracture healing, but its effect on bone growth and development is unknown. The longitudinal growth and bone density of the femur and tibia in young rats was measured after application of an ultrasound transducer emitting 1.5-MHz pulsed ultrasound (30 mW/cm2, SATA) for 20 min/day. After 28 days, no length difference was detected (< or = 2%) compared to the sham-treated leg or to unexposed controls. Also, no significant difference in bone mineral density (BMD) of the femur or tibia was found (< or = 6%). In a repeated experiment in which a periosteal trauma stimulus was created in the femoral diaphysis, the ultrasound also had no effect on growth or BMD. This results suggests that physeal bone growth is far less sensitive to this level of ultrasound application than is fracture repair. This may be related to the cascade of cellular events and regulatory factors that are present after a fracture.

Somatosensory cortical evoked potential changes after deformity correction.

The somatosensory cortical evoked potentials recorded during posterior spine fusion and instrumentation for 99 consecutive patients with idiopathic scoliosis, 18 years of age or younger, were retrospectively reviewed. The potentials were recorded from scalp electrodes while synchronously stimulating both tibial nerves near the ankles. Signal changes observed during consecutive 30-minute time intervals after deformity correction were analyzed. No changes in neurologic status were observed postoperatively. Latency values tended to remain constant on average. A small, but statistically significant, decrease in the first two interpeak amplitudes was observed during the first 30-minute interval after deformity correction. The first interpeak amplitude recovered, while the second remained statistically significantly decreased. No patient had a decrease of greater than 50% in both of the first two amplitudes, which persisted throughout the 60-minute interval immediately after deformity correction. This study demonstrated a tendency for somatosensory cortical evoked potential interpeak amplitudes to decrease during the first 30 minutes after deformity correction. There was a great deal of individual variation, including amplitude increases in many patients. There was no evidence supporting an association between dramatic, sustained amplitude decreases and uncomplicated deformity correction. The value of thoroughly evaluating somatosensory cortical evoked potential signal trends while making intraoperative decisions is emphasized.

Return to play after cervical spine injury.

STUDY DESIGN: A questionnaire survey was mailed to members of the Cervical Spine Research Society, the Herodiuus Sports Medicine Society, and to members of the authors' Department of Orthopaedics. OBJECTIVES: The purpose of our study was to evaluate what influence, if any, factors such as published guidelines, type of sport of the patient, number of years in practice, subspecialty interest, and sports participation of the respondent held in the "return to play" decision-making process after a cervical spine injury. SUMMARY OF BACKGROUND DATA: The consequences of cervical spine injury are potentially catastrophic, and return to play decisions in athletes with a history of neck injury can be agonizing. Although recent publications have addressed some of the concerns regarding cervical spine injuries in the athletic population, many questions remain unanswered. Factors such as published guidelines, type of sport of the patient, number of years in practice, subspecialty interest, and sports participation of the respondent have all been suggested as having a possible role in return to play decisions. METHODS: Representative radiographs and case histories of 10 athletes who had sustained neck injury were mailed to 346 physicians. For each case physicians selected every type of play (of six categories) that they felt comfortable recommending. Type of play was divided into six categories: Type 1, collision sports; Type 2, contact sports; Type 3, noncontact, high velocity sports; Type 4, noncontact, repetitive load sports (e.g., running); Type 5, noncontact, low impact sports; Type 6, no sports. In addition, demographic data regarding board certification, subspecialty interest, number of years in practice, use of guidelines in return to play decisions, and personal participation in sports were queried from all respondents. Statistical analysis was completed with Statview (Berkeley, CA). Basic descriptive statistics, chi2, and ANOVA were used where appropriate. RESULTS: Three hundred forty-six questionnaires were mailed and 113 were returned (response rate 32.7%). One hundred ten (97%) of the respondents who completed the questionnaire were board certified. Seventy-five were subspecialists in spine, 22 were subspecialists in sportsmedicine, and 13 reported interests in both sports medicine and spine. Use of Published Guidelines. Although 49% of respondents reported using guidelines in decision-making, the use of guidelines was statistically significant in only one case (P = 0.04). Hierarchy of Risk. In general, those physicians who participated in the study followed the hierarchy of risk that we established in this study (Type 1 [collision sports; highest level of risk] through Type 6 [no sports; lowest level of risk]). Twelve (10.6%) respondents, however, deviated from it in one or more cases. Years in Practice. In three cases there was a statistically significant association between the number of years a physician was in practice and the type of play selected (P < 0.05). In each case a lower level of play tended to be recommended by more senior physicians. Subspecialty Interest. In three cases those respondents with a spine subspecialty interest recommended returned to a higher level of play (P < 0.05). CONCLUSIONS: There is no consensus on the postinjury management of many cervical spine-injured patients. Further research, education, and discussion on this topic are needed.

Early clinical experience with the Syracuse I-Plate: an anterior spinal fixation device.

Sixteen patients were treated with a new anterior internal fixation device after thoracolumbar or lumbar decompression, and fusion with bone grafting. Ten patients had acute burst fractures, four had metastatic tumors, and two had old, healed fractures with deformity. In the acute fracture group, eight patients had neurologic deficits and seven patients experienced improvement. Six patients had lesions of the conus medullaris, all of which improved. The four patients with metastatic tumors underwent surgery for back and leg pain and all gained significant relief. Two patients had correction of old fracture deformity with satisfactory outcome. Complications were minimal. The new anterior stabilization device provided early stability, allowed early patient mobilization, was easy to insert, and has a low profile. Late collapse, non-union, and kyphotic deformity have not been noted thusfar.