Imaging of head and neck lipoblastoma: case report and systematic review.

Lipoblastoma is a rare and benign tumour arising from embryonal fat cells, predominantly diagnosed in children younger than 3 years old. The most frequent locations are the extremities and trunk, while the head and neck areas are more rarely affected (10-15% of total cases). Clinically, the most common presentation is a fast-growing painless mass. Ultrasound is the first-line imaging examination, but Magnetic Resonance Imaging (MRI) allows for better definition of the relationships with the adjacent vascular and muscular structures. It can help to identify the lipomatous components, and it is useful for preoperative planning. However, the definitive diagnosis is provided by histopathological examination. Complete surgical excision is the first-line treatment, with a good prognosis in case of total eradication. We report the case of a 7-month-old male child with a rapidly growing mass that had typical radiological features of lipoblastoma.

Ultrasound and Magnetic Resonance Imaging Diagnosis of Isolated Tear of the Accessory Soleus Tendon: A Case Report and Review of the Literatures.

INTRODUCTION: The accessory soleus muscle (also known as the supernumerary soleus or soleus secundus) is an uncommon congenital anatomical. The presence of this muscle is generally asymptomatic. In cases of symptomatic accessory soleus muscle, it manifests with painful swelling of the posteromedial region of the ankle. To the best of our knowledge, partial or complete accessory soleus tendon tears were reported in literature in only three cases; all of them were diagnosed with magnetic resonance imaging (MRI) examination while only one was diagnosed with both ultrasound (US) and MRI. CASE REPORT: We presented a case of a 63-year-old Caucasian woman presented to our emergency department with severe pain in the posteromedial region of her right ankle. US and MRI of the calf and ankle were performed and a complete tear of the right accessory soleus tendon with fluid gap and myotendinous retraction was diagnosed. CONCLUSION: An accessory soleus muscle partial or complete tears are very uncommon injuries. This condition can mimic many other pathologies, and therefore, radiologists should know the physiological and pathological imaging findings for a correct interpretation of ankle injuries, avoiding misinterpretations.

Human salivary Raman fingerprint as biomarker for the diagnosis of Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to progressive and irreversible muscle atrophy. The diagnosis of ALS is time-consuming and complex, with the clinical and neurophysiological evaluation accompanied by monitoring of progression and a long procedure for the discrimination of similar neurodegenerative diseases. The delayed diagnosis strongly slows the potential development of adequate therapies and the time frame for a prompt intervention. The discovery of new biomarkers could improve the disease diagnosis, as well as the therapeutic and rehabilitative effectiveness and monitoring of the pathological progression. In this work saliva collected from 19 patients with ALS, 10 affected by Parkinson's disease, 10 affected by Alzheimer's disease and 10 healthy subjects, was analysed using Raman spectroscopy, optimizing the parameters for detailed and reproducible spectra. The statistical multivariate analysis of the data revealed a significant difference between the groups, allowing the discrimination of the disease onset. Correlation of Raman data revealed a direct relationship with paraclinical scores, identifying multifactorial biochemical modifications related to the pathology. The proposed approach showed a promising accuracy in ALS onset discrimination, using a fast and sensitive procedure that can make more efficient the diagnostic procedure and the monitoring of therapeutic and rehabilitative processes in ALS.

CSF angiogenin levels in amyotrophic lateral Sclerosis-Frontotemporal dementia spectrum.

Objective: Angiogenin (ANG) is a pro-angiogenic and neurotrophic factor with an important role in stress-induced injury, by promoting neovascularization and neuronal survival. Identification of loss-of-function mutations and evidence of beneficial effect of ANG administration in transgenic SOD1G93A mice have linked ANG to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), stimulating interest in considering circulating ANG levels as an ALS disease biomarker although robust evidence is still lacking. Aim of our study was to assess differences of ANG levels in the cerebrospinal fluid (CSF) of a large cohort of patients with ALS and frontotemporal dementia (FTD) compared to controls and to explore correlations between ANG content and disease-related clinical variables. Methods: ANG levels were measured in CSF samples using a commercially available ELISA kit in 88 patients affected with ALS and/or FTD and 46 unrelated individuals (control group). Results: ANG levels didn't differ significantly between cases and controls. Patients with FTD or ALS-FTD showed significantly increased CSF concentration of ANG compared to ALS patients without dementia and controls in a multivariate regression model (p < 0.001). No correlations were found in ALS/FTD patients between ANG levels and clinical parameters, including age, presence of C9orf72 repeat expansion, body mass index (BMI). Conclusions: our findings highlight a role of ANG as CSF biomarker useful to identify ALS patients with concurrent FTD and suggest that it should be further explored as potential biomarker for FTD.

Bilateral unicompartmental knee arthroplasty: one stage or two stages?

BACKGROUND: Bilateral unicompartmental knee arthroplasty (UKA) may be performed as one- or two-stage procedure. Previous reports suggest that UKA provides a more rapid functional recovery than total knee arthroplasty. However, little data exist on whether bilateral UKA can be performed without increasing the perioperative risk compared with unilateral cases. METHODS: We retrospectively compared 51 patients treated between January 2014 and March 2017 with single-stage UKA (group A) with 51 patients who underwent unilateral procedure (group B) to evaluate perioperative complications. We noted no statistically significant difference between the two groups in terms of gender, age and body mass index. RESULTS: Patients who underwent single-stage bilateral UKA had longer operating room time with respect to single procedure (93.2 min vs. 50.7 min). However, the bilateral group had a shorter cumulative operating room time (93.2 min) compared to the unilateral group (101.5 min) with a statistically significant difference (p < 0.05). Average hemoglobin loss at discharge was 3.1 points for group A and 2.4 for group B, with a statistically significant difference (p < 0.05). CONCLUSION: Our results demonstrated that bilateral simultaneous UKA does not increase the risk for perioperative complications. Total blood loss at discharge is statistically higher in bilateral UKA rather than unilateral UKA; however, cumulative hemoglobin loss is statistically lower in bilateral group. Patients can benefit from a single hospital admission and anesthetic time, while the shorter total inpatient stay and lower blood loss can reduce hospital costs in cases of bilateral surgery. LEVEL OF EVIDENCE IV: Retrospective study.

Diagnostic accuracy of magnetic resonance imaging in assessing placental adhesion disorder in patients with placenta previa: Correlation with histological findings.

OBJECTIVE: To evaluate MRI accuracy in assessing placental adhesion disorders (PAD) in patients with placenta previa correlating imaging results with histological findings. MATERIALS AND METHODS: Sixty-one patients who underwent abdomino-pelvic magnetic resonance imaging (MRI) for ultrasound suspicion of PAD were prospectively evaluated. T1- and T2-weighted images, with and without fat suppression, were obtained in the three conventional planes using a 1.5 T MRI scanner. MRI accuracy to evaluate the presence of PAD was assessed on the basis of the occurrence of the following abnormal MRI signs: 1) intraplacental dark bands; 2) focal interruption of myometrial border; 3) intraplacental abnormal vascularity; 4) uterine bulging; 5) tenting of the bladder and/or 6) direct visualization of adjacent tissues invasion only in case of percretism. Imaging results were classified as suggestive or not of PAD using histological data as standard of reference; two methods of imaging analysis were used represented by the presence of at least one (Method A) or two (Method B) abnormal MRI signs; the correlation between the presence of each abnormal MRI sign of PAD and the corresponding histological finding was also assessed. RESULTS: The accuracy, as the area under the receiver operating characteristic curve, was significantly (p = 0.001) higher for Method B (0.92, C.I. 95%: 0.82-0.97) compared to Method A (0.764, C.I. 95%: 0.64-0.86). Among the abnormal MRI signs, intraplacental dark bands and focal interruption of myometrial border were those highly correlated with histological proof of PAD (ρ > 0.71, p < 0.001, for both); as result, a modified version of Method B (Method C) was identified considering as criterion for PAD the combined presence of the two abnormal MRI signs highly correlated with histologically proven PAD; however, the accuracy of Method C was significantly (p = 0.005) lower (0.80, C.I. 95%: 0.67-0.89) than Method B and comparable to Method A. CONCLUSIONS: MRI is a useful imaging technique to assess PAD in patients with placenta previa; in particular, the presence of at least two among all the abnormal MRI signs represents the most accurate criterion (Method B) to identify PAD. Although intraplacental dark bands and focal interruption of myometrial border showed the highest correlation with histological proof of PAD as well as this association was the most frequent in PAD, the combination of these latter MRI signs along with other abnormal signs should be considered diagnostic for PAD.

The diagnostic accuracy of magnetic resonance venography in the detection of deep venous thrombosis: a systematic review and meta-analysis.

AIM: To search the literature for further evidence for the use of magnetic resonance venography (MRV) in the detection of suspected DVT and to re-evaluate the accuracy of MRV in the detection of suspected deep vein thrombosis (DVT). MATERIALS AND METHODS: PubMed, EMBASE, Scopus, Cochrane, and Web of Science were searched. Study quality and the risk of bias were evaluated using the QUADAS 2. A random effects meta-analysis including subgroup and sensitivity analyses were performed. RESULTS: The search resulted in 23 observational studies all from academic centres. Sixteen articles were included in the meta-analysis. The summary estimates for MRV as a diagnostic non-invasive tool revealed a sensitivity of 93% (95% confidence interval [CI]: 89% to 95%) and specificity of 96% (95% CI: 94% to 97%). The heterogeneity of the studies was high. Inconsistency (I2) for sensitivity and specificity was 80.7% and 77.9%, respectively. CONCLUSION: Further studies investigating the use of MRV in the detection of suspected DVT did not offer further evidence to support the replacement of ultrasound with MRV as the first-line investigation. However, MRV may offer an alternative tool in the detection/diagnosis of DVT for whom ultrasound is inadequate or not feasible (such as in the obese patient).

Renal tubular dysfunction in human visceral leishmaniasis (Kala-azar).

BACKGROUND: There are few studies about the functional tubular disturbances in human Kala-azar. The aim of this study was to investigate alterations in tubular reabsorption of urinary proteins, sodium, potassium, chloride, glucose, uric acid, inorganic phosphate and amino acids in patients with the chronic form of kala-azar. PATIENTS AND METHODS: This is a cross-sectional study of 55 patients with visceral leishmaniasis (Kala-azar). The laboratorial investigation was: creatinine clearance and daily urinary excretion of total proteins, albumin, IgG, beta2-microglobulin, sodium, potassium, chloride, calcium, inorganic phosphate, uric acid and glucose. Plasma and urinary protein electrophoresis were performed in agarose gel. Urinary light chains were determined by the nephelometric method and amino acids by chromatography. All data were compared to those of a control group. RESULTS: Hypoalbuminemia, hypergammaglobulinemia as well as increased plasma levels of both IgG and beta2-microglobulins were found in all patients with Kala-azar. The mean urinary protein excretion was 277 +/- 66 mg/day. Increased albumin excretion was observed in 44% of patients accounting for 17% of the total urinary protein excretion. Proteinuria consisted predominantly of low molecular weight protein fractions that migrated with alpha1, alpha2, beta and especially gamma globulins. Urinary beta2-microglobulin excretion was elevated in all patients. Immune electrophoresis showed increased urinary excretion rates of kappa (27%) and lambda (42%) light chains. The Bence-Jones test was positive in 20% of patients. Immunofixation was negative for monoclonal peak. The principal alterations were hyponatremia 94.6%, hypokalemia 26%, hypochloremia 27.2%, hypocalcemia 32%, hypomagnesemia 41.8%, hypouricemia 14.3%, Increased urinary excretion fraction were: sodium 15%, potassium 26%, chloride 33.3%, calcium 32%, inorganic phosphate 27.2%, magnesium 100% with hypermagnesiuria, uric acid 44%. Glucosuria was found in one third of patients. CONCLUSION: There was evidence of renal proximal tubular damage with alterations in the reabsorption of proteins and light chains with characteristics of a tubular proteinuria, Disturbances of tubular reabsorption of uric acid, calcium, phosphate, glucose and magnesium were also observed.

Cell polarity: a tale of two Ts.

The microtubule cytoskeleton plays an important role in cell polarity. Central to this process in fission yeast is tea1p, a marker of polarized cell growth that is delivered to the cell surface in a microtubule-dependent fashion. Recent studies suggest that the actin-binding protein bud6p may be a tea1p effector.

The highly conserved protein methyltransferase, Skb1, is a mediator of hyperosmotic stress response in the fission yeast Schizosaccharomyces pombe.

The p21-activated kinase, Shk1, is required for cell viability, establishment and maintenance of cell polarity, and proper mating response in the fission yeast, Schizosaccharomyces pombe. Previous genetic studies suggested that a presumptive protein methyltransferase, Skb1, functions as a positive modulator of Shk1. However, unlike Shk1, Skb1 is not required for viability or mating of S. pombe cells and contributes only modestly to the regulation of cell morphology under normal growth conditions. Here we demonstrate that Skb1 plays a more significant role in regulating cell growth and polarity under conditions of hyperosmotic stress. We provide evidence that the inability of skb1Delta cells to properly maintain cell polarity in hyperosmotic conditions results from inefficient subcellular targeting of F-actin. We show that Skb1 localizes to cell ends, sites of septation, and nuclei of S. pombe cells. Hyperosmotic shock results in substantial delocalization of Skb1 from cell ends and nuclei, as well as stimulation of Skb1 protein methyltransferase activity. Taken together, our results demonstrate a new role for Skb1 as a mediator of hyperosmotic stress response in fission yeast. We show that the protein methyltransferase activity of the human Skb1 homolog, Skb1Hs, is also stimulated by hyperosmotic stress in fission yeast, providing evidence for evolutionary conservation of a role for Skb1-related proteins as mediators of hyperosmotic stress response, as well as mechanisms involved in regulating this novel class of protein methyltransferases.

[The effect of peroperative transfusion on survival in resected lung carcinomas]. / Influencia de la transfusión perioperatoria en la supervivencia de los carcinomas de pulmón resecados.

This paper analyzes the influence of perioperative transfusion on survival after lung cancer surgery. Between January 1991 and December 1995, we enrolled 405 patients, 196 of whom received transfusions and 209 of whom did not. Follow-up extended to December 1997. Excluded were patients undergoing exploratory thoracotomy (n = 92), those who died during the postoperative period (n = 19) and those lost to follow-up (n = 13). The final number of patients in the study was 281 (136 who received transfusions and 145 who did not). We analyzed age, sex, general clinical status measured on the Eastern Cooperative Oncology Group (ECOG) scale, histological type and TNM staging. Single and multiple variable analyses were performed. At the end of the study 158 patients were alive and 123 had died. Transfusions were used more often in pneumonectomies (p < 0.001) and in patients with an ECOG score of 2 (p < 0.01). Survival at 36 and 60 months, calculated using the Kaplan-Meier method was 52% and 30%, respectively, for those who had received transfusions, and 53% and 49%, respectively, for those who had not. The differences were not statistically significant (p > 0.1). Multivariant analysis failed to demonstrate an influence of transfusion on survival (relative risk of 1.08; 95% confidence interval 0.72-1.61; p > 0.1). We conclude that there is no negative prognostic effect of perioperative transfusion.

Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle.

The molecular mechanisms that coordinate cell morphogenesis with the cell cycle remain largely unknown. We have investigated this process in fission yeast where changes in polarized cell growth are coupled with cell cycle progression. The orb6 gene is required during interphase to maintain cell polarity and encodes a serine/threonine protein kinase, belonging to the myotonic dystrophy kinase/cot1/warts family. A decrease in Orb6 protein levels leads to loss of polarized cell shape and to mitotic advance, whereas an increase in Orb6 levels maintains polarized growth and delays mitosis by affecting the p34(cdc2) mitotic kinase. Thus the Orb6 protein kinase coordinates maintenance of cell polarity during interphase with the onset of mitosis. orb6 interacts genetically with orb2, which encodes the Pak1/Shk1 protein kinase, a component of the Ras1 and Cdc42-dependent signaling pathway. Our results suggest that Orb6 may act downstream of Pak1/Shk1, forming part of a pathway coordinating cell morphogenesis with progression through the cell cycle.

On growth and form: control of cell morphogenesis in fission yeast.

In the past year, we have gained considerable insight into the process of cell morphogenesis and the establishment of positional information in fission yeast. The highlights include a better understanding of the role of the microtubule cytoskeleton in the control of cell shape, as well as the identification of novel genes essential for the establishment of cell polarity and for the positioning of the site of cell division.

Distinct roles of PP1 and PP2A-like phosphatases in control of microtubule dynamics during mitosis.

Assembly of a mitotic spindle requires the accurate regulation of microtubule dynamics which is accomplished, at least in part, by phosphorylation-dephosphorylation reactions. Here we have investigated the role of serine-threonine phosphatases in the control of microtubule dynamics using specific inhibitors in Xenopus egg extracts. Type 2A phosphatases are required to maintain the short steady-state length of microtubules in mitosis by regulating the level of microtubule catastrophes, in part by controlling the the microtubule-destabilizing activity and phosphorylation of Op18/stathmin. Type 1 phosphatases are only required for control of microtubule dynamics during the transitions into and out of mitosis. Thus, although both type 2A and type 1 phosphatases are involved in the regulation of microtubule dynamics, they have distinct, non-overlapping roles.

Microtubules mediate mitochondrial distribution in fission yeast.

The Schizosaccharomyces pombe mutant, ban5-4, displays aberrant mitochondrial distribution. Incubation of this conditional-lethal mutant at the nonpermissive temperature led to aggregated mitochondria that were distributed asymmetrically within the cell. Development of this mitochondrial asymmetry but not mitochondrial aggregation required progression through the cell division cycle. Genetic analysis revealed that ban5-4 is an allele of atb2 encoding alpha 2-tubulin. Consistent with this finding, cells with the cold-sensitive nda3 mutation in beta-tubulin displayed aggregated and asymmetrically distributed mitochondria after incubation at lowered temperatures. These results indicate that microtubules mediate mitochondrial distribution in fission yeast and provide the first genetic evidence for the role of microtubules in mitochondrial movement.

Fission yeast cell morphogenesis: identification of new genes and analysis of their role during the cell cycle.

To identify new genes involved in the control of cell morphogenesis in the fission yeast Schizosaccharomyces pombe we have visually screened for temperature-sensitive mutants that show defects in cell morphology. We have isolated and characterized 64 mutants defining 19 independent genes, 10 of which have not been previously described. One class of mutants, defining 12 orb genes, become round and show a complete loss of cell polarity. A second class of mutants exhibits branched or bent morphologies. These mutants show defects in either selection of the growth site, defining two tea genes, or in the maintenance of growth direction, defining five ban genes. Immunofluorescence analysis of these morphological mutants shows defects in the organization of the microtubule and actin cytoskeleton. These defects include shortened, bundled, and asymmetrically localized microtubules and enlarged and mislocalized actin patches. Analysis of the mutant phenotypes has allowed us to order the genes into four groups according to their function during the cell cycle: genes required for the maintenance of cell polarity throughout the cell cycle; genes necessary only for the reestablishment of cell polarity after mitosis and not for maintaining cell polarity once it is established; genes essential for the transition from monopolar to bipolar growth and genes that severe as 'polarity markers'.

Control of microtubule dynamics and length by cyclin A- and cyclin B-dependent kinases in Xenopus egg extracts.

In eukaryotic cells, the onset of mitosis involves cyclin molecules which interact with proteins of the cdc2 family to produce active kinases. In vertebrate cells, cyclin A dependent kinases become active in S- and pro-phases, whereas a cyclin B-dependent kinase is mostly active in metaphase. It has recently been shown that, when added to Xenopus egg extracts, bacterially produced A- and B-type cyclins associate predominantly with the same kinase catalytic subunit, namely p34cdc2, and induce its histone H1 kinase activity with different kinetics. Here, we show that in the same cell free system, both the addition of cyclin A and cyclin B changes microtubule behavior. However, the cyclin A-dependent kinase does not induce a dramatic shortening of centrosome-nucleated microtubules whereas the cyclin B-dependent kinase does, as previously reported. Analysis of the parameters of microtubule dynamics by fluorescence video microscopy shows that the dramatic shortening induced by the cyclin B-dependent kinase is correlated with a several fold increase in catastrophe frequency, an effect not observed with the cyclin A-dependent kinase. Using a simple mathematical model, we show how the length distributions of centrosome-nucleated microtubules relate to the four parameters that describe microtubule dynamics. These four parameters define a threshold between unlimited microtubule growth and the establishment of steady-state dynamics, which implies that well defined steady-state length distributions can be produced by regulating precisely the respective values of the dynamical parameters. Moreover, the dynamical model predicts that increasing catastrophe frequency is more efficient than decreasing the rescue frequency to reduce the average steady state length of microtubules. These theoretical results are quantitatively confirmed by the experimental data.

Lattice defects in microtubules: protofilament numbers vary within individual microtubules.

We have used cryo-electron microscopy of vitrified specimens to study microtubules assembled both from three cycle purified tubulin (3x-tubulin) and in cell free extracts of Xenopus eggs. In vitro assembled 3x-tubulin samples have a majority of microtubules with 14 protofilaments whereas in cell extracts most microtubules have 13 protofilaments. Microtubule polymorphism was observed in both cases. The number of protofilaments can change abruptly along individual microtubules usually by single increments but double increments also occur. For 3x-tubulin, increasing the magnesium concentration decreases the proportion of 14 protofilament microtubules and decreases the average separation between transitions in these microtubules. Protofilament discontinuities may correspond to dislocation-like defects in the microtubule surface lattice.

Cyclin A is required at two points in the human cell cycle.

Cyclins play a fundamental role in regulating cell cycle events in all eukaryotic cells. The human cyclin A gene was identified as the site of integration of hepatitis B virus in a hepatocarcinoma cell line; in addition, cyclin A is associated with the E2F transcription factor in a complex which is dissociated by the E1A oncogene product. Such findings suggest that cyclin A is a target for oncogenic signals. We have now found that DNA synthesis and entry into mitosis are inhibited in human cells microinjected with anti-cyclin A antibodies at distinct times. Cyclin A binds both cdk2 and cdc2, giving two distinct cyclin A kinase activities, one appearing in S phase, the other in G2. These results suggest that cyclin A defines novel control points of the human cell cycle.