Splenic abscesses in childhood brucellosis: a case-based review.

OBJECTIVE: Human brucellosis is a zoonosis with an extremely wide spectrum of clinical manifestations. Focal splenic involvement is very uncommon, particularly in the pediatric age group, during the illness' acute phase. CASE REPORT: A 4-year-old boy, already receiving third-generation cephalosporin treatment, was transferred from a local hospital to the University Pediatric Department for fever, anemia, increased inflammation index, and multiple, hyper-echogenic splenic lesions on abdominal ultrasound. Initial diagnostic laboratory investigations for Brucella infection, including the Widal-Wright test, were found to be negative. However, further diagnostic laboratory analysis using the chemiluminescent immunoassay was positive for Brucella IgM antibodies. Treatment with rifampicin at a dose of 150 mg/Kg/twice daily and co-trimethoprim at a dose of 80 mg/Kg/twice daily was started and continued for 7 weeks. IgM antibodies were undetectable after 2 weeks of treatment, and after 6 weeks of treatment, abdominal ultrasound documented a reduction of the diameter of the major splenic infiltrate from 1 to 0.5 cm. At 3 and 5 months of follow-up, re-evaluation of the abdominal lesions displayed complete resolution of the splenic lesions and a complete clinical recovery. CONCLUSIONS: The present case and a literature review are presented in this study since a standard diagnostic laboratory evaluation for brucellosis may miss the diagnosis, and in suspected cases, the laboratory analysis should be extended. Splenic abscesses are known to be rare in brucellosis, but the diagnosis should be considered in children with severe focal lesions, as specific antibiotic treatment may result in complete clinical recovery.

Surface ruptures database related to the 26 December 2018, MW 4.9 Mt. Etna earthquake, southern Italy.

We provide a database of the surface ruptures produced by the 26 December 2018 Mw 4.9 earthquake that struck the eastern flank of Mt. Etna volcano in Sicily (southern Italy). Despite its relatively small magnitude, this shallow earthquake caused about 8 km of surface faulting, along the trace of the NNW-trending active Fiandaca Fault. Detailed field surveys have been performed in the epicentral area to map the ruptures and to characterize their kinematics. The surface ruptures show a dominant right-oblique sense of displacement with an average slip of about 0.09 m and a maximum value of 0.35 m. We have parsed and organized all observations in a concise database, with 932 homogeneous georeferenced records. The Fiandaca Fault is part of the complex active Timpe faults system affecting the eastern flank of Etna, and its seismic history indicates a prominent surface-faulting potential. Therefore, this database is essential for unravelling the seismotectonics of shallow earthquakes in volcanic areas, and contributes updating empirical scaling regressions that relate magnitude and extent of surface faulting.

Fascicular nerve stimulation and recording using a novel double-aisle regenerative electrode.

OBJECTIVE: As artificial prostheses become more refined, they are most often used as a therapeutic option for hand amputation. By contrast to extra- or intraneural interfaces, regenerative nerve electrodes are designed to enable electrical interfaces with regrowing axonal bundles of injured nerves, aiming to achieve high selectivity for recording and stimulation. However, most of the developed designs pose an obstacle to the regrowth mechanisms due to low transparency and cause impairment to the nerve regeneration. APPROACH: Here we present the double-aisle electrode, a new type of highly transparent, non-obstructive regenerative electrode. Using a double-side thin-film polyimide planar multi-contact electrode, two nerve fascicles can regenerate without physical impairment through two electrically isolated aisles. MAIN RESULTS: We show that this electrode can be used to selectively record and stimulate fascicles, acutely as well as chronically, and allow regeneration in nerve gaps of several millimeters without impairment. SIGNIFICANCE: This multi-aisle regenerative electrode may be suitable for neuroprosthetic applications, such as prostheses, for the restoration of hand function after amputation or severe nerve injuries.

The Walking Corsi Test (WalCT): a normative study of topographical working memory in a sample of 4- to 11-year-olds.

We report normative data on topographical working memory collected through the Walking Corsi Test (WalCT; Piccardi et al., 2008 ) for developing a standard administration procedure to be used in clinical and educational practice. A total of 268 typically developing Italian children aged 4-11 years performed both WalCT and Corsi Block-Tapping Test (CBT; Corsi, 1972 ) a well-known visuo-spatial memory test. WalCT has already been validated in adults, demonstrating sensitivity in detecting topographical memory deficits even in individuals who have no other memory impairments. Our results showed that age, but not sex, affected performances. Both girls and boys had a larger span on the CBT than the WalCT. The youngest group did not differ in performing WalCT and CBT, but from 5.6 years of age children performed better on CBT than WalCT, suggesting that memory in reaching space develops before topographical memory. Only after 5 years of age do children learn to process specifically topographical stimuli, suggesting that this happens when their environmental knowledge becomes operational and they increase environmental independence. We also discuss the importance to introduce WalCT in the clinical assessment.

Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

AIM: This retrospective multi-institutional study addresses the role of surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of multicystic peritoneal mesothelioma (MCPM). MCPM is an uncommon tumour with uncertain malignant potential and no current standard therapy. Additionally, poorly defined pathological and biological features of this disease were investigated. METHODS: Twelve patients with MCPM underwent 14 procedures of cytoreduction and HIPEC in two Italian referral centres. Nine patients had recurrent disease after previous debulking (one operation in six patients, two in two, four in one). Biological markers related to mesothelioma origin and clinical features were assessed by immunohistochemical studies. RESULTS: Median follow-up was 64 months (range 5-148). Optimal cytoreduction (residual tumour nodules ≤2.5 mm) was performed in all the procedures. One grade IV postoperative complication (NCI/CTCAE v.3.0) and no operative death occurred. All the patients are presently alive with no evidence of disease, including two patients who underwent the procedure twice, due to locoregional disease recurrence. Five- and ten-year progression-free survival was 90% and 72%, accounting for a. statistically significant difference (P = 0.0001) with progression-free survival following previous debulking surgery (median 11 months; range 2-31). All cases showed low proliferative activity assessed by mitotic rate and Ki-67 expression. CONCLUSIONS: MCPM is a borderline tumour with a high propensity to local-regional recurrence. Definitive tumour eradication by means of cytoreduction and HIPEC seems more effective than debulking surgery in preventing disease relapse. Low mitotic rate and poor Ki-67 expression might be related to the peculiar behaviour of MCMP.

Splenic lymphangiomatosis associated with skeletal involvement (Gorham's disease): a new case and review of literature.

Lymphangiomatosis is a well-recognized congenital benign tumour, frequently seen in infancy and childhood, characterized by the presence of multiple lymphangiomas. Diffuse lymphangiomatosis also involving bony tissue is called Gorham's disease. This condition generally affects somatic soft tissue, where lymphatics are normally found. A predilection of this affection for bone, thoracic and neck involvement is well known, while involvement of abdominal viscera is very unusual. In bone this non malignant proliferation of lymphatic channels results in destruction and resorption of the osseous matrix. We report on a child in whom lymphangiomatosis involved both the bone and the spleen. A review of 166 cases is also reported.

A novel technique for rectocele repair in elderly women.

We have developed a transvaginal technique for rectocele repair which we believe to be particularly suitable for older woman. A transverse incision was made in the mucocutaneous border of the vaginal introitus. The rectal wall was separated from the rectovaginal septum. The vaginal wall was divided in the middle. The first flap was sewn to the second and this onto the first. This intervention permits the contemporary correction of other pathologies frequently found in older women, such as cystocele and prolapse of the uterus. Twenty-two elderly women underwent operations using this technique; the mean follow-up period was 48 months (range, 24-84 months). The need to assist evacuation digitally disappeared in all patients.

Cold-adapted enzymes from marine Antarctic microorganisms.

The Antarctic marine environment is characterized by challenging conditions for the survival of native microorganisms. Indeed, next to the temperature effect represented by the Arrhenius law, the viscosity of the medium, which is also significantly enhanced by low temperatures, contributes to slow down reaction rates. This review analyses the different challenges and focuses on a key element of life at low temperatures: cold-adapted enzymes. The molecular characteristics of these enzymes are discussed as well as the adaptation strategies which can be inferred from the comparison of their properties and three-dimensional structures with those of their mesophilic counterparts. As these enzymes display a high specific activity at low and moderate temperatures associated with a relatively high thermosensitivity, the interest in these properties is discussed with regard to their current and possible applications in biotechnology.

Kinetics and energetics of ligand binding determined by microcalorimetry: insights into active site mobility in a psychrophilic alpha-amylase.

A new microcalorimetric method for recording the kinetic parameters k(cat), K(m) and K(i) of alpha-amylases using polysaccharides and oligosaccharides as substrates is described. This method is based on the heat released by glycosidic bond hydrolysis. The method has been developed to study the active site properties of the cold-active alpha-amylase produced by an Antarctic psychrophilic bacterium in comparison with its closest structural homolog from pig pancreas. It is shown that the psychrophilic alpha-amylase is more active on large macromolecular substrates and that the higher rate constants k(cat) are gained at the expense of a lower affinity for the substrate. The active site is able to accommodate larger inhibitory complexes, resulting in a mixed-type inhibition of starch hydrolysis by maltose. A method for recording the binding enthalpies by isothermal titration calorimetry in a low-affinity system has been developed, allowing analysis of the energetics of weak ligand binding using the allosteric activator chloride. It is shown that the low affinity of the psychrophilic alpha-amylase for chloride is entropically driven. The high enthalpic and entropic contributions of activator binding suggest large structural fluctuations between the free and the bound states of the cold-active enzyme. The kinetic and thermodynamic data for the psychrophilic alpha-amylase indicate that the strictly conserved side-chains involved in substrate binding and catalysis possess an improved mobility, responsible for activity in the cold, and resulting from the disappearance of stabilizing interactions far from the active site.

Predictors of glycaemic control in indigent patients presenting with diabetic ketoacidosis.

AIM: To derive predictors of good glycaemic control in patients presenting with diabetic ketoacidosis (DKA) followed prospectively in a specialized clinic. METHODS: One hundred and sixty-one adult patients were admitted during a 31-month period and followed for at least 12 months. After 1 year, the patients were classified into three groups: good control (GC) (HbA1c < or = 7%), intermediate control (IC) (HbA1c 7-9%) and poor control (PC) (HbA1c > 9%). Characteristics of patients in the three groups were compared both at baseline and during follow-up. RESULTS: At 12 months, 36% of the patients were classified as GC, 27% as IC and 37% as PC. GC patients had higher fasting serum C-peptide levels 0.7 +/- 0.54 compared to 0.38 +/- 0.29 and 0.16 +/- 0.21 nmol/l, respectively, for the IC and PC patients (p < 0.0001). A higher proportion GC patient had a C-peptide level greater than 0.33 nmol/l than that for IC and PC patients (86, 61 and 19%, respectively; p < 0.0001). Exogenous insulin was safely discontinued in 50, 30 and 3% of patients, respectively, in the GC, IC and PC groups (p < 0.0001). Compliance with life-style interventions was higher in the GC than that in IC and PC patients (87, 41 and 5%, respectively; p < 0.0001). In the logistic regression analysis, predictors of good glycaemic control were having baseline fasting serum C-peptide value > or =0.33 mmol/l, OR: 3.01 (95% CI 1.07-8.55, p = 0.03) and compliance with life-style interventions OR 12.66 (95% CI 3.73-51.57, p = 0.0001). CONCLUSION: Among adult patients with DKA, significant predictors of good glycaemic control are preserved beta-cell function and compliance with life-style modifications.

Separate neural systems for processing action- or non-action-related sounds.

The finding of a multisensory representation of actions in a premotor area of the monkey brain suggests that similar multimodal action-matching mechanisms may also be present in humans. Based on the existence of an audiovisual mirror system, we investigated whether sounds referring to actions that can be performed by the perceiver underlie different processing in the human brain. We recorded multichannel ERPs in a visuoauditory version of the repetition suppression paradigm to study the time course and the locus of the semantic processing of action-related sounds. Results show that the left posterior superior temporal and premotor areas are selectively modulated by action-related sounds; in contrast, the temporal pole is bilaterally modulated by non-action-related sounds. The present data, which support the hypothesis of distinctive action sound processing, may contribute to recent theories about the evolution of human language from a mirror system precursor.

A perspective on cold enzymes: current knowledge and frequently asked questions.

Studies on psychrophilic enzymes to determine the structural features important for cold-activity have attracted increased attention in the last few years. This enhanced interest is due to the attractive properties of such proteins, i.e. a high specific activity and a low thermal stability, and thus, these enzymes constitute a tremendous potential for fundamental research and biotechnological applications. This review examines the impact of low temperatures on life, the diversity of adaptation to counteract these effects and gives an overview of the features proposed to account for low thermal stability and cold-activity, following the chronological order of the catalytic cycle phases. Moreover, we present an overview of recent techniques used in the analysis of the flexibility of a protein structure which is an important concept in cold-adaptation; an overview of biotechnological potential of psychrophilic enzymes and finally, a few frequently asked questions about cold-adaptation and their possible answers.

Some like it cold: biocatalysis at low temperatures.

In the last few years, increased attention has been focused on a class of organisms called psychrophiles. These organisms, hosts of permanently cold habitats, often display metabolic fluxes more or less comparable to those exhibited by mesophilic organisms at moderate temperatures. Psychrophiles have evolved by producing, among other peculiarities, "cold-adapted" enzymes which have the properties to cope with the reduction of chemical reaction rates induced by low temperatures. Thermal compensation in these enzymes is reached, in most cases, through a high catalytic efficiency associated, however, with a low thermal stability. Thanks to recent advances provided by X-ray crystallography, structure modelling, protein engineering and biophysical studies, the adaptation strategies are beginning to be understood. The emerging picture suggests that psychrophilic enzymes are characterized by an improved flexibility of the structural components involved in the catalytic cycle, whereas other protein regions, if not implicated in catalysis, may be even more rigid than their mesophilic counterparts. Due to their attractive properties, i.e., a high specific activity and a low thermal stability, these enzymes constitute a tremendous potential for fundamental research and biotechnological applications.

Ambipolar transistors based on azurin proteins.

A new type of transistor is presented. It is realised by using a metalloprotein; namely, azurin. Thanks to their natural functional characteristics, which involve inter- and intramolecular electron transfer, metalloproteins are good candidates for biomolecular nanoelectronics. The implementation of a prototype of protein transistor operating in air and in the solid state based on self-organised films of azurins is reported. Experimental current-voltage characteristics are shown. The new device presents an ambipolar behaviour as the gate bias voltage is changed. Exploiting this peculiar characteristic, a fully integrated logic gate which can be a good starting point for a new class of nanoelectronics devices has been realised.

Surgical approach to cervical lymph node metastasis in differentiated thyroid cancer.

BACKGROUND: Precautionary locoregional lymph node dissection in thyroid carcinomas for diagnostic and/or staging purposes is useless both in differentiated (papillary and follicular) and undifferentiated forms. It is only indicated in medullary carcinomas because of their frequent spread to regional lymph nodes. The objective of lymphadenectomy is to contain tumor spread; however, the procedure may be associated with intraoperative complications and postoperative sequelae. In order to improve the therapeutic management of patients with thyroid carcinoma, diagnostic scintigraphy with 201T1 or 99mTc-sestamibi is used in the advanced and undifferentiated forms of this tumor. METHODS: We have treated a woman submitted three years previously to total thyroidectomy for papillary carcinoma (pT3) without subsequent radiometabolic treatment. On physical examination we noted a swelling on the left side of the neck. The lesion was confirmed by ultrasonography, CT scan, and scintigraphic examination with 99mTc-sestamibi 24 hours before planned lymphadenectomy. During the surgical procedure we performed radiodetection to localize metastatic lesions. RESULTS: Intraoperative radiodetection may help to identify residual disease, which is often difficult to trace in the presence of post-surgical fibrosis. In our patient, histological examination of the removed tissue specimens demonstrated that intraoperative radiolocalization had been highly accurate. The eradication of residual disease was confirmed by scintigraphic follow-up after 12 months. DISCUSSION AND CONCLUSIONS: Scintigraphy with 99mTc-sestamibi has been proposed as a means to localize metastatic spread and possible residual disease after a supposedly radical thyroidectomy. Surgical eradication of all residual tumor guarantees the best disease control without having to resort to radiometabolic therapy. This approach will reduce the incidence of iatrogenic comorbidity and consequently improve the patients' quality of life.

Did psychrophilic enzymes really win the challenge?

Organisms living in permanently cold environments, which actually represent the greatest proportion of our planet, display at low temperatures metabolic fluxes comparable to those exhibited by mesophilic organisms at moderate temperatures. They produce cold-evolved enzymes partially able to cope with the reduction in chemical reaction rates and the increased viscosity of the medium induced by low temperatures. In most cases, the adaptation is achieved through a reduction in the activation energy, leading to a high catalytic efficiency, which possibly originates from an increased flexibility of either a selected area of or the overall protein structure. This enhanced plasticity seems in return to be responsible for the weak thermal stability of cold enzymes. These particular properties render cold enzymes particularly useful in investigating the possible relationships existing between stability, flexibility, and specific activity and make them potentially unrivaled for numerous biotechnological tasks. In most cases, however, the adaptation appears to be far from being fully achieved.

Structural determinants of cold adaptation and stability in a large protein.

The heat-labile alpha-amylase from an antarctic bacterium is the largest known protein that unfolds reversibly according to a two-state transition as shown by differential scanning calorimetry. Mutants of this enzyme were produced, carrying additional weak interactions found in thermostable alpha-amylases. It is shown that single amino acid side chain substitutions can significantly modify the melting point T(m), the calorimetric enthalpy Delta H(cal), the cooperativity and reversibility of unfolding, the thermal inactivation rate constant, and the kinetic parameters k(cat) and K(m). The correlation between thermal inactivation and unfolding reversibility displayed by the mutants also shows that stabilizing interactions increase the frequency of side reactions during refolding, leading to intramolecular mismatches or aggregations typical of large proteins. Although all mutations were located far from the active site, their overall trend is to decrease both k(cat) and K(m) by rigidifying the molecule and to protect mutants against thermal inactivation. The effects of these mutations indicate that the cold-adapted alpha-amylase has lost a large number of weak interactions during evolution to reach the required conformational plasticity for catalysis at low temperatures, thereby producing an enzyme close to the lowest stability allowing maintenance of the native conformation.