Characterization of one alpha 2-macroglobulin with anticomplementary activity from pregnant women.

In 15 pregnant women during the third term of pregnancy, the immunomodulatory property of alpha 2-macroglobulin (alpha 2M) was initially detected by measuring the inhibitory effect on immune complement-dependent haemolysis of serum alpha 2M fractions obtained by gel filtration. By a two-step chromatography procedure consisting of gel filtration followed by anion-exchange chromatography, different sub-forms of alpha 2M in serum were separated. Amongst them, it was shown that the inhibition of complement activity was almost exclusively linked to one particular subform. Additional studies revealed that the observed effect was not due to proteases bound to alpha 2M during clotting since, by using protease-specific inhibitors, no change was observed in complement inhibition. This subform, though present at very low levels in control sera, appeared in strikingly increased amounts during the third trimester of pregnancy (35 mg/l) and comprised between 3 and 5% of the total alpha 2M. Results show that the increase of alpha 2M anticomplementary activity is linked to the increase in alpha 2M levels in serum.     

Color-doppler velocimetry of uterine arteries in pregnant and nonpregnant patients during multiovulation induction for IVF

Objectives To evaluate uterine artery resistance during multiovulation induction in relation to the implantation rate in patients attendingin vitro fertilization (IVF) cycles.Patients Multiovulation induction for IVF was monitored by daily determination of the pulsatility index (PI) of the uterine arteries, obtained by a transvaginal probe (6.5 MHz) implemented with color-flow imaging. Doppler data were obtained from 5 days before hCG administration to the day of follicular aspiration. One IVF cycle was monitored in 70 patients. In 17 patients, 41 IVF cycles were monitored until a successful attempt occurred.Results In the 70 patients studied during one IVF attempt, the PI of the uterine arteries significantly varied (P < 0.001) in the different phases of the cycle. In the 24 patients who conceived, a significantly lower PI (P < 0.03) was found throughout the cycle. This result was mainly due to a highly significant difference of PI values observed the day after hCG administration (P < 0.005). In the 17 patients who conceived after 1 to 4 negativein vitro fertilizations, no significant difference in PI was observed in the uterine artery resistance in cycles in which implantation was or was not successful.Conclusions Uterine artery resistance varies significantly during phases of the induction therapy. Uterine artery resistance is lower throughout the course of multiovulation induction in patients with higher pregnancy rates. The PI on the day after hCG administration was the best index of pregnancy rate. Low uterine artery resistance was present even in negative attempts in patients who eventually achieved a successful implantation. PI values 3 can be considered a favorable prognostic factor for future IVF cycles.Presented at the 49th Annual Meeting of the American Fertility Society, Montreal, 1993 and the 50th Annual Meeting of the American Fertility Society, November 5–10, 1994, San Antonio, Texas.     

Ear and eye representation in the frontal cortex,area 8b,of the macaque monkey: an electrophysiological study

We evoked both ear and eye movements in area 8b, the rostral area of frontal cortex, in two monkeys. In some sites it was possible to evoke only ear movements or only eye movements; in other locations we evoked both ear and eye movements by varying the intensity of electrical stimulation. The electrically evoked ear movements were forward, or backward, or oblique (upward-forward; upward-backward). In two penetrations the ear movements were bilateral, in the other penetrations they were contralateral. Ipsilateral ear movements were not observed. The evoked eye movements were mainly fixed-vector saccades, contralateral and with an upward orientation of about 45°. If we considered only the sites where the threshold was equal to or lower than 50 A, the stimulation of this area evoked mainly ear movements. In addition we recorded the electrical activity of 195 neurons. Of these neurons: 74% (145/195) discharged before ear movements (ear cells); 20% (40/195) discharged before ear and eye movements (ear-eye cells); 5% (10/195) discharged only before eye movements (eye cells). Ninety-one percent (132/145) of ear cells presented a preferred direction; 90% (36/40) of ear-eye cells presented a preferred direction for ear movements, and 15% (6/40) presented a preferred direction for eye movements. Eighty-five percent (34/40) of cells did not present a preferred direction for visually guided saccades and were active when the monkey made saccades toward the unlit targets (checking saccades). Our results show that a field of area 8b is related to ear movements and to eye-ear movements. The findings that it is possible to obtain both ear and eye movements with low-intensity currents and that there are cells firing for the two types of movements suggest that area 8b may be involved in the orientation and coordination of both ear and eye. This area might be considered a rostral extension of supplementary eye field (SEF) or a different region. However, based on its distinct functional characteristics and connectivity, it is probably better regarded as a separate field. Regardless, the combination of 8b and SEF may constitute a cortical center for orienting processes.     

Imaging breasts with silicone implants

Over the last two decades, the use of breast implants both for breast augmentation and for breast reconstruction following mastectomy has increased substantially. It is estimated that around two million women have undergone breast augmentation, while hundreds of thousands have had breast reconstruction surgery. Different types of material have been used for breast implants, but silicone gel implants have been the dominating implant type. Many implants can lead to complications, such as hardening and rupture, and may therefore need in vivo evaluation by imaging, particularly if they lead to clinical symptoms. They can also pose problems in the assessment of surrounding breast tissue by conventional mammography. In this respect, imaging modalities such as ultrasound, computed tomography and magnetic resonance imaging offer greater possibilities to assess a failing implant, as well as surrounding breast tissue. Several factors, mainly of a psychological nature, lead to requests for breast implants. In this review article, only the imaging aspects of breasts with silicone gel implants will be dealt with. Each modality is concisely presented with its possibilities and limitations. Received: 5 February 1998; Revision received: 18 May 1998; Accepted: 25 May 1998     

A new factor Xa inhibitor (lefaxin) from the Haementeria depressa leech

The salivary complex of the leech Haementeria depressa produces potent anticoagulant components. Among them, a protein named lefaxin inhibits factor Xa (FXa). Lefaxin was purified to homogeneity from dissected salivary complexes by gel filtration in Sephadex G-150 followed by two ion exchange chromatography steps in Mono-Q. Inhibition of FXa by lefaxin was demonstrated by the inhibition of its amidolytic activity, measured with chromogenic substrate S-2765 (apparent K(I) of 4 nM), and of its ability to inhibit thrombin generation in the prothrombinase complex (EC50 of 40 nM). Lefaxin has a molecular weight of 30 kDa and an isoelectric point of 5.7. It is made of a polypeptide chain whose N-terminal sequence shows no similarity with that of other FXa inhibitors (antistasin and ghilianten) isolated from leech saliva. On the other hand, the N-terminal sequence of lefaxin presents significant sequence similarity with nitric oxide carrier proteins myohemerythrin from the annelid Nereis diversicolor and prolixin S from the triatoma Rhodnius prolixus. Interestingly, prolixin S also proved to be an anticoagulant protein acting on FXa.     

Proline-rich tyrosine kinase Pyk2 regulates deep vein thrombosis

Deep vein thrombosis results from the cooperative action of leukocytes, platelets, and endothelial cells. The proline-rich tyrosine kinase Pyk2 regulates platelet activation and supports arterial thrombosis. In this study, we combined pharmacological and genetic approaches to unravel the role of Pyk2 in venous thrombosis. We found that mice lacking Pyk2 almost completely failed to develop deep venous thrombi upon partial ligation of the inferior vena cava. Pyk2-deficient platelets displayed impaired exposure of phosphatidylserine and tissue factor expression by endothelial cells and monocytes was completely prevented by inhibition of Pyk2. In human umbilical vein endothelial cells (HUVEC), inhibition of Pyk2 hampered IL-1β-induced expression of VCAM and P-selectin, and von Willebrand factor release. Pyk2-deficient platelets showed defective adhesion on von Willebrand factor and reduced ability to bind activated HUVEC under flow. Moreover, inhibition of Pyk2 in HUVEC strongly reduced platelet adhesion. Similarly, Pyk2-deficient neutrophils were unable to efficiently roll and adhere to immobilized endothelial cells under venous flow conditions. Moreover, platelets and neutrophils from Pyk2-knockout mice showed defective ability to form heterogeneous aggregates upon stimulation, while platelet monocyte interaction occurred normally. Consequently, platelet neutrophil aggregates, abundant in blood of wild-type mice upon inferior vena cava ligation, were virtually undetectable in Pyk2-knockout mice. Finally, we found that expression of Pyk2 was required for NETosis induced by activated platelets. Altogether our results demonstrate a critical role of Pyk2 in the regulation of the coordinated thromboinflammatory responses of endothelial cells, leukocytes and platelets leading to venous thrombosis. Pyk2 may represent a novel promising target in the treatment of deep vein thrombosis.     

Characterization of Vaccine Breakthrough Cases during Measles Outbreaks in Milan and Surrounding Areas,Italy, 2017–2021

Despite the existence of an effective live-attenuated vaccine, measles can appear in vaccinated individuals. We investigated breakthrough measles cases identified during our surveillance activities within the measles/rubella surveillance network (MoRoNet) in Milan and surrounding areas (Northern Italy). Between 2017 and 2021, we confirmed measles virus (genotypes B3 or D8) infections in 653 patients and 51 of these (7.8%) were vaccinees. Among vaccinated individuals whose serum was available, a secondary failure was evidenced in 69.4% (25/36) of cases while 11 patients (30.6%) were non-responders. Non-responders were more frequently hospitalized and had significantly lower Ct values in both respiratory and urine samples. Median age and time since the last immunization were similar in the two groups. Importantly, we identified onward transmissions from vaccine failure cases. Vaccinees were involved in 20 outbreaks, in 10 of them they were able to transmit the virus, and in 8 of them, they were the index case. Comparing viral hemagglutinin sequences from vaccinated and non-vaccinated subjects did not show a specific mutation pattern. These results suggest that vaccination failure was likely due to the poor immune response of single individuals and highlights the importance of identifying breakthrough cases and characterizing their clinical and virologic profiles.     

Filament Transport Control for Enhancing Mechanical Properties of Parts Realised by Fused Filament Fabrication

The fused filament fabrication (FFF) process is widely used for producing prototypes and functional parts for diverse applications. While FFF is particularly attractive due to its cost-effectiveness, on the other hand, the fabricated parts have limitations in terms of large manufacturing time and reduced mechanical properties. The latter is strongly influenced by the fabrication process parameters, which affect the interlayer bonding and the adhesion between consecutive layers. Several works presented in the literature analysed the correlation between mechanical properties and process parameters. It was demonstrated that an increase in the fabrication feed rate causes slippage between filament and the feeding system, which leads to a decrease in the extruded material flow, and thus in part density. This work aims to investigate how the limitation of the slippage phenomenon affects the mechanical properties of parts fabricated using the FFF process. A prototype machine, equipped with a closed-loop control system on filament transport, was used to fabricate samples for tensile tests and dynamical mechanical analysis. Samples fabricated enabling the filament transport control showed an increase both in ultimate tensile strength and elongation at break for those fabricated with disabled control, whilst a decrease in stiffness was observed. In addition, the results showed that the use of a filament transport control system on a FFF machine increases the possibility of fabricating high value-added parts.     

Newly Diagnosed Multifocal GBM: A Monocentric Experience and Literature Review

Simple SummaryGlioblastoma is an aggressive brain tumor with a dismal prognosis. In a minority of cases, it presents with multiple lesions already at the time of diagnosis, affecting patients’ survival and treatment. Our retrospective study aims to increase the current understanding and define a treatment for this sub-entity, to improve patient survival. Chemoradiotherapy is a also safe and efficacy treatment in patients with multiple lesions. Survival advantages from extensive resection remain unclear.AbstractGlioblastomas with multiple foci at presentation (mGBMs) account for 2–35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6–13.8), and median PFS was 4.2 months (95% CI 3.2–5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3–7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear.