Clinicoradiological application of the use of spectral cranial computed tomography in the management of acute ischemic stroke after mechanical thrombectomy. / Aplicación clinicorradiológica del uso de la tomografía computarizada craneal de tecnología espectral en el manejo del ictus isquémico agudo tras trombectomía mecánica.

INTRODUCTION: Acute ischemic stroke is one of the leading global causes of morbidity and mortality. Mechanical thrombectomy has improved the functional prognosis of this condition; however, hemorrhagic transformation is a common complication. Spectral computed tomography (CT) imaging, as a neuroimaging control test, distinguishes contrast extravasation from hemorrhagic transformation due to the differential behavior of materials at dual energy levels. This distinction is valuable in its clinical therapeutic management. MATERIAL AND METHODS: A single-center, observational, retrospective study was conducted in which the presence of various clinical, radiological, and therapeutic variables in patients with acute ischemic stroke treated with mechanical thrombectomy at our hospital between July 2022 and March 2023 was investigated using access to a dissociated database and medical records. RESULTS: Out of 155 included patients, spectral cranial CT was performed in 63, and conventional cranial CT in 75. In the spectral CT group, 21 hyperdense images were detected, compared to 28 in the conventional CT group. In 42.8% of cases where hyperdensity was detected in the conventional CT group, it was not possible to distinguish between contrast extravasation and hemorrhagic transformation, in contrast to the 4.8% in the spectral CT group (p < 0.001). CONCLUSIONS: Spectral CT provides high diagnostic confidence to the radiologist in identifying the type of detected hyperdensity, thereby offering significant therapeutic confidence to the neurologist in early resuming anticoagulation therapy.

TITLE: Aplicación clinicorradiológica del uso de la tomografía computarizada craneal de tecnología espectral en el manejo del ictus isquémico agudo tras trombectomía mecánica.Introducción. El ictus isquémico agudo es una de las principales causas globales de morbimortalidad. La trombectomía mecánica ha mejorado el pronóstico funcional de esta patología; sin embargo, la transformación hemorrágica es una complicación frecuente. La tomografía computarizada (TC) de tecnología espectral, como prueba de neuroimagen de control, diferencia la extravasación de contraste de la transformación hemorrágica gracias al diferente comportamiento de los materiales a la energía dual, y esta distinción es de utilidad en su manejo clinicoterapéutico. Material y métodos. Estudio unicéntrico, observacional y retrospectivo, en el cual se investigó, mediante el acceso a una base de datos disociada y a la historia clínica, la presencia de una serie de variables clínicas, radiológicas y terapéuticas en los pacientes con ictus isquémico agudo que fueron tratados con trombectomía mecánica en nuestro hospital entre julio de 2022 y marzo de 2023. Resultados. De los 155 pacientes incluidos, se realizó una TC craneal espectral en 63 y convencional en 75. En el grupo de TC espectral se detectaron 21 imágenes hiperdensas y en el grupo de TC convencional fueron 28. En el 42,8% de los casos en los que se detectó una hiperdensidad en el grupo de TC convencional no se pudo distinguir entre extravasación de contraste y transformación hemorrágica, en comparación con el 4,8% del grupo de TC espectral (p < 0,001). Conclusiones. La TC espectral confiere una gran confianza diagnóstica al radiólogo para establecer el tipo de hiperdensidad detectada y, por ello, proporciona también una gran confianza terapéutica al neurólogo para reiniciar precozmente la anticoagulación.

The S-Finger: A Synergetic Externally Powered Digit With Tactile Sensing and Feedback.

Partial hand amputation is by far the most common type of amputation worldwide. Nevertheless, regardless of their potential clinical and socioeconomic impact, battery-powered partial hand prostheses, namely, powered digits, have modestly progressed so far, and very few clinical solutions are available today. Here, we present a mechanical architecture, an alternative to state-of-the-art solutions, which exploits a high efficiency, non-back drivable mechanical transmission based on a face-gear pair and a miniaturized clutch. We took inspiration from the synergetic prehension approach proposed by Childress for whole hand amputation. The finger was equipped with a myoelectric controller and a tactile sensor able to provide users with discrete event sensory feedback. Measured speed (90°/s) and force (6.5 N) of the newly dubbed S-Finger proved comparable with those of clinically available prostheses. The design demonstrated to be compact and rugged enough to undergo a clinical viability test with two partial hand amputees, fitted with custom three-fingered research prostheses using the S-Finger. The subjects successfully completed several dexterity tests and gave relevant feedback for the development of a second-generation device. These results contribute to the increasing research endeavors in the field of partial hand amputation.

Rotator cuff degeneration of the healthy shoulder in patients with unilateral arm amputation is not worsened by overuse.

PURPOSE: In order to evaluate whether overuse has a significant role in rotator cuff tear (RCT) aetiology, we evaluated both shoulders of patients with old unilateral arm amputation expecting a higher rate of RC degeneration in the healthy side. METHODS: Nineteen males and six females (mean age: 57.3 ± 10.1) with an old (>20 years) unilateral arm amputation were submitted to an MRI of both shoulders. Tendon status and muscle tropism were evaluated according to Sugaya and Fuchs classifications, respectively; the acromion humeral distance was measured. Statistical analysis was performed to verify the prevalence of Sugaya and Fuchs categories in each sides. RESULTS: A significant prevalence of Sugaya type II in the amputated side (p = 0.02) and of type I in the healthy side (p < 0.001) was found. Rotator cuff was healthy in 28 and 52% of amputated and non-amputated side, respectively. The mean acromio-humeral distances of the amputated and healthy side were 0.8 cm (SD: 0.1) and 0.9 cm (SD: 0.1), respectively, (p = 0.02). A significant prevalence of Fuchs type II category in the healthy side (p < 0.001) was found. Fuchs III/IV were observed in 40 and 12% of amputated and healthy side, respectively. CONCLUSIONS: The present study resizes the role of overuse on the aetiology of RCT. Cuff tear prevalence in not amputated shoulders, inevitably submitted to functional overload, was not higher than that of coetaneous subjects with two functional upper limbs. Shoulder non-use is a risk factor for rotator cuff tear. As the prevalence of rotator cuff degeneration/tear is higher in the amputee side, non-use is a more relevant risk factor than overuse. In the daily clinical practice, patients with rotator cuff tear should be encouraged to shoulder movement because rotator cuff tendon status could be worsened by disuse. LEVEL OF EVIDENCE: III.

Nucleated erythrocytes in blood smears of dogs undergoing chemotherapy.

The frequency of normoblastemia in dogs receiving chemotherapy is unknown. To provide this information, we calculated the percentage and number of nucleated erythrocytes (nRBCs) in blood of dogs treated for lymphoma (n = 284), mast cell tumour (n = 40) or carcinoma (n = 46). Relative normoblastemia (>1 or >5%) and absolute normoblastemia (>0.1 or >0.4 × 103 µL-1 ) were found after administration of vincristine (49.3, 20.5, 42.5, 19.2%, respectively), carboplatin (37.0, 2.2, 34.8, 13.0%), cyclophosphamide (30.8, 7.7, 23.1, 7.7%), doxorubicin (25.0, 8.3, 21.7, 6.7%), vinblastine and prednisone (25.0; 5.0; 22.5; 7.5%). Absolute normoblastemia was very severe (>1.0 × 103 nRBC µL-1 ) after administration of vincristine (9.6%), doxorubicin (3.3%), vinblastine and prednisone (2.5%). Absolute normoblastemia negatively correlated with RBC counts (P < 0.001) and positively (P < 0.001) with reticulocyte and WBC counts, but correlation coefficients were low (-0.19, 0.37, 0.15). Vincristine, doxorubicin or vinblastine and prednisone may induce severe normoblastemia. This may increase WBC counts and mask neutropenia associated with chemotherapy.

CARM1 modulators affect epigenome of stem cells and change morphology of nucleoli.

CARM1 interacts with numerous transcription factors to mediate cellular processes, especially gene expression. This is important for the maintenance of ESC pluripotency or intervention to tumorigenesis. Here, we studied epigenomic effects of two potential CARM1 modulators: an activator (EML159) and an inhibitor (ellagic acid dihydrate, EA). We examined nuclear morphology in human and mouse embryonic stem cells (hESCs, mESCs), as well as in iPS cells. The CARM1 modulators did not function similarly in all cell types. EA decreased the levels of the pluripotency markers, OCT4 and NANOG, particularly in iPSCs, whereas the levels of these proteins increased after EML159 treatment. EML159 treatment of mouse ESCs led to decreased levels of OCT4 and NANOG, which was accompanied by an increased level of Endo-A. The same trend was observed for NANOG and Endo-A in hESCs affected by EML159. Interestingly, EA mainly changed epigenetic features of nucleoli because a high level of arginine asymmetric di-methylation in the nucleoli of hESCs was reduced after EA treatment. ChIP-PCR of ribosomal genes confirmed significantly reduced levels of H3R17me2a, in both the promoter region of ribosomal genes and rDNA encoding 28S rRNA, after EA addition. Moreover, EA treatment changed the nuclear pattern of AgNORs (silver-stained nucleolus organizer regions) in all cell types studied. In EA-treated ESCs, AgNOR pattern was similar to the pattern of AgNORs after inhibition of RNA pol I by actinomycin D. Together, inhibitory effect of EA on arginine methylation and effect on related morphological parameters was especially observed in compartment of nucleoli.

Cytological evidence for population-specific sex chromosome heteromorphism in Palaearctic green toads (Amphibia, Anura).

A chromosome study was carried out on a number of European and Central Asiatic diploid green toad populations by means of standard and various other chromosome banding and staining methods (Ag-NOR-, Q-, CMA3-, late replicating [LR] banding pattern, C-and sequential C-banding + CMA3 + DAPI). This study revealed the remarkable karyological uniformity of specimens from all populations, with the only exception being specimens from a Moldavian population, where one chromosome pair was heteromorphic. Though similar in shape, size and with an identical heterochromatin distribution,the difference in the heteromorphic pair was due to a large inverted segment on its long arms. This heteromorphism was restricted to females, suggesting a female heterogametic sex chromosome system of ZZ/ZW type at a very early step of differentiation.

Polymorphic Alu insertions in five North-West Italian populations.

We analyzed the frequencies of eight human polymorphic Alu insertion loci in population samples from five towns in North-West Italy: Postua, Cavaglià, Biella, Torino, and Genova. All loci under scrutiny were found to be polymorphic in all samples, with the two exceptions of locus A25 in Postua, which was fixed for the absence of the Alu element, and APO in Genova, where the Alu insertion was fixed. Heterozigosity values were highly variable in all loci. F(ST) values for all loci indicate that most of the variability is found within populations, while between population variability is lower. In the multidimensional scaling (MDS) analysis plot, the studied populations are separated from the main group represented by European populations. The Postua sample is set apart also from neighboring towns as Cavaglià and Biella, confirming previous observations of the demographic isolation of this population.

5-aryl-imidazo[2,1-c][1,4]benzodiazepine derivatives as tricyclic constrained analogues of diazepam and Ro5-4864. Synthesis and binding properties at peripheral and central benzodiazepine receptors.

Four series of 5-aryl-imidazo[2,-c][1,4]benzodiazepine derivatives 1a-f, 2a-f, 3a-f, and 4a-f were synthesized and tested for their affinity at both the peripheral and central benzodiazepine receptors. Among the four series, only N-10 and C-11 sites were changed, mainly [N(CH3)-CO], [N=CH], [NH-CO], [NH-CH2], and in each series the halogen site was varied at the positions C-7, C-2', and C-4'. In particular, 10-methyl-benzodiazepinones 1a and 1b were designed as tricyclic constrained analogues of diazepam and Ro5-4864. All the tested compounds did not show significant binding activity at central benzodiazepine receptors, but relatively good PBzR binding affinities were found for 10-methyl-benzodiazepinone 1c and benzodiazepines 2b, c. Benzodiazepinones 3a-f were prepared by cyclization with 1,1'-carbonyldiimidazole of the corresponding 2-(aryl-imidazol-1-yl-methyl)-arylamines, obtained from the suitable (2-amino-aryl)-aryl-methanols with 1,1'-carbonyldiimidazole in different conditions. N-Alkylation of 3a-f to 1a-f was achieved using dimethylformamide-dimethylacetal. Reduction of 3a-f to 4a-f was accomplished with lithium aluminum hydride or borane and oxidation of 4a-f to 2a-f was performed with manganese (IV) oxide.

Systemic and topical corticosteroid treatment of oral lichen planus: a comparative study with long-term follow-up.

BACKGROUND: Topical corticosteroids are the mainstay treatment for oral lichen planus (OLP), but some authors suggest that systemic corticosteroid therapy is the only way to control acute presentation of OLP. METHODS: Forty-nine patients with histologically proven atrophic-erosive OLP were divided into two groups matched for age and sex. The test group (26 patients) was treated systemically with prednisone (50 mg/day), and afterwards with clobetasol ointment in an adhesive medium plus antimicotics, whereas the control group (23 patients) was only treated topically with clobetasol plus antimycotics. RESULTS: Complete remission of signs was obtained in 68.2% of the test group and 69.6% of the control group, respectively (P = 0.94). Similar results were obtained for symptoms. Follow-up showed no significant differences between the two groups. One-third of the patients of the test group versus none in the control group experienced systemic side-effects (P = 0.003). CONCLUSIONS: The most suitable corticosteroid therapy in the management of OLP is the topical therapy, which is easier and more cost-effective than the systemic therapy followed by topical therapy.

Synthesis of 11-aryl-5H-imidazo[2,1-c][1,4]benzodiazepines and their benzodiazepine and A1 adenosine binding activity.

In the context of a research program aimed at elucidating the properties of the 5H-imidazo[2,1-c][1.4]benzodiazepine system, a series of 11-aryl-5H-imidazo[2,1-c][1,4]benzodiazepines (3a-i) and their 10,11-dihydro-derivatives (4a-i) has been synthesized. The synthetic strategy includes the preparation of the aryl-[1-(2-nitrobenzyl)-1H-imidazol-2-yl]methanones (5a-i) followed by their reduction and subsequent cyclization. Affinities of compounds 3a-i and 4a-i for central benzodiazepine as well as for adenosine A1-receptors were determined by radioligand binding assays. Among the unsaturated analogues, the highest activity at both receptors is displayed by 1H-(2-thienyl) derivative 3e. The hydrogenated analogues 4a-i do not exhibit considerable binding affinity either for central benzodiazepine or for adenosine A1-receptors.

Unilateral fibroadipose degeneration of the masticatory muscles.

A unique case of fatty replacement of the masticatory muscles, causing progressive limitation of mouth opening, is presented. Both CT and MRI revealed an almost total substitution of the masticatory muscles with fatty tissue, confirmed by the histopathology at surgery. Myotomy of masseter and internal pterygoid muscles and coronoidotomy improved his symptoms. There is no known cause of fibroadipose replacement of muscle fibres.

In silico identification of novel selenoproteins in the Drosophila melanogaster genome.

In selenoproteins, incorporation of the amino acid selenocysteine is specified by the UGA codon, usually a stop signal. The alternative decoding of UGA is conferred by an mRNA structure, the SECIS element, located in the 3'-untranslated region of the selenoprotein mRNA. Because of the non-standard use of the UGA codon, current computational gene prediction methods are unable to identify selenoproteins in the sequence of the eukaryotic genomes. Here we describe a method to predict selenoproteins in genomic sequences, which relies on the prediction of SECIS elements in coordination with the prediction of genes in which the strong codon bias characteristic of protein coding regions extends beyond a TGA codon interrupting the open reading frame. We applied the method to the Drosophila melanogaster genome, and predicted four potential selenoprotein genes. One of them belongs to a known family of selenoproteins, and we have tested experimentally two other predictions with positive results. Finally, we have characterized the expression pattern of these two novel selenoprotein genes.

New structural analogues of Tubulozole induce apoptosis, [Ca2+]i modifications and cytoskeletal disorganization in glial (GL15) and neuronal-like (PC12) cell lines.

The synthesis and the biological activity of (+/-)-cis- and (+/-)-trans-[4-[[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1, 3-dioxolan-4-yl]methylthio]phenyl]carbamic acid ethyl esters (2a and 2b) are discussed. They were designed as structural analogues of Tubulozole, a synthetic tubulin polymerisation inhibitor with antimitotic properties. Biological tests were carried out on PC12, a neuronal-like cell line derived from rat pheochromocytoma, and on GL15, a cell line derived from human glioblastoma. The exposure (from 5 to 20 h) of GL15 and PC12 cells to different concentrations (0.1-1000 microM; IC50 approximately 1 microM) of 2a or 2b resulted in a drastic decrease in the number of viable cells without an apparent effect on the cell distribution in the various phases of the cell cycle. Compound 2a or 2b (10 microM) induced cell death by activating apoptosis. This was correlated with the activation of an oscillating Ca(2+)-dependent mechanism which increased the intracellular calcium concentration ([Ca2+]i) via Ca(2+)-release from internal stores. Moreover, 2a (10 microM) also induced severe damage of cytoskeletal F-actin filaments after a 5 h incubation in GL15 cells. This was also observed but to a smaller extent, for 2b. Under the same experimental conditions, PC12 cells showed similar actin deregulation.

Design and synthesis of novel [60]fullerene derivatives as potential HIV aspartic protease inhibitors.

[structure] Two water-soluble fullerene derivatives have been computer-designed and synthesized. They may exhibit interesting anti-HIV activity owing to the presence of two ammonium groups strategically located on the spheroid surface.

Comparison of the ADP-ribosylating thermozyme from Sulfolobus solfataricus and the mesophilic poly(ADP-ribose) polymerases.

The poly(ADP-ribose) polymerase-like thermozyme purified from Sulfolobus solfataricus was characterised with respect to some physico-chemical properties. The archaeal protein exhibited a scarce electrophoretic mobility at both pH 2.9 and pH 7.5. Determination of the isoelectric point (pI=7.0-7.2) allowed us to understand the reason for the limited migration at pH 7.5, while amino acid composition analysis showed a moderate content of basic residues, which reduced mobility at pH 2.9. With respect to the charge, the archaeal enzyme behaved differently from the eukaryotic thermolabile poly(ADP-ribose) polymerase, described as a basic protein (pI=9.5). Well known inhibitors of the mesophilic polymerase like Zn(2+), nicotinamide and 3-aminobenzamide exerted a smaller effect on the enzyme from S. solfataricus, reducing the activity by at most 50%. Mg(2+) was a positive effector, although in a dose-dependent manner. It influenced the fluorescence spectrum of the archaeal protein, whereas NaCl had no effect.

A new class of antifungal agents. Synthesis and antimycotic activity of disubstituted N-azolylamines.

In this study we extended our exploration of the N-azolylamine moiety for its antifungal activity. We prepared a number of N-azolylamino derivatives. The synthetic sequence includes the preparation of aminoazole Schiff bases, and the reduction and the alkylation of the corresponding secondary amines. The title compounds were evaluated in vitro against several pathogenic fungi responsible for human disease. The most potent antimicrobial compound was the N-(biphenyl-4-yl)methyl-N-(2,4-dichlorophenyl)methyl-1H-imidazol-l-yl amine (21), which was found to be active against yeasts and dermatophytes; its potency and selectivity were comparable to those of miconazole.

Azole antifungal agents related to naftifine and butenafine.

The methyl group of naftifine (1) and butenafine (2) was replaced by an azolic nucleus to obtain the new compounds 3-8 which exhibit the characteristics of both allylamine (or benzylamine) and azole antifungals. The title compounds were evaluated in vitro against several pathogenic fungi responsible for human disease. Among these, compounds 5, 6, and 8 were found to inhibit the growth of dermatophytes with a potency comparable to that of naftifine. The synthetic sequence includes the preparation of aminoazole Schiff bases, reduction, and alkylation of the corresponding secondary amines.

Antimycobacterial activity of ionic fullerene derivatives.

Positively charged fullerene derivatives, moderately soluble in water:DMSO 9:1, have been tested using three strains of Mycobacterium spp. Some compounds inhibit the growth of Mycobacterium tuberculosis, a human clinical isolate, particularly virulent and resistant, at doses as low as 5 microg/mL.

Stabilizing and directional female choice for male calls in the European green toad.

We analysed variation in three temporal (pulse rate, call and intercall duration) and one spectral (fundamental frequency) acoustic properties of the green toad's, Bufo viridis, advertisement call, at different levels, from the single bout of an individual to between populations. Independent of the level, pulse rate and fundamental frequency were less variable than intercall and call durations. The former were classified as static, the latter as dynamic properties of the signal. We analysed the effects of body size and temperature, assumed to represent, respectively, morphological and physiological constraints on the signals. Static properties were under strong constraints, either morphologically (fundamental frequency) or physiologically (pulse rate), whereas no significant effects of size and temperature were observed on dynamic properties. We used two-choice discrimination experiments to investigate females' preferences for call properties. Females preferred extreme to mean values of the dynamic properties, even when these fell above the typical range of variation of the population. In contrast, females had weak preferences for mean values, and for lower than average compared with higher than average values, of static properties. We discuss the hypothesis that static and dynamic call properties may convey different information to females: static properties may be important for species recognition, whereas dynamic properties may be important for mate selection.1998 The Association for the Study of Animal Behaviour

Systemic corticosteroid therapy of oral vesiculoerosive diseases (OVED). An open trial.

BACKGROUND: We report the preliminary findings from our open study on how to optimize the doses and the response times to systemic corticosteroid therapy for three forms of oral vesiculoerosive diseases (OVED). METHODS: All twenty-one patients enrolled in the study were affected with OVED (10 OLP, 6 MMP, 5 EM) and received different doses of prednisone in relation to the type of disease and its severity. Daily mouthwashes with 0.12% chlorhexidine and application of miconazole gel were added to the therapy; its response time to treatment varied individually, the doses were reduced only after 75% of lesions had cleared. RESULTS: The average response time to treatment was 28 days. Clinical assessment showed that 95% of the patients had improved, whereas 71% had complete remission of oral signs and 48% experienced side effects. The degree of clinical resolution was: 70% complete remission after 26 days of therapy in patients with OLP, 33% complete remission after 38 days in patients with MMP, and 100% complete remission after ten days in patients with EM. CONCLUSIONS: Although a preliminary study, initial results showed different types and times of response to systemic corticosteroid treatment for the three diseases. Our findings strongly suggest that a unified therapeutic protocol for different OVED is not advisable, nor can systemic treatment be considered the first therapeutic approach.