Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): diagnostic contribution of vestibular function tests.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognised but underdiagnosed cause of late-onset hereditary ataxia. Symptoms may vary, and differential diagnoses can span several specialties. We report the case of a man in his 60 s who presented with a 10 year history of imbalance and progressive gait disturbance associated with a chronic spasmodic cough that preceded these symptoms by almost 30 years. He had previously undergone extensive testing for acquired and genetic causes of ataxia without a conclusive diagnosis. Brain MRI revealed cerebellar atrophy, and nerve conduction tests suggested a sensory ganglionopathy. Vestibular function testing was crucial for diagnosis, identifying a severe bilateral vestibulopathy. This led to the consideration of CANVAS, which was finally confirmed by genetic testing. This case raises awareness of this novel genetic disease, highlighting the importance of objective vestibular function tests in establishing an early diagnosis.

Association between the insertion type of the uncinate process and the development of Frontal Sinus Mucoceles - is there a relationship?

BACKGROUND: The frontal sinus drainage pathway is formed by either the ethmoid infundibulum or the middle meatus, which depends on the superior insertion of the uncinate process. According to Landsberg & Friedman the are 6 types of superior uncinate process insertion. The aim of this study is to find an association between the uncinate process insertion type and the development of frontal sinus mucoceles. METHODS: Fifty sinus CT scans were analysed. Exclusion criteria were previous nasal surgeries, malignancy, polyposis and an insufficient image quality. Superior insertions of the uncinate process were analysed according to the Landsberg & Friedman classification. The results were tabulated and analysed using SPSS 25.0. RESULTS: The analysis revealed type 1 insertion in 6% of the CT scans, type 2 in 32%, type 3 in 26%, type 4 in 0%, type 5 in 28% and type 6 in 8%. Despite 44% of the CT scans with frontal sinus mucocele showing a type 2 insertion of the uncinate process, both the Chi-Square test and the Cramer's V test showed no statistical significance (p>.05). Logistic regression also showed that uncinate process insertion type does not influence the likelihood of development of frontal sinuses mucoceles. CONCLUSIONS: The insertion of the uncinate process does not influence the development of frontal sinus mucoceles.

Association between the insertion type of the uncinate process and the development of Frontal Sinus Mucoceles - is there a relationship?

Background: The frontal sinus drainage pathway is formed by either the ethmoid infundibulum or the middle meatus, which depends on the superior insertion of the uncinate process. According to Landsberg & Friedman the are 6 types of superior uncinate process insertion.The aim of this study is to find an association between the uncinate process insertion type and the development of frontal sinus mucoceles.MethodsFifty sinus CT scans were analysed. Exclusion criteria were previous nasal surgeries, malignancy, polyposis and an insufficient image quality. Superior insertions of the uncinate process were analysed according to the Landsberg & Friedman classification. The results were tabulated and analysed using SPSS 25.0.ResultsThe analysis revealed type 1 insertion in 6% of the CT scans, type 2 in 32%, type 3 in 26%, type 4 in 0%, type 5 in 28% and type 6 in 8%. Despite 44% of the CT scans with frontal sinus mucocele showing a type 2 insertion of the uncinate process, both the Chi-Square test and the Cramer's V test showed no statistical significance (p>.05). Logistic regression also showed that uncinate process insertion type does not influence the likelihood of development of frontal sinuses mucoceles.ConclusionsThe insertion of the uncinate process does not influence the development of frontal sinus mucoceles. (AU)

Antecedentes: La vía de drenaje del seno frontal es formada por el infundíbulo etmoidal o por el meato medio, lo que depende de la inserción superior de la apófisis unciforme. Según Landsberg y Friedman hay seis tipos de inserción superior de la apófisis unciforme.El objetivo del estudio es entender si hay alguna correlación entre el tipo de inserción de la apófisis unciforme y el desarrollo de mucoceles del seno frontal.Material y métodosSe analizaron 50 tomografías computarizadas de los senos paranasales. Los criterios de exclusión fueron cirugías nasales previas, malignidad, poliposis y una calidad de imagen insuficiente. Las inserciones superiores de la apófisis unciforme fueron analizadas según la clasificación de Landsberg y Friedman. Los resultados se tabularon y analizaron usando el SPSS 25.0.ResultadosEl análisis reveló la inserción de tipo 1 en 6% de las tomografías computarizadas, tipo 2 en 32%, tipo 3 en 26%, tipo 4 en 0%, tipo 5 en 28% y tipo 6 en 8%. A pesar de que el 44% de las tomografías computarizadas con mucocele del seno frontal muestran una inserción de tipo 2 de la apófisis unciforme, tanto la prueba de X2 como la prueba de V de Cramer, no mostraron significación estadística (p > 0,05). La regresión logística también demostró que el tipo de inserción de la apófisis unciforme no influye en la probabilidad de desarrollo de mucoceles de los senos frontales.ConclusiónLa inserción de la apófisis unciforme no influye el desarrollo de los mucoceles en los senos frontales. (AU)

Structural features and stability of apo- and holo-forms of a simple iron-sulfur protein.

Iron-sulfur centers are widespread in living organisms, mostly performing electron transfer functions, either in electron transfer chains or as part of multi-enzymatic complexes, while being also present in enzyme active sites, handling substrate catalysis. Rubredoxin is the simplest iron-sulfur containing protein constituted by a single polypeptide chain of 50 to 60 amino acids, of which four cysteine residues are responsible for metal binding in a tetrahedral coordination sphere. In this manuscript we explore the structure and stability of both apo- and holo-forms of a Rubredoxin from Marinobacter hydrocarbonoclasticus using Synchrotron Radiation Circular Dichroism (SRCD) in combination with other biochemical and spectroscopic techniques. The results are consistent with a holo-protein form containing a monomeric iron center with UV-visible maxima at 760, 578, 494, 386, 356 and 279 nm, an intense EPR resonance with a g value around 4.3 and Mössbauer spectroscopy parameters of δ equal to 0.69 mm/s and ΔEQ equal to 3.25 mm/s, for the ferrous reconstituted state. SRCD data, obtained for the first time for the apo-form, show a quite defined structure with ∆ε maximum at 191 nm and minima at 203 and 231 nm. Most significantly, the presence of isosbestic points at 189 and 228 nm made the interconversion between the two stable apo- and holo-form solution structures clear. SRCD temperature dependence data shows that for both forms the denaturation process proceeds through an intermediate species.

Dps-DNA interaction in Marinobacter hydrocarbonoclasticus protein: effect of a single-charge alteration.

DNA-binding proteins from starved cells (Dps) are members of the ferritin family of proteins found in prokaryotes, with hollow rounded cube-like structures, composed of 12 equal subunits. These protein nanocages are bifunctional enzymes that protect the cell from the harmful reaction of iron and peroxide (Fenton reaction), thus preventing DNA damage by oxidative stress. Ferrous ions are oxidized at specific iron-binding sites in the presence of the oxidant and stored in its cavity that can accommodate up to ca. 500 iron atoms. DNA-binding properties of Dps are associated with the N-terminal, positive charge rich, extensions that can promote DNA binding and condensation, apparently by a cooperative binding mechanism. Here, we describe the binding and protection activities of Marinobacter hydrocarbonoclasticus Dps using Electrophoretic Mobility Shift Essays (EMSA), and synchrotron radiation circular dichroism (SRCD) spectroscopy. While no DNA condensation was observed in the tested conditions, it was possible to determine a Dps-DNA complex formation with an apparent dissociation constant of 6.0 ± 1.0 µM and a Hill coefficient of 1.2 ± 0.1. This interaction is suppressed by the inclusion of a single negative charge in the N-terminal region by point mutation. In Dps proteins containing a ferric mineral core (above 96 Fe/protein), DNA binding was impaired. SRCD data clearly showed that no significant modification existed either in secondary structure or protein stability of WT, Q14E variant and core containing proteins. It was, however, interesting to note that, in our experimental conditions, thermal denaturation induced protein aggregation that caused artifacts in thermal denaturation curves, which were dependent on radiation flux and vertical arrangement of the CD cell.

Supramolecular protein polymers using mini-ferritin Dps as the building block.

A missense mutant of a Dps protein (DNA-binding protein from starved cells) from Marinobacter hydrocarbonoclasticus was used as a building block to develop a new supramolecular assembly complex which enhances the iron uptake, a physiological function of this mini-ferritin. The missense mutation was conducted in an exposed and flexible region of the N-terminal, wherein a threonine residue in position 10 was replaced by a cysteine residue (DpsT10C). This step enabled a click chemistry approach to the variant DpsT10C, where a thiol-ene coupling occurs. Two methods and two types of linker were used resulting in two different mini-ferritin supramolecular polymers, which have maintained secondary structure and native iron uptake physiological function. Electrophoretic assays and mass spectrometry were utilized to confirm that both functionalization and coupling reactions occured as predicted. The secondary structure has been investigated by circular dichroism and synchrotron radiation circular dichroism. Size and morphology were obtained by dynamic light scattering, size exclusion chromatography and atomic force microscopy, respectively. The iron uptake of the synthesized protein polymers was confirmed by UV-Vis spectroscopy loading assays.