In vitro and In vivo Activity of Theaflavin–Epicatechin Combinations versus Multidrug-Resistant Acinetobacter baumannii

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Inheritance of Chiari-Like Malformation: Can a Mixed Breeding Reduce the Risk of Syringomyelia?

<div><p>Canine Chiari-like malformation (CM) is a complex abnormality of the skull and craniocervical junction associated with miniaturization and brachycephaly which can result in the spinal cord disease syringomyelia (SM). This study investigated the inheritance of CM in a Griffon Bruxellois (GB) family and feasibility of crossbreeding a brachycephalic CM affected GB with a mesaticephalic normal Australian terrier and then backcrossing to produce individuals free of the malformation and regain GB breed characteristics. The study family cohort (n = 27) included five founder dogs from a previous baseline study of 155 GB which defined CM as a global malformation of the cranium and craniocervical junction with a shortened skull base and increased proximity of the cervical vertebrae to the skull. T1-weighted sagittal DICOM images of the brain and craniocervical junction were analysed for five significant traits (two angles, three lines) identified from the previous study and subsequent Qualitative Trait Loci analysis. Mean measurements for mixed breed, pure-breed and baseline study groups were compared. Results indicated that mixed breed traits posed less risk for CM and SM and were useful to distinguish the phenotype. Moreover on the MR images, the filial relationships displayed by the traits exhibited segregation and those presenting the greatest risk for CM appeared additive towards the severity of the condition. The external phenotypes revealed that by outcrossing breed types and with careful selection of appropriate conformation characteristics in the first generation, it is possible to regain the GB breed standard and reduce the degree of CM. The four GB affected with SM in the study all exhibited reduced caudal skull development compared to their relatives. The craniocervical traits may be useful for quantifying CM and assessing the possibility of SM thus assisting breeders with mate selection. However, such a system requires validation to ensure appropriateness for all breeds at risk.</p></div

Boxplot distribution of significantly associated traits for CM and SM BVA/KC grades (n = 26).

<p>Top row; 0 = CM0 (normal), 1 = CM1 (intermediate), 2 = CM2 (affected). Bottom row; 0 = SM0 (normal), 1 = SM1 (intermediate), 2 = SM2 (affected).</p

Head conformation and associated angle FAC in six relatives of Bitch H with and without SM.

<p>TW1 sagittal MRI of the caudal fossa and cranial-cervical junctions with superimposed morphometric framework of lines and angles for parents and offspring enhances comparison. The differences in the size of angle FAC are reflected in the lack of skull development caudal to the ear pinna (behind the ears) for dogs with SM compared to dogs with no SM (‘normal’ caudal skull shaded aqua colour). The photos of the heads have been resized to allow comparison using two vertical lines (black) placed at the outer eye and the origin of the external pinna (red) a consistent distance apart.</p

Morphometric measurements for three generation the F2 backcross pedigree.

<p>Morphometric measurements for three generation the F2 backcross pedigree.</p

Descriptive Statistics for five traits in Mixed, Pure and control GB Groups.

<p>Descriptive Statistics for five traits in Mixed, Pure and control GB Groups.</p

Midline sagittal T1-weighted MRI of brain and craniocervical region of a female GB backcross.

<p>A framework of measured lines and angles is used to assess conformational features associated with CM verified in a previous study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151280#pone.0151280.ref001" target="_blank">1</a>]. (A) dorsum of spheno-occipital synchondrosis (B) basion of basioccipital bone (C) rostral edge of the dorsal lamina of the atlas (D) junction between the supraoccipital bone and the occipital crest (E) most dorsal point of intersection of the cerebellum with the occipital lobe circle (F) centre of occipital lobe circle placed on the extended cranial baseline (AB) (G) intersection point with the extended AB baseline and DC. The five traits measured in the study are lines ae, bc and f-diameter (blue) and angles FAC (yellow) and AGD (red).</p

Key morphometric measurements made on the MRIs of dogs in three generation pedigree of the F2 Backcross.

<p>The CM0 F1 hybrid ab1 provides an additional control comparison. The lines and angles have been linked together providing a visual representation of the interrelationships between the individual traits. Sire fg1 and son abfg1 have similar values for angle FAC(~70°) but different values for line bc. Similarly, dam ab4 and daughter abfg2 have similar trait values for line bc (~15.7) but different values for angle FAC.</p

Summary of CM and SM status in family study group.

<p>Summary of CM and SM status in family study group.</p

Study cohort GB family tree (n = 27) including a mixed cross to an Australian terrier and subsequent backcross.

<p>Offspring were designated the combined letters (lowercase) of their parents. Bitch C and Dog F were both a parent and an offspring so designated a single letter as a first generation parent (P1) to ease reading. Hence ed1 is renamed ‘C’ and ‘eh3’ renamed ‘F’.</p