The Relationship between Ischemic Optic Neuropathy and Internal Carotid Artery Dissection: A Systematic Review

Background: To evaluate and review the current evidence regarding the association between ischemic optic neuropathy (ION) and internal carotid artery dissection (ICAD). Methods: We systematically reviewed studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA), searching three databases (Scopus, Pubmed, and Embase) for relevant articles that clearly described the correlation between ION and ICAD. All studies that examined the association between ICAD and the development of ION were synthesized. Quality assessment using the Newcastle–Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and Case Series were conducted. Results: Our search yielded 198 manuscripts published in the English language. Following study screening, fourteen studies were selected. The number of participants with ION following ICAD ranged from one to four, with sixteen patients experiencing either anterior ION, posterior ION, or a combination of both. The anterior or posterior ischemic optic neuropathy (AION and PION) patients’ ages were 48.75 ± 11.75 and 49.62 ± 12.85, respectively. Fourteen out of sixteen patients experienced spontaneous ICAD, whereas the traumatic etiology was ascertained in two patients. Conclusions: Hence, albeit rare, ophthalmologists should consider ICAD a potential cause of ION, especially in young adults with concomitant cephalic pain and vision reduction

Retromode imaging modality of epiretinal membranes

(1) Purpose: To determine the characteristics of macular epiretinal membranes (ERM) using non-invasive retromode imaging (RMI) and to compare retromode images with those acquired via fundus autofluorescence (FAF) and fundus photography. (2) Methods: Prospective observational case-series study including patients with macular ERM with no other ocular disease affecting their morphology and/or imaging quality. We compared RMI, FAF and fundus photography features by cropping and overlapping images to obtain topographic correspondence. (3) Results: In total, 21 eyes (21 patients) affected by ERM were included in this study. The mean area of retinal folds detected by RMI was significantly higher than that detected by FAF (11.85 ± 3.92 mm2 and 5.67 ± 2.15 mm2, respectively, p < 0.05) and similar to that revealed by fundus photography (11.85 ± 3.92 mm2 and 10.58 ± 3.45 mm2, respectively, p = 0.277). (4) Conclusions: RMI appears to be a useful tool in the evaluation of ERMs. It allows for an accurate visualization of the real extension of the retinal folds and provides a precise structural assessment of the macula before surgery. Clinicians should be aware of RMI's advantages and should be able to use them to warrant a wide range of information and, thus, a more personalized therapeutic approach

Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Background. Our knowledge on long-term outcome in CAH remains incomplete. Methods. In a prospective study (33 CAH patients, 33 age-matched controls), reproductive outcomes, self-rating of genital appearance and function, and sexuality were correlated to degree of initial virilisation, genotype, and surgery. Results. Patients had larger median clitoral lengths (10.0 mm [range 2–30] versus 3.5 [2–8], P < .001), shorter vaginal length (121 mm [100–155] versus 128 [112–153], P = .12), lower uterine volumes (29.1 ml [7.5–56.7] versus 47.4 [15.9–177.5], P = .009), and higher ovarian volumes (4.4 ml [1.3–10.8] versus 2.8 [0.6–10.8], P = .09) than controls. Satisfaction with genital appearance was lower and negatively correlated to degree of initial virilisation (rs = ≤−0.39, P ≤ .05). More patients had never had intercourse (P = .001), and age at 1st intercourse was higher (18 yrs versus 16 yrs, P = .02). Conclusion. Despite overall acceptable cosmetic results, reproductive outcomes were suboptimal, supporting that multidisciplinary teams should be involved in adult follow up of CAH patients

Detection of poxtA-and optrA-carrying E. faecium isolates in air samples of a Spanish swine farm

Objective: Two linezolid-resistant Enterococcus faecium isolates, C10004 and C10009, were recovered from air samples of a Spanish swine farm and comprehensively characterized. Methods: Detection of linezolid resistance mechanisms (mutations and acquisition of resistance genes) was performed by PCR/sequencing. Isolates were characterized by multilocus sequence typing (MLST), antimicrobial susceptibility testing, detection of antimicrobial resistance and virulence genes, and analysis of the genetic environment of the linezolid resistance genes. The characterization of isolate C10009 was performed by Whole-Genome-Sequencing and of isolate C10004 by PCR and amplicon sequencing, where applicable. Conjugation experiments to assess the transferability of the optrA and poxtA genes implicated in linezolid resistance were performed. Results: The linezolid-resistant E. faecium isolates C10004 and C10009, assigned to ST128 and ST437, respectively, harbored the optrA and poxtA genes. Neither mutations in the 23S rRNA nor in the genes for the ribosomal proteins L3, L4 and L22 were detected. C10004 and C10009 carried fourteen and thirteen antimicrobial resistance genes, respectively. The sequence alignment indicated that the genetic environment of the poxtA gene was identical in both isolates, with a downstream-located fexB gene. The poxtA gene was transferred by conjugation together with the fexB gene, and also with tet(M) and tet(L) in the case of isolate C10004. The optrA gene could not be transferred. Conclusions: This is the first report of the poxtA gene in Spain. The presence of poxtA- and optrA-carrying E. faecium isolates in air samples represents a public health concern, indicating an involvement of swine farms in the spread of linezolid-resistant bacteria

Glucose Oxidation to Pyruvate Is Not Essential for Brucella suis Biovar 5 Virulence in the Mouse Model

Brucella species cause brucellosis, a worldwide extended zoonosis. The brucellae are related to free-living and plant-associated alpha 2-Proteobacteria and, since they multiply within host cells, their metabolism probably reflects this adaptation. To investigate this, we used the rodent-associated Brucella suis biovar 5, which in contrast to the ruminant-associated Brucella abortus and Brucella melitensis and other B. suis biovars, is fast-growing and conserves the ancestral Entner-Doudoroff pathway (EDP) present in the plant-associated relatives. We constructed mutants in Edd (glucose-6-phosphate dehydratase; first EDP step), PpdK (pyruvate phosphate dikinase; phosphoenolpyruvate pyruvate), and Pyk (pyruvate kinase; phosphoenolpyruvate -> pyruvate). In a chemically defined medium with glucose as the only C source, the Edd mutant showed reduced growth rates and the triple Edd-PpdK-Pyk mutant did not grow. Moreover, the triple mutant was also unable to grow on ribose or xylose. Therefore, B. suis biovar 5 sugar catabolism proceeds through both the Pentose Phosphate shunt and EDP, and EDP absence and exclusive use of the shunt could explain at least in part the comparatively reduced growth rates of B. melitensis and B. abortus. The triple Edd-PpdK-Pyk mutant was not attenuated in mice. Thus, although an anabolic use is likely, this suggests that hexose/pentose catabolism to pyruvate is not essential for B. suis biovar 5 multiplication within host cells, a hypothesis consistent with the lack of classical glycolysis in all Brucella species and of EDP in B. melitensis and B. abortus. These results and those of previous works suggest that within cells, the brucellae use mostly 3 and 4 C substrates fed into anaplerotic pathways and only a limited supply of 5 and 6 C sugars, thus favoring the EDP loss observed in some species

The fast-growing Brucella suis Biovar 5 depends on phosphoenolpyruvate carboxykinase and pyruvate phosphate dikinase but not on Fbp and GlpX fructose-1, 6-bisphosphatases or isocitrate lyase for full virulence in laboratory models

Bacteria of the genus Brucella infect a range of vertebrates causing a worldwide extended zoonosis. The best-characterized brucellae infect domestic livestock, behaving as stealthy facultative intracellular parasites. This stealthiness depends on envelope molecules with reduced pathogen-associated molecular patterns, as revealed by the low lethality and ability to persist in mice of these bacteria. Infected cells are often engorged with brucellae without signs of distress, suggesting that stealthiness could also reflect an adaptation of the parasite metabolism to use local nutrients without harming the cell. To investigate this, we compared key metabolic abilities of Brucella abortus 2308 Wisconsin (2308W), a cattle biovar 1 virulent strain, and B. suis 513, the reference strain of the ancestral biovar 5 found in wild rodents. B. suis 513 used a larger number of C substrates and showed faster growth rates in vitro, two features similar to those of B. microti, a species phylogenomically close to B. suis biovar 5 that infects voles. However, whereas B. microti shows enhanced lethality and reduced persistence in mice, B. suis 513 was similar to B. abortus 2308W in this regard. Mutant analyses showed that B. suis 513 and B. abortus 2308W were similar in that both depend on phosphoenolpyruvate synthesis for virulence but not on the classical gluconeogenic fructose-1, 6-bisphosphatases Fbp-GlpX or on isocitrate lyase (AceA). However, B. suis 513 used pyruvate phosphate dikinase (PpdK) and phosphoenolpyruvate carboxykinase (PckA) for phosphoenolpyruvate synthesis in vitro while B. abortus 2308W used only PpdK. Moreover, whereas PpdK dysfunction causes attenuation of B. abortus 2308W in mice, in B. suis, 513 attenuation occurred only in the double PckA-PpdK mutant. Also contrary to what occurs in B. abortus 2308, a B. suis 513 malic enzyme (Mae) mutant was not attenuated, and this independence of Mae and the role of PpdK was confirmed by the lack of attenuation of a double Mae-PckA mutant. Altogether, these results decouple fast growth rates from enhanced mouse lethality in the brucellae and suggest that an Fbp-GlpX-independent gluconeogenic mechanism is ancestral in this group and show differences in central C metabolic steps that may reflect a progressive adaptation to intracellular growth

Optical Coherence Tomography Angiography to estimate early retinal blood flow changes after uncomplicated cataract surgery

Background: To investigate macular microvascular changes after uncomplicated phacoemulsification surgery according to the cataract severity grade. Methods: Retrospective, cross-sectional study involving 23 eyes of 23 patients who underwent elective cataract extraction. All patients underwent routine ophthalmologic examination, including optical coherence tomography angiography (OCTA) at baseline (preoperative visit, T0) and seven days postoperatively (T7). OCTA scans were obtained with the spectral domain system Cirrus 5000 (Carl Zeiss Meditec, Inc., Dublin, CA, USA), and 3 mm × 3 mm raster fovea-centered scans were obtained to evaluate the superficial capillary plexus (SCP) vessel density, perfusion density, and foveal avascular zone (FAZ) parameters. Results: SCP perfusion density significantly increased from 28.3 ± 5.73% to 33.74 ± 4.13% after the surgery (p &lt; 0.001). Similarly, SCP vessel density significantly increased from 15.14 ± 3.41 mm-1 to 18.14 ± 2.57 mm-1 after surgery (p &lt; 0.001). The mean preoperative FAZ area significantly increased from 0.27 ± 0.12 mm to 0.24 ± 0.11 mm seven days postoperatively (p = 0.008). When comparing softer and harder cataracts, no significant variations in SCP vessel density, as well as SCP perfusion density parameters and the FAZ area, perimeter, and circularity index, were noted before and after surgery. Conclusions: Macular SPC vessel density and macular SCP perfusion density increase after uncomplicated cataract surgery regardless of the cataract severity

Extended Emission from Short Gamma-Ray Bursts Detected with SPI-ACS/INTEGRAL

The short duration (T90 < 2 s) gamma-ray bursts (GRBs) detected in the SPI-ACS experiment onboard the INTEGRAL observatory are investigated. Averaged light curves have been constructed for various groups of events, including short GRBs and unidentified short events. Extended emission has been found in the averaged light curves of both short GRBs and unidentified short events. It is shown that the fraction of the short GRBs in the total number of SPI-ACS GRBs can range from 30 to 45%, which is considerably larger than has been thought previously.Comment: 27 pages, 10 figure

Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.

The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O &lt;sub&gt;2&lt;/sub&gt; levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis