Candida parapsilosis complex consists of three species, the prevalence and geographical distribution of which might vary. Increasing rates of fluconazole resistance among C.parapsilosis complex were reported from various centres.

Aim of this study was to identify invasive C.parapsilosis complex strains up to species level, explore rates and molecular mechanisms of azole resistance and analyse temporal changes at a single centre.

Isolates from blood cultures from 1997 to 2017 were included. Species were identified using RFLP of the SADH gene and confirmed with ITS sequencing when needed. In vitro susceptibility to fluconazole, voriconazole and posaconazole was tested and evaluated using EUCAST guidelines. Sequences of ERG11 and MRR1 genes were analysed for fluconazole non-susceptible isolates.

A total of 283 isolates from 181 patients were tested for azole susceptibility. All were C.parapsilosis sensu stricto, except one C.orthopsilosis. All three azoles were effective against 213 of the isolates from 135 patients, including one C.orthopsilosis. Fluconazole resistance was 13.3% (24/181 patients). While the first fluconazole-resistant isolates were detected in 2004, increase was evident after 2011. In ERG11, Y132F mutation was the most common among fluconazole non-susceptible isolates (71.7%), followed by G458S (10.9%) and D421N (4.3%). In MRR1, R405K (56.5%) and G927C (8.7%) were detected. However, association of these mutations to azole resistance is yet to be investigated.

Rising azole resistance rates in C.parapsilosis sensu stricto isolates particularly after 2011 were of concern. The well-known Y132F mutation was the predominant mechanism of azole resistance while accompanied with other genetic mutations.

Rising azole resistance rates in C. parapsilosis sensu stricto isolates particularly after 2011 were of concern. The well-known Y132F mutation was the predominant mechanism of azole resistance while accompanied with other genetic mutations.Growing evidence indicates that innate immune molecules regulate microglial activation in Alzheimer’s disease (AD); however, their effects on amyloid pathology and neurodegeneration remain inconclusive. Here, we conditionally deleted one allele of myd88 gene specifically in microglia in APP/PS1-transgenic mice by 6 months and analyzed AD-associated pathologies by 9 months. We observed that heterozygous deletion of myd88 gene in microglia decreased cerebral amyloid β (Aβ) load and improved cognitive function of AD mice, which was correlated with reduced number of microglia in the brain and inhibited transcription of inflammatory genes, for example, tnf-α and il-1β, in both brain tissues and individual microglia. To investigate mechanisms underlying the pathological improvement, we observed that haploinsufficiency of MyD88 increased microglial recruitment toward Aβ deposits, which might facilitate Aβ clearance. Microglia with haploinsufficient expression of MyD88 also increased vasculature in the brain of APP/PS1-transgenic mice, which was associated with up-regulated transcription of osteopontin and insulin-like growth factor genes in microglia. Moreover, MyD88-haploinsufficient microglia elevated protein levels of LRP1 in cerebral capillaries of APP/PS1-transgenic mice. Cell culture experiments further showed that treatments with interleukin-1β decreased LRP1 expression in pericytes. In summary, haploinsufficiency of MyD88 in microglia at a late disease stage attenuates pro-inflammatory activation and amyloid pathology, prevents the impairment of microvasculature and perhaps also protects LRP1-mediated Aβ clearance in the brain of APP/PS1-transgenic mice, all of which improves neuronal function of AD mice.Solitary fibrous tumor (SFT) is a mesenchymal neoplasm mostly originates from pleura, but rarely from other parts of the body including pericardium. We report a case of a 44-year-old woman with dyspnea and intermittent edema in whom a large intrapericardial mass was discovered by echocardiography. Computed tomography (CT) revealed a focal pericardial calcification in right AV grove with pressure on right ventricle and right atrial, with no connection to cardiac chambers. Histopathological findings after complete resection of the mass revealed fibroconnective tissue with heavy calcification and no evidence of inflammation or malignancy. We reviewed the literature on pericardial solitary fibrous tumors up to 2020.Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated animals functional and structural outcomes over 24 weeks. For primary outcome measures, we performed histological evaluations and gene expression analysis of aggrecan, collagen types I and II, and cartilage oligomeric matrix protein in three regions of interest. As secondary outcome measures, we examined animals’ lameness, performed arthroscopic, radiographic, and computed tomography (CT) scan imaging and gross morphology assessment. We detected the highest treatment benefit following 100 μg sprifermin treatment. The overall histological assessment showed an improvement in the kissing region, and the expression of constitutive genes showed a concentration-dependent enhancement, especially in the peri-lesion area. We detected a significant improvement in lameness scores, arthroscopic evaluations, radiography, and CT scans following sprifermin treatment when results from three dose-treatment groups were combined. Our results demonstrated, for the first time, an enhancement on microfracture outcomes following sprifermin treatment suggesting a cartilage regenerative role and a potential benefit of sprifermin treatment in early cartilage injuries.

Benchmarking of flow and perfusion MR techniques on standardized phantoms can facilitate the use of advanced angiography and perfusion-mapping techniques across multiple sites, field strength, and vendors. Here, MRA and perfusion mapping by arterial spin labeling (ASL) using Fourier transform (FT)-based velocity-selective saturation and inversion pulse trains were evaluated on a commercial perfusion phantom.

The FT velocity-selective saturation-based MRA and FT velocity-selective inversion-based ASL perfusion imaging were compared with time-of-flight and pseudo-continuous ASL at 3 T on the perfusion phantom at two controlled flow rates, 175 mL/min and 350 mL/min. Velocity-selective MRA (VSMRA) and velocity-selective ASL (VSASL) were each performed with three velocity-encoding directions foot-head, left-right, and oblique 45°. The contrast-to-noise ratio for MRA scans and perfusion-weighted signal, as well as labeling efficiency for ASL methods, were quantified.

On this phantom with feeding tubes having ity-encoding directions along the major vessels is recommended for their applications in various organs.

Auditory neuropathy is a cause of hearing loss that has been studied in a number of animal models. Signal transmission from hair cells to spiral ganglion neurons plays an important role in normal hearing. CYLD is a microtubule-binding protein, and deubiquitinase involved in the regulation of various cellular processes. In this study, we used Cyld knockout (KO) mice and nerve cell lines to examine whether CYLD is associated with auditory neuropathy.

Hearing of Cyld KO mice was studied using the TDT RZ6 auditory physiology workstation. The expression and localization of CYLD in mouse cochlea and cell lines were examined by RT-PCR, immunoblotting, and immunofluorescence. CYLD expression was knocked down in SH-SY5Y cells by shRNAs and in PC12 and N2A cells by siRNAs. Nerve growth factor and retinoic acid were used to induce neurite outgrowth, and the occurrence and length of neurites were statistically analyzed between knockdown and control groups.

Cyld KO mice had mild hearing impairment. Moreover, CYLD was widely expressed in mouse cochlear tissues and different nerve cell lines. Knocking down CYLD significantly reduced the length and proportion of neurites growing from nerve cells.

The abnormal hearing of Cyld KO mice might be caused by a decrease in the length and number of neurites growing from auditory nerve cells in the cochlea, suggesting that CYLD is a key protein affecting hearing.

The abnormal hearing of Cyld KO mice might be caused by a decrease in the length and number of neurites growing from auditory nerve cells in the cochlea, suggesting that CYLD is a key protein affecting hearing.Mutations in the shelterin protein POT1 are associated with chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, angiosarcoma, melanoma, and other cancers. These cancer-associated POT1 (caPOT1) mutations are generally heterozygous, missense, or nonsense mutations occurring throughout the POT1 reading frame. Cancers with caPOT1 mutations have elongated telomeres and show increased genomic instability, but which of the two phenotypes promotes tumorigenesis is unclear. We tested the effects of CAS9-engineered caPOT1 mutations in human embryonic and hematopoietic stem cells (hESCs and HSCs, respectively). HSCs with caPOT1 mutations did not show overt telomere damage. In vitro and in vivo competition experiments showed the caPOT1 mutations did not confer a selective disadvantage. Since DNA damage signaling is known to affect the fitness of HSCs, the data argue that caPOT1 mutations do not cause significant telomere damage. Furthermore, hESC lines with caPOT1 mutations showed no detectable telomere damage response while showing consistent telomere elongation. Thus, caPOT1 mutations are likely selected for during cancer progression because of their ability to elongate telomeres and extend the proliferative capacity of the incipient cancer cells.This mini-narrative historical review presents views and recommendations of Ancient Greek and Byzantine physicians and philosophers, concerning the nutrition and lifestyle, collectively referred in antiquity as 'diet’, of pregnant and breastfeeding women, and the nutrition of the foetus and neonate. Pregnant and breastfeeding women in these eras were cared for with regard to their nutrition and well-being, in addition to their clothing, physical exercise and mental health. A number of ancient scholars taught that the foetus was fed through the umbilical cord. Breastfeeding by mothers was warmly recommended, but wet nurses and baby bottles were also available. Relevant information is found in preserved texts of well-known antique physicians and philosophers, who had studied medicine, or discussed medical issues.

Patients with triple-negative breast cancer (TNBC) face a major challenge of the poor prognosis, and N6-methyladenosine-(m6A) mediated regulation in cancer has been proposed. Therefore, this study aimed to explore the prognostic roles of m6A-related long non-coding RNAs (LncRNAs) in TNBC.

Clinical information and expression data of TNBC samples were collected from TCGA and GEO databases. Pearson correlation, univariate, and multivariate Cox regression analysis were employed to identify independent prognostic m6A-related LncRNAs to construct the prognostic score (PS) risk model. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PS risk model. A competing endogenous RNA (ceRNA) network was established for the functional analysis on targeted mRNAs.

We identified 10 independent prognostic m6A-related LncRNAs (SAMD12-AS1, BVES-AS1, LINC00593, MIR205HG, LINC00571, ANKRD10-IT1, CIRBP-AS1, SUCLG2-AS1, BLACAT1, and HOXB-AS1) and established a PS risk model accordingly. Relevant results suggested that TNBC patients with lower PS had better overall survival status, and ROC curves proved that the PS model had better prognostic abilities with the AUC of 0.