Chavezsalomonsen7164

Candida auris is an emerging fungal species able to develop multidrug resistance and outbreaks of invasive infections worldwide with high mortality rates. To increase the treatment options for C. auris infection, we assessed the efficacy of miltefosine (MFS), an anti-Leishmania agent that has demonstrated a broad-spectrum antifungal action in vitro. The aims of this work were (i) to evaluate the in vitro antifungal activity of MFS against C. auris clinical isolates in the planktonic and biofilm lifestyles; and (ii) to compare the activity of MFS in its free form and encapsulated in alginate nanoparticles (MFS-AN) in Galleria mellonella larvae infected by C. auris. MFS exhibited in vitro inhibitory effect at MICs ranging from 1 to 4 µg/mL and fungicidal activity against planktonic cells of C. auris clinical isolates. MFS antibiofilm activity was observed during biofilm formation (0.25 to 4 µg/mL) and on pre-formed biofilms (16 to 32 µg/mL). Moreover, the dispersed cells from C. auris biofilms had a similar susceptibility to those obtained for planktonic cells. Treatment with free MFS or MFS-AN resulted in significant improvements in the survival and morbidity rates of G. mellonella larvae infected by C. auris. In addition, reduction of fungal burden (0.5-1 log CFU/g) and granuloma formation were observed when compared with the untreated group. Our findings suggest that both the free MFS and MFS-AN have potential for the treatment of fungal infections caused by the emerging C. auris.Clonal complex 59 (CC59) is the dominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) strain in Taiwan and includes the Asian-Pacific clone with Panton-Valentine leukocidin (PVL)-negative/staphylococcal cassette chromosome mec (SCCmec) IVg and the Taiwan clone characterised as PVL-positive/SCCmec V (5C2&5). Nevertheless, data on the evolutionary history of the two dominant CC59 MRSA clones in Taiwan are scarce. In this study, a total of 258 CC59 S. aureus strains from Taiwan were classified by multiple-locus variable-number tandem repeat analysis (MLVA), which revealed two major clusters (MT1 and MT2) with distinct mobile genetic elements (MGEs). However, sequencing and PCR mapping of the β-lactamase-producing plasmid revealed no difference among all CC59 S. aureus strains. Bayesian evolutionary analysis of 18 of the CC59 S. aureus strains based on core genome alignment revealed two clades (i) Clade A, which shared the samples with MT1, had the features of mainly harbouring gentamicin-resistant MES6272-2 or MES4578, φSA3 translocation in νSaβ and SCCmec IVg; and (ii) Clade B, which shared the samples with MT2, had the features of mainly harbouring streptomycin-resistant MESPM1, PVL phage and SCCmec V (5C2&5). Based on the time-calibrated phylogenetic tree, the estimated time of divergence of the two clades was in the 1980s. These results suggest that the CC59 S. aureus progenitor acquired a β-lactamase-producing plasmid and then developed the varied genetic backgrounds, which were associated with the acquisition and maintenance of distinct MGEs, leading to differences in antimicrobial susceptibility profiles and molecular virulence determinants.Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) have disseminated worldwide and emerged as major threats to public health. The multidrug-resistant (MDR)-phenotype of KPC-KP are commonly associated with the presence of high molecular weight blaKPC plasmids. Restriction-modification (R-M) systems provide bacteria with innate defense against plasmids or other infectious gene elements. Because of blaKPC plasmids are favored by such MDR K. pneumoniae, it was of interest to examine the co-distribution of R-M and acquired blaKPC plasmids in KPC-KP. We collected 459 clinical K. pneumoniae isolates in China and 217 global whole-genome sequences in GenBank to determine the prevalence of type I R-M systems. We found the type I R-M system was significantly scarce in the KPC-positive group and high risk Klebsiella pneumoniae clonal group 258 (CG258). The polymorphisms of type I R-M we observed in K. pneumoniae reveled the relative ubiquity of their recognition sequences in DNA, which means the type I R-M systems were capable to attack most invading DNA elements, such as blaKPC genes. Overall, our work suggested the type I R-M systems may impact the acquisition of blaKPC genes in K. pneumoniae.Purpose Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. Methods We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. Results Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. Conclusions Together, these results suggest that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.Whey protein, a by-product of cheese industry, is harmful for the environment (i.e., surface and subterranean waters, soil) and, therefore, for humans due to its high polluting burden. Concomitantly, it has been reported that it is a mixture with potent antioxidant action since it is rich in cysteine residues, which are necessary for glutathione synthesis in vivo. On this basis, this study intended to examine the role of whey protein on the intensification of tissue antioxidant arsenal. To this end, a dose of sheep/goat whey protein equal to 1 g/kg of body weight/day dissolved in drinking water was administered to rats for 28 consecutive days. According to our findings, whey protein improved the antioxidant profile of liver, small intestine, lung and muscle whereas it did not affect the redox state of kidney. Our results were based on the alterations found in the protein expression of glutamate cysteine ligase, catalase and superoxide dismutase-1 measured in all tissues and the activity of glutathione S-transferase evaluated in muscle. Although tissue-specific, it is obvious that the action of whey protein is biologically beneficial and could serve as a biofunctional constituent for foods able to improve redox profile when administered against redox-related diseases.Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.Objective To demonstrate a robotic tumor debulking for management of locoregional endometrial cancer recurrence. Design A case report. Setting A tertiary referral center in New Haven, CT. Interventions 70-year-old with history of stage IB endometrioid endometrial cancer presented three years after completion of treatment with rectal bleeding. A mass involving the distal sigmoid colon/upper rectum and bilateral distal peri-ureteral masses were visualized on imaging. There was no distant metastatic disease. Colonoscopic biopsies were consistent with endometrial cancer recurrence. Given that patient was symptomatic with rectal bleeding and had no distant metastasis, she was recommended to undergo surgical resection for management of this locoregional recurrence. Patient was placed in reverse Trendelenburg position with a rightward tilt to mobilize the splenic flexure. Once the cephalad aspect of descending colon mobilization was completed, the patient was placed in Trendelenburg lithotomy position to expose the ate vascularization was confirmed with IV indocyanine green. Conclusion Robotic LAR and partial bladder resection were performed without any complications with negative margins. Robotic tumor debulking should be considered in appropriate patients, when managing locoregional recurrence of endometrial cancer (1,2).Purpose To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro-re-nata (PRN) regimen over 4-years in a real-life setting. Design 4-year, multicenter, retrospective comparative study PARTICIPANTS 264 patients with treatment-naïve nAMD. Methods Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n=163) or PRN (n=101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4-years and had annual fundus autofluorescence (FAF) and optical coherence tomography (OCT) imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. Main outcomes measures MA incidence and progression ovee treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and had better visual outcomes compared to those treated with a PRN approach.Objective To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations. Design Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. Participants Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye by clinical gonioscopy, and study eye baseline IOP (H0; 8 am±1 h) of 22-32 mmHg after washout. Methods Study eyes received bimatoprost implant 10 μg (n=198) or 15 μg (n=198) on Day 1 with readministration at Weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n=198). IOP was measured at Hours 0 and 2 at each visit. Main outcome measures Primary endpoints were IOP and change from baseline IOP through Week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration.