Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA ...strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of β-lactam-mediated HeR/HoR selection remains to be completed. In previous studies we demonstrated that acquisition of the HoR phenotype during exposure to β-lactam antibiotics depended on two key elements: (1) activation of the SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in order to increase the energy supply for cell-wall synthesis. In the present work, we identified that both main mechanistic components are associated through TCA cycle-mediated reactive oxygen species (ROS) production, which temporally affects DNA integrity and triggers activation of the SOS response resulting in enhanced mutagenesis. The present work brings new insights into a role of ROS generation on the development of resistance to β-lactam antibiotics in a model of natural occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Red wine is a relevant source of bioactive compounds, which contribute to its antioxidant activity and other beneficial advantages for human health. However, the bioavailability of phenols in humans ...is not well understood, and the inter-individual variability in the production of phenolic compounds has not been comprehensively assessed to date. The present work describes a new method for the extraction and analysis of phenolic compounds including gallic acid (Gal), vanillic acid (Van), caffeic acid (Caf), syringic acid (Sir); (−)-epicatechin (Epi); p-coumaric acid (Cum) and resveratrol (Rsv) in human saliva samples. The target analytes were extracted using Fabric Phase Sorptive Extraction (FPSE), and subsequently analysed by high-performance liquid chromatography (HPLC) coupled with photodiode array detector (PDA). Chromatographic separation was achieved using a Symmetry C18 RP column in gradient elution mode, with methanol and phosphate buffer as the mobile phases. The linearity (intercept, slope, and determination coefficient) was evaluated in the range from 1 to 50 µg/mL. The limit of quantification (LOQ) was 1 µg/mL (LLOQ ≥0.8 µg/mL), whereas limit of detection was 0.25 µg/mL. The intra and inter–day RSD% and BIAS% values were less than± 15%. The analytical performances were further tested on human saliva collected from healthy volunteers after administering red wine. To the best of our knowledge, this is the first FPSE procedure for the analysis of phenols in saliva, using a non-invasive and easy to perform sample collection protocol. The proposed fast and inexpensive approach can be deployed as a reliable tool to study other biological matrices to proliferate understanding of these compounds distribution in human body.
•Residual phenolic compounds analyzed in biological fluid using FPSE-HPLC-PDA.•Non-conventional matrices like saliva can be used for quantitative study.•Human saliva sample extraction using FPSE is highly selective, rapid and efficient.•Quantitative study using saliva presents a great potential in drug discovery.•Potential application of the FPSE to forensic and pharmacotoxicological studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. Because adipose tissue depots differ in the strength of their association with the ...adverse metabolic consequences of obesity, we studied the secretion of adiponectin in vitro from paired samples of isolated human omental and sc adipocytes and its regulation by insulin and rosiglitazone. Cells were incubated for 12 or 24 h with and without treatment with 100 nm insulin, 8 μm rosiglitazone, or both combined; adiponectin secreted into the culture medium was measured by a RIA with a human adiponectin standard and normalized for cellular DNA content. Secretion of adiponectin by omental cells was generally higher than sc cells and showed a strong negative correlation with body mass index (r = −0.78;P = 0.013). In contrast, secretion from the sc cells was unrelated to body mass index. Compared with sc-derived adipocytes, adiponectin secretion from omental cells was increased by insulin or rosiglitazone alone and was up to 2.3-fold higher following combined treatment with insulin and rosiglitazone, whereas secretion from sc adipose cells was unaffected by these treatments. These data suggest that reduced secretion from the omental adipose depot may account for the decline in plasma adiponectin observed in obesity. Furthermore, enhanced adiponectin secretion from fat cells derived from the visceral compartment in response to rosiglitazone alone or in combination with insulin may play a role in some of the systemic insulin-sensitizing and antiinflammatory properties of the thiazolidinediones.
Ceftaroline is the first member of a novel class of cephalosporins approved for use in the United States. Although prior studies have identified eight ceftaroline-resistant methicillin-resistant ...Staphylococcus aureus (MRSA) isolates in Europe and Asia with MICs ranging from 4 to 8 mg/liter, high-level resistance to ceftaroline (>32 mg/liter) has not been described in MRSA strains isolated in the United States. We isolated a ceftaroline-resistant (MIC > 32 mg/liter) MRSA strain from the blood of a cystic fibrosis patient and five MRSA strains from the respiratory tract of this patient. Whole-genome sequencing identified two amino acid-altering mutations uniquely present in the ceftaroline-binding pocket of the transpeptidase region of penicillin-binding protein 2a (PBP2a) in ceftaroline-resistant isolates. Biochemical analyses and the study of isogenic mutant strains confirmed that these changes caused ceftaroline resistance. Thus, we identified the molecular mechanism of ceftaroline resistance in the first MRSA strain with high-level ceftaroline resistance isolated in the United States.
Objective
This study was designed to identify quantifiable parameters to track performance improvements brought about by the implementation of a critical pathway for complex alimentary tract surgery.
...Background
Distal pancreatectomy is among the more complex general surgical procedures. This is primarily due to the possibility of blood loss from visceral vessels, splenic injury, and significant postoperative complications. The introduction of the laparoscopic approach to the distal pancreas has introduced a further level of surgical expertise required to fully address the clinical needs of this diverse patient population. Critical pathways have been one of the key tools used to achieve consistently excellent outcomes at high-quality, high-volume institutions. It remains to be determined if implementation of a critical pathway at an academic institution with prior moderate experience with distal pancreatectomy will result in performance gains and improved outcomes.
Methods
Between January 1, 2003 and August 15, 2007, 111 patients underwent distal pancreatectomy. Forty patients underwent resection during the 34-month period before the implementation of a critical pathway on October 15, 2005 and 71 during the 20 months after pathway implementation. Patients undergoing both open and laparoscopic procedures were included. Peri- and postoperative parameters were analyzed retrospectively to identify those that could be used to track performance improvement and outcomes.
Results
The two groups were not significantly different with respect to age, sex, race, diagnosis, operative blood loss, or mean operative duration. Postoperative length of hospital stay was significantly shorter when comparing pre- to postpathway implementation (10.2 days versus 6.7 days,
P
≤ 0.037). The rate of readmission to the hospital after discharge was significantly lower post pathway (25% versus 7%,
P
≤ 0.027). Hospital costs were also reduced.
Conclusion
Implementation of a critical pathway for a complex procedure can be demonstrated to improve short-term outcomes at an academic institution. This improvement can be quantified and tracked and has implications for better utilization of resources and overall cost containment while maintaining or improving upon an already high level of care.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Human body is colonized by trillions of microbes, influenced by several factors, both endogenous, as hormones and circadian regulation, and exogenous as, life-style habits and nutrition. The ...alteration of such factors can lead to microbial dysbiosis, a phenomenon which, in turn, represents a risk factor in many different pathologies including cancer, diabetes, autoimmune and cardiovascular disease, and infertility. Female microbiota dysbiosis (vaginal, endometrial, placental) and male microbiota dysbiosis (seminal fluid) can influence the fertility, determining a detrimental impact on various conditions, as pre-term birth, neonatal illnesses, and macroscopic sperm parameters impairments. Furthermore, unprotected sexual intercourse creates a bacterial exchange between partners, and, in addition, each partner can influence the microbiota composition of partner’s reproductive tracts. This comprehensive overview of the effects of bacterial dysbiosis in both sexes and how partners might influence each other will allow for better personalization of infertility management.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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