Optical detection of the ultrasound-induced pulsed thermal lens close to the ice-water phase transition.

Piezo-optic and thermo-optic coefficients are important material properties that play a critical role in the design and optimization of many optical devices. The ability to accurately measure and control these coefficients is essential for achieving high performance and reliability in a wide range of applications. In this article, we use the optical detection of the ultrasound-induced thermal lens effect to investigate these properties for water at low temperatures. The results show that the anomalous behavior of water around 4°C is easily observed. The thermal lens method is used to determine the temperature dependence of the piezo-optic and thermo-optic coefficients.

Leukemia cutis and eccrine squamous syringometaplasia.

Eccrine squamous syringometaplasia (ESS) is a histological term describing a mature squamous metaplasia of the eccrine ducts. Eccrine squamous syringometaplasia is not an infrequent histological finding and may be associated with chemotherapy or with a variety of non-specific conditions including infections, neoplastic conditions, and inflammatory skin diseases. We report a 75-year-old man who developed ESS within lesions of leukemia cutis (LC). The patient had an inaugural diagnosis of acute myeloid leukemia (AML) and he was not on chemotherapy when the biopsy was performed.

Activity of Aztreonam in Combination with Avibactam, Clavulanate, Relebactam, and Vaborbactam against Multidrug-Resistant Stenotrophomonas maltophilia.

The intrinsic L1 metallo- and L2 serine-ß-lactamases in Stenotrophomonas maltophilia make it naturally multidrug resistant and difficult to treat. There is a need to identify novel treatment strategies for this pathogen, especially against isolates resistant to first-line agents. Aztreonam in combination with avibactam has demonstrated potential, although data on other aztreonam-ß-lactamase inhibitor (BLI) combinations are lacking. Additionally, molecular mechanisms for reduced susceptibility to these combinations have not been explored. The objectives of this study were to evaluate and compare the in vitro activities and to understand the mechanisms of resistance to aztreonam in combination with avibactam, clavulanate, relebactam, and vaborbactam against S. maltophilia A panel of 47 clinical S. maltophilia strains nonsusceptible to levofloxacin and/or trimethoprim-sulfamethoxazole were tested against each aztreonam-BLI combination via broth microdilution, and 6 isolates were then evaluated in time-kill analyses. Three isolates with various aztreonam-BLI MICs were subjected to whole-genome sequencing and quantitative reverse transcriptase PCR. Avibactam restored aztreonam susceptibility in 98% of aztreonam-resistant isolates, compared to 61, 71, and 15% with clavulanate, relebactam, and vaborbactam, respectively. The addition of avibactam to aztreonam resulted in a ≥2-log10-CFU/ml decrease at 24 h versus aztreonam alone against 5/6 isolates compared to 1/6 with clavulanate, 4/6 with relebactam, and 2/6 with vaborbactam. Molecular analyses revealed that decreased susceptibility to aztreonam-avibactam was associated with increased expression of genes encoding L1 and L2, as well as the efflux pump (smeABC). Aztreonam-avibactam is the most promising BLI-combination against multidrug-resistant S. maltophilia Decreased susceptibility may be due to the combination of overexpressed ß-lactamases and efflux pumps. Further studies evaluating this combination against S. maltophilia are warranted.

Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia.

The production of an L1 metallo-ß-lactamase and an L2 serine active-site ß-lactamase precludes the use of ß-lactams for the treatment of Stenotrophomonas maltophilia infections. Preclinical data suggest that cefiderocol is the first approved ß-lactam with reliable activity against S. maltophilia, but data on strains resistant to current first-line agents are limited, and no studies have assessed cefiderocol-based combinations. The objective of this study was to evaluate and compare the in vitro activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole (TMP-SMZ) against a collection of highly resistant clinical S. maltophilia isolates. For this purpose, the MICs of cefiderocol, ceftazidime, levofloxacin, minocycline, polymyxin B, and TMP-SMZ for 37 S. maltophilia isolates not susceptible to levofloxacin and/or TMP-SMZ were determined. Nine strains with various cefiderocol MICs were then tested in time-kill experiments with cefiderocol alone and in combination with comparators. The only agents for which susceptibility rates exceeded 40% were cefiderocol (100%) and minocycline (97.3%). Cefiderocol displayed the lowest MIC50 and MIC90 values (0.125 and 0.5 mg/liter, respectively). In time-kill experiments, synergy was observed when cefiderocol was combined with levofloxacin, minocycline, polymyxin B, or TMP-SMZ against 4/9 (44.4%), 6/9 (66.7%), 5/9 (55.5%), and 6/9 (66.7%) isolates, respectively. These data suggest that cefiderocol displays potent in vitro activity against S. maltophilia, including strains resistant to currently preferred agents. Future dynamic and in vivo studies of cefiderocol alone and in combination are warranted to further define cefiderocol's synergistic capabilities and its place in therapy for S. maltophilia infections.

Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects.

The ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all experiments (5 Escherichia coli, 2 Klebsiella pneumoniae, and 1 Proteus mirabilis). MICs were performed via agar dilution. Urinary bactericidal titers (UBTs) were performed via modified Schlichter test using participant's drug-free urine as the diluent. Urinary time-kill analyses were performed on pooled 24-h urine aliquots from days 1 and 5. All experiments were performed in triplicate with and without the addition of 25 mg/liter of glucose-6-phosphate (G6P). Mean 24-h urine concentrations of fosfomycin ranged from 324.7 to 434.6 mg/liter regardless of study day or dosing regimen. The urinary antibacterial activity of fosfomycin was also similar across study days and dosing regimens. UBT values did not correlate with MICs determined in the presence of G6P. Fosfomycin was reliably bactericidal in urine only against the 5 E. coli strains, regardless of genotype or MIC value. Together, these data do not support the use of oral fosfomycin tromethamine for pathogens other than E. coli or at a dosing frequency higher than QOD. Fosfomycin MICs determined in the presence of G6P may not accurately reflect the in vivo activity given the lack of G6P in human urine. (This study has been registered at ClinicalTrials.gov under identifier NCT02570074.).

Activity of Potential Alternative Treatment Agents for Stenotrophomonas maltophilia Isolates Nonsusceptible to Levofloxacin and/or Trimethoprim-Sulfamethoxazole.

Stenotrophomonas maltophilia is difficult to treat due to the production of multiple intrinsic and acquired mechanisms of resistance. Trimethoprim-sulfamethoxazole (TMP-SMZ) and the fluoroquinolones have traditionally been considered the drugs of choice but are plagued by increasing resistance and adverse drug effects. The objective of this study was to evaluate the in vitro activities of 12 clinically relevant antimicrobials against clinical S. maltophilia isolates nonsusceptible to levofloxacin and/or TMP-SMZ. A diverse panel of 41 clinical S. maltophilia isolates collected through the SENTRY Antimicrobial Surveillance Program from 2008 to 2018 was evaluated against ceftazidime, ceftazidime-avibactam, chloramphenicol, delafloxacin, levofloxacin, moxifloxacin, eravacycline, minocycline, omadacycline, polymyxin B, and tigecycline. MICs were determined in triplicate via reference broth microdilution and interpreted according to CLSI guidelines where available. MIC distributions and susceptibilities were also compared across infection type, acquisition setting, and geographic origin. Susceptibilities to levofloxacin and TMP-SMZ were 29.3% and 36.6%, respectively. Minocycline displayed the highest susceptibility rate overall (92.7%) and the lowest MIC90 value (4 mg/liter) of any of the 12 agents tested. Only 3 isolates were resistant to levofloxacin, TMP-SMZ, and minocycline. Polymyxin B and tigecycline were the second most active agents. No significant differences were observed in MIC distributions across the 3 strata evaluated. These data demonstrate that few antimicrobials, old or new, maintain reliable activity against resistant S. maltophilia The role of minocycline in the treatment of infections due to S. maltophilia warrants further clinical investigation given its potent in vitro activity and favorable adverse effect profile.

PAH Profiles in Suspended Particulate Matter from an Urbanized River Within the Brazilian Amazon.

The distribution, seasonal variation and sources of 16 polycyclic aromatic hydrocarbons (PAH) from suspended particulate matter (SPM) of the Aurá River, a small amazon typical river located in Northern Brazil, were determined. Gas chromatography-mass spectrometry analysis of SPM revealed a mixture of PAH from different origins and a seasonal variation of PAH primary source for the studied area. Pyrene was the dominant PAH in both studied periods. Total PAH content (ΣPAH) ranged from lower than quantification limit (< LOQ) to 2498.2 ng g-1 dw during the dry season and < LOQ to 2865.8 ng g-1 dw during the wet season. Low molecular weight PAH (LMW) represented 51% of ΣPAH during the dry season and 29% during the wet season. It was noted, by comparing previous data, that the main source of these compounds was altered after the deactivation of an irregular landfill next to the river.

Risk Factors Associated with Probable Sleep Bruxism of Children and Teenagers with Cerebral Palsy.

AIM: To assess the association between probable sleep bruxism (PSB) and other occlusal characteristics in children and teenagers with Cerebral Palsy (CP). STUDY DESIGN: A cross-sectional study was carried out with 148 participants (74 with CP and 74 without special needs) aged between 2 and 14 years old. Participants underwent an oral clinical examination to evaluate the occlusal characteristics. Parents/caregivers filled out a questionnaire with information related to the typical sounds of PSB, sociodemographic factors and the presence of harmful oral habits in the study participants. Data analysis was carried out, using Chi-square or Fisher's exact test and Odds Ratio (p<0.05). RESULTS: PSB and malocclusion (68.9% and 95.9%, respectively) were more prevalent in participants with CP than in participants without CP. The association between PSB and the presence of a wear facet was statistically significant (p < 0.001) in participants with CP. In this group, 64.8% of participants with PSB presented tooth wear. CONCLUSION: Presence of dental wear facets was significantly associated with PSB in individuals with cerebral palsy.

Mycobacterium marinum lymphocutaneous infection.

Mycobacterium marinum is a nontuberculous mycobacteria with worldwide distribution that lives in fresh or salt water and is responsible for infections in fish, and sometimes in humans. Human disease consists mainly of cutaneous nodules, but deep structure involvement may also occur. Diagnosis of M. marinum infection remains a challenge, with a considerable time delay between onset of symptoms and diagnosis. We present a 33-year-old man with no immunosuppressive history who was seen in our department with skin nodules over his hand and forearm, distributed in a sporotrichoid pattern. His hobbies included maintaining an aquarium of tropical fish. Histological examination of the patient's skin biopsy was compatible with the diagnosis of mycobacterial infection, and the Ziehl-Neelsen staining revealed acid-fast bacilli. Molecular techniques confirmed the suspicion of M. marinum infection. A necropsy was performed on one of the patient's fish, more specifically, a Poecilia reticulata, and resulted in identification of M. marinum from its gut. The patient was treated with clarithromycin, ethambutol, and rifampicin for 9 months, with clearance of infection.

Evolving oxazolidinone resistance mechanisms in a worldwide collection of enterococcal clinical isolates: results from the SENTRY Antimicrobial Surveillance Program.

Objectives: This study evaluated the oxazolidinone resistance mechanisms among a global collection of enterococcal clinical isolates. The epidemiology of optrA-carrying isolates and the optrA genetic context were determined. Methods: Enterococcal isolates (26 648) from the SENTRY Antimicrobial Surveillance Program (2008-16) were identified by MALDI-TOF MS and MICs were determined by broth microdilution. Isolates with linezolid MICs of ≥4 mg/L were screened for resistance mechanisms. Isolates carrying optrA had their genome sequenced for genetic context and epidemiology information. Results: Thirty-six Enterococcus faecalis and 66 Enterococcus faecium had linezolid MICs of ≥4 mg/L (0.38% of surveillance enterococci). E. faecalis had a linezolid MIC range of 4-16 mg/L, while E. faecium displayed higher values (4-64 mg/L). Nine E. faecalis had G2576T mutations and optrA was detected in 26 (72.2%) isolates from the Asia-Pacific region, North America, Latin America and Europe; 3 isolates also produced Cfr [Thailand (1)] or Cfr(B) [Panama (2)]. All E. faecium isolates had G2576T alterations, while three isolates from the USA had concomitant presence of cfr(B). The optrA gene was plasmid- and chromosome-located in 22 and 3 E. faecalis, respectively. One isolate signalled hybridization on plasmid and chromosome. The genetic context of optrA varied. E. faecalis belonging to the same clonal complex were detected in distinct geographical regions. Also, genetically distinct isolates from Ireland had an identical optrA context, indicating plasmid dissemination. Conclusions: Alterations in 23S rRNA remained the main oxazolidinone resistance mechanism in E. faecium, while optrA prevailed in E. faecalis. These results demonstrate global dissemination of optrA and warrant surveillance for monitoring.

Influence of menopausal status on the main contributors of muscle quality.

BACKGROUND: Muscle quality is a strong independent predictor of physical function. Body mass and fatness, muscle mass and cardiorespiratory fitness are known to influence muscle quality. OBJECTIVE: To identify the contributors of muscle quality in young and postmenopausal women and whether hormone replacement therapy (HT) could influence this relationship at the age of menopause. METHODS: Fifty-four postmenopausal women, 27 not on HT (PMW) and 27 on HT (PMW-HT), and 33 young women (YW) were evaluated for (1) body composition (body mass index, BMI), total fat mass (FM, %), appendicular lean mass (ALM, in kg and %), and appendicular skeletal mass index (ASMI = ALM/height2 in kg/m2); (2) absolute peak oxygen uptake (VO2peak, in ml/min) and relative peak oxygen uptake (VO2peakRel in ml/kg/min); and (3) absolute isometric knee extension strength (iKES in kg) and relative isometric knee extension strength (iKES/BMI and iKES/ALM). RESULTS: YW, PMW and PMW-HT had similar BMI (32.1 ± 10.2, 27.3 ± 4.7 and 26.7 ± 4 kg/m2) and FM (39.8 ± 10.0, 39.8 ± 7.3 and 39.9 ± 7.1%), respectively. Correlations were found between iKES/BMI index and FM (r = -0.52), ALM (r = 0.32) and VO2peak (r = 0.31). Regression analysis demonstrated that, in YW, total amount of variance in iKES/BMI was mostly explained by ALM (42%), whereas, in PMW and PMW-HT, it was cumulatively explained by FM along with VO2peakRel (34 and 46%, respectively). CONCLUSION: The main contributors of muscle quality differ between young and postmenopausal women and HT does not seem to influence this relationship.

Update of the activity of telavancin against a global collection of Staphylococcus aureus causing bacteremia, including endocarditis (2011-2014).

The efficacy and safety of telavancin is under evaluation for the treatment of subjects with complicated Staphylococcus aureus bacteremia and S. aureus right-sided infective endocarditis. This study evaluated the telavancin activity against a global collection of S. aureus causing bloodstream infections (BSI), including endocarditis, to support the development of bacteremia/endocarditis clinical indications. This study included a total of 4191 S. aureus [1490 methicillin-resistant S. aureus (MRSA)], which were unique (one per patient) clinical isolates recovered from blood samples collected during 2011-2014 in a global network of hospitals. All isolates were deemed responsible for BSI, including endocarditis, by local guidelines. Isolates were tested for susceptibility by broth microdilution. Telavancin (MIC50/90, 0.03/0.06 µg/ml) inhibited all S. aureus at ≤0.12 µg/ml, the breakpoint for susceptibility. Equivalent minimum inhibitory concentration (MIC) values (MIC50/90, 0.03/0.06 µg/ml) were obtained for telavancin against methicillin-susceptible S. aureus (MSSA) and MRSA isolates, as well as MRSA from community and healthcare origins. Similar telavancin activities (MIC50, 0.03 µg/ml) were observed against MRSA subsets from North America and Europe, while isolates from the Asia-Pacific (APAC) and Latin America regions had MIC50 values of 0.06 µg/ml. MRSA with vancomycin MIC values of 2-4 µg/ml and the multidrug resistance (MDR) subset had telavancin MIC50 results of 0.06 µg/ml, although the MIC100 result obtained against these subsets remained identical to those of MSSA (MIC100, 0.12 µg/ml, respectively). This study updates the telavancin in vitro activity, which continues to demonstrate great potency against invasive S. aureus, regardless of the susceptibility phenotype or demographic characteristics (100.0% susceptible), and supports the sought-after subsequent indications.

Relationship between day 1 and day 2 Vancomycin area under the curve values and emergence of heterogeneous Vancomycin-intermediate Staphylococcus aureus (hVISA) by Etest® macromethod among patients with MRSA bloodstream infections: a pilot study.

BACKGROUND: In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline. METHODS: This was a retrospective cohort study of patients with methicillin-resistant Staphylococcus aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005 and June 2009. The vancomycin AUC exposure variables on day 1 (AUC0-24h) and day 2 (AUC24-48h) were estimated using the maximal a posteriori probability (MAP) procedure in ADAPT 5. RESULTS: There were 238 unique episodes of MRSA BSIs during the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in 7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not achieve area under the curve over broth microdilution minimum inhibitory concentration (AUC0-24h/MICBMD) ratio of 521 or an AUC24-48h/MICBMD ratio of 650. No associations between other day 1 and day 2 AUC variables and emergence of hVISA were noted. CONCLUSIONS: Although more data are needed to draw definitive conclusions, these findings suggest that hVISA emergence among patients with non-hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings support further study of the relationship between initial vancomycin exposure and hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center, prospective trial.

Solid lipid nanoparticles affect microbial colonization and enzymatic activity throughout the decomposition of alder leaves in freshwater microcosms.

Solid lipid nanoparticles (SLNs) are used as carriers for drug delivery, and are high biocompatible and designed to endure in the host organism. Despite its current industrial production is low, many of these substances are available on the market, and much more are in the production pipeline. As a result, many of them will end in aquatic systems raising the question whether they can pose a risk to aquatic biota and the associated ecological processes. Microbial decomposers of plant litter, play a key role in forested streams being responsible for the energy flow between terrestrial and aquatic environments. Here, we investigated the effects of SLNs on alder leaf litter decomposition by aquatic microbes. Alder leaves were immersed in a stream of Northeast Portugal to allow microbial colonization before being exposed in microcosms of two types of SLNs at two concentrations for 42 days. Results showed that rates of leaf decomposition decreased with exposure to SLNs. Bacterial biomass was not inhibited by SLNs, and cultivable fungi densities remained constant (SLN-A) or increased (SLN-C) compared with control microcosms. The type and concentration of SLNs influenced differently the leaf colonization by fungi as well as fungal sporulation rate. These effects were accompanied by changes in the community extraenzymatic profile: the activities of alkaline phosphatase, acidic phosphatase, Naphthol-AS-BI-phosphohydrolase (P cycle) and lipases increased in the SLNs microcosms. This study provided the first evidence of the adverse effects of the release of SLNs to streams on leaf litter decomposition. Those effects seem to depend on the composition and concentration of SLNs, as well on the microbial target group, or enzyme. Thus, prior to massive industrial production of these nanomaterials, some measures should be taken to avoid environmental impact affecting the microbial communities responsible for detritus decomposition.

A stratified analysis of the perioperative outcome of 17623 patients undergoing major head and neck cancer surgery in England over 10 years: Towards an Informatics-based Outcomes Surveillance Framework.

OBJECTIVES: To perform a national analysis of the perioperative outcome of major head and neck cancer surgery to develop a stratification strategy and outcomes assessment framework using hospital administrative data. DESIGN: A Hospital Episode Statistics N = near-all analysis. SETTINGS: The English National Health Service. MAIN OUTCOME MEASURES: Local audit data were used to assess and triangulate the quality of the administrative dataset. Within the national dataset, cancer sites, morbidities, social deprivation, treatment, complications, and in-hospital mortality were recorded. RESULTS: Within local audit datasets, the accuracy of assigning newly-derived Cancer Site Strata and Resection Strata were 92.3% and 94.2%, respectively. Accuracy of morbidities assignment was 97%. Within the national dataset, we identified 17 623 major head and neck cancer resections between 2002 and 2012. There were 12 413 males and mean age at surgery was 63 ± 12 years. The commonest cancer site strata were oral cavity (42%) and larynx-hypopharynx (32%). The commonest resection site was the larynx (n = 4217), and 13 211 and 11 841 patients had neck dissection and flap-based reconstruction, respectively. There were prognostically significant baseline differences between patients with oromandibular and pharyngolaryngeal malignancy. Patients with pharyngolaryngeal malignancies had a greater burden of morbidities, lower socio-economic status, fewer primary resections, and a sixfold increased risk of undergoing their major resection during an emergency hospital admission. Mean length of stay was 25 days and each complication linearly increased it by 9.6 days. There were 609 (3.5%) in-hospital deaths and a basket of seven medical and three surgical complications significantly increased the risk of in-hospital death. At least one potentially lethal complication occurred in 26% of patients. The risk of in-hospital death in a patient with no potentially lethal complication was 1.1% and this increased to 6% with one potentially lethal complication, and to 15.1% if two potentially lethal complications occurred in one patient. Complex oral-pharyngeal resections and pharyngolaryngectomies had the highest risks of complications and mortality. CONCLUSION: Mortality following head and neck cancer surgery shows variation across different resection strata. We propose an Informatics-based Framework for Outcomes Surveillance (IFOS) in Head and Neck Surgery for perpetual quality assurance, using the local hospital coding data or its collated destination, the national administrative dataset.

Oxidative stress in dairy cows naturally infected with the lungworm Dictyocaulus viviparus (Nematoda: Trichostrongyloidea).

The aim of this study was to analyse the oxidative and anti-oxidant status in serum samples from dairy cows naturally infected by Dictyocaulus viviparus and its relation with pathological analyses. The diagnosis of the disease was confirmed by necropsy of one dairy cow with heavy infection by the parasite in the lungs and bronchi. Later, blood and faeces were collected from another 22 cows from the same farm to measure reactive oxygen species (ROS) levels, thiobarbituric acid-reactive substances (TBARS), catalase (CAT) and superoxide dismutase (SOD) activities on day 0 (pre-treatment) and day 10 (post-treatment with eprinomectin). Faecal examination confirmed the infection in all lactating cows. However, the number of D. viviparus larvae per gram of faeces varied between animals. Cows showed different degrees of severity according to respiratory clinical signs of the disease (cough and nasal secretion). Further, they were classified and divided into two groups: those with mild (n = 10) and severe disease (n = 12). Increased levels of TBARS (P < 0.001), ROS (P = 0.002) and SOD activity (P < 0.001), as well as reduced CAT activity (P < 0.001) were observed in cows with severe clinical signs of the disease compared to those with mild clinical signs. Eprinomectin treatment (day 10) caused a reduction of ROS levels (P = 0.006) and SOD activity (P < 0.001), and an increase of CAT activity (P = 0.05) compared to day 0 (pre-treatment). TBARS levels did not differ with treatment (P = 0.11). In summary, increased ROS production and lipid peroxidation altered CAT and SOD activities, as an adaptive response against D. viviparus infection, contributing to the occurrence of oxidative stress and severity of the disease. Treatment with eprinomectin eliminated the infection, and thus minimized oxidative stress in dairy cows.