Few-cycle Yb laser source at 20 kHz using multidimensional solitary states in hollow-core fibers.

We demonstrate ultrashort pulse compression from 300 fs down to 17 fs at a repetition rate of 20 kHz and 160-µJ output pulse energy (3.2 W of average power) using multidimensional solitary states (MDSS) in a 1-meter hollow-core fiber (HCF) filled with N2O. Under static pressure, thermal limitations at this repetition rate annihilate the MDSS with suppression of spectral broadening. The results obtained in differential pressure configuration mitigate thermal effects and significantly increase the range of repetition rate over which MDSS can be used to compress sub-picosecond laser pulses.

Molecular detection and identification of spotted fever group rickettsiae in ticks collected from horses in Cuba.

Spotted fever group (SFG) rickettsiae are obligatory intracellular bacteria that cause disease in humans and other animals. Ixodid ticks are the principal vectors of SFG rickettsiae. The present study aimed to determine the prevalence and species identity of SFG rickettsiae in ticks and horses from urban and rural areas of western Cuba using PCR assays. Tick samples, collected from 79 horses, consisted of 14 Amblyomma mixtum adults, 111 Dermacentor nitens adults and 19 pools of D. nitens nymphs (2-5 individuals/pool). The PCR results revealed the presence of Rickettsia spp. in 64% of the A. mixtum adults, 16% of the D. nitens adults, and 11% of the pooled samples of D. nitens nymphs. In contrast, Rickettsia spp. was not detected in any of the 200 horse blood samples included in this study. DNA sequence data of the rickettsial 17 kDa antigen gene showed that Rickettsia amblyommatis was present in A. mixtum; and Rickettsia felis in D. nitens. This is the first report of R. felis in D. nitens in Cuba. The present study extends our knowledge of the potential vector spectrum and distribution of SFG rickettsiae pathogens in western Cuba.

High energy redshifted and enhanced spectral broadening by molecular alignment.

We demonstrate an efficient approach for enhancing the spectral broadening of long laser pulses and for efficient frequency redshifting by exploiting the intrinsic temporal properties of molecular alignment inside a gas-filled hollow-core fiber (HCF). We find that laser-induced alignment with durations comparable to the characteristic rotational time scale TRotAlign enhances the efficiency of redshifted spectral broadening compared to noble gases. The applicability of this approach to Yb lasers with (few hundred femtoseconds) long pulse duration is illustrated, for which efficient broadening based on conventional Kerr nonlinearity is challenging to achieve. Furthermore, this approach proposes a practical solution for high energy broadband long-wavelength light sources, and it is attractive for many strong field applications.

High frequency of gram-negative bacilli harboring blaKPC-2 in the different stages of wastewater treatment plant: A successful mechanism of resistance to carbapenems outside the hospital settings.

Wastewater treatment plants (WWTPs) are considered to be a reservoir and a source of bacterial resistance. Worryingly, the presence of carbapenem-resistant Gram-negative bacilli (CRGNB) in WWTPs has recently been reported, but there are still many research gaps regarding its emergence and impact. The distribution of CRGNB in the different stages of a WWTP in Colombia and the relationship between the physicochemical factors involved with their presence are described in this paper. Additionally, given the impact on public health, the CRGNB detected were compared with isolates previously found in hospital patients. Residual water samples were taken from five different stages of a WWTP between January and July 2017. A total of 390 GNB were isolated, and a significant frequency of CRGNB harboring blaKPC-2 (38.2%, n = 149/390) was detected, of which 57% were Enterobacteriaceae, 41.6% Aeromonadaceae, and 1.3% Pseudomonadaceae. The Enterobacteriaceae were more frequent in the raw effluent compared to the Aeromonadaceae, which in turn were more prevalent in the recycled activated sludge and final effluent. Environmental variables such as pH, oxygen, chemical oxygen demand, and temperature were significantly correlated with the quantification of carbapenem-resistant Enterobacteriaceae (CRE) at specific points in the WWTP. Interestingly, isolated K. pneumoniae harboring blaKPC-2 from the WWTPs were diverse and did not relate genetically to the hospital strains with which they were compared. In conclusion, these results confirm the worrying scenario of the dissemination and persistence of emerging contaminants such as CRGNB harboring blaKPC-2, and reinforce the need to establish strategies aimed at containing this problem using multifocal interventions.

High clonal diversity of multidrug-resistant and extended spectrum beta-lactamase-producing Escherichia coli in a wastewater treatment plant.

Increasing beta-lactam resistance has led to the exploration of different places, such as wastewater treatment plants (WWTPs) which have been considered to be reservoirs and sources of bacterial resistance. This work aims to determine the presence of beta-lactamase-producing-Enterobacteriaceae in different points of a WWTP in Colombia. Six samplings were carried out in 2017 in the raw influent, aeration tanks, recycled sludge and final effluent of a WWTP. The beta-lactamase-producing-Enterobacteriaceae were detected and identified using phenotypic and molecular methods. Of the 353 isolates included, 28.3% corresponded to enterobacteria. The most frequent microorganisms were Escherichia coli (83%), Citrobacter freundii (11%) and Enterobacter cloacae complex (4%). The 97% of enterobacteriaceae had at least one beta-lactamase, and the most prevalent were the blaTEM (43.8%) and blaCTX-M-1group (35.8%) which were detected specially in recycled sludge and final effluent sample points. High percentage of multidrug resistance (to beta-lactams and non-beta-lactam antibiotics) was detected in E. coli (63.2%). Additionally, the typing by PFGE and MLST showed high genotypic diversity and the presence of the successful ST131 clone, globally spread. This work highlights the strong role of E. coli as a vector for the dissemination of resistance and the beta-lactamases in aquatic environments.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Serious fungal infections in Ecuador.

There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (<200 CD4 cell counts) is ∼10,000, with a rate of 11.1% (1100) of histoplasma, 7% (700) of cryptococcal meningitis, and 11% (1070) of Pneumocystis pneumonia. The burden of candidemia is 1037. Recurrent Candida vaginitis (≥4 episodes per year) affects 307,593 women aged 15-50 years. Chronic pulmonary aspergillosis probably affects ∼476 patients following tuberculosis (TB). Invasive aspergillosis is estimated to affect 748 patients (∼5.5/100,000). In addition, allergic bronchopulmonary aspergillosis (ABPA) in asthma and severe asthma with fungal sensitization (SAFS) were estimated to affect 26,642 and 45,013 people, respectively. Our estimates indicate that 433,856 (3%) of the population in Ecuador is affected by serious fungal infection.

Predictive score of haematological toxicity in patients treated with linezolid.

OBJECTIVE: The aims of our study were to determine the factors associated with developing haematological toxicity (HT) in patients taking linezolid (LZD), to develop a predictive model of HT in these patients, and to evaluate factors associated with 30-day mortality. METHODS: This was an observational retrospective cohort study of patients treated for at least 5 days with LDZ in 2015. Demographic, clinical and analytical data were collected. Development of HT was defined as a 25% platelet count decrease between the basal count and the 1-week lab test. RESULTS: Five hundred forty-nine patients were finally included, mean age was 73.3 (SD 15.4) years, and 303 (55.2%) were men. One hundred seventy-five (30.1%) patients achieved HT criteria during treatment with LZD and 41 (7.5%) died. The final model included the presence of cerebrovascular disease (2 points), moderate or severe liver disease (2 points), renal failure (2 points) and basal platelet count less than 90,000/mm3 (8 points). This new model showed an AUC of 0.711 (IC 95% 0.664-0.757; p < 0.001) to predict the development of HT. The probability of HT based on this classification was 6.2, 29.9 and 76.5% for low (0-4 points), intermediate (5-10 points) and high risk (>10 points), respectively. The independent variables associated with 30-day mortality were metastatic solid tumor, lymphoma, age >75 years and HT. CONCLUSION: This score could help in the identification of patients with high risk for HT and assess the use of an antibiotic other than LZD, an important issue considering its relation with 30-day mortality observed in our study.

Antifungal activity of tyrosol and farnesol used in combination against Candida species in the planktonic state or forming biofilms.

AIM: This study examined the antifungal activity of the combination of tyrosol and farnesol against Candida albicans and Candida glabrata in the planktonic state or forming biofilms. METHODS AND RESULTS: The effect of drug association against Candida planktonic cells was assessed by the fractional inhibitory concentration index. Mono- and dual-species biofilms were developed during 24 h and then treated with the compounds for 3 days, with two daily treatments of 1 min each. After, the total biomass, metabolic activity and the number of cultivable cells were quantified. Planktonic cells of the two species showed a similar susceptibility to the drug combination, however, a synergistic effect was only verified for C. glabrata. Regarding biofilm susceptibility, significant reductions in C. glabrata biomass, metabolism of C. albicans and mixed biofilms, and cultivable cells of single biofilms were verified for the drug combination, indicating an additive effect. For all other experiments, the effects were classified as indifferent. CONCLUSION: The combined use of tyrosol and farnesol was advantageous for some of the analysed parameters against Candida species. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings may contribute to the development of oral care products containing tyrosol and farnesol to combat oral infections caused by Candida species.

Differential effects of the combination of tyrosol with chlorhexidine gluconate on oral biofilms.

OBJECTIVE: This study assessed the effect of tyrosol and chlorhexidine gluconate in combination against Candida albicans, Candida glabrata, and Streptococcus mutans in the planktonic state or forming biofilms in vitro. MATERIALS AND METHODS: Checkerboard assays were performed for determination of minimum inhibitory concentration. Biofilms were cultivated during 24 h on specimens of acrylic resin and hydroxyapatite and treated with the drugs alone or in combination twice a day for 1 min, during 3 days. The antibiofilm effect was determined by quantification of the metabolic activity and cultivable cells. The drug combination was also applied on C. albicans to investigate its action on the number of hyphae. Data were statistically examined by two-way ANOVA and Holm-Sidak test (P < 0.05). RESULTS: The effect of drug combination on planktonic cells was classified as antagonistic for C. albicans and indifferent for the other strains. Also, the drugs were ineffective against the tested biofilms. However, the drug combination showed a synergistic effect in reducing the number of hyphae by C. albicans. CONCLUSION: The combination of tyrosol with chlorhexidine gluconate was only effective in reducing the number of hyphae by C. albicans, a relevant virulence factor of this species.

Activity of tyrosol against single and mixed-species oral biofilms.

AIM: This study aimed to evaluate the effect of tyrosol on the formation of single and mixed biofilms of Candida albicans ATCC 10231, Candida glabrata ATCC 90030 and Streptococcus mutans ATCC 25175 formed on acrylic resin (AR) and hydroxyapatite (HA) surfaces. METHODS AND RESULTS: Single and mixed biofilms were formed on AR and HA in the presence of tyrosol at 50, 100 and 200 mmol l(-1), during 48 h. Next, antimicrobial activity was assessed through metabolic activity (XTT reduction assay) and the number of colony-forming units (CFUs). Scanning electron microscopy observations were performed in order to analyse biofilm structure. Tyrosol, mainly at 200 mmol l(-1), significantly decreased the metabolic activity and number of CFUs for all single and mixed-species biofilms formed on both surfaces. SEM images suggested cell damage caused by tyrosol. CONCLUSION: Tyrosol showed inhibitory effects against biofilms formed by important oral pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study showing the antibiofilm effect of tyrosol on Candida species and Strep. mutans in single and mixed cultures. These results may be useful in the development of topical therapies focused on preventing biofilm-associated oral diseases, such as denture stomatitis and dental caries.

Evaluation of efficacy and safety of conjugated estrogens/bazedoxifene in a Latin American population.

Introduction Conjugated estrogens/bazedoxifene (CE/BZA) relieves menopausal symptoms and increases bone mineral density (BMD). Objective To evaluate CE/BZA in a Latin American subpopulation from randomized, double-blind, phase-3, multinational trials. Methods Safety data were pooled from three trials from non-hysterectomized postmenopausal Latin American women assigned to CE 0.45 mg/BZA 20 mg (n = 227), CE 0.625 mg/BZA 20 mg (n = 222), or placebo (n = 193). Efficacy outcomes from one study included changes in hot flush frequency at week 12 in women with at least seven moderate/severe hot flushes/day or 50/week at baseline (n = 39), and from baseline to month 12 for BMD (n = 381) and genitourinary syndrome of menopause (GSM) (women with baseline GSM; n = 189). Results At week 12, women taking CE/BZA had four to five fewer moderate/severe hot flushes/day vs. placebo. At month 12, percentage changes in BMD with CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, and placebo were 1.2%, 1.6%, and -1.1% for lumbar spine and 1.1%, 1.2%, and -0.3% for total hip. GSM improved with treatment (percentage superficial cells: 4.5, 7.4, vs. 2.0; percentage parabasal cells: -9.3, -27.8 vs. 2.8). There were no new/unexpected safety trends. Conclusion CE/BZA improved vasomotor symptoms, GSM, and BMD in Latin American women, with efficacy/safety similar to the global population.

Impact of regulatory measures on antipsychotics drug consumption in Castilla y León, Spain.

OBJECTIVES: Antipsychotics are currently used to treat different diseases; even some off-labelled conditions are treated with this medication. Consumption and cost of antipsychotic drugs sharply increased in Spain after second-generation drugs were marketed; several regulatory measures were adopted to curb this trend. The aim of this study was to examine the impact of these measures upon the use and cost of antipsychotics. STUDY DESIGN: Study of drug use (SDU) from 1995 to 2012. Consumption and cost data were obtained from the CONCYLIA database; this database contains the retail community pharmacies sales of medicinal products reimbursed by the National Health System in Castilla y León (Spain). METHODS: Data are presented as defined daily doses per 1000 inhabitants per day (DID) and day treatment cost (DTC). RESULTS: First-generation antipsychotics prescriptions gradually decreased from 3.0 to 1.8 DID; meanwhile, prescriptions for second-generation antipsychotics considerably increased from 0.3 to 9.9 DID. The use of risperidone dropped after the marketing of its structural derivative paliperidone with a similar efficacy but with a substantially higher cost per day. In 2011 and thereafter, patients in Spain began to pay a part of the medications cost, but this did not decrease antipsychotics consumption. Global cost of antipsychotics only began to fall after measures were adopted to lower the price of medicines because of the economic collapse in Spain after May 2010. CONCLUSION: Several health policy measures have tried to reduce antipsychotics consumption in Spain, special ways of dispensing, marketing of generic drugs and special economic measures for patients. These measures eventually failed to avoid the increase in antipsychotics use. The cost only dropped when lowering prescription drug prices took place.

Resolving clinical diagnoses for syndromic cleft lip and/or palate phenotypes using whole-exome sequencing.

Individuals from three families ascertained in Bogota, Colombia, showing syndromic phenotypes, including cleft lip and/or palate, were exome-sequenced. In each case, sequencing revealed the underlying causal variation confirming or establishing diagnoses. The findings include very rare and novel variants providing insights into genotype and phenotype relationships. These include the molecular diagnosis of an individual with Nager syndrome and a family exhibiting an atypical incontinentia pigmenti phenotype with a missense mutation in IKBKG. IKBKG mutations are typically associated with preterm male death, but this variant is associated with survival for 8-15 days. The third family exhibits unusual phenotypic features and the proband received a provisional diagnosis of Pierre Robin sequence (PRS). Affected individuals share a novel deleterious mutation in IRF6. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndrome and contribute to nonsyndromic cleft lip phenotypes but have not previously been associated with a PRS phenotype. Exome sequencing followed by in silico screening to identify candidate causal variant(s), and functional assay in some cases offers a powerful route to establishing molecular diagnoses. This approach is invaluable for conditions showing phenotypic and/or genetic heterogeneity including cleft lip and/or palate phenotypes where many underlying causal genes have not been identified.

First reported long-term two- and three-dimensional echocardiographic follow-up with histopathological analysis of a transcatheter pulmonary valve implantation in a pet dog.

Transcatheter pulmonary valve implantation (TPVI) is indicated for use in the management of failing pulmonary valves in humans. We report here the long-term follow-up of the first documented transcatheter pulmonary valve implanted in a client-owned dog. A one-year-old Beagle dog with severe congenital type A valvular pulmonic stenosis first underwent percutaneous balloon pulmonary valvuloplasty, leading two years later to severe pulmonary regurgitation. A TPVI using a Melody™ bioprosthetic valve was then successfully performed, with normalization of the right heart cavities. Repeated two- and three-dimensional transthoracic echocardiographic examinations combined with Doppler modes confirmed the appropriate position and function of the valve for four years. Mitral myxomatous valvular degeneration led to refractory left-sided congestive heart failure, and the dog was humanely euthanized. After postmortem examination, X-ray imaging and histopathological evaluation of the stent and the valve were performed. Ex-vivo imaging of the implanted valve using a Faxitron® Path radiography system and microscopic evaluation of the implanted stent and bioprosthetic leaflets did not show any relevant leaflet or stent alterations. This case provides a proof of concept in interventional veterinary cardiology, showing that TPVI can be performed in dogs with subsequent long-term maintaining normal pulmonary valve function.

Hip fracture rates and bisphosphonate consumption in Spain. An ecologic study.

INTRODUCTION: Bisphosphonates are used worldwide to treat osteoporosis and, thus, to prevent fractures. Though they have been proven in clinical trials to avoid some fractures, their effectiveness in reducing hip fractures is unclear. The aim of the present study was to explore the relationship between bisphosphonate use and hip fracture trends in Spain. METHODS: For this purpose, an ecologic study spanning 2002 to 2008 was conducted in Spain. Consumption data were obtained from the Spanish Ministry of Health and Social Policy. The number of hip fractures was obtained from hospital discharges; annual hip fracture rates were determined and standardized using the Spanish 2002 population census. A linear regression was performed between fracture rate and use of bisphosphonates; R(2) and Pearson correlation coefficient were calculated. RESULTS: From 2002 to 2008, dispensed prescriptions of bisphosphonates in Spain increased from 3.28 to 17.66 DDD/1,000 inhabitants per day. In the same period, the crude hip fracture rate increased from 2.85 to 3.02 cases per 1,000 inhabitants older than 50 years; however, when age standardized rates were estimated, the rate declined from 2.85 to 2.79. Analyzed by sex, the standardized rate for men slightly increased from 1.45 to 1.48, while for women the rate significantly dropped from 4.00 to 3.91. CONCLUSION: A small effect of bisphosphonates on hip fracture rates can not be ruled out; however, other factors might partially explain this decline. Assuming this medication was the only cause for hip fracture rate reduction, the elevated medication cost to avoid a single hip fracture makes it necessary to explore less expensive interventions.

Real-time electrical impedance-based measurement to distinguish oral cancer cells and non-cancer oral epithelial cells.

In this study, electrical impedance-based measurements were used to distinguish oral cancer cells and non-cancer oral epithelial cells based on their cellular activities on the microelectrodes in a real-time and label-free manner. CAL 27 and Het-1A cell lines were used as the models of oral cancer cells and non-cancer oral epithelial cells, respectively. Various cellular activities, including cell adhesion, spreading, and proliferation were monitored. We found that both the kinetics of cell spreading and the static impedance-based cell index were feasible to distinguish the two cell types. At each given cell number, CAL 27 cell spreading produced a smaller cell index change rate that was 60-70% of those of Het-1A cells. When cells were fully spread, CAL 27 cells generated a cell index more than four times greater than that of Het-1A cells. Since cell spreading and attachment occurs in the first few hours when they were cultured on the microelectrodes, this impedance-based method could be a rapid label-free and non-invasive approach to distinguish oral cancer cells from non-cancer oral epithelial cells. Cell viability analysis was performed along with the impedance-based analysis. Confocal microscopic imaging analysis showed the difference in cell morphology and the thickness of cell monolayers between the two cell types.