In-vitro study on type I collagen synthesis in low-level laser therapy on the early ligament fibroblasts' healing process.

BACKGROUND: Low-level Laser Therapy (LLLT) has demonstrated its potential in promoting fiber matrix maturation, collagen synthesis, and fibroblast proliferation, contributing to tissue regeneration. Our study aimed to investigate the impact of LLLT on collagen type I synthesis, cell proliferation, and viability in human ligament fibroblasts derived from the Anterior Cruciate Ligament (ACL). METHODS: Tissue samples were obtained from individuals undergoing arthroscopic ACL reconstruction surgery. Primary human fibroblasts were isolated, and immunohistochemical assays confirmed their characteristics. LLLT at 850 nm was administered in three groups: Low dose (1.0 J/cm²), High dose (5.0 J/cm²), and Control (0.0 J/cm²). Cell viability was calculated using a membrane integrity assay, proliferation was determined by automated counting, and collagen type I concentration in cell culture was measured using an immunoassay. RESULTS: Fibroblasts showed decreased viability after low and high doses of LLLT, increased proliferation at the low dose, and increased collagen synthesis at the high dose on day 10 for both sexes after treatment. CONCLUSION: Our study demonstrated that LLLT may improve the early ligament healing process by increasing cell proliferation at the low dose and enhancing collagen type I synthesis at the high dose in human ligament fibroblasts.

A new species of Trichobius (Diptera: Streblidae) from Mexico and new record of Paratrichobius americanus.

A new species of Trichobius Gervais, 1844 (Diptera: Streblidae) is described from specimens collected in Jalisco, Mexico, from host bat Choeronycteris mexicana Tschudi. We place the new species within the "dugesii" group, because it shares certain characteristics with Trichobius urodermae Wenzel, 1966 T. angulatus Wenzel, 1976 and T. tiptoni Wenzel, 1976. However, it is easy to differentiate from all known species due to the chaetotaxy of the thorax, in which the prescutal and lateral setae are very long, while the discal setae are abruptly smaller and denser. It also possesses the metasternal lobe, which is very broad and translucent. We found a male of Paratrichobius americanus Peterson & Ross, 1972 on the same host individual, which expands the distribution area of P. americanus into Mexico because the unique holotype was collected in Arizona.

Association between the cardiac contact distance and the maximum dose at the left anterior descending coronary artery in post mastectomized patients.

The clinical information on the relationship between the cardiac contact distance (CCD), the maximum dose (Dmax) delivered to the left anterior descending (LAD) coronary artery and the mean heart dose has mostly focused on patients with breast-conserving surgery (BCS), being scarce in postmastectomy patients. The aim of this study is to determine the association between the CCD and the Dmax delivered to the LAD. The secondary objective was to evaluate the dosimetric results of comparing three-dimensional conformal radiotherapy (3D-CRT) to intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques for post mastectomized breast cancer patients with irradiation to the left chest wall. 53 cases of women who received adjuvant standard fractionated postmastectomy radiotherapy (PMRT) were used. Three types of plans were created for each patient: 3D-CRT, seven equidistant IMRT fields, and four partial VMAT arcs. Correlations were evaluated using Pearson's correlation coefficient. Plans made with IMRT and VMAT showed improved homogeneity and conformity. Associations between CCD and Dmax to LAD were positive for all three plan types. Compared to 3D-CRT, the modulated intensity plans obtained better dose homogeneity and conformity to the target volume. The LAD and heart doses were significantly lower for IMRT and VMAT plans. The CCD can be used as a predictor of the maximum and mean doses of the LAD. Modulated intensity techniques allow for better dose distribution and dose reduction to the heart and LAD.

Synergy between pyroelectric and photovoltaic effects for optoelectronic nanoparticle manipulation.

The combined action of the pyroelectric (PY) and photovoltaic (PV) effects, exhibited by z-cut LiNbO3:Fe substrates, has been investigated for particle trapping and patterning applications. The novel hybrid procedure provides new possibilities and versatility to optoelectronic manipulation on LiNbO3 substrates. It has allowed obtaining periodic and arbitrary 2D patterns whose particle density distribution is correlated with the light intensity profile but can be tuned through ΔT according to the relative strength of the PV and PY effects. A relevant result is that the PY and PV contributions compete for a ΔT range of 1-20 °C, very accessible for experiments. Moreover, the synergy of the PY and PV has provided two additional remarkable applications: i) A method to measure the PV field, key magnitude for photovoltaic optoelectronic tweezers. Using this method, the minimum field needed to obtain a particle pattern has been determined, resulting relatively high, E~60 kV/cm, and so, requiring highly doped crystals when only using the PV effect. ii) An strategy combining the PY and PV to get particle patterning in samples inactive for PV trapping when the PV field value is under that threshold.

What to expect and when: benznidazole toxicity in chronic Chagas' disease treatment.

Background: Benznidazole is one of the two most effective antiparasitic drugs for Chagas' disease treatment. However, knowledge about its toxicity profile is mostly based on post-marketing observational studies. Objectives: Our study combines data from two prospective clinical trials designed to assess the safety of the drug newly produced by ELEA Laboratories (Abarax®). Methods: Eligible participants were selected using a consecutive sampling strategy in the CINEBENZ and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012-002645-38, respectively, and clinicaltrials.gov NCT01755403 and NCT01755377, respectively). Enrolled subjects received treatment with 5 mg/kg/day benznidazole orally in two divided doses for 8 weeks and were followed up fortnightly. Results: We observed 305 adverse reactions in 85 of 99 participants (85.9%). Each patient had a median of three adverse reactions, 89.5% were mild and the median duration was 12 days. Most adverse reactions appeared in the first month of treatment except arthritis and peripheral neuropathy. Twenty-six patients did not complete treatment: 2 were withdrawn, 1 for ectopic pregnancy and 1 for epilepsy relapse due to cysticercosis; 2 were lost to follow-up; and 22 were owing to adverse reactions, two of them severe. We observed some unexpected adverse reactions that have not been described previously, such as psychiatric symptoms, erectile dysfunction, menstrual cycle alterations and lung infiltration. Conclusions: There is a very high frequency of adverse reactions to benznidazole. Most adverse reactions are mild, but the treatment burden is significant and unexpected reactions are not rare. Severe reactions are uncommon, but they can be life-threatening. Further studies are necessary to optimize treatment.

Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis.

Objectives: The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK) of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages and to compare these with summary estimates for higher dosages. Methods: A systematic search was performed for studies of rifampicin PK published in the English language up to May 2017. Data describing the Cmax and AUC were extracted. Meta-analysis provided summary estimates for PK parameter estimates at standard rifampicin dosages. Heterogeneity was assessed by estimation of the I2 statistic and visual inspection of forest plots. Summary AUC estimates at standard and higher dosages were compared graphically and contextualized using preclinical pharmacodynamic (PD) data. Results: Substantial heterogeneity in PK parameters was evident and upheld in meta-regression. Treatment duration had a significant impact on the summary estimates for rifampicin PK parameters, with Cmax 8.98 mg/L (SEM 2.19) after a single dose and 5.79 mg/L (SEM 2.14) at steady-state dosing, and AUC 72.56 mg·h/L (SEM 2.60) and 38.73 mg·h/L (SEM 4.33) after single and steady-state dosing, respectively. Rifampicin dosages of at least 25 mg/kg are required to achieve plasma PK/PD targets defined in preclinical studies. Conclusions: Vast inter-study heterogeneity exists in rifampicin PK parameter estimates. This is not explained by the available modifying variables. The recommended dosage of rifampicin should be increased to improve efficacy. This study provides an important point of reference for understanding rifampicin PK at standard dosages as efforts to explore higher dosing strategies continue in this field.

Estrogen receptor-beta genetic variations and overall survival in patients with locally advanced gastric cancer.

Estrogen has been shown not only to reduce the incidence of colorectal cancer but also gastric cancer (GC). Polymorphisms in estrogen receptor ß gene, ESR2, correlate with colorectal cancer survival. To better understand the role of ESR2 in GC, genomic DNA extracted from 169 Japanese patients and 172 patients from Los Angeles County (LAC) was analyzed for association of overall survival (OS) with three ESR2 polymorphisms, which are of biological significance using multivariable Cox proportional hazard regression. ESR2 rs1271572 (C>A) and rs3020443 (T>G) had univariate and multivariable associations with OS in the Japanese cohort, whereas the C allele of ESR2 rs2978381 (T>C) predicted favorable OS in the Japanese cohort but worse OS in the LAC cohort. The interaction term of the ESR2 rs2978381 and cohort group reached statistical significance. Our study provides evidence that genetic variations in ESR2 gene are significantly associated with survival in patients with locally advanced GC.

Genetic variants associated with colorectal brain metastases susceptibility and survival.

Colorectal brain metastases (BM) are rare (1-2%) and a late-stage disease manifestation. Molecular mechanisms for BM development are not well understood. We tested whether variants within genes involved in overcoming the blood-brain barrier (BBB) are associated with BM susceptibility and survival in patients with BM. Germline single-nucleotide polymorphisms (SNPs, n=17) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed from germline DNA in patients with resected BM (n=70) or no clinical evidence of BM after at least 24 months from diagnosis (control group, n=45). SNPs were evaluated for association with BM susceptibility and overall survival (OS) from BM diagnosis. ST6GALNAC5 rs17368584 and ITGB3 rs3809865 were significantly associated with BM susceptibility. In multivariable analysis adjusted for patient characteristics, KLF4 rs2236599, ITGAV rs10171481, ST6GALNAC5 rs1883778, CXCR4 rs2680880 and ITGB3 rs5918 were significant for OS. This study shows for the first time that variants within genes involved in breaching the BBB are associated with BM susceptibility and survival. These findings warrant further validation to develop better screening guidelines and to identify novel therapy targets for patients with BM.

CXCR4 polymorphism predicts progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy.

We analyzed associations between CXCR4/CXCL12 single-nucleotide polymorphisms and outcomes in metastatic colorectal cancer (mCRC) patients who underwent first-line bevacizumab-based chemotherapy. A total of 874 patients were included in this study: 144 treated with bevacizumab and FOLFOX or XELOX (training cohort), 653 treated with bevacizumab and FOLFIRI or FOLFOXIRI (validation cohort A or B) and 77 treated with cetuximab- and oxaliplatin-based regimens (control cohort). One CXCR4 polymorphism (rs2228014) and two CXCL12 polymorphisms (rs1801157 and rs3740085) were analyzed by PCR-based direct sequencing. Patients with a C/C genotype had a prolonged progression-free survival (PFS) compared with those with any T allele (P=0.030) in the training cohort. Similarly, patients with the C/C genotype had a superior PFS in the validation cohorts, but not in the control cohort. Our findings suggest that a common genetic variant, CXCR4 rs2228014, could predict PFS and may guide therapeutic decisions in mCRC patients receiving first-line bevacizumab-based chemotherapy.

Effluent Disinfection of Real Wastewater by Ag­TiO2 Nanoparticles Photocatalysis.

Currently pathogen microorganisms, presents in wastewater, are more resistant to conventional disinfection process, due to its constant change induced for the antibiotic for human diseases. One of the new options for the pathogen microorganisms is the heterogeneous photocatalysis, which has been used for remove microorganism, but never in real wastewater effluent. This paper shown the synthesis of Ag­TiO2 nanoparticles, its physical characterization was carried out by TEM, SEM, S-BET, XPS and band gap measurement by UV-vis spectroscopy showing that Ag­TiO2 are spherical particles with sizes around 50 nm with 1 and 10 %w of Ag, and a significant decrease in the band gap. The disinfection system was illuminated using the solar radiation of a spring day at Querétaro, Mexico, in lapses from 11:00 am to 03:00 pm; the microbiological tests were performed according to the Official Mexican Norm (NOM-003-SEMARNAT-1996), the results shows that after 3 hours of solar photocatalysis disinfection process the material 1 %w Ag­TiO2 at 0.2 gL⁻¹, removes the fecal and total coliform microorganisms from effluent, leaving Enterobacter, Escherichia, Citrobacter, Salmonella and Klebsiella microorganisms alive due to its capability of reactivation.

Atypical Exciton-Phonon Interactions in WS2 and WSe2 Monolayers Revealed by Resonance Raman Spectroscopy.

Resonant Raman spectroscopy is a powerful tool for providing information about excitons and exciton-phonon coupling in two-dimensional materials. We present here resonant Raman experiments of single-layered WS2 and WSe2 using more than 25 laser lines. The Raman excitation profiles of both materials show unexpected differences. All Raman features of WS2 monolayers are enhanced by the first-optical excitations (with an asymmetric response for the spin-orbit related XA and XB excitons), whereas Raman bands of WSe2 are not enhanced at XA/B energies. Such an intriguing phenomenon is addressed by DFT calculations and by solving the Bethe-Salpeter equation. These two materials are very similar. They prefer the same crystal arrangement, and their electronic structure is akin, with comparable spin-orbit coupling. However, we reveal that WS2 and WSe2 exhibit quite different exciton-phonon interactions. In this sense, we demonstrate that the interaction between XC and XA excitons with phonons explains the different Raman responses of WS2 and WSe2, and the absence of Raman enhancement for the WSe2 modes at XA/B energies. These results reveal unusual exciton-phonon interactions and open new avenues for understanding the two-dimensional materials physics, where weak interactions play a key role coupling different degrees of freedom (spin, optic, and electronic).

High heterogeneity in soil composition and quality in different mangrove forests of Venezuela.

Mangrove forests play an important role in biogeochemical cycles of metals, nutrients, and C in coastal ecosystems. However, these functions could be strongly affected by the mangrove soil degradation. In this study, we performed an intensive sampling characterizing mangrove soils under different types of environment (lagoon/gulf) and vegetation (Rhizophora/Avicennia/dead mangrove) in the Venezuelan coast. To better understand the spatial heterogeneity of the composition and characteristics of the soils, a wide range of the soil attributes were analyzed. In general, the soils were anoxic (Eh < 200 mV), with a neutral pH and low concentration in toxic metals; nevertheless, they varied widely in the soil and its quality-defining parameters (e.g., clay contents, total organic carbon, Fe, Al, toxic trace metals). It is noteworthy that the mangroves presented a low FePyrite content due to a limitation in the Fe oxyhydroxide contents, especially in soils with higher organic C content (TOC > 15%). Finally, the dead mangrove showed significantly lower amounts of TOC and fibers (in comparison to the well-preserved mangrove forest), which indicates that the C pools in mangrove soils are highly sensitive also to natural impact, such as ENSO.

Evidence for Gamow-Teller Decay of

The ß-delayed neutron emission of ^{83,84}Ga isotopes was studied using the neutron time-of-flight technique. The measured neutron energy spectra showed emission from states at excitation energies high above the neutron separation energy and previously not observed in the ß decay of midmass nuclei. The large decay strength deduced from the observed intense neutron emission is a signature of Gamow-Teller transformation. This observation was interpreted as evidence for allowed ß decay to ^{78}Ni core-excited states in ^{83,84}Ge favored by shell effects. We developed shell model calculations in the proton fpg_{9/2} and neutron extended fpg_{9/2}+d_{5/2} valence space using realistic interactions that were used to understand measured ß-decay lifetimes. We conclude that enhanced, concentrated ß-decay strength for neutron-unbound states may be common for very neutron-rich nuclei. This leads to intense ß-delayed high-energy neutron and strong multineutron emission probabilities that in turn affect astrophysical nucleosynthesis models.

Arthritis and benznidazole: more closely related than we thought.

Chagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. Benznidazole is the most commonly used drug for the etiological treatment of Chagas disease. Patients treated with benznidazole suffer frequent adverse drug reactions. Although arthralgia is common, arthritis has been reported as a very rare side effect. The objective of this study was to describe arthritis in a cohort of Trypanosoma cruzi-infected patients treated with benznidazole.

Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials.

BACKGROUND: Tumor-associated macrophages (TAMs) with the M2-like phenotype are regulated by mainly NF-kB pathway including TBK1, which can influence tumor progression by secretion of proangiogenic factors such as vascular endothelial growth factor. The CCL2/CCR2 axis, histidine-rich glycoprotein (HRG), and placenta growth factor (PIGF) play a critical role in the polarization of M1/M2 phenotypes and the recruitment of TAMs to tumor microenvironment. We therefore hypothesized that variations in genes involved in regulating TAMs may predict clinical outcomes of bevacizumab treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We analyzed genomic DNA extracted from samples of patients receiving bevacizumab plus FOLFIRI as a first-line treatment using PCR-based direct sequencing. Twelve functional single-nucleotide polymorphisms in eight genes (CCL2, CCR2, HRG, PIGF, NFKB1, TBK1, CCL18, and IRF3) were tested for associations with clinical outcomes in a discovery cohort of 228 participants in TRIBE trial (NCT00719797), then validated in 248 KRAS exon2 (KRAS) wild-type participants in FIRE3 trial (NCT00433927). FIRE3-cetuximab cohort served as a negative control. RESULTS: TBK1 rs7486100 was significantly associated with overall survival in 95 KRAS wild-type patients of TRIBE cohort in univariate analysis and had a strong trend in multivariable analysis; furthermore, the association of the T allele was observed for progression-free survival (PFS) in both univariate and multivariable analyses in FIRE3-bevacizumab but not cetuximab cohort. CCL2 rs4586, CCL18 rs14304, and IRF3 rs2304205 had univariate and multivariable correlations with PFS in KRAS mutant patients of the TRIBE cohort, whereas they had no correlations in KRAS wild-type patients of the TRIBE cohort. No association was seen in control cohort. CONCLUSIONS: Our study demonstrates for the first time that variations in genes regulating TAMs-related functions are significantly associated with clinical outcomes in mCRC patients treated with bevacizumab-containing chemotherapy. These results also suggest that some TAM-related gene variations may predict outcomes of bevacizumab treatment in KRAS status-dependent manner.

Prevalence of strongyloidiasis in Latin America: a systematic review of the literature.

Strongyloides stercoralis is rarely recognized as a major public health issue, probably because its burden is largely underestimated. We reviewed the literature (both PubMed and 'grey' literature) about the prevalence of strongyloidiasis in Latin America, an area of presumable high endemicity. There were finally 88 papers involved in the analysis, covering the period between 1981 and 2011. Studies were heterogeneous in several aspects, such as the populations screened and the diagnostic methods used. Most of the studies relied on direct coproparasitological examination, which has low sensitivity for the detection of S. stercoralis larvae. The following countries presented areas of high prevalence (>20%): Argentina, Ecuador, Venezuela, Peru and Brazil. Globally, for most of the included countries it was not possible to define reliable data because of paucity and/or inadequacy of studies. S. stercoralis requires specific diagnostic methods for its detection; therefore, surveys should be specifically designed in order to avoid underestimation of the infection.

Clinical utility of third-trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in small-for-gestational-age fetuses.

OBJECTIVE: To assess the clinical value of third-trimester uterine artery (UtA) Doppler ultrasound in the prediction of hemodynamic deterioration and adverse perinatal outcome in term small-for-gestational-age (SGA) fetuses. METHODS: UtA Doppler parameters, cerebroplacental ratio (CPR) and fetal middle cerebral artery (MCA) pulsatility index (PI) were evaluated weekly, starting from the time of SGA diagnosis until 24 h before induction of labor, in a cohort of 327 SGA fetuses with normal umbilical artery PI (< 95th centile), delivered at > 37 weeks' gestation. Differences in the sequence of CPR and MCA-PI changes < 5th centile, between the group with normal UtA Doppler indices at diagnosis and those with abnormal UtA indices, were analyzed by survival analysis. In addition, the use of UtA Doppler value, alone or in combination with a brain Doppler scan before delivery, to predict the risk of Cesarean section, Cesarean section for non-reassuring fetal status (NRFS), neonatal acidosis and neonatal hospitalization was evaluated by logistic regression analysis, adjusted for gestational age at birth and birth-weight percentile. RESULTS: Abnormal UtA Doppler at diagnosis of SGA was associated with a higher risk of developing abnormal brain Doppler indices before induction of labor than in those with a normal UtA at diagnosis (62.7% vs 34.6%, respectively; P < 0.01). Compared to those with normal UtA Doppler indices, those with abnormal UtA Doppler findings were associated with a higher risk of intrapartum Cesarean section (52.2% vs 37.3%, respectively; P = 0.03), Cesarean section for NRFS (35.8% vs 23.1%, respectively; P = 0.03), neonatal acidosis (10.4% vs 7.7%, respectively; P = 0.47) and neonatal hospitalization (23.9% vs 16.5%, respectively; P = 0.16). Logistic regression analysis indicated that UtA Doppler findings were not significantly associated with adverse perinatal outcome independent of brain Doppler findings. CONCLUSION: UtA Doppler indices predict adverse perinatal outcome, but do not help to improve the predictive value of brain Doppler indices. However, at the time of SGA diagnosis they identify the subgroup of fetuses at highest risk of progression to abnormal brain Doppler findings.

First approach to characterize tilts through multiple pistons in the classical Ronchi test.

In this work, it is shown how a tilt can be introduced into a segmented surface through several piston terms, by using the classical Ronchi test. We have developed tilt error simulations by adding multiple constant terms to each point on the sagitta surface of a segment using ray tracing. Thereby a comparison between simulated Ronchigrams for piston and tilt has been performed for two adjacent segments, so that it is possible to appreciate the tilt and piston effects on the shape of the patterns. As a result, we show the behavior of the central maximum of the fringes in the presence of tilt and/or piston. Additionally we present evidence of introducing tilting without changing the surface shape by adding multiple pistons, and a description of how to characterize both piston and tilt using the Ronchi test.