Role of EGFL7 in human cancers: A review.

EGFL7 is a proangiogenic factor. It has been widely described with having a vital role in tubulogenesis and regulation of angiogenesis, mainly during embryogenesis and organogenesis. It has been mainly associated with NOTCH pathway, but there are reports showing association with MAPK and integrin pathways. Given its association with angiogenesis and these other pathways, there are several studies associating EGFL7 with carcinogenesis. In fact, most of the studies have pointed to EGFL7 as an oncogene, and some of them suggest EGFL7 expression as a possible biomarker of prognosis or use for a patient's follow-up. Here, we review the molecular pathways which EGFL7 is associated and highlight several studies describing the role of EGFL7 in tumorigenesis, separated by tumor type. Besides its role on angiogenesis, EGFL7 may act in other pathways as oncogene, which makes it a possible biomarker and a candidate to targeted therapy.

Evaluation of a graphitic porous carbon modified with iron oxides for atrazine environmental remediation in water by adsorption.

In the last decades, the growth of world agricultural activity has significantly contributed to the increased presence of emerging pollutants such as atrazine (ATZ) in aquatic ecosystems. Due to its high stability to the natural or artificial degradation processes, the ATZ environmental remediation by adsorption has been investigated. In this study, a graphitic-porous-carbon- (GPC) based material with magnetic domains was applied to remove ATZ from aqueous solution. ATZ high adsorption efficiency in a reduced time was achieved in the presence of the GPC adsorbent, leading to a detailed investigation of the mechanisms involved in the adsorption processes. Pseudo-first-order (PFO), pseudo-second-order (PSO), Ritchie, Elovich, and Weber-Morris models were applied to calculate the kinetic process efficiency. Likewise, adsorption isotherms based on Langmuir, Freundlich, Temkin, and Redlich-Peterson models were applied for a detailed understanding of the adsorption mechanisms. GPC was successfully applied for ATZ remediation in natural waters, confirming its high potential for treating natural waters contaminated by ATZ using adsorption process. The material can also be recovered and reused for up to 4 application cycles due to its magnetic properties, showing that in addition to ATZ adsorption efficiency, its sustainable use can be achieved.

The coexistence of obesogenic behaviors among Brazilian adolescents and their associated factors.

BACKGROUND: The prevalence of obesity in adolescents has increased significantly in recent years. The growth of obesity is motivated by the association with modifiable behaviors, however, this behavioral are commonly evaluated individually, not considering the possibility of these factors coexisting in the individual. The purpose of this essay was to identify the coexistence of obesogenic behaviors among Brazilian adolescents and to assess the factors associated with the presence of these behaviors. METHODS: This a cross-sectional, national, school-based study with data from the Study of Cardiovascular Risks in Adolescents (ERICA), totaling a sample of 71,552 Brazilian adolescents. To identify the coexistence of obesogenic behaviors in adolescents, the Principal Component Analysis has been performed. To assess the association between factors that influence the coexistence of modifiable behaviors in the pattern of obesogenic behavior, logistic regression was used. The magnitude of the associations was estimated by the Odds Ratio (OR), with the respective 95% confidence intervals (95%CI). RESULTS: The component was characterized by a higher percentage of ultra-processed food intake, longer in front of screens, having a habit of snacking in front of the television, and not having the habit of eating breakfast. In the adjusted logistic model, it shows that female adolescents and who declare themselves black are more likely to belong to the third tertile of the pattern of obesogenic behavior. As for teenagers who sometimes or almost always or always have lunch or dinner with parents or guardians, who have longer hours of sleep and who live in economically disadvantaged regions have reduced chances of belonging to the third tertile of the pattern of obesogenic behavior. CONCLUSION: The identification of obesogenic behavior patterns allows assertive interventions to eliminate or reduce these changeable behaviors, also aiming at the possibility of reducing obesity among adolescents.

Evaluation of the prognostic potential of EGFL7 in pilocytic astrocytomas.

Pilocytic astrocytoma (PA) is the most frequent solid neoplasm in childhood. It has a good 5-year overall survival (90% in childhood and 52% in adults). However, up to 20% of patients experience residual tumor growth, recurrence, and death. Although the main genetic alteration of PAs, including KIAA1549:BRAF fusion, involves chromosome 7q34, we previously found frequent loss in chr9q34.3 locus in a small subset of these tumors. Among the genes present in this locus, EGFL7 is related to poor prognosis in several tumor types. In this study, we aimed to assess EGFL7 expression through immunohistochemistry, and to evaluate its prognostic value in a series of 64 clinically and molecularly well-characterized pilocytic astrocytomas. We found high expression of EGFL7 in 71.9% of patients. Low EGFL7 expression was associated with older patients, the mean age mainly older than 11 years (P = 0.027). EGFL7 expression was not associated with presence of KIAA1549:BRAF fusion, BRAF mutation, FGFR1 mutation, nor FGFR1 duplication. Moreover, high EGFL7 expression was associated with high FGFR1 (P = 0.037) and 5'-deoxy-5'-methyltioadenosine phosphorylase (MTAP) (P = 0.005) expression, and with unfavorable outcome of patients (P = 0.047). Multivariate analysis revealed low EGFL7 expression related to older patients and high EGFL7 expression related to retained expression of MTAP. In addition, we found a borderline significance of unfavorable outcome and high EGFL7 expression. Finally, EGFL7 expression was not associated with overall or event-free survival of PA patients. Our findings point to EGFL7 expression as a novel candidate prognostic marker in PA, which should be further investigated.

Increasing salinity concentrations determine the long-term participation of methanogenesis and sulfidogenesis in the biodigestion of sulfate-rich wastewater.

The competition between sulfate-reducing bacteria (SRB) and methanogenic archaea (MA) depends on several factors, such as the COD/SO42- ratio, sensitivity to inhibitors and even the length of the operating period in reactors. Among the inhibitors, salinity, a characteristic common to diverse types of industrial effluents, can act as an important factor. This work aimed to evaluate the long-term participation of sulfidogenesis and methanogenesis in the sulfate-rich wastewater process (COD/SO42- = 1.6) in an anaerobic structured-bed reactor (AnSTBR) using sludge not adapted to salinity. The AnSTBR was operated for 580 d under mesophilic temperature (30 °C). Salinity levels were gradually increased from 1.7 to 50 g-NaCl L-1. Up to 35 g-NaCl L-1, MA and SRB equally participated in COD conversion, with a slight predominance of the latter (53 ± 11%). A decrease in COD removal efficiency associated with acetate accumulation was further observed when applying 50 g-NaCl L-1. The sulfidogenic pathway corresponded to 62 ± 17% in this case, indicating the inhibition of MA. Overall, sulfidogenic activity was less sensitive (25%-inhibition) to high salinity levels compared to methanogenesis (100%-inhibition considering the methane yield). The wide spectrum of SRB populations at different salinity levels, namely, the prevalence of Desulfovibrio sp. up to 35 g-NaCl L-1 and the additional participation of the genera Desulfobacca, Desulfatirhabdium, and Desulfotomaculum at 50 g-NaCl-1 explain such patterns. Conversely, the persistence of Methanosaeta genus was not sufficient to sustain methane production. Hence, exploiting SRB populations is imperative to anaerobically remediating saline wastewaters.

Multimodal Transgastric Local Pancreatic Hypothermia Reduces Severity of Acute Pancreatitis in Rats and Increases Survival.

BACKGROUND & AIMS: Acute pancreatitis (AP) of different etiologies is associated with the activation of different signaling pathways in pancreatic cells, posing challenges to the development of targeted therapies. We investigated whether local pancreatic hypothermia, without systemic hypothermia, could lessen the severity of AP induced by different methods in rats. METHODS: A urethane balloon with 2 polyurethane tubes was placed inside the stomach of rats. AP was induced in Wistar rats by the administration of cerulein or glyceryl tri-linoleate (GTL). Then, cold water was infused into the balloon to cool the pancreas. Pancreatic temperatures were selected based on those found to decrease acinar cell injury. An un-perfused balloon was used as a control. Pancreatic and rectal temperatures were monitored, and an infrared lamp or heating pad was used to avoid generalized hypothermia. We collected blood, pancreas, kidney, and lung tissues and analyzed them by histology, immunofluorescence, immunoblot, cytokine and chemokine magnetic bead, and DNA damage assays. The effect of hypothermia on signaling pathways initiated by cerulein and GTL was studied in acinar cells. RESULTS: Rats with pancreatic cooling developed less severe GTL-induced AP compared with rats that received the control balloon. In acinar cells, cooling decreased the lipolysis induced by GTL, increased the micellar form of its fatty acid, lowered the increase in cytosolic calcium, prevented the loss of mitochondrial membrane potential (by 70%-80%), and resulted in a 40%-50% decrease in the uptake of a fatty acid tracer. In rats with AP, cooling decreased pancreatic necrosis by 48%, decreased serum levels of cytokines and markers of cell damage, and decreased markers of lung and renal damage. Pancreatic cooling increased the proportions of rats surviving 6 hours after induction of AP (to 90%, from <10% of rats that received the control balloon). In rats with cerulein-induced AP, pancreatic cooling decreased pancreatic markers of apoptosis and inflammation. CONCLUSIONS: In rats with AP, transgastric local pancreatic hypothermia decreases pancreatic necrosis, apoptosis, inflammation, and markers of pancreatitis severity and increases survival.

Carboxyl Ester Lipase May Not Mediate Lipotoxic Injury during Severe Acute Pancreatitis.

Acute lipolysis of visceral fat or circulating triglycerides may worsen acute pancreatitis (AP)-associated local and systemic injury. The pancreas expresses pancreatic triacylglycerol lipase (PNLIP), pancreatic lipase-related protein 2 (PNLIPRP2), and carboxyl ester lipase (CEL), which may leak into the visceral fat or systemic circulation during pancreatitis. We, thus, aimed to determine the pancreatic lipase(s) regulating lipotoxicity during AP. For this AP, associated fat necrosis was analyzed using Western blot analysis. Bile acid (using liquid chromatography-tandem mass spectrometry) and fatty acid (using gas chromatography) concentrations were measured in human fat necrosis. The fat necrosis milieu was simulated in vitro using glyceryl trilinoleate because linoleic acid is increased in fat necrosis. Bile acid requirements to effectively hydrolyze glyceryl trilinoleate were studied using exogenous or overexpressed lipases. The renal cell line (HEK 293) was used to study lipotoxic injury. Because dual pancreatic lipase knockouts are lethal, exocrine parotid acini lacking lipases were used to verify the results. PNLIP, PNLIPRP2, and CEL were increased in fat necrosis. Although PNLIP and PNLIPRP2 were equipotent in inducing lipolysis and lipotoxic injury, CEL required bile acid concentrations higher than in human fat necrosis. The high bile acid requirements for effective lipolysis make CEL an unlikely mediator of lipotoxic injury in AP. It remains to be explored whether PNLIP or PNLIPRP2 worsens AP severity in vivo.

Identification of research priorities in infertility and assisted reproduction: an international, multicentre study.

RESEARCH QUESTION: What are the main research interests among patients of assisted reproductive technologies (ART)? DESIGN: Cross-sectional study consisting of an anonymous online survey sent to 2112 patients from eight centres in four countries in 2018. Patients were asked to identify research questions relevant to them in the field of infertility and ART. Answers were categorized into topics and ranked by frequency. A long list of the top 30 research topics was extracted from the aggregate results, from which a short list of the top 10 research topics was created. Ten research questions were finally formulated. RESULTS: A total of 945 responses were analysed. Main interests were side-effects, success rates, infertility prevention and emotional support. The 10 research questions were: 1. What are the side-effects of drugs used in ART treatments? (51.6%). 2. What are the most effective methods to cope with infertility from the psychological point of view? (35.7%). 3. What effects could diet have on fertility? (25.9%). 4. What are ART success rates per clinical profile? (24.8%). 5. Are there some habits and lifestyle factors that could prevent infertility? (20.0%). 6. What are the long-term risks associated with ART in mother and child? (18.5%). 7. Are alternative therapies such as acupuncture, yoga and meditation effective to treat/prevent infertility? (18.5%). 8. What is the impact of exercise on fertility? (15.4%). 9. How does oocyte quantity and quality affect fertility? (9.5%). 10. What are the genetic patterns or hereditary conditions causing/related to infertility? (9.5%). CONCLUSIONS: Researchers and clinicians should keep in mind that, in addition to success rates and safety, patients greatly value research into causes, prevention and emotional aspects of infertility.

Differential liver histopathological responses to amphibian chytrid infection.

Amphibians have been facing a pandemic caused by the deadly fungus Batrachochytrium dendrobatidis (Bd). Although studies have elucidated cutaneous and homeostatic disturbances, it is still unknown if the hepatic function can be affected or if hepatic effects differ among host species. Thus, we evaluated the effects of an experimental Bd infection on the liver (histopathology and the hepatosomatic index) of 2 anuran species (Xenopus laevis and Physalaemus albonotatus) with different susceptibilities to Bd infection and compared them to uninfected controls. Bd infection increased the melanomacrophage cell area and induced leukocyte infiltration in both species. The effects were more pronounced in the sensitive species, P. albonotatus, which showed severe reduction in glycogen stores and liver atrophy, due to energetic imbalance. Hepatocytes of P. albonotatus also showed ballooning degeneration (vacuolization), which could lead to cell death and liver failure. Our results provide evidence that although the sensitive species showed more severe effects, the tolerant species also had hepatic responses to the infection. These findings indicate that hepatic function can play an important role in detoxification and in immune responses to chytridiomycosis, and that it may be used as a new biomarker of health status in chytrid infections.

Influence of functional variants Asp312Asn and Lys751Gln of Xeroderma Pigmentosum Group D (XPD) and Glutathione S-transferase Mu 1 (GSTM1) and Theta 1 (GSTT1) genes on cutaneous melanoma susceptibility and prognosis.

We aimed to evaluate whether variants in repair (XPD Asp312Asn, XPD Lys751Gln) and detoxification (GSTM1, GSTT1) genes alter risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Genotyping was performed in 229 CM patients and 258 controls. Individuals with XPD 312Asp/Asn or Asn/Asn plus GSTT1 null genotype were under 2.00 (95% CI: 1.06-3.79), and XPD 312Asn/Gln haplotype was under 1.44-fold (95% CI: 0.99-2.08) increased risks to CM than others. Individuals with GSTM1 plus GSTT1 null genotype had 9.61-fold (95% CI: 2.28-40.38) increased risk of metastatic CM. At 60 months of follow-up, patients with XPD 751Gln/Gln plus GSTT1 null and GSTM1 null plus GSTT1 null genotype presented 7.36 and 3.05 more chances of evolving to death in multivariate Cox analysis, respectively. In conclusion, our data indicate, for the first time, that specific variant combinations of XPD, GSTM1 and GSTT1 may increase susceptibility to CM and influence patients' clinicopathological features and survival.

Differences in bacterial composition between men's and women's restrooms and other common areas within a public building.

Humans distribute a wide range of microorganisms around building interiors, and some of these are potentially pathogenic. Recent research established that humans are the main drivers of the indoor microbiome and up to now significant literature has been produced about this topic. Here we analyzed differences in bacterial composition between men's and women's restrooms and other common areas within the same public building. Bacterial DNA samples were collected from restrooms and halls of a three-floor building from the Federal University of Pampa, RS, Brazil. The bacterial community was characterized by amplification of the V4 region of the 16S rRNA gene and sequencing. Throughout all samples, the most abundant phylum was Proteobacteria, followed by Actinobacteria, Bacteroidetes and Firmicutes. Beta diversity metrics showed that the structure of the bacterial communities were different among the areas and floors tested, however, only 6-9% of the variation in bacterial communities was explained by the area and floors sampled. A few microorganisms showed significantly differential abundance between men's and women's restrooms, but in general, the bacterial communities from both places were very similar. Finally, significant differences among the microbial community profile from different floors were reported, suggesting that the type of use and occupant demographic within the building may directly influence bacterial dispersion and establishment.

Cardiac biomarkers as sensitive tools to evaluate the impact of xenobiotics on amphibians: the effects of anionic surfactant linear alkylbenzene sulfonate (LAS).

Amphibian populations have been experiencing a drastic decline worldwide. Aquatic contaminants are among the main factors responsible for this decline, especially in the aquatic environment. The linear alkylbenzene sulfonate (LAS) is of particular concern, since it represents 84% of the anionic surfactants' trade. In Brazil, the maximal LAS concentration allowed in fresh waters is 0.5mgL-1, but its potential harmful effects in amphibians remain unknown. Therefore, this study aimed to analyze the effects of a sublethal concentration of LAS (0.5mgL-1) for 96h on sensitive cardiac biomarkers of bullfrog tadpoles, Lithobates catesbeianus (Shaw, 1802). For this, we measured the activity level (AL - % of animals), in situ heart rate (fH - bpm), relative ventricular mass (RVM - % of body mass), in vitro myocardial contractility and cardiac histology of the ventricles. Tadpoles' AL and fH decreased in LAS group. In contrast, the RVM increased, as a result of a hypertrophy of the myocardium, which was corroborated by the enlargement of the nuclear measures and the increase of myocytes' diameters. These cellular effects resulted in an elevation of the in vitro contractile force of ventricle strips. Acceleration in the contraction (TPT - ms) also occurred, although no alterations in the time to relaxation (THR -ms) were observed. Therefore, it can be concluded that even when exposed to an environmentally safe concentration, this surfactant promotes several alterations in the cardiac function of bullfrog tadpoles that can impair their development, making them more susceptible to predators and less competitive in terms of reproduction success. Thus, LAS concentrations that are considered safe by Brazilian by regulatory agencies must be revised in order to minimize a drastic impact over amphibian populations. This study demonstrates the relevance of employing cardiac biomarkers at different levels (e.g., morphological, physiological and cellular) to evaluate effects of xenobiotics in tadpoles.

Restructured low-fat cooked ham containing liquid whey fortified with lactulose.

BACKGROUND: Current health concerns have driven consumers to request products with nutritional and physiological advantages, which can be achieved by using prebiotic ingredients. Lactulose is a prebiotic with excellent functional properties and can be easily incorporated into meat products through the addition of liquid whey. This study investigated the technological and sensorial quality of restructured cooked ham elaborated without liquid whey added (control) and with liquid whey containing different contents (0, 30, 60 and 100 g kg-1 ) of lactulose. RESULTS: Liquid whey did not change any technological or sensorial characteristics of the product, but the general acceptability decreased due to addition of lactulose. Samples with higher lactulose concentrations had lower moisture content, pH and refreezing loss and increased carbohydrate content. Control and whey added samples had higher lightness and lower intense color than samples with lactulose. Liquid whey additions with higher lactulose content increased hardness and chewiness of the samples. CONCLUSION: Restructured cooked hams formulated with liquid whey and 30 g kg-1 of lactulose had minimal effects on the technological properties and sensory characteristics and, due to the possible benefits conferred by the prebiotic, is a potential alternative to provide meat products with prebiotic activity. © 2017 Society of Chemical Industry.

Characterization of starch-based bioplastics from jackfruit seed plasticized with glycerol.

Biodegradable films based on starches from different botanical sources exhibited physicochemical and functional properties which were related with the starch characteristics. However, had inadequate mechanical properties and were hard and brittle. In this research, jackfruit seed starch plasticized with glycerol were developed and characterized. The starch and glycerol concentrations ranged from 2 to 6% w/w and 20 to 60 g/100 g starch, respectively. Bioplastics were obtained by the casting method and characterized in terms of color, mechanical properties, solubility, water vapor permeability (WVP), morphology and free energy of the hydrophobic interaction. Electronic micrographics showed the presence of some intact starch granules. The bioplastics were hydrophilic and those of 6% starch and 40% glycerol were the most hydrophilic ([Formula: see text] = 41.35 mJ m-1). The solubility of the films presented a direct relationship with the starch concentration ranging from 16.42 to 23.26%. Increased opacity and color difference were observed with increasing starch concentration. The WVP ranged from 1.374 × 10-3 to 3.07 × 10-4 g m/day m2 which was positively related with the concentration of starch and glycerol. Tensile strength, percent elongation and Young's Modulus indicated that the jackfruit starch and glycerol provided a film with good mechanical properties. The results replaced that jackfruit starch can be used to develop films, with low opacity, moderate WVP and relatively high mechanical stability, by using glycerol in the gelatinized starch dispersions.

Fatty Acid Ethyl Esters Are Less Toxic Than Their Parent Fatty Acids Generated during Acute Pancreatitis.

Although ethanol causes acute pancreatitis (AP) and lipolytic fatty acid (FA) generation worsens AP, the contribution of ethanol metabolites of FAs, ie, FA ethyl esters (FAEEs), to AP outcomes is unclear. Previously, pancreata of dying alcoholics and pancreatic necrosis in severe AP, respectively, showed high FAEEs and FAs, with oleic acid (OA) and its ethyl esters being the most abundant. We thus compared the toxicities of FAEEs and their parent FAs in severe AP. Pancreatic acini and peripheral blood mononuclear cells were exposed to FAs or FAEEs in vitro. The triglyceride of OA (i.e., glyceryl tri-oleate) or OAEE was injected into the pancreatic ducts of rats, and local and systemic severities were studied. Unsaturated FAs at equimolar concentrations to FAEEs induced a larger increase in cytosolic calcium, mitochondrial depolarization, and necro-apoptotic cell death. Glyceryl tri-oleate but not OAEE resulted in 70% mortality with increased serum OA, a severe inflammatory response, worse pancreatic necrosis, and multisystem organ failure. Our data show that FAs are more likely to worsen AP than FAEEs. Our observations correlate well with the high pancreatic FAEE concentrations in alcoholics without pancreatitis and high FA concentrations in pancreatic necrosis. Thus, conversion of FAs to FAEE may ameliorate AP in alcoholics.

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections.

BACKGROUND AND AIMS: Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. METHODS: We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1ß and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. RESULTS: NCs had higher fatty acids, IL-8 and IL-1ß versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. CONCLUSIONS: UFAs, IL-1ß and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.

XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro), and GSTP1 (Ile105Val) polymorphisms in prognosis of cutaneous melanoma.

This study aimed to evaluate whether XPC A2920C, XPF T30028C, TP53 Arg72Pro, and GSTP1 Ile105Val polymorphisms alter outcomes of cutaneous melanoma (CM) patients. DNA from 237 CM patients seen at the University of Campinas Teaching Hospital from April 2000 to February 2014 was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays. The prognostic impact of genotypes of polymorphisms on progression-free survival (PFS) and overall survival (OS) of CM patients were examined using the Kaplan-Meier probability estimates and univariate and multivariate Cox regression analyses. At 60 months of follow-up, shorter PFS and OS were seen in patients with XPF CC genotype (48.9 vs. 66.7 %, P = 0.002; 77.9 vs. 83.5 %, P = 0.006, respectively) and XPF CC + TP53 ArgArg (43.6 vs. 65.9 %, P = 0.007; 71.6 vs. 84.8 %, P = 0.006, respectively) compared with those with remaining genotypes (Kaplan-Meier estimates). Patients with XPF CC (hazard ratio (HR) 2.45, P = 0.002; HR 3.77, P = 0.005) and XPF CC + TP53 ArgArg (HR 2.67, P = 0.009; HR 4.04, P = 0.03) genotypes had more chance to present tumor progression in univariate and multivariate analyses, whereas patients with XPF CC (HR 2.78, P = 0.009) and XPF CC + TP53 ArgArg (HR 3.84, P = 0.01) genotypes were under greater risk of progressing to death in univariate analysis, compared with those with the remaining genotypes. The data suggest, for the first time, that inherited abnormalities in DNA repair pathway related to XPF 30028C and TP53 Arg72Pro polymorphisms act as prognostic factors for PFS and OS of CM patients.

A Green Approach for Allylations of Aldehydes and Ketones: Combining Allylborate, Mechanochemistry and Lanthanide Catalyst.

Secondary and tertiary alcohols synthesized via allylation of aldehydes and ketones are important compounds in bioactive natural products and industry, including pharmaceuticals. Development of a mechanochemical method using potassium allyltrifluoroborate salt and water, to successfully perform the allylation of aromatic and aliphatic carbonyl compounds is reported for the first time. By controlling the grinding parameters, the methodology can be selective, namely, very efficient for aldehydes and ineffective for ketones, but by employing lanthanide catalysts, the reactions with ketones can become practically quantitative. The catalyzed reactions can also be performed under mild aqueous stirring conditions. Considering the allylation agent and its by-products, aqueous media, energy efficiency and use of catalyst, the methodology meets most of the green chemistry principles.

Transient receptor potential channel ankyrin-1 is not a cold sensor for autonomic thermoregulation in rodents.

The rodent transient receptor potential ankyrin-1 (TRPA1) channel has been hypothesized to serve as a temperature sensor for thermoregulation in the cold. We tested this hypothesis by using deletion of the Trpa1 gene in mice and pharmacological blockade of the TRPA1 channel in rats. In both Trpa1(-/-) and Trpa1(+/+) mice, severe cold exposure (8°C) resulted in decreases of skin and deep body temperatures to ∼8°C and 13°C, respectively, both temperatures being below the reported 17°C threshold temperature for TRPA1 activation. Under these conditions, Trpa1(-/-) mice had the same dynamics of body temperature as Trpa1(+/+) mice and showed no weakness in the tail skin vasoconstriction response or thermogenic response to cold. In rats, the effects of pharmacological blockade were studied by using two chemically unrelated TRPA1 antagonists: the highly potent and selective compound A967079, which had been characterized earlier, and the relatively new compound 43 ((4R)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5-one), which we further characterized in the present study and found to be highly potent (IC50 against cold of ∼8 nm) and selective. Intragastric administration of either antagonist at 30 mg/kg before severe (3°C) cold exposure did not affect the thermoregulatory responses (deep body and tail skin temperatures) of rats, even though plasma concentrations of both antagonists well exceeded their IC50 value at the end of the experiment. In the same experimental setup, blocking the melastatin-8 (TRPM8) channel with AMG2850 (30 mg/kg) attenuated cold-defense mechanisms and led to hypothermia. We conclude that TRPA1 channels do not drive autonomic thermoregulatory responses to cold in rodents.

Risk of sleep problems in a clinical sample of children who stutter.

PURPOSE: Previous studies have shown increased prevalence of sleep problems among people who stutter. However, there is a lack of knowledge about what these sleep problems may specifically be. METHOD: Fifty children who stutter (CWS) from 6;0 to 12;9 years of age and 50 age- and gender-matched controls participated in this study. Parents did not report coexisting conditions, excepting stuttering and/or sleep problems. Sleep problems were investigated using a standardized questionnaire answered by parents. The questionnaire shows cut-off scores to identify the risk of sleep problems as a whole and on each one of the six subscales (i.e., disorders of initiating and maintaining sleep; sleep breathing disorders; disorders of arousal; sleep-wake transition disorders; disorders of excessive somnolence; and sleep hyperhidrosis). Scores above the cut-off are suggestive of sleep problems. RESULTS: Twenty-one CWS scored higher than the cut-off on the sleep questionnaire compared to only two controls (p < 0.00001). Specifically, CWS scored higher than controls in disorders of initiating and maintaining sleep, sleep-wake transition disorders (especially jerking, sleep talking, and bruxism), and disorders of excessive somnolence (p < 0.0083, corrected for multiple comparisons). DISCUSSION: Compared to controls, CWS are at greater risk for sleep problems, which are not consequences of coexisting disorders. Present findings confirm and expand current knowledge about sleep problems in CWS. Directionality possibilities and clinical implications are discussed.