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Background Treatment of endoscopically resected T1 colorectal cancers is based on the risk of lymph node metastasis. Risk is based on histopathologic features, although there is lack of consensus as to what constitutes high-risk features. Objective The purpose of this study was to conduct a systematic review and meta-analysis of histopathologic risk factors for lymph node metastasis. Data sources A search of MEDLINE, Embase, Scopus, and Cochrane controlled register of trials for risk factors for lymph node metastasis was performed from inception until August 2018. Study selection Included patients must have had an oncologic resection to confirm lymph node status and reported at least 1 histopathologic risk factor. Intervention Rates of lymph node positivity were compared between patients with and without risk factors. Main outcome measures We report the results of the meta-analysis as ORs. Results Of 8592 citations, 60 met inclusion criteria. Pooled analyses found that lymphovascular invasion, vascular invasion, neural invasion, and poorly differentiated histology were significantly associated with lymph node metastasis, as were depths of 1000 µm (OR = 2.76), 1500 µm (OR = 4.37), 2000 µm (OR = 2.37), submucosal level 3 depth (OR = 3.08), and submucosal level 2/3 (OR = 3.08) depth. Depth of 3000 µm, Haggitt level 4, and widths of 3000 µm and 4000 µm were not significantly associated with lymph node metastasis. Tumor budding (OR = 4.99) and poorly differentiated clusters (OR = 14.61) were also significantly associated with lymph node metastasis. Limitations Included studies reported risk factors independently, making it impossible to examine the additive metastasis risk in patients with numerous risk factors. Conclusions We identified 1500 μm as the depth most significantly associated with lymph node metastasis. Novel factors tumor budding and poorly differentiated clusters were also significantly associated with lymph node metastasis. These findings should help inform guidelines regarding risk stratification of T1 tumors and prompt additional investigation into the exact contribution of poorly differentiated clusters to lymph node metastasis.

[Image: see text] Kratom is widely consumed in the United States for self-treatment of pain and opioid withdrawal symptoms. Mitragynine is the most abundant alkaloid in kratom and is a μ-opioid receptor agonist. 7-Hydroxymitragynine (7-HMG) is a mitragynine metabolite that is a more potent and efficacious opioid than its parent mitragynine. 7-HMG contributes to mitragynine’s antinociceptive effects in mice, but evidence suggests it may also have a higher abuse potential. This in vitro study demonstrates that 7-HMG is stable in rodent and monkey plasma but is unstable in human plasma. Surprisingly, in human plasma 7-HMG is converted to mitragynine pseudoindoxyl, an opioid that is even more potent than either mitragynine or 7-HMG. This novel metabolite is formed in human plasma to a much greater extent than in the preclinical species tested (mouse, rat, dog, and cynomolgus monkey) and due to its μ-opioid potency may substantially contribute to the pharmacology of kratom in humans to a greater extent than in other tested species.

Introduction. One of the pathogenic chains in neurodegenerative diseases, and the Alzheimer’s disease especially, is the disorder of cellular energy supply. Investigation of changes in the indices characterizing a functional state of the mitochondria in the cerebral cortex and hippocampus under the influence of carbacetam, a new modulator of GABA-system, is of a certain interest. The objective of the study was to evaluate the protective effect of carbacetam under conditions of mitochondrial dysfunction of the brain in rats with scopolamine-induced Alzheimer’s disease. Materials and methods. The experiments were conducted on laboratory nonlinear albino male rats with the body weight of 0.18-0.20 kg. To simulate Alzheimer’s disease, scopolamine hydrochloride (Sigma, USA) was injected in rats through the peritoneum, in the dose of 1 mg/kg for 27 days. Since the 28th day of the experiment, carbacetam was introduced through the peritoneum in the dose of 5 mg/kg, in 1 mL of 0.9 % NaCl solution, once a day for 14 days. Results. Under conditions of scopolamine-induced Alzheimer’s disease, light dispersion decreases and a relative rate of mitochondrial swelling increases in the mitochondrial fraction of the cerebral cortex and hippocampus of rats; free radical oxidation of lipids and proteins increases, and activity of Krebs cycle enzymes decreases – -ketoglutarate dehydrogenase and succinate dehydrogenase. After carbacetam administration for 14 days, a gradual decrease of light dispersion and relative rate of mitochondrial swelling are found in the mitochondrial fraction of the cerebral cortex and hippocampus. Moreover, the content of products reacting with 2-thiobarbituric acid and protein oxidation modification in the examined structures decreases; the activity of catalase, -ketoglutarate dehydrogenase, succinate dehydrogenase increases, and superoxide dismutase – only in the cerebral cortex Conclusions. Reduced intensity of mitochondrial swelling, improvement of the antioxidant system state and energy supply of mitochondria in the cerebral cortex and hippocampus of rats with scopolamine-induced Alzheimer’s disease are indicative of mitoprotective properties of carbacetam as a promising neuroprotector.

Kratom alkaloids have mostly been evaluated for their opioid activity but less at other targets that could contribute to their physiological effects. Here, we investigated the in vitro and in vivo activity of kratom alkaloids at serotonin receptors (5-HTRs). Paynantheine and speciogynine exhibited high affinity for 5-HT(1A)Rs and 5-HT(2B)Rs, unlike the principal kratom alkaloid mitragynine. Both alkaloids produced antinociceptive properties in rats via an opioid receptor-independent mechanism, and neither activated 5-HT(2B)Rs in vitro. Paynantheine, speciogynine, and mitragynine induced lower lip retraction and antinociception in rats, effects blocked by a selective 5-HT(1A)R antagonist. In vitro functional assays revealed that the in vivo 5-HT(1A)R agonistic effects may be due to the metabolites 9-O-desmethylspeciogynine and 9-O-desmethylpaynantheine and not the parent compounds. Both metabolites did not activate 5-HT(2B)R, suggesting low inherent risk of causing valvulopathy. The 5-HT(1A)R agonism by kratom alkaloids may contribute to the mood-enhancing effects associated with kratom use.

Dissolved organic matter (DOM) simultaneously with dissolved inorganic carbon (DIC), dissolved total carbon (TC) and cations (Na+, K+, Ca2+, Mg2+, Fe2+ and Mn2+) in sediment pore waters from Lake Baikal was investigated. That is the first detailed study of a relatively highly resolved DOC profile in benthic pore water profile from the Lake Baikal. We quantified DOC fluxes under different redox conditions in surface bottom sediment, which changed direction twice at the redox boundaries. Shown, that mobilization of DOC in oxygen-free sediments closely links to reductive dissolution of ferric minerals. Oxidized surface sediments are an efficient DOC trap where DOC is bound to ferric minerals. Redox conditions appears to be the primary regulator of the DOC exchange, resulting in sedimentary uptake of DOC (83 mol m-2d-1) under oxic conditions, and Lake Baikal sediment is a sink of DOC. The results of this study offer significant insight into the nature and properties of DOM in freshwater ecosystems.

Data of hygienic studies of air and soil during last 20 years have confirmed their correlating relationship with the general morbidity and a group of musculoskeletal diseases in children living in cities with the technogenic pollution of the environment. Their bones were established to grow unevenly and disproportionally, in 76% of children there have been violations in the development and growth of bones. The results of X-ray examination of hand bones in children and adolescents in the Irkutsk and Shelekhov cities are presented. Significant differences in morbidity patterns among children and adolescents including an increased incidence of musculoskeletal diseases by 5.6 in children and by 12 in adolescents have been revealed.

Introduction. One of medical-social chronic consequences of diabetes mellitus is encephalopathy, with an advancing course and development of neurodegenerative disorders in the central nervous system. Objective: to examine carbacetam effect as a new modulator of gamma-aminobutyric acid activity on protein peroxide oxidation and morphological condition of the cerebral cortex and hippocampus in rats under conditions of experimental neurodegeneration in case of type 2 diabetes mellitus. Materials and methods. Changes in the content of protein peroxide oxidation in the cerebral cortex and hippocampus under effect of carbacetam (5 mg/kg) are examined in nonlinear laboratory albino male rats with neurodegeneration under conditions of type 2 diabetes mellitus simulated by streptozotocin and high-fat diet. Results. In rats with type 2 diabetes mellitus, the degree of protein peroxide oxidation in the cerebral cortex and hippocampus increases, which is associated with increased amount of cells with karyopyknosis, decreased relative density of staining of the neuron tigroid substance and partial denudation of vessels. After carbacetam administration during 14 days in rats with type 2 diabetes mellitus in the cerebral cortex and hippocampus the level of protein peroxide oxidation decreases, the amount of cells with karyopyknosis reduces, a relative density of staining of the neuron tigroid substance increases, and denudation of vessels is lacking. Conclusions. Decreased intensity of the protein peroxide oxidation processes, histological destruction of the cerebral cortex and hippocampus are indicative of a neuroprotective potential of carbacetam under conditions of neurodegeneration caused by type 2 diabetes mellitus.

The objective of the study was to investigate the changes of the kidney functions in mature rats with rapid acetylation type, under conditions of subacute cadmium-nitrate intoxication and preventive introduction of Echinacea purpurea. Methods. Male rats, 6 months of age, with rapid acetylation type, were divided into 3 groups: І – control; ІІ – rats with of subacute cadmium-nitrate intoxication model; ІІІ – rats receiving intragastric alcohol tincture of fresh rhizomes with roots of Echinacea purpurea (LC “State Municipal Enterprise “Pharmaceutical Plant Vishpha””, Ukraine; 0,25 mk/rg). Results. Under the effect of preventive introduction of Echinacea purpurea in rats with rapid acetylation type and cadmium-nitrate lesion of the kidneys, diuresis and glomerular filtration rate became normal; distal transport of sodium ions increased; hyponatraemia and decreased natriuresis remained without changes; concentrations of creatinine in the blood plasma, potassium ions in the blood plasma and urine, kaliuresis decreased. Similar to the group of rats without Echinacea purpurea, proximal reabsorption of sodium ions, which is standardized by glomerular filtration, decreased. Conclusion. Under conditions of preventive introduction of Echinacea purpurea, volume regulating kidney function is maintained in mature rats with rapid acetylation type and subacute cadmium-nitrate intoxication, but it does not prevent the development of toxic nephropathy, with prevailing lesion of the nephron proximal portion, disorders of ion regulating kidney function and water-electrolytic balance.

The impacts of high-intensity light (HIL) (4 h) and UV-B radiation (1 h) on the photosynthetic activity, content of photosynthetic and UV-absorbing pigments (UAPs), activity of antioxidant enzymes (ascorbate peroxidase (APX) and guaiacol-dependent peroxidase (GPX)), content of thiobarbituric acid reactive substances (TBARs), expression of some light-regulated genes in 25-day-old wild type (WT) and the cryptochrome 1 (Cry1) hy4 mutant of A. thaliana Col-0 plants grown under blue light (BL) were studied. HIL and UV-B treatments led to decreases in the photosynthetic rate (Pn), photochemical activity of PSII (FV/FM) and PSII performance index (PIABS) of WT and mutant plants grown under high-intensity BL (HBL) and moderate intensity BL (MBL). However, in HBL plants, the decrease in the photosynthetic activity in hy4 plants was significantly greater than that in WT plants. In addition, hy4 HBL plants demonstrated lowered UAP and carotenoid contents as well as lower activity of APX and GPX enzymes. The difference in the decline in the photosynthetic activity of WT and hy4 plants grown at MBL in response to HIL was nonsignificant, while that in response to UV-B was small. We assume that the deficiency in cryptochrome 1 under HIL irradiation disrupts the interaction between HY5 and HFR1 transcription factors and photoreceptors, which affects the transcription of light-induced genes, such as CAB1, PSY and PAL1 linked to carotenoid and flavonoid biosynthesis. It was concluded that PA stress resistance in WT and hy4 plants depends on the light intensity and reduced stress resistance of hy4 at HBL, is likely linked to low UAP and carotenoid contents as well as lowered APX and GPX enzyme activities in hy4 mutants.

Kratom, Mitragyna speciosa Korth., is being widely consumed in the United States for pain management and the reduction of opioid withdrawal symptoms. The central nervous system (CNS) active alkaloids of kratom, including mitragynine, 7-hydroxymitragynine, and numerous additional compounds, are believed to derive their effects through opioid receptor activity. There is no literature describing the systemic exposure of many of these alkaloids after the consumption of kratom. Therefore, we have developed and validated a bioanalytical method for the simultaneous quantitation of 11 kratom alkaloids (mitragynine, 7-hydroxymitragynine, corynantheidine, speciogynine, speciociliatine, paynantheine, corynoxine, corynoxine-B, mitraphylline, ajmalicine, and isospeciofoline) in rat plasma. The validated method was used to analyze oral pharmacokinetic study samples of lyophilized kratom tea (LKT) and a marketed product, OPMS liquid shot, in rats. Among the 11 alkaloids, only mitragynine, 7-hydroxymitragynine, speciociliatine, and corynantheidine showed systemic exposure 8 h postdose, and the dose-normalized systemic exposure of these four alkaloids was higher (1.6-2.4-fold) following the administration of the commercial OPMS liquid. Paynantheine and speciogynine levels were quantifiable up to 1 h postdose, whereas none of the other alkaloids were detected. In summary, the method was successfully applied to quantify the exposure of individual kratom alkaloids after an oral dose of traditional or commercial products. This information will contribute to understanding the role of each alkaloid in the overall pharmacology of kratom and elucidating the pharmacokinetic differences between traditional and commercial kratom products.

Background In 2018, the Farm Bill mandated the United States Department of Agriculture to develop regulations governing the cultivation, processing, and marketing of industrial hemp. Industrial hemp is defined as Cannabis sativa L. with a total Δ-9-tetrahydrocannabinol (Δ-9-THC) content ≤0.3%. Therefore, for hemp to become an agricultural commodity, it is important to regulate production by developing standard methods for sampling and testing of the plant material. Methods An ultra-performance liquid chromatography-tandem mass spectrometry analytical method for the quantification of twelve cannabinoids was developed. The method was applied to a regulatory sampling trial of three hemp varieties cultivated for cannabidiol (CBD) production. Two samples were taken from 28 plants with one sample being flower only while the other was a composite sample that included flowers, leaves, and stems. Results The assay method was validated for specificity, range, repeatability, reproducibility, and recovery in accordance with all applicable standards for analytical methods. The results of the regulatory study indicated a significant decrease in the concentration of total Δ-9-THC and total CBD of 0.09% and 1.32%, respectively, between a flower only and a composite sample. Conclusions There are many factors that may influence reported total Δ-9-THC content in industrial hemp. A robust analytical method was developed to analyze hemp samples in a trial regulatory study. The results indicate that the way hemp is sampled and analyzed may influence the legality of a crop, which could have negative economic and legal consequences.

Author(s): Cahoon, Elizabeth K; Nadyrov, Eldar A; Polyanskaya, Olga N; Yauseyenka, Vasilina V; Veyalkin, Ilya V; Yeudachkova, Tamara I; Maskvicheva, Tamara I; Minenko, Victor F; Liu, Wayne; Drozdovitch, Vladimir; Mabuchi, Kiyohiko; Little, Mark P; Zablotska, Lydia B; McConnell, Robert J; Hatch, Maureen; Peters, Kamau O; Rozhko, Alexander V; Brenner, Alina V | Abstract: ContextAlthough radiation exposure is an important predictor of thyroid cancer on diagnosis of a thyroid nodule, the relationship between childhood radiation exposure and thyroid nodules has not been comprehensively evaluated.ObjectiveTo examine the association between internal I-131 thyroid dose and thyroid nodules in young adults exposed during childhood.Design, setting, and participantsIn this cross-sectional study, we screened residents of Belarus aged ≤18 years at the time of the Chernobyl nuclear accident for thyroid disease (median age, 21 years) with thyroid palpation, ultrasonography, blood/urine analysis, and medical follow-up when appropriate. Eligible participants (N = 11,421) had intact thyroid glands and doses based on direct individual thyroid activity measurements.Main outcome measuresExcess odds ratios per Gray (EOR/Gy, scaled at age 5 years at exposure) for any thyroid nodule and for nodules grouped by cytology/histology, diameter size, and singularity.ResultsRisk of any thyroid nodule increased significantly with I-131 dose and, for a given dose, with younger age at exposure. The EOR/Gy (95% confidence intervals) for neoplastic nodules (3.82; 0.87 to 15.52) was significantly higher than for nonneoplastic nodules (0.32; l0.03 to 0.70) and did not vary by size; whereas the EOR/Gy for nonneoplastic nodules did vary by size (P = 0.02) and was 1.55 (0.36 to 5.46) for nodules ≥10 mm and 0.02 (l-0.02 to 0.70) for nodules l10 mm. EORs/Gy for single and multiple nodules were comparable.ConclusionsChildhood exposure to internal I-131 is associated with increased risk of neoplastic thyroid nodules of any size and nonneoplastic nodules ≥10 mm.

No abstract available.

To determine if antenatal variables affect the risk of spontaneous intestinal perforation (SIP) among preterm infants when prophylactic indomethacin is used.Retrospective case-control study of infants29 weeks of gestational age between January 2010 and June 2018 at one hospital. SIP was defined as acute abdominal distension and pneumoperitoneum without signs of necrotizing enterocolitis at14 days of life. Each case (n = 57) was matched with 2 controls (n = 114) for gestational age and birth year. Maternal and infant data were abstracted until the SIP or equivalent day for controls. Univariate analyses were followed by adjusted conditional logistic regressions and reported as OR and 95% CI.Mothers of cases were younger, more often delivering multiples (31% vs 14%, P = .007), and less abruptions (15% vs 29%, P = .045) but did not differ in intra-partum betamethasone, magnesium, or indomethacin use. Prophylactic indomethacin was given on day 1 to 99% of infants. SIP was associated with a shorter interval from last betamethasone dose to delivery (46 hours vs 96 hours, P = .01). Dopamine use (14% vs 4%, P = .02), volume expansion (23% vs 8%, P = .003), and high grade intraventricular hemorrhage (28% vs 8%, P = .0008) were related postnatal factors. The adjusted odds of SIP increased by 1% for each hour decrease between the last dose of betamethasone and delivery (OR 1.01, 95% CI 1.002-1.019) and with multiple births (OR 2.66, 95% CI 1.05-6.77).Antenatal betamethasone given shortly before delivery is associated with an increased risk of SIP. Potential interaction with medications such as postnatal indomethacin needs study.

Background: Nutrition during pregnancy impacts the health of the fetus and the newborn, with effects at the epigenetic level determining long-term neurological consequences. Iron requirements in pregnancy are estimated at 27 mg/day. The best absorbed heme iron is found in meat: beef, pork, poultry, and fish.The determination of ferritin in umbilical cord blood can be used to assess iron deposits reached during the fetal stage. Ferritin levels were associated with long-term effects on child development.Methods: A descriptive, observational study with prospectively collected data was carried out during one-year period at the Department of Neonatology of the Pereira Rossell Hospital Center (CHPR) in Montevideo, Uruguay. A total of 188 patients met the inclusion criteria. Umbilical cord blood was drawn following a strict cord clamping after one minute of life. Ferritin was measured using the chemoimmunofluorescence method. A maternal nutritional survey was applied, using a qualitative-quantitative form measuring the frequency of consumption of iron source foods and approximated quantities consumed during the last trimester of pregnancy. This survey was focused on maternal consumption of beef as the major heminic iron source in Uruguay. The relationship between these variables was analysed.Results: Latent iron deficiency (ferritin in the umbilical cord Conclusions: This study considers adequate evidence that low levels of total iron and meat consumption during pregnancy will determine an increased risk of latent iron deficiency and lower levels of ferritin in newborns, and therefore, greater risk of long-term adverse effects on myelination and neurocognitive development.

We analysed the relationship between the chemical complex (concentration of dissolved ions, nutrients, pH) and biological parameters (primary production, biomass of phytoplankton, abundance and activity of bacterial communities) at estuaries of rivers and coastal waters of Southern Baikal during the under-ice period. Correlation network analysis revealed CO2 to be the main limiting factor for the development of algae and microbial communities in the coastal zone of Lake Baikal. This study indicates that primarily reverse synthesis of bicarbonate and carbonate ions associated with the development of phytoplankton and accumulation of dissolved CO2 during photosynthesis regulates pH in the Baikal water. We did not detect the anthropogenic factors that influence the change in pH and acidification. Near the Listvyanka settlement (Lake Baikal, Listvennichnaya Bay), there was a great number of organotrophs and thermotolerant bacteria with low bacterioplankton activity and high concentration of organic carbon. This evidences eutrophication due to the influx of organic matter having an anthropogenic source. Nutrients produced during the bacterial destruction of this matter may explain the changes in bottom phytocenoses of Listvennichnaya Bay.

The sigma-2 receptor has been cloned and identified as Tmem97, which is a transmembrane protein involved in intracellular Ca2+ regulation and cholesterol homeostasis. Since its discovery, the sigma-2 receptor has been an extremely controversial target, and many efforts have been made to elucidate the functional role of this receptor during physiological and pathological conditions. Recently, this receptor has been proposed as a potential target to treat neuropathic pain due to the ability of sigma-2 receptor agonists to relieve mechanical hyperalgesia in mice model of chronic pain. In the present work, we developed a highly selective sigma-2 receptor ligand (sigma-1/sigma-2 selectivity ratio > 1000), 1-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-3-methyl-1H- benzo[d]imidazol-2(3H)-one (CM398), with an encouraging in vitro and in vivo pharmacological profile in rodents. In particular, radioligand binding studies demonstrated that CM398 had preferential affinity for sigma-2 receptor compared with sigma-1 receptor and at least four other neurotransmitter receptors sites, including the norepinephrine transporter. Following oral administration, CM398 showed rapid absorption and peak plasma concentration (Cmax) occurred within 10 min of dosing. Moreover, the compound showed adequate, absolute oral bioavailability of 29.0%. Finally, CM398 showed promising anti-inflammatory analgesic effects in the formalin model of inflammatory pain in mice. The results collected in this study provide more evidence that selective sigma-2 receptor ligands can be useful tools in the development of novel pain therapeutics and altogether, these data suggest that CM398 is a suitable lead candidate for further evaluation.

BACKGROUND The College of American Pathologists has published guidelines for malignant colorectal polyp pathology reports that list histopathological features that are "core elements" and "optional." Lack of element reporting may result in inaccurate tumor risk stratification.This study aimed to perform a population-based assessment of pathology reporting for T1 colorectal cancers and determine the completeness of reporting for core and optional histopathological elements.This is a retrospective cohort study.This study reviews the pathology reports of endoscopically resected malignant colorectal polyps in Alberta, Canada between 2014 and 2016.Individuals aged 18 years or older with T1 colorectal polyps were selected.Histopathological elements were dichotomized into core and optional. Malignant polyps were classified as high risk or low risk for lymph node metastases and local intraluminal recurrence. Addendum reports were compared with first reports.After applying exclusion criteria, 431 polyps were analyzed. The mean age of patients was 65.5 years; 59.4% were male. Histological grade, deep margin, and lymphovascular invasion were reported in 82.4%, 86.8% and 75.6%; all 3 were reported in only 66.4%. Tumor budding (not in the 2016 guidelines) was reported in 14.4%. One hundred ninety polyps (44.1%) were high risk. Thirty-seven polyps (8.3%) had an addendum report. Following the addendum, 1 polyp was downgraded to low risk, and 9 polyps were upgraded to high risk.The main limitation of the study is its retrospective nature. The decision making surrounding treatment for T1 cancers is complex, and factors other than histopathological tumor features may have been part of treatment decisions.There is a high rate of incomplete reporting of core and optional elements for malignant colorectal polyp pathology reports in Alberta. Several variables used by colorectal surgeons for decision making, such as tumor budding and depth of submucosal invasion, are not considered core elements and are infrequently reported. A pathology review by a second pathologist often results in a change in risk stratification. See Video Abstract at http://links.lww.com/DCR/B98. PATOLOGIA DEL POLIPO COLORRECTAL MALIGNO: ?ESTAMOS OBTENIENDO INFORMACION SUFICIENTE PARA TOMAR DECISIONES?: El Colegio de Patologos Americanos publico pautas para informes de patologia de polipos colorrectales malignos que enumeran caracteristicas histopatologicas como "elementos centrales" y "opcionales". La falta de informacion elemental puede resultar en una estratificacion de riesgo tumoral imprecisa.Valoracion basada en una poblacion de los informes de patologia para los canceres colorrectales T1 y determinar la precision de los informes en cuanto los elementos histopatologicos centrales y opcionales.Estudio de cohorte retrospectivo.Este estudio revisa los informes de patologia de polipos colorrectales malignos resecados endoscopicamente en Alberta, Canada, entre 2014 y 2016.personas mayores de 18 anos con polipos colorrectales T1.Los elementos histopatologicos se dicotomizaron entre elementales y opcionales. Polipos malignos se clasificaron como de alto riesgo o bajo riesgo de metastasis en los ganglios linfaticos y recurrencia intraluminal local. Los informes enmendados se compararon con los informes originales.Despues de aplicar los criterios de exclusion, se analizaron 431 polipos. La edad media fue 65.5 anos, con 59.4% masculinos. El grado histologico, el margen profundo y la invasion linfovascular se informaron confirmaron en 82.4%, 86.8% y 75.6% respectivamente; las tres caracteristicas se demostraron en solo 66.4%. Un patron tumoral en ciernes se reporto en 14.4-una caracteristica que no se usaba en las guias de 2016. Ciento noventa polipos (44.1%) eran de alto riesgo. Treinta y siete polipos (8.3%) requirieron de un informe enmendado. Aplicacion de los nuevos criterios resulto en que 1 polipo se redujo a bajo riesgo y 9 polipos se actualizaron como a alto riesgo.La principal limitacion del estudio es el diseno retrospectivo. La toma de decisiones en torno al tratamiento de los canceres T1 es compleja y otros factores ademas de las caracteristicas histopatologicas del tumor pueden haber sido parte de las decisiones terapeuticas.Hay una alta tasa de informes incompletos de elementos centrales y opcionales para informes de patologia de polipos colorrectales malignos en Alberta. Algunas variables utilizadas por los cirujanos colorrectales para la toma de decisiones, como el patron tumoral en ciernes y la profundidad de la invasion submucosa, no se consideran elementos centrales y se informan con poca frecuencia. Una revision de patologia realizada por un segundo patologo a menudo resulta en un cambio en la estratificacion del riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B98. (Traduccion-Dr. Adrian E. Ortega).

In this chapter the effects of magnetic fields 30 mT, 50 Hz, 30 s (MF), temperature, and exogenous selenium on the plant growth, productivity, and changing in the metabolism of reactive forms of oxygen under stress conditions, induced by flooding and soil pollution with lead, are discussed. It was shown that seed processing with MF caused an enhancing of plant antioxidant potential under root hypoxia, induced by soil flooding. It is also considered the role of temperature in the changing of the oxidative process intensity as well as antioxidant enzyme activities induced by lead in the Plantago major L. plants. Increasing of the temperature from 20 to 28 °C resulted in a reduction of lead content in the leaves of plants exposed in the water solution of Pb(NO3)2, but increased the adverse effects of Pb, especially in the beginning of stress development. It has been also showed that the pros or cons effects of exogenous Se6+ on plant resistance to the lead pollution depended on the Se6+ concentration in the soil.

Aim. Evaluation of paraarticular tissues and of venous outflow by the data of ultrasound duplex scanning (USDS) after arthroscopic plasty of the anterior cruciate ligament (ACL). Materials and Methods. Analysis of the results of examination of 32 patients with ACL injury at the age of 18-50 (mean age 32.62±1.1 years). The technology of transtibial arthroscopic reconstruction of ACL was applied with use of RigidFix and Biointrafix systems of fixation. USDS of veins, paraosseous and paraarticular tissues was performed using «HITACHI» HI Vision Avius device. Results. The performed studies permitted to reveal a group of patients (with the share of 12%) in whom, by the moment of discharge from hospital to the outpatient treatment, hemodynamic signs of dysfunction of the valves of deepleg veins were recorded. According to sonography data, the volumes of the upper and lateral torsions remained increased, and tissue edema and hematomas along the anteromedial and posteromedial surfaces of the leg persisted. Taking into account the temporary character of these changes withtheir absenceon the follow-up examination after 1.5 months, we think, they were associated with increased traumatization of m. Semitendinosus and m. Gracili due to the anatomical peculiarities of the structure of tendinous-muscular complex (pes anserinum) in certain patients. Conclusions. The technique of USDS of vein and paraarticular tissue after arthroscopic reconstructionof ACL permits to identify a group of patients at risk for prolongation of rehabilitation period. The dysfunctions of the valves of the deep veinsof legs, the presence of hematomas at the stage of fibrotization require additional rehabilitation measures including medicinal treatment, physical therapy and exercise therapy under control of USDS.

Background Therapeutic hypothermia reduces the risk of death, or moderate to severe neurodevelopmental impairment (NDI) in term infants with hypoxic-ischemic encephalopathy (HIE). Reports of its safety and efficacy in preterm infants are scarce. Objective Report short and long-term outcomes of preterm infants with HIE who received therapeutic hypothermia. Methods A retrospective cohort analysis of all preterm infants Results 30 infants with a median gestational age and birthweight of 35 weeks' (range; 33–35) and 2575 g (1850–4840) and a median first postnatal blood pH of 6.81 (6.58–7.14). Complications included coagulopathy (50%), early clinical seizures (43.3%), arterial hypotension (40%), persistent metabolic acidosis (37%) and thrombocytopenia (20%). Four infants died before or soon after discharge (18.2%). Eighteen surviving infants (69.2%) had follow up data; 7 of them had moderate to severe NDI (38.9%). Cognitive, motor and language mean composite BSID III scores were 84 (54–110), 83 (46–118), and 78 (46–112). Death or moderate to severe NDI occurred in 11/22 (50%) infants with known outcomes. Conclusion Large randomized trials on efficacy and safety are needed in this highly vulnerable population as the incidence of complications and the combined outcome of death and NDI is concerning.

Resumen Introducción La infección por Streptococcus agalactiae (β-hemolítico del grupo B (SGB) continúa siendo una de las principales causas de sepsis precoz en países desarrollados a pesar de la implementación de profilaxis efectiva. Objetivos Describir la incidencia, características clínicas y mortalidad de sepsis precoz por SGB en recién nacidos del Centro Hospitalario Pereira Rossell (CHPR), y analizar las fallas de adherencia a las estrategias de prevención. Métodos Estudio retrospectivo de descripción de casos entre los años 2007 a 2015 identificados a partir de la base de datos del laboratorio de bacteriología. Resultados Se identificaron 15 casos de sepsis neonatal precoz a SGB con una incidencia en el período de estudio de 0,23‰. La quimioprofilaxis intraparto no fue realizada en caso alguno. Todos los recién nacidos se presentaron sintomáticos en las primeras 15 h de vida. La dificultad respiratoria fue el signo más frecuente (80%). En un caso se aisló SGB de líquido cefalorraquídeo. La mortalidad fue de 20%. Todas las muertes ocurrieron en las primeras 24 h de vida, siendo dos tercios prematuros. Conclusión La incidencia de sepsis precoz por SGB en el CHPR fue similar a la incidencia en centros donde se realiza quimioprofilaxis. Una mejor adherencia a las estrategias de prevención podría disminuir la incidencia.

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of monogenic diseases caused by a violation of collagen metabolism, the structure and function of myomatrix and the synthesis of proteoglycans. This pathology is characteri zed by hyperelasticity of the skin, subcutaneous globules, overextension of the joints, tissue vulnerability and hemorrhagic syndrome. EDS is one of the seven hereditary connective tissue disorders for which international diagnostic criteria are met. More than 30 years ago, the so-called Berlin nosology of hereditary connective tissue disorders was first compiled and approved (1986). For a long time, doctors used the “Villefranche Nosology” classification of EDS, adopted in 1998 and divided the disease into 6 types. The new criteria were published by the International Committee of Experts in 2017. In the clinical classification of EDS, 13 types with different inheritance, clinical features and biochemical defects are described. In most cases, it is inherited by an autosomal dominant type. True prevalence is unknown due to the complexity of verification and a large number of light forms, the frequency of diagnosed cases is 1 : 5000 births, severe forms are rare (1 : 100 000). Diagnosis of this syndromeis also based on the diagnostic criteria of the international classification. The lecture presents new data on classification diagnostic criteria of EDS, polymorphism of the clinical picture, genetic heterogeneity, the main principles of treatment of the disease. The new classification criteria take into account, in the main, the features of the clinical picture, they did not simplify the diagnosis, but they increased the specificity and increased the significance of the clinical and anamnestic features. The scope of the examination is determined by the presence of leading clinical signs. The genealogical examination and molecular genetic methods of diagnostics are of great importance.

During development, growth cones are essential for axon pathfinding by sensing numerous guidance cues in their environment. Retinoic acid, the metabolite of vitamin A, is important for neurite outgrowth during vertebrate development, but may also play a role in axon guidance, though little is known of the cellular mechanisms involved. Our previous studies showed that retinoid-induced growth cone turning of invertebrate motorneurons requires local protein synthesis and calcium influx. However, the signalling pathways that link calcium influx to cytoskeletal dynamics involved in retinoid-mediated growth cone turning are not currently known. The Rho GTPases, Cdc42 and Rac, are known regulators of the growth cone cytoskeleton. Here, we demonstrated that inhibition of Cdc42 or Rac not only prevented growth cone turning toward retinoic acid but could also induce a switch in growth cone responsiveness to chemorepulsion or growth cone collapse. However, the effects of Cdc42 or Rac inhibition on growth cone responsiveness differed, depending on whether the turning was induced by the all-trans or 9-cis retinoid isomer. The effects also differed depending on whether the growth cones maintained communication with the cell body. These data strongly suggest that Cdc42 and Rac are downstream effectors of retinoic acid during growth cone guidance.

Meningitis occurs most commonly in the neonatal period and is associated with significant morbidity and mortality. Examination of the cerebrospinal fluid is essential for diagnosis, identification of pathogens, and appropriate choice of therapy. However, the role of lumbar puncture in the diagnostic evaluation of neonatal sepsis remains controversial. Clinicians caring for infants in the neonatal intensive care unit often choose to defer lumbar puncture due to low suspicion for meningitis or due to presumed risk of the procedure. However, a significant proportion of infants with meningitis have negative blood cultures. Selective evaluation of infants with culture-proven bacteremia can also result in missed diagnoses of meningitis. In this chapter, we provide evidence-based recommendations for when lumbar puncture should be performed in infants at risk for meningitis in the neonatal intensive care unit.

Retinoic acid (RA), the active metabolite of vitamin A, functions through nuclear receptors, one of which is the retinoic acid receptor (RAR). Though the RAR is essential for various aspects of vertebrate development, little is known about the role of RAR in nonchordate invertebrates. Here, we examined the potential role of an invertebrate RAR in mediating chemotropic effects of retinoic acid. The RAR of the protostome Lymnaea stagnalis is present in the growth cones of regenerating cultured motorneurons, and a synthetic RAR agonist (EC23), was able to mimic the effects of retinoic acid in inducing growth cone turning. We also examined the ability of the natural retinoids, all-trans RA and 9-cis RA, as well as the synthetic RAR agonists, to disrupt embryonic development in Lymnaea. Developmental defects included delays in embryo hatching, arrested eye, and shell development, as well as more severe abnormalities such as halted development. Developmental defects induced by some (but not all) synthetic RAR agonists were found to mimic those induced by addition of high concentrations of the natural retinoid isomers. These pharmacological data support a possible physiological role for the RAR in axon guidance and embryonic development of an invertebrate protostome species.

Neonatal mortality rate varies between 4.2 and 18.6 per thousand by country in South America. There is little information regarding the outcomes of very low birth weight infants in the region and mortality rates are extremely variable ranging from 6% to over 50%. This group may represent up to 50-70% of the neonatal mortality and approximately 25-30% of infant mortality. Some initiatives, like the NEOCOSUR Network, have systematically collected and analyzed epidemiological information on VLBW infants’ outcomes in the region. Over a 16-year period, survival without major morbidity improved from 37 to 44%. However, mortality has remained almost unchanged at approximately 27%, despite an increase in the implementation of the best available evidence in perinatal practices over time. Implementing quality improvement initiatives in the continent is particularly challenging but represents a great opportunity considering that there is a wide margin for progress in both care and outcomes.

Fluctuation of the summer day-time temperatures in the mid-latitudes in a range from 16 to 30°C should not have irreversible negative effects on plants, but may influence metabolic processes including the oxidative stress. To test the effect of moderately high temperature on oxidative stress induced by lead in the leaves of Plantago major L.; the plants were incubated in a water solution of 0, 150, 450, and 900 μM Pb (NO3)2 at 20 and 28°C. Plant reactions were evaluated by the content of thiobarbituric acid reactive substances and ascorbate peroxidase and glutathione reductase activities in leaves after 2, 24, 48, and 72 h. The Pb concentration in the leaves rose with the increase in the Pb content and was higher at 20°C. The increase in stomatal resistance caused by Pb was higher at 28°C. The contents of TBARS increased after 2 h of plant exposure to Pb and the increase was the highest at 900 μM Pb, 28°C. The AsP activity increased up to 50% after 24 h of Pb-treatment at 28°C; the highest increase in glutathione reductase activity was observed after 72 h at 20°C. Thus, the moderately high temperature 28°C compared with optimal 20°C caused a decrease in Pb accumulation in Plantago leaves but amplified the negative effects of lead, especially in the beginning of stress development.

Monogenic forms of inherited disorders of connective tissue and multifactorial connective tissue dysplasia are quite common in the population. Despite the high level of modern molecular techniques, clarification of their nosology of today, still remains a distant prospect. These difficulties are due to a large variety of mutations expressed their phenotypic polymorphism clinical manifestations, the considerable size of the genes encoding the proteins of the connective tissue, a rarity major mutations and low availability of molecular genetic research methods to verify the diagnosis. Clarification of the incidence of connective tissue displasia hindered by the lack of common terminology, standardized diagnostic criteria, as well as the practical inaccessibility of modern molecular genetic techniques to identify this heterogeneous pathology. The first part is devoted to the recommendations of the pediatric aspects of diagnosis of hereditary disorders of connective tissue with agreed international diagnostic criteria, and connective tissue displasia. Details covered principles of tactics and treatment of patients with this pathology. The attention of researchers aimed at studying the problems of the modifying effect of this disease on the nature of the flow of almost all diseases. This proves the feasibility of making additions to the standards of inspection and management of these patients with the mandatory inclusion of a comprehensive treatment of the underlying disease additional treatment and rehabilitation, correcting disorders caused by comorbidities.

The effects of high-intensity light (HIL) on the activity of photosystem II (PSII) and photosynthesis in wild-type (WT) and single (phyB2, phyB1, phyA and cry1), double (phyB1B2, phyAB2 and phyAB1) and triple (phyAB1B2 and cry1phyAB1) mutants of Solanum lycopersicum were studied. In addition, changes in the activity of the antioxidant enzymes ascorbate peroxidase, glutathione reductase and guaiacol peroxidase as well as the photosynthetic pigment and anthocyanin contents in the leaves of phyB2 and cry1phAB1 mutants under HIL were examined. When plants were irradiated with HIL (2 h), the PSII resistance of the cry1phyAB1 mutant was the lowest, while the resistance of WT and single mutants excluding cry1 was the highest. The effect of HIL on PSII activity in all double mutants and the phyAB1B2 mutant was intermediate between the effects on the WT and the cry1phyAB1 mutant. The intensity of oxidative processes in the cry1phyAB1 mutant was higher than that in WT and phyB2, but in cry1phyAB1, the activity of antioxidant enzymes and the anthocyanin content were lower. The low resistance of the cry1phyAB1 mutant to HIL may be due to the low antioxidant activity of key enzymes and the reduced pigment content, which are consistent with the reduced expression of CHS and sAPX genes in the cry1phyAB1 mutant.

Background An expedited discharge protocol for uncomplicated appendicitis was developed at a Canadian academic hospital to determine if patients could be safely discharged home early without negatively impacting care and patient satisfaction. Methods A non-randomized prospective quality improvement project was completed between February 01, 2017 and January 31, 2018. The project included patients between 16 and 65 years with uncomplicated appendicitis managed with laparoscopic appendectomy. The primary outcome was average length of stay post PACU. 30 day ED visit, cross-sectional imaging and readmission rate were balancing measures. The CTM-3 tool was used to measure patient satisfaction. Results 450 patients had emergent laparoscopic appendectomy. 287 (63.8%) patients met the project inclusion criteria. The average length of stay decreased 41.0% to 13.1 h. The 30 day ED visit, cross-sectional imaging and readmission rate were 9.8%, 4.5% and 1.0% respectively compared with 8.1%, 4.5% and 2.5% at baseline. Patient satisfaction was 3.72/4 compared to 3.74/4. Conclusion An expedited discharge after an uncomplicated laparoscopic appendectomy is safe and feasible without a negative impact on 30-day ED visit, diagnostic imaging or readmission.

Background Antenatal corticosteroids (ACS) during preterm labour reduce neonatal mortality and morbidity. Evidence on preterm multiple pregnancies is limited and contradictory. Objective Compare the effect of ACS on very low birth weight infant's (VLBW) mortality and morbidity among singleton and multiple pregnancies. Study design Retrospective cohort study, employing prospectively collected data, of infants 23 to 34 weeks' gestation and 500 to 1500 g born at the Neocosur Neonatal Network centers during 2007–2016. Neonatal outcomes were compared among singleton and multiple pregnancies exposed to at least one dose of ACS to those not exposed using logistic regression analyses controlled for birthweight, gestational age, sex, small for gestational age (SGA) and mode of delivery. Results A total of 13,864 infants were studied; 2948 multiple (21.3%) and 10,904 singleton pregnancies (78.7%). Overall, 11,218 (81.4%) received at least one dose of ACS with a significant reduction in the risk of death, RDS and grade III or IV IVH compared to those not exposed. Both singleton and multiple pregnancies exposed to ACS showed similar reduced risk of death (aRR 0.41 [95% CI, 0.36–0.47] vs. aRR 0.46 [95% CI, 0.34–0.64]). However, ACS were not associated with reduced odds of RDS (aRR 0.89 [95% CI, 0.66–1.23]) or grade III or IV IVH (aRR 0.99 [95% CI, 0.67–1.48]) in multiple pregnancies. Conclusion The benefit of administration of at least one dose of ACS in VLBW multiple and singleton pregnancies is comparable in terms of death. However, ACS showed no relevant impact in short-term morbidity in multiple pregnancies.

Recent studies suggest both beneficial and detrimental role of increased reactive oxygen species and oxidative stress in heart failure (HF). However, it is not clear at which stage oxidative stress and oxidative modifications occur in the endothelium in relation to cardiomyocytes in non-ischemic HF. Furthermore, most methods used to date to study oxidative stress are either non-specific or require tissue homogenization. In this study, we used immuno-spin trapping (IST) technique with fluorescent microscopy-based detection of DMPO nitrone adducts to localize and quantify oxidative modifications of the hearts from Tgαq*44 mice; a murine model of HF driven by cardiomyocyte-specific overexpression of Gαq* protein. Tgαq*44 mice and age-matched FVB controls at early, transition, and late stages of HF progression were injected with DMPO in vivo and analyzed ex vivo for DMPO nitrone adducts signals. Progressive oxidative modifications in cardiomyocytes, as evidenced by the elevation of DMPO nitrone adducts, were detected in hearts from 10- to 16-month-old, but not in 8-month-old Tgαq*44 mice, as compared with age-matched FVB mice. The DMPO nitrone adducts were detected in left and right ventricle, septum, and papillary muscle. Surprisingly, significant elevation of DMPO nitrone adducts was also present in the coronary endothelium both in large arteries and in microcirculation simultaneously, as in cardiomyocytes, starting from 10-month-old Tgαq*44 mice. On the other hand, superoxide production in heart homogenates was elevated already in 6-month-old Tgαq*44 mice and progressively increased to high levels in 14-month-old Tgαq*44 mice, while the enzymatic activity of catalase, glutathione reductase, and glutathione peroxidase was all elevated as early as in 4-month-old Tgαq*44 mice and stayed at a similar level in 14-month-old Tgαq*44. In summary, this study demonstrates that IST represents a unique method that allows to quantify oxidative modifications in cardiomyocytes and coronary endothelium in the heart. In Tgαq*44 mice with slowly developing HF, driven by cardiomyocyte-specific overexpression of Gαq* protein, an increase in superoxide production, despite compensatory activation of antioxidative mechanisms, results in the development of oxidative modifications not only in cardiomyocytes but also in coronary endothelium, at the transition phase of HF, before the end-stage disease.

Hordeum vulgare L. cv. Bartom seedlings grown on a substrate without or with zeolite were exposed to 450 and 1,000 µmol of Cd(NO3)2. Adding the zeolite to a substrate (+Si) resulted in the accumulation of mono- and polysilicic acids in the leaves, an increase in the growth of seedlings and biomass production, a decrease of the contents of thiobarbituric acid reactive substances (TBARs), and an increase in the activities of the antioxidant enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX) and guaiacol peroxidase (GPX). The negative effects of Cd2+, which were reflected in loss of chlorophyll contents and a decrease of the photosynthesis rate, as well as an increase of TBARs contents were observed in the (−Si)-plants to a greater extent than in the (+Si)-plants. The activities of SOD, APX and GPX increased in the barley leaves of (−Si)- and (+Si)-seedlings with an increase of Cd2+ concentration in the acting solution. At the same time the values of the ratios between TBARs concentrations and the activities of SOD, APX and GPX in (−Si)-plants were higher than that in (+Si)-plants both under optimal conditions and with Cd stress. This suggests that the use of Si-rich mineral zeolite for growing barley stimulates metabolism and increases the resistance of plants to cadmium stress through a shift in the dynamic equilibrium between the rate of oxidative destruction and the activity of antioxidant systems in favor of the latter.

Sickle cell disease (SCD) is a major global health concern. Patients with SCD experience disproportionately greater morbidity and mortality in response to influenza infection than do others. Viral infection is one contributing factor for the development of Acute Chest Syndrome (ACS), a major cause of morbidity and mortality in SCD patients. We determined whether the heightened sensitivity to influenza infection could be reproduced in the two different SCD murine models to ascertain the underlying mechanisms of increased disease severity. In agreement with clinical observations, we found that both genetic and bone marrow-transplanted SCD mice had greater mortality in response to influenza infection than did wild-type animals. Despite similar initial viral titers and inflammatory responses between wild-type and SCD animals during infection, SCD mice continued to deteriorate and failed to resolve the infection, resulting in increased mortality. Histopathology of the lung tissues revealed extensive pulmonary edema and vascular damage following infection, a finding confirmed by heightened vascular permeability following virus challenge. These findings implicate the development of exacerbated pulmonary permeability following influenza challenge as the primary factor underlying heightened mortality. These studies highlight the need to focus on prevention and control strategies against influenza infection in the SCD population.

Oligo(N-vinyl-4,5,6,7-tetrahydroindole-co-butyl vinyl ethers) have been synthesized through free-radical cooligomerization with a yield of 84%. The copolymers are readily soluble in organic solvents (benzene, 1,4-dioxane, chloroform, and tetrahydrofuran), stable up to 380–400°C, and paramagnetic. (The concentration of paramagnetic centers is 1014 spin/g.) In addition, the copolymers exhibit the properties of organic semiconductors. (After being doped with iodine, σ = 1.1 × 10−7 S/cm.) The analysis of the 1H and 13C NMR spectra has shown that the oligomerization reaction is complicated by intramolecular cyclization involving carbon atoms located at the 2-position of pyrrole rings.

Pseudomonas aeruginosa and Escherichia coli are known to be involved in mixed communities in diverse niches. In this study we examined the influence of the predominant form of cell existence of and the exometabolite production by P. aeruginosa strains on interspecies interactions, in vitro. Bacterial numbers of P. aeruginosa and E. coli in mixed plankton cultures and biofilms compared with their numbers in single plankton cultures and biofilms changed in a different way, but were in accordance with the form of P. aeruginosa cell existence. The mass of a mixed-species biofilm was greater than the mass of a single-species biofilm. Among the mixed biofilms, the one with the “planktonic” P. aeruginosa strain had the least biomass. The total pyocyanin and pyoverdin levels were found to be lower in all mixed plankton cultures. Despite this, clinical P. aeruginosa strains irrespective of the predominant form of existence (“biofilm” or “planktonic”) had a higher total concentration of exometabolites than did the reference strain in 12–24 h mixed cultures. The metabolism of E. coli, according to its bioluminescence, was reduced in mixed cultures, and the decrease was by 20- to 100-fold greater with the clinical Pseudomonas strains than the reference Pseudomonas strain. Thus, both the predominant form of existence of and the exometabolite production by distinct P. aeruginosa strains should be considered to fully understand the interspecies relationship and bacteria survival in natural communities.