Treating cutaneous T-cell lymphoma with highly irregular surfaces with photon irradiation using rice as tissue compensator.

PurposeCutaneous T-cell lymphoma (CTCL) is known to have an excellent response to radiotherapy, an important treatment modality for this disease. In patients with extremity and digit involvement, the irregular surface and depth variations create difficulty in delivering a homogenous dose using electrons. We sought to evaluate photon irradiation with rice packing as tissue equivalence and determine clinical tolerance and response.Materials and methodsThree consecutive CTCL patients with extensive lower extremity involvement including the digits were treated using external beam photon therapy with rice packing for tissue compensation. The entire foot was treated to 30-40 Gy in 2-3 Gy per fraction using 6 MV photons prescribed to the mid-plane of an indexed box filled with rice in which the foot was placed. Treatment tolerance and response were monitored with clinical evaluation.ResultsAll patients tolerated the treatment without treatment breaks. Toxicities included grade 3 erythema and desquamation with resolution within 4 weeks. No late toxicities were observed. All patients had a partial response by 4 weeks after therapy with two patients achieving a complete response. Patients reported improved functionality after treatment. No local recurrence has been observed.ConclusionTissue compensation with rice packing offers a convenient, inexpensive, and reproducible method for the treatment of CTCL with highly irregular surfaces

Regional Distribution of GHG Emissions from Livestock Enteric Fermentation and Manure Management in the Republic of Macedonia in the Period 2007-2012

The estimation of GHG emission from domestic livestock in the Republic of Macedonia during the period from 2007-2012 is performed according to the IPCC Good Practice Guidance and Uncertainty Management in National Greenhouse Gas Inventories applying the Tier 1 method for calculation of emissions. This article has accepted the following gasses: Methane (CH4), Nitrous oxide and CO2-eq from the domestic livestock sub sector using data sources from the official Statistical Yearbooks of the Republic of Macedonia. According to available data for livestock species, distribution of total annual methane emission and nitrogen excretion was calculated in each planning region for the period 2007-2012. In the analyzed period two regions showed continuously highest (Southeast region) and lowest (Vardar region) CH4 emission and nitrogen excretion. In the period 2007-2012 CH4 emission ranged between 26.43 Gg (2007) and 23.78 Gg (2012), with the lowest value in 2012 (23.78 Gg). Depending on the animal waste management system the highest value for nitrogen excretion (solid storage and drylot) was observed in 2010 (kt/N/yr). Almost similar value for nitrogen excretion from pasture and paddock was observed in 2007 and 2008, 9.54 and 9.53 kt/N/yr respectively, with the lowest value for analyzed period noted in 2009 (8.82 kt/N/yr). In this period the highest value (3.32 kt/N/yr) for other type of AWMS was recorded in 2007. Separation of certain regions in the country regarding GHG emission can be clearly noted. Data for the period 2007-2012 show a downward trend in GHG emission. Applications of modern breeding technology, balanced feed as well as better feed quality in the future are the main objectives in order to reduce GHGs emission from this subsector

Proizvodnja i sastav mleka autohtone rase ovaca u Makedoniji

Several production traits have been examined in 180 Ovchepolian sheep during a four-year production period (2010-2013). The sheep ranged in age from the first to the 7th lactation and 4319 individual lactation controls were realized in total. Besides the basic statistics, all data were analysed using a multi-factorial fixed model. The influence of certain factors was studied using the F-test and the analyses were made using the SPSS set of programs. Most of the factors (year, lactation, lambing month and number of milk recording) had a highly significant influence (P (lt) 0.001) on daily milk production (milk from the morning, evening and the total amount of milk, % of milk fat and kg fat) in this breed of sheep. The month of milk recording also had a significant influence (P (lt) 0.05) on all traits. Only fertility had no impact on the variations in the tested parameters, aside from the total daily milk, on which a highly significant influence was manifested (P (lt) 0.01). The average milk lactation among the tested sheep population during all four years was, on average, 58 ± 0.247 l, while the production of milked milk for the same period was 37 ± 0.217 l. The length of the lactation period in these sheep for the four years studied averaged 182 ± 0.31 days. The maximal daily milk yield in this sheep population was measured in 2011 (0.302 ± 0.26 l). Regarding their age, the highest daily milk yield was determined in sheep in the third lactation (0.365 ± 0.26), while those in the 7th lactation had the lowest (0.255 ± 0.27).Ispitivano je nekoliko proizvodnih svojstava (laktacijska proizvodnja mleka, proizvodnja mleka u dojnom periodu, proizvodnja mleka u muznom periodu, dužina dojnog perioda, dužina laktacije, proizvodnja mleka u toku jutarnje muže, proizvodnja mleka u toku večernje muže i dnevna proizvodnja mleka) kod ukupno 180 ovcepoljskih ovaca, u toku četiri proizvodne godine (2010-2013). Uzrast ovaca bio je od prve do sedme laktacije, i kod njih je bilo realizovano ukupno 4319 individualnih laktacijskih kontrola. Osim bazične statistike, svi podaci su analizirani pomoću višefaktorijalnog fiksnog modela. Uticaj posebnih faktora ispitivan je pomoću F-testa, dok su analize urađene pomoću programskog paketa SPSS. Veći broj faktora (godina, laktacija, mesec jagnjenja i broj kontrole mleka), imali su visoko značajni uticaj (P (lt) 0,001), na dnevnu proizvodnju mleka (jutarnje, večernje i ukupno mleko, % mlečne masti i kg mlečne masti), kod ove rase ovaca. Mesec kontrole mleka u odnosu na sva svojstva imao je visoko značajni uticaj (P (lt) 0,001), osim na % mlečne masti (P>0,05). Jedino plodnost nije imala nikakav uticaj na varijacije ispitivanih parametara, osim na ukupnu dnevnu produkciju mleka, na koju je manifestovala visoko značajni uticaj (P (lt) 0,001). Prosečna laktacijska mlečnost kod ispitivane populacije ovaca, sa sve četiri godine u proseku je bila 58 ± 0,247 l, dok je proizvodnja muznog mleka u istom periodu bila 37 ± 0,217 l. Dužina laktacijskog perioda u toku četiri ispitivane godine u proseku je bila 182 ± 0,31 dana. Maksimalna dnevna mlečnost kod ove rase ovaca, izmerena je u toku 2011. godine (0,302 ± 0,26 l). U odnosu na starost, najveća dnevna mlečnost je utvrđena kod ovaca u trećoj laktaciji (0,365 ± 0,26), a najniža u sedmoj laktaciji (0,255 ± 0,27)

Egg Quality Characteristics in Autochthonous Genotypes of Chickens Raised on Macedonian Rural Farms

Egg quality characteristics of three different autochthonous chicken phenotypes (phenotype having ashy-silvery-brown leghorn laced plumage color, phenotype having light brown spangled plumage color and phenotype having black or blue plumage color) were examined. These types of chickens are mainly raised as backyard rural area flocks in the villages of R. Macedonia. The data were collected through first systematic approaches in phenotypical identification and characterisation of these autochthonous genotypes realized recently. Three small flocks of old hens collected from different villages and placed in control pens were established. No data about number of eggs/hen/year is available for the established flocks. Further investigations are needed to record productive (number of egg produced) and reproductive data. The plan was that additional, yearly production records be collected from the flock produced as offspring from established flock of old hens collected from different villages and placed in control pens. Set of 90 eggs was collected (30 eggs from each plumage phenotype) and basic egg quality parameters measured. Egg size (weight) was 50.71g for brown laced plumage phenotype, 60.48g for blue plumage phenotype and 52.6 g for light brown spangled plumage phenotype. Egg shell strength was 3965, 3628 and 3924 g/cm2 for brown laced, blue and brown spangled plumage phenotype, respectively. Light brown spangled plumage phenotype had the highest value of yolk color (10.29) and Hough Units (76.63) compared to brown laced (10.08 and 75.27) and blue (9.09 and 71.65) plumage phenotype

Ethanol-induced GABAA receptor alpha4 subunit plasticity involves phosphorylation and neuroactive steroids

GABAA receptors containing α4 subunits are widely implicated in acute ethanol sensitivity, and their spatial and temporal regulation prominently contributes to ethanol-induced neuroplasticity in hippocampus and cortex. However, it is unknown if α4-containing GABAA receptors in the thalamus, an area of high α4 expression, display similar regulatory patterns following ethanol administration, and if so, by which molecular mechanisms. In the current study, thalamic GABAA receptor α4 subunit levels were increased following a 6-week, but not a 2-week chronic ethanol diet. Following acute high-dose ethanol administration, thalamic GABAA receptor α4 subunit levels were regulated in a temporal fashion, as a decrease was observed at 2 hours followed by a delayed transient increase. PKCγ and PKCδ levels paralleled α4 temporal expression patterns following ethanol exposure. Initial decreases in α4 subunit expression were associated with reduced serine phosphorylation. Delayed increases in expression were not associated with a change in phosphorylation state, but were prevented by inhibiting neuroactive steroid production with the 5α-reductase inhibitor finasteride. Overall, these studies indicate that thalamic GABAA receptor α4 subunit expression following acute and chronic ethanol administration exhibits similar regulatory patterns as other regions and that transient expression patterns following acute exposure in vivo are likely dependent on both subunit phosphorylation state and neuroactive steroids

Differential hypothalamic–pituitary–adrenal activation of the neuroactive steroids pregnenolone sulfate and deoxycorticosterone in healthy controls and alcohol-dependent subjects

Ethanol and the neuroactive steroids have interactive neuropharmacological effects and chronic ethanol administration blunts the ethanol-induced increase in neuroactive steroid levels in rodent plasma and brain. Few studies have explored neuroactive steroid regulation in alcohol-dependent human subjects. In fact, the regulation of adrenal neuroactive steroids has not been well defined in healthy controls. We thus explored the regulation of two neuroactive steroids, pregnenolone sulfate (PREG-S) and deoxycorticosterone, by pharmacological challenges to the hypothalamic-pituitary-adrenal (HPA) axis in healthy controls and one-month abstinent alcohol-dependent patients with co-occurring nicotine dependence. Plasma levels of PREG-S and deoxycorticosterone were measured by radioimmunoassay in controls and alcohol-dependent patients after challenges of naloxone, ovine corticotrophin releasing hormone (oCRH), dexamethasone, cosyntropin, and cosyntropin following high-dose dexamethasone. In addition, basal diurnal measures of both hormones were obtained. PREG-S plasma levels in healthy controls were increased by cosyntropin challenge (with and without dexamethasone pretreatment) and decreased by dexamethasone challenge. However, PREG-S concentrations were not altered by naloxone or oCRH challenges, suggesting that PREG-S is not solely regulated by hypothalamic or pituitary stimulation. Deoxycorticosterone, in contrast, is regulated by HPA challenge stimulation in a manner similar to cortisol. Alcohol-dependent patients had a blunted PREG-S response to cosyntropin (with and without dexamethasone pretreatment). Furthermore, the time to peak deoxycorticosterone response following oCRH was delayed in alcohol-dependent patients compared to controls. These results indicate that plasma PREG-S and deoxycorticosterone levels are differentially regulated by HPA axis modulation in human plasma. Further, alcohol-dependent patients show a blunted PREG-S response to adrenal stimulation and a delayed deoxycorticosterone response to oCRH challenge

Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits.

Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene-trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits

Genetic Analysis of the Neurosteroid Deoxycorticosterone and Its Relation to Alcohol Phenotypes: Identification of QTLs and Downstream Gene Regulation

Deoxycorticosterone (DOC) is an endogenous neurosteroid found in brain and serum, precursor of the GABAergic neuroactive steroid (3α,5α)-3,21-dihydroxypregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) and the glucocorticoid corticosterone. These steroids are elevated following stress or ethanol administration, contribute to ethanol sensitivity, and their elevation is blunted in ethanol dependence.To systematically define the genetic basis, regulation, and behavioral significance of DOC levels in plasma and cerebral cortex we examined such levels across 47 young adult males from C57BL/6J (B6)×DBA/2J (D2) (BXD) mouse strains for quantitative trait loci (QTL) and bioinformatics analyses of behavior and gene regulation. Mice were injected with saline or 0.075 mg/kg dexamethasone sodium salt at 8:00 am and were sacrificed 6 hours later. DOC levels were measured by radioimmunoassay. Basal cerebral cortical DOC levels ranged between 1.4 and 12.2 ng/g (8.7-fold variation, p<0.0001) with a heritability of ∼0.37. Basal plasma DOC levels ranged between 2.8 and 12.1 ng/ml (4.3-fold variation, p<0.0001) with heritability of ∼0.32. QTLs for basal DOC levels were identified on chromosomes 4 (cerebral cortex) and 14 (plasma). Dexamethasone-induced changes in DOC levels showed a 4.4-fold variation in cerebral cortex and a 4.1-fold variation in plasma, but no QTLs were identified. DOC levels across BXD strains were further shown to be co-regulated with networks of genes linked to neuronal, immune, and endocrine function. DOC levels and its responses to dexamethasone were associated with several behavioral measures of ethanol sensitivity previously determined across the BXD strains by multiple laboratories.Both basal and dexamethasone-suppressed DOC levels are positively correlated with ethanol sensitivity suggesting that the neurosteroid DOC may be a putative biomarker of alcohol phenotypes. DOC levels were also strongly correlated with networks of genes associated with neuronal function, innate immune pathways, and steroid metabolism, likely linked to behavioral phenotypes