DHEA and response to antidepressant treatment: A Mendelian Randomization analysis.

Treatment response is hard to predict and detailed mechanisms unknown. Lower levels of the dehydroepiandrosterone sulphate (DHEA(S)) - a precursor to testosterone and estrogen - have been associated to depression and to response to antidepressant treatment. Previous studies however may have been ridden by confounding and reverse causation. The aim of this study is to evaluate whether higher levels of DHEA(S) are causally linked to response to antidepressants using mendelian randomization (MR). We performed a Two-sample MR analysis using data the largest publicly available GWAS of DHEA(S) levels (n = 14,846) using eight common genetic variants associated to DHEA(S) (seven single nucleotide polymorphisms and one variant rs2497306) and the largest GWAS of antidepressant response (n = 5218) using various MR methods (IVW, MR Egger, Weighted mean, weighted mode, MR-PRESSO) and single SNP analysis. We further investigated for pleiotropy conducting a look up on PhenoScanner and GWAS Catalog. Results show no evidence for DHEA(S) gene risk score from any of MR methods, however, we found a significant association on individual variant analysis for rs11761538, rs17277546, and rs2497306. There was some evidence for heterogeneity and pleiotropy. This is the first paper to show some evidence for a causal association of genetically-predicted DHEA and improvement of depressive symptoms. The effect is not a simple linear effect, and we were unable to dissect whether the effect was direct effect of DHEA(S), mediated by DHEA(S) or on the pathway is not yet clear. Further studies using more refined instrumental variables will help clarify this association.

Effect of a light-darkness cycle on the body weight gain of preterm infants admitted to the neonatal intensive care unit.

The Continuous bright light conditions to which premature infants are subjected while hospitalized in Neonatal Intensive Care Units (NICU) can have deleterious effects in terms of growth and development. This study evaluates the benefits of a light/darkness cycle (LDC) in weight and early hospital discharge from the NICU. Subjects were recruited from three participating institutions in Mexico. Eligible patients (n = 294) were premature infants who were hospitalized in the low-risk and high-risk neonatal units classified as stable. The subjects randomized to the experimental group (n = 150) were allocated to LDC conditions are as follows: light from 07:00 to 19:00 and darkness (25 lx) from 19:00 to 07:00. The control group (n = 144) was kept under normal room light conditions (CBL) 24 h a day. Main outcome was weight gain and the effect of reducing the intensity of nocturnal light in development of premature infants. Infants to the LDC gained weight earlier, compared with those randomized to CBL, and had a significant reduction in length of hospital stay. These results highlight those premature infants subjected to a LDC exhibit improvements in physiological development, favoring earlier weight gain and consequently a decrease in hospital stays. ClinicalTrials.gov; 02/09/2020 ID: NCT05230706.

SNPs rs471462296, rs456245081 and rs438495570 in the 5'UTR region of DGAT1 gene in Nelore / SNPs rs471462296, rs456245081 e rs438495570 na região 5'UTR do gene DGAT1 em Nelore

O objetivo desta pesquisa foi avaliar os SNPs rs471462296, rs456245081 e rs438495570 do gene DGAT1 em bovinos Nelore. Foram analisados 109 bovinos. A extração do DNA genômico foi realizada do sangue dos animais, usando-se o kit Ilustra Blood Genomic Prep Mini Spin® (GE Healthcare, UK). A concentração e o grau de pureza do DNA foram determinados por meio de espectrofotômetro (Nanodrop - Thermo Fisher Scientifc, USA). A genotipagem dos SNPs ocorreu mediante o emprego do ensaio Taqman® (Applied Biosystems, USA). Na análise genômica, não foram encontradas alterações nas frequências alélicas e genotípicas (P≥0,05) para os SNPs testados. Dessa forma, a região 5'UTR analisada apresentou-se monomórfica e a variação de SNPs não foi observada, o que limita seu uso como marcadores moleculares para o gene DGAT1 em Nelore.(AU)

CASE-REPORT Association between an ACAN gene variable number tandem repeat polymorphism and lumbar disc herniation: a case control study.

We investigated the association between an aggrecan gene (ACAN) polymorphism and lumbar disc herniation (LDH). This was a case-control study with quinquennial age and gender groups. The study comprised 119 men and women aged between 20 and 60 from Goiânia (Brazil). Of these, 39 were allocated to the case group (Ca) and 80 to the control group (Ct). We gathered sociodemographic and clinical data, and peripheral blood samples. DNA was isolated for genotyping the ACAN variable number tandem repeat (VNTR) via conventional polymerase chain reaction (PCR). Data were statistically analyzed using the chi-square test, multiple comparison analysis, the Student t-test, and odds ratios, with a level of significance set at 5% (P ≤ 0.05). The groups were homogenous in terms of sociodemographic, anthropometric, and life style variables. The allele score for the ACAN VNTR was significantly lower in volunteers with LDH; the A22 allele was significantly more prevalent in this same group; the Ca group presented greater frequency of short alleles A13-A25, whereas the Ct group presented a higher frequency of long alleles. However, this difference was not statistically significant. In both groups, the most common alleles were A28, A27, and A29, and the A26/A26 genotype was significantly more common in the Ca group. The results showed an association between short alleles and LDH among the investigated adults (Ca), corroborating the hypothesis that aggrecan with shorter repeat lengths can lead to a reduction in the physiological proteoglycan function of intervertebral disc hydration and, consequently, increased individual susceptibility to LDH.

Seasonal aspects of reproductive physiology in captive male maned wolves (Chrysocyon brachyurus, Illiger 1815).

The aim of the study was to evaluate the seasonality of andrological characteristics and hormonal profile of captive maned wolves (Chrysocyon brachyurus, Illiger 1811). Three adult males were evaluated from the Companhia Brasileira de Metalurgia e Mineração Scientific Breeding Center in Araxá, MG, Brazil, over 13 months. Semen was collected 2-3 times weekly and analysed. Scrotal circumference, biometrics and testicular volume were measured. Stool samples were collected 2-3 times weekly to analyse corticosteroid and testosterone metabolite concentrations. A success rate of 100% was achieved in the collection attempts during the breeding season (BS) and 77.8% during the non-breeding season (NBS). The interval to achieve penile erection was 1-5 min in the BS and 6-10 in the NBS (p < 0.001). Of the ejaculates collected, 80.0% contained sperm during BS, while 28.6% did during the NBS. The ejaculate had only one fraction, was odourless, predominantly translucent (72.4%), with a watery appearance, pH 6.7 and osmolarity of 352.8 mOsmol. Seasonal influences were seen in ejaculate volume (1.3 ml vs 0.4 ml), number of spermatozoa per ejaculate (73.9 × 10(6) vs 6.1 × 10(6) ) and percentage of live sperm (82.0% vs 66.1%) between the BS and NBS (p < 0.05), respectively. A high percentage of major sperm defects were observed in both seasons (50.1% in BS; 65.7% in NBS). Testicular volume was larger (p < 0.05; right testicles 13.1 cm(3) in BS vs 4.0 cm(3) in NBS, while left testicles 12.9 cm(3) in BS vs 5.3 cm(3) in NBS) and testicular consistency increased in the BS. No difference was seen in the basal faecal metabolite concentrations of testosterone; however, the corticosteroid concentrations were higher in the BS. Based on these results, it is possible to conclude that the collection of semen is feasible in captive maned wolves without compromising libido, seminal characteristics and reproductive behaviour and that sperm production is influenced by seasonality; however, it appears that there is no seasonal influence on basal testosterone concentrations.

Susceptibility to chemical insecticides of two Brazilian populations of the visceral leishmaniasis vector Lutzomyia longipalpis (Diptera: Psychodidae).

OBJECTIVES: To investigate the insecticide susceptibility of two geographically separated Lutzomyia longipalpis populations (Lapinha and Montes Claros) with different histories of insecticide exposure (i.e. no exposure and repeated exposure, respectively). METHODS: (i) Bioassay monitoring of sand fly survival over time when exposed to a range of insecticides; and (ii) analysis of the level of insecticide detoxification enzymes in individual sand flies caught at both study sites. Insecticides tested were the organophosphates malathion and fenitrothion and the pyrethroids lambda-cyhalothrin, permethrin and deltamethrin. RESULTS: Survival analyses showed that whilst there was no overall significant difference in susceptibility of both populations to organophosphates, Lapinha sand flies were significantly more susceptible to pyrethroids than those from Montes Claros. Multiple regression analyses also showed that insecticide susceptibility in both locations varied with sand fly sex. The relative susceptibilities of the two sand fly populations to tested insecticides were also compared. Thus, Montes Claros sand flies were most susceptible to malathion, followed by fenitrothion, deltamethrin and permethrin. Those from Lapinha were most susceptible to lambda-cyhalothrin, followed by malathion, permethrin, deltamethrin and fenitrothion. Biochemical analyses demonstrated that Montes Claros sand flies had significantly lower insecticide detoxification enzyme activity than Lapinha sand flies. CONCLUSIONS: Our results are the first record of significantly reduced susceptibility to the insecticides used in control of wild populations of Lu. longipalpis. They demonstrate the importance of evaluating chemicals against this species by conventional bioassay and microplate assays before and during spraying programmes.

Comparison of serum hormone levels of captive and free-living maned wolves Chrysocyon brachyurus.

Serum hormone levels were compared between captive and free-living maned wolves and seasonal variations of sex hormones were studied. Blood samples were collected from 16 male and 26 female adult animals from Brazilian zoos, and from 30 male and 24 female free-living adults to determine serum progesterone and testosterone by radioimmunoassay. Serum testosterone concentrations varied (P < 0.05) across seasons for 16 captive males, being higher in autumn (2184.7 +/- 355.1 pg/mL) than in summer (1080.7 +/- 205.4 pg/mL), winter (1270.1 +/- 276.6 pg/mL) and spring (963.9 +/- 248.1 pg/mL), although they did not differ between summer, winter and spring. Testosterone concentration of 30 free-living males differed (P < 0.05) between autumn (824.1 +/- 512.2 pg/mL), winter (14.4 +/- 8.0 pg/mL) and spring (151.9 +/- 90.5 pg/mL). Comparison between captive and free-living animals showed no difference in autumn (P > 0.05). Sixteen captive males showed higher testosterone concentration during winter and spring compared with 30 free-living animals (P < 0.05). Progesterone concentration varied among seasons in 26 captive females (P < 0.05), being higher in autumn (15.3 +/- 3.1 ng/mL) than in summer (6.6 +/- 1.5 ng/mL), winter (5.3 +/- 3.1 ng/mL) and spring (4.3 +/- 0.7 ng/mL). Progesterone concentration of 24 free-living females varied between autumn (17.1 +/- 6.0 ng/mL) and winter (1.7 +/- 0.3 ng/mL) (P < 0.05), but we could not obtain data for spring or summer. No difference in progesterone levels was observed between captive and free-living females in autumn and winter.

Comparison of serum hormone levels of captive and free-living maned wolves Chrysocyon brachyurus

Serum hormone levels were compared between captive and free-living maned wolves and seasonal variations of sex hormones were studied. Blood samples were collected from 16 male and 26 female adult animals from Brazilian zoos, and from 30 male and 24 female free-living adults to determine serum progesterone and testosterone by radioimmunoassay. Serum testosterone concentrations varied (P < 0.05) across seasons for 16 captive males, being higher in autumn (2184.7 ± 355.1 pg/mL) than in summer (1080.7 ± 205.4 pg/mL), winter (1270.1 ± 276.6 pg/mL) and spring (963.9 ± 248.1 pg/mL), although they did not differ between summer, winter and spring. Testosterone concentration of 30 free-living males differed (P < 0.05) between autumn (824.1 ± 512.2 pg/mL), winter (14.4 ± 8.0 pg/mL) and spring (151.9 ± 90.5 pg/mL). Comparison between captive and free-living animals showed no difference in autumn (P > 0.05). Sixteen captive males showed higher testosterone concentration during winter and spring compared with 30 free-living animals (P < 0.05). Progesterone concentration varied among seasons in 26 captive females (P < 0.05), being higher in autumn (15.3 ± 3.1 ng/mL) than in summer (6.6 ± 1.5 ng/mL), winter (5.3 ± 3.1 ng/mL) and spring (4.3 ± 0.7 ng/mL). Progesterone concentration of 24 free-living females varied between autumn (17.1 ± 6.0 ng/mL) and winter (1.7 ± 0.3 ng/mL) (P < 0.05), but we could not obtain data for spring or summer. No difference in progesterone levels was observed between captive and free-living females in autumn and winter.

Structure of human uropepsin at 2.45 A resolution.

The molecular structure of human uropepsin, an aspartic proteinase from the urine produced in the form of pepsinogen A in the gastric mucosa, has been determined by molecular replacement using human pepsin as the search model. Crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 50.99, b = 75.56, c = 89.90 A. Crystallographic refinement led to an R factor of 0.161 at 2.45 A resolution. The positions of 2437 non-H protein atoms in 326 residues have been determined and the model contains 143 water molecules. The structure is bilobal, consisting of two predominantly beta-sheet lobes which, as observed in other aspartic proteinases, are related by a pseudo-twofold axis. A model of the uropepsin-pepstatin complex has been constructed based on the high-resolution crystal structure of pepsin complexed with pepstatin.

Molecular model for the binary complex of uropepsin and pepstatin.

The three-dimensional structure of human uropepsin complexed with pepstatin has been modelled using human pepsin as a template. Uropepsin is an aspartic proteinase from the urine, produced in the form of pepsinogen A in the gastric mucosa. The structure is bilobal, consisting of two predominantly beta-sheet lobes which, as observed in other aspartic proteinases, are related by a pseudo twofold axis. A structural comparison between binary complexes of pepsin:pepstatin and uropepsin:pepstatin is discussed.

Crystallization, preliminary X-ray analysis and Patterson search of a new aspartic protease isolated from human urine.

Aspartic protease (EC 3.4.23) make up a widely distributed class of enzymes in animals, plants, microbes and, viruses. In animals these enzymes perform diverse functions, which range from digestion of food proteins to very specific regulatory roles. In contrast the information about the well-characterized aspartic proteases, very little is known about the corresponding enzyme in urine. A new aspartic protease isolated from human urine has been crystallized and X-ray diffraction data collected to 2.45 A resolution using a synchrotron radiation source. Crystals belong to the space group P2(1)2(1)2(1). The cell parameters obtained were a = 50.99, b = 75.56 and c = 89.90 A. Preliminary analysis revealed the presence of one molecule in the asymmetric unit. The structure was determined using the molecular replacement technique and is currently being refined using simulated annealing and conjugate gradient protocols.

Total serum IgE and parasite-specific IgG and IgA antibodies in human strongyloidiasis.

Total serum IgE, and Strongyloides-specific IgG and IgA antibodies were studied in 27 patients with parasitologically proven strongyloidiasis. Clinical manifestations in this case series were investigated by a retrospective study of the patient's records. Total serum IgE levels were elevated (greater than 250 IU/ml) in 59% of the patients (mean concentration = 1364 IU/ml). Parasite-specific IgG and IgA antibodies were detected by ELISA in the serum of 23 (85.2%) and 21 (77.8%) patients, respectively. Elevated serum IgE and clinical manifestations were not useful indexes of the presence of strongyloidiasis. On the other hand, our results support the view that serologic tests, particularly ELISA for detecting Strongyloides-specific IgG antibodies, can be usefully exploited for diagnostic purposes in strongyloidiasis.