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Before weaning, breast milk is the physiological form of neonatal nutrition, providing pups with all nutrient requirements. Maternal low-protein diet (LPD) during pregnancy and lactation induces adverse changes in key maternal organs, which have negative effects on pup development. We studied the effects of maternal LPD on liver weight, mammary gland (MG) cell differentiation, milk composition and production and pup development throughout lactation. We fed rats with control (C) or LPD (R) during pregnancy and lactation. At 7 d early, 14 d mid and 21 d late lactation stages, maternal biochemical parameters, body, liver and MG weights were analysed. MG cell differentiation was analysed by haematoxylin and eosin staining; milk nutrient composition and production were studied; pup body, liver and brain weights, hippocampal arachidonic acid (AA) and DHA were quantified. Results showed lower body and liver weights, minor MG cell differentiation and lower serum insulin and TAG in R compared with C. R milk contained less protein and higher AA at early and mid stages compared with C. R pup milk and fat intake were lower at all stages. R protein intake at early and mid stages and DHA intake at mid and late stages were lower compared with C. In R pups, lower body, liver and brain weights were associated with decreased hippocampal AA and DHA. We conclude that maternal LPD impairs liver and MG function and induces significant changes in maternal milk composition, pup milk intake and organ development.
Background: SMA1 is a neurodegenerative disease caused by bi-allelic survival motor neuron 1 gene (SMN1) deletion/mutation. In the phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA1 patients. We report preliminary data of STR1VE, a pivotal study (NCT03306277) evaluating efficacy and safety of a one-time intravenous AVXS-101 infusion. Methods: STR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged <6 months (bi-allelic SMN1 loss, 2xSMN2). Primary outcomes: independent sitting for ≥30 seconds (18 months) and survival (14 months). Secondary outcomes: ability to thrive and ventilatory support (18 months). Exploratory outcomes: CHOP-INTEND and Bayley Scales of Infant and Toddler Development scores. Results: Enrollment is complete with 22 patients dosed. Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support, and all exclusively fed by mouth. Mean baseline CHOP-INTEND score was 32.6 (17.0–52.0), which increased 6.9 (-4.0–16.0, n=20), 10.4 (2.0–18.0, n=12), and 11.6 (-3.0–23.0, n=9) points at 1, 2, and 3 months; updates provided at congress. Conclusions: Preliminary data from STR1VE show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.
The new species Lenonchium zanjanense sp. n. is described from a natural habitat of Zanjan province, Iran, including line, light microscopy and scanning electron microscopy illustrations and a molecular (18S, 28S) study. It is characterized by its 3.50–4.51 mm long body, rounded lip region, continuous and 13.5–15.5 µm broad, odontostyle 21–24 µm long, neck 362–490 µm long, double guiding ring, pharyngeal expansion 190–285 µm long, female genital system didelphic–amphidelphic, uterus simple and 185–320 µm long or 3.4–5.9 times the corresponding body diameter, vulva nearly equatorial (V = 45–53), tail conical-elongated to filiform (90–165 µm, c = 23–43, c′ = 2.4–5.3) with three or four mucro-like projections at the tip, spicules 58–64 µm long and 16–21 contiguous ventromedian supplements ending at the level of the anterior end of the spicules. The taxonomy of the genus is updated, with an emended diagnosis, list of species, key to their identification and a compendium of their main morphometrics. Lenonchium asterocaudatum is regarded as identical and a junior synonym of L. denticaudatum. New insights into the phylogeny of the group are also provided, and the classification of Lenonchium within Nordiidae is seriously questioned.
This work reports by the first time a method to control the geometry of Ga2O3 films nanocrystallites at 350 °C. The formation of controlled shaped nano-crystallites of γ-Ga2O3 from amorphous Ga2O3 films grown by RF-Sputtering at room temperature driven by nano-layers of group IB metals (Cu, Ag or Au) is studied. The reported results can be explained by the role of subsurface metal nano-layers and the non-equilibrium nature of the sputtering processes. To study the effects on the surface structure and their optical properties arrays of amorphous-Ga2O3/IB-metal/amorphous-Ga2O3 were annealed in dry N2 atmosphere at 350 °C by 50, 100 and 150 min. The experimental results can be explained by the evolution of the amorphous character of the films amorphous films towards the nanocrystalline γ-Ga2O3 phase driven by the metal nano-layer seed nature. As the annealing time was increased the transition from amorphous-Ga2O3 to the nanocrystalline γ-Ga2O3 phase was detected by X-ray diffraction analysis. The transition to the nanocrystalline γ-Ga2O3 is demonstrated by the formation of octahedral, triangle and ball shape nanocrystallites with sizes of ∼5 to 50 nm according to FE-SEM analysis. The influence of the metal nano-layer is clearly seen by the shift of the plasmon frequency resonance produced by the Ga2O3/IB-metal/Ga2O3 arrays in the region from 400 to 600 nm caused by the modification of the interface Ga2O3/IB-metal produced by the applied annealing stages.
Two new species of the genus Aporcelinus from the USA are described and illustrated. Aporcelinus floridensis sp. n. is characterized by its 1.12–1.52 mm long body, lip region offset by marked constriction and 14.5–17.0 μm broad with perioral liplets, odontostyle 16.5–20.0 μm at its ventral side and 1.1–1.2 times the lip region diameter, neck 316–395 μm long, pharyngeal expansion occupying 43–48% of total neck length, uterus simple and 33–56 μm long or 0.8–1.2 times the corresponding body diameter, V = 48–54, female tail conical (36–49 μm long, c = 27–41, c’ = 1.2–2.0) with finely rounded terminus and no hyaline portion, and male absent. Aporcelinus paolae sp. n. is characterized by its 1.29–1.80 mm long body, lip region offset by marked constriction and 14–16 μm broad, odontostyle 15–17 μm at its ventral side and 1.0–1.1 times the lip region diameter, neck 314–397 μm long, pharyngeal expansion occupying 43–53% of total neck length, uterus tripartite and 128–164 μm long or 2.6–3.6 times the corresponding body diameter, V = 53–57, female tail conical (30–39 μm long, c = 40–51, c’ = 1.1–1.3) with finely rounded terminus and variably re-curved dorsad, male tail conical (27–36 μm, c = 39–59, c’ = 0.9–1.2), ventrally straight and dorsally convex, spicules 48–54 μm long, and 7–9 irregularly spaced ventromedian supplements lacking hiatus. The analyses of the D2-D3 expansion segments of 28S rRNA (LSU) gene sequences of the two new species confirmed the monophyly of the genus, based upon currently available data, showing a close relationship between the genera Aporcelinus and Makatinus, and justified the placement of Aporcelaimellus, Makatinus and Aporcelinus under the subfamily Aporcelaimellinae.
Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.
Here we evaluated the effect of fermented milk supplemented with whey protein (approximately 80 % protein), probiotic (Bifidobacterium animalis subsp. lactis BB12) and pomegranate juice (Punica granatum L.) on the physical performance, intestinal motility and villi structure, inflammatory markers and intestinal microbiota of rats under high-intensity acute exercise. In all, twenty-four Wistar rats were separated into groups: control (Ctrl), supplemented (Supp), exercised (Exe) and exercised and supplemented (Exe+Supp). Rats in the Supp groups received fermented milk during 6 weeks by oral administration. At the end of the supplementation period, the Exe groups were submitted to high-intensity acute exercise on a treadmill. We found that intense acute exercise caused changes in the intestinal villi interspace, changes in the proportion of Lactobacillus species and an increase in Clostridium species, as well as a decrease in intestinal motility. Supplementation increased intestinal motility, and maintained the intestinal villi interspace and the natural microbiota proportions of the exercised rats. Physical performance was not improved by fermented milk supplementation. We conclude that the fermented milk containing whey protein, B. animalis (BB12) and pomegranate juice can re-establish intestinal microbiota and protect the animals from the undesirable effects of intense acute exercise.
A study of short period high amplitude Dwarf Cepheid stars has been undertaken in order to discriminate between the two possible models, namely Bessel's (1969) proposal of low mass Pop. II or old Pop. I. The telecsope utilized was the 1.5 m at the SPM Observatory. The Danish spectrophotometer that allows the simultaneous acquisition of data in the uvby filters and almost simultaneously in the Hβ narrow and wide niters was attached. With this advantage of simultaneous observations, no phasing adjustment was needed, eliminating the risks of losing information due to amplitude varition explained either by multiple periodicity or by the Blazhko effect. We have restricted our discussion to the descending branch and light minimum phase interval between 0.175 to 0.725. For this interval the unreddened indices (b – y)0 and (cl)0 were calculated as in Nissen (1988), which will serve to determine the effective gravity and temperature variation of both stars, through the model atmsphere calibrations by Breger (1974), based on the ATLAS and Kurucz model atmospheres. Mean log g values of 4.0 and 4.33, and mean temperatures of 7500 and 7700 K were determined for DY Her and BP Peg, respectively. It can be concluded that both pulsating stars DY Her and BP Peg are Pop.I, normal Dwarf Cepheid stars.
The new species Metaxonchium toroense n. sp. from natural habitats of Costa Rica is described, including light microscopy (LM), scanning electron microscopy (SEM) and molecular (D2–D3 28S rDNA) analyses. The new species is characterized by its general size, the dimensions and appearance of its lip region, the length of the odontostyle and its fusiform aspect, the length of the neck and its pharyngeal expansion, the reduction of the anterior genital branch to a very short uterine sac without any rudiment of ovary or oviduct, tripartite and non-echinophor posterior uterus, the somewhat posterior vulva position, the length and shape of the caudal region, and the absence of males. Molecular analyses, the first to be performed on a Metaxonchium species, show a close relationship of the new species with representatives of the genera Axonchoides and Syncheilaxonchium.
A new species belonging to the genus Belondira is described from natural areas in Iran. Belondira coomansi n. sp. is characterized by its general size, the dimensions and appearance of its lip region, presence of distinct labial and post-labial sclerotization, the length of the odontostyle and its inconspicuous lumen and aperture, the length of the neck and its pharyngeal expansion, the reduction of the female anterior genital branch to a simple uterine sac, a very short posterior uterus, the anterior position of the vulva, the length and shape of the caudal region with distinctly thick cuticle at its tip, the length of the spicules, and the presence of only one pair of ventromedian supplements. The new species is close to Belondira brevibulba, B. sacchari, B. tenuidens and B. thornei, and it is compared to them. Molecular characterization (D2–D3 expansion segments of the rRNA large subunit) of the new species is also provided, representing only the second species of this genus for which any DNA sequence data are available.
The central star of NGC 2346 is a well known binary with an A-type primary and a hot companion (Méndez and Niemela 1981). The star went through a series of periodic light variations which ceased in 1986 and were interpreted as an eclipse of a dust cloud passing in front of the binary system (e.g. Méndez et al. 1982, Costero et al. 1986). Recently, light variations reappeared with shallower minima compared to the previous eclipse (e.g. Kohoutek et al. 1992).
A new genus and new species, Tarantobelus arachnicida, was found in the oral opening of tarantula spiders bred in captivity in Poland. The new species is characterized by having a small body (0.77–0.95 mm long in females and 0.66–0.84 mm in males), cuticle poorly annulated by transverse incisures, lateral field inconspicuous, lips separated with small cuticular flaps topping each lip, stoma panagrolaimoid with gymnostom well developed with robust and refringent rhabdia, pharynx panagrolaimoid with isthmus slightly longer than the basal bulb, intestine with cardiac (anterior) and rectal (posterior) areas with narrower walls. Mature females with intestinal cells including needle crystal packs, excretory pore at isthmus level, female reproductive system panagrolaimoid with post-vulval sac 0.4–0.8 times the length of the corresponding body diameter and having very thick walls, vulva very prominent, female rectum 0.8–1.3 times the length of the anal body diameter, female tail conical with acute tip with phasmids at 58–62% of its length. Male tail conical with long and thin mucro, spicules ventrad bent having rounded manubrium and thick gubernaculum. Description, measurements and illustrations of the new species are provided. Molecular analyses show its relationship with Brevibucca and Cuticonema. On the other hand, Medibulla and its corresponding subfamily Medibullinae, previously in Osstellidae, are transferred to Panagrolaimidae, being Shahnematinae, the junior synonym of Medibullinae. Indocephalobus, recently proposed and located in the family Panagrolaimidae, is considered a junior synonym of Diplogastrellus (Diplogasteromorpha), and its only species, I. zebrae, is considered a junior synonym of D. gracilis. In addition, a key to identification of panagrolaimoid genera is included.
Slaughter is a crucial step in the meat production chain that could induce psychological stress on each animal, resulting in a physiological response that can differ among individuals. The aim of this study was to investigate the relationship between an animal’s emotional state, the subsequent psychological stress at slaughter and the cellular damage as an effect. In all, 36 entire male pigs were reared at an experimental farm and a cognitive bias test was used to classify them into positive bias (PB) or negative bias (NB) groups depending on their decision-making capabilities. Half of the animals, slaughtered in the same batch, were used for a complete study of biomarkers of stress, including brain neurotransmitters and some muscle biomarkers of oxidative stress. After slaughter, specific brain areas were excised and the levels of catecholamines (noradrenaline (NA) and dopamine (DA)) and indoleamines (5-hydroxyindoleacetic acid and serotonin (5HT)) were analyzed. In addition, muscle proteasome activity (20S), antioxidant defence (total antioxidant activity (TAA)), oxidative damage (lipid peroxidation (LPO)) and autophagy biomarkers (Beclin-1, microtubule-associated protein I light chain 3 (LC3-I) and LC3-II) were monitored during early postmortem maturation (0 to 24 h). Compared with PB animals, NB pigs were more susceptible to stress, showing higher 5HT levels (P<0.01) in the hippocampus and lower DA (P<0.001) in the pre-frontal cortex. Furthermore, NB pigs had more intense proteolytic processes and triggered primary muscle cell survival mechanisms immediately after slaughter (0 h postmortem), thus showing higher TAA (P<0.001) and earlier proteasome activity (P<0.001) and autophagy (Beclin-1, P<0.05; LC3-II/LC3-I, P<0.001) than PB pigs, in order to counteract the induced increase in oxidative stress, that was significantly higher in the muscle of NB pigs at 0 h postmortem (LPO, P<0.001). Our study is the first to demonstrate that pig’s cognitive bias influences the animal’s susceptibility to stress and has important effects on the postmortem muscle metabolism, particularly on the cell antioxidant defences and the autophagy onset. These results expand the current knowledge regarding biomarkers of animal welfare and highlight the potential use of biomarkers of the proteasome, the autophagy (Beclin-1, LC3-II/LC3-I ratio) and the muscle antioxidant defence (TAA, LPO) for detection of peri-slaughter stress.
In cattle, reduced reproductive efficiency of beef and milk production systems is attributed to nutritional factors, health, climate changes and ultimately to genetic characteristics of animals. However, under warm humid tropics genetic variations between breeds could reduce age first calving, calving interval and increase the life of cows. Sanmartinero and Casanareño creole breeds can improve cattle production due to the contribution of genetic variants that emerged in the process of adaptation to the harsh conditions of the Colombian Orinoqia. Currently, genes with known biological function are used as molecular markers to estimate livestock genetic diversity parameters, facilitating the identification and location of genetic loci within the genome that encode or regulate the expression of traits of economic interest. In Colombia Romosinuano cattle candidate genes of the Growth hormone / Insulin growth factor axis have been identified and are positively associated with age at first calving, calving interval, longevity and protection of the embryo growth to heat stress. However, native Colombian bovine breeds such as Casanareño and Sanmartinero, which are empirically recognized by having those characteristic, have not been subjected to those genetic analysis for candidate genes that may allow to promote added value to animals. The aim of this review is to document some reproductive and genetic parameters of Sanmartinero and Casanareño bovine brees that may give support the need to conduct molecular studies and justify their use in beef and milk production systems in the Colombian Orinoquia.
Glioblastoma (GBM) is the most common brain cancer. Most GBM tumors have unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT); a validated biomarker for MGMT protein-expression and ensuing temozolomide-resistance. Second-line treatment with bevacizumab has not improved overall survival (OS). Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent targeting N7-Guanine, thus MGMT-independently inducing interstrand cross-links, DNA double-strand breaks and cell-death in GBM cell-lines and cancer stem cells. VAL-083 is currently in Phase I/II clinical trial for recurrent GBM, post-TMZ and post-bevacizumab. In this Phase II clinical trial, the main goal is to assess the 9-month OS in MGMT-unmethylated, recurrent, bevacizumab-naive GBM. RATIONALE: The vast majority of GBM patients experience recurrent/progressive disease within a year from initial diagnosis and median survival after recurrence is 3-9 months. Chemotherapy regimens for these patients are lacking and there is a significant unmet medical need. Given VAL-083’s novel alkylating mechanism, promising clinical benefit, and favorable safety profile, a trial studying VAL-083 in MGMT-unmethylated recurrent GBM is warranted. METHOD: Randomized, non-comparative biomarker-driven Phase II clinical trial in MGMT-unmethylated GBM patients at first recurrence/progression, prior to bevacizumab. 48 patients will be randomized to receive VAL-083 or “standard-of-care” salvage drug lomustine. 32 patients will receive VAL-083 40mg/m2/day on days 1,2,3 of a 21-day cycle. 16 patients will receive lomustine 90 mg/m2/day on day 1 of a 42-day cycle. Patients will be followed until death or for at least 9 months from enrollment, whichever occurs earlier. Survival will be compared to the BELOB trial for recurrent MGMT-unmethylated GBM patients treated with lomustine.
The epidemiology of surgical site infections (SSIs) in surgical programmes in sub-Saharan Africa is inadequately described. We reviewed deep and organ-space SSIs occurring within a trauma project that had a high-quality microbiology partnership and active follow-up. Included patients underwent orthopaedic surgery in Teme Hospital (Port Harcourt, Nigeria) for trauma and subsequently developed a SSI requiring debridement and microbiological sampling. Data were collected from structured chart reviews and programmatic databases for 103 patients with suspected SSI [79% male, median age 30 years, interquartile range (IQR) 24–37]. SSIs were commonly detected post-discharge with 58% presenting >28 days after surgery. The most common pathogens were: Staphylococcus aureus (34%), Pseudomonas aeruginosa (16%) and Enterobacter cloacae (11%). Thirty-three (32%) of infections were caused by a multidrug-resistant (MDR) pathogen, including 15 patients with methicillin-resistant S. aureus. Antibiotics were initiated empirically for 43% of patients and after culture and sensitivity report in 32%. The median number of additional surgeries performed in patients with SSI was 5 (IQR 2–6), one patient died (1%), and amputation was performed or recommended in three patients. Our findings suggest the need for active long-term monitoring of SSIs, particularly those associated with MDR organisms, resulting in increased costs for readmission surgery and treatment with late-generation antibiotics.
This study examines the associations between subjective memory complaints (SMC) and health variables: multimorbidity, presence of certain diseases, health perceived state, difficulties seeing and hearing, pain, and use of medications and health services. Furthermore, we aim to identify risk groups based on multimorbidity and calculate the effect size for each of these relationships.
Cross-sectional epidemiological study using a face-to-face interview with a structured questionnaire. Sample size: 1,342 people aged 65 years and older taken from a random sample of the census tracts. SMC were studied using questions regarding memory complaints.
Multimorbidity and polypharmacy are associated with SMC, so are impaired vision and hearing. SMC are more frequently present in people who use health services more intensively and exhibit reduced functional activity as a result of diseases. With respect to specific diseases, only cerebrovascular accidents and chronic constipation were associated with SMC. In regression analysis, predictors of SMC were vision and hearing impairment, poor self-perceived health, pain, and general practitioner visits. However, the effect size of these factors is low. The variables that indicate risk groups are number of diseases, reduced functional activity, hearing impairment, and poor self-perceived health.
Memory complaints are a heterogeneous phenomenon. Our results confirm that multimorbidity, polypharmacy, greater use of health services, pain, and poor self-perceived health are associated with SMC. We identified two risk groups with a high percentage of complaints and a healthy group with a low percentage. Detecting these factors and these risk and healthy groups is useful in achieving proper patients management.
LMC-N66 is an extraordinary planetary nebula whose central star underwent a violent mass loss event which has lasted for 10 years. The outburst reached its maximum in 1994. Since then the star has been slowly fading. During the stellar outburst, the nebular lines have shown no changes.
The nebula shows a complex morphology. Two very bright lobes at both sides of the central star, almost aligned in the E-W direction, constitute the main body of the nebula. Several knots and filaments are conspicuous over the surface lying preferentially on the S-E and N-W directions. A couple of faint, extended loops are also detected in the S-E and N-W directions at both sides of the star. The extension of these loops are larger than 0.5 pc at the LMC distance. A no emitting-zone in the S-W quadrant, seems to be part of a dusty toroid around the central star, although the central star is not obscured by such a dark material (see Blades et ale 1992 for a description of N66 morphology).
HST UV and optical spectra of the early-type [WC] star SMP 61 in the LMC are analyzed by means of line blanketed non-LTE models for expanding atmospheres. The known distance to the LMC allows a reliable determination of the stellar parameters. The low iron surface abundance of the object possibly indicates a preceding evolution through a very late thermal pulse (VLTP).
This is part of a series which has the purpose of examining the nature of the stars belonging to open clusters. The aim of this series is, among others things, to study short period pulsating stars, mainly of the Delta Scuti type, by first establishing the membership of each star to the cluster, to determine the abundance of the Be and Ap phenomena and blue stragglers in open clusters for clusters of different ages and metalicities and, eventually, to study the chemical enrichment of the galaxy when age, dynamics and metalicity are known for a fair number of clusters.