The Effect of Fasting on Haematology Serum Biochemistry Parameters on STZ Induced CD1 Mice and Diabetic db/db Mice

Modest information is available on how fasting affects clinical pathology variables in (Streptozocin) STZ induced diabetes mice and db/db mice. This study was carried out to evaluate the influence of fasting on clinical pathology variables in diabetic mouse models. Seven male STZ induced diabetic CD1 mice and db/db mice were fasted for 18 hours and change in body weight (BW), hematologic and biochemical variables were evaluated. Fasting provoked significant variation in body weight, haematology and biochemical variables in diabetic animal models. The results suggested that clinical pathology variables will vary after fasting. The decision to feed or fast before blood collection for analyzing the results should be made based on fasting in animal models for diabetic research

Investigating the Anti-tumorigenic Properties of Synthetic Inhibitors of B7-H3 in Group 3 Medulloblastoma

Medulloblastomas (MB) are devastating brain tumors originating in the cerebellum most commonly in children. There are four distinct subgroups of medulloblastoma: WNT (wingless), SHH (sonic hedgehog), group 3, and group 4. The most malignant tumors possess an aggressive phenotype characterized by c-Myc amplification and deletions to chromosome 17p; they belong to group 3. Prior investigations into the significance of genes on 17p revealed that miR-1253, which is found on locus 17p13.3, is significantly downregulated in medulloblastoma and has important tumor suppressive properties. Amongst its oncogenic targets is B7-H3 (CD276), a highly deregulated oncoprotein that attenuates the immune response to MB tumors. We chose to elucidate the oncogenic properties of B7-H3 in group 3 MB using synthetic inhibitors. After screening 100,000 different compounds for: 1) docking ability, 2) oral bioavailability, 3) potential CNS activity, and 4) number of metabolic side reactions, we selected two N-terminal inhibitors: B7-H3-Ni1 and B7-H3-Ni3. In HDMB03 cells (with c-Myc amplification and i17q), we found an IC50 of 3.7 M for B7-H3-Ni1 and no discernible effect of B7-H3-Ni3. We confirmed CD276 expression inhibition using B7-H3-Ni1 via Western blotting and concurrently noted elevations in cleaved PARP (apoptosis) and reduction in p-Akt (proliferation marker), providing us preliminary insights into the mechanism of inhibition. Notably, a remarkable decline in migration and wound healing and abrogation of colony formation were observed with B7-H3-Ni1. Collectively, our findings substantiate the inhibitory properties of B7-H3-Ni1 in vitro, potentially serving as a therapeutic agent for in vivo group 3 MB tumors.https://digitalcommons.unmc.edu/surp2021/1049/thumbnail.jp

SERS multiplexing of methylxanthine drug isomers via host-guest size matching and machine learning

Multiplexed detection and quantification of structurally similar drug molecules, methylxanthine MeX, incl. theobromine TBR, theophylline TPH and caffeine CAF, have been demonstrated via solution-based surface-enhanced Raman spectroscopy (SERS), achieving highly reproducible SERS signals with detection limits down to ∼50 nM for TBR and TPH, and ∼1 μM for CAF. Our SERS substrates are formed by aqueous self-assembly of gold nanoparticles (Au NPs) and supramolecular host molecules, cucurbit[n]urils (CBn, n = 7, 8). We demonstrate that the binding constants can be significantly increased using a host–guest size matching approach, which enables effective enrichment of analyte molecules in close proximity to the plasmonic hotspots. The dynamic range and the robustness of the sensing scheme can be extended using machine learning algorithms, which shows promise for potential applications in therapeutic drug monitoring, food processing, forensics and veterinary science

Large gains in schooling and income are possible from minimizing adverse birth outcomes in 121 low- and middle-income countries: a modelling study

While the global contributions of adverse birth outcomes to child morbidity and mortality is relatively well documented, the potential long-term schooling and economic consequences of adverse birth outcomes has not been estimated. We sought to quantify the potential schooling and lifetime income gains associated with reducing the excess prevalence of adverse birth outcomes in 121 low- and middle-income countries. We used a linear deterministic model to estimate the potential gains in schooling and lifetime income that may be achieved by attaining theoretical minimum prevalence of low birthweight, preterm birth and small-for-gestational age births at the national, regional, and global levels. We estimated that potential total gains across the 121 countries from reducing low birthweight to the theoretical minimum were 20.3 million school years (95% CI: 6.0,34.8) and US$68.8 billion (95$ 41.9 billion (95% CI: 6.1,80.9) in lifetime income. The potential gains from small-for-gestational age were 39.5 million (95% CI: 19.1,60.3) school years and US$113.6 billion (95% CI: 55.5,174.2) in lifetime income gained. In summary, reducing the excess prevalence of low birthweight, preterm birth or small-for-gestational age births in low- and middle-income countries may lead to substantial long-term human capital gains in addition to benefits on child mortality, growth, and development as well as on risk of non-communicable diseases in adults and other consequences across the life course

Birth weight and adult earnings: a systematic review and meta-analysis

While substantial evidence has identified low birth weight (LBW; <2500 g) as a risk factor for early life morbidity, mortality and poor childhood development, relatively little is known on the links between birth weight and economic outcomes in adulthood. The objective of this study was to systematically review the economics (EconLit) and biomedical literature (Medline) and estimate the pooled association between birth weight and adult earnings. A total of 15 studies from mostly high-income countries were included. On average, each standard deviation increase in birth weight was associated with a 2.75% increase in annual earnings [(95% CI: 1.44 to 4.07); 9 estimates]. A negative, but not statistically significant, association was found between being born LBW and earnings, compared to individuals not born LBW [mean difference: -3.41% (95% CI: -7.55 to 0.73); 7 estimates]. No studies from low-income countries were identified and all studies were observational. Overall, birth weight was consistently associated with adult earnings, and therefore, interventions that improve birth weight may provide beneficial effects on adult economic outcomes

2,10-Dihydr­oxy-13-methyl-13-aza­tetra­cyclo­[9.3.1.02,10.03,8]penta­deca-3(8),4,6-triene-9,15-dione

In the title compound, C15H15NO4, the n-methyl­piperidone ring adopts a chair conformation and both five-membered rings adopt a twist conformation. An intra­molecular O—H⋯O hydrogen bond is observed. Inversion-related mol­ecules are linked into R 2 2(10) dimers by pairs of O—H⋯O hydrogen bonds. The crystal structure is further stabilized by C—H⋯O hydrogen bonds

Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging.

Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy

Studies on standardization and purification processes of VEERAM

In Siddha system of medicine Veeram is one of the toxins among the sixty four known toxins. Geologically it is called Calomel. It is a very toxic material therapeutically, these arsenic based medicines are used in Siddha system. Natural substances of milk, tender coconut water, bitter guard and lemon juice are used to purify the veeram. This research work analyzed the raw veeram and products obtained after purification. Geochemical, physico-chemical analysis, instrumentation techniques of XRF, TG-DTA, FE-SEM, EDAX and particle size analyzer. Among physicochemical parameters total ash value was low. Loss on drying increased in the products in the various intermediate stages which due to the impact of plant agents used in the process. XRF results revealed mercury is present in major concentration. Raw veeram showed 77.14% of mercury. In the raw veeram particles observed were distributed within the range of 0.0920 µm–0.948 µm. FE-SEM analysis suggested that the bitter gourd treated veeram consisted of individual particles with a size ranging from 94 nm to 144 nm. Milk treated samples when subjected to analysis revealed increased particle size which may be attributed to aggregation. Lemon juice treated samples showed particle size in the range of 82 nm to 96 nm and in tender coconut range was 78 nm to 91 nm. In the EDAX raw and other samples showed peak for mercury and chloride. TG-DTA analysis showed that the raw veeram sample had a sublimation temperature of 220°C where as in other treated samples sublimation temperature was reduced compared to raw veeram. The from the stydy depict that these purification processes forms new organic substances and transformation of the starting toxic metal. These processes have an important role in the formation of complexes and in altering toxic state to non-toxic state.