Ascariasis: A common disease with uncommon presentation in a resource limited setting. A case report.

Ascaris-induced intestinal obstruction is a rare complication primarily seen in children in areas with a high prevalence of worm infestations. It can occur through 2 mechanisms: immune-mediated reactions releasing neurotoxins that cause contractions and inflammation in the small intestine (aperistalsis), or mechanical obstruction by adult worms, commonly at the ileocecal valve. Partial obstructions are managed conservatively, while complete obstructions often require surgical intervention. In a recent case, a 19-year-old male presented with persistent abdominal pain, vomiting, and inability to pass stools, and gas. Imaging revealed partial obstruction, and conservative management with fluids, a nasogastric tube, and antibiotics led to the spontaneous passage of worms, relieving symptoms. The patient was discharged with anthelmintics and advised on follow-up and sanitary measures. This case is notable for the uncommon occurrence of Ascaris-induced intestinal obstruction in adults and the successful conservative management resulting in early worm expulsion.

A metagenome-level analysis of a microbial community fermenting ultra-filtered milk permeate.

Fermentative microbial communities have the potential to serve as biocatalysts for the conversion of low-value dairy coproducts into renewable chemicals, contributing to a more sustainable global economy. To develop predictive tools for the design and operation of industrially relevant strategies that utilize fermentative microbial communities, there is a need to determine the genomic features of community members that are characteristic to the accumulation of different products. To address this knowledge gap, we performed a 282-day bioreactor experiment with a microbial community that was fed ultra-filtered milk permeate, a low-value coproduct from the dairy industry. The bioreactor was inoculated with a microbial community from an acid-phase digester. A metagenomic analysis was used to assess microbial community dynamics, construct metagenome-assembled genomes (MAGs), and evaluate the potential for lactose utilization and fermentation product synthesis of community members represented by the assembled MAGs. This analysis led us to propose that, in this reactor, members of the Actinobacteriota phylum are important in the degradation of lactose, via the Leloir pathway and the bifid shunt, and the production of acetic, lactic, and succinic acids. In addition, members of the Firmicutes phylum contribute to the chain-elongation-mediated production of butyric, hexanoic, and octanoic acids, with different microbes using either lactose, ethanol, or lactic acid as the growth substrate. We conclude that genes encoding carbohydrate utilization pathways, and genes encoding lactic acid transport into the cell, electron confurcating lactate dehydrogenase, and its associated electron transfer flavoproteins, are genomic features whose presence in Firmicutes needs to be established to infer the growth substrate used for chain elongation.

Comparison of metagenomes from fermentation of various agroindustrial residues suggests a common model of community organization.

The liquid residue resulting from various agroindustrial processes is both rich in organic material and an attractive source to produce a variety of chemicals. Using microbial communities to produce chemicals from these liquid residues is an active area of research, but it is unclear how to deploy microbial communities to produce specific products from the different agroindustrial residues. To address this, we fed anaerobic bioreactors one of several agroindustrial residues (carbohydrate-rich lignocellulosic fermentation conversion residue, xylose, dairy manure hydrolysate, ultra-filtered milk permeate, and thin stillage from a starch bioethanol plant) and inoculated them with a microbial community from an acid-phase digester operated at the wastewater treatment plant in Madison, WI, United States. The bioreactors were monitored over a period of months and sampled to assess microbial community composition and extracellular fermentation products. We obtained metagenome assembled genomes (MAGs) from the microbial communities in each bioreactor and performed comparative genomic analyses to identify common microorganisms, as well as any community members that were unique to each reactor. Collectively, we obtained a dataset of 217 non-redundant MAGs from these bioreactors. This metagenome assembled genome dataset was used to evaluate whether a specific microbial ecology model in which medium chain fatty acids (MCFAs) are simultaneously produced from intermediate products (e.g., lactic acid) and carbohydrates could be applicable to all fermentation systems, regardless of the feedstock. MAGs were classified using a multiclass classification machine learning algorithm into three groups, organisms fermenting the carbohydrates to intermediate products, organisms utilizing the intermediate products to produce MCFAs, and organisms producing MCFAs directly from carbohydrates. This analysis revealed common biological functions among the microbial communities in different bioreactors, and although different microorganisms were enriched depending on the agroindustrial residue tested, the results supported the conclusion that the microbial ecology model tested was appropriate to explain the MCFA production potential from all agricultural residues.

Expectant management of advanced abdominal pregnancies: Is it justifiable?

OBJECTIVE: To evaluate the outcome of a case series of women with advanced abdominal pregnancies (AAP) who underwent expectant management. STUDY DESIGN: A retrospective study that utilized prospective data of 46 women who were admitted for expectant management at a tertiary hospital in Durban, South Africa. All data was analyzed descriptively and presented in percentages. RESULTS: The average period of expectant management was 27 days; thirty-three (72 %) of the 46 women were discharged from the hospital with live babies. There were 11 (24 %) neonatal deaths and two cases of stillbirths. There were no maternal deaths and morbidity was minimal. CONCLUSION: When diagnosed after the 24th week of gestation, an option is expectant management which includes careful patient selection, prolonged hospitalization, and close antenatal fetal and maternal surveillance to achieve fetal viability. Management by experienced clinicians and a multidisciplinary team in a tertiary institution is recommended. Informed consent needs to take into consideration the risks with interventional laparotomy, social separation from family and friends, and the guarded perinatal outcome.

Metagenomes and Metagenome-Assembled Genomes from Microbiomes Metabolizing Thin Stillage from an Ethanol Biorefinery.

Here, we report the metagenomes from five anaerobic bioreactors, operated under different conditions, that were fed carbohydrate-rich thin stillage from a corn starch ethanol plant. The putative functions of the abundant taxa identified here will inform future studies of microbial communities involved in valorizing this and other low-value agroindustrial residues.

Metagenome-Assembled Genomes from a Microbiome Grown in Dairy Manure Hydrolysate.

Anaerobic microbiomes can be used to recover the chemical energy in agroindustrial and municipal wastes as useful products. Here, we report a total of 109 draft metagenome-assembled genomes from a bioreactor-fed carbohydrate-rich dairy manure hydrolysate. Studying these genomes will aid us in deciphering the metabolic networks in anaerobic microbiomes.

Metagenomes and Metagenome-Assembled Genomes from Microbial Communities Fermenting Ultrafiltered Milk Permeate.

Fermentative microbial communities can be utilized for the conversion of various agroindustrial residues into valuable chemicals. Here, we report 34 metagenomes from anaerobic bioreactors fed lactose-rich ultrafiltered milk permeate and 278 metagenome-assembled genomes (MAGs). These MAGs can inform future studies aimed at generating renewable chemicals from dairy and other agroindustrial residues.

Metagenome-Assembled Genomes from a Microbiome Converting Xylose to Medium-Chain Carboxylic Acids.

There is growing interest in producing beneficial products from wastes using microbiomes. We previously performed multiomic analyses of a bioreactor microbiome that converted carbohydrate-rich lignocellulosic residues to medium-chain carboxylic acids. Here, we present draft metagenome-assembled genomes from this microbiome, obtained from reactors in which xylose was the primary carbon source.

Depressive symptoms in higher education students during the first wave of the COVID-19 pandemic. An examination of the association with various social risk factors across multiple high- and middle-income countries.

Higher-education students face substantial risks for developing depressive symptoms during the COVID-19 pandemic or experiencing exacerbated pre-existing depressive symptoms. This study uses data from the COVID-19 International Student Well-Being Study, which collected data through a non-representative convenience sample in 125 higher-education institutions (HEI) across 26 high- and middle-income countries (N: 20,103) during the first wave of the COVID-19 pandemic. It describes the prevalence of depressive symptoms in higher-education students. We find substantial cross-national variation in depressive symptoms, with lowest mean levels established in the Nordic countries and France, while highest mean levels of depressive symptoms were found in Turkey, South Africa, Spain and the USA. Elevated risk for depressive symptoms was found in female students, students with fewer social support resources and in a more disadvantaged socioeconomic position, and students with a migrant background. COVID-19 related stressors, such as reduced social contact, increased financial insecurity, and academic stress explained a relatively larger proportion of the variance in depressive symptoms compared to non-COVID-19 related stressors. This finding shows that not the pandemic itself, but rather the secondary effects of the pandemic relate to students' mental health. Our results enable HEIs to be better equipped to target groups that are particularly at risk during a pandemic.

Mixed Acid Fermentation of Carbohydrate-Rich Dairy Manure Hydrolysate.

Dairy manure (DM) is an abundant agricultural residue that is largely composed of lignocellulosic biomass. The aim of this study was to investigate if carbon derived from DM fibers can be recovered as medium-chain fatty acids (MCFAs), which are mixed culture fermentation products of economic interest. DM fibers were subjected to combinations of physical, enzymatic, chemical, and thermochemical pretreatments to evaluate the possibility of producing carbohydrate-rich hydrolysates suitable for microbial fermentation by mixed cultures. Among the pretreatments tested, decrystalization dilute acid pretreatment (DCDA) produced the highest concentrations of glucose and xylose, and was selected for further experiments. Bioreactors fed DCDA hydrolysate were operated. Acetic acid and butyric acid comprised the majority of end products during operation of the bioreactors. MCFAs were transiently produced at a maximum concentration of 0.17 mg CODMCFAs/mg CODTotal. Analyses of the microbial communities in the bioreactors suggest that lactic acid bacteria, Megasphaera, and Caproiciproducens were involved in MCFA and C4 production during DCDA hydrolysate metabolism.

Potent and orally bioavailable CDK8 inhibitors: Design, synthesis, structure-activity relationship analysis and biological evaluation.

CDK8 regulates transcription either by phosphorylation of transcription factors or, as part of a four-subunit kinase module, through a reversible association of the kinase module with the Mediator complex, a highly conserved transcriptional coactivator. Deregulation of CDK8 has been found in various types of human cancer, while the role of CDK8 in supressing anti-cancer response of natural killer cells is being understood. Currently, CDK8-targeting cancer drugs are highly sought-after. Herein we detail the discovery of a series of novel pyridine-derived CDK8 inhibitors. Medicinal chemistry optimisation gave rise to 38 (AU1-100), a potent CDK8 inhibitor with oral bioavailability. The compound inhibited the proliferation of MV4-11 acute myeloid leukaemia cells with the kinase activity of cellular CDK8 dampened. No systemic toxicology was observed in the mice treated with 38. These results warrant further pre-clinical studies of 38 as an anti-cancer agent.

Precious Metal-Free LaMnO3 Perovskite Catalyst with an Optimized Nanostructure for Aerobic C-H Bond Activation Reactions: Alkylarene Oxidation and Naphthol Dimerization.

In this article, we describe the development of a new aerobic C-H oxidation methodology catalyzed by a precious metal-free LaMnO3 perovskite catalyst. Molecular oxygen is used as the sole oxidant in this approach, obviating the need for other expensive and/or environmentally hazardous stoichiometric oxidants. The electronic and structural properties of the LaMnO3 catalysts were systematically optimized, and a reductive pretreatment protocol was proved to be essential for acquiring the observed high catalytic activities. It is demonstrated that this newly developed method was extremely effective for the oxidation of alkylarenes to ketones as well as for the oxidative dimerization of 2-naphthol to 1,1-binaphthyl-2,2-diol (BINOL), a particularly important scaffold for asymmetric catalysis. Detailed spectroscopic and mechanistic studies provided valuable insights into the structural aspects of the active catalyst and the reaction mechanism.

Targeting CDK2 in cancer: challenges and opportunities for therapy.

Cyclin-dependent kinase 2 (CDK2) plays a pivotal part in cell cycle regulation and is involved in a range of biological processes. CDK2 interacts with and phosphorylates proteins in pathways such as DNA damage, intracellular transport, protein degradation, signal transduction, DNA and RNA metabolism and translation. CDK2 and its regulatory subunits are deregulated in many human cancers and there is emerging evidence suggesting CDK2 inhibition elicits antitumor activity in a subset of tumors with defined genetic features. Previous CDK2 inhibitors were nonspecific and limited by off-target effects. The development of new-generation CDK2 inhibitors represents a therapeutic opportunity for CDK2-dependent cancers.

Synthesis of 2-D-L-Tryptophan by Sequential Ir-Catalyzed Reactions.

Herein, we report a practical synthesis of 2-D-L-tryptophan via sequential Ir-catalyzed C-H borylation, and Ir-catalyzed C-2-deborylative deuteration steps. In this synthetic sequence, deprotection of the Boc and methyl ester groups proved challenging, due to replacement of deuterium with hydrogen. However, mild deprotection conditions were developed to avoid this D/H scrambling. Further, 2-D-L-Tryptophan is stable in many buffers used for biological studies.

Male-specific deficits in natural reward learning in a mouse model of neurodevelopmental disorders.

Neurodevelopmental disorders, including autism spectrum disorders, are highly male biased, but the underpinnings of this are unknown. Striatal dysfunction has been strongly implicated in the pathophysiology of neurodevelopmental disorders, raising the question of whether there are sex differences in how the striatum is impacted by genetic risk factors linked to neurodevelopmental disorders. Here we report male-specific deficits in striatal function important to reward learning in a mouse model of 16p11.2 hemideletion, a genetic mutation that is strongly associated with the risk of neurodevelopmental disorders, particularly autism and attention-deficit hyperactivity disorder. We find that male, but not female, 16p11.2 deletion animals show impairments in reward-directed learning and maintaining motivation to work for rewards. Male, but not female, deletion animals overexpress mRNA for dopamine receptor 2 and adenosine receptor 2a in the striatum, markers of medium spiny neurons signaling via the indirect pathway, associated with behavioral inhibition. Both sexes show a 50% reduction of mRNA levels of the genes located within the 16p11.2 region in the striatum, including the kinase extracellular-signal related kinase 1 (ERK1). However, hemideletion males show increased activation in the striatum for ERK1, both at baseline and in response to sucrose, a signaling change associated with decreased striatal plasticity. This increase in ERK1 phosphorylation is coupled with a decrease in the abundance of the ERK phosphatase striatum-enriched protein-tyrosine phosphatase in hemideletion males. In contrast, females do not show activation of ERK1 in response to sucrose, but notably hemideletion females show elevated protein levels for ERK1 as well as the related kinase ERK2 over what would be predicted by mRNA levels. These data indicate profound sex differences in the impact of a genetic lesion linked with neurodevelopmental disorders, including mechanisms of male-specific vulnerability and female-specific resilience impacting intracellular signaling in the brain.

Exceptionally Small Statistical Variations in the Transport Properties of Metal-Molecule-Metal Junctions Composed of 80 Oligophenylene Dithiol Molecules.

Strong stochastic fluctuations witnessed as very broad resistance (R) histograms with widths comparable to or even larger than the most probable values characterize many measurements in the field of molecular electronics, particularly those measurements based on single molecule junctions at room temperature. Here we show that molecular junctions containing 80 oligophenylene dithiol molecules (OPDn, 1 ≤ n ≤ 4) connected in parallel display small relative statistical deviations-δR/R ≈ 25% after only ∼200 independent measurements-and we analyze the sources of these deviations quantitatively. The junctions are made by conducting probe atomic force microscopy (CP-AFM) in which an Au-coated tip contacts a self-assembled monolayer (SAM) of OPDs on Au. Using contact mechanics and direct measurements of the molecular surface coverage, the tip radius, tip-SAM adhesion force (F), and sample elastic modulus (E), we find that the tip-SAM contact area is approximately 25 nm2, corresponding to about 80 molecules in the junction. Supplementing this information with I-V data and an analytic transport model, we are able to quantitatively describe the sources of deviations δR in R: namely, δN (deviations in the number of molecules in the junction), δε (deviations in energetic position of the dominant molecular orbital), and Î´Γ (deviations in molecule-electrode coupling). Our main results are (1) direct determination of N; (2) demonstration that δN/N for CP-AFM junctions is remarkably small (≤2%) and that the largest contributions to δR are δε and δΓ; (3) demonstration that δR/R after only ∼200 measurements is substantially smaller than most reports based on >1000 measurements for single molecule break junctions. Overall, these results highlight the excellent reproducibility of junctions composed of tens of parallel molecules, which may be important for continued efforts to build robust molecular devices.

Use of placental vascularization indices and uterine artery peak systolic velocity in early detection of pregnancies complicated by gestational diabetes, chronic or gestational hypertension, and preeclampsia at risk.

AIM: We aimed to investigate correlations between uterine artery peak systolic velocity (AUtPSV), and placental vascularization in groups of normal blood pressure (NBP) and hypertensive disorders of pregnancy (chronic hypertension (CHT), gestational hypertension (GHT) and preeclampsia (PE)) alone or in combination with gestational diabetes mellitus (GDM), and hypothesized that AUtPSV rises when GDM complicates pregnancy hypertension. METHODS: Placental 3-dimensional power Doppler indices, such as vascularization index (VI), flow index (FI), and vascularization-flow index (VFI), and uterine artery peak systolic velocity (AUtPSV) were measured in CHT (N=43), CHT+GDM (N=15), GHT (N=57), GHT+GDM (N=23) and PE (N=17) pregnancies, and compared to NBP (N=109). Correlations were analyzed between vascularization indices, AUtPSV, pregestational BMI and adverse pregnancy outcome rates. RESULTS: In our results VI was higher in CHT (P=0.010), while FI was lower in CHT (P=0.009), GHT and PE (P=0.001) compared to NBP. In case of VFI, significant difference was found between CHT and GHT (P=0.002), and NBP and PE (P=0.001). FI was found prognostic for umbilical pH and neonatal birth weight. Pre-gestational BMI was significantly higher in GHT+GDM compared to GHT, and in CHT+GDM compared to the CHT group. As for AUtPSV, significant difference was found between NBP and CHT (P=0.012), NBP and CHT+GDM (P=0.045), NBP and GHT+GDM (P=0.007), NBP and PE (P=0.032), and GHT and GHT+GDM (P=0.048) groups. CONCLUSION: Our study revealed that vascularization indices and AUtPSV show significant differences due to gestational pathology, and can be useful in detection of pregnancies at risk.

Contributions to ultrasound monitoring of the process of milk curdling.

Ultrasound evaluation permits the state of milk being curdled to be determined quickly and cheaply, thus satisfying the demands faced by today's dairy product producers. This paper describes the non-invasive ultrasonic method of in situ monitoring the changing physical properties of milk during the renneting process. The basic objectives of the study were, on the one hand, to confirm the usefulness of conventional non-destructive ultrasonic testing (time-of-flight and attenuation of the ultrasound waves) in monitoring the process in the case of ewe's milk, and, on the other, to include other ultrasound parameters which have not previously been considered in studies on this topic, in particular, parameters provided by the Fast Fourier Transform technique. The experimental study was carried out in a dairy industry environment on four 52-l samples of raw milk in which were immersed 500kHz ultrasound transducers. Other physicochemical parameters of the raw milk (pH, dry matter, protein, Gerber fat test, and lactose) were measured, as also were the pH and temperature of the curdled samples simultaneously with the ultrasound tests. Another contribution of this study is the linear correlation analysis of the aforementioned ultrasound parameters and the physicochemical properties of the curdled milk.

The benefit of bone marrow concentrate in addition to a glass-reinforced hydroxyapatite for bone regeneration: An in vivo ovine study.

This study evaluates the ability of a Glass Reinforced Hydroxyapatite Composite (GRHC), in a new microporous pellet formulation with autologous bone marrow concentrate (BMC), to enhance bone regeneration and new bone formation. Ninety non-critical sized bone defects were created in the femurs of nine Merino breed sheep and randomly left unfilled (group A), filled with GRHC pellets alone (group B) or filled with GRHC pellets combined with BMC (group C). The sheep were sacrificed at 3 weeks (three sheep), 6 weeks (three sheep) and 12 weeks (three sheep) and histological analysis (Light Microscopy-LM), scanning electron microscopy (SEM) and histomorphometric analysis (HM) were performed. At 3, 6, and 12 weeks, HM revealed an average percentage of new bone of 48, 72, 83%; 25, 73, 80%, and 16, 38, 78% for Groups C, B and A respectively (significantly different only at 3 weeks p < 0.05). LM and SEM evaluation revealed earlier formation of well-organized mature lamellar bone in Group C. This study demonstrates that the addition of a bone marrow concentrate to a glass reinforced hydroxyapatite composite in a pellet formulation promotes early bone healing. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1176-1182, 2017.

Targeting expression to megakaryocytes and platelets by lineage-specific lentiviral vectors.

Essentials Platelet phenotypes can be modified by lentiviral transduction of hematopoietic stem cells. Megakaryocyte-specific lentiviral vectors were tested in vitro and in vivo for restricted expression. The glycoprotein 6 vector expressed almost exclusively in megakaryocytes. The platelet factor 4 vector was the strongest but with activity in hematopoietic stem cells. SUMMARY: Background Lentiviral transduction and transplantation of hematopoietic stem cells (HSCs) can be utilized to modify the phenotype of megakaryocytes and platelets. As the genetic modification in HSCs is transmitted onto all hematopoietic progenies, transgene expression from the vector should be restricted to megakaryocytes to avoid un-physiologic effects by ectopic transgene expression. This can be achieved by lentiviral vectors that control expression by lineage-specific promoters. Methods In this study, we introduced promoters of megakaryocyte/platelet-specific genes, namely human glycoprotein 6 (hGP6) and hGP9, into third generation lentiviral vectors and analyzed their functionality in vitro and in vivo in bone marrow transplantation assays. Their specificity and efficiency of expression was compared with lentiviral vectors utilizing the promoters of murine platelet factor 4 (mPf4) and hGP1BA, both with strong activity in megakaryocytes (MKs) used in earlier studies, and the ubiquitously expressing phosphoglycerate kinase (hPGK) and spleen focus forming virus (SFFV) enhancer/promoters. Results Expression from the mPf4 vector in MKs and platelets was the strongest similar to expression from the viral SFFV promoter, however, the mPf4 vector, also exhibited considerable off-target expression in hematopoietic stem and progenitor cells. In contrast, the newly generated hGP6 vector was highly specific to megakaryocytes and platelets. The specificity was also retained when reducing the promoter size to 350 bp, making it a valuable new tool for lentiviral expression in MKs/platelets. Conclusion MK-specific vectors express preferentially in the megakaryocyte lineage. These vectors can be applied to develop murine models to study megakaryocyte and platelet function, or for gene therapy targeting proteins to platelets.