Effects of three different stimulations (acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small toe on fetal behavior of breech presentation

The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments

A Tree-Loop Duality Relation at Two Loops and Beyond

The duality relation between one-loop integrals and phase-space integrals, developed in a previous work, is extended to higher-order loops. The duality relation is realized by a modification of the customary +i0 prescription of the Feynman propagators, which compensates for the absence of the multiple-cut contributions that appear in the Feynman tree theorem. We rederive the duality theorem at one-loop order in a form that is more suitable for its iterative extension to higher-loop orders. We explicitly show its application to two- and three-loop scalar master integrals, and we discuss the structure of the occurring cuts and the ensuing results in detail.Comment: 20 pages. Few typos corrected, some additional comments included, Appendix B and one reference added. Final version as published in JHE

Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma.

SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach. We show here that selective inhibition of the downstream Hh effectors HDAC1 and HDAC2 robustly counteracts SHH-MB growth in mouse models. These two deacetylases are upregulated in tumor and their knockdown inhibits Hh signaling and decreases tumor growth. We demonstrate that mocetinostat (MGCD0103), a selective HDAC1/HDAC2 inhibitor, is a potent Hh inhibitor and that its effect is linked to Gli1 acetylation at K518. Of note, we demonstrate that administration of mocetinostat to mouse models of SHH-MB drastically reduces tumor growth, by reducing proliferation and increasing apoptosis of tumor cells and prolongs mouse survival rate. Collectively, these data demonstrate the preclinical efficacy of targeting the downstream HDAC1/2-Gli1 acetylation in the treatment of SHH-MB

Techno-economic optimization of a process superstructure for lignin valorization

Lignin, the most abundant aromatic biopolymer on Earth, is often considered a biorefinery by-product, despite its potential to be valorized into high-added-value chemicals and fuels. In this work, an integrated superstructure-based optimization model was set up and optimized using mixed-integer non-linear programming for the conversion of technical lignin to three main biobased products: aromatic monomers, phenol-formaldehyde resins, and aromatic aldehydes/acids. Several alternative conversion pathways were simultaneously compared to assess the profitability of lignins-based processes by predicting the performance of technologies with different TRL. Upon employing key technologies such as hydrothermal liquefaction, dissolution in solvent, or high-temperature electrolysis, the technical lignins could have a market value of 200 €/t when the market price for aromatic monomers, resins, and vanillin is at least 2.0, 0.8, and 15.0 €/kg, respectively. When lower product selling prices were considered, the aromatic monomers and the resins were not profitable as target products

Degradation of biological macromolecules supports uncultured microbial populations in Guaymas Basin hydrothermal sediments

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Castro, S. P., Borton, M. A., Regan, K., de Angelis, I. H., Wrighton, K. C., Teske, A. P., Strous, M., & Ruff, S. E. Degradation of biological macromolecules supports uncultured microbial populations in Guaymas Basin hydrothermal sediments. Isme Journal. (2021), https://doi.org/10.1038/s41396-021-01026-5.Hydrothermal sediments contain large numbers of uncultured heterotrophic microbial lineages. Here, we amended Guaymas Basin sediments with proteins, polysaccharides, nucleic acids or lipids under different redox conditions and cultivated heterotrophic thermophiles with the genomic potential for macromolecule degradation. We reconstructed 20 metagenome-assembled genomes (MAGs) of uncultured lineages affiliating with known archaeal and bacterial phyla, including endospore-forming Bacilli and candidate phylum Marinisomatota. One Marinisomatota MAG had 35 different glycoside hydrolases often in multiple copies, seven extracellular CAZymes, six polysaccharide lyases, and multiple sugar transporters. This population has the potential to degrade a broad spectrum of polysaccharides including chitin, cellulose, pectin, alginate, chondroitin, and carrageenan. We also describe thermophiles affiliating with the genera Thermosyntropha, Thermovirga, and Kosmotoga with the capability to make a living on nucleic acids, lipids, or multiple macromolecule classes, respectively. Several populations seemed to lack extracellular enzyme machinery and thus likely scavenged oligo- or monomers (e.g., MAGs affiliating with Archaeoglobus) or metabolic products like hydrogen (e.g., MAGs affiliating with Thermodesulfobacterium or Desulforudaceae). The growth of methanogens or the production of methane was not observed in any condition, indicating that the tested macromolecules are not degraded into substrates for methanogenesis in hydrothermal sediments. We provide new insights into the niches, and genomes of microorganisms that actively degrade abundant necromass macromolecules under oxic, sulfate-reducing, and fermentative thermophilic conditions. These findings improve our understanding of the carbon flow across trophic levels and indicate how primary produced biomass sustains complex and productive ecosystems.We are grateful to the captain and crew of the R/V Atlantis AT37-06 as well as the crew of the human occupied vehicle Alvin for their tireless support. Sampling at Guaymas Basin was supported by NSF (OCE-1357238)

IGF-1 is not related to long-term outcome in hyperglycemic acute coronary syndrome patients

PURPOSE: Insulin-like growth factor-1 (IGF-1) has been associated with both protective and detrimental effects on the development of ischemic heart disease. The relationship between IGF-1 levels and major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients remains unclear. This study aimed to investigate the relationship between IGF-1 admission levels in hyperglycemic ACS patients and: (1) MACE over a 5 years follow-up, (2) type 2 diabetes at discharge, and (3) post-ACS myocardial infarct size and dysfunction. METHODS: This was a post hoc analysis of the BIOMArCS-2 randomized controlled trial. From July 2008 to February 2012, 276 ACS patients with admission plasma glucose level between 140 and 288 mg/dL were included. Records of the composite of all-cause mortality and recurrent non-fatal myocardial infarction were obtained during 5 years follow-up. Venous blood samples were collected on admission. IGF-1 was measured batchwise after study completion. Oral glucose tolerance test was performed to diagnose type 2 diabetes, whereas infarct size and left ventricular function were assessed by myocardial perfusion scintigraphy (MPS) imaging, 6 weeks post-ACS. RESULTS: Cumulative incidence of MACE was 24% at 5 years follow-up. IGF-1 was not independently associated with MACE (HR:1.00 (95%CI:0.99–1.00), p = 0.29). Seventy-eight patients (28%) had type 2 diabetes at discharge, and the highest quartile of IGF-1 levels was associated with the lowest incidence of diabetes (HR:0.40 (95%CI:0.17–0.95), p = 0.037). IGF-1 levels were not associated with post-ACS myocardial infarct size and dysfunction. CONCLUSIONS: IGF-1 carries potential for predicting type 2 diabetes, rather than long-term cardiovascular outcomes and post-ACS myocardial infarct size and dysfunction, in hyperglycemic ACS patients

Repressing Anarchy in Neutrino Mass Textures

The recent results that $\theta_{13}$ is relatively large, of the order of the previous upper bound, and the indications of a sizable deviation of $\theta_{23}$ from the maximal value are in agreement with the predictions of Anarchy in the lepton sector. The quark and charged lepton hierarchies can then be reproduced in a SU(5) GUT context by attributing non-vanishing $U(1)_{FN}$ charges, different for each family, only to the SU(5) tenplet states. The fact that the observed mass hierarchies are stronger for up quarks than for down quarks and charged leptons supports this idea. As discussed in the past, in the flexible context of $SU(5)\otimes U(1)_{FN}$, different patterns of charges can be adopted going from Anarchy to various types of hierarchy. We revisit this approach by also considering new models and we compare all versions to the present data. As a result we confirm that, by relaxing the extreme ansatz of equal $U(1)_{FN}$ charges for all SU(5) pentaplets and singlets, better agreement with the data than for Anarchy is obtained without increasing the model complexity. We also present the distributions obtained in the different models for the Dirac CP-violating phase. Finally we discuss the relative merits of these simple models.Comment: v1: 12 pages, 3 figures; v2: 13 pages, 3 figures, text improved, matches version accepted for publication; v3: submitted to add an acknowledgment to a networ

Cardiac Catheterizations in Patients With Prior Coronary Bypass Surgery:Impact of Access Strategy on Short-Term Safety and Long-Term Efficacy Outcomes

Little data are available on access strategy outcomes for cardiac catheterizations in patients with prior coronary artery bypass graft surgery (CABG). We investigated the effect of transradial access (TRA) and transfemoral access (TFA) on short-term major vascular complications (MVC) and long-term major adverse cardiovascular events (MACE). In this single-center, retrospective cohort study, 1084 patients met our inclusion criteria (TRA = 469; TFA = 615). The cumulative incidence for the primary safety endpoint MVC at 30 days (a composite of major bleeding, retroperitoneal hematoma, dissection, pseudoaneurysm, and arteriovenous fistula) was lower with TRA (0.7% vs 3.0%, P &lt;.01) and this difference remained significant after propensity score adjustment (odds ratio: 0.24; 95% CI, 0.07-0.83; P =.024). The cumulative incidence for the primary efficacy endpoint MACE at 36 months (a composite of all-cause mortality, myocardial infarction, stroke, and urgent target vessel revascularization) was 28.6% with TRA and 27.6% with TFA, respectively. Kaplan-Meier curves showed no difference for the primary efficacy endpoint (P =.65). Contrast use (mL) was significantly lower with TRA (130 [100-180] vs 150 [100-213], P &lt;.01). In conclusion, in patients with prior CABG, TRA was associated with significantly fewer short-term MVC and contrast use, but not with a difference in long-term MACE, compared with TFA.</p

Phase I trial of recombinant human nerve growth factor for neurotrophic keratitis

Neurotrophic keratitis/keratopathy (NK), a rare degenerative corneal disease, lacks effective pharmacologic therapies.1 Because NK pathology involves trigeminal nerve damage and loss of corneal innervation, nerve growth factor (NGF) is surmised to promote healing of NK.2 Preliminary studies with murine NGF demonstrated efficacy for treating corneal neurotrophic ulcers;3 however, the complex tertiary structure of NGF has complicated the production of recombinant human NGF (rhNGF) suitable for clinical development. To this end, we developed an Escherichia coli–derived rhNGF formulation that demonstrated to be well tolerated and safe for topical ophthalmic use in a phase I study in healthy volunteers.4 We report phase I results of topical rhNGF for patients with moderate-to-severe NK