Analysis of the Mental Foramen and Inferior Alveolar Canal pattern based on CBCT data

The mental foramen is located in a position where certain dental procedures may cause inadvertent damage to the mental nerve and lead to disorders of sensory functions such as altered sensa¬tion, complete numbness, and neuropathic pain, which are uncommon but severe treatment complications with significant medico-legal implications. Hence thorough knowledge of its anatomical relation to its surrounding structures is critical while undertaking dental procedures. To investigate the size, shape, and position of the mental foramen (MF), its distance from adjacent teeth and mandibular borders, and the pattern of the inferior alveolar canal using CBCT in the Indian subpopulation. This was a retrospective, cross-sectional study The study evaluated 310 CBCT scans (179 males, 131 females) in axial, sagittal, and coronal planes. CBCT scans were evaluated, mapped and measured for all the parameters listed above based on age and sex. Data were analyzed using ANOVA, independent‘t-test, and chi-square test. The size of MF is independent of age and sex; the most frequent shape of MF was Type III (round); location was below the apex of the second premolar (p>0.05). The distance of MF from the nearest root apex decreased with an increase in age and more in females than males (p>0.05). Inferior Alveolar Nerve Canal (IAC) pattern was perpendicular, and linear patterns of exit at MF were more common than anterior loops in all age groups

Novel allosteric mechanism of p53 activation by small molecules for targeted anticancer therapy

Given the immense significance of p53 restoration for anti-cancer therapy and that p53-activating molecules are in clinical trials, elucidation of the mechanisms of action of p53-activating molecules is of the utmost importance. Here we report a discovery of a novel allosteric modulation of p53 by small molecules, which is an unexpected turn in the p53 story. We identified a structural element involved in allosteric regulation of p53, whose targeting by small molecules RITA, PpIX and licofelone blocks the binding of two p53 inhibitors, MDM2 and MDMX, thereby restoring p53 function. Deletion and mutation analysis followed by molecular modeling and its thorough validation, identified the key p53 residues S33 and S37 targeted by RITA and PpIX. We propose that the binding of small molecules to the identified site in p53 induces a conformational trap preventing p53 from the interaction with MDM2 and MDMX. These results point to a high potential of allosteric activators as targeted drugs. Our study provides a basis for the development of therapeutics with a novel mechanism of action, thus extending the p53 pharmacopeia

Understanding the Surface Regeneration and Reactivity of Garnet Solid-State Electrolytes

Garnet solid electrolyte-based Li-ion batteries can be used in energy storage devices with high energy densities and thermal stability. However, the tendency of garnets to form lithium hydroxide and carbonate on the surface in an ambient atmosphere poses significant processing challenges. In this work, the decomposition of surface layers under various gas environments is studied by using the surface sensitive techniques, near ambient pressure x-ray photoelectron spectroscopy and grazing incidence diffraction. It is found that heating to 500 °C under oxygen atmosphere (of 1 mbar and above) leads to a clean garnet surface, whereas low oxygen partial pressures (i.e., in argon or vacuum) lead to additional graphitic carbon deposits. The clean surface of garnets reacts directly with moisture and carbon dioxide below 400 and 500 °C respectively. This suggests that additional CO2 concentration controls are needed for the handling of garnets. By heating under O2 along with avoiding H2O and CO2, symmetric cells with less than 10 Ωcm2 interface resistance are prepared without the use of any interlayers; plating currents of greater than 1 mAcm-2 without dendrite initiation are demonstrated.S.V. acknowledges funding from the Cambridge Commonwealth European and International Trust, Faraday Institution (SOLBAT, FIRG007) and Royal Society (RP/R1/180147). F.N.S also acknowledges funding from The Faraday Institution CATMAT project (FIRG016). S.N. thanks the Royal Society (United Kingdom) and Science and Engineering Research Board (Government of India) for the award of Newton-Bhabha International Fellowship (NIF/R1/180075). C.P.G thanks the EU via an Advanced EU ERC grant (EC H2020 835073). Professor Norman Fleck and Professor Vikram Deshpande are thanked for access to their laboratories for sample preparation and for helpful discussions. We thank Simon Marshall and Graham Smith for assistance in operating hot-press and Anthony Dennis and Harry Druiff for assistance in cutting hot-pressed samples. We thank Diamond Light Source, UK for access to beamline B07 (SI29728) for NAP-XPS measurements and DELTA, Germany for providing synchrotron radiation at beamline BL9 for grazing incidence X-ray diffraction measurements. We also acknowledge I11 beamline for synchrotron XRD at Diamond Light Source, UK under BAG proposal (CY28349)

Understanding the Surface Regeneration and Reactivity of Garnet Solid-State Electrolytes

Garnet solid-electrolyte-based Li-metal batteries can be used in energy storage devices with high energy densities and thermal stability. However, the tendency of garnets to form lithium hydroxide and carbonate on the surface in an ambient atmosphere poses significant processing challenges. In this work, the decomposition of surface layers under various gas environments is studied by using two surface-sensitive techniques, near-ambient-pressure X-ray photoelectron spectroscopy and grazing incidence X-ray diffraction. It is found that heating to 500 °C under an oxygen atmosphere (of 1 mbar and above) leads to a clean garnet surface, whereas low oxygen partial pressures (i.e., in argon or vacuum) lead to additional graphitic carbon deposits. The clean surface of garnets reacts directly with moisture and carbon dioxide below 400 and 500 °C, respectively. This suggests that additional CO2 concentration controls are needed for the handling of garnets. By heating under O2 along with avoiding H2O and CO2, symmetric cells with less than 10 Ωcm2 interface resistance are prepared without the use of any interlayers; plating currents of >1 mA cm–2 without dendrite initiation are demonstrated

Burkholderia pseudomallei stimulates low interleukin-8 production in the human lung epithelial cell line A549

Melioidosis is a life-threatening disease caused by Burkholderia pseudomallei. The lung is the most commonly affected organ, resulting in abscess formation in patients with chronic melioidosis. Previous study has shown that B. pseudomallei was able to invade and multiply in epithelial cells. In the present study, we have demonstrated that B. pseudomallei is able to stimulate interleukin 8 (IL-8) production from the human alveolar lung epithelium cell line A549. However, the level of IL-8 production was significantly lower than when the cells were infected with other Gram-negative bacteria such as Salmonella enterica serovar Typhi (S. typhi) which were used for comparison. The degree of IκBα degradation in the B. pseudomallei-infected cells was lower than that of the S. typhi-infected cells, suggesting that B. pseudomallei is also a poorer cell activator. Inhibition of B. pseudomallei invasion by cytochalasin D did not interfere with either IL-8 production or IκBα degradation, indicating that bacterial uptake is not required for the production of this chemokine. Thus, it appears that the signalling initiated by the interaction of B. pseudomallei with the epithelial cell surface is sufficient for epithelial cell activation

Understanding the Surface Regeneration and Reactivity of Garnet Solid-State Electrolytes

Garnet solid-electrolyte-based Li-metal batteries can be used in energy storage devices with high energy densities and thermal stability. However, the tendency of garnets to form lithium hydroxide and carbonate on the surface in an ambient atmosphere poses significant processing challenges. In this work, the decomposition of surface layers under various gas environments is studied by using two surface-sensitive techniques, near-ambient-pressure X-ray photoelectron spectroscopy and grazing incidence X-ray diffraction. It is found that heating to 500 °C under an oxygen atmosphere (of 1 mbar and above) leads to a clean garnet surface, whereas low oxygen partial pressures (i.e., in argon or vacuum) lead to additional graphitic carbon deposits. The clean surface of garnets reacts directly with moisture and carbon dioxide below 400 and 500 °C, respectively. This suggests that additional CO2 concentration controls are needed for the handling of garnets. By heating under O2 along with avoiding H2O and CO2, symmetric cells with less than 10 Ωcm2 interface resistance are prepared without the use of any interlayers; plating currents of >1 mA cm–2 without dendrite initiation are demonstrated

Forced Disorder in the Solid Solution Li3P-Li2S: A New Class of Fully Reduced Solid Electrolytes for Lithium Metal Anodes.

Funder: Cambridge TrustFunder: Blavatnik Family FoundationFunder: Studienstiftung des Deutschen VolkesFunder: Fonds der Chemischen IndustrieAll-solid-state batteries based on non-combustible solid electrolytes are promising candidates for safe energy storage systems. In addition, they offer the opportunity to utilize metallic lithium as an anode. However, it has proven to be a challenge to design an electrolyte that combines high ionic conductivity and processability with thermodynamic stability toward lithium. Herein, we report a new highly conducting solid solution that offers a route to overcome these challenges. The Li-P-S ternary was first explored via a combination of high-throughput crystal structure predictions and solid-state synthesis (via ball milling) of the most promising compositions, specifically, phases within the Li3P-Li2S tie line. We systematically characterized the structural properties and Li-ion mobility of the resulting materials by X-ray and neutron diffraction, solid-state nuclear magnetic resonance spectroscopy (relaxometry), and electrochemical impedance spectroscopy. A Li3P-Li2S metastable solid solution was identified, with the phases adopting the fluorite (Li2S) structure with P substituting for S and the extra Li+ ions occupying the octahedral voids and contributing to the ionic transport. The analysis of the experimental data is supported by extensive quantum-chemical calculations of both structural stability, diffusivity, and activation barriers for Li+ transport. The new solid electrolytes show Li-ion conductivities in the range of established materials, while their composition guarantees thermodynamic stability toward lithium metal anodes

Forced Disorder in the Solid Solution Li₃P–Li₂S: A New Class of Fully Reduced Solid Electrolytes for Lithium Metal Anodes

All-solid-state batteries based on non-combustible solid electrolytes are promising candidates for safe energy storage systems. In addition, they offer the opportunity to utilize metallic lithium as an anode. However, it has proven to be a challenge to design an electrolyte that combines high ionic conductivity and processability with thermodynamic stability toward lithium. Herein, we report a new highly conducting solid solution that offers a route to overcome these challenges. The Li–P–S ternary was first explored via a combination of high-throughput crystal structure predictions and solid-state synthesis (via ball milling) of the most promising compositions, specifically, phases within the Li3P–Li2S tie line. We systematically characterized the structural properties and Li-ion mobility of the resulting materials by X-ray and neutron diffraction, solid-state nuclear magnetic resonance spectroscopy (relaxometry), and electrochemical impedance spectroscopy. A Li3P–Li2S metastable solid solution was identified, with the phases adopting the fluorite (Li2S) structure with P substituting for S and the extra Li+ ions occupying the octahedral voids and contributing to the ionic transport. The analysis of the experimental data is supported by extensive quantum-chemical calculations of both structural stability, diffusivity, and activation barriers for Li+ transport. The new solid electrolytes show Li-ion conductivities in the range of established materials, while their composition guarantees thermodynamic stability toward lithium metal anodes

Evaluation of Liver Transplantation Among Advanced Age Recipients in a Large Multicenter U. S. Cohort

Purpose: The proportion of adults \u3e70 years (y) listed for liver transplant (LT) in the U. S. is rising. Outcomes in this growing population are limited to small, single-center cohorts or national database studies that lack granularity. We aimed to better characterize outcomes in LT recipients \u3e70y in a large multicenter cohort. Methods: All primaty LT recipients (LTR) \u3e65y~who underwent LT from 2010-16 at 13 centers were included. For LTRs \u3e70y, survival was estimated using Kaplan-Meier methods; other outcomes were assessed within ly post-LT and compared toLTRs\u3c70y. Results: Of 179 LTRs \u3e70y, median was age 71y (range 70-78), 64% were male. and 770/c Caucasian. Leading indications for LT were NASH (27%), alcohol (11%). HCV (17%). 52% had HCC, of which 63% had MELD exceptions. Median laboratory MELDNa at LT was 19 (IQR 13-26), and median allocation MELD was 22 (IQR16-29). Comorbidities included diabetes (39%), congestive heart failure (8%), cerebrovascular disease (6%), chronic pulmonaty disease (11%), renal disease (38%). and osteoporosis/osteopenia (42%). The median donor age was 48y (33-62); 8% were donations after cardiac death, 10% living donation LT, and 6% SLK During LT, 1. 70/0 received induction with a T-cell depleting agent compared to 9% of LTRs \u3c70y in the cohort. At discharge, 77% were on calcineurin inhibitors and 73% on steroids vs 85% and 84% respectively, of LTRs \u3c70y. Within ly post-LT, graft rejection occurred in 18% and biliary strictures in 26%. Cardiovascular complications occurred in 25% (12% afib, 3% MI, 8% stroke and 9% heart failure), delirium in 16% and seizures in 3%. Viral, bacterial and fungal infections occurred ly post-LT in 17% 39% and 7% respectively. Solid organ cancers ly post-LT occurred in 10% with recurrent HCC (40/0) and lung cancer (2%) being the most common; this is compared to 4% in the cohort \u3c70y (p=0. 002). One-year and three-year patient survival was 89% and 76% respectively, vs 90% and 84% in \u3c70y. Conclusions: In a large US multicenter cohort, ly and 3y survival in LTRs \u3e70y were acceptable. De novo solid organ cancers within ly post-LT occurred in 10% of LTRs \u3e70y, more frequently than in those \u3c70y. Our data provide further understanding of the comorbidities experienced in advanced age LTRs and lay the foundation for improved selection and management of older LTRs