Revealing an unusual transparent phase of superhard iron tetraboride under high pressure

First principles–based electronic structure calculations of superhard iron tetraboride (FeB₄) under high pressure have been undertaken in this study. Starting with a “conventional” superconducting phase of this material under high pressure leads to an unexpected phase transition toward a semiconducting one. This transition occurred at 53.7 GPa, and this pressure acts as a demarcation between two distinct crystal symmetries, metallic orthorhombic and semiconducting tetragonal phases, with Pnnm and I4₁/acd space groups, respectively. In this work, the electron–phonon coupling-derived superconducting T_c has been determined up to 60 GPa and along with optical band gap variation with increasing pressure up to 300 GPa. The dynamic stability has been confirmed by phonon dispersion calculations throughout this study.The shorter interatomic distances of metal under external pressure consequently increase the valence and conduction band widths, which leads to the enhancement of free electron-like behavior. The development of creating immensely substantial pressure at laboratories enables us to observe the core electrons overlapping under enormous compression and dramatically influences the electronic properties of normally free electron metals such as Li and Na (1–3). The metal-to-insulating phase transformation has been contrived both experimentally and theoretically for both the normal metals while exerting pressure on them. This observation propelled us to investigate the electronic and structural phase transformation of the experimentally synthesized superhard material iron tetraboride (FeB₄) under high pressure (4–8). The intriguing factor of choosing FeB₄ is that the material was proposed as a “conventional” Fe-based superconductor, in contradiction to the discovery of an “unconventional” Fe-based superconductor because of its large electron–phonon coupling. Here we report the exotic phase transition of FeB₄ from metal to semiconductor at 53.7 GPa, even though we started with the metallic orthorhombic phase Pnnm of FeB₄, which shows the superconducting temperature T_c up to 60 GPa. The new phase after 53.7 GPa has I4₁/acd space group symmetry with a finite fundamental band gap, which increases along with pressure monotonically. All of the considered structures have been tested to have a thermodynamic stability from phonon dispersion calculations. The reason behind the phenomena could be the overlap of atomic cores at higher pressure ranges, which increases the hybridization of valence electrons and their repulsive interactions with core electrons. The immediate technological outcome of this scenario of metal-to-semiconducting phase transition could be to search for a transparent state of a material that is a metal under ambient conditions. This drastic change of electronic and structural properties can be observed in other materials as well, and hence this can open a field of studying them from a high-pressure perspective.     

Quantifying a Rare Disease in Administrative Data: The Example of Calciphylaxis

BACKGROUND

Calciphylaxis, a rare disease seen in chronic dialysis patients, is associated with significant morbidity and mortality. As is the case with other rare diseases, the precise epidemiology of calciphylaxis remains unknown. Absence of a unique International Classification of Diseases (ICD) code impedes its identification in large administrative databases such as the United States Renal Data System (USRDS) and hinders patient-oriented research. This study was designed to develop an algorithm to accurately identify cases of calciphylaxis and to examine its incidence and mortality.

DESIGN, PARTICIPANTS, AND MAIN MEASURES

Along with many other diagnoses, calciphylaxis is included in ICD-9 code 275.49, Other Disorders of Calcium Metabolism. Since calciphylaxis is the only disorder listed under this code that requires a skin biopsy for diagnosis, we theorized that simultaneous application of code 275.49 and skin biopsy procedure codes would accurately identify calciphylaxis cases. This novel algorithm was developed using the Partners Research Patient Data Registry (RPDR) (n?=?11,451 chronic hemodialysis patients over study period January 2002 to December 2011) using natural language processing and review of medical and pathology records (the gold-standard strategy). We then applied this algorithm to the USRDS to investigate calciphylaxis incidence and mortality.

KEY RESULTS

Comparison of our novel research strategy against the gold standard yielded: sensitivity 89.2 %, specificity 99.9 %, positive likelihood ratio 3,382.3, negative likelihood ratio 0.11, and area under the curve 0.96. Application of the algorithm to the USRDS identified 649 incident calciphylaxis cases over the study period. Although calciphylaxis is rare, its incidence has been increasing, with a major inflection point during 2006–2007, which corresponded with specific addition of calciphylaxis under code 275.49 in October 2006. Calciphylaxis incidence continued to rise even after limiting the study period to 2007 onwards (from 3.7 to 5.7 per 10,000 chronic hemodialysis patients; r?=?0.91, p?=?0.02). Mortality rates among calciphylaxis patients were noted to be 2.5–3 times higher than average mortality rates for chronic hemodialysis patients.

CONCLUSIONS

By developing and successfully applying a novel algorithm, we observed a significant increase in calciphylaxis incidence. Because calciphylaxis is associated with extremely high mortality, our study provides valuable information for future patient-oriented calciphylaxis research, and also serves as a template for investigating other rare diseases.

     

RSSDI-ESI Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2020

International Journal of Diabetes in Developing Countries -     

Floating thumb with double dislocation of carpometacarpal and metacarpo-phalangeal joints

INTRODUCTION

Double dislocations of carpometacarpal and metacarpo-phanlageal joints are rare. We report an unusual case of simultaneous dislocation of both CMC and MCP joints in the thumb.

PRESENTATION OF CASE

A 31 year old male was admitted following a road traffic accident. He was complaining of pain and deformity of right thumb. The X-ray examination revealed simultaneous dislocation of both CMC and MCP joints. He underwent closed manipulative reduction and percutaneous K wire fixation. The wires were removed after six weeks. After a course of physiotherapy he regained full range of pain free movements.

DISCUSSION

The incidence of simultaneous dislocation of both CMC and MCP joints in thumb are associated with high energy injuries. The options of treatment are conservative with cast immobilisation and serial X-rays or operative including closed manipulative reduction and K wire fixation or open reduction and internal fixation.

CONCLUSION

The option of treating this rare injury with closed manipulative reduction and percutaneous K wiring gives excellent and predictable results.     

Ligament reconstruction/advancement for management of instability due to ligament insufficiency during total knee arthroplasty: a viable alternative to constrained implant

Background

We aimed to assess the results of ligament reconstruction/advancement for the management of ligament insufficiency during total knee arthroplasty.

Method

We retrospectively reviewed the results of ligament reconstruction/advancement for management of instability due to ligament insufficiency during total knee arthroplasty (TKA). Between January 2001 and January 2008 collateral ligament reconstruction/advancement was done in 15 patients. Wherever ligament advancement was not possible (mid-substance tear) ligament reconstruction was done using the hamstring tendon. Knee society scores were calculated and Kaplan–Meier survival analysis was done.

Results

Average follow-up was 6.2 years. No patient developed instability until the last follow-up, except one patient who required revision due to instability at six years after primary surgery.

Conclusion

We concluded from this study that ligament reconstruction/advancement during TKA is a viable option to address instability due to ligament insufficiency.     

Dietary supplementation of milk fermented with probiotic Lactobacillus fermentum enhances systemic immune response and antioxidant capacity in aging mice

Although probiotics are known to enhance the host immune response, their roles in modulating immunosenescence, resisting infection, and improving redox homeostasis during aging remain unclear. Therefore, the present study was devised in aging mice to assess the antiimmunosenescence potential from the consumption of milk that is fermented with probiotic Lactobacillus fermentum MTCC 5898 (LF). We hypothesized that probiotic supplementation would boost immunity, improve antioxidant capacity, and resist severity of pathogenic infection in aging mice. To test this hypothesis, during a trial period of 2 months, 16-month-old male Swiss mice were kept on 3 experimental diets: basal diet (BD), BD supplemented with skim milk, and BD supplemented with probiotic LF-fermented milk. A concurrent analysis of several immunosenescence markers that include neutrophil functions, interleukins profile, inflammation and antibody responses in the intestine as well as analysis of antioxidant enzymes in the liver and red blood cells was performed. Neutrophil respiratory burst enzymes and phagocytosis increased significantly in probiotic LF-fed groups, whereas no exacerbation in plasma levels of monocyte chemotactic protein 1 and tumor necrosis factor α was observed. Splenocytes registered increased interferon-γ but decreased interleukin 4 and interleukin 10 production, whereas humoral antibodies registered decreases in immunoglobulin G1 (IgG1)/IgG2a ratio and IgE levels in the probiotic-fed groups. Antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in LF-fed groups showed increased activities, which were more pronounced in the liver than in red blood cell. An Escherichia coli–based infection model in aging mice was also designed to validate the protective attributes of LF. Administration of probiotic LF significantly reduced E coli population in organs (intestine, liver, spleen, and peritoneal fluid), as compared with control groups, by enhancing E coli–specific antibodies and inflammatory proteins. Based on these results, it appears that LF supplementation alleviated immunosenescence, enhanced antioxidant enzyme activities, and resisted E coli infection in aging mice; thereby, signifying its potential in augmenting healthy aging.     

Convalescent plasma treatment for COVID-19: Tempering expectations with the influenza experience

The COVID-19 pandemic caused by the zoonotic coronavirus, SARS-CoV-2 has swept the world in 5 months. A proportion of cases develop severe respiratory tract infections progressing to acute respiratory distress syndrome and a diverse set of complications involving different organ systems. Faced with a lack of coronavirus-specific antiviral drugs and vaccines, hundreds of clinical trials have been undertaken to evaluate repurposed drugs. Convalescent plasma from recovered patients is an attractive option because antibodies can have direct or indirect antiviral activity and immunotherapy works well in principle, in animal models, and in anecdotal reports. However, the benefits of convalescent plasma treatment can only be clearly established through carefully designed randomized clinical trials. The experience from investigations of convalescent plasma products for severe influenza offers a cautionary tale. Despite promising pilot studies, large multicenter randomized controlled trials failed to show a benefit of convalescent plasma or hyperimmune intravenous globulin for the treatment of severe influenza A virus infection. These studies provide important lessons that should inform the planning of adequately powered randomized controlled trials to evaluate the promise of convalescent plasma therapy in COVID-19 patients.     

An advanced and efficient Co3O4/C nanocomposite for the oxygen evolution reaction in alkaline media

The design of efficient nonprecious catalysts for the hydrogen evolution reaction (HER) or the oxygen evolution reaction (OER) is a necessary, but very challenging task to uplift the water-based economy. In this study, we developed a facile approach to produce porous carbon from the dehydration of sucrose and use it for the preparation of nanocomposites with cobalt oxide (Co₃O₄). The nanocomposites were studied by the powder X-ray diffraction and scanning electron microscopy techniques, and they exhibited the cubic phase of cobalt oxide and porous structure of carbon. The nanocomposites showed significant OER activity in alkaline media, and the current densities of 10 and 20 mA cm⁻² could be obtained at 1.49 and 1.51 V versus reversible hydrogen electrode (RHE), respectively. The impedance study confirms favorable OER activity on the surface of the prepared nanocomposites. The nanocomposite is cost-effective and can be capitalized in various energy storage technologies.

The design of efficient nonprecious catalysts for the hydrogen evolution reaction (HER) or the oxygen evolution reaction (OER) is a necessary, but very challenging task to uplift the water-based economy.     

Venlafaxine alters microvascular perfusion, [I]-beta-CIT binding and BDI scores in flushing postmenopausal women

Background

Although 70% of postmenopausal women suffer from hot flashes the pathophysiology is poorly understood. The serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine provides relief of flushing although the mechanism is unknown and could involve a central effect and/or a peripheral effect. Using single photon emission computed tomography (SPECT) we studied the central serotonin transporter (SERT) in vivo using [¹²³I]-beta-carbomethoxy-3-β-(4-iodophenyl)tropane (beta-CIT) and, as previous studies have shown that reactivity of the skin blood vessels is enhanced in those who flush, we examined cutaneous microvascular perfusion.

Methods

Cutaneous microvascular perfusion was assessed in 31 postmenopausal women, with flushing, using laser Doppler imaging with iontophoresis (LDI + ION), before and after 8 weeks of treatment with venlafaxine. A sub-group of 14 of these women also had SPECT imaging at both time points to evaluate the availability of SERT in the brain. Flush frequency and score was recorded, and Beck Depression Inventory (BDI) II scores were assessed before and after treatment.

Results

Following treatment with venlafaxine, there was a significant reduction in the [¹²³I]-beta-CIT binding ratio, BDI scores, flushing and endothelial dependent perfusion response. [¹²³I]-Beta-CIT reduction was associated with BDI reduction (r² = 0.54; F = 8.8; p = 0.004), but not flushing reduction or perfusion reduction.

Conclusions

Venlafaxine resulted in a decrease in BDI II scores with an associated reduction in [¹²³I]-beta-CIT binding in a group of non-depressed women. It also improved flush frequency and severity which may be as a result of decreases seen in enhanced cutaneous microvascular perfusion.     

Pre-clinical pharmacokinetic and pharmacodynamic modelling study of 4-hydroxyisoleucine using validated ultra-performance liquid chromatography-tandem mass spectrometry

A reliable and sensitive ultra-performance liquid chromatography-tandem mass spectrometry-based method has been developed for the estimation of 4-hydroxyisoleucine (4-HI), a potent insulinotropic and hypolipidemic agent. The extraction of 4-HI from plasma was accomplished by the protein precipitation technique using l-isoleucine as an internal standard. The separation of analytes was achieved with a mobile phase consisting of acetonitrile and 0.1% formic acid in an isocratic flow system on a BEH Shield RP-18 column (150 mm × 2.1 mm, 1.7 μm). 4-HI and l-isoleucine were detected using an electrospray ionization (ESI) ion source, using multiple reaction monitoring (MRM) in positive ion mode. The precursor to product ion transitions of 4-HI and l-isoleucine were found at m/z values of 148.19 > 74.02 and 132.17 > 69.04, respectively. As per the guidelines for bioanalytical methods, all validation parameter results were within the acceptable range. The method exhibited a robust and reproducible linearity range of 1–5000 ng mL⁻¹ with a coefficient of regression of 0.9999. The method was successfully applied for the estimation of pharmacokinetic parameters after oral administration of 4-HI (10 mg kg⁻¹) in Wistar rats, by using Thoth Pro (version: 4.3) software. Herein, the two-compartment model was statistically fitted based on AIC and SBC values for evaluation of the pharmacokinetic parameters of 4-HI. Pharmacodynamic studies were also performed by measuring the levels of triglyceride and total cholesterol, and showed that the pharmacokinetic and pharmacodynamic data of 4-HI correlated with each other.

A reliable and sensitive UPLC-MS/MS based method has been developed for the estimation of 4-hydroxyisoleucine, a potent insulinotropic and hypolipidemic agent.