Leadless cardiac pacemaker implantations after infected pacemaker system removals in octogenarians

BackgroundManagement of pacemaker (PM) infections among advanced aged patients possesses particular clinical challenges due to higher rates of concurrent cardiovascular disease and medical comorbidities. Novel leadless cardiac pacemakers (LCPs) may provide new opportunities for better management options in this population, however, there is limited data especially in Asian populations to guide the decision making.MethodsWe reviewed 11 octogenarians (median age: 86 [minimum 82–maximum 90] years; male: 73%; median body mass index (BMI): 20.1 kg/m²) who received Micra Transcatheter Pacing System (Medtronic Inc, Minneapolis, MN) implantations following transvenous lead extractions (TLEs) for PM infections. ResultsAll patients had more than two medical comorbidities (average 3.7 comorbidities). The indications for LCP implantations were atrioventricular block in four patients, atrial fibrillation bradycardia in five, and sinus node dysfunction in two. Eight patients (73%) were bridged with temporary pacing using active fixation leads (median interval of 14.0 days), while one with severe dementia underwent a concomitant LCP implantation and TLE during the same procedure. Successful TLEs and LCP implantations were successfully accomplished in all without any complications. The median time from the TLE procedure to discharge was 22 days (minimum 7–maximum 136). All patients remained free of infections during a mean follow-up period of 17.2 ± 6.5 months.ConclusionsLCP implantations were safe and effective after removing the entire infectious PM system in all octogenarians. The novel LCP technology may offer an alternative option for considering a re-implantation strategy after transvenous PM infections in elderly patients, particularly those with severe frailty and PM dependency.

The incidence of cardiac pacemaker (PM) infections among patients with an advanced age has been increasing owing to the continually widening indications and growing number of generator replacements.^[1–3] In current clinical practice, there is a class l indication for removing all hardware in the case of a proven or suspected device infection, and after a recovery window, a new conventional PM is implanted in PM dependent patients.^[1,4,5] However, this management for the elderly population is one of the most sensitive issues, since they possess particular clinical challenges due to higher rates of concurrent cardiovascular disease and medical comorbidities.^[6–10]Recently, the implantation of a Micra Transcatheter Pacing System (Medtronic Inc, Minneapolis, MN) has emerged as a new option for PM re-implantations after the removal of infectious PMs.^[11–17] Without the use of leads and a device pocket, this leadless cardiac pacemaker (LCP) potentially reduces the risk of pocket infections and lead associated endocarditis.^[16,17] However, there have not been enough data supporting the feasibility of leadless PM implantations following the removal of infectious PMs in people with an older age, particularly in octogenarians. Furthermore, there has been no data regarding those therapeutic strategies in Asian populations who have a low body mass index (BMI) and are at a higher risk of a transvenous lead extraction (TLE) procedure. Therefore, in this case series, we sought to characterize the procedure for LCP implantations following TLEs of infected PMs in octogenarians at 2 Japanese high-volume centers.     

Induction of tumoricidal macrophages and production of cytokines by synthetic muramyl dipeptide analogues

The ability of various synthetic muramyl dipeptide (MDP) derivatives to induce the production of interleukin-1 (IL-1) and colony stimulating factor (CSF) in vitro and in vivo and to induce cytotoxic macrophages was studied. 6-O-L18-MDP(Me) and MDP-Lys(L18), which were potent inducers of IL-1 and CSF production and of cytotoxic macrophages, had protective activity against Sendai virus infection in mice. In contrast, 1-O-L18-(6-O-P)-MDP(Me) and 2-N-L18-MDP exhibited weak or no ability to induce IL-1 and CSF production and no induction of tumoricidal macrophages, and did not protect against infection of Sendai virus. MDP derivatives, except 2-N-L18-MDP, efficiently rendered macrophages cytotoxic against target cells in the presence of murine recombinant interferon-gamma in vitro. The derivatives that induced cytokines and cytotoxic macrophages appeared to produce anti-viral activity.     

GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein

Colorectal cancer (CRC) is one of the most common types of cancer and a significant cause of cancer mortality worldwide. Further improvements of CRC therapeutic approaches are needed. BCL2‐associated athanogene 6 (BAG6), a multifunctional scaffold protein, plays an important role in tumor progression. However, regulation of BAG6 in malignancies remains unclear. This study showed that guided entry of tail‐anchored proteins factor 4 (GET4), a component of the BAG6 complex, regulates the intercellular localization of BAG6 in CRC. Furthermore, GET4 was identified as a candidate driver gene on the short arm of chromosome 7, which is often amplified in CRC, by our bioinformatics approach using the CRC dataset from The Cancer Genome Atlas. Clinicopathologic and prognostic analyses using CRC datasets showed that GET4 was overexpressed in tumor cells due to an increased DNA copy number. High GET4 expression was an independent poor prognostic factor in CRC, whereas BAG6 was mainly overexpressed in the cytoplasm of tumor cells without gene alteration. The biological significance of GET4 was examined using GET4 KO CRC cells generated with CRISPR‐Cas9 technology or transfected CRC cells. In vitro and in vivo analyses showed that GET4 promoted tumor growth. It appears to facilitate cell cycle progression by cytoplasmic enrichment of BAG6‐mediated p53 acetylation followed by reduced p21 expression. In conclusion, we showed that GET4 is a novel driver gene and a prognostic biomarker that promotes CRC progression by inducing the cytoplasmic transport of BAG6. GET4 could be a promising therapeutic molecular target in CRC.     

Preparation of a platinum nanoparticle catalyst located near photocatalyst titanium oxide and its catalytic activity to convert benzyl alcohols to the corresponding ethers

A novel platinum nanoparticle catalyst closely located near the surface of titanium oxide, PtNP/TiO₂, has been prepared. This catalyst has both the properties of a photocatalyst and a metal nanoparticle catalyst, and acquired environmentally friendly catalytic activity, which cannot be achieved by just one of these catalysts, to afford ethers from benzyl alcohols under the wavelength of 420 nm.

A novel platinum nanoparticle catalyst closely located near the surface of titanium oxide, PtNP/TiO₂, has been prepared. It has catalytic activity to afford ethers from benzyl alcohols under the wavelength of 420 nm.

The electrolysis of water by a heterogeneous metal oxide semiconductor (MOS) photocatalyst, called the Honda–Fujishima effect,¹ received considerable attention because it enables the conversion of solar energy. As a result, photoreactions by heterogeneous photocatalysts based on MOS have been reported until now, including numerous practical applications such as carbon dioxide reduction² and pollutant removal.³Research on photocatalytic reactions using visible light is progressing steadily. Among them, TiO₂ has been extensively studied due to its high catalytic activity, low cost, non-toxicity, and long-term stability.^4,5Titanium oxide has a very strong oxidizing power, but it does not have a strong reducing power.⁶ By using a transition metal such as platinum on titanium oxide as a support, its reducing power can be increased, and the amount of hydrogen generated in the electrolysis of water can be improved eight times compared to the case of titanium oxide alone.⁷Furthermore, when MOS contacts the metal, a potential barrier called Schottky barrier is formed at the interface. The basic characteristic of this Schottky barrier lies in the Schottky barrier height (Φ), which represents the difference between the CB of the MOS distorted by the contact with a metal and the Fermi level (E_F) of the metal. Although it has been studied for almost half a century, how to determine the barrier is still not well understood. Due to the formation of the Schottky barrier height, the energy required to move the electrons from the valence band of MOS to the conductor changes from E_g to Φ, and the energy becomes smaller and it changes to a longer wavelength. As a result, a photoreaction with titanium oxide using light with a wavelength longer than 387 nm has also been reported (Scheme 1)⁸Open in a separate windowScheme 1Effect of sunlight exposure on aerobic oxidation of alcohols with the Pt/TiO₂ catalysts.On the other hand, we have recently developed a sulfur-modified Au-supported Pd NP catalyst (SAPd) that is applicable in Suzuki–Miyaura coupling^9a,9b and C–H functionalization^9c (Scheme 2a). It was constructed by approximately 10 layers of self-assembled Pd(0) NPs (mean size: <5 nm) supported on a sulfur-modified Au surface. We speculated that the self-assembled Pd NPs, which were encapsulated in a sulfated p-xylene polymer matrix,^9d were formed using in situ metal NP and nanospace simultaneous organization (PSSO), as illustrated in Scheme 2b: (i) the reduction of a high-valence metal source, (ii) growth of transition metal NPs, (iii) growth of a matrix with appropriately sized nanopores, and (iv) encapsulation of the metal NPs in these nanopores. To prepare SARu,¹⁰ SANi,¹¹ SAFe(ii),¹² and SAFe(0)¹³ (Scheme 2a), the PSSO method involves the in situ reduction of a noble metal precursor to produce in situ metal NPs.Open in a separate windowScheme 2(a) Preparation of SAPd, SARu, SANi, SAFe(II) and SAFe(0) by combining in situ PSSO with an organic reductant, (b) in situ metal nanoparticle and nanospace simultaneous organization (PSSO) method and the image of the SAPd structure and (c) the preparation of PtNP/TiO₂.In this research project, we decided to create a novel metal NP catalyst having metal NPs near the surface of TiO₂ by substituting the gold-supported SAPd for gold with a titanium oxide (TiO₂) photocatalyst. Alternatively, by substituting the solid gold support for a photocatalyst, we thought that we could create a novel metal NPs catalyst with an unprecedented reactivity by combining the properties of both photocatalyst and metal nanoparticle catalyst (Scheme 2c).     

Facile synthesis of ZnO nanobullets by solution plasma without chemical additives

ZnO nano-bullets were synthesized using solution plasma from only Zn electrode in water without any chemical agents. In this sustainable synthesis system, the rapid quenching reaction at the interface between the plasma/liquid phases facilitates the fast formation of nano-sized materials. The coil-to-pin type electrode geometry, which overcomes the discharge interruption owing to the electrode gap broadening of the typical pin-to-pin type enables the synthesis of numerous nanomaterials through a stable discharge for 1 h. The as-prepared samples exhibited a high crystalline ZnO structure without post calcination, and the length and width were 71.8 and 29.1 nm, respectively. The main exposed facet of ZnO nano-bullets was the (100) crystal facet, but interestingly, the (101) facet was confirmed at the inclined surfaces in the edges. The (101) crystal facet has an asymmetric Zn and O atom arrangement, and it could result in a focused electron density area with relatively high reactivity. Therefore, ZnO nano-bullets are promising materials for applications in advanced technologies.

ZnO nano-bullets were synthesized using only Zn electrode and water by solution plasma and new electrode geometry improved discharge time up to 1 h.     

Neurocognitive and psychiatric disorders-related axonal degeneration in Parkinson's disease

Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract-based spatial statistics and tract-of-interest analyses. LICA was applied to model inter-subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD.