Deep brain stimulation: practical insights and common queries.

The number of patients with deep brain stimulation (DBS) devices implanted is increasing. Although practices vary between centres, patients are typically given training and information from their DBS nurse or clinician, as well as a comprehensive device manual and contact details for their device manufacturer. However, for the lifetime of a patient with a DBS system, most of their secondary care often occurs in a centre without a co-located DBS service. The local neurologist is often asked pragmatic questions regarding the do's and don'ts for patients with DBS systems. While a DBS centre or device manufacturer can provide advice, we thought that it will be helpful to outline the overall management of DBS for movement disorders and the approach to commonly raised questions. We describe briefly the clinical application of DBS and discuss common scenarios where there are possible compatibility issues around the device.

Comparative Profiles of SARS-CoV-2 Spike-Specific Human Milk Antibodies Elicited by mRNA- and Adenovirus-Based COVID-19 Vaccines.

Background: Numerous COVID-19 vaccines are authorized globally. To date, ∼71% of doses comprise the Pfizer/BioNTech vaccine, and ∼17% the Moderna/NIH vaccine, both of which are messenger RNA (mRNA) based. The chimpanzee Ad-based Oxford/AstraZeneca (AZ) vaccine comprises ∼9%, while the Johnson & Johnson/Janssen (J&J) human adenovirus (Ad26) vaccine ranks fourth at ∼2%. No COVID-19 vaccine is yet available for children 0-4. One method to protect this population may be passive immunization through antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work and other reports have demonstrated that unlike the post-SARS-CoV-2 infection milk Ab profile, which is rich in specific secretory (s)IgA, the vaccine response is highly IgG dominant. Results: In this report, we present a comparative assessment of the milk Ab response elicited by Pfizer, Moderna, J&J, and AZ vaccines. This analysis revealed 86-100% of mRNA vaccine recipient milk exhibited Spike-specific IgG endpoint titers, which were 12- to 28-fold higher than those measured for Ad vaccine recipient milk. Ad-based vaccines elicited Spike-specific milk IgG in only 33-38% of recipients. Specific IgA was measured in 52-71% of mRNA vaccine recipient milk and 17-23% of Ad vaccine recipient milk. J&J recipient milk exhibited significantly lower IgA than Moderna recipients, and AZ recipients exhibited significantly lower IgA titers than Moderna and Pfizer. Less than 50% of milk of any group exhibited specific secretory Ab, with Moderna recipient IgA titers measuring significantly higher than AZ. Moderna appeared to most frequently elicit greater than twofold increases in specific secretory Ab titer relative to prevaccine sample. Conclusion: These data indicate that current Ad-based COVID-19 vaccines poorly elicit Spike-specific Ab in milk compared to mRNA-based vaccines, and that mRNA vaccines are preferred for immunizing the lactating population. This study highlights the need to design vaccines better aimed at eliciting an optimal milk Ab response.

State-resolved UV photofragmentation spectrum of the metal dication complex [Zn(pyridine)(4)](2+).

A combined theoretical and experimental study of electronic transitions in the complex [Zn(pyridine)(4)](2+) provides the first example of a state-resolved electronic spectrum to be recorded for a dication complex in the gas phase.

Migration towards SDF-1 selects angiogenin-expressing bone marrow monocytes endowed with cardiac reparative activity in patients with previous myocardial infarction.

INTRODUCTION: Chemokine-directed migration is crucial for homing of regenerative cells to the infarcted heart and correlates with outcomes of cell therapy trials. Hence, transplantation of chemokine-responsive bone marrow cells may be ideal for treatment of myocardial ischemia. To verify the therapeutic activity of bone marrow mononuclear cells (BM-MNCs) selected by in vitro migration towards the chemokine stromal cell-derived factor-1 (SDF-1) in a mouse model of myocardial infarction (MI), we used BM-MNCs from patients with previous large MI recruited in the TransACT-1&2 cell therapy trials. METHODS: Unfractioned BM-MNCs, SDF-1-responsive, and SDF-1-nonresponsive BM-MNCs isolated by patients recruited in the TransACT-1&2 cell therapy trials were tested in Matrigel assay to evaluate angiogenic potential. Secretome and antigenic profile were characterized by flow cytometry. Angiogenin expression was measured by RT-PCR. Cells groups were also intramyocardially injected in an in vivo model of MI (8-week-old immune deficient CD1-FOXN1(nu/nu) mice). Echocardiography and hemodynamic measurements were performed before and at 14 days post-MI. Arterioles and capillaries density, infiltration of inflammatory cells, interstitial fibrosis, and cardiomyocyte proliferation and apoptosis were assessed by immunohistochemistry. RESULTS: In vitro migration enriched for monocytes, while CD34(+) and CD133(+) cells and T lymphocytes remained mainly confined in the non-migrated fraction. Unfractioned total BM-MNCs promoted angiogenesis on Matrigel more efficiently than migrated or non-migrated cells. In mice with induced MI, intramyocardial injection of unfractionated or migrated BM-MNCs was more effective in preserving cardiac contractility and pressure indexes than vehicle or non-migrated BM-MNCs. Moreover, unfractioned BM-MNCs enhanced neovascularization, whereas the migrated fraction was unique in reducing the infarct size and interstitial fibrosis. In vitro studies on isolated cardiomyocytes suggest participation of angiogenin, a secreted ribonuclease that inhibits protein translation under stress conditions, in promotion of cardiomyocyte survival by migrated BM-MNCs. CONCLUSIONS: Transplantation of bone marrow cells helps post-MI healing through distinct actions on vascular cells and cardiomyocytes. In addition, the SDF-1-responsive fraction is enriched with angiogenin-expressing monocytes, which may improve cardiac recovery through activation of cardiomyocyte response to stress. Identification of factors linking migratory and therapeutic outcomes could help refine regenerative approaches.

Evidence of zinc superoxide formation in the gas phase: comparisons in behaviour between ligated Zn(I/II) and Cu(I/II) with regard to the attachment of O2 or H2O.

Singly and doubly charged atomic ions of zinc and copper have been complexed with pyridine and held in an ion trap. Complexes involving Zn(II) and Cu(I) (3d(10)) display a strong tendency to bind with H(2)O, whilst the Zn(I) (3d(10)4s(1)) complexes exhibit a strong preference for the attachment of O(2). DFT calculations show that this latter result can be interpreted as internal oxidation leading to the formation of superoxide complexes, [Zn(II)O(2)(-)](pyridine)(n), in the gas phase. The calculations also show that the oxidation of Zn(I) to form Zn(II)O(2)(-) is promoted by a mixing of the occupied 4s and vacant 4p orbitals on the metal cation, and that this process is facilitated by the presence of the pyridine ligands.