Morphological and Biochemical Changes During Aging and Photoaging of the Skin of C57BL/6J Mice

The differences between the dorsal skin of 11- and 16-week-old C57BL/6J mice were examined morphologically and biochemically. The dermis of the 16-week-old mice was thinner than that of the 11-week-old mice due to decreases in the amounts of soluble collagen and elastin. Next, the changes in dorsal skin exposed to UVA irradiation for 8 weeks (576 J/cm2) were examined in 3 (younger)- and 8 (older)-week-old C57BL/6J mice. The thickness of the dermis was not significantly different between the UVA-irradiated and control mice in either the younger or older group. The increase in the amount of collagen was related to the increase in the level of soluble collagen in the younger mice. In contrast, it was related to the increase in the level of insoluble collagen in the older mice. In the UVA-irradiated older mice, the activity of the latent form of MMP-13 was significantly higher than that in the control mice. These results suggest that aging and UVA-induced photoaging in the skin are histologically and biochemically different phenomena

Hornerin deposits in neuronal intranuclear inclusion disease : direct identification of proteins with compositionally biased regions in inclusions

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder, characterized by the presence of eosinophilic inclusions (NIIs) within nuclei of central and peripheral nervous system cells. This study aims to identify the components of NIIs, which have been difficult to analyze directly due to their insolubility. In order to establish a method to directly identify the components of NIIs, we first analyzed the huntingtin inclusion-rich fraction obtained from the brains of Huntington disease model mice. Although the sequence with expanded polyglutamine could not be identified by liquid-chromatography mass spectrometry, amino acid analysis revealed that glutamine of the huntingtin inclusion-rich fraction increased significantly. This is compatible with the calculated amino acid content of the transgene product. Therefore, we applied this method to analyze the NIIs of diseased human brains, which may have proteins with compositionally biased regions, and identified a serine-rich protein called hornerin. Since the analyzed NII-rich fraction was also serine-rich, we suggested hornerin as a major component of the NIIs. A specific distribution of hornerin in NIID was also investigated by Matrix-assisted laser desorption/ionization imaging mass spectrometry and immunofluorescence. Finally, we confirmed a variant of hornerin by whole-exome sequencing and DNA sequencing. This study suggests that hornerin may be related to the pathological process of this NIID, and the direct analysis of NIIs, especially by amino acid analysis using the NII-rich fractions, would contribute to a deeper understanding of the disease pathogenesis.Peer reviewe

Importance of pre pump arterial pres sure monitoring in hemodialysis patients

Pre-pump arterial pressure (PreAP) is monitored to avoid generating excessive negative pressure. National Kidney Foundation K/DOQI clinical practice guidelines for vascular access recommend that PreAP should not fall below-250 mmHg because excessive negative PreAP can lead to a decrease in the delivery of blood flow, inadequate dialysis, and hemolysis. Nonetheless, these recommendations are consistently disregarded in clinical practice and pressure sensors are often removed from the dialysis circuit.Thus far,delivered blood flow has been reported to decrease at values more negative than -150 mmHg of PreAP. These values have been analyzed by an ultrasonic flowmeter and not directly measured. Furthermore, no known group has evaluated whether PreAP-induced hemolysis occurs at a particular threshold. Therefore, the aim of this study was to clarify the importance of PreAP in the prediction of inadequate dialysis and hemolysis. By using different diameter needles, human blood samples from healthy volunteers were circulated in a closed dialysis circuit. The relationship between PreAP and delivered blood flow or PreAP and hemolysis was investigated. We also investigated the optimal value for PreAP using several empirical monitoring methods, such as a pressure pillow. Our investigation indicated that PreAP is a critical factor in the determination of delivered blood flow and hemolysis,both of which occured at pressure values more negative than -150 mmHg. With the exception of direct pressure monitoring, commonly used monitoring methods for PreAP were determined to be ineffective. We propose that the use of a vacuum monitor would permit regular measurement of PreAP

Effect of SARS-CoV-2 BNT162b2 mRNA vaccine on thyroid autoimmunity: A twelve-month follow-up study

ObjectivesGraves’ disease (GD) has been highlighted as a possible adverse effect of the respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. However, it is unknown if the SARS-CoV-2 vaccine disrupts thyroid autoimmunity. We aimed to present long-term follow-up of thyroid autoimmunity after the SARS-CoV-2 BNT162b2 mRNA vaccine.MethodsSerum samples collected from seventy Japanese healthcare workers at baseline, 32 weeks after the second dose (pre-third dose), and 4 weeks after the third dose of the vaccine were analyzed. The time courses of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibody, thyroid-stimulating hormone receptor antibody (TRAb), and thyroid function were evaluated. Anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were additionally evaluated in thirty-three participants.ResultsThe median age was 50 (IQR, 38-54) years and 69% were female. The median anti-spike IgG antibody titer was 17627 (IQR, 10898-24175) U/mL 4 weeks after the third dose. The mean TRAb was significantly increased from 0.81 (SD, 0.05) IU/L at baseline to 0.97 (SD, 0.30) IU/L 4 weeks after the third dose without functional changes. An increase in TRAb was positively associated with female sex (β = 0.32, P = 0.008) and low basal FT4 (β = -0.29, P = 0.02) and FT3 (β = -0.33, P = 0.004). TgAb was increased by the third dose. Increase in TgAb was associated with history of the thyroid diseases (β = 0.55, P <0.001).ConclusionsSARS-CoV-2 BNT162b2 mRNA vaccine can disrupt thyroid autoimmunity. Clinicians should consider the possibility that the SARS-CoV-2 vaccine may disrupt thyroid autoimmunity

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Microhardness and tensile strength of electrochemically synthesized nickel-cobalt binary alloy sheets exfoliated from a dumbbell-shaped titanium cathode

Nanocrystalline nickel–cobalt (Ni–Co) binary alloy sheets were fabricated through electroforming in an acidic aqueous bath using exfoliation from a metallic titanium cathode. Cobalt content in Ni–Co alloy sheets ranged from 28.8 at% to 72.0 at% depending on experimental parameters, such as cathodic overpotential and bath composition. The surface roughness ( R _a ) of the electroformed alloy sheets significantly decreased down to 1.5 μ m as saccharin sodium dihydrate was added as an additive to the acidic aqueous solution bath. X-ray diffraction profiles and transmission electron microscopy images indicated that the electroformed Ni–Co alloy sheets have a nanocrystalline structure (grain size ≈ 30 nm). The lattice constant of the electroformed Ni–Co alloy sheets increased with an increase in cobalt content (i.e. solute atom concentration). The mechanical properties were significantly improved because of the synergistic effects of crystal grain refinement and solid solution strengthening. The microhardness and tensile strength of the electroformed Ni–Co alloy sheets reached 609 kgf mm ^−2 and 1757 MPa ( X _Co = 49.9 at%), respectively. The tensile strength of the electroformed Ni–Co alloy sheets in this study significantly exceeded that of solidified Ni–Co alloys (approximately 370 MPa). Therefore, this study offers a technique to enhance the mechanical properties of electroformed Ni–Co alloy sheets