Effects of Switching from Degludec to Glargine U300 in Patients with Insulin-Dependent Type 1 Diabetes: A Retrospective Study.

Background and Objectives: Degludec (Deg) and glargine U300 (Gla-300) are insulin analogs with longer and smoother pharmacodynamic action than glargine U100 (Gla-100), a long-acting insulin that has been widely used for many years in type 1 and type 2 diabetes. Both improve glycemic variability (GV) and the frequency of hypoglycemia, unlike Gla-100. However, it is unclear which insulin analog affects GV and hypoglycemia better in patients with insulin-dependent type 1 diabetes. We evaluated the effects of switching from Deg to Gla-300 on the day-to-day GV and the frequency of hypoglycemia in patients with insulin-dependent type 1 diabetes treated with Deg-containing basal-bolus insulin therapy (BBT). Materials and Methods: We conducted a retrospective study on 24 patients with insulin-dependent type 1 diabetes whose treatment was switched from Deg-containing BBT to Gla-300-containing BBT. We evaluated the day-to-day GV measured as the standard deviation of fasting blood glucose levels (SD-FBG) calculated by the self-monitoring of blood glucose records, the frequency of hypoglycemia (total, severe, and nocturnal), and blood glucose levels measured as fasting plasma glucose (FPG) levels and hemoglobin A1c (HbA1c). Results: The characteristics of the patients included in the analysis with high SD-FBG had frequent hypoglycemic events, despite the use of Deg-containing BBT. For this population, SD-FBG and the frequency of nocturnal hypoglycemia decreased after the switch from Deg to Gla-300. Despite the decrease in the frequency of nocturnal hypoglycemia, the FPG and HbA1c did not worsen by the switch. The change in the SD-FBG had a negative correlation with the SD-FBG at baseline and a positive correlation with serum albumin levels. Conclusions: Switching from Deg to Gla-300 improved the SD-FBG and decreased the frequency of nocturnal hypoglycemia in insulin-dependent type 1 diabetes treated with Deg-containing BBT, especially in cases with low serum albumin levels and a high GV.

Fulminant type 1 diabetes developed after influenza split vaccination.

Summary: Fulminant type 1 diabetes (FT1D) is a subtype of diabetes characterized by rapid progression of ß-cell destruction, hyperglycemia, and diabetic ketoacidosis (DKA). The pathogenesis of this disease remains unclear. However, viral infections, HLA genes, and immune checkpoint inhibitor use were reportedly involved in this disease. A 51-year-old Japanese man with no chronic medical condition was admitted to our hospital with complaints of nausea and vomiting. Cough, sore throat, nasal discharge, and diarrhea were not noted. He had a medical history of at least two influenza infections. His vaccination history was notable for receiving an inactive split influenza vaccine 12 days prior to developing these symptoms. He was diagnosed with DKA associated with FT1D. His HLA class II genotypes were nonsusceptible to FT1D, and he had a negative history of immune checkpoint inhibitor use. The destruction of the pancreas by cytotoxic T cells is reported to be involved in FT1D. Inactive split influenza vaccines do not directly activate cytotoxic T cells. However, these could activate the redifferentiation of memory CD8-positive T cells into cytotoxic T cells and induce FT1D, as this patient had a history of influenza infections. Learning points: Influenza split vaccination could cause fulminant type 1 diabetes (FT1D). The mechanism of influenza split vaccine-induced FT1D might be through the redifferentiation of CD8-positive memory T cells into cytotoxic T cells.

Unity-order magnetochiral effects exhibited by a single metamolecule.

A numerical study predicts that a single metamolecule with magnetism and chirality has giant magnetochiral (MCh) effects at microwave frequencies. The magnetism is provided by the ferromagnetic resonance of ferrite under dc bias magnetic fields, while the chirality is provided by the spiral arrangement of dielectric cubes with Mie resonance. The dielectric and magnetic resonances interfere in the metamolecule, resulting in a two-order of magnitude enhancement of the MCh effect compared with that reported in previous studies. This prediction is verified experimentally. A unity-order directional difference in the refractive index caused by the MCh effect is also demonstrated. This study is a significant milestone in the practical use of the MCh effect.

Hiccups as the first presentation of secondary adrenal insufficiency associated with advanced cervical cancer.

Summary: Hiccups are a common symptom characterized by intermittent spasmodic contraction of the diaphragm. Most hiccups are transient, but some are refractory. Patients with intractable hiccups often have abnormalities of the diaphragm, medulla oblongata, and lesions affecting nerve fibers connecting them. Moreover, electrolyte abnormalities, including hyponatremia, are frequently observed in patients with intractable hiccups. Adrenal insufficiency (AI) is one of the causes of hyponatremia. However, hiccups are not commonly the first presentation. Herein, we describe a case of a 45-year-old woman complaining of refractory hiccups. The patient was initially diagnosed with hiccups associated with cervical cancer metastasis to the liver and peritoneum. The administration of chlorpromazine did not have a beneficial effect on her hiccup. Fasting hypoglycemia and hyponatremia were later found. Her serum cortisol level was low without an elevation of adrenocorticotropic hormone level. MRI of the pituitary gland showed metastatic lesion in the pituitary gland and stalk. Thus, the patient was diagnosed with secondary AI due to cervical cancer metastasis to the pituitary gland and stalk. Administration of hydrocortisone improved her hiccups with the normalization of serum sodium level. Therefore, differential diagnosis in advanced cancer patients with hiccups should include AI-induced hyponatremia. Learning points: Hiccups could be the first manifestation of adrenal insufficiency (AI). Hiccups in patients with AI are often mediated by hyponatremia. Hyponatremia is less frequent in secondary AI than in primary AI. However, hyponatremia can result from increased antidiuretic hormone due to loss of cortisol. The differential diagnosis should include AI-induced hyponatremia if hiccups occur in patients with advanced cancer, as metastasis to adrenal gland or pituitary gland could cause AI.

Fresh Cerebral Infarction-Like MRI Findings Mimicking Hyperosmolar Hyperglycemic Syndrome With Seizures.

Hyperosmolar hyperglycemic syndrome (HHS) is a severe diabetes-related condition. Patients with HHS can present with abnormal magnetic resonance imaging (MRI) findings similar to those of fresh cerebral infarction. Here, we present the case of a 95-year-old woman with HHS who was initially misdiagnosed with seizures due to fresh cerebral infarction of the pons. Her MRI revealed small abnormal lesions in bilateral pons which showed hyperintensity on T2-weighted imaging and diffusion-weighted imaging. Thus, the patient was initially diagnosed with seizures associated with fresh cerebral infarction of the pons. However, hyperglycemia and hyperosmolarity were later observed, and the patient was diagnosed with HHS. Intravenous insulin and saline infusions were administered, which led to improvements in laboratory findings and seizures. The MRI findings of the pons disappeared after the treatment of HHS. Cortical restricted diffusion is observed in about 60% of cases with HHS, even if no obstruction of the artery is detected. On the contrary, patients with HHS have an increased risk of stroke during the treatment of HHS. Therefore, it is crucial for clinicians to examine patients with neurological symptoms associated with HHS not only based on MRI findings but also on neurological examination over time. In conclusion, clinicians should be aware of fresh cerebral infarction-like MRI findings in patients with HHS.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Worsen after the Administration of Dulaglutide.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical polyarthritis and limb pitting edema. Although the detailed mechanisms of this syndrome have not been clearly understood, some agents including dipeptidyl peptidase-4 inhibitors have been reported to induce RS3PE syndrome. However, glucagon-like peptide-1 (GLP-1) analogues have not been reported to be associated with this syndrome. A 91-year-old woman was admitted to our hospital with complaints of severe polyarthritis and limb edema. She was diagnosed with RS3PE syndrome. Oral prednisolone improved her symptoms. However, her symptoms worsened after the administration of dulaglutide, with elevated serum inflammatory markers. Discontinuation of dulaglutide without additional treatment improved her symptoms and laboratory findings. This case might indicate the possibility of development and worsening of RS3PE syndrome caused after GLP-1 analogue.

Primary Aldosteronism with Parathyroid Hormone Elevation: A Single-center Retrospective Study.

Objective Primary aldosteronism (PA) is a major cause of secondary hypertension. The association between PA and other hormone disorders is unclear. The present study aimed to evaluate whether the parathyroid hormone (PTH) value is associated with PA subtypes or specific treatments. Methods We enrolled 135 patients with PA who had their PTH value measured before undergoing a specific treatment. We evaluated whether PTH value is associated with PA subtypes or with specific treatments. The present study is a single-center retrospective study (2011-2018). Results Our study showed that, among the patients with PA, the proportion of those with PTH elevation was >30%. The PTH value was significantly correlated with both the basal plasma aldosterone concentration (PAC) and PAC after a captopril challenge test. However, the PTH value was not significantly different between the patients with unilateral and bilateral PA. We observed that the serum PTH value decreased after treatment of PA with unilateral adrenalectomy or mineralocorticoid receptor antagonists. Conclusion Our findings suggest that the PTH value in PA patients might be associated with the autonomous production of aldosterone. However, there was no correlation between the PTH value and PA subtypes in our study. Additionally, our study showed that targeted treatment for PA may lead to a decrease in the serum PTH levels. Hence, the PTH value could potentially be used as an index for measuring the suitability for PA treatment.

X-ray microscope for imaging topological charge and orbital angular momentum distribution formed by chirality.

The distribution of topological charges on X-ray vortices was measured by differential Fourier space filtering microscope, differential radial Hilbert transform microscope. It was experimentally verified for the first time using a Spiral Fresnel zone plate objective lens. This X-ray microscope is highly sensitive to X-ray topological defects, such as edges and vortices, at the exit-face wave field of objects. Its efficient use is also discussed.

Effect of sodium glucose cotransporter 2 inhibitors on obstructive sleep apnea in patients with type 2 diabetes.

Obstructive sleep apnea syndrome (OSAS) is often associated with metabolic disorders such as obesity and type 2 diabetes and may contribute to cardiovascular events. A novel class of antidiabetic drugs, the sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce body weight (BW), although there is limited data on their impact on OSAS. We therefore evaluated the effect of SGLT2i on OSAS in patients with type 2 diabetes. The presented study was a retrospective design in 18 patients with type 2 diabetes with OSAS (4 males, age range 39-81 yr) administrated a SGLT2i. HbA1c, BW, body mass index (BMI), blood pressure (BP) and apnea hypopnea index (AHI) were evaluated before and after SGLT2i administration. The relationships between the reduction in AHI and the other variables were examined using Pearson correlation analysis. We have got result that SGLT2i reduced AHI from 31.9 ± 18.0 to 18.8 ± 11.5 events per hr (p = 0.003). HbA1c, BW and BMI decreased significantly, whereas BP did not. The Pearson correlation analysis showed a significant relationship between the reduction in AHI and pre-administration of AHI. In conclusion, SGLT2i reduced not only HbA1c, BW and BMI but also AHI significantly and therefore has potential as an effective treatment of OSAS.

Unidirectional x-ray output from a crystal waveguide affected by Berry's phase.

We show momentum-space characteristics of X-rays affected by Berry's phase in a deformed crystal, allowing a 15 keV beam inside a silicon crystal to be translated parallel to its optical axis while retaining its angular divergence and wave front. This data is the first evidence supporting the whole theoretical picture of Sawada et al., Phys. Rev. Lett. 96, 154802 (2006), consisting of two equations of motion about the X-ray propagation. An output beam was as much as 3.3% of the incident after propagating through 1.3 mm silicon along a lateral direction of the chip inclined at 17.722°. As its initial practical application we further utilized the device as an X-ray intensity modulator. Our results revealed a new aspect of the Berry phase and lead to an X-ray waveguide that can enhance the flexibility of future high-energy experiments.

Photon Drag Effect due to Berry Curvature.

A theoretical investigation reveals that the photon drag effect (PDE) is induced in a grating slab with deformation by the Berry curvature in phase space. It drifts the momentum of light, and gives asymmetric PDE signals in momentum space. Large PDE signals are observed even near the Γ point. This characteristic agrees well with our theoretical results.

Direct observation of magnetochiral effects through a single metamolecule in microwave regions.

We report direct observation of magnetochiral (MCh) effects for the X-band microwaves through a single metamolecule consisting of a copper chiral structure and ferrite rod. A fictitious interaction between chirality and magnetism is realized in the metamolecule without intrinsic electronic interactions. The MCh effects are induced at the resonant optical activities by applying a weak dc magnetic field of 1 mT, and are increased with the magnetic field. The nonreciprocal differences in refractive indices are evaluated to be 10^{-3} at 200 mT.

Diverse effects of prostaglandin E2 on vascular contractility.

Prostaglandin E2 (PGE2) is a major prostanoid produced under inflammatory situations. There have been controversial reports showing contractile or relaxant effect of PGE2 on vascular tone in various types of blood vessels. Thus, it is still elusive whether and how PGE2 modulates vascular tone. We here assessed the effects of PGE2 on vascular contractility using different types of vasculatures isolated form rat. In endothelium-denuded aortas and mesenteric arteries, PGE2 (1 nM-10 µM) concentration-dependently enhanced the contraction elicited by K(+) (35.4 mM) or norepinephrine (10 nM). In pulmonary arteries, PGE2 did not alter the both-induced contraction. Tail arteries were relaxed by a low dose of PGE2 (1-100 nM), but this response shifted to contraction by the higher dose of PGE2 (300 nM-10 µM). There are four types of PGE2 receptors EP1-4. RT-PCR showed that aortas and mesenteric arteries abundantly expressed EP3, while tail arteries abundantly expressed EP4. We next revealed that selective EP3 agonism enhanced the contraction in mesenteric arteries, whereas EP4 agonism induced relaxation in tail arteries. Taken together, PGE2 causes different contractile responses depending on the type of vascular bed. This phenomenon may be due to the difference in expression pattern and activity of EP receptors.

Controlling X-ray beam trajectory with a flexible hollow glass fibre.

A metre-length flexible hollow glass fibre with 20 µm-bore and 1.5 mm-cladding diameters for transporting a synchrotron X-ray beam and controlling the trajectory has been examined. The large cladding diameter maintains a moderate curvature to satisfy the shallow glancing angle of total reflection. The observed transmission efficiency was more than 20% at 12.4 keV. As a demonstration, a wide-area scan of a synchrotron radiation beam was performed to identify the elements for a fixed metal film through its absorption spectra.

Controlling the propagation of x-ray waves inside a heteroepitaxial crystal containing quantum dots using Berry's phase.

We study a new aspect of the Berry-phase effect as the collaborative x-ray translation by a crystal with undulated deformation. The macroscopic translation was observed around the interface of a heteroepitaxial crystal deformed by quantum dots of 4.1 germanium monolayers on a silicon substrate. The quantum dots formed a large local gradient of deformation at the interface, which triggered the x-ray translation into two directions. This effect provides a new probe for investigating the interfacial strain, and leads to a single-crystal beam splitter with parallel exit beams.

Chiral meta-molecules consisting of gold nanoparticles and genetically engineered tobacco mosaic virus.

We demonstrate a chiral meta-molecule in the ultraviolet (UV) and visible (VIS) regions using a complex of Au nanoparticles (NPs) and rod-shaped tobacco mosaic virus (TMV). Au NPs five nm in diameter are uniformly formed on peptide-modified TMV. The peptide-modified TMV with uniform-sized Au NPs has improved dispersion in solution. A negative circular dichroism (CD) peak is produced around 540 nm, at plasmonic resonance wavelength of Au NPs. Additionally, modification of a CD peak in the UV region is observed. Attaching NPs to a virus causes the enhancement and modification of CD peaks in both the UV and VIS regions. Our results open a new avenue for the preparation of three dimensional chiral metamaterials at optical frequencies.

Berry-phase translation of x rays by a deformed crystal.

We experimentally demonstrated an enhanced translation of an x-ray beam nearly parallel to the diffracting planes over millimeter distances in a deformed silicon crystal. This effect is a consequence of the Berry-phase effect in phase space [K. Sawada, Phys. Rev. Lett. 96, 154802 (2006)], which enables an interplay between the gap in the dispersion surface in momentum space and the atomic displacements in real space. Such an interplay in phase space enhances the beam translation by some 5 orders of magnitude, leading to the macroscopic effect.

Incongruence among mitochondrial, chloroplast and nuclear gene trees in Pinus subgenus Strobus (Pinaceae).

Introgression has been considered to be one of main factors leading to phylogenetic incongruence among different datasets at lower taxonomic levels. In the plants of Pinaceae, the mtDNA, cpDNA, and nuclear DNA (nrDNA) may have different evolutionary histories through introgression because they are inherited maternally, paternally and biparentally, respectively. We compared mtDNA, cpDNA, and two low-copy nrDNA phylogenetic trees in the genus Pinus subgenus Strobus, in order to detect unknown past introgression events in this group. nrDNA trees were mostly congruent with the cpDNA tree, and supported the recent sectional and subsectional classification system. In contrast, mtDNA trees split the members of sect. Quinquefoliae into two groups that were not observed in the other gene trees. The factors constituting incongruence may be divided into the following two categories: the different splits within subsect. Strobus, and the non-monophyly of subsect. Gerardianae. The former was hypothesized to have been caused by the past introgression of cpDNA, mtDNA or both between Eurasian and North American species through Beringia. The latter was likely caused by the chimeric structure of the mtDNA sequence of P. bungeana, which might have originated through past hybridization, or through a horizontal transfer event and subsequent recombination.

Discovery of novel halogenated polycyclic aromatic hydrocarbons in urban particulate matters: occurrence, photostability, and AhR activity.

Halogenated aromatic compounds (HACs) in the environment have created great concern because of the associated adverse health implications. In this study we investigated the atmospheric behavior and exposure risk of brominated polycyclic aromatic hydrocarbons (BrPAHs) larger than three rings which were associated with particles in the urban air in Japan, and which were discovered as novel HACs in the air. Furthermore, the ambient levels of chlorinated polycyclic aromatic hydrocarbons (CIPAHs) and PAHs, in addition to BrPAHs, were also simultaneously investigated to emphasize the differences. Seven of 11 target BrPAHs were newly detected from the urban air samples in Japan between 2004 and 2005. Of the BrPAHs detected, 5,7-Br2BaA was most abundant (mean concentration, 8.7 pg m(-3)), followed by 7,12-Br2BaA (6.3 pg m(-3)) and 6-BrBaP (3.3 pg m(-3)). The mean concentrations of total BrPAHs, CIPAHs, and PAHs detected were 8.6 pg m(-3), 15.2 pg m(-3), and 1.2 ng m(-3), respectively, which showed that concentrations of such halogenated PAHs (Br-/Cl-PAHs) tended to be approximately 100-fold lower than PAHs. The BrPAHs had photolysis rates that were relatively faster than the corresponding CIPAHs. Comparing the ambient profiles among the PAH congeners suggested that ambient BrPAHs that came from the specific local emission sources differed from CIPAHs and PAHs, and/or could be driven by various seasonal factors, including photodecay processes. Most of the BrPAHs used showed inherent AhR-mediated activities. Toxic equivalents based on the relative potencies of each AhR activity and the ambient concentrations showed that either BrPAHs or CIPAHs accounted for a smaller proportion (approximately 1%) of the total.

Determining x-ray nonlinear susceptibility of diamond by the optical Fano effect.

X-ray nonlinear optics, which has been considered as a scientific frontier to be explored with x-ray free-electron lasers, is accessible with existing synchrotron x-ray sources, revealing its unique features. We demonstrate that x-ray parametric down-conversion is observed indirectly through quantum mechanical interference known as the Fano effect. By introducing a novel concept of photonic discrete levels, we determine the second order nonlinear susceptibility of diamond, and find a strong resonance enhancement at the core absorption edge that presents firm experimental evidence to develop x-ray nonlinear optics.