Inhomogeneous Photosusceptibility of VO_{2} Films at the Nanoscale.

Pump-probe nano-optical experiments were used to study the light-induced insulator to metal transition (IMT) in thin films of vanadium dioxide (VO_{2}), a prototypical correlated electron system. We show that inhomogeneous optical contrast is prompted by spatially uniform photoexcitation, indicating an inhomogeneous photosusceptibility of VO_{2}. We locally characterize temperature and time dependent variations of the photoexcitation threshold necessary to induce the IMT on picosecond timescales with hundred nanometer spatial resolution. We separately measure the critical temperature T_{L}, where the IMT onsets and the local transient electronic nano-optical contrast at the nanoscale. Our data reveal variations in the photosusceptibility of VO_{2} within nanoscopic regions characterized by the same critical temperature T_{L} where metallic domains can first nucleate.

Lymphatic-draining nanoparticles deliver Bay K8644 payload to lymphatic vessels and enhance their pumping function.

Dysfunction of collecting lymphatic vessel pumping is associated with an array of pathologies. S-(-)-Bay K8644 (BayK), a small-molecule agonist of L-type calcium channels, improves vessel contractility ex vivo but has been left unexplored in vivo because of poor lymphatic access and risk of deleterious off-target effects. When formulated within lymph-draining nanoparticles (NPs), BayK acutely improved lymphatic vessel function, effects not seen from treatment with BayK in its free form. By preventing rapid drug access to the circulation, NP formulation also reduced BayK's dose-limiting side effects. When applied to a mouse model of lymphedema, treatment with BayK formulated in lymph-draining NPs, but not free BayK, improved pumping pressure generated by intact lymphatic vessels and tissue remodeling associated with the pathology. This work reveals the utility of a lymph-targeting NP platform to pharmacologically enhance lymphatic pumping in vivo and highlights a promising approach to treating lymphatic dysfunction.

An unusual anatomical variant of the left phrenic nerve encircling the transverse cervical artery.

During educational dissection of cadavers, we encountered anatomical variability of the left phrenic nerve (PN). In this cadaver, nerve fibres from C3 and C4 descended and crossed behind the transverse cervical artery (TCA), a branch of the thyrocervical trunk, at the level of the anterior scalene muscle. On the other hand, nerve fibres from C5 descended obliquely above the TCA and then joined the fibres from C3-C4 on the medial side of the anterior scalene muscle to form the PN. To our knowledge, the encircling of the TCA by the left PN in the neck has not yet been reported and may pose a potential risk for nerve compression during movement of the neck. We discuss several types of anatomical variants of the PN and the associated risk during thorax and neck dissection procedures.

T-type, but not L-type, voltage-gated calcium channels are dispensable for lymphatic pacemaking and spontaneous contractions.

The spontaneous contractions of collecting lymphatic vessels provide an essential propulsive force to return lymph centrally. These contractions are driven by an intrinsic electrical pacemaker, working through an unknown underlying ionic mechanism that becomes compromised in some forms of lymphedema. In previous studies, T-type voltage-gated Ca2+ channels (VGCCs) were implicated in this pacemaking mechanism, based on the effects of the reputedly selective T-type VGCC inhibitors mibefradil and Ni2+. Our goal was to test this idea in a more definitive way using genetic knock out mice. First, we demonstrated through both PCR and immunostaining that mouse lymphatic muscle cells expressed Cav3.1 and Cav3.2 and produced functional T-type VGCC currents when patch clamped. We then employed genetic deletion strategies to selectively test the roles of each T-type VGCC isoform in the regulation of lymphatic pacemaking. Surprisingly, global deletion of either, or both, isoform(s) was without significant effect on either the frequency, amplitude, or fractional pump flow of lymphatic collectors from two different regions of the mouse, studied ex vivo. Further, both WT and Cav3.1-/-; 3.2-/- double knock-out lymphatic vessels responded similarly to mibefradil and Ni2+, which substantially reduced contraction amplitudes and slightly increased frequencies at almost all pressures in both strains: a pattern consistent with inhibition of L-type rather than T-type VGCCs. Neither T-type VGCC isoform was required for ACh-induced inhibition of contraction, a mechanism by which those channels in smooth muscle are thought to be targets of endothelium-derived nitric oxide. Sharp intracellular electrode measurements in lymphatic smooth muscle revealed only subtle, but not significant, differences in the resting membrane potential and action potential characteristics between vessels from wild-type and Cav3.1-/-; 3.2-/- double knock-out mice. In contrast, smooth-muscle specific deletion of the L-type VGCC, Cav1.2, completely abolished all lymphatic spontaneous contractions. Collectively our results suggest that, although T-type VGCCs are expressed in mouse lymphatic smooth muscle, they do not play a significant role in modulating the frequency of the ionic pacemaker or the amplitude of spontaneous contractions. We conclude that the effects of mibefradil and Ni2+ in other lymphatic preparations are largely or completely explained by off-target effects on L-type VGCCs, which are essential for controlling both the frequency and strength of spontaneous contractions.

Imaging the nanoscale phase separation in vanadium dioxide thin films at terahertz frequencies.

Vanadium dioxide (VO2) is a material that undergoes an insulator-metal transition upon heating above 340 K. It remains debated as to whether this electronic transition is driven by a corresponding structural transition or by strong electron-electron correlations. Here, we use apertureless scattering near-field optical microscopy to compare nanoscale images of the transition in VO2 thin films acquired at both mid-infrared and terahertz frequencies, using a home-built terahertz near-field microscope. We observe a much more gradual transition when THz frequencies are utilized as a probe, in contrast to the assumptions of a classical first-order phase transition. We discuss these results in light of dynamical mean-field theory calculations of the dimer Hubbard model recently applied to VO2, which account for a continuous temperature dependence of the optical response of the VO2 in the insulating state.

Differences in the oral health status and oral hygiene practices according to the extent of post-stroke sequelae.

Oral health and hygiene are crucial parameters in stroke patients. However, few studies have evaluated the oral health status and oral hygiene practices according to the level of function in stroke patients. The aim of this study was to evaluate the oral health status and oral hygiene practices according to ambulation and personal hygiene levels in patients with stroke. Data from the fifth (2010-2012) and sixth (2013-2015) editions of the Korea National Health and Nutrition Examination Survey (KNHANES) for 6 years were combined. A total of 700 stroke patients were enrolled in our study. Subjective oral health was significantly poorer in patients who experienced a moderate problem with walking (adjusted OR [AOR], 1.68; 95% CI, 1.21-2.33) and bed-bound patients (AOR, 2.92; 95% CI, 1.01-8.44) than in patients who could walk without difficulty. Patients who were unable to bathe or dress independently exhibited a significantly higher risk of dental caries than did those who could perform the same activities unassisted. The probability of brushing teeth ≥2 times daily was 69% lower in bed-bound patients (AOR, 0.31; 95% CI, 0.11-0.87) than in patients who could walk without difficulty and 76% lower in patients who were unable to bathe or dress independently (AOR, 0.24; 95% CI, 0.09-0.62) than in those who could perform the same activities without difficulty. There were differences in oral health status and oral hygiene practices, according to ambulation level and functional independence, in the stroke patient group. These results indicate the need for oral care for stroke patients who exhibit ambulatory and functional limitations.

Performance of point-of-care diagnosis of AIDS: label-free one-step-immunoassay vs. lateral flow assay.

The objective of this study is to develop an accurate, rapid, simple, and label-free assay technology that enables point-of-care diagnosis of AIDS. For this, 3-dimensional (3D) probes to sensitively detect anti-HIV antibodies were designed and synthesized by genetically presenting a HIV antigen (gp41) on the surface of engineered human ferritin nanoparticles. The 3D probes also present multi-copies of the hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is essential for the generation and self-enhancement of assay signals. The developed new assay technology (named "one-step-immunoassay") quickly produced clear optical signals through a simple and convenient one-step procedure. The diagnostic performance of the one-step-immunoassay was compared with that of the conventional lateral flow assay (LFA) using 30 AIDS patient and 20 healthy sera. The sensitivity of LFA was only 63% when a single antigen (gp41) was used but enhanced to 90% when three different antigens (gp41, p24, and gp120) were used together as the assay probes. In contrast, the one-step-immunoassay using only gp41 produced strong optical signals within 15 min without causing any false negative/positive signals, showing 100% sensitivity and 100% specificity and holding promising potential for clinical point-of-care diagnosis of AIDS.

NAD(P)H-quinone oxidoreductase 1 silencing aggravates hormone-induced prostatic hyperplasia in mice.

NAD(P)H-quinone oxidoreductase 1 (NQO1) is a highly inducible flavoprotein known to involve in various cellular defence mechanisms. In this study, we explored whether NQO1 deletion affects hormone-induced prostatic hyperplasia. Testosterone propionate (3 mg/kg, IP) was injected into wild-type (WT) and NOQ1 knockout C57BL/6 mice (NQO1-/- ) for 14 consecutive days, and the samples were collected for biological and histochemical studies. The testosterone-treated NQO1-/- showed about 140% higher prostate weight than the testosterone-treated WT, with enhanced connective tissue and hyperplastic glands formations. However, increased dihydrotestosterone level after testosterone treatment was not significantly different between the WT and NQO1-/- . In contrast, the enhanced nuclear expression of proliferating cell nuclear antigen in NQO1-/- prostate confirmed aggravated prostatic hyperplasia in NQO1-/- . Moreover, the expression of heat shock protein (HSP) 90-α was markedly increased in the NQO1-/- , and this was supported by increased testosterone-induced nuclear androgen receptor expression in NQO1-silenced LNCaP cells. Testosterone-induced prostate-specific antigen expression was not reversed in NOQ1-silenced cells after finasteride treatment. Although the exact role of NQO1 in prostatic hyperplasia remains unclear, the hyperplasia exacerbation due to NQO1 deletion might be independent of type 2 5α-reductase and might be related to enhanced androgen receptor affinity due to enhanced HSP90-α expression.

Signal self-enhancement by coordinated assembly of gold nanoparticles enables accurate one-step-immunoassays.

Current immunoassays are in general performed through time-consuming multi-step procedures that depend on the use of premade signal-producing reporters and often cause assay inaccuracy. Here we report an advanced immunoassay technology that resolves the delayed, complex, and inaccurate assay problems of conventional immunoassays. We have developed an accurate, rapid, simple, and label-free one-step-immunoassay based on the self-enhancement of sensitive immunoassay signals in an assay solution. The nano-scale protein particles (hepatitis B virus capsid and human ferritin heavy chain particles) were genetically engineered to present many well-oriented antibody (or antigen) probes and multi-copies of poly-histidine peptides on their surface, resulting in the construction of 3-dimensional (3D) bioprobes that chemisorb gold ions via coordination bonding and sensitively detect both antigen and antibody analytes. Systematic numerical and experimental analyses show that the signal self-enhancement happens through two coupled reactions under reducing conditions: (1) 3D bioprobe-based sensitive immuno-detection of analytes and (2) coordinated assembly of free and chemisorbed gold nanoparticles around the 3D bioprobe-analyte-associated complexes, which is followed by the quick generation of apparent optical signals. This advanced one-step-immunoassay was successfully applied to diagnostic assays requiring high accuracy and/or speed, i.e. diagnosis of acute myocardial infarction and hepatitis C through detecting a cardiac protein (troponin I) and anti-hepatitis C virus antibodies in patient sera, indicating that it is applicable to the accurate and rapid detection of both antigen and antibody markers of a wide range of diseases.

Long-term Clinical Outcomes of First and Second Kidney Transplantation in Patients With Biopsy-Proven IgA Nephropathy.

INTRODUCTION: The recurrence of IgA nephropathy (IgAN) after kidney transplantation (KT) has an effect on graft survival, but there are few reports about long-term clinical outcomes of KT with recurrent IgAN. This study shows the long-term clinical outcomes of KT in patients with IgAN. METHODS: All recipients who had biopsy-proven IgAN were followed from February 1990 to February 2016. We analyzed overall graft and patient survival rates, incidence of recurrent IgAN, factors affecting graft survival, and IgAN recurrence. RESULTS: There were 88 patients with first KT. The mean follow-up duration was 82.5 months. Twenty patients went through graft loss and 1 patient died due to sepsis. IgAN recurred in 15 patients, and 11 patients experienced graft failure. Among the patients who had failed graft after first KT, 7 patients underwent retransplantation. The graft survival period, presence of rejection, and proteinuria were the relevant risk factors for recurrence of IgAN. In the first KT patients, presence of rejection and 1-year serum creatinine were the significant risk factors for graft loss. But recurrence of IgAN was not a relevant risk factor. Overall graft survival rates at 5 and 10 years were 93.8% and 73.1% in the first transplantation group and 100% and 100% in the retransplantation group, respectively. CONCLUSION: Although IgAN recurrence was a significant risk factor for graft failure, the patient who underwent retransplantation showed favorable results. Retransplantation should be considered in patients who lost their first graft after recurrence of IgAN.

Long-term Clinical Outcomes of Kidney Re-transplantation.

BACKGROUND: Kidney re-transplantation is commonly considered to have a higher immunological risk than first kidney transplantation. Because of the organ shortage and increasing waiting lists, long-term outcomes of kidney re-transplantation are being studied. However, reports of re-transplantation outcomes are not common. We have reported our 30 years of experience with second kidney transplantations. METHODS: Of 1210 kidney transplantations between November 1982 and August 2016 performed in our hospital, 105 were second kidney transplantations (2nd KT). Living donor KT was 44; deceased donor KT was 61. RESULTS: Patient survival rates at 1, 5, and 10 years were 100%, 97.2%, and 90.7%, and graft survival rates were 97.0%, 94.6%, and 71.5%, respectively. The leading cause of graft failure in the 2nd KT was chronic rejection (60%). In addition, induction immunosuppressant, maintenance immunosuppressant, delayed graft function, and graft survival time at the 1st KT had a significant impact on graft survival time at the 2nd KT. CONCLUSIONS: Reasonable results in both patient survival and graft survival rates were found in the 2nd KT. Careful monitoring of immunologic risk is needed.

Clinical Relationship between Cholestatic Disease and Pituitary-Dependent Hyperadrenocorticism in Dogs: A Retrospective Case Series.

BACKGROUND: A high prevalence of cholestatic disease, including gallbladder mucocele (GBM), has been reported in dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH). HYPOTHESIS/OBJECTIVES: Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane. ANIMALS: Sixty-five client-owned dogs with naturally occurring PDH. METHODS: This was a retrospective, observational case series. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group. RESULTS: The GBM group had more severe clinical signs and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = .003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Gallbladder disease associated with cholestatic disease is correlated with PDH in dogs, in both its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane.

Does quality of life impact the decision to pursue stem cell transplantation for elderly patients with advanced MDS?

The factors that influence utilization of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HCT) among medically fit older patients with advanced myelodysplastic syndromes (MDS) are largely unknown. The MDS Transplant-Associated Outcomes (MDS-TAO) study is an ongoing prospective observational study at the Dana-Farber Cancer Institute and Massachusetts General Hospital that enrolls transplant-eligible fit patients aged 60-75 years with advanced MDS and follows them through RIC HCT vs non-HCT treatment. In this analysis of 127 patients enrolled from May 2011 to June 2014, we examined the influence of age, gender, cytogenetics, International Prognostic Scoring System (IPSS) category, performance status, distance from HCT center and baseline patient-reported quality of life (QOL) from the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) on the likelihood of receiving RIC HCT using competing risk regression modeling. With a median follow-up of 16 months, 44 patients (35%) had undergone RIC HCT. In multivariable analyses, age (hazard ratio (HR) 0.87 per year, 95% confidence interval (CI): 0.81-0.92, P<0.001) and higher IPSS (intermediate-2/high; HR 2.29, 95% CI: 1.25-4.19, P=0.007) were significantly predictive of receipt of RIC HCT; neither global QOL score nor any QOL subscales scores were predictive. These data suggest that baseline patient-reported QOL has little influence on the decision to undergo RIC HCT for older patients with advanced MDS.

Simultaneous determination of water-soluble whitening ingredients and adenosine in different cosmetic formulations by high-performance liquid chromatography coupled with photodiode array detection.

OBJECTIVE: The Korean Cosmetic Act regulates the use of functional cosmetics) by the law. Four functional cosmetic groups, whitening, anti-wrinkle, UV protection and combination of whitening and anti-wrinkle, were categorized according to the Korean Cosmetic Act and Functional Cosmetics Codex. In this study, high-performance liquid chromatography (HPLC) coupled with photodiode array detection (DAD) was employed for the simultaneous detection of arbutin (and its decomposition product, hydroquinone), niacinamide, ascorbyl glucoside, ethyl ascorbyl ether and adenosine in functional cosmetic products such as creams, emulsions and lotions. METHODS: Separation by HPLC-DAD was conducted using a C18 column with a gradient elution of 5 mm KH2PO4 buffer (containing 0.1% phosphoric acid) and methanol (containing 0.1% phosphoric acid). The wavelengths for the detection of arbutin, hydroquinone, niacinamide, adenosine, ascorbyl glucoside and ethyl ascorbyl ether were 283, 289, 261, 257, 238 and 245 nm, respectively. RESULTS: This method exhibited good linearity (R(2) ≥ 0.999), precision (expressed as relative standard deviation (RSD) < 2%) and mean recoveries (89.42-104.89%). The results obtained by monitoring 100 market samples showed that the detected levels of the tested materials are within the acceptable authorized concentration. CONCLUSION: The method developed herein is simple and can be used for market survey and quality control of functional cosmetics.

Resection of a physeal bar with complete transverse osteotomy at the metaphysis and Ilizarov external fixation.

The traditional techniques involving an oblique tunnel or triangular wedge resection to approach a central or mixed-type physeal bar are hindered by poor visualisation of the bar. This may be overcome by a complete transverse osteotomy at the metaphysis near the growth plate or a direct vertical approach to the bar. Ilizarov external fixation using small wires allows firm fixation of the short physis-bearing fragment, and can also correct an associated angular deformity and permit limb lengthening. We accurately approached and successfully excised ten central- or mixed-type bars; six in the distal femur, two in the proximal tibia and two in the distal tibia, without damaging the uninvolved physis, and corrected the associated angular deformity and leg-length discrepancy. Callus formation was slightly delayed because of periosteal elevation and stretching during resection of the bar. The resultant resection of the bar was satisfactory in seven patients and fair in three as assessed using a by a modified Williamson-Staheli classification.

Whole-genome sequencing reveals activation-induced cytidine deaminase signatures during indolent chronic lymphocytic leukaemia evolution.

Patients with chromosome 13q deletion or normal cytogenetics represent the majority of chronic lymphocytic leukaemia (CLL) cases, yet have relatively few driver mutations. To better understand their genomic landscape, here we perform whole-genome sequencing on a cohort of patients enriched with these cytogenetic characteristics. Mutations in known CLL drivers are seen in only 33% of this cohort, and associated with normal cytogenetics and unmutated IGHV. The most commonly mutated gene in our cohort, IGLL5, shows a mutational pattern suggestive of activation-induced cytidine deaminase (AID) activity. Unsupervised analysis of mutational signatures demonstrates the activities of canonical AID (c-AID), leading to clustered mutations near active transcriptional start sites; non-canonical AID (nc-AID), leading to genome-wide non-clustered mutations, and an ageing signature responsible for most mutations. Using mutation clonality to infer time of onset, we find that while ageing and c-AID activities are ongoing, nc-AID-associated mutations likely occur earlier in tumour evolution.

Demonstration of a Circularly Polarized Plasma-Based Soft-X-Ray Laser.

We report the first experimental demonstration of a laser-driven circularly polarized soft-x-ray laser chain. It has been achieved by seeding a 32.8 nm Kr ix plasma amplifier with a high-order harmonic beam, which has been circularly polarized using a four-reflector polarizer. Our measurements testify that the amplified radiation maintains the initial polarization of the seed pulse in good agreement with our Maxwell-Bloch modeling. The resulting fully circular soft-x-ray laser beam exhibits a Gaussian profile and yields about 10^{10} photons per shot, fulfilling the requirements for laboratory-scale photon-demanding application experiments.

Successful treatment of disseminated adenovirus infection with ribavirin and intravenous immunoglobulin in an adult renal transplant recipient: a case report.

Disseminated adenovirus infection in recipients of renal transplants is a rare but often fatal complication. We present a case of a 32-year-old woman who underwent renal transplantation from a deceased donor. Ten months after transplantation, she presented with dysuria, hematuria, and febrile illness. Despite the use of antibiotics, the patient's symptoms continued and worsened and the serum creatinine level was increased. The results of urine and serum polymerase chain reaction were positive for adenovirus. Renal biopsy revealed viral interstitial nephritis. The patient was treated with ribavirin, intravenous immunoglobulin, and reduction in immunosuppression. Her symptoms progressively improved from 7 days after the treatment. Serum and urine polymerase chain reaction for adenovirus became negative 10 and 21 days after the treatment, respectively. She remained in good health with excellent allograft function 6 months later.