Safety and efficacy of transarterial embolisation for treatment of dorsal pancreatic artery haemorrhage.

AIM: To evaluate the safety and efficacy of transarterial embolisation (TAE) of dorsal pancreatic artery (DPA) haemorrhage. MATERIALS AND METHODS: Nineteen consecutive patients (M:F = 16:3, mean age 59.6 years) who underwent TAE of DPA in three tertiary medical centres between January 2001 to January 2020 were reviewed retrospectively. Angiographic features and the technical and clinical outcomes of TAE were analysed. RESULTS: The clinical presentations were a bloody drain from the Jackson-Pratt drainage tube (n=8), melaena (n=7), abdominal pain (n=4), and haematochezia (n=3). Angiographic findings included pseudoaneurysm (n=14), contrast media extravasation (n=4), or abrupt cut-off of the arterial branch (n=1). The NBCA (N-butyl-cyanoacrylate; n=4), microcoils (n=4), and a combination of these agents (n=7) were used as embolic agents. The most common origin of the DPA in the present study cohort was the splenic artery (n=7), followed by the coeliac trunk (n=4), common hepatic artery (n=4), and superior mesenteric artery (n=4). Technical and clinical success rates were 100% and 84.2% (16/19), respectively. Of the three clinically unsuccessful cases, two patients were revealed to have newly developed bleeding from another artery. The other patient expired 1 day after the TAE procedure due to a progression of hepatic failure. In one patient, an asymptomatic non-target embolisation occurred in the right posterior tibial artery as a procedure-related complication. No major complications were observed. CONCLUSION: TAE is safe and effective for the management of bleeding from the DPA. It is important to be aware of the DPA as a potential bleeding source, including the relevant clinical characteristics.

Observation of Bistable Turbulence in Quasi-Two-Dimensional Superflow.

Turbulent flow restricted to two dimensions can spontaneously develop order on large scales, defying entropy expectations and in sharp contrast with turbulence in three dimensions where nonlinear turbulent processes act to destroy large-scale order. In this work we report the observation of unusual turbulent behavior in steady-state flow of superfluid ^{4}He-a liquid with vanishing viscosity and discrete vorticity-in a nearly two-dimensional channel. Surprisingly, for a range of experimental parameters, turbulence is observed to exist in two bistable states. This bistability can be well explained by the appearance of large-scale regions of flow of opposite vorticity.

Stabilized Pair Density Wave via Nanoscale Confinement of Superfluid

Superfluid ^{3}He under nanoscale confinement has generated significant interest due to the rich spectrum of phases with complex order parameters that may be stabilized. Experiments have uncovered a variety of interesting phenomena, but a complete picture of superfluid ^{3}He under confinement has remained elusive. Here, we present phase diagrams of superfluid ^{3}He under varying degrees of uniaxial confinement, over a wide range of pressures, which elucidate the progressive stability of both the A phase, as well as a growing region of stable pair density wave state.

Interventional treatment of bleeding complications due to percutaneous cannulation for peripheral extracorporeal membrane oxygenation.

PURPOSE: This study aimed to evaluate the safety and effectiveness of interventional techniques as a treatment for bleeding complications secondary to percutaneous cannulation for peripheral extracorporeal membrane oxygenation (PECMO). MATERIALS AND METHODS: Out of 1264 patients who underwent PECMO at our hospital between January 2009 and September 2018, we reviewed the clinical characteristics and outcomes of eight patients (4 men, 4 women; mean age, 54.9 years [range, 31-77 years]) who underwent percutaneous interventional treatment for bleeding complications secondary to percutaneous cannulation for PECMO. RESULTS: Both hemodynamic instability and coagulopathy were present in 7 patients who had direct injury during PECMO insertion and absent in one patient with pseudoaneurysm at the PECMO removal site. Percutaneous ultrasound-guided thrombin injection was performed in three patients with pseudoaneurysm of the common or superficial femoral artery, and adjunctive embolization was combined with microcoils or n-butyl 2-cyanoacrylate in two of them. Stent graft was inserted in four patients with contrast extravasation (n=3) from external iliac artery (n=1) or common femoral or iliac veins (n=2) ruptures or the fistula between the superficial femoral artery and vein (n=1). N-butyl 2-cyanoacrylate and coil embolization was performed for pseudoaneurysm from the internal pudendal artery branch in the remaining one patient. Technical success was achieved in all eight patients. There were no procedure-related complications. There was no rebleeding during the follow-up. CONCLUSION: Interventional treatment is a safe, technically feasible and therapeutically effective modality for treating bleeding complications secondary to a percutaneous cannulation for PECMO.

Clinical outcomes of 23 patients who had repeat pelvic arterial embolisation for uncontrolled post-partum haemorrhage at a single centre.

AIM: To evaluate the safety and efficacy of repeated pelvic arterial embolisation (PAE) for uncontrolled postpartum haemorrhage (PPH) after a single session of PAE and to compare angiographic findings between the two sessions of PAE. MATERIALS AND METHODS: A total of 23 consecutive patients (age range, 23-44 years) who underwent repeated PAE for uncontrolled PPH between March 2001 and January 2016 in Severance Hospital were reviewed. The interval times between the two sessions of PAE, the angiographic findings, embolic materials, arteries embolised during PAE, and the clinical outcomes were reviewed retrospectively. RESULTS: Overall clinical success was achieved after repeated PAE in 21 of 23 patients (91.3%). There were no procedure-related, major complications. On angiography, active bleeding from the uterine collateral arteries was more frequently observed in the second session of PAE (p>0.05), and embolisation of the anterior division of the internal iliac artery was significantly higher during the second session of PAE. Use of permanent embolic materials was significantly higher during the second session of PAE. Recanalisation of a previously embolised artery was identified in 14 patients (60.9%) during the second session. CONCLUSION: Repeated PAE is safe and effective for managing recurrent bleeding after a single session of PAE. Repeated PAE is related to a higher chance of embolisation of the anterior division of the internal iliac artery, with the use of permanent embolic materials. Recanalisation of a previously embolised artery seems to be a principal source of rebleeding during a repeated session of PAE.

iNKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner.

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7-/- mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7-/- mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7-/- mice. Moreover, liver inflammation was detected in obese CCR7-/- mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d-/- or interleukin-10-deficient (IL-10-/-) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.

Magnetic actuation and feedback cooling of a cavity optomechanical torque sensor.

Cavity optomechanics has demonstrated remarkable capabilities, such as measurement and control of mechanical motion at the quantum level. Yet many compelling applications of optomechanics-such as microwave-to-telecom wavelength conversion, quantum memories, materials studies, and sensing applications-require hybrid devices, where the optomechanical system is coupled to a separate, typically condensed matter, system. Here, we demonstrate such a hybrid optomechanical system, in which a mesoscopic ferromagnetic needle is integrated with an optomechanical torsional resonator. Using this system we quantitatively extract the magnetization of the needle, not known a priori, demonstrating the potential of this system for studies of nanomagnetism. Furthermore, we show that we can magnetically dampen its torsional mode from room-temperature to 11.6 K-improving its mechanical response time without sacrificing torque sensitivity. Future extensions will enable studies of high-frequency spin dynamics and broadband wavelength conversion via torque mixing.

Approaching the standard quantum limit of mechanical torque sensing.

Reducing the moment of inertia improves the sensitivity of a mechanically based torque sensor, the parallel of reducing the mass of a force sensor, yet the correspondingly small displacements can be difficult to measure. To resolve this, we incorporate cavity optomechanics, which involves co-localizing an optical and mechanical resonance. With the resulting enhanced readout, cavity-optomechanical torque sensors are now limited only by thermal noise. Further progress requires thermalizing such sensors to low temperatures, where sensitivity limitations are instead imposed by quantum noise. Here, by cooling a cavity-optomechanical torque sensor to 25 mK, we demonstrate a torque sensitivity of 2.9 yNm/. At just over a factor of ten above its quantum-limited sensitivity, such cryogenic optomechanical torque sensors will enable both static and dynamic measurements of integrated samples at the level of a few hundred spins.

Optical microscope and tapered fiber coupling apparatus for a dilution refrigerator.

We have developed a system for tapered fiber measurements of optomechanical resonators inside a dilution refrigerator, which is compatible with both on- and off-chip devices. Our apparatus features full three-dimensional control of the taper-resonator coupling conditions enabling critical coupling, with an overall fiber transmission efficiency of up to 70%. Notably, our design incorporates an optical microscope system consisting of a coherent bundle of 37,000 optical fibers for real-time imaging of the experiment at a resolution of ∼1 µm. We present cryogenic optical and optomechanical measurements of resonators coupled to tapered fibers at temperatures as low as 9 mK.

Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-ß signaling.

Lactoferrin (LF), a pleiotropic iron-binding glycoprotein, is known to modulate the humoral immune response. However, its exact role in Ig synthesis has yet to be elucidated. In this study, we investigated the effect of LF on Ig production by mouse B cells and its underlying mechanisms. LF, like transforming growth factor (TGF)-ß1, stimulated B cells to produce IgA and IgG2b, while downregulating other isotypes. Using limiting dilution analysis, LF was shown to increase the frequency of IgA-secreting B-cell clones. This was paralleled by an increase in Ig germ-line α (GLα) transcripts, indicating that LF plays a role as an IgA switch factor. Interestingly, LF directly interacted with betaglycan (TGF-ß receptor III, TßRIII) and in turn induced phosphorylation of TßRI and Smad3 through formation of the TßRIII/TßRII/TßRI complex, leading to IgA isotype switching. Peroral administration of LF increased intestinal/serum IgA production as well as number of IgA plasma cells in lamina propria. Finally, we found that LF has an adjuvant activity when nontoxigenic Salmonella typhimurium was inoculated perorally, conferring protection against intragastrical infection of toxigenic S. typhimurium. These results suggest that LF has an important effect on the mucosal/systemic IgA response and can contribute to protection against intestinal pathogens.

Outcomes in patients undergoing nephrectomy for renal cancer on chronic anticoagulation therapy.

AIMS: To report our experience on surgical resection of renal tumors for patients with a history of chronic anticoagulation (ACT) or aspirin use. METHODS: We performed a retrospective analysis of 2473 patients who underwent surgery for renal tumors between 2005 and 2012. Prior to surgery, 172 were on chronic ACT and 695 on aspirin. Multivariable linear and logistic regression models were used to compare transfusion and overall complication rates between patients undergoing renal surgery who were on therapy to patients who were on aspirin and to patients with no therapy. RESULTS: Compared to no therapy and aspirin patients those on ACT were older (57.3 (IQR 48.4-66.10) vs 63.9, (IQR 57.3-71.5) vs 68.4, (IQR 60.4-73.5); p < 0.001), with a higher percentage having an ASA score of 3 or 4 (42.4 vs 57.9 vs 82.6%; p < 0.001), respectively. ACT patients had a higher 30-day transfusion rate, 22.7% vs 7.6% vs 6.9%, and 90-day complication rate, 17.4% vs 7.2% vs 7.3%, both p < 0.001. The median length of stay differed statistically between groups (p < 0.001), with a modest longer stay in the anticoagulation group (OR 1.11 SE 0.26; p < 0.001). Transfusion and complication rates for patients on therapy undergoing minimally invasive surgery vs open surgery were not statistically different. CONCLUSIONS: Patients on chronic ACT had higher transfusion and overall complication rates compared to patients on no treatment or on chronic aspirin. These findings did not correlate to clinical differences in length of stay or grade 3-5 complications.

Separated response function ratios in exclusive, forward π(±) electroproduction.

The study of exclusive π(±) electroproduction on the nucleon, including separation of the various structure functions, is of interest for a number of reasons. The ratio RL=σL(π-)/σL(π+) is sensitive to isoscalar contamination to the dominant isovector pion exchange amplitude, which is the basis for the determination of the charged pion form factor from electroproduction data. A change in the value of RT=σT(π-)/σT(π+) from unity at small -t, to 1/4 at large -t, would suggest a transition from coupling to a (virtual) pion to coupling to individual quarks. Furthermore, the mentioned ratios may show an earlier approach to perturbative QCD than the individual cross sections. We have performed the first complete separation of the four unpolarized electromagnetic structure functions above the dominant resonances in forward, exclusive π(±) electroproduction on the deuteron at central Q(2) values of 0.6, 1.0, 1.6 GeV(2) at W=1.95 GeV, and Q(2)=2.45 GeV(2) at W=2.22 GeV. Here, we present the L and T cross sections, with emphasis on RL and RT, and compare them with theoretical calculations. Results for the separated ratio RL indicate dominance of the pion-pole diagram at low -t, while results for RT are consistent with a transition between pion knockout and quark knockout mechanisms.

Germline single nucleotide polymorphisms associated with response of urothelial carcinoma to platinum-based therapy: the role of the host.

BACKGROUND: Variations in urothelial carcinoma (UC) response to platinum chemotherapy are common and frequently attributed to genetic and epigenetic variations of somatic DNA. We hypothesized that variations in germline DNA may contribute to UC chemosensitivity. PATIENTS AND METHODS: DNA from 210 UC patients treated with platinum-based chemotherapy was genotyped for 80 single nucleotide polymorphisms (SNPs). Logistic regression was used to examine the association between SNPs and response, and a multivariable predictive model was created. Significant SNPs were combined to form a SNP score predicting response. Eleven UC cell lines were genotyped as validation. RESULTS: Six SNPs were significantly associated with 101 complete or partial responses (48%). Four SNPs retained independence association and were incorporated into a response prediction model. Each additional risk allele was associated with a nearly 50% decrease in odds of response [odds ratio (OR) = 0.51, 95% confidence interval 0.39-0.65, P = 1.05 × 10(-7)). The bootstrap-adjusted area under the curves of this model was greater than clinical prognostic factors alone (0.78 versus 0.64). The SNP score showed a positive trend with chemosensitivity in cell lines (P = 0.115). CONCLUSIONS: Genetic variants associated with response of UC to platinum-based therapy were identified in germline DNA. A model using these genetic variants may predict response to chemotherapy better than clinical factors alone.

Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy.

Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.

Double E1B 19 kDa- and E1B 55 kDa-deleted oncolytic adenovirus in combination with radiotherapy elicits an enhanced anti-tumor effect.

Radiation therapy, a mainstay for anti-tumor therapeutic regimens for a variety of tumor types, triggers tumor cell apoptotic pathways by either directly eliciting DNA damage or indirectly inducing the formation of oxygen radicals. In an effort to augment radiation therapy, we generated a double E1B 19 kDa- and E1B 55 kDa-deleted oncolytic adenovirus (Ad-DeltaE1B19/55). In combination with radiotherapy, greater cytotoxicity was observed for Ad-DeltaE1B19/55 than for the single E1B 55 kDa-deleted oncolytic Ad (Ad-DeltaE1B55). Consistent with this observation, higher levels of p53, phospho-p53, phospho-Chk1, phospho-Chk2, PI3K (phosphatidylinositol-3-kinase), phospho-AKT, cytochrome c, and cleavage of PARP (poly (ADP-ribose) polymerase) and caspase-3 were observed in cells treated with Ad-DeltaE1B19/55 compared with those treated with Ad-DeltaE1B55, indicating that the E1B 19 kDa present in Ad-DeltaE1B55 may partially block radiation-induced apoptosis. A significant therapeutic benefit was also observed in vivo when oncolytic Ads and radiation were combined. Tumors treated with Ad-DeltaE1B19/55 and radiation showed large areas of necrosis and apoptosis with the corresponding induction of p53. Finally, consistent with in vitro observations, the combination of Ad-DeltaE1B19/55 and radiation was more efficacious than the combination of Ad-DeltaE1B55 and radiation. Taken together, these results present a strong therapeutic rationale for combining radiation therapy with E1B 19 kDa-deleted oncolytic Ad.

Gene structure dynamics and divergence of the polygalacturonase gene family of plants and fungus.

Whole copies of the polygalacturonase (PG) genes from rice (Oryza sativa subsp. japonica) and a filamentous fungus (Aspergillus oryzae) were isolated. The orthologs of the rice PGs were also retrieved from other plant species. The 106 plant PGs analyzed were divided into 5 clades, A, B, C, D, and E. The fungus PGs were classified into 3 clades, of which one formed a loose cluster with clade E of the plant PGs. Four domain motifs (I, II, III, IV) were identified in all PGs. Motifs II and III were split by introns such as G/DDC and CGPGHGIS/IGSLG, respectively. In plant PGs there were 446 introns in total and 3.98 introns per gene. Intron phase distribution was 65.5% for phase 0, 19.7% for phase 1, and 14.8% for phase 2 in plant PGs. In the PGs of A. oryzae there were 37 introns of phase 0 (59.5%), phase 1 (24.3%), and phase 2 (16.2%), with 2.47 introns per gene. The 5 clades of plant PGs were divided into 3 basic gene structure lineages. Intron positions and phases were conserved among the PGs in the first 2 lineages. The third lineage consisted of PGs of clade E, which also carried highly conserved introns at different positions from other PGs. Intron positions were not as highly conserved in fungus PGs as in plant PGs. The introns in the current PGs have been present since before the divergence of monocots from dicots. The results obtained show that differential losses of introns created gene diversity, which was followed by segmental and tandem duplication in plant PGs.

Ameroid rings for gradual chronic constriction of the sciatic nerve in rats: contribution of different nerves to neuropathic pain.

Mononeuropathy was induced by placing an ameroid ring around the sciatic nerve and was compared with chronic constriction injury (CCI) of the sciatic nerve [Pain 33 (1988) 87] in rats. Mechanical allodynia was assessed and the role of sciatic and saphenous afferents (Adelta and C) in thermal hyperalgesia investigated. A shorter duration of mechanical allodynia in ameroid rats as compared to CCI rats was observed. Thermal hyperalgesia was observed in the saphenous innervated skin of the hindpaw for Adelta and C nociceptors in ameroid and for Adelta nociceptors only in CCI rats, respectively. The sciatic innervated skin showed a thermal hypoalgesia with a fast onset for Adelta afferents and a slower onset for C afferents in CCI and ameroid rats. The duration of both thermal hypo- and hyperalgesia was longer in ameroid rats. We conclude that ameroid rings are a useful tool for the investigation of long-duration hyperalgesic effects of nerve injury, as the effects were more stable and seen for a longer time (>8 weeks) as compared to the CCI model. The uninjured saphenous afferents, in particular C fibers, mediate thermal hyperalgesia after chronic constriction of the sciatic nerve using an ameroid ring.

Risk factors for failure of 5-fluorouracil needling revision for failed conjunctival filtration blebs.

PURPOSE: To investigate the risk factors for failure of 5-fluorouracil (5-FU) needling revision, a useful procedure for restoring a failed filtration bleb. DESIGN: Interventional case series. METHODS: Retrospectively conducted study. SETTING: Institutional. STUDY POPULATION: Sixty-four eyes of 64 consecutive glaucoma patients that underwent 5-FU needling revisions for failed filtering bleb following either trabeculectomy or phaco-trabeculectomy with or without adjunctive mitomycin C (MMC). OBSERVATION PROCEDURES: Goldmann applanation tonometry, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. MAIN OUTCOME MEASURES: Successful outcome of the initial 5-FU needling revision, arbitrarily defined as target intraocular pressure (IOP) control with not more than two topical glaucoma medications and no additional 5-FU needling or other surgical procedures, was analyzed by Kaplan-Meier survival analysis, and risk factors for failure of the initial 5-FU needling revision were analyzed by Cox proportional hazards regression analysis. RESULTS: The cumulative success rate of the initial 5-FU needling revision was 45% at 1 year, 33% at 2 years, and 28% at 4 years. Failure of the initial 5-FU revision correlated significantly with preneedling IOP > 30 mm Hg (P =.0003), lack of MMC use during the previous filtration surgery (P =.013), and IOP >10 mm Hg immediately following needling revision (P =.0012) according to Cox's proportional hazards regression analysis. CONCLUSIONS: Pre-needling IOP > 30 mm Hg, lack of MMC use during the previous filtration surgery, and IOP > 10 mm Hg immediately after needling were found to be significant risk factors for failure of the initial 5-FU needling procedure. Therefore, it is important to monitor IOP closely following needling revision in those patients with such risk factors. They are more likely to require additional therapeutic interventions, including repeat needling revisions.

Capillary gel electrophoresis with sinusoidal voltammetric detection: a strategy to allow four-"color" DNA sequencing.

A novel detection strategy for DNA sequencing applications that utilizes a frequency-based electrochemical method is reported. Sinusoidal voltammetry is used to selectively identify four unique redox molecules that are covalently attached to the 5'-end of a 20-base sequencing primer. The tags used in this work are ferrocene derivatives with different substituents attached to the ferrocene ring, where the electron-donating or -withdrawing character of the substituent alters the half-wave potential of the modified ferrocene. Therefore, each tag has a unique SV frequency spectrum that can be easily identified in the frequency domain. In this work, the discrimination of one tag versus all others is accomplished through a "phase-nulling" technique. The signal for each tag is selectively eliminated while the other three responses remain virtually unchanged. This analysis scheme allows for the selective identification of each tagged oligonucleotide eluting in sieving polymer capillary gel electrophoresis with a separation efficiency of 2 x 10(6) theoretical plates per meter. This separation efficiency is sufficient to perform "low-resolution" DNA sequencing; the conditions used in this work have not yet been optimized for high-resolution sequencing applications.