Postoperative complications and prognosis based on type of surgery in ulcerative colitis patients with colorectal cancer: A multicenter observational study of data from the Japanese Society for Cancer of the Colon and Rectum.

Background: Patients with ulcerative colitis are reported to be at increased risk of colorectal cancer and are also at high risk of postoperative complications. However, the incidence of postoperative complications in these patients and how the type of surgery performed affects prognosis are not well understood. Methods: Data collected by the Japanese Society for Cancer of the Colon and Rectum on ulcerative colitis patients with colorectal cancer between January 1983 and December 2020 were analyzed according to whether total colorectal resection was performed with ileoanal anastomosis (IAA), ileoanal canal anastomosis (IACA), or permanent stoma creation. The incidence of postoperative complications and the prognosis for each surgical technique were investigated. Results: The incidence of overall complications was not significantly different among the IAA, IACA, and stoma groups (32.7%, 32.3%, and 37.7%, respectively; p = 0.510). The incidence of infectious complications was significantly higher in the stoma group (21.2%) than in the IAA (12.9%) and IACA (14.6%) groups (p = 0.048); however, the noninfectious complication rate was lower in the stoma group (13.7%) than in the IAA (21.1%) and IACA (16.2%) groups (p = 0.088). Five-year relapse-free survival was higher in patients without complications than in those with complications in the IACA group (92.8% vs. 75.2%; p = 0.041) and the stoma group (78.1% vs. 71.2%, p = 0.333) but not in the IAA group (90.3% vs. 90.0%, p = 0.888). Conclusion: The risks of infectious and noninfectious complications differed according to the type of surgical technique used. Postoperative complications worsened prognosis.

Modified side overlap esophagogastrostomy after laparoscopic proximal gastrectomy.

We report a new method of esophagogastrostomy after proximal gastrectomy, side overlap with fundoplication by Yamashita (SOFY) in 2017. Recently, even better treatment results can be obtained by modifying the SOFY method. We describe the technical details of the modified SOFY (mSOFY) after laparoscopic proximal gastrectomy. The stomach was dissected in the short axis direction and the esophagus was dissected in the left and right direction. After the proximal gastrectomy, the bilateral diaphragmatic crus were dissected to enhance gastric elevation. After confirming that the esophagus overlapped more than 5 cm at the center of the remnant stomach (we call it SOFY check), the remnant stomach was suture-fixed to the dissected diaphragmatic crus. The right wall of the esophageal stump and the remnant stomach were anastomosed using the full length of a 45 mm-linear stapler. The entry hole was closed in a direction that did not widen the anastomotic hole. Both sides of the esophagus, remnant stomach, and diaphragmatic crus were suture-fixed on the cranial side 1-2 cm away from the anastomosis. Moreover, the left wall and lower end of the esophagus was suture-fixed to the remnant stomach. The preserved dorsal esophageal wall is pressed and flattened by pressure from the pseudofornix, which is the reflux prevention mechanism. The mSOFY method had favorable treatment outcomes. In conclusion, mSOFY can be one of the safe and feasible reconstruction methods after laparoscopic proximal gastrectomy.

Dopamine activity in projection neurons regulates short-lasting olfactory approach memory in Drosophila.

Survival in many animals requires the ability to associate certain cues with danger and others with safety. In a Drosophila melanogaster aversive olfactory conditioning paradigm, flies are exposed to two odours, one presented coincidentally with electrical shocks, and a second presented 45 s after shock cessation. When flies are later given a choice between these two odours, they avoid the shock-paired odour and prefer the unpaired odour. While many studies have examined how flies learn to avoid the shock-paired odour through formation of odour-fear associations, here we demonstrate that conditioning also causes flies to actively approach the second odour. In contrast to fear memories, which are longer lasting and requires activity of D1-like dopamine receptors only in the mushroom bodies, approach memory is short-lasting and requires activity of D1-like dopamine receptors in projection neurons originating from the antennal lobes, primary olfactory centers. Further, while recall of fear memories requires activity of the mushroom bodies, recall of approach memories does not. Our data suggest that olfactory approach memory is formed using different mechanisms in different brain locations compared to aversive and appetitive olfactory memories.

A non-canonical on-demand dopaminergic transmission underlying olfactory aversive learning.

Dopamine (DA) is involved in various brain functions including associative learning. However, it is unclear how a small number of DA neurons appropriately regulates various brain functions. DA neurons have a large number of release sites and release DA non-specifically to a large number of target neurons in the projection area in response to the activity of DA neurons. In contrast to this "broad transmission", recent studies in Drosophila ex vivo functional imaging studies have identified "on-demand transmission" that occurs independent on activity of DA neurons and releases DA specifically onto the target neurons that have produced carbon monoxide (CO) as a retrograde signal for DA release. Whereas broad transmission modulates the global function of the target area, on-demand transmission is suitable for modulating the function of specific circuits, neurons, or synapses. In Drosophila olfactory aversive conditioning, odor and shock information are associated in the brain region called mushroom body (MB) to form olfactory aversive memory. It has been suggested that DA neurons projecting to the MB mediate the transmission of shock information and reinforcement simultaneously. However, the circuit model based on on-demand transmission proposes that transmission of shock information and reinforcement are mediated by distinct neural mechanisms; while shock transmission is glutamatergic, DA neurons mediates reinforcement. On-demand transmission provides mechanical insights into how DA neurons regulate various brain functions.

Ligand-Directed Approach to Activity-Based Sensing: Developing Palladacycle Fluorescent Probes That Enable Endogenous Carbon Monoxide Detection.

Carbon monoxide (CO) is an emerging gasotransmitter and reactive carbon species with broad anti-inflammatory, cytoprotective, and neurotransmitter functions along with therapeutic potential for the treatment of cardiovascular diseases. The study of CO chemistry in biology and medicine relative to other prominent gasotransmitters such as NO and H2S remains challenging, in large part due to limitations in available tools for the direct visualization of this transient and freely diffusing small molecule in complex living systems. Here we report a ligand-directed activity-based sensing (ABS) approach to CO detection through palladium-mediated carbonylation chemistry. Specifically, the design and synthesis of a series of ABS probes with systematic alterations in the palladium-ligand environment (e.g., sp3-S, sp3-N, sp2-N) establish structure-activity relationships for palladacycles to confer selective reactivity with CO under physiological conditions. These fundamental studies led to the development of an optimized probe, termed Carbon Monoxide Probe-3 Ester Pyridine (COP-3E-Py), which enables imaging of CO release in live cell and brain settings, including monitoring of endogenous CO production that triggers presynaptic dopamine release in fly brains. This work provides a unique tool for studying CO in living systems and establishes the utility of a synthetic methods approach to activity-based sensing using principles of organometallic chemistry.

Carbon Monoxide, a Retrograde Messenger Generated in Postsynaptic Mushroom Body Neurons, Evokes Noncanonical Dopamine Release.

Dopaminergic neurons innervate extensive areas of the brain and release dopamine (DA) onto a wide range of target neurons. However, DA release is also precisely regulated. In Drosophila melanogaster brain explant preparations, DA is released specifically onto α3/α'3 compartments of mushroom body (MB) neurons that have been coincidentally activated by cholinergic and glutamatergic inputs. The mechanism for this precise release has been unclear. Here we found that coincidentally activated MB neurons generate carbon monoxide (CO), which functions as a retrograde signal evoking local DA release from presynaptic terminals. CO production depends on activity of heme oxygenase in postsynaptic MB neurons, and CO-evoked DA release requires Ca2+ efflux through ryanodine receptors in DA terminals. CO is only produced in MB areas receiving coincident activation, and removal of CO using scavengers blocks DA release. We propose that DA neurons use two distinct modes of transmission to produce global and local DA signaling.SIGNIFICANCE STATEMENT Dopamine (DA) is needed for various higher brain functions, including memory formation. However, DA neurons form extensive synaptic connections, while memory formation requires highly specific and localized DA release. Here we identify a mechanism through which DA release from presynaptic terminals is controlled by postsynaptic activity. Postsynaptic neurons activated by cholinergic and glutamatergic inputs generate carbon monoxide, which acts as a retrograde messenger inducing presynaptic DA release. Released DA is required for memory-associated plasticity. Our work identifies a novel mechanism that restricts DA release to the specific postsynaptic sites that require DA during memory formation.

Optical characteristics of highly conductive n-type GaN prepared by pulsed sputtering deposition.

We have characterized highly conductive Si-doped GaN films with a high electron mobility of 112 cm2V-1s-1 at an electron concentration of 2.9 × 1020 cm-3, prepared using pulsed sputtering deposition (PSD). With an increase in the doping concentration, the absorption edge was found to shift toward a higher energy level, owing to the Burstein-Moss effect, thus making this material suitable for the transparent conductive tunneling electrodes of visible and ultraviolet-A light-emitting diodes. The full width at half maximum value of the near-band-edge (NBE) emissions in a photoluminescence spectrum measured at 77 K was as small as 185 meV, even for the sample with the highest electron concentration of 2.9 × 1020 cm-3. Such sharp NBE emissions from PSD-grown heavily Si-doped GaN films can be explained by an analytical model with a low compensation ratio θ of around 0.1, which is consistent with the exceptionally high observed electron mobility. These results indicate the strong potential of the low-temperature PSD growth technique for the formation of high-quality, heavily Si-doped GaN.

AlN/InAlN thin-film transistors fabricated on glass substrates at room temperature.

In this study, InAlN was grown on glass substrates using pulsed sputtering deposition (PSD) at room temperature (RT) and was applied to thin-film transistors (TFTs). The surface flatness of the InAIN films was improved by reducing the growth temperature from 350 °C to RT. Further, the electron mobility and concentration of the InAlN film that was grown at RT were observed to be strongly dependent on the In composition. It was also observed that the electron concentration could be reduced during the introduction of Al atoms into InN, which could most likely be attributed to the reduction in the position of the Fermi level stabilization energy with respect to the conduction band edge. Further, InAlN-TFT was fabricated, and successful operation with a field-effect mobility of 8 cm2 V-1 s-1 was confirmed. This was the first demonstration of the operation of TFTs based on the growth of InAlN on an amorphous substrate at RT.

Perovskite lattice oxygen contributes to low-temperature catalysis for exhaust gas cleaning.

A Pd catalyst supported on Ba-substituted LaAlO3 perovskite (Pd/La0.9Ba0.1AlO3-δ ) was investigated for NO reduction at low temperature by propylene, which revealed that Pd/La0.9Ba0.1AlO3-δ has remarkably higher activity than other Pd catalysts at low temperatures (≤573 K) for NO reduction by propylene. To elucidate the surface reaction pathway, transient response tests were conducted using 18O2. Also, X-ray photoelectron spectroscopy (XPS) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) measurements were conducted. Comparison with a Ba-impregnated catalyst (Pd/Ba/LaAlO3) demonstrated that Pd/La0.9Ba0.1AlO3-δ shows higher activity for the formation of oxygenated species (C x H y O z ) as an intermediate for NO reduction because the surface lattice oxygen has improved mobility via Ba2+ substitution in LaAlO3. Therefore, Pd/La0.9Ba0.1AlO3-δ have high activity for NO reduction, even at low temperatures in a humid condition.

Synaptic depression induced by postsynaptic cAMP production in the Drosophila mushroom body calyx.

KEY POINTS: Synaptic potentiation in Drosophila is observed at cholinergic synapses between antennal lobe (AL) and mushroom body (MB) neurons in the adult brain; however, depression at the AL-MB synapses has not yet been identified. By ex vivo Ca2+ imaging in an isolated cultured Drosophila brain, we found novel activity-dependent depression at the AL-MB synapses. The degree of Ca2+ responses after repetitive AL stimulation is significantly reduced in the dendritic region of MB neurons (calyx) compared with those before AL stimulation, and this reduction of Ca2+ responses remains for at least 30 min. The expression of rutabaga, which encodes Ca2+ /calmodulin-dependent adenylyl cyclase, is essential in the MB neurons for the reduction of Ca2+ responses in the calyx. Our study reveals that elevation of cAMP production in the calyx during repetitive AL stimulation induces the depression at the AL-MB synapses. ABSTRACT: Synaptic plasticity has been studied to reveal the molecular and cellular mechanisms of associative and non-associative learning. The fruit fly Drosophila melanogaster can be used to identify the molecular mechanisms of synaptic plasticity because vast genetic information or tools are available. Here, by ex vivo Ca2+ imaging of an isolated cultured Drosophila brain, we examined the novel activity-dependent synaptic depression between the projection neurons of the antennal lobe (AL) and mushroom body (MB). Ex vivo Ca2+ imaging analysis revealed that electrical stimulation of AL elicits Ca2+ responses in the dendritic (calyx) and axonal (α lobe) regions of MB neurons, and the responses are reduced after repetitive AL stimulation. Since the cAMP signalling pathway plays an important role in synaptic plasticity in invertebrates and vertebrates, we examined whether the reduction of Ca2+ responses is also regulated by the cAMP signalling pathway. The expression of rutabaga (rut), which encodes Ca2+ /calmodulin-dependent adenylyl cyclase, was essential for the reduction of Ca2+ responses in the calyx and α lobe. Furthermore, imaging analysis using a fluorescence resonance energy transfer-based cAMP indicator revealed that the cAMP level increased in the wild-type calyx during repetitive AL stimulation, whereas it decreased in rut1 mutant flies with a loss-of-function mutation of rut. Thus, our study suggests that an increase in postsynaptic cAMP level during repetitive AL stimulation contributes to the attenuation of inputs at AL-MB synapses.

A Drosophila ex vivo model of olfactory appetitive learning.

During olfactory appetitive learning, animals associate an odor, or conditioned stimulus (CS), with an unconditioned stimulus (US), often a sugar reward. This association induces feeding behavior, a conditioned response (CR), upon subsequent exposure to the CS. In this study, we developed a model of this behavior in isolated Drosophila brains. Artificial activation of neurons expressing the Gr5a sugar-responsive gustatory receptor (Gr5a GRNs) induces feeding behavior in starved flies. Consistent with this, we find that in dissected brains, activation of Gr5a GRNs induces Ca2+ transients in motor neurons, MN11 + 12, required for ingestion. Significantly, activation of Gr5a GRNs can substitute for presentation of sugar rewards during olfactory appetitive learning. Similarly, in dissected brains, coincident stimulation of Gr5a GRNs and the antennal lobe (AL), which processes olfactory information, results in increased Ca2+ influx into MN11 + 12 cells upon subsequent AL stimulation. Importantly, olfactory appetitive associations are not formed in satiated flies. Likewise, AL-evoked Ca2+ transients in MN11 + 12 are not produced in ex vivo brains from satiated flies. Our results suggest that a starved/satiated state is maintained in dissected brains, and that this ex vivo system will be useful for identification of neural networks involved in olfactory appetitive learning.

Fabrication of full-color GaN-based light-emitting diodes on nearly lattice-matched flexible metal foils.

GaN-based light-emitting diodes (LEDs) have been widely accepted as highly efficient solid-state light sources capable of replacing conventional incandescent and fluorescent lamps. However, their applications are limited to small devices because their fabrication process is expensive as it involves epitaxial growth of GaN by metal-organic chemical vapor deposition (MOCVD) on single crystalline sapphire wafers. If a low-cost epitaxial growth process such as sputtering on a metal foil can be used, it will be possible to fabricate large-area and flexible GaN-based light-emitting displays. Here we report preparation of GaN films on nearly lattice-matched flexible Hf foils using pulsed sputtering deposition (PSD) and demonstrate feasibility of fabricating full-color GaN-based LEDs. It was found that introduction of low-temperature (LT) grown layers suppressed the interfacial reaction between GaN and Hf, allowing the growth of high-quality GaN films on Hf foils. We fabricated blue, green, and red LEDs on Hf foils and confirmed their normal operation. The present results indicate that GaN films on Hf foils have potential applications in fabrication of future large-area flexible GaN-based optoelectronics.

Coincident postsynaptic activity gates presynaptic dopamine release to induce plasticity in Drosophila mushroom bodies.

Simultaneous stimulation of the antennal lobes (ALs) and the ascending fibers of the ventral nerve cord (AFV), two sensory inputs to the mushroom bodies (MBs), induces long-term enhancement (LTE) of subsequent AL-evoked MB responses. LTE induction requires activation of at least three signaling pathways to the MBs, mediated by nicotinic acetylcholine receptors (nAChRs), NMDA receptors (NRs), and D1 dopamine receptors (D1Rs). Here, we demonstrate that inputs from the AL are transmitted to the MBs through nAChRs, and inputs from the AFV are transmitted by NRs. Dopamine signaling occurs downstream of both nAChR and NR activation, and requires simultaneous stimulation of both pathways. Dopamine release requires the activity of the rutabaga adenylyl cyclase in postsynaptic MB neurons, and release is restricted to MB neurons that receive coincident stimulation. Our results indicate that postsynaptic activity can gate presynaptic dopamine release to regulate plasticity.

Short- and long-term outcomes after pancreaticoduodenectomy following total gastorectomy: Report of case series and literature review.

PURPOSE: Pancreaticoduodenectomy (PD) following gastrectomy (TG) should be considered challenging even currently although its procedure and clinical value have been being standardized. Short- and long-term outcomes as well as standard reconstruction method following these procedures remain unclear. In order to clarify these issues, we reviewed worldwide English literature and 4 of our own cases of PD for patients with previous TG. METHODS: Clinicopathological variables of 11 cases of PD for patients with previous TG were evaluated. Seven of these 11 were abstracted from a review of worldwide English literature and 4 of 11 were our own cases. RESULTS: 3 cases was reconstructed using Y-limb made in previous TG and afferent loop syndrome (ALS) was observed in 2 of 3, in these cases whereas no cases of ALS were found in cases reconstructed using newly-made Y-limb. In cases where PD was indicated for cancer, early cancer death, defined as death related to cancer recurrence observed within 2 years after PD, was observed in 6 of 9 cases. Notably in cases of pancreatic cancer recurrent cancer was diagnosed within 1year after PD in 5 of 7 cases and 4 of these patients died of pancreatic cancer soon after recurrence. CONCLUSION: In cases of PD following TG, previously-made Y-limb should not be used for reconstruction following PD because of probable cause of previously-made Y-limb for ALS. Long-term outcomes of PD after TG seemed unsatisfactory notably in cases of pancreatic cancer and thus application of PD for patients with previous TG should be carefully decided until reasonable explanation for this dismal outcome is obtained.

Fabrication of InGaN thin-film transistors using pulsed sputtering deposition.

We report the first demonstration of operational InGaN-based thin-film transistors (TFTs) on glass substrates. The key to our success was coating the glass substrate with a thin amorphous layer of HfO2, which enabled a highly c-axis-oriented growth of InGaN films using pulsed sputtering deposition. The electrical characteristics of the thin films were controlled easily by varying their In content. The optimized InGaN-TFTs exhibited a high on/off ratio of ~10(8), a field-effect mobility of ~22 cm(2) V(-1) s(-1), and a maximum current density of ~30 mA/mm. These results lay the foundation for developing high-performance electronic devices on glass substrates using group III nitride semiconductors.

Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity.

BACKGROUND: Reduced insulin/insulin-like growth factor signaling (IIS) is a major cause of symmetrical intrauterine growth retardation (IUGR), an impairment in cell proliferation during prenatal development that results in global growth defects and mental retardation. In Drosophila, chico encodes the only insulin receptor substrate. Similar to other animal models of IUGR, chico mutants have defects in global growth and associative learning. However, the physiological and molecular bases of learning defects caused by chico mutations, and by symmetrical IUGR, are not clear. RESULTS: In this study, we found that chico mutations impair memory-associated synaptic plasticity in the mushroom bodies (MBs), neural centers for olfactory learning. Mutations in chico reduce expression of the rutabaga-type adenylyl cyclase (rut), leading to decreased cAMP synthesis in the MBs. Expressing a rut (+) transgene in the MBs restores memory-associated plasticity and olfactory associative learning in chico mutants, without affecting growth. Thus chico mutations disrupt olfactory learning, at least in part, by reducing cAMP signaling in the MBs. CONCLUSIONS: Our results suggest that some cognitive defects associated with reduced IIS may occur, independently of developmental defects, from acute reductions in cAMP signaling.

Glial dysfunction causes age-related memory impairment in Drosophila.

Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.

Fabrication of full-color InGaN-based light-emitting diodes on amorphous substrates by pulsed sputtering.

InGaN-based light-emitting diodes (LEDs) have been widely accepted as highly efficient light sources capable of replacing incandescent bulbs. However, applications of InGaN LEDs are limited to small devices because their fabrication process involves expensive epitaxial growth of InGaN by metalorganic vapor phase epitaxy on single-crystal wafers. If we can utilize a low-cost epitaxial growth process, such as sputtering on large-area substrates, we can fabricate large-area InGaN light-emitting displays. Here, we report the growth of GaN (0001) and InGaN (0001) films on amorphous SiO2 by pulsed sputtering deposition. We found that using multilayer graphene buffer layers allows the growth of highly c-axis-oriented GaN films even on amorphous substrates. We fabricated red, green, and blue InGaN LEDs and confirmed their successful operation. This successful fabrication of full-color InGaN LEDs on amorphous substrates by sputtering indicates that the technique is quite promising for future large-area light-emitting displays on amorphous substrates.

Inventories of psychological skills for athletic clubs and school life.

Some students who participate in athletic activities transfer the skills acquired in a sports context into other areas of life, while others do not. To identify the specific skills that are transferred or not from sports to the school environment, two inventories were developed: the "Psychological Skills Inventory for Athletic Clubs" and the "Psychological Skills Inventory for School Life." These inventories enable a comparison of skills in a sport context with skills in a school context. In the first stage, 307 Japanese first-year university students who had participated in high school athletic clubs volunteered to take part in a survey to develop these inventories. Analyses indicated that both inventories comprised identical subscales of intrapersonal and interpersonal skills. In the second stage, the reliability and validity of these inventories was confirmed for 531 Japanese high school students who were members of athletic clubs for sports such as soccer and baseball.