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Endovascular treatment of wide-necked bifurcation aneurysms (WNBAs) remains challenging despite using a stent. PulseRider is a novel device specifically designed to treat WNBAs, protecting both daughter branches, but the outcomes have not been compared with conventional single stent-assisted embolization. This study aimed to compare the six-month outcomes of PulseRider and single stent-assisted embolization for intracranial unruptured WNBAs using propensity score adjustment. Between February 2012 and October 2021, 46 unruptured WNBAs (34 basilar and 12 middle cerebral arteries) smaller than 10 mm in diameter were treated with PulseRider-assisted embolization (n = 17) or single stent-assisted embolization (n = 29). The immediate and six-month outcomes were compared using inverse probability of treatment weighting analysis. The immediate adequate occlusion rates for the PulseRider- and single stent-assisted embolization were similar (47.1% vs. 62.1%). At six months, adequate occlusion rates for the two groups were also similar (94.1% vs. 86.2%). However, the complete obliteration rate was significantly high after PulseRider-assisted embolization (88.2% vs. 41.4%, adjusted OR 10.54, 95% CI 1.93-57.63). The angiographical improvement rate was also significantly high after PulseRider-assisted embolization (70.6% vs. 37.9%, adjusted OR 6.06, 95% CI 1.54-23.76). The neurologic thromboembolic complication rate was 0% after PulseRider-assisted embolization and 3.4% after single stent-assisted embolization. PulseRider-assisted embolization of WNBAs smaller than 10 mm in diameter was associated with complete obliteration and angiographical improvement at six months. The unique shape of the PulseRider might contribute to the improved midterm aneurysm occlusion.

Abstract Background Dietary modifications are considered a first-line intervention for chronic disease management, yet graduating doctors still report not feeling competent to counsel patients on their diet. Research has focused on methods to address this shortfall in physician competency, including culinary medicine. Culinary medicine is an approach to education that involves hands-on food and cooking learning experiences to equip participants with tools for improving the nutrition behaviour and health of their future patients. Despite positive findings in the efficacy of these interventions, they differ markedly in approach and target, which therefore fails to provide adequate evidence that could serve to guide future culinary medicine interventions. Objective A scoping review to synthesize the existing literature on culinary medicine interventions that are offered during medical training. Methods Online databases were used to identify literature published prior to April 2022 that involve a hands-on culinary medicine component to nutrition and examine academic impact, feasibility and acceptability. Results Twenty-four studies met the eligibility criteria. Despite promising gains in nutrition knowledge, confidence and high acceptability of the programs, large variations exist in delivery method, setting, and course content between programs. There is a lack of program cost reporting and long-term follow up of participants, inconsistent evidence for improved nutrition attitudes amongst participants, as well as geographically limited adoption of such programs. Conclusions The findings of this research demonstrate a clear increase in interest in the use of hands-on culinary medicine programs as educational tools, evidence of feasibility in implementation, and improved student nutritional knowledge, skill and counseling compared to a traditional didactic curriculum. The quality of culinary medicine research studies is increasing and the aims of research are narrowing to focus on how culinary medicine can positively impact medical education. The findings from this review will aid in legitimising culinary medicine as an effective delivery method of nutritional education in medical programs.

Abstract Background While breastfeeding provides benefits for infants and the mother, many women either do not breastfeed or terminate breastfeeding earlier than recommended. The aim of this analysis was to identify factors associated with early discontinuation of breastfeeding in Japanese women. Methods This study used data from medical records of women delivering a singleton live birth between March 2017 and August 2019 in Iwase General Hospital, Fukushima Prefecture, Japan to assess cessation of breastfeeding by the 1-month postpartum appointment. Demographic (age at birth, and employment status), medical (parity, and physical and mental condition of the mother; and infant medical factors, such as sex, Apgar score, and jaundice, among other), and family factors (husband/partner, family members living at the same house, among others) in 734 women who had initiated breastfeeding during their delivery hospital stay were examined, and multiple logistic regression was used to determine significant predictors of early cessation of exclusive breastfeeding. Results Bivariate analysis revealed that women who were primipara, unmarried, exposed to secondhand smoke, and employed; those who smoked before pregnancy; and those who had asthma were more likely to discontinue exclusive breastfeeding than other women. Infant factors associated with discontinuation were lower birthweight, earlier gestational age, neonatal intensive care unit admission, treatment for jaundice, or lower weight gain. Multivariable analysis revealed that primiparity, passive smoking before pregnancy, maternal employment, and neonatal jaundice therapy were associated with discontinuation of breastfeeding. Conclusions In particular, women whose partners smoked before pregnancy may need to be targeted for additional support for breastfeeding.

This study focused on a carbonation treatment that immobilizes trace elements such as lead (Pb) in incineration bottom ash (IBA) using the exhaust gas and the refined carbon dioxide generated (CO2) recovered at the Japan's first incineration facility, which recovers CO2 in the gaseous form. This study describes (1) the bearing capacity of IBA from the municipal solid waste (MSW) obtained through the California bearing ratio (CBR) test to investigate the possibility of using IBA as a base course material, (2) mechanical characteristics of IBA using the cone index test, to investigate the possibility of using as an embankment material, and (3) leaching properties of IBA from MSW obtained through a single batch leaching test and the long-term outdoor exposure of the leaching test to evaluate the effect of carbonation treatments. Results reveal that there was no effect of trace components not included in the separated and recovered CO2, and that the effect of carbonation could be obtained even if the exhaust gas was used directly. The carbonated IBA can be applied as a sub-base course material based on its mechanical properties, regardless of the carbonation conditions. In addition, carbonated IBA can be used as an embankment material owing to its sufficient cone index value. Regarding the heavy metal and metalloid leaching behavior, it was revealed that all the IBA samples satisfied the soil environmental standards set by the Ministry of the Environment, Japan, except for Cr (VI). The long-term leaching characteristics of carbonated IBA showed that Pb could be immobilized over a long period.

Abstract Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth. Red blood cell distribution width (RDW), a measure of the variation red blood cell size, could reflect oxidative stress and chronic inflammation in many diseases such as cardiovascular, pulmonary, and other diseases. The objectives of the present study were to evaluate perinatal factors affecting RDW and to validate whether RDW could be a potential biomarker for BPD. A total of 176 preterm infants born at

Abstract Background The α2-receptor agonist dexmedetomidine (Dex) has been shown to produce sedative and analgesic effects not only with systemic administration but also when administered in the extradural space and around peripheral nerves. The effects and mechanism of action of Dex on pulmonary arteries, however, have not been determined. This study therefore aimed to investigate the effect of Dex on pulmonary arterial vascular smooth muscle by evaluating changes in isometric contraction tension. We then attempted to determine the effects of Dex on depolarization stimulation and receptor stimulation. Methods Endothelium-denuded porcine pulmonary arteries were sliced into 2- to 3-mm rings. We then exposed them to certain substances at various concentrations under different conditions of baseline stimulation (with KCl, adrenaline, caffeine, or histamine) and to α2-receptor stimulants or antagonists, or α1-receptor antagonists (imidazoline, yohimbine, rauwolscine, prazosin), and different conditions of Ca2+ depletion of the intracellular reservoir or extracellular stores. We measured the changes in isometric contraction tension with each addition or change in conditions. Results Dex enhanced the contraction induced by high-concentration KCl stimulation. Dex-induced enhancement of contraction induced by high-concentration KCl was completely suppressed by yohimbine and rauwolscine, which are α2-receptor antagonists, but not by prazosin. Dex, imidazoline, yohimbine, and rauwolscine reduced the increases in contraction tension induced by the receptor stimulant adrenaline. Dex suppressed the adrenaline-induced increases in contraction tension after depletion of the Ca2+ reservoir. In the absence of extracellular Ca2+, Dex suppressed the adrenaline- and histamine-induced increases in contraction tension but did not affect caffeine-induced increases. Conclusions Dex-enhanced, high-concentration KCl-induced contraction was mediated by α2-receptors. Adrenaline-induced contraction was suppressed by the α2-receptor stimulant Dex and α2-receptor antagonists yohimbine and rauwolscine, suggesting that the effect of Dex on adrenaline-induced contraction is attributable to its α2-receptor-blocking action. Dex inhibited receptor-activated Ca2+ channels and phosphatidylinositol-1,4,5-triphosphate-induced Ca2+ release but not Ca2+-induced Ca2+ release.

Bronchopulmonary dysplasia (BPD) is a common cause of pulmonary disease in preterm infants. The soluble receptor for advanced glycation end products (sRAGE) is implicated in the development of various pulmonary diseases. The objectives of the current study were to investigate perinatal factors associated with serum sRAGE levels at birth and to establish whether serum sRAGE could be a biomarker for BPD. This retrospective single-center study was conducted at Fukushima Medical University Hospital's Department of Pediatrics Neonatal Intensive Care Unit from April 2014 to September 2020. Mechanically ventilated or oxygenated neonates born at

Background: Neonatal intracranial pial arteriovenous fistulas (AVFs) are rare vascular malformations. The pathophysiology of hydrocephalus in cases of pial AVF remains to be fully understood. Here, authors report a case of pial AVF with a large venous varix, which rapidly expanded after cerebrospinal fluid (CSF) diversion. Case description: A female neonate was born at full term following a normal pregnancy and delivery. A supracerebellar pial AVF with a large venous varix and the hydrocephalus due to complex mechanism were found on fetal imaging. She had no neurological deficits, but her head circumference was slightly larger than normal. The hydrocephalus was treated via CSF diversion, but this was followed by a remarkable expansion of the venous varix. Transarterial embolization of the AVF was subsequently performed, which resulted observable improvement of the hydrocephalus. Conclusion: Hydrocephalus complicating pial AVFs with a venous varix should not be treated by CSF diversion first. Instead, the initial step in the treatment should be obliteration of the AVFs. This restores the hydrodynamic balance between the CSF and intracranial venous system, resulting in the gradual improvement of the hydrocephalus.

An 84-year-old woman underwent soft palate resection and skin grafting with tie-over under general anesthesia. Fourteen years previously, she had undergone aortic valve replacement and coronary artery bypass grafting followed by lifelong warfarin and aspirin anticoagulation. We terminated the two drugs 8 and 6 days, respectively, before the present surgery and substituted intravenous heparin (10,000 units/day), which was terminated 6 h preoperatively. The surgery was uneventful. Heparin was restarted 2 days postoperatively but without warfarin potassium or aspirin because of postoperative soft palate bleeding, which continued for 10 days despite compression hemostasis. On day 10, she exhibited a suffocating large hemorrhagic mass, leading to cardiopulmonary arrest. Emergency consultation with medical doctors and dental anesthetists resulted in pulmonary resuscitation and tracheal intubation. After confirming spontaneous circulation/respiration, she was transferred to the intensive care unit. We now consider it essential that all medical/surgical/anesthesia specialists managing patients under anticoagulant therapy collaborate perioperatively.

1. Abstract: Multiple sclerosis (MS) is an inflammatory disease of unknown etiology in the central nervous system characterized by dissemination in time and space. Difficulties are associated with definitively diagnosing MS early because there are no disease-specific symptoms or diagnostic markers; therefore, a comprehensive judgment to differentiate MS from other diseases is made based on the clinical features of repeated relapses and remission and characteristic magnetic resonance imaging (MRI) findings. In this study, we attempted to construct a predictive classification model using a machine learning method that accurately distinguishes healthy controls (HC) and MS patients based on a quantitative assessment of brain atrophy characteristics caused by MS.We used brain volumes from 55 segments of each brain region calculated from the MRI images of 72 MS patients and 21 HC. These data were input into supervised learning methods (Bayesian regularized neural networks (BRNN) and support vector machine (SVM)) for training on fluctuation patterns in brain atrophy. The obtained accuracy of the model was 77.8% for sensitivity and 95.2% for specificity with cross-validation. The MS prediction rate, calculated by this model, was correlated with Expanded Disability Status Scale (EDSS) scores (r = 0.413, p

Background: Dopamine replacement therapy is an established treatment for motor symptoms of Parkinson's disease, but its long-term use is often limited by the eventual development of motor complications, including levodopa-induced dyskinesia. Genetic background, particularly polymorphisms of dopamine metabolism genes, may affect the occurrence of dyskinesia in Parkinson's disease patients. Methods: We investigated polymorphisms of dopamine metabolism genes, including catechol-O-methyltransferase, monoamine oxidase B, dopamine beta-hydroxylasedopamine, dopamine receptors D1, D2, and D3, and dopamine transporter, in 110 patients with Parkinson's disease. Cox proportional hazards regression was used to detect associations between genotypes and levodopa-induced dyskinesia. Results: Monoamine oxidase B rs1799836 was the only polymorphism correlated with risk of dyskinesia. Patients with an AG or GG genotype were more likely to have dyskinesia than those with an AA genotype (adjusted hazard ratio, 3.41; 95% confidence interval, 1.28–9.10). Also, Kaplan-Meier curves demonstrated that patients with an AG or GG genotype developed dyskinesia earlier than those with an AA genotype (log-rank test, p = .004). Conclusions: In Parkinson's disease patients, the monoamine oxidase B rs1799836 G allele is associated with a greater likelihood of developing dyskinesia than the A allele, possibly due to its association with lower monoamine oxidase B activity in the brain. Thus, detection of monoamine oxidase B polymorphisms may be useful for determining the optimal dosing of antiparkinson medications.

Background: Skull bone tumor resection is sometimes difficult, when tumor is hidden under the bone surface or similar to the normal bone in appearance. Indocyanine green (ICG) fluorescence has been used in various surgical fields for visualizing vascular and tumor tissues. This is the first report to show that intraoperative ICG fluorescence is useful for skull bone tumor resection. Case description: Four patients underwent skull bone tumor resection from June to December 2014. Two patients had Langerhans cell histiocytosis, and the others had hemangiomas. During surgical treatment, intraoperative ICG injection revealed the bone tumors hidden in normal bone tissue in real time. Three of the four tumors were identified as a high intensity area, and the other, a cavernous hemangioma, as an area lacking fluorescent enhancement. Each area was marked and then removed en bloc with an outside margin of 1 cm. On pathological examination, the surgical margin corresponded to the actual margin. In all cases, Postoperative course was uneventful, and there was no tumor recurrence. Conclusion: Our experience illustrates that intraoperative ICG fluorescence examination might be a useful supplemental method for skull bone tumor resection, especially for tumors extending under the bone surface or similar to normal bone in appearance.

Effects of gas temperature and oxygen concentration on the soot formation of the axial jet laminar diffusion flame have been studied experimentally for the ambient gas mixtures of carbon-dioxide and oxygen. These data were compared to those for the ambient gas mixture of nitrogen and oxygen of 21%. The experiments showed that the flame heights for the mixture of carbon-dioxide and oxygen of 21% and that of nitrogen and oxygen 21% were about same and decreased with the increase of gas temperature. When the oxygen concentration was 21% in the ambient gas mixtures, the total soot volume for the ambient gas of nitrogen and oxygen were higher than that of carbon-dioxide and oxygen and increased with the increase of the gas temperature. When the ambient gases were the carbon-dioxide and oxygen mixtures, the total soot volume increased with the gas temperature for the fixed values of the oxygen concentration in the ambient gases. But, for the fixed ambient gas temperatures, the total soot volume increased with the increase of the oxygen concentration in the ambient gas and reached to a maximum, and then decreased slightly with the increase of the oxygen concentration. The variations of total soot volume were discussed by using the adiabatic flame temperatures for the experimental conditions. The plots of logarithm of the total soot volume for the inverse value of the adiabatic flame temperature show that the oxygen concentration has the strong effect on the total soot volume compared to the effect of the adiabatic flame temperature.

Background: Transcranial Doppler (TCD) is used to monitor cerebral vasospasm after subarachnoid hemorrhage (SAH), but its diagnostic ability is reported to be limited. Therefore, the purpose of this study was to investigate the relationship between the diagnosability of TCD and the localization of the vasospasm. Methods: This retrospective study included 20 patients who presented with symptomatic vasospasm after SAH. All 20 patients underwent daily TCD examinations and cerebral angiography after the onset of delayed cerebral ischemia. We defined positive findings on TCD as a maximum flow velocity >200 cm/s or as a mean flow velocity >120 cm/s at the horizontal part of the middle cerebral artery (MCA). We also examined the site of vasospasm on cerebral angiography. Results: Fourteen patients had true-positive findings on TCD examination, and cerebral angiography showed diffuse vasospasm involving the horizontal segment of the MCA. However, 6 patients had false-negative findings on TCD examination, and cerebral angiography showed vasospasm localized at the distal part of the MCA (the insular and/or cortical segments). The patients with proximal vasospasm were significantly younger than those with distal vasospasm. Blood flow velocity at initial TCD and the increase in velocity at the onset of vasospasm were lower and smaller, respectively, in the distal vasospasm group. Conclusions: In patients with cerebral vasospasm localized at the distal part of the MCA, flow velocity at the horizontal segment of the MCA did not increase to the level we defined as positive. To avoid such false negatives, a slight increase in velocity on TCD should be considered as positive in distal vasospasm cases, especially in older patients.

Background: Giant pituitary adenomas continue to carry higher surgical risks, and postoperative acute catastrophic hemodynamic changes are associated with very poor outcome but remain difficult to predict. Method: Surgical planning based on information about the fine angioarchitecture was achieved using C-arm cone-beam computed tomography. Particular feeding systems and semi-quantitative evaluations for tumor staining were also investigated. Conclusion: Major blood supply was different from the normal supply to the anterior pituitary gland and did not necessarily correspond to tumor shape and extension. Surgical strategy should be established based on the tumor feeding systems and hemodynamics in giant pituitary adenomas.

Possibility of the higher combustion efficiency using the oxy-fuel combustion technology has been studied from the thermodynamic point of view. The energy consumption and the change in entropy were calculated for the case of the normal air combustion, the regenerative combustion, and the oxy-fuel combustion. The energy consumption and the change in entropy were compared and discussed for three cases. For the oxy-fuel combustion, the energy required to produce the pure oxygen from the air was considered. The regenerative combustion was the case in consideration of a heat recovery. As a result, the thermodynamical potential of the oxy-fuel combustion is higher than that of the normal air combustion when the exhaust gas temperature is high. The thermodynamical potential of the regenerative combustion depends on the heat recovery efficiency of the regenerative system. The thermodynamical potential of the oxy-fuel combustion is lower than that of the regenerative combustion for the lower exhaust gas temperature, but for the higher exhaust temperature that of the oxy-fuel combustion is higher than that of the regenerative combustion.

BACKGROUND: Apolipoprotein E (ApoE) typing is considered important because of the association between ApoE and Alzheimer's disease and familial dyslipidemia and is currently performed by genetic testing (APOE genotyping). ApoE levels in plasma and serum are clinically determined by immunoassay. METHODS: Combining an ApoE immunoassay reagent with proteomic analysis using an Orbitrap mass spectrometer, we attempted to resequence ApoE from trace amounts of serum for typing (serotyping). Most (24 of 33) ApoE mutant proteins registered to date with Online Mendelian Inheritance in Man, such as ApoE2 and ApoE4, involve lysine and arginine mutations. Digestion of mutant ApoE with trypsin will thus result in fragments that differ substantially from wild-type ApoE3 in terms of mass, making serotyping ideally suited to mass spectrometry analysis. RESULTS: The mean coverage of the amino acid sequence of full-length ApoE was 91.6% in the protein resequence. Residues 112 and 158 (which are mutated in ApoE2 and ApoE4) were covered in all samples, and the protein sequences were used for serotyping. Serotypes including all heterozygous combinations (ApoE2/E3, E2/E4, E3/E4) corresponded exactly to the APOE genotyping results in each of the subjects. CONCLUSION: Our novel ApoE serotyping method with protein resequencing requires no synthesis of stable isotope-labeled peptides or genome analysis. The method can use residual blood from samples collected for routine clinical tests, thus enabling retrospective studies with preserved body fluids. The test could be applied to samples from subjects whose DNA is unavailable. In future studies, we hope to demonstrate the capability of our method to detect rare ApoE mutations.

To investigate school-age children's perspectives on food and nutrition, we pilot tested a method to quantify and analyze crayon drawings collected from students in health education classes at two elementary schools in Fukushima, Japan. Included were 28 students in a mixed class of first and second graders and 26 students in a fourth-grade class. Specific foods, general shapes, and color choices in children's drawings were entered into a spreadsheet and analyzed quantitatively. From first- and second-graders' data, co-occurrence network analysis put meals into three groups: at home, eating out, and lunch boxes. Among fourth graders, co-occurrence network analysis called attention to the cucumber, noteworthy for being a local agricultural product. In addition, students who drew more side dishes also drew more staple foods and main dishes (p = 0.04), used more colors (p = 0.006), and showed satisfaction with their community (p = 0.04). These results suggest that students' understanding of eating was centered on the places where they eat and that they valued regional specialty products. Furthermore, the drawing of side dishes was indicative of a balanced diet, which in turn was associated with higher satisfaction with their community. Our trial indicates that children's drawings can be a useful tool for adults to grasp children's understanding of health-related information in daily living.

Abstract Spinocerebellar ataxia (SCA) 42 is caused by a mutation in CACNA1G, which encodes the low voltage-gated calcium channel CaV3.1 (T-type). Patients with SCA42 exhibit a pure form of cerebellar ataxia. We encountered a patient with the p.Arg1715His mutation, suffering from intractable resting tremor, particularly head tremor. This symptom improved with the administration of low-dose of zonisamide (ZNS), a T-type calcium channel blocker effective for treating Parkinson’s disease and epilepsy. Previous electrophysiological studies showed that the voltage dependence of this mutant CaV3.1 was shifted toward the positive potential. This abnormal shift was considered a factor related to disease onset and symptoms. In this study, we performed whole-cell recordings of GFP-expressing HEK293T cells that expressed wild-type or mutant CaV3.1 and investigated the changes in the abnormal shift of voltage dependence of the mutant CaV3.1. The results showed that ZNS in an amount equivalent to the patient’s internal dose significantly ameliorated the abnormal shift in the mutant CaV3.1, giving values close to those in the wild-type. On the other hand, ZNS did not affect the voltage dependence of wild-type CaV3.1. Because CaV3.1 is known to be involved in tremogenesis, modulation of the voltage dependence of mutant CaV3.1 by ZNS might have contributed to improvement in the intractable tremor of our patient with SCA42. Moreover, efonidipine, another T-type calcium channel blocker, had no effect on tremors in our patient with SCA42 and did not improve the abnormal shift in the voltage dependence of the mutant CaV3.1. This indicates that ZNS is distinct from other T-type calcium channel blockers in terms of modulation of the voltage dependence of the mutant CaV3.1.

HDL-bound ApoM and albumin are protein chaperones for the circulating bioactive lipid, sphingosine 1-phosphate (S1P); in this role, they support essential extracellular S1P signaling functions in the vascular and immune systems. We previously showed that ApoM- and albumin-bound S1P exhibit differences in receptor activation and biological functions. Whether the physiological functions of S1P require chaperones is not clear. We examined ApoM-deficient, albumin-deficient, and double-KO (DKO) mice for circulatory S1P and its biological functions. In albumin-deficient mice, ApoM was upregulated, thus enabling S1P functions in embryonic development and postnatal adult life. The Apom:Alb DKO mice reproduced, were viable, and exhibited largely normal vascular and immune functions, which suggested sufficient extracellular S1P signaling. However, Apom:Alb DKO mice had reduced levels (∼25%) of plasma S1P, suggesting that novel S1P chaperones exist to mediate S1P functions. In this study, we report the identification of ApoA4 as a novel S1P binding protein. Recombinant ApoA4 bound to S1P, activated multiple S1P receptors, and promoted vascular endothelial barrier function, all reflective of its function as a S1P chaperone in the absence of ApoM and albumin. We suggest that multiple S1P chaperones evolved to support complex and essential extracellular signaling functions of this lysolipid mediator in a redundant manner.

A 76-year-old man presented to our hospital with abdominal distention and loss of appetite. The 10% of weight lost relative to this patient in 1 month. Abdominal computed tomography and magnetic resonance imaging revealed a giant mass, with a major axis of 23 cm, containing solid components, not involving the upper abdominal organs. Esophagogastroduodenoscopy showed extramural compression from the middle gastric body to the antrum, as well as a normal mucosal surface. These findings were suggestive of a gastrointestinal stromal tumor attached to the anterior wall of the stomach without metastasis or invasion. Partial gastrectomy was performed for tumor resection, and the patient was subsequently treated with adjuvant imatinib. We report a rare case of a large extramural gastrointestinal stromal tumor of the stomach that was larger than 20 cm in diameter and present a pertinent literature review.

We propose a method to estimate and visualize effects of a binary covariate on the longitudinally observed text data. Our method consists of series of analytical methods: extracting keywords through a morphological analysis, estimating the time-varying regression coefficient of a binary covariate for keyword's appearance and frequency, classifying summary of estimates, and visualizing the time-varying effects of a binary covariate in animated scatter plots. The procedure is demonstrated with Peace Declaration text data observed for forty years in two cities.

Local anesthesia may induce systemic complications leading to parasympathetic activity leading to bradycardia and hypotension. We report a case of a 50-year-old man undergoing dental surgery under general anesthesia who experienced severe bradycardia and hypotension after local anesthesia infiltration. Concerns regarding the utilization of a relatively large lumen injection needle for local anesthesia during general anesthesia are discussed.

Pancreatic cancer is a highly aggressive and notoriously difficult to treat. As the vast majority of patients are diagnosed at advanced stage of the disease, only a small population is curative by surgical resection. Although gemcitabine-based chemotherapy is typically offered as standard of care, most patients do not survive longer than 6 months. Thus, new therapeutic approaches are needed. Pancreatic cancer cells that develop gemcitabine resistance would still be suitable targets for immunotherapy. Therefore, one promising treatment approach may be immunotherapy that is designed to target pancreatic-cancer-associated antigens. In this paper, we detail recent work in immunotherapy and the advances in concept of combination therapy of immunotherapy and chemotherapy. We offer our perspective on how to increase the clinical efficacy of immunotherapies for pancreatic cancer.