Evaluation of a Web-based learning system for skills in removing personal protective equipment for highly infectious diseases-A randomized controlled trial.

OBJECTIVE: Which educational method is best for 3-month retention of proper skills in removing personal protective equipment (PPE) in the setting of highly infectious diseases is unclear. We evaluated the effectiveness of a Web-based learning system after 3 months of use. SETTING: One general hospital in Japan. INTERVENTION: We conducted a randomized, nonblinded, parallel-group trial with 35 nurses using the substitution block method. At baseline, both groups received face-to-face training in putting on and removing PPE. The intervention group was given access to the Web-based learning system we developed using Modular Object-Oriented Dynamic Learning Environment (Moodle). After 3 months, we assessed both groups regarding knowledge and skills in removing PPE using a 34-point test, fluorescent markers, and video recordings. RESULTS: Overall, 34 participants completed the trial: 16 in the intervention group and 18 in the control group. Postintervention knowledge test scores (1.3 vs -0.8; P = .013; effect size r = .42) and deviations from the required procedure (-5.4 vs 1.9; P = .001; effect size r = .55) were significantly better in the intervention group than in the control group. The number of contaminated sites (-0.5 vs 0.4; P = .128; effect size r = .26) and contaminated participants (-18.7% vs 11.1% decreased in the intervention group, and increased in the control group, although this was not significant (P = .242; effect size ϕ = .47). CONCLUSIONS: This learning system was an effective educational method in maintaining and improving knowledge of proper PPE removal skills. The number of deviations from the required procedure decreased, and this reduction continued after 3 months. CLINICAL TRIALS IDENTIFIER: Evaluation of the Web materials for learning PPE removal skills in the setting of highly infectious diseases. University Hospital Medical Information Network, UMIN000042725: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000048767.

Discovery and pharmacological characterization of novel positive allosteric modulators acting on skeletal muscle-type nicotinic acetylcholine receptors.

Skeletal muscle-type nicotinic acetylcholine receptors (m-nAChRs) are ligand-gated ion channels that open after activation by ACh and whose signals cause muscle contraction. Defects in neurotransmission are reported in disorders such as myasthenia gravis (MG) and congenital myasthenia syndromes (CMS). Although treatments for these disorders exist, therapies which significantly increase muscle strength have yet to be reported. Positive allosteric modulators (PAMs), which promote ACh signaling through AChRs, are expected to be promising therapeutic agents. In this study, we identified an m-nAChR PAM called AS3513678 by high-throughput screening using human myotube cells and modified it to obtain novel compounds (AS3566987 and AS3580239) that showed even stronger PAM activity. AS3580239 caused a leftward shift in the ACh concentration-response curve and was 14.0-fold potent at 10 µM compared with vehicle. Next, we examined the effect of AS3580239 on electrically-induced isometric contraction of the extensor digitorum longus (EDL) muscle in wild-type (WT) and MG model rats. AS3580239 enhanced EDL muscle contraction in both WT and MG model rats at 30 µM. These data suggest that AS3580239 improved neurotransmission and enhanced muscle strength. Thus, m-nAChR PAMs may be a useful treatment for neuromuscular diseases.

Survival Benefits of Laparoscopic Gastrectomy in Elderly Patients With Gastric Cancer: Focusing on Preoperative Nutritional and Inflammatory Status.

BACKGROUND/AIM: Laparoscopic gastrectomy (LG) may have greater clinical benefits as a less invasive surgery for elderly patients with gastric cancer (GC). Therefore, we aimed to evaluate the survival benefit of LG in elderly patients with GC, especially focusing on preoperative comorbidities, and nutritional and inflammatory status. PATIENTS AND METHODS: Data collected from 115 patients aged ≥75 years with primary GC who underwent curative gastrectomy, comprising 58 patients who underwent open gastrectomy (OG) and 57 patients who underwent LG, were retrospectively reviewed (total cohort), and 72 propensity-matched patients (matched cohort) were selected for survival analysis. The aim of the study was to determine short- and long-term outcomes, and the clinical markers to identify a population who may benefit from LG in elderly patients. RESULTS: The complication and mortality rates as a short-term outcome in the total cohort and overall survival (OS) as a long-term outcome in the matched cohort did not differ significantly between the groups. In the total cohort, advanced tumor stage and ≥3 comorbidities were independent factors for poor prognosis in terms of OS [hazard ratio (HR)=3.73, 95% confidence interval (CI)=1.78-7.78, p<0.001 and HR=2.50, 95% CI=1.35-4.61, p<0.01, respectively]. The surgical approach was not an independent risk factor for postoperative complications (grade ≥III) and OS. In subgroup analysis of the total cohort, patients with a neutrophil-lymphocyte ratio (NLR) ≥3 in the LG group demonstrated a trend toward greater OS (HR=0.26, 95% CI=0.10-0.64, interaction p<0.05). CONCLUSION: LG might offer greater survival benefits than OG in frail patients such as those with high NLR.

Successful laparoscopic cholecystectomy for gallbladder hemorrhage from a Dieulafoy lesion in a patient on hemodialysis: a case report.

BACKGROUND: Patients on long-term dialysis are prone to hemorrhagic complications, particularly uremic bleeding, but gallbladder hemorrhage is rare, even in patients on dialysis. There have been occasional reports of a Dieulafoy lesion being a cause of gastrointestinal hemorrhage, but its occurrence within the gallbladder is quite rare. This report describes a case of gallbladder hemorrhage from a Dieulafoy lesion in a patient on hemodialysis that was diagnosed early and successfully treated by laparoscopic cholecystectomy. CASE PRESENTATION: The patient was a 68-year-old woman on long-term hemodialysis with end-stage renal failure who presented with epigastralgia and back pain. There was no history of trauma or oral administration of antiplatelet or anticoagulant agents. There were no signs of an inflammatory reaction or hyperbilirubinemia. Contrast-enhanced computed tomography revealed a slightly hyperdense area in the distended gallbladder and extravasation within the gallbladder lumen but no gallstones. A severe atherosclerotic lesion was also found. She was diagnosed to have gallbladder hemorrhage and emergency laparoscopic cholecystectomy was performed. Although the postoperative course was complicated by drug fever, she was discharged on postoperative day 10 in a satisfactory condition. Histology revealed hemorrhagic ulceration with an exposed blood vessel accompanied by abnormal arteries in the submucosa. Arteriosclerosis with eccentric intimal hyperplasia in a small-sized artery was also seen. The diagnosis was gallbladder hemorrhage from a Dieulafoy lesion. CONCLUSIONS: A Dieulafoy lesion should be kept in mind as a cause of gallbladder hemorrhage in a patient with severe arteriosclerosis and a bleeding diathesis, particularly if on dialysis, and treated as early as possible.

Invasive pulmonary aspergillosis with candidiasis: usefulness of molecular and ultrastructural morphological analysis on FFPE tissue for invasive fungal infections.

Invasive pulmonary aspergillosis (IPA) is one of the most frequent forms of invasive fungal infections (IFI); however, it is often difficult to identify the pathogenic fungal species and to select appropriate treatments for patients with IFI including IPA. Here, we describe the detailed pathophysiology of an autopsy case of severe respiratory failure due to IPA with candidiasis. The patient developed severe respiratory failure after influenza infection and died, and the autopsy revealed a mixed disease of IPA with candidiasis. In this study, in addition to the routine pathological examination, we further examined formalin-fixed paraffin-embedded (FFPE) tissues by scanning electron microscopy (SEM) and partial genomic DNA sequencing. Although optical microscopy alone was insufficient to identify the pathogenic organisms, SEM clearly depicted the characteristic morphology of Aspergillus sp. and Candida sp. as closely overlapping in a nested fashion, providing evidence of mixed infection of both fungal species in a focal site. The technique using FFPE tissue in combination with ultrastructural observation by SEM, elemental analysis by SEM-EDX, and DNA sequencing is promising for analyzing the pathophysiology of IFI.

Infusion of Variable Chemical Structure to Tune Stacking among Metal-Organic Layers in 2D Nano MOFs.

Invited for the cover of this issue is the group of Biplab Manna at the University of Kumamoto. The image depicts various kinds of stacking between the metal-organic layers of MOFs. Read the full text of the article at 10.1002/chem.202201665.

Vascular Anomaly Associated with Ectopic Pancreas in the Pylorus.

The ectopic pancreas is a relatively rare congenital condition, defined as pancreatic tissue lacking anatomical or vascular continuity with the normal pancreatic body. The ectopic pancreas is most frequently found in the stomach, usually asymptomatic and discovered incidentally. We report the case of a 72-year-old man who was diagnosed with cancer in the gastric vestibule. Distal gastrectomy was performed, and 3 cm of the ectopic pancreas was found on the anterior surface of the pylorus intraoperatively. The gastroduodenal artery was not found by approaching the inferior border of the pancreas but by following the branches from the common hepatic artery. Posterior view CT confirmed that the GDA terminated in the ectopic pancreas. An ectopic pancreas may be associated with vascular anomalies. Clinicians must consider the possibility of vascular anomalies when operating on patients with an ectopic pancreas. If the gastroduodenal artery cannot be found intraoperatively, identification should be attempted by following the common hepatic artery.

Infusion of Variable Chemical Structure to Tune Stacking among Metal-Organic Layers in 2D Nano MOF.

Thickness of two-dimensional (2D) metal-organic frameworks (MOFs) govern their intriguing functionalities. Primarily this thickness is controlled by the stacking between the metal-organic layers (MOL). It is observed that until now such modulating factors for stacking efficiency of MOL are not well studied. Here, we report a fundamental hypothesis to comprehend regulation of stacking efficiency among MOLs as a function of chemical structure of organic ligands (dicarboxylic acids and pillar linkers). This basically involves a series of isostructural three-dimensional (3D) MOFs which contain linkers of variable chemical nature that could be depillared to generate 2D stacked MOFs of different thickness. Depending on the linkers, we encountered the formation of single MOL to stacked multiple MOLs as evidenced from atomic force microscopic and other experimental analysis. The present study gives a concrete correlation between the stacking within 2D MOFs (from monolayer to multilayers), and their 3D counter parts, which may provide a thickness tuning pathway for 2D MOFs.

Complications of cerebral air embolism associated with pleural lavage for empyema.

Standard initial treatment for acute empyema involves antibiotic administration and chest tube drainage; however, pleural lavage with saline is another treatment that mitigates the need for surgical drainage. Although this treatment is recognised as non-invasive and safe, the complications of cerebral air embolism are less recognised.In this case, a man in his late 40s was diagnosed with acute empyema and treated with chest tube (28 Fr) drainage and antibiotics. Empyema remained on follow-up chest imaging; thus intrapleural fibrinolytic therapy (urokinase 120 000 units/day for a total of 3 days) and pleural lavage (0.9% saline 1000 mL/day daily) were administered. During the 10th pleural lavage, the patient suddenly became unconscious. Head imaging revealed a cerebral air embolism. Consequently, he received urgent hyperbaric oxygen therapy and improved without any neurological sequelae.Clinicians should be aware of the complications of sudden cerebral air embolism due to pleural lavage for empyema.

Contemporaneous Insufficiency Fractures of Bilateral Femoral Necks in an Older Patient Taking Bisphosphonate: A Case Report and Literature Review.

We report, to the best of our knowledge, the first case of simultaneous insufficiency fracture of the bilateral femoral neck in an older patient taking bisphosphonate. Femoral neck fractures frequently occur in older individuals because of traumatic incidents, such as a fall. A 74-year-old woman with osteoporosis was taking raloxifene hydrochloride and bisphosphonate for approximately 5 and 3 years, respectively. Despite no history of falls or any other traumatic incidence, the patient reported cooccurrence of pain on both sides of the hip. Imaging revealed bilateral femoral neck fractures. Bipolar hemiarthroplasty and internal fixation were conducted on the right and left hips, respectively. At 6 months postoperatively, the patient reported gradual disappearance of left hip pain, and a radiograph revealed that the fracture had healed. Overall, clinical and histological findings suggested an atypical fracture, thereby proving that this type of fracture can occur in areas other than the femoral shaft.

Development and Evaluation of a Web-Based System to Learn Skills for Removing Personal Protective Equipment for Highly Infectious Diseases.

We developed a web-based learning system for healthcare workers to learn the skills for removing personal protective equipment for highly infectious diseases. The system was implemented on a trial basis and healthcare workers evaluated its usability and their motivation to learn. Usability was similar to that of typical systems. Motivation scores were high, indicating confidence and satisfaction with the system.

Transient total blindness associated with alcoholic ketoacidosis.

BACKGROUND: Methanol poisoning is often suspected in patients with high anion gap metabolic acidosis and visual deficits. Although alcoholic ketoacidosis can cause high anion gap metabolic acidosis, reports on vision loss are limited. We report the case of a patient with alcoholic ketoacidosis with transient total blindness. CASE PRESENTATION: A 56-year-old man complaining of total blindness was transferred to our hospital. Physical examination revealed a clear consciousness and mydriasis with an absence of pupillary light reflex. Blood analysis revealed high anion gap metabolic acidosis with a high ketone body concentration. Alcoholic ketoacidosis was diagnosed because the patient had a chronic alcohol abuse history and denied methanol intake. As acidemia improved because of fluid infusion and glucose and vitamin B1 supplementation, his visual acuity recovered. He was discharged after 44 days without visual deficits. CONCLUSION: Patients with alcoholic ketoacidosis may present with acute vision loss, which recovers along with treatment.

[A Case of Unresectable Recurrent Colorectal Cancer with Regorafenib Treatment and Long-Term Survival].

This paper reports a case in which the patient has survived for 5 years and 6 months after recurrence of colorectal cancer by chemotherapy, and especially in regorafenib as fourth-line therapy has obtained stable disease(SD)for 2 years and 6 months. A man in his 70s underwent left hemicolectomy in the diagnosis of descending colon cancer. Four years and 4 months after the operation, abdominal CT revealed paraaortic lymph node metastasis. When SOX plus bevacizumab was performed as first-line therapy, partial response(PR)was obtained, and PR was maintained for a long time. After progressive disease(PD), IRIS was performed as second-line therapy, but the effect was not obtained. Panitumumab was started as third-line therapy, and PR was temporarily recognized, but since it became PD again, regorafenib was introduced as fourth- line therapy. After regorafenib administration, reduction of paraaortic lymph nodes and lowering of CEA are recognized, and long SD can be maintained. This case can be said to be 1 case in which the usefulness of regorafenib was shown as a salvage- line for unresectable colorectal cancer.

Analysis of the reciprocal changes in upper cervical profile and the risk factors for increasing cervical sagittal vertical axis after laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine.

OBJECTIVE: The purpose of this study was to elucidate the reciprocal changes in the upper cervical profile and the risk factors for increasing cervical sagittal vertical axis (cSVA) after laminoplasty for ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. PATIENTS AND METHODS: This retrospective study included thirty-nine consecutive patients (30 men and 9 women) with cervical OPLL who underwent cervical laminoplasty. We recorded the operative time, blood loss, Japanese Orthopaedic Association (JOA) score recovery rate. Radiological measurements were performed to analyze the following parameters: pre and 1- year postoperative chin-brow vertical angle (CBVA), McGregor's slope (McGS), occiput to C2 Cobb angle (O-C2 angle), C2-C7 Cobb angle (C2-C7 angle), T1-slope (T1S), C2-C7 sagittal vertical axis (cSVA) and calculated the change (Δ). Patients were divided into two groups according to ΔcSVA: positive (ΔcSVA ≥ 0) and negative (ΔcSVA < 0). RESULTS: Postoperative O-C2 angle (P = 0.028), ΔO-C2 angle (P = 0.019), ΔC2-C7 angle (P = 0.030) and T1S (P = 0.009) diff ;ered between the two groups. ΔcSVA showed a positive correlation with ΔO-C2 (R = 0.365, P = 0.022) and T1S (R = 0.472, P = 0.002). ΔO-C2 showed a positive correlation with T1S (R = 0.478, P = 0.002) and a negative correlation with ΔC2-C7 (R=-0.443, P = 0.005). ΔC2-C7 showed a negative correlation with T1S (R=-0.415, P = 0.009). Stepwise multiple linear regression analysis showed that ΔcSVA increased by 0.757 mm for each T1 slope and increased by 0.905 mm for each ΔMcGS. CONCLUSION: Increasing the lordosis in the O-C2 segment compensates for the loss of lordosis in the C2-C7 segment after cervical laminoplasty. Higher T1S is a risk factor for increasing cSVA after laminoplasty for OPLL of the cervical spine.

Involvement of Peptide Epimerization in Poly-γ-glutamic Acid Biosynthesis.

Poly-γ-glutamic acid (PGA) is a promising polymer that comprises d- and l-glutamic acid (Glu) connected via an amide bond. PGA is biosynthesized by a transmembrane enzyme complex composed of PgsB, PgsC, and PgsA. However, the detailed reaction, especially the mechanism for introducing d-Glu residues into PGA, remains elusive. We herein report isotope tracer experiments with deuterated l- and d-Glu and demonstrate that epimerization of a growing peptide is involved in PGA biosynthesis.

Characterization of Three Fungal Isomaltases Belonging to Glycoside Hydrolase Family 13 That Do not Show Transglycosylation Activity.

α-1,6-Glucosidase (isomaltase) belongs to glycoside hydrolase (GH) families 13 and 31. Genes encoding 3 isomaltases belonging to GH family 13 were cloned from filamentous fungi, Aspergillus oryzae (agl1), A. niger (agdC),and Fusarium oxysporum (foagl1), and expressed in Escherichia coli. The enzymes hydrolyzed isomaltose and α-glucosides preferentially at a neutral pH, but did not recognize maltose, trehalose, and dextran. The activity of AgdC and Agl1 was inhibited in the presence of 1 % glucose, while Foagl1 was more tolerant to glucose than the other two enzymes were. The three fungal isomaltases did not show transglycosylation when isomaltose was used as the substrate and a similar result was observed for AgdC and Agl1 when p-nitrophenyl-α-glucoside was used as the substrate.

Isolation and Characterization of Two Types of Xyloglucanases from a Phytopathogenic Fungus, Verticillium dahliae.

Xyloglucan is a major hemicellulosic component in plant cell walls. Phytopathogenic fungi secrete cell wall-degrading enzymes on their infection to hosts, while the nature of the cell wall-lytic enzymes of such fungi are yet to be fully understood. Verticillium dahliae is a soil-borne fungus that causes vascular wilt diseases in a variety of commercially important crops worldwide. We purified two types of xyloglucanases, XEG12A and XEG74B, from the culture of naturally isolated Verticillium dahliae strain 2148. XEG12A showed a molecular size of 23 kDa with its maximal activity at pH 7.5. XEG12A specifically hydrolyzed xyloglucan with no activity on other ß-glucans. XEG74B had a molecular size of 110 kDa with its optimum pH at 6.0. XEG74B primarily hydrolyzed xyloglucan, with a slight activity on ß-1,3-1,4-glucan. Analysis of hydrolytic products of xyloglucanooligasaccharide (XXXGXXXG) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that the both enzymes cleaved ß-1,4-glucosidic linkage at the position of unbranched chain, while XEG74B showed a little fluctuation with the cleavage site. Both enzymes did not hydrolyzed xyloglucanoheptasaccharide (XXXG) at all. N-Terminal and internal amino acid sequencing of the enzymes revealed that XEG12A and XEG74B belonged to Glycoside Hydrolase (GH) Families 12 and 74, respectively. Based on these results we concluded that V. dahliae XEG12A and XEG74B were xyloglucan-specific endo-ß-1,4-glucanases (EC 3.2.1.151).

Stimulating angiogenesis mitigates the unloading-induced reduction in osteogenesis in early-stage bone repair in rats.

Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced reduction in early-stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide-based contrast agent. Taking advantage of its absorption discontinuity at the K-absorption edge, vascular and bone images in the drill-hole defects were acquired by synchrotron radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10. The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU10 than in WB10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20-30, 30-40, and >40 µm were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 µm was smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf in the diameter ranges 10-20 and 20-30 µm was larger in DFOHU5 than in HU5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading.

Second generation synthesis of the neo-clerodane diterpenoid methyl barbascoate.

The second generation total synthesis of the neo-clerodane diterpenoid, methyl barbascoate, was accomplished in seven or nine linear steps via double enol triflation and subsequent palladium catalyzed double carbonylation, followed by regioselective samarium diiodide mediated conjugate reduction.