Functional Protein Dynamics in a Crystal.

Proteins are molecular machines and to understand how they work, we need to understand how they move. New pump-probe time-resolved X-ray diffraction methods open up ways to initiate and observe protein motions with atomistic detail in crystals on biologically relevant timescales. However, practical limitations of these experiments demands parallel development of effective molecular dynamics approaches to accelerate progress and extract meaning. Here, we establish robust and accurate methods for simulating dynamics in protein crystals, a nontrivial process requiring careful attention to equilibration, environmental composition, and choice of force fields. With more than seven milliseconds of sampling of a single chain, we identify critical factors controlling agreement between simulation and experiments and show that simulated motions recapitulate ligand-induced conformational changes. This work enables a virtuous cycle between simulation and experiments for visualizing and understanding the basic functional motions of proteins.

Unfermented ß-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation. METHODS: Colonic biopsies cultured ex vivo and cell lines in vitro were incubated with oligofructose (5 g/L), or fermentation supernatants (24-hour anaerobic fermentation) and immune responses (cytokine secretion [enzyme-linked immunosorbent assay/meso scale discovery] and expression [quantitative polymerase chain reaction]) were assessed. Influence of microbiota in mediating host response was examined and taxonomic classification of microbiota was conducted with Kraken2 and metabolic profiling by HUMAnN2, using R software. RESULTS: Unfermented dietary ß-fructan fibers induced proinflammatory cytokines in a subset of IBD intestinal biopsies cultured ex vivo, and immune cells (including peripheral blood mononuclear cells). Results were validated in an adult IBD randomized controlled trial examining ß-fructan supplementation. The proinflammatory response to intact ß-fructan required activation of the NLRP3 and TLR2 pathways. Fermentation of ß-fructans by human gut whole microbiota cultures reduced the proinflammatory response, but only when microbes were collected from patients without IBD or patients with inactive IBD. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance. CONCLUSION: Although fibers are typically beneficial in individuals with normal microbial fermentative potential, some dietary fibers have detrimental effects in select patients with active IBD who lack fermentative microbe activities. The study is publicly accessible at the U.S. National Institutes of Health database (clinicaltrials.gov identification number NCT02865707).

Airway obstruction time and outcomes in patients with foreign body airway obstruction: multicenter observational choking investigation.

Aim: Foreign body airway obstruction (FBAO) is a major public health concern worldwide for infants and older adults. This study determines the association between airway obstruction time and neurological outcomes to plan an effective response for patients with FBAO. Methods: This multicenter retrospective observational study was carried out among patients with life-threatening FBAO in Japan over a period of 4 years. The duration of airway obstruction was calculated from the time of the accident to the time of foreign body removal. The study examined the relationship between airway obstruction time and outcome. The primary outcome was vegetative state or death at hospital discharge. Results: Among 119 patients, 68 were in the category of vegetative state or death. Logistic regression analysis showed that longer airway obstruction time (adjusted odds ratio 1.04; 95% confidence interval 1.01-1.07) was associated with vegetative state or death. When the cut-off value was set at 10, the sensitivity was 0.88, the specificity 0.47, with the area under the curve 0.69. Using the other cut-off value of 4 min, the negative predictive value was 1.00. Conclusion: Longer airway obstruction time was associated with vegetative state or death for patients with FBAO. The incidence of vegetative state or death increased when the airway obstruction time exceeded 10 min. Meanwhile, 4 min or less may be set as a target time for foreign body removal in order to prevent vegetative state or death and plan an effective response.

Hemiballism, a rare complication of coil embilization

Thromboembolism is one of the major complications during coil embolization of an aneurysm, which usually causes familiar neurological deficits, such as, weakness, aphasia, etc. We report a rare complication by thromboembolism after coil embolization causing hemiballism. A 69-year-old female presented with unruptured posterior communicating artery aneurysm and was treated by coil embolization. After the procedure, the patient showed global aphasia and right hemiparesis, and there were small multiple, scattered infarctions on the left middle cerebral artery territory. The neurologic deficit subsided after five days, but hemballism occurred thereafter. There was no other medical history to explain the hemiballism. The patient was treated with clonazepam and antiepileptics and the hemiballism subsided at postoperative day 20. We report a case of rare complication, hemiballism, during coil embolization.

A Case of Migration of Pipeline Embolization Device Causing Rupture during Treatment of an Unruptured Vertebral Artery Dissecting Aneurysm

Endoluminal reconstruction of an intracranial aneurysm using flow-diverting devices, such as the pipeline embolization device (PED), is a new treatment modality with good clinical outcomes. The device was originally indicated for challenging cases, such as wide-necked large or giant aneurysms, and is gaining popularity as a reliable treatment for nearly all intracranial aneurysms. The overall complication rate of flow-diverting devices use is 17.0%, including occlusion of side-branching or perforating arteries, rerupture of the aneurysm, in-stent thrombosis, and, rarely, stent migration. We report a rare complication of the PED: delayed migration of the PED after successful stent implantation during treatment of an unruptured vertebral artery dissecting aneurysm, which resulted in rupture of the aneurysm. Further, we discuss technical steps that can be taken to prevent this potential complication.

Mandibular skeletal posterior anatomic limit for molar distalization in patients with Class III malocclusion with different vertical facial patterns / 대한치과교정학회지

Objective@#The aim of this study was to compare the differences in mandibular posterior anatomic limit (MPAL) distances stratified by vertical patterns in patients with skeletal Class III malocclusion by using cone-beam computed tomography (CBCT). @*Methods@#CBCT images of 48 patients with skeletal Class III malocclusion (mean age, 22.8 ± 3.1 years) categorized according to the vertical patterns (hypodivergent, normodivergent, and hyperdivergent; n = 16 per group) were analyzed. While parallel to the posterior occlusal line, the shortest linear distances from the distal root of the mandibular second molar to the inner cortex of the mandibular body were measured at depths of 4, 6, and 8 mm from the cementoenamel junction. MPAL distances were compared between the three groups, and their correlations were analyzed. @*Results@#The mean ages, sex distribution, asymmetry, and crowding in the three groups showed no significant differences. MPAL distance was significantly longer in male (3.8 ± 2.6 mm) than in female (1.8 ± 1.2 mm) at the 8-mm root level. At all root levels, MPAL distances were significantly different in the hypodivergent and hyperdivergent groups (p < 0.001) and between the normodivergent and hyperdivergent groups (p < 0.01). MPAL distances were the shortest in the hyperdivergent group. The mandibular plane angle highly correlated with MPAL distances at all root levels (p < 0.01). @*Conclusions@#MPAL distances were the shortest in patients with hyperdivergent patterns and showed a decreasing tendency as the mandibular plane angle increased. MPAL distances were significantly shorter (~3.16 mm) at the 8-mm root level.

Developmental Venous Anomaly Presenting Intracranial Hemorrhage without Associated Vascular Anomaly

Developmental venous anomalies (DVAs) are cited as the most common intracranial vascular anomaly. In the majority of cases, it has a benign clinical course, and complications such as intracranial hemorrhage (ICH) are rarely reported. In the rare cases of DVAs presenting ICH, the causes of hemorrhage are usually by a combined vascular anomaly, mostly cavernous malformation (CM) or complicated DVAs, such as thrombosis in the vein of DVAs. We report a rare case of uncomplicated DVA presenting hemorrhage without accompanied vascular anomaly, such as CM. The cause of hemorrhage is suggested to be a specific form of DVA, arterialized DVA. Arterialized DVAs should be noted that they have a greater risk of hemorrhage than classic DVAs.

Mandibular skeletal posterior anatomic limit for molar distalization in patients with Class III malocclusion with different vertical facial patterns / 대한치과교정학회지

Objective@#The aim of this study was to compare the differences in mandibular posterior anatomic limit (MPAL) distances stratified by vertical patterns in patients with skeletal Class III malocclusion by using cone-beam computed tomography (CBCT). @*Methods@#CBCT images of 48 patients with skeletal Class III malocclusion (mean age, 22.8 ± 3.1 years) categorized according to the vertical patterns (hypodivergent, normodivergent, and hyperdivergent; n = 16 per group) were analyzed. While parallel to the posterior occlusal line, the shortest linear distances from the distal root of the mandibular second molar to the inner cortex of the mandibular body were measured at depths of 4, 6, and 8 mm from the cementoenamel junction. MPAL distances were compared between the three groups, and their correlations were analyzed. @*Results@#The mean ages, sex distribution, asymmetry, and crowding in the three groups showed no significant differences. MPAL distance was significantly longer in male (3.8 ± 2.6 mm) than in female (1.8 ± 1.2 mm) at the 8-mm root level. At all root levels, MPAL distances were significantly different in the hypodivergent and hyperdivergent groups (p < 0.001) and between the normodivergent and hyperdivergent groups (p < 0.01). MPAL distances were the shortest in the hyperdivergent group. The mandibular plane angle highly correlated with MPAL distances at all root levels (p < 0.01). @*Conclusions@#MPAL distances were the shortest in patients with hyperdivergent patterns and showed a decreasing tendency as the mandibular plane angle increased. MPAL distances were significantly shorter (~3.16 mm) at the 8-mm root level.

Developmental Venous Anomaly Presenting Intracranial Hemorrhage without Associated Vascular Anomaly

Developmental venous anomalies (DVAs) are cited as the most common intracranial vascular anomaly. In the majority of cases, it has a benign clinical course, and complications such as intracranial hemorrhage (ICH) are rarely reported. In the rare cases of DVAs presenting ICH, the causes of hemorrhage are usually by a combined vascular anomaly, mostly cavernous malformation (CM) or complicated DVAs, such as thrombosis in the vein of DVAs. We report a rare case of uncomplicated DVA presenting hemorrhage without accompanied vascular anomaly, such as CM. The cause of hemorrhage is suggested to be a specific form of DVA, arterialized DVA. Arterialized DVAs should be noted that they have a greater risk of hemorrhage than classic DVAs.

Protocol for a nationwide prospective, observational cohort study of foreign-body airway obstruction in Japan: the MOCHI registry.

INTRODUCTION: Foreign body airway obstruction (FBAO) is a major public health issue worldwide. In 2017, there were more than 5000 fatal choking cases in the USA alone, and it was the fourth leading cause of preventable injury-related death in the home and community. In Japan, FBAO is the leading cause of accidental death and with almost 9000 fatalities annually. However, research on FBAO is limited, particularly on the impact of a foreign body (FB) removal manoeuvres by bystanders. The primary objective of this study is to determine the impact of bystander FB removal manoeuvres on 1 month neurological outcome. Our secondary objectives include (1) evaluating the efficacy of a variety of FB removal manoeuvres; (2) identifying risk factors for unsuccessful removal and (3) evaluating the impact of time intervals from incidents of FBAO to FB removal on neurological outcome. METHODS AND ANALYSIS: We will conduct a nationwide multi-centre prospective cohort study of patients with FBAO who present to approximately 100 emergency departments in both urban and rural areas in Japan. Research personnel at each participating site will collect variables including patient demographics, type of FB and prehospital variables, such as bystander FB removal manoeuvres, medical interventions by prehospital personnel, advanced airway management and diagnostic findings. Our primary outcome is 1 month favourable neurological outcome defined as cerebral performance category 1 or 2. Our secondary outcomes include success of FB removal manoeuvres and complications from the manoeuvres. We hypothesise that bystander FB removal manoeuvres improve patient survival with a favourable neurological outcome. ETHICS AND DISSEMINATION: This study received research ethics approval from Nippon Medical School Hospital (B-2019-019). Research ethics approval will be obtained from all participating sites before entering patients into the registry. The study was registered at the University Hospital Medical Information Network (UMIN) Clinical Trials Registry. TRIAL REGISTRATION NUMBER: UMIN 000039907.

Fixed prosthodontic rehabilitation of maxillary posterior teeth using functionally generated path technique and intraoral digital scan: Case report / 대한치과보철학회지

In order to deliver fixed partial denture to a patient successfully, dentist must take into many considerations beforehand. Patient’s occlusal pattern should be fully understood before delivering any type of prosthesis, whether it’s canine guidance or group function occlusion. In order to do so, movement of mandible should be recorded precisely. Introduced by Meyers in 1933, functionally generated path technique (FGP) has been successfully used to record mandibular movement with various materials, such as wax, and utilize it in fabricating precise prosthesis. In the following cases, patients showed secondary caries or endodontic-periodontic lesion on maxillary molars. Root canal treatment and subgingival curettage were done for each patient. Since the long term prognosis of each tooth was questionable, lateral force should be minimized. In order to do so, FGP technique was used to record mandibular movements precisely. Instead of using conventional plaster impression, intra-oral scanning of wax tracing was done to fabricate prosthesis efficiently. After delivery of fixed partial denture, favorable outcome was obtained.

Transradial Carotid Artery Stenting in a Patient with Leriche Syndrome

We report a case of the transradial approach for carotid artery stenting (CAS) as a useful alternative to the traditional transfemoral approach when femoral access is not available. A 50-year-old male visited our emergency room with dysarthria and right-side weakness. Magnetic resonance imaging showed acute cerebral infarction on the left middle cerebral artery territory and carotid stenosis on both sides. CAS for each carotid stenosis was attempted by the usual femoral access, but there was no pulse on either side of the femoral artery, and computed tomography angiogram of the lower extremity revealed Leriche syndrome, which is an aortoiliac occlusive disease. So, we changed the access to the radial artery and was successfully performed.

Transradial Carotid Artery Stenting in a Patient with Leriche Syndrome

We report a case of the transradial approach for carotid artery stenting (CAS) as a useful alternative to the traditional transfemoral approach when femoral access is not available. A 50-year-old male visited our emergency room with dysarthria and right-side weakness. Magnetic resonance imaging showed acute cerebral infarction on the left middle cerebral artery territory and carotid stenosis on both sides. CAS for each carotid stenosis was attempted by the usual femoral access, but there was no pulse on either side of the femoral artery, and computed tomography angiogram of the lower extremity revealed Leriche syndrome, which is an aortoiliac occlusive disease. So, we changed the access to the radial artery and was successfully performed.

New classifications for Life-threatening foreign body airway obstruction.

INTRODUCTION: Foreign body airway obstruction (FBAO) is a common medical emergency; however, few studies of life-threatening FBAO have been reported and no standard classification system is available. METHODS: We retrospectively evaluated patients who presented to the emergency departments of two hospitals and were diagnosed with FBAO. The primary outcome was cerebral performance category (CPC) score at discharge. To establish a new classification system for FBAO, FBAO was classified into three types based on the anatomical and physiological characteristics of the obstructed airway. RESULTS: A total of 137 patients were enrolled. Median age was 79.0 years. The most common cause of FBAO was meat, followed by bread, rice cake, and rice. Of all patients, 65.7% suffered cardiac arrest and 51.1% died. In contrast, 28.5% had favorable neurological outcomes, defined as CPC 1 and 2. Upper airway obstruction (type 1) was the most common (type 1, 78.1%), while trachea and/or bilateral main bronchus obstruction (type 2, 12.4%) showed significantly higher mortality than type 1 obstruction (82.4% vs 47.7%, P = 0.0078). Patients with unilateral bronchus and/or distal bronchus obstruction (type 3, 9.5%) were significantly more likely to consume a dysphagia diet than type 1 patients (23.1% vs 0%, P < 0.0001). CONCLUSION: The majority of patients with life-threatening FBAO were elderly and had poor neurological outcomes. Our new classification system divides FBAO into three types, and revealed that mortality was significantly higher with type 2 than type 1 obstruction. This classification system may improve the management of patients with FBAO and assessment of patient outcomes.

Functional and esthetic improvement through reconstruction of anterior guidance using the modified Dahl principle and copy-milled technique of CAD/CAM system: A case report / 대한치과보철학회지

The anterior guidance is one of the important factors in prosthodontic treatment of anterior teeth. The lingual surface shape of anterior restorations is so critical that small errors of treatment procedure can cause discomfort of the patient and disharmony of the dentition. If the anterior restorations are achieved harmonious anterior guidance through the fabrication and adjustment of provisional restorations, it is important to accurately reproduce the lingual surface shape of provisional restorations as the final prosthesis. In this case report, it was used the modified Dahl principle and copy-milled technique of computer-aided design/computer-aided manufacturing (CAD/CAM) system for systematic diagnosis and treatment. Therefore, we tried to reconstruct the restoration shape more precisely by setting the appropriate anterior guidance and superimposing the digital image of the abutment teeth and the provisional restorations. Thus, by promoting functional and esthetic recovery, this case report demonstrates satisfying results to both the patients and dentist.

10-Year retrospective study for complaints about medical malpractice in emergency department

OBJECTIVE: Among emergency department patient complaints, complaints related to medical malpractice can often lead to lawsuits. This study examined the reasons for medical malpractice complaints and find ways to improve the medical process and patient satisfaction in an emergency department. METHODS: This study analyzed 269 official complaints of emergency department patients between January 1, 2007, and December 31, 2016. From these complaints, 100 complaints of medical malpractice were analyzed and the complaints of the non-medical process, such as unkindness, cost, facilities and the others, were excluded. The patients' age, sex, relationship between the patient and complainer, insurance state and visiting hour were analyzed. Details of the medical malpractice complaints were assessed and classified into four reasons: diagnosis, examination, treatment, and explanation. This study attempted to analyze the hospital's response to the complaints made during the medical process. RESULTS: Among the 100 medical malpractice complaints, 75 occurred at night duty; 40 were related to treatment, 32 to diagnosis, 22 to examination, and six to explanation. Among the treatment, wound problems were the most frequent reason for 23 cases. The hospital made financial compensation to 16 of its patients. CONCLUSION: The medical malpractice complaints occurred mainly at night. Treatment, especially wound problems, was the most frequent reason for the complaints. The rate of monetary compensation was higher than that of the other studies.

Chronic Treatment with Combined Chemotherapeutic Agents Affects Hippocampal Micromorphometry and Function in Mice, Independently of Neuroinflammation

Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy.

Pharmaceutical Drug Poisoning after Deregulation of Over the Counter Drug Sales: Emergency Department Based In-depth Injury Surveillance

PURPOSE: The Korean government approved selected nonprescription drugs (Over-The-Counter drug; OTC drug) to be distributed in convenience stores from 15. Nov. 2012. This study examined the changes in the incidence and the clinical outcome of acute pharmaceutical drug poisoning after the deregulation of OTC drug sales. METHODS: This study analyzed the data of Emergency Department based Injury In-depth Injury Surveillance (EDIIS), Korea Centers for Disease Control and Prevention, from 2011 to 2014. The following items were examined: age, gender, intention, alcohol association, pharmaceutical drugs resulting acute poisoning, the clinical outcomes in emergency department, and the admission rate of intensive care unit (ICU). This is a retrospective cross section observational study. RESULTS: A total of 10,162 patients were subject to pharmaceutical drug poisoning. Acute poisoning by acetaminophen and other drugs were 1,015 (10.0%) and 9,147 (90.0%) patients, respectively. After the deregulation of OTC drug sales, acute poisoning by other drugs increased from 4,385 to 4,762 patients but acute poisoning by acetaminophen decreased from 538 to 477 patients (p < 0.05). The rate of admission of acetaminophen poisoning increased from 36.1% (194/538) to 46.8% (223/477). The admission rate to the ICU by acetaminophen poisoning increased from 4.6% (25/538) to 11.3% (54/477) after the deregulation of OTC drug sales (p < 0.05). CONCLUSION: Since the deregulation of OTC drugs sales, pharmaceutical drug poisoning has increased but acetaminophen poisoning has decreased. The rate of hospitalization and ICU admission by pharmaceutical drug poisoning with or without acetaminophen has also increased.

High-Set or Low-Set of Korean Face / 체질인류학회지

The face is the most important for individual identification, which showed racial and regional differences. The aim of the present study was to investigate that how much highly locate the facial structures in the face. In total, 551 Korean young adult volunteers with no deformity or surgical history of the face (218 males and 333 females) were selected. Subjects were photographed while sitting and assuming a standard head position, such that the porion and inferior orbital margin were in the same horizontal plane (Frankfurt plane), and they were gazing forward. The total face height was measured vertically from trichion to gnathion. And total face height was divided three heights such as upper, mid, and lower face height. Total face height of male was larger about 6% than female. The ratio of lower face height about upper face height was calculated, it showed 55.7% in male and 50.3 in female. The face was classified into three sets including high-set, mid-set, and low-set according the ratio. The male face showed relatively high-set face, while female face showed relatively low-set face. The present study is the first study to investigate about high- or low-set face, and the result is useful data to identify characteristics of the east Asian population including Korean.