Σάββατο 14 Απριλίου 2018
EMS inventions: Where did they come from?
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MedStar slalom
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MedStar AJody Stevens Banana Microphone
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MedStar: Clearing Intersection, OV does not stop
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EMS inventions: Where did they come from?
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MedStar slalom
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MedStar AJody Stevens Banana Microphone
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MedStar: Clearing Intersection, OV does not stop
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Q&A: Addressing EMS challenges through collaboration at Pinnacle 2018
By EMS1 Staff The Pinnacle EMS Leadership Forum brings together EMS leaders from every service model and every part of the nation for an exploration of the trends and challenges that face our profession. EMS1 is proud to be the premier media partner for this important event. Jay Fitch, PhD, founding partner of Fitch & Associates, which produces Pinnacle, tells us what to expect this year. Paramedic ...
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Inside EMS Podcast: Is 'Alexa' the future of patient care?
Download this podcast on iTunes, SoundCloud or via RSS feed In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss the recording of their 200th episode and reflect on the past four years of co-hosting the show. They also talk about a recent article about Brewster Ambulance Services in Quincy, Ma., installing Amazon Echos in its ambulances to assist their workforce. Learn ...
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Paramedic spends birthday saving life for the second time
By EMS1 Staff PLYMOUTH, Mass. — A paramedic spent her last two birthdays saving the lives of two different patients. FOX25 reported that Brewster Ambulance paramedic Erika Apicella chose to work on her birthday for the past two years, and was able to save two cardiac arrest patients. Last year on her birthday, Apicella and her partner, Chris King, responded to the home of John Sullivan and transported ...
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Texas paramedics honored at recognition ceremony
By Mike Parker Austin American Statesman WILLIAMSON COUNTY, Texas —The Williamson County EMS department held its annual Recognition Ceremony on March 29 to celebrate and honor exemplary service paramedics perform on a daily basis. During the ceremony, the department recognized paramedics that were involved in caring for and resuscitating patients going into cardiac arrest, patients going into ...
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EMS inventions: Where did they come from?
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MedStar slalom
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MedStar AJody Stevens Banana Microphone
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MedStar: Clearing Intersection, OV does not stop
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Crestline welcomes StarTrans Bus to the Crestline family of products
Saskatoon, SK, Canada — Crestline Coach, Canadian distributor of small to mid-sized buses and a global leader in ambulance and specialty vehicle manufacturing, announced the addition of StarTrans Bus to its portfolio of bus solutions and products. StarTrans Bus is a major builder of shuttle buses for both the public and private transportation markets. As a division of Forest River Inc., and being ...
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ESO Expands TrackEMS Capabilities and User Experience
Key enhancements include Health Data Exchange integration, status tracking and customizable patient conditions AUSTIN — ESO Solutions, Inc., the leading data and software company serving emergency medical services (EMS), hospitals and fire departments, today announced significant enhancements to the powerful TrackEMS platform. Key updates include integration into ESO's Health Data Exchange ...
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Video teaches CPR to the tune of ‘500 miles’
Save a Life for Scotland, a campaign by the Scottish government to raise CPR awareness, created the video in an effort to teach 500,000 people CPR
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Mo. county 911 dispatchers to view school cameras in emergencies
Marion County 911 and the Hannibal public school district are teaming up to access any of the security cameras in operation throughout the school district
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First-Trimester Maternal Thyroid Function Is Not Associated with Child Scores on Standardized Educational Tests
Clinical Thyroidology, Volume 30, Issue 4, Page 179-181, April 2018.
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During Active Surveillance of Papillary Thyroid Microcarcinomas Higher Serum TSH Is Associated with Nodule Growth
Clinical Thyroidology, Volume 30, Issue 4, Page 156-158, April 2018.
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Circulating BRAF V600E Levels Correlate with Treatment State in Thyroid Cancer
Clinical Thyroidology, Volume 30, Issue 4, Page 152-155, April 2018.
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Patients with Advanced Papillary Thyroid Cancer Have Fewer Recurrences after Undergoing Surgery by High-Volume Surgeons
Clinical Thyroidology, Volume 30, Issue 4, Page 159-161, April 2018.
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Should the TBG Level Be Included Routinely When Assessing Newborns for Congenital Hypothyroidism?
Clinical Thyroidology, Volume 30, Issue 4, Page 186-189, April 2018.
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Extent of Initial Surgery May Impact Overall Survival, Even for Low-Risk Papillary Thyroid Cancers
Clinical Thyroidology, Volume 30, Issue 4, Page 162-164, April 2018.
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A Patient Survey of Hypothyroid Individuals Demonstrates Dissatisfaction with Treatment and with Managing Physicians
Clinical Thyroidology, Volume 30, Issue 4, Page 175-178, April 2018.
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Protecting Parathyroid Glands During Thyroidectomy — The Challenges Remain
Clinical Thyroidology, Volume 30, Issue 4, Page 165-170, April 2018.
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Stable Isotope Methodology Confirms Body Weight to Be the Main Levothyroxine Dose Adjustment Variable
Clinical Thyroidology, Volume 30, Issue 4, Page 182-185, April 2018.
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Punctate Echogenic Foci with Comet-Tail Artifacts May Be Associated with Malignancy When Occurring in Solid Portions of a Thyroid Nodule
Clinical Thyroidology, Volume 30, Issue 4, Page 171-174, April 2018.
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Exposure to Per- and Polyfluoroalkyl Substances Is Associated with Lower Thyroid Hormone Availability during Pregnancy
Clinical Thyroidology, Volume 30, Issue 4, Page 190-192, April 2018.
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Fecal Calprotectin in Assessing Endoscopic and Histological Remission in Patients with Ulcerative Colitis
Abstract
Background
Persistent active endoscopic and histological inflammation is associated with poorer outcomes in ulcerative colitis (UC). Fecal calprotectin is a surrogate marker of endoscopic and histological remission.
Aims
To confirm the correlation between fecal calprotectin and endoscopic or histological disease activity and to define the optimal cutoff value to detect endoscopic and histological remission.
Methods
From a prospectively maintained database, we analyzed 61 UC patients who had fecal calprotectin measurement and endoscopy performed within 1 month. Endoscopic activity was graded using the Mayo endoscopic subscore (MES). Histological remission was defined as normal histology or quiescent histological activity.
Results
Eighteen patients (29.5%) and five patients (8.1%) had endoscopic remission defined as MES ≤ 1 or MES = 0, respectively. We observed a significantly lower median level of fecal calprotectin in patients with endoscopic remission than those with endoscopic activity for both definition of endoscopic remission, i.e., MES ≤ 1 (158 vs 490 µg/g, p = 0.0005) or MES = 0 (94 vs 414 µg/g, p = 0.013). Seven patients (11.5%) were in histological remission. They had a lower median level of fecal calprotectin than those with active histological inflammation (107 vs 416 µg/g, p = 0.016). Using a ROC curve, fecal calprotectin < 250 µg/g predicted endoscopic remission (MES ≤ 1) with a sensitivity of 67% and specificity of 77%, while fecal calprotectin < 200 µg/g predicted histological remission with a sensitivity of 71% and specificity of 76%.
Conclusion
Fecal calprotectin level correlated with both endoscopic activity and histological activity and is a reliable biomarker in assessing mucosal healing in UC.
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Adenoma Detection Rate in Asymptomatic Patients with Positive Fecal Immunochemical Tests
Abstract
Background and Aims
The adenoma detection rate (ADR) is a powerful measure of screening colonoscopy quality. Patients who undergo colonoscopy for the evaluation of a positive fecal immunochemical test (FIT) have increased prevalence of colorectal neoplasia, but it is not known whether separate quality benchmarks are required. The aim of this study was to compare the conventional ADR to the ADR of colonoscopies performed for the evaluation of positive FIT, in asymptomatic average-risk patients.
Methods
Patients ≥ 50 years old who underwent colonoscopy for the evaluation of a positive FIT between January 1, 2013, and July 31, 2014, at a tertiary Veterans Affairs Medical Center were identified. FIT performed for any indication other than average-risk screening was excluded. The comparison group included average-risk patients ≥ 50 years old undergoing screening colonoscopy during the same time frame. The two groups were compared for ADR, advanced neoplasm [adenoma ≥ 10 mm, tubulovillous, high-grade dysplasia, CRC, sessile serrated polyp (SSP) ≥ 10 mm], CRC, and SSP detection after propensity score adjustment using a logistic regression model adjusted for endoscopist.
Results
There were 207 patients in the FIT group and 601 in the screening colonoscopy comparison group. After propensity score adjustment, ADR (72.9 vs. 50.0%, p = 0.003), number of adenomas per colonoscopy (3.3 ± 3.6 vs. 1.4 ± 2.3, p = 0.033), and advanced neoplasm detection rate (32.4 vs. 11.0%, p < 0.0001) were significantly higher in the FIT group. There were no significant differences in the number of CRC and the SSP detection rate.
Conclusions
In this cohort of average-risk Veterans, the ADR of colonoscopies performed for the evaluation of a positive FIT was higher than the ADR of screening colonoscopies. Patients with a positive FIT also had significantly more adenomas per colonoscopy and advanced neoplasms. These findings suggest that the quality of colonoscopies performed for a positive FIT is insufficiently assessed by the conventional ADR and requires additional quality metrics.
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Severe Intestinal Inflammation in the Small Intestine of Mice Induced by Controllable Deletion of Claudin-7
Abstract
Background
As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development.
Aims
To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen.
Methods
We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis.
Results
After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin–eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened.
Conclusions
We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice.
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Co-expression Network Analysis Identified COL8A1 Is Associated with the Progression and Prognosis in Human Colon Adenocarcinoma
Abstract
Backgrounds and Aims
Human colon adenocarcinoma is one of the major causes of tumor-induced death worldwide. A complicated gene interconnection network significantly regulates its progression and prognosis. The aim of our study was to find hub genes associated with the progression and prognosis of colon adenocarcinoma and to illustrate the underlying mechanisms.
Methods
A weighted gene co-expression network analysis was performed in our study to identify significant gene modules and hub genes associated with the TNM stage of colon adenocarcinoma (n = 441).
Results
In the turquoise module of interest, 23 hub genes were initially selected, and 10 of them were identified as "real" hub genes with high connectivity in the protein–protein interaction network. In the terms of validation, COL8A1 had the highest correlation with clinical traits among all of the hub genes. Data obtained from the Oncomine and GEPIA databases showed a higher expression of COL8A1 in colon adenocarcinoma tissues compared with normal colon tissues. Kaplan–Meier survival curves showed that higher expression of COL8A1 resulted in a shorter overall survival time and disease-free survival time. Univariate and multivariate Cox proportional hazards analyses indicated that the COL8A1 expression was an independent prognostic factor for survival in colon adenocarcinoma patients. Finally, gene set enrichment analysis indicated that the gene sets associated with focal adhesion were significantly enriched in colon adenocarcinoma samples with COL8A1 highly expressed.
Conclusions
COL8A1 was identified and proved to be correlated with the progression and prognosis of human colon adenocarcinoma, probably through regulating focal adhesion-related pathways.
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Genetic and Structural Analysis of a SKIV2L Mutation Causing Tricho-hepato-enteric Syndrome
Abstract
Background
Advances in genomics have facilitated the discovery of monogenic disorders in patients with unique gastro-intestinal phenotypes. Syndromic diarrhea, also called tricho-hepato-enteric (THE) syndrome, results from deleterious mutations in SKIV2L or TTC37 genes. The main features of this disorder are intractable diarrhea, abnormal hair, facial dysmorphism, immunodeficiency and liver disease.
Aim
To report on a patient with THE syndrome and present the genetic analysis that facilitated diagnosis.
Methods
Whole-exome sequencing (WES) was performed in a 4-month-old female with history of congenital diarrhea and severe failure to thrive but without hair anomalies or dysmorphism. Since the parents were first-degree cousins, the analysis focused on an autosomal recessive model. Sanger sequencing was used to validate suspected variants. Mutated protein structure was modeled to assess the effect of the mutation on protein function.
Results
We identified an autosomal recessive C.1891G > A missense mutation (NM_006929) in SKIV2L gene that was previously described only in a compound heterozygous state as causing THE syndrome. The mutation was determined to be deleterious in multiple prediction models. Protein modeling suggested that the mutation has the potential to cause structural destabilization of SKIV2L, either through conformational changes, interference with the protein's packing, or changes at the protein's interface.
Conclusions
THE syndrome can present with a broad range of clinical features in the neonatal period. WES is an important diagnostic tool in patients with congenital diarrhea and can facilitate diagnosis of various diseases presenting with atypical features.
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Mortality from Spontaneous Bacterial Peritonitis Among Hospitalized Patients in the USA
Abstract
Background and Aim
Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis and is associated with significant morbidity and mortality. In this study, we examined the clinical characteristics and risk factors associated with mortality in hospitalized patients presenting with SBP.
Methods
The Nationwide Inpatient Sample was queried for all hospitalizations involving SBP from 2006 to 2014 using the International Classification of Disease-9-CM Code. Logistic regression was performed to evaluate the association between SBP mortality and factors such as age, gender, race/ethnicity, and concomitant medical conditions at presentation (e.g., variceal hemorrhage, hepatic encephalopathy, acute renal failure, coagulopathy, and other infections including pneumonia). The lengths of stay (LOS) and total charges were also examined.
Results
From 2006 to 2014, there were 88,167 SBP hospitalizations with 29,963 deaths (17.6% in-hospital mortality). The mean age of patients who died in the hospital was higher (58.2 years vs. 55.8, p < 0.01) than those who survived the admission. Acute alcoholic hepatitis was noted among a higher proportion of patients who died (7.0 vs. 5.9%, p < 0.01), who were also likely to have more medical comorbidities. In multivariable analysis, older age, female gender, hepatic encephalopathy, coagulopathy, variceal hemorrhage, sepsis, pneumonia, and acute kidney injury were associated with increased in-hospital mortality. This group also had longer LOS (11.6 days vs. 9.1, p < 0.01) and higher total charges ($138,273 vs. $73,533, p < 0.01).
Conclusion
SBP is associated with significant in-hospital mortality, especially in patients with concurrent risk factors. SBP remains a significant burden to the healthcare system.
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Early gastric cancer with lymphoid stroma presenting as a subepithelial lesion diagnosed by endoscopic submucosal dissection
Abstract
A 53-year-old man underwent an esophagogastroduodenoscopy that showed a 20-mm subepithelial lesion in the middle gastric body. Endoscopic ultrasound revealed a hypoechoic mass located in the submucosa. Biopsy specimens revealed a benign gastric mucosa with severe lymphocytic infiltration in the submucosa. Malignant lymphoma or gastric cancer with lymphoid stroma was suspected. We performed endoscopic submucosal dissection for definitive diagnosis. Histological examination showed undifferentiated adenocarcinoma, which showed positive Epstein–Barr virus-encoded RNA in situ hybridization results, invading the submucosa mixed with dense lymphocytic infiltration. Thus, Epstein–Barr virus-positive gastric cancer with lymphoid stroma was diagnosed. Gastric cancer with lymphoid stroma is a rare subtype of gastric cancer, which is associated with Epstein–Barr virus infection; it sometimes appears as a subepithelial lesion, which makes it difficult to diagnose using standard biopsy. Endoscopic submucosal dissection was useful in obtaining a sufficient tissue for full histological assessment, including immunostaining.
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Contrast-enhanced intraoperative ultrasound in the resection of colorectal liver metastases with intrabiliary growth
Abstract
A 68-year-old male who had undergone low anterior resection for primary rectal cancer 19 months ago presented with multiple CLM at Couinaud's segments IV, V, and VIII. There was no apparent macroscopic intrabiliary growth on preoperative computed tomography and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). However, the hepatobiliary phase of EOB-MRI revealed peritumoral low signal intensity in lesions in segments V and VIII, which indicates vascular invasion around hepatocellular carcinoma. Contrast-enhanced intraoperative ultrasound (CE-IOUS) clearly determined the extent of macroscopic glissonean growth from lesions in segments V and VIII, and more extensive resection was performed than was planned. Analysis of the resected specimens from segments V and VIII confirmed the presence of macroscopic intrabiliary growth with microscopic portal vein invasion. All three CLM were histopathologically diagnosed as well-to-moderately differentiated adenocarcinoma, and R0 resection was verified. Postoperative recovery was uneventful, and the patient was alive without evidence of recurrence 12 months after hepatic resection. CE-IOUS should be considered at the time of CLM resection, as it might enable more accurate detection of macroscopic intrabiliary growth of CLM, and enable resection with safer margins.
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Intestinal Microbiota in Hirschsprung Disease
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Anorectal Manometry May Reduce the Number of Rectal Suction Biopsy Procedures Needed to Diagnose Hirschsprung's Disease
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Birth Month as a Risk Factor for the Diagnosis of Celiac Disease Later in Life: A Population-based Study
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Pediatric Liver Transplant Teams’ Coping with Patient Death
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Pulmonary Function Test Abnormalities in Children With Inflammatory Bowel Disease: Is It Common?
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Celiac Disease 30 Years after Diagnosis: Struggling With Gluten-free Adherence or Gaining Gluten Tolerance?
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Early Serum Gut Hormone Concentrations Associated with Time to Full Enteral Feedings in Preterm Infants
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Therapeutic Plasma-Albumin Exchange for Hyperlipidemia Induced Acute Pancreatitis
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Small-Fiber Neuropathy in a Pediatric Patient Following Anti-TNF-α Therapy for Ulcerative Colitis
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A Rare Case of Gallbladder and Common Bile Duct Benign Capillary Hemangioma in a Toddler
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Autoimmune anti-N-methyl-D-aspartate receptor encephalitis — the current state of knowledge based on a clinical case
The aim of this article is to conduct an overview of the current state of knowledge about patients presenting anti-Nmethyl- D-aspartate receptor encephalitis associated with neoplastic process, as well as diagnosis and treatment. This disease concerns mainly young women and correlates with ovarian teratoma. Most important problems seems to be the difficulties in making a proper diagnosis ensuing from the rarity of this syndrome, the period from the appearance the first symptoms to starting treatment and the correct handling of intensive care complications. There are only a few articles describing severe, complicated cases of this type of encephalitis, requiring treatment in an intensive care unit.
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Day and time of admissions to intensive care units — does it matter?
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The impact of the blood glucose levels of non-diabetic critically ill patients on their clinical outcome
Background: Stress hyperglycaemia is thought to result from a hormonal response (release of catecholamines,
glucocorticoids, glucagon, etc.) following stress, sepsis or trauma. Although stress hyperglycaemia is a very common
finding in critically ill populations, there are many non-diabetic critically ill patients who do not develop a hyperglycaemic
stress response to trauma or acute illness. We suggest that the lack of a hyperglycaemic stress response
during the acute phase of a critical illness may correlate significantly with the clinical outcome of these critically ill
non-diabetic patients.
Methods: This was a retrospective study of 700 non-diabetic critically ill patients admitted to the general intensive
care unit (ICU) at Soroka Medical Center, Beer Sheva, Israel. We analyzed the clinical impact of the blood glucose levels
of these patients measured during their first week of ICU hospitalization on their clinical outcome.
Results: Age, male gender, and the Acute Physiology and Chronic Health Evaluation (APACHE) score were found to
be independent risk factors for new episodes of infection during the patients' stay in the ICU. Age and the APACHE
and Sequential Organ Failure Assessment scores were found to be independent risk factors for intra-ICU mortality. In
contrast, blood glucose analysis performed during the patients' stay in the ICU was not found to be an independent
predictor for new infectious events or for mortality during the ICU stay.
Conclusion: Our study did not demonstrate an association between blood glucose levels and clinical outcomes in
non-diabetic critically ill patients.
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Impact of anaemia on outcome in burn patients
Background: Currently, most critical care physicians maintain a patient's haemoglobin levels at 7 to 8 g dL-1. However,
little data have been available on haemoglobin-related outcomes in burn patients. The purpose of this study was
to evaluate inpatients with greater than 20% total body surface area burns and the effects of haemoglobin below
8 g dL-1 on clinical outcomes.
Methods: This study included 70 patients with burns amounting to greater than 20% of total body surface area. Data
were retrospectively evaluated and included age, gender, adult respiratory distress syndrome presence, length of
intensive care unit stay, length of mechanical ventilation, days requiring vasopressors, renal insufficiency, positive
cultures/infections, cardiovascular complications, number of operations, inhalation injury, and mortality. Logistic
regression analyses that were adjusted for age, sex, and percent total body surface area were used to assess the
relationships between haemoglobin and multiple clinical outcomes. Odds ratios (OR) were estimated with 99%
confidence intervals (99% CI).
Results: Haemoglobin below 8 g dL-1 was associated with a need for vasopressors (OR = 2.17; 99% CI = 1.03–8.22).
Furthermore, haemoglobin below 8 g dL-1 was associated with higher positive wound (OR = 2.86; 99% CI = 1.00–34.40),
urine (OR = 4.63; 99% CI = 1.15–67.00), and lung cultures (OR = 2.24; 99% CI = 1.06–5.47). These associations largely
remained after controlling for blood transfusions.
Conclusions: Contrary to most other patient groups, burn patients with burns amounting to greater than 20% of
total body surface area and low haemoglobin levels were more likely to develop positive cultures in urine, wounds,
and the lung and require vasopressor treatment.
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Gasping for a Diagnosis: Pediatric Vocal Cord Dysfunction
Vocal cord dysfunction is an obstruction of the upper airway, primarily on inspiration, due to the paradoxical adduction of the vocal cords. Vocal cord dysfunction continues to be underdiagnosed as its own entity. The lack of diagnosis can be attributed to the overlap of symptoms between asthma and exercise-induced bronchospasm. It is possible for patients diagnosed with asthma and/or exercise-induced bronchospasm to have underlying vocal cord dysfunction, which needs to be considered when prescribing asthma medications.
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Caring for Military Children: Implications for Nurse Practitioners
Nearly two million American children belong to a military family. Armed Forces families are located in almost every state and around the globe. Military children are a unique and at times vulnerable population. Military children and adolescents may face significant stressors throughout their lives compared to their civilian counterparts. Military families encounter frequent moves and over half of these children have encountered at least one parental deployment since September 11th, 2001. Civilian health care providers often care for military children and adolescents.
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Feasibility of Providing Pediatric Neurology Telemedicine Care to Youth with Headache
Telemedicine has been described as use of electronic communication between two sites to deliver medical information to improve a patient's clinical health status (American Telemedicine Association, 2010). It has been widely used since the 1990s in remote areas such as Alaska and the upper reaches of Canada in addition to other rural parts of the United States (Gifford, Niles, Rivkin, Koverola, & Polaha, 2012). The American Academy of Pediatrics (2015) has supported telemedicine as a way to deliver both primary care and certain specialty areas with provider shortages.
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Clinical impact of intratumoral HER2 heterogeneity on trastuzumab efficacy in patients with HER2-positive gastric cancer
Abstract
Background
There is growing interest in the clinical significance of intratumoral HER2 heterogeneity. Its prognostic and predictive impacts on trastuzumab efficacy were demonstrated in breast cancer. However, its clinical significance in gastric cancer is still unclear.
Methods
Twenty-eight HER2-positive gastric cancer patients who had gastrectomy prior to trastuzumab-based chemotherapy were consecutively enrolled. Intratumoral HER heterogeneity was evaluated using whole-tissue sections by immunohistochemistry. When all tumor cells overexpressed HER2 protein, the tumor was defined as homogeneously HER2 (Homo-HER2)-positive group. The others were defined as heterogeneously HER2 (Hetero-HER2)-positive group.
Results
There was no significant difference in clinicopathological features between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the Homo-HER2-positive group were significantly longer than those in the Hetero-HER2-positive group (PFS; 20.0 months [95% CI 17.8–22.2] vs. 6.0 months [95% CI 2.3–9.7]; HR 0.11; 95% CI 0.03–0.41; p < 0.001, OS; not reached vs. 14.0 months [95% CI 11.9–16.1]; HR 0.18; 95% CI 0.06–0.61; p = 0.003). In the multivariate analysis, these associations remained significant both in PFS (HR 0.12; 95% CI 0.03–0.46, p = 0.002) and OS (HR 0.21; 95% CI 0.06–0.72, p = 0.013). With respect to response rate, no statistical difference was found between two groups. However, deeper tumor shrinkage was obtained in the Homo-HER2-positive group compared with the Hetero-HER2-positive group (p = 0.046).
Conclusions
Intratumoral HER2 heterogeneity may have robust clinical impact on trastuzumab efficacy in patients with HER2-positive gastric cancer. These findings should be validated by larger independent cohorts and further molecular correlative analyses are warranted.
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Real-world efficacy and safety of ledipasvir and sofosbuvir in patients with hepatitis C virus genotype 1 infection: a nationwide multicenter study by the Japanese Red Cross Liver Study Group
Abstract
Background
We aimed to describe the real-world efficacy and safety of combination therapy with ledipasvir and sofosbuvir (LDV/SOF) for chronic hepatitis C virus (HCV) genotype 1 (GT1) infection.
Methods
This retrospective analysis of a prospective, nationwide, multicenter registry included GT1-infected patients treated with LDV/SOF for 12 weeks. We assessed the rate of sustained virological response at 12 weeks post-treatment (SVR12), incidence of adverse events, and serum markers of hepatocellular carcinoma (HCC).
Results
Among the 1461 patients included (mean age, 69 years; 29.5% aged > 75 years; cirrhosis, 23.8%; history of treatment for HCC, 10.9%), the overall SVR12 rate was 98.4% (1438/1461). Factors associated with treatment failure were cirrhosis (odds ratio, 4.19; p = 0.014) and resistance-associated substitutions (RASs) in NS5A at baseline (odds ratio, 7.78; p = 0.0004). The SVR12 rate in patients with cirrhosis and NS5A RASs was 93.0% compared to 100% in patients without cirrhosis or NS5A RASs. In patients with SVR, the levels of alpha-fetoprotein (AFP), AFP-L3, and Mac-2 binding protein glycosylation isomer (M2BPGi) decreased from baseline to end of treatment (from 13.4 ± 37.6 to 6.0 ± 10.6 ng/mL, p < 0.0001; from 2.2 ± 4.9 to 1.5 ± 6.3%, p < 0.005; and from 3.6 ± 3.7 to 2.0 ± 3.5 cut-off index, p < 0.0001; respectively). Adverse events were rare and not associated with age. No decrease in estimated glomerular filtration rate was observed in patients with baseline chronic kidney disease stage 3.
Conclusions
LDV/SOF therapy is highly effective and safe in elderly Japanese patients with HCV GT1, even in the presence of cirrhosis or NS5A RASs. Patients with SVR may have a lower risk of HCC.
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Reply to “Letter to Editor submitted by Rui Huang et al. entitled potential clinical application of strain elastography in chronic liver diseases”
A proposed treatment algorithm for mild to moderate ulcerative colitis—with an emphasis on budesonide foam and mucosal healing
Reply to the letter to the editor: Lymph node metastasis of adenocarcinoma and different definitions of sm1 cancer in the esophagus
Applications of Colon Capsule Endoscopy
Abstract
Purpose of Review
This is a review of colon capsule endoscopy (CCE) with a focus on its recent developments, technological improvements, and current and potential future indications.
Recent Findings
Based on the current literature, CCE II demonstrates comparable polyp detection rates as optical colonoscopy and CT colonography, and improved cost-effectiveness. The main limitation to patient acceptance is the requirement of a rigorous bowel preparation. Preliminary studies show good correlation between CCE and optical colonoscopy for assessment of colonic disease activity in inflammatory bowel disease (IBD).
Summary
CCE II is currently FDA, approved as an adjunctive test in patients with prior incomplete colonoscopy, and in the evaluation of patients with suspected lower gastrointestinal bleeding. The test is approved in Europe as one of the options for average-risk colorectal cancer screening, and high-risk screening in patients with contraindications or unwilling to undergo colonoscopy. CCE has a potential role in the evaluation and monitoring of colonic disease activity in IBD. Future technological advances should focus on minimizing bowel preparation, improvement in reading times, and development of therapeutic capabilities.
• With technological improvements, the second-generation colon capsule has a significantly higher sensitivity than the first-generation capsule for detection of colon polyps.
• Colon capsule endoscopy has been approved in Europe as an option for average-risk colorectal cancer screening, and high-risk screening in patients with contraindications or unwilling to undergo colonoscopy.
• Colon capsule endoscopy has received FDA approval as an option for colorectal cancer screening in patients with prior incomplete colonoscopy, and in evaluation of patients with suspected lower gastrointestinal bleeding.
• Colon capsule endoscopy may have a role in evaluation and monitoring of inflammatory bowel disease.
• Colon capsule endoscopy currently requires a bowel preparation that is more rigorous than colonoscopy.
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Update on the Therapeutic Management of Hepatic Encephalopathy
Abstract
Purpose of Review
Hepatic encephalopathy (HE) is a common and devastating complication to chronic liver disease. In this paper, we summarize the latest research and evidence of both conventional and up-coming treatments.
Recent Findings
Meta-analyses report beneficial effects of lactulose, branched-chain amino acids, rifaximin, and to some degree l-ornithine l-aspartate on the manifestations of HE in patients with cirrhosis, and generally the numbers needed to treat are low. Recent studies on newer HE treatments including ornithine phenylacetate, spherical carbon, and fecal microbiota transplant also report potentially beneficial effects on HE manifestations.
Summary
The conventional treatments benefit patients with HE. Newer treatments are under study and more research is needed for their validation.
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Considerations When Treating Hepatitis C in a Cirrhotic Transplant Candidate
Abstract
Purpose of Review
This review examines the issues in determining the decision to treat a HCV-positive patient who is a liver transplant (LT) candidate with highly effective and well-tolerated direct-acting antiviral (DAA) therapies.
Recent Findings
Cure of HCV with DAA can improve liver function and allow delisting in some patients. Beyond a threshold of hepatic impairment (likely MELD score > 16 to 20), patients may experience a decline in MELD score with HCV cure without improvement in liver-related complications resulting in decreased opportunity to receive a LT. Eradicating HCV from patients who need LT regardless also deprives them of the option of receiving HCV-positive donor organs. Patients with MELD > 16 or Child-Pugh B/C may also have reduced cure rates of HCV, increased risk of hepatic decompensation, and adverse events with DAA pre-LT compared to post-LT DAA therapy. Preliminary data demonstrates increase risk of hepatocellular carcinoma (HCC) recurrence after treatment with DAA with subsequent studies raising doubts about this association.
Summary
Patients with HCV cirrhosis on the LT waiting list with MELD score > 16, CTP-B/C, and HCC are best treated after LT with better response, tolerability, and the ability to receive organs from a larger donor pool that includes HCV-positive donors. Larger, prospective studies are needed to assess whether increased HCC recurrence after DAA is a true effect.
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Therapy for Crohn’s Disease: a Review of Recent Developments
Abstract
Purpose of Review
To review recent advances in the treatment of Crohn's disease.
Recent Findings
Several key advances are highlighted, including the increasing role of treatment algorithms and where new therapies can be used most effectively, the appropriate use of therapeutic drug monitoring, optimal management of post-surgical patients, and the role of multi-disciplinary clinics.
Summary
The last several years have seen a number of exciting developments in the field of Crohn's therapy. This review covers research advances including updated treatment algorithms focusing on identifying patient risk as well as the role of drug monitoring in managing the disease. We also review the optimal management of post-surgical patients as well as new biologics and biosimilars. Finally, we describe innovations in care delivery including multi-disciplinary clinics and emerging evidence from developing therapeutics.
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Food Allergy
Abstract
Purpose of Review
The goal of this review is to present an updated summary of the natural history of major childhood and adult food allergies and report recent advances in potential treatments for food allergy.
Recent Findings
The most common childhood food allergies are typically outgrown by adolescence or adulthood. However, peanut/tree nut allergies appear to more commonly persist into adulthood. Adults can develop new IgE-mediated food allergies; the most common is oral allergy syndrome. There are multiple different approaches being tried as possible treatments for food allergy.
Summary
The prevalence of food allergy appears to be increasing but the varied approaches to treatment are being actively pursued such that an approved modality may not be too far in the future.
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Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease
Abstract
Purpose of review
Therapeutic drug monitoring (TDM) has emerged as a useful tool to optimize the use of drug therapies in adults with inflammatory bowel disease (IBD), including both Crohn's disease (CD) and ulcerative colitis (UC), especially during the use of biological therapies, for which the pharmacokinetics and pharmacodynamics are highly variable among patients. Fewer data exist in children. This review examines the current literature on TDM in pediatric IBD.
Recent findings
Drug clearance is affected by a number of patient and disease factors. For thiopurines, adjusting dosing by monitoring 6-thioguanine (6TGN) and 6-methylmercaptopurine ((6MMP) levels is demonstrated to maximize response and minimize toxicity, while monitoring metabolite levels when treating with anti-tumor necrosis factor (anti-TNF) remain controversial. While in adults the use of TDM in the setting of loss of response to anti-TNF therapy is established, in children, only a small number of studies exist, but these too have encouraging results. There are however, conflicting data regarding the optimal timing of TDM, comparing "reactive" monitoring and "proactive" monitoring. No such data exist in pediatrics. TDM is cost-effective, and dose reduction may represent a safety benefit. There are limited adult data for use of TDM for the newer biologics, vedolizumab and ustekinumab, but early results suggest similarly promising utility.
Summary
The use of TDM in pediatric IBD is increasing in clinical practice, with similar efficacy to adults demonstrated in children with loss of response to anti-TNF therapy. More prospective studies are needed in children to examine proactive monitoring and utility of TDM with newer biologics.
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Colorectal Cancer in the Young
Abstract
Purpose of Review
Colorectal cancer incidence has been rapidly rising in those under the age of 50 over the last 20 years. This paper will review the epidemiology, clinicopathologic, molecular features, proposed risk factors, and prevention/treatment approach for early onset CRC (EOCRC) patients.
Recent Findings
EOCRC appears to have a different spectrum of clinical, pathologic, and molecular presentation compared to CRC diagnosed in older individuals. EOCRCs are disproportionately located in the distal colon; these patients tend to present with symptoms, and there is a longer interval between symptoms and diagnosis. There may be a distinct molecular signature, including progression through the microsatellite and chromosomal stable (MACS) pathway and LINE-1 hypomethylation for a subset of EOCRCs. The majority of EOCRCs are sporadic without clear risk factors that would have made the patient eligible for earlier screening.
Summary
There is an acute need for educational efforts aimed at both providers and patients to raise awareness about CRC in the young. Improving adherence to screening in young patients eligible for screening and emphasizing early evaluation of symptoms are important steps to decreasing the burden of CRC in younger patients. Modeling and empiric data are needed to determine whether our current screening approach should be modified and whether causation and treatment options may be different in a molecular subset EOCRCs.
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The Value and Significance of 25(OH) and 1,25(OH) vitamin D serum levels in adult coeliac patients: A review of the literature
Within the wide spectrum of symptoms and alteration of systems that characterizes CeD, several studies indicate a low-level of vitamin D, therefore recent guidelines suggest its evaluation at the time of diagnosis. This review examines the data from existing studies in which vitamin D has been assessed in CeD patients. Our review indicates that most of the studies on vitamin D in adult CeD report a 25 (OH) vitamin D deficiency at diagnosis that disappears when the patient goes on a gluten-free diet, independently of any supplementation.
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Entecavir Or Tenofovir Monotherapy Prevents HBV Recurrence In Liver Transplant Recipients: A 5-Year Follow-Up Study After Hepatitis B Immunoglobulin Withdrawal
Recent data suggest that oral third-generation nucleos(t)ide analogs (NA) monoprophylaxis following hepatitis B immunoglobulin (HBIg) withdrawal may be effective to prevent HBV reinfection after liver transplantation (LT).
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THE EPIDEMIOLOGY OF BUDD-CHIARI SYNDROME IN FRANCE
Epidemiological data is lacking on primary Budd-Chiari syndrome (BCS) in France.
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Acomparison study between Magniview high definition white light endoscopy in detecting villous atrophy coeliac disease: A single centre pilot study
Coeliac disease may be missed at gastroscopy. We aimed to assess the sensitivity of Pentax optical zoom technology endoscopes in detecting duodenal villous atrophy and the ease of image interpretation by non-coeliac specialists.
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Laparoscopic right hemicolectomy for a colon cancer patient with an ileal conduit
Asian Journal of Endoscopic Surgery, EarlyView.
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Outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis performed at a single institution
Asian Journal of Endoscopic Surgery, EarlyView.
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Older E-bike Users: Demographic, Health, Mobility Characteristics, and Cycling Levels
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Bone and Inflammatory Responses to Training in Female Rowers over an Olympic Year
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Temporal Changes in Cardiovascular Remodeling Associated with Football Participation
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Is Exercise the Right Medicine for Dystrophic Muscle?
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Effects of Neuromuscular Electrical Stimulation in People with Spinal Cord Injury
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The Role of Task Difficulty in Learning a Visuomotor Skill
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Benefits of 8-Week MBSR or Aerobic Training on Seasonal Declines in Physical Activity
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Black Carbon Reduces the Beneficial Effect of Physical Activity on Lung Function
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Role of fungal laccase in iodide oxidation in soils
Source:Journal of Environmental Radioactivity, Volume 189
Author(s): Reiko Nihei, Mizuki Usami, Taro Taguchi, Seigo Amachi
Previously, we hypothesized that microbial laccase oxidizes iodide (I−) in soils to molecular iodine (I2) or hypoiodous acid (HIO), both of which are easily incorporated into natural soil organic matter, and thus plays a role in iodine sorption on soils. In this study, soil iodide oxidase activity was determined by a colorimetric assay to evaluate if laccase is responsible for iodide oxidation in soils. Three types of Japanese soil showed significant iodide oxidase activities (0.751–2.87 mU g soil−1) at pH 4.0, which decreased with increasing pH, until it was no longer detected at pH 5.5. The activity was inhibited strongly by autoclaving or by the addition of common laccase inhibitors. Similar tendency of inhibition was observed in soil laccase activity, which was determined with 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a substrate. Significant positive correlations (R2 values of 0.855–0.896) between iodide oxidase activity and laccase activity were observed in two of three soils. Commercially available fungal laccases showed only very low iodide oxidase activities (4.68–18.0 mU mg−1), but enhanced activities of 102–739 mU mg−1 were observed in the presence of redox mediators. Finally, we successfully isolated fungal strains with iodide-oxidizing phenotype in the presence of redox mediators. Polyacrylamide gel electrophoresis of the culture supernatant of Scytalidium sp. strain UMS and subsequent active stain revealed that the fungal laccase actually oxidized iodide in the presence of redox mediators. These results suggest that at least part of iodide in soils is oxidized by fungal laccase through the laccase-mediator system.
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Radiocesium interaction with clay minerals: Theory and simulation advances Post–Fukushima
Publication date: September 2018
Source:Journal of Environmental Radioactivity, Volume 189
Author(s): Masahiko Okumura, Sebastien Kerisit, Ian C. Bourg, Laura N. Lammers, Takashi Ikeda, Michel Sassi, Kevin M. Rosso, Masahiko Machida
Insights at the microscopic level of the process of radiocesium adsorption and interaction with clay mineral particles have improved substantially over the past several years, triggered by pressing social issues such as management of huge amounts of waste soil accumulated after the Fukushima Dai–ichi nuclear power plant accident. In particular, computer–based molecular modeling supported by advanced hardware and algorithms has proven to be a powerful approach. Its application can now generally encompass the full complexity of clay particle adsorption sites from basal surfaces to interlayers with inserted water molecules, to edges including fresh and weathered frayed ones. On the other hand, its methodological schemes are now varied from traditional force–field molecular dynamics on large–scale realizations composed of many thousands of atoms including water molecules to first–principles methods on smaller models in rather exacting fashion. In this article, we overview new understanding enabled by simulations across methodological variations, focusing on recent insights that connect with experimental observations, namely: 1) the energy scale for cesium adsorption on the basal surface, 2) progress in understanding the structure of clay edges, which is difficult to probe experimentally, 3) cesium adsorption properties at hydrated interlayer sites, 4) the importance of the size relationship between the ionic radius of cesium and the interlayer distance at frayed edge sites, 5) the migration of cesium into deep interlayer sites, and 6) the effects of nuclear decay of radiocesium. Key experimental observations that motivate these simulation advances are also summarized. Furthermore, some directions toward future solutions of waste soil management are discussed based on the obtained microscopic insights.
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The spatial and developmental expression of mouse Vwa8 (von Willebrand domain-containing protein 8)
Source:Gene Expression Patterns
Author(s): Brian S. Grewe, Janet E. Richmond, David E. Featherstone
The Drosophila gene c12.2 was isolated in a screen examining mRNA binding proteins. Drosophila c12.2 is the mouse Vwa8 homolog. Various genome-wide associated studies have linked human Vwa8 to both neurological and oncological pathologies, which include autism, bipolar disorder, comorbid migraine, and acute myeloid leukemia, however, the function and role of the VWA8 protein remain poorly understood. To further analyze the Vwa8 gene in mouse, gene structure, protein homology modeling, and gene expression patterns were examined throughout mouse development. Our analyses indicate that the mouse Vwa8 gene produces two transcripts; the full-length Vwa8a is highly expressed relative to the truncated Vwa8b transcript across all developmental time points and tissues analyzed. Protein homology modeling indicates that VWA8a belongs to a novel protein superfamily containing both the midasin and cytoplasmic dynein 1 heavy chain 1 proteins. These data establish the development timeline and expression profile for both Vwa8a and Vwa8b, paving the way for future studies to determine the cellular role(s) of this highly conserved protein family.
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