bluuebunny/crossref_metadata_2025 huggingface dataset:
The value of MGMT promote methylation and IDH-1 mutation on diagnosis of pseudoprogression in patients with high-grade glioma
Authors: Zhou Min , Niu Chaoshi , Jia Li , He Hu
Published: December 2019

Objective:

To date, there are several published studies on the value of IDH-1 (isocitrate dehydrogenase-1) mutation and MGMT (O6-Methylguanine-DNA methyltransferas) promoter methylated status on the diagnosis of pseudoprogression (PSP) and true tumor progression after or within chemo-radiotherapy of high grade glioma (HGG). We performed a meta-analysis about the significant value of these 2 molecular markers on the diagnosis of PsP in high- grade glioma.

Methods:

We searched the eligible studies from PubMed, Medline, Embase, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wan Fang Database. The relevant studies published before October 2018 were identified. ORs (odds ratios) with 95%CIs (confidence intervals) were used to evaluate the value using fixed- or random-effect model.

Results:

Thirteen studies about MGMT promoter methylated status and 4 studies about IDH-1 mutations were found eligible for this present meta-analysis. Significant value of MGMT promoter methylation status (OR = 4.02, 95%CI = 2.76–5.87, P < .001) and IDH-1 mutations (OR = 12.78, 95%CI = 3.86–42.35, P < .001) were observed.

Conclusions:

This meta-analysis provided evidences that MGMT promoter methylation status and IDH-1 mutations could distinguish PSP from true tumor progression.
Association of obesity with the clinicopathological features of thyroid cancer in a large, operative population
Authors: Zhao Sitong , Jia Xiaomeng , Fan Xiaojing , Zhao Ling , Pang Ping , Wang Yajing , Luo Yukun , Wang Fulin , Yang Guoqing , Wang Xianling , Gu Weijun , Zang Li , Pei Yu , Du Jin , Ba Jianming , Dou Jingtao , Mu Yiming , Lyu Zhaohui
Published: December 2019

We aimed to investigate the association between excess body mass index (BMI) and papillary thyroid cancer (PTC) in an operative population, and the impact of higher BMI on clinicopathological aggressiveness of PTC.

Charts of 10,844 consecutive patients with thyroid nodules undergoing partial or total thyroidectomy between 1993 and 2015 were reviewed. Patients diagnosed with PTC were stratified in 4 groups: BMI < 18.5 (underweight), 18.5 ≤ BMI < 24 (normal-weight), 24 ≤ BMI < 28 (overweight) and BMI ≥ 28(obese). The impacts of high BMI on prevalence and clinicopathological parameters of PTC were retrospectively analyzed in both univariate and multivariate binary logistic regression analysis.

For every 5-unit increase in body mass, the odds of risk-adjusted malignance increased by 36.6%. The individuals who were obese and overweight were associated with high risk of thyroid cancer [odds ratio (OR)= 1.982, P < .001; OR= 1.377, P < .001; respectively] compared to normal weight patients, and this positive association was found in both genders. Obesity was independent predictors for tumors larger than 1 cm (OR = 1.562, P < .001) and multifocality (OR = 1.616, P < .001). However, there was no difference in cervical lymph node (LN) metastasis among BMI groups. Crude analysis showed BMI was associated with advanced tumor-node-metastasis (TNM) stage (relative risk, approximately 1.23 per 5 BMI units, P < .001), but this association disappeared after adjusting for confounding factors.

Obesity was significantly associated with the risk of PTC in a large, operative population. Higher BMI was significantly associated with larger tumor size and multifocal tumor.
Cardiopulmonary function after robotic exoskeleton-assisted over-ground walking training of a patient with an incomplete spinal cord injury
Authors: Jang Yun-Chol , Park Hyeng-Kyu , Han Jae-Young , Choi In Sung , Song Min-Keun
Published: December 2019

Rationale:

Spinal cord injury (SCI) patients who experience difficulties with independent walking use gait-assistive devices such as a cane, walker, or wheelchair. Few studies have explored gait patterns or cardiopulmonary function in chronic SCI patients after powered exoskeleton training. We investigated whether the cardiopulmonary function of a patient with an incomplete chronic cervical SCI and a hemiplegic gait pattern could be improved by walking training using a powered exoskeleton (Angelegs).

Patient concerns:

A 57-year-old male was diagnosed with an SCI at C3-C4. The right upper and lower limb motor functions differed when evaluated before entry into the program. Motor function was good in the right leg but poor in the left one. Before program entry, the patient could walk for about 10 m using a cane. He did not have a history of severe medical or psychological problems and was not cognitively impaired.

Diagnosis:

The patient was tetraplegia with incomplete SCI at C3-C4.

Interventions:

The patient was trained for 6 weeks using a powered exoskeleton. The training program consisted of sit-to-stand and stand-to-sit movements, maintenance of balanced standing for 5 minutes, and walking for 15 minutes.

Outcomes:

After 6 weeks of training, gait speed improved in the timed up-and-go test, and cardiac function was enhanced as measured by the metabolic equivalent and VO2 tests.

Lessions:

Walking training using a powered exoskeleton can facilitate the effective rehabilitation and improve the gait speed and cardiopulmonary function of patients with chronic SCIs or strokes.
Can preoperative neutrophil to lymphocyte, lymphocyte to monocyte, or platelet to lymphocyte ratios differentiate glioblastoma from brain metastasis?
Authors: Baran Oguz , Kemerdere Rahsan , Korkmaz Taha Sukru , Kayhan Ahmet , Tanriverdi Taner
Published: December 2019

This retrospective analysis of patients aims to show the blood levels of preoperative inflammatory markers in patients with glioblastoma and brain metastasis and to provide the diagnostic accuracy of the neutrophil–lymphocyte (NLR), lymphocyte–monocyte (LMR), and platelet–lymphocyte (PLR) ratios between the 2 groups of patients.

The retrospective reviews of the neutrophil, lymphocyte, monocyte, and platelet counts were analyzed in 80 patients with newly diagnosed glioblastoma and 70 patients with brain metastasis. The NLR, LMR, and PLR were calculated in each group. The differences in all the parameters were compared between the 2 groups.

Although the neutrophil, monocyte, and platelet counts were higher and the lymphocyte count was lower in patients with metastasis, the difference was not significant. A significantly higher PLR (P = .004) and a lower LMR (P = .01) were found in patients with brain metastasis. Although both PLR and LMR had diagnostic accuracy in differentiating glioblastoma from brain metastasis, LMR showed the highest diagnostic accuracy. NLR showed no diagnostic accuracy.

Systemic inflammation is more severe in glioblastoma than in brain metastasis, and LMR is more sensitive and/or specific than PLR in differentiating glioblastoma from brain metastasis. Therefore, LMR (less likely PLR) can be used as an index for differentiating between glioblastoma and brain metastasis before surgery.
The number of stents was an independent risk of stent restenosis in patients undergoing percutaneous coronary intervention
Authors: Tang Long , Cui Qian-Wei , Liu Dan-Ping , Fu Ying-Ying
Published: December 2019

Percutaneous coronary intervention (PCI) is one of the most effective therapies for coronary artery disease, but stent restenosis remains an important clinical challenge. The studies about the independent effect of the number of stents on stent restenosis were limited.

The purpose was to identify the independent effect of the number of stents on stent restenosis.

A retrospective cohort study of data reuse.

From July 2009 to August 2011, a total of 2338 cases met the inclusion and exclusion criteria.

The univariate analysis showed that the number of stents was a risk of stent restenosis, the OR value was 1.30 (95% CI:1.15 to 1.47, P < .001). The multi-factor regression analysis also showed that the number of stents was an independent risk of stent restenosis, the adjusted OR value was 1.38 (95% CI: 1.15 to 1.66, P < .001).Compared with 1–2 stents, the adjusted OR values of 3–5 stents and more than 6 stents were respectively 2.20 (95% CI: 1.24 to 3.90, P = .007) and 5.33 (95% CI: 1.89 to 15.08, P = .002), and the trend adjusted OR values was 2.26 (95% CI: 1.43 to 3.59, P < .001).The subgroup analysis of multi-factor regression analysis showed that when patients with the following conditions: 50 < Age, female, non-DES or SES, the risk of stent restenosis increased obviously.

The number of stents was an independent risk of stent restenosis in patients undergoing PCI, especially for patients with the following conditions: 2<the number of stents, 50 < age, female, Non-DES (Drug-eluting stents) or SES (sirolimus-eluting stent).
Beta wave enhancement neurofeedback improves cognitive functions in patients with mild cognitive impairment
Authors: Jang Jung-Hee , Kim Jieun , Park Gunhyuk , Kim Haesook , Jung Eun-Sun , Cha Ji-yun , Kim Chan-young , Kim Siyeon , Lee Jun-Hwan , Yoo Horyong
Published: December 2019

Background:

Mild cognitive impairment (MCI) is a symptom characterizing cognitive decline and a transitional state between normal aging and dementia; however, there is no definitive diagnosis and treatment for MCI. Neurofeedback (NF), which is a training mechanism that employs operant conditioning to regulate brain activity, has been increasingly investigated concerning its beneficial effects for dementia and MCI.

Methods:

This study investigated cognitive improvement and hemodynamic changes in the prefrontal cortex (PFC) following NF training in patients with MCI. Five patients with MCI received NF training for enhanced beta band activity in the dorsolateral PFC—16 sessions for 8 weeks—with each session divided into 9 5-minute trials. The primary outcome measure was a cognitive assessment tool: the Korean version of the Montreal Cognitive Assessment. The secondary outcome measures were the Central Nervous System Vital Signs for neurocognitive testing, hemodynamic changes using functional near-infrared spectroscopy in the PFC during a working-memory task, and Beck Depression Inventory scores.

Results:

After completing the training, patients’ cognitive function significantly improved in domains such as composite memory, cognitive flexibility, complex attention, reaction time, and executive function. Increased electroencephalogram beta power was observed over NF training sessions (Spearman rank correlation test: r = 0.746, P = .001). The threshold value for gaining positive feedback from pre-NF baseline on beta power significantly increased (Spearman rank correlation test: r = 0.805, P = .001). Hemodynamic response in PFC changed after NF training, and individual differences were identified. Specifically, hypoactivation of the hemodynamic response by emotional distraction recovered following NF training.

Conclusion:

We suggest that patients’ cognitive processing efficiency was improved by the NF training. These beneficial results suggest that NF training may have potential therapeutic applications to prevent the progression from MCI to dementia.

Trial registration number: Clinical Research Information Service (KCT0003433).
Late puerperal hemorrhage of a patient with Klippel–Trenaunay syndrome
Authors: Zhang Jian , Wang Kana , Mei Jie
Published: December 2019

Introduction:

The Klippel–Trenaunay syndrome (KTS) is a rare congenital disorder. The obstetric course of women with KTS varies. Complications include bleeding, disseminated intravascular coagulation (DIC), thromboembolic events, etc.

Patient concerns:

Here, we report a case of late puerperal hemorrhage of a Chinese puerpera with KTS. The repeating severe hemorrhage, the DIC, and the Kasabach–Merrit syndrome made the treatment more difficult.

Diagnosis:

KTS is a mixed malformation with a vascular component that is characterized by abnormal development of veins, capillaries, and lymphatics. Our patient was first diagnosed with KTS at the last trimester of pregnancy.

Interventions:

Massive infusion of blood products, two laparotomies, as well as bilateral internal iliac artery embolization was carried out.

Outcomes:

Although the patient survived from the life-threatening hemorrhage, she lost her uterus forever.

Conclusion:

An interdisciplinary cooperation of obstetrician, anesthesiologist, vascular surgeon, and intensive care physician is highly recommended. Prophylactic anticoagulation is generally advised in the gestational and postpartum period.
Cellular angiofibroma in the hypopharynx
Authors: Liu Ya , Xu Yaping , Wang Qinying , Chen Qiongqiong
Published: December 2019

Rationale:

Cellular angiofibroma is a rare benign mesenchymal tumor which mostly occurs in the superficial soft tissues of the genital region. Occurrence in the head and neck region is extremely rare. To our knowledge, this is the first case of cellular angiofibroma arising in the hypopharynx.

Patient's concerns:

A 54-year-old male complained of a mass moving through his throat for 1 month. A tumor was found in the right lateral wall of the pharyngeal at the level of the epiglottis by laryngoscope. Magnetic resonance imaging confirmed the presence of a mass in the right lateral pharyngeal area. A benign tumor was suspected based on the clinical symptoms and imaging findings.

Diagnosis:

A supporting laryngoscope was performed under general anesthesia and the lesion was resected. Immunohistochemical analysis revealed cellular angiofibroma.

Interventions:

The patient underwent surgical excision of the lesion.

Outcomes:

Thus far, no recurrence has been observed 6 months after excision.

Lessons:

Cellular angiofibroma located in the lateral pharyngeal is rare; however, immunohistochemical staining is helpful for its diagnosis. Treatment is relatively simple and requires local excision and follow-up.
Prognostic effect of different etiologies in patients with gastric cardia cancer
Authors: Kim Yeon-Ji , Chung Woo Chul , Cho Ik Hyun , Kim Jaeyoung , Kim Seonhoo
Published: December 2019

There are still many controversies about the characteristics and prognosis of gastric cardia cancer. We aimed to evaluate the clinical characteristics and outcome between cardia and noncardia cancer. Also, we evaluated the clinical outcome according to etiologic factors.

We performed a retrospective cohort study of 92 patients with gastric cardia cancer from January 2003 to December 2013. The patients with noncardia cancer were selected as age- and sex-matched control.

The frequencies of gastroesophageal reflux disease (GERD) and negative Helicobacter pylori infection without atrophy were significantly higher in gastric cardia cancers, but there was no difference in the frequency of obesity. The frequency of early gastric cancers was 40.0%, which was significantly lower than that of noncardia cancer. The rate of recurrence, disease-free survival, and overall survival duration were significantly lower in gastric cardia cancers (P < .01), even though there was no significant difference in the rate of curative resection (R0). In terms of the etiologic factors, there were no differences of disease prognosis, regardless of the presence of GERD, obesity, and H pylori infection with associated gastritis.

Gastric cardia cancer showed distinct clinical characteristics and a negative prognostic impact compared with gastric noncardia cancer.
Continuity of Care and Mental Health Service Use Among Medicaid-enrolled Youths
Authors: Pennap Dinci , Zito Julie M. , Santosh Paramala J. , Tom Sarah E. , Onukwugha Eberechukwu , Magder Laurence S.
Published: December 2019

Background:

Recent reports of increased national estimates of pediatric psychiatric emergency department (ED) visits and psychiatric hospitalizations emphasize the need to research these utilization patterns.

Objectives:

To assess the patient-provider continuity of care (CoC) and compare the risk of psychiatric ED visits or hospitalization according to the CoC level.

Research Design:

A cohort design was applied to Medicaid administrative claims data (2007–2014) for 3–16-year olds with a first psychiatric diagnosis between 2009 and 2013 (n=38,825).

Subjects:

Continuously enrolled youths with (1) ≥1 outpatient psychiatric visits and (2) ≥4 pediatric outpatient visits in the prior 24 months.

Measures:

The authors assessed CoC in the 24 months before the first psychiatric outpatient visit and quantified CoC using the Alpha Index. The authors assessed patient-provider CoC before first psychiatric diagnosis and the odds of psychiatric ED visits or psychiatric hospitalizations in the year after diagnosis.

Results:

Of the 38,825 youths, 88.9% received a first psychiatric diagnosis by age 14. The odds of ED visits were significantly higher among youths with low CoC [6.63%, adjusted odds ratio (AOR), 1.27; 95% confidence interval (CI), 1.13–1.41] or moderate CoC (5.76%; AOR, 1.14; 95% CI, 1.02–1.27) compared with those with high CoC (4.96%). Greater odds of psychiatric hospitalization related to low (7.53%; AOR, 1.17; 95% CI, 1.06–1.29) or moderate CoC (7.01%; AOR, 1.15; 95% CI, 1.03–1.27) compared with high CoC (6.06%).

Conclusions:

The odds of potentially disruptive clinical management and costly psychiatric ED visits or hospitalizations were lower for youths with high CoC. The findings support the need to research the impact of CoC on long-term pediatric mental health service use.
The Association Between Patient-reported Clinical Factors and 30-day Acute Care Utilization in Chronic Heart Failure
Authors: Chen Jinying , Sadasivam Rajani , Blok Amanda C. , Ritchie Christine S. , Nagawa Catherine , Orvek Elizabeth , Patel Kanan , Houston Thomas K.
Published: December 2019

Background:

Heart failure patients have high rates of repeat acute care use. Current efforts for risk prediction often ignore postdischarge data.

Objective:

To identify postdischarge patient-reported clinical factors associated with repeat acute care use.

Research Design:

In a prospective cohort study that followed patients with chronic heart failure for 30 days postdischarge, for 7 days after discharge (or fewer days if patients used acute care within 7 days postdischarge), patients reported health status, heart failure symptoms, medication management, knowledge of follow-up plans, and other issues using a daily interactive automatic phone call.

Subjects:

A total of 156 patients who had responded to phone surveys.

Measures:

The outcome variable was dichotomous 30-day acute care use (rehospitalization or emergency department visit). We examined the association between each patient-reported issue and the outcome, using multivariable logistic regression to adjust for confounders.

Results:

Patients were 63 years old (SD=12.4), with 51% African-American and 53% women. Within 30 days postdischarge, 30 (19%) patients used acute care. After adjustment, poor health status [odds ratio (OR)=3.53; 95% confidence interval (CI), 1.06–11.76], pain (OR=2.44; 95% CI, 1.02–5.84), and poor appetite (OR=3.05; 95% CI, 1.13–8.23) were positively associated with 30-day acute care utilization. Among 58 reports of pain in follow-up nursing notes, 39 (67%) were noncardiac, 2 (3%) were cardiac, and 17 (29%) were indeterminate.

Conclusions:

Patient-reported poor health status, pain, and poor appetite were positively associated with 30-day acute care utilization. These novel postdischarge markers require further study before incorporation into risk prediction to drive quality improvement efforts.
The Impact of Morphine Equivalent Daily Dose Threshold Guidelines on Prescribed Dose in a Workers’ Compensation Population
Authors: Heins Sara E. , Castillo Renan C.
Published: December 2019

Background:

Prescription opioid overdose has increased markedly and is of great concern among injured workers receiving workers’ compensation insurance. Given the association between high daily dose of prescription opioids and negative health outcomes, state workers’ compensation boards have disseminated Morphine Equivalent Daily Dose (MEDD) guidelines to discourage high-dose opioid prescribing.

Objective:

To evaluate the impact of MEDD guidelines among workers’ compensation claimants on prescribed opioid dose.

Methods:

Workers’ compensation claims data, 2010–2013 from 2 guideline states and 3 control states were utilized. The study design was an interrupted time series with comparison states and average monthly MEDD was the primary outcome. Policy variables were specified to allow for both instantaneous and gradual effects and additional stratified analyses examined evaluated the policies separately for individuals with and without acute pain, cancer, and high-dose baseline use to determine whether policies were being targeted as intended.

Results:

After adjusting for covariates, state fixed-effects, and time trends, policy implementation was associated with a 9.26 mg decrease in MEDD (95% confidence interval, −13.96 to −4.56). Decreases in MEDD also became more pronounced over time and were larger in groups targeted by the policies.

Conclusions:

Passage of workers’ compensation MEDD guidelines was associated with decreases in prescribed opioid dose among injured workers. Disseminating MEDD guidelines to doctors who treat workers’ compensation cases may address an important risk factor for opioid-related mortality, while still allowing for autonomy in practice. Further research is needed to determine whether MEDD policies influence prescribing behavior and patient outcomes in other populations.
Effect of Target Fortification on Osmolality and Microbiological Safety of Human Milk Over Time
Authors: Piemontese Pasqua , Liotto Nadia , Menis Camilla , Mallardi Domenica , Tabasso Chiara , Perrone Michela , Bezze Elena , Plevani Laura , Roggero Paola , Mosca Fabio
Published: December 2019

Objectives:

The fortification of human milk can result in increased osmolality, which may be associated with adverse effects for preterm infants. To evaluate the effect of target fortification on the osmolality and microbiological safety of donor human milk and raw mature milk during the first 72 hours of storage.

Methods: We performed target fortification of 63 pasteurized donor human milk (PDHM) and 54 raw mature milk (RMM) samples in a laminar flow hood. Osmolality (mOsm/kg) was evaluated before fortification (T0), immediately after fortification (T1), at 6 (T2), 24 (T3), 48 (T4), and 72 hours (T5) after fortification. Microbiological analysis was performed at T0, T4, and T5. During the study, all samples were stored at 4°C.

Results:

Mean osmolality at each study point for PDHM and RMM were, respectively: T0: 291.4 ± 11.0 versus 288.4 ± 5.6 (P = 0.06); T1: 384.8 ± 16.7 versus 398.3 ± 23.7; T2: 393.9 ± 17.7 versus 410.1 ± 27.0; T3: 397.8 ± 17.6 versus 417.9 ± 26.1; T4: 400.0 ± 16.5 versus 420.2 ± 24.9; T5: 399.6 ± 16.5 versus 425.2 ± 25.8 (P < 0.001 from T1 to T5). Microbiological analyses were negative at each study points for PDHM. At T0 16.1% of RMM samples had positive cultures, whereas the bacterial count remained stable thought the study.

Conclusions:

PDHM's osmolality increases during the first 6 hours after fortification and remains stable and safe until 72 hours. RMM's osmolality increases during the first 24 hours and remains stable and safe until 72 hours. The storage at 4°C and the manipulation of PDHM and RMM samples in a laminar flow hood seem to be safe and preserve the microbiological safety of fortified pasteurized human milk until 72 hours.
Late Rescue Collaborative: Reducing Non-ICU Arrests*
Authors: Dean Nathan P. , Ghebremariam Emanuel , Szeles Rosemary , Levin Amanda , Colyer Jessica , Steinhorn Robin H.
Published: December 2019

Objective:

To reduce the frequency of non-ICU arrests through the implementation of an intramural collaborative focused on patient deterioration.

Design:

Prospective quality improvement project.

Setting:

Single-center, free-standing, tertiary children’s hospital.

Patients:

All patients admitted to acute care units.

Interventions:

The Late Rescue Collaborative was formed in 2014 to monitor compliance with hospital escalation protocols and evaluate episodes of patient deterioration. The collaborative is a multidisciplinary team of physicians, nurses, and respiratory care providers. Three monthly meetings occur: 1) individual acute care unit–based meetings to evaluate trends and performance; 2) hospital-wide multidisciplinary whole group meetings to review hospital trends in deterioration and share lessons learned; and 3) steering committee to determine areas of focus. Based on these three meetings, unit- and hospital-based interventions have been put in place to improve recognition of deterioration and promote early rescue.

Measurements and Main Results:

Rates of rapid response team activations, unplanned transfers, and non-ICU arrest are reported. Non-ICU arrest rates fell from a baseline of 0.31 per 1,000 non-ICU patient days to a new centerline of 0.11 and sustained for 36 months. Days between non-ICU arrests increased from a baseline of 15.5 days in year 2014 to a new centerline of 61.5 days and sustained for 37 months. Mortality following non-ICU arrests fell from four in 2014 and 2015 to zero in years 2016–2018.

Conclusion:

The Late Rescue Collaborative is an effective tool to improve patient safety by reducing non-ICU arrests.
Accuracy of Remote Interpretation of Pediatric Emergency Ultrasound Over Third Generation Networks Across Continents
Authors: Whitney Rachel E. , Riera Antonio , Chen Lei
Published: December 2019

Objective

This study aimed to evaluate live-stream videos for evaluation of pediatric emergency medicine ultrasound using a third generation (3G) network.

Methods

The interrater reliability of a remote 3G network live-streaming assessment of ultrasound scans for abdominal free fluid, intussusception, and hip effusions was evaluated. Fifty-eight deidentified 6-second video clips in .mp4 format of focused assessment with sonography in trauma scans were downloaded to a laptop. A “bedside” ultrasound expert evaluated each scan and marked it positive or negative for the presence of free fluid. Using an iPhone 3G, Skype was used to connect to the second ultrasound expert located in Addis Ababa, Ethiopia, who reviewed the same scans. When the remote expert returned to the United States, evaluation of the scans was repeated as a second bedside reviewer. Interrater reliability was assessed using the κ statistic and percent agreement. This process was repeated for 44 intussusception scans and 28 hip effusion scans.

Results

The κ values (95% confidence interval) between the bedside and remote evaluators for focused assessment with sonography in trauma, intussusception, and hip effusion were 0.748 (0.576–0.92), 0.816 (0.648–0.984), and 0.764 (0.519–1.0), respectively. The percent agreements after adjusting for chance were 86%, 80%, and 88%, respectively. The κ values between the bedside assessments by each evaluator were 0.851 (0.71–0.992), 0.8 (0.616–0.984), and 0.747 (0.479–0.884), respectively. The percent agreements after adjusting for chance were 92%, 81%, and 88%, respectively.

Conclusions

Live-stream video conference using cellphones over 3G network is a feasible and accurate method for consultation of ultrasound scans from a remote location.
Determination of the Pretibial Soft Tissue Thickness in Children
Authors: Al-Shibli Amal , Lim Rodrick , Poonai Naveen , Istasy Victor , Lin Kangrui , Kilgar Jennifer
Published: December 2019

Objective

The EZ-IO intraosseous (IO) needle is available in 2 needle sizes for children based on the patient weight. To date, there is no published evidence validating the use of weight-based scaling in children. We hypothesized that pretibial subcutaneous tissue thickness (PSTT) does not correspond with patient weight but rather with age and body mass index (BMI). Our objective was to describe the relationship of a patient's PSTT to their weight, age, and BMI in children less than 40 kg.

Method

One hundred patients who weighed less than 40 kg were recruited prospectively from October 2013 to April 2015 at a tertiary care pediatric emergency department. All sonographic assessments were performed by 1 of 2 emergency physicians certified in point-of-care ultrasound. A single sonographic image was taken over the proximal tibia corresponding to the site of IO insertion. In patients where both sonographers performed independent measurements, a Pearson correlation coefficient was determined. Univariate linear regression was performed to determine the relationship between age, weight, and BMI with PSTT.

Results

One hundred participants were recruited and ranged in age from 10 days to 14 years (mean [SD], 5.01 [3.14] years). Fifty-seven percent of participants were male. Patients' weights ranged from 3.5 to 39.3 kg (mean [SD], 21.42 [9.12] kg), and BMI ranged from 12.1 to 45.0 kg/m2 (mean [SD], 17.31 [4.00]). The mean (SD) PSTT across participants was 0.68 (0.2) cm. The intraclass correlation coefficient for agreement between the 2 sonographers was moderate (intraclass correlation coefficient, 0.602 [confidence interval, 0.385–0.757]). There were significant positive correlations between BMI and PSTT (r = 0.562, P = <0.001) as well as weight and PSTT (r = 0.293, P < 0.003). There was a weak correlation between age and PSTT (0.065, P = 0.521).

Conclusions

Pretibial subcutaneous tissue thickness correlates most strongly with BMI, followed by weight, and weakly with age. Our findings suggest that current IO needle length recommendations should be based on BMI rather than weight. This would suggest that clinicians need to be aware that young patients in particular with large BMIs may pose problems with current weight-based needle length recommendations.
Are Postoperative Intravenous Antibiotics Indicated After Laparoscopic Appendicectomy for Simple Appendicitis? A Prospective Double-blinded Randomized Controlled Trial
Authors: Mennie Nicole , Panabokke Gayathri , Chang Annette , Tanny Sharman Tan , Cheng Wei , Pacilli Maurizio , Ferguson Peter , Nataraja Ramesh M.
Published: December 2019

Background:

There is limited evidence for the use of postoperative antibiotics for simple appendicitis (SA) in children. Our aim was to conduct a prospective double-blinded randomized controlled trial to investigate this after a laparoscopic appendicectomy.

Methods:

Following ethical approval, children (≤16 years) undergoing appendicectomy were recruited at a single institution. Patients were randomized intraoperatively to receive either 2 postoperative intravenous doses of placebo or antibiotics (Abx). All patients received a dose of Abx at induction of anesthesia. Primary outcome was the incidence of postoperative wound infection (WI), and secondary outcome was the incidence of intra-abdominal abscess formation. Data are reported as number of cases (%), median (range), relative risk, and analyzed using Mann Whitney U test, Chi-square test, as appropriate, a P-value ≤0.05 was considered significant.

Results:

A total of 304 patients were randomized. Sixty-one were subsequently excluded due to protocol violations or recruitment errors; therefore, 243 were included in the final analysis. One hundred twenty-two patients received placebo and 121 Intravenous Abx. There was no difference between the sex (50F/72 M vs 47F/74 M, P = 0.8), median age (12.4 vs 12.2 years, P = 0.5), and postoperative length of stay in a hospital (27.2 vs 25.6 hours, P = 0.7). There was also no difference in the preoperative blood results. A total of 9 WIs occurred: 8/122 (6.6%) placebo versus 1/121 (0.8%) Abx, P = 0.01 [relative risk for WI 7.9 (95% confidence interval: 1.0–62.4)]. There were no intra-abdominal abscess in either groups.

Conclusions:

This prospective randomized double blinded randomized controlled trial has revealed a significant decrease in WI rates by giving 2 postoperative intravenous doses of Abx, suggesting postoperative Abx are of benefit in SA.
PERSIST: A programmable RNA regulation platform using CRISPR endoRNases
Authors: DiAndreth Breanna , Wauford Noreen , Hu Eileen , Palacios Sebastian , Weiss Ron
Published: December 2019

Regulation of transgene expression is becoming an integral component of gene therapies, cell therapies and biomanufacturing. However, transcription factor-based regulation upon which the majority of such applications are based suffers from complications such as epigenetic silencing, which limits the longevity and reliability of these efforts. Genetically engineered mammalian cells used for cell therapies and biomanufacturing as well as newer RNA-based gene therapies would benefit from post-transcriptional methods of gene regulation, but few such platforms exist that enable sophisticated programming of cell behavior. Here we engineer the 5’ and 3’ untranslated regions of transcripts to enable robust and composable RNA-level regulation through transcript cleavage and, in particular, create modular RNA-level OFF- and ON-switch motifs. We show that genomically introduced transgenes exhibit resistance to silencing when regulated using this platform compared to those that are transcriptionally-regulated. We adapt nine CRISPR-specific endoRNases as RNA-level “activators” and “repressors” and show that these can be easily layered and composed to reconstruct genetic programming topologies previously achieved with transcription factor-based regulation including cascades, all 16 two-input Boolean logic functions, positive feedback, a feed-forward loop and a putative bistable toggle switch. The orthogonal, modular and composable nature of this platform as well as the ease with which robust and predictable gene circuits are constructed holds promise for their application in gene and cell therapies.
Structural studies of thyroid peroxidase show the monomer interacting with autoantibodies in thyroid autoimmune disease
Authors: Williams Daniel E. , Le Sarah N. , Hoke David E. , Chandler Peter G. , Gora Monika , Godlewska Marlena , Banga J. Paul , Buckle Ashley M.
Published: December 2019

Thyroid peroxidase (TPO) is a critical membrane-bound enzyme involved in the biosynthesis of multiple thyroid hormones, and is a major autoantigen in autoimmune thyroid diseases such as Graves’ disease and Hashimoto’s thyroiditis. Here we report the biophysical and structural characterisation of two novel TPO constructs containing only the ectodomain of TPO and lacking the propeptide. Both constructs were enzymatically active and able to bind the patient-derived TR1.9 autoantibody. Analytical ultra-centrifugation data suggests that TPO can exist as both a monomer and a dimer. Combined with negative stain electron microscopy and molecular dynamics simulations, these data show that TR1.9 autoantibody preferentially binds the TPO monomer, revealing conformational changes that bring together previously disparate residues into a continuous epitope. In addition to providing plausible structural models of a TPO-autoantibody complex, this study provides validated TPO constructs that will facilitate further characterization, and advances our understanding of the structural, functional and antigenic characteristics of TPO, a molecule behind some of the most common autoimmune diseases.
Estimating the effective sample size in association studies of quantitative traits
Authors: Ziyatdinov Andrey , Kim Jihye , Prokopenko Dmitry , Privé Florian , Laporte Fabien , Loh Po-Ru , Kraft Peter , Aschard Hugues
Published: December 2019

The effective sample size (ESS) is a quantity estimated in genome-wide association studies (GWAS) with related individuals and/or linear mixed models used in analysis. ESS originally measured relative power in family-based GWAS and has recently become important for correcting GWAS summary statistics in post-GWAS analyses. However, existing ESS approaches have been overlooked and based on empirical estimation. This work presents an analytical form of ESS in mixed-model GWAS of quantitative traits, which is derived using the expectation of quadratic form and validated in extensive simulations. We illustrate the performance and relevance of our ESS estimator in common GWAS scenarios and analytically show that (i) family-based studies are consistently underpowered compared to studies of unrelated individuals of the same sample size; (ii) conditioning on polygenic genetic effect by linear mixed models boosts power; and (iii) power of detecting gene-environment interaction can be substantially gained or lost in family-based designs depending on exposure distribution. We further analyze UK Biobank dataset in two samples of 336,347 unrelated and 68,910 related individuals. Analysis in unrelated individuals reveals a high accuracy of our ESS estimator compared to the existing empirical approach; and analysis of related individuals suggests that the loss in effective sample size due to relatedness is at most 0.94x. Overall, we provide an analytical form of ESS for guiding GWAS designs and processing summary statistics in post-GWAS analyses.
Inventive nesting behaviour in the keyhole waspPachodynerus nasidensLatreille (Hymenoptera: Vespidae) in Australia, and the risk to aviation safety
Authors: House Alan P.N. , Ring Jackson G. , Shaw Philip P.
Published: December 2019

The keyhole wasp (Pachodynerus nasidensLatreille 1812), a mud-nesting wasp native to South and Central America and the Caribbean, is a relatively recent (2010) arrival in Australia. In its native range it is known to use man-made cavities to construct nests. A series of serious safety incidents Brisbane Airport related to the obstruction of vital airspeed measuring pitot probes on aircraft possibly caused by mud-nesting wasps at prompted an assessment of risk. An experiment was designed to determine the species responsible, the types of aircraft most affected, the seasonal pattern of potential risk and the spatial distribution of risk on the airport. A series of replica pitot probes were constructed using 3D-printing technology, representing aircraft with high numbers of movements (landings and take-offs), and mounted at four locations at the airport. Probes were monitored for 39 months. Probes blocked by mud nesting wasps were retrieved and incubated in mesh bags. Emerging wasps were identified to species. Results show that all nests in probes were made byP. nasidens, and peak nesting occurs in the summer months. Nesting success (as proportion of nests with live adult emergents) was optimal between 24 and 31°C and that probes with apertures of more than 3 mm diameter are preferred. Not all areas on the airport are affected equally, with the majority of nests constructed in one area. The proportion of grassed areas within 1000 m of probes was a significant predictor of nesting, and probe volume may determine the sex of emerging wasps.
RhoGAP RGA-8 supports morphogenesis inC. elegansby polarizing epithelia through CDC-42
Authors: Raduwan Hamidah , Sasidharan Shashikala , Burgos Luigy Cordova , Wallace Andre G. , Soto Martha C.
Published: December 2019

CDC-42 regulation of non-muscle myosin/NMY-2 is required for polarity maintenance in the one-cell embryo ofC. elegans. CDC-42 and NMY-2 regulate polarity throughout embryogenesis, but their contribution to later events of morphogenesis are less understood. We have shown that epidermal enclosure requires the GTPase CED-10/Rac1 and WAVE/Scar complex, its effector, to promote protrusions that drive enclosure through the branch actin regulator Arp2/3. Our analysis here of RGA-8, a homolog of SH3BP1/Rich1/ARHGAP17/Nadrin, with BAR and RhoGAP motifs, suggests it regulates CDC-42, so that NMY-2 promotes two events of epidermal morphogenesis: ventral enclosure and elongation. Genetic and molecular data suggest RGA-8 regulates CDC-42, and the CDC-42 effectors WSP-1 and MRCK-1, in parallel to F-BAR proteins TOCA-1 and TOCA-2. The RGA-8-CDC-42-WSP-1 pathway enriches myosin in migrating epidermal cells during ventral enclosure. We propose TOCA proteins and RGA-8 use BAR domains to localize and regenerate CDC-42 activity, thus regulating F-actin levels, through the branched actin regulator WSP-1, and myosin polarity through the myosin kinase MRCK-1. Regulated CDC-42 thus polarizes epithelia, to control cell migrations and cell shape changes of embryonic morphogenesis.

RGA-8, a protein with membrane binding and actin regulatory motifs, promotes embryonic morphogenesis by localizing active CDC-42 in developing epithelia, thus controlling actin and actin motors during cell movements.
Microglial Calcium Signaling is Attuned to Neuronal Activity
Authors: Umpierre Anthony D. , Bystrom Lauren L. , Ying Yanlu , Liu Yong U. , Wu Long-Jun
Published: December 2019

Microglial calcium signaling underlies a number of key physiological processesin situ, but has not been studiedin vivoin an awake animal where neuronal function is preserved. Using multiple GCaMP6 variants targeted to microglia, we assessed how microglial calcium signaling responds to alterations in neuronal activity across a wide physiological range. We find that only a small subset of microglial somata and processes exhibited spontaneous calcium transients. However, hyperactive and hypoactive shifts in neuronal activity trigger increased microglial process calcium signaling, often concomitant with process extension. On the other hand, changes in somatic calcium activity are only observed days after severe seizures. Our work reveals that microglia have highly distinct microdomain signaling, and that processes specifically respond to bi-directional shifts in neuronal activity through calcium signaling.
Disassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species
Authors: Nachman Eliana , Wentink Anne , Madiona Karine , Bousset Luc , Katsinelos Taxiarchis , Kampinga Harm , McEwan William A. , Jahn Thomas R. , Melki Ronald , Mogk Axel , Bukau Bernd , Nussbaum-Krammer Carmen
Published: December 2019

The accumulation of amyloid Tau aggregates is implicated in Alzheimer’s disease and other Tauopathies. Molecular chaperones are known for their function in maintaining protein homeostasis by preventing the formation or promoting the disaggregation of amorphous and amyloid protein aggregates. Here we show that an ATP-dependent human chaperone system disassembles Tau fibrilsin vitro. This function is mediated by the core chaperone Hsc70, assisted by specific co-chaperones, in particular class B J-domain proteins and an Hsp110-type NEF. Recombinant fibrils assembled from all six Tau isoforms as well as Sarkosyl-resistant Tau aggregates extracted from cell culture were processed by the Hsp70 disaggregation machinery, demonstrating the ability of this machinery to recognize a broad range of Tau aggregates. Chaperone treatment released monomeric, and small oligomeric Tau species, which induced the aggregation of self-propagating Tau species in a Tau cell culture model. We infer from these results that the activity of the Hsp70 disaggregation machinery is a double-sided sword as it attempts to eliminate Tau amyloids but with the price of generating new seeds. The Hsp70 disaggregase therefore has a crucial function in the Tau propagation cycle, rendering it a potential drug target in Tauopathies.
SNAPSwitch: A Molecular Sensor to Quantify the Localization of Proteins, DNA and Nanoparticles in Cells
Authors: FitzGerald Laura I , Aurelio Luigi , Chen Moore , Yuen Daniel , Graham Bim , Johnston Angus P R
Published: December 2019

Intracellular trafficking governs receptor signalling, pathogenesis, immune responses and the cellular fate of nanomedicines. These processes are typically tracked by confocal microscopy, where colocalization of fluorescent markers implies an interaction or co-compartmentalization. However, this type of analysis is inherently low-throughput, is limited by the resolution of microscopy, and can miss fleeting interactions. To address this, we have developed a localization sensor composed of a quenched and attachable SNAP-tag substrate (SNAPSwitch). SNAPSwitchenables quantitative detection of protein, nucleic acid and nanoparticle trafficking to locations of interest within live cells using flow cytometry. Using this approach, we followed the trafficking of DNA complexes travelling from endosomes into the cytosol and to the nucleus. We also show that antibody targeted to the transferrin (CD71) or hyaluronan (CD44) receptor is initially sorted into different compartments following endocytosis. These results demonstrate SNAPSwitchis a high-throughput and broadly applicable tool to quantitatively track the localization of materials in cells.
Amyloid-like aggregates cause lysosomal defects in neurons via gain-of-function toxicity
Authors: Riera-Tur Irene , Schäfer Tillman , Hornburg Daniel , Mishra Archana , Fernández-Mosquera Lorena , Feigenbutz Dennis , Auer Patrick , Mann Matthias , Baumeister Wolfgang , Klein Rüdiger , Meissner Felix , Raimundo Nuno , Fernández-Busnadiego Rubén , Dudanova Irina
Published: December 2019

The autophagy-lysosomal pathway is impaired in many neurodegenerative diseases characterized by protein aggregation, but the link between aggregation and lysosomal dysfunction remains poorly understood. Here, we combine cryo-electron tomography, proteomics and cell biology studies to investigate the effects of protein aggregates in primary neurons. We use artificial amyloid-like β-sheet proteins (β proteins) to focus on the gain-of-function aspect of aggregation. These proteins form fibrillar aggregates and cause neurotoxicity. We show that late stages of autophagy are impaired by the aggregates, resulting in lysosomal alterations reminiscent of lysosomal storage disorders. Mechanistically, β proteins interact with and sequester AP-3μ1, a subunit of the AP-3 adaptor complex involved in protein trafficking to lysosomal organelles. This leads to destabilization of the AP-3 complex, missorting of AP-3 cargo, and lysosomal defects. Restoring AP-3μ1 expression ameliorates neurotoxicity caused by β proteins. Altogether, our results highlight the link between protein aggregation and neurotoxicity, pointing to lysosomes as particularly vulnerable organelles.
PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM
Authors: Wamp Sabrina , Rutter Zoe J. , Rismondo Jeanine , Jennings Claire E. , Möller Lars , Lewis Richard J. , Halbedel Sven
Published: December 2019

Peptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that sense PG fragments. However, only a few PG biosynthetic enzymes are direct kinase substrates. Here, we identify the conserved ReoM protein as a novel PASTA-eSTK substrate in the Gram-positive pathogenListeria monocytogenes. Our data show that the phosphorylation of ReoM is essential as it controls ClpCP-dependent proteolytic degradation of the essential enzyme MurA, which catalyses the first committed step in PG biosynthesis. We also identify ReoY as a second novel factor required for degradation of ClpCP substrates. Collectively, our data imply that the first committed step of PG biosynthesis is activated through control of ClpCP protease activity in response to signals of PG homeostasis imbalance.