bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of Anatomy and Imaging of the Anterolateral Structures of the Knee
Authors: Helito Camilo P. , Helito Paulo V.P.
Published: April 2018

Despite several previous articles in the literature, never before have so many studies with regard to anterolateral knee structures been performed. The anterolateral knee complex consists briefly of the iliotibial band, with its proximal and distal attachments, the joint capsule, and the anterolateral ligament (ALL). The recently introduced ALL has several different descriptions, making it difficult to build a consensus with regard to its anatomy. An extensive description of these structures, particularly the iliotibial band and the ALL, with regard to anatomy and imaging, will be provided in this article.
Role of polyphenols and nonpolyphenols against toxicity induced by fluoride: a comprehensive review
Authors: Claudio Samuel R. , Handan Bianca A. , Gomes de Moura Carolina F. , Viana Milena de Barros , Yamauchi Liria Y. , Aguiar Odair , Oshima Celina T.F. , Ribeiro Daniel A.
Published: April 2018

Since its discovery as an antimicrobial agent, fluoride has been used in the control of dental caries. Many studies have shown that the chronic exposure of fluoride in high concentrations causes adverse effects in multiple organs; the use of bioactive compounds present in foods as a tool to mitigate the effects of fluoride could potentially be useful for populations in different parts of the world are exposed to fluoride in a chronic and systemic way. Thus, the aim of this comprehensive review is to present and discuss the published papers that focused on the use of polyphenols and nonpolyphenols that can mitigate the harmful activities promoted by fluoride exposure. Certainly, these data will contribute toward a better understanding of the role of food compounds in the pathological outcomes induced by fluoride. The new information will be added to that already available for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.
Positive Surgical Margins in Favorable-Stage Differentiated Thyroid Cancer
Authors: Mercado Catherine E. , Drew Peter A. , Morris Christopher G. , Dziegielewski Peter T. , Mendenhall William M. , Amdur Robert J.
Published: April 2018

Objective:

The significance of positive margin in favorable-stage well-differentiated thyroid cancer is controversial. We report outcomes of positive-margin patients with a matched-pair comparison to a negative-margin group.

Materials and Methods:

A total of 25 patients with classic-histology papillary or follicular carcinoma, total thyroidectomy +/− node dissection, stage T1-3N0-1bM0, positive surgical margin at primary site, adjuvant radioactive iodine (I-131), and age older than 18 years were treated between 2003 and 2013. Endpoints were clinical and biochemical (thyroglobulin-only) recurrence-free survival. Matched-pair analysis involved a 1:1 match with negative-margin cases matched for overall stage and I-131 dose.

Results:

Recurrence-free survival in positive-margin patients was 71% at 10 years. No patient was successfully salvaged with additional treatment. Only 1 patient died of thyroid cancer. Recurrence-free survival at 10 years was worse with a positive (71%) versus negative (90%) margin (P=0.140).

Conclusions:

Cure with a microscopically positive margin was suboptimal (71%) despite patients having classic-histology papillary and follicular carcinoma, favorable stage, and moderate-dose I-131 therapy.
Correlation Between Extended Leukocyte Differential Count and Coronary Artery Disease
Authors: Chen Si , Zhang Shulan , Luan Haixia , Zeng Xiaoli , Li Yongzhe , Yuan Hui
Published: April 2018

Background:

Leukocyte count is closely associated with the risk of coronary artery disease (CAD). Levels of leukocyte subpopulations in patients with CAD, however, remain largely unknown.

Methods:

In this study, we compared the distributions and counts of 16 leukocyte subpopulations between 40 patients with CAD and 40 healthy controls using the CytoDiff flow cytometric system.

Results:

Our results demonstrated significant increases in the frequencies and counts of all monocytes, immature granulocytes, and B-lymphocytes in patients with CAD, suggesting that the levels of these leukocyte subpopulations may serve as potential biomarkers for diagnosis of CAD. By contrast, the levels of cytotoxic T/natural killer lymphocytes were markedly decreased in patients with CAD. In addition, the levels of T/natural killer lymphocytes, noncytotoxic T-lymphocytes, mature neutrophils, total neutrophils, eosinophils, basophils, and T-cell blasts in CAD patients with elevated levels of cardiac troponin I (cTnI), an independent indicator for poor prognosis in CAD, were significantly different from those in CAD patients with normal levels of cTnI. These data may help in the screening for biomarkers to discriminate between stable and unstable patients with CAD.

Conclusions:

Collectively, our results provide a detailed distribution profile of leukocyte subpopulations in patients with CAD and suggest their possible clinical application in predicting the risk and severity of CAD.
Embryo morphokinetic characteristics and euploidy
Authors: Pennetta Francesca , Lagalla Cristina , Borini Andrea
Published: April 2018

Purpose of review

The purpose of the current review is to provide an update on time-lapse morphokinetic assessment related to embryo ploidy status.

Recent findings

The main limitation of the available studies regarding correlation between morphokinetic variables and ploidy is that each embryo is considered as an independent unit whereas recent findings show that embryo kinetics may be affected by patient and ovarian stimulation-related factors, so that clustered data analysis is more appropriate. Moreover, some experimental evidences show how embryos with irregular developmental patterns, often used as deselection criteria, can evolve into usable embryos and give pregnancy.

Time lapse technology has allowed us to obtain a lot of information about human embryo development through the characterization of events that are otherwise not visible using static morphological observations. Many morphokinetic parameters have been tested in relation to a variety of outcomes including implantation potential, blastocyst development and ploidy status. Regarding to this last point, most efforts aim to unravel this relationship with conflicting results in their predictive ability. Furthermore, embryos originating from anomalous behaviour, although with a reduced developmental potential, may result in euploid and transferrable blastocysts.
Active Transcutaneous Bone Conduction Implant: Middle Fossa Placement Technique in Children With Bilateral Microtia and External Auditory Canal Atresia
Authors: Der Carolina , Bravo-Torres Sofía , Pons Nicolás
Published: April 2018

Aim:

The aim of this study is to present the middle fossa technique (MFT) as an alternative for patients who cannot undergo traditional surgery for active transcutaneous bone conduction implants (ATBCI) due to their altered anatomy or desire for future aesthetic reconstruction.

Design:

A case series descriptive study was designed. The MFT was developed. Preoperative and postoperative information from 24 patients with external auditory canal atresia (EACA) and implanted with ATBCI was reviewed.

Results:

A total of 24 children with bilateral EACA received implants in the middle cranial fossa. Their average age was 12. Of these patients, eight had an associated congenital disorder: Goldenhar Syndrome, Treacher Collins Syndrome or the Pierre Robin Sequence. The average follow-up was at 17 months (ranging from between 2– and 36 mo) and there were no major complications. Four patients showed skin erythema at the processor site after turn on, which was solved by lowering the magnet strength. One patient had a scalp hematoma that required puncture drainage. The hearing thresholds went down on average from 66.5 to 25.2 dB 1 month after turn on. Speech recognition improved respectively from 29.4% without and 78.9% with a bone conduction hearing aid to 96.4%.

Conclusion:

MFT placement of the ATBCI was proven to be safe and effective and a viable option for treating pediatric patients with EACA who cannot receive implants at the sinodural angle or in the retrosigmoidal position because of their altered anatomy and/or desire for future aesthetic reconstruction.
The Association Between Proton Pump Inhibitor Use With Acute Kidney Injury and Chronic Kidney Disease
Authors: Kamal Faisal , Khan Muhammad A. , Molnar Miklos Z. , Howden Colin W.
Published: April 2018

Proton pump inhibitors (PPIs) are among the most commonly prescribed medicines and are the mainstay of treatment for gastroesophageal reflux disease. Recently, there has been an increase in the use of these medicines for unclear and inappropriate indications. Although generally well tolerated and considered to be safe, several observational studies have linked PPI use with a variety of conditions such as pneumonia, Clostridium difficile infection, fractures, hypomagnesemia, and dementia. The well-established association between PPIs and acute interstitial nephritis has raised questions about whether they may also cause acute kidney injury and chronic kidney disease. Observational studies have evaluated these possible associations. This paper reviews the currently available literature about these associations and considers their possible underlying pathophysiological mechanisms. The level of evidence-linking PPI use with acute kidney injury and chronic kidney disease is weak and does not establish causality. More research is required to explore these possible associations further. The PPIs should be used in the lowest effective dose and inappropriate use should be avoided.
A Randomized Controlled Trial Comparing Nitazoxanide Plus Lactulose With Lactulose Alone in Treatment of Overt Hepatic Encephalopathy
Authors: Abd-Elsalam Sherief , El-Kalla Ferial , Elwan Nadia , Badawi Rehab , Hawash Nehad , Soliman Shaimaa , Soliman Samah , Elkhalawany Walaa , ElSawaf Mennat-Allah , Elfert Asem
Published: April 2018

Background and Aims:

Hepatic encephalopathy (HE) is a reversible spectrum of neuropsychiatric abnormalities associated with liver dysfunction. Lactulose is a nonabsorbable disaccharide presently used to treat HE. Nitazoxanide (NTZ) has a broad-spectrum activity against urease-producing bacteria, so it decreases ammonia production and is therefore expected to reverse the symptoms of HE. A previous pilot study on HE patients given NTZ and lactulose had encouraging results with regard to amelioration of the clinical picture. Patients showed improvement in mental status and the drug was well-tolerated. Results such as these are encouraging larger studies. The aim of this study was to compare the safety and adequacy of NTZ plus lactulose versus lactulose and placebo in management of overt HE.

Methods:

In total, 120 cirrhotic patients suffering from overt HE were randomly designated to take either NTZ plus lactulose (n=60) or lactulose and placebo (n=60). The Clinical Hepatic Encephalopathy Staging Scale (CHESS) score was assessed for all patients on inclusion to the study and 1 week from the start of treatment.

Results:

Both groups evinced an improvement in CHESS score at 1 week, yet the improvement was significantly better in the NTZ group as the score decreased from 4.15±2.09 to 0.00±0.00 compared with 4.96±2.29 to 1.28±0.91 in patients receiving lactulose and placebo (P-value <0.001).

Conclusions:

NTZ significantly decreases the CHESS score and improves mental status in the form of patient alertness, orientation, response to stimulation, and ability to talk. NTZ is safe and well-tolerated apart from infrequent epigastric pain.
Archaea
Authors: Brugère Jean-François , Ben Hania Wajdi , Arnal Marie-Edith , Ribière Céline , Ballet Nathalie , Vandeckerkove Pascal , Ollivier Bernard , O’Toole Paul W.
Published: April 2018

Pharmabiotics and probiotics in current use or under development belong to 2 of 3 domains of life, Eukarya (eg, yeasts) and Bacteria (eg, lactobacilli). Archaea constitute a third domain of life, and are currently not used as probiotics, despite several interesting features. This includes the absence of known pathogens in humans, animals, or plants and the existence of some archaea closely associated to humans in various microbiomes. We promote the concept that some specific archaea that naturally thrive in the human gut are potential next-generation probiotics that can be rationally selected on the basis of their metabolic phenotype not being encountered in other human gut microbes, neither Bacteria nor Eukarya. The example of the possible bioremediation of the proatherogenic compound trimethylamine into methane by archaeal microbes is described.
Choice Defines QALYs
Authors: Craig Benjamin M. , Rand Kim
Published: April 2018

Background:

The 5-level version of the EQ-5D (EQ-5D-5L) was introduced as an improvement on the original 3-level version (EQ-5D-3L). To date, 6 country-specific value sets have been published for EQ-5D-5L and 9 US value sets have been published for other instruments. Our aims were to (1) produce EQ-5D-5L values on a quality-adjusted life year (QALY) scale from the perspective of US adults and (2) compare them with US EQ-5D-3L values and the other country-specific EQ-5D-5L values.

Methods:

In 2016, 8222 US respondents from all 50 states and Washington, DC completed an online survey including a discrete choice experiment with 20 paired comparisons. Each comparison asked respondents, “Which do you prefer?” regarding a pair of alternatives described using EQ-5D-5L and lifespan attributes. On the basis of more than 50 choices on each of the 3160 pairs, we estimated EQ-5D-5L values on a QALY scale and compared them with the US EQ-5D-3L values and the other country-specific EQ-5D-5L values.

Results:

Ranging from −0.287 (55555) to 0.992 (11121) on a QALY scale, the estimated EQ-5D-5L values were similar to the US EQ-5D-3L values. Compared with the US EQ-5D-3L values, the values exhibited greater sensitivity and specificity and higher correlation with the EQ-5D-5L values of other countries, particularly England.

Conclusions:

Like previous US valuation studies, this study produced nationally representative EQ-5D-5L values on a QALY scale. The results further demonstrate the advantages of the EQ-5D-5L over its 3-level predecessor as a preference-based summary measure of health-related quality of life from the perspective of US adults.
Coverage of Medications That Treat Opioid Use Disorder and Opioids for Pain Management in Marketplace Plans, 2017
Authors: Huskamp Haiden A. , Riedel Lauren E. , Barry Colleen L. , Busch Alisa B.
Published: April 2018

Background:

Efficacious medications to treat opioid use disorders (OUDs) have been slow to diffuse into practice, and insurance coverage limits may be one important barrier.

Objectives:

To compare coverage for medications used to treat OUDs and opioids commonly prescribed for pain management in plans offered on the 2017 Health Insurance Marketplace exchanges.

Research Design:

We identified a sample of 100 plans offered in urban and in rural counties on the 2017 Marketplaces, weighting by population. We accessed publicly available plan coverage information on healthcare.gov for states with a federally facilitated exchange, the state exchange website for state-based exchanges, and insurer websites.

Results:

About 14% of plans do not cover any formulations of buprenorphine/naloxone. Plans were more likely to require prior authorization for any of the covered office-based buprenorphine or naltrexone formulations preferred for maintenance OUD treatment (ie, buprenorphine/naloxone, buprenorphine implants, injectable long-acting naltrexone) than of short-acting opioid pain medications (63.6% vs. 19.4%; P<0.0001). Only 10.6% of plans cover implantable buprenorphine, 26.1% cover injectable naltrexone, and 73.4% cover at least 1 abuse-deterrent opioid pain medication.

Conclusions:

Many Marketplace plans either do not cover or require prior authorization for coverage of OUD medications, and these restrictions are often more common for OUD medications than for short-acting opioid pain medications. Regulators tasked with enforcement of the Mental Health Parity and Addiction Equity Act, which requires that standards for formulary design for mental health and substance use disorder drugs be comparable to those for other medications, should focus attention on formulary coverage of OUD medications.
Examining Trends in Obstetric Quality Measures for Monitoring Health Care Disparities
Authors: Janevic Teresa , Egorova Natalia N. , Zeitlin Jennifer , Balbierz Amy , Hebert Paul L. , Howell Elizabeth A.
Published: April 2018

Background:

Elective delivery (ED) before 39 weeks, low-risk cesarean delivery, and episiotomy are routinely reported obstetric quality measures and have been the focus of quality improvement initiatives over the past decade.

Objective:

To estimate trends and differences in obstetric quality measures by race/ethnicity.

Research Design:

We used 2008–2014 linked birth certificate–hospital discharge data from New York City to measure ED before 39 gestational weeks (ED <39), low-risk cesarean, and episiotomy by race/ethnicity. Measures were following the Joint Commission and National Quality Forum specifications. Average annual percent change (AAPC) was estimated using Poisson regression for each measure by race/ethnicity. Risk differences (RD) for non-Hispanic black women, Hispanic women, and Asian women compared with non-Hispanic white women were calculated.

Results:

ED<39 decreased among whites [AAPC=−2.7; 95% confidence interval (CI), −3.7 to −1.7), while it increased among blacks (AAPC=1.3; 95% CI, 0.1–2.6) and Hispanics (AAPC=2.4; 95% CI, 1.4–3.4). Low-risk cesarean decreased among whites (AAPC=−2.8; 95% CI, −4.6 to −1.0), and episiotomy decreased among all groups. In 2008, white women had higher risk of most measures, but by 2014 incidence of ED<39 was increased among Hispanics (RD=2/100 deliveries; 95% CI, 2–4) and low-risk cesarean was increased among blacks (RD=3/100; 95% CI, 0.5–6), compared with whites. Incidence of episiotomy was lower among blacks and Hispanics than whites, and higher among Asian women throughout the study period.

Conclusions:

Existing measures do not adequately assess health care disparities due to modest risk differences; nonetheless, continued monitoring of trends is warranted to detect possible emergent disparities.
Osteopontin Levels in Human Milk Vary Across Countries and Within Lactation Period
Authors: Bruun Signe , Jacobsen Lotte Neergaard , Ze Xiaolei , Husby Steffen , Ueno Hiroshi M. , Nojiri Keisuke , Kobayashi Shunjiro , Kwon Jungil , Liu Xihong , Yan Shuyuan , Yang Jiyeon , Zachariassen Gitte , Chen Liang , Zhou Wei , Christensen Brian , Sørensen Esben S.
Published: April 2018

Objectives:

Osteopontin (OPN) is a multifunctional protein expressed in many cell types, tissues and body fluids with the highest concentrations found in milk; significantly higher in human than in bovine milk. Intervention studies have indicated beneficial effects of supplementing infant formula with bovine OPN. In this multicenter study, we determined the OPN content in human milk samples from 629 Chinese, Danish, Japanese and Korean mothers.

Methods:

At each study site, milk samples were collected and analyzed for OPN and protein concentration using ELISA and infrared spectroscopy, respectively.

Results:

A total of 829 milk samples from 629 women were included. When delivering the first sample, mean maternal age was 31.4 years (SD 4.0), and median infant age was 13.4 weeks (interquartile range 4.6–17.9). The median OPN concentration varied across sites; from 99.7 mg/L in Danish, 185.0 mg/L in Japanese, 216.2 mg/L in Korean to 266.2 mg/L in Chinese mothers (P < 0.001), corresponding to 1.3%, 2.4%, 1.8% and 2.7% of the total protein content (OPN/protein%) (P < 0.05), respectively. Based on 75 Chinese and 33 Japanese mothers delivering more than 1 sample, multilevel (mixed model) linear regression analysis showed a decrease in OPN concentration with infant age (β = (−11.3), 95% confidence interval (CI) = (−13.9) to (−8.8) and β = (−2.1), 95% CI = (−3.2) to (−0.9), respectively).

Conclusions:

In this large multicenter study, we observed statistically significant differences in the OPN concentration and the OPN/protein% in human milk samples between countries. Based on mothers delivering more than 1 sample, a significant decrease within the lactation period was observed.
Response to Long-term Vitamin D Therapy for Bone Disease in Children With Sickle Cell Disease
Authors: Williams Kristen M. , Lee Margaret T. , Licursi Maureen , Brittenham Gary M. , Fennoy Ilene
Published: April 2018

Patients with sickle cell disease (SCD) are at risk for bone fragility from multiple factors including vitamin D deficiency. To date, no studies have evaluated the efficacy and safety of long-term vitamin D therapy for bone disease in children with SCD. We report a cohort of 4 children with SCD found to have severe vitamin D deficiency, secondary hyperparathyroidism, and abnormal bone mineral density treated with monthly high-dose oral cholecalciferol over 2 years. All patients exhibited a positive response to therapy without hypervitaminosis D or hypercalcemia. Further studies are needed to standardize guidelines for optimal vitamin D dosing and prevention of toxicity.
Epigenetic Therapy in a Patient With Down Syndrome and Refractory Acute Myeloid Leukemia
Authors: Becktell Kerri , Houser Kerri , Burke Michael J.
Published: April 2018

Acute myeloid leukemia (AML) associated with Down syndrome (DS-AML) is a unique entity of AML with superior treatment response and overall survival compared with children with non–DS-AML. Despite good outcomes in DS-AML, those who relapse or have refractory disease have poor survival. Successful treatment of these patients is challenged by increased incidence of treatment-related toxicities often encountered with high-dose chemotherapy. Here we report the experience of epigenetic modifying agents (decitabine and vorinostat) followed by fludarabine, cytarabine, and granulocyte colony stimulating growth factor for a child with refractory DS-AML. This combination was well tolerated and resulted in a brief clinical response.
Trilineage Hematopoiesis Induced by Low-dose Eltrombopag in a Patient With Fanconi Anemia can be Used as a Bridge to Hematopoietic Stem Cell Transplant
Authors: Gupta Ashish , Palassery Rasmi , Meyerson Howard , Ahuja Sanjay , Matloub Yousif
Published: April 2018

Fanconi anemia (FA) is an autosomal recessive, progressive bone marrow failure disorder characterized by congenital defects and marked cancer predisposition. Hematopoietic stem cell transplant is the therapy of choice for FA patients with progressive pancytopenia. These patients receive multiple transfusions for cytopenias. Oxymetholone has been used with variable success to improve cytopenias. Eltrombopag has been shown to induce bilineage or trilineage hematopoiesis in aplastic anemia and patients with myelodysplastic marrow. We report a case of FA where eltrombopag in conjunction with oxymetholone induced trilineage hematopoiesis and eliminated transfusion requirement before transplant, thereby enhancing favorable outcome after hematopoietic stem cell transplant.
Self-reported upper limb functioning of pupils with cerebral palsy by the International Classification of Functioning, Disability, and Health
Authors: Lénárt Zoltán , Szabó-Szemenyei Eszter , Tóth Adrienn A. , Kullmann Lajos
Published: April 2018

International Classification of Functioning, Disability, and Health: Children and Youth Version has shown an increasing role in the assessment of children with cerebral palsy (CP), but just a few researchers use it for individuals’ self-assessment. In this study, we present the self-assessment of functioning of students with CP and changes by the end of a school year. Thirty-seven pupils with spastic CP involving upper limbs, 24 pupils with typical development, and 20 pupils with speech and language disorders were studied by International Classification of Functioning, Disability, and Health core sets for CP. The CP group reported limitations in sensory functions (P<0.05), movement-related functions (P<0.001), and mobility (P<0.001) as well as products and technology and support and relationships as supportive (P<0.05). Correlation between expert and self-evaluation was weak to moderate. The CP core set may appropriately serve in the self-assessment of pupils’ functioning in longitudinal studies.
Epstein-Barr Virus, High-Risk Human Papillomavirus and Abnormal Cervical Cytology in a Prospective Cohort of African Female Sex Workers
Authors: Cameron Jennifer E. , Rositch Anne F. , Vielot Nadja A. , Mugo Nelly R. , Kwatampora Jessie K.L. , Waweru Wairimu , Gilliland Aubrey E. , Hagensee Michael E. , Smith Jennifer S.
Published: April 2018

Background

High-oncogenic-risk human papillomavirus (hrHPV) is necessary, although insufficient, to promote cervical cancer. Like HPV, Epstein-Barr virus (EBV) is a common pathogen with the capacity to promote epithelial neoplasms. We examined the association between cervical EBV, hrHPV, and cytology in female sex workers in Nairobi, Kenya.

Methods

Women (n = 332) with known cervical cytology and hrHPV mRNA results were evaluated for cervical EBV DNA by conventional polymerase chain reaction. Prevalence ratios (PRs) were calculated to assess the relationships between EBV, hrHPV, and cervical cytology. Prospective analyses used risk ratios and time-to-event analyses to determine the association of EBV with hrHPV clearance and with abnormal cytology outcomes.

Results

Baseline prevalence of hrHPV and EBV was 29% and 19%, respectively. Higher EBV prevalence was found among women with older age, HIV, hrHPV, abnormal cytology, Mycoplasma genitalium infection, smoking habits, younger age at sexual debut, and less frequent condom use. At baseline, women with EBV had a higher prevalence of hrHPV infection than did EBV-negative women (52% vs. 24%; HIV-adjusted PR [95% confidence interval], 1.8 [1.3–2.6]). Epstein-Barr virus–positive women had a higher prevalence than did EBV-negative women of high-grade precancer (15% vs. 2%) and abnormal cytology (37% vs. 15%), although HIV- and hrHPV-adjusted associations were not significant (high-grade precancer: PR, 2.0 [0.7–5.9]; abnormal cytology: PR, 1.4 [0.9–2.2]). In prospective analyses, a marginal association was observed between baseline EBV detection and delayed hrHPV clearance.

Conclusions

Our data support a possible role for EBV as a high-risk marker or cofactor for HPV-mediated cervical cancer development.
The Proportion of Young Women Tested for Chlamydia Who Had Urogenital Symptoms in Physician Offices
Authors: Patel Chirag G. , Trivedi Shivika , Tao Guoyu
Published: April 2018

Using National Ambulatory Medical Care Survey data from 2006 to 2015, we estimated the proportions of young women tested for chlamydia who were symptomatic (urogenital symptoms) or asymptomatic in physician offices. Among women tested for chlamydia, the proportions of women with and without urogenital symptoms were 31.6% and 59.2%, respectively.
Tumor Syndromes Predisposing to Osteosarcoma
Authors: Hameed Meera , Mandelker Diana
Published: April 2018

Osteosarcoma (OS) is the most common primary bone tumor affecting predominantly adolescents and young adults. It accounts for about 5% of all childhood cancers. Although the majority of OSs are sporadic, a small percentage occur as a component of hereditary cancer syndromes. Early onset, bilateral, multifocal, and metachronous tumors suggest genetic predisposition. The inheritance patterns can be autosomal dominant or recessive. These syndromes predispose to a wide variety of mesenchymal and epithelial cancers with propensity for certain mutations being prevalent in specific cancer subtypes. Li-Fraumeni syndrome, retinoblastoma, Rothmund-Thompson syndrome (type 2), Werner syndrome, and Bloom syndrome, constitute the majority of the tumor syndromes predisposing to OS and will be the focus for this review.
Are Sporadic Eosinophilic Solid and Cystic Renal Cell Carcinomas Characterized by Somatic Tuberous Sclerosis Gene Mutations?
Authors: Parilla Megan , Kadri Sabah , Patil Sushant A. , Ritterhouse Lauren , Segal Jeremy , Henriksen Kammi J. , Antic Tatjana
Published: April 2018

Eosinophilic solid and cystic renal cell carcinomas (ESC RCC) is a rare, unique tumor type not yet included in the World Health Organization classification of renal neoplasia. Separately, RCCs found in patients with tuberous sclerosis complex (TSC) have recently been categorized into 3 morphologic groups: RCC with a tubulopapillary architecture separated by smooth muscle stroma, chromophobe-like, and eosinophilic-microcytic type. The third classification has been identified in ∼11% of TSC-associated RCC and have histology identical to ESC RCCs. The sporadic form of ESC RCC, not associated with TSC, have only been characterized on the cytogenetic level and the full molecular underpinnings have yet to be examined. Using next-generation sequencing we present 2 cases of sporadic ESC RCC in patients without clinical features of tuberous sclerosis, which demonstrate pathogenic somatic TSC2 gene mutations. These mutations are without other alterations in any other genes associated with RCC, suggesting that sporadic ESC RCC may be characterized by somatic tuberous sclerosis gene mutations (TSC2).
Traumatic Brain Injury and Infectious Encephalopathy in Children From Four Resource-Limited Settings in Africa*
Authors: Fink Ericka L. , von Saint Andre-von Arnim Amelie , Kumar Rashmi , Wilson Patrick T. , Bacha Tigist , Aklilu Abenezer Tirsit , Teklemariam Tsegazeab Laeke , Hooli Shubhada , Tuyisenge Lisine , Otupiri Easmon , Fabio Anthony , Gianakas John , Kochanek Patrick M. , Angus Derek C. , Tasker Robert C.
Published: April 2018

Objectives:

To assess the frequency, interventions, and outcomes of children presenting with traumatic brain injury or infectious encephalopathy in low-resource settings.

Design:

Prospective study.

Setting:

Four hospitals in Sub-Saharan Africa.

Patients:

Children age 1 day to 17 years old evaluated at the hospital with traumatic brain injury or infectious encephalopathy.

Interventions:

None.

Measurements and Main Results:

We evaluated the frequency and outcomes of children presenting consecutively over 4 weeks to any hospital department with traumatic brain injury or infectious encephalopathy. Pediatric Cerebral Performance Category score was assessed pre morbidity and at hospital discharge. Overall, 130 children were studied (58 [45%] had traumatic brain injury) from hospitals in Ethiopia (n = 51), Kenya (n = 50), Rwanda (n = 20), and Ghana (n = 7). Forty-six percent had no prehospital care, and 64% required interhospital transport over 18 km (1–521 km). On comparing traumatic brain injury with infectious encephalopathy, there was no difference in presentation with altered mental state (80% vs 82%), but a greater proportion of traumatic brain injury cases had loss of consciousness (80% vs 53%; p = 0.004). Traumatic brain injury patients were older (median [range], 120 mo [6–204 mo] vs 13 mo [0.3–204 mo]), p value of less than 0.001, and more likely male (73% vs 51%), p value of less than 0.01. In 78% of infectious encephalopathy cases, cause was unknown. More infectious encephalopathy cases had a seizure (69% vs 12%; p < 0.001). In regard to outcome, infectious encephalopathy versus traumatic brain injury: hospital lengths of stay were longer for infectious encephalopathy (8 d [2–30 d] vs 4 d [1–36 d]; p = 0.003), discharge rate to home, or for inpatient rehabilitation, or death differed between infectious encephalopathy (85%, 1%, and 13%) and traumatic brain injury (79%, 12%, and 1%), respectively, p value equals to 0.044. There was no difference in the proportion of children surviving with normal or mild disability (73% traumatic brain injury vs 79% infectious encephalopathy; p = 0.526).

Conclusions:

The epidemiology and outcomes of pediatric traumatic brain injury and infectious encephalopathy varied by center and disease. To improve outcomes of these conditions in low-resource setting, focus should be on neurocritical care protocols for pre-hospital, hospital, and rehabilitative care.
A Comparison of Robotic Versus Open Thyroidectomy for Papillary Thyroid Cancer
Authors: Paek Se Hyun , Kang Kyung Ho , Park Sung Jun
Published: April 2018

Objectives:

This study investigated the potential advantages of robotic thyroidectomy and determined whether it is safe and complete compared with conventional open surgery in patients with papillary thyroid cancer.

Materials and Methods:

A total 376 consecutive patients who underwent total thyroidectomy and central neck dissection for papillary thyroid cancer from February 2013 to July 2014 were retrospectively reviewed. Postoperative complication rates and surgical completeness were compared between the robotic and open groups.

Results:

Transient hypoparathyroidism was higher in the open group (10.5%) compared with the robotic group (2.8%; P=0.042). There were no differences in mean number of retrieved or metastatic lymph nodes. The mean values of stimulated thyroglobulin level were acceptably low in both groups. There was no difference in the proportion of patients with stimulated thyroglobulin levels <1 ng/mL.

Conclusion:

Our study results show that outcomes of robotic thyroidectomy may be similar to that of conventional thyroidectomy, with possible better preservation of the parathyroid blood supply.
Reinventing the wheel: Impact of prolonged antibiotic exposure on multidrug-resistant ventilator-associated pneumonia in trauma patients
Authors: Lewis Richard H. , Sharpe John P. , Swanson Joseph M. , Fabian Timothy C. , Croce Martin A. , Magnotti Louis J.
Published: April 2018

BACKGROUND

Multidrug-resistant (MDR) strains of both Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PA) as causative ventilator-associated pneumonia (VAP) pathogens are becoming increasingly common. Still, the risk factors associated with this increased resistance have yet to be elucidated. The purpose of this study was to examine the changing sensitivity patterns of these pathogens over time and determine which risk factors predict MDR in trauma patients with VAP.

METHODS

Patients with either AB or PA VAP over 10 years were stratified by pathogen sensitivity (sensitive [SEN] and MDR), age, severity of shock, and injury severity. Prophylactic and empiric antibiotic days, risk factors for severe VAP, and mortality were compared. Multivariable logistic regression was performed to determine which risk factors were independent predictors of MDR.

RESULTS

Three hundred ninety-seven patients were identified with AB or PA VAP. There were 173 episodes of AB (91 SEN and 82 MDR) and 224 episodes of PA (170 SEN and 54 MDR). The incidence of MDR VAP did not change over the study (p = 0.633). Groups were clinically similar with the exception of 24-hour transfusions (14 vs. 19 units, p = 0.009) and extremity Abbreviated Injury Scale (AIS) score (1 vs. 3, p < 0.001), both significantly increased in the MDR group. Antibiotic exposure as well as multiple episodes of inadequate empiric antibiotic therapy (mIEAT) (63% vs. 81%, p < 0.001) were significantly increased in the MDR group. Multivariable logistic regression identified prophylactic antibiotic days (odds ratio, 23.1; 95% confidence interval, 16.7–28, p < 0.001) and mIEAT (odds ratio, 18.1; 95% confidence interval, 12.2–26.1, p = 0.001) as independent predictors of MDR after adjusting for severity of shock, injury severity, severity of VAP, and antibiotic exposure.

CONCLUSION

Prolonged exposure to unnecessary antibiotics remains one of the strongest predictors for the development of antibiotic resistance. Multivariable logistic regression identified prophylactic antibiotic days and mIEAT an independent risk factors for MDR VAP. Thus, limiting prophylactic antibiotic days is the only potentially modifiable risk factor for the development of MDR VAP in trauma patients.

LEVEL OF EVIDENCE

Level IV Therapeutic; level III Prognostic.
Beyond Core Object Recognition: Recurrent processes account for object recognition under occlusion
Authors: Rajaei Karim , Mohsenzadeh Yalda , Ebrahimpour Reza , Khaligh-Razavi Seyed-Mahdi
Published: April 2018

Core object recognition, the ability to rapidly recognize objects despite variations in their appearance, is largely solved through the feedforward processing of visual information. Deep neural networks are shown to achieve human-level performance in these tasks, and explain the primate brain representation. On the other hand, object recognition under more challenging conditions (i.e. beyond the core recognition problem) is less characterized. One such example is object recognition under occlusion. It is unclear to what extent feedforward and recurrent processes contribute in object recognition under occlusion. Furthermore, we do not know whether the conventional deep neural networks, such as AlexNet, which were shown to be successful in solving core object recognition, can perform similarly well in problems that go beyond the core recognition. Here, we characterize neural dynamics of object recognition under occlusion, using magnetoencephalography (MEG), while participants were presented with images of objects with various levels of occlusion. We provide evidence from multivariate analysis of MEG data, behavioral data, and computational modelling, demonstrating an essential role for recurrent processes in object recognition under occlusion. Furthermore, the computational model with local recurrent connections, used here, suggests a mechanistic explanation of how the human brain might be solving this problem.

Author Summary

In recent years, deep-learning-based computer vision algorithms have been able to achieve human-level performance in several object recognition tasks. This has also contributed in our understanding of how our brain may be solving these recognition tasks. However, object recognition under more challenging conditions, such as occlusion, is less characterized. Temporal dynamics of object recognition under occlusion is largely unknown in the human brain. Furthermore, we do not know if the previously successful deep-learning algorithms can similarly achieve human-level performance in these more challenging object recognition tasks. By linking brain data with behavior, and computational modeling, we characterized temporal dynamics of object recognition under occlusion, and proposed a computational mechanism that explains both behavioral and the neural data in humans. This provides a plausible mechanistic explanation for how our brain might be solving object recognition under more challenging conditions.
A Whole-Plant Monocot from the Early Cretaceous
Authors: Liu Zhong-Jian , Chen Li-Jun , Wang Xin
Published: April 2018

The Yixian Formation (the Lower Cretaceous) of China is world famous for its fossils of early angiosperms. Although these diverse angiosperms demonstrate an unexpectedly great diversity, few are preserved as whole plants (not mention of monocots), making our understanding of them incomplete. Here, we report a fossil angiosperm,Sinoherba ningchenensisgen. et sp. nov (Sinoherbaceae fam. nov.), from the Yixian Formation of China; this fossil has a physically connected underground stem with fibrous rootlets, a stem with branches and nodes, leaves with parallel-reticulate veins, and a panicle of female flowers with an ovary surrounded by perianth. Morphological and phylogenetic analyses revealed thatSinoherbais an herbaceous monocot taxon. This newly discovered fossil underscores the great diversity of angiosperms in the Lower Cretaceous Yixian Formation.
Representation of auditory motion directions and sound source locations in the human planum temporale
Authors: Battal Ceren , Rezk Mohamed , Mattioni Stefania , Vadlamudi Jyothirmayi , Collignon Olivier
Published: April 2018

The ability to compute the location and direction of sounds is a crucial perceptual skill to efficiently interact with dynamic environments. How the human brain implements spatial hearing is however poorly understood. In our study, we used fMRI to characterize the brain activity of male and female humans listening to left, right, up and down moving as well as static sounds. Whole brain univariate results contrasting moving and static sounds varying in their location revealed a robust functional preference for auditory motion in bilateral human Planum Temporale (hPT). Using independently localized hPT, we show that this region contains information about auditory motion directions and, to a lesser extent, sound source locations. Moreover, hPT showed an axis of motion organization reminiscent of the functional organization of the middle-temporal cortex (hMT+/V5) for vision. Importantly, whereas motion direction and location rely on partially shared pattern geometries in hPT, as demonstrated by successful cross-condition decoding, the responses elicited by static and moving sounds were however significantly distinct. Altogether our results demonstrate that the hPT codes for auditory motion and location but that the underlying neural computation linked to motion processing is more reliable and partially distinct from the one supporting sound source location.

SIGNIFICANCE STATEMENT

In comparison to what we know about visual motion, little is known about how the brain implements spatial hearing. Our study reveals that motion directions and sound source locations can be reliably decoded in the human Planum Temporale (hPT) and that they rely on partially shared pattern geometries. Our study therefore sheds important new lights on how computing the location or direction of sounds are implemented in the human auditory cortex by showing that those two computations rely on partially shared neural codes. Furthermore, our results show that the neural representation of moving sounds in hPT follows a “preferred axis of motion” organization, reminiscent of the coding mechanisms typically observed in the occipital hMT+/V5 region for computing visual motion.
A neural signature of pattern separation in the monkey hippocampus
Authors: Sakon John J. , Suzuki Wendy A.
Published: April 2018

The CA3 and dentate gyrus (DG) regions of the hippocampus are considered key for disambiguating sensory inputs from similar experiences in memory, a process termed pattern separation. The neural mechanisms underlying pattern separation, however, have been difficult to compare across species: rodents offer robust recording methods with less human-centric tasks while humans provide complex behavior with less recording potential. To overcome these limitations, we trained monkeys to perform a visual pattern separation task similar to those used in humans while recording activity from single CA3/DG neurons. We find that when animals discriminate recently seen novel images from similar (lure) images, behavior indicative of pattern separation, CA3/DG neurons respond to lure images more like novel than repeat images. Using a population of these neurons, we are able to classify novel, lure, and repeat images from each other using this pattern of firing rates. Notably, one subpopulation of these neurons is more responsible for distinguishing lures and repeats—the key discrimination indicative of pattern separation.
Low-frequency direct cortical stimulation of left superior frontal gyrus enhances working memory performance
Authors: Alagapan Sankaraleengam , Lustenberger Caroline , Hadar Eldad , Shin Hae Won , Fröhlich Flavio
Published: April 2018

The neural substrates of working memory are spread across prefrontal, parietal and cingulate cortices and are thought to be coordinated through low frequency cortical oscillations in the theta (3 – 8 Hz) and alpha (8 – 12 Hz) frequency bands. While the functional role of many subregions have been elucidated using neuroimaging studies, the role of superior frontal gyrus (SFG) is not yet clear. Here, we combined electrocorticography and direct cortical stimulation in three patients implanted with subdural electrodes to assess if superior frontal gyrus is indeed involved in working memory. We found left SFG exhibited task-related modulation of oscillations in the theta and alpha frequency bands specifically during the encoding epoch. Stimulation at the frequency matched to the endogenous oscillations resulted in reduced reaction times in all three participants. Our results support the causal role of SFG in working memory and suggest that SFG may coordinate working memory through low-frequency oscillations thus bolstering the feasibility of targeting oscillations for restoring cognitive function.
The impact of fibronection stripe patterns on the cellular and nuclear morphology of fibroblasts
Authors: Mamaghani Pooya , Donald Athene M.
Published: April 2018

The effect of biochemical environmental signals on cell mechanisms has been the subject of numerous studies for a long time. However, the in-vitro studies of biophysical cues on cells and tissues have recently become a popular focus of research. The development of micro-fabrication techniques has allowed the study of certain aspects of cell-substrate interactions in a more detailed form. Micro-topographical patterns on the cell substrates have been used to study many cell functions such as cell migration, adhesion, gene expression, cell division and differentiation. An understanding of cell-substrate interactions and the potential ability to control the interactions have very important applications in the field of tissue engineering and regenerative medicine. We have fabricated ridge-groove micro patterns on polydimethylsiloxane (PDMS) substrates with different ridge widths (8μm, 10μm, 12 μm, 25μm and 50μm) using standard photolithography technique. We used these patterns to print fibronectin stripes on PDMS substrates. NIH/3T3 fibroblast cells were cultured on these stripes and the dynamics of morphological changes were monitored in steady spreading phase (S-phase). Our data revealed that the thickness of the cell, measured by confocal microscopy, is considerably larger (approximately 40%) among the cells spreading on narrower stripes (8μm, 10μm and 12μm) compared to the cells expanding on wider (including control) patterns. The number of perinuclear actin stress fibers is significantly lower among narrower stripes which probably explains the cell thickness results. Confocal microscopy revealed that the cellular volume increases during cell adhesion processes and volume increase is positively correlated with the width of stripes. Nuclear volume also increases considerably during cell adhesion; however, confining cells on fibronectin stripes reduces nuclear volume enlargement independent from the of stripe size.