bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Antiretroviral Therapy During Pregnancy and Adverse Birth Outcomes Among Women Living With HIV-1 in Low- and Middle-Income Countries: A Systematic Review
Authors: Saleska Jessica Londeree , Turner Abigail Norris , Maierhofer Courtney , Clark Jan , Kwiek Jesse J.
Published: May 2018

Background:

Worldwide, nearly 18 million women of reproductive age are living with HIV-1. Although increased access to antiretroviral therapy (ART) during pregnancy has significantly reduced HIV-1 mother-to-child transmission (MTCT), a similarly robust reduction in preterm birth (PTB) and low birthweight (LBW) among infants born to women living with HIV has not been observed. This study was designed to identify associations between classes of ART regimens and risk of PTB or LBW.

Setting:

Low- and middle-income countries.

Methods:

We conducted a systematic review of randomized and observational studies that assessed the effect of ART regimen on the risk of PTB (≤37 completed weeks of gestation) or LBW (<2500 g at birth) among pregnant women in low- and middle-income countries living with HIV-1. We searched Medline, COCHRANE, Web of Science, SCOPUS, and CPCI-S for included studies.

Results:

When compared to monotherapy, both nonnucleoside reverse transcriptase inhibitor– and protease inhibitor–based regimens had a consistent, harmful association with LBW. There is mixed evidence suggesting both potential harm and potential benefit for most other regimens on risk of LBW and PTB, and the harmful or protective effects of certain regimens varies depending on the drug backbone.

Conclusions:

Although the benefits of ART during pregnancy for prevention of MTCT are undisputed, this systematic review indicates that ART regimens vary substantially in their association with LBW and PTB. Although challenging, optimization of ART regimens could simultaneously promote maternal health, prevent MTCT, and also minimize risks of PTB and LBW.
Getting hypervirulent Klebsiella pneumoniae on the radar screen
Authors: Sellick John A. , Russo Thomas A.
Published: May 2018

Purpose of review

Two pathotypes of Klebsiella pneumoniae cause human infections, classical (cKp) and hypervirulent (hvKp) K. pneumoniae. The present understanding of genetic elements, the need for an accurate test to identify hvKp, the clinical implications of infection, the knowledge gap on how and why hvKp colonization transitions to infection, and potential infection prevention and control issues for hvKp are discussed.

Recent findings

Infections because of hvKp are increasingly recognized worldwide. Its ability to cause organ and life-threatening disease in healthy individuals from the community merits concern, which has been magnified by increasing descriptions of multiply drug-resistant (MDR) and extensively drug-resistant (XDR) strains. Increased capsule and siderophore production by hvKp relative to cKp are critical virulence traits. Asians are most commonly infected, but whether this is mediated by a genetic susceptibility, or increased exposure and colonization is unknown. Specific studies about the epidemiology and transmission of hvKp are lacking, but precautions are appropriate for MDR/XDR strains and perhaps all infected/colonized individuals.

hvKp is evolving into an increasingly concerning pathogen, in part because of the development of XDR strains. An accurate test to identify hvKp is needed for optimal clinical care, epidemiological, and research studies. An improved understanding of how infection develops, if a genetic susceptibility exists, and appropriate infection prevention and control measures also are needed.
Clinical Evaluation of a Multiparametric Deep Learning Model for Glioblastoma Segmentation Using Heterogeneous Magnetic Resonance Imaging Data From Clinical Routine
Authors: Perkuhn Michael , Stavrinou Pantelis , Thiele Frank , Shakirin Georgy , Mohan Manoj , Garmpis Dionysios , Kabbasch Christoph , Borggrefe Jan
Published: May 2018

Objectives

The aims of this study were, first, to evaluate a deep learning–based, automatic glioblastoma (GB) tumor segmentation algorithm on clinical routine data from multiple centers and compare the results to a ground truth, manual expert segmentation, and second, to evaluate the quality of the segmentation results across heterogeneous acquisition protocols of routinely acquired clinical magnetic resonance imaging (MRI) examinations from multiple centers.

Materials and Methods

The data consisted of preoperative MRI scans (T1, T2, FLAIR, and contrast-enhanced [CE] T1) of 64 patients with an initial diagnosis of primary GB, which were acquired in 15 institutions with varying protocols. All images underwent preprocessing (coregistration, skull stripping, resampling to isotropic resolution, normalization) and were fed into an independently trained deep learning model based on DeepMedic, a multilayer, multiscale convolutional neural network for detection and segmentation of tumor compartments. Automatic segmentation results for the whole tumor, necrosis, and CE tumor were compared with manual segmentations.

Results

Whole tumor and CE tumor compartments were correctly detected in 100% of the cases; necrosis was correctly detected in 91% of the cases. A high segmentation accuracy comparable to interrater variability was achieved for the whole tumor (mean dice similarity coefficient [DSC], 0.86 ± 0.09) and CE tumor (DSC, 0.78 ± 0.15). The DSC for tumor necrosis was 0.62 ± 0.30. We have observed robust segmentation quality over heterogeneous image acquisition protocols, for example, there were no correlations between resolution and segmentation accuracy of the single tumor compartments. Furthermore, no relevant correlation was found between quality of automatic segmentation and volume of interest properties (surface-to-volume ratio and volume).

Conclusions

The proposed approach for automatic segmentation of GB proved to be robust on routine clinical data and showed on all tumor compartments a high automatic detection rate and a high accuracy, comparable to interrater variability. Further work on improvements of the segmentation accuracy for the necrosis compartments should be guided by the evaluation of the clinical relevance.

Therefore, we propose this approach as a suitable building block for automatic tumor segmentation to support radiologists or neurosurgeons in the preoperative reading of GB MRI images and characterization of primary GB.
Galactocele, Pitfall for the Evaluation by 18F-FDG PET/CT
Authors: Ceyrat Quentin , Ziade Caroline , Tlili Ghoufrane , Fernandez Philippe , Meyer Marie
Published: May 2018

A high 18F-FDG uptake was found in mammary lesions in a 36-year-old woman who underwent a PET/CT scan for initial staging of diffuse large B-cell lymphoma. The patient has given birth 2 months ago and was breastfeeding. Ultrasound-guided fine-needle aspiration of 1 lesion yielded creamy liquid consistent with milk and confirmed the diagnosis of galactocele.
68Ga-PSMA PET/MR–Positive, Histopathology-Proven Prostate Cancer in a Patient With Negative Multiparametric Prostate MRI
Authors: Muehlematter Urs J. , Rupp Niels J. , Mueller Julian , Eberli Daniel , Burger Irene A.
Published: May 2018

Multiparametric MRI incorporating T2-weighted, diffusion-weighted, and dynamic contrast material–enhanced sequences is currently used for detection and localization of clinically important prostate cancer (PCa). The 68Ga-labeled PET tracer targeting the prostate-specific membrane antigen (PSMA, 68Ga-PSMA-11) is a promising diagnostic approach for staging and restating PCa. Recent studies suggest that 68Ga-PSMA could also be used for primary PCa detection and localization. We report a case of a 68Ga-PSMA PET/MR-positive lesion of the peripheral zone in a 73-year-old man with a negative preceding multiparametric MRI. Radical prostatectomy and subsequent histopathologic examination confirmed a Gleason 4 + 4 PCa.
Impact of Acellular Dermal Matrix on Postsurgical Wound Fluid Biomarkers in Prosthetic Breast Reconstruction
Authors: Hsia Henry C. , Weaver Michael R. , Schwarzbauer Jean E.
Published: May 2018

Background

Despite the widespread practice of using biologic scaffolds for soft tissue reinforcement over prosthetic implants, the impact of acellular dermal matrix (ADM) on surgical wound fluid biomarkers over the initial postoperative period after prosthetic breast reconstruction remains poorly understood.

Methods

Patients undergoing prosthetic breast reconstruction surgery where ADM was likely to be used were consented to have fluid samples collected from surgical drains after surgery. Sample collections occurred at an “Early” time point at 24 to 48 hours after surgery and then a “Late” time point approximately 1 to 2 weeks after surgery. All procedures were performed by a single surgeon. Acellular dermal matrix was placed when prosthetic coverage with autologous tissue could not be achieved. Laboratory analyses were performed in blinded fashion without the knowledge of whether the samples came from the ADM “Present” or “Not Present” group.

Results

Twenty-one patients were in the ADM Present group and 18 patients were in the Not Present group. Both groups showed similar demographics based on age and body mass index. Analyses for cell concentration, protein concentration, extracellular matrix protein levels, cell proliferation activity, and matrix metalloproteinase activity showed no significant differences between wound fluid samples from the 2 groups.

Conclusions

The presence of ADM does not appear to significantly impact wound biomarkers in prosthetic breast reconstruction. The current study provides useful data regarding the impact of ADM on surgical wound fluid during the initial postoperative period, laying important groundwork for more extensive future studies on the impact of biologic scaffolds on wound biology.
Single-Center Surgical Experience of the Treatment of Craniopharyngiomas With Emphasis on the Operative Approach: Endoscopic Endonasal and Open Microscopic Transcranial Approaches
Authors: Ozgural Onur , Kahilogullari Gokmen , Dogan Ihsan , Al-Beyati Eyyub S.M. , Bozkurt Melih , Tetik Bora , Comert Ayhan , Meco Cem , Unlu Agahan
Published: May 2018

This study aimed to report the authors’ single-center clinical experience about craniopharyngiomas and discuss surgical outcomes of these patients according to the type of surgical approach (endoscopic endonasal or open microscopic transcranial approach).

Twenty-four patients diagnosed with craniopharyngiomas between May 2013 and April 2017 were considered for inclusion. The patients were divided into 2 groups according to the surgical approach (open transcranial microscopic approach [group A] and endoscopic endonasal approach [group B]). These groups were compared in terms of postoperative surgical outcome scores (extent of tumor removal, visual deficit, hydrocephalus, metabolic disorders, and Glasgow coma scale) and hospitalization interval.

There was no patient of mortality in both groups. In this study, 4 of the 13 patients in group A and 9 of the 11 patients in group B underwent gross total resection. However, 1 patient in group B underwent repair because of cerebrospinal fluid leakage postoperatively. In addition, 1 patient in group A had a wound healing problem postoperatively. The postoperative outcome scores were 9.5 in group A and 11.5 in group B. The hospitalization interval in group A (range, 7–9 days) was longer than that in group B (range, 5–7 days).

The endoscopic endonasal approach should be considered the first-line surgical treatment modality in patients with a preliminary diagnosis of craniopharyngioma in terms of low complication risk, minimal invasiveness, and better outcome scores. Open microscopic transcranial procedures may be combined with this approach in a single session for challenging cases.
Autologous Fat Used for Facial Filling Can Lead to Massive Cerebral Infarction Through Middle Cerebral Artery or Facial Intracranial Branches
Authors: Wang Xian , Wu Min , Zhou Xing , Liu Hengdeng , Zhang Yongchao , Wang Haiping
Published: May 2018

Background:

Autologous fat injection is a procedure aimed at eliminating grave defects in the skin surface by subcutaneous injection of the patient's fatty tissue. Fat embolism is a rare but severe complication of this procedure, especially cerebral infarction. It is first reported by Thaunat in 2004.

Methods:

were presented to the hospital with sudden unconsciousness and left limb weakness in 24 hours after facial fat injection. Brain computed tomography and magnetic resonance imaging were performed immediately after admission. Frontal temporoparietal decompressive craniectomy plus multiple treatments scheduled for patients. Pictures and videos were taken during follow-up. Figures are edited with Adobe Photograph CS6.

Results:

Patients were diagnosed with extensive cerebral infarction of the right hemisphere through the middle cerebral artery or facial-intracranial branches.

Conclusion:

Routine cosmetic procedures of facial fat injections could cause devastating and even fatal complications to patients. The small volume of fat grafts can be inserted through the internal carotid artery or go through the communicating branches between the facial artery and the intracranial artery into the brain.
Resorbable Material for Pediatric Orbital Floor Reconstruction
Authors: Azzi Jayson , Azzi Alain Joe , Cugno Sabrina
Published: May 2018

Introduction:

The use of resorbable materials is becoming more popular for pediatric orbital floor reconstruction. The purpose of this systematic review is to evaluate the effectiveness and safety of the various materials used in pediatric orbital floor reconstruction.

Methods:

A systematic literature search was performed to identify all relevant articles reporting complications following pediatric orbital floor reconstruction. The search included published articles in three electronic databases—Ovid MEDLINE, EMBASE, and PubMed starting from database establishment to July 2017. Primary endpoints were enophthalmos, diplopia, and infection. Resorbable material was compared to autologous grafts and nonresorbable material.

Results:

A total of 14 studies containing 248 patients were included in this review. Fifty-four (21.8%) patients had reconstruction performed with autologous grafts, 72 (29.0%) patients with resorbable material, and 122 (49.2%) patients with nonresorbable material. Resorbable materials had the lowest rate of postoperative enophthalmos (3/52; 5.8%) and the highest rate of postoperative diplopia (19/72; 26.4%). In contrast, nonresorbable materials had the lowest rate of postoperative diplopia (5/122; 4.1%), the highest rate of postoperative enophthalmos (14/102; 13.7%). Autologous reconstruction was associated with an 11.1% (4/36) rate of postoperative enophthalmos and a 22.2% (12/54) rate of postoperative diplopia. Nine cases (8.8%) of postoperative infection were documented with nonresorbable materials. No cases of infection were reported with autologous grafts or resorbable materials.

Conclusion:

Newer resorbable implants are safe and have a similar complication profile as traditional autologous grafts in pediatric orbital floor reconstruction.
The Outcome Analysis of Traumatic Facial Nerve Palsy Treated With Systemic Steroid Therapy
Authors: Lee Ping-Hsun , Liang Chi-Cheng , Huang Shiang-Fu , Liao Han-Tsung
Published: May 2018

Purpose:

Although facial nerve palsy is uncommon after a blunt craniofacial injury, it will result in functional and aesthetic disability if full recovery is not achieved. Currently, the management is still controversial and mainly through systemic steroid therapy or surgical decompression. However, current studies mainly focus on the surgical intervention, and only a few of these studies discuss the details of the steroid treatments. Thus, the purpose of this study is to analyze possible prognosis factors of systemic steroid in managing traumatic facial nerve palsy after a blunt craniofacial injury retrospectively.

Methods:

During the period from May 2005 to April 2015 at Chang Gung Memorial Hospital, a total of 26 patients who suffered from post-traumatic facial nerve palsy receiving steroid therapy were enrolled in the study. All the patient's charts were reviewed, recorded, and analyzed including the general data, temporal bone fracture type, hospital courses, trauma-related data from emergency room records, and initial and final facial nerve palsy grading. The facial nerve palsy was graded using the House-Brackmann (HB) system; the final HB grade I was set as full recovery.

Results:

The outcome showed steroid therapy onset within 24 hours (odds ratio [OR] = 10.111; 95% confidence interval [CI] = 1.597–64.005; P = 0.014) and steroid therapeutic duration for longer than 14 days (OR = 11.571; 95% CI = 1.172–114.262; P = 0.036) possessed a significantly better recovery rate.

Conclusion:

This study recommends to apply steroids within 24 hours once post-traumatic facial palsy occurs and the therapy should persist longer than 14 days.
Virtual Surgical Planning Assisted Management for Three-Dimensional Dentomaxillofacial Deformities
Authors: Helal Hussein , Wang Yu , Qin Zhifan , Wang Peng , Xiang Zichao , Li Jihua
Published: May 2018

Objective:

Treatment of 3-dimensional dentomaxillofacial deformities remains a significant clinical challenge. This retrospective study aims to present the modalities of management for complex 3-dimensional dentomaxillofacial deformities with the assistance of virtual surgical planning (VSP) and 3-dimensional printed navigation templates.

Study Design:

Ten patients diagnosed with complex 3-dimensional dentomaxillofacial deformities received treatment of combined orthodontics and orthognathic surgery. Various surgical techniques as well as bone graft and distraction osteogenesis were used under the guidance of VSP and 3-dimensional printed navigation templates according to the characteristics of each patient. Follow-up included clinical examination and studies of spiral computed tomography preoperatively and for an average of 12 months postoperatively.

Result:

The clinical outcomes of patients showed that VSP was successfully transferred to actual surgery in all the 10 patients. Three-dimensional dentomaxillofacial deformities were corrected significantly. Satisfactory profiles and occlusion were achieved.

Conclusion:

The management of 3-dimensional dentomaxillofacial deformities required comprehensive consideration and detailed surgical planning. Virtual surgical planning serves as a reliable assistance in the management of 3-dimensional dentomaxillofacial deformities.
Heart Rate Variability, Clinical and Laboratory Measures to Predict Future Deterioration in Patients Presenting With Sepsis
Authors: Barnaby Douglas P. , Fernando Shannon M. , Herry Christophe L. , Scales Nathan B. , Gallagher Edward John , Seely Andrew J. E.
Published: May 2018

Background:

Risk stratification of patients presenting to the emergency department (ED) with sepsis can be challenging. We derived and evaluated performance of a predictive model containing clinical, laboratory, and heart rate variability (HRV) measures to quantify risk of deterioration in this population.

Methods:

ED patients aged 21 and older satisfying the 1992 consensus conference criteria for sepsis and able to consent (directly or through a surrogate) were enrolled (n = 1,247). Patients had clinical, laboratory, and HRV data recorded within 1 h of ED presentation, and were followed to identify deterioration within 72 h.

Results:

Eight hundred thirty-two patients had complete data, of whom 68 (8%) reached at least one endpoint. Optimal predictive performance was derived from a combination of laboratory values and HRV metrics with an area under the receiver-operating curve (AUROC) of 0.80 (95% CI, 0.65–0.92). This combination of variables was superior to clinical (AUROC = 0.69, 95% CI, 0.54–0.83), laboratory (AUROC = 0.77, 95% CI, 0.63–0.90), and HRV measures (AUROC = 0.76, 95% CI, 0.61–0.90) alone. The HRV+LAB model identified a high-risk cohort of patients (14% of all patients) with a 4.3-fold (95% CI, 3.2–5.4) increased risk of deterioration (incidence of deterioration: 35%), as well as a low-risk group (61% of all patients) with 0.2-fold (95% CI 0.1–0.4) risk of deterioration (incidence of deterioration: 2%).

Conclusions:

A model that combines HRV and laboratory values may help ED physicians evaluate risk of deterioration in patients with sepsis and merits validation and further evaluation.
Single-port Laparoscopic Appendectomy: Beyond the Learning Curve: A Retrospective Comparison With Multi-port Laparoscopic Appendectomy
Authors: Assali Sarah , Eapen Sarah , Carman Terry , Horattas Sophia , Daigle Christopher R. , Paranjape Charudutt
Published: May 2018

Objectives:

Previous comparisons between single-port laparoscopic appendectomy (SPLA) and multi-port laparoscopic appendectomy have been conflicting and limited. We compare our single-surgeon, SPLA experience with multi-port cases performed during the same time.

Methods:

A retrospective chart review of 128 single-surgeon single-port and 941 multi-port laparoscopic appendectomy cases from April 2009 to December 2014 was conducted.

Results:

Patient demographics and preoperative laboratory values were comparable. SPLA was associated with shorter operative time (P=0.0001). There was no statistically significant difference in length of hospitalization, postoperative pain medication use, cost, postoperative complication rates (ileus, urinary retention, deep space infection), or readmission between the 2 groups. There were no postoperative incisional hernias in the single-port group. The single-port group had more postoperative oxycodone use (P=0.0110).

Conclusions:

Our study supports recently published metaanalyses that fail to support older studies demonstrating longer operative times, and higher hernia rates with SPLA.
Acute hyperglycemia exacerbates trauma-induced endothelial and glycocalyx injury: An in vitro model
Authors: Diebel Lawrence N. , Diebel Mark E. , Martin Jonathan V. , Liberati David M.
Published: May 2018

BACKGROUND

Early hyperglycemia is associated with higher mortality in trauma and predicts multiple organ failure. Endothelial cell (EC) injury and glycocalyx (GC) degradation occur following traumatic shock and are key factors in the development of trauma-induced coagulopathy and result in impaired microvascular perfusion and accompanying organ failure. Acute hyperglycemia has been shown to result in the loss of the GC layer, EC inflammation, and activation of coagulation in vivo. We postulated that acute hyperglycemia would exacerbate trauma-induced EC injury and GC shedding and integrity. This was studied using a microfluidic device in a biomimetic in vitro model.

METHODS

Human umbilical vein endothelial cell monolayers established in the microfluidic channels of a microfluidic device well plate were perfused at constant shear overnight. Human umbilical vein endothelial cell monolayers were then exposed to hypoxia/reoxygenation and epinephrine followed by the addition of varying concentrations of glucose.

RESULTS

Glycocalyx shedding and loss of dimension, as well as EC injury/activation, were noted after exposure to the biomimetic conditions of trauma/shock in our study. Similar but less dramatic findings were noted after acute hyperglycemia. Exposure to hyperglycemia exacerbated the adverse effects on the GC and EC following hypoxia/reoxygenation plus epinephrine exposure and may be related to enhanced production of reactive oxygen species.

CONCLUSIONS

Microfluidic device study may allow the preclinical assessment and development of therapeutic strategies of the vascular barrier under stress conditions.
The impact of inpatient palliative care on end-of-life care among older trauma patients who die after hospital discharge
Authors: Lilley Elizabeth J. , Lee Katherine C. , Scott John W. , Krumrei Nicole J. , Haider Adil H. , Salim Ali , Gupta Rajan , Cooper Zara
Published: May 2018

BACKGROUND

Palliative care (PC) is associated with lower-intensity treatment and better outcomes at the end of life. Trauma surgeons play a critical role in end-of-life (EOL) care; however, the impact of PC on health care utilization at the end of life has yet to be characterized in older trauma patients.

METHODS

This retrospective cohort study using 2006 to 2011 national Medicare claims included trauma patients 65 years or older who died within 180 days after discharge. The exposure of interest was inpatient PC during the trauma admission. A non-PC control group was developed by exact matching for age, comorbidity, admission year, injury severity, length of stay, and post-discharge survival. We used logistic regression to evaluate six EOL care outcomes: discharge to hospice, rehospitalization, skilled nursing facility or long-term acute care hospital admission, death in an institutional setting, and intensive care unit admission or receipt of life-sustaining treatments during a subsequent hospitalization.

RESULTS

Of 294,665 patients who died within 180 days after discharge, 2.1% received inpatient PC. Among 5,693 matched pairs, inpatient PC was associated with increased odds of discharge to hospice (odds ratio [OR], 3.80; 95% confidence interval [CI], 3.54–4.09) and reduced odds of rehospitalization (OR, 0.17; 95% CI, 0.15–0.20), skilled nursing facility/long-term acute care hospital admission (OR, 0.43; 95% CI, 0.39–0.47), death in an institutional setting (OR, 0.34; 95% CI, 0.30–0.39), subsequent intensive care unit admission (OR, 0.51; 95% CI, 0.36–0.72), or receiving life-sustaining treatments (OR, 0.56; 95% CI, 0.39–0.80).

CONCLUSION

Inpatient PC is associated with lower-intensity and less burdensome EOL care in the geriatric trauma population. Nonetheless, it remains underused among those who die within 6 months after discharge.

LEVEL OF EVIDENCE

Therapeutic/Care management, level III.
Acute Kidney Injury After Liver Transplantation
Authors: Durand François , Francoz Claire , Asrani Sumeet K. , Khemichian Saro , Pham Thomas A. , Sung Randall S. , Genyk Yuri S. , Nadim Mitra K.
Published: May 2018

Since the implementation of the Model of End-stage Liver Disease score-based allocation system, the number of transplant candidates with impaired renal function has increased. The aims of this review are to present new insights in the definitions and predisposing factors that result in acute kidney injury (AKI), and to propose guidelines for the prevention and treatment of postliver transplantation (LT) AKI. This review is based on both systematic review of relevant literature and expert opinion. Pretransplant AKI is associated with posttransplant morbidity, including prolonged post-LT AKI which then predisposes to posttransplant chronic kidney disease. Prevention of posttransplant AKI is essential in the improvement of long-term outcomes. Accurate assessment of baseline kidney function at evaluation is necessary, taking into account that serum creatinine overestimates glomerular filtration rate. New diagnostic criteria for AKI have been integrated with traditional approaches in patients with cirrhosis to potentially identify AKI earlier and improve outcomes. Delayed introduction or complete elimination of calcineurin inhibitors during the first weeks post-LT in patients with early posttransplant AKI may improve glomerular filtration rate in high risk patients but with higher rates of rejection and more adverse events. Biomarkers may in the future provide diagnostic information such as etiology of AKI, and prognostic information on renal recovery post-LT, and potentially impact the decision for simultaneous liver-kidney transplantation. Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late chronic kidney disease.
Survey on Management of Transition and Transfer From Pediatric- to Adult-based Care in Pediatric Kidney Transplant Recipients in Europe
Authors: Kreuzer Martin , Prüfe Jenny , Tönshoff Burkhard , Pape Lars
Published: May 2018

Background

Transition from pediatric- to adult-based healthcare is a challenging period and bears a high risk of medication nonadherence and transplant loss in adolescents and young adults after kidney transplantation. Yet, it remains unclear how the 2011 International Society of Nephrology (ISN)/International Pediatric Nephrology Association (IPNA) guidelines on transition are implemented in practice and which healthcare transition modalities are currently used in Europe.

Methods

We performed an online survey inviting all members of the European Society of Paediatric Nephrology mailing list to participate. Adherence to ISN/IPNA guidelines was scored with a maximum of 15 points.

Results

Thirty-nine centers from 24 countries accounting for approximately 2500 children after kidney transplantation participated in the survey. At 3 centers, patients remained under pediatric care for their whole life, and 5 centers did not use any transition procedure. From the remaining 31 centers, 82% confirmed the existence of at least 1 unwritten transition procedure. None of these centers used IT or social media for patient training in transition. Specialized transition clinics are held at 15 of 31 centers for the patients. Most patients were transferred at 16 to 21 years of age. Transfer age was subject to regulation at 20 of 36 centers. Median score of guidelines adherence was 10 (range, 0-14). The adherence score was significantly correlated with gross national income (r
2 = 0.631, P < 0.0001).

Conclusions

The 2011 ISN/IPNA guidelines on transition are implemented insufficiently in European pediatric nephrology centers. Therefore, further development is needed, and the use of information technology and social media should be promoted.
De Novo Myoclonic Status Epilepticus After Benzodiazepine Withdrawal
Authors: Vicente Ferreira Naves Pedro , Calderaro Marcelo , Caboclo Luis Otavio
Published: May 2018

Myoclonic status epilepticus (MSE) in patients without epilepsy, or de novo MSE, is a rare condition associated with several acute symptomatic etiologies, including drugs and toxins. We describe a 94-year-old woman with Alzheimer dementia and long use of mirtazapine 30 mg/d and alprazolam 1 mg/d who developed MSE approximately 24 hours after abrupt discontinuation of alprazolam. The patient was taking sulfamethoxazole/trimethoprim for urinary tract infection, diagnosed 2 weeks before admission. She had no history of seizures. Routine laboratory examinations were normal and head computed tomography showed no acute injuries. She received a loading dose of 1000 mg of intravenous valproate (VPA). Continuous electroencephalogram monitoring revealed very frequent generalized spikes and polyspikes in a markedly slowed background activity. Intravenous VPA 500 mg thrice a day and alprazolam 0.5 mg twice a day were prescribed, and antibiotic was switched to piperacillin/tazobactam. Myoclonic jerks ceased completely and electroencephalogram showed no epileptiform discharges 2 days after VPA treatment onset, with recovery of baseline neurological status. This is, to the best of our knowledge, the first report of de novo MSE related to abrupt discontinuation of benzodiazepines. Seizures and status epilepticus are potential adverse events after abrupt withdrawal of chronically used benzodiazepines, especially in conditions with intrinsic epileptogenic susceptibility, such as Alzheimer disease.
Clinical Significance of A Waves in Acute Inflammatory Demyelinating Polyradiculoneuropathy
Authors: Lakshminarasimhan Sindhuja , Venkatraman Chandramouleeswaran , vellaichamy Kannan , Ranganathan Lakshminarasimhan
Published: May 2018

Purpose:

A wave is a late response recognized during recording of F waves. Though they might be seen in healthy subjects, their presence assumes significance in a patient presenting with polyradiculoneuropathy.

Methods:

In this prospective study, 75 patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) were enrolled. They were divided into two groups based on the presence or absence of A waves. Clinical features, electrophysiological parameters and extent of clinical recovery in short-term follow-up were analyzed.

Results:

A waves were present in 49 out of 75 patients (65%). Most common pattern observed was multiple A waves. Prevalence of A waves was more in lower limb nerves than upper limb nerves. Occurrence of A waves correlated with the presence of conduction block. Patients with A waves had higher Hughes grade (P = 0.003) and lower Medical Research Council sum score at 6 weeks of follow-up (P = 0.04) as compared to patients without A waves.

Conclusions:

A waves are common in acute inflammatory demyelinating polyradiculoneuropathy form of Guillain Barre syndrome and are considered as a marker of demyelination. Long-term follow-up studies are required to ascertain their significance in prognostication and assessing recovery.
A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice
Authors: Sun Fangmiao , Zeng Jianzhi , Jing Miao , Zhou Jingheng , Feng Jiesi , Owen Scott F. , Luo Yichen , Li Funing , Yamaguchi Takashi , Yong Zihao , Gao Yijing , Peng Wanling , Wang Lizhao , Zhang Siyu , Du Jiulin , Lin Dayu , Xu Min , Kreitzer Anatol C. , Cui Guohong , Li Yulong
Published: May 2018

Dopamine (DA) is a central monoamine neurotransmitter involved in many physiological and pathological processes. A longstanding yet largely unmet goal is to measure DA changes reliably and specifically with high spatiotemporal precision, particularly in animals executing complex behaviors. Here we report the development of novel genetically-encoded GPCR-Activation-Based-DA (GRABDA) sensors that enable these measurements. In response to extracellular DA rises, GRABDAsensors exhibit large fluorescence increases (ΔF/F0∼90%) with sub-second kinetics, nanomolar to sub-micromolar affinities, and excellent molecular specificity. Importantly, GRABDA sensors can resolve a single-electrical-stimulus evoked DA release in mouse brain slices, and detect endogenous DA release in the intact brains of flies, fish, and mice. In freely-behaving mice, GRABDA sensors readily report optogenetically-elicited nigrostriatal DA release and depict dynamic mesoaccumbens DA changes during Pavlovian conditioning or during sexual behaviors. Thus, GRABDAsensors enable spatiotemporal precise measurements of DA dynamics in a variety of model organisms while exhibiting complex behaviors.
Penalized matrix decomposition for denoising, compression, and improved demixing of functional imaging data
Authors: Buchanan E. Kelly , Kinsella Ian , Zhou Ding , Zhu Rong , Zhou Pengcheng , Gerhard Felipe , Ferrante John , Ma Ying , Kim Sharon , Shaik Mohammed , Liang Yajie , Lu Rongwen , Reimer Jacob , Fahey Paul , Muhammad Taliah , Dempsey Graham , Hillman Elizabeth , Ji Na , Tolias Andreas , Paninski Liam
Published: May 2018

Calcium imaging has revolutionized systems neuroscience, providing the ability to image large neural populations with single-cell resolution. The resulting datasets are quite large (with scales of TB/hour in some cases), which has presented a barrier to routine open sharing of this data, slowing progress in reproducible research. State of the art methods for analyzing this data are based on non-negative matrix factorization (NMF); these approaches solve a non-convex optimization problem, and are highly effective when good initializations are available, but can break down e.g. in low-SNR settings where common initialization approaches fail. Here we introduce an improved approach to compressing and denoising functional imaging data. The method is based on a spatially-localized penalized matrix decomposition (PMD) of the data to separate (low-dimensional) signal from (temporally-uncorrelated) noise. This approach can be applied in parallel on local spatial patches and is therefore highly scalable, does not impose non-negativity constraints or require stringent identifiability assumptions (leading to significantly more robust results compared to NMF), and estimates all parameters directly from the data, so no hand-tuning is required. We have applied the method to a wide range of functional imaging data (including one-photon, two-photon, three-photon, widefield, somatic, axonal, dendritic, calcium, and voltage imaging datasets): in all cases, we observe ~2-4x increases in SNR and compression rates of 20-300x with minimal visible loss of signal, with no adjustment of hyperparameters; this in turn facilitates the process of demixing the observed activity into contributions from individual neurons. We focus on two challenging applications: dendritic calcium imaging data and voltage imaging data in the context of optogenetic stimulation. In both cases, we show that our new approach leads to faster and much more robust extraction of activity from the video data.
Antimicrobial exposure in sexual networks drives divergent evolution in modern gonococci
Authors: Sánchez-Busó Leonor , Golparian Daniel , Corander Jukka , Grad Yonatan H. , Ohnishi Makoto , Flemming Rebecca , Parkhill Julian , Bentley Stephen D. , Unemo Magnus , Harris Simon R.
Published: May 2018

The sexually transmitted pathogenNeisseria gonorrhoeaeis regarded as being on the way to becoming an untreatable superbug. Despite its clinical importance, little is known about its emergence and evolution, and how this corresponds with the introduction of antimicrobials. We present a genome-based phylogeographic analysis of 419 gonococcal isolates from across the globe. Results indicate that modern gonococci originated in Europe or Africa as late as the 16thcentury and subsequently disseminated globally. We provide evidence that the modern gonococcal population has been shaped by antimicrobial treatment of sexually transmitted and other infections, leading to the emergence of two major lineages with different evolutionary strategies. The well-described multi-resistant lineage is associated with high rates of homologous recombination and infection in high-risk sexual networks where antimicrobial treatment is frequent. A second, multi-susceptible lineage associated with heterosexual networks, where asymptomatic infection is more common, was also identified, with potential implications for infection control.
Whole genome linkage disequilibrium and effective population size in a coho salmon (Oncorhynchus kisutch) breeding population
Authors: Barría Agustín , Christensen Kris A. , Yoshida Grazyella , Jedlicki Ana , Lhorente Jean P. , Davidson William S. , Yáñez José M.
Published: May 2018

The estimation of linkage disequilibrium between molecular markers within a population is critical when establishing the minimum number of markers required for association studies, genomic selection and for inferring historical events influencing different populations. This work aimed to evaluate the extent and decay of linkage disequilibrium in a coho salmon breeding population using ddRAD genomic markers.

Linkage disequilibrium was estimated between a total of 7,505 SNPs found in 62 individuals (33 dams and 29 sires) from the breeding population. The makers encompass all 30 coho salmon chromosomes and comprise 1,655.19 Mb of the genome. The average density of markers per chromosome ranged from 3.45 to 6.11 per 1 Mbp. The minor allele frequency averaged 0.20 (with a range from 0.08 to 0.50). The overall average linkage disequilibrium among SNPs pairs measured as r2was 0.054. The Average r2value decreased with increasing physical distance, with values ranging from 0.37 to 0.054 at distances lower than 1 kb and up to 10 Mb, respectively. An r2threshold of 0.1 was reached at distance of approximately 1.3 Mb. Chromosomes Okis05, Okis15 and Okis28 showed high levels of linkage disequilibrium (> 0.20 at distances lower than 1 Mb). Average r2values were lower than 0.1 for all chromosomes at distances greater than 4 Mb. Linkage disequilibrium values suggest that whole genome association and selection studies could be performed using about 75,000 SNPs in aquaculture populations (depending on the trait under investigation). From the identified SNPs, an effective population size of 100 was estimated for the population 10 generation ago, and 1,000, for 139 generations ago.

Based on the extent of r2decay, we suggest that at least 75,000 SNPs would be necessary for an association mapping study. Over 100,000 SNPs would be necessary for a high power study, in the current coho salmon population.
Aedes anphevirus (AeAV): an insect-specific virus distributed worldwide inAedes aegyptimosquitoes that has complex interplays withWolbachiaand dengue virus infection in cells
Authors: Parry Rhys , Asgari Sassan
Published: May 2018

Insect specific viruses (ISVs) of the yellow fever mosquitoAedes aegyptihave been demonstrated to modulate transmission of arboviruses such as dengue virus (DENV) and West Nile virus by the mosquito. The diversity and composition of the virome ofAe. aegypti, however, remains poorly understood. In this study, we characterised Aedes anphevirus (AeAV), a negative-sense RNA virus from the orderMononegavirales. AeAV identified fromAedescell lines were infectious to bothAe. aegyptiandAedes albopictuscells, but not to three mammalian cell lines. To understand the incidence and genetic diversity of AeAV, we assembled 17 coding-complete and two partial genomes of AeAV from available RNA-Seq data. AeAV appears to transmit vertically and be present in laboratory colonies, wild-caught mosquitoes and cell lines worldwide. Phylogenetic analysis of AeAV strains indicates that as theAe. aegyptimosquito has expanded into the Americas and Asia-Pacific, AeAV has evolved into monophyletic African, American and Asia-Pacific lineages. The endosymbiotic bacteriumWolbachia pipientisrestricts positive-sense RNA viruses inAe. aegypti. Re-analysis of a small RNA library ofAe. aegypticells co-infected with AeAV andWolbachiaproduces an abundant RNAi response consistent with persistent virus replication. We foundWolbachiaenhances replication of AeAV when compared to a tetracycline cleared cell line, and AeAV modestly reduces DENV replicationin vitro. The results from our study improve understanding of the diversity and evolution of the virome ofAe. aegyptiand adds to previous evidence that showsWolbachiadoes not restrict a range of negative strand RNA viruses.
Biological capacities clearly define a major subdivision in Domain Bacteria
Authors: Méheust Raphaël , Burstein David , Castelle Cindy J. , Banfield Jillian F.
Published: May 2018

Resume

Phylogenetic analyses separate candidate phyla radiation (CPR) bacteria from other bacteria, but the degree to which their proteomes are distinct remains unclear. Here, we leveraged a proteome database that includes sequences from thousands of uncultivated organisms to identify protein families and examine their organismal distributions. We focused on widely distributed protein families that co-occur in genomes, as they likely foundational for metabolism. Clustering of genomes using the protein family presence/absence patterns broadly recapitulates the phylogenetic structure of the tree, suggesting persistence of core sets of protein families after lineage divergence. CPR bacteria group together and away from all other bacteria and archaea, in part due to novel proteins, some of which may be involved in cell-cell interactions. The diversity of combinations of protein families in CPR may exceed that of all other bacteria. Overall, the results extend the phylogeny-based suggestion that the CPR represent a major subdivision within Bacteria.
Identification of a novel tetrameric structure for human apolipoprotein-D
Authors: Kielkopf Claudia S. , Low Jason K.K. , Mok Yee-Foong , Bhatia Surabhi , Palasovski Tony , Oakley Aaron J. , Whitten Andrew E. , Garner Brett , Brown Simon H.J.
Published: May 2018

Apolipoprotein-D is a 25 kDa glycosylated member of the lipocalin family that folds into an eight-stranded β-barrel with a single adjacent α-helix. Apolipoprotein-D specifically binds a range of small hydrophobic ligands such as progesterone and arachidonic acid and has an antioxidant function that is in part due to the reduction of peroxidised lipids by methionine-93. Therefore, apolipoprotein-D plays multiple roles throughout the body and is protective in Alzheimer’s disease, where apolipoprotein-D overexpression reduces the amyloid-β burden in Alzheimer’s disease mouse models.

Oligomerisation is a common feature of lipocalins that can influence ligand binding. The native structure of apolipoprotein-D, however, has not been conclusively defined. Apolipoprotein-D is generally described as a monomeric protein, although it dimerises when reducing peroxidised lipids.

Here, we investigated the native structure of apolipoprotein-D derived from plasma, breast cyst fluid (BCF) and cerebrospinal fluid. In plasma and cerebrospinal fluid, apolipoprotein-D was present in high-molecular weight complexes, potentially in association with lipoproteins. In contrast, apolipoprotein-D in BCF formed distinct oligomeric species. We assessed apolipoprotein-D oligomerisation using native apolipoprotein-D purified from BCF and a suite of complementary methods, including multi-angle laser light scattering, analytical ultracentrifugation and small-angle X-ray scattering. Our analyses showed that apolipoprotein-D predominantly forms a ∽95 to ∽100 kDa tetramer. Small-angle X-ray scattering analysis confirmed these findings and provided a structural model for apolipoprotein-D tetramer. These data indicate apolipoprotein-D rarely exists as a free monomer under physiological conditions and provide insights into novel native structures of apolipoprotein-D and into oligomerisation behaviour in the lipocalin family.
Photosynthesis under very high oxygen concentrations in dense microbial mats and biofilms
Authors: de Beer Dirk , Meyer Volker , Klatt Judith , Li Tong
Published: May 2018

Using microsensors O2concentrations were measured in photosynthetically active microbial mats of up to 3 mM, corresponding to a partial pressure of 3 bar. This could damage mats by internal gas formation, and be inhibitory by formation of reactive oxygen species (ROS) and reduced effectivity of RuBisCo. The reliability of the electrochemical microsensors was checked by creating elevated O2concentrations in a water volume placed inside a pressure tank. A microsensor mounted with the tip in the gassed water bath showed a response linearly proportional to 5.5 mM corresponding to 4 bar pure O2pressure. After release of the pressure the O2concentration reduced quickly to 2.5 mM, then stabilized and subsequently reduced slowly over 14 hours to approximately 2 mM. We concluded that the very high O2concentrations measured in phototrophic microbial mats are real and O2oversaturation in mats is a stable phenomenon. As consequence of high O2concentrations, net production of H2O2occurred. The accumulation was, however, limited to the respiratory zone under the photosynthetic layer. Despite the high gas pressure inside mats, no disruption of the mat structure was apparent by bubble formation inside the mats,and bubbles were only observed at mat surfaces. Additions of H2O2to high concentrations in the water column were efficiently removed in the photosynthetically active zone. As the removal rate was linearly proportional to the H2O2influx, this removal occurred possibly not enzymatically but by abiotic processes. Phototrophic microorganisms can produce O2at high rates under strongly elevated O2levels, despite the decreased efficiency due to the unfavorable kinetics of RuBisCo and energy costs for protection. Under non-limiting light conditions, this apparent dilemma is, however, not disadvantageous.

Importance

Biofilms are often used in photobioreactors for production of biomass, food or specialty chemistry. Photosynthesis rates can be limited by high O2levels or high O2/CO2ratios which are especially enhanced in biofilms and mats, due to mass transfer limitations. High O2may lead to reactive O2species (ROS) and reduce the efficiency of RuBisCo. Moreover, gas formation may destabilize their structure. Here we show that extremely high levels of O2are possible in mats and biofilms without ebullition, and while maintaining very high photosynthetic activity.