bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser-assisted Lipolysis Burn Safety: Proposed Detailed Parameters with Assessment of Their Efficacy and Safety
Authors: Ali Yasser Helmy
Published: October 2018

Background:

Many recent studies have evaluated the clinical safety and efficacy of therapeutic lasers in laser lipolysis, but without detailed description of the safe and effective parameters.

Purpose:

To propose a method for adjusting safe and effective parameters for laser lipolysis.

Methods:

Detailed calculations of the safe and effective laser parameters for fat melting are proposed in the study. Amount of energy delivered in joules was calculated based on data from Havenith research. External skin and internal tissues temperatures during the procedure were kept in a recommended range and monitored for safety and efficacy. Prospective statistical study was designed on a series of 300 patients who underwent laser-assisted lipolysis and /or liposuction using 2 different machine manufacturers, delivering 1,064/1,320 nm.

Results:

All areas submitted to laser-assisted liposuction in this series have resulted in no clinical thermal burns injury to the skin. There was improvement in the bulk of fats, skin tightening, skin textures, and cellulites.

Conclusion:

This study is proposing a simple method for calculations of safe and effective laser lipolysis. Skin burn injury could be highly prevented by following up the proposed detailed basic parameters for laser lipolysis treatment.
Low-Flow Orbital Venous Malformation Masquerading as Rhabdomyosarcoma
Authors: Pandit Saagar A. , Godfrey Kyle J. , Dunbar Kristen E. , Campbell Ashley A. , Kazim Michael
Published: October 2018

A 15-month-old male was referred for biopsy of presumed rhabdomyosarcoma in the setting of rapidly progressing left-sided proptosis. Examination revealed left periorbital edema and left hypoglobus. MRI revealed a soft-tissue density mass within the left lateral retrobulbar space. Several days later, he developed acute periorbital ecchymosis and increasing edema. With high suspicion for a vascular lesion, a CT scan was performed with dynamic arterial and venous imaging. Central filling was noted in the lateral retrobulbar component with increased enhancement on delayed venous imaging in the middle cranial fossa component favoring the diagnosis of a low-flow orbital venous malformation. In the setting of spontaneous orbital hemorrhage and risk of future vision loss, the decision was made to proceed with a combined neurosurgical approach treating the intracranial component and debulking the orbital component. This case highlights the importance of thorough radiographic evaluation prior to proceeding with a surgical procedure in the appropriate clinical context.
Renal replacement therapy in the ICU: intermittent hemodialysis, sustained low-efficiency dialysis or continuous renal replacement therapy?
Authors: Wang Amanda Ying , Bellomo Rinaldo
Published: October 2018

Purpose of review

Severe acute kidney injury in the ICU setting often requires renal replacement therapy (RRT). Intermittent hemodialysis (IHD), hybrid forms of RRT such as sustained low-efficiency dialysis (SLED), as well as continuous renal replacement therapy (CRRT) are the three common modalities of extracorporeal RRT used in the adult ICU setting in developed countries. This review summarizes recently published data regarding comparisons of these three RRT modalities on clinical outcomes (e.g., mortality and recovery of renal function) in severe acute kidney injury (AKI) patients.

Recent findings

There is still controversy on the superiority of one RRT modality over another in terms of clinical outcomes in patients with AKI in ICU. Although there is increasing acceptance that CRRT should be used in hemodynamic unstable patients, its survival advantages over IHD remains unproven because of inadequate evidence from suitably powered randomized controlled trials (RCTs). Moreover, CRRT does not show superiority to intermittent renal replacement therapy (IRRT) in hemodynamic stable patients. Although patients receiving sustained low-efficiency dialysis appear to have lower mortality than CRRT, its survival benefit is largely derived from observational studies and is confounded by selection bias. Current literature supports no differences in mortality among the three RRT modalities. However, the effect of choice of RRT modality on short-term and long-term renal outcomes need further studies, especially larger RCTs and longer duration of follow-up.

There is lack of solid evidence showing superiority of any mode of RRT in patients with severe AKI in terms of patient survival. However, based on observational data, IHD treatment of AKI may delay renal recovery. Patients’ hemodynamic status, coexisting medical conditions, local expertise, and availability of staff and resources as well as potential effect on long-term renal outcomes should be taken into consideration when selecting modalities of RRT for adult ICU patients.
Continuous renal replacement therapy: understanding circuit hemodynamics to improve therapy adequacy
Authors: Michel Thibault , Ksouri Hatem , Schneider Antoine G.
Published: October 2018

Purpose of review

The utilization of continuous renal replacement therapy (CRRT) increases throughout the world. Technological improvements have made its administration easier and safer. However, CRRT remains associated with numerous pitfalls and issues.

Recent findings

Even if new-generation CRRT devices have built-in safety features, understanding basic concepts remains of primary importance.

CRRT circuits’ maximum recommended lifespan (72 h) can often not be achieved. Such early artificial kidney failures are typically related to two processes: circuit clotting and membrane clogging. Although these processes are to some degree inevitable, they are facilitated by poor therapy management. Indeed, the majority of device-triggered alarms are associated with blood pump interruption, which through blood stasis, enhance clotting and clogging. If the underlying issue is not adequately managed, further alarms will rapidly lead to prolonged stasis and complete circuit clotting or clogging making its replacement mandatory. Hence, rapid recognition of issues triggering alarms is of paramount importance. Because most alarms are related to circuit's hemodynamics, a thorough understanding of these concepts is mandatory for the staff in charge of delivering the therapy.

This review describes CRRT circuits, measured and calculated pressures and the way their knowledge might improve therapy adequacy.
Personalization of arterial pressure in the perioperative period
Authors: Godet Thomas , Grobost Romain , Futier Emmanuel
Published: October 2018

Purpose of review

This review aims to discuss recent findings on the relationship between intraoperative arterial hypotension and organ dysfunction in surgical patients and examines the available evidence for personalizing blood pressure (BP) management as a strategy to improve patient outcome.

Recent findings

Hypotension contributes to oxygen supply–demand mismatch and may cause an ischemia–reperfusion injury which may manifest as organ dysfunction. Evidence is accumulating suggesting that hypotension is associated with acute postoperative myocardial and kidney injury, and increased risk of mortality in surgical patients. In contrast to traditional BP management in which BP targets are empirically chosen, personalized BP management aims at individualizing BP targets according to individual patient physiology considering clinical conditions that may influence organ pressure-flow autoregulation. Recent randomized data provide clinically meaningful findings that a treatment strategy aims at targeting individualized BP values which may help improving outcome in surgical patients.

Hypotension is a common complication in surgical patients and is an important trigger of organ injury in surgical patients. Personalized BP management may contribute at reducing postoperative organ dysfunction in surgical patients.
Community-acquired pneumonia as an emergency condition
Authors: Cillóniz Catia , Dominedò Cristina , Garcia-Vidal Carolina , Torres Antoni
Published: October 2018

Purpose of review

Despite the improvements in its management, community-acquired pneumonia (CAP) still exhibits high global morbidity and mortality rates, especially in elderly patients. This review focuses on the most recent findings on the epidemiology, cause, diagnosis and management of CAP.

Recent findings

There is consistent evidence that the trend in CAP mortality has declined over time. However, the mortality of pneumococcal CAP has not changed in the last two decades, with an increase in the rate of hospitalization and more severe forms of CAP. Streptococcus pneumoniae remains the most frequent cause of CAP in all settings, age groups and regardless of comorbidities. However, the implementation of molecular diagnostic tests in the last years has identified respiratory viruses as a common cause of CAP too. The emergency of multidrug-resistance pathogens is a worldwide concern. An improvement in our ability to promptly identify the causative cause of CAP is required in order to provide pathogen-directed antibiotic therapy, improve antibiotic stewardship programs and implement appropriate vaccine strategies.

It is time to apply all the knowledge generated in the last decade in order to optimize the management of CAP.
Resuscitation fluids
Authors: Casey Jonathan D. , Brown Ryan M. , Semler Matthew W.
Published: October 2018

Purpose of review

Intravenous fluid administration is a fundamental therapy in critical care, yet key questions remain unanswered regarding optimal fluid composition and dose. This review evaluates recent evidence regarding the effects of fluid resuscitation on pathophysiology, organ function, and clinical outcomes for critically ill patients.

Recent findings

Recent findings suggest that intravenous fluid composition affects risk of kidney injury and death for critically ill adults. Generally, the risk of kidney injury and death appears to be greater with semisynthetic colloids compared with crystalloids, and with 0.9% sodium chloride compared with balanced crystalloids. Whether a liberal, restrictive, or hemodynamic responsiveness-guided approach to fluid dosing improves outcomes during sepsis or major surgery remains uncertain.

As evidence on fluid resuscitation evolves, a reasonable approach would be to use primarily balanced crystalloids, consider 2–3 l for initial fluid resuscitation of hypovolemic or distributive shock, and use measures of anticipated hemodynamic response to guide further fluid administration.
Updates in emergency airway management
Authors: Carlson Jestin N. , Wang Henry E.
Published: October 2018

Purpose of review

Historically, most evidence supporting emergency airway management strategies have been limited to small series, retrospective analyses and extrapolation from other settings (i.e. the operating room). Over the past year, several large, randomized clinical trials have offered new findings to inform emergency airway management techniques.

Recent findings

One large, randomized clinical trial, found improved first attempt success rates with bougie facilitated intubation compared with traditional intubation. Two randomized clinical trials suggested better outcomes in adult out-of-hospital cardiac arrest (OHCA) with supraglottic airways (SGA) than intubation. A randomized clinical trial in OHCA patients could not identify outcome differences between endotracheal intubation (ETI) and bag-valve mask (BVM) ventilation but suggested higher rates of aspiration with BVM.

These studies offer new findings to inform the practice of emergency airway management. Bougie use should be considered as a first-line approach in emergency intubation. SGA-based strategies should be considered as a first-line approach in the management of OHCA.
RNA-targeted therapeutics for lipid disorders
Authors: Tsimikas Sotirios
Published: October 2018

Purpose of review

To summarize recent developments in the field of RNA-directed therapeutics targeting lipid disorders that are not effectively managed.

Recent findings

Despite a number of approved therapies for lipid disorders, significant unmet needs are present in treating persistently elevated LDL-cholesterol, remnant-cholesterol, triglycerides and lipoprotein(a) [Lp(a)]. Small molecules and antibodies are effective modalities, but they are unable to adequately treat many patients with abnormal lipid parameters. Targeting mRNA with oligonucleotides to prevent protein translation is a relatively novel method to reduce circulating atherogenic lipoproteins. Small inhibiting RNA (siRNA) molecules targeting proprotein convertase subtilisin kexin type 9 to reduce LDL-C, and antisense oligonucleotides (ASO) targeting apolipoprotein C-III (apoC-III) to reduce triglycerides, angiopoietin-like 3 (ANGPTL3) to reduce LDL-C and triglycerides and apolipoprotein(a) (LPA) to reduce Lp(a) are currently in or just completed phase 1–3 trials. Fundamental differences exist in chemistry, delivery and mechanism of action of siRNA and ASOs.

Novel RNA therapeutics are poised to provide highly potent, specific and effective therapies to reduce atherogenic lipoproteins. As these compounds are approved, clinicians will be able to choose from a broad armamentarium to treat nearly all patients to acceptable goals in order to reduce risk of cardiovascular disease and events.
Swallowing function in advanced age
Authors: Jardine Marie , Miles Anna , Allen Jacqui E.
Published: October 2018

Purpose of review

To present current literature regarding swallowing function in advanced age, including healthy ageing, dysphagia and trends in multidisciplinary team service delivery.

Recent findings

Normative studies support swallowing efficiency but greater variability in healthy advanced age, through to 100 years old. Deviations from normative data and symptoms of dysphagia leading to aspiration or nutritional risk, imply swallowing disorder, rather than simply the ageing process. Quantitative and qualitative studies are emerging that promote management of swallow dysfunction for an ageing society, including innovative assessment, home treatment, swallowing exercise and optimized mealtimes.

Current literature on swallowing function in advanced age provides multidisciplinary perspectives and initiatives, with clear commitment to improving quality of life for older adults. The diversity of the older population and serious consequences of swallowing difficulties calls for routine screening tools for swallowing impairment and malnutrition risk. Representation of ‘oldest old’ in future normative studies is essential to guide swallowing management in adults over 85 years old.
Laryngopharyngeal reflux disease: clinical presentation, diagnosis and therapeutic challenges in 2018
Authors: Lechien Jerome R. , Saussez Sven , Karkos Petros D.
Published: October 2018

Purpose of review

To review the recent literature on presentation, diagnosis and treatment of laryngopharyngeal reflux.

Recent findings

Patients with laryngopharyngeal reflux have a higher risk for gastroesophageal reflux and respiratory-related diseases. Many symptoms and findings are underestimated, contributing to the inconclusive results of many therapeutic trials. Additionally, little significance is given to nonacid and mixed refluxates, although a significant prevalence. The association between symptoms, signs, impedance-pH studies and pepsin detection could be the most accurate way for a clear diagnosis. ‘Reflux profiling’ is also important for the administration of a personalized treatment based on diet, proton pump inhibitors, alginate, magaldrate and other second-line drugs. There are only a handful of studies focusing on the addition of alginate or magaldrate to the treatment of laryngopharyngeal reflux, although their contribution has extensively been demonstrated.

Diagnosis remains controversial despite improvement in impedance and availability of pepsin detection in daily practice. With recent studies exhibiting a significant prevalence of nonacid or mixed refluxes, the addition of alginate or magaldrate to proton pump inhibitors should be considered. Future studies are needed to assess these new therapeutic schemes in moderate and severe laryngopharyngeal reflux.
Techniques for evaluation and management of tongue-base obstruction in pediatric obstructive sleep apnea
Authors: Ishman Stacey L. , Chang Katherine W. , Kennedy Aimee A.
Published: October 2018

Purpose of review

Tongue-base obstruction (TBO) is a common cause of persistent obstructive sleep apnea (OSA) after tonsillectomy and adenoidectomy in children. This review discusses available diagnostic modalities and surgical treatment options for the management of TBO.

Recent findings

Recently, a systematic review that included nine studies using drug-induced sleep endoscopy (DISE) in the evaluation of children with persistent OSA after tonsillectomy and adenoidectomy identified the tongue-base as the most common site of obstruction.

TBO is a common and correctable cause of persistent OSA in children. Diagnostic modalities include awake flexible laryngoscopy, plain neck films, DISE, and cine MRI. Because DISE and cine MRI are performed in a sleep-like state, they are fairly reliable in identifying the site of obstruction. As continuous positive airway pressure is often poorly tolerated in the pediatric population, there is considerable interest in surgical options for TBO. Depending on the location and the severity of the obstruction, interventions such as lingual tonsillectomy, posterior midline glossectomy, tongue suspension suture, epiglottopexy, hypoglossal nerve stimulation, tongue–lip adhesion, and hyoid suspension may play a role in management.
High-resolution manometry: what about the pharynx?
Authors: Omari Taher , Schar Mistyka
Published: October 2018

Purpose of review

High-resolution pharyngeal manometry (HRPM) is a well tolerated, catheter-based, method for recording the pressures and bolus flow generated by the pharyngeal muscles during swallowing. Despite a body of published evidence and a critical mass of investigators in the field, there is a lack of consensus surrounding what biomechanical phenomena to measure. The purpose of this review is to provide some insights into the information on swallowing physiology that can be gathered using HRPM.

Recent findings

HRPM literature has focused on measuring biomechanical phenomena that may be relevant to measure in relation to dysphagia research. This review focuses on the measurement of pharyngeal luminal occlusive forces, intrabolus distension pressure, bolus presence and bolus flow timing as key features of pharyngeal swallowing that require measurement and allow for derivation of the Swallow Risk Index, a global measure of swallow function indicative of swallowing functional reserve.

HRPM allows objective derivation of measures of swallow function that may have value for diagnosis and research in relation to swallowing disorders. HRPM has demonstrated clinical applicability in specific patient populations and offers unique advantages that compliment current assessment methods.
Pediatric Chronic Inflammatory Bowel Disease in a German Statutory Health INSURANCE—Incidence Rates From 2009 to 2012
Authors: Wittig Regina , Albers Lucia , Koletzko Sibylle , Saam Joachim , von Kries Rüdiger
Published: October 2018

Objective:

The incidence of pediatric inflammatory bowel disease (PIBD) varies over time and geographic region. We attempted to generate incidence rates form German health insurance data.

Methods:

We used health care data for 2009–2015 provided by BARMER, a major statutory health insurance company in Germany, insuring approximately 8% of the pediatric population. We applied a Canadian case definition for PIBD based on International Classification of Diseases coding, documentation of (ileo)colonoscopy and the number of PIBD related visits, without external validation for Germany. An internal validation of the specificity of the diagnosis by checking whether the identified incident cases had also prescriptions of PIPD specific drugs was performed.

Results:

In 2012, 187 pediatric patients were newly diagnosed, accounting for an overall PIBD incidence of 17.41 (95% CI 15.08–20.10) per 100,000 insured children and adolescents from 0 to 17.9 years per year compared with 13.65/100,000 (95% CI 11.63–16.01) in 2009. The age‐specific incidence showed a steep increase as of the age of 7 years. The PIBD prevalence in 2012 was 66.29/100,000.

Conclusions:

In conclusion, the incidence of PIBD in 0 to 17.9‐year‐olds in Germany with health BARMER health insurance in 2012 is among the highest reported in the literature.
VSTM2A Overexpression Is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney
Authors: Wang Lisha , Zhang Yuping , Chen Ying-Bei , Skala Stephanie L. , Al-Ahmadie Hikmat A. , Wang Xiaoming , Cao Xuhong , Veeneman Brendan A. , Chen Jin , Cieślik Marcin , Qiao Yuanyuan , Su Fengyun , Vats Pankaj , Siddiqui Javed , Xiao Hong , Sadimin Evita T. , Epstein Jonathan I. , Zhou Ming , Sangoi Ankur R. , Trpkov Kiril , Osunkoya Adeboye O. , Giannico Giovanna A. , McKenney Jesse K. , Argani Pedram , Tickoo Satish K. , Reuter Victor E. , Chinnaiyan Arul M. , Dhanasekaran Saravana M. , Mehra Rohit
Published: October 2018

Our recent study revealed recurrent chromosomal losses and somatic mutations of genes in the Hippo pathway in mucinous tubular and spindle cell carcinoma (MTSCC). Here, we performed an integrative analysis of 907 renal cell carcinoma (RCC) samples (combined from The Cancer Genome Atlas and in-house studies) and the Knepper data set of microdissected rat nephrons. We identified VSTM2A and IRX5 as novel cancer-specific and lineage-specific biomarkers in MTSCC. We then assessed their expression by RNA in situ hybridization (ISH) in 113 tumors, including 33 MTSCC, 40 type 1 papillary RCC, 8 type 2 papillary RCC, 2 unclassified RCC, 15 clear cell RCC, and 15 chromophobe RCC. Sensitivity and specificity were calculated as the area under the receiver operating characteristics curve (AUC). All MTSCC tumors demonstrated moderate to high expression of VSTM2A (mean ISH score=255). VSTM2A gene expression assessed by RNA sequencing strongly correlated with VSTM2A ISH score (r
2=0.81, P=0.00016). The majority of non-MTSCC tumors demonstrated negative or low expression of VSTM2A. IRX5, nominated as a lineage-specific biomarker, showed moderate to high expression in MTSCC tumors (mean ISH score=140). IRX5 gene expression assessed by RNA sequencing strongly correlated with IRX5 ISH score (r
2=0.69, P=0.00291). VSTM2A (AUC: 99.2%) demonstrated better diagnostic efficacy than IRX5 (AUC: 87.5%), and may thus serve as a potential diagnostic marker to distinguish tumors with overlapping histology. Furthermore, our results suggest MTSCC displays an overlapping phenotypic expression pattern with the loop of Henle region of normal nephrons.
“Atrophic Kidney”–like Lesion
Authors: Herlitz Leal , Hes Ondrej , Michal Michal , Tretiakova Maria , Reyes-Múgica Miguel , Nguyen Jane K. , Troxell Megan L. , Przybycin Christopher G. , Magi-Galluzzi Cristina , McKenney Jesse K.
Published: October 2018

Renal mass lesions with a follicular architecture resembling atrophic kidney have been described, but their distinction from thyroid-like follicular carcinoma of the kidney remains controversial. We collected 8 cases of this purported “atrophic kidney”–like lesion to fully describe their clinical and histologic spectrum, their possible etiology, and to discuss their distinction from other renal neoplasms. Eight total cases were identified with patient ages ranging from 9 to 48 years (mean: 29 y; median: 28.5 y). Four patients were female and 4 were male. The tumors were unifocal and size ranged from 1.6 to 4.9 cm (mean: 3.4 cm; median: 3.4 cm). All 8 tumors had a remarkably similar histology. Each was enveloped by a smooth muscle rich capsule and had an overall low power “follicular” architecture. The luminal spaces of the “follicles” (or cysts) contained eosinophilic secretions and the lining epithelium was often flattened and atrophic, but some had more rounded cells with a distinctive hobnail arrangement. Many cysts contained discohesive round cells floating within the eosinophilic material, and some contained small intraluminal tufts with features of markedly atrophic glomeruli. Periodic acid-Schiff stains highlighted basement membrane material extending into these glomerular-like tufts, and some contained small distinct capillaries surrounded by endothelial cells, interspersed mesangial-like cells, and rare surrounding podocyte-like cells, providing additional evidence for glomerulocystic structures. Scattered calcifications were present within cysts (or within cyst walls) in varying numbers and were characterized by 2 types: psammoma body–like or more amorphous deposits. The tissue between cystic glomeruli contained predominantly small atrophic tubular structures, but collagenized stroma and smaller collapsed glomeruli were also present. The 2 tumors from the oldest 2 patients (48 and 39 y) had a more striking degree of stromal hyalinization. Immunohistochemically, the cyst lining cells had a predominant WT-positive/PAX-8 negative/CK7-negative phenotype, while tubules were typically WT-1 negative/PAX-8 positive/CK7-positive. Upon comparison to a control group of 10 kidneys containing incidental non–mass-forming glomerulocystic change, the morphologic features and immunophenotype were identical. To date, no patient has had any recurrence or aggressive clinical behavior based on follow status in 7 of 8 cases (follow-up range: 9 to 168 mo; median: 24 mo; mean: 40 mo). In summary, we describe the clinicopathologic features of 8 unique, benign “atrophic kidney”–like lesions that may simply represent a non-neoplastic form of organizing tubular atrophy and glomerulocystic change, and emphasize their distinction from thyroid-like follicular carcinoma of the kidney.
Treatment-Resistant Hodgkin Lymphoma
Authors: Blum Kristie A.
Published: October 2018

Autologous hematopoietic stem cell transplant (AHCT) remains the current standard of care for patients with relapsed or refractory Hodgkin lymphoma (HL) after frontline chemotherapy. However, treatment paradigms for HL are rapidly changing with positron emission tomography–adapted therapy, as well as the incorporation of brentuximab vedotin and checkpoint inhibitors into frontline, salvage, and maintenance therapy for HL. Patients who relapse or are refractory to these novel agents are likely to have different responses and outcomes with AHCT than the 3-year event-free survivals of 50% historically reported with AHCT for patients failing conventional combination chemotherapy. This article reviews the current data on the efficacy of AHCT, pretransplant prognostic markers, pretransplant salvage regimens, peritransplant radiation therapy, and posttransplant maintenance therapy in classic HL. Future research should reexamine the efficacy, timing, risk factors, pretransplant salvage regimens, and maintenance approaches posttransplant in the era of brentuximab vedotin and checkpoint inhibitors for HL.
Immunotherapy of Hodgkin Lymphoma: Mobilizing the Patient's Immune Response
Authors: Ansell Stephen M.
Published: October 2018

Classic Hodgkin lymphoma has a unique tumor composition in that there is a paucity of malignant cells present, and most of the tumor consists of normal immune and stromal cells. Despite the presence of an immune infiltrate within the tumor microenvironment, the malignant cells effectively evade the immune system and appear to utilize the presence of immune cells to promote the growth and survival of Hodgkin-Reed-Sternberg cells. Hodgkin-Reed-Sternberg cells evade immune detection because of overexpression of programmed death 1 ligands, PD-L1 and PD-L2, which suppress T-cell activation, and loss of expression of major histocompatibility complex molecules that prevent effective immune recognition. Recognition of these immune defects has led to clinical use of immune checkpoint blockade in classic Hodgkin lymphoma. Clinical trials using antibodies that block programmed death 1/PD-L1 signaling have shown remarkable responses to therapy and have led to the approval of nivolumab and pembrolizumab for use in patients with relapsed and refractory disease. Trials are currently testing immune checkpoint blockade in earlier lines of therapy.
Enhancing Autophagy Protects Against Sepsis-Induced Neuromuscular Dysfunction Associated with Qualitative Changes to Acetylcholine Receptors
Authors: Chen Jingyuan , Min Su , Xie Fei , Yang Jun , Wang Xin
Published: October 2018

Sepsis-induced myopathy is a heavy burden for patients during respiratory failure as well as after discharge, which could be characterized with qualitative changes to nAChR in a rat model of sepsis, regulated by NRG-1. Autophagy is an innate immune defense mechanism against microbial challenges. We found neuromuscular dysfunction in anterior tibial muscle of male Sprague-Dawley rats 24 h after cecal ligation and puncture (CLP). CLP resulted in increased systemic and local inflammation in anterior tibial muscle tissue. The start-up phase of autophagy, as measured by LC3II, was activated immediately after CLP and continued until 24 h; the degradation phase was suppressed until 24 h, after a brief increase at 4 h (revealed by p62). NRG-1 first increased, and then decreased to a level lower than that in the sham group. Meanwhile, expression of γ- and α7- acetylcholine receptors was detected at 8 and 16 h after CLP; levels increased continuously until 24 h. Subsequently, we investigated the significance of autophagy in CLP-induced neuromuscular dysfunction by treatment with rapamycin or 3-methyladenine, which were classical pharmaceuticals for enhancing or suppressing autophagy. Rapamycin activated autophagy, limited the CLP-induced systemic pro-inflammatory response and blood bacterial load without affecting local inflammatory response, upregulated NRG-1, downregulated γ- and α7-acetylcholine receptors, and improved 7-day neuromuscular function and survival rate. In contrast, 3-methyladenine enhanced local inflammatory response, suppressed autophagy, worsened 7-day neuromuscular function. We conclude that impaired autophagy may contribute to sepsis-induced neuromuscular dysfunction in young male rats. Enhancing autophagy with rapamycin alleviated qualitative changes to acetylcholine receptors without triggering local anti-inflammatory response and improved anterior tibial muscle function in septic early phase (24 h) as well as in septic chronic phase (7d). Enhancing autophagy soon after sepsis is a potential strategy for treatment of sepsis-induced myopathy.
Palliative care for all? How can Brazil develop a palliative care service founded on principles of equity and access for all?
Authors: Corrêa Santiago Rodríguez , Abel Julian
Published: October 2018

Purpose of review

Despite the historical international development of palliative care over the last 50 years, provision of equity of care and access to appropriate medication remains a major problem in many countries across the world. Interest in the public health approach to end-of-life care has grown over the last 20 years. Models of palliative care, which are affordable and provide equity of care are changing through these new concepts. We describe an existing model of practice in a primary care setting in Rio Grande in Brazil, which could act as a template for redesign of palliative care services.

Recent findings

Traditional models of palliative care have focussed on the physical, social, psychological and spiritual domains. Abel and Kellehear have proposed a new model, uniting specialist and generalist palliative care with compassionate communities and the civic component encapsulated in the compassionate city charter. This model is more comprehensive, emphasizing both harm reduction and health and well being promotion, and is currently being rolled out within the Family Health Strategy in Rio Grande in Brazil.

An existing model of palliative care, which includes the public health approach in Rio Grande be used as a basis for more equitable palliative care in Brazil, to meet a large unmet need.
Benzodiazepines for agitation in patients with delirium: selecting the right patient, right time, and right indication
Authors: Hui David
Published: October 2018

Purpose of review

To provide an evidence-based synopsis on the role of benzodiazepines in patients with agitated delirium.

Recent findings

Existing evidence supports the use of benzodiazepines in two specific delirium settings: persistent agitation in patients with terminal delirium and delirium tremens. In the setting of terminal delirium, the goal of care is to maximize comfort, recognizing that patients are unlikely to recover from their delirium. A recent randomized trial suggests that lorazepam in combination with haloperidol as rescue medication was more effective than haloperidol alone for the management of persistent restlessness/agitation in patients with terminal delirium. In patients with refractory agitation, benzodiazepines may be administered as scheduled doses or continuous infusion for palliative sedation. Benzodiazepines also have an established role in management of delirium secondary to alcohol withdrawal. Outside of these two care settings, the role of benzodiazepine remains investigational and clinicians should exercise great caution because of the risks of precipitating or worsening delirium and over-sedation.

Benzodiazepines are powerful medications associated with considerable risks and benefits. Clinicians may prescribe benzodiazepines skillfully by selecting the right medication at the right dose for the right indication to the right patient at the right time.
Pelvic Floor Disorders After Obstetric Avulsion of the Levator Ani Muscle
Authors: Handa Victoria L. , Blomquist Joan L. , Roem Jennifer , Muñoz Alvaro , Dietz Hans Peter
Published: October 2018

Objectives

With vaginal childbirth, 10% to 30% of women sustain levator ani muscle avulsion. The objective of this study was to estimate the cumulative incidence of prolapse and other pelvic floor disorders (PFDs), comparing vaginally parous women with and without levator avulsion.

Methods

Parous women enrolled in a longitudinal study were assessed annually for PFDs with the Pelvic Organ Prolapse Quantification Examination (for prolapse) and the Epidemiology of Prolapse and Incontinence Questionnaire (for stress incontinence, overactive bladder, and anal incontinence). Three-dimensional transperineal ultrasound was used to identify levator avulsion. Women with and without levator avulsion after vaginal delivery were compared for the cumulative incidence of PFDs. Further analysis also stratified by forceps delivery.

Results

At the time of assessment, 453 participants were 6 to 17 years from first delivery (median, 11 years). Levator avulsion was identified in 15% (66/453) and was more common among those who had undergone forceps-assisted delivery (P < 0.001). Levator avulsion was strongly associated with prolapse beyond the hymen (odds ratio, 2.7; 95% confidence interval, 1.3–5.7) and with symptoms of prolapse (odds ratio, 3.0; 95% confidence interval–1.2, 7.3). These associations persisted after controlling for forceps-assisted delivery. In contrast, the odds of stress incontinence, overactive bladder, and anal incontinence were marginally (but not significantly) increased among women with levator avulsion in this cohort.

Conclusions

Obstetric levator avulsion is strongly associated with pelvic organ prolapse. The relationship between levator avulsion and other PFDs may not be significant.
Clostridium butyricum MIYAIRI 588 as Adjunctive Therapy for Treatment-Resistant Major Depressive Disorder: A Prospective Open-Label Trial
Authors: Miyaoka Tsuyoshi , Kanayama Misako , Wake Rei , Hashioka Sadayuki , Hayashida Maiko , Nagahama Michiharu , Okazaki Shihoh , Yamashita Satoko , Miura Shoko , Miki Hiroyuki , Matsuda Hiroyuki , Koike Masahiro , Izuhara Muneto , Araki Tomoko , Tsuchie Keiko , Azis Ilhamuddin Abdul , Arauchi Ryosuke , Abdullah Rostia Arianna , Oh-Nishi Arata , Horiguchi Jun
Published: October 2018

Aim

Up to 60% of depressed patients do not obtain sufficient relief from a course of antidepressant therapy, and these treatment-resistant major depressive disorder (TRD) patients are at increased risk for relapse, chronicity, persistent psychosocial impairments, and suicide. Probiotics actively participate in treatment of neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and depression remains unclear. We performed a prospective study to evaluate the effects of Clostridium butyricum MIYAIRI 588 (CBM588).

Methods

This was an 8-week open-label study to evaluate the efficacy and safety of CBM588 in combination with antidepressants in adult patients diagnosed with TRD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Forty antidepressant-treated inpatients were included. Patients were randomized to adjuvant treatment with CBM588 (n = 20) or control (n = 20). The primary endpoint was the change in the 17-item Hamilton Depression Rating Scale score from baseline to week 8. Secondary end points were changes in the Beck Depression Inventory and the Beck Anxiety Inventory scale scores from baseline to week 8. The Systematic Assessment of Treatment Emergent Events—General Inquiry was used to assess adverse effects.

Results

CBM588 (60 mg/d) in combination with antidepressants (flvoxamine, paroxetine, escitalopram, duroxetine, and sertraline) provided significant improvement in depression. All patients completed the trial, and 70% responded to treatment; the remission rate was 35.0%. No serious adverse events occurred.

Conclusions

These preliminary data suggest that CBM588 in combination with antidepressants is effective and well tolerated in the treatment of TRD. Further studies using a larger, double-blind, parallel-group design are warranted to confirm these findings.
Distinct Sources of a Bovine Blastocyst Digital Image do not Produce the Same Classification by a Previously Trained Software using Artificial Neural Network
Authors: Bertogna Guilherme Vitória , Pronunciate Micheli , Helena dos Santos Priscila , de Souza Ciniciato Diego , Beatriz Takahashi Maria , Celso Rocha José , Fábio Gouveia Nogueira Marcelo
Published: October 2018

We develop an online graphical and intuitive interface connected to a server aiming to facilitate access to professionals worldwide that face problems with bovine blastocysts classification. The interface Blasto3Q (3Q is referred to the three qualities of the blastocyst grading) contains a description of 24 variables that are extracted from the image of the blastocyst and analyzed by three Artificial Neural Networks (ANNs) that classifies the same loaded image. The same embryo (i.e., the biological specimen) was submitted to digital image capture by the control group (inverted microscope with 40x of magnification) and to experimental group (stereomicroscope with maximum of magnification plus 4x zoom from the cell phone). The 36 images obtained from control and experimental groups were uploaded on the Blasto3Q. Each image from both sources was evaluated for segmentation and submitted (only if it could be properly or partially segmented) to the quality grade classification by the three ANNs of the Blasto3Q program. In the group control, all the images were properly segmented, whereas 38.9% (07/18) and 61.1% (11/18) of the images from the experimental group, respectively could not be segmented or were partially segmented. The percentage of agreement was calculated when the same blastocyst was evaluated by the same ANN from the two sources (control and experimental groups). On the 54 potential evaluations of the three ANNs (i.e., 18 images been evaluated by the three networks) from the experimental group only 22.2% agreed with evaluations of the control (12/54). Of the remaining 42 disagreed evaluations from experimental group, 21 were unable to be performed and 21 were wrongly processed when compared with control evaluation.
chroGPS2: differential analysis of epigenome maps in R
Authors: Reina Oscar , Azorin Fernando , Stephan-Otto Attolini Camille
Published: October 2018

1

1.1

Backgrounds

In the last years we have faced an unprecedented growth in the availability of high-throughput epigenomics data related to the genomic distribution of epigenetic marks, namely transcription factors, histone modifications and other DNA binding proteins. This also pointed out the need for efficient tools for integration, visualization and functional analysis of genomics and epigenomics data. On this subject, we previously developed a computational framework, chroGPS, to integrate and visualize the associations between epigenetic factors and their relation to functional genetic elements in low-dimensional maps. We demonstrated the usefulness of our approach with several practical case studies based on well-defined biological hypothesis.

1.2

Results

Here we introduce chroGPS version 2, a major update of our previously developed software with new functionalities for differential analysis of epigenomes. Methods are provided for efficient integration and comparison of data from different conditions or biological backgrounds, accounting and adjusting for systematic biases in order to provide an efficient and statistically robust base for differential analysis. We also include new useful functionalities for general data assessment and quality control prior to comparing maps, such as functions to study chromatin domain conservation between epigenomic backgrounds, to detect gross technical outliers and also to help in the selection of candidate marks for de-novo epigenome mapping. Our software, implemented in R as a Bioconductor package, provides detailed reference and user manuals to allow the final user to reproduce the presented case studies and use them as a starting point for generating and exploring epigenetic maps according to their own experimental needs.

1.3

Conclusion

chroGPS2 extends our previously developed software, providing now a complete, intuitive, efficient and statistically robust framework for generation, visualization, characterization and differential analysis of epigenomic maps, in a way which is easy to adapt to different biological and technical backgrounds allowing exploration and hypothesis testing in multiple biological scenarios.
Widespread cytoplasmic polyadenylation programs asymmetry in the germline and early embryo
Authors: Boag Peter R. , Harrison Paul F. , Barugahare Adele A. , Pattison Andrew D. , Swaminathan Angavai , Raymant Greta , Monk Stephanie , Tsyganov Kirill , Heinz Eva , Davis Gregory M. , Powell David R. , Beilharz Traude H.
Published: October 2018

BACKGROUND

The program of embryonic development is launched by selective activation of a silent maternal transcriptome. InCaenorhabditis elegans, nuclei of the adult germline are responsible for the synthesis of at least two distinct mRNA populations; those required for housekeeping functions, and those that program the oocyte-to-embryo transition. We mapped this separation by changes to the length-distribution of poly(A)-tails that depend on GLD-2 mediated cytoplasmic polyadenylation and its regulators genome-wide.

RESULTS

More than 1000 targets of cytoplasmic polyadenylation were identified by differential polyadenylation. Amongst mRNA with the greatest dependence on GLD-2 were those encoding RNA binding proteins with known roles in spatiotemporal patterning such asmex-5andpos-1. In General, the 3’ UTR of GLD-2 targets were longer, contained cytosine-patches, and were enriched for non-standard polyadenylation-motifs. To identify the deadenylase that initiated transcript silencing, we depleted the known deadenylases in thegld-2(0)mutant background. Only the loss of CCF-1 suppressed the short-tailed phenotype of GLD-2 targets suggesting that in addition to its general role in RNA turnover, this is the major deadenylase for regulatory silencing of maternal mRNA. Analysis of poly(A)-tail length-change in the embryo lacking specific RNA-binding proteins revealed new candidates for asymmetric expression in the first embryonic divisions.

CONCLUSION

The concerted action of RNA binding proteins exquisitely regulates GLD-2 activity in space and time. We present our data as interactive web resources for a model where GLD-2 mediated cytoplasmic polyadenylation regulates target mRNA at each stage of worm germline and early embryonic development.
mirtronDB: a mirtron knowledge base
Authors: Ribeiro Da Fonseca Bruno Henrique , Silva Domingues Douglas , Rossi Paschoal Alexandre
Published: October 2018

Motivation

Mirtrons are originated from short introns with atypical cleavage from the miRNA canonical pathway by using the splicing mechanism. Several studies describe mirtrons in chordates, invertebrates and plants but in the current literature there is no repository that centralizes and organizes these public and available data. To fill this gap, we created the first knowledge database dedicated to mirtron, called mirtronDB, available at http://mirtrondb.cp.utfpr.edu.br/. MirtronDB has a total of 1,407 mirtron precursors and 2,426 mirtron mature sequences in 18 species.

Results

Through a user-friendly interface, users can browse and search mirtrons by organism, organism group, type and name. MirtronDB is a specialized resource to explore mirtrons and their regulations, providing free, user-friendly access to knowledge on mirtron data.

Availability

MirtronDB is available at http://mirtrondb.cp.utfpr.edu.br/.

Contact

paschoal@utfpr.edu.br

Supplementary information

Supplementary data are available.
Managing Marek’s disease in the egg industry
Authors: Rozins Carly , Day Troy , Greenhalgh Scott
Published: October 2018

The industrialization of farming has had an enormous impact. To most, this impact is viewed solely in the context of productivity, but the denser living conditions and shorter rearing periods of industrial livestock farms provide pathogens with an ideal opportunity to spread and evolve. For example, the industrialization of poultry farms drove the Marek’s disease virus (MDV) to evolve from causing a mild paralytic syndrome to causing a highly contagious, globally prevalent, disease that can have up to a 100% mortality rate. Fortunately, the economic catastrophe that would occur from MDV evolution has been prevented through widespread use of live imperfect vaccines that limit disease symptoms, but fail to prevent transmission. Unfortunately, the continued rollout of such imperfect vaccines is steering the evolution of MDV towards an even greater virulence and an ability to evade vaccine protection. Thus, there is a need to investigate alternative economically viable control measures for their ability to inhibit MDV spread and evolution. In what follows we examine the economic viability of standard husbandry practices for their ability to inhibit the spread of both virulent MDV and very virulent MDV throughout an industrialized egg farm. To do this, we parameterized a dynamic MDV transmission model and calculate the loss in egg production due to disease. We find that the MDV strain as well as the cohort duration had the greatest influence on disease burden and hence egg production. Additionally, we find that the standard husbandry practice involving conventional cages, often referred to as “battery cages”, results in the least per capita loss in egg production due to MDV infection when compared to alternative enriched or aviary (free-run) systems for virulent MDV, but not very virulent MDV, in which case the Aviary system performs the best. These results highlight an important cost that managers will face when implementing new hen husbandry practices.