bluuebunny/crossref_metadata_2025 huggingface dataset:
AvalonElite Double Lumen Cannula for Total Cavopulmonary Assist in Failing Fontan Sheep Model with Valved Extracardiac Conduit
Authors: Zhou Cheng , Wang Dongfang , Condemi Francesca , Zhao Guangfeng , Topaz Stephen , Ballard-Croft Cherry , Zwischenberger Joseph B.
Published: May 2018

The AvalonElite double lumen cannula (DLC) provides total cavopulmonary assist (CPA) in failing Fontan sheep, but recirculation limits reliability. To improve CPA performance, a two-valve extracardiac conduit (ECC) was used to bracket infusion blood toward pulmonary artery (PA). A total cavopulmonary connection with failing Fontan circulation adult sheep model was created with valved ECC (n = 6). The valved ECC was connected to superior/inferior venae cavae (SVC/IVC) and right PA. The AvalonElite DLC was inserted from right jugular vein with infusion opening between the ECC valves. The DLC drainage lumen withdrew blood from SVC/IVC, and the infusion lumen returned blood to ECC. A failing Fontan sheep model with valved ECC was successfully created. Central venous pressure increased from 9 ± 1 to 17 ± 1 mm Hg, systolic arterial pressure decreased from 103 ± 9 to 51 ± 13 mm Hg, and cardiac output decreased from 3.6 ± 0.3 to 1.4 ± 0.2 L/min. Serum lactate significantly increased, indicating poor tissue perfusion. At 4 L/min pumping flow, the AvalonElite DLC returned hemodynamics/lactate to baseline levels throughout 6 hour CPA. Necropsy revealed intact/well-functioning ECC valves and well-positioned DLC with no visible thrombosis. The AvalonElite DLC provides reliable CPA performance in failing Fontan sheep with valved ECC.
The current state of long-acting growth hormone preparations for growth hormone therapy
Authors: Yuen Kevin C.J. , Miller Bradley S. , Biller Beverly M.K.
Published: May 2018

Purpose of review

To discuss the rationale of developing long-acting growth hormone (LAGH) preparations, to describe the technologies designed to prolong GH action, and to address key issues regarding efficacy, safety, and monitoring while on treatment.

Review findings

Recombinant human GH is currently approved for daily use and has been shown to restore longitudinal growth, and improve body composition with relatively few side-effects in children and adults with GH deficiency, respectively. However, daily injections can be inconvenient, painful and distressing for some patients, resulting in decreased adherence and efficacy. Over a dozen pharmaceutical companies have designed LAGH preparations that are at various stages of development using a number of different methods to prolong GH action.

LAGH will represent an advancement over daily recombinant human GH injections because of fewer injections that may offer increased acceptance, tolerability, and therapeutic flexibility to patients that potentially can improve treatment outcomes. However, given the unphysiological profile of LAGH preparations, long-term surveillance of efficacy and safety are needed. This review summarizes recent developments of LAGH preparations, and highlights the importance of long-term surveillance registries to assess for efficacy and safety that will be essential for understanding the impact of prolonged exposure to these compounds.
Sexual Functioning in Hyperprolactinemic Patients Treated With Cabergoline or Bromocriptine
Authors: Krysiak Robert , Okopień Bogusław
Published: May 2018

Background:

Elevated prolactin levels were found to be associated with impaired sexuality.

Study Question:

The aim of the study was to compare the impact of bromocriptine and cabergoline on sexual functioning in both genders.

Study Design:

The study enrolled 39 young women and 18 young men receiving bromocriptine treatment. In 19 women and 8 men, because of poor tolerance, bromocriptine was replaced with cabergoline, whereas the remaining ones continued bromocriptine treatment.

Measures and Outcomes:

Apart from measuring serum levels of prolactin and insulin sensitivity, at the beginning of the study and 16 weeks later, all included patients completed questionnaires evaluating female or male sexual functioning (Female Sexual Function Index; International Index of Erectile Function-15).

Results:

Irrespective of the gender, posttreatment prolactin levels were lower in cabergoline-treated patients than in bromocriptine-treated patients. Baseline sexual functioning did not differ between patients well and poorly tolerating bromocriptine treatment. Neither in men nor in women receiving bromocriptine, posttreatment sexual functioning differed from baseline one. In both genders, cabergoline improved sexual desire. Moreover, in men, the drug improved erectile and orgasmic function, whereas in women, it improved sexual arousal. All these effects correlated with the impact of this drug on prolactin levels and on insulin sensitivity.

Conclusions:

Cabergoline is superior to bromocriptine in affecting male and female sexual functioning and should be preferred in hyperprolactinemic men and women with sexual dysfunction.
Homeless Status, Postdischarge Health Care Utilization, and Readmission After Surgery
Authors: Titan Ashley , Graham Laura , Rosen Amy , Itani Kamal , Copeland Laurel A. , Mull Hillary J. , Burns Edith , Richman Joshua , Kertesz Stefan , Wahl Tyler , Morris Melanie , Whittle Jeffery , Telford Gordon , Wilson Mark , Hawn Mary
Published: May 2018

Introduction:

Homeless Veterans are vulnerable to poor care transitions, yet little research has examined their risk of readmission following inpatient surgery. This study investigates the predictors of surgical readmission among homeless relative to housed Veteran patients.

Methods:

Inpatient general, vascular, and orthopedic surgeries occurring in the Veterans Health Administration from 2008 to 2014 were identified. Administrative International Classification of Diseases, Ninth Revision, Clinical Modification codes and Veterans Health Administration clinic stops were used to identify homeless patients. Bivariate analyses examined characteristics and predictors of readmission among homeless patients. Multivariate logistic models were used to estimate the association between homeless experience and housed patients with readmission following surgery.

Results:

Our study included 232,373 surgeries: 43% orthopedic, 39% general, and 18% vascular with 5068 performed on homeless patients. Homeless individuals were younger (56 vs. 64 y, P<0.01), more likely to have a psychiatric comorbidities (51.3% vs. 19.4%, P<0.01) and less likely to have other medical comorbidities such as hypertension (57.1% vs. 70.8%, P<0.01). Homeless individuals were more likely to be readmitted [odds ratio (OR), 1.43; confidence interval (CI), 1.30–1.56; P<0.001]. Discharge destination other than community (OR, 0.57; CI, 0.44–0.74; P<0.001), recent alcohol abuse (OR, 1.45; CI, 1.15–1.84; P<0.01), and elevated American Society Anesthesiologists classification (OR, 1.86; CI, 1.30–2.68; P<0.01) were significant risk factors associated with readmissions within the homeless cohort.

Conclusions:

Readmissions are higher in homeless individuals discharged to the community after surgery. Judicious use of postoperative nursing or residential rehabilitation programs may be effective in reducing readmission and improving care transitions among these vulnerable Veterans. Relative costs and benefits of alternatives to community discharge merit investigation.
Predischarge and Postdischarge Risk Factors for Hospital Readmission Among Patients With Diabetes
Authors: Karunakaran Abhijana , Zhao Huaqing , Rubin Daniel J.
Published: May 2018

Background:

Hospital readmission within 30 days of discharge (30-d readmission) is an undesirable outcome. Readmission of patients with diabetes is common and costly. Most of the studies that have examined readmission risk factors among diabetes patients did not include potentially important clinical data.

Objectives:

To provide a more comprehensive understanding of 30-day readmission risk factors among patients with diabetes based on predischarge and postdischarge data.

Research Design:

In this retrospective cohort study, 48 variables were evaluated for association with readmission by multivariable logistic regression.

Subjects:

In total, 17,284 adult diabetes patients with 44,203 hospital discharges from an urban academic medical center between January 1, 2004 and December 1, 2012.

Measures:

The outcome was all-cause 30-day readmission. Model performance was assessed by c-statistic.

Results:

The 30-day readmission rate was 20.4%, and the median time to readmission was 11 days. A total of 27 factors were statistically significant and independently associated with 30-day readmission (P<0.05). The c-statistic was 0.82. The strongest risk factors were lack of a postdischarge outpatient visit within 30 days, hospital length-of-stay, prior discharge within 90 days, discharge against medical advice, sociodemographics, comorbidities, and admission laboratory values. A diagnosis of hypertension, preadmission sulfonylurea use, admission to an intensive care unit, sex, and age were not associated with readmission in univariate analysis.

Conclusions:

There are numerous risk factors for 30-day readmission among patients with diabetes. Postdischarge factors add to the predictive accuracy achieved by predischarge factors. A better understanding of readmission risk may ultimately lead to lowering that risk.
Update on complications in cleft orthognathic surgery
Authors: Ohrmann Dörte , Hoyte-Williams Paa Ekow , Chen Philip Kuo-Ting
Published: May 2018

Purpose of review

To give an update on recent publications and tendencies concerning complications in cleft orthognathic surgery.

Recent findings

Cleft-specific changes after orthognathic surgery and their impact on surgical outcomes are discussed. Focus lays on the causes and mechanisms of cleft-related surgical complications and strategies to prevent or minimize these complications. Bimaxillary surgery is seen as a safe procedure for cleft patients. Maxillary distraction, total or segmental, is pointed out as an alternative method to improve outcomes. Different techniques for osteotomies and maxillary mobilization could decrease adverse events.

Cleft patients are more susceptible to the occurrence of complications because of peculiar presurgical conditions. Different surgical approaches and techniques are presented to overcome these difficulties, to achieve better results and to increase patient safety. The importance of communication between patient, family and cleft team members is emphasized.
Modern postoperative monitoring of free flaps
Authors: Kääriäinen Minna , Halme Elina , Laranne Jussi
Published: May 2018

Purpose of review

Flap failure in microvascular reconstruction is a costly complication with total flap loss being the worst-case scenario. With the aim to rapidly identify a postoperative circulatory problem, some susceptible flaps can be saved by careful clinical monitoring or by various technical monitoring methods. In head and neck surgery, where the flaps are often buried and difficult to monitor clinically, a reliable technical monitoring method would be useful. A broad range of different techniques are in use varying according to practical and personal preferences among clinics and surgeons. However, no evidence for any particular technique being superb has emerged. We review reports of some frequently used and modern free flap monitoring techniques.

Recent findings

Clinical monitoring is still the gold standard to which other techniques are compared to. Laser Doppler flowmetry and near-infrared spectroscopy have been reported to identify early circulatory problems, but both techniques are not well suited for buried flaps. Implantable Doppler, flow coupler, partial tissue oxygen pressure and microdialysis are invasive monitoring methods suitable for buried flaps.

More research with practical and clinically relevant parameters, that is flap salvage rate, false positive rate and cost-efficiency are needed before objective comparisons between different monitoring techniques can be made.
Human leukocyte antigen matching in organ transplantation: what we know and how can we make it better (Revisiting the past, improving the future)
Authors: Tambur Anat R.
Published: May 2018

Purpose of review

A renaissance for human leukocyte antigen (HLA) testing emerged with the understanding that donor-specific HLA antibodies play a significant role in long-term allograft survival. This renewed focus on donor/recipient histocompatibility led to a recent quest to decipher antibody responses or, as introduced into the transplantation lexicon, ‘HLA-epitope matching’.

Recent findings

Whether matching is at the antigen or the epitope level, in-depth understanding of how histo-incompatibility leads to activation of an immune response is required. HLA-DQ donor-specific antibody (DSA) has the highest association with poor graft survival. However, HLA-DQ antigens and antibodies are understudied and significant gaps still exist in understanding the function of HLA-DQ in immune activation. Much of our knowledge about HLA class-II molecules is derived from studies performed on HLA-DR, whether it is crystallography, antigen processing and presentation analysis, or activation of T-cell signal-transduction pathways. Indeed, HLA-DQ molecules are less amenable for laboratory testing, but the limited studies that were performed indicate that HLA-DQ might have, at least to some extent, a different role compared with HLA-DR.

This review highlights qualities of HLA-DQ that may be associated with different pathways of activating an immune response. Understanding the consequences of such differences may lead to better appreciation and significance of HLA-DQ for matching purposes.
Comorbidities in Childhood Celiac Disease
Authors: Prinzbach Ariana , Moosavinasab Soheil , Rust Steve , Boyle Brendan , Barnard John A. , Huang Yungui , Lin Simon
Published: May 2018

Objectives:

Celiac disease (CD) is associated with a variety of extraintestinal autoimmune and inflammatory findings that manifest clinically as symptoms and comorbidities. Understanding these comorbidities may improve identification of the disease and prevent sequelae. In this study, we use an unbiased electronic health record (EHR)‐based Phenome Wide Association Study (PheWAS) method to confirm known comorbidities, discover novel associations and enhance characterization of the clinical presentation of CD in children.

Methods:

Data were extracted from the Nationwide Children's Hospital EHR. Confirmed CD cases (n = 433) were matched with 4330 randomly selected controls. Utilizing an EHR‐based PheWAS method to analyze associations of phenotypes with CD, we conducted an unbiased screening of all International Classification of Diseases, 10th revision diagnostic codes and examined significance by performing Fisher's Exact tests. We further tested for the association between CD and 14 previously identified comorbidities in an a priori fashion.

Results:

We found 45 International Classification of Diseases, 10th revision codes significantly associated with CD. Thirteen are known comorbidities and nine are expected symptoms of CD, thus validating our study methods. Further investigation found symptoms that characterized CD clinically and discovered a significant association between eosinophilic disorders of the esophagus and CD. Of 14 previously identified comorbidities, 8 were significantly associated with CD.

Conclusions:

An EHR‐based PheWAS method is a powerful, efficient, and cost‐effective method to screen for possible CD comorbidities and validate associations at the population level. Ours is the first PheWAS of CD to confirm a significant association of eosinophilic disorders of the esophagus with CD in a controlled study.
Nutritional Considerations in Pediatric Pancreatitis
Authors: Abu‐El‐Haija Maisam , Uc Aliye , Werlin Steven L. , Freeman Alvin Jay , Georgieva Miglena , Jojkić‐Pavkov Danijela , Kalnins Daina , Kochavi Brigitte , Koot Bart G.P. , Van Biervliet Stephanie , Walkowiak Jaroslaw , Wilschanski Michael , Morinville Veronique D.
Published: May 2018

Objectives:

Wide variations exist in how physicians manage the nutritional aspects of children affected by acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic (CP) pancreatitis. Better consensus for optimal management is needed.

Methods:

This consensus statement on nutrition in pediatric pancreatic diseases was developed through a joint ESPGHAN‐NASPGHAN working group that performed an evidence‐based search of the literature on nutrition in AP, ARP, and CP with a focus on pediatrics. The literature was summarized, quality of evidence reviewed, and expert recommendations developed. The authorship met to discuss the evidence and statements. Voting on recommendations occurred over 2 rounds based on feedback. A consensus of at least 75% was required to approve a recommendation. Areas requiring further research were identified.

Results and Discussion:

The literature on nutrition in pediatric pancreatitis is limited. Children with mild AP benefit from starting an early nutritional regimen in the course of the attack. Early nutrition should be attempted in severe AP when possible; enteral nutrition is preferred over parenteral nutrition. Children with ARP are likely to tolerate and benefit from a regular diet. Children with CP need ongoing assessment for growth and nutritional deficiencies, exocrine and endocrine insufficiencies.

Conclusions:

This document presents the first authoritative recommendations on nutritional considerations in pediatric pancreatitis. Future research should address the gaps in knowledge particularly relating to optimal nutrition for AP in children, role of diet or dietary supplements on recurrent attacks of pancreatitis and pain episodes, monitoring practices to detect early growth and nutritional deficiencies in CP and identifying risk factors that predispose children to these deficiencies.
Hematologic Findings of Inherited Metabolic Disease: They are More Than Expected
Authors: Sal Ertan , Yenicesu Idil , Okur Ilyas , Kaya Zuhre , Ezgu Fatih S. , Kocak Ulker , Tumer Leyla , Gursel Turkiz , Hasanoglu Alev
Published: May 2018

Inherited metabolic diseases are pathologic conditions that generally develop as a result of impairment of the production or breakdown of protein, carbohydrate, and fatty acids. Early determination of hematological findings has a positive effect on the prognosis of metabolic diseases. Three hundred eighteen patients who were being followed-up within the previous 6 months at Department of Pediatric Nutrition and Metabolism, Gazi University, Turkey, were included in the study. The hematological findings were classified under 7 main groups: anemia of chronic disease, iron deficiency anemia, vitamin B12 deficiency anemia, hemophagocytosis, leukocytosis, and thrombocytosis. Nine hundred twenty-two hematological examinations of the 319 patients were included in the study, and 283 hematological findings were determined, 127 anemia of chronic disease, 81 iron deficiency anemia, 56 cytopenia, and 4 vitamin B12 deficiency anemia. Leukocytosis (n=1), thrombocytosis (n=5), and hemophagocytosis (n=9) were also observed. It was determined that, although anemia of chronic disease and nutritional anemia are the most common hematological findings, these may be diagnosed late, whereas neutropenia, thrombocytopenia, pancytopenia, and hemostasis disorders may be diagnosed earlier. Our study is the most comprehensive one in the literature, and we think it would positively contribute to the monitoring and prognosis of congenital metabolic diseases.
Reducing RN Vacancy Rate
Authors: Hisgen Stephanie A. , Page Nancy E. , Thornlow Deirdre K. , Merwin Elizabeth I.
Published: May 2018

OBJECTIVE

The aim of this study was to reduce the RN vacancy rate at an academic medical center by improving the hiring process in the Nursing Recruitment Office.

BACKGROUND

Inability to fill RN positions can lead to higher vacancy rates and negatively impact staff and patient satisfaction, quality outcomes, and the organization's bottom line.

METHODS

The Model for Improvement was used to design and implement a process improvement project to improve the hiring process from time of interview through the position being filled.

RESULTS

Number of days to interview and check references decreased significantly, but no change in overall time to hire and time to fill positions was noted. RN vacancy rate also decreased significantly. Nurse manager satisfaction with the hiring process increased significantly.

CONCLUSION

Redesigning the recruitment process supported operational efficiencies of the organization related to RN recruitment.
Laxative-Induced Contact Dermatitis
Authors: Melvin Jennifer E. , Hickey Robert W.
Published: May 2018

A 5-year-old female with Charcot-Marie-Tooth neuropathy and a history of constipation presented to the emergency department with a new blistering buttocks rash, which was initially concerning for nonaccidental burn. Upon further investigation, it was found that Ex-Lax had been given to the patient for constipation. This had resulted in a bowel movement, which led to an irritant dermatitis. The patient was eventually diagnosed with senna-induced erosive diaper dermatitis. This case report highlights the importance of a thorough history and physical examination to prevent an unnecessary child abuse work-up.
Infusion of cytotoxic T lymphocytes for the treatment of viral infections in hematopoetic stem cell transplant patients
Authors: Baugh Katherine A. , Tzannou Ifigeneia , Leen Ann M.
Published: May 2018

Purpose of review

Allogeneic hematopoietic stem cell transplantation has proven curative for a range of malignant and nonmalignant disorders. However, the clinical success of this therapy is marred by the morbidity associated with viral infections, which are frequent (cytomegalovirus 15.6–28%, adenovirus 3–21%, BK virus 18.5–20.7%) post-transplant. These infections occur as a consequence of transplant conditioning regimens designed to eliminate not only malignant cells but also host immune cells that might interfere with stem cell engraftment. The result is a transient period of immune compromise when hematopoietic stem cell transplant recipients are at risk of infectious complications associated with both latent (cytomegalovirus, Epstein–Barr virus, BK virus, human herpes virus 6, herpes simplex virus, varicella-zoster virus) and community-acquired viruses including adenovirus, respiratory syncytial virus, and parainfluenza virus.

Recent findings

Current standard of care for many of these infections involves pharmacologic agents, which are often ineffective and associated with side effects including nephrotoxicity and hepatotoxicity. Ultimately, because these agents do not address the underlying immune compromise, viral rebound often occurs. Thus, a number of groups have explored the clinical potential of adoptively transferred virus-specific T cells (VSTs) as an approach to prevent/treat virus-associated complications.

The current review will highlight recent publications showcasing VST manufacturing technologies and clinical experience with such cells.
Detection of Cerebrospinal Fluid Dissemination of Recurrent Glioblastoma Using TSPO-PET With 18F-GE-180
Authors: Unterrainer Marcus , Fleischmann Daniel F. , Lindner Simon , Brendel Matthias , Rupprecht Rainer , Tonn Joerg C. , Belka Claus , Bartenstein Peter , Niyazi Maximilian , Albert Nathalie L.
Published: May 2018

PET targeting the translocator protein (TSPO) represents an interesting approach for glioma visualization, as TSPO is highly expressed in tumor cells. We present a 32-year-old man with recurrent glioblastoma after multimodal treatment. PET with the novel TSPO ligand 18F-GE-180 was performed after reirradiation. Here, the previously reirradiated tumor showed a remaining circular TSPO expression. Moreover, cerebrospinal fluid dissemination was detected by a high focal uptake at the right lateral and at the fourth ventricle, whereas only a faint contrast enhancement was present in MRI. This case demonstrated the diagnostic potential of TSPO-PET for glioma imaging by visualizing even minimal disease burden.
Impressive Response to Tandem Treatment With [90Y]DOTATOC and [177Lu]DOTATOC in Grade 3 Pancreatic Neuroendocrine Carcinoma
Authors: Lorenzoni Alice , Capozza Antonella , Artale Salvatore , Maccauro Marco , Seregni Ettore Cesare
Published: May 2018

Peptide receptor radionuclide therapy is an effective, well-tolerated, treatment for well-differentiated neuroendocrine tumors, resulting in a significant survival benefit and improvement of quality of life. Very few data are available on peptide receptor radionuclide therapy effectiveness in grade 3 neuroendocrine carcinomas with high somatostatin receptor expression. We report the case of a 70-year-old woman with metastatic pancreatic grade 3 neuroendocrine carcinoma who underwent 6 cycles of tandem treatment with investigational radiopharmaceuticals 90Y-DOTATOC and 177Lu-DOTATOC achieving an impressive response.
Do Sepsis-3 Criteria Facilitate Earlier Recognition of Sepsis and Septic Shock? A Retrospective Cohort Study
Authors: Scheer Christian S. , Kuhn Sven-Olaf , Fuchs Christian , Vollmer Marcus , Modler Arnd , Brunkhorst Frank , Shankar-Hari Manu , Hahnenkamp Klaus , Gründling Matthias , Rehberg Sebastian
Published: May 2018

Background:

New Sepsis-3 criteria are supposed to “facilitate earlier recognition … of patients with sepsis.” To test this, we performed novel and direct comparisons of Sepsis-1 vs. Sepsis-3 criteria with respect to time differences of sepsis onset.

Methods:

In a cohort of intensive care unit (ICU) patients prospectively diagnosed with severe sepsis or septic shock according to Sepsis-1 criteria between 01/2010 and 12/2015, the time differences between meeting Sepsis-1 vs. Sepsis-3 criteria as time of sepsis onset and the corresponding differences in illness severity were tested. Similar comparisons were performed for septic shock subset meeting different Sepsis-1 vs. Sepsis-3 criteria. Patients with non-ICU-acquired sepsis and patients with sepsis onset more than 48 h postadmission (ICU-acquired sepsis) were analyzed separately to account for differences in availability of routinely collected organ dysfunction data.

Results:

A total of 10,905 ICU patients were screened; 862 patients met Sepsis-1 criteria, of whom 834 (97%) also met Sepsis-3 criteria. In patients, admitted to the ICU with sepsis, Sepsis-3 criteria compared with Sepsis-1 criteria were more frequently fulfilled within the first 3 h (84% vs. 75%, P < 0.001).

In patients with ICU-acquired sepsis, sepsis onset was in 50% at least 1 day earlier after application of Sepsis-3 (P = 0.011). These patients were systemic inflammatory response syndrome negative at the earlier sepsis onset, but suffered already from organ dysfunction. Sepsis-3 criteria were timely in 86% and 1 day delayed in 7%. Only 7% (8 patients) did not meet Sepsis-3 criteria in this group. These patients had already an increased SOFA score and did develop neither a further increase nor the new septic shock criteria. Classification according to Sepsis-3 reduced the proportion of septic shock (51% vs. 75%, P < 0.001).

Twenty-eight-day mortality was 38% for new septic shock compared with 33% of Sepsis-1 septic shock (P > 0.05). Patients not detected by Sepsis-3 had a 28-day mortality of 11%.

Conclusions:

Sepsis-3 criteria facilitate an earlier and more predictive recognition of sepsis and septic shock in patients with non-ICU and ICU-acquired sepsis primarily diagnosed by Sepsis-1 criteria. These results require further validation with prospectively collected data.
Using a Video-Laparoscope for Intraoperative Colonoscopy: An Experimental Study on Intraluminal Temperature Values and Tissue Damage
Authors: Şimşek Turgay , Büyükgebiz Oğuzhan , Şahin Deniz , Güneş Abdullah , Gürbüz Yeşim
Published: May 2018

Laparoscopy systems possess remarkable heat production. Video-laparoscopy was used for colonoscopy intraoperatively in rabbits. Rod lens type laparoscopes 5 and 10 mm in diameter connected with 175 and 300-W xenon light sources were used in combination. Physiological parameters including blood pressure, pulse, oxygen saturations, and luminal temperatures were investigated during 20 minutes of colonoscopy. Thermal damage scores were obtained by histopathologic analysis of the intestinal wall. The changes were categorized as physiological and structural. Damage scores were not different when 175-W light source was used with 5- and 10-mm laparoscopes. Intraluminal heat values most increased with 300 W plus 10-mm laparoscope and caused significant increase in damage scores. Structural damage indicating tissue necrosis was not observed with any of the combination in all groups. Video-laparoscopy systems did not cause significant tissue damage when used at low and moderate levels of xenon light source in the rabbit bowel intraoperatively.
Update in therapeutic strategies for Parkinson's disease
Authors: Kulisevsky Jaime , Oliveira Lais , Fox Susan H.
Published: May 2018

Purpose of review

To review recent advances in therapeutics for motor and nonmotor symptoms of Parkinson's disease.

Recent findings

Neuroprotection remains a large area of investigation with preliminary safety data on alpha synuclein immunotherapy and glucagon-like peptide-1 agonists. Novel Monoamine Oxidase B and Caetchol-O-methyltransferase-inhibitors for motor fluctuations have shown benefit and are recently approved for clinical use. Long-acting amantadine has also been approved to reduce dyskinesia. Alternative delivery strategies (sublingual, inhaled) dopaminergics may prove useful for rapid reversal of Parkinson's disease motor symptoms. Advanced therapies (surgery and infusional therapies) continue to be useful in subgroups of patients for motor complications with improved safety and also benefit on some nonmotor symptoms, including neuropsychiatric issues. Specific therapeutics for cognition, swallowing, sleep, and mood disorders had moderate to limited benefits. Exercise-based therapy appears beneficial at all stages of Parkinson's disease.

The motor symptoms of Parkinson's disease can be reasonably treated and managed. However, therapies to slow or prevent disease progression remain a focus of research. Despite increased studies, treating nonmotor symptoms remains a challenge and an ongoing priority.
Dystonia as a network disorder: a concept in evolution
Authors: Schirinzi Tommaso , Sciamanna Giuseppe , Mercuri Nicola B. , Pisani Antonio
Published: May 2018

Purpose of review

This survey takes into consideration the most recent advances in both human degenerative ataxias, disorders with a well established cerebellar origin, and discoveries from dystonia rodent models aimed at discussing the pathogenesis of dystonia.

Recent findings

One common recurrent term that emerges when describing dystonia is heterogeneity. Indeed, dystonia encompasses a wide group of ‘hyperkinetic’ movement disorders, with heterogeneous causes, classification, anatomical and physiological substrates. In addition, the clinical heterogeneity of age at onset, symptom distribution and appearance of non-motor symptoms has supported the concept of dystonia as ‘network’ disorder. Pathophysiological alterations are thought to arise from dysfunction at cortico-thalamic-basal ganglia level, whereas, more recently, a role for cerebellar pathways emerged. Results from human and animal studies thus fuel the evolving concept of the network disorder.

Current evidence suggests the involvement of multiple brain regions and cellular mechanisms, as part of the neural dysfunction observed at system level in dystonia.
The patchy tremor landscape: recent advances in pathophysiology
Authors: Nieuwhof Freek , Panyakaew Pattamon , van de Warrenburg Bart P. , Gallea Cecile , Helmich Rick C.
Published: May 2018

Purpose of review

We focus on new insights in the pathophysiology of Parkinson's disease tremor, essential tremor, tremor in dystonia, and orthostatic tremor.

Recent findings

Neuroimaging findings suggest that Parkinson's disease resting tremor is associated with dopaminergic dysfunction, serotonergic dysfunction, or both. Not all tremors in Parkinson's disease have the same pathophysiology: postural tremor in Parkinson's disease can be subdivided into pure postural tremor, which involves nondopaminergic mechanisms, and re-emergent tremor, which has a dopaminergic basis. Unlike Parkinson's disease tremor, essential tremor has an electrophysiological signature suggestive of a single (or several tightly coupled) oscillators. Visual feedback increases essential tremor and enhances cerebral activity in the cerebello-thalamo-cortical circuit, supplementary motor area, and parietal cortex. Little is known about dystonic tremor but the available evidence suggests that both the basal ganglia and the cerebellum play a role. Finally, recent work in orthostatic tremor points towards the role of the pontine tegmentum and dysfunctional cerebellar-SMA circuitry.

Many pathological tremors involve the cerebello-thalamo-cortical circuitry, and the clinical and pathophysiological boundaries between tremor disorders are not always clear. Differences between tremor disorders – or even individual patients – may be explained by the specific balance of neurotransmitter degeneration, by distinct circuit dynamics, or by the role of regions interconnected to the cerebello-thalamo-cortical circuit.
Measuring Clinically Relevant Knee Motions With A Self-Calibrated Wearable Sensor
Authors: Hullfish Todd J. , Qu Feini , Stoeckl Brendan D. , Gebhard Peter M. , Mauck Robert L. , Baxter Josh R.
Published: May 2018

Low-cost sensors provide a unique opportunity to continuously monitor patient progress during rehabilitation; however, these sensors have yet to demonstrate the fidelity and lack the calibration paradigms necessary to be viable tools for clinical research. Therefore, the purpose of this study was to validate a low-cost wearable sensor that accurately measured peak knee extension during clinical exercises and needed no additional equipment for calibration. Knee flexion was quantified using a 9-axis motion sensor and directly compared to motion capture data. Peak extension values during seated knee extensions were accurate within 5 degrees across all subjects (RMS error: 2.6 degrees, P = 0.29) but less accurate during sit-to-stand exercises (RMS error: 16.6 degrees, P = 0.48). Knee flexion during gait strongly correlated (0.84 ≤ rxy ≤ 0.99) with motion capture measurements but demonstrated average errors of 10 degrees. This study demonstrated a low-cost sensor that satisfied our criteria: a simple calibration procedure resulting in accurate measures of joint function during clinical exercises, making it a feasible tool for continuous patient monitoring to guide regenerative rehabilitation.
Similarity judgments and cortical visual responses reflect different properties of object and scene categories in naturalistic images
Authors: King Marcie L. , Groen Iris I. A. , Steel Adam , Kravitz Dwight J. , Baker Chris I.
Published: May 2018

Numerous factors have been reported to underlie the representation of complex images in high-level human visual cortex, including categories (e.g. faces, objects, scenes), animacy, and real-world size, but the extent to which this organization is reflected in behavioral judgments of real-world stimuli is unclear. Here, we compared representations derived from explicit similarity judgments and ultra-high field (7T) fMRI of human visual cortex for multiple exemplars of a diverse set of naturalistic images from 48 object and scene categories. Behavioral judgements revealed a coarse division between man-made (including humans) and natural (including animals) images, with clear groupings of conceptually-related categories (e.g. transportation, animals), while these conceptual groupings were largely absent in the fMRI representations. Instead, fMRI responses tended to reflect a separation of both human and non-human faces/bodies from all other categories. This pattern yielded a statistically significant, but surprisingly limited correlation between the two representational spaces. Further, comparison of the behavioral and fMRI representational spaces with those derived from the layers of a deep neural network (DNN) showed a strong correspondence with behavior in the top-most layer and with fMRI in the mid-level layers. These results suggest that there is no simple mapping between responses in high-level visual cortex and behavior – each domain reflects different visual properties of the images and responses in high-level visual cortex may correspond to intermediate stages of processing between basic visual features and the conceptual categories that dominate the behavioral response.

Significance Statement

It is commonly assumed there is a correspondence between behavioral judgments of complex visual stimuli and the response of high-level visual cortex. We directly compared these representations across a diverse set of naturalistic object and scene categories and found a surprisingly and strikingly different representational structure. Further, both types of representation showed good correspondence with a deep neural network, but each correlated most strongly with different layers. These results show that behavioral judgments reflect more conceptual properties and visual cortical fMRI responses capture more general visual features. Collectively, our findings highlight that great care must be taken in mapping the response of visual cortex onto behavior, which clearly reflect different information.
Molecularly distinct astrocyte subpopulations spatially pattern the adult mouse brain
Authors: Batiuk Mykhailo Y. , Martirosyan Araks , Voet Thierry , Ponting Chris P. , Belgard T. Grant , Holt Matthew G.
Published: May 2018

Astrocytes are a numerous cell type of the central nervous system. They perform many important functions in synapse formation and maintenance, control of local homeostasis and modulation of synaptic transmission. However, the degree to which specialist astrocyte subtypes fulfil these specific tasks is currently unclear. Here we use single cell transcriptomics to demonstrate that astrocytes, even those lying within the same region of adult mouse brain, show distinct molecular and spatial profiles, with profound implications for local CNS functions, including axon guidance, synaptogenesis and synaptic transmission.
The Microbiome Modeling Toolbox: from microbial interactions to personalized microbial communities
Authors: Baldini Federico , Heinken Almut , Heirendt Laurent , Magnusdottir Stefania , Fleming Ronan M.T. , Thiele Ines
Published: May 2018

Motivation

The application of constraint-based modeling to functionally analyze metagenomic data has been limited so far, partially due to the absence of suitable toolboxes.

Results

To address this shortage, we created a comprehensive toolbox to model i) microbe-microbe and host-microbe metabolic interactions, and ii) microbial communities using microbial genome-scale metabolic reconstructions and metagenomic data. The Microbiome Modeling Toolbox extends the functionality of the COBRA Toolbox.

Availability

The Microbiome Modeling Toolbox and the tutorials athttps://git.io/microbiomeModelingToolbox.
Silencing cuticular pigmentation genes enables RNA FISH in intact chemosensory appendagess
Authors: Pentzold Stefan , Grabe Veit , Ogonkov Andrei , Schmidt Lydia , Boland Wilhelm , Burse Antje
Published: May 2018

Optical imaging of gene expression by RNA-fluorescentin situhybridisation (FISH) in whole-mount sensory appendages of insects is often impeded by their highly pigmented cuticle. Since most chemical bleaching agents are incompatible with imaging fluorescent-labelled nucleotides, we developed a RNA interference-based method for clearing cuticular pigmentation that allows imaging of fluorescent mRNA in whole-mount appendages of insects. Silencing key genes of the tyrosine-derived pigmentation pathway by injecting dsRNA oflaccase2ortyrosine hydroxylasein two leaf beetles species (Chrysomela populi, Phaedon cochleariae) resulted in clearance of the highly pigmented cuticle and in significant decreased light absorbance. Intact chemosensory appendages (palps, antennae and legs) from RNAi-cleared individuals were used to image expression and spatial distribution of antisense mRNA of two chemosensory genes (gustatory receptor, odorant-binding protein) via RNA FISH and confocal laser scanning microscopy. Imaging of these genes did neither work for RNAi-controls (dsGfp) due to retained pigmentation, nor for FISH-controls using sense mRNA. Furthermore, we show that several chemical bleaching agents are not feasible with FISH, either due to significant degradation of polynucleotides, lack of clearing efficacy or long incubation times. Overall, silencing pigmentation genes is a significant improvement over bleaching agents allowing fluorescence imaging in whole-mount appendages and organs.
Energetic stress and infection generate immunity-fecundity tradeoffs in Drosophila
Authors: Buchanan Justin L. , Meiklejohn Colin D. , Montooth Kristi L.
Published: May 2018

Physiological responses to short-term environmental stress, such as infection, can have long-term consequences for fitness, particularly if the responses are inappropriate or nutrient resources are limited. Genetic variation affecting energy acquisition, storage, and usage can limit cellular energy availability and may influence resource-allocation tradeoffs even when environmental nutrients are plentiful. Here, we utilize well-characterized Drosophila mitochondrial-nuclear genotypes to test whether disrupted energy metabolism interferes with nutrient-sensing pathways, and whether this disruption has consequences for tradeoffs between immunity and fecundity. We find that this energetically compromised genotype is resistant to rapamycin – a drug that stimulates nutrient-sensing pathways that are activated when resources are limited. Resource limitation also compromises survival in energetically-compromised genotypes, suggesting that this genotype may have little excess energetic capacity and fewer cellular nutrients, even when environmental nutrients are not limiting. Accordingly, we find that immune function is compromised in this genotype, but only in females, and that these females experience immunity-fecundity tradeoffs that are not evident in genotypic controls with normal energy metabolism. Thus, genetic variation in energy metabolism may act to limit the resources available for allocation to life-history traits in ways that generate tradeoffs even when environmental resources are not limiting.
Intrinsically regulated learning is modulated by synaptic dopamine availability
Authors: Ripollés Pablo , Ferreri Laura , Mas-Herrero Ernest , Alicart Helena , Gómez-Andrés Alba , Marco-Pallarés Josep , Antonijoan Rosa , Noesselt Toemme , Valle Marta , Riba Jordi , Rodriguez-Fornells Antoni
Published: May 2018

We recently provided evidence that an intrinsic reward-related signal—triggered by successful learning in absence of any external feedback—modulated the entrance of new information into long-term memory via the activation of the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop; Ripollés et al., 2016). Here, we used a double-blind, within-subject randomized pharmacological intervention to test whether this learning process is indeed dopamine-dependent. A group of healthy individuals completed three behavioural sessions of our learning task after the intake of different pharmacological treatments: a dopaminergic precursor, a dopamine receptor antagonist or a placebo. Results show that the pharmacological intervention bidirectionally modulated behavioral measures of both learning and pleasantness, inducing memory benefits after 24 hours only for those participants with a high sensitivity to reward. These results provide causal evidence for a dopamine-dependent mechanism instrumental in intrinsically regulated learning, and further suggest that subject-specific dopamine sensitivity drastically alters learning success.
Refining fine-mapping: effect sizes and regional heritability
Authors: Benner Christian , Havulinna Aki S. , Salomaa Veikko , Ripatti Samuli , Pirinen Matti
Published: May 2018

Recent statistical approaches have shown that the set of all available genetic variants explains considerably more phenotypic variance of complex traits and diseases than the individual variants that are robustly associated with these phenotypes. However, rapidly increasing sample sizes constantly improve detection and prioritization of individual variants driving the associations between genomic regions and phenotypes. Therefore, it is useful to routinely estimate how much phenotypic variance the detected variants explain for each region by taking into account the correlation structure of variants and the uncertainty in their causal status. Here we extend the FINEMAP software to estimate the effect sizes and regional heritability under the probabilistic model that assumes a handful of causal variants per each region. Using the UK Biobank data to simulate GWAS regions with only a few causal variants, we demonstrate that FINEMAP provides higher precision and enables more detailed decomposition of regional heritability into individual variants than the variance component model implemented in BOLT or the fixed-effect model implemented in HESS. Using data from 51 serum biomarkers and four lipid traits from the FINRISK study, we estimate that FINEMAP captures on average 24% more regional heritability than the variant with the lowest P-value alone and 20% less than BOLT. Our simulations suggest how an upward bias of BOLT and a downward bias of FINEMAP could together explain the observed difference between the methods. We conclude that FINEMAP enables computationally efficient estimation of effect sizes and regional heritability in the era of biobank scale data.
Binocular Integration Manifests as a Transient Spiking Increase Followed by Selective Suppression in Primary Visual Cortex
Authors: Cox Michele A. , Dougherty Kacie , Westerberg Jacob A. , Schall Michelle S. , Maier Alexander
Published: May 2018

Research throughout the past decades revealed that neurons in primate primary visual cortex (V1) rapidly integrate the two eyes’ separate signals into a combined binocular response. The exact mechanisms giving underlying this binocular integration remain elusive. One open question is whether binocular integration occurs at a single stage of sensory processing or in a sequence of computational steps. To address this question, we examined the temporal dynamics of binocular integration across V1’s laminar microcircuit of awake behaving monkeys. We find that V1 processes binocular stimuli in a dynamic sequence that comprises at least two distinct phases: A transient phase, lasting 50-150ms from stimulus onset, in which neuronal population responses are significantly enhanced for binocular stimulation compared to monocular stimulation, followed by a sustained phase characterized by widespread suppression in which feature-specific computations emerge. In the sustained phase, incongruent binocular stimulation resulted in response reduction relative to monocular stimulation across the V1 population. By contrast, sustained responses for binocular congruent stimulation were either reduced or enhanced relative to monocular responses depending on the neurons’ selectivity for one or both eyes (i.e., ocularity). These results suggest that binocular integration in V1 occurs in at least two sequential steps, with an initial additive combination of the two eyes’ signals followed by the establishment of interocular concordance and discordance.

Significance Statement

Our two eyes provide two separate streams of visual information that are merged in the primary visual cortex (V1). Previous work showed that stimulating both eyes rather than one eye may either increase or decrease activity in V1, depending on the nature of the stimuli. Here we show that V1 binocular responses change over time, with an early phase of general excitation and followed by stimulus-dependent response suppression. These results provide important new insights into the neural machinery that supports the combination of the two eye’s perspectives into a single coherent view.