bluuebunny/crossref_metadata_2025 huggingface dataset:
In Defence of High-Speed Memory Scanning
Authors: Sternberg Saul
Published: August 2016

This paper reviews some of the evidence that bears on the existence of a mental high-speed serial exhaustive scanning process (SES) used by humans to interrogate the active memory of a set of items to determine whether it contains a test item. First proposed in the 1960s, based on patterns of reaction times (RTs), numerous later studies supported, elaborated, extended, and limited the generality of SES, while critics claimed that SES never occurred, that predictions from SES were violated, and that other mechanisms produced the RT patterns that led to the idea. I show that some of these claims result from ignoring variations in experimental procedure that produce superficially similar but quantitatively different RT patterns and that, for the original procedures, the most frequently repeated claims that predictions are violated are false. I also discuss evidence against the generality of competing theories of active-memory interrogation, especially those that depend on discrimination of directly accessible “memory-strength”. Some of this evidence has been available since the 1960s but has been ignored by some proponents of alternative theories. Other evidence presented herein is derived from results of one relevant experiment described for the first time, results of another described in more detail than heretofore, and new analyses of old data. Knowledge of brain function acquired during the past half century has increased the plausibility of SES. The conclusion: SES is alive and well, but many associated puzzles merit further investigation, suggestions for which are offered.
Decoding the principles underlying the frequency of association with nucleoli for RNA polymerase III–transcribed genes in budding yeast
Authors: Belagal Praveen , Normand Christophe , Shukla Ashutosh , Wang Renjie , Léger-Silvestre Isabelle , Dez Christophe , Bhargava Purnima , Gadal Olivier
Published: August 2016

The association of RNA polymerase III (Pol III)–transcribed genes with nucleoli seems to be an evolutionarily conserved property of the spatial organization of eukaryotic genomes. However, recent studies of global chromosome architecture in budding yeast have challenged this view. We used live-cell imaging to determine the intranuclear positions of 13 Pol III–transcribed genes. The frequency of association with nucleolus and nuclear periphery depends on linear genomic distance from the tethering elements—centromeres or telomeres. Releasing the hold of the tethering elements by inactivating centromere attachment to the spindle pole body or changing the position of ribosomal DNA arrays resulted in the association of Pol III–transcribed genes with nucleoli. Conversely, ectopic insertion of a Pol III–transcribed gene in the vicinity of a centromere prevented its association with nucleolus. Pol III–dependent transcription was independent of the intranuclear position of the gene, but the nucleolar recruitment of Pol III–transcribed genes required active transcription. We conclude that the association of Pol III–transcribed genes with the nucleolus, when permitted by global chromosome architecture, provides nucleolar and/or nuclear peripheral anchoring points contributing locally to intranuclear chromosome organization.
MenaINV mediates synergistic cross-talk between signaling pathways driving chemotaxis and haptotaxis
Authors: Oudin Madeleine J. , Miller Miles A. , Klazen Joelle A. Z. , Kosciuk Tatsiana , Lussiez Alisha , Hughes Shannon K. , Tadros Jenny , Bear James E. , Lauffenburger Douglas A. , Gertler Frank B.
Published: August 2016

Directed cell migration, a key process in metastasis, arises from the combined influence of multiple processes, including chemotaxis—the directional movement of cells to soluble cues—and haptotaxis—the migration of cells on gradients of substrate-bound factors. However, it is unclear how chemotactic and haptotactic pathways integrate with each other to drive overall cell behavior. MenaINV has been implicated in metastasis by driving chemotaxis via dysregulation of phosphatase PTP1B and more recently in haptotaxis via interaction with integrin α5β1. Here we find that MenaINV-driven haptotaxis on fibronectin (FN) gradients requires intact signaling between α5β1 integrin and the epidermal growth factor receptor (EGFR), which is influenced by PTP1B. Furthermore, we show that MenaINV-driven haptotaxis and ECM reorganization both require the Rab-coupling protein RCP, which mediates α5β1 and EGFR recycling. Finally, MenaINV promotes synergistic migratory response to combined EGF and FN in vitro and in vivo, leading to hyperinvasive phenotypes. Together our data demonstrate that MenaINV is a shared component of multiple prometastatic pathways that amplifies their combined effects, promoting synergistic cross-talk between RTKs and integrins.
Assembly ofCaenorhabditis elegansacentrosomal spindles occurs without evident microtubule-organizing centers and requires microtubule sorting by KLP-18/kinesin-12 and MESP-1
Authors: Wolff Ian D. , Tran Michael V. , Mullen Timothy J. , Villeneuve Anne M. , Wignall Sarah M.
Published: August 2016

Although centrosomes contribute to spindle formation in most cell types, oocytes of many species are acentrosomal and must organize spindles in their absence. Here we investigate this process in Caenorhabditis elegans, detailing how acentrosomal spindles form and revealing mechanisms required to establish bipolarity. Using high-resolution imaging, we find that in meiosis I, microtubules initially form a “cage-like” structure inside the disassembling nuclear envelope. This structure reorganizes so that minus ends are sorted to the periphery of the array, forming multiple nascent poles that then coalesce until bipolarity is achieved. In meiosis II, microtubules nucleate in the vicinity of chromosomes but then undergo similar sorting and pole formation events. We further show that KLP-18/kinesin-12 and MESP-1, previously shown to be required for spindle bipolarity, likely contribute to bipolarity by sorting microtubules. After their depletion, minus ends are not sorted outward at the early stages of spindle assembly and instead converge. These proteins colocalize on microtubules, are interdependent for localization, and can interact, suggesting that they work together. We propose that KLP-18/kinesin-12 and MESP-1 form a complex that functions to sort microtubules of mixed polarity into a configuration in which minus ends are away from the chromosomes, enabling formation of nascent poles.
Molecular Biology
Authors: Divan Aysha , Royds Janice
Published: August 2016

Molecular biology is the story of the molecules of life, their relationships, and how these interactions are controlled. Its applications are wide and growing; the power of molecular biology can now be harnessed to treat diseases, solve crimes, map human history, and produce genetically modified organisms and crops. Starting with the building blocks established by Darwin, Wallace, and Mendel, and the discovery of the structure of DNA in 1953, Molecular Biology: A Very Short Introduction considers the wide range of applications for molecular biology today, including the development of new drugs and DNA fingerprinting, and looks forward to two key areas of evolving research: personalized medicine and synthetic biology.
Public Administration
Authors: Theodoulou Stella Z. , Roy Ravi K.
Published: August 2016

Public administration ensures the development and delivery of the essential public services required for sustaining modern civilization. Covering areas from public safety and social welfare to transportation and education, the services provided through the public sector are inextricably part of our daily lives. Public Administration: A Very Short Introduction offers practical insight into the major challenges confronting the public sector in the globalized era. Tackling some of the most hotly debated issues of our time, including the privatization of public services and government surveillance, it takes the reader on a global journey through history to examine the origins, development, and continued evolution of public administration.
The Use of Telmisartan and the Incidence of Cancer
Authors: Tascilar Koray , Azoulay Laurent , Dell’Aniello Sophie , Bartels Dorothee B. , Suissa Samy
Published: August 2016

BACKGROUND

A meta-analysis reported an 8% increased risk of cancer with the use of angiotensin receptor blockers (ARBs), but subsequent meta-analyses and observational studies did not confirm this risk. However, telmisartan comprised 85% of the data in the original meta-analysis. Thus, the objective of this study was to determine whether the use of telmisartan, compared with other ARBs, is associated with an increased risk of cancer.

METHODS

We used the United Kingdom Clinical Practice Research Datalink to assemble a cohort of all patients newly treated with ARBs between 2000 and 2008, and followed until December 2010. Time-dependent cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer associated with telmisartan, compared with other ARBs, adjusted for potential confounders. Secondary analyses assessed the risk with each of the 4 most common cancers (lung, breast, prostate, colorectal).

RESULTS

The cohort consisted of 62,109 new ARB users, which included 3,438 telmisartan and 58,671 other ARB users. Compared with other ARBs, telmisartan use was not associated with an increased risk of cancer overall (16.3 vs. 15.0 per 1,000 person-years, respectively; adjusted HR: 0.93, 95% CI: 0.81–1.06) or by cancer site (lung, HR: 0.91, 95% CI: 0.55–1.51; breast, HR: 1.28, 95% CI: 0.90–1.82; prostate, HR: 0.79, 95% CI: 0.53–1.18; colorectal, HR: 1.41, 95% CI 0.95–2.10).

CONCLUSIONS

Compared with other ARBs, telmisartan is not associated with an increased risk of cancer. This study provides reassurance as to the short-term safety of telmisartan.
Clinical Impact on Tuberculosis Treatment Outcomes of Discordance Between Molecular and Growth-Based Assays for Rifampin Resistance, California 2003–2013
Authors: Shah Neha S. , Grace Lin SY , Barry Pennan M. , Cheng Yi-Ning , Schecter Gisela , Desmond Ed
Published: August 2016

Background.  Data from international settings suggest that isolates of Mycobacterium tuberculosis with rpoB mutations testing phenotypically susceptible to rifampin (RIF) may have clinical significance. We analyzed treatment outcomes of California patients with discordant molecular-phenotypic RIF results.

Methods.  We included tuberculosis (TB) patients, during 2003–2013, whose specimens tested RIF susceptible phenotypically but had a rpoB mutation determined by pyrosequencing. Demographic data were abstracted from the California TB registry. Phenotypic drug-susceptibility testing, medical history, treatment, and outcomes were abstracted from medical records.

Results.  Of 3330 isolates tested, 413 specimens had a rpoB mutation (12.4%). Of these, 16 (3.9%) had molecular-phenotypic discordant RIF results. Seven mutations were identified: 511Pro, 516Phe, 526Asn, 526Ser (AGC and TCC), 526Cys, and 533Pro. Fourteen (88%) had isoniazid (INH) resistance, 6 of whom were also phenotypically resistant to ethambutol (EMB) and/or pyrazinamide (PZA). Five patients (25%), 1 with 511Pro and 4 with 526Asn, relapsed or failed treatment. The initial regimen for 3 patients was RIF, PZA, and EMB; 1 patient received RIF, PZA, EMB, and a fluoroquinolone (FQN); and 1 patient received RIF, EMB, FQN, and some second-line medications. Upon retreatment with an expanded regimen, 3 (75%) patients completed treatment, 1 patient moved before treatment completion, and 1 patient continues on treatment. The remaining 11 patients had a successful outcome with 9 having received a FQN and/or a rifamycin.

Conclusions.  Rifampin molecular-phenotypic discordance was rare, and most isolates had INH resistance. Patients who did not receive an expanded regimen had poor outcomes. These mutations may have clinical importance, and expanded treatment regimens should be considered.
A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome
Authors: Greiss Hess Laura , Fitzpatrick Sarah E. , Nguyen Danh V. , Chen Yanjun , Gaul Kimberly N. , Schneider Andrea , Lemons Chitwood Kerrie , Eldeeb Marwa Abd Al Azaim , Polussa Jonathan , Hessl David , Rivera Susan , Hagerman Randi J.
Published: August 2016

Objective:

Observational studies and anecdotal reports suggest that sertraline, a selective serotonin reuptake inhibitor, may improve language development in young children with fragile X syndrome (FXS).

Methods:

The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 52 children with FXS aged 2 to 6 years.

Results:

Eighty-one subjects were screened for eligibility, and 57 were randomized to sertraline (27) or placebo (30). Two subjects from the sertraline arm and 3 from the placebo arm discontinued. Intent-to-treat analysis showed no difference from placebo on the primary outcomes: the Mullen Scales of Early Learning (MSEL) expressive language (EL) age equivalent and Clinical Global Impression Scale—Improvement. However, analyses of secondary measures showed significant improvements, particularly in motor and visual perceptual abilities and social participation. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events occurred.

Conclusion:

This randomized controlled trial of 6 months of sertraline treatment showed no primary benefit with respect to early EL development and global clinical improvement. However, in secondary exploratory analyses, there were significant improvements seen on motor and visual perceptual subtests, the cognitive T score sum on the MSEL, and on one measure of social participation on the Sensory Processing Measure—Preschool. Furthermore, post hoc analysis found significant improvement in early EL development as measured by the MSEL among children with autism spectrum disorder on sertraline. Treatment appears safe for this 6-month period in young children with FXS, but the authors do not know the long-term side effects of this treatment. These results warrant further studies of sertraline in young children with FXS using refined outcome measures as well as longer term follow-up studies to address long-term side effects of low-dose sertraline in early childhood.
Fractional CO2 Laser Pretreatment to Autologous Hair Transplantation and Phototherapy Improves Perifollicular Repigmentation in Refractory Vitiligo: A Randomized, Prospective, Half-Lesion, Comparative Study
Authors: Feily Amir , Seifi Vahid , Ramirez-Fort Marigdalia K.
Published: August 2016

BACKGROUND

Fractional CO2 laser and autologous hair transplantation are independently effective in the treatment of refractory and stable vitiligo.

OBJECTIVE

The authors' purpose was to evaluate the therapeutic efficacy of fractional CO2 laser pretreatment compared with autologous hair transplantation and phototherapy alone for refractory and stable vitiligo.

METHODS

A total of 20 patients with refractory and stable vitiligo were enrolled from our clinic. Resistant lesions randomly divided into 2 regions as follows: (1) Part A: fractional CO2 laser pretreatment followed by autologous transplantation and phototherapy, and (2) Part B: autologous transplantation and phototherapy alone. Five days after fractional CO2 laser application to Part A, both treatment regions received a transplant of scalp grafts. On Day 11, the entire lesion was exposed to narrow-band UVB phototherapy, twice a week for 12 weeks. The diameter of perifollicular repigmentation was measured monthly with a caliper.

RESULTS

Perifollicular repigmentation was detectable surrounding 74% of grafted hair follicles by Month 3. Furthermore, Part A demonstrated a significantly greater diameter of repigmentation with 6.6 ± 5.8 mm in Part A compared with 4.3 ± 1.8 mm in Part B (p = <.001).

CONCLUSION

In this study, our results demonstrate improved efficacy of autologous hair transplantation and narrow-band UVB with fractional CO2 laser pretreatment in refractory and stable vitiligo.
Cardamonin Alleviates Pressure Overload-induced Cardiac Remodeling and Dysfunction Through Inhibition of Oxidative Stress
Authors: Li Wei , Wu Xiangqi , Li Minghui , Wang Zhimei , Li Bing , Qu Xinliang , Chen Shaoliang
Published: August 2016

Pressure overload-induced cardiac remodeling and dysfunction progress to heart failure, which is mainly due to excessive oxidative stress. Hence, our study aimed to illustrate whether cardamonin, a kind of chalcone, could attenuate maladaptive cardiac changes and ameliorate cardiac insufficiency through its antioxidant mechanism. In vivo, our study revealed that cardamonin treatment could attenuate transverse aortic contraction-induced cardiac remodeling and dysfunction. Histological observations have suggested that cardamonin inhibited the occurrence of excessive cardiac oxidative stress and apoptosis. In vitro, we found that 3 treatments with angiotensin II (Ang II), hydrogen peroxide, and Nox4 overexpression in H9C2 cells markedly augmented intracellular oxidative stress as measured by superoxide dismutase, l-glutathione, and malonaldehyde. Conversely, cardamonin treatment notably alleviated oxidative stress induced by the 3 above-mentioned treatments. Furthermore, all 3 treatments resulted in increased apoptotic cell death, whereas cardamonin treatment reduced apoptosis in H9C2 cells. Moreover, cardamonin significantly abrogated the expression of Bax, apoptosis inducing factor, cytochrome c, and caspase-3 and caspase-9 and enhanced the expression of Bcl-2 and Bcl-xl. In conclusion, these findings provide a new possibility for cardamonin to alleviate pressure overload-induced heart failure.
“Lull pgm System” for Autologous Fat Grafting: A Simple Closed System with Minimal Equipment and No Extra Cost
Authors: Morselli Paolo Giovanni , Micai Alessandro , Giorgini Federico Armando
Published: August 2016

The “Lull pgm system” is a closed system for purifying harvested fat. It processes the collected tissue safely without any additional cost. The system was conceived by referring to the targets described in the literature with the aim of creating a simple system that guarantees a high standard of purification and requires minimal equipment that is available in every operating room. Cost must be always considered: even the most prosperous hospitals must keep within tight annual budgets. “Lull” can be used instead of expensive devices or disposable kits, without substantially increasing the operating time. The system has been used in clinical practice for many plastic reconstructive procedures and has obtained positive results and patient satisfaction, and no contraindications or disadvantages have been observed.
Radiofrequency-assisted Liposuction for Neck and Lower Face Adipodermal Remodeling and Contouring
Authors: Keramidas Evangelos , Rodopoulou Stavroula
Published: August 2016

Background:

The purpose of this study is to report our experience using radiofrequency-assisted liposuction (RFAL) for neck and face contouring. This article details the operative technique, selection, complications, third-party surgeon appraisal, and patient satisfaction survey.

Methods:

From November 2009 to November 2013, 55 patients who underwent RFAL treatment were enrolled in the study. Postoperative patient satisfaction surveys were conducted, and 2 independent plastic surgeons evaluated contour and skin quality with randomized preoperative and postoperative photographs at 6 months postoperatively. The different parameters recorded involved age, sex, weight, body mass index, operative time, amount of fat aspirated and energy delivered, complications, and aesthetic outcome in 1 and 4 weeks and 3 and 6 months. Our longest follow-up was 4 years. Patients were asked 6 months postoperatively to grade their satisfaction as poor, no change, moderate, good, and excellent.

Results:

The mean age was 51 years (range, 35–61 years), and the mean amount of fat aspirated was 30 mL (range, 10–200 mL). Five out of 55 patients (9.1%) developed tissue hardness that resolved with massage. All patients were followed up for a minimum of 6 months. Eighty-five percent of patients were satisfied with their contouring result and degree of skin tightening (48/55 patients). Two independent plastic surgeons considered the improvement in contouring and degree of skin tightening good to excellent in 52 of 55 cases.

Conclusions:

In appropriately selected patients, RFAL neck and face contouring represent a safe procedure to achieve significant improvement of the skin laxity and fat deposits of the cervicomental zone and jowls.
Single-layer Closure with Tongue Flap for Palatal Fistula in Cleft Palate Patients
Authors: Alsalman Abdulla K. , Algadiem Emran A. , Alwabari Mufeed Saeed , Almugarrab Fatimah Jawad
Published: August 2016

Background:

Tongue flap is a good option to close a complicated palatal fistula in cleft patients. Most surgeons advocate a double-layer closure to decrease the recurrence rates. In this study, we have reported our experience with a modified single-layer closure with tongue flap in cleft patients.

Method:

All cases done by a single surgeon using this modified technique in a period of 10 years were retrospectively reviewed. A thorough description of this technique is also provided in the study.

Results:

Only 5 cases were operated on using this technique. The success rate of all these cases was 100%, with no recurrence of fistula and few complications.

Conclusions:

This technique provides a way to avoid nasal layer closure in cases where nasal layer is difficult or impossible to close. It also limits the need for a second flap for nasal layer closure.
Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson's disease
Authors: Cury Rubens G. , Galhardoni Ricardo , Teixeira Manoel J. , dos Santos Ghilardi Maria G. , Silva Valquiria , Myczkowski Martin L. , Marcolin Marco A. , Barbosa Egberto R. , Fonoff Erich T. , Ciampi de Andrade Daniel
Published: August 2016

Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN-DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement.
What People Want in a Prosthetic Foot: A Focus Group Study
Authors: Fogelberg Donald J. , Allyn Katheryn J. , Smersh Monica , Maitland Murray E.
Published: August 2016

Introduction

Most people with lower-limb amputation (LLA) rely on a prosthetic foot for participation at home and in the community. The published literature describes problems with mobility after LLA, yet there have been few published accounts of peoples' participation experiences. The purpose of this study was to increase understanding of the impact of prosthetic feet on participation in the activities of daily life by examining the experience of prosthetic users and professionals.

Materials and Methods

Users of prosthetic feet and health care professionals who prescribe prosthetic feet were invited to complete a brief online questionnaire before participating in one of five focus groups. Descriptive statistics were used to summarize questionnaire data. Focus group sessions were audio recorded and transcribed. Each transcript was thematically coded independently by four researchers. Emergent themes were discussed, categorized, and cross-referenced.

Results

Eleven prosthetic foot users (68.8%) and 11 professionals (100%) completed the online questionnaires. Although the prosthetic foot users rated their difficulty with usual activities as none to slight, 36% reported falling within the last 6 months, and 45% indicated that they modified their participation because of the potential for falls. Sixteen prosthetic foot users and 11 health care professionals took part in focus groups. There was a significant overlap in themes discussed by prosthetic foot users and health care professionals. Identified barriers to full participation included the ability to stand for extended periods, navigate in confined spaces, carry heavy objects, and change body posture. Absence of sensory feedback created significant concerns about safety when driving a car, navigating uneven terrain, or climbing ladders. Characteristics of existing prosthetic feet that impact participation included limited durability, lack of waterproofing, and limited range of motion. Current designs limited choices of footwear and created difficulties donning and doffing shoes.

Conclusions

Participants' reported confidence in forward walking on even ground suggests that current prosthetic feet are well-suited for this limited use. However, they also identified a number of situations in which their current prosthetic feet caused significant difficulties, often with safety implications. While some stories, such as rocks on the sidewalk, are consistent with the literature, other stories describe situations such as ladders and stepstools that are not well documented. Our study highlights the utility of focus groups in identifying previously unrecognized needs and concerns, with significant implications for the design of prosthetic feet. Future studies should include more diverse participants, particularly with regard to age and overall physical health.
A Pilot Investigation of the Effect of Postural Control Strategies and Balance in Children with Unilateral Lower-Limb Amputation
Authors: Geil Mark D. , Wasco Kevin J. , Wu Jianhua , Coulter Colleen , Safaeepour Zahra , Tai Wang Yong
Published: August 2016

Introduction

Previous research has addressed the effects of backpack loads on balance in adults and children, but there is a gap in the literature concerning children with lower-limb amputation. The purpose of this study was to assess the effect of backpack loads on postural sway in children with lower-limb amputation.

Materials and Methods

Four children with unilateral Syme amputation and five controls were assessed in quiet standing with backpacks loaded with 0%, 10%, 20%, and 25% of body weight. Kinetic data were collected using force platforms, and the path of the center of pressure was calculated.

Results

Considering the sway parameters, the control group showed the expected increase with each successive weight level, whereas the group of children with amputation showed an unexpected nonlinear response as weight increased.

Conclusions

Postural control mechanisms used by the children with amputation may be different from their able-bodied counterparts.
Neurological Management of Von Hippel-Lindau Disease
Authors: Hodgson Trent S. , Nielsen Sarah M. , Lesniak Maciej S. , Lukas Rimas V.
Published: August 2016

Von Hippel-Lindau disease is a genetic condition due to mutation of the Von Hippel-Lindau gene, which leads to an increased risk in the development of hemangioblastomas of the brain and spinal cord. The pathophysiology of disease and its clinical manifestations, as they pertain to the general neurologist, are discussed. Therapeutic management of central nervous system hemangioblastomas ranging from neurosurgical resection, radiation therapy, and systemic therapies is reviewed.
Transient Impact of Rituximab in H1N1 Vaccination–associated Narcolepsy With Severe Psychiatric Symptoms
Authors: Sarkanen Tomi , Alén Reija , Partinen Markku
Published: August 2016

Introduction:

Narcolepsy type 1 is an organic sleep disorder caused by the destruction of hypocretin producing neurons in hypothalamus. In addition to daytime sleepiness, the spectrum and severity of symptoms are very variable. Psychiatric comorbidity and phenomena resembling psychotic symptoms are also common. Current treatment options for narcolepsy are symptomatic but there are few case reports of positive effect of immunotherapy. We report a very severely affected young boy treated with rituximab (RXB).

Case Report:

A 12-year-old boy developed narcolepsy after Pandemrix H1N1 vaccination in 2010. He started to express severe psychiatric symptoms shortly after the onset. Cataplexy and sleepiness were devastatingly disabling. Conventional treatments did not have any effect on symptoms so we decided to try RXB, chimeric human monoclonal antibody against CD20+ expressed in B lymphocytes. After the first treatment his condition ameliorated dramatically. Unfortunately, the effect lasted only for 2 months. Following attempts did not show any effect.

Conclusions:

Effect of RXB on narcolepsy has not been reported before. Remarkable but short-lasting effect of RXB in narcolepsy is intriguing as it could imply that there is still ongoing B cell–mediated autoimmune response possible contributing to symptoms in narcolepsy.
Effect of Target Luminance on Optimum Pupil Diameter for Presbyopic Eyes
Authors: Xu Renfeng , Thibos Larry , Bradley Arthur
Published: August 2016

Purpose

To quantify the optimum pupil diameters for presbyopic eyes when environmental light levels vary from high photopic to low mesopic.

Methods

We computed the white light visual Strehl ratio from the polychromatic optical transfer function (VSOTF). The impact on image quality of retinal illuminance and the accompanying changes in photon noise were reflected in changing neural contrast sensitivity. VSOTF was calculated for focused and −2D defocused images, over a wide range of photopic and mesopic target luminances, and for pupil diameters ranging from 1 to 7 mm. We compare these modeling data to logMAR visual acuity measured under the same conditions.

Results

Optimum pupil depends on the relative gain of optical factors (diffraction and aberrations) and neural thresholds (photon noise effect). When light levels are reduced from 1000 to 2 cd/m2, the pupil size that optimizes VSOTF for a well-focused presbyopic eye model also maximizes visual acuity and it increases from 2.5 to 4 mm. A 1-mm-diameter pupil maximizes VSOTF at all light levels when −2D of defocus are included, but at 2 cd/m2the optimum pupil diameter for acuity increases slightly to 1.4 mm. At 0.2 cd/m2, the pupil size that optimizes VSOTF remains 4 and 1 mm for a focused and −2D defocused eye, respectively, but significantly larger pupils are needed for maximal visual acuity. Reducing pupils to 30% of their natural size is beneficial for distance and near image quality and visual acuity at all light levels, producing more gains for near than for distance.

Conclusions

A fixed 2- to 3-mm small pupil or a 30% pupil miosis can both produce near visual acuity gains without significant losses to distance acuity or image quality, and therefore can be considered as optimal for a presbyope experiencing a wide range of light levels.
Topographic Anatomy of the Inferior Medial Palpebral Artery and Its Relevance to the Pretarsal Roll Augmentation
Authors: Cong Li-Yao , Lee Sang-Hee , Tansatit Tanvaa , Hu Kyung-Seok , Kim Hee-Jin
Published: August 2016

Background:

A detailed analysis of the topography of the inferior medial palpebral artery is needed to optimize the safety and efficacy of pretarsal roll augmentation.

Methods:

Thirty-one hemifaces from 13 Korean and 8 Thai cadavers (15 male and six female cadavers) were dissected. The distributions of the inferior medial palpebral artery were determined with respect to the superior medial palpebral artery and the supratrochlear artery.

Results:

Four distribution patterns were observed. The inferior and superior medial palpebral arteries branched individually from the ophthalmic artery, with the ophthalmic artery terminating as the supratrochlear artery on the forehead (type I); a short trunk branched from the ophthalmic artery and divided into the inferior medial palpebral artery and superior medial palpebral artery, and the ophthalmic artery terminated as the supratrochlear artery (type II); the inferior and superior medial palpebral arteries arose together from the ophthalmic artery, and the ophthalmic artery terminated as the supratrochlear artery (type III); or the inferior and superior medial palpebral arteries were the terminal branches of the ophthalmic artery, with the supratrochlear artery arising from the angular artery (type IV). The diameter of the artery was 0.94 ± 0.22 mm at the entry point and 0.37 ± 0.11 mm at the lateral canthus.

Conclusions:

The inferior medial palpebral artery was located along the tarsal plate deep to the pretarsal part of the orbicularis oculi in the lower eyelid. Injections to augment the pretarsal roll should be made between the subcutaneous tissue and this pretarsal part of the orbicularis oculi.
Effect of Cold Preservation on Chronic Rejection in a Rat Hindlimb Transplantation Model
Authors: Bonastre Jorge , Landín Luis , Bolado Pedro , Casado-Sánchez César , López-Collazo Eduardo , Díez Jesús
Published: August 2016

Background:

Previous studies on solid organ transplantation have shown that cold ischemia contributes to the development of chronic allograft vasculopathy. The authors evaluated the effect of cold ischemia on the development of chronic rejection in vascularized composite allotransplantation.

Methods:

Thirty rat hindlimbs were transplanted and divided into two experimental groups: immediate transplantation and transplantation after 7 hours of cold ischemia. The animals received daily low-dose immunosuppression with cyclosporine A for 2 months. Intimal proliferation, arterial permeability rate, leukocyte infiltration, and tissue fibrosis were assessed. The CD3+, CD4+, CD8+, CD20+, and CD68+ cells per microscopic field (200×) were counted, and C4d deposition was investigated. Cytokine RNA analysis was performed to measure tumor necrosis factor-α, interleukin-6, and interleukin-10 levels.

Results:

Significant differences were found in the intimal proliferation and arterial permeability rate between the two groups (p = 0.004). The arterial permeability rate worsened in the most distal and small vessels (p = 0.047). The numbers of CD3+, CD8+, CD20+, and CD68+ were also statistically higher in the cold ischemia group (p < 0.05, all levels). A trend toward significance was observed with C4d deposition (p = 0.059). No differences were found in the RNA of cytokines.

Conclusions:

An association between cold ischemia and chronic rejection was observed in experimental vascularized composite allotransplantation. Chronic rejection intensity and distal progression were significantly related with cold ischemia. The leukocyte infiltrates in vascularized composite allotransplantation components were a rejection marker; however, their exact implication in monitoring and their relation with cold ischemia are yet to be clarified.
A Novel Three-Dimensional Platform to Investigate Neoangiogenesis, Transendothelial Migration, and Metastasis of MDAMB-231 Breast Cancer Cells
Authors: Hooper Rachel C. , Jacoby Adam , Asanbe Ope , Osoria Hector L. , Morrison Kerry A. , Hernandez Karina , Boyko Tatiana , Joyce Jeremiah , Landford Wilminia , Spector Jason A.
Published: August 2016

Background:

A crucial step in the progression of cancer involves the transendothelial migration of tumor cells into the bloodstream and invasion at distant sites. Most in vitro models of malignant cell behavior do not account for the presence of and interaction with vascular cells. Three-dimensional platforms to further explore the factors responsible for metastatic cellular behavior are under intensive investigation.

Methods:

Hydrogels with encapsulated MDAMB-231 breast cancer cells were fabricated with a central microchannel. The microchannel was lined with a co-culture of human umbilical vein endothelial cells and human aortic smooth muscle cells. For comparison, co-culture–seeded microchannels without breast cancer cells (MDAMB-negative) were fabricated.

Results:

After 7 and 14 days, the endoluminal lining of encapsulated MDAMB-231 co-culture–seeded microchannels demonstrated aberrant endothelial cell and smooth muscle cell organization and breast cancer cell transendothelial migration. MDAMB-231 cells performed matrix remodeling, forming tumor aggregates within the bulk, migrating preferentially toward the hydrogel “neovessel.” In contrast, MDAMB-negative constructs demonstrated maintenance of an intact endoluminal lining composed of endothelial cells and smooth muscle cells that organized into discrete layers. Furthermore, the thicknesses of the endoluminal lining of MDAMB-negative constructs were significantly greater than encapsulated MDAMB-231 co-culture–seeded constructs after 7 and 14 days (p = 0.012 and p < 0.001, respectively).

Conclusion:

The authors have created a powerful tool that may have tremendous impact on furthering our understanding of cancer recurrence and metastasis, shedding light on these poorly understood phenomena.
Free Functioning Gracilis Muscle Transfer versus Intercostal Nerve Transfer to Musculocutaneous Nerve for Restoration of Elbow Flexion after Traumatic Adult Brachial Pan-Plexus Injury
Authors: Maldonado Andrés A. , Kircher Michelle F. , Spinner Robert J. , Bishop Allen T. , Shin Alexander Y.
Published: August 2016

Background:

After complete five-level root brachial plexus injury, free functional muscle transfer and intercostal nerve transfer to the musculocutaneous nerve are two potential reconstructive options for elbow flexion. The aim of this study was to determine the outcomes of free functional muscle transfer versus intercostal nerve–to–musculocutaneous nerve transfers with respect to strength.

Methods:

Sixty-two patients who underwent free functional muscle transfer reconstruction or intercostal nerve–to–musculocutaneous nerve transfer for elbow flexion following a pan-plexus injury were included. The two groups were compared with respect to postoperative elbow flexion strength according to the British Medical Research Council grading system; preoperative and postoperative Disabilities of the Arm, Shoulder, and Hand questionnaire scores.

Results:

In the free functional muscle transfer group, 67.7 percent of patients achieved M3 or M4 elbow flexion. In the intercostal nerve–to–musculocutaneous nerve transfer group, 41.9 percent of patients achieved M3 or M4 elbow flexion. The difference was statistically significant (p < 0.05). Changes in Disabilities of the Arm, Shoulder, and Hand questionnaire scores were not statistically significant. Average time from injury to surgery was significantly different (p < 0.01) in both groups. The number of intercostal nerves used for the musculocutaneous nerve transfer did not correlate with better elbow flexion grade.

Conclusions:

Based on this study, gracilis free functional muscle transfer reconstruction achieves better elbow flexion strength than intercostal nerve–to–musculocutaneous nerve transfer for elbow flexion after pan-plexus injury. The role of gracilis free functional muscle transfer should be carefully considered in acute reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Regional Oxygen Saturation Index: A Novel Criterion for Free Flap Assessment Using Tissue Oximetry
Authors: Akita Shinsuke , Mitsukawa Nobuyuki , Tokumoto Hideki , Kubota Yoshitaka , Kuriyama Motone , Sasahara Yoshitaro , Yamaji Yoshihisa , Satoh Kaneshige
Published: August 2016

Background:

Tissue oximetry is a useful tool for postoperative free flap monitoring. Reported criterion values have been accurate; however, there are various complicated author-dependent criteria, and sometimes it is too late for flap salvage. The authors offer a new, simple criterion for faster and accurate detection of perfusion problems.

Methods:

Intraoperatively, perfusion areas of various free perforator flaps were assessed by both indocyanine green angiography and regional oxygen saturation. The elevated flap was categorized into the early-stained area, the delayed-stained area, and the no-stained area by indocyanine green angiography. The regional oxygen saturation index (regional oxygen saturation on the flap on the control nondissected portion) of each area was calculated. Postoperative continuous flap monitoring was conducted, recording the value of the regional oxygen saturation index at the early-stained area. The blood glucose measurement index was also recorded periodically.

Results:

In 60 cases of perforator-based free flaps, intraoperative indocyanine green areas were significantly correlated with the values of regional oxygen saturation index. The postoperative regional oxygen saturation index showed very stable values in various types of perforator flaps, provided that no vascular problem occurred, and it never went below 0.75. When vascular problems occurred, the regional oxygen saturation index dropped below 0.75 in all three cases before the blood glucose measurement index and the absolute value of regional oxygen saturation dropped below the criterion value.

Conclusion:

The regional oxygen saturation index may be a simple and fast criterion for detecting vascular problems following free flap reconstruction compared with existing criteria.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Diagnostic, II.
Phalloplasty: A Review of Techniques and Outcomes
Authors: Morrison Shane D. , Shakir Afaaf , Vyas Krishna S. , Kirby Johanna , Crane Curtis N. , Lee Gordon K.
Published: August 2016

Background:

Acquired or congenital absence of the penis can lead to severe physical limitations and psychological outcomes. Phallic reconstruction can restore various functional aspects of the penis and reduce psychosocial sequelae. Moreover, some female-to-male transsexuals desire creation of a phallus as part of their gender transition. Because of the complexity of phalloplasty, there is not an ideal technique for every patient. This review sets out to identify and critically appraise the current literature on phalloplasty techniques and outcomes.

Methods:

A comprehensive literature search of the MEDLINE, PubMed, and Google Scholar databases was conducted for studies published through July of 2015 with multiple search terms related to phalloplasty. Data on techniques, outcomes, complications, and patient satisfaction were collected.

Results:

A total of 248 articles were selected and reviewed from the 790 identified. Articles covered a variety of techniques on phalloplasty. Three thousand two hundred thirty-eight patients underwent phalloplasty, with a total of 1753 complications reported, although many articles did not explicitly comment on complications. One hundred four patients underwent penile replantation and two underwent penile transplantation. Satisfaction was high, although most studies did not use validated or quantified approaches to address satisfaction.

Conclusions:

Phalloplasty techniques are evolving to include a number of different flaps, and most techniques have high reported satisfaction rates. Penile replantation and transplantation are also options for amputation or loss of phallus. Further studies are required to better compare different techniques to more robustly establish best practices. However, based on these studies, it appears that phalloplasty is highly efficacious and beneficial to patients.
Deciphering the tissue specificity of the protein secretory pathway in humans
Authors: Feizi Amir , Gatto Francesco , Uhlen Mathias , Nielsen Jens
Published: August 2016

Proteins that are components of the secretory machinery form a cellular pathway of paramount importance for physiological regulation, development and function of human tissues. Consistently, most secretory pathway components are ubiquitously expressed in all tissues. At the same time, recent studies identified that the largest fraction of tissue-specific proteins consists of secreted and membrane proteins and not intracellular proteins. This suggests that the secretory pathway is distinctively regulated in a tissue-specific fashion. However, a systematic analysis on how the protein secretory pathway is tuned in different tissues is lacking, and it is even largely unexplored if the secretome and membrane proteome differs in, for example, posttranslation modifications across tissues. Here, analyzing publically available transcriptome data across 30 human tissues, we discovered the expression level of key components previously categorized as housekeeping proteins were specifically over-expressed in a certain tissue compared with the average expression of their corresponding secretory pathway subsystem (e.g. protein folding). Theseextreme genesdefine an exceptional fine-tuning in specific subnetworks, which neatly differentiated for example the pancreas and liver from 30 other tissues. Moreover, the subnetwork expression tuning correlated with the nature and number of post translational modification sites in the pancreas or liver-specific secretome and membrane proteome. These patterns were recurrently observed also in other tissues, like the blood, the brain and the skeletal muscle. These findings conciliate both the housekeeping and tissue-specific nature of the protein secretory pathway, which we attribute to a fine-tuned regulation of defined subnetworks in order to support the diversity of secreted proteins and their modifications.
Canu: scalable and accurate long-read assembly via adaptivek-mer weighting and repeat separation
Authors: Koren Sergey , Walenz Brian P. , Berlin Konstantin , Miller Jason R. , Bergman Nicholas H. , Phillippy Adam M.
Published: August 2016

Long-read single-molecule sequencing has revolutionizedde novogenome assembly and enabled the automated reconstruction of reference-quality genomes. However, given the relatively high error rates of such technologies, efficient and accurate assembly of large repeats and closely related haplotypes remains challenging. We address these issues with Canu, a successor of Celera Assembler that is specifically designed for noisy single-molecule sequences. Canu introduces support for nanopore sequencing, halves depth-of-coverage requirements, and improves assembly continuity while simultaneously reducing runtime by an order of magnitude on large genomes versus Celera Assembler 8.2. These advances result from new overlapping and assembly algorithms, including an adaptive overlapping strategy based ontf-idfweighted MinHash and a sparse assembly graph construction that avoids collapsing diverged repeats and haplotypes. We demonstrate that Canu can reliably assemble complete microbial genomes and near-complete eukaryotic chromosomes using either PacBio or Oxford Nanopore technologies, and achieves a contig NG50 of greater than 21 Mbp on both human andDrosophila melanogasterPacBio datasets. For assembly structures that cannot be linearly represented, Canu provides graph-based assembly outputs in graphical fragment assembly (GFA) format for analysis or integration with complementary phasing and scaffolding techniques. The combination of such highly resolved assembly graphs with long-range scaffolding information promises the complete and automated assembly of complex genomes.