bluuebunny/crossref_metadata_2025 huggingface dataset:
The Marriage of Sartorius and Tensor Fasciae Latae in Treating Vascular Prosthetic Graft Infections
Authors: Zoepke Simone N. , de Weerd Louis
Published: April 2017

Background:

Vascular prosthetic graft infection in the groin is associated with high morbidity and mortality. This article presents a case series on the use of 2 flaps in the treatment of this condition.

Methods:

Five patients, mean age 65 years (range, 49–74 years), with significant comorbidity were treated for an exposed and infected vascular prosthetic graft in the groin with a combination of sartorius muscle (SM) flap and tensor fascia lata (TFL) myocutaneous flap after debridement and start of microbiologic culture–guided antibiotic treatment. The SM flap was used to cover the exposed graft. To obtain stable wound coverage, the SM and remaining groin defect were closed with a pedicle TFL flap.

Results:

All flaps survived, with only 1 TFL flap suffering a small tip necrosis. All patients obtained stable wound coverage. Donor-site morbidity was minimal. During the follow-up, mean 46 months (range, 15–79 months), 1 patient had a recurrence after 15 months due to a kink in the elongated prosthetic graft that protruded through the skin alongside the SM and TFL flaps.

Conclusions:

The combination of SM and TFL flaps could be a new treatment option for patients who have an exposed and infected vascular prosthetic graft in the groin. This flap combination could also be used as a prophylactic procedure for those patients with a high risk to develop such a serious complication.
Digital Joint Reconstruction with Osteotendinous Joint Allograft: Experimental Study in Rats
Authors: Iglesias Martin , Cruz-Reyes Ángel Uriel , Butrón Patricia , Hernández-Agallo Ricardo , de la Barrera Víctor Antonio Torres , Reyes-Montero Claudio , Durand-Carbajal Marta , Torres-Villalobos Gonzalo
Published: April 2017

Background:

Fresh or frozen nonvascularized osteotendinous joint allografts (OTJA) have not been used previously, clinically or experimentally, for metacarpophalangeal joint reconstruction. Therefore, we evaluated the viability of OTJA for metatarsophalangeal joint (MTJ) reconstruction in rats.

Methods:

In the experimental group of 12 Lewis rats, we reconstructed the MTJ of the third digit of the hindlimb with a fresh, nonvascularized OTJA obtained from the same digit from 12 donor rats. In the control group of 6 Lewis rats, an autologous composite osteotendinous graft of the MTJ of the same digit was obtained and repositioned in situ as an auto-transplant. Weight, pain, edema, dehiscence, and wound infection were evaluated every 24 hours for 30 days postoperatively. At the end of 30 days, we evaluated digit position, flexion and extension, passive mobility, radiological bone healing, and histological grades of rejection.

Results:

We found no statistically different changes in weight, edema, pain, digit position, or radiological bone healing in either group. No wound dehiscence or infection was seen in any of the rats. Ten degrees of flexion and extension mobility were lost in the control group; the experimental group lost up to 30 degrees (P = 0.009). Histologically, 9 of the experimental group rats (9/12, 75%) showed rejection reactions compared with none of the controls (0%) (P = 0.009).

Conclusions:

Fresh nonvascularized OTJA caused an immune reaction without exposure of the graft, but with bone resorption. However, the rats maintained digital form and alignment with decreased passive flexion and extension of 10–30 degrees.
RESULTS OF MACULAR HOLE SURGERY
Authors: Liu Laura , Enkh-Amgalan Ijilmurun , Wang Nan-Kai , Chuang Lan-Hsin , Chen Yen-Po , Hwang Yih-shiou , Chang Chee-Jen , Chen Kuan-Jen , Wu Wei-chi , Chen Tun-Lu , Lai Chi-Chun
Published: April 2017

Purpose:

To evaluate the differences in anatomical and visual function changes after macular hole (MH) surgery using the International Vitreomacular Traction Study classification.

Methods:

Patients who underwent vitrectomy and blood-assisted internal limiting membrane peeling because of MHs were enrolled in the present study. The patients were divided into three groups according to the sizes of their MHs (small: ≤250 μm, medium: >250 μm and ≤400 μm, and large: >400 μm). The effect of vitreomacular traction on the outcome was also analyzed. All the patients were followed for at least 12 months. The changes in best-corrected visual acuity and the outer retina at the foveal area were monitored using spectral-domain optical coherence tomography.

Results:

A total of 146 eyes of 146 patients were enrolled. The patients with small MHs showed significantly better mean final visual acuity (mean: 20/58) than patients with large MHs (20/178, P < 0.05). There was no significant difference between patients with small- and medium-sized MHs (20/69). Longitudinal analysis showed that the presence of vitreomacular traction was related to a better restoration of the outer retinal structure and visual acuity.

Conclusion:

Patients with smaller MHs and vitreomacular adhesion had superior final visual acuity and better restoration of the outer retinal structure after MH surgery.
Rhabdomyolysis Complicating Typhoid Fever in a Child and Review of the Literature
Authors: Snelling Peter James , Moriarty Paul , Vaska Vikram L. , Levitt David , Nourse Clare
Published: April 2017

Typhoid fever is an important cause of morbidity and mortality in the developing world, particularly in children, but is infrequently observed in the developed world and can occur in patients without a significant travel history. Rhabdomyolysis as a complication has rarely been reported, and never in a child. A child with Salmonella enterica serovar Typhi septicemia, complicated by rhabdomyolysis, encephalopathy and pancreatitis is described and all 15 reported cases to date are summarized.
Rare Pleurostomophora richardsiae Mass Causing Transient Nasolacrimal Duct Obstruction
Authors: Alam Md. Shahid , Vaidehi D. , Therese K. Lily , Ali Mohammad Javed
Published: April 2017

Transient nasolacrimal duct obstruction secondary to a mass lesion compressing the sac or sac-duct junction is rare. The authors report a case of a young female who presented to the authors with complaints of watering and a mass lesion in the lacrimal sac region. An organized perilacrimal mass filled with thick pultaceous material was noted during surgery. Following the drainage of the mass lesion, irrigation of the lacrimal system was freely patent. Microbiological examination and DNA sequencing targeting interspacer region was suggestive of Pleurostomophora richardsiae species. To the best of the authors’ knowledge, this is only the second case report of a subcutaneous perilacrimal mass causing transient nasolacrimal duct obstruction by Pleurostomophora richardsiae.
Subepidermal Calcinosis in the Ocular Adnexa: A Systematic Review
Authors: Khine Kay T. , Shi Dallas S. , Bernhisel Ashlie , Gertsch Kevin R. , Mamalis Nick , Patel Bhupendra C. K. , Dutton Jonathan J.
Published: April 2017

Purpose:

To review the clinical and histopathologic findings associated with subepidermal calcinosis of the eyelids.

Methods:

A systematic review of the literature on subepidermal calcinosis of the eyelids was performed. Cases included were idiopathic in nature and met the histologic criteria for subepidermal calcinosis with calcium deposits in the dermis of the skin.

Results:

Twenty-one publications presenting 53 cases of subepidermal calcinosis involving the eyelids were published between 1970 and 2016. Males were affected more than females (67% vs. 33%), and 89% of patients were 21 years of age or younger. A total of 63% were non-Caucasian. Most cases involved a single lesion (82%), and lesions were most frequently located on the upper eyelid (63%). In 81% of cases, the lesion was less than 5 mm in diameter. When reported, the treatment of choice was complete surgical excision.

Conclusions:

Subepidermal calcinosis should be considered in the differential diagnosis of idiopathic lesions on the eyelid, particularly in young males with no history of systemic disease or laboratory abnormalities. These nodules usually present as painless, small, firm, mobile solitary cutaneous lesions with a predilection for the upper eyelid. Diagnosis is confirmed by histopathology, and treatment is with surgical excision.
Cervicovaginal Levels of Human β-Defensin 1, 2, 3, and 4 of Reproductive-Aged Women With Chlamydia trachomatis Infection
Authors: Noda-Nicolau Nathália Mayumi , Bastos Larissa Brito , Bolpetti Aline Nascimento , Pinto Gabriel Vitor Silva , Marcolino Larissa Doddi , Marconi Camila , Ferreira Carolina Sanitá Tafner , Polettini Jossimara , Vieira Eliane Passarelli , da Silva Márcia Guimarães
Published: April 2017

Objective

This study included women attending primary health care units in Botucatu, São Paulo, Brazil, to assess the cervicovaginal levels of human β-defensin (hBD) 1, 2, 3, and 4 during Chlamydia trachomatis infection.

Patients and Methods

Cervicovaginal samples were collected for Pap testing and assessing the presence of infection by C. trachomatis, human papillomavirus, Neisseria gonorrhoeae, and Trichomonas vaginalis. Vaginal smears were taken to evaluate local microbiota. Human β-defensin levels were determined using enzyme-linked immunosorbent assay in cervicovaginal fluid samples. Seventy-four women with normal vaginal microbiota and no evidence of infection were included in hBD quantification assays; 37 tested positive for C. trachomatis and 37 were negative. Statistical analysis was performed using Mann-Whitney U test.

Results

Women positive for C. trachomatis had significantly lower cervicovaginal hBD-1, hBD-2, and hBD-3 compared with those who tested negative (hBD-1: 0 pg/mL [0–2.1] vs 1.6 pg/mL [0–2.4], p < .0001; hBD-2: 0 pg/mL [0–3.9] vs 0.61 pg/mL [0–8.9], p = .0097; and hBD-3: 0 pg/mL [0–4.3] vs 0.28 pg/mL [0–8.4], p = .0076). Human β-defensin 4 was not detected.

Conclusions

Lower levels of hBD-1, hBD-2, and hBD-3 in cervicovaginal fluid were detected in the presence of C. trachomatis infection.
Lamotrigine Uses in Psychiatric Practice
Authors: Naguy Ahmed , Al-Enezi Najah
Published: April 2017

Background:

Lamotrigine (LAM), an antiepileptic, with panoply of indications and uses in neurology, is FDA approved, in psychiatry, for bipolar prophylaxis. Apart from this indication, trend of its use in psychiatry is on the rise addressing a multitude of disorders.

Study Question:

LAM remains one of only few psychotropic drugs with antiglutamate activity. This might render LAM a potential therapeutic option in treatment-resistant major psychiatric disorders. We reviewed LAM pharmacology and its diverse indications while examining the extant evidence.

Methods:

EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant studies up to date of June 2016.

Results:

Sound evidence supports use of LAM for acute bipolar depression and prophylaxis, treatment-resistant schizophrenia, treatment-resistant obsessive–compulsive disorder, posttraumatic stress disorder, depersonalization disorder, and affective dysregulation and behavioral dyscontrol domains of borderline personality disorder. Less compelling evidence is present for use in behavioral and psychological symptoms of dementia and neuropsychiatric sequelae of traumatic brain injury. No evidence supports use in autism spectrum disorder or acute unipolar depression.

Conclusions:

LAM is an important addition to the psychopharmacological armamentarium. Level of evidence supporting the use of LAM in off-label indications is highly variable, and hence, sound clinical judgment is necessary for its proper use and placement in real-life psychiatric practice and psychopharmacotherapy algorithms.
The Refractive Error of Professional Baseball Players
Authors: Laby Daniel M. , Kirschen David G.
Published: April 2017

Purpose

High levels of visual acuity are required to hit a baseball effectively. Research has shown that any decrease in vision is likely caused by low-order optical aberrations. This study is designed to validate the SVOne autorefractor, and describe the amount and type, of low-order optical aberrations present in a large cohort of professional baseball players.

Methods

A retrospective chart review on the 608 Major League Baseball players evaluated during the 2016 Spring Training Season was performed. Results for a subset of players who had both manifest refraction as well as autorefraction were calculated. Subsequently, after determining the accuracy of the autorefraction system in this population, refractive results for the entire population were determined.

Results

There was a borderline statistically significant difference in mean spherical refractive error (M) between the manifest refraction and the SVOne auto refraction (−0.273D in the manifest refraction method vs. −0.503D in the SVOne method, P = .06) in the subset of athletes who underwent both tests. Additionally, there was no difference in the J0 or J45 cylindrical component vectors for each method. For the entire eligible population, the SVOne autorefraction system found a mean spherical refractive error (M) of −0.228D, a J0 value of −0.013D, and a J45 value of −0.040D.

Conclusions

These data suggest that the SVOne autorefraction system is generally able to measure the refractive error in the baseball population. The system was slightly biased, often reporting more myopia in myopic subjects. Thus, careful evaluation of the refractive status of these athletes coupled with careful subjective refractive correction for those with less than average vision for baseball is strongly suggested.
Can training in empathetic validation improve medical students' communication with patients suffering pain? A test of concept
Authors: Linton Steven J. , Flink Ida K. , Nilsson Emma , Edlund Sara
Published: April 2017

Introduction:

Patient-centered, empathetic communication has been recommended as a means for improving the health care of patients suffering pain. However, a problem has been training health care providers since programs may be time-consuming and difficult to learn. Validation, a form of empathetic response that communicates that what a patient experiences is accepted as true, has been suggested as an appropriate method for improving communication with patients suffering pain.

Objectives:

We study the immediate effects of providing medical students with a 2-session (45-minute duration each) program in validation skills on communication.

Methods:

A one group, pretest vs posttest design was employed with 22 volunteer medical students. To control patient variables, actors simulated 1 of 2 patient scenarios (randomly provided at pretest and posttest). Video recordings were blindly evaluated. Self-ratings of validation and satisfaction were also employed.

Results:

Observed validation responses increased significantly after training and corresponded to significant reductions in invalidating responses. Both the patient simulators and the medical students were significantly more satisfied after the training.

Conclusions:

We demonstrated that training empathetic validation results in improved communication thus extending previous findings to a medical setting with patients suffering pain. Our results suggest that it would be feasible to provide validation training for health care providers and this warrants further investigation in controlled studies.
Colpocleisis: A Survey of Current Practice Patterns
Authors: Jones Keisha , Wang Gary , Romano Robert , St Marie Peter , Harmanli Oz
Published: April 2017

Background

Currently, there are no standard treatment guidelines for colpocleisis. Clinical practice varies widely for this safe and effective procedure.

Objective

The aim of this study was to evaluate the current practice patterns in the United States among surgeons who perform colpocleisis.

Methods

A 27-item anonymous Web-based survey was sent to all practicing physicians affiliated with the American Urogynecologic Society. It consisted of questions regarding the demographic background of the physicians and their current practice as it relates to colpocleisis.

Results

Of the 1422 physicians contacted, 322 responded (23%) to the questionnaire. Slightly more than half were female with an average time of 15 years in practice. The majority of respondents (79%) were urogynecologists. Most surgeons chose colpocleisis for its high success rate, short operating time, and low risk of complications. Approximately half of the providers performed both LeFort and total colpocleisis. Only 18% performed a routine hysterectomy at the time of surgery. Routine preoperative endometrial evaluation was preferred by 68% of the respondents, with 81% utilizing a transvaginal ultrasound first. Almost all providers would perform concomitant incontinence procedures, with 54% requiring a positive cough stress test and normal postvoid residual.

Conclusions

There is variation in the current practice of colpocleisis in the United States. LeFort colpocleisis is most commonly performed, and routine hysterectomy is uncommon. Two thirds of surgeons evaluate the endometrium prior to surgery. Concomitant anti-incontinence procedures appear to be standard.
Changing Referral Patterns to Urogynecology
Authors: Geynisman-Tan Julia , Brown Oluwateniola , Mueller Margaret , Leader-Cramer Alix , Dave Bhumy , Bochenska Katarzyna , Collins Sarah , Lewicky-Gaupp Christina , Kenton Kimberly
Published: April 2017

Objective

The study aims to identify sources of and changes in referral patterns for pelvic floor disorders.

Methods

All new patient visits to urogynecology at our institution between January 2010 and December 2015 were identified. Patient demographics, referral source, insurance type, and visit diagnoses using ICD-9 codes were abstracted. ICD-9 codes were grouped into 18 urogynecologic diagnoses. Data were analyzed using SPSS (Version 20; Chicago, IL).

Results

Five thousand seven hundred ninety-nine new patient visits were included in the analysis. The mean age was 54 ± 17 years and 59% were Caucasian. Forty-four percent were referred by obstetrician/gynecologists (OB/GYNs), 32% by primary care providers (PCPs), 14% by self-referral, and 9% by other specialties. New patient visits increased overall by 280% over 6 years; self- and PCP referrals increased by 480% and 320%, respectively. In comparison, OB/GYN referrals increased by only 229%. Patients diagnosed with prolapse and stress incontinence were more likely to be referred by an OB/GYN (P < 0.001), whereas PCPs were more likely to refer for urinary tract infections (P < 0.005) and urgency urinary incontinence (P < 0.001) than OB/GYNs.

Conclusions

Demand for pelvic floor specialists is growing quickly, with PCP and self-referrals outpacing referrals from obstetrician-gynecologists to tertiary care urogynecology practices.
Vaginal Mesh Removal Outcomes: Eight Years of Experience at an Academic Hospital
Authors: Cardenas-Trowers Olivia O. , Malekzadeh Pouran , Nix David E. , Hatch Kenneth D.
Published: April 2017

Objectives

The purpose of this study is to describe the clinical history leading up to and the outcomes after vaginal mesh removal surgery at an academic hospital.

Methods

A retrospective case series of patients who underwent vaginal mesh removal from 2008 to 2015 was conducted. Demographics, clinical history, physical examination, pre- and postoperative symptoms, and number and type of reoperations were abstracted.

Results

Between February 2008 and November 2015, 83 patients underwent vaginal mesh removal surgery at our hospital. The median time interval from initial mesh placement to removal was 58 months (range, 0.4–154 months). The most common preoperative symptoms were vaginal pain (n = 52, 62%), dyspareunia (n = 46, 55%), and pelvic pain (n = 42, 50%). Intraoperative complications were infrequent (n = 3, 4%). Of patients presenting for follow-up within 4 to 6 weeks postoperatively, the most common symptoms were urinary incontinence (n = 15, 28%), vaginal pain (n = 7, 13%), buttock pain (n = 5, 9%), and urinary tract infection (n = 5, 9%). There were no identifiable risk factors to predict which patients would have persistent postoperative symptoms or who would require more than 1 mesh removal surgery. After vaginal mesh removal, 29 patients (35%) required 1 or more reoperations, with 3 being the highest number of reoperations per patient. The total number of reoperations was 43, with a total of 63 individual procedures performed. Forty-four percent (n = 28) of the procedures were graft removals, 40% (n = 25) were pelvic organ prolapse surgeries (only native tissue repairs), and 16% (n = 10) were stress incontinence surgeries. More than 1 procedure was performed in 49% (n = 21) of the reoperations.

Conclusions

Vaginal mesh removal surgery is safe; however, some patients require more than 1 procedure, and the risk factors for reoperations are unclear.
Continuous EEG in Pediatric Critical Care: Yield and Efficiency of Seizure Detection
Authors: Sansevere Arnold J. , Duncan Elizabeth D. , Libenson Mark H. , Loddenkemper Tobias , Pearl Phillip L. , Tasker Robert C.
Published: April 2017

Purpose:

Our goal was to define the duration of continuous EEG (cEEG) monitoring needed to adequately capture electrographic seizures and EEG status epilepticus in the pediatric intensive care unit using clinical and background EEG features.

Methods:

Retrospective study of patients aged 1 month to 21 years admitted to a tertiary pediatric intensive care unit and undergoing cEEG (>3 hours). Clinical data collected included admission diagnosis, EEG background features, and time variables including time to first seizure after initiation of cEEG.

Results:

Four hundred fourteen patients aged 4.2 (0.75–11.3) years (median, interquartile range) were included. With a median duration of 21 (16–42.2) hours of cEEG monitoring, we identified electrographic seizure or EEG status epilepticus in 25% of subjects. We identified three features that could improve the efficiency of cEEG resources and provide a decision-making framework: (1) clinical history of acute encephalopathy is not predictive of detecting electrographic seizure or EEG status epilepticus, whereas a history of status epilepticus or seizures is; (2) normal EEG background or absence of epileptiform discharges in the initial 24 hours of recording informs the decision to discontinue cEEG; (3) failure to record electrographic ictal events within the first 4 to 6 hours of monitoring may be sufficient to predict the absence of subsequent ictal events.

Conclusions:

Individualized monitoring plans are necessary to increase seizure detection yield while improving resource utilization. A strategy using information from the clinical history, initial EEG background, and the first 4 to 6 hours of recording may be effective in determining the necessary duration of cEEG monitoring in the pediatric intensive care unit.
The evolution of intelligence in mammalian carnivores
Authors: Holekamp Kay E. , Benson-Amram Sarah
Published: April 2017

Although intelligence should theoretically evolve to help animals solve specific types of problems posed by the environment, it is unclear which environmental challenges favour enhanced cognition, or how general intelligence evolves along with domain-specific cognitive abilities. The social intelligence hypothesis posits that big brains and great intelligence have evolved to cope with the labile behaviour of group mates. We have exploited the remarkable convergence in social complexity between cercopithecine primates and spotted hyaenas to test predictions of the social intelligence hypothesis in regard to both cognition and brain size. Behavioural data indicate that there has been considerable convergence between primates and hyaenas with respect to their social cognitive abilities. Moreover, compared with other hyaena species, spotted hyaenas have larger brains and expanded frontal cortex, as predicted by the social intelligence hypothesis. However, broader comparative study suggests that domain-general intelligence in carnivores probably did not evolve in response to selection pressures imposed specifically in the social domain. The cognitive buffer hypothesis, which suggests that general intelligence evolves to help animals cope with novel or changing environments, appears to offer a more robust explanation for general intelligence in carnivores than any hypothesis invoking selection pressures imposed strictly by sociality or foraging demands.
Is behavioural flexibility evidence of cognitive complexity? How evolution can inform comparative cognition
Authors: Mikhalevich Irina , Powell Russell , Logan Corina
Published: April 2017

Behavioural flexibility is often treated as the gold standard of evidence for more sophisticated or complex forms of animal cognition, such as planning, metacognition and mindreading. However, the evidential link between behavioural flexibility and complex cognition has not been explicitly or systematically defended. Such a defence is particularly pressing because observed flexible behaviours can frequently be explained by putatively simpler cognitive mechanisms. This leaves complex cognition hypotheses open to ‘deflationary’ challenges that are accorded greater evidential weight precisely because they offer putatively simpler explanations of equal explanatory power. This paper challenges the blanket preference for simpler explanations, and shows that once this preference is dispensed with, and the full spectrum of evidence—including evolutionary, ecological and phylogenetic data—is accorded its proper weight, an argument in support of the prevailing assumption that behavioural flexibility can serve as evidence for complex cognitive mechanisms may begin to take shape. An adaptive model of cognitive-behavioural evolution is proposed, according to which the existence of convergent trait–environment clusters in phylogenetically disparate lineages may serve as evidence for the same trait–environment clusters in other lineages. This, in turn, could permit inferences of cognitive complexity in cases of experimental underdetermination, thereby placing the common view that behavioural flexibility can serve as evidence for complex cognition on firmer grounds.
Sampling and tracking a changing environment: persistence and reward in the foraging decisions of bumblebees
Authors: Dunlap Aimee S. , Papaj Daniel R. , Dornhaus Anna
Published: April 2017

The question of when to collect new information and how to apply that information is central to much of behaviour. Theory suggests that the value of collecting information, or sampling, depends on environmental persistence and on the relative costs of making wrong decisions. However, empirical tests of how these variables interact are lacking. We tested whether bumblebee foraging decisions are indeed influenced by these two factors. We gave bees repeated choices between a resource providing a steady, mediocre reward and a resource fluctuating between a low reward and a high reward. In this paradigm, we manipulated environmental persistence by changing how long the quality of a fluctuating resource remained stable at one reward level. We manipulated the costs of decision errors by changing the relative values of the available rewards. Bees sampled the fluctuating resource more frequently when it changed quality more frequently, indicating that they measured environmental persistence and reacted to it as predicted by theory. Bees showed surprisingly suboptimal tracking, not reliably choosing the currently best resource except when the fluctuating resource was very persistent and the potential rewards high. While bees modify their choices in response to different levels of change and potential rewards, they do not always do so according to optimality predictions.
Role of somatostatin-positive cortical interneurons in the generation of sleep slow waves
Authors: Funk Chadd M. , Peelman Kayla , Bellesi Michele , Marshall William , Cirelli Chiara , Tononi Giulio
Published: April 2017

Cortical slow waves – the hallmark of NREM sleep - reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer 1 and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation triggers neuronal OFF periods during sleep. Next, we show that chemogenetic activation of SOM+ cells increases slow wave activity (SWA), the slope of individual slow waves, and the duration of NREM sleep; whereas their chemogenetic inhibition decreases SWA and slow wave incidence without changing time spent asleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing. These results indicate that SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated.
STRT-seq-2i: dual-index 5′ single cell and nucleus RNA-seq on an addressable microwell array
Authors: Hochgerner Hannah , Lönnerberg Peter , Hodge Rebecca , Mikes Jaromir , Heskol Abeer , Hubschle Hermann , Lin Philip , Picelli Simone , Manno Gioele La , Ratz Michael , Dunne Jude , Husain Syed , Lein Ed , Srinivasan Maithreyan , Zeisel Amit , Linnarsson Sten
Published: April 2017

Single-cell RNA-seq has become routine for discovering cell types and revealing cellular diversity, but currently no high-throughput platform has been used successfully on archived human brain samples. We present STRT-seq-2i, an addressable 9600-microwell array platform, combining sampling by limiting dilution or FACS, with imaging and high throughput at competitive cost. We applied the platform to fresh single mouse cortical cells and to frozen post-mortem human cortical nuclei, matching the performance of a previous lower-throughput platform.
Nanopore sequencing and assembly of a human genome with ultra-long reads
Authors: Jain Miten , Koren S , Quick J , Rand AC , Sasani TA , Tyson JR , Beggs AD , Dilthey AT , Fiddes IT , Malla S , Marriott H , Miga KH , Nieto T , O’Grady J , Olsen HE , Pedersen BS , Rhie A , Richardson H , Quinlan AR , Snutch TP , Tee L , Paten B , Phillippy AM , Simpson JT , Loman NJ , Loose M
Published: April 2017

Nanopore sequencing is a promising technique for genome sequencing due to its portability, ability to sequence long reads from single molecules, and to simultaneously assay DNA methylation. However until recently nanopore sequencing has been mainly applied to small genomes, due to the limited output attainable. We present nanopore sequencing and assembly of the GM12878 Utah/Ceph human reference genome generated using the Oxford Nanopore MinION and R9.4 version chemistry. We generated 91.2 Gb of sequence data (∼30× theoretical coverage) from 39 flowcells.De novoassembly yielded a highly complete and contiguous assembly (NG50 ∼3Mb). We observed considerable variability in homopolymeric tract resolution between different basecallers. The data permitted sensitive detection of both large structural variants and epigenetic modifications. Further we developed a new approach exploiting the long-read capability of this system and found that adding an additional 5×-coverage of ‘ultra-long’ reads (read N50 of 99.7kb) more than doubled the assembly contiguity. Modelling the repeat structure of the human genome predicts extraordinarily contiguous assemblies may be possible using nanopore reads alone. Portablede novosequencing of human genomes may be important for rapid point-of-care diagnosis of rare genetic diseases and cancer, and monitoring of cancer progression. The complete dataset including raw signal is available as an Amazon Web Services Open Dataset at:https://github.com/nanopore-wgs-consortium/NA12878.
Reversal of cardiac and skeletal manifestations of Duchenne muscular dystrophy by cardiosphere-derived cells and their exosomes inmdxdystrophic mice and in human Duchenne cardiomyocytes
Authors: Aminzadeh Mark A. , Rogers Russell G. , Gouin Kenneth , Fournier Mario , Tobin Rachel E. , Guan Xuan , Childers Martin K. , Andres Allen M. , Taylor David J. , Ibrahim Ahmed , Ding Xiangming , Torrente Angelo , Goldhaber Joshua M. , Victor Ronald A. , Gottlieb Roberta A. , Lewis Michael , Marbán Eduardo
Published: April 2017

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy, affecting the heart as well as skeletal muscle. Here we report that cardiosphere-derived cells (CDCs), which are being tested clinically for the treatment of Duchenne cardiomyopathy, improve cardiac and skeletal myopathy in themdxmouse model of DMD and in human Duchenne cardiomyocytes. Injection of CDCs into the hearts ofmdxmice augments cardiac function, ambulatory capacity and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs inmdxmice and in human Duchenne cardiomyocytes. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.
Audio-visual synchrony and spatial attention enhance processing of dynamic visual stimulation independently and in parallel: a frequency-tagging study
Authors: Covic Amra , Keitel Christian , Porcu Emanuele , Schröger Erich , Müller Matthias M
Published: April 2017

The neural processing of a visual stimulus can be facilitated by attending to its position or by a co-occurring auditory tone. Using frequency-tagging we investigated whether facilitation by spatial attention and audio-visual synchrony rely on similar neural processes. Participants attended to one of two flickering Gabor patches (14.17 and 17 Hz) located in opposite lower visual fields. Gabor patches further “pulsed” (i.e. showed smooth spatial frequency variations) at distinct rates (3.14 and 3.63 Hz). Frequency-modulating an auditory stimulus at the pulse-rate of one of the visual stimuli established audio-visual synchrony. Flicker and pulsed stimulation elicited stimulus-locked rhythmic electrophysiological brain responses that allowed tracking the neural processing of simultaneously presented stimuli. These steady-state responses (SSRs) were quantified in the spectral domain to examine visual stimulus processing under conditions of synchronous vs. asynchronous tone presentation and when respective stimulus positions were attended vs. unattended. Strikingly, unique patterns of effects on pulse- and flicker driven SSRs indicated that spatial attention and audiovisual synchrony facilitated early visual processing in parallel and via different cortical processes. We found attention effects to resemble the classical top-down gain effect facilitating both, flicker and pulse-driven SSRs. Audio-visual synchrony, in turn, only amplified synchrony-producing stimulus aspects (i.e. pulse-driven SSRs) possibly highlighting the role of temporally co-occurring sights and sounds in bottom-up multisensory integration.
High-resolution analysis of spatiotemporal virulence gene regulation during food-borne infection withEscherichia coliO157:H7 within a live host
Authors: Stones Daniel H , Fehr Alexander GJ , Madhavan Thekke P , Voelz Kerstin , Krachler Anne Marie
Published: April 2017

Food-borne infection with enterohemorrhagicEscherichia coli(EHEC) is a major cause of diarrheal illness in humans, and can lead to severe complications such as hemolytic uremic syndrome. Cattle and other ruminants are the main reservoir of EHEC, which enters the food-chain through contaminated meat, dairy, or vegetables. However, how EHEC transitions from the transmission vector to colonizing the intestinal tract, and how virulence-specific genes are regulated during this transition, is not well understood. Here, we describe the establishment of a vertebrate model for food-borne EHEC infection, using the protozoanParamecium caudatumas a vector and the zebrafish (Danio rerio) as a host. At 4 days post fertilization, zebrafish have a fully developed intestinal tract, yet are fully transparent. This allows us to follow intestinal colonization, microbe-host cell interactions, and microbial gene induction within the live host and in real time throughout the infection. Additionally, this model can be adapted to compare food- and water-borne infections, under gnotobiotic conditions or against the backdrop of an endogenous (and variable) host microbiota. Finally, the zebrafish allows for investigation of factors affecting shedding and transmission of bacteria to naïve hosts. High-resolution analysis of EHEC gene expression within the zebrafish host emphasizes the need for tight transcriptional regulation of virulence factors for within-host fitness.

IMPORTANCE

EnterohemorrhagicEscherichia coli(EHEC) is a food-borne pathogen which can cause diarrhea, vomiting and in some cases, severe complications such as kidney problems in humans. Up to 30% of cattle are colonized with EHEC, which can enter the food-chain through contaminated meat, dairy and vegetables. In order to control infections and stop transmission, it is important to understand what factors allow EHEC to colonize its hosts, cause virulence and aid transmission. Since this cannot be systematically studied in humans, it is important to develop animal models of infection and transmission. We developed a model which allows us to study food-borne infection in zebrafish, a vertebrate host that is transparent and genetically tractable. Using the zebrafish host, we can follow the bacterial infection cycle in real time, and gain important information regarding bacterial physiology and microbe-host interactions. This will allow us to identify potential new targets for infection control and prevention.
Host population structure and treatment frequency maintain balancing selection on drug resistance
Authors: Cobey Sarah , Baskerville Edward B. , Colijn Caroline , Hanage William , Fraser Christophe , Lipsitch Marc
Published: April 2017

It is a truism that antimicrobial drugs select for resistance, but explaining pathogen- and population-specific variation in patterns of resistance remains an open problem. Like other common commensals,Streptococcus pneumoniaehas demonstrated persistent coexistence of drug-sensitive and drug-resistant strains. Theoretically, this outcome is unlikely. We modeled the dynamics of competing strains ofS. pneumoniaeto investigate the impact of transmission dynamics and treatment-induced selective pressures on the probability of stable coexistence. We find that the outcome of competition is extremely sensitive to structure in the host population, although coexistence can arise from age-assortative transmission models with age-varying rates of antibiotic use. Moreover, we find that the selective pressure from antibiotics arises not so much from the rate of antibiotic use per se but from the frequency of treatment: frequent antibiotic therapy disproportionately impacts the fitness of sensitive strains. This same phenomenon explains why serotypes with longer durations of carriage tend to be more resistant. These dynamics may apply to other potentially pathogenic, microbial commensals and highlight how population structure, which is often omitted from models, can have a large impact.
Integrative Structural Brain Network Analysis In Diffusion Tensor Imaging
Authors: Chung Moo K. , Hanson Jamie L. , Adluru Nagesh , Alexander Andrew L. , Davidson Richard J. , Pollak Seth D.
Published: April 2017

In diffusion tensor imaging, structural connectivity between brain regions is often measured by the number of white matter fiber tracts connecting them. Other features such as the length of tracts or fractional anisotropy (FA) are also used in measuring the strength of connectivity. In this study, we investigated the effects of incorporating the number of tracts, the tract length and FA-values into the connectivity model. Using various node-degree based graph theory features, the three connectivity models are compared. The methods are applied in characterizing structural networks between normal controls and maltreated children, who experienced maltreatment while living in post-institutional settings before being adopted by families in the US.
Single-virion Sequencing of Lamivudine Treated HBV Populations Reveal Population Evolution Dynamics and Demographic History
Authors: Zhu Yuan O , Aw Pauline PK , de Sessions Paola Florez , Hong Shuzhen , See Lee Xian , Hong Lewis Z , Wilm Andreas , Li Chen Hao , Hue Stephane , Lim Seng Gee , Nagarajan Niranjan , Burkholder William F , Hibberd Martin
Published: April 2017

Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients – once before antiviral treatment and once after viral rebound due to resistance. We obtained 248-8,796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were also able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently on PacBio and Illumina sequencers. Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance, differentiating between soft or hard selective sweeps, and the reconstruction of intra-host viral population demographic history.
Estimating wildlife vaccination coverage using genetic methods
Authors: Smith Freya , Robertson Andrew , Smith Graham C. , Gill Peter , McDonald Robbie A. , Wilson Gavin , Delahay Richard J.
Published: April 2017

Vaccination is a potentially useful approach for the control of disease in wildlife populations. The effectiveness of vaccination is contingent in part on obtaining adequate vaccine coverage at the population level. However, measuring vaccine coverage in wild animal populations is challenging and so there is a need to develop robust approaches to estimate coverage and so contribute to understanding the likely efficacy of vaccination.

We used a modified capture mark recapture technique to estimate vaccine coverage in a wild population of European badgers (Meles meles) vaccinated by live-trapping and injecting with Bacillus Calmette-Guérin as part of a bovine tuberculosis control initiative in Wales, United Kingdom. Our approach used genetic matching of vaccinated animals to a sample of the wider population to estimate the percentage of badgers that had been vaccinated. Individual-specific genetic profiles were obtained using microsatellite genotyping of hair samples which were collected both directly from trapped and vaccinated badgers and non-invasively from the wider population using hair traps deployed at badger burrows.

We estimated the percentage of badgers vaccinated in a single year and applied this to a simple model to estimate cumulative vaccine coverage over a four year period, corresponding to the total duration of the vaccination campaign.

In the year of study, we estimated that between 44-65% (95% confidence interval, mean 55%) of the badger population received a vaccine dose. Using the model, we estimated that 70-85% of the total population would have received at least one vaccine dose over the course of the four year vaccination campaign.

This study represents the first application of this novel approach for measuring vaccine coverage in wildlife. This is also the first attempt at quantifying the level of vaccine coverage achieved by trapping and injecting badgers. The results therefore have specific application to bovine tuberculosis control policy, and the approach is of significance to the wider field of wildlife vaccination.
Sofosbuvir protects Zika virus-infected mice from mortality, preventing short- and long-term sequela
Authors: Ferreira André C. , Valle Camila Z. , Reis Patricia A. , Barbosa-Lima Giselle , Vieira Yasmine Rangel , Mattos Mayara , de Paiva Silva Priscila , Sacramento Carolina , de Castro Faria Neto Hugo C. , Campanati Loraine , Tanuri Amilcar , Brüning Karin , Bozza Fernando A. , Bozza Patrícia T. , Souza Thiago Moreno L.
Published: April 2017

Zika virus (ZIKV) caused significant public health concern, because of its association with congenital malformations, neurological disorders in adults and, more recently, with deaths. Considering the necessity to mitigate the cases ZIKV-associated diseases, antiviral interventions against this virus are an urgent necessity. Sofosbuvir, a drug in clinical use against Hepatitis C Virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated thein vivoactivity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 x 107PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90 % in different anatomical compartments, such as in blood plasma, spleen, kidney and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals, despite the aggressive virus challenge assayed and also prevented the acute neuromotor impairment triggered by the virus. On the long-term behavior analysis of ZIKV-associated sequelae, sofosbuvir prevented loss of hippocampal- and amygdala-dependent memory. Our results point out that sofosbuvir inhibits ZIKV replicationin vivo, which is consistent with the prospective necessity of antiviral drugs to treat ZIKV-infected individuals.
Crystal structure of 10-ethyl-7-(9-ethyl-9H-carbazol-3-yl)-10H-phenothiazine-3-carbaldehyde
Authors: Mahalakshmi Vairavan , Gouthaman Siddan , Sugunalakshmi Madurai , Bargavi Srinivasan , Lakshmi Srinivasakannan
Published: April 2017

The title compound, C29H24N2OS, contains a phenothiazine moiety linked to a planar carbazole unit (r.m.s. deviation = 0.029 Å) by a C—C single bond. The phenothiazine moiety possesses a typical non-planar butterfly structure with a fold angle of 27.36 (9)° between the two benzene rings. The dihedral angle between the mean planes of the carbazole and phenothiazine units is 27.28 (5)°. In the crystal, molecules stack in pairs along the c-axis direction, linked by offset π–π interactions [intercentroid distance = 3.797 (1) Å]. There are C—H...π interactions present linking these dimers to form a three-dimensional structure.