bluuebunny/crossref_metadata_2025 huggingface dataset:
Pain sensitization associated with nonresponse after physiotherapy in people with knee osteoarthritis
Authors: O'Leary Helen , Smart Keith M. , Moloney Niamh A. , Blake Catherine , Doody Catherine M.
Published: May 2018

In knee osteoarthritis (OA), pain sensitization has been linked to a more severe symptomatology, but the prognostic implications of pain sensitivity in people undergoing conservative treatment such as physiotherapy are not established. This study aimed to prospectively investigate the association between features of pain sensitization and clinical outcome (nonresponse) after guideline-based physiotherapy in people with knee OA. Participants (n = 156) with moderate/severe knee OA were recruited from secondary care. All participants completed self-administered questionnaires and underwent quantitative sensory testing at baseline, thereby establishing subjective and objective measures of pain sensitization. Participants (n = 134) were later classified after a physiotherapy intervention, using treatment responder criteria (responder/nonresponder). Quantitative sensory testing data were reduced to a core set of latent variables using principal component analysis. A hierarchical logistic regression model was constructed to investigate whether features related to pain sensitization predicted nonresponse after controlling for other known predictors of poor outcome in knee OA. Higher temporal summation (odds ratio 2.00, 95% confidence interval 1.23-3.27) and lower pressure pain thresholds (odds ratio 0.48, 95% confidence interval 0.29-0.81) emerged as robust predictors of nonresponse after physiotherapy, along with a higher comorbidity score. The model demonstrated high sensitivity (87.8%) but modest specificity (52.3%). The independent relationship between pain sensitization and nonresponse may indicate an underlying explanatory association between neuroplastic changes in nociceptive processing and the maintenance of ongoing pain and disability in knee OA pain. These preliminary results suggest that interventions targeting pain sensitization may warrant future investigation in this population.
Middle Ear Pressures in Wind Instrument Musicians
Authors: Osborne Max Sallis , Morris Simon , Clark Matthew P. , Begg Philip
Published: May 2018

Objectives:

This study aimed to assess if playing wind instruments leads to a measurable increase in middle ear pressure during note generation and to provide evidence to clinicians to advise musicians undergoing middle ear surgery.

Study Design:

An observational cohort study of 40 volunteers in 7 different wind instrument categories underwent tympanometry at rest and during note production.

Setting:

Community.

Patients:

Recreational musicians aged over 18 years recruited from the student body attending Birmingham University, UK.

Intervention:

None.

Main Outcome Measures:

Tympanometry is used as a noninvasive measure of middle ear pressure. The pressure at which peak compliance occurred was taken as an indirect measure of middle ear pressure. The data produced at rest and during note production was statistically analysed with paired t testing and significance set at a p value less than 0.01.

Results:

Overall a statistically significant increase in middle ear pressure change of 0.63 mm Hg (p = 0.0001) during note production was identified. Musicians playing the oboe and trumpet demonstrate the largest increase in middle ear pressure of 1.46 mm Hg (p = 0.0053) and 0.78 mm Hg (p = 0.0005) respectively.

Conclusion:

The data provided by this study gives evidence for the first time that playing wind instruments does increase middle ear pressure. Although the clinical significance of this is yet to be determined the authors would advise that musicians who undergo otological procedures should refrain from playing their instruments until full recovery has been achieved as advised by their clinician following direct microscopic review.
Drug-resistant cytomegalovirus: clinical implications of specific mutations
Authors: Razonable Raymund R.
Published: May 2018

Purpose of review

Cytomegalovirus (CMV) infection can be refractory to antiviral treatment. Although refractoriness can be due impaired host immunity, it can also be due to viral mutations that confer antiviral drug resistance. This article provides a succinct review of mutations in CMV genes that confer drug resistance, and offer guidance on clinical management.

Recent findings

Recent advances in medical and research technology have confirmed traditional mutations and identified novel ones that confer resistance to current antiviral drugs. Resistance to ganciclovir is commonly predicted by mutations in UL97, which encode for viral kinase that catalyzes its phosphorylation. Mutations in UL54, which encode for CMV DNA polymerase, confer resistance (or cross-resistance) to ganciclovir, cidofovir and/or foscarnet. Resistance to letermovir, the new drug approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients, has emerged and mapped most commonly to mutations in UL56 and less commonly UL51 and UL89, the gene complex that encode for viral terminase.

Mutations in CMV genes can be selected during antiviral drug exposure, and manifests phenotypically as nonresponsive drug-resistant disease. Knowledge of specific mutations informs clinicians in selecting appropriate antivirals for managing transplant patients with CMV disease.
Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease?
Authors: Herrera Sabina , Husain Shahid
Published: May 2018

Purpose of review

The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools.

Recent findings

A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented.

Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease.
Plasma Hepcidin Levels in Healthy Children: Review of Current Literature Highlights Limited Studies
Authors: Kumar Surjeet , Bhatia Prateek , Jain Richa , Bharti Bhavneet
Published: May 2018

Background:

There are few studies that highlight pediatric hepcidin reference ranges especially from Asian subcontinent. In current study, plasma from 131 children (72 boys and 59 girls; 1 to 12 y) was analyzed for hepcidin-25 by enzyme-linked immunosorbent assay.

Observations:

The median (interquartile range) plasma hepcidin in boys was 21.89 ng/mL (16.50 to 51.70 ng/mL) and girls was 21.95 ng/mL (19.20 to 47.70 ng/mL). No statistically significant difference (P=0.937) of plasma hepcidin levels in sex was noted. However, multiple regression analysis revealed a significant correlation between plasma hepcidin levels and ferritin (P=0.000).

Conclusions:

Our study results highlight relatively lower median hepcidin values in children 1 to 12 years of age as compared with western data. This may be attributed to either lack of a harmonized and standard enzyme-linked immunosorbent assay detection methodology or to presence of clinically significant polymorphisms in hepcidin gene in our population.
Effectiveness of Physiotherapy Interventions on Spasticity in People With Multiple Sclerosis
Authors: Etoom Mohammad , Khraiwesh Yazan , Lena Francesco , Hawamdeh Mohannad , Hawamdeh Ziad , Centonze Diego , Foti Calogero
Published: May 2018

Objective

The aim of the study was to examine the effectiveness of physiotherapy (PT) interventions on spasticity in people with multiple sclerosis.

Design

A systematic search was performed using PRISMA guidance. Studies evaluate the effect of PT interventions on spasticity were included. People with multiple sclerosis, spasticity, disability and PT interventions characteristics were extracted in included studies. Level of evidence was synthesized by the Grade of Recommendation, Assessment, Development and Evaluation approach. Meta-analyses were performed by calculating Hedges g at 95% confidence interval.

Results

A total of 29 studies were included in the review, and 25 were included in the meta-analyses. The included PT interventions were exercise therapy, electrical stimulation, radial shock wave therapy, vibration, and standing. The review and meta-analyses showed different evidences of benefits and nonbenefits for PT interventions on some spasticity outcomes. The best quality evidences were for beneficial effects of exercise therapy especially robot gait training and outpatient exercise programs on self-perceived spasticity and muscle tone respectively. The review results were positive regarding the acute effects, follow-up measurements, safety, progressive MS, and nonambulatory people with multiple sclerosis. The included articles were heterogeneous and badly reported in PT interventions and people with multiple sclerosis characteristics.

Conclusions

Physiotherapy interventions can be a safe and beneficial option for spasticity in people with multiple sclerosis. No firm conclusion can be drawn on overall spasticity. Further researches in different spasticity aspects are needed.
Nerve Stimulation Enhances Task-Oriented Training for Moderate-to-Severe Hemiparesis 3–12 Months After Stroke
Authors: Carrico Cheryl , Westgate Philip M. , Salmon Powell Elizabeth , Chelette Kenneth C. , Nichols Laurie , Pettigrew L. Creed , Sawaki Lumy
Published: May 2018

Objective

The aim of the study was to determine whether somatosensory stimulation affects outcomes of motor training for moderate-to-severe upper limb hemiparesis less than 12 mos before stroke.

Design

Fifty-five adults participated in 18 intervention sessions pairing 2 hours of active (n = 33) or sham (n = 22) somatosensory stimulation with 4 hours of intensive task-oriented motor training. Wolf Motor Function Test, Action Research Arm Test, Fugl-Meyer Assessment, and Stroke Impact Scale were administered at baseline, postintervention, and 1- and 4-mo follow-up.

Results

Statistically significant between-groups differences favored the active condition on Wolf Motor Function Test at post (P = 0.04) and Action Research Arm Test at post (P = 0.02), 1 mo (P = 0.01), and 4 mos (P = 0.01) but favored the sham condition on Stroke Impact Scale at 1 mo (P = 0.03). There were no significant between-groups differences on Fugl-Meyer Assessment.

Conclusions

Somatosensory stimulation can improve objective outcomes of motor training for moderate-to-severe hemiparesis less than 12 mos after stroke, although it needs to be determined whether the magnitude of between-groups differences in this study is clinically relevant. Future studies should investigate the intervention's impact on disability and functional recovery for this population as well as neurophysiological mechanisms underlying intervention effects.
Prospective Evaluation of Obese Patients Undergoing Autologous Abdominal Free Flap Breast Reconstruction
Authors: Chang Edward I. , Liu Jun
Published: May 2018

Background:

Obesity has been viewed as a relative contraindication against autologous free flap breast reconstruction because of increased risks of complications, including flap loss.

Methods:

The authors conducted a prospective analysis of obese patients undergoing autologous breast reconstruction.

Results:

Overall, 72 patients (average age, 48.5 years; average body mass index, 35.7 kg/m2) underwent abdominal free flap breast reconstruction. There were 43 bilateral reconstructions and the remainder were unilateral (n = 115 flaps). There were 67 muscle-sparing transverse rectus abdominis musculocutaneous (TRAM) flaps (58.3 percent), 44 deep inferior epigastric perforator (DIEP) flaps (38.2 percent), two free bipedicle DIEP flaps, one superficial inferior epigastric perforator flap, and one free TRAM flap. Forty-two patients (58.3 percent) had prior radiation, and 51 (70.8 percent) had prior chemotherapy. Forty-three patients (59.7 percent) underwent delayed reconstruction and 21 (29.2 percent) underwent immediate reconstruction. Eight patients (11.1 percent) had bilateral reconstruction, with one breast reconstructed in an immediate and the other in a delayed fashion. Half of the patients (n = 36) had mesh placed in an underlay fashion to reinforce the donor site. Regarding breast complications, there were 11 wound dehiscences, one hematoma, one infection, and two patients with mastectomy skin flap necrosis. Twelve patients had donor-site wound healing complications, there were four infections, and three patients developed a bulge/hernia. There were no flap losses. Comparison to historic controls demonstrated no significant differences in overall flap loss rates (p = 0.061) or donor-site bulge/hernia (p = 0.86).

Conclusion:

Autologous abdominal free flaps can be performed safely in obese patients without increased risks for donor-site bulge/hernia or flap loss compared to nonobese patients; however, patients should be counseled carefully regarding the potential risks of complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV
The Implications of Barbed Sutures on Scar Aesthetics: A Systematic Review
Authors: Motosko Catherine C. , Zakhem George A. , Saadeh Pierre B. , Hazen Alexes
Published: May 2018

Background:

Barbed sutures have become increasingly popular in the field of aesthetic plastic surgery, particularly in body contouring and breast operations, in which the use of barbed sutures may offer both time and cost savings. Scar aesthetics is an important outcome for both surgeons and patients in these procedures; however, there is a paucity of studies assessing the aesthetic outcome of barbed sutures with regard to scarring.

Methods:

A systematic review of the PubMed, EMBASE, and Cochrane databases was performed from the date of their inception through July of 2017 using the search terms “barbed suture” combined with “scar” or “wound.” Studies were included if they were prospective, evaluator-blind, randomized, controlled trials; closed the dermal layer of incisions using barbed sutures; and included an evaluator-blind aesthetic assessment of scarring.

Results:

Six prospective, randomized, controlled trials met inclusion criteria. The cosmetic result of scars in 926 patients was evaluated after an average of 8.1 months. Five of the six controlled trials found the aesthetic results of wounds closed with barbed sutures to be equivalent to those closed with traditional sutures, and one study showed significantly superior aesthetic results with barbed sutures. Use of barbed sutures resulted in shorter operating times in four of the five studies that timed incision closure. Similar complication rates were observed in all evaluated studies.

Conclusion:

Based on this systematic review, the majority of studies concluded that there were no differences in scarring aesthetics when dermal layers were closed using barbed sutures compared with traditional suturing techniques.
Treatment of Facial Hypopigmented Scars by the Laser Hole Technique Using a Nonfractional Carbon Dioxide Laser in Asians
Authors: Burm Jin Sik , Lee Yung Ki , Young Cho Jae
Published: May 2018

Background:

Facial hypopigmented scars are usually characterized by white color and a glossy surface. To correct the two problems simultaneously, the authors attempted to induce persistent postinflammatory hyperpigmentation for color and to build multiple pitted scars like facial skin pores for texture. This study describes a laser hole method using a traditional nonfractional carbon dioxide laser for treatment of facial hypopigmented scars and evaluates the clinical results.

Methods:

Forty-three facial hypopigmented scars in 27 patients were treated, excluding protruding or thick scars. A carbon dioxide laser was set in the superpulse mode by continuous delivery. Multiple small holes were made in the scar at a distance of 1 to 3 mm. Each laser hole was produced by continuously repeated shots at one point until the deep dermis was involved. All lesions were exposed without protection. At 1 or 2 months after initial treatment, the remaining hypopigmentation was treated by the same procedure.

Results:

Treatment sessions were performed once for nine scars, twice for 22 scars, and three times for 12 scars. In most cases, postinflammatory hyperpigmentation was slightly diminished but maintained until the last follow-up. The fine irregular surface with multiple pitted scars was similar to that of normal skin. Scar improvement evaluation showed marked or excellent in 39 scars (90.7 percent) and minimal or partial in four deep or thick scars.

Conclusion:

The laser hole technique using a nonfractional carbon dioxide laser may be an excellent option for simultaneously treating the color and texture of superficial or thin hypopigmented facial scars in Asians.
Legionella: a reemerging pathogen
Authors: Herwaldt Loreen A. , Marra Alexandre R.
Published: May 2018

Purpose of review

The present review summarizes new knowledge about Legionella epidemiology, clinical characteristics, community-associated and hospital-based outbreaks, molecular typing and molecular epidemiology, prevention, and detection in environmental and clinical specimens.

Recent findings

The incidence of Legionnaire's disease is rising and the mortality rate remains high, particularly for immunocompromised patients. Extracorporeal membrane oxygenation may help support patients with severe respiratory failure. Fluoroquinolones and macrolides appear to be equally efficacious for treating Legionnaires’ disease. Whole genome sequencing is an important tool for determining the source for Legionella infections and for understanding routes of transmission and mechanisms by which new pathogenic clones emerge. Real-time quantitative polymerase chain reaction testing of respiratory specimens may improve our ability to diagnose Legionnaire's disease. The frequency of viable but nonculturable organisms is quite high in some water systems but their role in causing clinical disease has not been defined.

Legionellosis remains an important public health threat. To prevent these infections, staff of municipalities and large buildings must implement effective water system management programs that reduce Legionella growth and transmission and all Medicare-certified healthcare facilities must have water management policies. In addition, we need better methods for detecting Legionella in water systems and in clinical specimens to improve prevention strategies and clinical diagnosis.
Coffee and Tea Consumption in Relation to Risk of Rheumatoid Arthritis in the Women's Health Initiative Observational Cohort
Authors: Lamichhane Diman , Collins Christopher , Constantinescu Florina , Walitt Brian , Pettinger Mary , Parks Christine , Howard Barbara V.
Published: May 2018

Objective

The aim of this study was to evaluate whether tea or coffee consumption is associated with an increased risk of older-onset rheumatoid arthritis (RA) using the Women's Health Initiative Observational Study.

Methods

The Women's Health Initiative Observational Study is a longitudinal prospective cohort study conducted from 1993 to 1998. There were 76,853 women who completed a self-administered questionnaire about their daily consumption of tea and coffee. One hundred eighty-five women self-reported and validated incident cases of RA were observed after 3 years of observation. Multivariable Cox proportional hazards models were performed to assess the relationship between consumption habits and disease incidence. Trend tests were calculated using categorical variables modeled as a continuous variable without collapsing.

Results

There was no increase in the hazard ratio for incident RA in those participants who drank coffee compared with those who did not. The amount of coffee consumed and the method of preparation (caffeinated/decaffeinated; filtered/unfiltered) also did not alter the risk of incident RA. There was a positive association of incident RA and caffeinated tea consumption in the trend test (p = 0.03). When assessing any caffeinated tea consumption versus no tea consumption, the hazard ratio for incident RA was 1.40 (confidence interval, 1.01–1.93; p = 0.04).

Conclusions

In a large prospective cohort of older women, there was no association between coffee consumption and incident RA. A small association between daily caffeinated, nonherbal tea consumption and incident RA was found.
Shear Wave Elastography to Assess Perineal Body Stiffness During Labor
Authors: Rostaminia Ghazaleh , Awad Charbel , Chang Cecilia , Sikdar Siddhartha , Wei Qi , Shobeiri S. Abbas
Published: May 2018

Objectives

The objective of this study was to evaluate perineal body stiffness intrapartum using shear wave elastography ultrasound and to study its association with maternal and labor characteristics.

Methods

This was a prospective observational study. Pregnant women with term pregnancy who had been admitted for labor management were recruited into the study. Transperineal shear wave elastography of perineal body was performed. Maternal and labor data were retrieved from electronic medical charts.

Results

Thirty-two patients’ data were available for analysis. Mean (SD) melastography modulus was 15.33 (5.49). While comparing the mean elastography modulus across maternal and labor characteristics, the difference was statistically different between parity, cervical dilation, and perineal laceration presence groups (P < 0.05). The mean of elastography modulus of primiparous women with cervical dilation less than 3 cm was 21.47 kPa, whereas that of multiparous women was 13.17 kPa (P = 0.0511). Perineal laceration was more prevalent in women with stiffer perineal body. The risk of having perineal laceration compared with no perineal laceration was 29.1% higher for each additional unit increase in perineal body elastography modulus (odds ratio, 0.709; 95% confidence interval, 0.507–0.992).

Conclusions

Shear wave elastography can be used to quantify perineal body stiffness. Primiparous women in early stages of labor have stiffer perineal body than multiparous women in any stage of labor and primiparous women in late stage of labor.
Pertinence of Titration and Age-Based Dosing Methods for Electroconvulsive Therapy
Authors: Lemasson Morgane , Rochette Louis , Galvão Filipe , Poulet Emmanuel , Lacroix André , Lecompte Maxime , Auriacombe Marc , Patry Simon , Haesebaert Frédéric
Published: May 2018

Background

Although the dosage of electroconvulsive therapy (ECT) stimulus has a major impact on the efficacy and safety of this treatment, the method used to determine an optimal dosage remains a matter of debate.

Objective

We investigated factors influencing the seizure threshold (ST) in a large-sample study and compared age-based and titration dosing methods in terms of charge.

Methods

A retrospective study examined data from 503 patients across France and Canada. The patients underwent right unilateral (RUL) or bitemporal (BT) ECT during a titration session before undergoing ECT. Seizure threshold and charge differences between age-based and titration-predicted methods were derived for each RUL and BT patient and compared according to sex, age, and anesthetic agents.

Results

Based on our results, ST is a function of electrode placement, sex, age, and anesthetic agents. Titration and age-based methods led to completely different patterns of charges for the same electrode placement, especially in elderly and in women in the RUL group. Regression models showed that differences between the age-based and titration methods varied with respect to age, sex, and anesthetic agent. Specifically, significant effects of sex and age were observed for RUL ECT and of sex and anesthetics for BT ECT.

Conclusions

This study revealed that several factors significantly influence the prediction of ECT dose, depending on individuals and treatment modalities. Caution should be exercised when using nonindividualized methods to calculate ST.
Predicting the viscosity of digesta from the physical characteristics of particle suspensions using existing rheological models
Authors: Hardacre Allan K. , Lentle Roger G. , Yap Sia-Yen , Monro John A.
Published: May 2018

The measurement of the viscosity of digesta is complicated by settling and compositional changes that accompany digestion. The current work determined whether the apparent and relative viscosities (
η
a
and
η
r
) of digesta could be accurately determined from the actual and maximum solid volume fractions (
ϕ
and
ϕ
max
, respectively) using the Maron–Pierce equation. The rheological properties of digesta from the small intestine of six pigs were determined at a shear rate of 1 s
−1
at 37°C. A series of suspensions of plant fibre in a Newtonian liquid (70% aqueous fructose) were made at viscosities similar to pig digesta by adjusting
ϕ
. The relationships between the apparent and relative viscosities (
η
a
and
η
r
) and the plant fibre properties; aspect ratio (AR) and
ϕ
and
ϕ
max
were then determined for digesta and the suspensions. The ARs for the digesta and plant fibre particles were determined using image analysis of scanning electron micrographs and
η
a
from rheometric flow curves at 37°C,
ϕ
from image analysis and gas pycnometry, and
ϕ
max
from AR and suspension viscosity. The
η
r
of pig digesta and the test suspensions calculated using the Maron–Pierce equation were, with the exception of two outliers, in proportion with
η
a
determined using a rheometer, indicating that
η
r
could be successfully predicted from the Maron–Pierce equation.
Logical modelling uncovers developmental constraints for primary sex determination of chicken gonads
Authors: Sánchez Lucas , Chaouiya Claudine
Published: May 2018

In the chicken, sex determination relies on a ZZ (male)/ZW (female) chromosomal system, but underlying mechanisms are still not fully understood. The Z-dosage and the dominant W-chromosome hypotheses have been proposed to underlie primary sex determination. We present a modelling approach, which assembles the current knowledge and permits exploration of the regulation of this process in chickens. Relying on published experimental data, we assembled a gene network, which led to a logical model that integrates both the Z-dosage and dominant W hypotheses. This model showed that the sexual fate of chicken gonads results from the resolution of the mutual inhibition between DMRT1 and FOXL2, where the initial amount of DMRT1 product determines the development of the gonads. In this respect, at the initiation step, a W-factor would function as a secondary device, by reducing the amount of DMRT1 in ZW gonads when the sexual fate of the gonad is settled, that is when the SOX9 functional level is established. Developmental constraints that are instrumental in this resolution were identified. These constraints establish qualitative restrictions regarding the relative transcription rates of the genes DMRT1, FOXL2 and HEMGN. Our model further clarified the role of OESTROGEN in maintaining FOXL2 function during ovary development.
Sex-specific effects of inbreeding on reproductive senescence
Authors: de Boer Raïssa A. , Eens Marcel , Müller Wendt
Published: May 2018

Inbreeding depression plays a significant role in evolutionary biology and ecology. However, we lack a clear understanding of the fitness consequences of inbreeding depression. Studies often focus on short-term effects of inbreeding in juvenile offspring, whereas inbreeding depression in adult traits and the interplay between inbreeding depression and age are rarely addressed. Inbreeding depression may increase with age and accelerate the decline in reproductive output in ageing individuals (reproductive senescence), which could be subject to sex-specific dynamics. We test this hypothesis with a longitudinal experimental study in a short-lived songbird. Adult inbred and outbred male and female canaries were paired in a 2 × 2 factorial design, and survival and annual reproductive performance were studied for 3 years. We found inbreeding depression in female egg-laying ability, male fertilization success and survival of both sexes. Annual reproductive success of both males and females declined when paired with an inbred partner independent of their own inbreeding status. This shows that inbreeding can have fitness costs in outbred individuals when they mate with an inbred individual. Further, inbred females showed faster reproductive senescence than outbred females, confirming that inbreeding depression and age can interact to affect fitness. By contrast, there was no evidence for an interaction between inbreeding depression and reproductive senescence in male fertilization success. Our findings highlight the importance of considering sex-specific effects and age to determine the full range of fitness consequences of inbreeding and demonstrate that inbreeding depression can accelerate reproductive senescence.
Evidence for atypical nest overwintering by hatchling lizards,
Heloderma suspectum
Authors: DeNardo Dale F. , Moeller Karla T. , Seward Mark , Repp Roger
Published: May 2018

The timing of reproductive events (e.g. oviposition and hatching) to coincide with favourable seasonal conditions is critical for successful reproduction. However, developmental time may not match the duration between the optimal time for oviposition and the optimal time for hatchling survival. Thus, strategies that alter the time between oviposition and hatchling emergence can be highly advantageous. Arrested development and the resulting extension of the duration between oviposition and hatching has been widely documented across oviparous amniotes, but nest overwintering by hatchlings has only been documented in aquatic chelonians that live where winters are quite cold. Herein, we present a compilation of evidence regarding reproductive phenology by hatchlings of the Gila monster (
Heloderma suspectum
), a lizard inhabiting the Sonoran Desert of North America. Our data demonstrate that (i) Gila monster hatchlings from eggs oviposited in July do not emerge from their nests until late spring or summer of the following year, yet (ii) Gila monster eggs artificially incubated at field-relevant temperatures hatch in 4–5 months. Furthermore, we describe a fortuitous excavation of a hatching Gila monster nest in late October, which coincides with the artificial incubation results. Together, these results provide strong support for the existence of overwintering in the nest by a lizard, and suggest that this reproductive strategy should be explored in a broader array of taxa.
Major QTL controls adaptation to serpentine soils inMimulus guttatus
Authors: Selby Jessica P. , Willis John H.
Published: May 2018

Spatially varying selection is a critical driver of adaptive differentiation. Yet, there are few examples where the fitness effects of naturally segregating variants that contribute to local adaptation have been measured in the field. This project investigates the genetic basis of adaption to serpentine soils inMimulus guttatus. Reciprocal transplant studies show that serpentine and non-serpentine populations ofM. guttatusare genetically differentiated in their ability to survive on serpentine soils. We mapped serpentine tolerance by performing a bulk segregant analysis on F2 survivors from a field transplant study and identify a single QTL where individuals that are homozygous for the non-serpentine allele do not survive on serpentine soils. This same QTL controls serpentine tolerance in a second, geographically distant population. A common garden study where the two serpentine populations were grown on each other′s soil finds that one of the populations has significantly lower survival on this “foreign” serpentine soil compared to its home soil. So, while these two populations share a major QTL they either differ at other loci involved in serpentine adaptation or have different causal alleles at this QTL. This raises the possibility that serpentine populations may not be broadly tolerant to serpentine soils but may instead be locally adapted to their particular patch. Nevertheless, despite the myriad chemical and physical challenges that plants face in serpentine habitats, adaptation to these soils inM. guttatushas a simple genetic basis.
Heterocellular coupling between amacrine cell and ganglion cells
Authors: Marc Robert E. , Sigulinsky Crystal , Pfeiffer Rebecca L. , Emrich Daniel , Anderson James R. , Jones Bryan W.
Published: May 2018

All superclasses of retinal neurons display some form of electrical coupling including the key neurons of the inner plexiform layer: bipolar cells (BCs), amacrine or axonal cells (ACs) and ganglion cells (GCs). However, coupling varies extensively by class. For example, mammalian rod bipolar cells form no gap junctions at all, while all cone bipolar cells form class-specific coupling arrays, many of them homocellular in-superclass arrays. Ganglion cells are unique in that classes with coupling predominantly form heterocellular cross-class arrays of ganglion cell::amacrine cell (GC::AC) coupling in the mammalian retina. Ganglion cells are the least frequent superclass in the inner plexiform layer and GC::AC gap junctions are sparsely arrayed amidst massive cohorts of AC::AC, bipolar cell BC::BC, and AC::BC gap junctions. Many of these gap junctions and most ganglion cell gap junctions are suboptical, complicating analysis of specific ganglion cells. High resolution 2 nm TEM analysis of rabbit retinal connectome RC1 allows quantitative GC::AC coupling maps of identified ganglion cells. Ganglion cells classes apparently avoid direct cross-class homocellular coupling altogether even though they have opportunities via direct membrane touches, while transient OFF alpha ganglion cells and transient ON directionally selective (DS) ganglion cells are strongly coupled to distinct amacrine / axonal cell cohorts.

A key feature of coupled ganglion cells is intercellular metabolite flux. Most GC::AC coupling involves GABAergic cells (γ+ amacrine cells), which results in significant GABA flux into ganglion cells. Surveying GABA coupling signatures in the ganglion cell layer across species suggests that the majority of vertebrate retinas engage in GC::AC coupling.

Multi-hop synaptic queries of the entire RC1 connectome clearly profiles the coupled amacrine and axonal cells. Photic drive polarities and source bipolar cell class selec-tivities are tightly matched across coupled cells. OFF alpha ganglion cells are coupled to OFF γ+ amacrine cells and transient ON DS ganglion cells are coupled to ON γ+ amacrine cells including a large interstitial axonal cell (IAC). Synaptic tabulations show close matches between the classes of bipolar cells sampled by the coupled amacrine and ganglion cells. Further, both ON and OFF coupling ganglion networks show a common theme: synaptic asymmetry whereby the coupled γ+ neurons are also presynaptic to ganglion cell dendrites from different classes of ganglion cells outside the coupled set. In effect, these heterocellular coupling patterns enable an excited ganglion cell to directly inhibit nearby ganglion cells of different classes. Similarly, coupled γ+ amacrine cells engaged in feedback networks can leverage the additional gain of bipolar cell synapses in shaping the signaling of a spectrum of downstream targets based on their own selective coupling with ganglion cells.
Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons
Authors: Halikere Apoorva , Popova Dina , Hamod Aula , Swerdel Mavis R. , Moore Jennifer C. , Tischfield Jay A. , Hart Ronald P. , Pang Zhiping P.
Published: May 2018

Background

The OPRM1 A118G gene variant (N40D) encoding the µ-opioid receptor (MOR) has been associated with dependence on opiates and other abused drugs but its mechanism is unknown. With opioid abuse-related deaths rising at unprecedented rates, understanding these mechanisms may provide a path to therapy.

Methods

Seven human induced pluripotent stem (iPS) cell lines from homozygous N40D subjects (4 with N40 and 3 with D40 variants) were generated and human induced neuronal cells (iNs) were derived from these iPS cell lines. Morphological, gene expression as well as synaptic physiology analyses were conducted in human iN cells carrying N40D MOR variants; Two pairs of isogenic pluripotent stem cells carrying N40D were generated using CRISPR/Cas9 genome-editing and iN cells derived from them were analyzed.

Results

Inhibitory human neurons generated from subjects carrying N40D MOR gene variants show mature properties in morphological and functional analyses. Gene expression revealed that they express mature neuronal marker and MORs. Activation of MORs suppressed inhibitory synaptic transmission in human neurons carrying both N40 or D40 MOR variants but D40 show stronger effects. To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were validated in two sets of independently generated isogenic N40D iNs.

Conclusions

Activations of N40D MOR variants show different regulatory effects on synaptic transmission in inhibitory human neurons. This study identifies neurophysiological differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
The 5’ untranslated region of theEFG1transcript promotes its translation to regulate hyphal morphogenesis inCandida albicans
Authors: Desai Prashant R. , Lengeler Klaus , Kapitan Mario , Janßen Silas Matthias , Alepuz Paula , Jacobsen Ilse D. , Ernst Joachim F.
Published: May 2018

Extensive 5’ untranslated regions (UTR) are a hallmark of transcripts determining hyphal morphogenesis inCandida albicans.The major transcripts of theEFG1gene, which are responsible for cellular morphogenesis and metabolism, contain a 5’ UTR of up to 1170 nt. Deletion analyses of the 5’ UTR revealed a 218 nt sequence that is required for production of the Efg1 protein and its functions in filamentation, without lowering the level and integrity of theEFG1transcript. Polysomal analyses revealed that the 218 nt 5’ UTR sequence is required for efficient translation of the Efg1 protein. Replacement of theEFG1ORF by the heterologous reporter geneCaCBGlucconfirmed the positive regulatory importance of the identified 5’ UTR sequence. In contrast to other reported transcripts containing extensive 5’ UTR sequences, these results indicate the positive translational function of the 5’ UTR sequence in theEFG1transcript, which is observed in context of the nativeEFG1promoter. The results suggest that the 5’ UTR recruits regulatory factors, possibly during emergence of the native transcript, which aid in translation of theEFG1transcript.

IMPORTANCE

Many of the virulence traits that makeCandida albicansan important human fungal pathogen are regulated on a transcriptional level. Here we report an important regulatory contribution of translation, which is exerted by the extensive 5’ untranslated regulatory sequence (5’ UTR) of the transcript for the protein Efg1, which determines growth, metabolism and filamentation in the fungus. Presence of the 5’ UTR is required for efficient translation of Efg1, to promote filamentation. Because transcripts for many relevant regulators contain extensive 5’ UTR sequences, it appears that virulence ofC. albicansdepends on the combination of transcriptional and translation regulatory mechanisms.
New sequential touch method for determining bacterial contact transfer rate from finger to surface
Authors: Zhao Pengcheng , Li Yuguo
Published: May 2018

Bacteria can be transferred via surface touch. To evaluate the transfer rate, traditional single-touch methods require measuring the number of bacteria on donor and recipient surfaces, which is typically characterized by high levels of uncertainty. In this study, two concentrations ofStaphylococcus aureusATCC 25923 were inoculated on a clean thumb. For each set of trials, sequential touches were made between the thumb and each of 30 sterile glass slides, and each slide was placed in a sterile petri dish. The transferred bacteria on each slide were directly cultured in situ, and the colony-forming units (CFUs) were counted. The bacterial contact transfer rate was calculated by fitting the series of CFUs with the formula established. The average transfer rate was 12.9% under these conditions. The goodness of fit was compared in terms of the number of slides used in a set of trials and the number of CFUs counted on the slides. The use of more slides in a set of trials allowed more accurate evaluation of the transfer rate. The use of fewer than 20 slides was unacceptable. The high density of CFUs on the slides made counting them difficult, but if fewer than five CFUs were counted in a set of trials, the fit would be significantly influenced. To further evaluate the method, the dermal resident microflora on the thumb were also used to perform contact transfer tests. No statistically significant difference was found in the estimated transfer rate between the standard strain and the resident microflora.

IMPORTANCE

Diseases can be transferred indoors via the surface route because bacteria and viruses can be transferred to and from the hands when a fomite is touched. Various methods have been used to estimate the bacterial contact transfer rate between hands and surfaces. Evaluated transfer rates have had significant deviations and varied significantly across studies, partially due to the use of the single hand-surface touch method, inefficient hand/surface sampling, and complicated bacteria culture.

In this study, the bacterial contact transfer rate was evaluated with a new method involving sequential touches between a donor and a series of recipients. The bacteria on the recipients were cultured in situ without hand/surface sampling, which simplified the process of surface bacteria quantification. The new method significantly reduces experimental complexity, decreases random errors in the data, and provides a new method for understanding microbial transfers between surfaces.
Inhibitor of sarco/endoplasmic reticulum calcium-ATPase impairs paramyxovirus replication
Authors: Kumar Naveen , Barua Sanjay , Khandelwal Nitin , Chaubey Kundan Kumar , Kumar Ram , Rawat Krishan Dutt , Chander Yogesh , Riyesh Thachamvally , Singh Shoor Vir , Tripathi Bhupendra Nath
Published: May 2018

Sarco/endoplasmic reticulum calcium-ATPase (SERCA) is a membrane bound cytosolic enzyme that is known to regulate the uptake of calcium into the sarco/endoplasmic reticulum. Herein, we demonstrate for the first time that SERCA can also regulate paramyxovirus [Peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV)] replication. Treatment of Vero cells with SERCA specific inhibitor (Thapsigargin) at a concentration that is nontoxic to the cells significantly reduced virus replication. Conversely, overexpression of SERCA rescued the inhibitory effect of Thapsigargin on virus replication. PPRV/NDV infection induced SERCA expression in Vero cells which could be blocked by Thapsigargin. With the help of time-of-addition and virus step-specific assays, it was observed that Thapsigargin specifically inhibits viral entry and subcellular localization of the viral proteins. Furthermore, NDV, but not PPRV acquired a significant resistance to Thapsigargin on long-term passage (P=70) in Vero cells. To the best of our knowledge, this is the first report describing virus supportive role of SERCA and a rare report suggesting that viruses may acquire resistance even in the presence of an inhibitor that targets a cellular factor. This study will contribute in understanding paramyxovirus replication and development of antiviral therapeutics using SERCA (host factor) as a candidate drug target.
Investigation of lanthanide-dependent methylotrophy uncovers complementary roles for alcohol dehydrogenase enzymes
Authors: Good Nathan M. , Walser Olivia N. , Moore Riley S. , Suriano Carly J. , Huff Anna F. , Martínez-Gómez N. Cecilia
Published: May 2018

The discovery that methylotrophic bacteria can utilize lanthanides as catalysts for methanol metabolism has opened new areas of biology and biochemistry. Recent studies of lanthanide-dependent enzymes have focused on biochemical and kinetic properties or the regulation of encoding genes. Kinetic analysis of a pyrroloquinoline quinone methanol dehydrogenase, XoxF1 (MexAM1_1746), from the model methylotrophMethylobacterium extorquensAM1 confirms the use of different lanthanides as cofactors and formaldehyde as a product of methanol oxidation, showing that not all XoxF MDH produce formate as the only end productin vivo. The dephosphotetrahydromethanopterin pathway for formaldehyde oxidation is still required for lanthanide-methylotrophic growth, as afaemutant does not grow with methanol in the presence of exogenous lanthanides. Increases of 15-22% in growth rate and 10-12.5% in growth yield are observed whenM. extorquensAM1 is grown in the presence of lanthanides with methanol. RNA-sequencing transcriptomics indicates remodeling of methanol, formaldehyde and formate oxidation gene expression, and targeted metabolomics shows increased accumulation of intracellular formate and decreased pools of several assimilatory intermediates. Methanol sensitivity growth assays show that the lanthanide-dependent pyrroloquinoline quinone alcohol dehydrogenase ExaF (MexAM1_1139), but not XoxF1, can reduce formaldehyde toxicity when lanthanides are present, providing evidence of a role for ExaF during lanthanide-dependent methylotrophy. We conclude from these results that lanthanide-dependent methylotrophy is more efficient than calcium-dependent methylotrophy inM. extorquensAM1, and that this change is due, at least in part, to the lanthanide-dependent enzymes XoxF1 and ExaF.

IMPORTANCE

Lanthanides serve as cofactors for pyrroloquinoline quinone containing alcohol dehydrogenase enzymes in methylotrophic bacteria. The present study addresses a fundamental gap in our understanding of how lanthanides impact metabolism, including a detailed assessment of the metabolic modifications to accommodate enhanced efficiency during methylotrophy. Kinetic characterization of XoxF1 provides a detailed description of the impact of diverse lanthanides on catalytic function for a lanthanide-dependent methanol dehydrogenase. We further show that the lanthanide-dependent ethanol dehydrogenase ExaF can oxidize formaldehydein vivo, revealing complementary roles for these enzymes. This study provides novel insight into the effects of lanthanides on bacterial metabolism, highlighting the implementation of multiple, redundant and complementary oxidation systems.
Sharp wave-associated activity patterns of olfactory cortical neurons in the mouse piriform cortex
Authors: Katori Kazuki , Manabe Hiroyuki , Nakashima Ai , Dunfu Eer , Sasaki Takuya , Ikegaya Yuji , Takeuchi Haruki
Published: May 2018

The olfactory piriform cortex is thought to participate in olfactory associative memory. Like the hippocampus, which is essential for episodic memory, it belongs to an evolutionally conserved paleocortex and comprises a three-layered cortical structure. During slow-wave sleep, the olfactory piriform cortex becomes less responsive to external odor stimuli and instead displays sharp wave (SPW) activity similar to that observed in the hippocampus. Neural activity patterns during hippocampal SPW have been intensively studied in terms of memory consolidation; however, little is known about the activity patterns of olfactory cortical neurons during olfactory cortex sharp waves (OC-SPWs). In this study, we recorded multi-unit neural activities in the anterior piriform cortex in urethane-anesthetized mice. We found that the activity patterns of olfactory cortical neurons during OC-SPWs were non-randomly organized. Individual olfactory cortical neurons varied in the timings of their peak firing rates during OC-SPW events. Moreover, specific pairs of olfactory cortical neurons were more frequently activated together than expected by chance. On the basis of these observations, we speculate that coordinated activation of specific subsets of olfactory cortical neurons repeats during OC-SPWs, thereby facilitating synaptic plasticity underlying the consolidation of olfactory associative memories.