bluuebunny/crossref_metadata_2025 huggingface dataset:
High Levels of Interest in Reproductive Genetic Information in Parents of Children and Adults With Hirschsprung Disease
Authors: Berrios Courtney D. , Chakravarti Aravinda , Biesecker Barbara B.
Published: May 2019

Objectives:

Families affected by Hirschsprung disease (HSCR) have opportunities to learn recurrence risks to their children from statistical genetic and empiric studies and, in some cases, prenatal genetic testing or preimplantation genetic diagnosis (PGD). This study aimed to assess interest in reproductive genetic information for HSCR and factors that predict this interest in 2 groups with elevated risk of having a child with HSCR.

Methods:

Adult patients with HSCR and parents of children with HSCR were surveyed about their interest in learning reproductive genetic information regarding HSCR through genetic counseling, prenatal testing, and PGD. Covariates assessed in this cross‐sectional study included quality of life, illness perceptions, depressive symptoms, and adaptation to the condition. Bivariate analyses assessed differences between affected adults and parents. Logistic modeling was used to identify predictors of interest in reproductive genetic information.

Results:

Study participants (n = 368) reported high interest in reproductive genetic information through genetic counseling (yes = 60%/unsure = 16%), prenatal testing (yes = 59%/unsure = 16%), and PGD (yes = 43%/unsure = 18%). Illness perceptions differed between affected adults and parents, but perceived severity of HSCR was high among all participants (μ = 3.42, SD = 0.67, 4‐point scale). Interest in reproductive information was associated with being an affected adult, not having a family history of HSCR, negative emotional representations, and adaptation to the condition.

Conclusions:

Findings from this study support a desire among the surveyed HSCR patient groups to attend genetic counseling and be offered testing when available. Exploration of perceptions and experiences with the condition should be incorporated into the counseling to insure informed preference‐based decision making.
Systematic Review and Meta-analysis of Psychosocial Uncertainty Management Interventions
Authors: Zhang Yingzi , Kwekkeboom Kristine , Kim Kyung Soo , Loring Sarah , Wieben Ann M.
Published: May 2019

Background

Psychosocial uncertainty management interventions (UMIs) targeting patients and their family members might help to alleviate the negative influences of illness-related uncertainty, such as diminished quality of life and poor adjustment.

Objectives

The aims of this study were to evaluate the key characteristics of psychosocial UMIs and assess intervention effects on patients' and their family members' short-term and long-term illness-related uncertainty.

Methods

We conducted a systematic review and meta-analysis of psychosocial UMIs published through 2017. We performed a comprehensive electronic search and manual review. The outcome indicator was illness-related uncertainty experienced by patients or their family members.

Results

We included 29 studies in the systematic review and 14 studies in the meta-analysis. The main intervention components were information and resource provision, coping skills training, social and emotional support, communication skills, symptom management and self-care, coordination of care, and exercise. Compared to usual care, patients who received UMIs reported less uncertainty immediately after intervention delivery (g = −0.44, 95% confidence interval [CI] [−0.71, −0.16]) and at later follow-up points (g = −0.47, 95% CI [−0.91, −0.03]). Family members who received UMIs also reported less uncertainty immediately after intervention delivery (g = −0.20, 95% CI [−0.33, −0.06]) and at later follow-up points (g = −0.20, 95% CI [−0.36, −0.04]).

Discussion

Psychosocial UMIs had small to medium beneficial effects for both patients and their family members. Questions remain regarding what intervention components, modes of delivery, or dosages influence effect size. More rigorously designed randomized controlled trials are needed to validate intervention effects on patients' and family members' uncertainty management.
New Subtype B Containing HIV-1 Circulating Recombinant of sub-Saharan Africa Origin in Nigerian Men Who Have Sex With Men
Authors: Billings Erik , Kijak Gustavo H. , Sanders-Buell Eric , Ndembi Nicaise , O'Sullivan Anne Marie , Adebajo Sylvia , Kokogho Afoke , Milazzo Mark , Lombardi Kara , Baral Stefan , Nowak Rebecca , Ramadhani Habib , Gramzinski Robert , Robb Merlin L. , Michael Nelson L. , Charurat Manhattan E. , Ake Julie , Crowell Trevor A. , Tovanabutra Sodsai ,   for the MHRP Viral Sequencing Core and the TRUST/RV368 Study Group
Published: May 2019

Background:

HIV-1 circulating recombinant forms (CRF) containing subtype B are uncommon in sub-Saharan Africa. Prevalent infections observed during enrollment of a prospective study of men who have sex with men (MSM) from Lagos, Nigeria, revealed the presence of a family of subtype B and CRF02_AG recombinants. This report describes the HIV-1 genetic diversity within a high-risk, high-prevalence, and previously undersampled cohort of Nigerian MSM.

Methods:

Between 2013 and 2016, 672 MSM were enrolled at the Lagos site of the TRUST/RV368 study. Prevalent HIV-1 infections were initially characterized by pol sequencing and phylogenetic subtyping analysis. Samples demonstrating the presence of subtype B were further characterized by near full-length sequencing, phylogenetic, and Bayesian analyses.

Results:

Within this cohort, HIV-1 prevalence was 59%. The major subtype was CRF02_AG (57%), followed by CRF02/B recombinants (15%), subtype G (13%), and smaller amounts of A1, B, and other recombinants. Nine clusters of closely related pol sequences indicate ongoing transmission events within this cohort. Among the CRF02_AG/B, a new CRF was identified and termed CRF95_02B. Shared risk factors and Bayesian phylogenetic inference of the new CRF95_02B and the similarly structured CRF56_cpx indicate a Nigerian or West African origin of CRF56_cpx before its observation in France.

Conclusion:

With high HIV-1 prevalence, new strains, and multiple transmission networks, this cohort of Nigerian MSM represents a previously hidden reservoir of HIV-1 strains, including the newly identified CRF95_02B and closely related CRF56_cpx. These strains will need to be considered during vaccine selection and development to optimize the design of a globally effective HIV-1 vaccine.
HIV Transmission Chains Exhibit Greater HLA-B Homogeneity Than Randomly Expected
Authors: Nguyen Huyen , Thorball Christian W. , Fellay Jacques , Böni Jürg , Yerly Sabine , Perreau Matthieu , Klimkait Thomas , Kusejko Katharina , Bachmann Nadine , Chaudron Sandra E. , Paioni Paolo , Thurnheer Maria C. , Battegay Manuel , Cavassini Matthias , Vernazza Pietro , Bernasconi Enos , Günthard Huldrych F. , Kouyos Roger ,   the Swiss HIV Cohort Study
Published: May 2019

Background:

HIV's capacity to escape immune recognition by human leukocyte antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to the host HLA type and could better improve therapeutic strategies against HIV.

Materials and Methods:

Three hundred one to 325 transmission pairs and 469–496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA class I data were compiled at 3 specificity levels: 4-digit, 2-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as 2 measures: the proportion of transmission pairs, which are HLA concordant, and the average percentage of allele matches within all clusters. These measures were compared with the mean value across randomizations with randomly assorted individuals.

Results:

We repeated the analysis for different HLA classification levels and separately for HLA-A, -B, and -C. Subanalyses by the risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs. 0.251, P value = 0.009; supertype clusters: 0.659 vs. 0.611, P value = 0.002; supertype pairs: 0.655 vs. 0.608, P value = 0.014). Risk group restriction caused the effect to disappear for men-who-have-sex-with-men but not for other risk groups. We also examined if protective HLA alleles B27 and B57 were under- or overrepresented in the transmission chains, although this yielded no significant pattern.

Conclusions:

The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.
Brief Report: High Rates of Adverse Birth Outcomes in HIV and Syphilis Coinfected Women in Botswana
Authors: Shava Emily , Moyo Sikhulile , Zash Rebecca , Diseko Modiegi , Dintwa Eldah N. , Mupfumi Lucy , Mabuta Judith , Mayondi Gloria , Chen Jennifer Y. , Lockman Shahin , Mmalane Mompati , Makhema Joseph , Shapiro Roger
Published: May 2019

Background:

Little is known about the combined impact of HIV/syphilis coinfection on birth outcomes.

Methods:

Antenatal HIV and syphilis test results, obstetric history, and infant birth outcomes were collected from obstetric records in maternity wards in Botswana between 2008 and 2011 (5 sites) and 2014 and 2016 (8 sites). We used logistic regression to compare adverse birth outcomes by HIV and syphilis status. Outcomes included stillbirth, preterm delivery, low birth weight, and in-hospital neonatal death.

Results:

Of 76,466 women, 75,770 (99.1%) had HIV test results, and 20,520 (27.1%) were HIV positive. Syphilis test results were available for 67,290 (88.0%), and 697 (1.0%) had reactive rapid plasma reagin. Among 692 women with syphilis and an HIV test result, 261 (37.7%) were coinfected. HIV-infected women were more likely to be infected with syphilis than HIV-uninfected women [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.44 to 1.96]. From 2008–2011 to 2014–2016, the proportion of women with syphilis remained constant (1.1% vs. 1.0%,P= 0.41), but HIV/syphilis coinfection declined from 45% to 27% (P< 0.0001). Stillbirth occurred in 5.8% of coinfected women, compared with 1.9% with no HIV/syphilis (OR = 3.09; 95% CI: 1.83 to 5.23); 3.4% with HIV alone (OR = 1.75; 95% CI: 1.03 to 2.97), or 3.7% with syphilis alone (OR = 1.58; 95% CI: 0.77 to 3.25). Low birth weight occurred in 24.1% of coinfected women, compared with 12.1% with no HIV/syphilis (OR 2.31; 95% CI: 1.74 to 3.08; 20% with HIV alone (OR = 1.27; 95% CI: 0.96 to 1.69); or 14.6% with syphilis alone (OR = 1.85; 95% CI: 1.26 to 2.74).

Conclusions:

Although HIV/syphilis coinfection in pregnancy has declined in the past decade, coinfection was associated with adverse birth outcomes.
COMT Val158Met Polymorphism, Cardiometabolic Risk, and Nadir CD4 Synergistically Increase Risk of Neurocognitive Impairment in Men Living With HIV
Authors: Saloner Rowan , Marquine Maria J. , Sundermann Erin E. , Hong Suzi , McCutchan John Allen , Ellis Ronald J. , Heaton Robert K. , Grant Igor , Cherner Mariana
Published: May 2019

Objective:

The Val allele of the Val158Met single-nucleotide polymorphism of the catechol-o-methyltransferase gene (COMT) results in faster metabolism and reduced bioavailability of dopamine (DA). Among persons living with HIV, Val carriers display neurocognitive deficits relative to Met carriers, presumably due to exacerbation of HIV-related depletion of DA.COMTmay also impact neurocognition by modulating cardiometabolic function, which is often dysregulated among persons living with HIV. We examined the interaction ofCOMT, cardiometabolic risk, and nadir CD4 on neurocognitive impairment (NCI) among HIV+ men.

Methods:

Three hundred twenty-nine HIV+ men underwentCOMTgenotyping and neurocognitive and neuromedical assessments. Cohort-standardized z scores for body mass index, systolic blood pressure, glucose, triglycerides, and high-density lipoprotein cholesterol were averaged to derive a cardiometabolic risk score (CMRS). NCI was defined as demographically adjusted global deficit score of ≥0.5. Logistic regression modeled NCI as a function ofCOMT, CMRS, and their interaction, covarying for estimated premorbid function, race/ethnicity, and HIV-specific characteristics. Follow-up analysis included the 3-way interaction ofCOMT, CMRS, and nadir CD4.

Results:

Genotypes were 81 (24.6%) Met/Met, 147 (44.7%) Val/Met, and 101 (30.7%) Val/Val.COMTinteracted with CMRS (P= 0.02) such that higher CMRS increased risk of NCI among Val/Val [odds ratio (OR) = 2.13,P< 0.01], but not Val/Met (OR = 0.93,P> 0.05) or Met/Met (OR = 0.92,P> 0.05) carriers. Among Val/Val, nadir CD4 moderated the effect of CMRS (P< 0.01) such that higher CMRS increased likelihood of NCI only when nadir CD4 <180.

Discussion:

Results suggest a tripartite model by which genetically driven low DA reserve, cardiometabolic dysfunction, and historical immunosuppression synergistically enhance risk of NCI among HIV+ men, possibly due to neuroinflammation and oxidative stress.
Norovirus in health care and implications for the immunocompromised host
Authors: Chong Pearlie P. , Atmar Robert L.
Published: May 2019

Purpose of review

The majority of norovirus outbreaks in the United States occur in healthcare facilities. With the growing population of immunocompromised hosts who are in frequent contact with healthcare facilities, norovirus is not only a threat to hospitals and nursing homes but also to these individuals. This review summarizes the impact of norovirus infection on healthcare facilities and immunocompromised hosts.

Recent findings

The natural history of norovirus infection in immunocompromised individuals remains poorly understood. Although host immune responses play a critical role in reducing duration of viral shedding and viral load in norovirus-infected individuals, why some immunocompromised patients spontaneously recover while others develop a chronic and protracted course of illness remains unclear. Norovirus outbreaks occur in healthcare facilities because the virus is highly contagious, resistant to disinfection and efficiently transmitted. The use of real-time metagenomic next-generation sequencing and phylogenetic analyses has provided valuable information on transmission patterns in complex hospital-associated norovirus outbreaks. The development of human intestinal enteroid cultures enables the determination of effectiveness of disinfectants against human noroviruses, circumventing the validity questions with surrogate virus models due to differences in susceptibility to inactivation and disinfectants.

Metagenomics next-generation sequencing can enhance our understanding of norovirus transmission and lead to more timely mitigation strategies to curb norovirus outbreaks in healthcare facilities. With new in-vitro cultivation methods for human noroviruses, candidate vaccines and effective antivirals could be available in the near future.
Size of the Tonsil on Ultrasound in Children Without Tonsil-Associated Symptoms
Authors: Hosokawa Takahiro , Yamada Yoshitake , Takahashi Hiroaki , Tanami Yutaka , Sato Yumiko , Hosokawa Mayumi , Oguma Eiji
Published: May 2019

This study was performed to establish the reference for tonsil size in children, including neonates, without tonsil-associated symptoms, in relation to anthropometric indices (sex/age/height/weight/body mass index).

We evaluated the size of both tonsils in 362 children by ultrasonography. Tonsil size was calculated as 0.523abc (a, transverse diameter on the transverse image; b, longitudinal diameter on the transverse image; c, longitudinal diameter on the longitudinal image) and compared between each age year using the Wilcoxon signed rank sum test with Bonferroni correction. We evaluated the relationships between tonsil size and anthropometric indices.

Among these children, tonsil size was significantly increased by the age of 3 years (0–1 vs 1–2 [volume (right) = 210.15 ± 205.27 vs 737.83 ± 335.72 mm3, P (right) < 0.0001 and volume (left) = 218.26 ± 207.23 vs 645.33 ± 240.31 mm3, P (left) < 0.0001]; 1–2 vs 2–3 [volume (right) = 737.83 ± 335.72 vs 1073.86 ± 468.21 mm3, P (right) = 0.004 and volume (left) = 645.33 ± 240.31 vs 1109.73 ± 563.20 mm3, P (left) < 0.0001]). Although there was a tendency for the tonsil size to increase in years 3–12, there was no significant difference. Using single linear regression analysis, we found a correlation between tonsil size and age (r right/left = 0.67/0.65), height (r right/left = 0.72/0.70), and weight (r right/left = 0.66/0.64), with height having the strongest correlation.

In conclusion, tonsil size significantly increased by 3 years of age. Tonsil size was correlated with anthropometric indices, with height showing the strongest correlation.
Reliability of Real-Time Sonoelastography in the Diagnosis of Supraspinatus Tendinopathy
Authors: Aydın Elçin , Söylev Gözde Özcan , Muratlı Sedit Kıvanç , Limnili Bora , Boya Hakan , Tekindal Mustafa Agah , Ağıldere Muhteşem
Published: May 2019

The practicality of real-time sonoelastography in the diagnosis of tendinopathy is being discussed since the beginning of its use in musculoskeletal system. The aims of this study were to compare the elasticity of pathologic supraspinatus tendon with the uninvolved side by sonoelastography and to determine the relationship between the sonoelastographic findings and magnetic resonance imaging (MRI) grade of the tendinosis. Eighty-2 patients (50 males, 32 females, mean ± SD age = 53.61 ± 16.15 years, range = 20–84 years) with unilateral supraspinatus tendinosis were included in this study. Three grades of tendinosis were identified in MRI (grade 1: mild, grade 2: moderate, and grade 3: severe). The strain ratio (SR) of the tendinosis area to the healthy normal area of the same tendon tissue and SR of the tendinosis area to ipsilateral subcutaneous fat tissue were evaluated with sonoelastography. The SRs of the tendinosis areas were also compared with the control (contralateral) side tendon tissue and subcutaneous fat tissue of the same patients. Between-groups comparisons were also done according to the MRI grading. Statistical analysis was done using paired t test (P < 0.005 was considered statistically significant). There was a statistically significant difference in the comparison of the SRs of the tendinosis areas to subcutaneous fat tissues on ipsilateral shoulders (TA/SFT) and the healthy supraspinatus tendon area (TA/ST) of the same shoulder. There was also statistically significant difference when compared with the control side measurements (P < 0.01). In patients who have grade 1 and grade 3 tendinosis on MRI, there was statistically significant difference between elastrographic evaluation of affected and unaffected sides. Real-time sonoelastography is a reliable diagnostic method in patients with rotator cuff tendinosis and shall be kept in mind as a noninvasive, inexpensive, and practical diagnostic test in suitable cases.
A Novel Use of Buccal Fat Pad Flap for Immediate Reconstruction of Palatal Tumor Resection Defect
Authors: Koç Onur , Tüz Hakan H. , Tosun Emre
Published: May 2019

Integrity of the palatal mucosa may be disrupted due to various pathological and congenital factors. In maxillofacial defects, the buccal fat pad has been used frequently to repair the palatal region and close oro-nasal communications. In this case report, the use of buccal fat pad for the closure of a surgical palatal defect is presented with a 3-year follow-up. A 75-year-old female patient visited our clinic with a complaint of a non-adaptive maxillary denture. During clinical and radiographic examination, a well-demarcated mass on the palatal mucosa extending to the soft palate of the left side was observed. Subsequent to resection of the tumor, a defect occurred on the palatal region extending toward the soft palate. The pedicled buccal fat pad was chosen for closure of the defect. The patient was followed-up at 3, 7, 14, and 30 days after surgery. Epithelization and healing of the surgical wound were uneventful. At the 3-year follow-up, functional closure of the left palatal region was observed with no recurrence. Buccal fat pad is an easily manipulated flap with predictable results for the reconstruction of medium-sized defects of the oral and maxillofacial region with minimal postoperative discomfort for the patient.
The Trends of Pediatric Facial Fractures Due to Violence in a Level One Trauma Population
Authors: Wainwright D’Arcy J. , Moffitt Joseph K. , Bartz-Kurycki Marisa , Wainwright David J. , Anderson Kathryn , Demian Nagi , Teichgraeber John F. , Greives Matthew R.
Published: May 2019

Introduction:

Pediatric facial fractures due to intentionally violent mechanisms represent a unique subset of facial fractures. The objective of our research is to identify how violence affects patterns of facial fractures and their management in pediatric patients.

Methods:

An IRB approved, retrospective study of our institution's pediatric patients ≤18 years of age who presented with ≥1 facial fracture due to violence from January 2006 to December 2015 was performed. Violence was defined as trauma intended to hurt another or self. Demographics, fractures, mechanism, concomitant injuries, and management were analyzed.

Results:

The 1274 patients were diagnosed with facial fractures, with 235 of these due to violence (18%). These patients of violence (POV) had 332 fractures, with an average fracture per patient of 1.4 ± .0.8. The majority (86%) were male, Non-Hispanic African American (35%), and the average age was 15.9 ± 2.8 years. The most common fracture was the mandible (50% of patients) and most common mechanism was assault (76%). The POV were older, male, and of minority race/ethnic groups when compared to patients of non-violence (PONV) (P <0.01). The POV presented with fewer concomitant injuries, were less likely to be admitted to the intensive care unit, and more often surgically managed when compared to the PONV (P <0.01).

Conclusion:

This study represents the largest US, single institution, Level 1 trauma center study of pediatric facial fractures. Pediatric patients with facial fractures due to a violent mechanism represent a distinct category of trauma patients with a unique profile of injuries.
Correlation Between Speech Outcomes and the Amount of Maxillary Advancement After Orthognathic Surgery (Le Fort I Conventional Osteotomy and Distraction Osteogenesis) in Patients With Cleft Lip and Palate
Authors: Chung Jeehyeok , Lim Joonho , Park Hyunyoung , Yoo Anna , Kim Sukwha , Koo Yountaek
Published: May 2019

Background:

The purpose of this study is to evaluate the factors affecting the speech outcome following Le fort I conventional osteotomy(CO) or Le Fort I distraction osteogenesis(DO) in patients with cleft lip and palate at a single institution.

Method:

Records of cleft lip and palate patients who underwent orthognathic surgery between 2010 and 2015 were reviewed. Data included age at orthognathic surgery, sex, cleft lip and palate type, type of orthognathic surgery, the amount of maxillary advancement, and speech assessment. Speech outcomes were classified into 2 categories. Compared with the pre and post-operative Pittsburgh Weighted speech scale scores, in case that the post-operative total score is increased the authors define it as “Speech deterioration” and if not, the authors define it as “Speech preservation.”

Result:

The 44 patients were identified, 33 patients underwent CO and 11 patients underwent DO. The mean age was 19.4 ± 1.4. The mean period time of speech evaluation after orthognathic surgery was 1.0 ± 0.46 year. The mean amount of maxillary advancement was 7.2 ± 3.2 mm and show significant correlation with speech outcomes. (P = 0.012) . In CO group, the patients who had the maxilla 1∼5 mm advancement maintained their speech completely and 44% of patients with 6∼8 mm deteriorated their speech. In DO group, patients with 9∼10 mm maintained their speech completely, 50% of patients with 11∼12 mm deteriorated their speech and 100% of patients with 13∼16 mm deteriorated their speech. According to the relationship between the amount of maxillary advancement and speech outcomes, there was a statistically significant correlation in both CO and DO groups. (P = 0.04, 0.029).

Conclusion:

It was found that speech of the patients with more amount of maxillary advancement tended to get worse. Also, it was observed that there exist some stable ranges of maxillary advancement for speech safety which does not effect on speech. (1∼5 mm in CO group and 9∼10 mm in DO group).
Three-Dimension–Printed Surgical Guide for Accurate and Safe Mandibuloplasty in Patients With Prominent Mandibular Angles
Authors: Yi Chang Ryul , Choi Jong-Woo
Published: May 2019

Performance of mandibuloplasty is highly dependent on each surgeon's experience, and reproducing the results of simulation surgery is often difficult. In order to obtain successful clinical outcomes, a fast and efficient surgery technique that minimizes operation time and risk to patients is needed. The authors designed a 3D-printed mandible fit surgical guide for use as a bridge between simulation and actual surgery.

The authors enrolled 7 patients with prominent mandibular angle who visited the outpatient clinic of the Department of Plastic and Reconstructive Surgery at Asan Medical Center in Seoul, Korea between December 2013 and May 2017.

The surgical guides were made with a 3D printer and simulated based on individual facial bone CT scans. The surgical guides were designed to fit the lower border of the mandible and to cover the portion planned for removal.

The resulting personalized 3D-printed surgical guides were applied on both mandibular angles to the body and along the lower border of the mandible. Osteotomy of the mandibular angle and body were performed along the surgical guide. All patients recovered without any immediate postoperative complications. The use of 3D-printed surgical guide was effective in simplifying the process of mandibuloplasty.

Our results demonstrate the value of 3D printing technology in mandibuloplasty.
Temporal Hollowing Augmentation With Polyetheretherketone Patient-Specific Implant
Authors: Doh GyeongHyeon , Eo SuRak , Hong Ki Yong
Published: May 2019

Temporal hollowing is a common complication of surgical dissection in the temporal region. As it is a serious cosmetic problem, the need for reconstruction is increasing. Advances in medical imaging, computer software, 3-dimensional printing technology, and biochemistry have enabled surgeons to use patient-specific implants for correction of craniofacial deformities. Titanium, polymethylmethacrylate, and polyetheretherketone are representative materials of the alloplastic implant. In this article, the authors report the first case of temporal hollowing augmentation using a polyetheretherketone patient-specific implant.
Reduced Peripapillary and Macular Vessel Density in Unilateral Postgeniculate Lesions With Retrograde Transsynaptic Degeneration
Authors: Jaumandreu Laia , Sánchez-Gutiérrez Veronica , Muñoz-Negrete Francisco J. , de Juan Victoria , Rebolleda Gema
Published: May 2019

Background:

Retrograde transsynaptic degeneration (RTSD) of the retinal ganglion cells and retinal nerve fiber layer after postgeniculate injury has been well documented, but to the best of our knowledge, associated retinal microvascular changes have not been examined. The purpose of our study was to assess vessel density (VD) at macular and peripapillary regions in patients with RTSD.

Methods:

Cross-sectional study including 16 patients with homonymous visual field defects secondary to unilateral postgeniculate visual pathway injury and 18 age-matched controls. All participants were examined with AngioVue optical coherence tomography angiography to measure the peripapillary vessel density and macular vessel density (pVD/mVD) as well as the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell complex (GCC) thicknesses. The pRNFL and macular ganglion cell–inner plexiform layer (GCIPL) thicknesses also were evaluated using Cirrus OCT. A normalized asymmetry score (NAS) was calculated for GCIPL and GCC thickness, and mVD.

Results:

Average pRNFL and macular GCIPL/GCC thicknesses were significantly thinner in both eyes of patients compared with control eyes (all P ≤ 0.05). Eight patients (50%), who showed a RTSD of the GCIPL map, had a relative thinning of the GCIPL/GCC ipsilateral to the brain lesion in both eyes (represented by a positive GCIPL-NAS/GCC-NAS). The mean pVD and mVD also were significantly reduced in patients (all P ≤ 0.05). There was a strong correlation between GCIPL-NAS/GCC-NAS and mVD-NAS index in both eyes (all r > 0.7, P = 0.001). Furthermore, there was a similar spatial pattern of damage for the macular GCC thickness and VD values.

Conclusions:

We demonstrated a significant VD decrease in peripapillary and macular areas of patients with RTSD because of postgeniculate lesions. The structural and microvascular asymmetry indexes were significantly correlated. These findings provide new insights regarding transsynaptic degeneration of the visual system.
Retrospective Association Analysis of Longitudinal Binary Traits Identifies Important Loci and Pathways in Cocaine Use
Authors: Wu Weimiao , Wang Zhong , Xu Ke , Zhang Xinyu , Amei Amei , Gelernter Joel , Zhao Hongyu , Justice Amy C. , Wang Zuoheng
Published: May 2019

Longitudinal phenotypes have been increasingly available in genome-wide association studies (GWAS) and electronic health record-based studies for identification of genetic variants that influence complex traits over time. For longitudinal binary data, there remain significant challenges in gene mapping, including misspecification of the model for the phenotype distribution due to ascertainment. Here, we propose L-BRAT, a retrospective, generalized estimating equations-based method for genetic association analysis of longitudinal binary outcomes. We also develop RGMMAT, a retrospective, generalized linear mixed model-based association test. Both tests are retrospective score approaches in which genotypes are treated as random conditional on phenotype and covariates. They allow both static and time-varying covariates to be included in the analysis. Through simulations, we illustrated that retrospective association tests are robust to ascertainment and other types of phenotype model misspecification, and gain power over previous association methods. We applied L-BRAT and RGMMAT to a genome-wide association analysis of repeated measures of cocaine use in a longitudinal cohort. Pathway analysis implicated association with opioid signaling and axonal guidance signaling pathways. Lastly, we replicated important pathways in an independent cocaine dependence case-control GWAS. Our results illustrate that L-BRAT is able to detect important loci and pathways in a genome scan and to provide insights into genetic architecture of cocaine use.
easyCLIP Quantifies RNA-Protein Interactions and Characterizes Recurrent PCBP1 Mutations in Cancer
Authors: Porter Douglas F. , Khavari Paul A.
Published: May 2019

RNA-protein interactions mediate a host of cellular processes, underscoring the need for methods to quantify their occurrence in living cells. RNA interaction frequencies for the average cellular protein are undefined, however, and there is no quantitative threshold to define a protein as an RNA-binding protein (RBP). Ultraviolet (UV) cross-linking immunoprecipitation (CLIP)-sequencing, an effective and widely used means of characterizing RNA-protein interactions, would particularly benefit from the capacity to quantitate the number of RNA cross-links per protein per cell. In addition, CLIP-seq methods are difficult, have high experimental failure rates and many ambiguous analytical decisions. To address these issues, the easyCLIP method was developed and used to quantify RNA-protein interactions for a panel of known RBPs as well as a spectrum of random non-RBP proteins. easyCLIP provides the advantages of good efficiency compared to current standards, a simple protocol with a very low failure rate, troubleshooting information that includes direct visualization of prepared libraries without amplification, and a new form of analysis. easyCLIP, which uses sequential on-bead ligation of 5’ and 3’ adapters tagged with different infrared dyes, classified non-RBPs as those with a per protein RNA cross-link rate of <0.1%, with most RBPs substantially above this threshold, including Rbfox1 (18%), hnRNPC (22%), CELF1 (11%), FBL (2%), and STAU1 (1%). easyCLIP with the PCBP1L100 RBP mutant recurrently seen in cancer quantified increased RNA binding compared to wild-type PCBP1 and suggested a potential mechanism for this RBP mutant in cancer. easyCLIP provides a simple, efficient and robust method to both obtain both traditional CLIP-seq information and to define actual RNA interaction frequencies for a given protein, enabling quantitative cross-RBP comparisons as well as insight into RBP mechanisms.
A systems genetics approach reveals environment-dependent associations between SNPs, protein co-expression and drought-related traits in maize
Authors: Blein-Nicolas Mélisande , Negro Sandra Sylvia , Balliau Thierry , Welcker Claude , Bosquet Llorenç Cabrera , Nicolas Stéphane Dimitri , Charcosset Alain , Zivy Michel
Published: May 2019

The effect of drought on maize yield is of particular concern in the context of climate change and human population growth. However, the complexity of drought-response mechanisms make the design of new drought-tolerant varieties a difficult task that would greatly benefit from a better understanding of the genotype-phenotype relationship. To provide novel insight into this relationship, we applied a systems genetics approach integrating high-throughput phenotypic, proteomic and genomic data acquired from 254 maize hybrids grown under two watering conditions. Using association genetics and protein co-expression analysis, we detected more than 22,000 pQTLs across the two conditions and confidently identified fifteen loci with potential pleiotropic effects on the proteome. We showed that even mild water deficit induced a profound remodeling of the proteome, which affected the structure of the protein co-expression network, and a reprogramming of the genetic control of the abundance of many proteins, notably those involved in stress response. Co-localizations between pQTLs and QTLs for ecophysiological traits, found mostly in the water deficit condition, indicated that this reprogramming may also affect the phenotypic level. Finally, we identified several candidate genes that are potentially responsible for both the co-expression of stress response proteins and the variations of ecophysiological traits under water deficit. Taken together, our findings provide novel insights into the molecular mechanisms of drought tolerance and suggest some pathways for further research and breeding.
Hitting a moving target: Microbial evolutionary strategies in a dynamic ocean
Authors: Walworth Nathan G. , Zakem Emily J. , Dunne John P. , Collins Sinéad , Levine Naomi M.
Published: May 2019

Marine microbes form the base of ocean food webs and drive ocean biogeochemical cycling. Yet little is known about how microbial populations will evolve due to global change-driven shifts in ocean dynamics. Understanding adaptive timescales is critical where long-term trends (e.g. warming) are coupled to shorter-term advection dynamics that move organisms rapidly between ecoregions. Here we investigated the interplay between physical and biological timescales using a model of adaptation and an eddy-resolving ocean circulation climate model. Two criteria (α and β) were identified that relate physical and biological timescales and determine the timing and nature of adaptation. Genetic adaptation was impeded in highly variable regimes (α<1) but promoted in more stable environments (α>1). An evolutionary trade-off emerged where greater short-term transgenerational effects (low-β-strategy) enabled rapid responses to environmental fluctuations but delayed genetic adaptation, while fewer short-term transgenerational effects (high-β-strategy) allowed faster genetic adaptation but inhibited short-term responses. Our results suggest that organisms with faster growth rates are better positioned to adapt to rapidly changing ocean conditions and that more variable environments will favor a bet-hedging, low-β-strategy. Understanding the relationship between evolutionary and physical timescales is critical for robust predictions of future microbial dynamics.
Identification of microRNA-target interactions for antioxidant defense response under drought stress by high-throughput sequencing in Zanthoxylum bungeanum Maxim
Authors: Fei Xitong , Hu Haichao , Li Jingmiao , Liu Yulin , Wei Anzhi
Published: May 2019

When the plant is in an unfavorable environment such as drought or high temperature, it will accumulate a large amount of active oxygen, which will seriously affect the normal growth and development of the plant. The antioxidant system can remove the reactive oxygen species produced under drought conditions and so mitigate oxidative damage. We examined the trends of antioxidant enzymes, miRNAs and their target genes in Zanthoxylum bungeanum under drought stress. According to the changes of antioxidant enzymes, miRNAs and their target genes expression patterns of Zanthoxylum bungeanum under drought stress, an interaction model was constructed to provide a reference for further understanding of plant antioxidant mechanism. The results indicate that under drought stress, POD, CAT, APX, proline, MDA and related genes all show positive responses to drought, while SOD and its genes showed a negative response. It is speculated that in the antioxidant process of Zanthoxylum bungeanum, POD, CAT, and APX play a major role, and SOD plays a supporting role. In addition, the expression levels of miRANs and their target genes were basically negatively correlated, indicating that miRNAs are involved in the regulation of the antioxidant system of Zanthoxylum bungeanum.
Antibiotics can be used to contain drug-resistant bacteria by maintaining sufficiently large sensitive populations
Authors: Hansen Elsa , Karslake Jason , Woods Robert J. , Read Andrew F. , Wood Kevin B.
Published: May 2019

Standard infectious disease practice calls for aggressive drug treatment that rapidly eliminates the pathogen population before resistance can emerge. When resistance is absent, this elimination strategy can lead to complete cure. However, it also removes drug-sensitive cells as quickly as possible, removing competitive barriers that may slow the growth of resistant cells. In contrast to the elimination strategy, the containment strategy aims to maintain the maximum tolerable number of pathogens, exploiting competitive suppression to achieve chronic control. Here we combine in vitro experiments in computer-controlled bioreactors with mathematical modeling to investigate whether containment strategies can delay failure of antibiotic treatment regimens. To do so, we measured the “escape time” required for drug-resistant E. coli populations to eclipse a threshold density maintained by adaptive antibiotic dosing. Populations containing only resistant cells rapidly escape containment, but we found that matched populations with the maximum possible number of sensitive cells could be contained for significantly longer. The increase in escape time occurs only when the threshold density–the acceptable bacterial burden–is sufficiently high, an effect that mathematical models attribute to increased competition. The findings provide decisive experimental confirmation that maintaining the maximum number of sensitive cells can be used to contain resistance when the size of the population is sufficiently large.
Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction
Authors: Barth Zachary K , Silvas Tania V , Angermeyer Angus , Seed Kimberley D
Published: May 2019

Phage-inducible chromosomal island-like elements (PLEs) are bacteriophage satellites found inVibrio cholerae. PLEs parasitize the lytic phage ICP1, excising from the bacterial chromosome, replicating, and mobilizing to new host cells following cell lysis. PLEs protect their host cell populations by completely restricting the production of ICP1 progeny. Previously, it was found that ICP1 replication was reduced during PLE(+) infection. Despite robustly replicating its genome, PLE produces relatively few transducing units, leading us to investigate if PLE DNA replication itself is antagonistic to ICP1 replication. Here we identify key constituents of PLE replication and assess their role in interference of ICP1. PLE encodes a RepA_N initiation factor that is sufficient to drive replication from the PLE origin of replication during ICP1 infection. In contrast to previously characterized bacteriophage satellites, expression of the PLE initiation factor was not sufficient for PLE replication in the absence of phage. Replication of PLE was necessary for interference of ICP1 DNA replication, but replication of a minimalized PLE replicon was not sufficient for ICP1 DNA replication interference. Despite restoration of ICP1 DNA replication, non-replicating PLE remained broadly inhibitory against ICP1. These results suggest that PLE DNA replication is one of multiple mechanisms contributing to ICP1 restriction.
Novel strategy for treating neurotropic viral infections using hypolipidemic drug Atorvastatin
Authors: Mallick Suvadip , Chakraborty Surajit , Hazra Bibhabasu , Dev Sujata , Mukherjee Sriparna , Wani Masood Ahmad , Basu Anirban
Published: May 2019

Chandipura virus (CHPV) and Japanese Encephalitis Virus (JEV) are known to infect neurons followed by their successful propagation. Increased incidences of central nervous system invasion by the abovementioned viruses have been reported in case of children and elderly thus culminating into severe neurological damage. Literature suggests induction of endoplasmic reticulum (ER)-stress related proteins upon CHPV and JEV infection which help promote viral reproduction. Since earlier studies underscore the pleotropic role of atorvastatin (AT) in neuroprotection against flaviviruses like Hepatitis C and dengue, it was hypothesized that AT might also act as a neuroprotective agent against RNA viruses like CHPV and JEV. AT-mediated antiviral activity was evaluated by assessing survivability of virus-infected mouse pups treated with the drug. Balb C mice were used for in vivo experiments. Neuro2A cell line was used as the model for in vitro experiments. Cells subjected to AT treatment were infected by CHPV and JEV followed by evaluation of ER stress-related and apoptosis-related proteins by immunoblotting technique and immunofluorescence microscopy. Interaction of host protein with viral genome was assessed by RNA-Co-IP. AT treatment exhibited significant anti-viral activity against CHPV and JEV infections via hnRNPC-dependent manner. Viral genome-hnRNPC interaction was found to be abrogated upon AT action. AT was also observed to reduce secretion of proinflammatory cytokines by the neurons in response to viral infection. Moreover, AT treatment was also demonstrated to reduce neuronal death by abrogating virus-induced miR-21 upregulation in hnRNPC-dependent fashion. This study thus suggests probable candidature of AT as antiviral against CHPV and JEV infections.
www.Malaria.tools - comparative genomic and transcriptomic database for Plasmodium species
Authors: Tan Qiao Wen , Mutwil Marek
Published: May 2019

Malaria is a tropical parasitic disease caused by the Plasmodium genus, which resulted in an estimated 219 million cases of malaria and 435,000 malaria-related deaths in 2017. Despite the availability of the P. falciparum genome since 2002, almost 50% of the genes remain unannotated. To remedy this paucity of functional information, we used transcriptomic data to build gene co-expression networks for two Plasmodium species (P. falciparum and P. berghei), and included genomic data of four other Plasmodium species, P. yoleii, P. knowlesi, P. vivax and P. cynomolgi, as well as two non-Plasmodium species from the Apicomplexa, Toxoplasma gondii and Theileria parva. The database is preloaded with tools that allow the identification and cross-species comparison of co-expressed gene neighborhoods, clusters, and life stage-specific expression, thus providing sophisticated tools to predict gene function. Moreover, we exemplify how the tools can be used to easily identify genes relevant for pathogenicity and various life stages of the malaria parasite. The database is freely available at www.malaria.tools.
Feasibility of a surface-coated lung model for the quantification of active agent deposition for preclinical studies
Authors: Dörner Philipp , Müller Philipp M. , Reiter Jana , Gruhlke Martin C. , Slusarenko Alan J. , Schröder Wolfgang , Klaas Michael
Published: May 2019

Multiple drug resistance (MDR) of a growing number of bacterial pathogens represents an increasing challenge in conventional curative treatments of infectious diseases. However, the development and testing of new antibiotics is associated with a high number of animal experiments. A symmetrical parametrized lung test rig allowing the exposure of air-passage surfaces to antibiotics was designed and tested to demonstrate proof-of-principle with aerosols containing allicin, which is an antimicrobial natural product from garlic. An artificial lung surface is coated with bacteria embedded in a hydrogel and growth inhibition is visualized by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), that is reduced from colourless to the dark blue formazan in the presence of metabolically active, living cells. A nebulizer is used to generate the aerosols. The results show that allicin has an antibiotic effect as an aerosol and that the deposition pattern of the active agent occurred mainly around the carinal regions. The model represents an integral system for continuous, spatial detection of aerosol deposition and allows the analysis of bacterial behaviour and the toxicity of the active agent. In this way the deposition of antimicrobial aerosols on the bronchial surfaces is characterized in preliminary tests without any animal experiments.
Neural oscillations while remembering traumatic memories in PTSD
Authors: Reuveni Inbal , Herz Noa , Bonne Omer , Peri Tuvia , Schreiber Shaul , Harpaz Yuval , Goldstein Abraham
Published: May 2019

Background

In posttraumatic stress disorder (PTSD), the traumatic event is often re-experienced through vivid sensory fragments of the traumatic experience. Though the sensory phenomenology of traumatic memories is well established, neural indications for this qualitative experience are lacking. The current study aimed at monitoring the oscillatory brain activity of PTSD patients during directed and imaginal exposure to the traumatic memory using magnetoencephalography (MEG), in a paradigm resembling exposure therapy.

Methods

Brain activity of healthy trauma-exposed controls and PTSD participants was measured with MEG as they listened to individualized trauma narratives as well as to a neutral narrative and as they imagined the narrative in detail. Source localization analysis on varied frequency bands was conducted in order to map neural generators of altered oscillatory activity.

Results

PTSD patients exhibited increased power of high-frequency bands over visual areas and increased delta and theta power over auditory areas in response to trauma recollection compared to neutral recollection, while controls did not show such differential activation. PTSD participants also showed abnormal modulation of lower frequencies in the medial prefrontal cortex.

Conclusions

Elicitation of traumatic memories results in a distinct neural pattern in PTSD patients compared to healthy trauma-exposed individuals. Investigating the oscillatory neural dynamics of PTSD patients can help us better understand the processes underlying trauma re-experiencing.