bluuebunny/crossref_metadata_2025 huggingface dataset:
Symplasmic phloem unloading and post-phloem transport during bamboo internode elongation
Authors: Deng Lin , Li Pengcheng , Chu Caihua , Ding Yulong , Wang Shuguang
Published: December 2019

In traditional opinions, no radial transportation was considered to occur in the bamboo internodes but was usually considered to occur in the nodes. Few studies have involved the phloem unloading and post-phloem transport pathways in the rapid elongating bamboo shoots. Our observations indicated a symplastic pathway in phloem unloading and post-unloading pathways in the culms of Fargesiayunnanensis Hsueh et Yi, based on a 5,6-carboxyfluorescein diacetate tracing experiment. Significant lignification and suberinization in fiber and parenchyma cell walls in maturing internodes blocked the apoplastic transport. Assimilates were transported out of the vascular bundles in four directions in the inner zones but in two directions in the outer zones via the continuum of parenchyma cells. In transverse sections, assimilates were outward transported from the inner zones to the outer zones. Assimilates transport velocities varied with time, with the highest values at 0):00 h, which were affected by water transport. The assimilate transport from the adult culms to the young shoots also varied with the developmental degree of bamboo shoots, with the highest transport velocities in the rapidly elongating internodes. The localization of sucrose, glucose, starch grains and the related enzymes reconfirmed that the parenchyma cells in and around the vascular bundles constituted a symplastic pathway for the radial transport of sugars and were the main sites for sugar metabolism. The parenchyma cells functioned as the ‘rays’ for the radial transport in and between vascular bundles in bamboo internodes. These results systematically revealed the transport mechanism of assimilate and water in the elongating bamboo shoots.
Antipsychotic-like profile of CIQ isomers in animal models of schizophrenia
Authors: Gawai Pushparaj , Upadhyay Rohit , Gakare Sukanya G. , Sarode Lopmudra , Dravid Shashank M. , Ugale Rajesh R.
Published: December 2019

Earlier, we have shown the efficacy of racemic (±) CIQ, a positive allosteric modulator of GluN2C/2D receptor against MK-801 induced impairment of prepulse inhibition as well as working memory. The present study investigated the antipsychotic-like profile of different CIQ (±, +, −) isomers against schizophrenia-like symptoms in series of behavioural animal models like apomorphine climbing, social isolation behaviour and NMDA receptor antagonist MK-801 induced cognitive deficits. Further, we also tested CIQ (±, +, −) isomers in neurodevelopmental model against MK-801induced deficits using open field test, Y-maze test and novel object recognition test. CIQ (±, +, −) isomers decreased climbing behaviour, increased social interaction and improved the MK-801 induced deficits in working memory in Y-maze. Further, CIQ (±, +) but not CIQ (−) improved the recognition memory in novel object recognition test as well as reduced hyperlocomotion and stereotyped behaviour. We conclude that CIQ (±, +) but not CIQ (−) exhibit the significant antipsychotic-like profile.
A valepotriate-enriched fraction from Valeriana glechomifolia decreases DNA methylation and up-regulate TrkB receptors in the hippocampus of mice
Authors: Müller Liz G. , Biojone Caroline , Sales Amanda J. , Betti Andresa H. , Herzfeldt Vivian , Joca Sâmia R.L. , Rates Stela M.K.
Published: December 2019

DNA methylation, an epigenetic modification that mediates gene silencing, has been shown to play a role in the neurobiology of major depression. Studies suggested that terpenes inhibit DNA methylation and increase gene expression. The present study investigated the involvement of DNA methylation in the antidepressant-like activity of diene valepotriates, non-glicosilated carbocyclic iridoids that comprise a family of terpenes obtained from Valeriana glechomifolia. The antidepressant-like effect of diene valepotriates acute administration (5 mg/kg, p.o.) in mice submitted to the forced swimming test was followed by a decrease in global DNA methylation in animals’ hippocampus (but not in the pre-frontal cortex). Mice pretreatment with anysomicin (a protein synthesis inhibitor) and K252a (an inhibitor of Trk receptors) attenuated diene valepotriates-induced antidepressant-like effect in the forced swimming test. Diene valepotriates elicited an upregulation in the TrkB receptor and a tendency to increase BDNF levels in mice hippocampus. These results demonstrate that DNA methylation could be an in vivo molecular target of diene valepotriates. The diene valepotriates-triggered reduction in hippocampal DNA methylation is accompanied by increased protein synthesis, which is involved in its antidepressant-like activity. Furthermore, BDNF-mediated TrkB signaling may contribute for diene valepotriates antidepressant-like effect.
Treatment of Neuroma-induced Chronic Pain and Management of Nerve Defects with Processed Nerve Allografts
Authors: Ducic Ivica , Yoon Joshua , Eberlin Kyle R.
Published: December 2019

Background:

Symptomatic neuromas can cause significant chronic pain and negatively impact quality of life. Symptoms often persist despite narcotics and nonoperative interventions, which are largely ineffective. With the opioid crisis, treatments for chronic pain that limit narcotics are needed. Traditional surgical options may result in neuroma recurrence. Autograft reconstruction often results in donor-site morbidity. Processed nerve allografts facilitate axonal growth, nerve regeneration, and eliminate donor-site morbidity.

Methods:

A literature review was performed to identify studies in which chronic neuroma pain was treated with excision and processed nerve allograft reconstruction. PubMed was queried, and data from the studies were grouped into treatment effective and ineffective groups. Statistical analyses were performed on these groups, and further subgroup analysis was performed on overall change of preoperative and postoperative pain scores using a paired t test.

Results:

Seven studies fulfilled inclusion criteria yielding 42 patients. Greater than 90% of patients had improvement of pain postoperatively. The preoperative and postoperative pain scores could be determined for 40 patients. The mean preoperative score was 7.9, and the mean postoperative score was 3.54. These results were statistically significant using a paired t test with a P value of <0.001.

Conclusions:

Chronic pain resulting from symptomatic neuromas can be treated with neuroma excision and nerve stump reconstruction with processed nerve allograft. This obviates autograft-associated donor-site morbidity and provides a platform to potentially restore sensation to the involved nerve whenever a distal nerve end is available. Addressing the root cause is an important paradigm shift for treating symptomatic neuromas.
FOVEAL SPARING INTERNAL LIMITING MEMBRANE PEELING FOR IDIOPATHIC MACULAR HOLES
Authors: Murphy Declan C. , Fostier Will , Rees Jon , Steel David H.
Published: December 2019

Purpose:

Muller cells seem to be important in maintaining foveal morphology through connections between their foot processes and the internal limiting membrane (ILM). Internal limiting membrane peeling causes Muller cell trauma. We hypothesized that leaving a rim of unpeeled ILM around idiopathic macular holes undergoing vitrectomy surgery would improve postoperative foveal morphology and vision.

Methods:

Prospective pilot study of fovea-sparing ILM peeling in a consecutive cohort of patients with macular holes over a 12-month period. Spectral-domain optical coherence tomography and Early Treatment Diabetic Retinopathy Study letters best-corrected visual acuity were assessed preoperatively and postoperatively, and foveal morphology and metamorphopsia postoperatively. The foveal sparing group was compared with a second consecutive cohort who received standard ILM peeling (control group).

Results:

Thirty-four eyes of 34 patients were included in each group. Groups showed no significant preoperative differences. 34/34 holes were successfully closed with surgery in the foveal sparing group and 32/34 in the control group. The foveal sparing group showed better postoperative best-corrected visual acuity (67.7 vs. 63.8, P = 0.003) and best-corrected visual acuity improvement (25.1 vs. 20.2, P = 0.03). The foveal sparing group demonstrated thicker minimum foveal thickness (211 vs. 173 μm, P = 0.002) and less steep foveal depression (158 vs. 149, P = 0.002).

Conclusion:

Preserving nonpeeled ILM around macular holes resulted in a high closure rate, improved foveal morphology, and better postoperative best-corrected visual acuity. An appropriately powered randomized controlled study is warranted.
Electronic Nose Analysis of Exhaled Breath Volatiles to Identify Lung Cancer Cases: A Systematic Review
Authors: Swanson Barbara , Fogg Louis , Julion Wrenetha , Arrieta Maryan T.
Published: December 2019

The purpose of our review was to analyze evidence of the validity of electronic noses to discriminate persons with lung cancer from healthy control subjects and to advance implications for this technology in the care of people living with HIV. A computerized database search of the literature (published 1946–2018) was conducted to identify studies that used electronic nose-generated smellprints to discriminate persons with lung cancer from healthy control subjects. Fifteen articles met the sampling criteria. In 14 studies, mean sensitivity and specificity values from a single training sample were 84.1% and 80.9%, respectively. Five studies applied the prediction model obtained from the training sample to a separate validation sample; mean sensitivity was 88.2%, and mean specificity was 70.2%. Findings suggest that breath smellprints are valid markers of lung cancer and may be useful screening measures for cancer. No studies included people living with HIV; additional studies are needed to assess generalizability to this population.
Prognosis and Long-Term Outcome of Women With Idiopathic Recurrent Vulvovaginal Candidiasis Caused by Candida albicans
Authors: Collins Laura M. , Moore Rachelle , Sobel Jack D.
Published: December 2019

Objectives

This study evaluated use of long-term fluconazole beyond an initial 6-month course of weekly fluconazole in premenopausal patients with idiopathic recurrent vulvovaginal candidiasis (RVVC) due to Candida albicans.

Materials and Methods

A retrospective chart review was performed of women seen in Wayne State University Vaginitis Clinic with culture-confirmed idiopathic RVVC due to Candida albicans during a 10-year period (January 2006 to December 2015). Only patients without risk factors for secondary VVC and who initiated a 6-month course of weekly fluconazole therapy were selected. Data included long-term use of fluconazole therapy, treatment efficacy, and development of fluconazole resistance. Questionnaires were mailed to evaluate patient's experience after fluconazole therapy.

Results

Of 883 patients with RVVC based on clinical records, 191 with culture positive idiopathic RVVC due to C. albicans were started on the maintenance fluconazole regimen, and 147 (77.0%) completed 6 months of therapy. Of these, 107 (72.8%) continued or received maintenance past 6 months. The most common reason for additional fluconazole therapy was culture-confirmed VVC recurrence (55.1%), unconfirmed but possible VVC recurrence (16.8%), and patient preference (10.3%). The mean duration of fluconazole maintenance was 35.7 (range = 7–288) months. Fluconazole resistance emerged in 7.5% completing 6-month therapy. Upon questionnaire follow-up, 93.6% of 51 respondents reported benefit during maintenance regimen; however, 80.9% described relapse after discontinuing weekly therapy.

Conclusions

Fluconazole suppression therapy was highly effective in preventing VVC symptoms but was rarely curative and VVC relapse occurred frequently after discontinuation of maintenance therapy. The development of drug resistance in C. albicans isolates after long-term fluconazole maintenance therapy although uncommon is a previously unrecognized complication.
Assessment of Anal Cancer Screening Tools in Detecting High-Grade Anal Squamous Intraepithelial Lesions in Women
Authors: Ramos-Cartagena Jeslie M. , Pérez Cynthia M. , Guiot Humberto M. , Amaya-Ardilla Claudia P. , Tirado-Gómez Maribel , Ortiz Ana P.
Published: December 2019

Objective

The aim of the study was to evaluate the validity of anal cytology against high-resolution anoscopy in the detection of anal high-grade squamous intraepithelial lesions (HSILs) among women in a clinical setting in Puerto Rico, alone and in combination with high-risk human papillomavirus (HR-HPV) typing.

Materials and Methods

A cross-sectional study was done among 128 eligible women who attended the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Center between 2014 and 2019. Kappa (κ) coefficient, sensitivity, specificity, positive predictive value, and negative predictive value were calculated using high-resolution anoscopy with biopsy as the criterion standard test. Poisson regression was used to estimate the adjusted prevalence ratio of anal HR-HPV infection.

Results

Overall, 71.1% of women were HIV infected and 78.9% had anal HR-HPV infection. Squamous intraepithelial lesions were detected with anal cytology and histology in 70.3% and 81.3% of women, respectively. The κ statistic between the tests (cytology and histology) was 0.32 (p < .05). Measured against the results from histology, the sensitivity of anal cytology alone to detect HSIL was 85.4% (95% CI = 72.2%–93.9%), whereas specificity was 38.8% (95% CI = 28.1%-50.3%). Although the sensitivity of the 2 tests combined (anal cytology and HR-HPV typing) to detect histologically confirmed HSIL increased (100.0%, 95% CI = 92.6%–100.0%), the specificity decreased (16.3%, 95% CI = 9.0%–26.2%). Meanwhile, women with HSIL had a higher prevalence of anal HR-HPV infection than those with no SIL/LSIL (prevalence ratio = 6.23, 95% CI = 1.50–25.83).

Conclusions

Anal cytology in combination with HR-HPV typing for the screening of anal intraepithelial neoplasia improved the detection of HSIL in women.
Early Detection of Anal High-Grade Squamous Intraepithelial Lesion: Do We Have an Impact on Progression to Invasive Anal Carcinoma?
Authors: Maugin Florent , Lesage Anne-Carole , Hoyeau Nadia , Fléjou Jean-François , Zuber Kevin , Atienza Patrick , Etienney Isabelle
Published: December 2019

Objective

Anal high-grade squamous intraepithelial lesion (HSIL) may precede invasive cancer and can be detected clinically or during high-resolution anoscopy (HRA). The aims of this study were to compare the characteristics of HSIL discovered by HRA or in a surgical specimen without clinically visible lesion when diagnosed versus macroscopic HSIL when first diagnosed and then to compare their progression to invasive cancer.

Patients and Methods

Clinical records of all patients with at least one HSIL lesion confirmed by histology and evaluated by HRA in a single center between September 1, 2009, and April 30, 2017, were retrospectively reviewed. The center's histological anal cancer data base was questioned in December 2017 to identify all cases.

Results

During a median (interquartile range) follow-up of 19.1 (5.6–40.2) months, 12 (2.9%) anal cancers were diagnosed in patients with a diagnosis of HSIL. Period of time between the first diagnosis of anal lesion and the cancer was 28.8 months (interquartile range = 15.4–65.6), and 11 (92%) of 12 were diagnosed as superficially invasive squamous cell carcinoma or T1N0M0. The rate of progression to anal cancer differed significantly between patients with macroscopic HSIL at diagnosis (5.4%) and patients with microscopic HSIL diagnosed during HRA (0.9%) (p = .01).

Conclusions

Patients with macroscopic histologically proven HSIL at first diagnosis of anal intraepithelial lesion have a significantly higher risk of anal cancer compared with patients with microscopic lesions diagnosed during HRA, but the duration between the first diagnosis of HSIL and cancer does not differ between the 2 groups.
Assessment of Temporal Fine Structure Processing Among Older Adults With Cochlear Implants
Authors: Sladen Douglas P. , Peterson Ann , Olund Amy
Published: December 2019

Objectives:

The purpose of this study was to determine if older adults with cochlear implants are able to take advantage of coding schemes that preserve temporal fine structure (TFS) cues.

Design:

A total of 19 older adults with cochlear implants participated in a prospective, repeated measures, A to B design. Participants entered the study using TFS. The participants used strategy A (high definition continuous interleaved sampling [HDCIS]) for 3 months and strategy B (TFS) for 3 months. Endpoint testing was administered at the end of each 3-month period. Testing included consonant recognition, speech understanding in noise, temporal modulation thresholds, and self-perceived benefit.

Results:

Older adults were able to use TFS successfully. Speech perception performance was improved using TFS compared with HDCIS for voicing, but not manner or place of articulation. There were no differences between the two strategies for speech understanding in noise, temporal modulation detection, or self-perceived benefit. At the end of the study, 13 out of 19 (68%) of participants chose to continue using TFS processing.

Conclusions:

Advanced age does not prevent adults with cochlear implants from using TFS coding strategies. Performance outcomes using TFS and HDCIS were similar, with the exception of voicing which was improved when using TFS. The data support the idea of using various sound processing strategies with older adults.
The impact of atherosclerotic risk factors on disease progression in patients with previously diagnosed nonobstructive coronary artery disease: factors affecting coronary artery disease progression
Authors: Durmaz Eser , Ikitimur Baris , Karadag Bilgehan , Barman Hasan Ali , Atici Adem , Koca Damla , Raimoglu Utku , Karaca Orhan Furkan , Mutlu Deniz , Ongen Zeki
Published: December 2019

Objective

Since coronary artery disease (CAD) is a slow progressive disease, management and appropriate follow-up of patients with nonobstructive coronary artery disease (NOCAD) remains challenging, and there are no clear guidelines recommending a follow-up strategy and indications for repeat invasive coronary angiography (ICA). We investigated the predictors of the development of obstructive CAD in patients with previously diagnosed NOCAD.

Methods

We prospectively included 186 patients who previously received a diagnosis of NOCAD with invasive coronary angiogram and underwent repeat ICA. Patients’ demographics, clinical characteristics, biochemical analyses were recorded. Obstructive CAD is defined as >50% luminal narrowing in any epicardial coronary artery with a diameter of >2 mm.

Results

A total of 186 patients (105 male) were assigned into our study. Mean age was 64.77 ± 10.31 in patients with obstructive CAD (n = 60) vs. 61.87 ± 9.94 in NOCAD patients (n = 126) (P value: 0.068). The median time interval between index and follow-up coronary angiograms was 8 (5–10) years. There was no significant difference between groups with respect to LDL and Hs-CRP levels (P value: 461 and 354, respectively). Although patients with obstructive CAD have more comorbidities, multivariate analyses revealed that there was no significant difference between groups. On the contrary, the total number of risk factors were significantly associated with the development of obstructive CAD during follow-up. Receiver operating characteristic analyses revealed with a cut-off value of 3.5 risk factors, the sensitivity of 71%, the specificity of 61% and the area under the curve was 0.71 for prediction of obstructive CAD.

Conclusion

Our results indicate that no single risk factor alone is related with development of obstructive CAD; however, patients with high number of multiple risk factors are more prone to develop obstructive disease and require closer follow-up.
Interobserver reproducibility of mercaptoacetyltriglicine renography in children and adults with suspected obstruction: parameters of drainage and function calculated by International Atomic Energy Agency software
Authors: Radulović Marija , Janković Milica M. , Durutović Otaš , Šobić-Šaranović Dragana P. , Ajdinović Boris , Artiko Vera M. , Žeravica Radmila , Beatović Slobodanka Lj.
Published: December 2019

Objective

The aim of this study was to estimate interobserver reproducibility of Tc-99m mercaptoacetyltriglycine renography in children and adults by assessing the parameters of the International Atomic Energy Agency (IAEA) software for the analysis of dynamic renal studies.

Methods

The renograms of 65 children and 65 adults covered a wide age range, different quality of drainage, overall function and differential renal function (DRF). Three observers were processing parameters of the IAEA software. Normalized residual activity at 20 min (NORA20), NORA on the postmicturition acquisition (NORApm), PM to maximum renal count ratio (PM/max), output efficiency at 20 min (OE20), OE 20 min after diuretic stimulation (OEF + 20), whole kidney mean transit time (MTT) and DRF by integral and Rutland-Patlak were calculated by observers.

Results

The overall agreement between three observers was almost perfect [the average intraclass correlation coefficient (ICC) above 0.99] in children and adults, with no significant difference between the parameters of renal drainage, transit and DRF. ICCs for all parameters were higher than 0.980 in children under 12 months, even slightly greater for PM/max and OEF+20. In children with poor/incomplete drainage and DRF below 40%, ICCs were above 0.98. In the subgroup of adults with impaired overall tubular extraction rate, level of reproducibility was almost perfect. Slightly lower but still insignificant values of ICC were presented in adults with poor/incomplete drainage.

Conclusion

Our results indicate an excellent interobserver reproducibility for all quantitative parameters of IAEA software in both pediatric and adult patients.
Early Complications Following Articular Calcaneus Fracture Repair
Authors: Knapik Derrick M. , Hermelin Michael J. , Tanenbaum Joseph E. , Vallier Heather A.
Published: December 2019

Objectives:

To assess complications and secondary operations in patients treated with either open reduction and internal fixation (ORIF) versus percutaneous fixation of displaced intra-articular calcaneus fractures.

Design:

Retrospective comparative study.

Setting:

Level 1 trauma center.

Patients/Participants:

Ninety-three adult patients with 111 fractures treated by a single orthopaedic traumatologist between 2001 and 2014.

Intervention:

ORIF through an extensile lateral approach or percutaneous reduction and internal fixation.

Main Outcome Measurements:

Wound-healing complications, infections, posttraumatic arthrosis (PTOA), and secondary procedures.

Results:

Fifty patients with 58 fractures underwent ORIF, and 43 patients with 53 fractures had percutaneous fixation. Mean age was 43 years, and 80% were male. Open fractures and two-part fractures were more often treated percutaneously (26% vs 8%, P = 0.03) and (49% vs 31%, P = 0.02), respectively. Patients undergoing percutaneous fixation were more often tobacco users (58% vs 36%, P = 0.04) and with history of alcohol and other substance abuse. Twenty-seven patients (29%) had 28 complications, including 21% with PTOA, with no differences based on type of treatment. Six patients had secondary procedures, with no difference based on type of treatment. Patients with open fractures (P = 0.001) or tobacco abuse (P = 0.005) were more likely to experience complications.

Conclusions:

No differences in complication rates were found for ORIF versus percutaneous fixation. Regardless of fixation technique, patients with open fractures or history of tobacco abuse were more likely to develop complications. Percutaneous reduction and fixation represents an alternative to extensile ORIF in terms of similar early and late complications, particularly in high risk patients.

Level of Evidence:

Therapeutic Level III
Incidence of Postoperative Adverse Events after Rhinoplasty: A Systematic Review
Authors: Sharif-Askary Banafsheh , Carlson Anna R. , Van Noord Megan G. , Marcus Jeffrey R.
Published: December 2019

Background:

Adverse events after rhinoplasty vary in etiology and severity, a fact that is reflected in the current American Society of Plastic Surgeons rhinoplasty consent form. However, there is currently no literature providing a comprehensive summation of evidence-based quantifiable risk of adverse events after rhinoplasty. Given this limitation, patients considering rhinoplasty are unable to fully ascertain preoperative risk, and the ability of physicians to obtain true informed consent is similarly flawed. This systematic review provides the first rigorous, comprehensive, and quantitative reporting of adverse events after rhinoplasty.

Methods:

This review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (registration no. CRD42018081826) in April of 2018. Eligible articles were published in peer-reviewed journals with available abstracts and full-text articles. Interventions included primary functional, aesthetic, and combined functional/aesthetic rhinoplasty. The following data were extracted: study size, population characteristics, indication, surgical approach, concomitant procedures, and incidence of adverse events.

Results:

A search yielded 3215 publications for title and abstract screening. Three hundred twenty-two were eligible for full-text review. Thirty-six met final inclusion criteria. A total of 13 adverse events were reported among these studies and included need for revision (0 to 10.9 percent), infection (0 to 4 percent), dehiscence (0 to 5 percent), bleeding (0 to 4.1 percent), septal perforation (0 to 2.6 percent), nasal airway obstruction requiring revision (0 to 3 percent), and hypertrophic scarring (0 to 1.5 percent).

Conclusions:

This systematic review presents the first comprehensive and quantitative reporting of adverse event frequency after rhinoplasty. This is a crucial tool for preoperative patient counseling and an essential adjunct in the acquisition of informed consent. Future investigations will benefit from transparency and standardization of reporting to further quantify adverse event rates.
Long-Term Growth following Trigonocephaly Repairs: Are Overcorrections Necessary?
Authors: Fearon Jeffrey A. , Ditthakasem Kanlaya , Chan Wing Nam J. , Herbert Morley
Published: December 2019

Background:

Does bifrontal width change with growth following trigonocephaly corrections? Postoperative long-term growth was assessed, along with the impacts of phenotypic severity, surgical timing, and operative technique, to determine how wide to surgically set bifrontal width.

Methods:

A retrospective review of all trigonocephaly repairs was performed. Exclusion criteria included syndromic conditions, incomplete records, and follow-up under 1 year. Anthropometric measurements taken through completion of growth were evaluated and compared to sex- and age-matched normal standards for Z score conversion.

Results:

Of 370 consecutive patients undergoing repairs, 95 had sufficient anthropometric data. The mean surgical age was 10.8 months (range, 2 months to 7 years) and mean follow-up was 54.3 months (range, 12 months to 17.8 years). Sequential measurements revealed progressive increases in bifrontal width. However, following conversion to Z scores, the initial overcorrection (mean overcorrection, 8.7 mm; mean Z score, +2.3) steadily diminished to an undercorrection (mean measurement, −5.5 mm; mean Z score, −1.1). Compared to treatment at an older age (10 to 12 months), repairs performed in those younger than 8 months showed worse growth (p = 0.004). Those more severely affected (lowest bifrontal Z scores) had growth similar to that of those more mildly impacted. Only two patients (2.1 percent) underwent secondary procedures for recurrences. No correlation was found between anthropologic measurements and observers’ severity assessments.

Conclusions:

Subnormal bifrontal growth occurs following trigonocephaly corrections, especially with earlier corrections. Repairs performed at approximately 11 months of age had to be overcorrected by approximately 1.5 cm to produce a normal bifrontal width at maturity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Secondary Unilateral Cleft Rhinoplasty Using Natural Curvature of Rib Cartilage as Alar Rim Graft: A Three-Dimensional Evaluation of Long-Term Results
Authors: Liu Clarence Sze-Wai , Hsiao Yen-Chang , Huang Jung-Ju , Chen Jyh-Ping , Pascasio Dax , Chang Chun-Shin , Lo Lun-Jou , Chen Philip Kuo-Ting , Chen Yu-Ray , Ku Peter Ka-Ming
Published: December 2019

Background:

Since 2012, the senior author has incorporated the natural curvature of rib cartilage as an alar rim graft in addition to the diced cartilage technique for unilateral cleft rhinoplasty. The aim of this study is to describe this modification and evaluate its long-term results regarding nasal symmetry using three-dimensional stereophotogrammetric assessment (3dMDface system).

Methods:

From 2012 to 2018, 47 consecutive patients that underwent secondary unilateral cleft rhinoplasty were reviewed retrospectively. Sixteen patients with both preoperative and postoperative three-dimensional photographs taken at least 6 months after the operation were included. SimPlant O&O software was used to measure parameters on three-dimensional photographs: nostril heights, nostril widths, nasal dorsum heights, alare width, nostril areas, overlapping nostril area, nasal tip protrusion, nasal length, and nasal height before and after surgery. The ratios between cleft and noncleft sides were calculated. In addition, the overlapping nostril area ratio, tip protrusion-width index, and nasal index were compared before and after surgery.

Results:

The preoperative nostril height ratio (0.79), nostril width ratio (1.24), and nasal dome height ratio (0.84) between cleft and noncleft sides were significantly improved after surgery to 0.93, 1.06, and 0.97, respectively. The preoperative overlapping nostril area ratio (72.33 percent), nasal tip protrusion-width index (0.48), and nasal index (0.81) also showed significant improvement postoperatively to 83.91 percent, 0.57, and 0.74, respectively.

Conclusion:

This preliminary study supports the use of natural curvature of rib cartilage as alar rim graft in secondary unilateral cleft rhinoplasty, with long-term improvement regarding nasal symmetry and nasal profile.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Taxonomic reassessment of the genus Pseudocitrobacter using whole genome sequencing: Pseudocitrobacter anthropi is a later heterotypic synonym of Pseudocitrobacter faecalis and description of Pseudocitrobacter vendiensis sp. nov.
Authors: Kämpfer Peter , Fuglsang-Damgaard David , Overballe-Petersen Søren , Hasman Henrik , Hammerum Anette M. , Fuursted Kurt , Blom Jochen , Glaeser Stefanie P. , Hansen Frank
Published: December 2019

The taxonomic status of all

Pseudocitrobacter

species was re-evaluated by comparative genomics based on whole genome sequencing. As a result, it is obvious that

Pseudocitrobacter anthropi

is a later heterotypic synonym of

Pseudocitrobacter faecalis

. In addition, genome-based analysis of strain CPO20170097T, isolated from a patient in northern Denmark was allocated to the genus

Pseudocitrobacter

. This strain showed significant genotypic and phenotypic differences from

P. faecalis

and it is proposed that this strain represents a novel species of the genus, for which the name Pseudocitrobacter vendiensis sp. nov. is proposed with the type strain CPO20170097T (=CCUG 73096T=LMG 31042T).
Rhodobacter flagellatus sp. nov., a thermophilic bacterium isolated from a hot spring
Authors: Xian Wen-Dong , Liu Ze-Tao , Li Meng-Meng , Liu Lan , Ming Yu-Zhen , Xiao Min , Salam Nimaichand , Li Wen-Jun
Published: December 2019

A thermophilic bacterium, designated SYSU G03088T, was isolated from Moincer hot spring, Tibet, PR China. Polyphasic taxonomic analyses and whole-genome sequencing were used to determine the taxonomic position and genomic profiles of the strain. Phylogenetic analysis using 16S rRNA gene sequence indicated that SYSU G03088T showed highest sequence similarity to

Rhodobacter blasticus

CGMCC 1.3365T (96.0 % sequence identity). The strain could be differentiated from most recognized species of the genus

Rhodobacter

by its slightly purple colony colour, distinct phenotypic characters and low ANI values. Cells were Gram-staining negative, and oval-to-rod shaped. Poly-β-hydroxybutyrate and vesicular intracytoplasmic membrane structures were formed inside cells. Growth occurred optimally at 45 °C and pH 7.0. Ubiquinone 10 was the only respiratory quinone. The major fatty acids (>10 %) were C18 : 0, C18 : 1ω7c 11-methyl and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The detected polar lipids of SYSU G03088T included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylmethylethanolamine. The DNA G+C content of SYSU G03088T was 67.7 % (genome). On the basis of the differences in the phenotypic characteristics and phylogenetic analyses, SYSU G03088T is considered to represent a novel species of the genus

Rhodobacter

, for which the name Rhodobacter flagellatus sp. nov. is proposed. The type strain is SYSU G03088T (=CGMCC 1.16876T=KCTC 72354T).
Mechanical model of muscle contraction. 3. The orientation of the levers belonging to the myosin heads in working stroke follows the same uniform law in all half-sarcomeres of an isometrically stimulated fiber
Authors: Louvet S.
Published: December 2019

A myosin II head is modelled during the working stroke (WS) by three rigid segments articulated between them: the motor domain (S1a), the lever (S1b) and the rod (S2). Hypothesis 4 introduced in accompanying Paper 2 states that the lever of a WS head moves in a fixed plane where the position of S1b is characterized by the angle θ. This assumption allows the geometrization of a cross-bridge, i.e. the poly-articulated chain consisting of five rigid segments: the actin filament (Afil), S1a, S1b, S2, and the myosin filament (Mfil). The equations established in Paper 2 are operative to calculate the number of heads potentially in WS for a Mfil surrounded by six Afil. In addition, the value of the angles θ of the levers belonging to these WS heads is accessible. This census leads to an integer number (Np) of angular positions (θi) distributed discretely between θupand θdown, the two values that delimit θ during the WS. The number of Mfil per half-sarcomere (hs) is estimated between 400 and 2000 depending on the typology, figures that induce Gaussian variability for each of the Npvalues θi calculated for a single Mfil. By summing the Gaussian Npdensities and after normalization, we obtain a probability density (dG) of the continuous variable θ between θupand θdown. The function dGis calculated for a random length of a hs between 1 and 1.1 μm where the binding rate of the myosin heads is maximum. From this reference length, the hs is shortened 11 times with a step of 1 nm, i.e. a total of 11 nm. For each shortening, a count of the new θi positions is performed, which leads to a new probability density dG. The classic statistical law that approximates these 12 distributions of θ is the Uniform law between θupand θdown. Other conditions and values given to the data of the algorithmic procedure lead to a similar result, hence the formulation of hypothesis 5: the distribution of the angle θ follows an identical uniform law in all the hs of a muscle fiber stimulated in isometric conditions.
Mechanical model of muscle contraction. 4. Theoretical calculations of the tension during the isometric tetanus plateau and the tension exerted at the end of phase 1 of a length step
Authors: Louvet S.
Published: December 2019

Hypothesis 4 presented in accompanying Paper 2 states that the lever of a myosin II head in working stroke (WS) moves in a fixed plane, the orientation of the lever being defined by the angle θ. From this conjecture can be deduced the hypothesis 5 developed in accompanying Paper 3: the distribution of θ is identical and uniform in each half-sarcomere (hs) of a muscle fiber stimulated under isometric conditions. We propose a sixth hypothesis that establishes a linear relationship between the θ angle and the motor moment (ℳ) exerted on the lever. These three hypotheses lead to calculations of the tension during isometric tetanus plateau (T0) and the tension applied at the end of phase 1 of a length step when the only internal actions are the forces of elastic origin produced by the myosin heads in WS (T1Elas). However, the T1Elasvalues are higher than those observed experimentally. The model introduces the presence of viscosity as the seventh hypothesis. The internal actions resulting from the coupling of the elasticity of the WS heads and the viscosity make it possible to explain all the observed phenomena that contribute to the phase 1 of a length step. An adequate adjustment between the theoretical tension from the model (T1) and the tension representative of the end of phase 1 exposed in examples from the physiological literature is proven (r2> 98%). Other parameters such as stiffness (e), compliance (C) and strain (Y) are deduced; their investigation enables the construction of an analytical “nanoscope” by means of which the uniform density of θ is explored. The equations for T0, T1, e, C and Y explain and predict the influence of factors such as the duration of phase 1, the initial length of the sarcomere, the concentration of calcium, the presence of an inhibitor, the tension rise to the isometric tetanus plateau, relaxation after tetanization or shortening at constant speed. The results obtained during a slack-test are indicated by the model, the slack of the fiber being interpreted as an event of purely viscous origin.
Mechanical model of muscle contraction. 6. Calculations of the tension exerted by a skeletal fiber during a shortening staircase
Authors: S. Louvet
Published: December 2019

Accompanying Paper 1 tests a theoretical relationship between force and shortening velocity of a muscle fiber without justifying its validity. Paper 2 determines the kinematics and dynamics of a myosin II head during the working stroke (WS). Paper 3 imposes the Uniform law as a density representative of the orientation of the levers belonging to the WS heads. By support of these works, Papers 4 and 5 put into equation the evolution of the tension during the four phases of a length step. The present paper closes all six articles by imposing two tasks on itself. The first purpose is to apply the theoretical elements developed for a length step to a succession of identical length steps, otherwise known as shortening staircase. With the values of the geometric and temporal parameters assigned to a myosin head in Papers 1 to 5, a correct adjustment is established between the theoretical tension deduced from our model and the experimental tension published in 1997 by a team of Italian researchers relating to nine shortening staircases performed on the same fiber. In particular, we obtain the equation of the tension reached at the time end of the step (T*) which remains constant step by step as soon as the shortening of a half-sarcomere exceeds 17 nm. The second objective is to find and explain the equation of the Force-Velocity curve introducedex abruptointo Paper 1: by decreasing the size and duration of the steps, the staircase tends towards a constant slope line corresponding to a continuous speed shortening. By applying the methods of infinitesimal calculus to the different formulations leading to T*, we deduce the Force-Velocity relationship (see Supplement S6.L). And the circle is complete.
MSL3 coordinates a transcriptional and translational meiotic program in female Drosophila
Authors: McCarthy Alicia , Sarkar Kahini , Martin Elliot T , Upadhyay Maitreyi , James Joshua R , Lin Jennifer M , Jang Seoyeon , Williams Nathan D , Forni Paolo E , Buszczak Michael , Rangan Prashanth
Published: December 2019

Gamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation and meiotic entry are incompletely understood. Set2, which deposits H3K36me3 modifications, is required for differentiation of GSCs duringDrosophilaoogenesis. We discovered that the H3K36me3 reader Male-specific lethal 3 (MSL3) and the histone acetyltransferase complex Ada2a-containing (ATAC) cooperate with Set2 to regulate entry into meiosis in femaleDrosophila. MSL3 expression is restricted to the mitotic and early meiotic stages of the female germline, where it promotes transcription of genes encoding synaptonemal complex components and a germline enrichedribosomal protein S19paralog,RpS19b.RpS19bupregulation is required for translation of Rbfox1, a known meiotic cell cycle entry factor. Thus, MSL3 is a master regulator of meiosis, coordinating the expression of factors required for recombination and GSC differentiation. We find that MSL3 is expressed during mouse spermatogenesis, suggesting a conserved function during meiosis.
The vagus nerve mediates the suppressing effects of peripherally administered oxytocin on methamphetamine self-administration and seeking in rats
Authors: Everett Nicholas A. , Turner Anita J , Costa Priscila A , Baracz Sarah J. , Cornish Jennifer L.
Published: December 2019

Background

The neuropeptide oxytocin has emerged as a promising pharmacotherapy for methamphetamine (METH) addiction, and clinical trials of intranasal oxytocin are underway. However, there is debate as to how peripherally administered oxytocin alters brain signaling to modulate addiction processes. Interestingly, there is evidence for functional interactions between peripheral oxytocin administration and the vagus nerve. Therefore, this study investigated whether the effects of peripherally administered oxytocin require vagal signaling to reduce METH self-administration and reinstatement of METH-seeking behaviours.

Methods

Male and female Sprague-Dawley rats underwent surgery for jugular catheterization and either subdiaphragmatic vagotomy (SDV) or a sham operation. Rats were trained to self-administer METH, and the effect of peripherally administered oxytocin on METH intake was assessed. Rats then underwent extinction, and effects of oxytocin were assessed on cue- and METH-induced reinstatement of METH-seeking.

Results

Oxytocin treatment robustly attenuated METH intake in both sexes. Strikingly, SDV entirely prevented the suppressant effect of oxytocin (0.3 mg/kg) on METH intake, and partially prevented the effects of 1 mg/kg oxytocin in both sexes. After extinction, SDV impaired the suppressing effects of oxytocin on cue- and METH-primed reinstatement in males, but not females. SDV was functionally confirmed by measuring food intake following administration of the vagal dependent peptide, cholecyostokin-8.

Conclusion

Our data suggest that vagus nerve signaling is required for the anti-addiction effects of peripherally administered oxytocin, and that this vagal dependency is partially mediated by sex and drug withdrawal. This study has considerable implications for the applicability of oxytocin as a therapy for METH use disorder for both sexes.
Collective cell migration and residual stress accumulation: modeling consideration
Authors: Pajic-Lijakovic I. , Milivojevic M.
Published: December 2019

Stress generation during collective cell migration represents one of the key factors which influence the configuration of migrating cells, viscoelasticity of multicellular systems and their inter-relation. Local generation of stress (normal and shear) is significant even in 2D (up to ~100 − 150Pa). Compressive stress is primarily accumulated (1) within a core region of migrating cell clusters during their movement through the dense environment and (2) during the collisions of migrating cell clusters caused by uncorrelated motility. Shear stress can be significant within perturbed boundary layers around migrating clusters. Cells are more sensitive to the action of shear stress compared with compressive stress. Shear stress of a fewPasignificantly influences cell state. Deeper insight into cell strategy to minimize undesirable shear stress is a priority in order to understand various biological processes such as morphogenesis, wound healing and cancer invasion. We pointed out to cause-consequence relations of these complex phenomena based on rheological modeling consideration in order to stimulate further experimental work.

Cell strategy should be connected with the type and distribution of adhesion contacts such as adherens junctions and tight junctions per migrating clusters in order to (1) reinforce the cluster structure perpendicular to the direction of cell migration and (2) ensure structural elasticity of cluster in the direction of migration. These conditions lead to the stiffness inhomogeneity per single migrating clusters. Cell strategy should also be related to the state of the perturbed boundary layer around the cluster in the context of its thickness and slip effects.

Statement of Significance

Collective cell migration induces a local generation of stress (normal and shear) significant even in 2D (up to100-150 Pa). Cells well tolerate compressive stress up to a fewkPa. However, shear stress of a fewPacan induce severe damage to vimentin and keratin intermediate filament networks during 1 h, while shear stress of ~60Pacan cause the inflammation in epithelial cells during 5.5 h. Deeper insight into cell strategy to minimize undesirable shear stress is a priority in order to understand various biological processes. Cell strategy should be connected with the type and distribution of adhesion contacts such as adherens junctions and tight junctions per migrating clusters and surrounding perturbed boundary layers.
ATM and PRDM9 Regulate SPO11-bound Recombination Intermediates During Meiosis
Authors: Paiano Jacob , Wu Wei , Yamada Shintaro , Sciascia Nicholas , Callen Elsa , Cotrim Ana Paola , Deshpande Rajashree A. , Maman Yaakov , Day Amanda , Paull Tanya T. , Nussenzweig André
Published: December 2019

Meiotic recombination is initiated by genome-wide SPO11-induced double-strand breaks (DSBs) that are processed by MRE11-mediated release of SPO11. The DSB is then resected and loaded with DMC1/RAD51 filaments that invade homologous chromosome templates. In most mammals, DSB locations (“hotspots”) are determined by the DNA sequence specificity of PRDM9. Here, we demonstrate the first direct detection of meiotic DSBs and resection in vertebrates by performing END-seq on mouse spermatocytes using low sample input. We find that DMC1 limits both the minimum and maximum lengths of resected DNA, whereas 53BP1, BRCA1 and EXO1 play surprisingly minimal roles in meiotic resection. Through enzymatic modifications to the END-seq protocol that mimic thein vivoprocessing of SPO11, we identify a novel meiotic recombination intermediate (“SPO11-RI”) present at all hotspots. The SPO11-bound intermediate is dependent on PRDM9 and caps the 3’ resected end during engagement with the homologous template. We propose that SPO11-RI is generated because chromatin-bound PRDM9 asymmetrically blocks MRE11 from releasing SPO11. InAtm−/−spermatocytes, SPO11-RI is reduced while unresected DNA-bound SPO11 accumulate because of defective MRE11 initiation. Thus in addition to their global roles in governing SPO11 breakage, ATM and PRDM9 are critical local regulators of mammalian SPO11 processing.