bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with developing vaginal dryness symptoms in women transitioning through menopause: a longitudinal study
Authors: Waetjen L. Elaine , Crawford Sybil L. , Chang Po-Yin , Reed Barbara D. , Hess Rachel , Avis Nancy E. , Harlow Sioban D. , Greendale Gail A. , Dugan Sheila A. , Gold Ellen B.
Published: June 2018

Objective:

To evaluate factors associated with incident self-reported vaginal dryness and the consequences of this symptom across the menopausal transition in a multiracial/ethnic cohort of community-dwelling women.

Methods:

We analyzed questionnaire and biomarker data from baseline and 13 approximately annual visits over 17 years (1996-2013) from 2,435 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used discrete-time Cox proportional-hazards regression to identify predictors of incident vaginal dryness and to evaluate vaginal dryness as a predictor of pain during intercourse and changes in sexual intercourse frequency.

Results:

The prevalence of vaginal dryness increased from 19.4% among all women at baseline (ages 42-53 years) to 34.0% at the 13th visit (ages 57-69 years). Advancing menopausal stage, surgical menopause, anxiety, and being married were positively associated with developing vaginal dryness, regardless of partnered sexual activity. For women not using hormone therapy, higher concurrent levels of endogenous estradiol were inversely associated (multivariable-adjusted hazard ratio: 0.94 per 0.5 standard deviation increase, 95% confidence interval: 0.91-0.98). Concurrent testosterone levels, concurrent dehydroepiandrosterone sulfate levels, and longitudinal change in any reproductive hormone were not associated with developing vaginal dryness. Both vaginal dryness and lubricant use were associated with subsequent reporting of pain during intercourse, but not with a decline in intercourse frequency.

Conclusion:

In these longitudinal analyses, our data support many clinical observations about the relationship between vaginal dryness, menopause, and pain during intercourse, and suggest that reporting of vaginal dryness is not related to androgen level or sexual intercourse frequency.
Outcomes and Complications of Ahmed Tube Implantation in Asian Eyes
Authors: Choo Jessica Q.H. , Chen Z.D. , Koh Victor , Liang Shen , Aquino Cecilia M. , Sng Chelvin , Chew Paul
Published: June 2018

Purpose:

There is a lack of long-term Asian studies on the efficacy and safety of Ahmed glaucoma valve (AGV) implantation. This study seeks to determine the outcomes and complications of AGV implantation in Asians.

Methods:

A retrospective review of AGV surgeries performed at a single center in Singapore was conducted. A total of 76 patients with primary and secondary glaucoma who underwent their first AGV surgery from January 1, 2010 to December 31, 2012 were considered for our study. Primary outcomes evaluated were as follows: failure, intraocular pressure, best-corrected visual acuity, number of intraocular pressure (IOP)-lowering medications, and complications. Failure was defined by the following: IOP >21 mm Hg on 2 consecutive visits after 3 months, IOP≤5 mm Hg on 2 consecutive visits after 3 months, reoperation for glaucoma, removal of implant, or loss of light perception vision.

Results:

Mean follow-up duration was 33.2±6.9 months. There was significant reduction in IOP (mean reduction, 25.9%; P<0.001) and number of IOP-lowering medications (mean reduction, 77.8%; P<0.001) at 3 years. Absolute failure rate was 23.9% at 3 years with no difference between eyes with or without previous trabeculectomy and between eyes with primary or secondary glaucoma. Occurrence of postoperative hyphema was a significant risk factor for failure. The commonest postoperative complications were hyphema and tube exposure.

Conclusions:

At 3 years after AGV surgery in Asian eyes, less than one-quarter of the eyes fulfilled the criteria for surgical failure.
Reduction of Intraocular Pressure by Additional Trabeculotomy Ab Externo in Eyes With Primary Open-angle Glaucoma
Authors: Otsu Yayoi , Matsuoka Masato , Koshibu Kayo , Miwa Kayako , Kuro Maki , Minamino Keizo , Takahashi Kanji , Nishimura Tetsuya
Published: June 2018

Purpose:

The purpose of this study was to determine whether a second trabeculotomy (LOT) can reduce the intraocular pressure (IOP) in eyes with primary open-angle glaucoma (POAG) that had undergone an unsuccessful LOT as the initial surgery.

Patients and Methods:

LOT ab externo was performed as a second surgery on 37 eyes of 34 POAG patients who had undergone an unsuccessful LOT as the initial surgery. The main outcome measure was the postoperative IOPs, and surgical failures were defined as eyes with a post-LOT IOP>20 mm Hg. The eyes were divided into 3 groups; those that underwent LOT as both the initial and additional surgery (L-L group), those that underwent LOT as the initial surgery and combined LOT and cataract surgery (cLOT-IOL) as the additional surgery (L-cL group), and those that underwent cLOT-IOL as the initial surgery and LOT as the additional surgery (cL-L group).

Results:

The IOP was reduced after the additional LOT at postoperative 24 months in the L-L group from 20.0±3.0 mm Hg to 15.3±2.6 mm Hg (P<0.001), the L-cL group from 19.8±1.6 mm Hg to 15.8±3.2 mm Hg (P=0.029), and the cL-L group from 20.1±2.7 mm Hg to 15.5±2.3 mm Hg (P=0.014). There were no differences in the preoperative and postoperative IOPs between the initial-operated and additional-operated eyes. The success rates were improved by the additional surgery in the L-L group (P<0.001) and the L-cL group (P=0.029), but the rate was worsened in the cL-L group (P<0.001).

Conclusions:

These results indicate that LOT is a reasonable choice as an additional glaucoma surgery after failure of an initial LOT.
Donor-derived infections, lessons learnt from the past, and what is the future going to bring us
Authors: Grossi Paolo Antonio
Published: June 2018

Purpose of review

Donor-derived transmission of infectious diseases is a well-recognized complication of solid organ transplantation (SOT). Most donor-derived disease transmissions are expected. Although uncommon, unexpected donor-derived infections can be associated with significant morbidity and mortality, and as the volume of patients undergoing SOT increases, the number of infections transmitted through organ donation can also be expected to rise. The growing gap between the number of patients waiting for transplantation and available organs continue in fact to be the number one issue facing the transplant community. As a consequence the major focus in organ transplantation has been developing strategies to increase the available organs, including the use of organs from donors with infections or risky behaviors that have disqualified them from the donation in the past.

Recent findings

In addition to the commonly reported donor-derived transmissions, an increasing number of studies have reported unusual infections transmitted by SOT.

Transplant surgeons and physicians should increase their awareness toward uncommon donor-derived infections including them in the differential diagnosis of unusual clinical pictures in their recipients.
Infant Feeding Practices and the Effect in Reducing Functional Constipation 6 Years Later
Authors: Sangalli Caroline Nicola , Leffa Paula dos Santos , de Morais Mauro Batista , Vitolo Márcia Regina
Published: June 2018

Objective:

The aim of this study is to assess the impact of health worker training on infant feeding practices on the prevalence of functional constipation (FC) among children at 6 years of age.

Methods:

Cluster randomized field trial conducted in Porto Alegre, Brazil. Health centers were randomly allocated into intervention (n = 9) or control (n = 11) groups. In intervention sites, health workers joined training sessions on the “Ten Steps for Healthy Feeding for Children from Birth to Two Years of age”. Pregnant women in the last trimester of both groups were identified, invited to participate and enrolled in the study as the potential mothers to receive the dietary counseling provided by the health workers. At 6 years of age, the prevalence of FC was evaluated based on Rome III, defined by 2 or more of the following: infrequent defecation, fecal incontinence, history of retentive posturing, or/and history of painful defecation.

Results:

Among 387 mother‐child pairs (206 intervention, 181 control) evaluated at 6 years of age, the prevalence of FC was lower in the intervention group compared with the control group (15.0% vs 23.9%, respectively). The probability of being constipated was 38% lower in the intervention group (PR = 0.62; 95% CI 0.44–0.87; P < 0.01).

Conclusion:

The health workers training to promote the “Ten Steps” was an effective way to reduce the prevalence of constipation among children at 6 years of age.
Going Along With It
Authors: Miller Alaina R. , Fenstermacher Kimberly , Buchko Barbara L.
Published: June 2018

Background and Purpose:

Donor human milk (DHM) is used when a mother's own milk is not available. Donor human milk is available as a frozen pasteurized or commercially sterilized product. An abrupt change in practice in use of donor milk products raised concerns among nurses caring for infants in the neonatal intensive care unit (NICU). The change in practice occurred without the input of nurses and without the sharing of supportive evidence with them. The purpose of this study was to explore NICU nurses' perceptions of the practice change from using frozen pasteurized DHM to using sterilized DHM in this context.

Study Design and Methods:

A grounded theory study was conducted in a 38-bed Level III NICU. Nurse participants were interviewed using open-ended questions aimed at eliciting their perceptions of using pasteurized and sterilized DHM.

Results:

There were nine nurse participants. They described their perceptions of feeling confident about pasteurized DHM to feeling uncertain about sterilized DHM. The core category of going along with it was linked to judging DHM based upon attributes, questioning benefits of sterilized DHM, and preferring past practice of using pasteurized DHM. Nurses noted that they could move from feeling uncertain about the practice change to feeling certain if they had evidence to support the practice change. Barriers to seeking evidence were time, knowledge, and waiting for someone else to do it.

Clinical Implications:

Practice change without interprofessional collaboration is threatened by uncertainty and lack of support for the new practice. Nurses want to give evidence-based care, but they often face barriers to seeking evidence. Removing barriers to evidence-based practice and including nurses as stakeholders in practice change decisions are suggested.
Comparative Pathologic Analysis of Breast Cancers Classified as HER2/neu-Amplified by FISH Using a Standard HER2/CEP17 Dual Probe and an Alternative Chromosome 17 Control Probe
Authors: Zare Somaye , Lin Leo , Alghamdi Abrar G. , Daehne Svenja , Roma Andres A. , Hasteh Farnaz , Dell’Aquila Marie , Fadare Oluwole
Published: June 2018

At our institution, breast cancer cases that generate an equivocal HER2/neu (HER2) result by fluorescence in situ hybridization (FISH) using the dual HER2/chromosome enumeration probe (CEP17) are reflexed to an assay that utilizes an alternative control probe (lissencephaly gene1 [LIS1] [17p13.3]/retinoic acid receptor α [RARA] [17q21.2]). This study examines whether cancers that are classified as HER2-amplified with an alternate probe are clinicopathologically similar to those that are classified as such using the HER2/CEP17 probe. Reports for 1201 breast cancers were reviewed, and clinicopathologic findings were compared between HER2/CEP17-equivocal cases that became HER2-amplified using the alternate probe (group A: n=48), HER2-amplified cases using the HER2/CEP17 probe (group B: n=169), and HER2-nonamplified cases using the HER2/CEP17 probe (group C: n=910). Of 1201 cases tested using the HER2/CEP17 probe, 169 (14%) were HER2-amplified, 122 (10%) were equivocal, and 910 (76%) were nonamplified. Additional testing with the alternative probe on the 122 equivocal cases reclassified 48 (39%) of them to HER2-amplified, and such cases comprised 22% of all HER2-amplified tumors. A higher proportion of tumors with HER2 copy number between 5.0 and 5.9 became positive upon additional testing when compared with those with a priori HER2 copy numbers between 4.0 and 4.9 (P=0.0362). Group A cases, compared with group B cases, were more frequently positive for estrogen receptor (97.91% vs. 72.18%, P<0.0001) and progesterone receptor (85.41% vs. 59.17%, P=0.0009). Most group A cases (71%) were HER2 equivocal (score 2+) by immunohistochemistry, whereas most group B cases (60%) were positive (score 3+). Groups A and B showed no significant differences regarding patient age, lymph node status, tumor grade, histotype, and stage distribution. In summary, among our HER2-amplified cohort of breast cancers, alternative probe-detected cases were more frequently estrogen receptor and progesterone receptor positive than HER2/CEP17-detected cases, and were more frequently discordant with HER2 immunohistochemistry results. These findings raise the possibility of underlying biologic differences between these 2 groups, which warrants further study. However, the tumors were largely comparable regarding all other clinicopathologic variables. As it is unknown whether HER2-targeted therapy is truly beneficial in this subgroup of patients, future clinical trials should specifically evaluate this subset.
Safety and Efficacy of IV Lidocaine in the Treatment of Children and Adolescents With Status Migraine*
Authors: Ayulo Marco Antonio , Phillips Keri Ellen , Tripathi Sandeep
Published: June 2018

Objectives:

To evaluate the safety and efficacy of IV lidocaine in treating children and adolescents with status migraine.

Design:

Retrospective observational study.

Setting:

Single center PICU.

Patients:

Children and adolescents admitted with status migraine.

Intervention:

IV lidocaine.

Measurement and Main Results:

Thirty-three lidocaine infusions were administered to 28 patients with status migraine. Two patients were excluded from analysis, leaving 31 infusions administered to 26 patients for analysis. Patients’ ages ranged from 10 to 19 years with an average of 14.9 ± 2.4 years. Mean duration of hospitalization was 4.6 ± 1.5 days. Lidocaine was administered as a bolus (2.9 ± 0.18 mg/kg) in 80.6% (95% CI, 63.7–90.8%) of the patients, followed by an infusion, which was started at a mean rate of 1.29 ± 0.2 mg/kg/hr with mean maximum dose of 1.56 ± 0.27 mg/kg/hr. The highest lidocaine drip was 2.25 mg/kg/hr and lowest 1.125 mg/kg/hr. Lidocaine was interrupted in one patient secondary to side effects: chest pain and anxiety. On average, it took 16.3 ± 12.9 hours for 50% reduction in pain scores (range, 1.3–40.4 hr) and 19.3 ± 19.3 hours for complete resolution (0.8–72.1). 90.3% of cases (95% CI, 75.1–96.6%) experienced pain resolution with 51.6% (95% CI, 34.8–68%) encountering a relapse of pain. Mean pain scores at the time of discharge were 1 ± 1.6 (median, 0). Both mean reported highest and lowest scores dropped over the course of the 5 days from 5.1 ± 1.9 and 2.1 ± 2.4 on day 1 to 1.0 ± 1.4 and 0 on day 5 of therapy. One-way analysis by analysis of variance for high pain score by day was statistically significant with a p value of less than 0.01.

Conclusions:

In the appropriate patient population, IV lidocaine may be a safe and effective treatment for children and adolescents with status migraine. Larger prospective studies need to be done not only to evaluate safety and efficacy but also the analgesic longevity of IV lidocaine post discharge.
Strategies for Improving Hepatitis C Treatment Access in the United States: State Officials Address High Drug Prices, Stigma, and Building Treatment Capacity
Authors: Kapadia Shashi N. , Johnston Carrie D. , Marks Kristen M. , Schackman Bruce R. , Martin Erika G.
Published: June 2018

Context:

Curative treatments for hepatitis C virus (HCV) can alter the course of a devastating epidemic, but high drug prices have contributed to restrictions on HCV treatment access.

Objective:

We aimed to learn how state health agencies have responded to the challenges of treatment access for HCV.

Design:

Qualitative study using semistructured key informant interviews focused on aspects of HCV treatment access between June 2016 and March 2017. Content analysis was used to identify dominant themes.

Setting:

United States.

Participants:

Eighteen health officials and treatment advocates across 6 states selected using purposive sampling.

Results:

Drug pricing is the most important barrier to access, encouraging restrictive authorization criteria from payers that in turn discourage providers from offering treatment. However, payers have not experienced the budget impact that was initially feared. Although authorization criteria are being lifted for fee-for-service Medicaid programs, ensuring that managed care organizations follow suit remains a challenge. The effect of stigma, a shortage of treating providers, and lack of political motivation are additional challenges to expanding treatment. The response to the human immunodeficiency virus epidemic can augment or inform strategies for HCV treatment delivery, but this is limited by the absence of dedicated funding.

Conclusions:

While treatment eligibility criteria for HCV treatment are improving, many other barriers remain to achieving the scale-up needed to end the epidemic. Political disinterest, stigma, and a lack of specialty providers are continued barriers in some jurisdictions. States may need to invest in strategies to overcome these barriers, such as engaging in public and provider education and ensuring that treatment by primary care providers is reimbursed. Despite uncertainty about how federal policy changes to Medicaid may affect states' ability to respond, states can identify opportunities to improve access.
68Ga-PSMA-HBED-CC–Avid Synchronous Urinary Bladder Paraganglioma in a Patient With Metastatic Prostate Carcinoma
Authors: Parihar Ashwin Singh , Vadi Shelvin Kumar , Mittal Bhagwant Rai , Kumar Rajender , Bal Amanjit , Singh Shrawan Kumar
Published: June 2018

68Ga-PSMA-HBED-CC PET/CT has proven to be a useful modality in patients with prostate carcinoma, especially in those with suspected recurrence and in detection of locoregional and distant metastases. However, with expanding use of this tracer, several recent reports of in vivo expression of PSMA in nonprostatic benign and malignant entities have been published. We report a patient with PSMA-avid synchronous urinary bladder paraganglioma and metastatic prostate carcinoma.
Optimal Timing of Alveolar Cleft Bone Grafting for Maxillary Clefts in the Cleft Palate Population
Authors: Kaura Arminder S. , Srinivasa Dhivya R. , Kasten Steven J.
Published: June 2018

Purpose:

Timing of bone grafting for maxillary alveolar clefts is not standardized. Secondary bone grafting is often performed; however, consensus does not exist regarding use of chronologic versus dental age to guide treatment. Several authors suggest an early chronologic age is associated with greater success. Available literature was systematically reviewed for evidence for optimal timing for grafting maxillary alveolar clefts.

Methods:

PubMed, MEDLINE, and Cochrane Central Registrar of Controlled Trials databases were queried for manuscripts pertaining to maxillary alveolar cleft bone grafting. Inclusion criteria included manuscripts with level of evidence 4 or greater. Studies not using bone graft, lacking postoperative follow up, and clinical reports were excluded. Seventeen articles met criteria.

Results:

Nine manuscripts recommended grafting based on dental age prior to eruption of the permanent canines, while 8 recommended grafting between ages 7 to 12. The most commonly reported complication was wound dehiscence, followed by graft-site infection. Ten studies used perioperative treatment protocols, 8 of which included preoperative and/or postoperative orthodontia for maxillary expansion. Correlation between chronologic age and success was not significant, but trended towards greater success with increasing age.

Conclusion:

Success of secondary grafting is high, but significant variability exists in the timing of grafting. Evidence is lacking to support specific chronologic age; rather, perioperative protocols, systematic surgical technique, and a multidisciplinary discussion are likely more substantial in achieving success, and may be confounders in studies where an early age at grafting appears associated with success. The timing of bone grafting for maxillary alveolar clefts would benefit from a prospective randomized study.
The U-Shaped Maxillary Osteotomy: A Novel Resource for the Treatment of the Middle Third Facial Hypoplasia
Authors: Malagón Héctor O. , Ayala-Ugalde Fernan-Alejandra , García-Cano Eugenio , Chang-Contreras Jorge-Eduardo
Published: June 2018

The purpose of orthognathic surgery procedures is to manipulate the elements of the facial skeleton to reestablish normal anatomy and function. These elements could be repositioned with the technique known as Le Fort I osteotomy. This technique can be modified to be adapted on each patient, depending on the anomaly presented and the planned objective. The versatility, offered by the modifications of the Le Fort I osteotomy, has taken us to design one that allows the capability to correct the malar region hypoplasia in the same surgical procedure. A total of 9 patients were included with malocclusion as indication for orthognathic surgery who also presented with malar hypoplasia diagnosed clinically and cephalometrically. A modified technique, the “U”-shaped maxillary osteotomy, was performed with excellent functional and aesthetics results, and none of the patients presented complications associated directly to the maxillary osteotomy. Some patients with maxillary zygomatic deficiency combined with malocclusion continue to present a special challenge to clinicians treating these deformities. This technique is useful in improving zygomatic projection in bloc with the Le Fort I advancement without the need to place a bone graft and the advantage of rigid fixation along with the one used in the Le Fort I osteotomy. The U-shaped maxillary osteotomy is a safe, trustworthy, and reproducible technique that allows the resolution of the maxillomalar hypoplasia in a single surgical time, providing satisfactory aesthetic results. Any surgeon with adequate training in orthognathic or craniofacial surgery could perform it and incorporate it to his technical armamentarium.
Van der Woude and Popliteal Pterygium Syndromes
Authors: Bennun Ricardo D. , Stefano Eduardo , Moggi Luis E.
Published: June 2018

Van der Woude syndrome is the most generic form of syndromic orofacial cleft, present in approximately 2% of all cleft patients. The lower lip pits with or without cleft lip and/or palate is typical of this syndrome. Popliteal pterygium syndrome (PPS), also known as popliteal web syndrome or fasciogenito-popliteal syndrome, was first described by Trelat in 1869, the incidence is approximately 1 in 300,000 live births. The term PPS was coined by Gorlin et al in 1968 based on the most unusual anomaly, the popliteal pterygium. Popliteal pterygium syndrome shares features with van der Woude syndrome but, in addition, is characterized by genital anomalies, syndactyly of fingers and toes, and toenail dysplasia. In some patients, oral or eyelid synechiae are present. Van der Woude syndrome and PPS are autosomal dominantly inherited disorders caused by heterozygous mutations in IRF6.

Objective:

To report the familial nature of the disease in the mother and son, and to summarize the clinical characteristics, treatment, and outcomes in both patients.
Mandibular Reconstruction for Pediatric Patients
Authors: Castellon Loreto , Jerez Daniel , Mayorga Jaime , Gallego Alejandra , Fuenzalida Carlos , Laissle German
Published: June 2018

Mandibular reconstruction in pediatric patients is controversial. The scant pediatric experience and the infrequent occurrence of this type of pathology in children complicate therapeutic decisions. The literature contains different treatment protocols and describes the bone graft alternatives to be used.

Materials and Method:

This is a retrospective review of patients under the age of 15 who were subjected to resection and reconstruction.

Results:

A total of 18 patients were included in the study: 8 women and 10 men. The age on the date of diagnosis ranged from 2 years to 13 years and the average was 7 years. Five patients underwent resective surgery for a malign pathology, 7 for a benign pathology, 4 for aggressive lesions of odontogenic origin, and 1for the effects of a fracture that was complicated by osteomyelitis.

Conclusions:

In conclusion, treating pediatric patients with tumor pathology requires an experience pediatric team to get good outcomes. Surgeons must consider that pediatric patients are in constant growth and development but that must not be an issue in resection and reconstruction decisions. Literature review shows that, as in adults, free flaps seem to be the criterion standard for big resections in mandibles defects, and are safe to use in pediatric patients.
Le Fort II Osteotomy and Modified Technique Presentation
Authors: Malagón-Hidalgo Héctor-Omar , Vilchis-López Roberto , González-Chapa Diego-Raúl , Silva-Suárez Richael-Antonio , García-Cano Eugenio , Lastiri-Barrios José-Luis , González-Magaña Fernando
Published: June 2018

Introduction:

The LeFort II osteotomy has a specific number of indications, thus this is true, there is less experience with the technique. The authors present a modification to the technique and extensive step-by-step procedure explanation in order to share their experience for making a safe surgery.

Material and Methods:

A clinical report is presented of a nonsyndromatic patient with nasomaxillary hypoplasia, in which the authors make an LeFort II osteotomy with circumvestibular, transcaruncular, and “W”-shaped approaches, with minimal scar showing, in order to offer better aesthetic outcomes as well as functional and skeletal.

Results:

Patient presenting with an optimal postoperative clinical and skeletal results. Cephalometic measurments in normal ranges. Obtaining during the process of the surgery, description the surgery, and potential complications.

Conclusion:

Using the Le Fort II osteotomy in nonsyndromic nasomaxillary hypoplasia is a helpful and left away technique, because of its complexity. The authors give a step-by-step detailed description of the surgical technique with perioperative management. In summary, the steps provided give unique information about this reproducible and aesthetic technique.
Surgical-Based Classification for Microtia
Authors: Campo Armando Apellaniz , Victor-Baldin André , Contreras-Mérida Sara M.
Published: June 2018

The known classifications for microtia have been cumbersome and difficult to apply in daily consultation. The lack of a progressive surgical behavior according to each degree of affection also contributes to confusion and in a lower success rate in clinical application. The authors propose a progressive surgical classification that takes into consideration the principal anatomical defect and the corresponding correction with modern techniques, having eliminated from previous classifications, those elements that are now considered deformations of the ear, capable of conservative treatment in early stages of life.
First-year Analysis of the Operating Room Black Box Study
Authors: Jung James J. , Jüni Peter , Lebovic Gerald , Grantcharov Teodor
Published: June 2018

Objective:

To characterize intraoperative errors, events, and distractions, and measure technical skills of surgeons in minimally invasive surgery practice.

Background:

Adverse events in the operating room (OR) are common contributors of morbidity and mortality in surgical patients. Adverse events often occur due to deviations in performance and environmental factors. Although comprehensive intraoperative data analysis and transparent disclosure have been advocated to better understand how to improve surgical safety, they have rarely been done.

Methods:

We conducted a prospective cohort study in 132 consecutive patients undergoing elective laparoscopic general surgery at an academic hospital during the first year after the definite implementation of a multiport data capture system called the OR Black Box to identify intraoperative errors, events, and distractions. Expert analysts characterized intraoperative distractions, errors, and events, and measured trainee involvement as main operator. Technical skills were compared, crude and risk-adjusted, among the attending surgeon and trainees.

Results:

Auditory distractions occurred a median of 138 times per case [interquartile range (IQR) 96–190]. At least 1 cognitive distraction appeared in 84 cases (64%). Medians of 20 errors (IQR 14–36) and 8 events (IQR 4–12) were identified per case. Both errors and events occurred often in dissection and reconstruction phases of operation. Technical skills of residents were lower than those of the attending surgeon (P = 0.015).

Conclusions:

During elective laparoscopic operations, frequent intraoperative errors and events, variation in surgeons’ technical skills, and a high amount of environmental distractions were identified using the OR Black Box.
The Evolution of Kidney Transplantation Surgery Into the Robotic Era and Its Prospects for Obese Recipients
Authors: Hameed Ahmer M. , Yao Jinna , Allen Richard D.M , Hawthorne Wayne J. , Pleass Henry C. , Lau Howard
Published: June 2018

Robotic-assisted kidney transplantation (RAKT) represents the most recent innovation in the evolution of kidney transplantation surgery. Vascular techniques enabling kidney transplantation have existed since the early 20th century and contributed to the first successful open kidney transplant procedure in 1954. Technical advances have since facilitated minimally invasive laparoscopic and robotic techniques in live-donor surgery, and subsequently for the recipient procedure. This review follows the development of surgical techniques for kidney transplantation, with a special focus on the advent of robotic-assisted transplantation because of its potential to facilitate transplantation of those deemed previously too obese to transplant by standard means. The different techniques, indications, advantages, disadvantages, and future directions of this approach will be explored in detail. Robot-assisted kidney transplantation may become the preferred means of transplanting morbidly obese recipients, although its availability to such recipients remains extremely limited and strategies targeting weight loss pretransplantation should never be abandoned in favor of a “RAKT-first” approach.
Aripiprazole in a Patient of PLA2G6-Associated Neurodegeneration With Psychosis
Authors: Huang Mao-Hsuan , Chiu Yu-Chuan , Tsai Chia-Fen
Published: June 2018

PLA2G6-associated neurodegeneration is a major subtype of neurodegeneration with brain iron accumulation. Patients with PLA2G6-associated neurodegeneration usually present degenerative motor symptoms with neuropsychiatric disturbance. This report presents a patient withPLA2G6-related dystonia-parkinsonism, who had neuropsychiatric symptoms preceding movement symptoms. Antipsychotic drug was prescribed, and he developed parkinsonism years later. Differential diagnosis between drug-induced parkinsonism andPLA2G6-related dystonia-parkinsonism could be challenging. PLA2G6 sequencing has to be considered facing a patient with adulthood parkinsonism, especially when it is associated with initial psychiatric symptoms. Our case highlights a common problem treating psychiatric symptoms in neurodegenerative diseases that lead to parkinsonism. The use of antipsychotics requires a special caution in these patients because it may cause extrapyramidal symptoms. Aripiprazole had therapeutic effect on both mood and psychotic symptoms and less impact on motor features, which may be considered an ideal pharmacological approach in treating these patients.
Auditory Brainstem Pathology in Autism Spectrum Disorder: A Review
Authors: Pillion Joseph P. , Boatman-Reich Dana , Gordon Barry
Published: June 2018

Atypical responses to sound are common in individuals with autism spectrum disorder (ASD), and growing evidence suggests an underlying auditory brainstem pathology. This review of the literature provides a comprehensive account of the structural and functional evidence for auditory brainstem abnormalities in ASD. The studies reviewed were published between 1975 and 2016 and were sourced from multiple online databases. Indices of both the quantity and quality of the studies reviewed are considered. Findings show converging evidence for auditory brainstem pathology in ASD, although the specific functions and anatomical structures involved remain equivocal. Two main trends emerge from the literature: (1) abnormalities occur mainly at higher levels of the auditory brainstem, according to structural imaging and electrophysiology studies; and (2) brainstem abnormalities appear to be more common in younger than older children with ASD. These findings suggest delayed maturation of neural transmission pathways between lower and higher levels of the brainstem and are consistent with the auditory disorders commonly observed in ASD, including atypical sound sensitivity, poor sound localization, and difficulty listening in background noise. Limitations of existing studies are discussed, and recommendations for future research are offered.
Collision and annihilation of nonlinear sound waves and action potentials in interfaces
Authors: Shrivastava Shamit , Kang Kevin H. , Schneider Matthias F.
Published: June 2018

Nerve impulses, previously proposed as manifestations of nonlinear acoustic pulses localized at the plasma membrane, can annihilate upon collision. However, whether annihilation of acoustic waves at interfaces takes place is unclear. We previously showed the propagation of nonlinear sound waves that propagate as solitary waves above a threshold (super-threshold) excitation in a lipid monolayer near a phase transition. Here we investigate the interaction of these waves. Sound waves were excited mechanically via a piezo cantilever in a lipid monolayer at the air–water interface and their amplitude is reported before and after a collision. The compression amplitude was observed via Förster resonance energy transfer between donor and acceptor dyes, measured at fixed points along the propagation path in the lipid monolayer. We provide direct experimental evidence for the annihilation of two super-threshold interfacial pulses upon head-on collision in a lipid monolayer and conclude that sound waves propagating in a lipid interface can interact linearly, nonlinearly, or annihilate upon collision depending on the state of the system. Thus we show that the main characteristics of nerve impulses, i.e. solitary character, velocity, couplings, all-or-none behaviour, threshold and even annihilation are also demonstrated by nonlinear sound waves in a lipid monolayer, where they follow directly from the thermodynamic principles applied to an interface. As these principles are equally unavoidable in a nerve membrane, our observations strongly suggest that the underlying physical basis of action potentials and the observed nonlinear-pules is identical.
Multiple optimal phenotypes overcome redox and glycolytic intermediate metabolite imbalances inEscherichia coli pgiknockout evolutions
Authors: McCloskey Douglas , Xu Sibei , Sandberg Troy E. , Brunk Elizabeth , Hefner Ying , Szubin Richard , Feist Adam M. , Palsson Bernhard O.
Published: June 2018

A mechanistic understanding of how new phenotypes develop to overcome the loss of a gene product provides valuable insight on both the metabolic and regulatory function of the lost gene. Thepgigene, whose product catalyzes the second step in glycolysis, was deleted in a growth optimizedEscherichia coliK-12 MG1655 strain. The knock-out (KO) strain exhibited an 80% drop in growth rate, that was largely recovered in eight replicate, but phenotypically distinct, cultures after undergoing adaptive laboratory evolution (ALE). Multi omic data sets showed that the loss ofpgisubstantially shifted pathway usage leading to a redox and sugar phosphate stress response. These stress responses were overcome by unique combinations of innovative mutations selected for by ALE. Thus, we show the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after loss of a major gene product.

Importance

A mechanistic understanding of how new phenotypes develop to overcome the loss of a gene product provides valuable insight on both the metabolic and regulatory function of the lost gene. Thepgigene, whose product catalyzes the second step in glycolysis, was deleted in a growth optimizedEscherichia coliK-12 MG1655 strain. Eight replicate adaptive laboratory evolution (ALE) resulted in eight phenotypically distinct endpoints that were able to overcome the gene loss. Utilizing multi-omics analysis, we show the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after loss of a major gene product.
Th17/regulatory T cells balance is predictive ofCoccidioidesinfection outcome in pediatric patients
Authors: Davini Dan , Naeem Fouzia , Phong Aron , Al-Kuhlani Mufadhal , Valentine Kristen M. , McCarty James , Ojcius David M. , Gravano David M. , Hoyer Katrina K.
Published: June 2018

Background

Protective immunity against the fungal pathogen Coccidioides requires specific T helper responses. Mouse vaccine and infection studies have defined CD4+T helper (Th)1 and Th17 cells in the resolution of infection and in effective protection. Patients with persistentCoccidioidesinfection demonstrate reduced cellular responses.

Methods

Peripheral blood and serum were collected from 30 pediatricCoccidioides-infected patients and 20 healthy controls in the California San Joaquin Valley. Samples were evaluated by flow cytometry for innate and adaptive immune populations and cytokines to define the early immune response and identify clinically useful biomarkers for predicting disease outcome. Clinical and flow data were evaluated according to disease outcome (resolved or persistent) using principal component analysis, high-dimensional flow cytometry analysis tools, chi-square automatic interaction detection, and individual cell population comparisons.

Results

Patients with persistent infection had lower Th17 and higher Treg frequencies, but similar Th1 responses, relative to patients that resolved disease. Treg frequency, eosinophil numbers and neutrophil numbers together distinguish patients that resolve infection from those that develop persistent infection.

Conclusions

The inability to resolveCoccidioidesinfection may be a result of elevated Treg frequency and functional capacity, and Treg frequency may predict patient disease outcome at diagnosis. In our study, Th1 responses were similar in persistent and resolved infection, in contrast to prior human studies. Instead, our data suggest that Th17 cells provide an effective protection duringCoccidioidesinfection, and that elevated Treg frequency inhibits protective immunity.
Linear stability analysis of morphodynamics during tissue regeneration in plants
Authors: Reijne Anne-Mieke , Pruessner Gunnar , Sena Giovanni
Published: June 2018

One of the key characteristics of multicellular organisms is the ability to establish and maintain shapes, or morphologies, under a variety of physical and chemical perturbations. A quantitative description of the underlying morphological dynamics is a critical step to fully understand the self-organising properties of multicellular systems. Although many powerful mathematical tools have been developed to analyse stochastic dynamics, rarely these are applied to experimental developmental biology.

Here, we take root tip regeneration in the plant model system Arabidopsis thaliana as an example of robust morphogenesis in living tissue, and present a novel approach to quantify and model the relaxation of the system to its unperturbed morphology. By generating and analysing time-lapse series of regenerating root tips captured with confocal microscopy, we are able to extract and model the dynamics of key morphological traits at cellular resolution. We present a linear stability analysis of its Markovian dynamics, with the stationary state representing the intact root in the space of morphological traits. We find that the resulting eigenvalues can be classified into two groups, suggesting the co-existence of two distinct temporal scales during the process of regeneration.

We discuss the possible biological implications of our specific results, and suggest future experiments to further probe the self-organising properties of living tissue.
Statistical loadings and latent significance simplify and improve interpretation of multivariate projection models
Authors: Jonsson Pär , Björkblom Benny , Chorell Elin , Olsson Tommy , Antti Henrik
Published: June 2018

Multivariate projection methods are unique in being both multivariable by combining many variables into stronger predictive features (latent variables), and multivariate for being able to model systematic variation both related and orthogonal to an observed response. Orthogonal partial least squares (OPLS) is a versatile multivariate projection method for analysis of correlation, discrimination and effect changes. However, currently OPLS is not fully using its multivariate potential since orthogonal systematic variation is not considered in model interpretation, resulting in univariate interpretation of variable significance. We present a strategy for improved interpretation of OPLS models based upon a post-hoc linear regression analysis that can be used with or without the orthogonal OPLS score(s) as a covariate to make the interpretation multivariate or univariate respectively. By selecting the observed response y or estimated response yhat as a one of the factors in the linear regression the results are related to either of the OPLS loadings w or p. Furthermore, converting the OPLS loading values to statistical t-values creates a direct link to statistical significance. Finally, by applying three different Boolean loadings W, P and W∧P variable significance can be summarized based on three criteria. W and P reveal if the values in w or p respectively are outside the statistical limits with W∧P being the logical conjunction of W and P (significant if outside limits in both W and P). Two examples are used to verify the proposed strategy. First, a synthetic example, simulating a mix of mass spectra, and second a clinical metabolomics study of a dietary intervention. In the simulated example we show that multivariate interpretation gives higher accuracy for estimation of true differences, mainly due to higher true positive rate. Furthermore, we highlight how application of W∧P for summarizing variable significance leads to higher accuracy. For the metabolomics example, we show that a more detailed interpretation, i.e. larger number of significant metabolites of relevance, is obtained using the multivariate interpretation. In summary, the suggested strategy provides means for facilitated interpretation of OPLS models, beyond univariate statistics, and offers a multivariate tool for discovery of biomarker patterns, i.e. latent biomarkers.
Genome-wide association study of circadian rhythmicity in 71 500 UK Biobank participants and polygenic association with mood instability
Authors: Ferguson Amy , Lyall Laura M. , Ward Joey , Strawbridge Rona J. , Cullen Breda , Graham Nicholas , Niedzwiedz Claire L. , Johnston Keira J.A. , MacKay Daniel , Biello Stephany M. , Pell Jill P. , Cavanagh Jonathan , McIntosh Andrew M. , Doherty Aiden , Bailey Mark E.S. , Lyall Donald M. , Wyse Cathy A. , Smith Daniel J.
Published: June 2018

Background

Circadian rhythms are fundamental to health and are particularly important for mental wellbeing. Disrupted rhythms of rest and activity are recognised as risk factors for major depressive disorder and bipolar disorder.

Methods

We conducted a genome-wide association study (GWAS) of low relative amplitude (RA), an objective measure of circadian rhythmicity derived from the accelerometer data of 71 500 UK Biobank participants. Polygenic risk scores (PRS) for low RA were used to investigate potential associations with psychiatric phenotypes.

Outcomes

Two independent genetic loci were associated with low RA, within genomic regions for Neurofascin (NFASC) and Solute Carrier Family 25 Member 17 (SLC25A17). A secondary GWAS of RA as a continuous measure identified a locus within Meis Homeobox 1 (MEIS1). There were no significant genetic correlations between low RA and any of the psychiatric phenotypes assessed. However, PRS for low RA was significantly associated with mood instability across multiple PRS thresholds (at PRS threshold 0·05: OR=1·02, 95% CI=1·01-1·02, p=9·6×10−5), and with major depressive disorder (at PRS threshold 0·1: OR=1·03, 95% CI=1·01-1·05, p=0·025) and neuroticism (at PRS threshold 0·5: Beta=0·02, 95% CI=0·007-0·04, p=0·021).

Interpretation

Overall, our findings contribute new knowledge on the complex genetic architecture of circadian rhythmicity and suggest a putative biological link between disrupted circadian function and mood disorder phenotypes, particularly mood instability, but also major depressive disorder and neuroticism.
Parasitoid wasp venom elevates sorbitol and alters expression of metabolic genes in human kidney cells
Authors: Siebert Aisha L. , Doucette Luticha A. , Simpson-Haidaris PJ , Werren John H.
Published: June 2018

Venom from the parasitoid waspNasonia vitripennisdramatically elevates sorbitol levels in its natural fly hosts. In humans, sorbitol elevation is associated with complications of diabetes. Here we demonstrate that venom also induces this disease-relevant phenotype in human cells, and investigate possible pathways involved. Key findings are that (a) low doses ofNasoniavenom elevate sorbitol levels in human renal mesangial cells (HRMCs) without changing glucose or fructose levels; (b) venom is a much more potent inducer of sorbitol elevation than glucose; (c) low venom doses significantly alter expression of genes involved in sterol and alcohol metabolism, transcriptional regulation, and chemical/stimulus response; (d) although venom treatment does not alter expression of the key sorbitol pathway gene aldose reductase (AR); (e) venom elevates expression of a related gene implicated in diabetes complications (AKR1C3) as well as the fructose metabolic gene (GFPT2). Although elevated sorbitol is accepted as a major contributor to secondary complications of diabetes, the molecular mechanism of sorbitol regulation and its contribution to diabetes complications are not fully understood. Our findings suggest that genes other than AR could contribute to sorbitol regulation, and more broadly illustrate the potential of parasitoid venoms for medical application.