Source:Clinical Neurophysiology
Author(s): Jürgen Kayser
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Δευτέρα 2 Ιουλίου 2018
Craig Emery Tenke, 1950–2017
Source:Clinical Neurophysiology
Author(s): Jürgen Kayser
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Genome-Wide Association and Regional Heritability Mapping of Plant Architecture, Lodging and Productivity in Phaseolus vulgaris
The availability of high-density molecular markers in common bean has allowed to explore the genetic basis of important complex agronomic traits with increased resolution. Genome-Wide Association Studies (GWAS) and Regional Heritability Mapping (RHM) are two analytical approaches for the detection of genetic variants. We carried out GWAS and RHM for plant architecture, lodging and productivity across two important growing environments in Brazil in a germplasm of 188 common bean varieties using DArTseq genotyping strategies. The coefficient of determination of G x E interaction (c2int) was equal to 17, 21 and 41%, respectively for the traits architecture, lodging, and productivity. Trait heritabilities were estimated at 0.81 (architecture), 0.79 (lodging) and 0.43 (productivity), and total genomic heritability accounted for large proportions (72% to 100%) of trait heritability. At the same probability threshold, three marker-trait associations were detected using GWAS, while RHM detected eight QTLs encompassing 145 markers along five chromosomes. The proportion of genomic heritability explained by RHM was considerably higher (35.48 to 58.02) than that explained by GWAS (28.39 to 30.37). In general, RHM accounted for larger fractions of the additive genetic variance being captured by markers effects inside the defined regions. Nevertheless, a considerable proportion of the heritability is still missing (~42% to ~64%), probably due to LD between markers and genes and/or rare allele variants not sampled. RHM in autogamous species had the potential to identify larger-effect QTLs combining allelic variants that could be effectively incorporated into whole-genome prediction models and tracked through breeding generations using marker-assisted selection.
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Genomics-Assisted Identification and Characterization of the Genetic Variants Underlying Differential Nitrogen Use Efficiencies in Allotetraploid Rapeseed Genotypes
Nitrogen (N) is a non-mineral macronutrient essential for plant growth and development. Oilseed rape (AnAnCnCn, 2n=4x=38) has a high requirement for N nutrients whereas showing the lowest N use efficiency (NUE) among crops. The mechanisms underlying NUE regulation in Brassica napus remain unclear because of genome complexity. In this study, we performed high-depth and -coverage whole-genome re-sequencing (WGS) of an N-efficient (higher NUE) genotype "XY15" and an N-inefficient (lower NUE) genotype "814" of rapeseed. More than 687 million 150-bp paired-end reads were generated, which provided about 93% coverage and 50x depth of the rapeseed genome. Applying stringent parameters, we identified a total of 1,449,157 single-nucleotide polymorphisms (SNPs), 335,228 InDels, 175,602 structure variations (SVs) and 86,280 copy number variations (CNVs) between the N-efficient and -inefficient genotypes. The largest proportion of various DNA polymorphisms occurred in the inter-genic regions. Unlike CNVs, the SNP/InDel and SV polymorphisms showed variation bias of the An and Cn subgenomes, respectively. Gene ontology analysis showed the genetic variants were mapped onto the genes involving N compound transport and ATPase complex metabolism, but not including N assimilation-related genes. On basis of identification of N-starvation responsive genes through high-throughput expression profiling, we also mapped these variants onto some key NUE-regulating genes, and validated their significantly differential expression between the N-efficient and -inefficient genotypes through qRT-PCR assays. Our data provide genome-wide high resolution DNA variants underlying NUE divergence in allotetraploid rapeseed genotypes, which would expedite the effective identification and functional validation of key NUE-regulating genes through genomics-assisted improvement of crop nutrient efficiency.
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Prevalence and risk factors for helicobacter pylori infection in gastroduodenal diseases in Kano, Nigeria
African Journal of Medical and Health Sciences 2018 17(1):41-46
Background: Helicobacter pylori (H. pylori) has been well noted as a causative agent of many diseases in the gastrointestinal (GI) tract notably, gastritis, peptic ulcer disease, and gastric adenocarcinoma. Determining the burden and the risk factors for acquiring this infection may be crucial to containing it and its sequelae in Kano, Nigeria. Methodology: The study was cross-sectional in design. Questionnaires were administered in dyspeptic patients to obtain the relevant clinical, and sociodemographic data. Upper GI endoscopy was performed in the patients, and gastric biopsy specimens were taken and sent to the histopathology laboratory for assessment and H. pylori identification. Results: Of the 306 participants, 136 (44.4%) were males, while 170 (55.6%) were females, with male: female ratio of 1:1.3. The ages of the participants ranged from 18 to 84 years with a mean of 41.2 ± 15.3 years. Of the 306 samples, 250 (81.7%) were positive for H. pylori. This gives H. pylori prevalence of 81.7%. Only 4 (1.3%) of the participants belonged to the higher social class, out of which 25% had positive H. pylori, while 230 (75.2%) participants belonged to the lower socioeconomic class with 87.8% H. pylori prevalence. The lower social class had a significant association (P < 0.0001) with increased H. pylori infection. A total of 290 subjects (94.8%) shared a room with three or more other siblings in childhood, out of which 233 (80.3%) had H. pylori. Only 80 subjects (26.1%) used pipe-borne water in childhood, while 226 (73.9%) sourced their water from either well, pond or stream during childhood. Conclusion: This study showed a high prevalence of H. pylori in Kano, and low socioeconomic status, unclean water source, overcrowding, and cigarette smoking were significant risk factors for H. pylori infection.
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The effect of bacterial colonization of the embryo transfer catheter on Outcome of In vitro Fertilization–Embryo transfer treatment
African Journal of Medical and Health Sciences 2018 17(1):7-13
Background: In vitro fertilization–embryo transfer (IVF − ET) has become a core treatment method for managing infertility. Bacterial contamination of the ET catheter may affect outcome, but there is still no consensus of evidence. Objectives: This study aims to assess the effect of bacterial colonization of the ET catheter tip on the clinical pregnancy rate in an IVF–ET treatment. Methods: An analytical cross-sectional study among women undergoing IVF–ET treatment was undertaken. The patients selected had both cervical swab and the tip of the ET catheter cultured. The patients were grouped into positive (bacterial isolated) and negative (no bacterial isolated) based on the culture result. The clinical pregnancy rate (primary outcome) between the two groups was compared. Results: A total of 80 patients were selected. In 34 patients (42.25%), the cervical culture was positive, while 46 patients (57.50%) had negative cervical culture. Catheter tip culture was positive in 27 patients (33.75%) and negative in 53 patients (66.25%). The predominant microorganisms isolated were Escherichia coli (23.75%), Staphylococcus spp. (18.75%), and Streptococcus spp. (15.00%). The clinical pregnancy rate was 26.25%. The significant factors affecting clinical pregnancy were the age of the patient (P = 0.044), duration of infertility (P = 0.01), and culture result (P = 0.03). Conclusion: Bacterial colonization of the ET catheter tip is associated with a reduction in the clinical pregnancy rate. Utility of routine cervical swab; microscopy, culture, and sensitivity at recruitment of patients for IVF–ET treatment is highlighted.
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Nutritional status of perinatally HIV-infected children on antiretroviral therapy from a resource-poor rural South African community
African Journal of Medical and Health Sciences 2018 17(1):1-6
Objective: In Sub-Saharan Africa, millions of children are suffering from HIV and coexisting child undernutrition. Despite efforts to curb the spread of HIV through the availability of treatment and various nutritional programmes, it has been argued that undernutrition remains highly prevalent in rural areas. The objective of this study was to describe the prevalence and psychosocial factors influencing the nutritional status in the sample of rural-based HIV-infected children on antiretroviral therapy. Materials and Methods: Anthropometric and home environment data were collected from 152 perinatally HIV-infected children on antiretroviral therapy who lived with their primary caregivers in a rural Eastern Cape community. Results: More than half of the sample of children had inadequate nutritional status. The prevalence of stunting particularly was high (36.2%), while 12% were underweight and only 2.7% presented with wasting. Coexisting poor quality home-environment (P < 0.01) added to this burden. Younger age children who lived with a younger biological caregiver were found to present more with stunting than older age children (χ2 [n = 152] = 14.79, P = 0.005), but no significant differences were observed for underweight or wasting. Conclusion: It is important in a context such as South Africa, with the double burden of HIV infection and poverty, that all efforts be directed at alleviating undernutrition. Early pediatric HIV management should not only focus on the provision of treatment but should also prioritize the quality of care of HIV-positive children in the home to improve on their nutritional health.
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Prevalence and antibiogram pattern of Salmonella enterica serotypes in Garhwal Region: First report from foothills of himalayas
African Journal of Medical and Health Sciences 2018 17(1):14-19
Introduction: Enteric fever, caused by Salmonella enterica subsp. enterica serotype Typhi and Paratyphi, is endemic in India with an incidence of 102–2219/100,000 populations. The definitive diagnosis of enteric fever in patients with compatible clinical picture is isolation of Salmonellae from blood, bone marrow, stool or urine, and demonstration of four-fold rise in antibody titer to both O and H antigen of the organism between acute and convalescent-phase sera. Aim: The aim of the study was to study the prevalence of various serotypes of S. enterica and their antibiogram in foot hills of Himalayas. Materials and Methods: During February 2012–January 2013, all clinically suspected patients were screened for enteric fever by Widal tube agglutination test. For the isolation of etiology, venous blood, stool and urine specimen were obtained from patients with antibody titer of ≥80 and 160 for anti-O agglutinin and anti-H agglutinin of Salmonella typhi, respectively, and ≥20 for anti-H agglutinin of S. paratyphi A and S. paratyphi B. Characterization and antibiogram determination of the isolates was done by conventional microbiological methods including Kirby–Bauer's disc diffusion technique. Result: Among 1173 suspected cases, 373 showed a high titer of antibodies against O (≥80), H (≥160), AH (≥20), and BH (≥20) antigens. A total of 81 isolates were obtained from 76 patients (29 from blood and 49 from stool and three from urine), of which 54 were identified as Salmonella typhi, 20 as Paratyphi A and seven as Paratyphi B. Extended-spectrum beta-lactamase production was observed in four isolates of S. typhi. Ciprofloxacin followed by co-trimoxazole was resistant to 46.5 and 36.5% of the isolates, respectively. Conclusion: This report indicates a significant percentage of drug resistance in S. enterica serotypes in Garhwal region. Periodic monitoring of the antibiogram pattern along with the implementation of strict antibiotic policies and patient education is needed.
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Diagnostic reference levels for mammography examinations in North Eastern Nigeria
African Journal of Medical and Health Sciences 2018 17(1):54-59
Background: Diagnostic reference levels (DRLs) plays an important role in health-care delivery and radiation safety of patients. This study was carried out as part of a comprehensive project to establish DRLs for the radiological examinations for the first time in North Eastern Nigeria. Objective of the Study: The aim is to establish DRL for mammography examination in North Eastern Nigeria and to compare it with other established works. Materials and Methods: This study is a prospective cross-sectional study conducted in two university teaching hospitals in North Eastern Nigeria. Sixty patients were recruited for the study. Thermoluminescent dosimeter (TLD) chips were exposed for craniocaudal (CC) and mediolateral examinations to record the entrance skin dose (ESD). TLD readings were obtained at the Center for Energy Research and Training Zaria, Kaduna State, Nigeria. Dance formula was used to convert ESD to mean glandular dose (MGD). Student's t-test was used to determine the relationship between the mean ESD obtained in the two centers and Pearson's correlation was used to determine the relationship between the MGD and anthropotechnical parameters. Statistical significance was set at P < 0.05. Results: The total MGD for this study was 0.31 ± 0.05 mGy and 0.69 ± 0.11 mGy for CC and mediolateral oblique (MLO), respectively. DRL was 0.63 mGy and 1.04 mGy for CC and MLO, respectively. There was no statistically significant relationship (P > 0.05) between the MGD and anthropotechnical parameters. The DRL in this work were higher when compared with international established work. Conclusion: There is need for optimization of our radiology practice in North Eastern Nigeria and most centers in Nigeria.
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Musculoskeletal tumors of the extremities: Challenges and outcome of management in a Nigeria Tertiary Hospital
African Journal of Medical and Health Sciences 2018 17(1):20-25
Background: Patients with musculoskeletal tumors in developing countries often present late to the hospital and this poses serious challenges to the management, especially for malignant tumors. This study aims to highlight the various types of musculoskeletal extremity tumors seen in a Nigerian tertiary health center during the study period, the challenges encountered in managing them, and the outcome of the management. Materials and Methods: A prospective study in which all consenting patients with musculoskeletal extremity tumors who presented to the center from April 2015 to March 2017 were recruited. Results: Seventy-two patients were managed during the study period. The mean age was 22.1 ± 4.5 years and the age group most affected was the 11–20 years group, n = 22 (30.6%). Male-to-female ratio was 1.6:1. The femur was the most commonly involved bone. Forty tumors were benign while 32 were malignant tumors. Osteochondroma was the most common benign tumor while osteosarcoma was the most common malignant tumor. The challenges encountered during the management were a late presentation, poverty, and traditional bonesetter intervention before the presentation. Patients with benign tumor had excision with good outcome in all. Twenty (62.5%) of the patients with a malignant tumor had the ablative procedure, two of these 20 patients died within 6 months of treatment, while 12 (37.5%) of the patients with malignant tumor refused the treatment. Conclusion: Management of musculoskeletal extremity tumors is highly challenging in this part of the country, especially the malignant types, due to the challenges mentioned. There is a need for more awareness about the disease, the Government should subsidize the cost of management of this disease, and more specialty training of personnel is necessary for appropriate management of the diseases.
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Incidence and pattern of dog bite injuries treated in the emergency room of a teaching hospital South East Nigeria
African Journal of Medical and Health Sciences 2018 17(1):35-40
Background: Dog bite injury treated in the emergency room varies from and within subregions in pattern and potential risk of transmission of rabies. This variation has implications in its morbidity and mortality. The aim of this study was to determine the incidence and pattern of dog bite injuries treated in a teaching hospital emergency room setting of a developing country. Patients and Methods: This was a retrospective study of the entire patients with dog bite injury treated in the emergency room of Federal Teaching Hospital Abakaliki from January 2006 to December 2015. Results: Dog bite injury necessitated visit in 74 patients with an incidence of 2 per 1000 emergency room attendances, and a male to female ratio of 1:1.1. The mean age of the patients was 25.5 ± 1.87 years, and peak age group incidence was 5–9 years. Lower extremity was involved in 77.5% of the injuries, and buttock was the predominant site of injury in 0–4 years old. Fifty-one (68.9%) owned dogs and 23 (31.1%) stray dogs were involved in the attack. There was unprovoked attack in 81.1% of cases, and 51 (68.9%) sustained Grade II injury. Twenty-eight (37.8%) of the dogs had anti-rabies vaccination. Fifty-four (73%) patients had no prehospital care while 64 (86.5%) received postexposure anti-rabies vaccine. Majority of the patients 73 (98.7%) recovered fully. One (1.4%) patient that presented with clinical rabies self-discharged against medical advice. Conclusion: The incidence of dog bite injury is within worldwide range though the female gender bias is unprecedented. We recommend preventive strategies based on the observed pattern and improvement in the rate of prehospital care and higher coverage of anti-rabies vaccination of dogs.
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Lead in potable water sources in Anambra State, South East, Nigeria
African Journal of Medical and Health Sciences 2018 17(1):26-30
Introduction: Due to lack of treated water supply in major cities and settlements in Anambra state, Nigeria, majority of the population obtain potable water directly from boreholes, streams, sachet, harvested rain, and well water sources. Lead-laden potable water may be a major cause of mortality and morbidity in Anambra state, Nigeria. Objective: This study was conducted to determine the presence of lead in potable water sources in Anambra state, Nigeria. Materials and Methods: Water samples were systematically collected from 81 water sampling sites in different senatorial zones of the state. Lead was estimated in the water samples using Varian AA240 atomic absorption spectrophotometer. Results: The mean levels of lead in the water samples in all the senatorial zones of the state were higher than the maximum contaminant limit (0.01 mg/L) set by the World Health Organization (WHO). The mean level of lead in harvested rain, sachet, and stream waters (0.34 ± 0.23, 0.37 ± 0.08, and 0.23 ± 0.06 mg/L, respectively) was higher in Anambra South senatorial zone compared to the WHO maximum contaminant limit. Furthermore, Anambra South has higher (P < 0.001) mean lead level compared to the North and Central senatorial zones. Conclusion: This study reveals significantly high lead levels in potable water sources in Anambra state, Nigeria. The water samples should be well treated to remove this harmful toxic heavy metal which is very dangerous to health.
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Work-Related respiratory symptoms and cardiopulmonary function impairment of factory workers in a cement company in South-West Nigeria
African Journal of Medical and Health Sciences 2018 17(1):47-53
Background: Cement factory workers are exposed to dangerous cement dust while at workplace especially in the developing countries where little or no safety standards are followed. This study investigated the work-related respiratory symptoms and cardiopulmonary functions' impairment in cement factory workers in South-West, Nigeria. Materials and Methods: Seventy cement exposed workers and 70 age-matched unexposed individuals participated in this cross-sectional study. A self-administered questionnaire was used to assess their sociodemographic characteristics, clinical details, and respiratory symptoms. Selected cardiopulmonary parameters of participants were measured. Data were analyzed using the Statistical Package for Social Sciences version 20.0. Independent t-test was used to compare the selected cardiopulmonary parameters of the two groups. Results: The mean age of cement-exposed group was 31.57 ± 8.32 years, and the unexposed group was 31.50 ± 8.57 years. The prevalence of respiratory symptoms among the cement-exposed group were as follows: 71.4% for cough, 45.7% for phlegm, 67.1% for wheeze, 38.6% for breathlessness, and 48.6% for chest tightness while those for the unexposed group were as follows: 50% for cough, 15.7% for phlegm, 5.7% for wheeze, 2.9% for breathlessness, and 7.1% for chest tightness. There were significant differences between the mean values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)/FVC ratio, peak expiratory flow rate, systolic blood pressure, and diastolic blood pressure (P < 0.05) of the cement-exposed group and those of the unexposed group. Conclusion: Respiratory symptoms were higher among cement factory workers than the age-matched unexposed individuals. FVC, FEV1, FEV1/FVC ratio, and peak expiratory flow rate were reduced while blood pressure was increased in cement factory workers.
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Anesthesia for emergency cesarean section: A comparison of spinal versus general anesthesia on maternal and neonatal outcomes
African Journal of Medical and Health Sciences 2018 17(1):31-34
Background: Despite the relative safety of cesarean section (CS), increasing CS rate is a cause for concern to obstetricians and anesthetists because of the attendant increased health risk one of which is the risk of anesthesia. The choice of anesthesia for cesarean section depends on the indication for the surgery, the urgency of intervention required, the maternal and/or fetal status, and the patient's desires. Despite the paradigm shift toward spinal anesthesia, general anesthesia is still commonly administered in our facility for some specific indications. Objective: This study was aimed to evaluate the maternal and neonatal outcomes in patients who had emergency CS under spinal anesthesia compared with those who had general anesthesia. Materials and Methods: This was a retrospective study comparing the obstetric outcome of patients who had emergency CS under spinal anesthesia compared with those who had the surgery under general anesthesia. Data analysis was done using statistical Epi Info version 7.2.1. Results: The most common indication for surgery in the spinal group was cephalopelvic disproportion while that for the general anesthesia group was antepartum hemorrhage/placenta previa. Patients who had spinal anesthesia had less intraoperative blood loss compared with those who had general anesthesia (814 ± 124 vs. 842 ± 324; P = 0.0007). There was a significant difference in the intraoperative blood loss >1000 ml among women who had spinal anesthesia relative to women who had general anesthesia (odds ratio [OR]: 0.6832, 95% confidence interval [CI]: 0.3390–0.9779; P = 0.0005). Spinal anesthesia was associated with a reduced risk of having a 1st-min Apgar score <7 (OR: 0.6096, 95% CI: 0.4066–0.9140; P = 0.016). There was no significant difference in the 5th-min Apgar score in both groups. There was also no significant difference in the number of neonates admitted into the Intensive Care Units. The maternal and perinatal mortality was not different in both groups. Conclusion: Spinal anesthesia was associated with reduced risk of blood loss and reduced risk of low Apgar score in the 1st min. There was no difference in the 5th-min Apgar score and maternal and neonatal mortality.
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A 10-Year review of ultrasonographic findings of scrotal diseases in Ibadan, South Western, Nigeria
African Journal of Medical and Health Sciences 2018 17(1):60-65
Introduction: Despite the importance of a thorough clinical evaluation, ultrasonography has emerged as the mainstay of imaging of the scrotum and its contents. Differentiation of testicular lesions and that of adjacent scrotum and content is usually difficult clinically. Scrotal ultrasound (SUSS) is highly sensitive in the detection of intrascrotal abnormalities and in differentiating testicular from paratesticular lesions. SUSS accurately determines the location and nature of palpable lesions and reveals nonpalpable scrotal masses. The aim of this study is to report the various indications for SUSS in this setting and to describe the sonographic findings in these patients. Materials and Methods: A retrospective and descriptive study carried out to evaluate scrotal ultrasound scans performed on 442 patients referred for various clinical indications from the clinics and units of the University College Hospital, to the Radiology department of the same hospital which serves as referral center in Ibadan, and the South-Western Nigeria; over a 10 year period from January 2006 to December 2015, a tertiary health Institution. Results: The mean age of the study population was 36.13 years ± standard deviation 15.88 years. Most of the patients (57.1%) were within the age group of 30 and 49 years. The leading clinical indication for ultrasound referral was infertility/infertility related issues in 56.1% of the total patients. Testicular masses were clinically detected and required SUSS for confirmation in 4.5% of the study population. On USS, the average testicular volume in adults with normal study was 16.38 cm3 and 15.99 cm3 on the right and left side, respectively. The most common USS findings were varicocele (29.4%), this was bilateral in more than half of the cases. Hydrocele was the second most common finding in 18.78% and often bilateral. Testicular masses were seen in 11.1% and were cystic in nature in more than half of the study population. Conclusion: Infertility/infertility related diagnosis were the most frequent indications for testicular ultrasound in adults in our environment. We recommend SUSS as a routine investigation in suspected scrotal/testicular pathologies.
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Changing trends and outcomes associated with the adoption of minimally invasive hepatectomy: a contemporary single-institution experience with 400 consecutive resections
Abstract
Background
Several studies published mainly from pioneers and early adopters have documented the evolution of minimally invasive hepatectomy (MIH). However, questions remain if these reported experiences are applicable and reproducible today. This study examines the changing trends, safety, and outcomes associated with the adoption of MIH based on a contemporary single-institution experience.
Methods
This is a retrospective review of 400 consecutive patients who underwent MIH between 2006 and 2017 of which 360 cases (90%) were performed since 2012. To determine the evolution of MIH, the study population was stratified into four equal groups of 100 patients. Analyses were also performed of predictive factors and outcomes of open conversion.
Results
Four hundred patients underwent MIH of which 379 (94.8%) were totally laparoscopic/robotic. Eighty-eight (22.0%) patients underwent major hepatectomy and 160 (40.0%) had resection of tumors located in the posterosuperior segments. There were 38 (9.5%) open conversions. Comparison across the four groups demonstrated that patients were older, had higher ASA score, and had increased frequency of previous abdominal surgery and repeat liver resections. There was also an increase in the proportion of patients who underwent totally laparoscopic/robotic surgery, major liver resection, resection of ≥ 3 segments, and multiple resections. Comparison of outcomes demonstrated that there was a significant decrease in open conversion rate, longer operation time, and increased use of Pringles maneuver. The presence of cirrhosis and institution experience (1st 100 cases) were independent predictors of open conversion. Patients who required open conversion had significantly increased operation time, blood loss, blood transfusion rate, morbidity, and mortality.
Conclusion
The case volume of MIH performed increased rapidly at our institution over time. Although the indications of MIH expanded to include higher risk patients and more complex hepatectomies, there was a decrease in open conversion rate and no change in other perioperative outcomes.
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A prospective study of the safety and usefulness of a new miniature wide-angle camera: the “BirdView camera system”
Abstract
Background
The performance of endoscopic surgery has quickly become widespread as a minimally invasive therapy. However, complications still occur due to technical difficulties. In the present study, we focused on the problem of blind spots, which is one of the several problems that occur during endoscopic surgery and developed "BirdView," a camera system with a wide field of view, with SHARP Corporation.
Methods
In the present study, we conducted a clinical trial (Phase I) to confirm the safety and usefulness of the BirdView camera system. We herein report the results.
Results
In this study, surgical adverse events were reported in 2 cases (problems with ileus and urination). There were no cases of device failure, damage to the surrounding organs, or mortality.
Conclusions
We evaluated the safety of the BirdView camera system. We believe that this camera system will contribute to the performance safe endoscopic surgery and the execution of robotic surgery, in which operators do not have the benefit of tactile feedback.
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Review of an emergency general surgery process improvement program at a verified military trauma center
Abstract
Introduction
Decreasing combat-based admissions to our military facility have made it difficult to maintain a robust trauma process improvement (PI) program. Since emergency general surgery (EGS) and trauma patients share similarities, we merged the care of our EGS and trauma patients into one acute care surgery (ACS) team. An EGS PI program was developed based on trauma PI principles to facilitate continued identification of opportunities for improvement despite our decline in trauma admissions. Analysis of the first 18 months of combined ACS PI data is presented.
Methods
EGS registry inclusion criteria was based on published Association for the Surgery of Trauma's recommendations. Program components and PI categories were based on our existing trauma PI program. Dedicated coordinators actively reviewed and cataloged patient care and outcomes. Deviations from standard practice patterns, unplanned interventions, and other complications were abstracted, categorized, and evaluated through levels of review similar to accepted trauma PI principles. Data for the first six quarters were collated and trends were analyzed.
Results
Over 18 months, 696 EGS patients met registry inclusion criteria, with 468 patients (67%) undergoing operative intervention. Over the same time, 353 trauma patients were admitted with 158 undergoing operative intervention (56.4%). Of the 696 EGS patients and 353 trauma patients, 226 (32%) and 243 (69%) PI events were identified, respectively. Common events included unplanned therapies, re-admissions, and unplanned ICU admissions. Based on analysis of all events, four new areas for improvement initiatives were identified. Results of these initiatives included implementation of a multi-disciplinary EGS PI committee, consensus protocols, and departmental and hospital-wide actions.
Conclusion
In an 18-month period, integration of our EGS patients into a novel, combined ACS PI program facilitated recognition of an additional 226 PI events and provided a substrate for continued improvements in patient care.
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The E3 Ubiquitin Ligase MIB-1 Is Necessary To Form the Nuclear Halo in Caenorhabditis elegans Sperm
Unlike the classical nuclear envelope with two membranes found in other eukaryotic cells, most nematode sperm nuclei are not encapsulated by membranes. Instead, they are surrounded by a nuclear halo of unknown composition. How the halo is formed and regulated is unknown. We used forward genetics to identify molecular lesions behind three classical fer (fertilization defective) mutations that disrupt the ultrastructure of the Caenorhabditis elegans sperm nuclear halo. We found fer-2 and fer-4 alleles to be nonsense mutations in mib-1. fer-3 was caused by a nonsense mutation in eri-3. GFP::MIB-1 was expressed in the germline during early spermatogenesis, but not in mature sperm. mib-1 encodes a conserved E3 ubiquitin ligase homologous to vertebrate Mib1 and Mib2, which function in Notch signaling. Here, we show that mib-1 is important for male sterility and is involved in the regulation or formation of the nuclear halo during nematode spermatogenesis.
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The domino SWI2/SNF2 Gene Product Represses Cell Death in Drosophila melanogaster
The Drosophila domino locus encodes DNA-dependent ATPases of the SWI2/SNF2 class. This class of chromatin remodeler is associated with an array of cellular activities encompassing transcription, replication, repair and recombination. Moreover, domino was observed initially to maintain a repressive chromatin state via genetic interaction studies with homeotic genes. Although domino mutations were also characterized with a cell death phenotype, its association with a death pathway has not been investigated. Here we have used targeted RNA interference to depress domino function in the wing. Resultant wing damage phenotypes were found to be enhanced through overexpression of pro-apoptotic loci, and suppressed through loss of function of these loci. Loss of wing margin and blade tissue was correlated with activation of the effector Caspase Dcp-1, a marker for apoptosis. The affected wing regions also exhibited lower levels of the DIAP1 protein, an inhibitor of apoptosis. The lower level of DIAP1 protein was not correlated with an effect on the activity of a DIAP1 gene transgenic reporter (thread-LacZ), suggesting that loss of DIAP1 occurred post transcriptionally. In some cases excessive cell proliferation within the targeted tissue, measured through BrdU incorporation, was also observed. Finally, we used a transgenic reporter construct to monitor the chromatin state upstream of the proapoptotic reaper locus. In genotypes exhibiting targeted domino loss and wing phenotypes, we observed increased reporter activity only in the affected areas. These data support the conclusion that domino normally functions to maintain pro-apoptotic genes in a repressed state.
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A High Quality Genome for Mus spicilegus, a Close Relative of House Mice with Unique Social and Ecological Adaptations
Genomic data for the closest relatives of house mice (Mus musculus species complex) are surprisingly limited. Here, we present the first complete genome for a behaviorally and ecologically unique member of the sister clade to house mice, the mound-building mouse, Mus spicilegus. Using read cloud sequencing and de novo assembly we produced a 2.50 Gbp genome with a scaffold N50 of 2.27 Mbp. We constructed >25 000 gene models, of which the majority had high homology to other Mus species. To evaluate the utility of the M. spicilegus genome for behavioral and ecological genomics, we extracted 196 vomeronasal receptor (VR) sequences from our genome and analyzed phylogenetic relationships between M. spicilegus VRs and orthologs from M. musculus and the Algerian mouse, M. spretus. While most M. spicilegus VRs clustered with orthologs in M. musculus and M. spretus, 10 VRs with evidence of rapid divergence in M. spicilegus are strong candidate modulators of species-specific chemical communication. A high quality assembly and genome for M. spicilegus will help to resolve discordant ancestry patterns in house mouse genomes, and will provide an essential foundation for genetic dissection of phenotypes that distinguish commensal from non-commensal species, and the social and ecological characteristics that make M. spicilegus unique.
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Assessment of an Organ-Specific de Novo Transcriptome of the Nematode Trap-Crop, Solanum sisymbriifolium
Solanum sisymbriifolium, also known as "Litchi Tomato" or "Sticky Nightshade," is an undomesticated and poorly researched plant related to potato and tomato. Unlike the latter species, S. sisymbriifolium induces eggs of the cyst nematode, Globodera pallida, to hatch and migrate into its roots, but then arrests further nematode maturation. In order to provide researchers with a partial blueprint of its genetic make-up so that the mechanism of this response might be identified, we used single molecule real time (SMRT) sequencing to compile a high quality de novo transcriptome of 41,189 unigenes drawn from individually sequenced bud, root, stem, and leaf RNA populations. Functional annotation and BUSCO analysis showed that this transcriptome was surprisingly complete, even though it represented genes expressed at a single time point. By sequencing the 4 organ libraries separately, we found we could get a reliable snapshot of transcript distributions in each organ. A divergent site analysis of the merged transcriptome indicated that this species might have undergone a recent genome duplication and re-diploidization. Further analysis indicated that the plant then retained a disproportionate number of genes associated with photosynthesis and amino acid metabolism in comparison to genes with characteristics of R-proteins or involved in secondary metabolism. The former processes may have given S. sisymbriifolium a bigger competitive advantage than the latter did.
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Genomic Variation Among and Within Six Juglans Species
Genomic analysis in Juglans (walnuts) is expected to transform the breeding and agricultural production of both nuts and lumber. To that end, we report here the determination of reference sequences for six additional relatives of Juglans regia: Juglans sigillata (also from section Dioscaryon), Juglans nigra, Juglans microcarpa, Juglans hindsii (from section Rhysocaryon), Juglans cathayensis (from section Cardiocaryon), and the closely related Pterocarya stenoptera. While these are 'draft' genomes, ranging in size between 640Mbp and 990Mbp, their contiguities and accuracies can support powerful annotations of genomic variation that are often the foundation of new avenues of research and breeding. We annotated nucleotide divergence and synteny by creating complete pairwise alignments of each reference genome to the remaining six. In addition, we have re-sequenced a sample of accessions from four Juglans species (including regia). The variation discovered in these surveys comprises a critical resource for experimentation and breeding, as well as a solid complementary annotation. To demonstrate the potential of these resources the structural and sequence variation in and around the polyphenol oxidase loci, PPO1 and PPO2 were investigated. As reported for other seed crops variation in this gene is implicated in the domestication of walnuts. The apparently Juglandaceae specific PPO1 duplicate shows accelerated divergence and an excess of amino acid replacement on the lineage leading to accessions of the domesticated nut crop species, Juglans regia and sigillata.
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A Dense Linkage Map of Lake Victoria Cichlids Improved the Pundamilia Genome Assembly and Revealed a Major QTL for Sex-Determination
Genetic linkage maps are essential for comparative genomics, high quality genome sequence assembly and fine scale quantitative trait locus (QTL) mapping. In the present study we identified and genotyped markers via restriction-site associated DNA (RAD) sequencing and constructed a genetic linkage map based on 1,597 SNP markers of an interspecific F2 cross of two closely related Lake Victoria cichlids (Pundamilia pundamilia and P. sp. 'red head'). The SNP markers were distributed on 22 linkage groups and the total map size was 1,594 cM with an average marker distance of 1.01 cM. This high-resolution genetic linkage map was used to anchor the scaffolds of the Pundamilia genome and estimate recombination rates along the genome. Via QTL mapping we identified a major QTL for sex in a ~1.9 Mb region on Pun-LG10, which is homologous to Oreochromis niloticus LG 23 (Ore-LG23) and includes a well-known vertebrate sex-determination gene (amh).
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BLAST-XYPlot Viewer: A Tool for Performing BLAST in Whole-Genome Sequenced Bacteria/Archaea and Visualize Whole Results Simultaneously
One of the most commonly used tools to compare protein or DNA sequences against databases is BLAST. We introduce a web tool that allows the performance of BLAST-searches of protein/DNA sequences in whole-genome sequenced bacteria/archaea, and displays a large amount of BLAST-results simultaneously. The circular bacterial replicons are projected as horizontal lines with fixed length of 360, representing the degrees of a circle. A coordinate system is created with length of the replicon along the x-axis and the number of replicon used on the y-axis. When a query sequence matches with a gene/protein of a particular replicon, the BLAST-results are depicted as an "x,y" position in a specially adapted plot. This tool allows the visualization of the results from the whole data to a particular gene/protein in real time with low computational resources.
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Phenotypic Data from Inbred Parents Can Improve Genomic Prediction in Pearl Millet Hybrids
Pearl millet is a non-model grain and fodder crop adapted to extremely hot and dry environments globally. In India, a great deal of public and private sectors' investment has focused on developing pearl millet single cross hybrids based on the cytoplasmic-genetic male sterility (CMS) system, while in Africa most pearl millet production relies on open pollinated varieties. Pearl millet lines were phenotyped for both the inbred parents and hybrids stage. Many breeding efforts focus on phenotypic selection of inbred parents to generate improved parental lines and hybrids. This study evaluated two genotyping techniques and four genomic selection schemes in pearl millet. Despite the fact that 6x more sequencing data were generated per sample for RAD-seq than for tGBS, tGBS yielded more than 2x as many informative SNPs (defined as those having MAF > 0.05) than RAD-seq. A genomic prediction scheme utilizing only data from hybrids generated prediction accuracies (median) ranging from 0.73-0.74 (1000-grain weight), 0.87-0.89 (days to flowering time), 0.48-0.51 (grain yield) and 0.72-0.73 (plant height). For traits with little to no heterosis, hybrid only and hybrid/inbred prediction schemes performed almost equivalently. For traits with significant mid-parent heterosis, the direct inclusion of phenotypic data from inbred lines significantly (P < 0.05) reduced prediction accuracy when all lines were analyzed together. However, when inbreds and hybrid trait values were both scored relative to the mean trait values for the respective populations, the inclusion of inbred phenotypic datasets moderately improved genomic predictions of the hybrid genomic estimated breeding values. Here we show that modern approaches to genotyping by sequencing can enable genomic selection in pearl millet. While historical pearl millet breeding records include a wealth of phenotypic data from inbred lines, we demonstrate that the naive incorporation of this data into a hybrid breeding program can reduce prediction accuracy, while controlling for the effects of heterosis per se allowed inbred genotype and trait data to improve the accuracy of genomic estimated breeding values for pearl millet hybrids.
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Development of Diagnostic SNP Markers To Monitor Hybridization Between Sika Deer (Cervus nippon) and Wapiti (Cervus elaphus)
Sika deer (Cervus Nippon) and wapiti (Cervus elaphus) are closely related species and their hybridization can result in significant allele-shift of their gene pool. Additive genetic effects and putative heterotic effects of their hybridization on growth performance could confer considerable economic advantage in deer farming. Here, we used double-digest restriction site-associated DNA sequencing technology (ddRAD-seq) and detected ~320,000 genome-wide SNPs from 30 captive individuals: 7 sika deer, 6 wapiti and 17 F1 hybrids (reciprocal cross). By screening observed heterozygosity of each SNP across four taxonomic groups, we report for the first time a resource of 2,015 putative diagnostic SNP markers (species-specific SNPs for sika deer and wapiti), which can be used to design tools for assessing or monitoring the degree of hybridization between sika deer and wapiti. These ddRAD-seq data and SNP datasets are also valuable resources for genome-wide studies, including trait discovery for breeders of domestic deer.
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Dynamic Changes in Yeast Phosphatase Families Allow for Specialization in Phosphate and Thiamine Starvation
Convergent evolution is often due to selective pressures generating a similar phenotype. We observe relatively recent duplications in a spectrum of Saccharomycetaceae yeast species resulting in multiple phosphatases that are regulated by different nutrient conditions – thiamine and phosphate starvation. This specialization is both transcriptional and at the level of phosphatase substrate specificity. In Candida glabrata, loss of the ancestral phosphatase family was compensated by the co-option of a different histidine phosphatase family with three paralogs. Using RNA-seq and functional assays, we identify one of these paralogs, CgPMU3, as a thiamine phosphatase. We further determine that the 81% identical paralog CgPMU2 does not encode thiamine phosphatase activity; however, both are capable of cleaving the phosphatase substrate, 1-napthyl-phosphate. We functionally demonstrate that members of this family evolved novel enzymatic functions for phosphate and thiamine starvation, and are regulated transcriptionally by either nutrient condition, and observe similar trends in other yeast species. This independent, parallel evolution involving two different families of histidine phosphatases suggests that there were likely similar selective pressures on multiple yeast species to recycle thiamine and phosphate. In this work, we focused on duplication and specialization, but there is also repeated loss of phosphatases, indicating that the expansion and contraction of the phosphatase family is dynamic in many Ascomycetes. The dynamic evolution of the phosphatase gene families is perhaps just one example of how gene duplication, co-option, and transcriptional and functional specialization together allow species to adapt to their environment with existing genetic resources.
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Tissue-Specific Transcriptome for Poeciliopsis prolifica Reveals Evidence for Genetic Adaptation Related to the Evolution of a Placental Fish
The evolution of the placenta is an excellent model to examine the evolutionary processes underlying adaptive complexity due to the recent, independent derivation of placentation in divergent animal lineages. In fishes, the family Poeciliidae offers the opportunity to study placental evolution with respect to variation in degree of post-fertilization maternal provisioning among closely related sister species. In this study, we present a detailed examination of a new reference transcriptome sequence for the live-bearing, matrotrophic fish, Poeciliopsis prolifica, from multiple-tissue RNA-seq data. We describe the genetic components active in liver, brain, late-stage embryo, and the maternal placental/ovarian complex, as well as associated patterns of positive selection in a suite of orthologous genes found in fishes. Results indicate the expression of many signaling transcripts, "non-coding" sequences and repetitive elements in the maternal placental/ovarian complex. Moreover, patterns of positive selection in protein sequence evolution were found associated with live-bearing fishes, generally, and the placental P. prolifica, specifically, that appear independent of the general live-bearer lifestyle. Much of the observed patterns of gene expression and positive selection are congruent with the evolution of placentation in fish functionally converging with mammalian placental evolution and with the patterns of rapid evolution facilitated by the teleost-specific whole genome duplication event.
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The Protein Arginine Methyltransferase PRMT-5 Regulates SER-2 Tyramine Receptor-Mediated Behaviors in Caenorhabditis elegans
G protein-coupled receptors are 7-pass transmembrane receptors that couple to heterotrimeric G proteins to mediate cellular responses to a diverse array of stimuli. Understanding the mechanisms that regulate G protein-coupled receptors is crucial to manipulating their signaling for therapeutic benefit. One key regulatory mechanism that contributes to the functional diversity of many signaling proteins is post-translational modification. Whereas phosphorylation remains the best studied of such modifications, arginine methylation by protein arginine methyltransferases is emerging as a key regulator of protein function. We previously published the first functional evidence that arginine methylation of G protein-coupled receptors modulates their signaling. We report here a third receptor that is regulated by arginine methylation, the Caenorhabditis elegans SER-2 tyramine receptor. We show that arginines within a putative methylation motif in the third intracellular loop of SER-2 are methylated by PRMT5 in vitro. Our data also suggest that this modification enhances SER-2 signaling in vivo to modulate animal behavior. The identification of a third G protein-coupled receptor to be functionally regulated by arginine methylation suggests that this post-translational modification may be utilized to regulate signaling through a broad array of G protein-coupled receptors.
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Defects in the Neuroendocrine Axis Contribute to Global Development Delay in a Drosophila Model of NGLY1 Deficiency
N-glycanase 1 (NGLY1) Deficiency is a rare monogenic multi-system disorder first described in 2014. NGLY1 is evolutionarily conserved in model organisms. Here we conducted a natural history study and chemical-modifier screen on the Drosophila melanogaster NGLY1 homolog, Pngl. We generated a new fly model of NGLY1 Deficiency, engineered with a nonsense mutation in Pngl at codon 420 that results in a truncation of the C-terminal carbohydrate-binding PAW domain. Homozygous mutant animals exhibit global development delay, pupal lethality and small body size as adults. We developed a 96-well-plate, image-based, quantitative assay of Drosophila larval size for use in a screen of the 2,650-member Microsource Spectrum compound library of FDA approved drugs, bioactive tool compounds, and natural products. We found that the cholesterol-derived ecdysteroid molting hormone 20-hydroxyecdysone (20E) partially rescued the global developmental delay in mutant homozygotes. Targeted expression of a human NGLY1 transgene to tissues involved in ecdysteroidogenesis, e.g., prothoracic gland, also partially rescues global developmental delay in mutant homozygotes. Finally, the proteasome inhibitor bortezomib is a potent enhancer of global developmental delay in our fly model, evidence of a defective proteasome "bounce-back" response that is also observed in nematode and cellular models of NGLY1 Deficiency. Together, these results demonstrate the therapeutic relevance of a new fly model of NGLY1 Deficiency for drug discovery and gene modifier screens.
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Key Transport and Ammonia Recycling Genes Involved in Aphid Symbiosis Respond to Host-Plant Specialization
Microbes are known to influence insect-plant interactions; however, it is unclear if host-plant diet influences the regulation of nutritional insect symbioses. The pea aphid, Acyrthosiphon pisum, requires its nutritional endosymbiont, Buchnera, for the production of essential amino acids. We hypothesize that key aphid genes that regulate the nutritional symbioses respond to host-plant diet when aphids feed on a specialized (alfalfa) compared to a universal host-plant diet (fava), which vary in amino acid profiles. Using RNA-Seq and whole genome bisulfite sequencing, we measured gene expression and DNA methylation profiles for such genes when aphids fed on either their specialized or universal host-plant diets. Our results reveal that when aphids feed on their specialized host-plant they significantly up-regulate and/or hypo-methylate key aphid genes in bacteriocytes related to the amino acid metabolism, including glutamine synthetase in the GOGAT cycle that recycles ammonia into glutamine and the glutamine transporter ApGLNT1. Moreover, regardless of what host-plant aphids feed on we observed significant up-regulation and differential methylation of key genes involved in the amino acid metabolism and the glycine/serine metabolism, a metabolic program observed in proliferating cancer cells potentially to combat oxidative stress. Based on our results, we suggest that this regulatory response of key symbiosis genes in bacteriocytes allows aphids to feed on a suboptimal host-plant that they specialize on.
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Sex Determination in Ceratopteris richardii Is Accompanied by Transcriptome Changes That Drive Epigenetic Reprogramming of the Young Gametophyte
The fern Ceratopteris richardii is an important model for studies of sex determination and gamete differentiation in homosporous plants. Here we use RNA-seq to de novo assemble a transcriptome and identify genes differentially expressed in young gametophytes as their sex is determined by the presence or absence of the male-inducing pheromone called antheridiogen. Of the 1,163 consensus differentially expressed genes identified, the vast majority (1,030) are up-regulated in gametophytes treated with antheridiogen. GO term enrichment analyses of these DEGs reveals that a large number of genes involved in epigenetic reprogramming of the gametophyte genome are up-regulated by the pheromone. Additional hormone response and development genes are also up-regulated by the pheromone. This C. richardii gametophyte transcriptome and gene expression dataset will prove useful for studies focusing on sex determination and differentiation in plants.
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Genome-Wide Analysis of Multidrug and Toxic Compound Extrusion (MATE) Family in Gossypium raimondii and Gossypium arboreum and Its Expression Analysis Under Salt, Cadmium, and Drought Stress
The extrusion of toxins and substances at a cellular level is a vital life process in plants under abiotic stress. The multidrug and toxic compound extrusion (MATE) gene family plays a large role in the exportation of toxins and other substrates. We carried out a genome-wide analysis of MATE gene families in Gossypium raimondii and Gossypium arboreum and assessed their expression levels under salt, cadmium and drought stresses. We identified 70 and 68 MATE genes in G. raimondii and G. arboreum, respectively. The majority of the genes were predicted to be localized within the plasma membrane, with some distributed in other cell parts. Based on phylogenetic analysis, the genes were subdivided into three subfamilies, designated as M1, M2 and M3. Closely related members shared similar gene structures, and thus were highly conserved in nature and have mainly evolved through purifying selection. The genes were distributed in all chromosomes. Twenty-nine gene duplication events were detected, with segmental being the dominant type. GO annotation revealed a link to salt, drought and cadmium stresses. The genes exhibited differential expression, with GrMATE18, GrMATE34, GaMATE41 and GaMATE51 significantly upregulated under drought, salt and cadmium stress, and these could possibly be the candidate genes. Our results provide the first data on the genome-wide and functional characterization of MATE genes in diploid cotton, and are important for breeders of more stress-tolerant cotton genotypes.
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Survey of Human Chromosome 21 Gene Expression Effects on Early Development in Danio rerio
Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS), one of the most genetically complex conditions compatible with human survival. Assessment of the physiological consequences of dosage-driven overexpression of individual Hsa21 genes during early embryogenesis and the resulting contributions to DS pathology in mammals are not tractable in a systematic way. A recent study looked at loss-of-function of a subset of Caenorhabditis elegans orthologs of Hsa21 genes and identified ten candidates with behavioral phenotypes, but the equivalent over-expression experiment has not been done. We turned to zebrafish as a developmental model and, using a number of surrogate phenotypes, we screened Hsa21 genes for effects on early embyrogenesis. We prepared a library of 164 cDNAs of conserved protein coding genes, injected mRNA into early embryos and evaluated up to 5 days post-fertilization (dpf). Twenty-four genes produced a gross morphological phenotype, 11 of which could be reproduced reliably. Seven of these gave a phenotype consistent with down regulation of the sonic hedgehog (Shh) pathway; two showed defects indicative of defective neural crest migration; one resulted consistently in pericardial edema; and one was embryonic lethal. Combinatorial injections of multiple Hsa21 genes revealed both additive and compensatory effects, supporting the notion that complex genetic relationships underlie end phenotypes of trisomy that produce DS. Together, our data suggest that this system is useful in the genetic dissection of dosage-sensitive gene effects on early development and can inform the contribution of both individual loci and their combinatorial effects to phenotypes relevant to the etiopathology of DS.
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CORL Expression in the Drosophila Central Nervous System Is Regulated by Stage Specific Interactions of Intertwined Activators and Repressors
CORL proteins (SKOR in mice and Fussel in humans) are a subfamily of central nervous system (CNS) specific proteins related to Sno/Ski oncogenes. Their developmental and homeostatic roles are largely unknown. We previously showed that Drosophila CORL (dCORL; fussel in Flybase) functions between the Activin receptor Baboon and Ecdysone Receptor-B1 (EcR-B1) activation in mushroom body neurons of third instar larval brains. To better understand dCORL regulation and function we generated a series of reporter genes. We examined the embryonic and larval CNS and found that dCORL is regulated by stage specific interactions between intertwined activators and repressors spanning numerous reporters. The reporter AH.lacZ, which contains sequences 7-11kb upstream of dCORL exon1, reflects dCORL brain expression at all stages. Surprisingly, AH.lacZ was not detected in EcR-B1 expressing mushroom body neurons. In larvae AH.lacZ is coexpressed with Elav and the transcription factor Drifter in dILP2 insulin producing cells of the pars intercerebralis. The presence of dCORL in insulin producing cells suggests that dCORL functions non-autonomously in the regulation of EcR-B1 mushroom body activation via the modulation of insulin signaling. Overall, the high level of sequence conservation seen in all CORL/SKOR/Fussel family members and their common CNS specificity suggest that similarly complex regulation and a potential function in insulin signaling are associated with SKOR/Fussel proteins in mammals.
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Whole Genome Sequence and Comparative Genomics Analysis of Multi-drug Resistant Environmental Staphylococcus epidermidis ST59
Staphylococcus epidermidis is a major opportunistic pathogen primarily recovered from device-associated healthcare associated infections (DA-HAIs). Although S. epidermidis and other coagulase-negative staphylococci (CoNS) are less virulent than Staphylococcus aureus, these bacteria are an important reservoir of antimicrobial resistance genes and resistance-associated mobile genetic elements that can be transferred between staphylococcal species. We report a whole genome sequence of a multidrug resistant S. epidermidis (strain G6_2) representing multilocus sequence type (ST) 59 and isolated from an environmental sampling of a hotel room in London, UK. The genome of S. epidermidis G6_2 comprises of a 2408357 bp chromosome and six plasmids, with an average G+C content of 32%. The strain displayed a multi-drug resistance phenotype which was associated with carriage of 7 antibiotic resistance genes (blaZ, mecA, msrA, mphC, fosB, aacA-aphD, tetK) as well as resistance-conferring mutations in fusA and ileS. Antibiotic resistance genes were located on plasmids and chromosome. Comparative genomic analysis revealed that antibiotic resistance gene composition found in G6_2 was partly preserved across the ST59 lineage.
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Genomic Prediction Accounting for Genotype by Environment Interaction Offers an Effective Framework for Breeding Simultaneously for Adaptation to an Abiotic Stress and Performance Under Normal Cropping Conditions in Rice
Developing rice varieties adapted to alternate wetting and drying water management is crucial for the sustainability of irrigated rice cropping systems. Here we report the first study exploring the feasibility of breeding rice for adaptation to alternate wetting and drying using genomic prediction methods that account for genotype by environment interactions. Two breeding populations (a reference panel of 284 accessions and a progeny population of 97 advanced lines) were evaluated under alternate wetting and drying and continuous flooding management systems. The predictive ability of genomic prediction for response variables (index of relative performance and the slope of the joint regression) and for multi-environment genomic prediction models were compared. For the three traits considered (days to flowering, panicle weight and nitrogen-balance index), significant genotype by environment interactions were observed in both populations. In cross validation, predictive ability for the index was on average lower (0.31) than that of the slope of the joint regression (0.64) whatever the trait considered. Similar results were found for progeny validation. Both cross-validation and progeny validation experiments showed that the performance of multi-environment models predicting unobserved phenotypes of untested entrees was similar to the performance of single environment models with differences in predictive ability ranging from -6–4% depending on the trait and on the statistical model concerned. The predictive ability of multi-environment models predicting unobserved phenotypes of entrees evaluated under both water management systems outperformed single environment models by an average of 30%. Practical implications for breeding rice for adaptation to alternate wetting and drying system are discussed.
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Minimally invasive surgery for stage III colon adenocarcinoma is associated with less delay to initiation of adjuvant systemic therapy and improved survival
Abstract
Background
Minimally invasive surgery (MIS) may improve surgical recovery and reduce time to adjuvant systemic therapy after colon cancer resection. The objective of this study was to determine the effect of MIS on the initiation of adjuvant systemic therapy and survival in patients with stage III colon cancer.
Methods
The 2010–2014 National Cancer Database was queried for patients with resected stage III colon adenocarcinoma, and divided into MIS, which included laparoscopic and robotic approaches, and open surgery. Propensity-score matching was used to balanced open and MIS groups. The main outcome measures were delayed initiation of adjuvant systemic therapy (defined as > 8 weeks after surgery) and 5-year overall survival (OS). Multiple Cox regression was performed to identify independent predictors for 5-year OS, including an interaction between delayed systemic therapy and MIS, and adjusted for clustering at the hospital level.
Results
There were 86,680 patients that were included in this study. Overall, 45% (38,713) underwent MIS colectomy, of which 93% underwent laparoscopic and 7% robotic surgery. After matching, 33,183 open patients were balanced to 33,183 MIS patients. Patient, tumor, and facility characteristics were similar in the matched cohort. More patients in the MIS group received adjuvant therapy within 8 weeks of surgery (49% vs. 42%, p < 0.001), and fewer MIS patients did not receive any systemic therapy (30% vs. 35%, p < 0.001). Delayed initiation of systemic therapy > 8 weeks was associated with worse 5-year OS (HR 1.27, 95%CI 1.19–1.36). MIS was independently associated with improved survival (HR 0.92, 95%CI 0.86–0.97). This relationship remained even if 90-day mortality was excluded.
Conclusions
MIS approaches are associated with less delay to the initiation of adjuvant systemic therapy and improved survival in patients with stage III colon adenocarcinoma. Surgeons should favor MIS approaches for the treatment of stage III colon adenocarcinoma whenever possible.
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Residual mesorectum on postoperative magnetic resonance imaging following transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LapTME) in rectal cancer
Abstract
Background
The standard treatment for mid- and low-rectal cancer is total mesorectal excision. Incomplete excision is an important predictor of local recurrence after rectal cancer surgery. Transanal TME (TaTME) is a new treatment option in which the rectum is approached with both laparoscopic and transanal endoscopic techniques. The aim of the present study was to determine the prevalence and localisation of residual mesorectal tissue by postoperative magnetic resonance imaging (MRI) of the pelvis and compare this between TaTME and laparoscopic TME (LapTME) patients. In addition, we assessed correspondence with histopathological quality.
Methods
Two groups of patients with cT1–T3 rectal cancer who underwent TME surgery with primary anastomosis were included, each group consisting of 32 patients. Postoperative T2-weighted MRI of the pelvis was performed at least 6 months after TME surgery and evaluated by two radiologists independently. Residual mesorectum was defined as any residual mesorectal tissue detectable after TME. Localisation of the tissue was categorised in relation to height in the pelvis and position of the level of anastomosis.
Results
Residual mesorectal tissue was detected in 3.1% of TaTME patients and of 46.9% in LapTME patients (p < 0.001). Multivariate analysis identified only type of surgery as a significant risk factor for leaving residual mesorectum. Other known risk factors for incomplete TME, such as body mass index (BMI) and male gender, were not significant. No relation was seen between specimen quality and prevalence of residual mesorectum.
Conclusions
The completeness of mesorectal excision was significantly better with TaTME than with standard laparoscopic technique.
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Short-term outcomes of transanal completion total mesorectal excision (cTaTME) for rectal cancer: a case-matched analysis
Abstract
Background
Local excision of early rectal tumors as a rectal preserving treatment is gaining popularity, especially since bowel cancer screening programs result in a shift towards the diagnosis of early stage rectal cancers. However, unfavorable histological features predicting high risk for recurrence within the "big biopsy" may mandate completion total mesorectal excision (cTME). Completion surgery is associated with higher morbidity, poorer specimen quality, and less favorable oncological outcomes compared to primary TME. Transanal approach potentially improves outcome of completion surgery for rectal cancer. The aim of this study was to compare radical completion surgery after local excision for rectal cancer by the transanal approach (cTaTME) with conventional abdominal approach (cTME).
Methods
All consecutive patients who underwent cTaTME for rectal cancer between 2012 and 2017 were case-matched with cTME patients, according to gender, tumor height, preoperative radiotherapy, and tumor stage. Surgical, pathological, and short-term postoperative outcomes were evaluated.
Results
In total, 25 patients underwent completion TaTME and were matched with 25 patients after cTME. Median time from local excision to completion surgery was 9 weeks in both groups. In the cTaTME and cTME groups, perforation of the rectum occurred in 4 and 28% of patients, respectively (p = 0.049), leading to poor specimen quality in these patients. Number of harvested lymph nodes was higher after cTaTME (median 15; range 7–47) than after cTME (median 10; range 0–17). No significant difference was found in end colostomy rate between the two groups. Major 30-day morbidity (Clavien–Dindo≥ III) was 20 and 32%, respectively (p = 0.321). Hospital stay was significantly longer after cTME.
Conclusion
TaTME after full-thickness excision is a promising technique with a significantly lower risk of perforation of the rectum and better specimen quality compared to conventional completion TME.
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Intraocular pressure increases after complex simulated surgical procedures in residents: an experimental study
Abstract
Background
Surgeons' overload is one of the main causes of medical errors that might compromise patient safety. Due to the drawbacks of current options to monitor surgeons' load, new, sensitive, and objective indices of task (over)load need to be considered and tested. In non-health-care scenarios, intraocular pressure (IOP) has been proved to be an unbiased physiological index, sensitive to task complexity (one of the main variables related to overload), and time on task. In the present study, we assessed the effects of demanding and complex simulated surgical procedures on surgical and medical residents' IOP.
Methods
Thirty-four surgical and medical residents and healthcare professionals took part in this study (the experimental group, N = 17, and the control group, N = 17, were matched for sex and age). The experimental group performed two simulated bronchoscopy procedures that differ in their levels of complexity. The control group mimicked the same hand-eye movements and posture of the experimental group to help control for the potential effects of time on task and re-measurement on IOP. We measured IOP before and after each procedure, surgical performance during procedures, and perceived task complexity.
Results
IOP increased as consequence of performing the most complex procedure only in the experimental group. Consistently, residents performed worse and reported higher perceived task complexity for the more complex procedure.
Conclusions
Our data show, for the first time, that IOP is sensitive to residents' task load, and it could be used as a new index to easily and rapidly assess task (over)load in healthcare scenarios. An arousal-based explanation is given to describe IOP variations due to task complexity.
Graphical Abstract
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Quality of life after rectal cancer surgery: differences between laparoscopic and transanal total mesorectal excision
Abstract
Background
Transanal total mesorectal excision (TaTME) is a safe alternative to laparoscopic TME for mid and low rectal cancer. TaTME allows improved visualization of the surgical planes and margins, and may potentially improve oncological outcomes. However, functional results after total mesorectal excision (TME) are variable and there are currently only a few published studies that include functional data related to the outcomes of TaTME.
Methods
Fifty-four consecutive patients were included in this study: one group included 27 patients who underwent laparoscopic low anterior and the other included 27 patients who underwent TaTME. All patients were asked to complete five questionnaires related to quality of life (QOL) and function [EQ-5D-3L, EORTC-QLQ C30, EORTC-QLQ C29, Low Anterior Resection Syndrome score (LARS), and International Prostate Symptom Score IPSS]. All TaTME patients were operated on at The Gelderse Vallei Hospital by a single surgeon and had a follow-up of at least 6.6 months.
Results
The EORTC-QLQ C30 and EQ-5D-3L questionnaires showed comparable outcomes in terms of QOL between the two groups. Almost all items evaluated by the EORTC-QLQ C29, including sexual outcomes, were similar between the two groups. One item concerning fecal incontinence, however, was scored worse for TaTME. There were no significant differences between the groups in terms of LARS symptoms or urinary function.
Conclusions
Patients undergoing laparoscopic or transanal TME showed comparable functional and QOL outcomes. Although the TaTME technique is still evolving, this study indicates that this technique is a safe alternative to laparoscopic surgery in terms of functional outcomes for mid and low rectal cancers.
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Three- dimensional microstructural reconstruction of the ovine intervertebral disc using ultra-high field MRI
The intervertebral disc (IVD) is a complex organ which acts as a flexible coupling between two adjacent vertebral bodies and must therefore accommodate compression, bending and torsion. It consists of three main components which are elegantly structured to allow this: the annulus fibrosus (AF), the nucleus pulposus (NP) and the end-plates (EP).
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Responsiveness of the PROMIS, NDI and ODI Instruments in Patients with Spinal Disorders
The Patient-Reported Outcomes Information System (PROMIS) instruments are an important advancement in the use of PROs, but need to be evaluated with longitudinal data to determine whether they are responsive to change in specific clinical populations.
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Jingshu Keli attenuates cervical spinal nerve ligation-induced allodynia in rats through inhibition of spinal microglia and Stat3 activation
Cervical radicular pain resulting from mechanical compression of a spinal nerve secondary to spinal degenerative alternations negatively impacts patients' quality of life. Jingshu Keli (JSKL), a traditional Chinese medicine formula with multiple active compounds, has been prescribed for pain management in patients with cervical radiculopathy for decades. Two major components of JSKL, ferulic acid and cinnamaldehyde, were identified to have anti-inflammation effect via inhibiting activation of Stat3.
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Does the site of primary colorectal cancer influence the outcome after resection of isolated liver metastases?
In unresectable patients with metastatic colorectal cancer (CRC), the site of the primary is a strong prognostic factor warranting major adjustments in palliative medical treatment. Initial results suggested that the site of CRC influences prognosis after curative resection of colorectal liver metastases (CLM). In this study, we evaluated outcome after resection of isolated CLM with regard to the location of the primary.
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Outcome after liver transplantation in elderly recipients (>65 years) – a single-center retrospective analysis
Liver transplantation (LT) in elderly recipients is controversially discussed in the literature with only little data on long-term outcome available. We aimed to evaluate the safety and efficiency of LT in elderly recipients ( > 65yrs).
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Temporal relationship between arousals and Cheyne-Stokes respiration with central sleep apnea in heart failure patients
Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is a common disorder in patients with heart failure and reduced left ventricular ejection fraction (Oldenburg et al. 2016), and is typically associated with a high number of arousals from sleep (Hanly et al., 1989; Sin et al., 1999; Vazir et al., 2007). Both phenomena occur predominantly during stage 1 (N1) and 2 (N2) non-rapid eye movement (NREM) sleep (Hanly et al., 1989).
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Visual Rehabilitation Training Alters Attentional Networks in Hemianopia: an fMRI study
Post-geniculate damage of the visual system leads to homonymous hemianopia which affects about 30% or more of all cases of stroke or brain trauma (Pambakian et al. , 1997). Hemianopia greatly reduces quality of life, affecting reading, driving and spatial navigating of patients (Das et al. , 2010). Several strategies for visual field restoration have been introduced (for review see Sabel et al. (2011)). For example, Kasten et al. (1998) showed that patients trained with light detection tasks in areas of residual vision (ARV) had significantly enlarged visual fields.
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Optimal timing and differential significance of postoperative awake and sleep EEG to predict seizure outcome after temporal lobectomy
Postoperative EEG is useful for predicting the seizure outcome and to make decisions about antiepileptic drug (AED) withdrawal following epilepsy surgery (Rathore and Radhakrishnan, 2010; Rathore et al., 2011c). Presence of interictal epileptiform discharges (IEDs) on a single postoperative EEG is associated with an increased risk of unfavorable seizure outcome and a higher risk of seizure recurrence on AED withdrawal following temporal and extratemporal surgeries (Menon et al., 2012; Rathore et al., 2011b,2011c; Rathore and Radhakrishnan, 2010).
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Retinal ganglion cell function in recovered optic neuritis: faster is not better
Multiple sclerosis (MS) is a chronic demyelinating disease affecting neurons and their axons at multiple sites in the central nervous system (Peterson et al., 2001, Martinez-Lapiscina et al., 2014). The visual system is highly susceptible to damage from MS (Balcer et al., 2015, Graham and Klistorner, 2017). In fact, optic neuritis (ON) is a common ophthalmological feature in MS patients, which is characterized by loss of visual acuity (VA) and visual field (Chen and Gordon, 2005, Jasse et al., 2013) that generally recover to normal after several months.
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Small sharp spikes as EEG markers of mesiotemporal lobe epilepsy
Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy (Asadi-Pooya et al., 2016; Stern and Engel Jr., 2015). It classically presents with focal seizures with aura, automatisms, impaired awareness, and sometimes progression to generalized convulsive seizures. However, the diagnostic evaluation of patients with mTLE can be prolonged and imperfect because pathological hippocampal activity cannot consistently be identified on scalp EEG (Koessler et al., 2015; Ramantani et al., 2016).
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Resting cranial and upper cervical muscle activity is increased in patients with migraine
The International Classification of Headache Disorders (ICHD) considers muscle to be relevant in tension-type headache, but does not address its relevance in migraine (Headache Classification Committee of the International Headache, 2013). There have been many studies since the 1970s examining the role of muscle in migraine as well as in tension-type headache, mostly qualitative (Bakal et al., 1977, Tfelt‐Hansen et al., 1981, Bakke et al., 1982, Clifford et al., 1982, Lous et al., 1982, Ahles et al., 1988, Celentano et al., 1990, Lebbink et al., 1991, Jensen et al., 1993, Blau et al., 1994, Burnett et al., 2000, Hagen et al., 2002, Ebinger, 2006, Leistad et al., 2006, Fernández‐de‐las‐Peñas et al., 2008, Hung et al., 2008, Oksanen et al., 2008, Blaschek et al., 2012, Watson et al., 2012, Didier et al., 2015, Landgraf et al., 2015).
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Dextromethorphan/Quinidine for Pseudobulbar Affect Following Stroke: Safety and Effectiveness in the PRISM II Trial
Dextromethorphan (DM)/quinidine (Q) was approved for pseudobulbar affect (PBA) treatment based upon efficacy and safety trials in patients with PBA secondary to amyotrophic lateral sclerosis or multiple sclerosis. The PRISM II trial evaluated DM/Q as PBA treatment in patients with stroke, dementia or traumatic brain injury.
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Pregnancy Results in Lasting Changes in Knee Joint Laxity
Altered joint laxity may contribute to joint dysfunction. Knee joint laxity has been shown to increase during pregnancy, but its long-term persistence is unknown.
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Cardiovascular Risk Factors Among Older Adults With Long-Term Spinal Cord Injury
Individuals with spinal cord injury (SCI) now live longer, which increases the risk of cardiovascular disease. Knowledge of cardiovascular risk factors amenable to intervention are therefore needed to support their healthy aging.
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Safety Considerations in Prescription of NSAIDs for Musculoskeletal Pain: A Narrative Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the treatment of painful musculoskeletal conditions. When prescribing oral NSAIDs, clinicians must consider coexisting cardiovascular, cerebrovascular, gastrointestinal and renal disease as oral NSAIDs are associated with a broad spectrum of adverse effects on these systems. The varying safety profiles of NSAIDs can be attributed to differences in the extent to which the drug inhibits cyclooxygenase (COX)-1 versus COX-2 and their potential for drug-drug interactions.
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Predictors of Performance on the American Board of Physical Medicine and Rehabilitation Maintenance of Certification Examination
Maintenance of certification (MOC) in Physical Medicine and Rehabilitation is a process of lifelong learning which begins after successfully completing an Accreditation Council of Graduate Medical Education (ACGME) accredited residency and passing the American Board of Physical Medicine and Rehabilitation (ABPMR) Part I and Part II Examinations. We seek to identify factors predictive of successful MOC Examination performance.
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Quantifying and reducing retained botulinum toxin post-injection
Retained botulinum toxin solution may be visible in vials and syringe tips after mixing and presumed complete injections, leaving patients without the full prescribed dose.
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Can a brief training session prepare physician sonographers of differing experience to measure the ischiofemoral space? A reliability study
The primary aim of this study was to determine the inter-rater and intra-rater reliability of ultrasound (US) measurements of the ischiofemoral space (IFS) following a brief training session. A secondary aim was to determine if reliability correlated with sonographer experience.
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Botulinum toxin: Techniques within pediatric physiatry
Intramuscular botulinum toxin injections are utilized for treatment of focal spasticity in children, particularly in those with a diagnosis of cerebral palsy. There are a variety of techniques used when performing botulinum toxin injections without clear standards for pediatric providers.
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Breakdancing on actin
Breakdancing on actin
Breakdancing on actin, Published online: 02 July 2018; doi:10.1038/s41576-018-0033-y
Two independent studies now show that polymerization of branched actin at DNA double-strand breaks (DSBs) mediates chromatin dynamics associated with homology-directed repair and is required for a robust and error-free DSB repair process.
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Effects of Warm-Up, Post-Warm-Up, and Re-Warm-Up Strategies on Explosive Efforts in Team Sports: A Systematic Review
Abstract
Background
In team sports, it is imperative that the warm-up improves acute explosive performance. However, the exact strategies, methods, and consequences of different warm-up practices remain unclear. A time delay between the warm-up and match and during half-time could negate the positive metabolic effects of the warm-up.
Objectives
We conducted a systematic review to synthesize and analyze the potential effects of strategies during a warm-up (before match), post-warm-up (time between the end of warm-up and the start of a match), and re-warm-up (half-time break within a match) on explosive performance in team sports. Furthermore, we examined optimal warm-up strategies based on the included studies.
Methods
We performed a search of four databases (Web of Science, Scopus, PubMed, and ScienceDirect) for original research articles published between January 1981 and August 2017. A total of 30 articles met the inclusion criteria, and the Cochrane risk of bias tool was used to assess the risk of bias. The results of the included studies were recalculated to determine effect sizes using Cohen's d.
Results
A warm-up comprising 8 sets of 60-m sprints (− 2.19%, d = 1.20) improved sprint performance. Additionally, 7 min of dynamic exercises after 5 min of jogging improved sprint (− 7.69%, d = 1.72), jumping (8.61%, d = 0.61), and agility performance (− 6.65%, d = 1.40). The use of small-sided games also seems to be a valid strategy, especially for jumping performance (6%, d = 0.8). These benefits resulted from the warm-up strategies combined with some passive rest (between 2 and 10 min) before the main performance. In this post-warm-up period, the use of heated garments could result in better outcomes than simple rest (− 0.89%, d = 0.39). However, if the transition was longer than 15 min, before entering the match, performing a re-warm-up with short-term explosive tasks to reactivate was the most effective approach (− 1.97%, d = − 0.86). At half-time, heated garments maintained better sprint (− 1.45%, d = 2.21) and jumping performance (3.13%, d = 1.62).
Conclusion
Applying properly structured strategies in the warm-up and avoiding a long rest in the post-warm-up improves explosive performance. Studies tend to recommend a short active warm-up strategy (10–15 min), gradually increasing intensity (~ 50–90% of maximum heart rate), and the use of heated garments soon after the warm-up to maintain muscle temperature. However, 2 min of active re-warm-up with short-term sprints and jumps should be needed for transitions longer than 15 min (~ 90% of maximum heart rate). Last, at the half-time re-warm-up, combining heated garments to maintain muscle temperature and performing an active strategy, with explosive tasks or small-sided games for 5 min before re-entering the game, resulted in better explosive performance than 15 min of resting.
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Depression, Anxiety, Post-traumatic Stress Disorder and a History of Pervasive Gender-Based Violence Among Women Asylum Seekers Who Have Undergone Female Genital Mutilation/Cutting: A Retrospective Case Review
Abstract
We sought to evaluate the frequency of anxiety, depression, PTSD, and any experiences of violence in women who had undergone Female Genital Mutilation/Cutting (FGM/C) and were seeking asylum in the United States. We undertook a retrospective qualitative descriptive study of FGM/C cases seen in an asylum clinic over a 2-year period. Standardized questionnaires provided quantitative scores for anxiety, depression and PTSD. Clients' personal and physician medical affidavits were analyzed for experiences of violence. Of the 13 cases, anxiety and depression were exhibited by 92 and 100% of women, while all seven women screened for PTSD had symptoms. Qualitative analysis revealed extensive violence perpetrated against these women, demonstrating that FGM/C is only part of the trauma experienced. The high level of mental health disorders and endured violence has implications for providers working with FGM/C survivors and indicates the need for accessible mental health services and trauma-informed care.
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Breast and Colorectal Cancer Screening Barriers Among Immigrants and Refugees: A Mixed-Methods Study at Three Community Health Centres in Toronto, Canada
Abstract
Mammography and fecal occult blood testing (FOBT) improve the detection, management, and prognosis of breast and colorectal cancer, respectively, but are underperformed in the recent immigrant and refugee population. We aimed to identify barriers to screening and potential solutions in this population. A mixed-methods study involving a retrospective chart review and focus group interviews was conducted, with data analyzed using univariate logistic regression and thematic analysis, respectively. Mammography completion was associated with greater time in Canada (p = 0.01) and region of origin (p = 0.04), while FOBT completion was associated with region of origin (p = 0.03). Barriers included time constraints, language and cultural differences, and poor interprofessional communication. This study of recent immigrants and refugees identifies barriers to screening and supports potential solutions including culturally-congruent peer workers, targeted screening workshops, and visual screening aids. Further work is needed to address the unique healthcare needs of this diverse and growing population.
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