bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for latent tuberculosis in patients with inflammatory bowel disease under antitumor necrosis factor: data from a Portuguese center
Authors: Sousa Mafalda , Ladeira Inês , Ponte Ana , Fernandes Carlos , Rodrigues Adélia , Silva Ana P. , Silva João , Gomes Catarina , Afeto Edgar , Carvalho João
Published: June 2019

Introduction

Portugal is one of the countries with the highest tuberculosis (TB) burden in the European Union. Patients who are receiving antitumor necrosis factor (TNF) treatment should be screened and treated for latent tuberculosis infection (LTBI). This study aimed to evaluate the prevalence of LTBI and the number of active TB cases in patients with inflammatory bowel disease (IBD) treated with anti-TNF agents.

Patients and methods

This was a retrospective study from a Portuguese center that included patients with IBD who started anti-TNF treatment between 2013 and 2017. LTBI screening was considered positive in case of positive tuberculin skin test, positive/indeterminate interferon gamma release test, or history of exposure to TB irrespective of the results of the screening.

Results

One hundred and seventeen patients were included, 56% female, mean age 40 years; 91% had Crohn’s disease; infliximab was initiated in 79%, adalimumab in 21%, and golimumab in 1%. Of these, 37 (32%) presented LTBI – tuberculin skin test was positive in 18 (49%) patients; interferon gamma release test was positive in 14 (38%) patients and undetermined in seven (19%); and there was a history of exposure in 12 (32%) patients. All patients screened with LTBI were on isoniazid for 9 months. During follow-up (mean 21.6 months), one patient under infliximab developed pleural TB 5 years after receiving treatment with isoniazid. None of the patients with negative LTBI screening developed active TB.

Conclusion

In this sample of patients with IBD, the prevalence of LTBI before starting anti-TNF treatment was significant (32%), but only one patient had active TB after LTBI treatment.
Sarcopenia impairs health-related quality of life in cirrhotic patients
Authors: Ando Yusuke , Ishigami Masatoshi , Ito Takanori , Ishizu Yoji , Kuzuya Teiji , Honda Takashi , Ishikawa Tetsuya , Fujishiro Mitsuhiro
Published: June 2019

Aim

Sarcopenia is associated with poor health-related quality of life (HRQOL) in the general population. However, in cirrhotic patients, as the development of sarcopenia is closely related to declined liver function, which also impairs HRQOL, whether sarcopenia deteriorates HRQOL independently from declined liver function remains unclear. The aim of this study was to clarify the impact of sarcopenia on HRQOL impairment in cirrhotic patients.

Patients and methods

A total of 88 cirrhotic patients [median age, 69 years; range: 31–79 years; 49 male (55.7%), 45 with hepatocellular carcinoma (51.1%)] were analyzed. We measured HRQOL using the 36-item Short-Form Health Survey version 2 questionnaire and identified factors contributing to scores lower than 50 in physical component summary (PCS), mental component summary, and role-social component summary (RCS) scores.

Results

Twenty-four (27.2%) patients had sarcopenia. PCS and RCS scores were significantly lower in patients with sarcopenia compared with those without sarcopenia. Patients with Child–Pugh (CP) classification B or C showed significantly lower scores in PCS and RCS than those with CP classification A. On multivariate analysis, the presence of sarcopenia was the only factor associated with low PCS scores [odds ratio (OR): 11.6; P = 0.031]. Female sex (OR: 3.34; P = 0.034), CP classification B or C (OR: 3.19; P = 0.037), and presence of sarcopenia (OR: 4.64; P = 0.016) were identified as independent factors for low RCS scores.

Conclusion

Sarcopenia independently impairs physical and role-social HRQOL in cirrhotic patients.
Gastrointestinal Polyposis in Pediatric Patients
Authors: MacFarland Suzanne P. , Zelley Kristin , Katona Bryson W. , Wilkins Benjamin J. , Brodeur Garrett M. , Mamula Petar
Published: June 2019

Gastrointestinal polyps are mucosal overgrowths that, if unchecked, can undergo malignant transformation. Although relatively uncommon in the pediatric age group, they can be the harbingers of multiorgan cancer risk and require close management and follow‐up. Additionally, as many polyposis syndromes are inherited, appropriate genetic testing and management of relatives is vital for the health of the entire family. In this review, we discuss both common and uncommon childhood gastrointestinal polyposis syndromes in terms of clinical presentation, management, and surveillance. We also detail any additional malignancy risk and surveillance required in the pediatric age group (<21 years old). Through this review, we provide a framework for gastroenterologists to manage the multifaceted nature of pediatric polyposis syndromes.
Diagnostic Delays in Children With Coeliac Disease in the Central European Region
Authors: Riznik Petra , De Leo Luigina , Dolinsek Jasmina , Gyimesi Judit , Klemenak Martina , Koletzko Berthold , Koletzko Sibylle , Korponay‐Szabó Ilma Rita , Krencnik Tomaz , Not Tarcisio , Palcevski Goran , Sblattero Daniele , Vogrincic Matej , Werkstetter Katharina Julia , Dolinsek Jernej
Published: June 2019

Objectives:

Coeliac disease (CD) is a systemic autoimmune disorder affecting about 1% of the population. Many patients remain undiagnosed or are diagnosed with substantial delay. We assessed diagnostic delays in symptomatic CD children in Central Europe (CE).

Methods:

Paediatric gastroenterologists in 5 CE countries retrospectively reported data of their patients diagnosed in 2016. Age at first CD‐related symptom(s), first visit to paediatric gastroenterologist and confirmed diagnosis were used to determine diagnostic delays.

Results:

Data from 393 children (65% girls, median age 7 years, range 7 months to 18.5 years) from Croatia, Hungary, Germany, Italy, and Slovenia were analysed. Median duration from first symptom(s) to visit to paediatric gastroenterologist was 5 months (range 0–10 years; preschool 4 months, school‐aged 5 months), and further duration until final diagnosis was 1 month (range 0–5 years) with significant regional differences (P < 0.001). Median diagnostic delay was 6 months (range 0–10 years; preschool 5 months, school‐aged 7 months). Type of clinical presentation had little, however, significant effect on delays. Reduced body mass in delays longer than 3 years compared with delays shorter than 1 year was found (z score −0.93 vs −0.39, P < 0.05).

Conclusions:

Time from first symptoms to CD diagnosis in children in 5 CE countries is slightly shorter compared with few other small paediatric studies, and significantly shorter than reported for adults. Nevertheless, delays of more than 3 years in 6.6% of children are worrisome. Raising awareness about the variable symptoms and implementation of reliable diagnostic tools will further reduce diagnostic delays.
Retroperitoneal Hemorrhage Caused by Trephine Biopsy
Authors: Mirtella Dora , Fedeli Piergiorgio , Cingolani Mariano , Vacchiano Giuseppe
Published: June 2019

The bone marrow biopsy is usually a safe procedure; however, it can occasionally present important complications. These complications are not always immediately evident or quickly diagnosed and may include pain at the biopsy site, trauma to neighboring structures, vascular injuries, infection, transient pressure neuropathies, pneumoretroperitoneum, and hemorrhage. Several risk factors are recognized, including thrombocytopenia, concurrent use of anticoagulants, and the presence of an underlying myeloproliferative disorder. While several reports of adverse events have been published, only 2 deaths attributable to this procedure have been reported. We present 2 cases of fatal hemorrhage after bone marrow biopsy.
Storage Conditions and Immunoreactivity of Breast Cancer Subtyping Markers in Tissue Microarray Sections
Authors: Omilian Angela R. , Zirpoli Gary R. , Cheng Ting-Yuan David , Yao Song , Stein Leighton , Davis Warren , Head Karen L. , Nair Priya , Khoury Thaer , Ambrosone Christine B. , Bshara Wiam
Published: June 2019

Loss of immunoreactivity in tissue sections has been shown to occur when slide sections are stored at room temperature for prolonged periods of time. We conducted a systematic investigation to determine the extent of staining loss in various storage conditions to determine an optimal storage method. We investigated 6 antibodies that are commonly used for breast cancer subtyping in research studies with immunohistochemistry (ER, PR, HER2, CK5/6, EGFR, and Ki67) in formalin-fixed paraffin-embedded breast tissue microarrays consisting of 148 patients. Tissue microarrays were sectioned at various time points: fresh, 1 week, 1 month, 6 months, and 12 months before staining. Slides sectioned at each time point were stored in 5 storage conditions: desiccator, paraffin dipped, 4°C, −20°C, and −80°C. Immunohistochemistry scores were assessed over time with McNemar Test and Bowker Test of Symmetry. Desiccator storage was the only storage condition that did not show any loss in immunoreactivity for any antibody or time point in our study. Paraffin coated slides were the most difficult storage method operationally and also showed the most loss in immunoreactivity. Storing sections in a desiccator was the most effective method for minimizing immunoreactivity loss. Cold storage at 4°C is an intermediate option that is not as protective as a desiccator, but offers the advantage of being accessible to virtually all research labs.
Not Always as It Seems
Authors: Staszel Joseph P. , Miknevich MaryAnn
Published: June 2019

Although generally presenting as a chronic, progressive peripheral neuropathy, we present a case of acute alcoholic neuropathy initially mistaken for acute Guillain-Barré syndrome. Electrodiagnostic evaluation of alcoholic neuropathy reveals an axonal neuropathy and may be complicated by demyelination if comorbid nutritional deficiencies are present. This is in contrast to the significant demyelination classically associated with Guillain-Barré syndrome. F waves, which are absent or prolonged in Guillain-Barré syndrome, are unaffected in alcoholic neuropathy. Further evaluation with lumbar puncture demonstrates normal protein and white blood cell counts in alcoholic neuropathy, as opposed to albuminocytologic dissociation characteristically present in acute Guillain-Barré syndrome.
Exercise Interventions for Individuals With Neurological Disorders
Authors: Lai Chien-Hung , Chen Hung-Chou , Liou Tsan-Hon , Li Wei , Chen Shih-Ching
Published: June 2019

Fall prevention requires a multifaceted approach that should include individual risk assessment and intervention strategies. Exercise interventions may mitigate most risk factors for falls (eg, balance impairment, gait impairment, and muscle weakness). Numerous systematic reviews or meta-analyses have assessed the effectiveness of exercise interventions among people with various types of neurological disorders; however, the evidence obtained has not been synthesized into an overview. Therefore, the present systematic review assessed systematic reviews of exercise intervention for fall prevention among people with neurological disorders. The research sources were the Cochrane Database of Systematic Reviews, PubMed, and Embase. Eligible studies were selected, and data were extracted independently by two reviewers. A total of 15 studies (six systematic reviews and nine meta-analyses) were included. These systematic reviews examined in this study have demonstrated that exercise interventions reduced the number, frequency, and rate of falls among people with neurological disorders, including cognitive impairment, dementia, and Parkinson disease. Furthermore, the current study presented insufficient evidence regarding the effectiveness of exercise interventions for fall prevention among people with stroke, multiple sclerosis, and diabetes mellitus with polyneuropathy. Therefore, additional investigations are necessary to evaluate the effectiveness of exercise for fall prevention among people with multiple sclerosis, stroke, and diabetes mellitus with polyneuropathy.
Decreased Striatal Vesicular Monoamine Transporter Type 2 Correlates With the Nonmotor Symptoms in Parkinson Disease
Authors: Shi Xinchong , Zhang Yan , Xu Shaohua , Kung Hank F. , Qiao Hongwen , Jiang LuLu , Zhu Lin , Guo Qiyi , Yi Chang , Luo Ganhua , Wu Lei , Pei Zhong , Wang Jian , Zhang Xiangsong , Chen Ling
Published: June 2019

Objective

Nonmotor symptoms (NMS) are critical players in the patients' quality of life in Parkinson disease (PD). Vesicular monoamine transporter type 2 (VMAT2) has been reported owing to a role in affecting dopamine neurons in the striatum. Therefore, this study set out to characterize the relationship between VMAT2 distribution in the striatum in relation to the NMS in PD.

Methods

Totally, 21 age-matched normal controls and 37 patients with PD in the moderate stages were included, followed by examination using 18F-DTBZ (18F-AV133) PET/CT. The specific uptake ratio (SUR) of each striatal subregion was then determined with the occipital cortex as the reference background region. The overall NMSs of each individual patient were evaluated. Finally, the role of the striatal SURs in the clinical symptom scores were evaluated through the application of a Spearman correlation analysis as well as a multivariable stepwise regression analysis.

Results

Patients with PD, particularly those at a more advanced stage, exhibited a more pronounced reduction in SURs in the bilateral putamen and caudate nucleus (P < 0.05, vs healthy controls). Meanwhile, patients at more advanced PD stages were found to have significantly worse scores in NMS except cognitive function. The Spearman correlation analysis demonstrated that NMS scores, with the exception of cognition scores, were correlated with striatal SURs (P < 0.05).

Conclusion

The key findings of the study identified a correlation between decreased striatal VMAT2 with a broad spectrum of NMS in patients with PD, highlighting the association between diminished dopamine supply and the development of NMS in PD.
Total and Unilateral Peak Nasal Inspiratory Flow and Unilateral Visual Analogue Scale: Rationale in Indication and Outcomes of Septoplasty?
Authors: Schalek Petr , Guha Anasuya , Ondrová Tereza , Svoboda Milan
Published: June 2019

Septoplasty is one of the most frequently performed procedures in otorhinolaryngology. Proper selection of patients for septoplasty as well as examination is essential for good outcome of surgery. The aim of this study was to evaluate the suitability of combination of 2 simple, cheap, and easily performed examinations for indication and outcomes of septoplasty to evaluate the effectiveness in this type of surgery. Seventy patients were enrolled from 2 tertiary centers from the period of April 2017 to March 2018, who all underwent septoplasty for nasal septal deviation. Total and unilateral peak nasal inspiratory flow (PNIF), unilateral visual analogue scale, and nasal endoscopy for indication and outcomes of septoplasty were performed. Furthermore, assessment of possible correlation between subjective and objective data before and 3 months after septoplasty was done. Statistical analysis was carried out on the obtained data. Postoperatively the total and both unilateral PNIF measurements increased significantly compared with corresponding preoperative values and similarly means of visual analogue scale scores on both sides decreased 3 months after the procedure. No significant correlation was seen between objective and subjective outcomes neither before the surgery, nor postoperatively. The study confirmed the suitability of using PNIF as a simple and inexpensive tool that can be a reasonable alternative to rhinomanometry and which is able to reflect changes after septoplasty. Simultaneously, along with the expected improvement in the total PNIF and unilateral PNIF on deviated side, a slight but significant improvement in PNIF values on the nondeviated side was also demonstrated.
Examining outcomes in cases of elderly patients who fell from ground level at home with normal vital signs at the scene: An analysis of the National Trauma Data Bank
Authors: Ahmed Nasim , Greenberg Patricia
Published: June 2019

BACKGROUND

The purpose of the study was to evaluate whether the higher level of care significantly affected the outcomes of elderly patients who fell from ground level at home and had a normal physiological examination at the scene.

METHODS

Patients 65 years and older, with normal physiological measures at the scene (Glasgow Coma Scale score = 15, systolic blood pressure > 90 and <160 mm Hg, heart rate (HR) ≥ 60 and ≤100) from the 2012 to 2014 National Trauma Data Bank data sets were included in the study. Patients' characteristics, existing comorbidities, and outcomes were compared between Level I or Level II designated trauma centers (higher level care [group 1]) and Levels III, IV, and unranked/nontrauma centers (lower level care [group 2]). Following initial analyses, propensity score matching was performed, and the rate of in-hospital mortality, median time (days) to death or discharge, and discharge disposition were compared.

RESULTS

Of the 40,800 patients who met inclusion criteria, 18,813 patients were matched from each group on age, sex, race, systolic blood pressure, HR, respiratory rate, Injury Severity Score, and comorbidity statuses. There was no evidence of a significant difference regarding in-hospital mortality (2.5% vs. 2.3%), time to death (median [interquartile range]: 6 [3–11] vs. 6 [3–11]), or time to hospital discharge (median [interquartile range]: 5 [5–5] vs. 5 [5–5]). However, the rate of required postdischarge care (78.9% vs. 81.7%) varied significantly between the groups.

CONCLUSION

Higher levels of care failed to show any significant survival benefits or shorten the time to hospital discharge; however, a significantly higher proportion of patients from lesser-care facilities required follow-up services after discharge.

LEVEL OF EVIDENCE

Therapeutic/Care management, level IV.

STUDY TYPE

Observational case-control.
Optimizing energy expenditure and oxygenation toward ventilator tolerance is associated with lower ventilator and intensive care unit days
Authors: Ang Darwin , Chari Ravi , Garcia Alejandro , Clark Jason , Farrah Jason , Hagan Joshua , Watson Carrie , Richards Winston , Liu Huazhi , Donaldson Dinah , Barde Jason , Alderman Ted
Published: June 2019

BACKGROUND

We hypothesize that if both energy expenditure and oxygenation are optimized (EEOO) toward ventilator tolerance, this would provide patients with the best condition to be liberated from the ventilator. We defined ventilator tolerance as having a respiratory quotient value between 0.7 and 1.0 while maintaining saturations above 98% with FIO2 70% or less and a normal respiratory rate without causing disturbances to the patient's pH.

METHODS

This is a single-institution prospective cohort study of ventilator dependent patients within a closed trauma intensive care unit (ICU). The study period was over 52 months. A total of 1,090 patients were part of the primary analysis. The test group (EEOO) was compared to a historical cohort, comparing 26 months in each study group. The primary outcome of this study was number of ventilator days. Secondary outcomes included in-hospital mortality, ICU length of stay (LOS), overall hospital length of stay, tracheostomy rates, reintubation rates, and in-hospital complication rates, such as pneumonia and Acute Respiratory Distress Syndrome (ARDS) ARDS. Both descriptive and multivariable regression analyses were performed to compare the effects of the EEOO protocol with our standard protocols alone.

RESULTS

The primary outcome of number of ventilator days was significantly shorter the EEOO cohort by nearly 3 days. This was significant even after adjustment for age, sex, race, comorbidities, nutrition type, and injury severity, (4.3 days vs. 7.2 days, p = 0.0001). The EEOO cohort also had significantly lower ICU days, hospital days, and overall complications rates.

CONCLUSION

Optimizing the patient's nutritional regimen to ventilator tolerance and optimizing oxygenation by means of targeted pulmonary mechanics and inspired FIO2 may be associated with lower ventilator and ICU days, as well as overall complication rates.

LEVEL OF EVIDENCE

Therapeutic, Level IV.
Performance of Creatinine Clearance and Estimated GFR in Assessing Kidney Function in Living Donor Candidates
Authors: Garg Neetika , Snyder Grace , Li Jianbo , Mandelbrot Didier , Poggio Emilio D.
Published: June 2019

Background.

Glomerular filtration rate (GFR) assessment is a key aspect in the evaluation of living kidney donor candidates; however, data on performance of commonly used methods are limited.

Methods.

We examined 769 living kidney donor candidates with 24-hour urine collections assessed as accurate by comparing measured creatinine excretion rate (CER) to CER estimated using a 4-variable equation previously developed and validated using robust methodology.

Results.

Of all collections, 42.6% would have been deemed inaccurate, mostly under-collections, using the conventional weight- and gender-based CER estimation. Creatinine clearance (CrCl) overestimated 125I-iothalamate GFR (iGFR), estimated GFR (eGFR), underestimated iGFR, and their average [Avg (CrCl and eGFR)] essentially eliminated the GFR bias (median bias = +2.2, −5.4, and −1.0 mL/min/1.73 m,2 respectively; P < 0.001). This held true for all subgroups except blacks, where all 3 measures overestimated iGFR. Avg (CrCl and eGFR) also offered modestly improved accuracy compared with CrCl alone, as measured by the proportion of values falling within 10% (50.7% versus 45.3%; P = 0.009) and 30% of iGFR (94.5% versus 89.3%; P < 0.001).

Conclusions.

When measured GFR is unavailable, the Avg (CrCl and eGFR) provides a better estimate of kidney function in kidney donor candidates than either measure alone, although in blacks the estimates are neither better nor worse.
Long-term Effects of Hypothermic Ex Situ Perfusion on Skeletal Muscle Metabolism, Structure, and Force Generation After Transplantation
Authors: Gok Emre , Kubiak Carrie A. , Guy Erin , Ponder Mathew , Hoenerhoff Mark J. , Rojas-Pena Alvaro , Kemp Stephen W.P. , Bartlett Robert H. , Ozer Kagan
Published: June 2019

Background.

Hypothermic ex situ perfusion (HESP) systems are used to prolong allograft survival in solid organ transplantations and have been shown to be superior to static cold storage (SCS) methods. However, the effect of this preservation method on limb allograft survival and long-term function has not yet been tested. In this study, we investigated the long-term effects of the HESP on skeletal muscle metabolism, structure, and force generation and compared it with the current standard of preservation.

Methods.

Forty male Lewis rats (250 ± 25 g) were divided into 5 groups, including naive control, sciatic nerve transection or repair, immediate transplantation, SCS, and HESP. For the SCS group, limbs were preserved at 4°C for 6 hours. In the HESP group, limbs were continuously perfused with oxygenated histidine-tryptophan-ketoglutarate (HTK) solution at 10–15°C for 6 hours. Hemodynamic and biochemical parameters of perfusion were recorded throughout the experiment. At 12 weeks, electromyography and muscle force measurements (maximum twitch and tetanic forces) were obtained along with muscle samples for histology and metabolomics analysis.

Results.

Histology demonstrated 48% myocyte injury in the HESP group compared with 49% in immediate transplantation (P = 0.96) and 74% in the SCS groups (P < 0.05). The maximum twitch force measurement revealed a significantly higher force in the HESP group compared with the SCS group (P = 0.029). Essential amino acid levels of the gastrocnemius muscle did not reach significance, with the exception of higher proline levels in the HESP group.

Conclusions.

HESP using HTK protects viability of the limb but fails to restore muscle force in the long term.
Amyloidosis Diagnosed in Solid Organ Transplant Recipients
Authors: Sharpley Faye A. , Fontana Marianna , Gilbertson Janet A. , Gillmore Julian D. , Hawkins Philip N. , Mahmood Shameem , Manwani Richa , Martinez-Naharro Ana , Quarta Cristina , Rezk Tamer M. , Rowczenio Dorota , Sachchithanantham Sajitha , Whelan Carol J. , Wechalekar Ashutosh D. , Lachmann Helen J.
Published: June 2019

Background.

Development of amyloidosis post solid-organ transplantation has not been reported, although plasma cell neoplasms are a rare form of posttransplant lymphoproliferative disorder, which could be complicated by light chain amyloidosis (AL) amyloidosis.

Methods.

We searched our database of 5112 patients seen between 1994 and 2018 with a diagnosis of amyloidosis post solid-organ transplant. Patients were excluded if the amyloid diagnosis preceded the transplant date. The indication and type of organ transplant were recorded in addition to the amyloidosis type, organs involved, treatment given, and survival.

Results.

Thirty patients were identified. The median age at diagnosis with amyloidosis was 52 years (range 33–77). The median time from transplantation to diagnosis was 10.5 years (0.58–36). The grafts were kidney (N = 25, 83.3%), liver (N = 2, 6.7%), heart (N = 2, 6.7%), and combined heart, lung, and kidney (N = 1, 3.3%). The type of amyloidosis was systemic AL (N = 14, 47%), serum amyloid A amyloidosis (AA) (N = 11, 37%), localized AL (N = 3, 10%), wild-type transthyretin amyloidosis (ATTR) (N = 1, 3.3%), and amyloid of uncertain type (N = 1, 3.3%). Renal graft dysfunction was seen in 11 of 25 (44%) cases. Median graft survival was 185 months (96–269), and median survival from diagnosis with amyloidosis was 45 months (2–89); median survival by amyloidosis type was localized AL: 64 months (20–67), systemic AL: 23.5 months (0–95), ATTR amyloidosis: 17 months, and AA, 15 months (0–77).

Conclusions.

This series is the first description of amyloidosis post solid-organ transplant; 30 cases among 5112 amyloid patients >24 years suggests that amyloidosis may occur post solid-organ transplantation with an overall poor survival.
Geographic Differences in Population Health and Expected Organ Supply in the Gulf Coast Region of the United States Compared to Non-Gulf States
Authors: Reed Rhiannon D. , Shelton Brittany A. , Mustian Margaux N. , MacLennan Paul A. , Sawinski Deirdre , Locke Jayme E.
Published: June 2019

Background.

The Final Rule aimed to reduce geographic disparities in access to transplantation by prioritizing the need for transplant over donor proximity. However, disparities in waiting times persist for deceased donor kidney transplantation. The kidney allocation system implemented in 2014 does not account for potential local supply based on population health characteristics within a donation service area (DSA). We hypothesized that regions with traditionally high rates of comorbid disease, such as the states located along the Gulf of Mexico (Gulf States), may be disadvantaged by limited local supply secondary to poor population health.

Methods.

Using data from the Robert Wood Johnson Foundation County Health Rankings, the United States Renal Data System, and the Scientific Registry of Transplant Recipients, we compared population-level characteristics and expected kidney donation rates by Gulf States location.

Results.

Prevalence of African American ethnicity, end-stage renal disease, diabetes, fair/poor self-rated health, physical inactivity, food insecurity, and uninsurance were higher among Gulf State DSAs. On unadjusted analyses, Gulf State DSAs were associated with 3.52 fewer expected kidney donors per 100 eligible deaths than non-Gulf States. After adjustment, there was no longer a statistically significant difference in expected kidney donation rate.

Conclusions.

Although Gulf State DSAs have lower expected donation rates, these differences appear to be driven by the prevalence of health factors negatively associated with donation rate. These data suggest the need to discuss population health characteristics when examining kidney allocation policy, to account for potential lower supply of donors and to further address geographic disparities in access to kidney transplantation.
Effects of Left Versus Right Dorsolateral Prefrontal Cortex Repetitive Transcranial Magnetic Stimulation on Affective Flexibility in Healthy Women: A Pilot Study
Authors: Lantrip Crystal , Delaloye Sibylle , Baird Lauren , Dreyer-Oren Sarah , Brady Robert E. , Roth Robert M. , Gunning Faith , Holtzheimer Paul
Published: June 2019

Objective:

To determine the antidepressant mechanism of action for repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) in healthy women. Our primary hypothesis was that a single session of left DLPFC rTMS, compared with a session of right DLPFC rTMS, would result in better (reduced) negative nonaffective switch costs in healthy women.

Background:

The antidepressant mechanism of action for rTMS is not clear. It is possible that rTMS to the DLPFC improves emotion regulation, which could be a part of its antidepressant mechanism.

Methods:

Twenty-five healthy women were randomized to receive left high-frequency (HF) rTMS versus right HF rTMS in one session and then contralateral stimulation during a second session. Emotion regulation was assessed via switch costs for reappraisal of negatively valenced information on an affective flexibility task.

Results:

For negative nonaffective switch costs, the interaction effect in the two-way ANOVA was not significant (F
1,19=3.053, P=0.097). Given that left HF rTMS is the approved treatment for depression, post hoc t tests were completed with particular interest in the left-side findings. These tests confirmed that negative nonaffective switch costs significantly improved immediately after left rTMS (t
1,19=2.664, P=0.015) but not right rTMS.

Conclusions:

These findings suggest that left DLPFC HF rTMS may lead to antidepressant effects by improving the regulation of emotion.
Circulating concentrations of micro-nutrients and risk of breast cancer: A Mendelian randomization study
Authors: Papadimitriou N. , Dimou N. , Gill D. , Tzoulaki I. , Murphy N. , Riboli E. , Lewis S. J. , Martin R. M. , Gunter M. J. , Tsilidis K. K.
Published: June 2019

Background

The epidemiological literature reports inconsistent associations between consumption or circulating concentrations of micro-nutrients and breast cancer risk. We investigated associations between genetically determined concentrations of 11 micro-nutrients (beta-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, vitamin B12 and zinc) and breast cancer risk using Mendelian randomization (MR).

Materials and methods

A two-sample MR study was conducted using 122,977 women with breast cancer, of whom 69,501 were estrogen receptor positive (ER+ve) and 21,468 were ER−ve, and 105,974 controls from the Breast Cancer Association Consortium. MR analyses were conducted using the inverse variance weighted approach, and sensitivity analyses were conducted to assess the impact of potential violations of MR assumptions.

Results

One standard deviation (SD: 0.08 mmol/L) higher genetically determined concentration of magnesium was associated with a 17% (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.10 to 1.25, P=9.1 × 10−7) and 20% (OR: 1.20, 95% CI: 1.11 to 1.30, P=3.17 × 10−6) higher risk of overall and ER+ve breast cancer, respectively. An inverse association was observed for a SD (0.5 mg/dL) higher genetically determined phosphorus concentration and ER−ve breast cancer (OR: 0.84, 95% CI: 0.72 to 0.98, P=0.03). A suggestive inverse association was observed for a SD (0.48 mg/dL) higher genetically determined calcium concentration with overall breast cancer (OR: 0.91, 95% CI: 0.83 to 1.00, P=0.06). There was little evidence that any of the other nutrients were associated with breast cancer. The results for magnesium were robust under all sensitivity analyses.

Conclusions

Higher circulating concentrations of magnesium, phosphorus and calcium may affect breast cancer risk. Further work is required to replicate these findings and investigate underlying mechanisms.

key message

We conducted a Mendelian randomization study to investigate whether concentrations of 11 micro-nutrients are associated with risk of breast cancer. An increased risk of overall and oestrogen-receptor positive disease was observed for genetically higher concentrations of magnesium and inverse associations were observed for phosphorus and calcium concentrations

Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.
Kv4.1, a key ion channel for low frequency firing of dentate granule cells, is crucial for pattern separation
Authors: Kim Kyung-Ran , Lee Seung Yeon , Kim Yoonsub , Kwon Min Jeong , Jeong Hyeon-Ju , Lee Sanghyeon , Suh Young Ho , Kang Jong-Sun , Cho Hana , Lee Suk-Ho , Kim Myoung-Hwan , Ho Won-Kyung
Published: June 2019

The dentate gyrus (DG) in the hippocampus may play key roles in remembering distinct episodes through pattern separation, which may be subserved by the sparse firing properties of granule cells (GCs) in the DG. Low intrinsic excitability is characteristic of mature GCs, but ion channel mechanisms are not fully understood. Here, we investigated ionic channel mechanisms for firing frequency regulation in GCs of the rat hippocampus, and identified Kv4.1 as a key player. Immunofluorescence analysis showed that Kv4.1 was preferentially expressed in the DG, and its expression level was higher at 8-week than 3-week-old mice, suggesting a developmental regulation of Kv4.1 expression. With respect to firing frequency, GCs are categorized into two distinctive groups: low frequency (LF) and high frequency (HF) firing GCs. Input resistance (Rin) of most LF-GCs is lower than 200 MΩ, suggesting that LF-GCs are fully mature GCs. Kv4.1 channel inhibition by intracellular perfusion of Kv4.1 antibody increased firing rates and gain of the input-output relationship selectively in LF-GCs with no significant effect on resting membrane potential and Rin, but had no effect in HF-GCs. Importantly, mature GCs from mice depleted of Kv4.1 transcripts in the DG showed increased firing frequency, and these mice showed an impairment in contextual discrimination task. Our findings suggest that Kv4.1 expression occurring at late stage of GC maturation is essential for low excitability of DG networks and thereby contributes to pattern separation.
Opioid mortality following implementation of medical marijuana programs (1999-2017) in the United States
Authors: Kaufman Daniel E. , Nihal Asawer M. , Leppo Janan D. , Staples Kelly M. , McCall Kenneth L. , Piper Brian J.
Published: June 2019

The United States is in the midst of an opioid overdose epidemic. A prior report using the Center for Disease Control’s Wide-ranging Online Data for Epidemiologic Research (WONDER) database discovered that opioid overdoses decreased by 24.8% from 1999 to 2010 in states with medical cannabis (MC+) relative to those without (MC−). The present study evaluated any differences following MC legislation on WONDER reported opioid overdoses, corrected for population, from 1999 to 2017 using an interrupted time series. Overdoses were significantly higher in MC+ states from 2012-2017. The slope of opioid overdose deaths over time increased significantly post-implementation in states without MC (3-years Pre = 0.1 ± 0.1, 3-years Post = 0.7 ± 0.2, t(16) = 2.88, p ≤ .011). Overdose deaths showed a non-significant elevation in states with MC (Pre = 1.3 ± 0.3, Post = 2.8 ± 0.8, t(11) = 2.01, p = .069). Post-legalization slopes were significantly higher in MC+ than MC− (t(11.95) = 2.70, p < .05). Overall, any impact of medical cannabis laws on opioid overdoses appears modest. There are other confounds (e.g. death determination reporting quality) which differ non-randomly among states and are non-trivial to account for in ecological investigations of cannabis policy. Alternatively, the potency of fentanyl analogues may obscure any protective effects of MC against illicit opioid harms.
Evidence for transposable element control by Argonautes in a parasitic flatworm lacking the piRNA pathway
Authors: Protasio Anna V. , Rawlinson Kate A. , Miska Eric A. , Berriman Matt , Rinaldi Gabriel
Published: June 2019

Transposable elements (TEs) are mobile parts of the genome that can jump or self-replicate, posing a threat to the stability and integrity of the host genome. TEs are prevented from causing damage to the host genome by defense mechanisms such as nuclear silencing, where TE transcripts are targeted for degradation in an RNAi-like fashion. These pathways are well characterised in model organisms but very little is known about them in other species. Parasitic flatworms present an opportunity to investigate evolutionary novelties in TE control because they lack canonical pathways identified in model organisms (such as the piRNA pathways) but have conserved central players such as Dicer and Ago (argonaute) enzymes. Notably, parasitic flatworm Ago proteins are phylogenetically distinct from classical Ago, raising the question of whether they play special roles in these organisms. In this report, we investigate the role of Ago proteins in the parasitic flatworm Schistosoma mansoni. We show that transcript abundance of two retrotransposable elements increases upon silencing of S. mansoni Ago genes. We further demonstrate that SmAgo2 protein is primarily localised in the germ line of adult worms and its sub-cellular localisation is both nuclear and cytoplasmic. These findings provide further evidence of active TE control under a yet not fully unveiled pathway.
Chromosome level draft genomes of the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), an alien invasive pest in China
Authors: Liu Huan , Lan Tianming , Fang Dongming , Gui Furong , Wang Hongli , Guo Wei , Cheng Xiaofang , Chang Yue , He Shuqi , Lyu Lihua , Sahu Sunil Kumar , Cheng Le , Li Haimeng , Liu Ping , Fan Guangyi , Liu Tongxian , Hao Ruoshi , Lu Haorong , Chen Bin , Zhu Shusheng , Lu Zhihui , Huang Fangneng , Dong Wei , Dong Yang , Kang Le , Yang Huanming , Sheng Jun , Zhu Youyong , Liu Xin
Published: June 2019

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) is a severely destructive pest native to the Americas, but has now become an alien invasive pest in China, and causes significant economic loss. Therefore, in order to make effective management strategies, it is highly essential to understand genomic architecture and its genetic background. In this study, we assembled two chromosome scale genomes of the fall armyworm, representing one male and one female individual procured from Yunnan province of China. The genome sizes were identified as 542.42 Mb with N50 of 14.16 Mb, and 530.77 Mb with N50 of 14.89 Mb for the male and female FAW, respectively. We predicted about 22,201 genes in the male genome. We found the expansion of cytochrome P450 and glutathione s-transferase gene families, which are functionally related to the intensified detoxification and pesticides tolerance. Further population analyses of corn strain (C strain) and rice strain (R strain) revealed that the Chinese fall armyworm was most likely invaded from Africa. These strain information, genome features and possible invasion source described in this study will be extremely important for making effective strategies to manage the fall armyworms.
Chromatin nanoscale compaction in live cells visualized by acceptor-donor ratio corrected FRET between DNA dyes
Authors: Pelicci Simone , Diaspro Alberto , Lanzanò Luca
Published: June 2019

Chromatin nanoscale architecture in live cells can be studied by Forster Resonance Energy Transfer (FRET) between fluorescently labeled chromatin components, such as histones. A higher degree of nanoscale compaction is detected as a higher FRET level, since this corresponds to a higher degree of proximity between donor and acceptor molecules. However, in such a system the stoichiometry of the donors and acceptors engaged in the FRET process is not well defined and, in principle, FRET variations could be caused by variations in the acceptor-donor ratio rather than distance. Here we show that a FRET value independent of the acceptor-donor ratio can be obtained by Fluorescence Lifetime Imaging (FLIM) detection of FRET combined with a normalization of the FRET level to a pixel-wise estimation of the acceptor-donor ratio. We use this method to study FRET between two DNA binding dyes staining the nuclei of live cells. We show that acceptor-donor ratio corrected FRET imaging reveals variations of nanoscale compaction in different chromatin environments. As an application, we monitor the rearrangement of chromatin in response to laser-induced micro-irradiation and reveal that DNA is rapidly decompacted, at the nanoscale, in response to DNA damage induction.
Lop-eared rabbits have more aural and dental problems than erect-eared rabbits: a rescue population study
Authors: Johnson Jade C. , Burn Charlotte C.
Published: June 2019

This research aimed to assess whether rabbits having lop-ears is a welfare issue by investigating the occurrence of aural and dental pathology in lop-eared compared with erect-eared rabbits.

Thirty rabbits (15 lop-eared and 15 erect-eared) from a rabbit-only rescue shelter were examined. An otoscope was used to visualise the ear canals and mouth. Samples were taken from each ear to examine for mites, bacteria and yeast. Medical records were also examined.

Lop-eared rabbits showed statistically significantly more frequent ear canal stenosis, higher scores of cerumen and erythema, and more frequent potential pain response during ear examination, compared with erect-eared rabbits. We also found statistically significantly more frequent incisor pathology, molar overgrowth, molar sharpness, molar spurs and history of veterinary dental treatment in lop-eared compared with erect-eared rabbits. The effect sizes were often large. Age was not statistically significant between the lop- and erect-eared rabbit groups.

Thus, lop-eared rabbits are at an increased risk of aural and dental pathology. This brings into debate the ethics of breeding and buying lop-eared rabbits, as they are more likely to suffer conditions that negatively impact welfare, such as pain, and potentially deafness and difficulty eating.
Dissociating activation and integration of discourse referents: evidence from ERPs and oscillations
Authors: Coopmans Cas W. , Nieuwland Mante S.
Published: June 2019

A key challenge in understanding stories and conversations is the comprehension of ‘anaphora’, words that refer back to previously mentioned words or concepts (‘antecedents’). In psycholinguistic theories, anaphor comprehension involves the initial activation of the antecedent and its subsequent integration into the unfolding representation of the narrated event. A recent proposal suggests that these processes draw upon the brain’s recognition memory and language networks, respectively, and may be dissociable in patterns of neural oscillatory synchronization (Nieuwland & Martin, 2017). We addressed this proposal in an electroencephalogram (EEG) study with pre-registered data acquisition and analyses, using event-related potentials (ERPs) and neural oscillations. Dutch participants read two-sentence mini stories containing proper names, which were repeated or new (ease of activation) and coherent or incoherent with the preceding discourse (ease of integration). Repeated names elicited lower N400 and Late Positive Component amplitude than new names, and also an increase in theta-band (4-7 Hz) synchronization, which was largest around 240-450 ms after name onset. Discourse-coherent proper names elicited an increase in gamma-band (60-80 Hz) synchronization compared to discourse-incoherent names. This effect was largest around 690-1000 ms after name onset and was localized to the left frontal cortex. We argue that the initial activation and subsequent discourse-level integration of referents can be dissociated with event-related EEG activity, and are associated with respectively theta- and gamma-band activity. These findings further establish the link between memory and language through neural oscillations.
Cellular contractility coordinates cytoskeletal dynamics and cell behaviour duringDrosophilaabdominal morphogenesis
Authors:   Pau Pulido Companys, Norris Anneliese , Bischoff Marcus
Published: June 2019

During morphogenesis, cells undergo various behaviours, such as migration and constriction, which need to be coordinated. How this is achieved remains elusive. During morphogenesis of theDrosophilaadult abdominal epidermis, larval epithelial cells (LECs) migrate directedly before constricting apically and undergoing apoptosis. Here, we study the mechanisms underlying the transition from migration to constriction. We show that LECs possess a pulsatile apical actomyosin network and that a change in network polarity underlies behavioural change. Exploring the properties of the contractile network, we find that the level of cell contractility impacts on the network’s behaviour, as well as on overall cytoskeletal architecture and cell behaviour. We also find that pulsed contractions occur only in cells with intermediate levels of contractility. Furthermore, increasing levels of the small Rho GTPase Rho1 disrupts pulsed contractions, and instead leading to cells that cycle between two states, characterised by a junctional cortical and an apicomedial actin network. Our results highlight that behavioural change relies on tightly controlled cellular contractility. Moreover, we show that constriction can occur without pulsed contractions, raising questions about their contribution to constriction.
Optimizing Phylogenomics with Rapidly Evolving Long Exons: Comparison with Anchored Hybrid Enrichment and Ultraconserved Elements
Authors: Karin Benjamin R. , Gamble Tony , Jackman Todd R.
Published: June 2019

Abstract

Marker selection has emerged as an important component of phylogenomic study design due to rising concerns of the effects of gene tree estimation error, model misspecification, and data-type differences. Researchers must balance various trade-offs associated with locus length and evolutionary rate among other factors. The most commonly used reduced representation datasets for phylogenomics are ultraconserved elements (UCEs) and Anchored Hybrid Enrichment (AHE). Here, we introduce Rapidly Evolving Long Exon Capture (RELEC), a new set of loci that targets single exons that are both rapidly evolving (evolutionary rate faster thanRAG1) and relatively long in length (greater than 1,500 bp), while at the same time avoiding paralogy issues across amniotes. We compare the RELEC dataset to UCEs and AHE in squamate reptiles by aligning and analyzing orthologous sequences from 17 squamate genomes, composed of ten snakes and seven lizards. The RELEC dataset (179 loci) outperforms AHE and UCEs by maximizing per-locus genetic variation while maintaining presence and orthology across a range of evolutionary scales. RELEC markers show higher phylogenetic informativeness than UCE and AHE loci, and RELEC gene trees show greater similarity to the species tree than AHE or UCE gene trees. Furthermore, with fewer loci, RELEC remains computationally tractable for full Bayesian coalescent species tree analyses. We contrast RELEC to and discuss important aspects of comparable methods, and demonstrate how RELEC may be the most effective set of loci for resolving difficult nodes and rapid radiations. We provide several resources for capturing or extracting RELEC loci from other amniote groups.