bluuebunny/crossref_metadata_2025 huggingface dataset:
Olfactometric Comparison of the Volatile Insecticide, Metofluthrin, Through Behavioral Responses of Aedes albopictus (Diptera: Culicidae)
Authors: Bibbs Christopher S , Kline Jedidiah , Kline Daniel L , Estaver Jim , Strohschein Rudolph , Allan Sandra A , Kaufman Phillip E , Xue Rui-De , Batich Christopher D
Published: October 2019

Testing behavioral response to insecticidal volatiles requires modifications to the existing designs of olfactometers. To create a testing apparatus in which there is no chemical memory to confound tests, we detail the technical aspects of a new tool with design influences from other olfactometry tools. In addition, this new tool was used to evaluate a novel formulation of metofluthrin for use as an outdoor residual treatment. After sourcing materials to prioritize glass and metal construction, a modular wind tunnel was developed that hybridizes wind tunnel and olfactometer specifications. Volatile contaminants were removed by strong ultraviolet light within the chamber before and between trials. Repellent trials were conducted with an experimental formulation of metofluthrin and a commercial formulation of esfenvalerate, prallethrin, and piperonyl butoxide (Onslaught Fast Cap) against Aedes albopictus (Skuse). Toxicant vapors were delivered with attractants from a lure with behavioral responses scored 20 min post-exposure. Upwind attraction to the attractant lure and the Onslaught Fast Cap plus lure resulted in 90 and 75% capture, respectively. In contrast, metofluthrin vapors resulted in less than 10% attraction, while also causing repellency, disorientation, knockdown, and mortality effects. Our findings demonstrated that an inert modular wind tunnel was functional for mitigating toxic secondary exposures of spatial repellents amidst complex behavioral analysis in mosquitoes. The resulting observations with formulated metofluthrin positively reinforce the merit of transitioning metofluthrin into expanded roles in mosquito management.
Rapid Peptides Generator: fast and efficient in silico protein digestion
Authors: Maillet Nicolas
Published: October 2019

Recent developments in mass spectrometry techniques used in proteomics and proteogenomics have led to a constantly increasing interest in proteases. These proteases are used in different mass spectrometry analyses requiring protein digestions. To perform such digestions, one or multiple proteases are used. Few software exist that predict cleavage sites of proteases and simulate in silico digestions. In this work, Rapid Peptides Generator (RPG), a new software developed in order to predict proteases-induced cleavage sites on sequences, is presented. RPG offers extra features and overcomes most issues of existing software in different ways. First, for each generated peptide, RPG gives its sequence, length and estimation of mass, measurements already provided by other software, as well as the peptide’s isoelectric point. Moreover, contrary to existing software that limit the option of proteases to be used to a predefined list, users of RPG are able to easily define new proteases using a simple yet powerful grammar. This feature allows users to stay up-to-date to new or more specific proteases available on the market and optimizes time and effort before the actual mass spectrometry experiment. RPG is freely available through the well established package management system ‘pip’ and follows the standards for software development.
Robotic Surgical Assistant (ROSA™) Rehearsal: Using 3-Dimensional Printing Technology to Facilitate the Introduction of Stereotactic Robotic Neurosurgical Equipment
Authors: Bonda David J , Pruitt Rachel , Goldstein Todd , Varghese Anish , Mittler Mark , Schneider Steven , Shah Amar , Rodgers Shaun
Published: October 2019

BACKGROUND

The use of frameless stereotactic robotic technology has rapidly expanded since the Food and Drug Administration's approval of the Robotic Surgical Assistant (ROSA™) in 2012. Although the safety and accuracy of the ROSA platform has been well-established, the introduction of complex robotic technology into an existing surgical practice poses technical and logistical challenges particular to a given institution.

OBJECTIVES

To better facilitate the integration of new surgical equipment into the armamentarium of a thriving pediatric neurosurgery practice by describing the use of a three-dimensional (3D)-printed patient model with in situ 3D-printed tumor for presurgical positioning and trajectory optimization in the stereotactic biopsy of a pontine lesion in a pediatric patient.

METHODS

A 3D model was created with an added silicone mock tumor at the anatomical position of the lesion. In a preoperative rehearsal session, the patient model was pinned and registered using the ROSA platform, and a mock biopsy was performed targeting the in Situ silicone tumor.

RESULTS

Utilization of the 3D-printed model enabled workflow optimization and increased staff familiarity with the logistics of the robotic technology. Biopsy trajectory successfully reached intralesional tissue on the 3D-printed model. The rehearsal maneuvers decreased operative and intubation time for the patient and improved operative staff familiarity with the robotic setup.

CONCLUSION

Use of a 3D-printed patient model enhanced presurgical positioning and trajectory planning in the biopsy of a difficult to reach pontine lesion in a pediatric patient. The ROSA rehearsal decreased operative time and increased staff familiarity with a new complex surgical equipment.
Risks of suicide attempts after prescription of zolpidem in people with depression: a nationwide population study in South Korea
Authors: Kim Hyewon , Kim Yuwon , Myung Woojae , Fava Maurizio , Mischoulon David , Lee Unjoo , Lee Hyosang , Jin Na Eun , Woo Choi Kwan , Shin Myung-Hee , Jin Jeon Hong
Published: October 2019

Objectives

To investigate the association between zolpidem prescription and suicide attempts in people with depression

Methods

A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment Service of South was used to investigate the incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts in people with depression before and after zolpidem prescription using self-controlled case series design.

Results

In a total of 445 people who attempted suicide and 23 141 people who attempted probable suicide attempt, the IRRs of suicidal behavior during the risk periods before and after zolpidem prescription increased compared with those at the baseline. The IRRs gradually increased and peaked immediately before the prescription of zolpidem. The IRR was 70.06 (95% CI: 25.58–191.90) on day 2 before zolpidem prescription and 63.35 (95% CI: 22.99–174.59) on day 1 after zolpidem prescription in the suicide attempt group. The IRR was 24.07 (95% CI: 20.50–28.26) on the day before zolpidem prescription and 14.96 (95% CI: 12.21–18.34) on the day after zolpidem prescription in the probable suicide attempt group. The ratios declined eventually after zolpidem was prescribed.

Conclusions

Although zolpidem prescription was associated with an increased risk of suicide attempts in people with depression, the risk increased and peaked immediately before zolpidem prescription. The risk declined gradually thereafter. This result indicates that the risk of suicide attempts increases at the time of zolpidem prescription. However, zolpidem prescription does not contribute to additional increase in the risk of suicide attempts.
Oscillating and static dietary crude protein supply: II. Energy and protein requirements of young Nellore bulls
Authors: Menezes Ana Clara B , V. Filho Sebastião C , Pucetti Pauliane , C. Pacheco Marcos V , Godoi Letícia A , Zanetti Diego , Alhadas Herlon M , Paulino Mário F , Caton Joel S
Published: October 2019

The objective of this study was to evaluate whole body chemical composition and energy and protein nutrient requirements for maintenance and gain of Nellore bulls. Fifty young bulls, with an average age of 7 ± 1 mo and initial body weight (BW) of 260.0 ± 8.1 kg, were used in this experiment. Four bulls were used as baseline reference animals and were slaughtered at the beginning of the experiment. Four bulls were fed at maintenance (12 g dry matter [DM]/kg of BW), whereas 42 bulls were divided into six groups (n = 7/group) and were randomly assigned to the following dietary treatments 105 (low [LO]), 125 (medium [MD]), or 145 (high [HI]) g crude protein (CP)/kg DM, LO to HI (LH), LO to MD (LM), or MD to HI (MH) oscillating CP at a 48-h interval for 140 d. At the end of the experiment, bulls were slaughtered and samples of the whole body were collected. All samples were lyophilized, ground, and composed as percentage of component of empty body weight (EBW) from each bull. A power model was used to estimate carcass, non-carcass components, and gastrointestinal content of the shrunk body weight (SBW), and CP and water present in the empty body, whereas an exponential model was used to estimate adipose tissue and ether extract (EE) present in the EBW. Nonlinear regression equations were developed to predict heat production from metabolizable energy (ME) intake and retained energy (RE). The net energy requirements for maintenance and ME for maintenance were 77 and 122.75 kcal/EBW0.75/d, respectively. The efficiency of ME utilization for maintenance was 62.7%. The equation obtained for net energy for gain (NEg) was: NEg (Mcal/EBW0.75/d) = 0.0535 × EBW0.75 × EBG0.7131, where EBG is the empty body gain, and the efficiency was 24.25%. Net protein requirement for growth (NPg) was: NPg (g/d) = 227.372 × EBG – 19.479 × RE. There was a linear increase for carcass, CP, and water present in the EBW as the animal grew. The EE deposition exponentially increased as EBW increased.
A web-based intervention to increase weight loss treatment initiation: results of a cluster randomized feasibility and acceptability trial
Authors: McVay Megan A , Yancy William S , Bennett Gary G , Levine Erica , Jung Seung-Hye , Jung Soyeon , Anton Steve , Voils Corrine I
Published: October 2019

Evidence-based behavioral weight loss treatment is under-utilized. To increase initiation of treatment, we developed a single-session, online, primary care-based intervention (“mobilization tool”). We evaluated the mobilization tool's acceptability for primary care patients with obesity, trial design feasibility, and signal of an effect of the tool on treatment initiation. In this cluster randomized feasibility trial, primary care providers (PCPs) were randomized to a mobilization tool or comparator tool arm. Patients with obesity and a scheduled appointment with a randomized PCP were assigned to complete the mobilization or comparator tool prior to their appointment. The online mobilization tool asks patients to answer questions about a variety of weight-related topics and then provides automated, tailored feedback that addresses psychosocial determinants of weight loss treatment initiation. The comparator tool provided a nontailored description of treatments. All participants were offered free enrollment in behavioral weight loss treatments. Six PCPs were randomized. Sixty patients (57% female; 66% white; aged 55 ± 13 years) participated in this study of 296 contacted for eligibility evaluation (20.2%). Six-month follow-up assessments were completed by 65% (22/34) of the mobilization and 73% (19/26) of comparator tool participants. Participants completing the acceptability survey reported that the mobilization tool was usable, enjoyable, informative, and useful. Weight loss treatment was initiated by 59% (n = 19) of mobilization and 33% (n = 8) of comparator tool participants. The mobilization tool shows promise for increasing treatment initiation among primary care patients, which may increase population weight loss.

Trial Registration: Clinicaltrials.gov identifier: NCT02708121.
Crystal structures of Babesia microti lactate dehydrogenase BmLDH reveal a critical role for Arg99 in catalysis
Authors: Yu Long , Shen Zhou , Liu Qin , Zhan Xueyan , Luo Xiaoyin , An Xiaomeng , Sun Yali , Li Muxiao , Wang Sen , Nie Zheng , Ao Yangsiqi , Zhao Yangnan , Peng Guiqing , Mamoun Choukri Ben , He Lan , Zhao Junlong
Published: October 2019

The tick‐ and transfusion‐transmitted human pathogen Babesia microti infects host erythrocytes to cause the pathologic symptoms associated with human babesiosis, an emerging disease with worldwide distribution and potentially fatal clinical outcome. Drugs currently recommended for the treatment of babesiosis are associated with a high failure rate and significant adverse events, highlighting the urgent need for more‐effective and safer babesiosis therapies. Unlike other apicomplexan parasites, B. microti lacks a canonical lactate dehydrogenase (LDH) but instead expresses a unique enzyme, B. microti LDH (BmLDH), acquired through evolution by horizontal transfer from a mammalian host. Here, we report the crystal structures of BmLDH in apo state and ternary complex (enzyme‐NADH‐oxamate) solved at 2.79 and 1.89 Å. Analysis of these structures reveals that upon binding to the coenzyme and substrate, the active pocket of BmLDH undergoes a major conformational change from an opened and disordered to a closed and stabilized state. Biochemical assays using wild‐type and mutant B. microti and human LDHs identified Arg99 as a critical residue for the catalytic activity of BmLDH but not its human counterpart. Interestingly, mutation of Arg99 to Ala had no impact on the overall structure and affinity of BmLDH to NADH but dramatically altered the closure of the enzyme's active pocket. Together, these structural and biochemical data highlight significant differences between B. microti and human LDH enzymes and suggest that BmLDH could be a suitable target for the development of selective antibabesial inhibitors.—Yu, L., Shen, Z., Liu, Q., Zhan, X., Luo, X., An, X., Sun, Y., Li, M., Wang S., Nie, Z., Ao, Y., Zhao, Y., Peng, G., BenMamoun, C., He, L., Zhao, J. Crystal structures of Babesia microti lactate dehydrogenase BmLDH reveal a critical role for Arg99 in catalysis. FASEB J. 33, 13669‐13682 (2019). www.fasebj.org
Pitavastatin slows tumor progression and alters urine‐derived volatile organic compounds through the mevalonate pathway
Authors: Wang Luqi , Wang Yue , Chen Andy , Teli Meghana , Kondo Rika , Jalali Aydin , Fan Yao , Liu Shengzhi , Zhao Xinyu , Siegel Amanda , Minami Kazumasa , Agarwal Mangilal , Li Bai‐Yan , Yokota Hiroki
Published: October 2019

Bone is a frequent site of metastasis from breast cancer, and a desirable drug could suppress tumor growth as well as metastasis‐linked bone loss. Currently, no drug is able to cure breast cancer‐associated bone metastasis. In this study, we focused on statins that are known to inhibit cholesterol production and act as antitumor agents. After an initial potency screening of 7 U.S. Food and Drug Administration‐approved statins, we examined pitavastatin as a drug candidate for inhibiting tumor and tumor‐induced bone loss. In vitro analysis revealed that pitavastatin acted as an inhibitor of tumor progression by altering stress to the endoplasmic reticulum, down‐regulating peroxisome proliferator‐activated receptor γ, and reducing Snail and matrix metalloproteinase 9. In bone homeostasis, it blocked osteoclast development by suppressing transcription factors c‐Fos and JunB, but stimulated osteoblast mineralization by regulating bone morphogenetic protein 2 and p53. In a mouse model, pitavastatin presented a dual role in tumor inhibition in the mammary fat pad, as well as in bone protection in the osteolytic tibia. In mass spectrometry‐based analysis, volatile organic compounds (VOCs) that were linked to lipid metabolism and cholesterol synthesis were elevated in mice from the tumor‐grown placebo group. Notably, pitavastatin‐treated mice reduced specific VOCs that are linked to lipid metabolites in the mevalonate pathway. Collectively, the results lay a foundation for further investigation of pitavastatin's therapeutic efficacy in tumor‐induced bone loss, as well as VOC‐based diagnosis of tumor progression and treatment efficacy.—Wang, L., Wang Y., Chen, A., Teli, M., Kondo, R. Jalali A. Fan Y. Liu S. Zhao X. Siegel A. Minami K. Agarwal M. Li B.‐Y., Yokota, H. Pitavastatin slows tumor progression and alters urine‐derived volatile organic compounds through the mevalonate pathway. FASEB J. 33, 13710‐13721 (2019). www.fasebj.org
Deficiency in the short‐chain acyl‐CoA dehydrogenase protects mice against diet‐induced obesity and insulin resistance
Authors: Chen Yulong , Chen Jinglu , Zhang Caixia , Yang Shanshan , Zhang Xueping , Liu Yin , Su Zhiguang
Published: October 2019

Acyl‐CoA dehydrogenases (CADs) participate in mitochondrial fatty acid oxidation; abnormal fatty acid oxidation is associated with obesity and related metabolic disorders. We decipher the impact of short‐chain CAD (SCAD) on adiposity and insulin resistance. BALB/cBy strain mice derived from BALB/c strain are deficient in SCAD activity because of a spontaneous deletion in the acyl‐CoA dehydrogenases (Acads) gene. Adiposity, lipogenesis, and insulin sensitivity were compared in BALB/c and BALB/cBy mice subjected to high‐fat diets (HFDs). A whole hepatic transcriptome profiling experiment with microarrays was performed to evaluate the mechanisms by which SCAD deficiency protects against insulin resistance. Acads‐deficient mice were significantly resistant to HFD‐induced obesity and insulin resistance as compared with control mice. Reduced obesity results from decreased triglyceride content due to activation of AMPK in liver that would reduce hepatic content of malonyl‐CoA, resulting in decreased hepatic de novo lipogenesis. Improved insulin sensitivity was associated with reduced diacylglycerol content commensurate with reduced PKC‐ε activity and increased protein kinase B (AKT) activation in liver and skeletal muscle. Additionally, Acads‐deficient mice displayed significantly higher expression of the endoplasmic chaperone 78‐kDa glucose‐regulated protein, which was further associated with the AKT activation in the primary hepatocytes. Modulation of SCAD expression may therefore be a novel therapeutic approach to manage and prevent obesity and related metabolic diseases, such as diabetes.—Chen, Y., Chen, J., Zhang, C., Yang, S., Zhang, X., Liu, Y., Su, Z. Deficiency in the short‐chain acyl‐CoA dehydrogenase protects mice against diet‐induced obesity and insulin resistance. FASEB J. 33, 13722‐13733 (2019). www.fasebj.org
Localization of group II and III metabotropic glutamate receptors at pre‐ and postsynaptic sites of inner hair cell ribbon synapses
Authors: Klotz Lisa , Wendler Olaf , Frischknecht Renato , Shigemoto Ryuichi , Schulze Holger , Enz Ralf
Published: October 2019

Glutamate is the major excitatory neurotransmitter in the CNS binding to a variety of glutamate receptors. Metabotropic glutamate receptors (mGluR1 to mGluR8) can act excitatory or inhibitory, depending on associated signal cascades. Expression and localization of inhibitory acting mGluRs at inner hair cells (IHCs) in the cochlea are largely unknown. Here, we analyzed expression of mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, and mGluR8 and investigated their localization with respect to the presynaptic ribbon of IHC synapses. We detected transcripts for mGluR2, mGluR3, and mGluR4 as well as for mGluR7a, mGluR7b, mGluR8a, and mGluR8b splice variants. Using receptor‐specific antibodies in cochlear wholemounts, we found expression of mGluR2, mGluR4, and mGluR8b close to presynaptic ribbons. Super resolution and confocal microscopy in combination with 3‐dimensional reconstructions indicated a postsynaptic localization of mGluR2 that overlaps with postsynaptic density protein 95 on dendrites of afferent type I spiral ganglion neurons. In contrast, mGluR4 and mGluR8b were expressed at the presynapse close to IHC ribbons. In summary, we localized in detail 3 mGluR types at IHC ribbon synapses, providing a fundament for new therapeutical strategies that could protect the cochlea against noxious stimuli and excitotoxicity.—Klotz, L., Wendler, O., Frischknecht, R., Shigemoto, R., Schulze, H., Enz, R. Localization of group II and III metabotropic glutamate receptors at pre‐ and postsynaptic sites of inner hair cell ribbon synapses. FASEB J. 33, 13734‐13746 (2019). www.fasebj.org
Elimination of human folypolyglutamate synthetase alters programming and plasticity of somatic cells
Authors: Srivastava Avinash C. , Thompson Yesenia Guadalupe , Singhal Jyotsana , Stellern Jordan , Srivastava Anviksha , Du Juan , O'Connor Timothy R. , Riggs Arthur D.
Published: October 2019

Folates are vital cofactors for the regeneration of S‐adenosyl methionine, which is the methyl source for DNA methylation, protein methylation, and other aspects of one‐carbon (C1) metabolism. Thus, folates are critical for establishing and preserving epigenetic programming. Folypolyglutamate synthetase (FPGS) is known to play a crucial role in the maintenance of intracellular folate levels. Therefore, any modulation in FPGS is expected to alter DNA methylation and numerous other metabolic pathways. To explore the role of polyglutamylation of folate, we eliminated both isoforms of FPGS in human cells (293T), producing FPGS knockout (FPGSko) cells. The elimination of FPGS significantly decreased cell proliferation, with a major effect on oxidative phosphorylation and a lesser effect on glycolysis. We found a substantial reduction in global DNA methylation and noteworthy changes in gene expression related to C1 metabolism, cell division, DNA methylation, pluripotency, Glu metabolism, neurogenesis, and cardiogenesis. The expression levels of NANOG, octamer‐binding transcription factor 4, and sex‐determining region Y‐box 2 levels were increased in the mutant, consistent with the transition to a stem cell‐like state. Gene expression and metabolite data also indicate a major change in Glu and GABA metabolism. In the appropriate medium, FPGSko cells can differentiate to produce mainly cells with characteristics of either neural stem cells or cardiomyocytes.—Srivastava, A. C., Thompson, Y. G., Singhal, J., Stellern, J., Srivastava, A., Du, J., O'Connor, T. R., Riggs, A. D. Elimination of human folypolyglutamate synthetase alters programming and plasticity of somatic cells. FASEB J. 33, 13747‐13761 (2019). www.fasebj.org
Postgraduate education among family and community physicians in Brazil: theTrajetórias MFCproject
Authors: Fontenelle Leonardo Ferreira , Rossi Stephani Vogt , de Oliveira Miguel Henrique Moraes , Brandão Diego José , Sarti Thiago Dias
Published: October 2019

Neither primary health care or family and community medicine are recognized as knowledge areas in Brazil, for the purpose of postgraduate education (master’s, Ph.D.) or research. Our objective was to describe the postgraduate education trajectories of family and community physicians in Brazil. In this observational, exploratory study, we used data from SBMFC and SisCNRM to compile the list of physicians and community physicians, and then downloaded their curricula vitae from the Lattes Platform, verifying all data for consistency. A master’s degree was held by one in eight, and a Ph.D., by one in forty; most degrees were in collective health. Women (versus men) were less likely to hold master’s degrees, and even less likely to hold Ph.D. degrees. Professional (versus academic) master’s degrees and those in other areas (versus in medicine or collective health) were also associated with lower probability of obtaining a Ph.D. degree. Certified specialists (versus those with a medical residency) with a postgraduate degree were more likely to have earned it before becoming family and community physicians. We suggest that researchers in public health critically examine the relative benefits of different postgraduate trajectories for the professional performance of family and community physicians.
BAck Complaints in the Elders - Chiropractic (BACE-C): Design of a cohort study in chiropractic care
Authors: Jenks Alan D. , Hoekstra Trynke , Axén Iben , de Luca Katie , Field Jonathan , Newell Dave , Hartvigsen Jan , French Simon D. , Koes Bart , van Tulder Maurits W. , Rubinstein Sidney M.
Published: October 2019

Background

Low back pain is a common condition among older adults that significantly influences physical function and participation. Compared to their younger counterparts, there is limited information available about the clinical course of low back pain in older people, in particularly those presenting for chiropractic care. Improving our understanding of this patient population and the course of their low back pain may provide input for studies researching safer and more effective care than is currently provided.

Objectives

The primary objectives are to examine the clinical course over one year of the intensity, healthcare costs and improvement rates of low back pain in people 55 years and older who visit a chiropractor for a new episode of low back pain.

Methods

An international prospective, multi-center cohort study with one-year follow-up. Chiropractic practices are to be recruited in the Netherlands, Sweden, United Kingdom and Australia. Treatment will be left to the discretion of the chiropractor. Inclusion/Exclusion criteria: Patients 55 years and older who are accepted for care having presented to a chiropractor with a new episode of low back pain and who have not been to a chiropractor in the previous six months for an episode of low back pain are to be included, independent of whether or not they have seen another type of health care provider. Patients who are unable to complete the web-based questionnaires because of language restrictions or those with computer literacy restrictions will be excluded as well as those with cognitive disorders. In addition, those with a suspected tumor, fracture, infection or any other potential red flag or condition considered to be a contraindication for chiropractic care will be excluded. Data will be collected using online questionnaires at baseline, and at 2 and 6 weeks and at 3, 6, 9 and 12 months.

Trial Registration

Nederlandse Trial Registrar NL7507
Machine learning prediction of motor response after deep brain stimulation in Parkinson’s disease
Authors: Habets J , Duits A , Sijben L , De Greef B , Mulders A , Temel Y , Kuijf M , Kubben P , Herff C , Janssen M
Published: October 2019

Introduction

Despite careful patient selection for subthalamic nucleus deep brain stimulation (STN DBS), some Parkinson’s disease patients show limited improvement of motor disability. Non-conclusive results from previous prediction studies maintain the need for a simple tool for neurologists that reliably predicts postoperative motor response for individual patients. Establishing such a prediction tool facilitates the clinician to improve patient counselling, expectation management, and postoperative patient satisfaction. Predictive machine learning models can be used to generate individual outcome predictions instead of correlating pre- and postoperative variables on a group level.

Methods

We developed a machine learning logistic regression prediction model which generates probabilities for experiencing weak motor response one year after surgery. The model analyses preoperative variables and is trained on 90 patients using a ten-fold cross-validation. We intentionally chose to leave out pre-, intra- and postoperative imaging and neurophysiology data, to ensure the usability in clinical practice.

Weak responders (n = 27) were defined as patients who fail to show clinically relevant improvement on Unified Parkinson Disease Rating Scale (UPDRS) II, III or IV.

Results

The model predicts weak responders with an average area under the curve of the receiver operating characteristic of 0.88 (standard deviation: 0.14), a true positive rate of 0.85 and a false positive rate of 0.25, and a diagnostic accuracy of 78%. The reported influences of the individual preoperative variables are useful for clinical interpretation of the model, but cannot been interpreted separately regardless of the other variables in the model.

Conclusion

The very good diagnostic accuracy of the presented prediction model confirms the utility of machine-learning based motor response prediction one year after STN DBS implantation, based on clinical preoperative variables.

After reproduction and validation in a prospective cohort, this prediction model holds a tremendous potential to be a supportive tool for clinicians during the preoperative counseling.
Examining the effect of smoking on suicidal ideation and attempts: A triangulation of epidemiological approaches
Authors: Harrison Ruth , Munafò Marcus R , Smith George Davey , Wootton Robyn E
Published: October 2019

Background

Previous literature has demonstrated a strong association between cigarette smoking and suicide-related behaviours, characterised as ideation, plans, attempts and suicide related death. This association has not previously been examined in a causal inference framework and has important implications for suicide prevention strategies.

Aims

We aimed to examine the evidence for an association between smoking behaviours (initiation, smoking status, heaviness, lifetime smoking) and suicidal thoughts or attempts by triangulating across observational and Mendelian randomisation (MR) analyses.

Methods

First, in the UK Biobank, we calculate observed associations between smoking behaviours and suicidal thoughts or attempts. Second, we used Mendelian randomisation (MR) to explore the relationship between smoking and suicide using genetic variants as instruments to reduce bias from residual confounding and reverse causation.

Results

Our observational analysis showed a relationship between smoking behaviour and suicidal behaviour, particularly between smoking initiation and suicidal attempts (OR = 2.07, 95% CI = 1.91 to 2.26, p<0.001). The MR analysis and single SNP analysis, however, did not support this. Despite past literature showing a positive dose-response relationship our results showed no clear evidence for a causal effect of smoking on suicidal behaviours.

Conclusion

This was the first MR study to explore the effect of smoking on suicidal behaviours. Our results suggest that, despite observed associations, there is no strong evidence for a causal effect of smoking behaviour on suicidal behaviour. Our evidence suggests that further research is needed into alternative risk factors for suicide which might make better intervention targets.
The day-to-day experiences of caring for children with Osteogenesis Imperfecta: A qualitative descriptive study
Authors: Castro Aimee R. , Marinello Jessica , Chougui Khadidja , Morand Marilyn , Bilodeau Claudette , Rauch Frank , Tsimicalis Argerie
Published: October 2019

Aims and objectives

This study aimed to explore the day-to-day experiences of caregivers who are caring for children with Osteogenesis Imperfecta (OI).

Background

OI is a rare genetic condition known to cause bone fragility. Family caregivers, such as parents, of children with OI play an important role in helping these children live well at home.

Design

The design was qualitative description.

Methods

A qualitative descriptive study was conducted which adheres to the COREQ guidelines. Adult caregivers (n=18) of children with OI were recruited at a children’s hospital in Montréal, Canada to participate in individual interviews. The interviews were transcribed verbatim and inductively thematically analysed.

Results

The following caregiving themes were identified in these interviews: regular day-to-day caregiving activities, including morning routines, evening routines, and the facilitation of their child’s mobilization; periods that made the caregiving routine more challenging, such as fractures, surgeries, and pain; and the long-term strategies caregivers developed to support day-to-day care, such as managing the environment, accessing medical and school resources, and coordinating care and respite.

Conclusions

The results showcase what being a caregiver for a child with OI involves on a day-to-day basis.

Relevance to clinical practice

The recommendations include suggestions for future clinical, policy, and research endeavours to develop better policies and interventions to support the unique needs of family caregivers of children with OI. These recommendations may be relevant to other clinicians and policymakers working with families living with rare and chronic physical conditions.
Measuring Total Healthcare Utilization Among Intimate Partner Violence Survivors In Primary Care
Authors: Logeais Mary E. , Wang Qi , Renner Lynette M. , Clark Cari Jo
Published: October 2019

Rising health care costs are influenced by health care utilization, which encompasses hospital, ambulatory and non-face-to-face episodes of care. In this study, we created a novel a health care utilization-scoring tool that was used to examine whether one psychosocial factor, intimate partner violence (IPV), leads to higher utilization of health care services when controlling for relevant confounders. We sought to fill gaps about how social and behavioral issues impact utilization—particularly non-face-to-face episodes of care.

We conducted a retrospective cross-sectional study in 2017 examining patients seen at 11 University-affiliated primary care clinics from January 2015 to December 2016 who were screened for IPV. A total of 31,305 patients were screened, of which 280 screened positive. We controlled for medical complexity by deriving the revised Charlson Comorbidity Index for each patient. We calculated a novel utilization score, which was a weighted sum of hospital, ambulatory and non-face-to-face encounters. Missed appointments were also measured.

IPV-positive and IPV-negative patients were similar with respect medical complexity. IPV-positive patients had significantly higher mean utilization scores (54 vs. 40, p<0.001) and more missed appointments (3 vs. 1.3, p<0.001). IPV was associated with increased total utilization (p=0.015), as well as non-face-to-face and ambulatory visits (p=0.025 and p=0.015, respectively) for female patients and was associated with more missed appointments for both males and females (p< .001).

These data support more inclusive population-specific interventions focusing on social determinants of health to reduce both face-to-face and non-face-to-face utilization, which may improve health care expenditures, outcomes and provider satisfaction.
Estimating youth diabetes risk using NHANES data and machine learning
Authors: Vangeepuram Nita , Liu Bian , Chiu Po-hsiang , Wang Linhua , Pandey Gaurav
Published: October 2019

Background

Prediabetes and diabetes mellitus (preDM/DM) have become alarmingly prevalent among youth in recent years. However, simple questionnaire-based screening tools to reliably assess diabetes risk are only available for adults, not youth.

Methods

As a first step in developing such a tool, we used a large-scale dataset from the National Health and Nutritional Examination Survey (NHANES) to examine the performance of a published pediatric clinical screening guideline in identifying youth with preDM/DM based on American Diabetes Association diagnostic biomarkers. We assessed the agreement between the clinical guideline and biomarker criteria using established evaluation measures (sensitivity, specificity, positive/negative predictive value, F-measure for the positive/negative preDM/DM classes, and Kappa). We also compared the performance of the guideline to those of machine learning (ML) based preDM/DM classifiers derived from the NHANES dataset.

Results

Approximately 29% of the 2858 youth in our study population had preDM/DM based on biomarker criteria. The clinical guideline had a sensitivity of 43.1% and specificity of 67.6%, positive/negative predictive values of 35.2%/74.5%, positive/negative F-measures of 38.8%/70.9%, and Kappa of 0.1 (95%CI: 0.06-0.14). The performance of the guideline varied across demographic subgroups. Some ML-based classifiers performed comparably to or better than the screening guideline, especially in identifying preDM/DM youth (p=5.23×10−5).

Conclusions

We demonstrated that a recommended pediatric clinical screening guideline did not perform well in identifying preDM/DM status among youth. Additional work is needed to develop a simple yet accurate screener for youth diabetes risk, potentially by using advanced ML methods and a wider range of clinical and behavioral health data.

Key Messages

As a first step in developing a youth diabetes risk screening tool, we used a large-scale dataset from the National Health and Nutritional Examination Survey (NHANES) to examine the performance of a published pediatric clinical screening guideline in identifying youth with prediabetes/diabetes based on American Diabetes Association diagnostic biomarkers.

In this cross-sectional study of youth, we found that the screening guideline correctly identified 43.1% of youth with prediabetes/diabetes, the performance of the guideline varied across demographic subgroups, and machine learning based classifiers performed comparably to or better than the screening guideline in identifying youth with prediabetes/diabetes.

Additional work is needed to develop a simple yet accurate screener for youth diabetes risk, potentially by using advanced ML methods and a wider range of clinical and behavioral health data.
Mathematical modeling of directed acyclic graphs to explore competing causal mechanisms underlying epidemiological study data
Authors: Havumaki Joshua , Eisenberg Marisa C.
Published: October 2019

1

Accurately estimating the effect of an exposure on an outcome requires understanding how variables relevant to a study question are causally related to each other. Directed acyclic graphs (DAGs) are used in epidemiology to understand causal processes and determine appropriate statistical approaches to obtain unbiased measures of effect. Compartmental models (CMs) are also used to represent different causal mechanisms, by depicting flows between disease states on the population level. In this paper, we extend a mapping between DAGs and CMs to show how DAG–derived CMs can be used to compare competing causal mechanisms by simulating epidemiological studies and conducting statistical analyses on the simulated data. Through this framework, we can evaluate how robust simulated epidemiological study results are to different biases in study design and underlying causal mechanisms. As a case study, we simulated a longitudinal cohort study to examine the obesity paradox: the apparent protective effect of obesity on mortality among diabetic ever-smokers, but not among diabetic never-smokers. Our simulations illustrate how study design bias (e.g., reverse causation), can lead to the obesity paradox. Ultimately, we show the utility of transforming DAGs into in silico laboratories within which researchers can systematically evaluate bias, and inform analyses and study design.
PROBLEM BASED LEARNING APPLIED TO PRACTICE IN MEDICAL SCHOOLS IN BRAZIL: A MINI-SYSTEMATIC REVIEW
Authors: Bussolaro Frederico Alberto , Thereza-Bussolaro Claudine
Published: October 2019

Background

Active learning is a well-established educational methodology in medical schools worldwide, although its implementation in Brazilian clinical settings is quite challenging. The objective of this study is to review the literature in a systematic manner to find and conduct a reflective analysis of how problem-based learning (PBL) has been applied to clinical teaching in medical schools in Brazil.

Material & methods

A systematic literature search was conducted in three databases. A total of 250 papers related to PBL in Brazilian medical schools were identified through the database searches. Four studies were finally selected for the review.

Results

Four fields of medicine were explored on the four selected papers: gynecology/family medicine, medical semiology, psychiatry, and pediatrics. Overall, all the papers reported some level of strategic adaptability of the original PBL methodology to be applied in the Brazilian medical school’s curricula and to the peculiar characteristics specific to Brazil.

Conclusion

PBL application in Brazilian medical schools require some level of alteration from the original format, to better adapt to the characteristics of Brazilian students’ maturity, health system priorities and the medical labor market.
Safety of Flexible Sigmoidoscopy in Pregnant Patients with known or suspected Inflammatory Bowel Disease
Authors: Ko Myung S. , Rudrapatna Vivek A. , Avila Patrick , Mahadevan Uma
Published: October 2019

I.

Background and Aims

Lower gastrointestinal endoscopy is the gold standard for the diagnosis and staging of Inflammatory Bowel Disease (IBD). However, there is limited safety data in pregnant populations, resulting in conservative society guidelines and practice patterns favoring diagnostic delay. The aim of this study is to investigate if the performance of flexible sigmoidoscopy is associated with adverse events in pregnant patients with known or suspected IBD.

II.

Methods

A retrospective cohort study was conducted at the University of California San Francisco (UCSF) between April 2008 and April 2019. Female patients aged between 18 and 48 years who were pregnant at the time of endoscopy were identified. All patient records were reviewed to determine disease, pregnancy course, and lifestyle factors. Two independent reviewers performed the data abstraction. Adverse events were assessed for temporal relation (defined as within 4 weeks) with endoscopy. Any discrepancies in the two reviewers’ data were reviewed by a third independent investigator. Descriptive statistics of data were calculated, and comparison of continuous and categorical data were made using a one-sided Wilcoxon rank-sum test and Fisher’s exact test, respectively.

III.

Results

We report the outcomes of 48 pregnant patients across all trimesters who underwent lower endoscopy for suspected or established IBD. There were no hospitalizations or adverse obstetric events temporally associated with sigmoidoscopy. 78% of patients experienced a change in treatment following sigmoidoscopy. 12% of the patients with known IBD were found to have no endoscopic evidence of disease activity despite symptoms.

IV.

Conclusions

Lower endoscopy in the pregnant patient with known or suspected IBD is low risk and affects therapeutic decision making. It should not be delayed in patients with appropriate indications.
Can the impact of childhood adiposity on disease risk be reversed? A Mendelian randomization study
Authors: Richardson Tom G. , Sanderson Eleanor , Elsworth Benjamin , Tilling Kate , Davey Smith George
Published: October 2019

Objective

To evaluate whether early life adiposity has an independent effect on later life disease risk or whether its influence is mediated by adulthood body mass index (BMI).

Design

Two-sample univariable and multivariable Mendelian randomization.

Setting

The UK Biobank (UKB) prospective cohort study and four large-scale genome-wide association study (GWAS) consortia.

Participants

453,169 participants enrolled in the UKB and a combined total of over 700,000 individuals from different GWAS consortia.

Exposures

Measured BMI during adulthood (mean age: 56.5) and self-reported adiposity at age 10.

Main outcome measures

Coronary artery disease (CAD), type 2 diabetes (T2D), breast cancer and prostate cancer.

Results

Individuals with genetically predicted higher BMI in early life had increased odds of CAD (OR:1.49, 95% CI:1.33-1.68) and T2D (OR:2.32, 95% CI:1.76-3.05) based on univariable MR (UVMR) analyses. However, there was little evidence of a direct effect (i.e. not via adult BMI) based on multivariable MR (MVMR) estimates (CAD OR:1.02, 95% CI:0.86-1.22, T2D OR:1.16, 95% CI:0.74-1.82). In the MVMR analysis of breast cancer risk, there was strong evidence of a protective direct effect for early BMI (OR:0.59, 95% CI:0.50-0.71), although adult BMI did not appear to have a direct effect on this outcome (OR:1.08, 95% CI:0.93-1.27). Adding age of menarche as an additional exposure provided weak evidence of a total causal effect (UVMR OR:0.98, 95% CI:0.91-1.06) but strong evidence of a direct causal effect, independent of early and adult BMI (MVMR OR:0.90, 95% CI:0.85-0.95). Weak evidence of a causal effect was observed in the MVMR analysis of prostate cancer (early life BMI OR:1.06, 95% CI:0.81-1.40, adult BMI OR:0.87, 95% CI:0.70-1.08).

Conclusions

Our findings suggest that increased CAD and T2D risk attributed to early life adiposity can be mitigated if individuals reduce their weight in later life. However, having a low BMI during childhood may increase risk of breast cancer regardless of changes to weight in later life, with timing of puberty also putatively playing an important role.
Potential impact of outpatient stewardship interventions on antibiotic exposures of bacterial pathogens
Authors: Tedijanto Christine , Grad Yonatan H , Lipsitch Marc
Published: October 2019

The relationship between antibiotic stewardship and population levels of antibiotic resistance remains unclear. In order to better understand shifts in selective pressure due to stewardship, we use publicly available data to estimate the effect of changes in prescribing on exposures to frequently used antibiotics experienced by potentially pathogenic bacteria that are asymptomatically colonizing the microbiome. We quantify this impact under four hypothetical stewardship strategies. In one scenario, we estimate that elimination of all unnecessary outpatient antibiotic use could avert 6 to 48% (IQR: 17 to 31%) of exposures across pairwise combinations of sixteen common antibiotics and nine bacterial pathogens. All scenarios demonstrate that stewardship interventions, facilitated by changes in clinician behavior and improved diagnostics, have the opportunity to broadly reduce antibiotic exposures across a range of potential pathogens. Concurrent approaches, such as vaccines aiming to reduce infection incidence, are needed to further decrease exposures occurring in “necessary” contexts.
Quantifying the success of measles vaccination campaigns in the Rohingya refugee camps
Authors: Chin Taylor , Buckee Caroline O. , Mahmud Ayesha S.
Published: October 2019

In the wake of the Rohingya population’s mass migration from Myanmar, one of the world’s largest refugee settlements was constructed in Cox’s Bazar, Bangladesh to accommodate nearly 900,000 new refugees. Refugee populations are particularly vulnerable to infectious disease outbreaks due to many population and environmental factors. A large measles outbreak, with over 2,500 cases, occurred among the Rohingya population between September and December 2017. Here, we estimate key epidemiological parameters and use a dynamic mathematical model of measles transmission to evaluate the effectiveness of the reactive vaccination campaigns in the refugee camps. We also estimate the potential for subsequent outbreaks under different vaccination coverage scenarios. Our modeling results highlight the success of the vaccination campaigns in rapidly curbing transmission and emphasize the public health importance of maintaining high levels of vaccination in this population, where high birth rates and historically low vaccination coverage rates create suitable conditions for future measles outbreaks.