bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx
Authors: Barbee Lindley A , Soge Olusegun O , Morgan Jennifer , Leclair Angela , Bass Tamara , Werth Brian J , Hughes James P , Golden Matthew R 
Published: November 2019

Abstract

Background
Centers for Disease Control and Prevention (CDC) guidelines recommend 240 mg gentamicin plus 2 g azithromycin for the treatment of gonorrhea in cephalosporin-allergic patients. The efficacy of gentamicin alone in the treatment of pharyngeal gonorrhea is uncertain.

Methods
Between September 2018 and March 2019, we enrolled men who have sex with men with nucleic acid amplification test–diagnosed pharyngeal gonorrhea in a single-arm, unblinded clinical trial. Men received a single 360-mg intramuscular dose of gentamicin and underwent test of cure by culture 4–7 days later. The study measured creatinine at enrollment and test of cure, serum gentamicin concentration postdose to establish peak concentration (Cmax), and standard antimicrobial minimum inhibitory concentrations (MICs) by agar dilution. The trial was designed to establish a point estimate for gentamicin’s efficacy for pharyngeal gonorrhea. We planned to enroll 50 evaluable participants; assuming gentamicin was 80% efficacious, the trial would establish a 95% confidence interval (CI) of 66%–90%. We planned interim analyses at n = 10 and n = 25.

Results
The study was stopped early due to poor efficacy. Of 13 enrolled men, 10 were evaluable, and only 2 (20% [95% CI, 2.5%–55.6%]) were cured. Efficacy was not associated with gentamicin Cmax or MIC. No participants experienced renal insufficiency. The mean creatinine percentage change was +5.2% (range, −6.7% to 21.3%). Six (46%) participants experienced headache, all deemed unrelated to treatment.

Conclusions
Gentamicin alone failed to eradicate Neisseria gonorrhoeae from the pharynx. Clinicians should use caution when treating gonorrhea with the CDC’s current alternative regimen (gentamicin 240 mg plus azithromycin 2 g) given increases in azithromycin resistance and gentamicin’s poor efficacy at the pharynx.

Clinical Trials Registration
NCT03632109.
Abnormal neurovascular coupling as a cause of excess cerebral vasodilation in familial migraine
Authors: Staehr Christian , Rajanathan Rajkumar , Postnov Dmitry D , Hangaard Lise , Bouzinova Elena V , Lykke-Hartmann Karin , Bach Flemming W , Sandow Shaun L , Aalkjaer Christian , Matchkov Vladimir V 
Published: November 2019

AbstractAimsAcute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na, K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R mice) were shown to have elevated cerebrovascular tone and, thus, hypoperfusion that might lead to elevated concentrations of local metabolites. We hypothesize that these α2+/G301R mice also have increased cerebrovascular hyperaemic responses to these local metabolites leading to hyperperfusion in the affected part of the brain.Methods and resultsNeurovascular coupling was compared in α2+/G301R and matching wild-type (WT) mice using Laser Speckle Contrast Imaging. In brain slices, parenchymal arteriole diameter and intracellular calcium changes in neuronal tissue, astrocytic endfeet, and smooth muscle cells in response to neuronal excitation were assessed. Wall tension and smooth muscle membrane potential were measured in isolated middle cerebral arteries. Quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to assess the molecular background underlying the functional changes. Whisker stimulation induced larger increase in blood perfusion, i.e. hyperaemic response, of the somatosensory cortex of α2+/G301R than WT mice. Neuronal excitation was associated with larger parenchymal arteriole dilation in brain slices from α2+/G301R than WT mice. These hyperaemic responses in vivo and ex vivo were inhibited by BaCl2, suggesting involvement of inward-rectifying K+ channels (Kir). Relaxation to elevated bath K+ was larger in arteries from α2+/G301R compared to WT mice. This difference was endothelium-dependent. Endothelial Kir2.1 channel expression was higher in arteries from α2+/G301R mice. No sex difference in functional responses and Kir2.1 expression was found.ConclusionThis study suggests that an abnormally high cerebrovascular hyperaemic response in α2+/G301R mice is a result of increased endothelial Kir2.1 channel expression. This may be initiated by vasospasm-induced accumulation of local metabolites and underlie the hyperperfusion seen in FHM2 patients during migraine attack.
Impact of simplified therapeutic guidelines on antibiotic prescriptions: a prospective multicentre comparative study
Authors: Roger Pierre-Marie , Peyraud Ingrid , Vitris Michel , Romain Valérie , Bestman Laura , Blondel Lionel , Gras Hélène , Hauchart Christine , Morandi Véronique , Rancezot Agnès , Borredon Gaelle , Dautezac Véronique 
Published: November 2019

Abstract

Objectives
We studied the impact of simplified therapeutic guidelines (STGs) associated with accompanied self-antibiotic reassessment (ASAR) on antibiotic use.

Methods
Prospective antibiotic audits and feedback took place at 15 hospitals for 12 months, allowing STGs with ≤15 drugs to be devised. STGs were explained to prescribers through sessions referred to as ASAR. Optimal therapy was defined by the conjunction of a diagnosis and the drug specified in the STGs. Analysis of consumption focused on critical drugs: amoxicillin/clavulanic acid, third-generation cephalosporins and fluoroquinolones.

Results
We compared prescriptions in five hospitals before (n = 179) and after (n = 168) the implementation of STGs + ASAR. These tools were associated with optimal therapies and amoxicillin/clavulanic acid prescriptions [adjusted odds ratio (AOR) 3.28, 95% CI 1.82–5.92 and 2.18, 95% CI 1.38–3.44, respectively] and fewer prescriptions for urine colonization [AOR 0.20 (95% CI 0.06–0.61)]. Comparison of prescriptions (n = 1221) from 10 departments of three clinics with STGs + ASAR for the first quarters of 2018 and 2019 revealed that the prescriptions by 23 ASAR participants more often complied with STGs than those by 28 other doctors (71% versus 60%, P = 0.003). STGs alone were adopted by 10 clinics; comparing the prescriptions (n = 311) with the 5 clinics with both tools, we observed fewer unnecessary therapies in the latter [AOR 0.52 (95% CI 0.34–0.80)]. The variation in critical antibiotic consumption between 2017 and 2018 was −16% for the 5 clinics with both tools and +20% for the other 10 (P = 0.020).

Conclusions
STGs + ASAR promote optimal antibiotic therapy and reduce antibiotic use.
Can miRNAs Serve as Potential Markers in Thermal Burn Injury: An In Silico Approach
Authors: Shukla Sandeep K , Sharma Ajay K , Bharti Rhythm , Kulshrestha Vidit , Kalonia Aman , Shaw Priyanka 
Published: November 2019

Abstract
Burn injury has been a major cause of morbidity at global levels. They can occur by multiple agents, such as thermal radiation and chemicals. Among all, thermal burn is predominant and may require specialized treatment in some patients. Although various biomarkers are reportedly used in thermal burn for understanding the pathophysiology of the injury, their limitations prompt for the search of suitable markers that can address the depth and severity of the burn. MicroRNAs (miRNAs) are conserved noncoding molecules that seem to be the promising marker due to their role in multiple pathways and participation in different physiological processes of the body. The present review highlights the role of miRNAs in the repair of the wound and their interaction with specific genes in response to burn stress. Key miR candidates include miR-21, miR-29a, miR-378a-5p, miR-100, miR-27b, miR-200c, miR-150, miR-499-5p, miR-92a, miR-194, and miR-146b, which are identified for their respective targets involved in wound repair. Furthermore, bioinformatics and computational tools were used to confirm the miRNAs and their specific targets. Gene and miRNA expression data sets were downloaded from Research Collaboratory for Structural Bioinformatics Protein Data Bank Database and RNAComposer, respectively, and docked by PatchDock. The possible implications of the identified miRNAs could be in understanding the mechanism of burn injury. These can also be studied with the available drugs being used for burn injury. Apart from that, new intended molecules may also be tested for their effect on these miRNAs.
Comparative Study of Promastigote- and Amastigote-Initiated Infection of Leishmania infantum (Kinetoplastida: Trypanosomatidae) in Phlebotomus perniciosus (Diptera: Psychodidae) Conducted in Different Biosafety Level Laboratories
Authors: Vaselek Slavica , Prudhomme Jorian , Myskova Jitka , Lestinova Tereza , Spitzova Tatiana , Bañuls Anne-Laure , Volf Petr 
Published: November 2019

Abstract
Sand flies (Diptera: Psychodidae) are natural vectors of Leishmania. For the initiation of sand fly experimental infections either Leishmania amastigotes or promastigotes can be used. In order to obtain comparable results, it is necessary to adjust and standardize procedures. During this study, we conducted promastigote- and amastigote-initiated infections of Leishmania infantum Nicolle, 1908 parasites in Phlebotomus (Larroussius) perniciosus Newstead, 1911 in two laboratories with different levels of biosafety protection. Protocol originally designed for a biosafety level 2 facility was modified for biosafety level 3 facility and infection parameters were compared. Particularly, specially designed plastic containers were used for blood feeding; feeders were placed outside the sand fly cage, on the top of the mesh; feeding was performed inside the climatic chamber; separation of engorged females was done in Petri dishes kept on ice; engorged females were kept in the cardboard containers until dissection. All experiments, conducted in both laboratories, resulted in fully developed late stage infections with high number of parasites and colonization of the stomodeal valve. We demonstrated that protocol originally designed for biosafety level 2 facilities can be successfully modified for other biosafety facilities, depending on the special requirements of the individual institution/laboratory.
Spring temperatures affect senescence and N uptake in autumn and N storage for winter in Rhynchospora alba (Cyperaceae)
Authors: Byne Kyelle , Ryser Peter 
Published: November 2019

AbstractEnvironmental and physiological factors underlying variation in timing of autumn senescence are not well known. We investigated how the time of the onset of the growth in spring affects senescence and its functional consequences for nitrogen (N) uptake in autumn and storage of N for the winter, in a species that each year develops its bulbils for storage and overwintering anew. Rhynchospora alba was grown outdoors with two treatments, identical except for a 3 week difference in the start of growth in May. Leaf and root growth and senescence, and N uptake were recorded from August to November. By August, late-starting plants had caught up in size and total N content, but had smaller bulbils. They had a higher δ 13C, indicating a higher stomatal conductance during growth. Leaf and root senescence were delayed, extending 15N tracer uptake by 4 weeks. Nevertheless, after senescence, plants with an early start had 55% more N in their overwintering bulbils, due to earlier and more efficient remobilization. We conclude that timing of senescence in R. alba is a result of an interplay between the status of winter storage and cold temperatures, constrained by a trade-off between prolonged nutrient uptake and efficient remobilization of nutrients.
Targeted insertional mutagenesis libraries for deep domain insertion profiling
Authors: Coyote-Maestas Willow , Nedrud David , Okorafor Steffan , He Yungui , Schmidt Daniel 
Published: November 2019

AbstractDomain recombination is a key principle in protein evolution and protein engineering, but inserting a donor domain into every position of a target protein is not easily experimentally accessible. Most contemporary domain insertion profiling approaches rely on DNA transposons, which are constrained by sequence bias. Here, we establish Saturated Programmable Insertion Engineering (SPINE), an unbiased, comprehensive, and targeted domain insertion library generation technique using oligo library synthesis and multi-step Golden Gate cloning. Through benchmarking to MuA transposon-mediated library generation on four ion channel genes, we demonstrate that SPINE-generated libraries are enriched for in-frame insertions, have drastically reduced sequence bias as well as near-complete and highly-redundant coverage. Unlike transposon-mediated domain insertion that was severely biased and sparse for some genes, SPINE generated high-quality libraries for all genes tested. Using the Inward Rectifier K+ channel Kir2.1, we validate the practical utility of SPINE by constructing and comparing domain insertion permissibility maps. SPINE is the first technology to enable saturated domain insertion profiling. SPINE could help explore the relationship between domain insertions and protein function, and how this relationship is shaped by evolutionary forces and can be engineered for biomedical applications.
Epigenetic reprogramming and chromatin accessibility in pediatric diffuse intrinsic pontine gliomas: a neural developmental disease
Authors: Mendez Flor M , Núñez Felipe J , Garcia-Fabiani Maria B , Haase Santiago , Carney Stephen , Gauss Jessica C , Becher Oren J , Lowenstein Pedro R , Castro Maria G 
Published: November 2019

Abstract
Diffuse intrinsic pontine glioma (DIPG) is a rare but deadly pediatric brainstem tumor. To date, there is no effective therapy for DIPG. Transcriptomic analyses have revealed DIPGs have a distinct profile from other pediatric high-grade gliomas occurring in the cerebral hemispheres. These unique genomic characteristics coupled with the younger median age group suggest that DIPG has a developmental origin. The most frequent mutation in DIPG is a lysine to methionine (K27M) mutation that occurs on H3F3A and HIST1H3B/C, genes encoding histone variants. The K27M mutation disrupts methylation by polycomb repressive complex 2 on histone H3 at lysine 27, leading to global hypomethylation. Histone 3 lysine 27 trimethylation is an important developmental regulator controlling gene expression. This review discusses the developmental and epigenetic mechanisms driving disease progression in DIPG, as well as the profound therapeutic implications of epigenetic programming.
Effect of sucralose and aspartame on glucose metabolism and gut hormones
Authors: Ahmad Samar Y , Friel James K , Mackay Dylan S 
Published: November 2019

Abstract
Non-nutritive sweeteners are thought to be useful replacements for caloric sweeteners in sweet food and beverages, since the reduction in energy and carbohydrate intake may lead to health benefits stemming from weight management and glycemic control. However, the potential effects of non-nutritive sweeteners on glucose metabolism and gut hormones have not been determined definitively. Here, the available evidence of the effects of aspartame and sucralose consumption on glucose metabolism and gut hormones is reviewed. A majority of studies have found that consumption of aspartame or sucralose has no effect on concentrations of blood glucose, insulin, or gut hormones; however, 2 trials have shown that aspartame consumption affects glucose, insulin, and glucagon-like peptide 1 concentrations, while only a few trials have shown that sucralose consumption affects glucose, insulin, and glucagon-like peptide 1 concentrations. One study found higher glucose concentrations after sucralose consumption, while 3 studies found lower concentrations and 33 studies found no change in glucose concentrations. Moreover, only 4 studies reported increased concentrations of glucagon-like peptide 1. Three studies reported decreased insulin sensitivity following sucralose consumption, while 1 trial reported an increase in insulin sensitivity. In summary, the evidence from the clinical trials conducted to date is contradictory because of the different protocols used.
Lipid-modifying effects of krill oil vs fish oil: a network meta-analysis
Authors: Kim Myeong Gyu , Yang Inkyou , Lee Han Sol , Lee Jae-Young , Kim Kyungim 
Published: November 2019

AbstractContextKrill oil is a good source of n-3 phospholipids and has greater bioavailability than fish oil, which contains n-3 triglycerides. However, it is unclear whether krill oil affects circulating lipid concentrations more beneficially than fish oil.ObjectiveA network meta-analysis was conducted to compare the lipid-modifying effects of krill oil and fish oil.Data SourcesPubMed and Embase databases were searched.Study SelectionA total of 64 randomized controlled trials that determined the lipid-modifying effects of krill oil or fish oil were selected.Data ExtractionThe MetaXL program was used for meta-analysis. A subgroup analysis and a network meta-regression were conducted to investigate the dose-response effect of the n-3 fatty acid content of fish oil and krill oil.ResultsKrill oil was associated with significantly lower triglyceride levels than control supplements (weighted mean difference [WMD] −23.26 [95%CI, −38.84 to −7.69]). However, the net differences in triglycerides (WMD −4.07 [95%CI, −15.22 to 7.08]), low-density lipoprotein cholesterol (WMD 3.01 [95%CI, −5.49 to 11.51]), high-density lipoprotein cholesterol (WMD 1.37 [95%CI, −3.73 to 6.48]), and total cholesterol (WMD 1.69 [95%CI, −6.62 to 10.01]) were not significantly different between the krill oil and fish oil groups. One gram of n-3 fatty acids contained in fish oil and krill oil lowered median triglycerides by 8.971 mg/dL (95% credible interval [CrI], 2.27 to 14.04) and 9.838 mg/dL (95%CrI, 0.72 to 19.40), respectively.ConclusionsThe lipid-modifying effects of krill oil and fish oil do not differ. The reduction in triglycerides depends on the dose of n-3 fatty acids consumed.
Teaching Health Advocacy: A Systematic Review of Educational Interventions for Postgraduate Medical Trainees
Authors: Scott Michael D. , McQueen Sydney , Richardson Lisa 
Published: November 2019

Purpose
A systematic review was undertaken to characterize the training approaches that are currently being implemented in postgraduate medical education to teach residents advocacy skills.

Method
An initial search was conducted in MEDLINE, PubMed, Embase, ERIC, and PsycINFO in November 2016 (updated in December 2017) for articles discussing postgraduate medical education interventions covering advocacy. Articles published between 1995 and 2017 were included. Two authors independently reviewed titles and abstracts (and, if needed, the full text) for inclusion; disagreements were resolved by consensus. Data were extracted from studies to characterize the content and pedagogy of the interventions by mapping them to the CanMEDS health advocate core competencies and key concepts.

Results
A total of 3,027 unique abstracts were retrieved; 2,864 were excluded upon title and abstract review, and another 85 were excluded upon full-text review. Seventy-eight total articles were included. More studies involved residents from pediatrics, psychiatry, primary care or preventative medicine, or internal medicine than from emergency medicine, surgery, obstetrics and gynecology, or neurology. Published interventions varied widely by pedagogical approach and assessment method.

Conclusions
Using the CanMEDS framework, this review maps the breadth and nature of postgraduate medical education interventions in health advocacy, with applicability to community organizations, program directors, educators, and administrators working to develop advocacy training interventions. Areas of focus included adapting practice to respond to the needs of or advocacy in partnership with patients, communities, or populations served; determinants of health; health promotion; mobilizing resources as needed; and social accountability.
A Study of the Validity of the New MCAT Exam
Authors: Violato Claudio , Gauer Jacqueline L. , Violato Efrem M. , Patel Dimple 
Published: November 2019

Purpose
To conduct a study of the validity of the new Medical College Admission Test (MCAT).

Method
Deidentified data for first- and second-year medical students (185 women, 54.3%; 156 men, 45.7%) who matriculated in 2016 and 2017 to the University of Minnesota Medical School–Twin Cities were included. Of those students, 220 (64.5%) had taken the new MCAT exam and 182 (53.4%) had taken the old MCAT exam (61 [17.9%] had taken both). The authors calculated descriptive statistics and Pearson product moment correlations (r) between new and old MCAT section scores. They conducteda regression analysis of MCAT section scores with Step 1 scores and with preclerkship course performance. They also conducted an exploratory factor analysis (principal component analysis with varimax rotation) of MCAT scores, undergraduate grade point average, Step 1 scores, and course performance.

Results
The new MCAT exam section mean score percentiles ranged from 72 to 78 (mean composite score percentile of 80). The old MCAT exam section mean score percentiles ranged from 84 to 88 (mean composite score percentile of 83). The pattern of correlations among and between new and old MCAT exam section scores (range of r: 0.03–0.67; P < .01) provided evidence of both divergent and convergent validities. Backward multiple regression of new MCAT exam section scores and Step 1 scores resulted in a multiple R of .440; the same analysis with Human Behavior course performance as the dependent variable provided a similar solution with the expected sections of the new MCAT exam (multiple R = .502). The factor analysis resulted in 4 cohesive, theoretically meaningful factors: biomedical knowledge, basic science concepts, cognitive reasoning, and general achievement.

Conclusions
This study provided empirical evidence of multiple types of validity for the new MCAT exam.
Impact of Rectus Muscle Injury during Perforator Dissection on Functional Donor Morbidity after Deep Inferior Epigastric Perforator Flap Breast Reconstruction
Authors: Lee Kyeong-Tae , Park Jin-Woo , Mun Goo-Hyun 
Published: November 2019

Background:This study aimed to assess the extent of rectus muscle damage in deep inferior epigastric perforator (DIEP) flap harvest and to evaluate its association with functional donor morbidity.Methods:A prospective cohort of 76 patients who underwent DIEP flap breast reconstruction was evaluated preoperatively and followed up for 1 year. Abdominal wall strength was assessed using the upper and lower rectus abdominis manual muscle function tests. Functional weakness was defined as a postoperative decrease in function by at least 2 scores. The effects of patient- and operation-related characteristics on adverse outcomes were also assessed.Results:The mean width of the transected rectus muscle was 2.2 cm (partial thickness, 1.8 cm; full thickness, 0.4 cm). The mean width ratio of the overall injured muscle to the entire bilateral muscle was 0.18. Muscle injury was more severe in the cases with bipedicled flap elevation and in those with 4 or more perforators harvested. Functional weakness was detected in 13 patients (17.1%). Multivariate analyses demonstrated that the width ratio of the muscle injury was an independent predictor of functional weakness. The width ratio achieved maximal discrimination regarding the rate of functional weakness at a threshold value of 0.12, indicating that functional weakness did not develop in all 19 cases with a width ratio of <0.12.Conclusions:The extent of rectus muscle injury during perforator dissection may be associated with functional donor morbidity after DIEP flap harvest. This may be beneficial in achieving proper balance between securing flap perfusion and preserving donor functions.