bluuebunny/crossref_metadata_2025_split huggingface dataset:
The development of an indirect computed tomography lymphography protocol for sentinel lymph node detection in head and neck cancer and comparison to other sentinel lymph node mapping techniques
Authors: Randall Elissa K. , Jones Matthew D. , Kraft Susan L. , Worley Deanna R. 
Published: March 2020

AbstractIdentification of metastatic disease critically impacts the care and prognosis of patients with neoplasia. Multiple techniques exist for identifying the sentinel or first lymph node(s) that receive draining tumour lymph. Identification of the sentinel lymph node enables accurate tissue sampling for determination of lymphatic metastasis. The aims of this study were to develop a computed tomography (CT) protocol for identifying the sentinel lymph node in dogs with tumours of the head and neck. In addition, indirect CT lymphography was compared to lymphoscintigraphy and vital dye injection to determine which technique more reliably identified the sentinel lymph node. CT indirect lymphography using intratumoral injection of iodinated contrast identified draining lymphatic vessels in eight of 18 dogs and identified the sentinel lymph node in five of 18 dogs. CT indirect lymphography employing four‐quadrant peritumoral injection of iodinated contrast identified draining lymphatic vessels in 18 of 20 dogs and identified the sentinel lymph node in 11 of 20 dogs. Vital dye injection and lymphoscintigraphy identified the sentinel lymph node in 17 of 18 and 20 of 20 dogs, respectively. Identified sentinel lymph nodes were either ipsilateral or bilateral to the primary tumour. Both CT techniques were found to be safe and simple. Peritumoral injection has the greatest promise for the detection of sentinel lymph nodes in various head and neck cancers using CT, while lymphoscintigraphy had the greatest success of the compared techniques.
A murine model of Staphylococcus aureus infected chronic diabetic wound: A new tool to develop alternative therapeutics
Authors: Huon Jean‐François , Gaborit Benjamin , Caillon Jocelyne , Boutoille David , Navas Dominique 
Published: March 2020

AbstractDiabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL‐17A compared to control mice that resulted in an IL‐17/IFN‐γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL‐10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL‐10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL‐10/IFN‐γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.
The effects of hypoxia and fatigue on skeletal muscle electromechanical delay
Authors: Jacunski Mark , Rafferty Gerrard F. 
Published: March 2020

New Findings
What is the central question of this study?
What are the mechanisms underlying impaired muscular endurance and accelerated fatigue during acute hypoxia?
What is the main finding and its importance?
Hypoxia had no effect on the electrochemical latency associated with muscle contraction elicited by supramaximal electrical motor nerve stimulation in vivo. This provides greater insight into the effects of hypoxia and fatigue on the mechanisms of muscle contraction in vivo.AbstractAcute hypoxia impairs muscle endurance and accelerates fatigue, but the underlying mechanisms, including any effects on muscle electrical activation, are incompletely understood. Electromyographic, mechanomyographic and force signals, elicited by common fibular nerve stimulation, were used to determine electromechanical delay (EMDTOT) of the tibialis anterior muscle in normoxia and hypoxia ( 0.125) at rest and following fatiguing ankle dorsiflexor exercise (60% maximum voluntary contraction, 5 s on, 3 s off) in 12 healthy participants (mean (SD) age 27.4 (9.0) years). EMDTOT was determined from electromyographic to force signal onset, electrical activation latency from electromyographic to mechanomyographic (EMDE‐M) and mechanical latency from mechanomyographic to force (EMDM‐F). Twitch force fell significantly following fatiguing exercise in normoxia (46.8 (14.7) vs. 20.6 (14.3) N, P = 0.0002) and hypoxia (52.9 (15.4) vs. 28.8 (15.2) N, P = 0.0006). No effect of hypoxia on twitch force at rest was observed. Fatiguing exercise resulted in significant increases in mean (SD) EMDTOT in normoxia (Δ 4.7 (4.57) ms P = 0.0152) and hypoxia (Δ 3.7 (4.06) ms P = 0.0384) resulting from increased mean (SD) EMDM‐F only (normoxia Δ 4.1 (4.1) ms P = 0.0391, hypoxia Δ 3.4 (3.6) ms P = 0.0303). Mean (SD) EMDE‐M remained unchanged during normoxic (Δ 0.6 (1.08) ms) and hypoxic (Δ 0.25 (0.75) ms) fatiguing exercise. No differences in percentage change from baseline for twitch force, EMDTOT, EMDE‐M and EMDM‐F between normoxic and hypoxic fatigue conditions were observed. Hypoxia in isolation or in combination with fatigue had no effect on the electrochemical latency associated with electrically evoked muscle contraction.
Protease‐dependent excitation of nodose ganglion neurons by commensal gut bacteria
Authors: Pradhananga Sabindra , Tashtush Ayssar A. , Allen‐Vercoe Emma , Petrof Elaine O. , Lomax Alan E. 
Published: March 2020

Key points
The vagus nerve has been implicated in mediating behavioural effects of the gut microbiota on the central nervous system. This study examined whether the secretory products of commensal gut bacteria can modulate the excitability of vagal afferent neurons with cell bodies in nodose ganglia.
Cysteine proteases from commensal bacteria increased the excitability of vagal afferent neurons via activation of protease‐activated receptor 2 and modulation of the voltage dependence of Na+ conductance activation.
Lipopolysaccharide, a component of the cell wall of gram‐negative bacteria, increased the excitability of nodose ganglia neurons via TLR4‐dependent activation of nuclear factor kappa B.
Our study identified potential mechanisms by which gut microbiota influences the activity of vagal afferent pathways, which may in turn impact on autonomic reflexes and behaviour.
AbstractBehavioural studies have implicated vagal afferent neurons as an important component of the microbiota‐gut‐brain axis. However, the mechanisms underlying the ability of the gut microbiota to affect vagal afferent pathways are unclear. We examined the effect of supernatant from a community of 33 commensal gastrointestinal bacterial derived from a healthy human donor (microbial ecosystem therapeutics; MET‐1) on the excitability of mouse vagal afferent neurons. Perforated patch clamp electrophysiology was used to measure the excitability of dissociated nodose ganglion (NG) neurons. NG neuronal excitability was assayed by measuring the amount of current required to elicit an action potential, the rheobase. MET‐1 supernatant increased the excitability of NG neurons by hyperpolarizing the voltage dependence of activation of Na+ conductance. The increase in excitability elicited by MET‐1 supernatant was blocked by the cysteine protease inhibitor E‐64 (30 nm). The protease activated receptor‐2 (PAR2) antagonist (GB 83, 10 μm) also blocked the effect of MET‐1 supernatant on NG neurons. Supernatant from Lactobacillus paracasei 6MRS, a component of MET‐1, recapitulated the effect of MET‐1 supernatant on NG neurons. Lastly, we compared the effects of MET‐1 supernatant and lipopolysaccharide (LPS) from Escherichia coli 05:B5 on NG neuron excitability. LPS increased the excitability of NG neurons in a toll‐like receptor 4 (TLR4)‐dependent and PAR2‐independent manner, whereas the excitatory effects of MET‐1 supernatant were independent of TLR4 activation. Together, our findings suggest that cysteine proteases from commensal bacteria increase the excitability of vagal afferent neurons by the activation of PAR2.
Central corneal basal cell density and nerve parameters in ocular surface disease and limbal stem cell deficiency: a review and meta-analysis
Authors: Bhattacharya Pradipta , Edwards Katie , Harkin Damien , Schmid Katrina L 
Published: March 2020

ObjectiveTo conduct a review and meta-analysis for investigating the relative reduction of central corneal basal cell density (BCD) and nerve parameters in ocular surface disease (OSD) and limbal stem cell deficiency (LSCD).MethodsA systematic literature search using the terms ((1) “ocular surface disease” or “ocular surface disorder”; (2) “in vivo confocal microscopy”; (3) “limbal stem cell deficiency”; (4) “basal cell density” or “corneal basal cell density” or “central corneal basal cell density”; (5) “corneal nerves” or “corneal nerve parameters” or “central corneal nerve parameters”) was performed. The results are presented as weighted mean difference (WMD) with corresponding 95% CI.Results16 studies that reported the central corneal BCD and 21 studies that reported the central corneal nerve parameters in OSD (including LSCD) were included. A significant reduction in central corneal BCD was observed in patients with various OSDs (WMD=−9.50, 95% CI −14.04 to −4.97, p<0.01) as well as in patients with LSCD (WMD=−22.14, 95% CI −37.91 to −6.37, p<0.01) compared with healthy controls, however, no significant difference in BCD was observed between the two groups (WMD=−11.61, 95% CI −15.96 to −7.26, p=0.13). There was no conclusive difference in various central corneal nerve parameters between OSDs and LSCD.ConclusionCentral corneal BCD and nerve parameters are reduced in LSCD, there is a similar reduction in other OSDs.
Comparison of true-colour wide-field confocal scanner imaging with standard fundus photography for diabetic retinopathy screening
Authors: Olvera-Barrios Abraham , Heeren Tjebo FC , Balaskas Konstantinos , Chambers Ryan , Bolter Louis , Tufail Adnan , Egan Catherine , Anderson John 
Published: March 2020

BackgroundScreening of diabetic retinopathy (DR) reduces blindness by early identification of retinopathy. This study compares DR grades derived from a two-field imaging protocol from two imaging platforms, one providing a single 60-degree horizontal field of view (FOV) and the other, a standard 45-degree FOV.MethodsCross-sectional study which included 1257 diabetic patients aged ≥18 years attending their DR screening visit in the English National Diabetic Eye Screening Programme (NDESP). Patients with maculopathy (M1), preproliferative (R2) or proliferative DR (R3) were referred to an ophthalmologist. Patients with ungradable images (U) are examined in a slit-lamp biomicroscopy clinic. Image acquisition under mydriasis of two images per eye was carried out with the EIDON and with standard fundus cameras. Evaluation was performed by masked graders.ResultsAgreement after consensus with kappa statistic was 0.89 (quadratic weights (95% CI 0.87 to 0.92)) for NDESP severity grade, 0.88 (quadratic weights (95% CI 0.82 to 0.94)) for referable disease and 0.92 (linear weights (95% CI 0.88 to 0.95)) for maculopathy. The EIDON detected clinically relevant DR features outside the 45-degree fields in two patients (0.16%): one with intraretinal microvascular abnormalities (IRMAs) and one with neovascularisation. In eight patients (0.64%), the EIDON allowed DR feature visualisation inside the 45-degree fields that were not identified in the NDESP images: three patients (0.24%) with IRMA and five patients (0.40%) with maculopathy. The rates of ungradable encounters were 12 (0.95%) and 13 (1.03%) with the EIDON and NDESP images, respectively.ConclusionThe EIDON identifies a small number of additional patients with referable disease which are not detected with standard imaging. This is due to the EIDON finding disease outside the standard FOV and greater clarity finding disease within the standard FOV.
Acceptability, adherence and economic analyses of a new clinical pathway for the identification of non-responders to glaucoma eye drops: a prospective observational study
Authors: Waterman Heather , Read Simon , Morgan James Edwards , Gillespie David , Nollett Claire , Allen Davina , Weiss Marjorie , Anderson Pippa 
Published: March 2020

Background/aimsAssess whether a new clinical pathway for glaucoma was acceptable to patients and healthcare professionals and whether it provided useful clinical information on non-responsiveness and non-adherence to the treatment of elevated intraocular pressure with latanoprost eye drops.MethodsA single arm non-randomised prospective observational study incorporating new glaucoma/ocular hypertension patients. To assess issues of acceptability, qualitative observation and interviews were conducted with patients and healthcare professionals. To determine clinical responsiveness, intraocular pressures were measured before and 4 hours after a clinician-instilled eye drop over two distinct appointments. Adherence data were collected using a Medicine Event Monitoring System. Economic analyses compared the costs between novel and standard care pathways.ResultsOf 72 patients approached, 53 entered the study (74.3%) and 50 completed all procedures (94.3%). Intraocular pressure was reduced more than 15% in 83 out of 92 study eyes by final visit (90.2%). The non-response rate was 5.1% once the effect of low adherence was minimised. For the 1376 drop instillation days under observation, eye drops were instilled as prescribed on 1004 days (73.0%), over-instilled on 137 days (9.9%) and not instilled on 235 days (17.1%). The Cardiff Model of Glaucoma Care involved negligible cost, although acceptance for healthcare professionals showed variation.ConclusionsThe Cardiff Model of Glaucoma Care offers novel clinical and adherence insights at marginal costs while acceptable to patients. Healthcare professionals felt that 4 hour and 4 week follow-up appointments could cause administrative problems. A streamlined version of the pathway has therefore been developed to facilitate clinical adoption.Trial registration numberISRCTNID:ISRCTN75888393
Incidence and associates of diabetic ketoacidosis in a community-based cohort: the Fremantle Diabetes Study Phase II
Authors: Davis Timothy M E , Davis Wendy 
Published: March 2020

ObjectiveTo assess the incidence and associates of diabetic ketoacidosis (DKA) in a representative community-based cohort.MethodsAll hospitalizations of 1724 participants in the Fremantle Diabetes Study Phase II for/with DKA (plasma glucose >13.8 mmol/L, urinary/serum ketones, serum bicarbonate <18 mmol/L and/or arterial/venous pH <7.30) were identified between study entry from 2008 to 2011 and end-2013. Details of each episode were categorized by chart review as confirmed/probable DKA, possible DKA or not DKA. Incidence rates by diabetes type were calculated. Cox proportional hazards modeling determined predictors of first episode, and negative binomial regression identified predictors of frequency.ResultsThere were 53 coded DKA episodes (41 first episodes, 12 recurrences), of which 19 (35.8%) were incorrectly coded, 9 (17.0%) had possible DKA and 25 (47.2%) had confirmed/probable DKA. Of this latter group, 44% had type 1 diabetes, 32% had type 2 diabetes, 12% had latent autoimmune diabetes of adults (LADA) and 12% had secondary diabetes. The overall incidence of confirmed/probable DKA (95% CI) was 35.6 (23.0 to 52.6)/10 000 person-years (178.6 (85.7 to 328.5)/10 000 person-years for type 1 diabetes, 13.3 (5.7 to 26.1)/10 000 person-years for type 2 diabetes, 121.5 (33.1 to 311.0)/10 000 person-years for LADA and 446.5 (92.1 to 1304.9)/10 000 person-years for secondary diabetes). Baseline ln(fasting serum C-peptide) (inversely), glycated hemoglobin and secondary diabetes predicted both incident first confirmed/probable DKA episode and the frequency of DKA (p<0.001).ConclusionsThese data highlight the contribution of poor glycemic control and limited pancreatic beta cell function to incident DKA, and show that people with types of diabetes other than type 1, especially secondary diabetes, are at risk.
Prevalence and major risk factors of type 2 diabetes mellitus among adult psychiatric inpatients from 2005 to 2018 in Beijing, China: a longitudinal observational study
Authors: Yang Fude , Ma Qiuyue , Liu Jue , Ma Botao , Guo Moning , Liu Fangchao , Li Juan , Wang Zhiren , Liu Min 
Published: March 2020

ObjectiveWe aim to investigate the prevalence, trends, and major risk factors of type 2 diabetes mellitus (T2DM) among adult psychiatric inpatients in Beijing, China.Research design and methodsWe did a longitudinal observational study using data from the Beijing Municipal Commission of Health and Family Planning Information Center, including 157 570 adult psychiatric inpatients in 19 specialized psychiatric hospitals from 2005 to 2018 in Beijing. Data on demographic characteristics and antipsychotic medication use were obtained from electronic health records. Schizophrenia, T2DM, and comorbidities were defined according to the International Classification of Diseases, 10th revision codes of discharge diagnosis. The overall prevalence of T2DM in adult psychiatric inpatients was calculated, and the annual prevalence of T2DM was calculated and adjusted to the overall participant population. Univariate and multivariate logistic regression analyses were performed to obtain crude ORs and adjusted ORs (aORs) on the risk of T2DM in patients with different demographic characteristics, schizophrenia, antipsychotic medication use, and different comorbidities. Age-specific prevalence of T2DM under a stratification of schizophrenia or other psychiatric disorders was calculated in the subgroup analysis.ResultsOut of 157 570 adult inpatients, 16 939 had T2DM, with a prevalence of 10.75% (95% CI 10.60% to 10.90%). The prevalence was 11.63% (95% CI 11.37% to 11.88%) among patients with schizophrenia and 10.17% (95% CI 9.98% to 10.37%) among patients with other psychiatric disorders. During 2005–2018, the prevalence of T2DM in adult patients increased over the years, from an adjusted prevalence of 5.20% in 2005, to 10.98% in 2010, 12.50% in 2015, and 12.71% in 2018. Results from the multivariate analysis showed that increasing age, diagnosis of schizophrenia (aOR=1.23, 95% CI 1.18 to 1.29), and comorbidities of hypertension (aOR=3.09, 95% CI 2.97 to 3.22), lipid disorders (aOR=1.95, 95% CI 1.88 to 2.04), and fatty liver (aOR=1.93, 95% CI 1.84 to 2.03) were major risk factors of T2DM in adult psychiatric inpatients.ConclusionsThe prevalence of T2DM was high among adult psychiatric inpatients in Beijing, China. Elderly patients, those with schizophrenia, and those with hypertension, lipid disorders, and fatty liver had higher prevalence of T2DM. Prevention and treatment of T2DM are of utmost relevance in hospitalized psychiatric patients.
Glucagon receptor antagonist upregulates circulating GLP-1 level by promoting intestinal L-cell proliferation and GLP-1 production in type 2 diabetes
Authors: Lang Shan , Yang Jin , Yang Kun , Gu Liangbiao , Cui Xiaona , Wei Tianjiao , Liu Junling , Le Yunyi , Wang Haining , Wei Rui , Hong Tianpei 
Published: March 2020

ObjectiveGlucagon receptor (GCGR) blockage improves glycemic control and increases circulating glucagon-like peptide-1 (GLP-1) level in diabetic animals and humans. The elevated GLP-1 has been reported to be involved in the hypoglycemic effect of GCGR blockage. However, the source of this elevation remains to be clarified.Research design and methodsREMD 2.59, a human GCGR monoclonal antibody (mAb), was administrated for 12 weeks indb/dbmice and high-fat diet+streptozotocin (HFD/STZ)-induced type 2 diabetic (T2D) mice. Blood glucose, glucose tolerance and plasma GLP-1 were evaluated during the treatment. The gut length, epithelial area, and L-cell number and proliferation were detected after the mice were sacrificed. Cell proliferation and GLP-1 production were measured in mouse L-cell line GLUTag cells, and primary mouse and human enterocytes. Moreover, GLP-1 receptor (GLP-1R) antagonist or protein kinase A (PKA) inhibitor was used in GLUTag cells to determine the involved signaling pathways.ResultsTreatment with the GCGR mAb lowered blood glucose level, improved glucose tolerance and elevated plasma GLP-1 level in bothdb/dband HFD/STZ-induced T2D mice. Besides, the treatment promoted L-cell proliferation and LK-cell expansion, and increased the gut length, epithelial area and L-cell number in these two T2D mice. Similarly, our in vitro study showed that the GCGR mAb promoted L-cell proliferation and increased GLP-1 production in GLUTag cells, and primary mouse and human enterocytes. Furthermore, either GLP-1R antagonist or PKA inhibitor diminished the effects of GCGR mAb on L-cell proliferation and GLP-1 production.ConclusionsThe elevated circulating GLP-1 level by GCGR mAb is mainly due to intestinal L-cell proliferation and GLP-1 production, which may be mediated via GLP-1R/PKA signaling pathways. Therefore, GCGR mAb represents a promising strategy to improve glycemic control and restore the impaired GLP-1 production in T2D.
Prevalence and severity of periodontal disease among Spanish military personnel
Authors: Bárcena García Millán , Cobo Plana J M , Arcos González P I 
Published: March 2020

IntroductionPeriodontal disease ranges from simple gums inflammation to major damage to the periodontal tissues, even losing teeth. Severe periodontitis has a world overall prevalence of 11.2%. These are evaluated with periodontal probes and oral epidemiological indices. Our aim is to estimate the prevalence and severity of periodontal disease of a Spanish military population according to the 2013 WHO criteria.MethodsObservational study of prevalence carried out in a representative random sample of 221 military staff from the Spanish Army base ‘Conde de Gazola’. Prevalence was estimated by calculating the Community Periodontal Index modified, loss of attachment, Plaque Index and Gingival Bleeding Index measured with a third-generation electronic ‘Pa-on’ periodontal probe.ResultsAverages of probing depth, recession and clinical attachment level were 2.17, 0.19 and 2.36 mm. Plaque and gingival bleeding indices were 71% and 40.3%. All subjects bled in some tooth after probing. 3.6% of subjects had no periodontal pockets, 58.8% mild periodontal pockets and 37.1% severe periodontal pockets. All had some loss of attachment, 52% mild loss of attachment and 47.5% severe loss of attachment. Teeth present with and without bleeding were 24.4 (86.5%) and 3.6 (13.1%). 28% of teeth had periodontal pockets and 40.4% loss of attachment. Sextant averages with periodontal pockets and loss of attachment were 2.79 and 3.56.ConclusionsOur plaque and gingival bleeding indices were high and we found a higher prevalence and severity of periodontal disease than other Spanish and foreign military populations. This could be related to differences in context, life habits and insufficient dental hygiene.