Exercise-Induced Plasma Metabolomic Profiles in Patients With Peripheral Arterial Disease

Aim: A better knowledge of the biological consequences in the blood of these exercise-induced ischemic events in lower extremity artery disease (LEAD) may improve the prospects of disease management. We explored the preminus postexercise metabolomic difference in 39 patients with LEAD referred for a treadmill oximetry test [transcutaneous oximetry (TcPO2)].Methods: Ischemia was estimated through the sum of decrease from rest of oxygen pressure (DROPs) (limb TcPO2 changes minus chest TcPO2 changes) at buttocks, thighs, and calves regions. Targeted metabolomic analyses measuring 188 metabolites were performed on a few microliters blood samples taken at the earlobe at rest and 3 min after exercise.Results: Maximum walking distance (MWD) was 290 m (120–652 m) and ankle brachial index (ABI) was 0.67 ± 0.17. Supervised paired partial least squares discriminant analysis based on 23,345 models showed good predictive performance for test sets with a median area under the receiver operating characteristic (AUROC) curve value of 0.99 and a p-value of 0.00049. The best discriminant metabolites contributing to the model included a subset of 71 (47%) of the 150 accurately measured metabolites in the plasma, comprising 3 acylcarnitines, 3 amino acids, 5 biogenic amines, 9 sphingomyelin, 7 lysophosphatidylcholines, and 44 phosphatidylcholines. In addition, 16 of these metabolites were found to correlate with one or more severity scores of the LEAD.Conclusion: Our results provide new insights into the biological changes that accompany exercise in LEAD and contribute to a better understanding of walking impairment pathophysiology in LEAD, highlighting new candidate biomarkers.

Model-Informed Precision Dosing during Infliximab Induction Therapy Reduces Variability in Exposure and Endoscopic Improvement between Patients with Ulcerative Colitis

Model-informed precision dosing (MIPD) may be a solution to therapeutic failure of infliximab for patients with ulcerative colitis (UC), as underexposure could be avoided, and the probability of endoscopic improvement (pEI; Mayo endoscopic subscore ≤1) could be optimized. To investigate in silico whether this claim has merit, four induction dosing regimens were simulated: 5 mg/kg (label dosing), 10 mg/kg, covariate-based MIPD (fat-free mass, corticosteroid use, and presence of extensive colitis at baseline), and concentration-based MIPD (based on the trough concentration at day 14). Covariate- and concentration-based MIPD were chosen to target the same median area under the infliximab concentration-time curve up to endoscopy at day 84 (AUCd84), as was predicted from 10 mg/kg dosing. Dosing at 5 mg/kg resulted in a mean ± standard deviation pEI of 55.7% ± 9.0%. Increasing the dose to 10 mg/kg was predicted to improve pEI to 65.1% ± 6.1%. Covariate-based MIPD reduced variability in exposure and pEI (65.1% ± 5.5%). Concentration-based MIPD decreased variability further (66.0% ± 3.9%) but did so at an increased average dose of 2293 mg per patient, as compared to 2168 mg for 10 mg/kg dosing. Mean pEI remained unchanged between 10 mg/kg dosing and MIPD, since the same median AUCd84 was targeted. In conclusion, quantitative simulations predict MIPD will reduce variability in exposure and pEI between patients with UC during infliximab induction therapy.

Two new feather mites of the genus Trouessartia Canestrini, 1899 (Acariformes: Trouessartiidae) from tyrant flycatchers (Passeriformes: Tyrannidae) in Argentina

Two new species of the feather mite genus Trouessartia (Analgoidea: Trouessartiidae) are described from tyrant flycatchers (Tyrannidae) in Argentina: Trouessartia salvadori sp. nov. from the White-crested Tyrannulet Serpophaga subcristata (Vieillot) and T. gonzalezacunai sp. nov. from the Vermilion Flycatcher Pyrocephalus rubinus (Boddaert). Trouessartia salvadori sp. nov. is close to T. longiducta Hernandes et Valim, 2015 and most clearly differs from the latter in having, in males, the genital apparatus with wedge-shaped hyaline extensions and the anterior genital papillae situated more distant from the midline than posterior ones, and in females, setae h1 not extending beyond the margin of the interlobar membrane, and the posterior part of the hysteronotal shield bearing well outlined ovate lacunae except in the narrow median area. Trouessartia gonzalezacunai sp. nov. is similar to T. savanae Hernandes, 2014, but is distinguished from that species in having, in males, the terminal lamellae shaped as a fishtail, the epiandrum shaped as a goblet, the apophyses of adanal apodemes represented by thick spine-like tubercles, and in females, setae h1 minute spiculiform about 10 long, and the external copulatory tube shaped as a small rounded tubercle near the margin of interlobar membrane.

Development of a bedside score to predict dengue severity

Background In 2017, New Caledonia experienced an outbreak of severe dengue causing high hospital burden (4379 cases, 416 hospital admissions, 15 deaths). We decided to build a local operational model predictive of dengue severity, which was needed to ease the healthcare circuit. Methods We retrospectively analyzed clinical and biological parameters associated with severe dengue in the cohort of patients hospitalized at the Territorial Hospital between January and July 2017 with confirmed dengue, in order to elaborate a comprehensive patient’s score. Patients were compared in univariate and multivariate analyses. Predictive models for severity were built using a descending step-wise method. Results Out of 383 included patients, 130 (34%) developed severe dengue and 13 (3.4%) died. Major risk factors identified in univariate analysis were: age, comorbidities, presence of at least one alert sign, platelets count < 30 × 109/L, prothrombin time < 60%, AST and/or ALT > 10 N, and previous dengue infection. Severity was not influenced by the infecting dengue serotype nor by previous Zika infection. Two models to predict dengue severity were built according to sex. Best models for females and males had respectively a median Area Under the Curve = 0.80 and 0.88, a sensitivity = 84.5 and 84.5%, a specificity = 78.6 and 95.5%, a positive predictive value = 63.3 and 92.9%, a negative predictive value = 92.8 and 91.3%. Models were secondarily validated on 130 patients hospitalized for dengue in 2018. Conclusion We built robust and efficient models to calculate a bedside score able to predict dengue severity in our setting. We propose the spreadsheet for dengue severity score calculations to health practitioners facing dengue outbreaks of enhanced severity in order to improve patients’ medical management and hospitalization flow.

Yield Performance of Spring Oats Varieties as a Response to Fertilization and Sowing Distance

The main objective of this paper is to evaluate the yield potential of 25 different varieties of oat as a reaction to seeding distance and fertilization for improvement of crop technology and identification of the most adapted varieties. Based ANOVA test, the main influence on yield is due to climate, followed by the amount of fertilizers. The sowing distance reveals its influence when combined with the fertilization, this aspect pointing out the differences between studied varieties. The triple interactions gradually reduce the influence of the factors, their combination being very significant in the case year X sowing distance X variety. The spatial comparative analysis of the three experimental years presents an overlap in the median area of the PCA ordering of the 12.5 cm sowing distance, fertilized with N50P50 with the 25 cm sowing distance fertilized with N100P50. There are differences between the oat varieties regarding the reaction to the nitrogen fertilization, highlighting especially the Mureşana variety where comparable yields are obtained on both levels of fertilization: 5.18 t ha−1 (N50P50) and 5.59 t ha−1 (N100P50).

A new species of Odontepyris (Hymenoptera: Bethylidae: Bethylinae) from East Asia

Odontepyris costatus sp. nov. is described from Japan and Taiwan. This new species is most similar to O. formosicola Terayama, 1997 known from Cambodia and Taiwan according to the key to the Eastern Palaearctic Odontepyris. O. costatus sp. nov. can be distinguished from the latter by the relatively small eye and the wide metapectal-propodeal disc. It is also similar to O. telortis Lim & Lee, 2009 known from South Korea, but it is distinguished from O. telortis by the imbricate median area of metapostnotum. The morphological variations and diagnostic characters of the Eastern Palaearctic species are briefly discussed and the modified key to species is provided. Key words: new species, Japan, Taiwan, wing venation

Development of a bedside score to predict dengue severity

BackgroundIn 2017, New Caledonia experienced an outbreak of severe dengue causing high hospital burden (4,379 cases, 416 hospital admissions, 15 deaths). We decided to build a local operational model predictive of dengue severity, which was needed to ease the healthcare circuit.MethodsWe retrospectively analyzed clinical and biological parameters associated with severe dengue in the cohort of patients hospitalized at the Territorial Hospital between January and July 2017 with confirmed dengue, in order to elaborate a comprehensive patient’s score. Patients were compared in univariate and multivariate analyses. Predictive models for severity were built using a descending step-wise method.ResultsOut of 383 included patients, 130 (34%) developed severe dengue and 13 (3.4%) died. Major risk factors identified in univariate analysis were: age, comorbidities, presence of at least one alert sign, platelets count <30×109/L, prothrombin time <60%, AST and/or ALT >10N, and previous dengue infection. Severity was not influenced by the infecting dengue serotype nor by previous Zika infection. Two models to predict dengue severity were built according to sex. Best models for females and males had respectively a median Area Under the Curve = 0.80 and 0.88, a sensitivity = 84.5% and 84.5%, a specificity = 78.6% and 95.5%, a positive predictive value = 63.3% and 92.9%, a negative predictive value = 92.8% and 91.3%. Models were secondarily validated on 130 patients hospitalized for dengue in 2018.ConclusionWe built robust and efficient models to calculate a bedside score able to predict dengue severity in our setting. We propose the spreadsheet for dengue severity score calculations to health practitioners facing dengue outbreaks of enhanced severity in order to improve patients’ medical management and hospitalization flow.

PCT Kinetics in the First Week Postburn for Sepsis Diagnosis and Death Prognosis—An Accuracy Study

Despite continuous advances in burn care, sepsis is still the main cause of death in burn patients. Procalcitonin (PCT) has been reported as an accurate sepsis biomarker and also as a fair predictor of death. The aim of this study was to assess PCT kinetics in the first week postburn regarding sepsis diagnosis and death prognosis. Sample included 142 patients with ≥15% TBSA, admitted from January 2011 to December 2014 at Coimbra Burns Unit, Portugal. Sepsis diagnosis was done according to American Burn Association criteria. PCT range and median values in the first 7 days after burns were statistically analyzed for its potential for sepsis diagnosis and death prognosis. A subanalysis was done regarding TBSA, sex, age, and inhalation injury. First week PCT range and median were significant for sepsis diagnosis and death prognosis, but the median area under the curve was greater in the last case. TBSA influenced PCT accuracy, which was greater for TBSA less than 40% either for diagnosis or prognosis. Age was inversely related to the accuracy, being better in younger than 40 years in both cases. PCT diagnostic accuracy was not affected by sex, opposing to the prognostic one which is better in women. Inhalation injury had no effect on diagnostic accuracy, but it happens with prognostic accuracy. PCT levels’ variation is related to sepsis evolution and outcome. Its median performs better than its range. Always coupled with clinical examination, monitoring PCT levels kinetics may help early sepsis detection, potentially reducing morbidity and mortality, being also useful for death prognosis.

THE MORPHOLOGICAL AND FUNCTIONAL STATE OF THE ARCUATE NUCLEUS OF THE HYPOTHALAMUS OF RATS IN BURN INJURY DYNAMICS

Morphological and morphometric features of cells of arcuate nucleus of hypothalamus in dynamics of thermal burn trauma of skin are considered. The relevance of the study is due to the important role of reactive changes in the neuroendocrine regulatory complex in the pathogenesis of skin burn wounds. Since the hypothalamus is part of neuroendocrine cooperation, it shows the most pronounced signs of neuronal damage. In this regard, the aim of the study was to study qualitative and quantitative structural changes in the arcuate nucleus of the middle hypothalamus of rats in the simulation of thermal burn injury to the skin. Burn exposure was simulated in male nonlinear rats weighing 200-230 g by applying contact thermal trauma in the interblade region of the back. The functional activity of the arcuate nucleus of the hypothalamus was evaluated by quantitative analysis of the morphometric parameters of neurocyte nuclei because these organoids correlate with transcription intensity and can serve as a tool for assessing their functional state. To carry out quantitative analysis of histological preparations of hypothalamus, planimetric properties of neurons and their structures were determined: absolute values of neurons, such as: area of pericaryons, area of neurons nuclei, area of cytoplasm of neurons, nuclear-cytoplasmic ratio of neurons of arcuate nuclei of hypothalamus. On the basis of the obtained data on absolute values of neurons relative values were calculated - median area of pericaryons, median area of nuclei, median area of cytoplasm of pericaryons, median of nuclear-cytoplasmic ratio of neurons of arcuate nuclei of hypothalamus. The study revealed destructive transformations of this hypothalamic brain zone in all stages of inflammatory-regenerative reaction: on 2, 4, 7, 10 days after burn exposure. Comparative analysis of hypothalamus preparations of laboratory animals showed characteristic destructive changes in arcuate nuclei in conditions of thermal skin injury, which reflected the development of processes of reversible and irreversible damage to neurons. The detected features are generally consistent with existing ideas about the disruption of morphofunctional organization of neurons in this zone due to the implementation of adaptive mechanisms characterized by activation of local and systemic compensatory-restorative processes, focal gliosis and development of edema changes of nerve cells.

The challenge of performing mastoidectomy using the operating microscope with coronavirus disease 2019 personal protective equipment (PPE)

ObjectiveMastoidectomy is considered an aerosol-generating procedure. This study examined the effect of wearing personal protective equipment on the view achieved using the operating microscope.MethodsENT surgeons assessed the area of a calibrated target visible through an operating microscope whilst wearing a range of personal protective equipment, with prescription glasses when required. The distance between the surgeon's eye and the microscope was measured in each personal protective equipment condition.ResultsEleven surgeons participated. The distance from the eye to the microscope inversely correlated with the diameter and area visible (p < 0.001). The median area visible while wearing the filtering facepiece code 3 mask and full-face visor was 4 per cent (range, 4–16 per cent).ConclusionThe full-face visor is incompatible with the operating microscope. Solutions offering adequate eye protection for aerosol-generating procedures that require the microscope, including mastoidectomy, are urgently needed. Low-profile safety goggles should have a working distance of less than 20 mm and be compatible with prescription lenses.