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Serum metabolomic research of the anti-pulmonary fibrosis effects of Shuangshen Pingfei Formula on bleomycin-induced pulmonary fibrosis rats

J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Mar 12;1197:123225. doi: 10.1016/j.jchromb.2022.123225. Online ahead of print.

ABSTRACT

Our previous studies showed that Shuangshen Pingfei Formula (SSPF) exhibited anti-fibrosis effect, but its biochemical changes at the metabolic level remain unclear. In this study, an integrative approach of gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS)-based non-targeted metabolomics and multivariate statistical analysis was employed to explore the metabolic changes of serum samples from different stages of bleomycin-induced pulmonary fibrosis (PF) rats (PFRs: M7, M14, M21 and M28) treated with SSPF extracts. Potential biomarkers for PF were screened. Benzenebutanoic acid, pyroglutamic acid, cholic acid, 1-monopalmitin, succinic acid and palmitoleic acid may be potential biomarkers of the early inflammation stage of PF (M7-M14). 3,4-dimethylbenzoic acid, glutamic acid, glycine, proline, serine, taurine, etc. may be potential biomarkers for the advanced pulmonary fibrosis stage (M21-M28) of PF. The disturbance was mainly related to the disorder of lipid, amino acid metabolism. After SSPF treatment, the disorder was regulated and 67 metabolites were restored to a certain extent. Serine, proline, glutamine, 4-guanidinobutyric acid, phosphatidylethanolamine, lecithin and 9,10-epoxyoctadecene acids may be useful as biomarkers of the anti-fibrosis effect of SSPF.

PMID:35397413 | DOI:10.1016/j.jchromb.2022.123225

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Characterization of lesions in the temporal muscle and the male reproductive system (epididymis and testicle) of dogs experimentally infected with Leishmania infantum with different clinical stages

Vet Parasitol. 2022 Mar 26;305:109700. doi: 10.1016/j.vetpar.2022.109700. Online ahead of print.

ABSTRACT

Leishmaniosis is a zoonotic disease with a very complex pathogenesis modulated by the interaction between the parasite, the vector and the host. Although the pathological characteristics have been extensively studied in the typically affected organs, some locations such as muscles and reproductive organs have been less studied. The objective of this study was to evaluate the presence of lesions in the temporal muscle and the male reproductive organs (testicle and epididymis) and correlate their characteristics with the presence of the parasite and with the clinical status of the dogs. The temporal muscle was studied in 25 infected beagle dogs (nine females and 16 males) and five uninfected control dogs (two females and three males) and the testicle and epididymis in the 19 males. Dogs were euthanized one year after infection and clinical signs, anti-Leishmania serum antibodies, and lymph node parasite load were assessed. Muscular and reproductive lesions were characterized by H&E and immunohistochemistry (IHC). The presence of the parasite in the lesions was evaluated using IHC and molecular techniques. Myositis was observed in 72% (18/25) of the dogs and was characterized by lymphoplasmacytic or histiocytic lesions. Mild and severe lesions were detected, the latter being statistically associated with the presence of the parasite and with the clinical status of the dogs. Orchitis was observed in 50% (8/16) of the dogs and was mainly mild and lymphoplasmacytic. No statistical relationship was found between testicular lesions and the presence of the parasite or the clinical status. Epididymitis was observed in 87.5% (14/16) of the dogs, and the lesions were often infiltrated by numerous histiocytes and neutrophils. Epididymal lesions were statistically associated with the clinical status of the dogs and with the presence of the parasite in the lesions. IgG and IgM immunoglobulins were found in all lesions, suggesting a local immune response with reactivation of the infection. Leishmania was more frequently detected in severe and histiocytic lesions, although some lesions had no detectable parasites. These results have shown that lesions in the temporal muscle, epididymis, and testicles are common in dogs infected by Leishmania infantum and that dogs may show a different response to infection. This response is characterized by varying degrees of cellular and immune responses associated with a variable presence of the parasite.

PMID:35397378 | DOI:10.1016/j.vetpar.2022.109700

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Are UK medical schools using recommended national curricula for the teaching of clinical neuroscience?

Clin Neurol Neurosurg. 2022 Mar 26;216:107224. doi: 10.1016/j.clineuro.2022.107224. Online ahead of print.

ABSTRACT

BACKGROUND: Medical schools are responsible for training medical students to recognise and commence management for a broad spectrum of diseases, including clinical neuroscience conditions. To guide medical schools on topics that should be taught, speciality bodies have produced speciality-based core curricula. It is unknown to what extent these guidelines are used in designing each medical school’s curriculum. This survey aimed at assessing the use of these guidelines in designing clinical neuroscience curricula.

METHODS: This is a national survey. A 21-item questionnaire was sent to faculty members involved in the development of the clinical neuroscience curriculum in each medical school in the UK. Data collection occurred from1st September 2020-31 st August 2021. The Association of British Neurologists (ABN) and the Royal College of Surgeons England (RCSEng) guidelines were used as a benchmark. Descriptive statistics are reported.

RESULTS: Data was collected from 91.9% of eligible UK medical schools. 61.8% respondents were aware of ABN guidelines and 35.3% were aware of RCSEng guidelines. 17/28 (60.7%) topics recommended by the guidelines were taught in the neuroscience curricula of over 90% of the medical schools. Neurologists were involved in the design of the clinical neuroscience curriculum in 94.1% (n = 32/34) of medical schools, and neurosurgeons in 61.8%. Tutorials/seminars were used by all medical schools to teach clinical neuroscience content. Neurologists were involved in teaching at all schools and neurosurgeons in 70.6%. Objective Structured Clinical Examination (OSCE)/oral examinations and single best answer (SBA)/multiple-choice question (MCQ) tests were used in all medical schools as methods of assessment.

CONCLUSIONS: There is variation between medical schools on what clinical neuroscience topics are taught and by whom. Multi-modality educational delivery was evident. Some medical schools did not currently use, advertise, or recommend external clinical neuroscience educational resources; but there was support for future use of external resources including guidelines.

PMID:35397346 | DOI:10.1016/j.clineuro.2022.107224

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Efficacy of myofascial therapy and kinesitherapy in improving function in shoulder pathology with prolonged immobilization: A randomized, single-blind, controlled trial

Complement Ther Clin Pract. 2022 Apr 4;48:101580. doi: 10.1016/j.ctcp.2022.101580. Online ahead of print.

ABSTRACT

BACKGROUND: The best physiotherapeutic approach in shoulder pathology that generates prolonged immobilization is still uncertain. Kinesitherapy remains the most widely used option. Myofascial therapy is a therapeutic approach in which the aim is to release fascial tension and regain mobility although its efficacy in shoulder pathology has not been sufficiently studied. This Prospective, single-blind randomized controlled trial in a university hospital setting aimed to compare the efficacy of myofascial therapy and kinesitherapy in improving function in shoulder pathology with prolonged immobilization.

METHODS: Patients were randomly assigned to a control group or to the intervention group.Both groups completed a therapeutic exercise program.

MAIN OUTCOME MEASURES: The QuickDash questionnaire was the primary outcome, Pain Visual Analog Scale and the Range Of Motion of the shoulder were the secondary outcomes. The outcomes were evaluated at baseline (T0), at 4 (T2), 8 (T2), and 12 weeks (T3) RESULTS: 44 participants were included. In the analysis of evolution over time, a significant improvement in functionality and range of motion measurements was observed in both groups (p < 0.05), although at 12 weeks only Myofasical Group achieved a clinically and statistically significant reduction in pain. Comparative analysis at 12 weeks revealed no statistically significant differences between the two therapies in the variables explored.

CONCLUSIONS: Both, myofascial therapy and kinesitherapy can improve function, mobility, and pain in patients with painful shoulder associated with prolonged immobilization, with no significant differences between therapies, although in the medium term only myofascial therapy achieves a clinically and statistically significant improvement in pain.

TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov NCT04944446.

PMID:35397306 | DOI:10.1016/j.ctcp.2022.101580

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Lupus nephritis diagnosis using enhanced moth flame algorithm with support vector machines

Comput Biol Med. 2022 Apr 2;145:105435. doi: 10.1016/j.compbiomed.2022.105435. Online ahead of print.

ABSTRACT

Systemic lupus erythematosus is a chronic autoimmune disease that affects the kidney in most patients. Lupus nephritis (LN) is divided into six categories by the International Society of Nephrology/Renal Pathology Society (ISN/RPS). The purpose of this research is to build a framework for discriminating between ISN/RPS pure class V(MLN) and classes III ± V or IV ± V (PLN) using real clinical data. The framework is developed by merging a hybrid stochastic optimizer, moth-flame algorithm (HMFO), with a support vector machine (SVM), dubbed HMFO-SVM. The HMFO is constructed by enhancing the original moth-flame algorithm (MFO) with a bee-foraging learning operator, which guarantees that the algorithm speeds convergence and departs from the local optimum. The HMFO is used to optimize parameters and select features simultaneously for SVM on clinical SLE data. On 23 benchmark tests, the suggested HMFO method is validated. Finally, clinical data from LN patients are analyzed to determine the efficacy of HMFO-SVM over other SVM rivals. The statistical findings indicate that all measures have predictive capabilities and that the suggested HMFO-SVM is more stable for analyzing systemic LN. HMFO-SVM may be used to analyze LN as a feasible computer-assisted technique.

PMID:35397339 | DOI:10.1016/j.compbiomed.2022.105435

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Standardizing nursing degree curriculum structure in Spain: A mixed-methods study

Nurse Educ Today. 2022 Apr 4;112:105360. doi: 10.1016/j.nedt.2022.105360. Online ahead of print.

ABSTRACT

BACKGROUND: Legislation regulating Spanish and European academic curricula prescribes a certain level of knowledge and skills any student must master. Spanish universities freely decide the number of credits assigned to each subject and in which year the subject will be taught. We hypothesize that this flexibility may give way to excessively heterogeneous training across universities in nursing degrees. Such curricula heterogeneity hinders inter-university transfers and weakens educational excellence.

OBJECTIVES: 1) To review the existing differences in nursing degrees in Spanish universities; 2) to compare our results against current legislation; 3) to propose changes in the legislation, if necessary.

DESIGN: Mixed-methods approach.

SETTING: Spain.

METHODS: We reviewed nursing degree curricula of all 60 Spanish universities. Inter-university differences were analyzed and checked against current legislation. A focus group proposed legislative changes accordingly.

RESULTS: Several differences between public and private universities were statistically significant. During the first cycle, public universities´ course loads include more theoretical teachings, more credits in core subjects during the first year, and more compulsory subjects in second year. Private universities are more likely to offer external internships during the first cycle whereas the public ones are more likely to offer them during the second cycle. Public universities offer more credits under the following curricular blocks than private ones: “Nutrition/Dietetics,” “Psychiatry,” “Public and Community Health,” and “Geriatrics.” In turn, private universities offer more credits in the areas of “Theory/Methodology,” “Ethics/Legislation,” “English,” and “Theology.” Academic curricula meet most of the criteria established by the Spanish and European legislation. The proposed legislative changes aim at standardizing curricula by associating specific credits and their timeline to the teaching blocks.

CONCLUSIONS: Nursing degree curricula among Spanish universities are highly heterogeneous. Legislative changes to homogenize teaching blocks would facilitate credit validations and student mobility across universities, in addition to increasing nursing degrees´ standardization and excellence.

PMID:35397295 | DOI:10.1016/j.nedt.2022.105360

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A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial

Mult Scler Relat Disord. 2022 Mar 19;61:103747. doi: 10.1016/j.msard.2022.103747. Online ahead of print.

ABSTRACT

INTRODUCTION: Most women develop MS before menopause. Menopausal hot flashes can worsen MS symptoms, and could be relieved with hormone therapy. Our objective was to evaluate feasibility, tolerability and symptom response of Duavee® (bazedoxifene + conjugated estrogen) in a Phase Ib/IIa double-blind randomized controlled clinical trial.

METHODS: We randomized 24 peri/postmenopausal women with MS and symptomatic hot flashes 1:1 to Duavee® versus placebo. Evaluations occurred at baseline and 2 months.

RESULTS: Groups were balanced for age (mean 51.2 ± 3.6 years), EDSS [median 3 (IQR:2.5, 4.5)], and MS duration. 21/24 participants completed the study.

FEASIBILITY: Enrollment was protracted (34 months), partially due to concerns about hormone therapy safety.

TOLERABILITY: treatment group participants reported greater satisfaction and fewer missed doses; one participant (placebo) developed new MRI lesions; liver function testing remained normal for all patients.

SYMPTOMS: Hot Flash Related Daily Interference scale at 2 months was lower in treatment vs. placebo group [median (IQR) of 4 (0.5, 14) vs. 9 (0, 33)]. Between-group differences were not statistically significant.

CONCLUSION: Despite perceived benefits in MS, estrogens have perceived risks that represent a hurdle to enrollment. With appropriate education and screening of participants, the favorable study retention (87%) and treatment satisfaction observed in the current study support the feasibility of a longer, powered trial to evaluate whether a proven treatment for menopausal symptoms, Duavee®, could also improve MS-related function in menopausal women with MS.

PMID:35397292 | DOI:10.1016/j.msard.2022.103747

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Isolating two sources of variability of subcortical stimulation to quantify fluctuations of corticospinal tract excitability

Clin Neurophysiol. 2022 Feb 24;138:134-142. doi: 10.1016/j.clinph.2022.02.009. Online ahead of print.

ABSTRACT

OBJECTIVE: Investigate the variability previously found with cortical stimulation and handheld transcranial magnetic stimulation (TMS) coils, criticized for its high potential of coil position fluctuations, bypassing the cortex using deep brain electrical stimulation (DBS) of the corticospinal tract with fixed electrodes where both latent variations of the coil position of TMS are eliminated and cortical excitation fluctuations should be absent.

METHODS: Ten input-output curves were recorded from five anesthetized cats with implanted DBS electrodes targeting the corticospinal tract. Goodness of fit of regressions with a conventional single variability source as well as a dual variability source model was quantified using a Schwarz Bayesian Information approach to avoid overfitting.

RESULTS: Motor evoked potentials (MEPs) through DBS of the corticospinal tract revealed short-term fluctuations in excitability of the targeted neuron pathway reflecting endogenous input-side variability at similar magnitude as TMS despite bypassing cortical networks.

CONCLUSION: Input-side variability, i.e., variability resulting in changing MEP amplitudes as if the stimulation strength was modulated, also emerges in electrical stimulation at a similar degree and is not primarily a result of varying stimulation, such as minor coil movements in TMS. More importantly, this variability component is present, although the cortex is bypassed. Thus, it may be of spinal origin, which can include cortical input from spinal projections. Further, the nonlinearity of the compound variability entails complex heteroscedastic non-Gaussian distributions and typically does not allow simple linear averages in statistical analysis of MEPs. As the average is dominated by outliers, it risks bias. With appropriate regression, the net effects of excitatory and inhibitory inputs to the targeted neuron pathways become noninvasively observable and quantifiable.

SIGNIFICANCE: The neural responses evoked by artificial stimulation in the cerebral cortex are variable. For example, MEPs in response to repeated presentations of the same stimulus can vary from no response to saturation across trials. Several sources of such variability have been suggested, and most of them may be technical in nature, but localization is missing.

PMID:35397278 | DOI:10.1016/j.clinph.2022.02.009

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Perinatal risk factors for mortality in very preterm infants – a nationwide, population-based discriminant analysis

Acta Paediatr. 2022 Apr 9. doi: 10.1111/apa.16356. Online ahead of print.

ABSTRACT

AIM: To assess the strength of associations between interrelated perinatal risk factors and mortality in very preterm infants.

METHODS: Information on all liveborn infants delivered in Sweden at 22-31 weeks of gestational age (GA) from 2011 to 2019 was gathered from the Swedish Neonatal Quality Register, excluding infants with major malformations or not resuscitated because of anticipated poor prognosis. Twenty-seven perinatal risk factors available at birth were exposures and in-hospital mortality outcome. Orthogonal partial least squares discriminant analysis was applied to assess proximity between individual risk factors and mortality, and receiver operating characteristics (ROC) curve was used to estimate discriminant ability.

RESULTS: In total, 638/8396 (7.6%) infants died. Thirteen risk factors discriminated reduced mortality, the most important were higher Apgar scores at 5 and 10 minutes, GA and birthweight. Restricting the analysis to preterm infants <28 weeks GA (n=2939, 16.9% mortality) added antenatal corticosteroid therapy as significantly associated with lower mortality. The area under the ROC-curve (the C-statistic) using all risk factors was 0.86, as determined after both internal and external validation.

CONCLUSION: Apgar scores, gestational age and birthweight show stronger associations with mortality in very preterm infants than several other risk perinatal factors available at birth.

PMID:35397189 | DOI:10.1111/apa.16356

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Loss of the incretin effect in type 2 diabetes: a systematic review and meta-analysis

J Clin Endocrinol Metab. 2022 Apr 9:dgac213. doi: 10.1210/clinem/dgac213. Online ahead of print.

ABSTRACT

CONTEXT: Loss of the incretin effect (IE) in type 2 diabetes (T2D) contributes to hyperglycemia and the mechanisms underlying this impairment are unclear.

OBJECTIVE: To quantify the IE impairment in T2D and to investigate the factors associated with it using a meta-analytic approach.

DATA SOURCES: PubMed, Scopus and Web-of-Science.

STUDY SELECTION: Studies measuring IE by the gold-standard protocol employing an OGTT and an intravenous glucose infusion at matched glucose levels.

DATA EXTRACTION: We extracted IE, sex, age, BMI, HbA1c, fasting values and areas-under-curve (AUC) of glucose, insulin, C-peptide, GIP and GLP-1. In T2D subjects, we also recorded T2D duration, age at diagnosis, and the percentage of subjects taking antidiabetic medications.

DATA SYNTHESIS: The IE weighted mean difference between T2D and NGT subjects was -27.3% (CI [-36.5 -18.1]%; p<0.001; I 2 = 86.6%) and was affected by age (p<0.005). By meta-regression of combined NGT and T2D data, IE was inversely associated with glucose tolerance (lower IE in T2D), BMI, and fasting GIP (p<0.05). By meta-regression of T2D studies only, IE was associated with the OGTT glucose dose (p<0.0001). IE from insulin was larger than IE from C-peptide (weighted mean difference 11.2%, CI [9.2-13.2]%; p<0.0001; I 2=28.1%); the IE difference was inversely associated with glucose tolerance and fasting glucose.

CONCLUSIONS: The IE impairment in T2D vs NGT is consistent though considerably variable, age being a possible factor affecting the IE difference. Glucose tolerance, BMI, and fasting GIP are independently associated with IE; in T2D subjects only, the OGTT dose is a significant covariate.

PMID:35397169 | DOI:10.1210/clinem/dgac213