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Nevin Manimala Statistics

Use of FreeStyle Libre for continuous glucose monitoring in adult horses

J Vet Emerg Crit Care (San Antonio). 2024 Mar 8. doi: 10.1111/vec.13367. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the feasibility of using the FreeStyle Libre (a continuous glucose monitoring system [CGMS]) for instantaneous continuous monitoring of interstitial glucose in adult horses and examine the applicability and accuracy of this system in horses submitted to combined glucose-insulin test (CGIT).

DESIGN: Laboratory measurements and continuous glucose monitoring system (CGMS) readings were analyzed using a 2 × 2 factorial statistical model with repeated measures over time. This analysis assessed the effects of the test (factor 1), group (factor 2), and their interactions (test × group, test × time, and group × time). Pearson’s correlation analysis was applied to blood glucose values. Mean comparisons were conducted using the t-test, and agreement between techniques was assessed via the Bland-Altman method, with a 95% confidence interval.

SETTING: Field study on private horse farms in association with a veterinary school.

ANIMALS: Ten healthy stallions were assigned to one of two groups based on their body condition scores (BCS). Group 1 (G1, n = 5) consisted of nonobese horses with a BCS of 5 or 6, while Group 2 (G2, n = 5) consisted of obese horses with a BCS of 7 or higher.

INTERVENTIONS: A CGMS sensor was attached to the dorsolateral aspect of the proximal one third of each horse’s neck. Laboratory blood glucose measurements and CGMS interstitial glucose readings were compared at different time points for up to 7 days after sensor fixation. Obese horses were also submitted to CGIT on Day 4.

MEASUREMENTS AND MAIN RESULTS: A comparative analysis of glucose measurements obtained in G1 and G2 horses using the CGMS and enzymatic methods revealed significant group × time interactions (P < 0.001) and time effects (P < 0.001). No interactions were detected between group (P = 0.45), test (P = 0.62), group and test (P = 0.28), or time and test (P = 0.92). In G1 and G2, tests were significantly correlated (r = 0.84 and P = 0.00) at all time points (T0-T5). Agreement between the glucose values obtained using different methods was excellent despite a small time delay in CGMS detection of rapid changes in blood glucose.

CONCLUSIONS: It was concluded that the CGMS can be used for indirect assessment of glycemic status (ie, based on interstitial glucose measurements) in nonobese and obese adult horses submitted to CGIT.

PMID:38459745 | DOI:10.1111/vec.13367

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CTLA-4 Blockade of Natural Killer Cells Increases Cytotoxicity against Acute Lymphoid Leukaemia Cells Neda

Cell J. 2024 Feb 1;26(2):150-157. doi: 10.22074/cellj.2024.2015187.1444.

ABSTRACT

OBJECTIVE: There is interest in using cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy to treat blood cancers. Unfortunately, patients with acute lymphoblastic leukaemia (ALL) frequently exhibit resistance to treatment and natural killer (NK) cell exhaustion. This study aims to increase the cytotoxic potency of natural killer cells by using CTLA-4 to block the Nalm-6 leukaemia cell line.

MATERIALS AND METHODS: In this experimental study, NK cells were purified from the peripheral blood mononuclear cells (PBMCs) of 10 healthy people and assessed by flow cytometry for purity and viability. The purified cells were activated overnight at 37°C and 5% CO2 with interleukin-15 (IL-15, 10 ng/ml) followed by evaluation of expressions of CTLA-4, activating and inhibitory receptors, and the release of interferon gamma (IFN-γ) and granzyme B (GZM B). CTLA-4 expression on NK cells from recurrent ALL patients was also evaluated. Finally, the cytotoxic activity of NK cells was assessed after the CTLA-4 blockade.

RESULTS: The purity of the isolated cells was 96.58 ± 2.57%. Isolated NK cells activated with IL-15 resulted in significantly higher CTLA-4 expression (8.75%, P<0.05). Similarly, CTLA-4 expression on the surface of NK cells from patients with ALL was higher (7.46%) compared to healthy individuals (1.46%, P<0.05). IL-15 reduced NKG2A expression (P<0.01), and increased expressions of NKP30 (P<0.05) and NKP46 (P<0.01). The activated NK cells released more IFN-γ (P<0.5) and GZM B (P<0.01) compared to unactivated NK cells. Blockade of CTLA-4 enhanced the NK cell killing potential against Nalm-6 cells (56.3%, P<0.05); however, IFN-γ and GZM B levels were not statistically different between the blocked and non-blocked groups.

CONCLUSION: Our findings suggest that CTLA-4 blockage of Nalm-6 cells causes an increase in antitumour activity of NK cells against these cells. Our study also provides evidence for the potential of cancer immunotherapy treatment using blocking anti-CTLA-4 mAbs.

PMID:38459732 | DOI:10.22074/cellj.2024.2015187.1444

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Nevin Manimala Statistics

Mendelian randomization analysis using multiple biomarkers of an underlying common exposure

Biostatistics. 2024 Mar 8:kxae006. doi: 10.1093/biostatistics/kxae006. Online ahead of print.

ABSTRACT

Mendelian randomization (MR) analysis is increasingly popular for testing the causal effect of exposures on disease outcomes using data from genome-wide association studies. In some settings, the underlying exposure, such as systematic inflammation, may not be directly observable, but measurements can be available on multiple biomarkers or other types of traits that are co-regulated by the exposure. We propose a method for MR analysis on latent exposures (MRLE), which tests the significance for, and the direction of, the effect of a latent exposure by leveraging information from multiple related traits. The method is developed by constructing a set of estimating functions based on the second-order moments of GWAS summary association statistics for the observable traits, under a structural equation model where genetic variants are assumed to have indirect effects through the latent exposure and potentially direct effects on the traits. Simulation studies show that MRLE has well-controlled type I error rates and enhanced power compared to single-trait MR tests under various types of pleiotropy. Applications of MRLE using genetic association statistics across five inflammatory biomarkers (CRP, IL-6, IL-8, TNF-α, and MCP-1) provide evidence for potential causal effects of inflammation on increasing the risk of coronary artery disease, colorectal cancer, and rheumatoid arthritis, while standard MR analysis for individual biomarkers fails to detect consistent evidence for such effects.

PMID:38459704 | DOI:10.1093/biostatistics/kxae006

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The utility of the surprise question by nurses to identify hospitalised older patients nearing the end-of-life and promotion of advance care planning: An interventional study

J Clin Nurs. 2024 Mar 8. doi: 10.1111/jocn.17096. Online ahead of print.

ABSTRACT

AIMS AND OBJECTIVES: To assess the prognostic accuracy of the surprise question (SQ) when used by nurses working in hospital wards to determine 1-year mortality in acutely hospitalised older patients.

BACKGROUND: The predictive accuracy of the SQ, when used by general nurses caring for older hospitalised patients, has not been comprehensively studied.

DESIGN: A prospective cohort study.

METHODS: This cohort study recruited consecutive 10,139 older patients (aged ≥65 years) who were admitted to Taipei City Hospital and were evaluated for the needs of palliative care in 2015. All patients were followed up for 12 months or until their death. The c-statistic value was calculated to indicate the predictive accuracy of the SQ and Palliative Care Screening Tool (PCST).

RESULTS: Of all participants, 18.8% and 18.6% had a SQ response of ‘no’ and a PCST score ≥4, respectively. After controlling for other covariates, an SQ response of ‘no’ (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.83-2.31) and a PCST score ≥4 (AHR = 1.50; 95% CI: 1.29-1.75) were found to be the independent predictors for patients’ 12-month mortality. The C-statistic values of the SQ and the PCST at recognising patients in their last year of life were .663 and .670, respectively. Moreover, there was moderate concordance (k = .44) between the SQ and the PCST in predicting 12-month mortality.

CONCLUSIONS: SQ response of ‘no’ and a PCST score ≥4 were independent predictors of 12-month mortality in older patients.

RELEVANCE TO CLINICAL PRACTICE: The SQ, when used by nurses working in hospital wards, is effective in identifying older patients nearing the end of life, as well as in providing advance care planning for patients.

PATIENT OR PUBLIC CONTRIBUTION: Patients’ palliative care needs at admission were assessed by general nurses using the SQ and PCST.

PMID:38459702 | DOI:10.1111/jocn.17096

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Comparison of Dry Needling and Cold-Spray-Stretching Treatments by Ultrasonography and Electrophysiology: Prospective, Randomized Controlled Trial

J Ultrasound Med. 2024 Mar 8. doi: 10.1002/jum.16445. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the efficacy of dry needling (DN) and cold-spray-stretching treatments using surface electromyography (sEMG) and ultrasound (US) in the treatment of patients with myofascial pain syndrome (MPS) with active trigger point (ATrP) in the upper trapezius muscle.

METHODS: This prospective randomized single-blind study included 60 MPS patients aged 18-65 years who have ATrP in the upper trapezius muscle. Patients were randomized into two treatment groups as DN and cold spray stretching. Both treatment groups received 1 treatment per week and totally 3 sessions. Evaluation parameters were pain level assessed by Numeric Rating Scale and algometer, neck range of motion angles, neck disability index (NDI). The effects of the treatments on ATrP were evaluated by sEMG and US histogram. All parameters were evaluated at the beginning of the treatment and at the end. Algometer and sEMG were performed also before and after the first and third sessions.

RESULTS: There was no significant difference between the two groups regarding demographic data. The mean age of the participants was 39.7 ± 11.6 years. Fifty-one patients were female. Significant improvement in terms of pain level, functionality, sEMG, and US histogram were achieved in both groups (P < .05). When comparing the two groups, algometer scores and the NDI score were statistically higher in the cold-spray-stretching group than in the DN group (P < .008 and P < .028, respectively).

CONCLUSION: Both treatment options should be preferred. The efficacy of both treatments was observed via sEMG and US histograms.

PMID:38459670 | DOI:10.1002/jum.16445

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Enhancing mouthguard longevity: Impact of surface treatment against aging from brushing and disinfectant exposure

Dent Traumatol. 2024 Mar 8. doi: 10.1111/edt.12941. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The study aimed to assess the surface characteristics of sports mouthguards under mechanical stresses during cleaning, either by brushing or immersion in disinfectant solutions.

MATERIAL AND METHODS: Ethylene-vinyl acetate samples, 4 mm thick, were randomly assigned to cleaning methods: control (C-no cleaning), brushing with water (B.W), brushing with neutral liquid soap (B.S), brushing with toothpaste (B.T), immersion in distilled water for 10 min (I.W), immersion in 2.25% sodium hypochlorite solution for 10 min (I.SH), and immersion in sodium bicarbonate solution for 5 min (I.SB). All cleaning methods were applied for 28 days. Surface roughness average (Ra) and wettability were measured at baseline for the control group (n = 9), and after cleaning for all the other groups.

RESULTS: One-way ANOVA with Tukey tests (5% significance) indicated significant differences among groups (p < .05). The I.SB group had higher surface roughness than B.S and B.T (p < .05). B.W showed the lowest wettability, significantly lower than B.T, I.W, and I.SB (p < .05). I.SB exhibited the highest wettability, significantly different from sodium hypochlorite, neutral liquid soap, brushing with water, and control groups (p < .05). The sodium bicarbonate immersion group (I.SB) demonstrated greater statistical variation, displaying higher susceptibility to aging compared to brushing with neutral liquid soap.

CONCLUSION: Cleaning mouthguards with a toothbrush, water, and neutral liquid soap emerged as the most promising method, causing minimal surface changes in the material.

PMID:38459667 | DOI:10.1111/edt.12941

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The severity assessment of Parkinson’s disease based on plasma inflammatory factors and third ventricle width by transcranial sonography

CNS Neurosci Ther. 2024 Mar;30(3):e14670. doi: 10.1111/cns.14670.

ABSTRACT

BACKGROUND: Predicting Parkinson’s disease (PD) can provide patients with targeted therapies. However, disease severity can be roughly evaluated in clinical practice based on the patient’s symptoms and signs.

OBJECTIVE: The current study attempted to explore the factors linked with PD severity and construct a predictive model.

METHOD: The PD patients and healthy controls were recruited from our study center while recording their basic demographic information. The serum inflammatory markers levels, such as Cystatin C (Cys C), C-reactive protein (CRP), RANTES (regulated on activation, normal T cell expressed and secreted), Interleukin-10 (IL-10), and Interleukin-6 (IL-6) were determined for all the participants. PD patients were categorized into early and mid-advanced groups based on the Hoehn and Yahr (H-Y) scale and evaluated using PD-related scales. LASSO logistic regression analysis (Model C) helped select variables based on clinical scale evaluations, serum inflammatory factor levels, and transcranial sonography measurements. The optimal harmonious model coefficient λ was determined via 10-fold cross-validation. Moreover, Model C was compared with multivariate (Model A) and stepwise (Model B) logistic regression. The area under the curve (AUC) of a receiver operator characteristic (ROC), brier score, calibration curve, and decision curve analysis (DCA) helped determine the discrimination and calibration of the predictive model, followed by configuring a forest plot and column chart.

RESULTS: The study included 113 healthy individuals and 102 PD patients, with 26 early and 76 mid-advanced patients. Univariate analysis of variance screened out statistically significant differences among inflammatory markers Cys C and RANTES. The average Cys C level in the mid-advanced stage was significantly higher than in the early stage (p < 0.001) but not for RANTES (p = 0.740). The LASSO logistic regression model (λ.1se = 0.061) associated with UPDRS-I, UPDRS-II, UPDRS-III, HAMA, PDQ-39, and Cys C as the included independent variables revealed that the Model C discrimination and calibration (AUC = 0.968, Brier = 0.049) were superior to Model A (AUC = 0.926, Brier = 0.079) and Model B (AUC = 0.929, Brier = 0.071) models.

CONCLUSION: The study results show multiple factors are linked with PD assessment. Moreover, the inflammatory marker Cys C and transcranial sonography measurement could objectively predict PD symptom severity, helping doctors monitor PD evolution in patients while targeting interventions.

PMID:38459662 | DOI:10.1111/cns.14670

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Nevin Manimala Statistics

Telephone follow-up after outpatient nail surgery – a retrospective analysis

J Dtsch Dermatol Ges. 2024 Mar 8. doi: 10.1111/ddg.15341. Online ahead of print.

ABSTRACT

BACKGROUND: One of the areas of care in dermatosurgery is the surgical treatment of diseases of the nail organ. Side effects and complications after nail surgery were investigated by telephone follow-up (TFU), and its suitability for postoperative monitoring and consultation was assessed.

PATIENTS AND METHODS: All patients who underwent nail surgery at the Department of Dermatology at the Ludwigshafen City Hospital from October 2019 to December 2021 in outpatient setting were contacted by telephone on the second to third postoperative day and questioned in a standardized manner about postoperative complaints and counselled if necessary.

RESULTS: A total of 100 cases were followed up. The most common procedures performed were phenol matricectomy (41%), nail avulsion (16%), and nail matrix biopsies (9%). 50% and 21% of patients reported pain on the day of the procedure and the day after surgery, respectively. After nail avulsion, pain was statistically significantly more frequently reported on the day following the procedure and pain medication was statistically significantly more frequently required (p = 0.002). Serious adverse events did not occur after nail surgery. 10% of the respondents raised specific questions and needed counseling by TFU.

CONCLUSIONS: All nail surgeries were well tolerated in the outpatient setting. Pain was the most common side effect, although only half of all patients reported pain on the day of surgery and only 21% on the day after the procedure. The TFU proved to be an effective and practical as well as easy to establish method for postoperative follow-up and consultation after outpatient nail surgery.

PMID:38459639 | DOI:10.1111/ddg.15341

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Eradication of skin microbiota restores cytokine production and release in polymorphic light eruption

Exp Dermatol. 2024 Mar;33(3):e15034. doi: 10.1111/exd.15034.

ABSTRACT

Polymorphic light eruption (PLE) has been mechanistically linked to cytokine abnormalities. Emerging preclinical evidence posits the skin microbiome as a critical modulator of ultraviolet (UV)-induced cytokine expression, thereby influencing subsequent immune responses. This intricate relationship remains underexplored in the context of PLE. Hence, we investigated the differential responses between disinfected and non-disinfected skin following both single and repetitive exposures to solar-simulated UV radiation in patients with PLE. An experimental, half-body pilot study was conducted involving six PLE patients and 15 healthy controls. Participants’ skin was exposed to single and multiple doses of solar-simulated UV radiation, both in disinfected and in non-disinfected skin areas. The co-primary outcomes were PLE score and cytokine expression in blister fluid analysed through OLINK proteomic profiling. Secondary outcomes were erythema, pigmentation, induction of apoptotic cells in vacuum-generated suction blisters, and density of infiltrate in skin biopsies of PLE patients. Among the 71 cytokines analysed, baseline expression levels of 20 specific cytokines-integral to processes such as apoptosis, inflammation, immune cell recruitment, cellular growth, and differentiation-were significantly impaired in PLE patients compared with healthy controls. Notably, skin disinfection reversed the observed cytokine imbalances following a single UV exposure at the minimal erythema dose (MED) level and exhibited even more pronounced effects after multiple UV exposures. However, no significant differences were evident in PLE score, erythema, pigmentation, or rates of apoptotic cell induction upon UV radiation. These findings provide evidence for UV-driven cytokine regulation by the skin microbiota and imply microbiome involvement in the PLE immune response.

PMID:38459631 | DOI:10.1111/exd.15034

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Transdiagnostic psychopathology in the light of robust single-trial event-related potentials

Psychophysiology. 2024 Mar 8:e14562. doi: 10.1111/psyp.14562. Online ahead of print.

ABSTRACT

Recent evidence indicates that event-related potentials (ERPs) as measured on the electroencephalogram (EEG) are more closely related to transdiagnostic, dimensional measures of psychopathology (TDP) than to diagnostic categories. A comprehensive examination of correlations between well-studied ERPs and measures of TDP is called for. In this study, we recruited 50 patients with emotional disorders undergoing 14 weeks of transdiagnostic group psychotherapy as well as 37 healthy comparison subjects (HC) matched in age and sex. HCs were assessed once and patients three times throughout treatment (N = 172 data sets) with a battery of well-studied ERPs and psychopathology measures consistent with the TDP framework The Hierarchical Taxonomy of Psychopathology (HiTOP). ERPs were quantified using robust single-trial analysis (RSTA) methods and TDP correlations with linear regression models as implemented in the EEGLAB toolbox LIMO EEG. We found correlations at several levels of the HiTOP hierarchy. Among these, a reduced P3b was associated with the general p-factor. A reduced error-related negativity correlated strongly with worse symptomatology across the Internalizing spectrum. Increases in the correct-related negativity correlated with symptoms loading unto the Distress subfactor in the HiTOP. The Flanker N2 was related to specific symptoms of Intrusive Cognitions and Traumatic Re-experiencing and the mismatch negativity to maladaptive personality traits at the lowest levels of the HiTOP hierarchy. Our study highlights the advantages of RSTA methods and of using validated TDP constructs within a consistent framework. Future studies could utilize machine learning methods to predict TDP from a set of ERP features at the subject level.

PMID:38459627 | DOI:10.1111/psyp.14562