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Differences of water barrier function between keloid and normal skin of keloid patients and its related mechanism

Zhonghua Shao Shang Za Zhi. 2021 Dec 24;37:1-6. doi: 10.3760/cma.j.cn501120-20210427-00156. Online ahead of print.

ABSTRACT

Objective: To compare the differences of water barrier function of skin between keloid and surrounding normal skin in keloid patients and to explore the primary mechanism. Methods: A cross-sectional observational study was conducted. From October 2020 to March 2021, 30 keloid patients who met the inclusion criteria visited the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, including 18 females and 12 males, aged 20-48 years. The transepidermal water loss (TEWL) of their keloid tissues and the surrounding normal skin of the 30 patients were measured by multi probe adapter on the reception day. Hematoxylin-eosin staining was performed on keloid skin and normal skin of 5 patients after scar repair surgeries to measure the thickness of epidermis. Immunohistochemistry was used on samples from 3 patients to detect the expressions of cytokeratin-10, involucrin, and filaggrin in epidermis of keloid skin and normal skin. Data were statistically analyzed with paired sample t test and independent sample t test. Results: On the reception day, the TEWL of keloid skin of 30 patients is 9.0 (6.9, 13.4) g·m-2·h-1 and the TEWL of the normal skin was 8.1(6.4, 18.1) g·m-2·h-1, which showed no statistically significant differences (t=0.44, P>0.05). The thickness of epidermis in the keloid skin of 5 patients was (194±44) μm, which was significantly greater than (44±11) μm of the normal skin (t=6.88, P<0.01). Furthermore, increased keratinocytes, lack of normal epidermal ridge structures, and thickened stratum corneum were observed in the keloid area. The expression level of cytokeratin-10 in epidermis in the keloid skin was significantly lower than that in normal skin (t=8.50, P<0.01), but there were no statistically significant differences in the expression levels of involucrin and filaggrin between epidermis in the keloid skin and normal skin (with t values of 0.07 and 0.96, respectively, P>0.05). Conclusions: Keloid tissues present increased keratinocytes and thickened epidermis. But their water barrier function is similar to the surrounding normal skin, suggesting that transdermal water loss may not play a critical role in the prolonged development of keloids.

PMID:34954936 | DOI:10.3760/cma.j.cn501120-20210427-00156

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Effects of oral stimulation with breast milk in preterm infants oral feeding: a randomized clinical trial

J Perinat Med. 2021 Dec 22. doi: 10.1515/jpm-2020-0282. Online ahead of print.

ABSTRACT

OBJECTIVES: This study was performed to evaluate the effect of oral stimulation with breast milk for preterm infants.

METHODS: A total of 68 subjects form neonatal intensive care unit were randomly assigned into control group (n=20), premature infant oral motor intervention (PIOMI) group (n=25) and premature infant oral motor intervention with breast milk (BM-PIOMI) group (n=23).

RESULTS: BM-PIOMI group had significant shorter initiation of oral feeding (IOF) time compared to PIOMI group (2.95 days, 95% CI [0.42-5.48]) or control group (9.79 days, 95% CI [7.07-12.51]). BM-PIOMI group had significant sooner transition time from IOF to full oral feeding (FOF) compared to control group (6.68 days, 95% CI [2.2-11.16]), but not to PIOMI group (2.09 days, 95% CI [-2.07 to 6.25]). Length of hospital stay (LOS) did not show statistical different between three groups (control 38.85 ± 14.40 vs. PIOMI 38.48 ± 11.76 vs. BM-PIOMI 38.04 ± 12.2). Growth mixture model identified improvement in non-nutritive sucking (NNS) score in BM-PIOMI group compared to control and PIOMI group (0.8293, p<0.0001, and 0.8296, p<0.0001, respectively).

CONCLUSIONS: Oral stimulation with breast milk can better promotes the oral feeding process of premature infants than the simple oral stimulation, by shorten IOF time and improve early NNS score, but does not shorten transition time from IOF to FOF and LOS.

TRIAL REGISTRATION: The trial identification number is ChiCTR1800019134 (Chinese Clinical Trial Registry http://www.who.int/ictrp/network/chictr2/en/).

PMID:34954933 | DOI:10.1515/jpm-2020-0282

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A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with osteogenesis imperfecta

J Pediatr Endocrinol Metab. 2021 Dec 23. doi: 10.1515/jpem-2021-0587. Online ahead of print.

ABSTRACT

OBJECTIVES: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited connective tissue disorders, characterised by skeletal fragility. Patients with OI may also exhibit extra-skeletal features like blue or grey scleral colour, fragile skin, easy bruising, joint laxity, short stature, deafness, cardiac valve abnormalities and abnormal pulmonary function. The objective of this study is to describe genetic mutations, prevalence of hearing issues, cardiac complications and impaired pulmonary function in children with OI.

METHODS: This is a cross-sectional study of 23 Saudi children aged 6 months to 18 years who were diagnosed with OI. The revised Sillence classification (2,105) was used to classify the OI type. Whole exome sequencing was performed for genetic mutations. The hearing was assessed by either pure-tone audiometry and/or otoacoustic emission testing. Cardiac defects were screened by echocardiograms. Spirometry was performed to assess pulmonary function. Data were analysed with descriptive statistics.

RESULTS: Based on the Sillence classification, 16 patients had OI type III, 6 had type IV and 1 had type I. Of the18 patients who had genetic sequencing, 66.6% had autosomal dominant and 33.3% had autosomal recessive mutations. Among children who had screening, hearing loss was diagnosed in 53% (9/17), congenital cardiac malformations in 26% (5/19) and restrictive lung disease in 70% (7/10).

CONCLUSIONS: We found significant extra-skeletal features and a high yield of genetic mutations associated with OI. We suggest further studies to develop a screening protocol for extra-skeletal features in children with OI.

PMID:34954934 | DOI:10.1515/jpem-2021-0587

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Noninvasive Assessment of Fibrosis Regression after Direct-acting Antiviral Treatment in Hepatitis C Virus Patients

Isr Med Assoc J. 2021 Dec;23(12):794-800.

ABSTRACT

BACKGROUND: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited.

OBJECTIVES: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest.

METHODS: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two-dimensional SWE or FibroTest©; APRI and FIB-4 scores.

RESULTS: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6-33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5-100), 13.4 kPa (range 5.5-51) at 6 months, and 11.4 kPa (range 6.1-35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment.

CONCLUSIONS: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis.

PMID:34954919

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Complete Pathologic Response Prediction by Radiomics Wavelets Features of Unenhanced CT Simulation Images in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiation

Isr Med Assoc J. 2021 Dec;23(12):805-810.

ABSTRACT

BACKGROUND: For locally advanced rectal cancer patients a watch-and-wait strategy is an acceptable treatment option in cases of complete tumor response. Clinicians need robust methods of patient selection after neoadjuvant chemoradiation.

OBJECTIVES: To predict pathologic complete response (pCR) using computer vision. To analyze radiomic wavelet transform to predict pCR.

METHODS: Neoadjuvant chemoradiation for patients with locally advanced rectal adenocarcinoma who passed computed tomography (CT)-based simulation procedures were examined. Gross tumor volume was examind on the set of CT simulation images. The volume has been analyzed using radiomics software package with wavelets feature extraction module. Statistical analysis using descriptive statistics and logistic regression was performed was used. For prediction evaluation a multilayer perceptron algorithm and Random Forest model were used.

RESULTS: In the study 140 patients with II-III stage cancer were included. After a long course of chemoradiation and further surgery the pathology examination showed pCR in 38 (27.1%) of the patients. CT-simulation images of tumor volume were extracted with 850 parameters (119,000 total features). Logistic regression showed high value of wavelet contribution to model. A multilayer perceptron model showed high predictive importance of wavelet. We applied random forest analysis for classifying the texture and predominant features of wavelet parameters. Importance was assigned to wavelets.

CONCLUSIONS: We evaluated the feasibility of using non-diagnostic CT images as a data source for texture analysis combined with wavelets feature analysis for predicting pCR in locally advanced rectal cancer patients. The model performance showed the importance of including wavelets features in radiomics analysis.

PMID:34954921

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Predictors of Immunogenicity to Infliximab among Patients with Inflammatory Bowel Disease: Does Ethnicity Matter?

Isr Med Assoc J. 2021 Dec;23(12):788-793.

ABSTRACT

BACKGROUND: Up to 60% of inflammatory bowel disease (IBD) patients treated with infliximab develop antibodies to infliximab (ATI), which are associated with low drug levels and loss of response (LOR). Hence, mapping out predictors of immunogenicity toward infliximab is essential for tailoring patient-specific therapy. Jewish Sephardi ethnicity, in addition to monotherapy, has been previously identified as a potential risk factor for ATI formation and infliximab failure.

OBJECTIVES: To explore the association between Jewish sub-group ethnicity among patients with IBD and the risk of infliximab immunogenicity and therapy failure. To confirm findings of a previous cohort that addressed the same question.

METHODS: This retrospective cohort study included all infliximab-treated patients of Jewish ethnicity with regular prospective measurements of infliximab trough levels and ATI. Drug and ATI levels were prospectively measured, clinical data was retrieved from medical charts.

RESULTS: The study comprised 109 Jewish patients (54 Ashkenazi, 55 Sephardi) treated with infliximab. There was no statistically significant difference in proportion of ATI between Sephardi and Ashkenazi patients with IBD (32% Ashkenazi and 33% Sephardi patients developed ATI, odds ratio [OR] 0.944, P = 0.9). Of all variables explored, monotherapy and older age were the only factors associated with ATI formation (OR 0.336, 95% confidence interval 0.145-0.778, P = 0.01, median 34 vs. 28, interquartile range 28-48, 23-35 years, P = 0.02, respectively).

CONCLUSIONS: Contrary to previous findings, Sephardi Jewish ethnicity was not identified as a risk factor for ATI formation compared with Ashkenazi Jewish ethnicity. Other risk factors remained unchanged.

PMID:34954918

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Statistical estimates of multiple transcription factors binding in the model plant genomes based on ChIP-seq data

J Integr Bioinform. 2021 Dec 21. doi: 10.1515/jib-2020-0036. Online ahead of print.

ABSTRACT

The development of high-throughput genomic sequencing coupled with chromatin immunoprecipitation technologies allows studying the binding sites of the protein transcription factors (TF) in the genome scale. The growth of data volume on the experimentally determined binding sites raises qualitatively new problems for the analysis of gene expression regulation, prediction of transcription factors target genes, and regulatory gene networks reconstruction. Genome regulation remains an insufficiently studied though plants have complex molecular regulatory mechanisms of gene expression and response to environmental stresses. It is important to develop new software tools for the analysis of the TF binding sites location and their clustering in the plant genomes, visualization, and the following statistical estimates. This study presents application of the analysis of multiple TF binding profiles in three evolutionarily distant model plant organisms. The construction and analysis of non-random ChIP-seq binding clusters of the different TFs in mammalian embryonic stem cells were discussed earlier using similar bioinformatics approaches. Such clusters of TF binding sites may indicate the gene regulatory regions, enhancers and gene transcription regulatory hubs. It can be used for analysis of the gene promoters as well as a background for transcription networks reconstruction. We discuss the statistical estimates of the TF binding sites clusters in the model plant genomes. The distributions of the number of different TFs per binding cluster follow same power law distribution for all the genomes studied. The binding clusters in Arabidopsis thaliana genome were discussed here in detail.

PMID:34953471 | DOI:10.1515/jib-2020-0036

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Mechanical properties of porcine spinal dura mater and pericranium

J Mech Behav Biomed Mater. 2021 Dec 18;126:105056. doi: 10.1016/j.jmbbm.2021.105056. Online ahead of print.

ABSTRACT

BACKGROUND: The objective of this study was to characterize and compare the mechanical properties of porcine pericranium and spinal dura mater, to evaluate the mechanical suitability of pericranium as a dural graft.

METHOD: Eighty-eight spinal dura (cervical, thoracic, and lumbar regions, in ventral longitudinal, dorsal longitudinal and circumferential orientations) and eighteen pericranium samples (ventral-dorsal, and lateral orientations) from four pigs, were harvested and subjected to uniaxial loading while hydrated. The stiffness, strain at toe-linear regions transition, strain at linear-yield regions transition and other structural and mechanical properties were measured. Stress-strain curves were fitted to a one-term Ogden model and Ogden parameters were calculated. Linear regression models with cluster-robust standard errors were used to assess the effect of region and orientation on material and structural properties.

RESULTS: Both spinal dura and pericranium exhibited distinct anisotropy and were stiffer in the longitudinal direction. The tissues exhibited structural and mechanical similarities especially in terms of stiffness and strains in the linear region. Stiffness ranged from 1.28 to 5.32 N/mm for spinal dura and 2.42-3.90 N/mm for pericranium. In the circumferential and longitudinal directions, the stiffness of spinal dura specimens was statistically similar to that of pericranium in the same orientation. The strain at the upper bound of the linear region of longitudinal pericranium (28.0%) was statistically similar to that of any spinal dura specimens (24.4-32.9%).

CONCLUSIONS: Autologous pericranium has advantageous physical properties for spinal duraplasty. The present study demonstrated that longitudinally oriented pericranium is mechanically compatible with spinal duraplasty procedures. Autologous pericranium grafts will likely support the mechanical loads transmitted from the spinal dura, but further biomechanical analyses are required to study the effect of the lower yield strain of circumferential pericranium compared to spinal dura. Finally, the Ogden parameters calculated for pericranium, and the spinal dura at each spinal level, will be useful for computational models incorporating these soft tissues.

PMID:34953436 | DOI:10.1016/j.jmbbm.2021.105056

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Clinician perspectives on reasons for, implications and management of unplanned patient returns to the Emergency Department: A descriptive study

Int Emerg Nurs. 2021 Dec 22;60:101125. doi: 10.1016/j.ienj.2021.101125. Online ahead of print.

ABSTRACT

BACKGROUND: Unplanned return visits to the emergency department (ED) have been associated with adverse outcomes and may reflect the quality of care delivered. Several studies speculate the reasons for return and suggest clinician behaviour as potentially influencing a patient’s decision to return to the ED. There is little research about this issue from the clinician’s perspective, which is necessary to inform future practice improvement.

METHODS: A descriptive cross sectional design was employed to ascertain perspectives on identification and management of return visits occurring within 48 hours of discharge. An electronic survey was distributed to all medical, nursing, and clerical staff at one ED. Descriptive statistics were used for quantitative data and content analysis was performed on textual data. Results were categorised as barriers or facilitators, then mapped to the Theoretical Domains Framework.

RESULTS: A response rate of 59.7% (n=86/144) was achieved. Staff reported increased levels of concern for this patient group but not all staff were aware of the policy for managing return patients (40.7%). Five barriers and three facilitators were identified that mapped to eight influencers of behaviour including knowledge, memory and environmental factors.

CONCLUSION: Overall, staff were aware of return patients but lacked familiarity with policy and processes to identify and commence relevant protocols. Further review of current practice as well as the patient perspective is required before any intervention to improve practice is developed.

PMID:34953437 | DOI:10.1016/j.ienj.2021.101125

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A feasible method for independently evaluating the mechanical properties of glial LC and RGC axons by combining atomic force microscopy measurement with image segmentation

J Mech Behav Biomed Mater. 2021 Dec 11;126:105041. doi: 10.1016/j.jmbbm.2021.105041. Online ahead of print.

ABSTRACT

PURPOSE: The deformation of lamina cribrosa (LC) under the elevated intraocular pressure (IOP) might squeeze the retinal ganglion cell (RGC) axons and impair the visual function. Mechanical behaviors of LC and RGC axons are supposed to be related to the optic nerve damage of glaucoma patients. However, they cannot be independently studied with the existing methods because the LC and RGC axons intertwine in the LC area. This study proposed a feasible method to evaluate the respective mechanical properties of glial LC and RGC axons of rats.

METHODS: The atomic force microscope (AFM) nano-indentation experiment was performed on unfixed cryosection samples acquired from the glial LC tissues of eight eyes from four rats. For each sample, three regions of interests (ROIs) with sizes of 20 × 20 μm2 were selected from the ventral, central and dorsal regions of the sample, respectively, and the nano-indentation was performed on 128 × 128 points within each ROI to obtain a Young’s modulus image. The glial LC and RGC axons were segmented on each modulus images using Otsu thresholding segmentation method, and their respective Young’s modulus was further extracted for statistical analysis.

RESULTS: Young’s modulus of glial LC and RGC axons are 297 ± 98 kPa and 76 ± 36 kPa in ventral regions, 342 ± 84 kPa and 84 ± 32 kPa in central regions, 280 ± 104 kPa and 75 ± 30 kPa in dorsal regions, respectively. No significant differences are found among the Young’s modulus of different regions, both for glial LC and RGC axons.

CONCLUSIONS: This study takes the nature property of the LC area as a composite material into consideration, and proposes a feasible method to distinguish between the glial LC and RGC axons and measure their respective Young’s modulus. These findings may provide useful information for establishing finite element models of the optic nerve head and promote the study on the deformation of the optic nerve under high intraocular pressure, and finally contribute to the early diagnosis of glaucoma.

PMID:34953434 | DOI:10.1016/j.jmbbm.2021.105041