Semiquantitative Scoring Research Articles

Hypertensive myocardial disease screening in low-income settings using smartphone-based technologies: a prospective multicenter trial

Abstract Background Mobile health technologies are revolutionizing cardiovascular (CV) medicine. However, more than 80% of heart disease related deaths occur in low-income settings, that are unable to take advantage of such technologies for healthcare awareness and prevention. Purpose To assess the feasibility of a pilot telemedicine-based CV screening campaign with D-Heart, a validated low-cost 8-lead smartphone portable ECG, coupled with blood-pressure (BP) monitoring in three regions of Africa. Methods A total of 950 patients (60%) men, age 29±21) were enrolled at 5 African rural dispensaries, 2 in Kenya, 2 in Senegal and at a hospital (Uganda). ECGs recording were obtained by community health workers with D- Heart smartphone ECG; BP was measured with a validated smartphone BP recorder. Global burden of ECG abnormalities was defined by a semi-quantitative score based on the sum of 9 criteria, identifying four classes of increasing severity. ECGs that were moderately and severely abnormal and from patients with severe hypertension, were sent for consultation via smartphone to D-Heart tele-cardiology centre: an advice on how to manage the patient was sent back to the community health worker’s smartphone within 15 minutes. If referral was needed, patients were sent to the local hospital. Results Mean BMI was 26.2 ± 8.5 (men 22.3±1.5 vs women 27.2±1.1, p<0.01). Active/recent history of smoking and alcohol intake were 327 (45%, 298 men) and 232/590 (40%, 198 men) respectively. A total of 142 (15%) patients had been previously diagnosed with diabetes, 199(25%) had known hypertension of whom 95/199 on treatment), whereas 43(4%) had a previous myocardial infarction. A total of 487 (51%) patients never had their blood pressure measured, whereas 798(91%) never received an ECG. Mean SBP/DBP were 138±31/71±12 mmHg respectively. Patients with normal BP were 304(32%), whereas 380(40%) were mildly-moderately hypertensive (SBP/DBP 148±7/91±5 mmHg) and 130 (29%) with severe hypertension (SBP/DBP 162±8/99±6 mmHg). D-Heart ECGs tracings were respectively classified as: normal: 361(38%); mildly abnormal: 332(35%); moderately abnormal: 199 (21%) and severely abnormal 58(6%). Most common ECG abnormality was a positive Romhilt-Estes index in 361, 38%. For 174(18%) patients smartphone tele-report advised referral to the local hospital, but only 121 69%) presented to the visit: 9 (8%) were found to have normal hearts, 57(47%) with hypertensive heart disease, 35 (29%) with rheumatic heart disease, 20 (16%) with HFrEF. Visit time was 8±2 minutes; cost of screening per patient was 1.10€: 0,30€ for consumable electrodes, 0.80€ for the community health worker visit time. Conclusions D-Heart ECG screening combined with smartphone BP measurement proved feasible and cost-effective. This should encourage to develop and extend low-cost/high-technology community-based CV screening programs in low-income settings.

Composite dietary antioxidant index and abdominal aortic calcification: a national cross-sectional study

PurposeThe Composite Dietary Antioxidant Index (CDAI) is a novel, inclusive measure for evaluating the antioxidant potential of diets. We aim to explore the link between the CDAI and abdominal aortic calcification (AAC) in U.S. adults aged ≥ 40 years.MethodsThis cross-sectional study collected dietary and AAC data for individuals aged ≥ 40 years from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) database. The CDAI was calculated using six dietary antioxidants. AAC was evaluated using a semi-quantitative scoring system known as AAC-24, with an AAC score greater than 6 as severe AAC (SAAC). To examine the association between CDAI and AAC, including SAAC, liner/logistic regression analyses and smooth curve fitting were applied.ResultsA total of 2,640 participants were included in this study, and significant decreases in AAC score and SAAC prevalence were observed with ascending CDAI levels (P < 0.01). After adjusting for confounding factors, a clear link was established between the CDAI and both AAC score (β = -0.083, 95% CI -0.144–0.022, P = 0.008) and SAAC (OR = 0.883, 95% CI 0.806–0.968, P = 0.008), respectively. Further smooth curve fitting indicated a negative correlation between CDAI and both AAC score and SAAC.ConclusionsDietary antioxidant consumption, as quantified by the CDAI, shows an inverse relationship with AAC risk. Additional longitudinal and intervention studies are essential.

Semi-quantitative CT score reflecting the degree of pulmonary infection as a risk factor of hypokalemia in COVID-19 patients: a cross-sectional study

BackgroundHypokalemia is a common electrolyte disorder observed in patients afflicted with coronavirus disease 2019 (COVID-19). When COVID-19 is accompanied by pulmonary infection, chest computed tomography (CT) is the preferred diagnostic modality. This study aimed to explore the relationship between CT semi-quantitative score reflecting the degree of pulmonary infection and hypokalemia from COVID-19 patients.MethodsA single-center, cross-sectional study was conducted to investigate patients diagnosed with COVID-19 between December 2022 and January 2023 who underwent chest CT scans upon admission revealing typical signs. These patients were categorized into two groups based on their blood potassium levels: the normokalemia group and the hypokalemia group. Medical history, symptoms, vital signs, laboratory data, and CT severity score were compared. Binary regression analysis was employed to identify risk factors associated with hypokalemia in COVID-19 patients with pulmonary infection.ResultsA total of 288 COVID-19 patients with pulmonary infection were enrolled in the study, of which 68 (23.6%) patients had hypokalemia. The CT severity score was found to be higher in the hypokalemia group compared to the normokalemia group [4.0 (3.0–5.0) vs. 3.0 (2.0–4.0), p = 0.001]. The result of binary logistic regression analysis revealed that after adjusting for sex, vomiting, sodium, and using potassium-excretion diuretics, higher CT severity score was identified as an independent risk factor for hypokalemia (OR = 1.229, 95% CI = 1.077–1.403, p = 0.002).ConclusionIn this cohort of patients, semi-quantitative CT score reflecting the degree of pulmonary infection may serve as a risk factor of hypokalemia in COVID-19 patients.

Comparative evaluation of hyaluronic acid-based dressing versus hydrocolloid dressing in rat dermal wound healing

Background: Wound healing is a complex process influenced by a variety of environmental factors. Dressing materials play a critical role in creating barriers against contaminants, maintaining optimal moisture levels, and absorbing wound exudate. Therefore, selecting materials tailored to wound characteristics is crucial for enhancing outcomes. Hyaluronic acid (HA) is a natural biocompatible polymer that supports healing by regulating inflammation and promoting tissue repair. This study compared HA- and hydrocolloid-based hydrogels in a rat model to optimize wound care strategies.Methods: Full-thickness dermal wounds (diameter, 8 mm) were created on the dorsal skin of 12 Sprague-Dawley rats under sevoflurane anesthesia. The wounds were treated with HA/silver sulfadiazine gel (group A), hydrocolloid gel (group B), or left untreated (control), all covered with a transparent dressing. Biopsy specimens on days 3, 7, and 21 were used to assess histological parameters: inflammatory cell infiltration, fibroblast infiltration, collagen deposition, neovascularization, and epithelial thickness, using a semi-quantitative scoring system. Histological analyses were conducted blindly, and statistical analyses were performed using the Kruskal-Wallis test (&lt;i&gt;p&lt;/i&gt;&lt; 0.05).Results: On day 3, group A showed significantly higher inflammatory cell infiltration and collagen deposition than other groups, indicating extracellular matrix formation. By day 7, angiogenesis was highest in group A, followed by group B and controls. By day 21, all wounds had completely healed. Epithelial layer thickness, reflecting inflammation and fibroblast maturity, was significantly higher in group A.Conclusion: This study compared HA-based hydrogel and hydrocolloid-based dressings through histological analyses to elucidate wound healing mechanics. HA-based hydrogel dressings significantly enhanced wound recovery. However, generalizing these outcomes requires future studies to expand the range of effective wound treatment materials. These findings underscore the potential of HA-based dressings to enhance clinical outcomes in wound management, suggesting avenues for improving therapeutic strategies.

Ex vivo comparison of full-thickness biopsy techniques in the equine small intestine.

To compare the practicability and tissue sample quality between different intestinal biopsy techniques. Experimental, randomized ex vivo study. Small intestine of nine horses. Four different biopsy techniques were evaluated in the aboral jejunum and the ileum within 1 h after euthanasia. One segment was used as control (C), and the applied techniques included an 8 mm biopsy punch (BP), transverse wedge resection (TW), longitudinal wedge resection with transverse closure (LW) and a longitudinal sample using Eppendorfer biopsy forceps (EF). Defects were closed using a single-layer continuous Lembert pattern. Duration of the procedure, intestinal diameter, contamination, and bursting pressure were determined. The quality of the obtained tissue samples for histological assessment was evaluated using a semiquantitative score. The jejunal and ileal samples were analyzed separately. All biopsy procedures including defect closure were completed within 5 min, with shorter closure times for BP (p = .03). Minimal contamination could be noted in 1/8 TW and 2/8 LW cases, without significant differences between the groups. Longitudinal closure techniques (BP, EF) showed more constriction than transverse closures (TW, LW) (p < .05). Bursting pressure was >75 mmHg in all cases. Technique BP showed significantly lower biopsy quality scores (p = .009). The tested biopsy techniques could all be applied effectively within a reasonable time frame, yet the biopsy punch was associated with significant artifacts and risk of missing mucosa. The findings provide insights into the possible advantages and limitations of the different techniques and alert the surgeon to potential issues with the quality of the tissue sample.

Radiology of bronchiectasis

Bronchiectasis is an irreversible bronchial dilatation. It is chronically progressive through avicious circle of secretion retention, infection, inflammation and structural damage. The underlying causes are diverse and the severity of the disease is variable, which makes both the diagnostics and treatment challenging. Computed tomography (CT) is the gold standard in the diagnosis of bronchiectasis and can be helpful in clarifying the etiology. The type of bronchiectasis, the distribution of the bronchiectasis within the lungs and associated findings are particularly relevant. Imaging is also important in monitoring the progression of bronchiectasis. In the usual report of the findings this is carried out visually and descriptively, while semiquantitative scores and computer-aided quantitative analysis of the respiratory tract enable amore precise assessment and are used in particular for clinical studies.

MRI-based Zero Echo Time and Black Bone Pseudo-CT Compared with Whole-Body CT to Detect Osteolytic Lesions in Multiple Myeloma.

Background MRI is highly sensitive for assessing bone marrow involvement in multiple myeloma (MM) but does not enable detection of osteolysis. Purpose To assess the diagnostic accuracy, repeatability, and reproducibility of pseudo-CT MRI sequences (zero echo time [ZTE], gradient-echo black bone [BB]) in detecting osteolytic lesions in MM using whole-body CT as the reference standard. Materials and Methods In this prospective study, consecutive patients were enrolled in our academic hospital between June 2021 and December 2022. Inclusion criteria were newly diagnosed MM, monoclonal gammopathy of undetermined significance at high risk for MM, or suspicion of progressive MM. Participants underwent ZTE and BB sequences covering the lumbar spine, pelvis, and proximal femurs as part of 3-T whole-body MRI examinations, as well as clinically indicated fluorine 18 fluorodeoxyglucose PET/CT examination within 1 month that included optimized whole-body CT. Ten bone regions and two scores (categorical score = presence/absence of osteolytic lesion; semiquantitative score = osteolytic lesion count) were assessed by three radiologists (two experienced and one unfamiliar with pseudo-CT reading) on the ZTE, BB, and whole-body CT images. The accuracy, repeatability, and reproducibility of categorical scores (according to Gwet agreement coefficients AC1 and AC2) and differences in semiquantitative scores were assessed at the per-sequence, per-region, and per-patient levels. Results A total of 47 participants (mean age, 67 years ± 11 [SD]; 27 male) were included. In experienced readers, BB and ZTE had the same high accuracy (98%) in the per-patient analysis, while BB accuracy ranged 83%-100% and ZTE accuracy ranged 74%-94% in the per-region analysis. An increase of false-negative (FN) findings in the spine ranging from +17% up to +23%, according to the lumbar vertebra, was observed using ZTE (P < .013). Regardless of the region (except coxal bones), differences in the BB score minus the ZTE score were positively skewed (P < .021). Regardless of the sequence or region, repeatability was very good (AC1 ≥0.87 for all), while reproducibility was at least good (AC2 ≥0.63 for all). Conclusion Both MRI-based ZTE and BB pseudo-CT sequences of the lumbar spine, pelvis, and femurs demonstrated high diagnostic accuracy in detecting osteolytic lesions in MM. Compared with BB, the ZTE sequence yielded more FN findings in the spine. ClinicalTrials.gov Identifier: NCT05381077 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Soluble allogenic telocollagen as a direct protein therapeutic: Results of serial injections in a rodent rotator cuff tear model

HypothesisDelivery of soluble allogeneic type I telocollagen (allo-telocollagen) will accelerate and improve the healing of damaged tendons. Our hypothesis draws from known mechanochemical properties of type I collagen that direct its incorporation into damaged connective tissue. We further suggest that allo-telocollagen will raise a minimal immunogenic reaction due to homology within species. MethodsSeventy-eight shoulders (39 Sprague-Dawley rats) had their supraspinatus tendon surgically detached from its footprint on the humerus and repaired (72 shoulders) or left uninjured (6 shoulders). The repaired tissue was treated with an injection of 100 μl of saline, 10 mg/ml allogeneic atelocollagen (allo-atelocollagen), or 10 mg/ml allo-telocollagen at 0-, 1-, and 2-weeks post-surgery. At 30- and 60-days post-surgery, the tendons were assessed by mechanical testing (failure load, failure stress, stiffness, and relaxation) and by semiquantitative histological scoring. ResultsAt 30-days post-surgery, the mechanical and histological outcomes were not statistically different. However, at day 60, allo-telocollagen improved the failure strength of the supraspinatus (29.9 ± 4.7 N) relative to saline (20.0 ± 3.5 N; P value <= 0.001) or allo-atelocollagen (23.2 ± 1.5 N; P value = 0.025) treated tendons, and it approached that of uninjured controls (36.9 ± 5.0 N; P value = 0.021). Allo-telocollagen improved the failure stress of the supraspinatus (34.1 ± 9.3 MPa) relative to the saline treated tendons (21.4 ± 6.0 MPa; P value = 0.031; 160% improvement) and was no different than uninjured controls (33.4 ± 9.9 MPa; P value = 0.999) or allo-atelocollagen (32.3 ± 7.4 MPa; P value = 0.977). The stiffness of uninjured controls was far greater than any of injured/treated tendons (>200% stiffer). Histological scoring showed that the allo-telocollagen treated tendons produced better collagen fiber arrangement (1.55 ± 0.17) than saline (2.50 ± 0.29; P value = 0.001) or allo-atelocollagen (2.23 ± 0.28; P value = 0.042) treated tendons and that it did not increase markers of immunogenesis (1.10 ± 0.42) relative to either saline (1.44 ± 0.20; P value = 0.369) or allo-atelocollagen (0.68 ± 0.41; P value = 0.1058). ConclusionsWhile all three treatments produced similar results at 30 days, by 60 days, soluble allo-telocollagen clearly separated from the other interventions, yielding better mechanical and histological outcomes in a torn/repaired rotator cuff rat model. Allo-telocollagen treated tendons also approached the failure strength and matched the failure stresses of uninjured control tendons. The data suggest a new use for allo-telocollagen as a deliverable direct protein mechanotherapeutic that can improve both healing quality and speed.

Transcription Factor Forkhead Box Protein 3 (FOXP3) as a Prognostic Indicator for Postoperative Outcomes in Patients with Breast Cancer: Establishment of a Prognostic Nomogram.

The current investigation is to assess FOXP3 expression in breast cancer patients and evaluate the predictive significance of FOXP3. A cohort of 313 cases between January 2015 and November 2015 were enrolled this research. Immunohistochemistry (IHC) assay was utilized to detect the expression levels of FOXP3 in primary breast carcinoma specimens. These patients were separated into two groups by semiquantitative scoring approach. Chi-square test and Fisher's exact test were conducted to investigate the correlations between FOXP3 expression in tumors and clinicopathological variables. Kaplan-Meier method and Log rank test were utilized to generate survival curves for disease-free survival (DFS) and overall survival (OS). The independent factors were examined using Cox regression analysis. Nomogram models were created for assessing DFS and OS rates. Depending on the levels of FOXP3 expression in tumors, these patients were categorized into two groups: low FOXP3 expression (174 cases) and high FOXP3 expression (139 cases). The patients exhibiting low levels of FOXP3 expression in tumors demonstrated a longer survival duration contrasted with those with high expression (DFS: 88.75 vs 65.87 months, χ2=36.1100, P<0.0001; OS: 89.70 vs 78.37 months, χ2=32.4900, P<0.0001). Multivariate analysis revealed that FOXP3 was a significant prognostic factor [DFS: hazard ratio (HR): 2.822, 95% CI: 1.595-4.992, P<0.0001; OS: HR: 3.232, 95% CI: 1.812-5.763, P<0.0001]. The good predictive clinical utility of FOXP3-based nomograms within the threshold probability range for different survival rates was demonstrated by calibration curve and decision curve analyses. FOXP3 expression serves as a crucial prognostic indicator in breast cancer patients, and may aid preoperative evaluation in clinical practice.

EFFECT OF ADDING BIOACTIVE COMPOUNDS FROM BROWN ALGAE (Sargassum sp.) IN FEED ON INTESTINE AND LIVER HISTOLOGY OF SIAM PATIN FISH (Pangasius hypopthalmus) SEEDS

Addition of Sargassum sp. into feed as a feed supplement is one effort that can be done to increase fish growth and immunity. This research aims to determine the effect of adding bioactive compounds from Sargassum sp. extract in feed on the health picture of Siamese catfish through structural changes that occur in the intestines and liver. Fish observations were carried out for 40 days. The results obtained regarding the survival rate (SR) value of Siamese catfish seeds show that there is no difference or has the same percentage, namely 100%. The results of observations on the histopathology of intestinal organs analyzed in a comparative descriptive manner showed that Siamese catfish fry were fed with Sargassum sp. extract experienced damage than fish seeds fed without the addition of Sargassum sp. extract (control). The damage that occurs includes leukocyte infiltration (IfL), necrosis (Ne), goblet cell proliferation (Psg), hyperplasia (Hpl), and hemorrhage, with a damage score analyzed using the semiquantitative scoring method, namely 1. Damage to the liver, namely experiencing congestion in the blood vessels.

Validation of a Paralimbic-Related Subcortical Brain Dysmaturation MRI Score in Infants with Congenital Heart Disease.

Background: Brain magnetic resonance imaging (MRI) of infants with congenital heart disease (CHD) shows brain immaturity assessed via a cortical-based semi-quantitative score. Our primary aim was to develop an infant paralimbic-related subcortical-based semi-quantitative dysmaturation score, termed brain dysplasia score (BDS), to detect abnormalities in CHD infants compared to healthy controls and secondarily to predict clinical outcomes. We also validated our BDS in a preclinical mouse model of hypoplastic left heart syndrome. Methods: A paralimbic-related subcortical BDS, derived from structural MRIs of infants with CHD, was compared to healthy controls and correlated with clinical risk factors, regional cerebral volumes, feeding, and 18-month neurodevelopmental outcomes. The BDS was validated in a known CHD mouse model named Ohia with two disease-causing genes, Sap130 and Pchda9. To relate clinical findings, RNA-Seq was completed on Ohia animals. Findings: BDS showed high incidence of paralimbic-related subcortical abnormalities (including olfactory, cerebellar, and hippocampal abnormalities) in CHD infants (n = 215) compared to healthy controls (n = 92). BDS correlated with reduced cortical maturation, developmental delay, poor language and feeding outcomes, and increased length of stay. Ohia animals (n = 63) showed similar BDS findings, and RNA-Seq analysis showed altered neurodevelopmental and feeding pathways. Sap130 mutants correlated with a more severe BDS, whereas Pcdha9 correlated with a milder phenotype. Conclusions: Our BDS is sensitive to dysmaturational differences between CHD and healthy controls and predictive of poor outcomes. A similar spectrum of paralimbic and subcortical abnormalities exists between human and Ohia mutants, suggesting a common genetic mechanistic etiology.

Learning precise segmentation of neurofibrillary tangles from rapid manual point annotations.

Accumulation of abnormal tau protein into neurofibrillary tangles (NFTs) is a pathologic hallmark of Alzheimer disease (AD). Accurate detection of NFTs in tissue samples can reveal relationships with clinical, demographic, and genetic features through deep phenotyping. However, expert manual analysis is time-consuming, subject to observer variability, and cannot handle the data amounts generated by modern imaging. We present a scalable, open-source, deep-learning approach to quantify NFT burden in digital whole slide images (WSIs) of post-mortem human brain tissue. To achieve this, we developed a method to generate detailed NFT boundaries directly from single-point-per-NFT annotations. We then trained a semantic segmentation model on 45 annotated 2400μm by 1200μm regions of interest (ROIs) selected from 15 unique temporal cortex WSIs of AD cases from three institutions (University of California (UC)-Davis, UC-San Diego, and Columbia University). Segmenting NFTs at the single-pixel level, the model achieved an area under the receiver operating characteristic of 0.832 and an F1 of 0.527 (196-fold over random) on a held-out test set of 664 NFTs from 20 ROIs (7 WSIs). We compared this to deep object detection, which achieved comparable but coarser-grained performance that was 60% faster. The segmentation and object detection models correlated well with expert semi-quantitative scores at the whole-slide level (Spearman's rho ρ=0.654 (p=6.50e-5) and ρ=0.513 (p=3.18e-3), respectively). We openly release this multi-institution deep-learning pipeline to provide detailed NFT spatial distribution and morphology analysis capability at a scale otherwise infeasible by manual assessment.

Common variable immunodeficiency disorder (CVID)-related liver disease: assessment of the main histological aspects using novel semiquantitative scoring systems, image analysis and correlation with clinical parameters of liver stiffness and portal hypertension

AimsWe aimed to investigate the relationship between T-cell-mediated sinusoidal injury, nodular regenerative hyperplasia like changes (NRH-LC) and fibrosis, clinical measures of fibrosis and portal hypertension, and progression rate in common...

Psychiatric symptoms and TDP-43 pathology in amyotrophic lateral sclerosis

BackgroundALS is not a pure motor neuron disease but co-occurs with cognitive impairment and psychiatric symptoms. The neuropathological origin of the psychiatric symptoms is unclear. This study examined the association between the psychiatric symptoms and neuropathology of ALS. MethodsWe investigated the clinicopathological characteristics of 15 autopsy cases of ALS, including neuronal loss, gliosis, and the burden of TDP-43 pathology. We divided TDP-43–positive structures by morphology into four categories (neuronal cytoplasmic inclusion, dystrophic neurite, dot, and glial cytoplasmic inclusion) and gave each a semiquantitative score in nine brain regions. Braak neurofibrillary tangle stage, Thal amyloid phase, Lewy-related pathology, and argyrophilic grains were also assessed. ResultsOf the 15 ALS patients, seven had presented with psychiatric symptoms and eight had not. Significantly higher TDP-43 pathology scores were found in the group with psychiatric symptoms in the temporal tip, transentorhinal cortex, entorhinal cortex, subiculum, and the hippocampal CA1 region and dentate gyrus. Cognitive impairment was not significantly associated with the degree of TDP-43 pathology. There were no significant differences in the degree of neuronal loss/gliosis or in other concurrent pathologies between patients with and without psychiatric symptoms. Morphological evaluation showed that neuronal cytoplasmic inclusions, dystrophic neurites, and dots tended to be more common in the group with psychiatric symptoms. ConclusionPsychiatric symptoms in ALS may be related to TDP-43 pathology in the perforant pathway. (224 words).

Novel multitarget analgesic candidate SZV-1287 demonstrates potential disease-modifying effects in the monoiodoacetate-induced osteoarthritis mouse model.

Monoiodoacetate (MIA)-induced osteoarthritis (OA) is the most commonly used rodent model for testing anti-OA drug candidates. Herein, we investigated the effects of our patented multitarget drug candidate SZV-1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl) propanal oxime) that is currently under clinical development for neuropathic pain and characterized the mouse model through complex functional, in vivo imaging, and morphological techniques. Knee OA was induced by intraarticular MIA injection (0.5 and 0.8mg). Spontaneous pain was assessed based on weight distribution, referred pain by paw mechanonociception (esthesiometry), edema by caliper, neutrophil myeloperoxidase activity by luminescence, matrix metalloproteinase activity, vascular leakage and bone remodeling by fluorescence imaging, bone morphology by micro-CT, histopathological alterations by semiquantitative scoring, and glia activation by immunohistochemistry. Then, SZV-1287 (20mg/kg/day) or its vehicle was injected intraperitoneally over a 21-day period. MIA induced remarkably decreased thresholds of weight bearing and paw withdrawal, alterations in the tibial and femoral structures (reactive sclerosis, increased trabeculation, and cortical erosions), histopathological damage (disorganized cartilage structure, hypocellularity, decreased matrix staining and tidemark integrity, and increased synovial hyperplasia and osteophyte formation), and changes in the astrocyte and microglia density in the lumbar spinal cord. There were no major differences between the two MIA doses in most outcome measures. SZV-1287 inhibited MIA-induced weight bearing reduction, hyperalgesia, edema, myeloperoxidase activity, histopathological damage, and astrocyte and microglia density. SZV-1287 may have disease-modifying potential through analgesic, anti-inflammatory, and chondroprotective effects. The MIA mouse model is valuable for investigating OA-related mechanisms and testing compounds in mice at an optimal dose of 0.5mg.

SIRT6 alleviates senescence induced by Porphyromonas gingivalis in human gingival fibroblasts.

Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs). Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related β-galactosidase (SA-β-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry. Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-β-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05). P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway.

RAP1-GTPase immunostaining is altered in human precancerous and cancerous cervical lesions.

Aim: This study investigated RAP1 immunostaining variation in different cell types during CC progression.Methods: Paraffin-embedded cervical tissues from 101 patients were categorized into control, pre-neoplastic and neoplastic groups. RAP1 immunolocalization, HPV detection and genotyping were performed. A semiquantitative immunoreactive score was employed to compare labeling intensity, cellular localization, nuclear labeling, percentage and distribution of reactive cells.Results: 73% (72/99) of cervical specimens were HPV+. RAP1 was localized in the nucleus and cytoplasm of all samples. Cytoplasmic RAP1 immunoscore was higher than nuclear score in all CC groups. RAP1 intensity increased with lesion severity. SCC samples exhibited predominantly intense RAP1 immunostaining.Conclusion: RAP1 is an efficient biomarker for detecting invasive CC lesions but has limited utility in distinguishing SCC grades.

Comprehensive ultrasonographic evaluation of normal and fibrotic kidneys in a mouse model with an ultra-high-frequency transducer.

This study aimed to establish baseline morphological and functional data for normal mouse kidneys via a clinical 33 MHz ultra-high-frequency (UHF) transducer, compare the data with the findings from fibrotic mice, and assess correlations between ultrasonography (US) parameters and fibrosis-related markers. This retrospective study aggregated data from three separate experiments (obstructive nephropathy, diabetic nephropathy, and acute-to-chronic kidney injury models). Morphological parameters (kidney size, parenchymal thickness [PT]) and functional (shear-wave speed [SWS], stiffness, resistive index [RI], and microvascular imaging-derived vascular index [VI]) were assessed and compared between normal and fibrotic mouse kidneys. Semi-quantitative histopathologic scores were calculated and molecular markers (epithelial cadherin), Collagen 1A1 [Col1A1], transforming growth factor-β, and α-smooth muscle actin [α-SMA]) were evaluated using western blots. Correlations with US parameters were explored. Clinical UHF US successfully imaged the kidneys of the experimental mice. A three-layer configuration was prevalent in the normal mouse kidney parenchyma (34/35) but was blurred in most fibrotic mouse kidneys (33/40). US parameters, including size (11.14 vs. 10.70 mm), PT (2.07 vs. 1.24 mm), RI (0.64 vs. 0.77), VI (22.55% vs. 11.47%, only for non-obstructive kidneys), SWS (1.67 vs. 2.06 m/s), and stiffness (8.23 vs. 12.92 kPa), showed significant differences between normal and fibrotic kidneys (P&lt;0.001). These parameters also demonstrated strong discriminative ability in receiver operating characteristic curve analysis (area under the curve, 0.76 to 0.95; P&lt;0.001). PT, VI, and RI were significantly correlated with histological fibrosis markers (ρ=-0.64 to -0.68 for PT and VI, ρ=0.71-0.76 for RI, P&lt;0.001). VI exhibited strong negative correlations with Col1A1 (ρ=-0.76, P=0.006) and α-SMA (ρ=-0.75, P=0.009). Clinical UHF US effectively distinguished normal and fibrotic mouse kidneys, indicating the potential of US parameters, notably VI, as noninvasive markers for tracking fibrosis initiation and progression in mouse kidney fibrosis models.

A Cross-Sectional Study Conducted in Tehran, Iran, Analyzed the Typical Patterns of Primary Lung CT Scans in Critically Ill COVID-19 Patients Using a Semi-Quantitative Scoring System

Background: Given the ongoing COVID-19 global pandemic and the potential for respiratory failure in several COVID-19 patients, early diagnosis and timely treatment are of paramount importance. Objectives: In this context, we aimed to investigate the role of initial chest computed tomography (CT) in predicting the severity of COVID-19. Methods: The study, conducted at Imam Hossein Hospital between March 6, 2020, and May 6, 2020, was cross-sectional in nature. All patients diagnosed with severe to critical COVID-19 underwent high-resolution chest CT (HRCT), and the findings of the chest CT were meticulously analyzed using a semi-quantitative scoring system. Results: Out of 47 patients with severe to critical COVID-19, 72.4% were male, with a mean age of 62 ± 14 years. The most common chest CT findings were ground-glass opacity (55%) and consolidation (30%). Bilateral involvement was observed in all patients, with the most frequently affected areas being the peribronchovascular distribution (76%) and peripheral distribution (74%). Most patients had pulmonary involvement across all five lobes, with scores ranging from a minimum of 3.25 to a maximum of 21.25 (CI: 12 - 15; mean: 13.25). Conclusions: This study suggests a relationship between the initial chest CT scan findings and the severity of respiratory disease in COVID-19 patients. However, further studies are needed to confirm these findings.

P-glycoprotein expression is decreased in placenta accreta and placenta previa disorders.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are multidrug resistance (MDR) transporters that function as placental gatekeepers, lowering the fetal levels of diverse xenobiotics and toxins that may be circulating in the maternal blood throughout pregnancy. Placenta accreta spectrum (PAS) and the placenta previa (PP) disorders are obstetric pathologies encompassed by an abnormal invasion of chorionic villous tissue in the uterine wall or at the endocervical os, respectively. Given the fact that MDR transporters are involved in placentation and are highly responsive to inflammation, we hypothesized that immunostaining of P-gp and BCRP would be altered in PAS and in PP specimens. A total of 32 placental histological specimens, sorted in control (N.=8; physiological pregnancies), PAS (N.=14), and PP (N.=10), were subjected to immunohistochemistry for P-gp and BCRP transporters. Semi-quantitative scoring of the resulting immunostained area and intensity was undertaken. Decreased P-gp staining intensity in the syncytiotrophoblast of the PAS compared to the control group (P<0.05) and in the PP compared to the PAS group was detected (P<0.05). Fetal blood vessel P-gp immunostaining was decreased in PAS and PP groups (P<0.001). We conclude that PAS and PP histological specimens exhibit decreased immunostaning of the drug transporter P-gp, and that fetuses born from these pregnancies may be exposed to greater levels of drugs and toxins present at the maternal circulation. Futures studies should attempt to investigate the mechanisms underlying P-gp down-regulation in these obstetric pathologies.