The value of APGA score, fibrosis index for diagnosing liver fibrosis in patients with chronic hepatitis B.

Background: Various non-invasive methods have been studied for assessing the fibrosis stage in patients with chronic hepatitis B. However, the performance of APGA, Fibrosis index in diagnosing liver fibrosis remains unclear globally and specifically in Vietnam. Methods: An analytical cross-sectional study was performed among 242 patients treated at Thong Nhat Hospital. Results: Both the APGA index and Fibrosis index showed good accuracy in diagnosing significant fibrosis (≥ F2), advanced liver fibro-sis (≥ F3), and cirrhosis (F4) with an area under the curve (AUROC) greater than 0.7. AUROC value of APGA index, Fibrosis index for diagnosing signifcant fibrosis (≥ F2) were 0.828, 0.767 respectively. AUROC value of APGA index, Fibrosis index for diagnosing advanced liver fibrosis (≥ F3) were 0.784, 0.755 respectively. AUROC value of APGA index, Fibrosis index for diagnosing cirrhosis (F4) were 0.736, 0.782 respectively. APGA index and the Fibrosis index were significantly positively correlated with the fibrosis stage (p < 0.001), with the APGA index showing the strongest correlation (r = 0.51, p < 0.001). Conclusions: The APGA values of 6.23, 7.88, and 8.99 can serve as cutoff points for the diagnosis of significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) when combined with ARFI data.

Management of Pediatric Supracondylar Humerus Fractures Using Lateral Cross-Wiring Technique Under Fluoroscopic Guidance.

BACKGROUND:  Supracondylar humeral fractures are the most prevalent elbow fractures in pediatric patients. Current treatment modalities typically involve closed reduction and fixation using percutaneous Kirschner wires. The lateral cross-wiring technique has demonstrated favorable functional and cosmetic outcomes, thereby reducing the incidence of ulnar nerve injury. OBJECTIVES:  This study aimed to assess the efficacy of the lateral cross-wiring technique in achieving optimal functional and cosmetic recovery while mitigating the risk of ulnar nerve injury in pediatric patients with displaced supracondylar humeral fractures. MATERIALS AND METHODS: A prospective analysis was conducted on 48 patients who underwent lateral cross-wiring for displaced supracondylar fractures (Gartland type III, including extension and flexion types) of the humerus. Follow-up assessments were performed over a minimum period of eight months post-surgery. RESULTS: Among the 48 patients, all demonstrated satisfactory restoration of the carrying angle and functional ability postoperatively. Notably, no iatrogenic cases of radial or ulnar nerve injury were observed during the follow-up period. CONCLUSION:  The lateral cross-wiring technique emerges as an effective treatment option for displaced supracondylar fractures of the humerus in pediatric patients. It facilitates both functional and cosmetic recovery while concurrently reducing the risk of ulnar nerve injury, thus warranting consideration in the management of such fractures.

In Vivo Fluticasone Absorption in Surgical Patients.

BACKGROUND: Intranasal corticosteroids (INCS) are a treatment mainstay of chronic rhinosinusitis and allergic rhinitis. Current computational models demonstrate that >90% of INCS drug deposition occurs on the head of the inferior turbinate and nasal valve, rather than the actual sinuses. These models do not consider mucociliary clearance which propels mucus posteriorly, nor do they consider the absorption of the drug. The purpose of this study is to better understand the exact anatomical location where INCS are absorbed. METHODS: Patients with chronic rhinosinusitis and allergic rhinitis taking fluticasone pre-operatively who were scheduled for functional endoscopic sinus surgery and inferior turbinate reduction, respectively, were recruited. Intra-operative tissue samples were obtained from predetermined locations within the sinonasal cavity. Mass spectrometry was then used to quantify the amount of absorption in each specific anatomic location to determine the largest amount of absorption. RESULTS: Eighteen patients were included in our study. The greatest fluticasone absorption levels across the sinonasal anatomy were at the anterior inferior turbinate (5.7 ngl/mL), ethmoid sinus, (4.4 ng/mL), posterior inferior turbinate (3.7 ng/mL), maxillary sinus (1.3 ng/mL), and the sphenoethmoidal recess (0.72 ng/mL) respectively. Absorption was significantly higher in revision surgery compared to surgically naïve patients. CONCLUSIONS: Computation fluid dynamic models of the nasal passage are useful models to help predict intranasal particle flow. However, these models do not incorporate or consider the important mucociliary clearance system, leading to absorption of fluticasone throughout the sinonasal cavity far beyond that predicted by these models. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1551-1555, 2024.

Association between nonalcoholic fatty liver disease and carotid intima-media thickness.

Background: Many non-invasive methods have been studied for assessing the severity of fatty liver disease and carotid intima-media thickness (CIMT). However, the correlation between hepatic steatosis and CIMT has not been fully studied, either globally or in Vietnam. This study investigated the association between nonalcoholic fatty liver disease (NAFLD) and CIMT. Methods: A cross-sectional study was performed on 125 patients at the Cardiology Department, the Emergency Interventional Cardiology Department, and the Internal Cardiology Clinic of Thong Nhat Hospital. Results: Among the 125 patients in our study population, NAFLD was diagnosed in 56%, and the mean CIMT was 0.89 ± 0.48 mm. Normal CIMT was measured in 21% of patients, whereas 79% had an elevated CIMT. The NAFLD rates were significantly different between patients with normal and increased CIMT, at 26.9% and 69.6%, respectively (p = 0.001). Conclusions: Our study revealed a strong association between NAFLD and CIMT. NAFLD is currently considered a feature of metabolic syndrome, and an increase in the prevalence of NAFLD might result in an increase in the incidence of cardiovascular disease.

Correlation between nonalcoholic fatty liver disease and coronary atherosclerosis.

Background: Various non-invasive methods have been studied for assessing the severity of fatty liver disease and coronary atherosclero-sis. However, the correlation between hepatic steatosis and coronary atherosclerosis has not been fully studied, either globally or specifically in Vietnam. This study investigated the association between nonalcoholic fatty liver disease (NAFLD) and coronary atherosclerosis using coronary computed tomography angiography (CCTA). Methods: An analytical cross-sectional study was performed, including 223 patients treated by the Cardiology Department, the Emergency Interventional Cardiology Departments, and the Internal Cardiology Clinic of Thong Nhat Hospital. Results: In our cohort of 223 patients, the NAFLD was detected in 66% of the population, the mean coronary artery stenosis (CAS) was 44.54% ± 20.23%, and the mean coronary artery calcium score (CACS) was 3569.05 ± 425.99, as assessed using the Agatston method. The proportion of patients with significant atherosclerotic plaque (CAS 50%) >was 32%, whereas the remaining 68% had insignificant stenosis. Among our study population, 16% had no coronary artery calcification, 38% had mild calcification, and 46% had moderate to severe calcification. In the group of NAFLD patients, 33.3% had significant atherosclerotic plaque, which was not significantly different from the rate in individuals without NAFLD (p = 0.51). Mild coronary artery calcification was detected in 37.4% of NAFLD patients, and moderate to severe calcification was detected in 48.3% (p = 0.45). Conclusions: NAFLD was not found to be strongly associated with coronary atherosclerosis in this study. More studies with larger sample sizes remain necessary to verify whether any correlation exists.

Factors contributing to ice nucleation and sequential freezing of leaves in wheat.

MAIN CONCLUSION: Anatomical, metabolic and microbial factors were identified that contribute to sequential freezing in wheat leaves and likely contribute to supercooling in the youngest leaves and potentially meristematic regions. Infrared thermography (IR) has been used to observe wheat leaves freezing independently and in an age-related sequence with older leaves freezing first. To determine mechanisms that might explain this sequence of freezing several analytical approaches were used: (1) The size of xylem vessels, in proximity to where freezing initiated, was measured to see if capillary freezing point depression explained sequential freezing. The sequence of freezing in the four youngest leaves was correlated, with the largest vessels freezing first. (2) Carbohydrate and amino acids were analyzed to determine if solute concentrations as well as interactions with membranes explained the freezing sequence. Sucrose was highly correlated to the freezing sequence for all leaves suggesting a prominent role for this sugar as compared to other simple sugars and fructans. Among individual free amino acids proline and serine were correlated to the freezing sequence, with younger leaves having the highest concentrations. (3) Microflora within and on leaf surfaces were determined to measure potential freezing initiation. Levels of bacteria and fungi were correlated to the freezing sequence for all leaves, and species or genera associated with high ice nucleation activity were absent in younger leaves. Moisture content and transcript expression of ice binding proteins were also measured. As expected, our results show that no single mechanism explains the freezing sequence observed via infrared analyses. While these multiple mechanisms are operative at different levels according to the leaf age, they seem to converge when it comes to the protection of vital meristematic tissues. This provides potential phenotypic characters that could be used by breeders to develop more winter-hardy genotypes.

A conditional mouse expressing an activating mutation in NRF2 displays hyperplasia of the upper gastrointestinal tract and decreased white adipose tissue.

Activation of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) transcription factor is a critical and evolutionarily conserved cellular response to oxidative stress, metabolic stress, and xenobiotic insult. Deficiency of NRF2 results in hypersensitivity to a variety of stressors, whereas its aberrant activation contributes to several cancer types, most commonly squamous cell carcinomas of the esophagus, oral cavity, bladder, and lung. Between 10% and 35% of patients with squamous cell carcinomas display hyperactive NRF2 signaling, harboring activating mutations and copy number amplifications of the NFE2L2 oncogene or inactivating mutations or deletions of KEAP1 or CUL3, the proteins of which co-complex to ubiquitylate and degrade NRF2 protein. To better understand the role of NRF2 in tumorigenesis and more broadly in development, we engineered the endogenous Nfe2l2 genomic locus to create a conditional mutant LSL-Nrf2E79Q mouse model. The E79Q mutation, one of the most commonly observed NRF2-activating mutations in human squamous cancers, codes for a mutant protein that does not undergo KEAP1/CUL3-dependent degradation, resulting in its constitutive activity. Expression of NRF2 E79Q protein in keratin 14 (KRT14)-positive murine tissues resulted in hyperplasia of squamous cell tissues of the tongue, forestomach, and esophagus, a stunted body axis, decreased weight, and decreased visceral adipose depots. RNA-seq profiling and follow-up validation studies of cultured NRF2E79Q murine esophageal epithelial cells revealed known and novel NRF2-regulated transcriptional programs, including genes associated with squamous cell carcinoma (e.g. Myc), lipid and cellular metabolism (Hk2, Ppard), and growth factors (Areg, Bmp6, Vegfa). These data suggest that in addition to decreasing adipogenesis, KRT14-restricted NRF2 activation drives hyperplasia of the esophagus, forestomach, and tongue, but not formation of squamous cell carcinoma. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mometasone absorption in cultured airway epithelium.

BACKGROUND: Topical mometasone is frequently used as an intranasal spray, on drug-eluting stents, and compounded by specialty pharmacies as a sinus rinse. A typical sinus rinse contains 1.2 mg of mometasone dissolved in 240 mL of buffered saline and is flushed through the sinonasal cavity. The mometasone irrigation rapidly flows to the contralateral sinonasal cavity or the nasopharynx with a contact time on the order of 5 to 10 seconds. However, no information is available on the absorption rate of topical mometasone on the sinonasal surface. METHODS: To determine the absorption characteristics of mometasone, we harvested nasal epithelium from 2 healthy donors and differentiated them into a mature ciliated epithelium on Millicell membranes. We applied mometasone to the apical surface for various time intervals and then rinsed off non-absorbed mometasone with phosphate-buffered saline. Millicell membranes with the adherent epithelial cells were then harvested and stored in guanidine hydrochloride for quantification using high-performance liquid chromatography-mass spectrometry. RESULTS: Fifty percent of the maximal absorption occurred after an average of 38 minutes after application, and maximal absorption occurred after an average of 114 minutes. CONCLUSION: Our data provide an estimate for rates of absorption of mometasone applied to the sinonasal cavity and suggest that the absorption rates poorly match contact time during saline lavage.

Single Cell Chemical Cytometry of Akt Activity in Rheumatoid Arthritis and Normal Fibroblast-like Synoviocytes in Response to Tumor Necrosis Factor α.

The etiology of rheumatoid arthritis (RA) is poorly understood, and 30% of patients are unresponsive to established treatments targeting tumor necrosis factor α (TNFα). Akt kinase is implicated in TNFα signaling and may act as a barometer of patient responses to biologic therapies. Fluorescent peptide sensors and chemical cytometry were employed to directly measure Akt activity as well as proteolytic activity in individual fibroblast-like synoviocytes (FLS) from RA and normal subjects. The specificity of the peptide reporter was evaluated and shown to be a valid measure of Akt activity in single cells. The effect of TNFα treatment on Akt activity was highly heterogeneous between normal and RA subjects, which was not observable in bulk analyses. In 2 RA subjects, a bimodal distribution of Akt activity was observed, primarily due to a subpopulation (21.7%: RA Subject 5; 23.8%: RA Subject 6) of cells in which >60% of the reporter was phosphorylated. These subjects also possessed statistically elevated proteolytic cleavage of the reporter relative to normal subjects, suggesting heterogeneity in Akt and protease activity that may play a role in the RA-affected joint. We expect that chemical cytometry studies pairing peptide reporters with capillary electrophoresis will provide valuable data regarding aberrant kinase activity from small samples of clinical interest.

Mitigation of nutrient losses via surface runoff from rice cropping systems with alternate wetting and drying irrigation and site-specific nutrient management practices.

Resource-conserving irrigation and fertilizer management practices have been developed for rice systems which may help address water quality concerns by reducing N and P losses via surface runoff. Field experiments under three treatments, i.e., farmers' conventional practice (FCP), alternate wetting and drying (AWD), and AWD integrated with site-specific nutrient management (AWD + SSNM) were carried out during two rice seasons at two sites in the southwest Yangtze River delta region. Across site years, results indicated that under AWD irrigation (i.e., AWD and AWD + SSNM), water inputs were reduced by 13.4~27.5 % and surface runoff was reduced by 30.2~36.7 % compared to FCP. When AWD was implemented alone, total N and P loss masses via surface runoff were reduced by 23.3~30.4 % and 26.9~31.7 %, respectively, compared to FCP. However, nutrient concentrations of surface runoff did not decrease under AWD alone. Under AWD + SSNM, total N and P loss masses via surface runoff were reduced to a greater extent than AWD alone (39.4~47.6 % and 46.1~48.3 % compared to FCP, respectively), while fertilizer inputs and N surpluses significantly decreased and rice grain yields increased relative to FCP. Therefore, by more closely matching nutrient supply with crop demand and reducing both surface runoff and nutrient concentrations of surface runoff, our results demonstrate that integration of AWD and SSNM practices can mitigate N and P losses via surface runoff from rice fields while maintaining high yields.

3D volumes constructed from pixel-based images by digitally clearing plant and animal tissue.

Construction of three-dimensional volumes from a series of two-dimensional images has been restricted by the limited capacity to decrease the opacity of tissue. The use of commercial software that allows colour-keying and manipulation of two-dimensional images in true three-dimensional space allowed us to construct three-dimensional volumes from pixel-based images of stained plant and animal tissue without generating vector information. We present three-dimensional volumes of (1) the crown of an oat plant showing internal responses to a freezing treatment, (2) a sample of a hepatocellular carcinoma from a woodchuck liver that had been heat-treated with computer-guided radiofrequency ablation to induce necrosis in the central portion of the tumour, and (3) several features of a sample of mouse lung. The technique is well suited to images from large sections (greater than 1 mm) generated from paraffin-embedded tissues. It is widely applicable, having potential to recover three-dimensional information at virtually any resolution inherent in images generated by light microscopy, computer tomography, magnetic resonance imaging or electron microscopy.

Murine cytomegalovirus containing a mutation at open reading frame M37 is severely attenuated in growth and virulence in vivo.

A pool of murine cytomegalovirus (MCMV) mutants was generated by using a Tn3-based transposon mutagenesis procedure. One of the mutants, RvM37, which contained the transposon sequence at open reading frame M37, was characterized both in tissue culture and in immunocompetent BALB/c and immunodeficient SCID mice. Our results provide the first direct evidence to suggest that M37 is not essential for viral replication in vitro in NIH 3T3 cells. Compared to the wild-type strain and a rescued virus that restored the M37 region, the viral mutant was severely attenuated in growth in both BALB/c and SCID mice after intraperitoneal infection. Specifically, titers of the Smith strain and rescued virus in the salivary glands, lungs, spleens, livers, and kidneys of the SCID mice at 21 days postinfection were about 5 x 10(5), 2 x 10(5), 5 x 10(4), 5 x 10(3), and 1 x 10(4) PFU/ml of organ homogenate, respectively; in contrast, titers of RvM37 in these organs were less than 10(2) PFU/ml of organ homogenate. Moreover, the virulence of the mutant virus appeared to be significantly attenuated because none of the SCID mice infected with RvM37 had died by 120 days postinfection, while all animals infected with the wild-type and rescued viruses had died by 26 days postinfection. Our results suggest that M37 probably encodes a virulence factor and is required for MCMV virulence in SCID mice and for optimal viral growth in vivo.