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OBJECTIVES: Several scoring systems are used to predict prognosis in acute pancreatitis (AP), but their predictive success varies. This study compares the validity of the commonly used Bedside Index of Severity in AP (BISAP) score with the newly developed WL score and the Chinese Simple Scoring System (CSSS) score in predicting mortality and unfavorable prognostic outcomes in AP patients. METHODS: This retrospective descriptive study included all AP patients presenting to the emergency department from June 2, 2019, to June 2, 2022. Patient demographics, vital signs, laboratory values, and imaging findings were recorded, and WL, CSSS, and BISAP scores were calculated. The effectiveness of these scores in predicting adverse outcomes and mortality was compared. RESULTS: Among 357 patients, 53.2% were male, with a median age of 62 years (interquartile range: 48-75). Area under the curve (AUC) values for 7-day outcomes were 0.956 for WL, 0.759 for CSSS, and 0.871 for BISAP; for 30-day outcomes, AUC values were 0.941 for WL, 0.823 for CSSS, and 0.901 for BISAP; and for poor prognostic outcomes, AUC values were 0.792 for WL, 0.769 for CSSS, and 0.731 for BISAP. CONCLUSION: In AP patients, WL, CSSS, and BISAP scores are effective predictors of unfavorable prognosis and mortality. WL score outperforms the CSSS and BISAP scores in predicting 7-day and 30-day mortality and poor prognosis. After WL, BISAP is the second-best system for predicting mortality. For predicting unfavorable prognoses, CSSS is the second-best system after WL. The simplicity of calculating the WL score based on four laboratory parameters makes it a preferable choice.

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Wireless capsule endoscopy (CE) has revolutionized gastrointestinal diagnostics, offering a non-invasive means to visualize and monitor the GI tract. This review traces the evolution of CE technology. Addressing the limitations of traditional white light (WL) CE, the paper explores non-WL technologies, integrating diverse sensing modalities and novel biomarkers to enhance diagnostic capabilities. Concluding with an assessment of Technology Readiness Levels, the paper emphasizes the transformative impact of non-WL colon CE devices on GI diagnostics, promising more precise, patient-centric, and accessible healthcare for GI disorders.

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With the development of PD-1/PD-L1 immune checkpoint inhibitor therapy, the ability to monitor PD-L1 expression in the tumor microenvironment is important for guiding therapy. This study was performed to develop a novel radiotracer with optimal pharmacokinetic properties to reflect PD-L1 expression in vivo via single-photon emission computed tomography (SPECT) imaging. [99mTc]Tc-HYNIC-WL12-tricine/M (M = TPPTS, PDA, ISONIC, 4-PSA) complexes with high radiochemical purity (>97%) and suitable molar activity (from 100.5 GBq/µmol to 300 GBq/µmol) were prepared through a kit preparation process. All 99mTc-labeled HYNIC-WL12 radiotracers displayed good in vitro stability for 4 h. The affinity and specificity of the four radiotracers for PD-L1 were demonstrated both in vitro and in vivo. The results of biodistribution studies displayed that the pharmacokinetics of the 99mTc-HYNIC-conjugated radiotracers were significantly influenced by the coligands of the radiotracers. Among them, [99mTc]Tc-HYNIC-WL12-tricine/ISONIC exhibited the optimal pharmacokinetic properties (t1/2α = 8.55 min, t1/2ß = 54.05 min), including the fastest clearance in nontarget tissues, highest tumor-to-background contrast (e.g., tumor-to-muscle ratio, tumor-to-blood ratio: 40.42 ± 1.59, 14.72 ± 2.77 at 4 h p.i., respectively), and the lowest estimated radiation absorbed dose, highlighting its potential as a clinical SPECT imaging probe for tumor PD-L1 detection.

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Assessing programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer (NSCLC), particularly in metastatic cases, remains challenging. In this study, surface plasmon resonance (SPR) analysis and [68Ga]Ga-DOTA-WL12 micro-PET/CT imaging are performed. [68Ga]Ga-DOTA-WL12 PET/CT and [18F]FDG PET/CT are performed on a cohort of 20 patients with NSCLC. Semi-quantitative assessments include SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and target-to-background ratio (TBR). DOTA-WL12 exhibits robust PD-L1 binding with a KD value of 0.2 nM. Subsequent human studies reveal significant correlations between PD-L1 expression and the [68Ga]Ga-DOTA-WL12 SUVmax in primary and metastatic lesions, surpassing the [18F]FDG results (r = 0.8889, p <0.0001 vs r = 0.0469, p = 0.8127). Notably, [68Ga]Ga-DOTA-WL12 imaging discerned SUVmax and TBR differences between PD-L1 TPS ≤1% and PD-L1 TPS > 1% groups (p all <0.001). In an NSCLC patient with brain metastases, [68Ga]Ga-DOTA-WL12 shows a SUVmean of 0.04 in the brain background, with TBR values of 17 and 23, underscoring its potential for detecting brain metastases. The study provides initial evidence for the clinical utility of [68Ga]Ga-DOTA-WL12 PET/CT for lesion detection, immunotherapy selection, and therapeutic efficacy evaluation in PD-L1-expressing NSCLC, demonstrating its potential as a valuable tool in NSCLC research and management.

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The fermentation of the high-viscosity polysaccharide WL gum has always been associated with poor mass transfer. Appropriate impeller configurations are key factors in maintaining homogeneity and sufficient mass transfer conditions. Therefore, a flat-folded disc turbine impeller (FFDT) taking into account both the reduced cavitation effect and the increased contact area was designed. Besides, a curved cross impeller (CC) and a fishbone-shaped impeller (FS) generating axial flow were also designed. The energy consumption and efficiency of the designed impellers and eight reported impellers were evaluated through fermentation and principal component analysis (PCA). Compared to the commonly-used six-blade flat-blade disc turbine (FBDT), the ungassed power number of FFDT was reduced by 50 %. Combinations of six-blade Brumajin impeller (BM) + FFDT and CC + FFDT produced high WL gum production and viscosity (34.0 g/L, 35.50 g/L, and 62.64 Pa·s, 61.68 Pa·s, respectively) and were suitable impellers for WL biosynthesis. WL gum from BM + FFDT showed higher viscosity, viscoelasticity, and molecular weight than that from FBDT + FBDT. In addition, fewer amino acids and pyruvic acid intermediates were formed using BM + FFDT, indicating a greater metabolic flux towards WL gum synthesis. This work provided an important reference for the design of impellers in high-viscosity fermentation systems.

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AIM: To analyze laparotomy closure quality (suture/wound length ratio; SL/WL) and short term complications (surgical site occurrence; SSO) of conventional midline and transverse abdominal incisions in elective and emergency laparotomies with a longterm, absorbent, elastic suture material. METHOD: Prospective, monocentric, non-randomized, controlled cohort study on short stitches with a longterm resorbable, elastic suture (poly-4-hydroxybutyrate, [p-4OHB]) aiming at a 6:1 SL/WL-ratio in midline and transverse, primary and secondary laparotomies for elective and emergency surgeries. RESULTS: We included 351 patients (♂: 208; ♀: 143) with midline (n = 194), transverse (n = 103), and a combined midline/transverse L-shaped (n = 54) incisions. There was no quality difference in short stitches between elective (n = 296) and emergency (n = 55) operations. Average SL/WL-ratio was significantly higher for midline than transverse incisions (6.62 ± 2.5 vs 4.3 ± 1.51, p < 0.001). Results in the first 150 patients showed a reduced SL/WL-ratio to the following 200 suture closures (SL/WL-ratio: 5.64 ± 2.5 vs 6.1 ± 2.3; p < 0.001). SL/WL-ratio varied insignificantly among the six surgeons participating while results were steadily improving over time. Clinically, superficial surgical site infections (SSI, CDC-A1/2) were encountered in 8%, while 4,3% were related to intraabdominal complications (CDC-A3). An abdominal wall dehiscence (AWD) occurred in 22/351 patients (6,3%)-twice as common in emergency than elective surgery (12,7 vs 5,1%)-necessitating an abdominal revision in 86,3% of cases. CONCLUSION: We could show that a short stitch 6:1 SL/WL-ratio with a 2-0 single, ultra-long term, absorbent, elastic suture material can be performed in only 43% of cases (85% > 4:1 SL/WL-ratio), significantly better in midline than transverse incisions. Transverse incisions should preferably be closed in two layers to achieve a sufficient SL/WL-ratio equivalent to the median incision. GOV IDENTIFIER: NCT01938222.

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Osteonecrosis of the femoral head (ONFH) is a devastating bone disease that is caused by a disruption of blood supply leading to necrotic cell death. Clinically, it was found that obesity has a high prevalence with ONFH. However, it remains unclear how obesity may directly affect tissue regeneration and bone healing in osteonecrosis (ON). The purpose of this study is to investigate the effects of obesity and weight loss (WL) on ON healing. In this study, we induced obesity and WL in an established surgery-induced ON mouse model via feeding a high-fat diet (HFD) and altering the diet respectively. All mice received a surgical induction of ON of distal femoral epiphysis at the age of 12 weeks. HFD was switched to normal diet (ND) after ON surgery to induce WL. Mouse body weight was recorded weekly. Mouse body composition was scanned by DEXA (Dual-energy X-ray absorptiometry) right after sacrifice at the age of 16 weeks. The distal femoral bone samples were fixed and embedded for histology such as H&E, immunohistochemistry, and TRAP staining. In this study, we found that HFD-induced obesity impaired revascularization and bone remodeling showing decreased vessel areas and reduced osteoblast and osteoclast numbers. WL could rescue obesity-induced bone healing defects. Our study is the first to test the direct effects of obesity and WL on ON bone healing. We believe our work may provide new concepts for osteonecrosis treatment in obese patients.

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This investigation examined the antioxidant, antimicrobial, cytotoxic, and anti-inflammatory activities of the acetone extract of the lichen Platismatia glauca (L.) W.L. Culb. & C.F. Culb. (PGAE). The phytochemical study of PGAE showed presence of seven compounds: salazinic acid, ß-orcinol carboxylic acid, 3-hydroxyphysodalic acid, physodalic acid, physodic acid, atranorin, and chloroatranorin. The antimicrobial potential was determined by microdilution which showed that S. aureus was most sensitive to the effect of PGAE with MIC value 0.312 mg/ml. Antioxidant activity was evaluated by using DPPH method. The obtained IC50 value for PGAE was 194.30 ± 3.32 µg/ml. The cytotoxic effect of the extract was evaluated by MTT test and the strongest activity was towards human epithelial carcinoma cells with IC50 value of 59.10 ± 0.46 µg/ml. The findings revealed that the application of lichen extracts decreased the paw edoema in a dose-dependent manner at 1, 2, 3, and 4 h following carrageenan administration.

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[This corrects the article DOI: 10.3389/fmicb.2023.1201505.].

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Herpes simplex virus 1 (HSV-1) is a widely distributed virus. HSV-1 is a growing public health concern due to the emergence of drug-resistant strains and the current lack of a clinically specific drug for treatment. In recent years, increasing attention has been paid to the development of peptide antivirals. Natural host-defense peptides which have uniquely evolved to protect the host have been reported to have antiviral properties. Cathelicidins are a family of multi-functional antimicrobial peptides found in almost all vertebrate species and play a vital role in the immune system. In this study, we demonstrated the anti-HSV-1 effect of an antiviral peptide named WL-1 derived from human cathelicidin. We found that WL-1 inhibited HSV-1 infection in epithelial and neuronal cells. Furthermore, the administration of WL-1 improved the survival rate and reduced viral load and inflammation during HSV-1 infection via ocular scarification. Moreover, facial nerve dysfunction, involving the abnormal blink reflex, nose position, and vibrissae movement, and pathological injury were prevented when HSV-1 ear inoculation-infected mice were treated with WL-1. Together, our findings demonstrate that WL-1 may be a potential novel antiviral agent against HSV-1 infection-induced facial palsy.

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This study aimed to identify the regulatory mechanisms of white, blue, red lights on carotenoid and tocochromanol biosynthesis in mung bean sprouts. Results showed that three lights stimulated the increase of the predominated lutein (3.2-8.1 folds) and violaxanthin (2.1-6.1 folds) in sprouts as compared with dark control, as well as ß-carotene (20-36 folds), with the best yield observed under white light. Light signals also promoted α- and γ-tocopherol accumulation (up to 1.8 folds) as compared with dark control. The CRTISO, LUT5 and DXS (1.24-6.34 folds) exhibited high expression levels under light quality conditions, resulting in an overaccumulation of carotenoids. The MPBQ-MT, TC and TMT were decisive genes in tocochromanol biosynthesis, and were expressed up to 4.19 folds as compared with control. Overall, the results could provide novel insights into light-mediated regulation and fortification of carotenoids and tocopherols, as well as guide future agricultural cultivation of mung bean sprouts.

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Background: Deceased donor liver transplantation (DDLT) is increasing in India and now constitutes nearly one-third of all liver transplantation procedures performed in the country. There is currently no uniform national system of allocation of deceased donor livers. Methods: A national task force consisting of 19 clinicians involved in liver transplantation from across the country was constituted under the aegis of the Liver Transplantation Society of India to develop a consensus document addressing the above issues using a modified Delphi process of consensus development. Results: The National Liver Allocation Policy consensus document includes 46 statements covering all aspects of DDLT, including minimum listing criteria, listing for acute liver failure, DDLT wait-list management, system of prioritisation based on clinical urgency for adults and children, guidelines for allocation of paediatric organs and allocation priorities for liver grafts recovered from public sector hospitals. Conclusion: This document is the first step in the setting up of a nationally consistent policy of deceased donor liver allocation.

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Accrued evidence has indicated that epigenetic mechanisms altered by alcohol have been implicated in the progression and development of alcoholic liver disease (ALD). SIRT1 plays an important role in ALD progression and has emerged as a promising therapeutic target for treating ALD. The purpose of this study is to investigate the efficacy of [11C]WL-1 for quantitative imaging of SIRT1 in mouse models of early-stage ALD. Positron emission tomography/computerized tomography (PET/CT) imaging was carried out 60 min following the injection of [11C]WL-1 in mouse models of early-stage ALD and normal control mice. The time-activity curves for ALD mouse livers showed remarkably decreased total uptake of [11C]WL-1 relative to that for control mouse livers. Moreover, compared with the normal control mice, decreased uptake in the cortex, hippocampus, and cerebellum was also observed in early-stage ALD mice, while the uptake of [11C]WL-1 in amygdala showed no significant changes. Western blot analysis confirmed that the protein levels of SIRT1 in the brains of early-stage ALD mice were decreased significantly when compared to the normal control mouse brains. Collectively, PET imaging with [11C]WL-1 would facilitate future clinical studies, aiming to demonstrate the roles of SIRT1 in ALD.

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The polysaccharide WL gum is produced by the marine microorganism Sphingomonas sp. WG and presents great commercial utility potential in many industries especially in oil industries. However, the high fermentation cost limits its wide application. Therefore, an efficient production system at a lower cost was established using beet molasses to partially replace the commonly used carbon sources. Four different molasses were screened and their composition was investigated. One-factor design and RSM statistical analysis were employed to optimize the WL gum fermentation medium. The effects of molasses on the rheological properties and gene expression of WL gum were also investigated. The results showed that the pretreated beet molasses generated both high broth viscosity and WL gum production (12.94 Pa·s and 11.16 g/L). Heavy metal ions and ash were found to be the key factors in unpretreated and pretreated molasses affecting WL production. The cost-efficient production medium contained (g/L): sucrose 61.79, molasses 9.95, yeast extract 1.23, K2HPO4 1, MgSO4 0.1, ZnSO4 0.1 and the WL gum production reached 40.25 ± 1.15 g/L. The WL gum product WL-molasses showed the higher apparent viscosity, and viscous modulus and elastic modulus than WL-sucrose and WL-mix, which might be related to its highest molecular mass. The higher expressional level of genes such as pgm, ugp, ugd, rmlA, welS, and welG in WL gum synthesis in the mixed carbon source medium caused the high production and broth viscosity. This work provided a cost-efficient method for WL gum production.

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BACKGROUND: The effects of caffeine on cognitive impairment have not been conclusively determined. This study aimed to objectively assess the correlation between the urinary caffeine and caffeine metabolites and cognitive decline in older adults. METHODS: Data on urinary caffeine and caffeine metabolites and the cognitive performance of participants aged 60 years and older were extracted from the National Health and Nutrition Examination Surveys 2011-2014. Binary logistic regression and restricted cubic splines (RCS) analyses were used to evaluate the association between urinary caffeine and caffeine metabolites and cognitive performance. RESULTS: Eight hundred twenty-seven individuals were enrolled in this cross-sectional study. We observed that 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, 1,7-dimethylxanthine, and 3,7-dimethylxanthine levels were significantly and inversely associated with cognitive decline. The RCS results suggested an approximately linear dose-response relationship between the aforementioned metabolites and cognitive performance. Moreover, the effects of urinary caffeine and caffeine metabolites on cognitive function assessed using the AFT were more evident in men. CONCLUSIONS: Our study suggested that urinary caffeine and caffeine metabolite levels were associated with a reduced risk of cognitive impairment in a linear manner, especially in men.

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Background/objective: Poor subjective well-being is a risk factor for poor health; and threatens school administrators' leadership roles and overall occupational and personal outcomes. Online digital care and coaching such as Zoom-delivered GROW (Z-GROW) coaching may be an invaluable approach to building resilience and improving well-being. This study investigated the effectiveness of the Z-GROW coaching model in enhancing self-reported well-being in a sample of school administrators in South-East Nigeria. Method: A randomized control trial was conducted with a sample of 109 school administrators who met the inclusion criteria. Participants were allocated into Z-GROW (N = 55) and waitlist control (N = 54) groups. A 2-hour Z-GROW programme was delivered to the Z-GROW intervention group weekly for 9 weeks. Subjective well-being was measured using the Satisfaction with Life Scale (SWLS), the Scale of Positive and Negative Experience (SPANE), and the Flourishing Scale (FS). Data were collected on three occasions: pre-intervention, post-intervention, and follow-up using the same measures. All data were analyzed using descriptive and inferential statistics. The presentation of data was supported by figures and charts. Results: Results revealed that school administrators' three dimensions of subjective well-being significantly improved following the Z-GROW intervention. It was further shown that the improved state of participants was sustained through a 3-monthfollow-up assessment. Conclusion: Based on the findings, it can be concluded that intervention using GROW coaching in the zoom platform improves the self-reported well-being of school administrators. The outcomes of this study present the Z-GROW model as a viable intervention for subjective well-being and other mental health conditions among school administrators. Through the Z-GROW model, employees can access occupational health coaching from the comfort of their homes.

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INTRODUCTION: Levodopa/carbidopa intestinal gel (LCIG) is an effective treatment in patients with advanced Parkinson's disease (PD) with consolidated evidence of clinical efficacy. However, only few studies have assessed long-term safety, causes of discontinuation, mortality, and relative predictors. METHODS: We conducted a retrospective analysis of 79 PD patients treated with LCIG between 2005 and 2020 in two Italian Neurological Centers, recording all adverse events (AEs), including weight loss (WL). Kaplan-Meier curve was used to estimate the time to discontinuation and survival. Cox proportional hazard model was employed to identify predictors of discontinuation and mortality, while Pearson's correlation was used to analyze predictors of WL. RESULTS: The average follow-up was 47.7 ± 40.5 months and the median survival from disease onset was 25 years. There were three cases of polyradiculoneuropathy Guillain-Barre syndrome-like, all occurred in the early years of LCIG treatment. Twenty-five patients died (32%), 18 on LCIG (including one suicide) and seven after discontinuation. The mean WL was 3.62 ± 7.5 kg, which correlated with levodopa dose at baseline (p = 0.002), levodopa equivalent daily dose (LEDD) baseline (p = 0.017) and off-duration (p = 0.0014), but not dyskinesia. Peristomal complications emerged as a negative predictor of discontinuation (p = 0.008). CONCLUSIONS: LCIG has a relatively satisfactory long-term safety profile and efficacy and a relatively low rate of discontinuation. Peristomal complications may represent a predictor of longer duration of therapy. According to the mortality analysis, LCIG patients show a long lifespan. Delaying the initiation of LCIG does not affect the sustainability of LCIG therapy.

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Sphingan WL gum (WL), a kind of exopolysaccharides, is produced by Sphingomonas sp. WG. In this study, citric acid (CA) crosslinked WL hydrogel films were firstly developed for potential wound dressing application. ATR-FTIR and TG results suggested the occurrence of esterification crosslinking. SEM analysis showed that this aided covalent crosslinking could prevent their porous structures from collapsing when swelling. Due to the deprotonation of carboxyl groups, the water absorption capacity of WL-CA hydrogel films increased with the increase of pH (maximum swelling ratio = 38 g/g). The covalent crosslinked swollen WL-CA hydrogels exhibited certain hydrolytic stability, high porosity (>60%), moderate tissue adhesion, and good rheological property (G' > G″, G' up to 2 kPa). WL-CA-CIP hydrogel films loaded with antibiotic ciprofloxacin (CIP) showed sustained drug release properties, long-lasting antibacterial activity, and superior biocompatibility. All the results indicated that WL-based hydrogels were potential candidates for wound dressing applications.

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As an important microbial exopolysaccharide, the sphingan WL gum could be widely used in petroleum, food, and many other fields. However, its lower production is still limiting its wider application. Therefore, to gain insights into the bottlenecks of WL gum production by identifying the key enzymes in the WL gum biosynthesis pathway, more than 20 genes were over-expressed in Sphingomonas sp. WG and their effects on WL gum production and structure were investigated. Compared to the control strain, the WL gum production of welB over-expression strain was increased by 19.0 and 21.0% at 36 and 84 h, respectively. The WL gum production of both atrB and atrD over-expression strains reached 47 g/L, which was approximately 34.5% higher than that of the control strain at 36 h. Therefore, WelB, AtrB, and AtrD may be the key enzymes in WL production. Interestingly, the broth viscosity of most over-expression strains decreased, especially the welJ over-expression strain whose viscosity decreased by 99.3% at 84 h. Polysaccharides' structural features were investigated to find the critical components in viscosity control. The uronic acid content and total sugar content was affected by only a few genes, therefore, uronic acid and total sugar content may be not the key composition. In comparison, the acetyl degrees were enhanced by over-expression of most genes, which meant that acetyl content may be the critical factor and negatively correlated with the apparent viscosity of WL gum. This work provides useful information on the understanding of the bottlenecks of WL gum biosynthesis and will be helpful for the construction of high WL gum-yielding strains and rheological property controlling in different industries.

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Applying biotechnological tools to the selection of higher-yielding bioeconomic crops is a promising and remarkable means of reducing the burden on production on a global scale. In the present study, 25 germplasms of Indian ginseng (Withania somnifera (L.) Dunal) were examined for their genetic diversity by using morphological, biochemical, and molecular markers for twenty plant growth traits. The properties of plant growth differed significantly in the maximum genotypes of Indian ginseng, the markers of randomly amplified polymorphic DNA (RAPD), and inter simple sequence repeat (ISSR) showed considerable diversity between the genotypes. The combined unweighted pair group technique with arithmetic mean (UPGMA) dendrogram of morphological, biochemical, and molecular markers grouped all 25 genotypes into two main clusters at 0.61 coefficient value. In addition to this, secondary metabolite profiling by high-performance liquid chromatography (HPLC), there were high variations for withanolide B (WL-B), withanoside-V (WS-V), wedelolactone (WDL), withanoside-IV (WS-IV), and withaferin A (WF-A) content between different genotypes. For the total alkaloid and withanolide concentration in the roots and leaves, high heritability with an increased genetic gain was observed, indicating that selection based on these traits could be an effective method in breeding programs. Furthermore, the path coefficient analysis showed a direct positive impact of the total root fiber, WL-B (leaves), WF-A (leaves), WS-IV (roots), WDL (roots), and the total alkaloid content on the dry root yield. High content of WDL, a high-quality bioactive withanolide, was also described for the first time in the genotype UWS23. These properties can further be exploited to improve the dry root yield in W. somnifera genotypes. The outcomes of the present study also provide an essential foundation for the selection of high-yielding bioeconomic varieties that could be utilized to improve Ashwagandha breeding programs.