Analogue Treatment Research Articles

Successful results of early nucleos(t)ide analogue treatment for liver transplantation candidates with severe acute hepatitis B infection.

Early treatment of severe acute hepatitis B virus (HBV) infection with nucleos(t)ide analogues may prevent progression to acute liver failure (ALF). The charts of 24 patients who were treated for severe acute HBV infection (either INR ≥ 1.5 or INR≥ 1.4 and total bilirubin ≥ 20 mg/dL at the referring institution or after admission) between April 2021 and May 2023 (inclusive) were evaluated retrospectively. Twelve patients were women; median [range] age: 48 [35-68]. Entecavir (0.5 mg/day) (n = 16) or tenofovir disoproxil fumarate (245 mg/day) (n =8) were used depending on availability. Two patients required liver transplant which was performed successfully in one (no suitable donor for the other). Deterioration to ALF was prevented in 22 of the 24 cases (92%); these patients could be discharged after median (range) 12 (5-24) days following initiation of the antiviral drug. There was no significant difference in efficacy between the two antiviral agents. The anti-HBsAg antibody became positive in 16 patients (73%); one other patient became HBsAg negative at 1 month after discharge but was lost to follow up. Five patients (23%) are still HBsAg positive but all except one have started treatment in the last 6 months. One of the recently treated 4 patients stopped taking the antiviral drug at his own will and one has become anti-HIV antibody positive during follow up. Early treatment of severe acute HBV infection with entecavir or tenofovir disoproxil fumarate prevents the need for liver transplant and consideration of living donors.

THU194 Growth Pattern And Related Predictors Of Gonadotropin-releasing Hormone Analog Treatment In Girls With Precocious Puberty

Abstract Disclosure: L. Ouyang: None. F. Yang: None. Purpose: The purpose of this study was to analyze the height growth pattern during gonadotropin-releasing hormone analog (GnRHa) treatment in girls with central precocious puberty (CPP) and early and fast puberty (EFP), calculate the incidence of prominent height deceleration and explore the relevant predictors of prominent height deceleration, which may provide useful information for the application of GnRHa as treatement and other adjunctive treatments such as growth hormone (GH). Methods: Ninety-nine girls diagnosed with CPP and 47 girls with EFP were enrolled in this retrospective analysis, they were treated with GnRHa from 6 months to 2 years. Clinical indicators such as hormone levels, bone age (BA), and B-ultrasound indicators were included and shown every 6 months. The growth velocity (GV) of height and the change of height standard deviation score (SDS) were shown every 6 months and once a year. The incidence of height deceleration was calculated in both the first and second years of GnRHa treatment. Multivariate logistic regression analysis was used to explore the predictive indicators of height deceleration. Results: There was a statistically significant difference between girls with CPP and EFP in physical growth indicators, hormone levels, BA, BA advancement, and B-ultrasound indicators at the time of diagnosis (P < 0.05); however, these statistical differences gradually disappeared as treatment progressed. The treatment of GnRHa decreases the GV, BA, and levels of hormones in girls with CPP and EFP. The GV during GnRHa treatment in two groups reached a trough at 18 months, followed by a gradual rebound, but the rebound was significantly greater in CPP than in girls with EFP. The GV of girls with CPP was higher than that of girls with EFP, and the decrease in height-SDS of girls with EFP was more than girls with CPP during the entire of GnRHa treatment. The incidence of growth deceleration in CPP in the first and second year of treatment was 17.35% (17/98) and 42.86% (24/56), and EFP was 25.53% (12/47) and 76.92% (10/13), respectively. No significant indicators predicted the occurrence of growth deceleration (P<0.05). Conclusions: GnRHa is effective in slowing the GV of height, the maturation of BA, and hormone levels in patients with precocious puberty, and the treatment time of 2 years or more can lead to an adult height benefit. The girls with EFP seem to suffer more damage in GV, which might affect AH, so the use of GnRHa in treating EFP should be done with more caution than in CPP. An adequate period of observation in CPP is needed before adjunctive treatments such as GH are used due to the height ascent in the later stage of treatment (18 months to 24 months). None of the factors we studied predicted the incidence of height deceleration during the period of GnRHa treatment. Presentation: Thursday, June 15, 2023

Fourth-year Results of HBeAg Negative Chronic Hepatitis B Patients Discontinuing Nucleos(t)ide Analogue Therapy

Objective: There is not a definitive virological treatment for chronic hepatitis B . Withdrawal of nucleos(t)ide analogue (NA) therapy frequently results in viral recurrence, necessitating lifetime treatment. We aimed to look into the results of discontinuation of nucleos(t)ide analogue therapy in HBeAg negative patients. Methods: Treatment of HBeAg-negative patients without cirrhosis who had suppressed HBV DNA for a mean of ≥7 years and underwent nucleos(t)ide analogue therapy for a mean of ≥7 years were stopped according to the EASL guideline stopping rule. Standard laboratory tests, such as HBV DNA viral load, HBsAg, alanine aminotransferase, and adverse events, were monitored for more than four years during therapy and afterwards. Results: HBsAg loss was not observed in any of the patients during the four-year follow-up period. After the first 12 weeks, HBV-DNA was detected in all patients whose nucleos(t)ide analogue treatment was discontinued. The percentage of patients with HBV DNA >2000 IU/mL was 70% at 6 months, 74% at 12 months, 78% at 24 months, and 79.7% at 36 months, HBV DNA >2000 IU/mL was not detected in remaining patients over a four-year period. In the first year, 26% (n=18) of patients were started treatment for relapse, 46% (n=32) in the second year, 49% (n=34) in the third year, and 55% (n=38) in the fourth year. 45% (n=31) of the patients were still being followed without treatment at the end of the fourth year. Conclusion: Although the follow-up of hepatitis B e antigen-negative CHB patients on NA therapy was longer than in the literature, our recurrence rates were similar to other studies, and no patient lost HBsAg. The most significant benefit was that we were able to follow half of the patients without therapy for more than four years, eliminating the need for the patients to use drugs.

Apulian infectious diseases network: survey on the prevalence of delta infection among chronic HBV carriers in Apulia.

The current prevalence and clinical burden of Hepatitis Delta Virus (HDV) infection in Apulia are unknown. This study aimed to define the current epidemiological scenario of delta infection and to detect difficulties in the diagnosis and clinical management of HDV patients in Apulia. From May to September 2022, a fact-finding survey was conducted at eight Infectious Diseases Units of the Apulian region; each Unit was asked to complete a questionnaire on screening and diagnosis of HDV infection and demographic, virological, and clinical characteristics of HDV patients. A total of 1,461 HBsAg-positive subjects were followed up on an outpatient basis. Screening for HDV ranged from 30 to 90% of HBsAg + carriers in a single center. Overall, 952 HBsAg ± subjects (65%) were tested for HDV, and 80/952 (8.4%) were anti-HDV positive. Serum HDV RNA was detected only in 15/80 (19%) anti-HDV-positive subjects, and 12/15 patients (80%) were viremic. Sixty-five anti-HDV-positive subjects (81%) were from Italy; risk factors for HDV acquisition included the presence of HDV infection in the family (29/80 = 36%), drug addiction (12/80 = 15%), and co-infection with HCV or HIV (7/80 = 9%). Liver cirrhosis and hepatocellular carcinoma were diagnosed in 41 (51%) and 4 (5%) patients, respectively. Fifty-seven patients (71%) received nucleos(t)ide analog treatment. The results of this survey show that HDV screening is variable and insufficient, thus real prevalence data on delta infection are lacking in Apulia. Moreover, the HDV RNA test is not available in most laboratories and is not provided by the national health system. These results underline the need for an organizational model to optimize the management of HDV patients throughout the Apulian region.

Discontinuation of Nucleos(t)ide Analog treatment in HBeAg-Negative Non-Cirrhotic Chronic Hepatitis B Patients: Real-Life Data of 20 Years.

Discontinuation of nucleos(t)ide analog is controversial in HBeAg-negative chronic hepatitis B patients not achieved HBsAg loss. We aimed to evaluate re-treatment rates and risk factors in non-cirrhotic HbeAg-negative chronic hepatitis B patients for whom nucleosi(t)ides analogs were discontinued. Demographic, clinical, and laboratory data before and at the end after discontinuation of nucleos(t)ide analogs were collected retrospectively. Seventy-two patients followed up between January 2000 and December 2019 were included; 43 were male, with a mean age of 46.3 (±10.8). Baseline median alanine aminotransferase (ALT) and hepatitis B virus DNA levels were 55.5 IU/L and 465 925 IU/mL, respectively. The median histologic activity index was 5.5 and the fibrosis score was 2. The median duration of treatment and consolidation therapy were 59 and 56 months, respectively. The median follow-up time after discontinuation of treatment was 55 months. Among 56 patients eligible for evaluation according to proposed re-treatment criteria, 29 (51.7%) patients were re-treated. The median time for relapse was 11 months. Re-treatment was significantly common in males (P = .034) and patients treated with tenofovir/entecavir (P = .04). Baseline hepatitis B virus DNA and levels of ALT, aspartate aminotransferase (AST) at the third and sixth months of treatment and at the end of treatment were statistically significantly higher in re-treated patients. A cutoff value of ≥405 000 IU/L for hepatitis B virus DNA discriminated patients for re-treatment. HBsAg was lost permanently in 2 non-re-treated patients. In resource-limited areas where follow-up of HBsAg or other markers is not possible, nucleos(t)ide analog discontinuation can be considered in patients in the early stage, with low baseline hepatitis B virus DNA and ALT levels, after a long consolidation therapy.

Usefulness of the Fibrosis-4 index and alanine aminotransferase at 1year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitisB patients.

Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitisB virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development. Among a total of 882 chronically hepatitisB virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1year of treatment was obtained were evaluated for the incidence of HCC. The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1year (P<0.001), but the reduction was small at 2years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5years, the area under the curve of FIB-4 at 1year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10years, P<0.001). Additionally, an abnormal alanine aminotransferase (≥31U/L) at 1year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1)score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10years, P<0.001). FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.

Stopping nucleos(t)ide analogues treatment in non-cirrhotic HBeAg-negative patients: Yes, we can!

Stopping nucleos(t)ide analogues treatment in non-cirrhotic HBeAg-negative patients: Yes, we can!

Isospin-breaking effects in the three-pion contribution to hadronic vacuum polarization

Isospin-breaking (IB) effects are required for an evaluation of hadronic vacuum polarization at subpercent precision. While the dominant contributions arise from the e+e−→ π+π− channel, also IB in the subleading channels can become relevant for a detailed understanding, e.g., of the comparison to lattice QCD. Here, we provide such an analysis for e+e−→ 3π by extending our dispersive description of the process, including estimates of final-state radiation (FSR) and ρ–ω mixing. In particular, we develop a formalism to capture the leading infrared-enhanced effects in terms of a correction factor η3π that generalizes the analog treatment of virtual and final-state photons in the 2π case. The global fit to the e+e−→ 3π data base, subject to constraints from analyticity, unitarity, and the chiral anomaly, gives {left.{a}_{mu}^{3pi}right|}_{le 1.8 textrm{GeV}}=45.91(53)times {10}^{-10} for the total 3π contribution to the anomalous magnetic moment of the muon, of which {a}_{mu}^{textrm{FSR}}left[3pi right]=0.51(1)times {10}^{-10} and {a}_{mu}^{rho -omega}left[3pi right]=-2.68(70)times {10}^{-10} can be ascribed to IB. We argue that the resulting cancellation with ρ–ω mixing in e+e−→ 2π can be understood from a narrow-resonance picture, and provide updated values for the vacuum-polarization-subtracted vector-meson parameters Mω = 782.70(3) MeV, Mϕ = 1019.21(2) MeV, Γω = 8.71(3) MeV, and Γϕ = 4.27(1) MeV.

Antiviral Therapy Favors a Lower Risk of Liver Cirrhosis in HBeAg-negative Chronic Hepatitis B with Normal Alanine Transaminase and HBV DNA Positivity.

Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment is lacking. HBeAg-negative patients with normal ALT and positive HBV DNA (≥20 IU/mL) were retrospectively enrolled. The endpoints included virological response (HBV DNA<100 IU/mL), changes in aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), and the incidence of liver nodules, cirrhosis, and hepatocellular carcinoma (HCC). This cohort (n=194) was divided into three subgroups, untreated (n=67), treatment-continued (n=87), and treatment-discontinued patients (n=40), with a median follow-up of 54 months. The treatment-continued group achieved 100% (95% CI: 94.7-100) virological response, and significantly reduced APRI and FIB-4 scores (both p<0.001). The risk of liver nodules and cirrhosis in that group was reduced by 76% (HR: 0.24, 95% CI: 0.11-0.54, p<0.001) and 89% (HR: 0.11, 95% CI: 0.14-0.91, p=0.041) vs. the untreated group and by 77% (HR: 0.23, 95% CI: 0.10-0.49, p<0.001) and 95% (HR: 0.05, 95% CI: 0.01-0.44, p=0.006) vs. the treatment-discontinued group. For patients with HBV DNA≥2,000 IU/mL, adherence to treatment lowered the risks of liver cirrhosis by 92% (95% CI: 0.01-0.67) and 93% (95% CI: 0.01-0.53) vs. the untreated and treatment-discontinued patients, respectively. No patient adhering to treatment developed HCC, but one in each of the remaining groups did. Continuous nucleos(t)ide analog (NA) treatment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase, especially in those with HBV DNA≥2,000 IU/mL.

Hepatocellular carcinoma reduced, HBsAg loss increased, and survival improved after finite therapy in hepatitis B patients with cirrhosis.

Long-term nucleos(t)ide analog (Nuc) treatment can reduce HCC in patients with HBV-related liver cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in HBeAg-negative patients with HBV-LC who stopped and those continued Nuc therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up. From 2 centers, 494 HBeAg-negative patients with HBV-LC who stopped (finite group) and 593 who continued (continuous group) Nuc therapy were recruited. HCC, HBsAg loss, liver-related mortality/transplantation, and overall survival rates were compared between 2 groups with 1:1 propensity score matching of sex, treatment history, types of Nuc, age, transaminases, platelet count, and HBsAg levels at end of therapy in finite group or 3-year on-therapy in continuous groups. During a median follow-up of 6.2 (3.4-8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6 vs. 3.3%/y and 10-y 15.7% vs. 26.8%, respectively; log-rank test, p <0.0001). The finite group showed greater HBsAg decline/year (-0.116 vs. -0.095 log 10 IU/mL, p =0.0026) and 7.6 times higher 10-year incidence of HBsAg loss (22.7% vs. 3%, p <0.0001). Multivariate Cox regression showed finite therapy an independent factor for HBsAg loss (adjusted HR: 11.79) but protective against HCC (adjusted HR: 0.593), liver-related mortality/transplantation (adjusted HR: 0.312), and overall mortality (adjusted HR: 0.382). Finite Nuc therapy in HBeAg-negative HBV-LC may reduce HCC incidence, increase HBsAg loss, and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis.

Phenolic Extract from Olive Leaves as a Promising Endotherapeutic Treatment against Xylella fastidiosa in Naturally Infected Olea europaea (var. europaea) Trees.

(1) Background: Since 2013, the pathogenic bacterium Xylella fastidiosa has been severely affecting olive production in Apulia, Italy, with consequences for the economy, local culture, landscape and biodiversity. The production of a phenolic extract from fresh olive leaves was employed for endotherapeutic injection into naturally infected olive trees by Xylella fastidiosa in Apulia region, Italy. (2) Methods: The effectiveness of the extract was tested in vitro and in planta in comparison with analogous treatments based on garlic powder and potassium phosphite. (3) Results: The uptake of phenolic compounds from olive leaves through a trunk injection system device resulted in a statistically significant increase in leaf area index and leaf area density, as well as in the growth of newly formed healthy shoots. Plant growth-promoting effects were also observed for potassium phosphite. Moreover, the bacteriostatic activities of the phenolic extract and of the garlic-powder-based solution have been demonstrated in in vitro tests. (4) Conclusions: The results obtained and the contained costs of extraction make the endotherapeutic treatment with phenolic compounds a promising strategy for controlling X fastidiosa to be tested on a larger scale, although the experiments conducted in this study proved not to be suitable for centenary trees.

Quantitative uptake in 99m Tc-EDDA/HYNIC-TOC somatostatin receptor imaging - the effect of long-acting release somatostatin analogue therapy.

Withdrawal of long-acting release somatostatin analogue (LAR-SSA) treatment before somatostatin receptor imaging is based on empirical reasoning that it may block uptake at receptor sites. This study aims to quantify differences in uptake of 99m Tc-EDDA/HYNIC-TOC between patients receiving LAR-SSA and those who were not. Quantification of 177 patients (55 on LAR-SSA) imaged with 99m Tc-EDDA/HYNIC-TOC was performed, with analysis of pathological tissue and organs with physiological uptake using thresholded volumes of interest. Standardised uptake values (SUVs) and tumour/background (T/B) ratios were calculated and compared between the two patient groups. SUVs were significantly lower for physiological organ uptake for patients on LAR-SSA (e.g. spleen: SUV max 13.3 ± 5.9 versus 33.9 ± 9.0, P < 0.001); there was no significant difference for sites of pathological uptake (e.g. nodal metastases: SUV max 19.2 ± 13.0 versus 17.4 ± 11.5, P = 0.552) apart from bone metastases (SUV max 14.1 ± 13.5 versus 7.7 ± 8.0, P = 0.017) where it was significantly higher. LAR-SSA has an effect only on physiological organ uptake of 99m Tc-EDDA/HYNIC-TOC, reducing uptake. It has no significant effect on pathological uptake for most sites of primary and metastatic disease. This should be taken into account if making quantitative measurements, calculating T/B ratios or assigning Krenning Scores. There is the potential for improved dosimetric results in Peptide Receptor Radionuclide Therapy by maintaining patients on LAR-SSA.

Overexpression of BmJHBPd2 Repressed Silk Synthesis by Inhibiting the JH/Kr-h1 Signaling Pathway in Bombyx mori.

The efficient production of silkworm silk is crucial to the silk industry. Silk protein synthesis is regulated by the juvenile hormone (JH) and 20-Hydroxyecdysone (20E). Therefore, the genetic regulation of silk production is a priority. JH binding protein (JHBP) transports JH from the hemolymph to target organs and cells and protects it. In a previous study, we identified 41 genes containing a JHBP domain in the Bombyx mori genome. Only one JHBP gene, BmJHBPd2, is highly expressed in the posterior silk gland (PSG), and its function remains unknown. In the present study, we investigated the expression levels of BmJHBPd2 and the major silk protein genes in the high-silk-producing practical strain 872 (S872) and the low-silk-producing local strain Dazao. We found that BmJHBPd2 was more highly expressed in S872 than in the Dazao strain, which is consistent with the expression pattern of fibroin genes. A subcellular localization assay indicated that BmJHBPd2 is located in the cytoplasm. In vitro hormone induction experiments showed that BmJHBPd2 was upregulated by juvenile hormone analogue (JHA) treatment. BmKr-h1 upregulation was significantly inhibited by the overexpression of BmJHBPd2 (BmJHBPd2OE) at the cell level when induced by JHA. However, overexpression of BmJHBPd2 in the PSG by transgenic methods led to the inhibition of silk fibroin gene expression, resulting in a reduction in silk yield. Further investigation showed that in the transgenic BmJHBPd2OE silkworm, the key transcription factor of the JH signaling pathway, Krüppel homolog 1 (Kr-h1), was inhibited, and 20E signaling pathway genes, such as broad complex (Brc), E74A, and ultraspiracle protein (USP), were upregulated. Our results indicate that BmJHBPd2 plays an important role in the JH signaling pathway and is important for silk protein synthesis. Furthermore, our findings help to elucidate the mechanisms by which JH regulates silk protein synthesis.

Prevalence of Polycystic Ovarian Syndrome in Girls with a History of Idiopathic Central Precocious Puberty

Introduction: The prevalence of polycystic ovarian syndrome (PCOS) in adolescent girls is between 1 and 4.3%. It remains controversial whether women with a history of idiopathic central precocious puberty (ICPP) are at increased risk for PCOS. Our objective was to assess the prevalence of PCOS in adolescents with a history of ICPP compared with healthy adolescents and the prevalence of PCOS among ICPP girls who have received or not gonadotropin-releasing hormone analogue (GnRHa) treatment. Methods: We assessed post-menarcheal girls with a history of ICPP. Girls were evaluated at gynecological age ≥2.5 years. Data collected were age at menarche, menstrual cycle characteristics, BMI, clinical hyperandrogenism (HA), total and free testosterone levels. PCOS diagnosis was defined by criteria for adolescents. Subjects were also analyzed regarding whether or not they had received GnRHa treatment. Results: Ninety-four subjects were assessed, and 63 had been treated with GnRHa. Menstrual disorders were found in 29%, clinical HA in 36%, and biochemical HA in 23%. Twelve percent met the diagnostic criteria for PCOS. There was no difference in BMI or in the incidence of menstrual dysfunction or hyperandrogenemia between treated and untreated patients. A higher proportion of clinical HA was found in untreated patients when compared to treated girls. The relative risk (RR) of developing PCOS in ICPP girls was 2.5 compared to a population of healthy adolescents. This RR was not higher in patients who received treatment with GnRHa than in those who did not. Conclusion: Adolescent girls with a history of ICPP have an increased risk of PCOS. This risk seems not to be related to GnRHa treatment.

Triboranate derivatives of calcium and strontium

This contribution reports the alkaline earth-mediated formation of homonuclear sigma bonding between the metalloid element, boron. The resultant triborane anions result from the formal dismutation of bis(pinacolato)diboron (B2pin2) and the generation of putative heavier group 2 boryl intermediates. Initial reactions of the heavier alkaline earth bis-(trimethylsilyl)amides, [Ae{N(SiMe3)2}2] (Ae = Ca or Sr), with an equimolar quantity of bis(pinacolato)diboron (B2pin2) provided the 4-coordinate group 2 silazide diborane adducts [Ae(B2pin2){N(SiMe3)2}2] in which the diborane acts as a bidentate ligand via κ2-O,O' coordination. Reaction of the calcium species at 60 °C with a further three molar equivalents of B2pin2 induced the elimination of pinBN(SiMe3)2 and the formation of the bis-triboranate derivative, [Ca(B3pin3)2], in which the 6-coordinate calcium centre is bound in a κ3-O,O',O''-coordination mode by the three contiguous pinacolate oxygen atoms of both catena-B(sp2)-B(sp3)-B(sp2) bonded anions. Although analogous treatment of [Ae(B2pin2){N(SiMe3)2}2] provided similar triboranate anion formation, in this case two equivalents of the strontium silazide were retained within the structure of the trimetallic species, [Sr(B3pin3)2(Sr{N(SiMe3)2}2)2]. Despite these contrasting outcomes both triboranate complexes provide rare examples of catena-boron species beyond the common diboranes, (R2B-BR2), in which the homologated unit is propagated by electron precise and otherwise unsupported B-B bonds.

Removal of insecticides from waters and soils by sulfate radical‐based advanced oxidation processes

AbstractInsecticides are toxic compounds widely used to prevent, destroy, and control any insect pests. A larger food production with increasing agricultural activity has been ensured from their application to farmlands. Insecticides have been detected in waters and soils being dangerous for living beings. Due to their high biorecalcitrance and stability at ambient conditions, they cannot be destroyed in conventional wastewater treatment plants (WWTPs) and powerful advanced oxidation processes (AOPs) are being developed for their removal. This review presents a detailed and critical analysis over the application of sulfate radical‐based AOPs to the remediation of waters and soils polluted with insecticides. Persulfate (PS) and peroxymonosulfate (PMS) are used as parent oxidants but they need to be activated to produce strong effective oxidizing radicals such as sulfate radical (SO4●−) and hydroxyl radical (●OH). Alkaline, thermal, catalytic, UV, UV with Fe, photocatalytic, and other methods applied as activators of PS and/or PMS are separately analyzed in waters and soils. For each hybrid procedure, the fundamentals are briefly detailed and the best results reported in the literature are summarized and discussed. The effect of operating parameters on the oxidation power of treatments in pure water, real waters, WWTPs effluents, and contaminated soils are remarked to show the viability of sulfate radical‐based AOPs for insecticides removal from waters and soils. The effect of added common anions and natural organic matter, the detection of oxidizing radicals by selective scavengers and electron paramagnetic resonance, and the identification of the generated by‐products in waters are described. Comparisons with analogous treatments with H2O2 and Fenton are discussed as well. Further research efforts should consider a deeper study of PS‐ and/or PMS‐based processes of insecticides not only in actual agricultural and real wastewaters, but also in many soils to confirm their possible suitability at the industrial level.

Host sex disparity and viral genotype dependence of the glycosylation level of small Hepatitis B surface protein in patients with HBeAg-positive chronic Hepatitis B

BackgroundHepatitis B surface antigen (HBsAg) consists of six components of large/middle/small HBs proteins (L/M/SHBs) with non-glycosylated (ng)- or glycosylated (g)- isomers at sN146 in their shared S domain. g-SHBs plays a crucial role in hepatitis B virus (HBV) secretion. However, the host and viral factors impacting sN146 status in natural HBV infection remain revealed mainly due to the technical difficulty in quantifying g-SHBs and ng-SHBs in serum samples.MethodsTo establish a standardized Western blot (WB) assay (WB-HBs) for quantifying the SHBs isomers in serum samples of 328 untreated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with genotype B or C HBV infection. The 1.3-mer HBV genotype B or C plasmids were transiently transfected into HepG2 cells for in vitro study.ResultsThe median level of ng-SHBs was significantly higher than that of g-SHBs (N = 328) (2.6 vs. 2.0 log10, P < 0.0001). The median g-/ng-SHBs ratio in female patients (N = 75) was significantly higher than that of male patients (N = 253) (0.35 vs. 0.31, P < 0.01) and the median g-/ng-SHBs ratio in genotype C patients (N = 203) was significantly higher than that of the genotype B patients (N = 125) (0.33 vs. 0.29, P < 0.0001).ConclusionsOur findings suggest that the g-/ng-SHBs ratio is host-sex-biased and viral genotype dependent in treatment naïve patients with HBeAg-positive chronic hepatitis B, which indicates the glycosylation of SHBs could be regulated by both host and viral factors. The change of ratio may reflect the fitness of HBV in patients, which deserves further investigation in a variety of cohorts such as patients with interferon or nucleos(t)ide analogues treatment.

Mental health and psychosocial support in response to onset of the COVID-19 pandemic: Emotional and Stress Management Intervention in Liberia, Sierra Leone, and Ivory Coast.

In response to the psychological distress experienced by people affected by the onset of the COVID-19 pandemic, Action Against Hunger (Action contre la Faim, ACF) developed and implemented the Emotional and Stress Management Intervention (ESMI) in Liberia, Sierra Leone, and Ivory Coast. ESMI is a person-to-person two-session, non-specialized, mental health and psychosocial support intervention for adults and adolescents in the general population based in problem solving therapy and principles of emotional regulation. Using de-identified programmatic data for each country, we conducted paired t-tests to assess whether adults and adolescents who received ESMI experienced changes in reported psychological distress and perceived social support following the intervention. We also performed pairwise correlations to test whether there were associations between changes in distress and social support over the course of participation in ESMI. Descriptive analyses were performed for presenting problems and coping strategies reported during the sessions. Mean scores for psychological distress at baseline and follow-up were significantly different in all countries: Sierra Leone (mean (m) = -6.11; 95% confidence interval (CI) = -6.25 to -5.96); Ivory Coast (m = -3.21; 95% CI = -3.33 to -3.10); and Liberia (m = -2.86; 95% CI = -3.15 to -2.56). Changes in perceived social support were also statistically significant for Sierra Leone (m = 6.87; 95% CI = 6.72-7.02); Ivory Coast (m = 3.12; 95% CI = 2.97-3.27); and Liberia (m = 1.13; 95% CI = 1.00-1.27). Correlations (r) between changes in distress and changes in social support varied by country, and ranged from negative in Liberia, (r = -0.88, P = 0.001), to positive in Ivory Coast (r = 55, P = 0.001), and null in Sierra Leone (r = -0.07, P = 0.11). Our findings show changes in psychological distress and perceived social support for participants who completed two sessions of ESMI, suggesting a potential benefit of ESMI as a person-to-person mental health and psychosocial support for individuals in distress affected by a pandemic. A future randomized controlled trial with a focus on key implementation factors (i.e., pre-testing visual analogue scales, treatment fidelity, and comparison of in-person vs remote) is recommended as next steps in research.

Aldo-keto reductase family 1 member B10 is regulated by nucleos(t)ide analogues for chronic hepatitis B

The number of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients persists even under nucleos(t)ide analogues (NAs) treatment. Aldo-keto reductase family 1 member B10 (AKR1B10) expression has been reported in advanced chronic liver diseases as well as cancer tissues. We observed an association between related to HCC incidence and serum AKR1B10 by analyzing patients under treatment with NAs. Serum AKR1B10 levels measured by ELISA were higher in HCC cases under NA treatment compared with non-HCC cases and were associated with lamivudine- and adefovir pivoxil-, but not entecavir- or tenofovir alafenamide-treated cases. The latter drugs did not increase AKR1B10 values even in HCC cases, suggesting that they influence the reduction of AKR1B10 in any cases. This analysis was supported by in-vitro examination, which showed reduced AKR1B10 expression by entecavir and tenofovir via immunofluorescence staining. In conclusion there was a relationship between HBV-related HCC incidence and AKR1B10 under nucleos(t)ide analogues, especially in the use of lamivudine and adefovir pivoxil, but entecavir and tenofovir had suppressive effects of AKR1B10.

Lower end of treatment HBsAg and HBcrAg were associated with HBsAg loss after nucleos(t)ide analog cessation

BackgroundSince hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analog (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that some patients remain virologically responsive even after NA cessation. However, there is still controversy surrounding whether NA discontinuation increases the HBsAg loss rate. Therefore, this study aimed to assess the cumulative rate of HBsAg loss and identify the predictors of HBsAg loss after NA discontinuation.MethodsThis multicenter prospective study included HBV e antigen (HBeAg)-positive patients without cirrhosis from 12 hospitals in China who met the inclusion criteria. The enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occurred.ResultsOverall, 158 patients were classified into two groups. Group A included patients with HBsAg positivity at NA cessation (n = 139), and Group B included patients with HBsAg negativity at NA cessation (n = 19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were4.3%and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P < 0.001) and EOT hepatitis B core-related antigen (HBcrAg) (HR = 0.257, P = 0.001) were associated with HBsAg loss. The areas under the receiver operating characteristic curves for EOT HBsAg and HBcrAg levels were 0.952 (P < 0.001) and 0.765 (P < 0.001), respectively. Patients with EOT HBsAg ≤ 135 IU/mL (59.2% vs. 1.3%, P < 0.001) or HBcrAg ≤ 3.6 logU/mL (17% vs. 5.4%, P = 0.027) had a higher 24-month cumulative HBsAg loss rate. In Group B, none of the patients experienced virological relapse after NA cessation. Only 1 (5.3%) patient had HBsAg reversion.ConclusionsEOT HBsAg ≤ 135 IU/mL or HBcrAg ≤ 3.6 logU/mL can be used to identify patients with a higher likelihood of HBsAg loss after NA cessation. Patients with HBsAg negativity after NA cessation have favorable clinical outcomes, and HBsAg loss was durable in most cases.