A review on peptide functionalized graphene derivatives as nanotools for biosensing.

Peptides exhibit unique binding behavior with graphene and its derivatives by forming bonds on its edges and planes. This makes them useful for sensing and imaging applications. This review with (155 refs.) summarizes the advances made in the last decade in the field of peptide-GO bioconjugation, and the use of these conjugates in analytical sciences and imaging. The introduction emphasizes the need for understanding the biotic-abiotic interactions in order to construct controllable peptide-functionalized graphitic material-based nanotools. The next section covers covalent and non-covalent interactions between peptide and oxidized graphene derivatives along with a discussion of the adsorption events during interfacing. We then describe applications of peptide-graphene conjugates in bioassays, with subsections on (a) detection of cancer cells, (b) monitoring protease activity, (c) determination of environmental pollutants and (d) determination of pathogenic microorganisms. The concluding section describes the current status of peptide functionalized graphitic bioconjugates and addresses future perspectives. Graphical abstractSchematic representation depicting biosensing applications of peptide functionalized graphene oxide.

In vivo efficacy of artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria: an open-randomized, non-inferiority clinical trial in South Kivu, Democratic Republic of Congo.

BACKGROUND: Between 2009 and 2012, malaria cases diagnosed in a Médecins sans Frontières programme have increased fivefold in Baraka, South Kivu, Democratic Republic of the Congo (DRC). The cause of this increase is not known. An in vivo drug efficacy trial was conducted to determine whether increased treatment failure rates may have contributed to the apparent increase in malaria diagnoses. METHODS: In an open-randomized non-inferiority trial, the efficacy of artesunate-amodiaquine (ASAQ) was compared to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in 288 children aged 6-59 months. Included children had directly supervised treatment and were then followed for 42 days with weekly clinical and parasitological evaluations. The blood samples of children found to have recurring parasitaemia within 42 days were checked by PCR to confirm whether or not this was due to reinfection or recrudescence (i.e. treatment failure). RESULTS: Out of 873 children screened, 585 (67 %) were excluded and 288 children were randomized to either ASAQ or AL. At day 42 of follow up, the treatment efficacy of ASAQ was 78 % before and 95 % after PCR correction for re-infections. In the AL-arm, treatment efficacy was 84 % before and 99.0 % after PCR correction. Treatment efficacy after PCR correction was within the margin of non-inferiority as set for this study. Fewer children in the AL arm reported adverse reactions. CONCLUSIONS: ASAQ is still effective as a treatment for uncomplicated malaria in Baraka, South Kivu, DRC. In this region, AL may have higher efficacy but additional trials are required to draw this conclusion with confidence. The high re-infection rate in South-Kivu indicates intense malaria transmission. Trial registration NCT02741024.

Proposal for a new morphological "combined type" of gallbladder cancer: description of radiopathological characteristics and comparison with other morphological types.

OBJECTIVE: To describe the radiopathological characteristics of a new morphological "combined type" of gallbladder cancer (GBC) and compare it with the mass replacing gallbladder and thickening types of GBC. MATERIALS AND METHODS: The imaging and pathological details of consecutive patients with GBC between August 2020 and December 2022 were retrospectively reviewed. Two radiologists reviewed computed tomography/magnetic resonance imaging in consensus for the morphological type of GBC. The radiologists classified GBC as mass replacing gallbladder, wall thickening, and combined type. The combined type was defined as a mass arising from the thickened wall of an adequately distended gallbladder that extended exophytically into the adjacent liver parenchyma. The presence of calculi, site, and size of lesion, biliary/portal vein involvement, liver, lymph node, and omental metastases was compared among the various types. The pathological characteristics were also compared. RESULTS: Of the 481 patients (median age 55 years, 63.2% females) included in the study, mass replacing gallbladder, wall thickening, and combined-type GBC were seen in 42.8% (206/481), 40.5% (195/481), and 16.6% (80/481) of patients, respectively. In the combined type of GBC, biliary/portal vein involvement was seen in 63.7% (51/80) and 7.5% (6/80) of patients. Liver, lymph node, and omental metastases were seen in 67.5% (54/80), 40% (32/80), and 41.2% (33/80) patients, respectively. Liver metastases were significantly more common in the combined type (p = 0.002). There were no significant differences in pathological characteristics among the various types. CONCLUSION: Combined-type GBC is less common than the mass replacing gallbladder and thickening types and is associated with a higher risk of liver metastases.

Outcomes of Self-expandable Metal Stents in Patients With Unresectable Gallbladder Cancer Undergoing Percutaneous Biliary Drainage.

Background: Biliary obstruction in gallbladder cancer (GBC) is associated with worse prognosis and needs drainage. In patients with biliary confluence involvement, percutaneous biliary drainage (PBD) is preferred over endoscopic drainage. However, PBD catheters are associated with higher complications compared to endoscopic drainage. PBD with self-expandable metal stents (SEMS) is desirable for palliation. However, the data in patients with unresectable GBC is lacking. Materials and methods: This retrospective study comprised consecutive patients with proven GBC who underwent PBD-SEMS insertion between January 2021 and December 2022. Technical success, post-procedural complications, clinical success, duration of stent patency, and biliary reinterventions were recorded. Clinical follow-up data was analysed at 30 days and 180 days of SEMS insertion and mortality was recorded. Results: Of the 416 patients with unresectable GBC, who underwent PBD, 28 (median age, 50 years; 16 females) with PBD-SEMS insertion were included. All SEMS placement procedures were technically successful. There were no immediate/early post-procedural complications/deaths. The procedures were clinically successful in 63.6% of the patients with hyperbilirubinemia (n = 11). Biliary re-interventions were done in 6 (21.4%). The survival rate was 89.3 % (25/28) at 30 days and 50% at 180 days. The median follow-up duration was 80 days (range, 8-438 days). Conclusion: PBD-SEMS has moderate clinical success and 6-months patency in almost half of the patients with metastatic GBC and must be considered for palliation.

Agreement of Gallbladder Reporting and Data System for Gallbladder Wall Thickening at Ultrasonography: A Multireader Validation Study.

Objective: This article aims to evaluate the intrareader and interreader agreement of ultrasound (US) gallbladder reporting and data system (GB-RADS) and validate the risk of malignancy in each GB-RADS category. Materials and methods: This retrospective study comprised consecutive patients with nonacute gallbladder wall thickening who underwent US evaluation between January 2019 and December 2022. Three radiologists independently read the static US images and cine-loops for GB-RADS findings and assigned GB-RADS categories. The intraobserver (static images) and interobserver (static images and cine-loops) agreement was calculated using kappa statistics and Krippendorff's alpha. Another radiologist assigned a consensus GB-RADS category. The percentage of malignancy in each GB-RADS category was calculated. Results: Static US images of 414 patients (median age, 56 years; 288 women, benign = 45.6% and malignant = 54.4%) and cine-loops of 50 patients were read. There was weak to moderate intrareader agreement for most GB-RADS findings and moderate intrareader agreement for the GB-RADS category for all readers. On static images, the interreader agreement was acceptable for GB-RADS categories. On cine-loops, the interreader agreement for GB-RADS findings and categories was better than static images. The percentage of malignancy was 1.2%, 37%, 71.1%, and 89.1% in GB-RADS 2, 3, 4, and 5 categories. Conclusion: GB-RADS has moderate intrareader for GB-RADS categories. As originally proposed, the risk of malignancy is negligible in GB-RADS 2 category and highest in GB-RADS 5 category. However, the discriminatory performance of GB-RADS 3 and 4 categories is low. Larger multicenter studies with more readers must assess the reader agreement and validate the GB-RADS systems for wider clinical utilization.

Adherence to HIV post-exposure prophylaxis in victims of sexual assault: a systematic review and meta-analysis.

OBJECTIVE: To assess adherence to post-exposure prophylaxis (PEP) for the prevention of HIV infection in victims of sexual assault. METHODS: The authors carried out a systematic review, random effects meta-analysis and meta-regression of studies reporting adherence to PEP among victims of sexual violence. Seven electronic databases were searched. Our primary outcome was adherence; secondary outcomes included defaulting, refusal and side effects. RESULTS: 2159 titles were screened, and 24 studies matching the inclusion criteria were taken through to analysis. The overall proportion of patients adhering to PEP (23 cohort studies, 2166 patients) was 40.3% (95% CI 32.5% to 48.1%), and the overall proportion of patients defaulting from care (18 cohorts, 1972 patients) was 41.2% (95% CI 31.1% to 51.4%). Adherence appeared to be higher in developing countries compared with developed countries. CONCLUSIONS: Adherence to PEP is poor in all settings. Interventions are needed to support adherence.

Green synthesis of peptide functionalized reduced graphene oxide (rGO) nano bioconjugate with enhanced antibacterial activity.

Bioengineered nanoconjugates have enormous potential as a multifunctional platform for biomedical applications. Conjugation between biotic and abiotic materials enables formulation of nanoconjugates with enhanced physico-chemical properties, increased stability and ability to overcome the inherent shortcomings of individual materials. In this study, we report the preparation and biophysical characterization of an antibacterial system formulated by functionalizing reduced graphene oxide (rGO) with an antimicrobial peptide via covalent as well as non-covalent interaction mechanisms. Environmentally benign synthesis approach was adopted for the formation of rGO, using L-ascorbic acid as a reducing agent. Covalently conjugated peptide-graphitic conjugate displayed improved antibacterial efficacy against Escherichia coli with considerably low cytotoxic activity towards erythrocytes in comparison to self-assembled conjugate and rGO alone. The studies described herein are highly significant in the field of biomaterials and aims to open new avenues of research focusing on a plethora of applications as a prospective non-toxic substitute to conventional antibacterial approaches.

Reactive and pre-emptive vaccination strategies to control hepatitis E infection in emergency and refugee settings: A modelling study.

BACKGROUND: Hepatitis E Virus (HEV) is the leading cause of acute viral hepatitis globally. Symptomatic infection is associated with case fatality rates of ~20% in pregnant women and it is estimated to account for ~10,000 annual pregnancy-related deaths in southern Asia alone. Recently, large and well-documented outbreaks with high mortality have occurred in displaced population camps in Sudan, Uganda and South Sudan. However, the epidemiology of HEV is poorly defined, and the value of different immunisation strategies in outbreak settings uncertain. We aimed to estimate the critical epidemiological parameters for HEV and to evaluate the potential impact of both reactive vaccination (initiated in response to an epidemic) and pre-emptive vaccination. METHODS: We analysed data from one of the world's largest recorded HEV epidemics, which occurred in internally-displaced persons camps in Uganda (2007-2009), using transmission dynamic models to estimate epidemiological parameters and assess the potential impact of reactive and pre-emptive vaccination strategies. RESULTS: Under baseline assumptions we estimated the basic reproduction number of HEV in three separate camps to range from 3.7 (95% Credible Interval [CrI] 2.8, 5.1) to 8.5 (5.3, 11.4). Mean latent and infectious periods were estimated to be 34 (95% CrI 28, 39) and 40 (95% CrI 23, 71) days respectively. Assuming 90% vaccine coverage, reactive two-dose vaccination of those aged 16-65 years excluding pregnant women (for whom vaccine is not licensed), if initiated after 50 reported cases, led to mean camp-specific reductions in mortality of 10 to 29%. Pre-emptive vaccination with two doses reduced mortality by 35 to 65%. Both strategies were more effective if coverage was extended to groups for whom the vaccine is not currently licensed. For example, two dose pre-emptive vaccination, if extended to include pregnant women, led to mean reductions in mortality of 66 to 82%. CONCLUSIONS: HEV has a high transmission potential in displaced population settings. Substantial reductions in mortality through vaccination are expected, even if used reactively. There is potential for greater impact if vaccine safety and effectiveness can be established in pregnant women.

Estimating the impact of childhood influenza vaccination programmes in England and Wales.

There is increasing interest in routine vaccination of children against influenza. We use an age-structured model to demonstrate that the long-term incidence of influenza A could decrease by 11-21% in the overall population by vaccinating individuals aged 6 to <24 months, and by 22-38% and 65-97% through targeting those aged 6 to <60 months and 6 months to 16 years, respectively. The corresponding reductions predicted for influenza B were 25-35%, 44-69% and 85-96%, respectively. These results are sensitive to assumptions about contact patterns and several parameters, including the vaccine efficacy among those aged <24 months, require further study. Consistently high levels of vaccination coverage among pre-school children has the potential to bring benefits to both those vaccinated and the community.