Thermal stability and in vitro digestive behavior of Pickering emulsion stabilized by high-amylose starch nanocrystals.

In this study, high-amylose starch (HAS) was processed using sulfuric acid-ultrasonic cross-linking to produce high-amylose starch nanocrystals (HASNC). These nanocrystals were used to stabilize Pickering emulsions and assess their effectiveness in encapsulating ß-carotene. Normal starch nanocrystals (NSNC) were prepared similarly for comparison. The HASNC retained key HAS properties, such as heat and enzyme resistance, providing several advantages to HASNC-stabilized emulsions. First, after exposure to 100 °C heat and in vitro tests simulating the mouth and stomach, the HASNC-stabilized emulsions demonstrated significantly greater stability and higher ß-carotene retention compared to the NSNC-stabilized emulsions. This enhanced stability is attributed to the lower gelatinization degree and increased resistance to α-amylase hydrolysis of HASNC, which provides stronger steric stabilization of the oil droplets. Second, during in vitro small intestine tests, the greater enzyme resistance of HASNC allowed for the formation of a denser barrier around the oil droplets, effectively preventing lipase and bile salts from contacting the oil droplets. This led to a reduced rate and extent of lipid digestion and facilitated a sustained-release effect. Consequently, HASNC, as a starch-based emulsifier, show great potential as an effective delivery system for the sustained release of bioactive compounds.

Navigating the evolving landscape of atopic dermatitis: Challenges and future opportunities: The 4th Davos declaration.

The 4th Davos Declaration was developed during the Global Allergy Forum in Davos which aimed to elevate the care of patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care. The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to collaborate to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world.

Thermoresponsive and Substrate Self-Cycling Nanoenzyme System for Efficient Tumor Therapy.

Cerium oxide (CeO2-x) performs well in photothermal and catalytic properties due to its abundance of oxygen vacancies. Based on this, we designed a thermosensitive therapeutic nanoplatform to achieve continuous circular drug release in tumor. It can solve the limitation caused by insufficient substrate in the process of tumor treatment. Briefly, CeO2-x and camptothecin (CPT) were wrapped in an agarose hydrogel, which could be melted by the photothermal effect of CeO2-x. At the same time, the local temperature increase provided photothermal treatment, which could induce the apoptosis of tumor cell. After that, CPT was released to damage the DNA in tumor cells to realize chemical treatment. In addition, CPT could active nicotinamide adenine dinucleotide oxidase to react with O2 to increase the intracellular H2O2. After that, the exposed CeO2-x could catalyze H2O2 to generate cytotoxic reactive oxygen species for chemodynamic therapy. More importantly, CeO2-x could catalyze H2O2 to produce O2, which could combine with the catalytic action of CPT to construct a substrate self-cycling nanoenzyme system. Overall, this self-cycling nanoplatform released hypoxia in the tumor microenvironment and built a multimode tumor treatment, which achieved an ideal antitumor affect.

Update on current and new potential immunotherapies in breast cancer, from bench to bedside.

Impressive advances have been seen in cancer immunotherapy during the last years. Although breast cancer (BC) has been long considered as non-immunogenic, immunotherapy for the treatment of BC is now emerging as a new promising therapeutic approach with considerable potential. This is supported by a plethora of completed and ongoing preclinical and clinical studies in various types of immunotherapies. However, a significant gap between clinical oncology and basic cancer research impairs the understanding of cancer immunology and immunotherapy, hampering cancer therapy research and development. To exploit the accumulating available data in an optimal way, both fundamental mechanisms at play in BC immunotherapy and its clinical pitfalls must be integrated. Then, clinical trials must be critically designed with appropriate combinations of conventional and immunotherapeutic strategies. While there is room for major improvement, this updated review details the immunotherapeutic tools available to date, from bench to bedside, in the hope that this will lead to rethinking and optimizing standards of care for BC patients.

High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana.

Background: Approximately 30,000 non-citizens are living with HIV in Botswana, all of whom as of 2020 are eligible to receive free antiretroviral treatment (ART) within the country. We assessed the prevalence of HIV-1 mutational profiles [pre-treatment drug resistance (PDR) and acquired drug resistance (ADR)] among treatment-experienced (TE) and treatment-naïve (TN) non-citizens living with HIV in Botswana. Methods: A total of 152 non-citizens living with HIV were enrolled from a migrant HIV clinic at Independence Surgery, a private practice in Botswana from 2019-2021. Viral RNA isolated from plasma samples were genotyped for HIV drug resistance (HIVDR) using Sanger sequencing. Major known HIV drug resistance mutations (DRMs) in the pol region were determined using the Stanford HIV Drug Resistance Database. The proportions of HIV DRMs amongst TE and TN non-citizens were estimated with 95% confidence intervals (95% CI) and compared between the two groups. Results: A total of 60/152 (39.5%) participants had a detectable viral load (VL) >40 copies/mL and these were included in the subsequent analyses. The median age at enrollment was 43 years (Q1, Q3: 38-48). Among individuals with VL > 40 copies/mL, 60% (36/60) were treatment-experienced with 53% (19/36) of them on Atripla. Genotyping had a 62% (37/60) success rate - 24 were TE, and 13 were TN. A total of 29 participants (78.4, 95% CI: 0.12-0.35) had major HIV DRMs, including at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) associated DRM. In TE individuals, ADR to any antiretroviral drug was 83.3% (20/24), while for PDR was 69.2% (9/13). The most frequent DRMs were nucleoside reverse transcriptase inhibitors (NRTIs) M184V (62.1%, 18/29), NNRTIs V106M (41.4%, 12/29), and K103N (34.4%, 10/29). No integrase strand transfer inhibitor-associated DRMs were reported. Conclusion: We report high rates of PDR and ADR in ART-experienced and ART-naïve non-citizens, respectively, in Botswana. Given the uncertainty of time of HIV acquisition and treatment adherence levels in this population, routine HIV-1C VL monitoring coupled with HIVDR genotyping is crucial for long-term ART success.

Use of Serum Biomarkers to Aid Antidepressant Selection in Depressive Patients.

Objective: : This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in out-patients with depressive disorders receiving stepwise psychopharmacotherapy, according to the main antidepressant used during the treatment period. Methods: : This study included 1,024 depressive outpatients initially treated using antidepressant monotherapy, followed by alternating pharmacological strategies during the acute phase (3-12 weeks; 3-week interval). Fourteen serum biomarkers, sociodemographics, and clinical characteristics were evaluated at baseline. Based on the use frequency and mechanism of action, four main antidepressant types were distinguished: escitalopram, other selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. A Hamilton Depression Rating Scale score ≤ 7 was take to indicate remission. Results: : Lower high-sensitivity C-reactive protein levels were correlated with remission at 12 weeks for all antidepressant types. Lower interleukin (IL)-6 levels and tumor necrosis factor-alpha levels were associated with remission using escitalopram and other SSRIs respectively. Lower IL-1ß and leptin levels, predicted remission in association with SSRIs including escitalopram. For SNRIs, remission at 12 weeks was predicted by lower IL-4 and IL-10 levels. For mirtazapine, remission at 12 weeks was associated with lower leptin levels, and higher serotonin and folate levels. Conclusion: : Baseline serum status, as estimated by nine serum markers, may help clinicians determine the most appropriate antidepressant to achieve remission in the acute phase of depression.

Influence of microwave temperature and power on the biomethanation of food waste under mesophilic anaerobic conditions.

Food waste is an attractive feedstock for Anaerobic Digestion due to its high biodegradability and moisture content. Nevertheless, due to its complex structure and composition, methane yield is typically compromised with 50-60% of the theoretical maximum obtained. The well-known limitation of the hydrolysis step can be circumvented by adopting feedstock pre-treatments, such as microwave irradiation. It improves solubilization of various FW components making them more readily available for the microorganisms and reducing AD process duration. In this work different heating rates (7.8, 3.9 and 1.9 °C/min) and temperatures (85, 115, 145, 175 °C) were applied when pre-treating food waste as a substrate for AD. Increase in the solubilization of organic matter in the form of Soluble Chemical Oxygen Demand was the most significative change in FW characteristics after pre-treatment, with final temperature of 175 °C and heating rate of 3.9 °C showing a 73.19% increment. Nevertheless, process performance of AD of MW FW was optimum at 85 °C 7.8 ramp, showing no intermediate products accumulation, up to 77% more methane produced in the first week of digestion compared to the other conditions tested and reduction of 96.36% on the lag phase duration, compared to the control. On the other hand, samples treated at 175 °C, regardless of heating rate, consistently showed poor process performance, with low methane yield, possibly due to the formation of hard-to-digest compounds. This work underlines the importance of adjusting microwave temperature and power when pre-treating FW for biomethane production so the process is optimized.

Comparing the Dosing Period in Package Inserts of Antimicrobial Agents Between Japan and the United States.

Introduction: The duration of antimicrobial therapy is a critical evaluation index of antimicrobial stewardship (AS). The inclusion of the dosing period on package inserts provides a strong reason for clinical intervention by pharmacists in cases where physicians prescribe inappropriate dosing periods. This study investigated differences in the description of dosing periods in antimicrobial package inserts between Japan and the U.S. Methods: We conducted a survey comparing differences in the dosing period of oral and injectable antimicrobials approved and marketed in Japan and the U.S. as of May 1, 2021. The Fisher exact test was used to compare the presence or absence of a description of the dosing period on the package insert between these two countries. Results: We evaluated 69 antimicrobial agents, of which 34 were oral; and 35 were injectable agents. In Japan, 20 (29.0%) of the antimicrobials had package inserts stating the dosing periods, compared with 58 (84.1%) in the U.S. (p < 0.001). Conclusions: It was found that the information on the duration of administration was missing from the package insert in Japan compared to the U.S. Lack of information on the duration of administration may lead to long-term administration by the treating physician and also make it difficult for the pharmacist to inquire about the administration. It is expected that the inclusion of scientifically-based dosing periods in all package inserts will promote AS among physicians and pharmacists who are not specialists in infectious disease therapy.

Cancer treatment data available in European cancer registries: Where are we and where are we going?

Population-based cancer registries are responsible for collecting incidence and survival data on all reportable neoplasms within a defined geographical area. During the last decades, the role of cancer registries has evolved beyond monitoring epidemiological indicators, as they are expanding their activities to studies on cancer aetiology, prevention, and quality of care. This expansion relies also on the collection of additional clinical data, such as stage at diagnosis and cancer treatment. While the collection of data on stage, according to international reference classification, is consolidated almost everywhere, data collection on treatment is still very heterogeneous in Europe. This article combines data from a literature review and conference proceedings together with data from 125 European cancer registries contributing to the 2015 ENCR-JRC data call to provide an overview of the status of using and reporting treatment data in population-based cancer registries. The literature review shows that there is an increase in published data on cancer treatment by population-based cancer registries over the years. In addition, the review indicates that treatment data are most often collected for breast cancer, the most frequent cancer in women in Europe, followed by colorectal, prostate and lung cancers, which are also more common. Treatment data are increasingly being reported by cancer registries, though further improvements are required to ensure their complete and harmonised collection. Sufficient financial and human resources are needed to collect and analyse treatment data. Clear registration guidelines are to be made available to increase the availability of real-world treatment data in a harmonised way across Europe.

Ligelizumab impairs IgE-binding to plasmacytoid dendritic cells more potently than omalizumab and restores IFN-α production and FOXP3+ Treg generation.

BACKGROUND: Ligelizumab is an anti-IgE monoclonal antibody binding IgE with higher affinity than omalizumab that is under clinical investigation for several IgE-mediated diseases. We previously showed that omalizumab removes IgE bound to FcεRI on plasmacytoid dendritic cells (pDCs) and restores their ability to produce IFN-α and regulatory T cells (Tregs). The aim of this work is to investigate the capacity of ligelizumab to regulate functional properties of pDCs in comparison with omalizumab. METHODS: pDCs were isolated from atopic donors and IgE was detached from FcεRI on pDCs with designed ankyrin repeat protein (DARPin) bi53-79. pDCs were resensitized with IgE alone or in the presence of ligelizumab or omalizumab prior to IgE-FcεRI crosslinking and Toll-like receptor 9 (TLR9) stimulation. Flow cytometry, ELISA, coculture experiments and intranuclear staining were performed to determine cytokine production and Treg generation. An antigen-specific model of resensitization and IgE-crosslinking was also performed. RESULTS: The levels of serum total free IgE show a non-linear positive correlation with the frequency of IgE+ pDCs displaying IgE bound to FcεRI within the 43 individual donors included in the study. Ligelizumab displays stronger capacity than omalizumab to block the binding of free IgE to FcεRI on human pDCs, resulting in a greater restoration of TLR9-L-induced IFN-α production. Ligelizumab also restores the ability of pDCs to generate FOXP3+ Tregs as previously reported for omalizumab. CONCLUSIONS: The uncovered novel molecular mechanisms of ligelizumab to regulate functional properties of pDCs from atopic donors might have important clinical implications for anti-IgE treatments in different IgE-mediated diseases.

Current status and prospect of transcutaneous auricular vagus nerve stimulation for disorders of consciousness.

Disordered Consciousness (DOC) is among neurological disorders for which there is currently no admitted treatment. The pathogenesis of DOC is still unclear, covering a variety of indistinguishable types of diseases, high misdiagnosis rate and poor prognosis. Most treatments remain to be clarified in the future to provide adequate evidence for clinical guidance. Neuromodulation technology aims to regulate neural circuits to promote awakening more directly. At present, it is confirmed that the potential of transcutaneous auricular vagus nerve stimulation (taVNS) as a therapeutic tool is worth exploring in the context of consciousness disorders, as previously proposed for invasive forms of VNS, in which the means of stimulating the vagus nerve to change the brain areas related to cosciousness have also received widespread attention. In this paper, we review the literature on taVNS and DOC to better understand the current status and development prospect of taVNS treament as a non-invasive neuromodulation method with sensitivity and/or specificity at the single subject.

Treatment of olecranon fractures in childhood: A systematic review.

Background: Literature over the last 20 years provides evidence for a surgical treatment of displaced olecranon fractures in children, this is usually obtained with commonly proposed methods, although there is no general agreement about the best recommended technique. Aim: Identifying the best surgical technique in displaced olecranon fractures in children and the role of associated fractures in the prognosis of these lesions, by analyzing the most relevant studies on this topic. Methods: A literature search was performed in MEDLINE database and Scopus database. Articles reporting clinical outcomes of pediatric patients affected by olecranon fractures treated surgically were identified. Results: The initial search produced 111 studies, with 8 fulfilling the eligibility criteria of our study. Selected articles (2002-2022) included 122 patients overall. Conclusion: Displaced olecranon fractures, occurring during skeletal growth and surgically treated, generally have good results, although we are unable to recommend the best surgical treatment based on our review. In most cases, they are intra-articular fractures; thus, the overall goal is to get an anatomic reduction that in some cases cannot be obtained by percutaneous techniques. Tension band suture is the preferred device, although it is not recommended in adolescence for the high risk of fixation failure. Associated lesions may affect results.

Efficient catalytic degradation of methylene blue by a novel Fe3+-TiO2@CGS three-dimensional photoelectric system.

In this study, a novel three-dimensional photoelectric system was designed and constructed for the degradation of methylene blue (MB) via photocatalysis, electrocatalysis, and photoelectric catalysis. To this end, a Ti/RuO2-IrO2-SnO2-CeO2 electrode was prepared via a thermal oxidation coating method and used as a dimensionally-stable anode (DSA). The cathode was made of a titanium sheet with Fe3+-doped TiO2 loaded on coal gasification slag (CGS) (Fe3+-TiO2@CGS) as a photocatalyst. The factors affecting the degradation efficiency, such as the supporting electrolyte, current density, and initial pH were systematically investigated. The results revealed Fe3+-TiO2@CGS three-dimensional photoelectric system exhibiting efficient synergistic performance of photocatalysis and electrocatalysis with a synergistic factor of 1.11. Photo-generated holes (h+) were generated by light irradiation and direct anodic oxidation. Furthermore, hydroxyl radicals (HO·) radicals were induced via other pathways. Such active species showed highly-oxidizing abilities, beneficial to the degradation of methylene blue (MB). The representative Fe3+-TiO2@CGS three-dimensional photoelectric system showed super high degradation efficiency at pH 11 and current density of 18.76 mA cm-2. Using NaCl as a supporting electrolyte, the degradation yield reached 99.98% after 60 min of photoelectrical treatment. Overall, the novel Fe3+-TiO2@CGS three-dimensional photoelectrical system looks very promising for the highly efficient catalytic degradation of organic contaminants.

Recent Advances in Dual PI3K/mTOR Inhibitors for Tumour Treatment.

The PI3K-Akt-mTOR pathway is a viable target for cancer treatment and can be used to treat various malignant tumours, including follicular lymphoma and breast cancer. Both enzymes, PI3K and mTOR, are critical in this pathway. Hence, in recent years, an array of inhibitors targeting these two targets have been studied, showing dual PI3K/mTOR inhibition compared with single targeting small molecule inhibitors. Inhibitors not only inhibit cell proliferation but also promote cell apoptosis. These inhibitors show high potency and little drug resistance even at low doses, suggesting that PI3K/mTOR inhibitors are promising cancer drugs. Herein, we summarised the recent research of PI3K/mTOR dual inhibitors-for example, structure-activity relationship, pharmacokinetics, and clinical practice, and briefly commented on them. Clinical Trial Registration: https://clinicaltrials.gov.

Allergen immunotherapy for asthma prevention: A systematic review and meta-analysis of randomized and non-randomized controlled studies.

BACKGROUND: Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated diseases. Randomized controlled trials (RCTs) support AIT's potential role in asthma prevention but evidence from non-randomized studies of interventions (NRSI) and longitudinal observational studies has been poorly addressed. Therefore, we aimed to conduct a systematic review and meta-analysis to assess clinical data from all study types to evaluate quantitatively the preventive role of AIT in asthma onset. METHODS: We search three databases. Studies were screened, selected and evaluated for quality using risk-of-bias (ROB) tools. Data were descriptively summarized and meta-analysed using random effects. We performed a sensitivity, influence and subgroup analyses. Publication bias and heterogeneity were assessed. RESULTS: From the 4549 identified studies, 24 (12 RCTs and 12 NRSI) were included in the qualitative synthesis and 18 underwent meta-analysis. One study was at low ROB, seven had moderate ROB, and 15 were proven of high ROB. Random-effects analysis showed a significant decrease in the risk of developing asthma following AIT by 25% (RR, 95% CI: 0.75, 0.64-0.88). This effect was not significant in the sensitivity analysis. Publication bias raised concerns, together with the moderate heterogeneity between studies (I2  = 58%). Subgroup analysis showed a remarkable preventive effect of AIT in children (RR, 95% CI: 0.71, 0.53-0.96), when completing 3 years of therapy (RR, 95% CI: 0.64, 0.47-0.88), and in mono-sensitized patients (RR, 95% CI: 0.49, 0.39-0.61). CONCLUSIONS: Our findings support a possible preventive effect of AIT in asthma onset and suggest an enhanced effect when administered in children, mono-sensitized, and for at least 3 years, independently of allergen type.

Cannabis-related allergies: An international overview and consensus recommendations.

Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic. Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein. Other allergens may also be relevant, and recognition of allergens may vary between countries and continents. Cannabis also has the potential to provoke allergic cross-reactions to plant foods. Since cannabis is an illegal substance in many countries, research has been hampered, leading to challenges in diagnosis since no commercial extracts are available for testing. Even in countries such as Canada, where cannabis is legalized, diagnosis may rely solely on the purchase of cannabis for prick-to-prick skin tests. Management consists of avoidance, with legal issues hindering the development of other treatments such as immunotherapy. Education of healthcare professionals is similarly lacking. This review aimed to summarize the current status of cannabis allergy and proposes recommendations for the future management of this global issue.

Case Report: Osteomyelitis of the Proximal Phalanx of the Finger in Patient With Ollier Disease.

Ollier disease is a rare congenital pathology characterized by the growth of enchondromas in bones, accompanied with their deformities, fractures, and the risk of malignancy. A 39-year-old patient with Ollier disease (acroform with lesions of hands and feet) suffered a rapid development of osteomyelitis of the proximal phalanx of the ring finger after a mosquito bite. The condition localized in the area of enchondroma. Surgical treatment included osteonecrectomy in the phalanx and enchondroma with excision of non-viable surrounding soft tissues, drainage of the surgical wound and the imposition of primary sutures. Morphological analysis confirmed the presence of ectopic embryonic cartilage specific for Ollier disease and the bone destruction. The excised tissues were infiltrated with immune cells and had signs of periosteal chronic inflammation including fibrosis and hyalinosis. These changes, which occurred long before the mosquito bite, became a favorable background for the development of a purulent infection.