Search Results (111)

The varicella attenuated virus vaccine, developed in Japan in the 1970s, has dramatically reduced the number of pediatric chickenpox cases over the past 30 years due to its widespread use. However, a small number of cases of chickenpox, shingles, aseptic meningitis, and acute retinal necrosis caused by vaccine strains have been reported. There are also issues that need to be addressed, such as breakthrough infections and the persistence of the preventive effect of vaccination. In addition, there is the possibility of the emergence of revertants or mutations in the vaccine strain. In recent years, subunit vaccines have been developed, their immune-stimulating effects have been demonstrated, and they are being applied clinically. In addition, development of an mRNA varicella vaccine is underway. In this review, the history and impact of the varicella vaccine are overviewed, as well as its future challenges. Full article

Asphalt recycling technologies have advanced considerably over the last few decades with the utilization of reclaimed asphalt pavements (RAP) and recycled asphalt shingles (RAS). Characterizing aged and heterogeneous binders in these mixtures is challenging, particularly with limited extracted binders. This study suggests a data-driven framework that considers the rheological, chemical, and thermal characteristics to predict the binders’ performance. Ninety-seven mixtures with 0–35% of the asphalt binder replaced with RAP/RAS binders were included as cores from the field, plant-produced mixtures, and laboratory-fabricated mixtures. The binders were chemically quantified using aging, aromatic, and aliphatic indices. Thermal analyses of the binders involved the percentage of the thermal residue. The framework predicted the rheological resistance of the binders to rutting and cracking using linear and nonlinear machine learning models. The nonlinear models outperformed the linear models for the three rheological parameters. The nonlinear models achieved a 69% reduction in the root mean square error (RMSE) for rutting, a 37% reduction in the RMSE for fatigue cracking, and a 21% reduction in the RMSE for thermal cracking. However, the nonlinear models overfitted for block cracking and had an RMSE 41% higher than the linear models, despite a perfect correlation (R = 1.00). The feature importance demonstrated the strong effects of the chemical and thermal parameters on rheological prediction. The data-driven framework can successfully support efforts to better manage asphalt recycling by predicting the binder performance. Full article

Introduction: Herpes zoster (HZ), or shingles, is a vaccine-preventable disease with two approved vaccines: the live-attenuated vaccine (LZV) and the adjuvanted recombinant zoster vaccine (RZV). Evidence on the immunogenicity and adverse events (AEs) following co-administration with other vaccines in adults is limited. This systematic review and meta-analysis aims to evaluate the immunogenicity and safety of HZ vaccines when co-administered with other vaccines. Methods: We followed PRISMA 2020 guidelines and systematically searched multiple databases (January 1950 to February 2024) for studies on HZ vaccination with concomitant vaccines in adults (≥18 years). Observational studies, randomized controlled trials (RCTs), and non-randomized controlled trials were included, excluding reviews, case series, case reports, editorials, and non-English publications. Risk of bias was assessed using Cochrane tools (RoB 2 and ROBINS-I). A meta-analysis compared geometric mean concentration (GMC) ratios and vaccine response rates (VRRs) for RZV, applying the Hartung–Knapp adjustment. For LZV, meta-analysis was not feasible, and results were described narratively. AEs were analyzed using risk ratios and presented in forest plots. Results: Out of 369 search hits, ten RCTs were included. In six RCTs, RZV was co-administered with influenza, COVID-19, pneumococcal vaccines (PCV13, PPSV23), or Tdap. The pooled GMC mean difference was −0.04 (95% CI: −0.10 to 0.02, p = 0.19), and the pooled VRR was 1.00 (95% CI: 0.99 to 1.01, p = 0.59). Local and systemic AEs showed pooled relative risks of 0.99 (95% CI: 0.95 to 1.03, p = 0.73) and 1.01 (95% CI: 0.91 to 1.11, p = 0.90), respectively. LZV co-administration was investigated in four RCTs and was safe; however, co-administration with PPSV23 resulted in reduced immunogenicity. Conclusions: The co-administration of RZV with other vaccines was safe and immunogenic. However, limited evidence suggests that co-administration of LZV with PPSV23 reduced the immunogenicity of LZV through an unknown mechanism. Still, RZV co-administration could enhance vaccine uptake in vulnerable populations. Full article

Introduction: Over the past few decades, the rising incidence of herpes zoster (HZ) rates appears to have been a global phenomenon. In Türkiye, there is a lack of comprehensive studies addressing the HZ burden of disease, risk factors, and clinical characteristics. The aim of the VARICOMP-Adult study was to evaluate the clinical and demographic findings of adult patients with HZ. Patients and Methods: We enrolled the medical records of 1955 patients, 1010 females and 945 males, aged between 18 and 97 years between 2009 and 2014. Results: The presence of underlying conditions was present in 35.5% of patients and 345 patients (17.6%) had immunosuppression; 18.0% of patients required hospitalization. The mean age, the presence of underlying conditions, and immunosuppression in hospitalized cases with HZ were higher than those in outpatients. Logistic regression analysis revealed the following risk factors for hospitalization: age, immunosuppression, hypertension, hematological disorders, transplantation, COPD, and the presence of HZ opthalmicus or disseminated disease. We observed seven HZ cases with mortality aged between 58 and 80 years, and all cases had an underlying condition; 9.9% of the entire population reported postherpetic neuralgia (PHN), and age and no previous antiviral medications were the risk factors for PHN. Conclusions: This is the largest nationwide study of adult patients with HZ. Effective healthcare interventions such as antiviral therapy and immunization could prove beneficial in combating disease and treating HZ complications, especially in the high-risk population and individuals of older ages. Full article

Background/Objectives: Herpes zoster (shingles), caused by reactivation of the varicella zoster virus, often leads to acute pain that may progress to postherpetic neuralgia (PHN). Current evidence is insufficient to determine the optimal interventional treatment for these conditions. This study aimed to evaluate the effectiveness of shared decision-making (SDM) forms developed by MacKay Memorial Hospital (MMH) in reducing patient anxiety and improving personalized care. Method: Between 1 August 2022 and 30 August 2024, we retrospectively reviewed SDM records of patients with shingles pain and PHN who were referred to the pain clinic for interventional treatment due to unresolved pain. The SDM forms were developed, reviewed, and authorized by the MMH Committee of Medical Quality and Safety. We analyzed the chosen interventions, anxiety levels, pain intensity, and patient preferences regarding treatment selection. Results: A total of 51 individuals (36 with shingles pain, 15 with PHN) were included in this cohort study. Most patients with acute or chronic zoster pain opted for subcutaneous steroid injections. Anxiety scores significantly decreased following SDM intervention, from 5.0 (IQR: 3.5–5.0) to 3.0 (IQR: 2.0–3.0) in shingles patients and from 5.0 (IQR: 4.0–5.0) to 2.0 (IQR: 2.0–3.0) in PHN patients. Pain intensity, measured using the numerical rating scale (NRS), also improved markedly after interventional pain management, with scores reducing from 8.0 (IQR: 6.0–9.0) to 3.0 (IQR: 1.0–6.5) in shingles patients and from 5.0 (IQR: 4.0–8.0) to 2.0 (IQR: 1.0–3.0) in PHN patients. Shingles patients expressed greater concern about the risks of interventional therapy complications, whereas PHN patients prioritized cost, complication rates, treatment frequency, and continuity of care. Additionally, SDM forms received high scores for promoting patient participation and knowledge, indicating that they improved their understanding of their condition and treatment options. Conclusions: SDM significantly improved patient comprehension, reduced anxiety, facilitated informed treatment decisions, and strengthened doctor–patient communication for those with shingles pain and PHN. Full article

Background: The varicella–zoster virus (VZV) is a human herpesvirus that primarily causes varicella (chickenpox) as an initial infection, characterized by distinctive skin lesions. It can later reactivate, leading to herpes zoster (shingles). Once reactivated, VZV infection may result in serious complications, the most common being postherpetic neuralgia. Fortunately, vaccination can prevent this condition. Objectives: In this study, we provide a comprehensive analysis of zoster vaccines, including clinical trials, safety profiles, and reimbursement guidelines across various countries. Results: Our findings confirm the vaccine’s effectiveness and safety across diverse populations, aligning with previous clinical trials and real-world data, and summarize global vaccination guidelines. Full article

This study proposes that a proactive quality assurance (QA) framework for asphalt mixes with recycled materials, i.e., reclaimed asphalt pavement and recycled asphalt shingles, should be developed. Quality control (QC) is generally concerned with the contractor’s obligation to produce mixes which meet the job mix formula (JMF) targets. However, QA considers the variability in fabrication processes and materials and offers monitoring by evaluating the contractor’s performance. Although both aggregate gradations and asphalt contents were within the JMF specifications, the recovered binders revealed significant differences from the contract binders in the JMF. Rheological tests indicated increased stiffness and elasticity but reduced capability to relax thermal stresses in binders recovered from plant–lab- and lab-fabricated mixtures, compared to field mixtures. Thermal-rheological analysis models corroborated these results by demonstrating reduced decomposition areas for more aged binders, enhancing performance prediction—especially for limited binder amounts. The creation of a QA decision matrix facilitated uniform, performance-oriented assessments. The matrix indicated only 23% of the mixtures satisfied JMF criteria and reported QC data—predominantly field mixtures—underscoring the impact of the fabrication mechanisms and the use of soft binders. This matrix integrates statistical analysis and binder performance assessments as a tool for verifying material compliance and tracking contractor efficiency. It reflects a transition from traditional QC toward a more proactive QA framework for sustainable pavements. Full article

Background/Objectives: An overwhelming burden to clinics, herpes zoster (HZ), or shingles, is a painful disease that occurs frequently among aged individuals with a varicella-zoster virus (VZV) infection history. The cause of shingles is the reactivation of dormant VZV in the dorsal root ganglia/cranial nerves of the human body. Patients with HZ experience sharp, intense, electric shock-like pain, which makes their health-related quality of life (HRQoL) extremely low. Methods: Various mRNA constructs were designed based on intracellular organelle-targeting strategies and AI algorithm-guided high-throughput automation platform screening and were then synthesized by in vitro transcription and encapsulated with four-component lipid nanoparticles (LNPs). Immunogenicity was evaluated on a naïve mouse model, long-term mouse model, and VZV-primed mouse model. Safety was evaluated by a modified “nestlet shredding” method for potential adverse effects induced by vaccines. Comparison between muscular and intradermal administrations was conducted using different inoculated approaches as well. Results: The best vaccine candidate, CVG206, showed robust humoral and cellular immune responses, durable immune protection, and the fewest adverse effects. The CVG206 administered intradermally revealed at least threefold higher humoral and cellular immune responses compared to intramuscular vaccination. The manufactured and lyophilized patch of CVG206 demonstrated good thermal stability at 2–8 °C during 9 months of storage. Conclusions: The lyophilized mRNA vaccine CVG206 possesses remarkable immunogenicity, long-term protection, safety, and thermal stability, and its effectiveness could even be further improved by intradermal administration, revealing that CVG206 is a promising vaccine candidate for HZ in future clinical studies. Full article

Background: The varicella-zoster virus is a highly contagious human herpesvirus that primarily causes varicella (chickenpox) as an initial infection, targeting T cells, neurons, as well as skin cells, and can later reactivate to cause herpes zoster (shingles). Following reactivation, the varicella-zoster virus infection can lead to severe complications, the most common of which is postherpetic neuralgia. Risk factors include aging, immunosuppression, chronic diseases such as diabetes, cardiovascular disorders, respiratory conditions, and others. Objective: In this article, we present an analysis of factors increasing the risk of herpes zoster occurrence, complications, and recurrences (in particular in immunocompromised patients). Full article

The semi-circular bending method (SCB) is a useful test for evaluating the cracking resistance of asphalt mixtures with added reclaimed asphalt shingles. A mixture of the asphalt concrete AC 16 with 50/70 paving bitumen was used for the binder course test as a reference mix. The purpose of the paper is to evaluate two aging conditions (short-term and long-term) of the above-mentioned asphalt mixtures in relation to their fracture properties. Laboratory experiments are enhanced with the application of image processing techniques (digital image correlation and image segmentation) that account for the asphalt mixture heterogeneity. Consequently, they can provide a more detailed description of the specimen performance. Statistical analyses of the laboratory results indicate that the best sensitivity in terms of differentiating the tested mixtures, especially taking into account the aging conditions of the mixtures, was observed for the post-peak parameters such as the flexibility index (FI), toughness index (TI), and, above all, cracking resistance index (CRI), for which the average coefficient of the result variability is approximately 10%, while for the FI and TI parameters it is approximately 30%. Digital image correlation analyses provided a confirmative illustration of the aforementioned observation. Full article

Drug development faces significant financial and time challenges, highlighting the need for more efficient strategies. This study evaluated the druggability of the entire human proteome using Fpocket. We identified 15,043 druggable pockets in 20,255 predicted protein structures, significantly expanding the estimated druggable proteome from 3000 to over 11,000 proteins. Notably, many druggable pockets were found in less studied proteins, suggesting untapped therapeutic opportunities. The results of a pairwise pocket similarity analysis identified 220,312 similar pocket pairs, with 3241 pairs across different protein families, indicating shared drug-binding potential. In addition, 62,077 significant matches were found between druggable pockets and 1872 known drug pockets, highlighting candidates for drug repositioning. We repositioned progesterone to ADGRD1 for pemphigus and breast cancer, as well as estradiol to ANO2 for shingles and medulloblastoma, which were validated via molecular docking. Off-target effects were analyzed to assess the safety of drugs such as axitinib, linking newly identified targets with known side effects. For axitinib, 127 new targets were identified, and 46 out of 48 documented side effects were linked to these targets. These findings demonstrate the utility of pocket similarity in drug repositioning, target expansion, and improved drug safety evaluation, offering new avenues for the discovery of new indications and side effects of existing drugs. Full article

For decades, Alzheimer’s Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut–brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut–brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide’s antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions. Full article

The burden of herpes zoster (HZ) is recognized worldwide; however, there is seemingly limited information on incidence and vaccination practices in Southeast Asia (SEA). A scientific workshop was held by the Zoster Experts’ Network to exchange and consolidate insights on the burden of HZ and the patient pathway in SEA. The workshop included practicing clinical experts and public health specialists/epidemiologists from Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. It aimed to identify gaps in the literature, outline patient pathways, and evaluate HZ vaccine recommendations among these countries. Consensus was identified on the substantial lack of epidemiological data on HZ in SEA and the need to investigate the impact of age, immunocompromising conditions, and comorbidities on the incidence and severity of HZ in the region. However, available data in SEA did indicate a rising disease and socioeconomic burden of HZ, with concerns that current treatment strategies for HZ are suboptimal. The HZ patient pathways generated by the experts highlighted common themes and differences between the five countries. Furthermore, the experts highlighted the lack of awareness of HZ and its impact on patients’ quality of life, among patients and healthcare professionals. Evaluation of the current local HZ vaccine recommendations further showed differences in age and the inclusion of at-risk populations between countries. The workshop outcomes emphasize the need for further HZ surveillance in SEA. Efforts to align and address leakage within the patient pathway and raise awareness on the impact of HZ should be prioritized. Awareness initiatives and alignment on vaccine recommendations are also needed. Full article

Background/Objectives: This study investigates the relationship between psychiatric disorders and herpes zoster (HZ). Emergency and outpatient admissions to Kırşehir Education and Research Hospital between 2019 and 2023 were examined. Psychiatric disorders are known in the literature as one of the factors that weaken the immune system, thereby increasing the risk of infection. Methods: In our study, the past diagnoses and sociodemographic data of all individuals over the age of 18 who applied to the Kırşehir Education and Research Hospital between 2019 and 2023 were obtained from hospital system records. Patients receiving immunosuppressive treatment or those with diseases that could affect immune system function were excluded from the study. The sample was divided into two groups: those with and without psychiatric disorders diagnosed with HZ. Sociodemographic features, change of HZ frequency over the years, and differences among psychiatric diagnosis subgroups were examined between the groups. Results: Individuals with psychiatric diseases had a significantly higher frequency of HZ compared to those without psychiatric diseases (0.0040% vs. 0.0016%, p < 0.001). No significant difference was found in the frequency of HZ among different types of psychiatric disorders (p = 0.60). Additionally, no statistically significant difference was found in the median age between the groups (p = 0.11). In terms of gender distribution, it was determined that women were more frequently diagnosed with HZ compared to men. Conclusions: The frequency of HZ was found to be higher in individuals with psychiatric disorders. However, further research is needed to explore the association between specific psychiatric diagnoses and HZ frequency. Full article

In North America and Europe, asphalt shingle waste created during the installation of roofing membranes and tear-off shingles retrieved at the end of the membrane’s life cycle are two major sources of municipal solid waste. Since almost 15–35% of recycled asphalt shingles (RAS) consist of an asphalt binder, the effective recycling of RAS into asphalt mixtures could also allow a reduction in the consumption of non-renewable resources such as asphalt binders. In this context, several studies investigating the use of RAS in asphalt mixtures can be found in the literature, although they exhibit widespread and sometimes conflicting information about the investigated materials, the mix preparation and testing methodologies and the experimental findings. Given this background, this review paper aims at summarizing the existing information and research gaps, providing a synthetic and rational picture of the current literature, where similar attempts cannot be found. In particular, different research studies show that the use of RAS in asphalt mixtures is an economical as well as an eco-friendly option. RAS with up to 20% by weight of binder or 5% by weight of aggregate/mixtures (eventually in combination with 15% reclaimed asphalt pavement aggregate) were found to be relatively suitable to improve the performance properties of asphalt mixtures, both in the laboratory and in the field. Adding RAS to asphalt mixtures could enhance their stiffness, strength and rutting resistance (i.e., high-temperature properties), while negatively affecting the mixtures’ fatigue and thermal cracking resistance. However, the addition of specific biomaterials (e.g., bio-binders, bio-oils) or additives to asphalt mixtures can mitigate such issues, resulting in lower brittleness and shear susceptibilities and thus improving the anti-cracking performance. On the other hand, the literature review revealed that several aspects still need to be studied in detail. As an example, RAS-modified porous asphalt mixtures (fatigue, rutting, moisture susceptibility and thermal cracking) need specific research, and there are no comprehensive research studies on the effects of the RAS mixing time, size and mixing temperature in asphalt mixtures. Moreover, the addition of waste cooking/engine oils (biomaterials) as asphalt binder rejuvenators in combination with RAS represents an attractive aspect to be studied in detail. Full article