Following the coronavirus disease-2019 outbreak caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an ongoing need to seek drugs that target COVID-19. First off, novel drugs have a long development cycle, high investment cost, and are high risk. Second, novel drugs must be evaluated for activity, efficacy, safety, and metabolic performance, contributing to the development cycle, investment cost, and risk. We searched the Cochrane COVID-19 Study Register (including PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and WHO COVID-19 Coronaviral Disease Global Literature to identify completed and ongoing studies as of February 20, 2024. We evaluated the pharmacological effects, in vivo and in vitro data of the 16 candidates in the paper. The difficulty of studying these candidates in clinical trials involving COVID-19 patients, dosage of repurposed drugs, etc. is discussed in detail. Ultimately, Metformin is more suitable for prophylactic administration or mildly ill patients; the combination of Oseltamivir, Tamoxifen, and Dexamethasone is suitable for moderately and severely ill patients; and more clinical trials are needed for Azvudine, Ribavirin, Colchicine, and Cepharanthine to demonstrate efficacy.

Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating the development of an effective prophylactic vaccine. This review paper presents the current landscape of HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, and more modern, such as subunit protein, vectored, based on nucleic acids (DNA and mRNA) and virus-like particles. The concept of the HCV vaccine is first put in the context of viral genetic diversity and adaptive responses to HCV infection, an understanding of which is crucial in guiding the development of an effective vaccine against such a complex virus. Because ethical dimensions are also significant in vaccine research, development, and potential deployment, we also address them in this paper. The road to a safe and effective vaccine to prevent HCV infection remains bumpy due to the genetic variation of HCV and its ability to evade immune responses. The progress in cell-culture systems allowed for the production of an inactivated HCV vaccine candidate, which can induce cross-neutralizing antibodies in vitro, but whether this could prevent infection in humans is unknown. Subunit protein vaccine candidates that entered clinical trials elicited HCV-specific humoral and cellular responses, though it remains to be shown whether they translate into effective prevention of HCV infection or progression of infection to a chronic state. Such responses were also induced by a clinically tested vector-based vaccine candidate, which decreased the viral HCV load but did not prevent chronic HCV infection. These disappointments were not readily predicted from preclinical animal studies. The vaccine platforms employing virus-like particles, DNA, and mRNA provide opportunities for the HCV vaccine, but their potential in this context has yet to be shown. Ensuring the designed vaccine is based on conserved epitope(s) and elicits broadly neutralizing immune responses is also essential. Given failures in developing a prophylactic HCV vaccine, it is crucial to continue supporting national strategies, including funding for screening and treatment programs. However, these actions are likely insufficient to permanently control the HCV burden, encouraging further mobilization of significant resources for HCV vaccine research as a missing element in the elimination of viral hepatitis as a global public health.

UNASSIGNED: To assess the effect of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in reducing vertigo, tinnitus, and hearing loss among patients with Meniere\'s disease (MD).
UNASSIGNED: The following databases were utilized in this scoping review: Ovid Medline, PubMed-NCBI, CINAHL, Cochrane Library, Web of Science, and Clinicaltrials.gov.
UNASSIGNED: Studies were identified through the following search phrases: \"serotonin specific reuptake inhibitors\" OR \"tricyclic antidepressants\" AND \"Meniere\'s disease.\" References from included manuscripts were examined for possible inclusion of additional studies.
UNASSIGNED: The literature search yielded 23 results, which were screened by three independent reviewers. Seventeen studies and three duplicates were excluded. An examination of references from the included studies yielded two additional publications. A total of four published studies assessing SSRIs and TCAs among 147 patients with MD were ultimately included. Four studies described significant reductions in vertigo attack frequency among patients treated with either SSRIs or TCAs compared to their pretreatment baseline. Three studies assessed the drugs\' effects on hearing, of which none found a significant difference among patients treated with SSRIs or TCAs. One study found a significant decrease in patient-reported tinnitus following treatment with TCAs or SSRIs compared to their pretreatment baseline.
UNASSIGNED: Data exploring SSRIs and TCAs among patients with MD suggests that these medications may reduce the frequency of tinnitus and vertigo, although there was significant heterogeneity in outcome reporting. There remains a need for larger-scale prospective studies that emphasize objective data to evaluate their effectiveness in reducing common MD symptoms.

Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, Epstein‑Barr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5‑year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.

UNASSIGNED: Oral feeding for preterm infants has been a challenging issue globally. In an effort to enhance the effectiveness of oral feeding in preterm infants, oral motor intervention (OMI) was developed. Present systematic review and meta-analysis study aims to examine the impact of various OMI techniques on key outcomes, including body weight at the time of discharge, the duration required to achieve independent oral feeding, and the length of hospital stay for preterm infants.
UNASSIGNED: A systematic search of the literature was performed across various databases such as PubMed, Scopus, and Web of Science and Google Scholar up to September 28, 2023. Quality assessment was conducted using the Joanna Briggs Institute (JBI) checklist. The overall effect measure was calculated using a random-effects model and was presented as the standard difference of the mean (SDM), accompanied by the standard error and a 95% confidence interval (CI). We used I 2 statistic for investigating the heterogeneity between studies. Data analysis was performed by CMA software (Version 2).
UNASSIGNED: Finally, 22 articles included in this review. The overall effect for body weight at discharge was found to be statistically significant in the prefeeding oral stimulation (PFOS) (SDM = 7.91, 95% CI: 5.62, 10.2, p = 0.000, I 2 = 86.31) and Premature Infant OMI (PIOMI) (SDM = 3.71, 95% CI: 0.72, 6.69, p = 0.01, I 2 = 96.64) groups versus control group. The overall effect of independent oral feeding was significant for PFOS-only (SDM = -0.64, 95% CI: -1.1, -0.17, p = 0.007, I 2 = 75.45), PIOMI only (SDM = -1.48, 95% CI: -2.49, -0.46, p = 0.004, I 2 = 93.73) and nonnutritive sucking (NNS) only (SDM = -0.53, 95% CI: -0.76, -0.30, p = 0.001, I 2 = 0) groups versus control groups. The overall effect of length of hospital stay was significant for NNS group (SDM = -0.45, 95% CI: -0.67, -0.23, p = 0.067, I 2 = 0) and PIOMI group (SDM = -0.42, 95% CI: -0.69, -0.15, p = 0.002, I 2 = 20.18) versus control group.
UNASSIGNED: Among OMIs, the PIOMI approach generally exhibited a more favorable impact on body weight gain at discharge, the duration required to achieve independent oral feeding, and the length of hospital stay.

Polyphenols are plant metabolites with potential anti-inflammatory and anti-proliferative effects, which may be advantageous for disorders like colorectal cancer (CRC). Despite promising in vitro and in vivo evidence, human clinical trials have yielded mixed results. The present study aimed to evaluate the clinical evidence of polyphenols for CRC prevention or treatment. A systematic review was performed according to PRISMA. Based on a PROSPERO registered protocol (CRD42024560044), online databases (PubMed and COCHRANE) were utilized for the literature search. A total of 100 studies articles were initially identified. After reviewing, 12 studies with a low risk of bias were selected, examining the effect of a variety of compounds. Curcumin demonstrated promise in various trials, mainly decreasing inflammatory cytokines, though results varied, and it did not lower intestinal adenomas or improve outcomes after chemotherapy. Neither epigallocatechin gallate nor artepillin C reduced the incidence of adenomas. Finally, fisetin seemed to improve the inflammatory status of patients under chemotherapy (5-fluorouracil). In summary, although certain polyphenols appear to exert some effect, their role in the prevention or treatment of CRC is inconclusive, and more clinical studies under more controlled conditions are needed.

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin\'s effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin\'s potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2256 documents, leading to the selection of 15 clinical trials for synthesis. Here, we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

BACKGROUND: The management of pediatric dermatological conditions such as alopecia areata (AA), psoriasis, atopic dermatitis (AD), and hidradenitis suppurativa (HS) has significantly evolved with the introduction of biologics and small molecule targeted therapies. The advancement in understanding the immunopathogenesis of these chronic skin conditions has led to the development and approval of novel biologics and small molecule therapies. Initially approved by the United States Food and Drug Administration (FDA) for adults, most of these therapies are now being evaluated in clinical trials for safety and efficacy in adolescents and children, expanding new treatment options for pediatric patients. The role of the FDA in drug approval is multifaceted from drug inception, ensuring that research, data, and evidence show that the proposed drug is effective and safe for the intended use.
OBJECTIVE: The goal of this review article is to provide an overview of the recently FDA-approved and potential biologic and oral small molecule therapies in clinical trials for AA, psoriasis, AD, and HS in pediatric patients.
METHODS: The search for this review included keywords in ClinicalTrials.gov, PubMed, and Google Scholar for the latest research and clinical trials relevant to these conditions and treatments without the PRISMA methodology.
RESULTS: For pediatric AA, ritlecitinib is FDA-approved, while baricitinib and updacitinib are in phase 3 clinical trials for pediatric approval. The FDA-approved drugs for pediatric psoriasis include secukinumab, ustekinumab, ixekizumab, etanercept, and apremilast. Other phase 3 clinical trials for pediatric psoriasis include risankizumab, guselkumab, tildrakizumab, brodalumab, and deucravacitinib. For pediatric AD, the FDA-approved drugs are dupilumab, tralokinumab, abrocitinib, and upadacitinib, with many other drugs in phase 3 trials. Adalimumab is an FDA-approved biologic for pediatric HS, with various clinical trials ongoing for adults. The approved biologics and small molecule therapies had higher efficacy and improved safety profiles compared to traditional medications.
CONCLUSIONS: With numerous ongoing trials, the success of these clinical trials could lead to their inclusion in treatment guidelines for these chronic skin conditions. Biologics and small molecule therapies offer new avenues for effective disease management, enabling personalized therapeutic interventions and improving pediatric health outcomes.

OBJECTIVE: Demonstrate the immunogenicity of the human papillomavirus (HPV) vaccine for the older age group (above 26 years) to prevent HPV infection with high-risk types and argue for extending vaccination recommendations for the older age group.
METHODS: Two authors searched PubMed, Embase, and the Cochrane Library from inception to December 2023 to collect information on clinical trials of HPV vaccine immunogenicity. The database search strategy used a combination of subject terms and free terms. Two authors first identified studies by reading the title, abstract, and full texts and, subsequently, based on the inclusion criteria. Studies eligible to be included are the clinical trials using one of the following types of HPV vaccines: 2vHPV, 4vHPV, and 9vHPV, and measuring the immunogenicity by the geometric mean concentration or titer (GMC/T) and seroconversion rate (SCR) among healthy women aged 9 to 55 years who had never received a prophylactic HPV vaccine, known serostatus for HPV, non-immunocompetence, or non-pregnant.
RESULTS: This review included nine articles, seven RCTs, and two open-labeled studies.
CONCLUSIONS: In summary, we have demonstrated that the immunogenicity of the HPV vaccines is non-inferior in the older age group. Even though the GMT declines with age, the SCR is similar in all age groups regardless of the serostatus. The immunogenicity of the bivalent vaccine is superior to that of the quadrivalent vaccine for the older age group. Additionally, the vaccine is more efficient in women under the age of 26, but older women will benefit from it.

Immunosuppressive medications play a pivotal role in kidney transplantation, and the calcineurin inhibitors (CNIs), including cyclosporine A (CsA) and tacrolimus (TAC), are considered as the backbone of maintenance immunosuppressive regimens. Since the introduction of CNIs in kidney transplantation, the incidence of acute rejection has decreased, and allograft survival has improved significantly. However, CNI nephrotoxicity has been a major concern, believed to heavily impact long-term allograft survival and function. To address this concern, several CNI-sparing regimens were developed and studied in randomized, controlled, clinical trials, aiming to reduce CNI exposure and preserve long-term allograft function. However, more recent information has revealed that CNI nephrotoxicity is not the primary cause of late allograft failure, and its histopathology is neither specific nor pathognomonic. In this review, we discuss the historical development of maintenance immunosuppressive regimens in kidney transplantation, covering the early era of transplantation, the CNI-sparing era, and the current era where the alloimmune response, rather than CNI nephrotoxicity, appears to be the major contributor to late allograft failure. Our goal is to provide a chronological overview of the development of maintenance immunosuppressive regimens and summarize the most recent information for clinicians caring for kidney transplant recipients (KTRs).