Adminstration

With the advent of targeted agents and immunological therapies, the medical research community has become increasingly aware that conventional methods for determining the best dose or schedule of a new agent are inadequate. It has been well established that conventional phase I designs cannot reliably identify safe and effective doses. This problem applies, generally, for cytotoxic agents, radiation therapy, targeted agents, and immunotherapies. To address this, the US Food and Drug Administration's Oncology Center of Excellence initiated Project Optimus, with the goal "to reform the dose optimization and dose selection paradigm in oncology drug development...

INTRODUCTION: Uterine fibroids affect 30%-77% of reproductive-age women and are a significant cause of infertility. Surgical myomectomies can restore fertility, but they often have limited and temporary benefits, with postoperative complications such as adhesions negatively impacting fertility. Existing medical therapies, such as oral contraceptives, gonadotropin hormone-releasing hormone (GnRH) analogues and GnRH antagonists, can manage fibroid symptoms but are not fertility friendly...

BACKGROUND: Autologous bone grafts, sourced from the iliac crest, are the gold standard for bone substitution in spine surgery. However, harvesting autografts increases the risk of postoperative complications. Bone allografts are another popular source of graft material, but their use is rapidly surpassing their availability. There has been considerable interest in manufactured bone graft substitutes, commonly referred to as osteobiologics, which mimic the properties of autologous bone and may be osteoconductive, osteoinductive, osteogenic, or a combination...

BACKGROUND: This paper analyzed the cases of dural arteriovenous fistula (DAVF) with spinal dural arteriovenous fistula (SDAVF) in the diagnosis and treatment process. CASE PRESENTATION: One case involving dural arteriovenous fistula (DAVF) with spinal dural arteriovenous fistula (SDAVF) from the 306th Hospital of PLA was retrospectively analyzed. The patient consulted the doctor due to lower limb sensory and motor disorders while exhibiting symptoms of urinary dysfunction...

Rationale: Pneumococcal pneumonia remains a global health problem. Pneumococcal colonization increases local and systemic protective immunity, suggesting that nasal administration of live attenuated Streptococcus pneumoniae (Spn) strains could help prevent infections. Objectives: We used a controlled human infection model to investigate whether nasopharyngeal colonization with attenuated S. pneumoniae strains protected against recolonization with wild-type (WT) Spn (SpnWT). Methods: Healthy adults aged 18-50 years were randomized (1:1:1:1) for nasal administration twice (at a 2-wk interval) with saline solution, WT Spn6B (BHN418), or one of two genetically modified Spn6B strains, SpnA1 ( Δfhs/piaA ) or SpnA3 ( ΔproABC/piaA ) (Stage I)...

This study aimed to evaluate the effectiveness of the embryonic injection of silver nanoparticles (SilNPs) on some productive traits and hepatic gene expression of lipopolysaccharide (LPS)-challenged broilers after a 42 d rearing period. 560 fertile eggs were randomly allocated to four groups and received either of the following treatments at d 7 of incubation, control (no injection), placebo (1 mL saline), SilNP20 (20 mg/kg silver nanoparticles), or SilNP40 (40 mg/kg silver nanoparticles)...

A progressively essential bird of high economic significance for meat production and commercial egg is the Japanese quail, and so more experiments are necessary to improve the productivity of these birds under stressful encounters. The current work was performed to define the influences of Coenzyme Q10 (CoQ10) on growth, sexual behavior, and testicular characteristics (size of the gonad, traits of spermatic features, levels of plasma testosterone, steroidogenic-related gene expression) of Japanese quail (Coturnix coturnix japonica) aganist cadmium (Cd) administration...

To explore the action time and molecular mechanism underlying the effect of acetaminophen (APAP) on liver injury. APAP was used to establish drug-induced liver injury (DILI) model in mice. Mice in the model group were intraperitoneally injected 300 mg/kg APAP for 6, 12, and 24 h respectively, and control group mice were given the same volume of normal saline. The mice were anesthetized through intravenous injection of sodium pentobarbital at 6, 12, and 24 h after APAP poisoning. Analysis of ALT, AST and ALP in serum, liver histopathological observation, oxidative damage and western blot were performed...

BACKGROUND: REGEN-COV is a non-Food and Drug Adminstration approved monoclonal antibody combination of casirivimab/imdevimab. Casirivimab/imdevimab was previously used for the treatment of SARS-CoV-2 infection (COVID-19), under an emergency use authorization, and has demonstrated a reduction in hospitalizations and death. With the ability to administer this monoclonal antibody combination subcutaneously in an outpatient setting, limited community pharmacies became a treatment location for patients...

Alveolar hemorrhage following thrombolytic agents administration is an extremely rare entity that has only been reported in twenty two patients in the medical literature. We herein report a case of a 60-year old male with an acute ST-elevation myocardial infarction who was treated with Streptokinase. Twelve hours after streptokinase adminstration, the patient developed severe hemoptysis and dyspnea and radiological studies were highly suggestive for acute alveolar hemorrhage. His past medical history is significant for severe chest trauma ten months prior to presentation...

BACKGROUND AND OBJECTIVE: Patients on parenteral nutrition (PN) are at high risk of both liver and pancreatic injury. More efforts were focused on liver, however, limited data is available to evaluate the effects of PN on pancreas. Thus, we performed a retrospective observational study to evaluate the association between PN and pancreatic injury in Chinese adult patients. METHODS: Adult patients (18-80 years), who received PN for a week or longer, and with repeated measurements of pancreatic enzymes, were included in the analysis...

Introduction: Knowledge of chemotherapeutic drug (CD) handling, administration, and waste disposal are important among nurses involved in cancer therapy. Inadequate knowledge of the management of CD could cause environmental contamination and potential harm to patients and nurses. To assess the knowledge of safe handling, administration, and waste management of CD among oncology nurses working at Khartoum Oncology Hospital, Sudan. Methods: A questionnaire was developed by a team of experts to assess the knowledge in three domains of oncology nursing practice (handling, administration, and disposal)...

Objective: Adults with end-stage of chronic liver diseases have lower antibody titers after Hepatits-B vaccination. We have less amount of knowlegdge about the effect of non-viral cause chronic liver fibrosis on vaccination. In this study we investigated the effect of non-viral chronic liver fibrosis on Hepatitis B vaccine and the effect of tetanous toxoid co-adminsitration at the level of humoral and cellular immune responses in an experimental model. Methods: Hepatitis B vaccine was administered either alone or in combination with tetanus toxoid in thioacetamide induced fibrotic BALB/c mice...

Experienced senior living leaders (SLLs) report the impact of spirituality and religious practice on SLL role adaptation and continuation. The sample included 18 SLLs in 18 skilled care settings representing public, non-profit, and for-profit types of incorporation, with oversampling of for-profit facilities. The average years of SLL experience was 24 years. In-depth interviews were examined through a thematic analysis approach using Excel software. Seventy-eight percent described how a higher power, religious beliefs, and faith practices were associated with their role...

Human cytomegalovirus (HCMV) is a β-herpesvirus that increases morbidity and mortality in immunocompromised individuals including transplant recipients and newborns. New anti-HCMV therapies are an urgent medical need for diverse patient populations. HCMV infection of a broad range of host tissues is dependent on the gH/gL/gO trimer and gH/gL/UL28/UL130/UL131A pentamer complexes on the viral envelope. We sought to develop safe and effective therapeutics against HCMV by generating broadly-neutralizing, human monoclonal antibodies (mAbs) from VelocImmune® mice immunized with gH/gL cDNA...

BACKGROUND: Bleeding is a potential complication after neuraxial and peripheral nerve blocks. The risk is increased in patients on antiplatelet and anticoagulant drugs. This joint guideline from the European Society of Anaesthesiology and Intensive Care and the European Society of Regional Anaesthesia aims to provide an evidence-based set of recommendations and suggestions on how to reduce the risk of antithrombotic drug-induced haematoma formation related to the practice of regional anaesthesia and analgesia...

Vitamin K2 serves an important role in cardiovascular health through regulation of calcium homeostasis. Its effects on the cardiovascular system are mediated through activation of the anti-calcific protein known as matrix Gla protein. In its inactive form, this protein is associated with various markers of cardiovascular disease including increased arterial stiffness, vascular and valvular calcification, insulin resistance and heart failure indices which ultimately increase cardiovascular mortality. Supplementation of vitamin K2 has been strongly associated with improved cardiovascular outcomes through its modification of systemic calcification and arterial stiffness...

BACKGROUND: Neurotrauma is a worldwide public health problem which can be divided into primary and secondary damge. The primary damge is caused by external forces and triggers the overproduction of peroxides and superoxides, leading to long-lasting secondary damage including oxidative stress, wound infection and immunological reactions. The emerging catalysts have shown great potential in the treatment of brain injury and neurogenic inflammation, but are limited to biosafety issues and delivery efficiency...

BACKGROUND: Triptans are a highly effective substance class in the acute treatment of migraine attacks. They contribute to a substantial improvement in the quality of life and help to reduce the socioeconomic burden of the disease. RESULTS: Sumatriptan is the only triptan that is available for subcutaneous administration. It is primarily indicated in patients with the need for rapid relief or insufficient enteral resorption due to nausea and vomiting. In the treatment of migraine attacks with 6 mg subcutaneous sumatriptan the number needed to treat (NNT) is 2...

Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 and γδ lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and in target organ damage. Preclinical studies in mice have shown that systemic adminstration of IL-17A increases blood pressure, probably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are already elevated in patients with mild or moderate hypertension. Many studies in hypertensive mice models have detected IL-17A-producing cells in target organs such as the heart, vessels and kidneys...