Commentary: Ovarian Cancer: Path to Effective Treatments.

Despite advancements in cancer therapeutics such as checkpoint inhibitors and some targeted therapies, we have not achieved success in effectively treating ovarian cancer, since these therapeutics only benefit a subset of patients, and also provide short-term protection. The use of chemotherapy and radiation therapy can cause depletion and/or lack of immune cells' function. Chimeric antigen receptor T (CAR-T) cell therapy is found to be effective against several blood-based cancers, but limited success was seen against solid tumors.

Comparison of risk-adjusted cumulative quality control charts compared with standardized mortality ratios in critical care.

Purpose: The optimal method for monitoring intensive care unit (ICU) performance is unknown. We sought to compare process control charts using standardized mortality ratio (SMR), p-charts, and cumulative sum (CUSUM) charts for detecting increases in risk-adjusted mortality within ICUs.

Methods: Using data from 17 medical-surgical ICUs that included 29,592 patients in Ontario, Canada, we created risk-adjusted p-charts and SMRs on monthly intervals and CUSUM charts.

Ameliorating Racial Disparities in HIV Prevention via a Nurse-Led, AI-Enhanced Program for Pre-Exposure Prophylaxis Utilization Among Black Cisgender Women: Protocol for a Mixed Methods Study.

Background: HIV pre-exposure prophylaxis (PrEP) is a critical biomedical strategy to prevent HIV transmission among cisgender women. Despite its proven effectiveness, Black cisgender women remain significantly underrepresented throughout the PrEP care continuum, facing barriers such as limited access to care, medical mistrust, and intersectional racial or HIV stigma. Addressing these disparities is vital to improving HIV prevention outcomes within this community.

Comparative effectiveness of preemptive administration of ibuprofen and ibuprofen-arginine on the anesthetic success of inferior alveolar nerve block in teeth with symptomatic irreversible pulpitis - A double-blind randomized clinical trial.

Objectives: This study examined the impact of premedication with ibuprofen and ibuprofen-arginine and the influence of preoperative pain and anxiety on inferior alveolar nerve block (IANB) efficacy in cases of symptomatic irreversible pulpitis.

Materials And Methods: The study involved 150 SIP patients who were randomly assigned to receive ibuprofen (600 mg), ibuprofen-arginine (1,155 mg), or a placebo 30 min before IANB. Preoperative anxiety and pain levels were assessed using the Modified Dental Anxiety Scale and the Heft-Parker visual scale.

Role of Natural Killer Cells as Cell-Based Immunotherapy in Oral Tumor Eradication and Differentiation Both In Vivo and In Vitro.

Despite advancements in the field of cancer therapeutics, the five-year survival rate remains low in oral cancer patients. Therefore, the effective therapeutics are needed against oral cancer. Also, several studies including ours, have shown severely suppressed function and number of NK cells in oral cancer patients.

Current and Future States of Natural Killer Cell-Based Immunotherapy in Hepatocellular Carcinoma.

Natural killer (NK) cells are innate lymphoid cells that exhibit high levels of cytotoxicity against NK-specific targets. NK cells also produce various cytokines, and interact with T cells, B cells, and dendritic cells to effectively serve as frontliners of the innate immune system. Produce various cytokines, and interact with T cells, B cells, and dendritic cells to effectively serve as frontliners of the innate immune system.

Femoral internal torsion greater than twenty-five degrees and/or external tibial torsion greater than thirty degrees as measured by computed tomography are threshold values for axial alignment correction in patellofemoral instability.

Objectives: Patellofemoral instability (PFI) has multiple predisposing anatomic factors, including ligamentous hyperlaxity, coronal and axial malalignment, patella alta, trochlea dysplasia, excessive lateral patellar tilt, and excessive lateral Q vector. Yet, few studies have analyzed surgical thresholds for performing axial alignment corrective osteotomies in the treatment of PFI and patella maltracking. The objective of this systematic literature review was to determine if there is a threshold for axial plane alignment that triggers surgical correction for the treatment of patellar instability in the published literature.

Osteoclasts and Probiotics Mediate Significant Expansion, Functional Activation and Supercharging in NK, γδ T, and CD3+ T Cells: Use in Cancer Immunotherapy.

Our previous studies have introduced osteoclasts (OCs) as major activators of NK cells. It was found that OCs exhibit the capabilities of inducing cell expansion as well as increasing the cytotoxic activity of NK cells by granule release and increasing the secretion of TNF-α and TRAIL, leading to increased lysis of tumors in short-term as well as long-term periods, respectively. OC- induced expanded NK cells were named supercharged NK cells (sNK) due to their significantly high functional activity as well as their significantly higher cell expansion rate.

Similarities and Differences between Osteoclast-Mediated Functional Activation of NK, CD3+ T, and γδ T Cells from Humans, Humanized-BLT Mice, and WT Mice.

This study is focused on assessing the activation in NK, CD3+ T, and γδ T cells when they interact with osteoclasts (OCs) and monocytes in the presence or absence of zoledronate (ZOL), both in humans and WT mice. OCs resulted in increased IFN-γ secretion in NK, CD3+ T, and γδ T cells, however, the significantly highest increase was seen when cells were co-cultured with ZOL-treated OCs. Our previous studies have demonstrated increased IFN-γ secretion in the peripheral blood-derived immune cells of bisphosphonate-related osteonecrosis of the jaw (BRONJ) mice model.

Incomplete (partial) left anterior hemiblock.

This report describes two electrocardiograms (ECGs) showing unusual manifestations of left anterior hemiblock (LAH). One revealed different degrees of incomplete LAH and the other documented the occurrence of 2:1 LAH. Understanding different degrees of LAH helps to interpret the ECG with regard to intraventricular conduction disorders and other ECG abnormalities.

Characterizing hepatocellular carcinoma stem markers and their corresponding susceptibility to NK-cell based immunotherapy.

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the fourth-leading cause of all cancer-related deaths around the world. Liver transplantation, surgery, and local ablation are curative therapies for early-stage HCC. However, post-treatment outcomes can vary based on histopathologic stage.

Supercharged NK Cell-Based Immuotherapy in Humanized Bone Marrow Liver and Thymus (Hu-BLT) Mice Model of Oral, Pancreatic, Glioblastoma, Hepatic, Melanoma and Ovarian Cancers.

In this paper, we review a number of in vitro and in vivo studies regarding the efficacy of supercharged NK (sNK) cell therapy in elimination or treatment of cancer. We have performed studies using six different types of cancer models of oral, pancreatic, glioblastoma, melanoma, hepatic and ovarian cancers using hu-BLT mice. Our in vitro studies demonstrated that primary NK cells preferentially target cancer stem-like cells (CSCs)/poorly differentiated tumors whereas sNK cells target both CSCs/poorly-differentiated and well-differentiated tumors significantly higher than primary activated NK cells.

The Potential Role of Cytotoxic Immune Effectors in Amyotrophic Lateral Sclerosis (ALS); A Longitudinal Case Study Comparing Patients with Genetically Identical Healthy Twin.

Amyotrophic lateral sclerosis (ALS) is an auto-immune neurodegenerative disorder affecting the motor-neurons. The causes of ALS are heterogeneous, and are only partially understood to date. We studied percentage and function of immune cell subsets in particular natural killer (NK) and CD8+ T cells in an ALS patient and compared the results to those obtained from his genetically identical healthy twin in a longitudinal study.

Regulation of Cytotoxic Immune Effector Function by AJ3 Probiotic Bacteria in Amyotrophic Lateral Sclerosis (ALS).

Our recent studies indicated that amyotrophic lateral sclerosis (ALS) patients suffer from significantly elevated levels of interferon-gamma (IFN-γ) secretion by natural killer (NK) and CD8+ T cells, which may be responsible for the immune-pathologies seen in central nervous system and in peripheral organs of the patients. In order to counter such elevated induction of IFN-γ in patients we designed a treatment strategy to increase anti-inflammatory cytokine interleukin-10 (IL-10) by the use of probiotic strains which significantly increase the levels of IL-10. Therefore, in this paper we demonstrate disease specific functions of Al-Pro (AJ3) formulated for the adjunct treatment of auto-immune diseases including ALS, and compared the function with CA/I-Pro (AJ4) for the treatment of cancer and viral diseases, and NK-CLK (AJ2) for maintenance of immune balance and promotion of disease prevention.

Successes and Challenges in Taming the Beast: Cytotoxic Immune Effectors in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive loss of motor neurons in the brain and spinal cord. No effective therapeutic strategies have been established thus far, and therefore there is a significant unmet need for effective therapeutics to arrest the disease and reverse the pathologies induced by it. Although the cause of ALS is not well-defined, it appears to be heterogenous.

Sequential therapy with supercharged NK cells with either chemotherapy drug cisplatin or anti-PD-1 antibody decreases the tumor size and significantly enhances the NK function in Hu-BLT mice.

Introduction And Methods: In this study we report that sequential treatment of supercharged NK (sNK) cells with either chemotherapeutic drugs or check-point inhibitors eliminate both poorly differentiated and well differentiated tumors in humanized-BLT mice.

Background And Results: sNK cells were found to be a unique population of activated NK cells with genetic, proteomic, and functional attributes that are very different from primary untreated or IL-2 treated NK cells. Furthermore, NK-supernatant differentiated or well-differentiated oral or pancreatic tumor cell lines are not susceptible to IL-2 activated primary NK cell-mediated cytotoxicity; however, they are greatly killed by the CDDP and paclitaxel in in-vitro assays.

Impact of COVID-19 state-wide lockdown on older adult presentations to Queensland emergency departments.

Objective: To determine the impact of the COVID-19 state-wide lockdown on ED presentations for older adults in Queensland, Australia.

Methods: A retrospective cohort study pertaining to adults aged 70+ years who presented to Queensland public hospital EDs across three separate time periods; 11 March to 30 June 2018 and 2019 (pre-pandemic average), 2020 (COVID-19 state-wide lockdown) and 2021 (post-state-wide lockdown). The primary outcome was change in presentation rates to ED.

Transfer status may not be associated with worse outcomes in elderly trauma patients.

Purpose: To compare outcomes of elderly patients who arrive directly to a lead trauma centre to those who are transferred from a peripheral hospital.

Methods: This study used a retrospective cohort design and data obtained from the local trauma registry. The study population was patients 65 years and older who presented with an Injury Severity Score (ISS) of 12 or greater, or for whom the trauma team was activated, over a 10-year period.

Differences in Tumor Growth and Differentiation in NSG and Humanized-BLT Mice; Analysis of Human vs. Humanized-BLT-Derived NK Expansion and Functions.

There is significant interest and debate regarding the best mouse model of human disease, since studies in wild-type mice may not always recapitulate human diseases. The NSG mouse model has been one of the most commonly used mouse models to study cancer; however, this mouse model, even though it has several advantages in regard to the ease of tumor implantation and financial feasibility, does not represent human disease due to the immunodeficient nature of this model. In this study, we performed oral and pancreatic tumor studies in NSG and hu-BLT mice and found several distinguishing features that make hu-BLT model more suitable for studying human cancer.

Editorial for the Special Issue-'HIV Testing, Prevention, and Care Cascade'.

Since the early 1980s, HIV/AIDS has been an ongoing public health concern [...