High-affinity antibodies specific to the core region of the tau protein exhibit diagnostic and therapeutic potential for Alzheimer's disease.

Background: Recent advances in blood-based biomarker discovery are paving the way for simpler, more accessible diagnostic tools that can detect early signs of Alzheimer's disease (AD). Recent successes in the development of amyloid-targeting immunotherapy approaches mark an important advancement in providing new options for the treatment of AD. We have developed a set of high-affinity monoclonal antibodies (mAbs) to tau protein that have the potential as tools for diagnosis and treatment of AD.

Considerations for biomarker strategies in clinical trials investigating tau-targeting therapeutics for Alzheimer's disease.

The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have ensured the correct selection of patients on these trials, supported target engagement and have been used to support claims of disease modification and clinical efficacy. Ultimately, this has recently led to approval of disease-modifying, amyloid-targeting therapies for AD; something that should be noted for clinical trials investigating tau-targeting therapies for AD.

Chromatin- and nucleosome-associated features in liquid biopsy: implications for cancer biomarker discovery.

Cell-free DNA (cfDNA) from the bloodstream has been studied for cancer biomarker discovery, and chromatin-derived epigenetic features have come into the spotlight for their potential to expand clinical applications. Methylation, fragmentation, and nucleosome positioning patterns of cfDNA have previously been shown to reveal epigenomic and inferred transcriptomic information. More recently, histone modifications have emerged as a tool to further identify tumor-specific chromatin variants in plasma.

Closing the miscommunication gap: A user guide to developing picture-based communication tools for Aboriginal and Torres Strait Islander peoples in emergency departments.

Objective: To document an illustration-based methodology for culturally safe communication between Indigenous patients and clinicians in an urban ED.

Methods: We co-designed a pre-ED visual tool to minimise miscommunication when triaging First Nations patients. Our steps included establishing project governance, conducting a literature review, obtaining ethics approval and designing illustrations.

Utility of Blood-Based Tau Biomarkers for Mild Cognitive Impairment and Alzheimer's Disease: Systematic Review and Meta-Analysis.

Objectives: With the development of new technologies capable of detecting low concentrations of Alzheimer's disease (AD) relevant biomarkers, the idea of a blood-based diagnosis of AD is nearing reality. This study aims to consider the evidence of total and phosphorylated tau as blood-based biomarkers for mild cognitive impairment (MCI) and AD when compared to healthy controls.

Methods: Studies published between 1 January 2012 and 1 May 2021 (Embase and MEDLINE databases) measuring plasma/serum levels of tau in AD, MCI, and control cohorts were screened for eligibility, including quality and bias assessment via a modified QUADAS.

Understanding experiences of Aboriginal and/or Torres Strait Islander patients at the emergency departments in Australia.

Objectives: The present study describes the experiences of Aboriginal and/or Torres Strait Islander patients and the factors that shaped their experiences of ED visits in regional settings.

Methods: This is a qualitative descriptive study. We conducted semi-structured in-depth interviews with Aboriginal and/or Torres Strait Islander patients who used the ED services at three hospitals in New South Wales, Northern Territory and South Australia.

Closing the Equity Gap: An Intervention to Improve Chlamydia and Gonorrhea Testing for Adolescents and Young Adults in Primary Care.

Background: and are the most reported sexually transmitted infections in the United States. Testing rates remain suboptimal and may be subject to implicit bias. We evaluated the effectiveness of an opt-out chlamydia and gonorrhea testing program for adolescents and young adults in improving testing rates and promoting equity.

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

Background: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel.

Laboratory Structure And Resource: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists.

An Intervention to Improve Chlamydia and Gonorrhea Testing Among Adolescents in Primary Care.

Background And Objectives: Rates of chlamydia and gonorrhea among adolescents continue to rise. We aimed to evaluate if a universal testing program for chlamydia and gonorrhea improved testing rates in an urban general pediatric clinic and an urban family medicine clinic within a system of federally qualified health care centers and evaluated the feasibility, cost, and logistic challenges of expanding implementation across 28 primary care clinics within a federally qualified health care centers system.

Methods: A universal testing quality improvement program for male and female patient 14 to 18 years old was implemented in a general pediatrics and family medicine clinic in Denver, Colorado.

Global seroprevalence of SARS-CoV-2 antibodies: A systematic review and meta-analysis.

Background: Many studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making.

Methods: In this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020.

Coiling directions in the planktonic foraminifer Pulleniatina: A complex eco-evolutionary dynamic spanning millions of years.

Planktonic foraminifera are heterotrophic sexually reproducing marine protists with an exceptionally complete fossil record that provides unique insights into long-term patterns and processes of evolution. Populations often exhibit strong biases towards either right (dextral) or left (sinistral) shells. Deep-sea sediment cores spanning millions of years reveal that some species show large and often rapid fluctuations in their dominant coiling direction through time.

Current Progress and Future Directions for Tau-Based Fluid Biomarker Diagnostics in Alzheimer's Disease.

Despite continued efforts, there remain no disease-modifying drugs approved by the United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) to combat the global epidemic of Alzheimer's disease. Currently approved medicines are unable to delay disease progression and are limited to symptomatic treatment. It is well established that the pathophysiology of this disease remains clinically silent for decades prior to symptomatic clinical decline.

Neurological rehabilitation following heat illness in the UK Armed Forces.

Heat illness remains a significant threat to health in the UK Armed Forces despite recent improvements in the prevention of cases. A small number of heat illness survivors develop long-term neurological sequelae. Here we briefly review the background literature and present our experience of treating UK Armed Forces patients with neurological consequences of heat illness.

Gonorrhea and Chlamydia Rates Among 12- to 24-Year-Old Patients in an Urban Health System.

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection rates continue to rise. Screening guidelines have largely focused on sexually active female individuals and men who have sex with men populations. Health care system testing and infection rates, particularly among heterosexual male individuals, are poorly understood.

The challenges for cancer chemoprevention.

The incidence of cancer is rising in parallel with an ageing populous thus increasing the strain on both treatment options and budgets for healthcare providers worldwide. New cancer therapies are being developed but at what cost? The new treatments are expensive and poor survival rates still exist for some cancers. What is needed now is to prevent or at least limit the disease occurring in the first place.

Quiescence of Memory CD8(+) T Cells Is Mediated by Regulatory T Cells through Inhibitory Receptor CTLA-4.

Immune memory cells are poised to rapidly expand and elaborate effector functions upon reinfection yet exist in a functionally quiescent state. The paradigm is that memory T cells remain inactive due to lack of T cell receptor (TCR) stimuli. Here, we report that regulatory T (Treg) cells orchestrate memory T cell quiescence by suppressing effector and proliferation programs through inhibitory receptor, cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4).

Vitamin D receptor signals regulate effector and memory CD8 T cell responses to infections in mice.

Background: Vitamin D insufficiency is associated with broad-ranging human disease sequelae such as bone disease, cancer, cardiovascular disease, allergy, autoimmune disorders, diabetes, and infectious diseases. Disease risk and severity of a large proportion of the nonskeletal disorders heavily involve the cytotoxic cluster of differentiation (CD) 8 T lymphocyte (CTL) arm of cellular adaptive immunity. Considering the importance of vitamin D in CTL-dependent diseases, there is a critical need for systematic in-depth explorations into the role of vitamin D deficiency in generation and maintenance of CTL immunity during infections and vaccinations.

MicroRNA-17~92 regulates effector and memory CD8 T-cell fates by modulating proliferation in response to infections.

The precise microRNAs and their target cellular processes involved in generation of durable T-cell immunity remain undefined. Here we show a dynamic regulation of microRNAs as CD8 T cells differentiate from naïve to effector and memory states, with short-lived effectors transiently expressing higher levels of oncogenic miR-17-92 compared with the relatively less proliferating memory-fated effectors. Conditional CD8 T-cell-intrinsic gain or loss of expression of miR-17-92 in mature cells after activation resulted in striking reciprocal effects compared with wild-type counterparts in the same infection milieu-miR-17-92 deletion resulted in lesser proliferation of antigen-specific cells during primary expansion while favoring enhanced IL-7Rα and Bcl-2 expression and multicytokine polyfunctionality; in contrast, constitutive expression of miR-17-92 promoted terminal effector differentiation, with decreased formation of polyfunctional lymphoid memory cells.

Microfluidic strategies applied to biomarker discovery and validation for multivariate diagnostics.

Complex diseases are caused by combinatorial genetic, environmental and lifestyle factors. The emergence of multibiomarker tests to define these diseases and to identify the early, presymptomatic stages offers several advantages to the conventional use of single marker tests. The development of multibiomarker protein-based tests remains constrained by technological and operational limitations in assaying hundreds to thousands of proteins in thousands of samples.

The impact of tailored diabetes registry report cards on measures of disease control: a nested randomized trial.

Background: Most studies of diabetes self-management that show improved clinical outcome performance involve multiple, time-intensive educational sessions in a group format. Most provider performance feedback interventions do not improve intermediate outcomes, yet lack targeted, patient-level feedback.

Methods: 5,457 low-income adults with diabetes at eight federally-qualified community health centers participated in this nested randomized trial.

Admission intervention team: medical center based intensive case management of the seriously mentally ill.

The purpose of this study was to investigate the effect a medical center based intensive case management team had on utilization of inpatient psychiatric treatment. A frequent user of inpatient psychiatric hospitalization was defined as any patient who had 3 or more admissions during the 12 months prior to referral to the program. A within-subjects design was used comparing rates of hospital admissions and hospital days before and after program enrollment for 185 patients in the program for 1 year, and for 50 of those patients in the program for 7 years.