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Parkinson's disease is a progressive neurodegenerative disorder with an unclear etiology and a long preclinical phase. The multitude of challenges of studying this in humans highlight the need for robust preclinical animal models that accurately reflect the disease's preclinical progression. While traditional neurotoxin models fail to capture the slow, genetic nature of PD, genetic models, such as the phosphatase and tensin homolog-induced putative kinase 1 (Pink1-/-) knockout rat, offer a preclinical, translational approach. This review synthesizes the current understanding of the Pink1-/- rat model, focusing on two key aspects: neuroinflammation and vocalization deficits. The Pink1-/- rat presents early non-motor symptoms, including vocalization deficits, which can serve as a non-invasive, objective, and longitudinal biomarker of disease progression. This review further proposes a direct link between the model's neuroinflammatory profile, characterized by chronic glial activation and the upregulation of inflammatory pathways, and the observed vocal dysfunctions. By bridging these two critical areas, neuroinflammation as a pathological mechanism and vocalizations as a functional readout, this review provides a framework for future investigations into the diagnosis and treatment of Parkinson's disease and suggests that targeting specific inflammatory pathways could be a viable therapeutic strategy.

Adult diffuse gliomas are primary brain tumors notorious for leading to devastating neurologic consequences from both tumor progression and therapeutic interventions. The arsenal of current established treatments primarily includes surgery, radiotherapy, and DNA alkylating chemotherapy agents. Unfortunately, even with aggressive treatments, long-term cure is typically not attainable, except in certain cases of low-grade gliomas amenable to complete surgical resection. Grade 4 glioblastoma (GBM) represents the most aggressive and most common type of glioma in adults, is often resistant to current therapies, and is associated with a median survival of approximately 15 months. While biomarker-based therapies for gliomas are limited, O6-methylguanine-DNA methyltransferase (MGMT) is one well-established prognostic marker in GBM and is associated with improved response to the alkylating agent temozolomide (TMZ). Methylation of the MGMT promoter leading to loss of MGMT expression occurs in approximately half of GBMs and 70-80% of anaplastic and low-grade gliomas. While MGMT promoter-methylated gliomas are responsive to TMZ, a characteristic resistance mechanism of mismatch repair loss often emerges, resulting in recurrent drug-resistant disease. In prior work, we identified a new TMZ derivative "KL-50" which overcomes resistance to TMZ driven by loss of mismatch repair in preclinical glioma models. KL-50 functions via a novel DNA-modifying mechanism involving evolution of a primary alkyl lesion to a DNA interstrand crosslink specifically in the absence of MGMT. Research is ongoing to establish this new class of agents as a potential improved therapy in human gliomas. In this review, we provide an overview of the history and evolution of alkylator use in GBM, discuss the mechanisms and pitfalls of current therapies including toxicity or susceptibility to resistance mechanisms, and present the potential of a new wave of DNA modifiers to improve outcomes in gliomas.

Background: The causes of individual headache attacks are commonly sought, yet the multiple potential influences make this task difficult. Information theory provides a framework for addressing this challenge by quantifying how unexpected an exposure is through surprisal. Prior research has shown that higher surprisal scores predict migraine onset, but the extent to which this relationship generalizes to tension-type headache remains unknown.

Aims: This study aimed to determine whether surprisal is associated with incident tension-type headache attacks among individuals with episodic migraine.

Methods: This secondary analysis proceeded from a prospective daily diary study in which 109 participants with migraine recorded potential triggers, headache activity, and symptoms twice daily for up to 28 days. Surprisal values were computed from person-specific probability distributions of diary responses, aggregated to yield average surprisal scores per diary entry. Associations between current surprisal and the onset of headache attacks within 12- and 24-hour intervals were evaluated. Analyses were conducted for all headaches combined and separately for migraine-only and tension-type headache-only attack sets.

Results: Headache attacks occurred in 1,345 of 4,530 (29.7%) of 12-hour and 2,122 of 4,947 (42.9%) of 24-hour windows. Stratified analyses showed a strong association for migraine attacks, OR: 2.18 (95%CI: 1.15 - 4.14) at 12 hours and OR: 2.88 (95%CI: 1.77 - 4.69) at 24 hours. In contrast, associations with tension-type headache were weak and nonsignificant, OR: 1.01 (95%CI: 0.45 - 2.23) at 12 hours and OR: 1.40 (95%CI: 0.69 -2.86) at 24 hours. Exploratory nonlinear and contextual analyses within the tension-type headache subset revealed no consistent gradients or effect modification by prior-day surprisal.

Conclusions: Surprisal was associated with migraine but not tension-type headache attacks in this cohort. These findings suggest that migraine may be more sensitive to contextual unpredictability in the environment than tension-type headache. Future research should examine surprisal in populations with primary tension-type headache diagnoses to clarify whether the absence of association reflects true diagnostic differences or misclassification of attacks.

Despite decades of research, survival rates following cardiac arrest remain dismal. The recent use of pressure-volume (PV) loop analysis has provided important insights into the underlying physiology of cardiopulmonary resuscitation (CPR). During conventional CPR (C-CPR), ventricular ejection is limited, contributing to poor circulatory effectiveness. In contrast, automated head-up CPR (AHUP-CPR)-which combines active compression-decompression (ACD) CPR, an impedance threshold device (ITD), and controlled head-thorax elevation-generates favorable negative intrathoracic pressure, promoting cerebral venous drainage and increases right heart preload, resulting in enhanced stroke volume, cardiac output, and end-tidal CO₂ (ETCO₂) by improving ventricular-pulmonary-arterial circulation. This article summarizes recent advances related to AHUP-CPR with a focus on novel physiological findings derived from intraventricular conductance catheter recordings during ventricular fibrillation, C-CPR, and AHUP-CPR. The PV loop observations shed new light on the mechanisms through which AHUP-CPR improves circulatory efficiency and neurological outcomes.

Purpose: Previous studies have suggested that minimally invasive peripheral venous and arterial pressure waveforms provide a greater ability to detect acute changes in blood volume than traditional vital signs. Many of these studies are using Fast Fourier Transforms and power spectral densities to evaluate changes in the power at the heart rate frequency. Using the frequency domain requires a segment of the time domain to be converted into the frequency domain, which means that the heart rate derived from frequency domain analysis is an average of the segment used. However, in clinical settings the heart rate is changing continuously.

Methods: This study evaluates the changing heart rate frequency power under varying time segments and compares the heart rate obtained from Fast Fourier Transform and power spectral density analysis with the instantaneous heart rate to gain a better insight into how a changing heart rate may influence the heart rate frequency power.

Results: Spectral analysis revealed non-linear trends in heart rate frequency power, with changes that correspond to changes in the heart rate. We found the time segment chosen and the absolute difference between the instantaneous heart rate and the average heart rate obtained from power spectral density analysis influences the heart rate frequency power, such that as the instantaneous heart rate approaches the average heart rate, the heart rate frequency power increases.

Conclusion: These results suggest that the time segment chosen for frequency domain analysis influences the power spectrum of the pressure waveforms. Furthermore, this study emphasizes the importance of utilizing a continuously changing heart rate in pressure waveform analysis.

Background: In low and middle-income countries, nine out of every ten persons is unable to access safe and timely surgery. The limited perioperative data in resource-limited settings compromises surgical and research capacity growth. By increasing data availability, surgical disparities may be addressed through research efforts and quality initiatives. This project aimed to implement and evaluate a perioperative registry in a tertiary care hospital in a low-income country.

Methods: A prospective emergency laparotomy perioperative registry was implemented in Zambia's largest teaching and referral hospital. Over the first 6-months of implementation, 162 patients were included. Data was collected postoperatively, before discharge, and at 30 days. The registries feasibility was assessed by evaluating patient accrual, retention, and 30-day completion rates. The registries fidelity was measured by evaluating data missingness. A participant acceptance survey was retrospectively collected and analyzed for the first 25 consecutively enrolled patients.

Results: The capture rate of the registry could not be calculated due to a destroyed theatre logbook. The participant accrual and retention rates were 99.4% and 95.1%, respectively. The participant completion rate at 30-days was 75.6%. The overall incidence of missing information in the registry was 3.5%. More than 75% of participant responses to the acceptance survey were positive in each category regarding the ethical conduct of research and the storing of personal data.

Conclusion: The value of this study is the reporting and evaluation of a successful perioperative registry implementation with minimal external funding. This framework is being used to develop new data registries and may provide a roadmap for other hospitals with resource constraints.

Background: For the past century, the Wiggers Diagram has been universally taught as defining the phases of the cardiac cycle. However, the concepts underlying this diagram have never been fully and directly tested on intact, beating hearts.

Methods: In vivo datasets from sheep recorded left ventricular and aortic pressures and flows along with simultaneous 4-D coordinates of 30 miniature strategically placed radiopaque markers. This allowed hemodynamic synchronization with tracking of key anatomical landmarks every 16.7 msec to test Wiggers' concepts.

Results: The Wiggers Diagram is not supported as there were no consistent isovolumic periods; the mitral valve closed anywhere during the rising phase of left ventricular pressure, and aortic valve closure and mitral valve opening were simultaneous at the end of the systolic pressure drop.

Conclusions: The Wiggers Diagram describes valve opening and closing solely in terms of pressure differences which can be transmitted almost instantaneously through incompressible blood in the ventricle. However, pressure differences do not open and close the valves; it is inertial flow through the valves. The present study redefines the description of the interaction between the left ventricle and its valves and shows that the periods of isovolumic contraction and relaxation are mythical concepts.

Background: The initial response to hemorrhage is mediated by the autonomic nervous system. A method for detecting autonomic nervous system activity may provide the ability to detect acute changes in blood volume. Previous work has indicated that heart rate variability may be able to detect acute hemorrhage in a porcine model. This study evaluates the ability of pulse rate variability, used as a surrogate for heart rate variability, and obtained from peripheral arterial pressure waveforms, to detect hemorrhage in a porcine model.

Methods: Using a model consisting of four subjects, peripheral arterial pressure waveforms were collected over 15-minute intervals before, during, and after hemorrhage. Percent changes for pulse rate variability metrics were evaluated for the 15-minute signals. These longer signals were subsequently divided into three 5-minute signals for short term pulse rate variability analysis. A One-Way Analysis of Variance with a significance level of 0.05 was used to evaluate the sensitivity of pulse rate variability metrics for detecting hemorrhage.

Results: At the onset of hemorrhage, an increase in standard deviation, root mean squared error, low frequency power, high frequency power, total power, and the ratio of low to high frequency power was observed, followed by an opposing decrease at the conclusion of hemorrhage. The low frequency power and the ratio of low to high frequency power had the greatest sensitivity to detecting changes in hemorrhage levels.

Conclusion: These results suggest that pulse rate variability metrics obtained from arterial pressure waveforms have the potential to serve as a diagnostic method for acute hemorrhage.

Our recent study demonstrated that immunizations with nonreplicable MC38 colorectal cancer cells plus a novel recombinant protein adjuvant, the amino-terminus region of dense granule protein 6 (rGRA6Nt) of Toxoplasma gondii (a protozoan parasite), effectively activate the cancer cell-specific CD8⁺ T cytotoxic cells and inhibit the growth of implanted tumors of the identical cancer cells after its challenge implantation. In the present study, we first examined whether rGRA6Nt activates mRNA expression for IFN-γ, IL-12, IL-15, and IL-18, which are known to assist an activation of the CD8⁺ T cells, in innate immune cells. Following an intraperitoneal injection of rGRA6Nt (40 μg) into SCID mice deficient in both T and B cells, markedly increased levels of mRNA for only IFN-γ and IL-18 were detected in their peritoneal exudate innate immune cells. When C57BL/6 mice were immunized with nonreplicable MC38 colorectal cancer cells plus rGRA6Nt adjuvant twice and challenged with replication-capable cancer cells of the identical colorectal cancer, more than one fifth (22.2%, 6/27) of the immunized mice rejected the growth of the implanted tumors, whereas none (0/27, P<0.05) of unimmunized control mice rejected the implanted tumors. These results indicate that rGRA6Nt protein adjuvant has a unique capability to selectively activate expression of IFN-γ and IL-18 in innate immune cells, and that immunizations with nonreplicable cancer cells in combination with this protein adjuvant can induce a protection to reject the growth of the identical tumor cells after its challenge implantation in a significant portion of the immunized mice.

Background: There is a wide-reaching consensus that health should be a priority in national development plans. This is why the Sustainable Development Goal (SDG) 3 is aimed at securing good health for all. If the SDG 3 is to be a reality, there is a need to consider alternatives to the present traditional health system in sub-Saharan African countries. The implementation of health informatics, which is currently the focus of attention in the health sector, presents a huge opportunity with the potential to revolutionize the health systems of developing nations, particularly those in sub-Saharan Africa. In addition to reducing child mortality and infant death rates, providing high-quality healthcare in the region will help combat the challenges posed by preventable diseases and premature deaths that affect many sub-Saharan countries. Ensuring the quality of healthcare also depends on improving information quality, as accurate, timely, and reliable data are essential for effective decision-making and patient care. If the Sustainable Development Goals (SDG) is to be achieved, this issue must be addressed.

Methods: This study reviews research on health information systems in sub-Saharan Africa. The search used medical databases (PubMed and Scopus) and found articles with keywords like "health," "information," "Africa," and "informatics." It also focused on both benefits and challenges of digital health systems in sub-Saharan Africa. The articles were categorized into health information's potential benefits, its application, and barriers and opportunities to set up these systems. This review summarizes the current state of health technology in sub-Saharan Africa, identifies key trends and research gaps, and provides useful insights for health workers, governments, and NGOs.

Results: Studies show that health informatics implementation in sub-Saharan Africa is still far behind where it should be. This analysis uncovers challenges in the deployment of health informatics into the health sector. It identifies infrastructure as well as other limitations and how they can be overcome to help enable the realization of quality healthcare in the region. This will improve the quality of healthcare information, helping to facilitate effective healthcare delivery. Documenting the insufficient current status of healthcare informatics in the health sectors of SSA countries' health systems helps to highlight the potential contribution that informatics can make to health care in the region.

Conclusion: The findings help provide a baseline of current knowledge to support efforts to implement health informatics in sub-Saharan Africa.