Deciphering the role of the MALT1-RC3H1 axis in regulating GPX4 protein stability.

Ferroptosis, a unique form of iron-dependent cell death triggered by lipid peroxidation accumulation, holds great promise for cancer therapy. Despite the crucial role of GPX4 in regulating ferroptosis, our understanding of GPX4 protein regulation remains limited. Through FACS-based genome-wide CRISPR screening, we identified MALT1 as a regulator of GPX4 protein.

Combined inhibition of class 1-PI3K-alpha and delta isoforms causes senolysis by inducing p21 proteasomal degradation in senescent cells.

The targeted elimination of radio- or chemotherapy-induced senescent cells by so-called senolytic substances represents a promising approach to reduce tumor relapse as well as therapeutic side effects such as fibrosis. We screened an in-house library of 178 substances derived from marine sponges, endophytic fungi, and higher plants, and determined their senolytic activities towards DNA damage-induced senescent HCT116 colon carcinoma cells. The Pan-PI3K-inhibitor wortmannin and its clinical derivative, PX-866, were identified to act as senolytics.

Exploring Patients' and Chaplains' Perspectives About a Spiritual Care Program in the Primary Care Setting.

Background: Spirituality is an important component of social and cultural identity that influences health-related beliefs, decision-making, and coping behaviors. Despite the importance of addressing spirituality in healthcare, research about its impact is limited, especially in the primary care setting.

Objective: This study aimed to explore patients' and chaplains' experiences of receiving or providing spiritual care in the primary care setting.

Network medicine-based epistasis detection in complex diseases: ready for quantum computing.

Most heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs). Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs.

CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1.

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear.

Adaptation of a Human Diagnostic Kit to Detect Dengue, Zika, and Chikungunya Viruses in Mosquito Samples ( and ): A Contribution to Public Health in the International Triple Border (Brazil, Paraguay, and Argentina).

The objective of this work was to adapt a diagnostic kit developed for humans to identify Dengue (DENV1, DENV2, DENV3, DENV4), Zika (ZIKV) and Chikungunya virus (CHIKV) in females of and and to verify if the occurrence of mosquitoes infected with these three arboviruses are being found in regions with high occurrence of these diseases in humans. For this purpose, live mosquitoes were captured between January and June 2020 using 3,476 traps permanently installed in the field were used. After capture, the species were identified, then the females were placed in a pool of 2 to 10 specimens and sent to the laboratory for detection of DENV1, DENV2, DENV3, DENV4, ZIKV and CHIKV by RT-PCR using a commercial human kit for arboviruses.

Tiger salamanders' (Ambystoma tigrinum) response retention and usage of visual cues following brumation.

Brumation enables tiger salamanders (Ambystoma tigrinum) to survive changes in temperature. However, it is unclear how this affects memory retention. We explored how brumation impacted salamanders' retention of a learned response to a visual cue through two experiments.

Tiger salamanders' (Ambystoma tigrinum) response learning and usage of visual cues.

We explored tiger salamanders' (Ambystoma tigrinum) learning to execute a response within a maze as proximal visual cue conditions varied. In Experiment 1, salamanders learned to turn consistently in a T-maze for reinforcement before the maze was rotated. All learned the initial task and executed the trained turn during test, suggesting that they learned to demonstrate the reinforced response during training and continued to perform it during test.

Evaluation of health literacy tools for correct prescription understanding.

Objectives: To evaluate two brief health literacy prediction tools for understanding of a prescription label and using a drug correctly.

Methods: Patients who visited the Family HealthCare Pharmacy were asked to complete the Newest Vital Sign (NVS) and Rapid Estimate of Adult Literacy in Medicine (REALM-R) and to interpret a prescription medication label. Each patient received a bottle of amoxicillin suspension with one of four prescription labels randomly varied in directions for frequency and amount.

Transabdominal uterosacral suspension: outcomes and complications.

Objective: The objective of the study was to report outcomes and complications following abdominal uterosacral suspension (AUSS) for treatment of pelvic organ prolapse.

Study Design: This was a surgical case series of consecutive women who underwent AUSS between 2002 and 2005.

Results: One hundred seven women underwent AUSS using permanent suture (mean age, 55 years; range, 32-83; and mean follow-up, 21; range, 3-74 months).

The seventh prototype of the mini-spindle-pump: does it fulfill the expectations of a short-term pump?

According to recent trends to develop implantable nonpulsatile blood pumps for different function modes and times, our intention was and still is to build a Mini-Spindle-Pump for a pumping duration of about 14 days. Initial conception for this plan was the premise that the device in a mock circuit should move 4 L of water/min at a speed of 12,000 to 15,000 rpm against a pressure difference of 90 mm Hg between pump inlet and outlet. Despite the development of 6 different prototypes, this project was not realized.

Considerations and problems in the development of the mini-spindle pump.

The premise for the development of the mini-spindle pump, planned as an implantable device for assisted circulation, was to transport 4 L of water/min in mock circulation with a speed of 12-15,000 rpm against an afterload of 90 mm Hg. After calculations, the resulting first prototype had a spindle rotor with 3 threads (outer diameter, 18 mm; inner diameter, 6.2 mm; length, 45 mm) in a U-shaped housing, driven by an electric motor with a cooling system.

Self-reports of memory problems in relatives of patients with probable Alzheimer's disease.

This study examined the relationship between subjective memory complaints and performance on tests of memory by relatives of patients with probable Alzheimer's disease (AD) and by older adults without a family history of dementia. Relatives of AD patients did not differ significantly from controls either in level of complaint or in performance on neuropsychological tests. However, among relatives of patients with early-onset AD, significant correlations were found between performance on memory tests and self-rated changes in everyday memory.

Depression, cognition, and functional ability in patients with Alzheimer's disease.

Objective: To investigate the relationship of depression to functional and cognitive impairment in patients with Alzheimer's disease (AD).

Design: Clinic-based study comparing AD patients with and without depression.

Setting: Geriatric outpatient clinic at the University of Washington Medical Center, Seattle, WA.

Hooper Visual Organization Test performance in lateralized brain injury.

The Hooper Visual Organization Test (VOT) is frequently used in measuring the cognitive functioning of brain-damaged patients. It is not clear, however, whether the VOT measures general or specific neurological dysfunction, specifically those resulting from right parietal lesions. The present study addressed this issue by examining archival data from 41 brain-damaged patients who were seen in a medical hospital's acute rehabilitation unit.

Effect of dietary potassium on blood pressure, renal function, muscle sympathetic nerve activity, and forearm vascular resistance and flow in normotensive and borderline hypertensive humans.

We evaluated the effect of a low potassium diet on blood pressure in normotensive (NT) and in borderline hypertensive subjects (BHT). There were 11 BHT men (age, 24.6 +/- 1.

Dietary salt produces abnormal renal vasoconstrictor responses to upright posture in borderline hypertensive subjects.

We studied the effect of high and low NaCl diets in normotensive and borderline hypertensive subjects to determine if a high NaCl diet produces abnormal renal vasoconstriction during the stress of upright posture in borderline hypertensive subjects. We studied 13 normotensive young men with diastolic blood pressures below 85 mm Hg and nine borderline hypertensive young men defined by diastolic blood pressures intermittently above 90 mm Hg. The subjects achieved comparable sodium balance during 6 days of low NaCl (10 mEq Na, 40 mEq Cl, 100 mEq K) and high NaCl (400 mEq Na, 400 mEq Cl, 100 mEq K) diets.

Can dropout and other noncompliance be minimized in a clinical trial? Report from the Veterans Administrative National Heart, Lung and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

Long-term clinical trials must face the problem of participants who drop out before the study is closed or who in other ways do not comply with the protocol. In a joint Veterans Administration-National Heart, Lung and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups and followed for up to 30 months. The data were analyzed for factors related to dropout and to medication and visit noncompliance.

Long-term treatment of Hypertension with methyldopa. II. Therapeutic efficacy.

Efficacy and dosage data were analyzed for patients who received methyldopa up to 4.5 years. A prompt initial response to methyldopa was observed, and the blood pressure reduction was maintained throughout the follow-up period.

Abnormal urinary kallikrein in hypertension is not related to aldosterone or plasma renin activity.

The relationships between urinary kallikrein (Ukal), and plasma renin activity (PRA), urinary aldosterone (Ualdo), Na+ balance, SK+, and renal function were studied in essential hypertensives (EHT) and normals. Ukal was measured by a radiochemical esterolytic assay. We studied 18 white patients with EHT (15 men, 3 women) ages 31.

Serum lipoprotein levels during chlorthalidone therapy. A Veterans Administration-National Heart, Lung, and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

In a joint Veterans Administration-National Heart, Lung, and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age and with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups. Subjects in the active group received chlorthalidone or chlorthalidone plus reserpine, while the other subjects received matching placebo tablets. After one year of treatment, the chlorthalidone group had increases of 10.

Urinary kallikrein in postobstructive diuresis.

We studied urinary kallikrein excretion in the rat during unilateral release of 24-hr bilateral ureteral ligation (BUL). In six rats studied after 24 hr of BUL, the glomerular filtration rate was 20 per cent of that in the five sham-operated controls. In the BUL group, the urine flow rate was 5 fold greater, fractional sodium excretion 100 times greater, and fractional potassium excretion 5 times greater than in controls.