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Home blood pressure telemonitoring reveals race-specific patterns of target organ damage.

BACKGROUND: Racial differences in cardiac and renal target organ damage (TOD) may persist at comparable blood pressure levels. This study compared TOD in high-risk, non-African-American Black and White patients in relation to the home blood pressure (HBP). METHODS: UPRIGHT-HTM (NCT04299529) is an ongoing international trial comparing risk stratification strategies in asymptomatic patients, aged 55-75 &#x200a;years, with &#x2265;5 risk factors. Patients engage in HBP telemonitoring (OMRON HEM 9210-T). After 34.7&#x200a;months (median), 287 Black and 154 White patients underwent echocardiography. At baseline, their chronic kidney disease (CKD) grade was assessed by cross-classification of the race-free estimated glomerular filtration rate and albuminuria (2024 KDIGO guideline). HBP was stratified by the 2024 ESC thresholds. Linear and logistic regression models, including a race-by-HBP interaction term, were applied to assess associations with the home systolic HBP. RESULTS: The number of HBP readings was 252 215. Median systolic/diastolic HBP was 127/77&#x200a;mmHg with 142 patients (32.2%) having home hypertension. Fewer Black patients received statins or combination therapy for hypertension or diabetes. Among nonhypertensive White compared to Black patients, left atrial dimensions, mitral annular s', and stroke volume had a steeper slope in relation to systolic HBP. All patients had concentric left ventricular remodeling, but only 4 Black and 13 White patients had an ejection fraction&#x200a;<&#x200a;50%. CKD grade was worse in Black than White patients without association with HBP. CONCLUSIONS: TOD primarily affects the kidney in Black and the heart in White patients. Intensifying pharmacological treatment in sub-Saharan Africa, including antihypertensives, lipid-lowering agents, antidiabetic medications, and aspirin, should create an opportunity for improved overall cardiovascular and metabolic prevention.

Aged

Hypertension continuation adherence: natural history and role as an indicator condition.

We analyzed a random sample of general medicine clinic patients to determine the natural history of newly treated hypertensive (NH) patients: discontinuation patterns, critical intervention periods, and hypertension's (HBP) utility as an indicator condition. The NH patients exhibited a 48% dropout rate in the first year and better continuation adherence than new nonhypertensive (NNH) patients. Patients with HBP and other chronic diseases had better continuation adherence than those with HBP alone, although no predictive patterns emerged. New patients displayed rapid early discontinuation, with further linear decline by four months for NNH and by eight months for NH patients. All patients showed similar subsequent falloff: linear annual decline at 13% to 36%. We conclude that discontinuation rates are unacceptably high, that interventions must be continued throughout treatment, and that HBP has limited utility as an indicator chronic disease.

Adult

Further studies on cell-mediated immunity to myelin basic protein in schizophrenic patients.

Cell-mediated immunity (CMI) toward myelin human basic protein (HBP) was studied in 19 chronic drug-free schizophrenic patients and in 30 patients with primary affective disorders receiving psychoactive drugs, 74% of the schizophrenics showed an inhibition of macrophage migration, whereas only one patient from the affective group showed such a response. These results indicate that drugs are not responsible for the appearance of CMI to HBP in schizophrenics. One out of 9 ECT-treated patients developed a CMI to HBP.

Adult

Intracardiac electrography in children and young adults.

The interpretation of IE recorded in children has been hampered by a lack of agreement regarding normal values. We recorded IE in 158 children and young adults (ages, three days to 33 years) to define the various conduction intervals in normal and disease states. The HBP was recorded in 156 subjects. In 85 subjects with normal conduction indicated by surface ECG, including 19 subjects with normal hearts, there were no statistically significant age-related differences in internodal, A-V nodal, or His-Purkinje conduction intervals. Therapeutic levels of digitalis did not alter the conduction intervals. In 11 subjects with first degree A-V block and in five subjects with congenital complete A-V block, the site of block as determined by IE could not be predicted from the surface ECG. No abnormalities in conduction intervals were found in 18 subjects with right bundle branch block (surgically induced in 17 cases). Intracardiac electrography with recording of the HBP was found to be a safe, informative technique for electrophysiologic investigations in children and young adults.

Adolescent

A social-psychological perspective on successful community control of high blood pressure: a review.

This review brings together studies dealing with factors that affect participation in screening, referral, and treatment for high blood pressure (HBP). Community-based screening programs are examined first, in order to describe the changing and the current distribution of hypertensives as "unaware," untreated, treated but uncontrolled, and controlled by treatment. Factors influencing this distribution are examined. Next, data on referral, acceptance of treatment, and staying in treatment are discussed, with a special reference to intervention studies. The review then brings in the broader social science literature on the psychosocial dynamics of health-maintaining and risk-reducing behaviors. The article concludes with an interpretive summary and some suggestions for further action.

Attitude to Health

Isovolumic relaxation time in normal subjects and patients with cardiac disease: comparison of determinations made with echocardiographic techniques and apex cardiography.

Isovolumic relaxation time (IVRT) was determined in 17 controls and 41 patients. Nine patients had ischemic heart disease (IHD), 7 mitral prolapse (MVPS), 13 hypertension (HPB), 7 pregnancy (P), and 5 cardiomyopathy (CM). Echocardiographic measurements of IVRT were made from the aortic second sound to the rapid opening of the mitral valve (A2D1). Determinations by apexcardiography were made from the aortic second sound to the 0 point (A2O). The IVRT was distinctly shorter when assessed by A2D1 than by conventional apexdardiography in conventional apexcardiography in controls (69.2 +/- 16.4 msec vs 118.7 +/- 16.5 msec) and in patients with cardiac disease. The IVRT in 9 older normal controls (mean age 47.7 years) was longer than in 8 younger ones (age 26.3 +/- 4.9 years). Patients with myocardial disease (IHD, HBP, and CM) had prolonged IVRTs when compared to normal subjects. Pregnant subjects had shortened intervals. IVRT may be a sensitive indicator of disturbances in myocardial contractility and may be shortened and enhanced contractility.

Adolescent

Gfa1 (glutamine fructose-6-phosphate aminotransferase) is essential for Aspergillus fumigatus&#xa0;growth and virulence.

BACKGROUND: Aspergillus fumigatus, the primary etiological agent of invasive aspergillosis, causes over 1.8 million deaths annually. Targeting cell wall biosynthetic pathways offers a promising antifungal strategy. Gfa1, a rate-limiting enzyme in UDP-GlcNAc synthesis, plays a pivotal role in the hexosamine biosynthetic pathway (HBP). RESULTS: Deletion of gfa1 (&#x394;gfa1) results in auxotrophy for glucosamine (GlcN) or N-acetylglucosamine (GlcNAc). Under full recovery (FR) conditions, where minimal medium is supplemented with 5&#xa0;mM GlcN as the sole carbon source, the &#x394;gfa1 mutant shows growth comparable to the wild-type (WT). However, when supplemented with 5&#xa0;mM GlcN and 55&#xa0;mM glucose, growth is partially repressed, likely due to carbon catabolite repression, a condition termed partial repression (PR). Under PR conditions, &#x394;gfa1 exhibits compromised growth, reduced conidiation, defective germination, impaired cell wall integrity, and increased sensitivity to endoplasmic reticulum (ER) stress and high temperatures. Additionally, &#x394;gfa1 demonstrates disruptions in protein homeostasis and iron metabolism. Transcriptomic analysis of the mutant under PR conditions reveals significant alterations in carbohydrate and amino acid metabolism, unfolded protein response (UPR) processes, and iron assimilation. Importantly, Gfa1 is essential for A. fumigatus virulence, as demonstrated in Caenorhabditis elegans and Galleria mellonella infection models. CONCLUSIONS: These findings underscore the critical role of Gfa1 in fungal pathogenicity and suggest its potential as a therapeutic target for combating A. fumigatus infections.

Aspergillus fumigatus

Purification of a hexokinase-binding protein from the outer mitochondrial membrane.

Brain hexokinase (ATP:D-hexose-6-phosphotransferase, EC 2.7.1.1) binds selectively to the outer membrane of rat liver mitochondria but not to inner mitochondrial or microsomal membranes nor to the plasma membrane of human erythrocytes. A protein having subunit molecular weight of 31,000, determined by sodium dodecyl sulfate-gel electrophoresis, has been highly purified from the outer mitochondrial membrane by repetitive solubilization with octyl-beta-D-glucopyranoside followed by reconstitution into membranous vesicles when the detergent is removed by dialysis. When incorporated into lipid vesicles, the protein confers the ability to bind brain hexokinase in a Glc-6-P-sensitive manner as is seen with the intact outer mitochondrial membrane. Hexokinase binding ability and the 31,000 subunit molecular weight protein co-sediment during sucrose density gradient centrifugation. Both hexokinase binding ability and the 31,000 subunit molecular weight protein are resistant to protease treatment of the intact outer mitochondrial membrane while other membrane proteins are extensively degraded. It is concluded that this protein, designated the hexokinase-binding protein (HBP), is an integral membrane protein responsible for the selective binding of hexokinase by the outer mitochondrial membrane.

Animals

Early Cardiomyopathy in Prediabetic NDPK-B-Deficient Mice Is Associated with Remodeling of the Mitochondrial O-GlcNAc Proteome.

Diabetic cardiomyopathy (DCM) is characterized by myocardial remodeling that may already be evident during prediabetes, yet the molecular alterations accompanying these early changes remain poorly understood. The present study examined mouse models of Nucleoside diphosphate kinase B (NDPK-B)-deficient prediabetes and streptozotocin-induced diabetes using O-GlcNAc-associated proteomic profiling to define stage-specific molecular alterations during the progression from prediabetic to diabetic cardiomyopathy. Both models exhibited increased left ventricular extracellular matrix deposition and impaired diastolic function, together with activation of the hexosamine biosynthesis pathway. Profiling of O-GlcNAc-associated proteins uncovered extensive remodeling of the mitochondrial proteome already at the prediabetic stage, with respiratory complex I among the most prominently altered targets, alongside changes in substrate metabolism and inflammatory signaling. In overt DCM, the putative O-GlcNAc proteomic profile was associated with a shift toward wider lipid-dependent metabolic reprogramming and remodeling of mitochondrial proteins. These findings identify early remodeling of the mitochondrial O-GlcNAc-associated proteome as a molecular signature of prediabetic cardiomyopathy and highlight respiratory complex I proteins as candidate targets for future mechanistic investigations.

Animals