Clinical effectiveness of orange peel polymethoxy-flavonoids rich fraction as a palatal dressing material compared to Alveogyl: randomized clinical trial.

This study assessed the clinical effectiveness of orange peel polymethoxy-flavonoids rich fraction (OPMF) solid dispersion as a palatal dressing material, compared with Alveogyl, in a randomized clinical trial. After harvesting free gingival grafts for 18 patients in three groups, the donor site in group I received OPMF; group II received Alveogyl; and group III received placebo dough material. The visual analog scale (VAS) pain score in group I showed the lowest value in week one without a significant difference. In week 2, there was a substantial decrease in pain in group I compared to group III. Week 4 showed reduced pain scores in all groups without significant differences. The results of the number of analgesic pills revealed, after 1 week, the lowest number of pills consumed in group I, with a considerable difference compared to group III. Healing process results showed that group I had the highest healing values in each interval, with a significant difference between group I and group III at 1 and 2 weeks. Color matching parameter showed slight differences between the groups' readings in favor of group I in all intervals without a statistically significant difference. The results suggest OPMF as a palatal dressing material that facilitates hemostasis, pain relief, and palatal wound healing.

Impact of porous microsponges in minimizing myotoxic side effects of simvastatin.

Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV microsponges that have the potential to minimize the myotoxicity accompanying the oral administration of the drug. SV microsponges were prepared by exploiting the emulsion solvent evaporation technique. The % entrapment efficiency (%EE) of the drug approached 82.54 ± 1.27%, the mean particle size of SV microsponges ranged from 53.80 ± 6.35 to 86.03 ± 4.79 µm in diameter, and the % cumulative drug release (%CDR) of SV from microsponges was significantly higher than that from free drug dispersion much more, the specific surface area of the optimized microsponges formulation was found to be 16.6 m2/g revealed the porosity of prepared microsponges. Histological and glycogen histochemical studies in the skeletal muscles of male albino rats revealed that microsponges were safer than free SV in minimizing myotoxicity. These findings were proven by Gene expression of Mitochondrial fusion and fission (Mfn1) & (Fis1) and (Peroxisome proliferator-activated receptor gamma co-activator 1α) PGC-1α. Finally, our study ascertained that SV microsponges significantly decreased the myotoxicity of SV.

Histologic and proteomic remodeling of the pulmonary veins and arteries in a porcine model of chronic pulmonary venous hypertension.

AIMS: In heart failure (HF), pulmonary venous hypertension (PVH) produces pulmonary hypertension (PH) with remodeling of pulmonary veins (PV) and arteries (PA). In a porcine PVH model, we performed proteomic-based bioinformatics to investigate unique pathophysiologic mechanisms mediating PA and PV remodeling. METHODS AND RESULTS: Large PV were banded (PVH, n = 10) or not (Sham, n = 9) in piglets. At sacrifice, PV and PA were perfusion labelled for vessel-specific histology and proteomics. The PA and PV were separately sampled with laser-capture micro-dissection for mass spectrometry. Pulmonary vascular resistance [Wood Units; 8.6 (95% confidence interval: 6.3, 12.3) vs. 2.0 (1.7, 2.3)] and PA [19.9 (standard error of mean, 1.1) vs. 10.3 (1.1)] and PV [14.2 (1.2) vs. 7.6 (1.1)] wall thickness/external diameter (%) were increased in PVH (P < 0.05 for all). Similar numbers of proteins were identified in PA (2093) and PV (2085) with 94% overlap, but biological processes differed. There were more differentially expressed proteins (287 vs. 161), altered canonical pathways (17 vs. 3), and predicted upstream regulators (PUSR; 22 vs. 6) in PV than PA. In PA and PV, bioinformatics indicated activation of the integrated stress response and mammalian target of rapamycin signalling with dysregulated growth. In PV, there was also activation of Rho/Rho-kinase signalling with decreased actin cytoskeletal signalling and altered tight and adherens junctions, ephrin B, and caveolae-mediated endocytosis signalling; all indicating disrupted endothelial barrier function. Indeed, protein biomarkers and the top PUSR in PV (transforming growth factor-beta) suggested endothelial to mesenchymal transition in PV. Findings were similar in human autopsy specimens. CONCLUSION: These findings provide new therapeutic targets to oppose pulmonary vascular remodeling in HF-related PH.

Using a Machine Learning Algorithm to Predict Online Patient Portal Utilization: A Patient Engagement Study.

Objective: There is a low rate of online patient portal utilization in the U.S. This study aimed to utilize a machine learning approach to predict access to online medical records through a patient portal. Methods: This is a cross-sectional predictive machine learning algorithm-based study of Health Information National Trends datasets (Cycles 1 and 2; 2017-2018 samples). Survey respondents were U.S. adults (≥18 years old). The primary outcome was a binary variable indicating that the patient had or had not accessed online medical records in the previous 12 months. We analyzed a subset of independent variables using k-means clustering with replicate samples. A cross-validated random forest-based algorithm was utilized to select features for a Cycle 1 split training sample. A logistic regression and an evolved decision tree were trained on the rest of the Cycle 1 training sample. The Cycle 1 test sample and Cycle 2 data were used to benchmark algorithm performance. Results: Lack of access to online systems was less of a barrier to online medical records in 2018 (14%) compared to 2017 (26%). Patients accessed medical records to refill medicines and message primary care providers more frequently in 2018 (45%) than in 2017 (25%). Discussion: Privacy concerns, portal knowledge, and conversations between primary care providers and patients predict portal access. Conclusion: Methods described here may be employed to personalize methods of patient engagement during new patient registration.

Confirmation of Cause of Death Via Comprehensive Autopsy and Whole Exome Molecular Sequencing in People With Epilepsy and Sudden Unexpected Death.

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. Methods and Results Mayo Clinic Sudden Death Registry containing cases (ages 0-90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non-SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2. Conclusions This study examined one of the largest single-center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A; postmortem whole exome sequencing identified 18 ultrarare variants.

Prevalence of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction.

Importance: Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized. Objective: To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening. Design, Setting, and Participants: This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort). Exposures: Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis. Main Outcomes and Measures: The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex. Results: A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002). Conclusions and Relevance: In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.

Frataxin deficiency promotes endothelial senescence in pulmonary hypertension.

The dynamic regulation of endothelial pathophenotypes in pulmonary hypertension (PH) remains undefined. Cellular senescence is linked to PH with intracardiac shunts; however, its regulation across PH subtypes is unknown. Since endothelial deficiency of iron-sulfur (Fe-S) clusters is pathogenic in PH, we hypothesized that a Fe-S biogenesis protein, frataxin (FXN), controls endothelial senescence. An endothelial subpopulation in rodent and patient lungs across PH subtypes exhibited reduced FXN and elevated senescence. In vitro, hypoxic and inflammatory FXN deficiency abrogated activity of endothelial Fe-S-containing polymerases, promoting replication stress, DNA damage response, and senescence. This was also observed in stem cell-derived endothelial cells from Friedreich's ataxia (FRDA), a genetic disease of FXN deficiency, ataxia, and cardiomyopathy, often with PH. In vivo, FXN deficiency-dependent senescence drove vessel inflammation, remodeling, and PH, whereas pharmacologic removal of senescent cells in Fxn-deficient rodents ameliorated PH. These data offer a model of endothelial biology in PH, where FXN deficiency generates a senescent endothelial subpopulation, promoting vascular inflammatory and proliferative signals in other cells to drive disease. These findings also establish an endothelial etiology for PH in FRDA and left heart disease and support therapeutic development of senolytic drugs, reversing effects of Fe-S deficiency across PH subtypes.

Efficacy of topical versus intradermal injection of Tranexamic Acid In Egyptian melasma Patients: A randomised clinical trial.

BACKGROUND: Melasma is one of the common pigmentary problems affecting females in our community, owing to the frequent use of hormonal contraceptives as well as our sunny climate. A lot of treatment options are available but none of them is completely satisfactory. Many patients prefer the use of topical preparations and minimally invasive methods. Tranexamic acid (TA) is a potential treatment option for hyperpigmentation with different delivery routes. AIM: We designed the study in order to evaluate the efficacy of TA in melasma using 2 different routes of delivery. PATIENTS AND METHODS: A randomised clinical trial was performed on 60 female patients with melasma, they randomly divided into three groups; A, B and C. Group (A) patients received TA (4 mg/mL) intradermal injections every 2 weeks with, group B received TA (10 mg/mL) intradermal injections every 2 weeks, group C received TA cream (10% concentration) twice daily, treatment continued for 12 weeks in all groups. Melasma Area and Severity Index (MASI) scores were measured for each patient before and after completion of treatment. RESULTS: The percentage of MASI score reduction was highest in group B (62.7%) versus (39.1%) in group A, while the percentage of MASI reduction was the lowest in group C (4.2%). CONCLUSION: Tranexamic acid is a safe effective and well-tolerated treatment option for melasma patients. Intradermal injection of TA leads to better results than the topical application. Topical TA cream (even in a high concentration) produce fair improvement of melasma.

Obese-Inflammatory Phenotypes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Comorbidity-driven microvascular inflammation is posited as a unifying pathophysiologic mechanism for heart failure with preserved ejection fraction (HFpEF). Obesity is proinflammatory and common in HFpEF. We hypothesized that unique obesity-inflammation HFpEF phenotypes exist and are associated with differences in clinical features, fibrosis biomarkers, and functional performance. METHODS: Patients (n=301) from 3 HFpEF clinical trials were studied. Unsupervised machine learning (hierarchical clustering) with obese status and 13 inflammatory biomarkers as input variables was performed. Associations of clusters with HFpEF severity and fibrosis biomarkers (PIIINP [procollagen III N-terminal peptide], CITP [C-telopeptide for type I collagen], IGFBP7 [insulin-like growth factor-binding protein-7], and GAL-3 [galectin-3]) were assessed. RESULTS: Hierarchical clustering revealed 3 phenotypes: pan-inflammatory (n=129; 64% obese), noninflammatory (n=83; 55% obese), and obese high CRP (C-reactive protein; n=89; 98% obese). The pan-inflammatory phenotype had more comorbidities and heart failure hospitalizations; higher left atrial volume, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and fibrosis biomarkers; and lower glomerular filtration rate, peak oxygen consumption, 6-minute walk distance, and active hours/day (P<0.05 for all). The noninflammatory phenotype had the most favorable values for all measures. The obese high CRP phenotype resembled the noninflammatory phenotype except for isolated elevation of CRP and lower functional performance. Hierarchical cluster assignment was independent of CRP genotype combinations that alter CRP levels and more biologically plausible than other clustering approaches. Multiple traditional analytic techniques confirmed and extended the hierarchical clustering findings. CONCLUSIONS: Unique obesity-inflammation phenotypes exist in HFpEF and are associated with differences in comorbidity burden, HFpEF severity, and fibrosis. These data support comorbidity-driven microvascular inflammation as a pathophysiologic mechanism for many but not all HFpEF patients.

Quantification of U, Th and specific radionuclides in coal from selected coal fired power plants in South Africa.

Most of South Africa's energy is derived from the combustion of coal in pulverized coal-fired power plants (CFPP). However, when compared with the rest of the world, limited information regarding the main radioactive elements (U and Th) and specific radionuclides of interest (K40, Ra226 and Th232) from South African CFPP is available in the public domain. This paper aims to quantify the U, Th and specific radionuclides found in the coal used in selected South African CFPP in comparison to world averages found in literature. The U and Th concentrations were obtained by ICP-MS. The main radionuclides, K40, Ra226 and Th238, were quantified using gamma spectrometry. The U concentration and Th concentrations for the coal used in all the power plants was above the world average of 1.9 mg/kg and 3.2 mg/kg respectively. The coals with the highest Th content originated from the Mpumalanga power plant, while the U content in the Freestate power plant samples was the highest of the three. The concentrations of the K40 were between 88.43±10.75-110.76±8.92 Bq/kg, which are in-line with world averages of 4-785 Bq/kg. Similarly, the Ra226 and Th232 values were between 21.69±2.83-52.63±4.04 Bq/kg and 19.91±1.24-22.97±1.75 Bq/kg respectively, which are also in line with the world averages of 1-206 Bq/kg and 1-170 Bq/kg respectively. Radiological hazard indices such as radium equivalent (Raeq); external hazard index (Hex) and internal hazard index (Hin), that were estimated from these average radionuclide concentrations were less than the prescribed values found in literature. This indicated that no significant health risk was posed by the coal being used from these coal fields.

A Proteomic Atlas of Cardiac Amyloid Plaques.

BACKGROUND: In vivo mechanisms of amyloid clearance and cardiac tissue damage in cardiac amyloidosis are not well understood. OBJECTIVES: We aimed to define and quantify the amyloid plaque proteome in cardiac transthyretin amyloidosis (ATTR) and light chain amyloidosis (AL) and identify associations with patient characteristics and outcomes. METHODS: A proteomics approach was used to identify all proteins in cardiac amyloid plaques, and to compare both normal and diseased controls. All proteins identified within amyloid plaques were defined as the expanded proteome; only proteins that were enriched in comparison to normal and disease controls were defined as the amyloid-specific proteome. RESULTS: Proteomic data from 292 patients with ATTR and 139 patients with AL cardiac amyloidosis were included; 160 and 161 unique proteins were identified in the expanded proteomes, respectively. In the amyloid-specific proteomes, we identified 28 proteins in ATTR, 19 in AL amyloidosis, with 13 proteins overlapping between ATTR and AL. ATTR was characterized by a higher abundance of complement and contractile proteins and AL by a higher abundance of keratins. We found that the proteome of kappa AL had higher levels of clusterin, a protective chaperone, and lower levels of light chains than lambda despite higher levels of circulating light chains. Hierarchical clustering identified a group of patients with worse survival in ATTR, characterized by high levels of PIK3C3, a protein with a central role in autophagy. CONCLUSIONS: Cardiac AL and ATTR have both common and distinct pathogenetic mechanisms of tissue damage. Our findings suggest that autophagy represents a pathway that may be impaired in ATTR and should be further studied.

Amyloidosis in surgically resected atrial appendages: a study of 345 consecutive cases with clinical implications.

Histomorphologic parameters of atrial appendages removed during the Cox-Maze procedure have been shown to correlate with recurrence of atrial fibrillation. While amyloid deposition has been noted within atrial appendages, the incidence and significance remains incompletely understood. More accurate amyloid typing methodologies and targeted pharmacotherapeutics have recently been developed, prompting pathologists to provide more detailed information about the type of amyloid identified in such samples. This study sought to fully characterize the morphologic characteristics of atrial amyloid as well as its incidence and clinical significance. Tissue archives were queried for atrial appendages removed during the cardiac surgeries (2010-2014). Patient demographics, imaging features, and salient clinical findings were recorded. Pattern and extent of amyloid deposition were recorded. Typing of the amyloid protein, when present, was performed on a subset of cases by laser capture microdissection with mass spectrometry-based proteomic analysis. A total of 383 atrial appendages from 345 consecutive patients were included in the study (mean age, 69 years; range, 26-92 years). Amyloid was present in 46% of patients. A linear relationship was observed between age and presence of atrial amyloidosis. Women were more likely to have atrial amyloidosis. Two distinct morphologies of amyloid were observed: filamentous and nonfilamentous, and correlated perfectly with amyloid type (filamentous = AANF-type amyloid; nonfilamentous = ATTR-type amyloid). Filamentous deposits were observed in 91% of those with amyloid. Amyloid was more likely to be found in the left atrial appendage than the right. Patients with atrial amyloid, irrespective of type, were more likely to have experienced stroke or TIA and more likely to have atrial arrhythmia preoperatively. Postoperatively, those with atrial amyloid are more likely to experience recurrence of arrhythmia than those who did not have atrial amyloid. Understanding the morphologic characteristics of AANF-type amyloid will allow for identification by the light microscopy and obviates the need for expensive ancillary typing techniques. The finding of nonfilamentous amyloid, should still prompt confirmation of amyloid type so that targeted therapy may be employed.

The Association Between Patient Sociodemographic Characteristics and Generic Drug Use: A Systematic Review and Meta-analysis.

BACKGROUND: Generic drugs are bioequivalent and cost-effective alternatives to brand drugs. In 2014, $254 billion was saved because of the use of generic drugs in the United States. OBJECTIVE: To critically assess evidence on the association between patient characteristics and generic drug use in order to inform the development of educational outreach for improving generic drug use among patients. METHODS: We systematically searched the literature between January 2005 and December 2016 using PubMed, Web of Science, Ovid MEDLINE, Google Scholar, and EBSCO IPA-MEDLINE for potentially relevant studies. The titles and abstracts of identified articles were assessed independently by 2 reviewers. Titles and abstracts that were not written in English, were published before 2005, were not empirical, did not contain sociodemographic data, or were not policy or methodologically relevant to generic drug use were excluded. Data were pooled in a meta-analysis using the RStudio software to assess the association of patient-related factors with generic drug use. RESULTS: Our searches resulted in 11 articles on patient-level factors, and 6 of these articles had sufficient information to conduct meta-analyses in the domains of patients' gender, age, race/ethnicity, and income. Quantitative analysis indicated that no differences in generic drug use existed between subgroups of patients defined by gender, age, or race/ethnicity. However, patients with lower income (i.e., < 200% federal poverty level [FPL]) were more likely to use generic drugs than those with higher income (≥ 200% FPL; pooled OR = 1.32, 95% CI = 1.15-1.52). Heterogeneity was high (I 2 > 75%) for all analyses but income. CONCLUSIONS: Patients with lower income were more likely to use generic drugs, whereas evidence was heterogeneous regarding an association between generic drug use and gender, age, or race/ethnicity. Educational outreach targeting patients with higher incomes to understand their perspectives in generic drugs may help improve generic drug use within that population. DISCLOSURES: Funding for this study was made possible, in part, by the U.S. Food and Drug Administration through grant U01FD005486. Hansen has provided expert testimony for Daiichi Sankyo. No other authors have declared a potential conflict of interest. Views expressed in written materials or publications and by speakers do not necessarily reflect the official policies of the U.S. Department of Health and Human Services, nor does any mention of trade names, commercial practices, or organization imply endorsement by the U.S. government. Study concept and design were contributed by Howard, Harris, Kiptanui, Hansen, and Qian. Frank, Mishuk, Howard, Harris, and Kiptanui collected the data, and data interpretation was performed by Mishuk and Hansen, along with Qian, Harris, and Kiptanui. The manuscript was written and revised primarily by Mishuk, along with Qian and Hansen.

Breast Imaging Reporting and Data Systems category 3 (probably benign) breast lesions detected on diagnostic breast ultrasound: The prevalence, outcome and malignancy detection rate in Zaria, Nigeria.

BACKGROUND: Probably benign breast lesions in the Breast Imaging Reporting and Data Systems (BI-RADS 3) constitute a crucial category and a considerable number of all palpable breast masses. Local data concerning the outcome of such lesions in the Nigerian environment is almost non-existent. OBJECTIVES: The goal of this article is to report the frequency, outcome and malignancy detection rate among palpable breast masses that were categorised on ultrasound as BI-RADS category 3 (probably benign) according to the American College of Radiology (ACR). METHODS: Between January 2015 and July 2017, 603 patients had diagnostic whole-breast ultrasound scans. There were 277 women who complained of palpable breast masses, of whom 151 women were diagnosed as having BI-RADS 3 lesions. The final lesion outcome was determined by either biopsy or ultrasound follow-up examination for a total of 2 years. All data were recorded and analysed with Statistical Package for the Social Sciences (SPSS) version 20 (Chicago, USA). RESULTS: The frequency of BI-RADS category 3 lesions among all the women who underwent breast ultrasound was 25% (151/603); and 54% (151/277) in patients with palpable breast masses. There were 25 patients who were excluded because of incomplete data or who were lost to follow-up. A total of 122 patients had both ultrasound examination and histopathologic diagnosis, while only 4 were followed up for 2 years on ultrasound alone. Of the 122 women biopsied, 117 (95.9%) had benign histologic outcomes, and of the remaining 5, cancer was confirmed in 2 (1.6%), while the remaining 3 patients (2.5%) had lesions considered intermediate at histology (juvenile papillomatosis, borderline phylloides and atypical ductal hyperplasia). Three out of four patients who had ultrasound follow-up alone had stable lesions after 2 years, while one patient had complete resolution. CONCLUSION: This study found a significantly high biopsy rate of 80% (122/151) for probably benign lesions but a low detection rate for malignancy (1.6%). Follow-up with imaging rather than biopsy for lesions sonographically described as probably benign, will reduce medical costs and unwarranted invasive procedures.

Global Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Heart Failure and Preserved or Reduced Ejection Fraction.

BACKGROUND: We hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with the severity of pulmonary hypertension (PH) in HF. METHODS: Patients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure [PASP] ≥40 mm Hg) were compared to normal controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (control, HF-PH, and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4949), veins (n=7630), and small indeterminate vessels (IV; n=2168) to define percent medial thickness (arteries) and percent intimal thickness (%IT) (arteries, veins, and IV) relative to external diameter. RESULTS: The average arterial percent medial thickness (control, 6.9; HF-PH, 11.0; PVOD, 15.0), arterial %IT (control, 4.9; HF-PH, 14.9; PVOD, 31.1), venous %IT (control, 14.0; HF-PH, 24.9; PVOD, 43.9), and IV %IT (control, 10.6; HF-PH, 25.8; PVOD, 50.0) in HF-PH were higher than controls (P<0.0001 for all) but lower than PVOD (P≤0.005 for all). PASP (mm Hg) was lower in HF-PH (median, 59 [interquartile range, 50-70]) than in PVOD (median, 91 [interquartile range, 82-103]). PASP correlated with arterial percent medial thickness (r=0.41) and arterial %IT (r=0.35) but more strongly with venous %IT (r=0.49) and IV %IT (r=0.55) (P<0.0001 for all). Associations between PASP and venous or IV %IT remained significant after adjusting for arterial percent medial thickness and %IT and did not vary by HF type. In patients with right heart catheterization (30 HF-PH, 14 PVOD), similar associations between the transpulmonary gradient and pulmonary vascular remodeling existed, with numerically stronger associations for venous and IV %IT. Although the PASP was slightly higher in patients with HF-PH with right ventricular dysfunction, pulmonary vascular remodeling was not more severe. Pulmonary vascular remodeling severity was associated with reductions in the diffusing capacity of the lungs. CONCLUSIONS: In HF, PH is associated with global pulmonary vascular remodeling, but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.

Breast Imaging Reporting and Data Systems category 3 (probably benign) breast lesions detected on diagnostic breast ultrasound: The prevalence, outcome and malignancy detection rate in Zaria, Nigeria

Background: Probably benign breast lesions in the Breast Imaging Reporting and Data Systems (BI-RADS 3) constitute a crucial category and a considerable number of all palpable breast masses. Local data concerning the outcome of such lesions in the Nigerian environment is almost non-existent. Objectives: The goal of this article is to report the frequency, outcome and malignancy detection rate among palpable breast masses that were categorised on ultrasound as BI-RADS category 3 (probably benign) according to the American College of Radiology (ACR). Methods: Between January 2015 and July 2017, 603 patients had diagnostic whole-breast ultrasound scans. There were 277 women who complained of palpable breast masses, of whom 151 women were diagnosed as having BI-RADS 3 lesions. The final lesion outcome was determined by either biopsy or ultrasound follow-up examination for a total of 2 years. All data were recorded and analysed with Statistical Package for the Social Sciences (SPSS) version 20 (Chicago, USA). Results: The frequency of BI-RADS category 3 lesions among all the women who underwent breast ultrasound was 25% (151/603); and 54% (151/277) in patients with palpable breast masses. There were 25 patients who were excluded because of incomplete data or who were lost to follow-up. A total of 122 patients had both ultrasound examination and histopathologic diagnosis, while only 4 were followed up for 2 years on ultrasound alone. Of the 122 women biopsied, 117 (95.9%) had benign histologic outcomes, and of the remaining 5, cancer was confirmed in 2 (1.6%), while the remaining 3 patients (2.5%) had lesions considered intermediate at histology (juvenile papillomatosis, borderline phylloides and atypical ductal hyperplasia). Three out of four patients who had ultrasound follow-up alone had stable lesions after 2 years, while one patient had complete resolution. Conclusion: This study found a significantly high biopsy rate of 80% (122/151) for probably benign lesions but a low detection rate for malignancy (1.6%). Follow-up with imaging rather than biopsy for lesions sonographically described as probably benign, will reduce medical costs and unwarranted invasive procedures

Taurine abated subacute dichlorvos toxicity.

The aim of the study was to determine the effects of taurine in rats exposed to subacute dichlorvos toxicity. Fifty rats were weighed and assigned into five groups of ten rats each. The groups received: distilled water, soya oil (1 ml/kg), taurine (50 mg/kg), dichlorvos (10 mg/kg) and the combination treatment group received taurine first and then dichlorvos 30 min later. The treatments were administered once daily by oral gavage for 4 weeks. The rats were euthanized and blood samples were collected after the termination of the study. Serum samples were analysed for malondialdehyde concentration and activities of antioxidant enzymes (superoxide dismutase and catalase). Dichlorvos increased malondialdehyde concentration and reduced the activities of superoxide dismutase and catalase. There was attenuation of malondialdehyde concentration and improvement of activities of superoxide dismutase (P = 0.0273) and catalase (P < 0.0001) in rats treated with taurine. It is postulated that taurine ameliorated dichlorvos-induced oxidative stress through the reduction of malondialdehyde concentration and the enhancement of activities of antioxidant enzymes.

Self injection of foreign materials into the penis.

Injection of the subcutaneous tissues of the penis for enlargement of penile girth has been practised for many years by laypeople and medical practitioners alike. However, with recognition of the complications, the practice has died out. We report a series of five patients who presented having injected foreign materials into the subcutaneous tissues of their penises, including paraffin and mineral oils. Our patients had a variable time course of presentation ranging from 1 day following injection to over 26 years. Self-injection of the subcutaneous tissues of the penis is an unusual presentation for a penile mass but should be considered as a differential diagnosis in patients with a long latent period to presentation or with characteristic magnetic resonance imaging and histological appearances.

FOXO3a regulates BNIP3 and modulates mitochondrial calcium, dynamics, and function in cardiac stress.

The forkhead box O3a (FOXO3a) transcription factor has been shown to regulate glucose metabolism, muscle atrophy, and cell death in postmitotic cells. Its role in regulation of mitochondrial and myocardial function is not well studied. Based on previous work, we hypothesized that FOXO3a, through BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3), modulates mitochondrial morphology and function in heart failure (HF). We modulated the FOXO3a-BNIP3 pathway in normal and phenylephrine (PE)-stressed adult cardiomyocytes (ACM) in vitro and developed a cardiotropic adeno-associated virus serotype 9 encoding dominant-negative FOXO3a (AAV9.dn-FX3a) for gene delivery in a rat model of HF with preserved ejection fraction (HFpEF). We found that FOXO3a upregulates BNIP3 expression in normal and PE-stressed ACM, with subsequent increases in mitochondrial Ca2+, leading to decreased mitochondrial membrane potential, mitochondrial fragmentation, and apoptosis. Whereas dn-FX3a attenuated the increase in BNIP3 expression and its consequences in PE-stressed ACM, AAV9.dn-FX3a delivery in an experimental model of HFpEF decreased BNIP3 expression, reversed adverse left ventricular remodeling, and improved left ventricular systolic and, particularly, diastolic function, with improvements in mitochondrial structure and function. Moreover, AAV9.dn-FX3a restored phospholamban phosphorylation at S16 and enhanced dynamin-related protein 1 phosphorylation at S637. Furthermore, FOXO3a upregulates maladaptive genes involved in mitochondrial apoptosis, autophagy, and cardiac atrophy. We conclude that FOXO3a activation in cardiac stress is maladaptive, in that it modulates Ca2+ cycling, Ca2+ homeostasis, and mitochondrial dynamics and function. Our results suggest an important role of FOXO3a in HF, making it an attractive potential therapeutic target.