Drought stress-responsive abscisic acid and salicylic acid crosstalk with the phenylpropanoid pathway in soybean seeds.

Crosstalk between hormones and secondary metabolites regulates the interactions between plants and stress. However, little is known about the effects of hormone crosstalk on the concentration of flavonoids in seeds. In this study, we identified abscisic acid (ABA) as a negative regulator of flavonoid accumulation in soybean seeds under drought-stress conditions. Alterations in flavonoid accumulation at several intensities of water stress, followed by a recovery period, were measured during the soybean seed-filling stage. Low soil moisture (SM 10%) significantly decreased the total flavonoid content in seeds. The decline in flavonoid content was proportional to the severity of drought stress and was dependent on the activities of phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), two key phenylpropanoid pathway enzymes. The expression of phenylalanine ammonia-lyase 1 (GmPAL1), chalcone isomerase 1A (GmCHI1A), and chalcone synthase 8 (GmCHS8) was associated with phenolic and flavonoid accumulation in soybean seeds of plants subjected to drought stress. Interestingly, the expression levels of GmCHS8 were highly correlated with flavonoid levels under drought stress and water recovery conditions. Cinnamic acid, which is a biosynthesis precursor shared by both phenylpropanoid metabolism and salicylic acid (SA) biosynthesis, decreased under drought stress conditions. Notably, exogenous ABA suppressed the expression of GmPAL1, which encodes the first rate-limiting enzyme in the phenylpropanoid biosynthesis pathway and affects downstream products such as SA and flavonoids. In conclusion, drought stress altered the phenylpropanoid-derived compounds, at least with regard to flavonoid and SA accumulation in seeds, which was regulated by antagonistic interactions with ABA.

Estimation of the Acoustic Transducer Beam Aperture by Using the Geometric Backscattering Model for Side-Scan Sonar Systems.

In this paper, we propose an algorithm for estimating the beam aperture of the acoustic transducers by using the geometric backscattering model for side-scan sonar systems. The geometric backscattering model is developed to describe the propagation paths of the signal transmitted from the transducers towards the seabed and backscatters to the hydrophones. To evaluate our proposed algorithm, we have developed a side-scan sonar system. The side-scan sonar system uses two transducers, operating on two different frequencies and focusing on two different wave beams, to scan the images of the seabed. The proposed algorithm provides the estimated beam apertures of each transducer. Our obtained results agree quite well with the parameters provided by the manufacturers. Moreover, these results are used to calibrate the scanned images. We provide the scanned sonar 3D images of the Dong Do lakebed, Vietnam, to justify our proposal.

Investigation on Methylene Blue Dye Adsorption in Aqueous by the Modified Mussel Shells: Optimization, Kinetic, Thermodynamic and Equilibrium Studies.

This study assessed the methylene blue adsorption using natural and modified mussel shell powders in the aqueous solution. The mussel shell samples were processed in a NaClO solution then modified with sodium dodecyl sulfate and ethylenediaminetetraacetic acid. The characteristics of mussel shell samples before and after modification were demonstrated using infared spectroscopy, thermogravimetric analysis, scanning electron microscopy, nitrogen adsorption/desorption, energy dispersive X-ray, water contact angle, and dynamic light scattering methods. Some factors such as the pH of the medium, adsorption temperature, and adsorption time had a significant effect on the methylene blue adsorption of mussel shell samples. The adsorption isotherm models and kinetics of methylene blue adsorption by mussel shell samples were also studied. A quadratic regression equation was selected with experimental planning following the Box-Behnken model combined with Design Expert 11.1.0.1 software to optimize the methylene blue adsorption process by mussel shell samples. These results open a promising direction for using naturally derived materials to remove organic pollutants from contaminated water.

Vertical financial disparity, energy prices and emission reduction: Empirical insights from Pakistan.

The economic and environmental aspects of energy production have become important due to the increasing complexity energy sector and envoirnmental pollution, warranting to test the connection between financial imbalances, energy prices and carbon emission. The study aims to test the impact of vertical fiscal imbalances (VFI) on energy prices and carbon emission trends by considering the dual-perspectives of environmental regulation and industrial structure. The empirical outcomes indicated that vertical fiscal imbalances limited the environmental quality of Pakistan. Furthermore, VFI also caused environmental degradation by affecting industrial structure. VFI inhibits the intensity of environmental regulation, promotes the upgrade of industrial structures, both of which cause additional carbon emissions. The study suggest to energy ministries and energy regulation offices to revisit the machinism of energy prices determination and revised machanisim should provide a user-friendly assessment to understand the actual costs associated with the rising concern of environmental pollution. By this, envoirnmental protection maximization and optimal energy conservation is expacted to increase. Based on empirical findings, the study extends the suggestion that vertical fiscal imbalances should be considered an active indicator by the key policy makers and other stakeholders for energy prices determination and environmental quality upgradation.

On the Inhibitability of Natural Products Isolated from Tetradium ruticarpum towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study.

Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC50 values of 24.3 ± 0.8, and 47.7 ± 1.1 µM) and α-glucosidase (IC50 values of 92.1 ± 0.8, and 167.4 ± 0.4 µM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure-activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.

Genome-wide identification and analysis of rice genes preferentially expressed in pollen at an early developmental stage.

Microspore production using endogenous developmental programs has not been well studied. The main limitation is the difficulty in identifying genes preferentially expressed in pollen grains at early stages. To overcome this limitation, we collected transcriptome data from anthers and microspore/pollen and performed meta-expression analysis. Subsequently, we identified 410 genes showing preferential expression patterns in early developing pollen samples of both japonica and indica cultivars. The expression patterns of these genes are distinguishable from genes showing pollen mother cell or tapetum-preferred expression patterns. Gene Ontology enrichment and MapMan analyses indicated that microspores in rice are closely linked with protein degradation, nucleotide metabolism, and DNA biosynthesis and regulation, while the pollen mother cell or tapetum are strongly associated with cell wall metabolism, lipid metabolism, secondary metabolism, and RNA biosynthesis and regulation. We also generated transgenic lines under the control of the promoters of eight microspore-preferred genes and confirmed the preferred expression patterns in plants using the GUS reporting system. Furthermore, cis-regulatory element analysis revealed that pollen specific elements such as POLLEN1LELAT52, and 5659BOXLELAT5659 were commonly identified in the promoter regions of eight rice genes with more frequency than estimation. Our study will provide new sights on early pollen development in rice, a model crop plant.

Cardiac metabolism in heart failure: implications beyond ATP production.

The heart has a high rate of ATP production and turnover that is required to maintain its continuous mechanical work. Perturbations in ATP-generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure (HF) revealed several metabolic alterations called metabolic remodeling, ranging from changes in substrate use to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during HF. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to HF by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in HF not only results in impaired cardiac energetics but also induces other processes implicated in the development of HF such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in HF may have significant therapeutic relevance that goes beyond the energetic aspect.

Synthesis of new bioisosteric hemiasterlin analogues with extremely high cytotoxicity.

In this Letter, the synthesis and the evaluation of the cytotoxicity of new hemiasterlin analogues were reported. The indole moiety was replaced respectively by benzofurane, naphthalene and 4-bromobenzene groups. Most of these derivatives possess strong cytotoxic activity on two human tumour cell lines (KB and Hep-G2), and some analogues showed comparable cytotoxic activity to that observed for paclitaxel and ellipticine, against KB and Hep-G2 cancer cell lines.

Effect of Strain Rate on Hydrogen Embrittlement of Ti6Al4V Alloy.

The phenomenon of hydrogen embrittlement (HE) in metals and alloys, which determines the performance of components in hydrogen environments, has recently been drawing considerable attention. This study explores the interplay between strain rates and solute hydrogen in inducing HE of Ti6Al4V alloy. For the hydrogen-charged sample, as the strain rate was decreased from 10-2/s to 10-5/s, the ductility decreased significantly, but the HE effect on mechanical strength was negligible. The low strain rate (LSR) conditions facilitated the development of high-angle grain boundaries, providing more pathways for hydrogen diffusion and accumulation. The presence of solute hydrogen intensified the formation of nano/micro-voids and intergranular cracking tendencies, with micro-crack occurrences observed exclusively in the LSR conditions. These factors expanded the brittle hydrogen-damaged region more deeply into the interior of the lattice. This, in turn, accelerated both crack initiation and intergranular crack propagation, finally resulting in a considerable HE effect and a reduction in ductility at the LSR. The current study underscores the influence of strain rate on HE, enhancing the predictability of longevity and improving the reliability of components operating in hydrogen-rich environments under various loading conditions.

Deciphering Hydrogen Embrittlement Mechanisms in Ti6Al4V Alloy: Role of Solute Hydrogen and Hydride Phase.

Ti6Al4V (Ti64) is a versatile material, finding applications in a wide range of industries due to its unique properties. However, hydrogen embrittlement (HE) poses a challenge in hydrogen-rich environments, leading to a notable reduction in strength and ductility. This study investigates the complex interplay of solute hydrogen (SH) and hydride phase (HP) formation in Ti64 by employing two different current densities during the charging process. Nanoindentation measurements reveal distinct micro-mechanical behavior in base metal, SH, and HP, providing crucial insights into HE mechanisms affecting macro-mechanical behavior. The fractography and microstructural analysis elucidate the role of SH and HP in hydrogen-assisted cracking behaviors. The presence of SH heightens intergranular cracking tendencies. In contrast, the increased volume of HP provides sites for crack initiation and propagation, resulting in a two-layer brittle fracture pattern. The current study contributes to a comprehensive understanding of HE in Ti6Al4V, essential for developing hydrogen-resistant materials.

Verticillium dahliae VdPBP1 Transcription Factor Is Required for Hyphal Growth, Virulence, and Microsclerotia Formation.

Verticillium dahliae, a fungal pathogen that affects more than 200 plant species, including tomatoes, requires specific proteins for its early steps in plant infection. One such crucial protein, VdPBP1, exhibits high expression in the presence of tomato roots. Its 313-amino acid C-terminal section restores adhesion in nonadhesive Saccharomyces cerevisiae strains. To uncover its role, we employed a combination of bioinformatics, genetics, and morphological analyses. Our findings underscore the importance of VdPBP1 in fungal growth and pathogenesis. Bioinformatic analysis revealed that the VdPBP1 gene consists of four exons and three introns, encoding a 952-codon reading frame. The protein features a 9aaTAD domain, LsmAD, and PAB1 DNA-binding sites, as well as potential nuclear localization and transmembrane helix signals. Notably, the deletion of a 1.1 kb fragment at the gene's third end impedes microsclerotia formation and reduces pathogenicity. Mutants exhibit reduced growth and slower aerial mycelial development compared to the wild type. The VdPBP1 deletion strain does not induce disease symptoms in tomato plants. Furthermore, VdPBP1 deletion correlates with downregulated microsclerotia formation-related genes, and promoter analysis reveals regulatory elements, including sites for Rfx1, Mig1, and Ste12 proteins. Understanding the regulation and target genes of VdPBP1 holds promise for managing Verticillium wilt disease and related fungal pathogens.

Spatial epidemiology of human anthrax in Son La province, Vietnam, 2003-2022.

AIMS: Anthrax is reported with frequency but poorly understood in Southeast Asian countries including Vietnam. In Vietnam, anthrax surveillance is national. However, case detection, prevention, and control are implemented locally at the provincial level. Here, we describe the epidemiological characteristics, identify spatial clusters of human anthrax, and compare the variation in livestock anthrax vaccine coverage to disease incidence in humans and livestock using historical data in Son La province, Vietnam (2003-2020). METHODS AND RESULTS: Most human cases occurred between April and September. Most of the patients were male, aged 15-54 years old. The human cases were mainly reported by public district hospitals. There was a delay between disease onset and hospitalization of ~5 days. We identified spatial clusters of high-high incidence communes in the northern communes of the province using the local Moran's I statistic. The vaccine coverage sharply decreased across the study period. The province reported sporadic human anthrax outbreaks, while animal cases were only reported in 2005 and 2022. CONCLUSIONS: These results suggest underreporting for human and livestock anthrax in the province. Intersectoral information sharing is needed to aid livestock vaccination planning, which currently relies on reported livestock cases. The spatial clusters identify areas for targeted surveillance and livestock vaccination, while the seasonal case data suggest prioritizing vaccination campaigns for February or early March ahead of the April peak. A regional approach for studying the role of livestock trading between Son La and neighbouring provinces in anthrax occurrence is recommended.

The Roles of NOTCH3 p.R544C and Thrombophilia Genes in Vietnamese Patients With Ischemic Stroke: Study Involving a Hierarchical Cluster Analysis.

BACKGROUND: The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms. OBJECTIVE: We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors. METHODS: We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models. RESULTS: We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) µmol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively. CONCLUSIONS: The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95% CI 1.53-15.04) and 3.13 (95% CI 1.60-6.11), respectively (Pfisher<.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients.

Targeting Mitochondrial Metabolism to Save the Failing Heart.

Despite considerable progress in treating cardiac disorders, the prevalence of heart failure (HF) keeps growing, making it a global medical and economic burden. HF is characterized by profound metabolic remodeling, which mostly occurs in the mitochondria. Although it is well established that the failing heart is energy-deficient, the role of mitochondria in the pathophysiology of HF extends beyond the energetic aspects. Changes in substrate oxidation, tricarboxylic acid cycle and the respiratory chain have emerged as key players in regulating myocardial energy homeostasis, Ca2+ handling, oxidative stress and inflammation. This work aims to highlight metabolic alterations in the mitochondria and their far-reaching effects on the pathophysiology of HF. Based on this knowledge, we will also discuss potential metabolic approaches to improve cardiac function.

Primary malignant melanoma of the male urethra: Case report and review of literature.

INTRODUCTION: We report a rare case of primary malignant melanoma with inguinal lymph node metastasis in the male urethra. CASE PRESENTATION: A 57-year-old male patient presented with a small tumor on the ventral surface of the penis, which was discovered 5 months ago and did not cause pain or discomfort. In the past month, the patient has developed symptoms of urinary incontinence. MRI and PET/CT scans revealed a primary tumor in the penile urethra, but no metastases were found. The patient underwent partial penectomy surgery and laparoscopic bilateral inguinal lymphadenectomy within one month. The pathological combined with immunohistochemical staining confirmed primary malignant melanoma in the urethra with right inguinal lymph node metastasis. Despite complying with surgical and immunotherapy treatment with Pembrolizumab for 18 cycles, the patient was diagnosed with recurrent cancer in the penile stump after 05 months and he passed away after 18 months. DISCUSSION: Urethral melanoma is a rare and highly invasive type of cancer. It was often diagnosed at a late stage because the initial symptoms were not obvious in the lower urinary tract. Additionally, cancer progressed very quickly, making it difficult to treat. CONCLUSION: Urethral melanoma, if detected at a late stage with lymph node metastasis, has a significantly poor prognosis irrespective of the treatment method employed. However, to our best knowledge, very few publications can be found on this disease, and the strategic treatment remained unknown.

To stay or re-migrate after the pandemic shock? Labor re-migration intention to the coastal areas of Thua Thiên Hue province in Vietnam.

This study applied the extended theory of planned behavior (ETPB) to explore factors that shape the behavioral intention of migrant laborers returning to the coastal region of Thua Thiên Hue province during the peak of the COVID-19 pandemic to remigrate. Data collection included 210 interviews with returned migrants aged 18 and above in 4 coastal communes of Thua Thiên Hue province, in-depth interviews (8 key informants) and a group discussion (5 persons). Exploratory factor analysis and a multivariate linear regression model were applied to analyze the data. Results showed that in addition to individual socio-demographic characteristics (i.e. level of education, age, income level and sex), attitudes, subjective norms, perceived behavioral control, and perceived risk were also determinant factors of migrants' intention to remigrate. This research suggested that in order to build resilience of rural migration workers, related departments should seriously consider the following recommendations: (i) raise awareness and encourage young rural people to complete their education and necessary skills; (ii) organize related psychological training programs for rural laborers; (iii) raise awareness about the necessity to participate in social insurance; (iv) promote rural job creation programs suitable for low education and low-skilled rural laborers; (v) raise awareness for local people, particularly school children, about the value and opportunities of being smart farmers in the context of 4.0 technology and social risks at the destination for low education and low-skilled laborers; (vi) digitalize migration labor management and provide digital information services regarding job opportunities for rural laborers.

Bioglue endovascular treatment of fusiform aneurysm rupture of the distal anterior temporal artery of the middle cerebral artery: a case report.

The treatment of a ruptured fusiform distal anterior temporal artery aneurysm is a challenge for the stroke physician, however surgical closure and coil endovascular intervention are options. A total blockage can result in memory problems as well as object-related questions. We'd like to provide the clinical example of a 56-year-old woman with many underlying medical illnesses who was admitted to the hospital with a grade 7/10 headache and a Glasgow score of 15, but no focal neurological deficits, and was diagnosed with a ruptured distal temporal artery aneurysm. The aneurysm is positioned in the distal region, making endovascular intervention difficult to perform. As a result, we used an endovascular approach to repair with bioglue. When a patient develops fusiform aneurysms of the distal temporal artery, our findings provide an additional therapy option.

A giant fusiform middle cerebral artery treated by low-flow superficial temporal artery bypass: A case report.

A giant fusiform aneurysm of the middle cerebral artery is a disease that causes many difficulties for endovascular intervention as well as surgery. No 1 solution is optimal for all cases, however for post-bifurcation aneurysms, trapping the aneurysms with a reanastomosis reimplantation, an in situ side to side bypass is feasible and has good results. We reported a 28-year-old male patient, admitted to the hospital because of severe headache, Glasgow Coma Scale 13 points, left hemiplegia, was diagnosed with subarachnoid hemorrhage due to rupture of a giant fusiform aneurysm of the middle cerebral artery in the M2 segment, Hunt and Hess grade 4. The patient underwent microsurgery with clipping aneurysm combined with a low-flow technique connecting the superficial temporal artery to the middle cerebral artery. Our findings suggest that surgery to connect the superficial temporal artery to the M2 segment and at the same time obstructing the parent artery occlusion of selected giant MCA aneurysm is an option to consider.

Steel slag quality control for road construction aggregates and its environmental impact: case study of Vietnamese steel industry-leaching of heavy metals from steel-making slag.

Steel slag is an industrial by product of steel manufacturing processes and has been widely utilized within civil and construction materials for road materials and environmental remediation in countries like Japan, USA, and European Union nations. However, the current utilization of steel slag in Vietnam is very low mainly because of lack of quality control of slag treatment and chances for reuse of treated steel slag. This paper presents the up to date steel slag production status in Vietnam through the extensive survey and sampling at seven large steel factories. The paper also highlights the environmental and quality control issues of these steel slags to use as road construction aggregates by assessing the heavy metals concentration in the leachate. The basic oxygen furnace (BOF) and electric arc furnace (EAF) slag samples were collected to evaluate leaching properties of metals leached from the slags. The two standardized batch leaching tests of steel slag roadbed material in Japan (JIS K 0058-1) and toxicity characteristics leaching procedure (TCLP-EPA method 1311) were performed to the evaluated the hazardous metals. The results of the leaching test show that almost all of the concentration of the metals in the leached solution does not exceed the National Standard for Industrial Wastewater Discharge (QCVN 40-2011). The pH and parameters such as total chromium, nickel, copper, lead, arsenic, and manganese differ from the two test methods. The acidic conditions employed in the EPA 1311 were not representative of condition excepted during slag reuse in road constructions because in the operation condition of the road, acidic liquid is absent. The leaching test results confirmed that JIS test which uses deionized water with gentle mixing prevents the slag sample from size degradation is suitable for the environmental assessment of steel slag use for roadbed material. This research suggests that the adjustment of pH value prior to disposal or reuse as base materials and official guideline should be promulgate by the authorities to ensure the leachate meet the surface water quality standard.

Acute Respiratory Distress Syndrome Associated with Multisystem Inflammatory Syndrome in a Child with Covid-19 and Diabetic Ketoacidosis: A Case Report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (Covid-19), has uncontrollable effects on many organs. A great number of previously published scientific reports have revealed that patients with diabetes mellitus face a more severe form of Covid-19 with a higher death rate. Here we present the case of a 13-year-old unvaccinated boy who was admitted to an intensive care unit (ICU) with a history of fever, cough, dyspnea, throat pain, nausea, and confusion that progressed to lethargy after 24 h. On clinical examination, he was in a coma with Kussmaul's breathing, and was anuric. His blood biochemical analysis demonstrated hyperglycemia, severe metabolic acidosis, kidney failure, electrolyte disturbances, and inflammation. Chest x-ray showed pneumonia and a pleural effusion. The results of the SARS-CoV-2 real-time polymerase chain reaction were positive. The patient was diagnosed with Covid-19-induced acute respiratory distress syndrome associated with multisystem inflammatory syndrome in children secondary to his acute respiratory failure, acute kidney injury, and new-onset type 1 diabetes mellitus with diabetic ketoacidosis. He was intubated for invasive mechanical ventilation and received a normal saline infusion and continuous insulin infusion (0.1 IU/kg/h) for the treatment of his diabetic ketoacidosis. He was also treated with methylprednisolone, aspirin, and heparin, and underwent continuous renal replacement therapy for acute renal failure for 9 days. The patient was discharged from ICU on day 16 and was followed up regularly as an outpatient with daily treatment, including subcutaneous insulin injection (30 IU/day) and a calcium channel blocker for hypertension (nifedipine 20 mg/day).