Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

Adaptation analysis and fusion correction method of CMIP6 precipitation simulation data on the Qinghai-Tibetan Plateau

In order to obtain more accurate precipitation data and better simulate the precipitation on the Tibetan Plateau,the simulation capability of 14 Coupled Model Intercomparison Project Phase 6(CMIP6)models of historical precipitation(1982-2014)on the Qinghai-Tibetan Plateau was evaluated in this study.Results indicate that all models exhibit an overestimation of precipitation through the analysis of the Taylor index,temporal and spatial statistical parameters.To correct the overestimation,a fusion correction method combining the Backpropagation Neural Network Correction(BP)and Quantum Mapping(QM)correction,named BQ method,was proposed.With this method,the historical precipitation of each model was corrected in space and time,respectively.The correction results were then analyzed in time,space,and analysis of variance(ANOVA)with those corrected by the BP and QM methods,respectively.Finally,the fusion correction method results for each model were compared with the Climatic Research Unit(CRU)data for significance analysis to obtain the trends of precipitation increase and decrease for each model.The results show that the IPSL-CM6A-LR model is relatively good in simulating historical precipitation on the Qinghai-Tibetan Plateau(R=0.7,RSME=0.15)among the uncorrected data.In terms of time,the total precipitation corrected by the fusion method has the same interannual trend and the closest precipitation values to the CRU data;In terms of space,the annual average precipitation corrected by the fusion method has the smallest difference with the CRU data,and the total historical annual average precipitation is not significantly different from the CRU data,which is better than BP and QM.Therefore,the correction effect of the fusion method on the historical precipitation of each model is better than that of the QM and BP methods.The precipitation in the central and northeastern parts of the plateau shows a significant increasing trend.The correlation coefficients between monthly precipitation and site-detected precipitation for all models after BQ correction exceed 0.8.

Correction: Surface Patterning of Metal ZincElectrode with an In-Region Zincophilic Interfacefor High-Rate and Long-Cycle-Life Zinc MetalAnode

Correction to:Nano-Micro Letters(2024)16:112 https://doi.org/10.1007/s40820-024-01327-2 In the supplementary information the following corrections have been carried out:1.Institute of Energy and Climate Research,Materials Synthesis and Processing,Forschungszentrum Jülich GmbH,52425 Jülich,Germany.Corrected:Institute of Energy and Climate Research:Materials Synthesis and Processing(IEK-1),Forschungszentrum Jülich GmbH,52425 Jülich,Germany.

Correction to:Error Calculation of Large-Amplitude Internal Solitary Waves Within the Pycnocline Introduced by the Strong Stratification Approximation

In the original publication the third author name is published incorrectly as“Hayatdavoodi Masoud”.The correct author name should be read as“Masoud Hayatdavoodi”.The correct author name is available in this correction.

A growth-regulating factor 7(GRF7)-mediated gene regulatory network promotes leaf growth and expansion in sugarcane

Knowledge of the function of growth-regulating factors(GRFs)in sugarcane(Saccharum officinarum and S.spontaneum)growth and development could assist breeders in selecting desirable plant architectures.However,limited information about GRFs is available in Saccharum due to their polyploidy.In this study,22 GRFs were identified in the two species and their conserved domains,gene structures,chromosome location,and synteny were characterized.GRF7 expression varied among tissues and responded to diurnal rhythm.SsGRF7-YFP was localized preferentially in the nucleus and appears to act as a transcriptional cofactor.SsGRF7 positively regulated the size and length of rice leaves,possibly by regulating cell size and plant hormones.Of seven potential transcription factors binding to the SsGRF7 promoter in S.spontaneum,four showed positive expression patterns,and two showed negative expression patterns relative to SsGRF7.

Predictive factors for percutaneous nephrolithotomy bleeding risks

Objective:This study aimed to identify predictive factors for percutaneous nephrolithotomy(PCNL)bleeding risks.With better risk stratification,bleeding in high-risk patient can be anticipated and facilitates early identification.Methods:A prospective observational study of PCNL performed at our institution was done.All adults with radio-opaque renal stones planned for PCNL were included except those with coagulopathy,planned for additional procedures.Factors including gender,co-morbidities,body mass index,stone burden,puncture site,tract dilatation size,operative position,surgeon's seniority,and operative duration were studied using stepwise multivariate regression analysis to identify the predictive factors associated with higher estimated hemoglobin(Hb)deficiency.Results:Overall,4.86%patients(n=7)received packed cells transfusion.The mean estimated Hb deficiency was 1.3(range 0-6.5)g/dL and the median was 1.0 g/dL.Stepwise multivariate regression analysis revealed that absence of hypertension(p=0.024),puncture site(p=0.027),and operative duration(p=0.023)were significantly associated with higher estimated Hb deficiency.However,the effect sizes are rather small with partial eta-squared of 0.037,0.066,and 0.038,respectively.Observed power obtained was 0.621,0.722,and 0.625,respectively.Other factors studied did not correlate with Hb difference.Conclusion:Hypertension,puncture site,and operative duration have significant impact on estimated Hb deficiency during PCNL.However,the effect size is rather small despite adequate study power obtained.Nonetheless,operative position(supine or prone),puncture number,or tract dilatation size did not correlate with Hb difference.The mainstay of reducing bleeding in PCNL is still meticulous operative technique.Our study findings also suggest that PCNL can be safely done by urology trainees under supervision in suitably selected patient,without increasing risk of bleeding.

The application of the strip-shaped cymba conchae orthosis in the nonsurgical correction of complex auricular deformity

Objective: This study aims to evaluate the efficacy and safety of using a strip-shaped cymba conchae orthosis for the nonsurgical correction of complex auricular deformities. Methods: Clinical data were collected from 2020 to 2021 for 6 patients who underwent correction using a stripshaped cymba conchae orthosis. The indications, corrective effects, and complications associated with use of the orthosis were analyzed. Results: There were four indications for treatment: cryptotia with helix adhesion;cryptotia with grade I microtia;cryptotia with excessive helix thickness;and auricular deformity beyond the treatment time window(≥6 months). Excellent corrective effects were observed in all 6 patients. Complications occurred in one patient, who recovered after symptomatic treatment. Conclusion: The use of a strip-shaped cymba conchae orthosis alone or combined with a U-shaped helix orthosis presents a feasible approach for correcting complex auricular deformities or deformities beyond the treatment time window in pediatric patients.

Thermodynamics in a quantum corrected Reissner-Nordstr?m-AdS black hole and its GUP-corrections

We calculate the thermodynamic quantities in the quantum corrected Reissner-Nordstr?m-AdS(RN-AdS)black hole,and examine their quantum corrections.By analyzing the mass and heat capacity,we give the critical state and the remnant state,respectively,and discuss their consistency.Then,we investigate the quantum tunneling from the event horizon of massless scalar particle by using the null geodesic method,and charged massive boson W^(±)and fermions by using the Hamilton-Jacob method.It is shown that the same Hawking temperature can be obtained from these tunneling processes of different particles and methods.Next,by using the generalized uncertainty principle(GUP),we study the quantum corrections to the tunneling and the temperature.Then the logarithmic correction to the black hole entropy is obtained.

Risk factors,prognostic factors,and nomograms for distant metastasis in patients with diagnosed duodenal cancer:A population-based study

BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer,and distant metastasis(DM)in this type of cancer still leads to poor prognosis.Although nomograms have recently been used in tumor areas,no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer.AIM To develop and evaluate nomograms for predicting the risk of DM and person-alized prognosis in patients with duodenal cancer.METHODS Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer,and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM.Two novel nomograms were established,and the results were evaluated by receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).RESULTS A total of 2603 patients with duodenal cancer were included,of whom 457 cases(17.56%)had DM at the time of diagnosis.Logistic analysis revealed independent risk factors for DM in duodenal cancer patients,including gender,grade,tumor size,T stage,and N stage(P<0.05).Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM,including age,histological type,T stage,tumor grade,tumor size,bone metastasis,chemotherapy,and surgery(P<0.05).The accuracy of the nomograms was validated in the training set,validation set,and expanded testing set using ROC curves,calibration curves,and DCA curves.The results of Kaplan-Meier survival curves(P<0.001)indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer.CONCLUSION The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM,potentially enhancing clinical decision-making.

Survey on Knowledge of Cardiovascular Disease Risk Factors in the Dakar Region

Introduction: Non-communicable diseases constitute a major public health problem, due to their morbi-mortality. The aim was to study knowledge of cardiovascular risk factors among residents of Dakar. Patients and Methods: This was a descriptive cross-sectional study. Our investigations were recruited over a six-month period (October 17, 2021 to March 21, 2022). Results: Two hundred and twenty-six (226) patients were enrolled. The mean age was 45.9 years. The under-40 age group was the most represented with 37.2%. There were 129 men (57.1%), giving a male/female sex ratio of 1.33. The highest level was represented by 159 people (70.4%). Those who responded (heart disease) were in the majority (38.1%). Hypertension was the most common CVD for 101 people (44.7%). One hundred and ninety (190) people (84%) knew the risk factors for CVD. Good knowledge of risk factors concerned 103 people (54.2%). Obesity was the best-known risk factor in 156 cases (69%). The media was the most important source of information for 121 people (53.5%). Hypertensives were the most represented with 8.4%. One hundred and thirty (130) people (57.5%) had previously paid attention to these FDRCVs. Awareness campaigns were the most effective means of communication for 170 cases (75.2%). Sixteen (16) people (35.6%) were taking antihypertensive medication. Walking was the most popular physical activity for 102 people (45%). People with a balanced diet were in the majority, with 174 respondents (77.0%). Conclusion: NCDs are a major cause of morbidity and mortality. It is essential to develop and implement a prevention and management program.

Factors Contributing to Contamination of Street Foods in Bamako, Mali

The World Health Organization states that foodborne diseases are a worldwide public health issue. Although street foods can provide nutritious and affordable ready-to-eat meals for city dwellers, their health risks can outweigh the benefits. A cross-sectional study was conducted in the Bamako district, focusing on street food vendors near schools, universities, extensive markets, administrative centers, and major roads. We aimed to sample fifty (50) sellers per municipality, making 300 sellers for the Bamako district. We developed a survey sheet to collect data, and six teams rotated between the municipalities each month. Before starting the collection, the teams were provided administrative papers approved by the municipal authority. The survey revealed three types of sales sites: fixed (65%), semi-fixed (30%), and mobile (4.40%). The proportion of sellers was 26.8%, 23.2%, 19.7%, and 4.2% in municipalities III, IV, and I. In municipalities I, II, III, IV, and VI, respectively, 92%, 95.70%, 93%, 87.2%, and 100% of the sellers were female. The age distribution of sellers was 65.63%, 46.81%, 40.82%, 38.30%, 36.17%, 36%, and 32% in the 25-34 and 35 - 44 age groups. Illiteracy rates were 59.20%, 61.70%, 55.30%, 75%, and 56% in municipalities I, II, III, IV, and VI, respectively. The study identified two categories of sellers: 48.3% in type 1 and 51.7% in type 2. The first category comprised 154 sellers, and the second 165 sellers. The survey found that 66.00%, 56.00%, 48.90%, 44.90%, 38.30%, and 34.40% of municipal V, VI, III, I, II, and IV sales sites were open-air. In municipality I, 63.30% of the sites were under hangars, while in municipalities II and IV, the corresponding percentages were 51.10% and 59.40%, respectively. Moreover, 46.00%, 31.90%, 31.30%, 30.60%, and 27.70% of the sites in municipalities VI, II, IV, I, and III were located next to gutters. In conclusion, this study identified several factors that could compromise the quality of street foods sold in the six municipalities of Bamako.

Methodology for local correction of the heights of global geoid models to improve the accuracy of GNSS leveling

At present,one of the methods used to determine the height of points on the Earth’s surface is Global Navigation Satellite System(GNSS)leveling.It is possible to determine the orthometric or normal height by this method only if there is a geoid or quasi-geoid height model available.This paper proposes the methodology for local correction of the heights of high-order global geoid models such as EGM08,EIGEN-6C4,GECO,and XGM2019e_2159.This methodology was tested in different areas of the research field,covering various relief forms.The dependence of the change in corrected height accuracy on the input data was analyzed,and the correction was also conducted for model heights in three tidal systems:"tide free","mean tide",and"zero tide".The results show that the heights of EIGEN-6C4 model can be corrected with an accuracy of up to 1 cm for flat and foothill terrains with the dimensionality of 1°×1°,2°×2°,and 3°×3°.The EGM08 model presents an almost identical result.The EIGEN-6C4 model is best suited for mountainous relief and provides an accuracy of 1.5 cm on the 1°×1°area.The height correction accuracy of GECO and XGM2019e_2159 models is slightly poor,which has fuzziness in terms of numerical fluctuation.

Prevalence of Hepatitis B and Associated Factors in the Garoua Central Prison, Cameroon: A Cross-Sectional Study

Introduction: Hepatitis B virus (HBV) infection is a major public health problem in Cameroon. Garoua city is the headquarters of the North Region of Cameroon, where the HBV prevalence is among the highest of the country. The aim of this study was to determine the prevalence of HBsAg carriage and associated factors among persons incarcerated in the Garoua Central Prison. Methods: It was a cross-sectional study conducted from July 1 to July 31, 2023 at the Garoua Central prison. We included all prisoners willing to participate in the study and who gave their verbal consent. We collected data using a pre-established data entry form and we used rapid test for blood screening for HBV surface antigen (HBs Ag) with ELISA confirmation. Data were analyzed using the R® software for Windows. After the univariate analysis, we selected associated variables to HBV infection with p-value p-value was set at 5%. Results: We included 1389 prisoners out of which 97.6% were male. The median age (IQR) of the study population was 28 (23 - 35) years. The median (IQR) duration of incarceration was 12 (6 - 26) months and the mean (±sd) number of incarcerations was 1.24 (±0.6). HBV prevalence was estimated at 14.8% (95% CI: 13.0 - 16.7). Upon uni- and multivariate analysis, no risk factor was significantly associated with viral hepatitis B infection in our study population. Conclusion: The prevalence of Hepatitis B was high in the Garoua Central Prison, but there were no additional risk factors for HBV infection. There is a need to include the Garoua Central Prison and by the way other prisons in the country in the chronic viral hepatitis care program.

Risk and Protective Factors Associated with Depression and Anxiety among Pregnant Women during the COVID-19 Pandemic

Background: The coronavirus disease (COVID-19) pandemic has impacted perinatal women’s mental health. However, protective factors associated with depression among pregnant Japanese women during the pandemic have not been reported. Purpose: The present study investigated the risk and protective factors associated with depression and anxiety among pregnant women during the COVID-19 pandemic. Methods: An online questionnaire was administered to 157 pregnant women between October 2022 and May 2023 at two general hospitals in Japan. The Japanese versions of the Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7) were used to assess symptoms of depression and anxiety. The χ2 test or Fisher’s exact test and multivariate logistic regression model were used to examine factors associated with depression and anxiety among pregnant women. Results: Overall, 47.1% and 35.7% of the pregnant women reported depressive and anxiety symptoms, respectively. A “history of mental illness” was a risk factor for depression and anxiety among pregnant women during the COVID-19 pandemic. Additionally, unmarried status was a risk factor for anxiety among pregnant women, whereas outdoor and indoor exercises were protective factors against depression and anxiety, respectively. Conclusions: Exercise may have protected pregnant women from depression and anxiety during the COVID-19 pandemic. Encouraging exercise may help maintain the mental health of pregnant women who do not have exercise restrictions.

Balancing act:The dilemma of rapid hyperglycemia correction in diabetes management

The global diabetes surge poses a critical public health challenge,emphasizing the need for effective glycemic control.However,rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications,necessitating a reevaluation of the speed and intensity of glycemic correction.Theories suggest swift blood sugar reductions may cause inflammation,oxidative stress,and neurovascular changes,resulting in complications.Healthcare providers should cautiously approach aggressive glycemic control,especially in long-standing,poorly controlled diabetes.Preventing and managing these complications requires a personalized,comprehensive approach with education,monitoring,and interdisciplinary care.Diabetes management must balance short and longterm goals,prioritizing overall well-being.This editorial underscores the need for a personalized,nuanced approach,focusing on equilibrium between glycemic control and avoiding overcorrection.

Identifying the best common factor model via exploratory eactor analysis

Currently,there is no solid criterion for judging the quality of the estimators in factor analysis.This paper presents a new evaluation method for exploratory factor analysis that pinpoints an appropriate number of factors along with the best method for factor extraction.The proposed technique consists of two steps:testing the normality of the residuals from the fitted model via the Shapiro-Wilk test and using an empirical quantified index to judge the quality of the factor model.Examples are presented to demonstrate how the method is implemented and to verify its effectiveness.

The roles of macrophage migration inhibitory factor in retinal diseases

Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.

Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

Epidemiological Aspects of Obesity, Overweight and Cardiovascular Risk Factors at Associes in Semi-Urban Areas (Case of Sébikotane)

Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Patients and Methods: This was a cross-sectional, descriptive study conducted on November 28 and 29, 2023 in Sébikotane. It focused on volunteers for screening for chronic non-communicable diseases. Epidemiological and clinical data were evaluated. Results: One hundred and twenty-nine cases of obesity were recorded (28%). Two hundred and eighty-two cases were overweight or obese (61.3%). The mean age was 49.55 years, with a standard deviation of 12.41 years. The age group [40 - 49 years] was the most representative, with 85 cases (30.1%), and the majority were female, with 264 cases (93.6%). Primary education was the most common, with 75 cases (46.3%). Grade 1 obesity concerned ninety-seven cases (75.2%), and diabetes was present in thirty cases (23%). Hypertension was present in ninety-five cases (33.7%). Obesity was more marked in the age group [40 - 49 years] with 45 cases (36%). Conclusion: Obesity and overweight are a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.

The Burden of Undiagnosed Hypertension and Associated Risk Factors among Adults in a Rural Community in Imo Sate, South-East Nigeria

Background: Cardiovascular diseases are the leading cause of death globally and hypertension is a major contributor to this burden. Many people with hypertension have poorly controlled blood pressure and up to half of the adults with hypertension are unaware of their hypertensive status due to factors that bother on poor management and poor screening approaches. The implication is that people who have poor access to healthcare especially those in the rural communities are at increased risk of cardiovascular complications and all-cause mortality. Unfortunately, not much has been done to ascertain the burden of undiagnosed hypertension and associated risk factors in rural communities in Nigeria. Methods: We conducted a community-based cross-sectional study in a rural community in Imo State, Nigeria, on burden of undiagnosed hypertension with participants recruited via a multi-stage sampling method. An interviewer-administered questionnaire was used, and standardized instruments were applied to obtain, process and analyze the data. Tests of association between the independent variables and outcome were conducted using logistic regression. P-value of Results: A total of 380 adults participated in the study. The mean age was 44.2 years. The prevalence of undiagnosed hypertension was 35.8%. Logistic regression revealed that age, with the respondents in the age groups 26 - 35 years (OR = 10.647, 1.910 - 59.345, p-value = 0.007), 36 - 45 (OR = 3.680, 1.263 - 10.723, p-value = 0.017), 46 - 55 years (OR = 2.737, 1.114 - 6.727, p-value = 0.039), 56 - 65 years old (OR = 3.384, 1.610 - 7.115, p-value = 0.001);and being married (OR = 3.846, 1.118 - 13.233, p-value = 0.033), were independent risk factors for undiagnosed hypertension. Conclusion: The prevalence of undiagnosed hypertension in the rural population of South-East Nigeria is high. Younger age (26 - 35 years) had the highest odds of risk for occurrence of hypertension. Also being married was identified as a risk factor for undiagnosed hypertension.