Electrically tunable dual polarization states of light using lithium niobate-based nanograting.

Tuning polarization states of light electrically has unique advantages in the integration of optoelectronic devices. Here, a lithium niobate-based nanograting is proposed to dynamically tune the polarization state of both the reflected and transmitted lights simultaneously in the near-infrared range. By judiciously designing the nanograting, a quasi-bound state in the continuum (qBIC) is excited under the excitation of an obliquely incident plane wave. The excited mode with a high quality-factor and enhanced local electric field can respond to a refractive index change in nanograting structures as small as 10-4 level, which can be generated with a low external voltage via the electro-optic effect. As a result, both the polarization states of reflected and transmitted lights can be dynamically tuned from a right circular polarization to a linear polarization state. The proposed lithium niobate-based nanograting for tuning dual polarization states of light with a qBIC mode suggests a promising electrical scheme for achieving high speed optoelectronic devices.

Phenotypic findings and pregnancy outcomes of fetal rare autosomal aneuploidies detected using chromosomal microarray analysis.

BACKGROUND: Aneuploidies are the most common chromosomal abnormality and the main genetic cause of adverse pregnancy outcomes. Since numerous studies have focused on common trisomies, relatively little is known about the association between phenotypic findings and rare autosomal aneuploidies (RAAs). We conducted a retrospective study of 48,904 cases for chromosomal microarray analysis in a large tertiary referral center and reported the overall frequencies, clinical manifestations, and outcomes of prenatal RAAs. RESULTS: A total of 90 RAAs were detected, of which 83 cases were mosaic trisomies and 7 were non-mosaic trisomies. Chromosomes 16, 22, and 9 were identified as the major chromosomes involving RAAs. The four predominant indications for prenatal diagnosis in our RAA cases were RAA-positive in noninvasive prenatal screening, advanced maternal age, ultrasound abnormalities, and high-risk for serum prenatal screening. Cardiovascular defects were the most frequently observed structural abnormalities, followed by musculoskeletal anomalies. Increased nuchal translucency and persistent left superior vena cava, the major soft marker abnormalities involved, were also observed in our RAA cases. Clinical outcomes were available for all RAAs, with 63 induced abortions and 27 live births recorded. CONCLUSIONS: Variable phenotypes and outcomes were observed, which were highly heterogeneous in cases of prenatal RAAs. Thus, a cautious and comprehensive strategy should be implemented during prenatal counseling for RAAs.

Shortened fetal long bones: A notable intrauterine phenotypic feature in SHOX-associated skeletal dysplasia.

OBJECTIVE: To explore the intrauterine phenotypic spectrum of short stature homeobox-containing (SHOX) gene-associated skeletal dysplasia and provide genetic counseling at-risk pregnancies. METHOD: We analyzed the fetuses with SHOX-microdeletions identified by single nucleotide polymorphism (SNP)-array. The intrauterine phenotypes and outcomes were further elaborated. RESULTS: Nine fetuses carrying a single SHOX-microdeletion were reported, with deletion sizes ranging from 0.134 to 1.35 Mb. Shortened long bones were observed in all fetuses, varying from -2.0 standard deviation (SD) to -5.3 SD. Moreover, all cases had a femur length/foot ratio less than 0.87 and a femur/abdominal circumference ratio greater than 0.16, suggesting that non-lethal skeletal dysplasia may be involved. Two fetuses showed intrauterine growth restriction, and two had nasal bone hypoplasia. Prenatal ultrasonography did not reveal other obvious anomalies, including the Madelung deformity. Five microdeletions were inherited and one was de novo. Five terminations and four newborns were recorded. Two newborns had normal stature, and two were short-statured (height <3rd percentile), with one having inflexible wrists. CONCLUSIONS: SHOX haploinsufficiency may manifest with shortened fetal long bones. The combination of history taking, prenatal ultrasonography, and SNP-array can prompt early prenatal diagnosis and timely postnatal treatment of SHOX-associated skeletal dysplasia.

Performance of noninvasive prenatal testing for twin pregnancies in South China.

OBJECTIVE: The purpose of this study was to evaluate the performance of noninvasive prenatal testing (NIPT) for the detection of chromosomal aneuploidies and copy number variations (CNVs) in twin pregnancies. METHOD: A cohort of 2010 women with twin pregnancies was recruited. 1331 patients opted for NIPT, and 679 patients opted for expanded NIPT (NIPT-plus). All high-risk patients were advised to undergo invasive prenatal diagnosis. All participants were followed up until 6 months after birth. RESULTS: Twenty-two cases were predicted to have a high risk of chromosome abnormalities by NIPT, of which 14 pregnant women underwent invasive prenatal diagnosis. The 14 cases included 3 cases of trisomy 21, 1 case of trisomy 18, 1 case of trisomy 7, 2 cases of sex chromosome aneuploidies (SCAs), and 7 cases of CNVs, of which the confirmed cases numbered 2, 1, 0, 1, and 0, respectively. Twenty cases were predicted to have a high risk of chromosome abnormalities by NIPT-plus, of which 16 pregnant women underwent invasive prenatal diagnosis. The 16 cases included 1 case of trisomy 21, 1 case of trisomy 7, 7 cases of SCAs, and 7 cases of CNVs, of which were confirmed in 1, 0, 3, and 2, respectively. No false-negative result was reported during the follow-up period. CONCLUSION: The NIPT/NIPT-plus has excellent performance in the detection of chromosome aneuploidies in twin pregnancies. But for CNVs, the effectiveness of NIPT is poor, and the NIPT-plus have a certain detection efficiency. It is worth noting that pre- and post-genetic counseling is especially important, and the chorionicity, mode of conception, clinical indications, and fetal fraction should be considered as influencing factors.

Combined fetal fraction to analyze the Z-score accuracy of noninvasive prenatal testing for fetal trisomies 13, 18, and 21.

OBJECTIVE: This study aims to evaluate the correlation combined fetal fraction and Z-score for fetal trisomies 13, 18, and 21 of NIPT by the semiconductor sequencing platform and further analyze the differences of different sequencing depths. METHODS: A cohort of 61,581 pregnancies were recruited for NIPT. Invasive prenatal diagnostic confirmation is recommended in all high-risk NIPT cases. Logistic regression and rank correlation analysis were applied to analyze the relationship between different parameters. ROC curve analysis was adopted to analyze the cutoff values of Z-score and fetal fraction. RESULTS: A total of 278 common trisomy pregnancies were verified in 377 NIPT-positive results. The fitted logistic regression models revealed that Z-scores of NIPT-positive results were significantly associated with PPVs (p < 0.05). The ROC curve analysis showed that the optimal cutoff value of Z-scores for T21, T18, and T13 was 7.597, 4.944, and 9.135 for NIPT and 9.489, 8.004, and 12.4 for NIPT-plus. If combing fetal fraction as another evaluation factor, the PPV of trisomy 21 gradually improved. We analyzed the correlation between the fetal fraction and the PPV, which revealed that the fetal fraction was significantly correlated with PPV. By analyzing the PPV of different groups divided by the associated criteria obtained from ROC curve, the PPV of high Z-score and high fetal fraction is higher in groups of Z-score > the optimal cutoff value. CONCLUSION: The results of this study show that the fetal fraction is significantly correlated with the PPV. Combining fetal fraction with Z-score is significantly better than in groups of Z-score-associated criteria; clinicians can give more accurate and efficient prenatal genetic counseling.

Performances of NIPT for copy number variations at different sequencing depths using the semiconductor sequencing platform.

OBJECTIVE: To evaluate the performance of noninvasive prenatal testing (NIPT) and NIPT-PLUS for the detection of genome-wide microdeletion and microduplication syndromes (MMSs) at different sequencing depths. The NIPT sequencing depth was 0.15X, and the data volume was 3 million reads; the NIPT-PLUS sequencing depth was 0.4X, and the data volume was 8 million reads. METHODS: A cohort of 50,679 pregnancies was recruited. A total of 42,969 patients opted for NIPT, and 7710 patients opted for NIPT-PLUS. All high-risk cases were advised to undergo invasive prenatal diagnosis and were followed up. RESULTS: A total of 373 cases had a high risk of a copy number variation (CNV) as predicted by NIPT and NIPT-PLUS: NIPT predicted 250 high-risk CNVs and NIPT-PLUS predicted 123. NIPT-PLUS increased the detection rate by 1.02% (0.58% vs 1.60%, p < 0.001). A total of 291 cases accepted noninvasive prenatal diagnosis, with 197 cases of NIPT and 94 cases of NIPT-PLUS. The PPV of CNV > 10 Mb for NIPT-PLUS was significantly higher than that for NIPT (p = 0.02). The total PPV of NIPT-PLUS was 12.56% higher than that of NIPT (43.61% vs 30.96%, p = 0.03). CONCLUSION: NIPT-PLUS had a better performance in detecting CNVs in terms of the total detection rate and total PPV. However, great care must be taken in presenting results and providing appropriate counseling to patients when deeper sequencing is performed in clinical practice.

Light modulation based on the enhanced Kerr effect in molybdenum disulfide nanostructures with curved features.

A novel type of molybdenum disulfide (MoS2) nanoparticles (NPs) was chemically synthesized, which possessed curved features with three-dimensional (3D) freedom compared with planar two-dimensional (2D) materials. Due to the introduction of curved features, the synthesized NPs exhibited a strongly enhanced nonlinear refractive index (n2 ∼ 10-5 cm-2 W-1) and third-order susceptibility (χ(3) ∼ 10-7 esu), which were experimentally verified by the spatial self-phase modulation effect in the visible wavelength range. Both the nonlinear parameters were two orders of magnitude higher than their planar MoS2 nanostructure counterparts. In addition, the relative change of the effective nonlinear refractive index Δn2/n2 was found to be distinctly dependent on the intensity of the applied electromagnetic field. Moreover, an all-optical modulation was experimentally realized based on the spatial cross-phase modulation effect. Our results demonstrate planar MoS2 materials with 3D features as potential candidates for next generation all-optical applications and open a substantial approach for the design of efficient nanomaterials with favorable optical nonlinearity.

Noninvasive prenatal detection of fetal sex chromosome abnormalities using the semiconductor sequencing platform (SSP) in Southern China.

BACKGROUND: Noninvasive prenatal testing (NIPT) has been widely used to screen for fetal aneuploidies, including fetal sex chromosome aneuploidies (SCAs). However, there is less information on the performance of NIPT in detecting SCAs. METHODS: A cohort of 47,800 pregnancies was recruited to review the high-risk NIPT results for SCAs. Cell-free fetal DNA (cffDNA) was extracted and sequenced. All NIPT high-risk cases were recommended to undergo invasive prenatal diagnosis for karyotyping analysis and chromosome microarray analysis (CMA). RESULTS: A total of 238 high-risk cases were detected by NIPT, including 137 cases of 45,X, 27 cases of 47,XXX, and 74 cases of 47,XYY/47,XXY. Prenatal diagnosis, including karyotyping analysis and CMA, was available in 170 cases. The positive predictive value (PPV) was 30.00% for 45,X, 70.58% for 47,XXX, and 81.13% for 47,XYY/47,XXY. In addition, 13 cases of sex chromosome mosaicism and 9 cases of sex chromosome CNVs were incidentally found in this study. CONCLUSION: Our study showed that NIPT was reliable for screening SCAs based on a large sample, and it performed better in predicting sex chromosome trisomies than monosomy X. Our study will provide an important reference for clinical genetic counseling and further processing of the results.

[Analysis of the results of chromosomal trisomies 21, 18 and 13 screening among 40 628 women by non-invasive prenatal testing].

OBJECTIVE: To assess the clinical value of non-invasive prenatal testing (NIPT) for the screening of trisomy and copy number variations (CNVs) of chromosomes 21, 18 and 13. METHODS: From January 2015 to December 2019, 40 628 pregnant women underwent NIPT testing using high-throughput sequencing and bioinformatics analysis to test the cell-free fetal DNA in maternal plasma. High-risk pregnant women underwent invasive prenatal diagnosis, while low-risk ones were followed up by telephone. RESULTS: The three most common indications included intermediate risk of serological screening, high risk of serological screening and advanced maternal age. Among all pregnant women, 257 cases were detected as trisomy 21, 18 and 13 (170, 49 and 38 cases, respectively). 227 cases chose invasive prenatal diagnosis, with respectively 122, 28 and 10 cases confirmed. The positive predictive value (PPV) was 81.33% (122/150), 65.12% (28/43), 29.41% (10/34), respectively. Two false negative cases of trisomy 18 were found during follow-up. Meanwhile, NIPT has detected 46 cases (15, 16 and 15 cases, respectively) CNVs on chromosomes 21, 18 and 13, among which 37 cases underwent invasive prenatal diagnosis. There were 5, 3 and 5 positive cases, which yielded a PPV of 41.67% (5/12), 25%(3/12) and 33.33%(5/15), respectively. Two other chromosome CNVs were accidentally discovered among the false positive samples. CONCLUSION: The incidence of chromosomal abnormalities in the serological screening high-risk group was 52.02%, which was significantly higher than other groups. NIPT has a high sensitivity and specificity for the screening of trisomies 21, 18 and 13, while its accuracy for detecting CNVs of chromosomes 21, 18 and 13 needs to be improved. As a screening method, NIPT has a great clinical value, though there are still limitations of false positive and false negative results.Comprehensive pre- and post-test genetic counseling should be provided to the patients.

The significance of trisomy 7 mosaicism in noninvasive prenatal screening.

BACKGROUND: This study was an evaluation of the role of noninvasive prenatal testing (NIPT) in the detection of trisomy 7 in prenatal diagnosis. METHOD: A total of 35 consecutive cases underwent screening for trisomies by cell-free DNA testing between April 2015 and November 2017 due to suspicious NIPT results; these cases represented 0.11% of patients (35/31,250) with similar frequencies of abnormal results among the laboratories performing the tests. NIPT was offered to further screen for common fetal chromosomal abnormalities. Karyotype analysis, chromosomal microarray analysis (CMA), and next-generation sequencing (NGS) were used to detect 20, 14, and 25 patients, respectively, who accepted confirmatory diagnostic testing. RESULTS: High-risk results by NIPT were recorded for trisomy 7 alone in 29 women: dual aneuploidy in 4 patients and multiple aneuploidy in 2 patients. Karyotype analysis of amniotic fluid cells was normal in all 20 pregnancies, suggesting a probability of confined placental mosaicism. Further CMA data were obtained in 14 of the cases mentioned above, and 2 fetuses were detected with positive results with copy number variation. The NGS results suggested that all these samples were placental chimerisms of chromosome 7, except for one sample that was found to be an additional chimerism of chromosome 2, which was also consistent with the NIPT result. CONCLUSION: Our results may be useful for the counseling of pregnant women in the detection of trisomy 7 by NIPT.

Factors affecting cell-free DNA fetal fraction: statistical analysis of 13,661 maternal plasmas for non-invasive prenatal screening.

BACKGROUND: The identification of cell-free fetal DNA (cffDNA) facilitated non-invasive prenatal screening (NIPS) through analysis of cffDNA in maternal plasma. However, challenges regarding its clinical implementation become apparent. Factors affecting fetal fraction should be clarified to guide its clinical application. RESULTS: A total of 13,661 pregnant subjects with singleton pregnancies who undertook NIPS were included in the study. Relationship of gestational age, maternal BMI, and maternal age with the cffDNA fetal fraction in maternal plasmas for NIPS was investigated. Compared with 13 weeks (12.74%) and 14-18 weeks group (12.73%), the fetal fraction in gestational ages of 19-23 weeks, 24-28 weeks, and more than 29 weeks groups significantly increased to 13.11%, 16.14%, and 21.17%, respectively (P < 0.01). Compared with fetal fraction of 14.54% in the maternal BMI group of < 18.5 kg/m2, the percentage of fetal fraction in the group of 18.5-24.9 kg/m2 (13.37%), 25-29.9 kg/m2 (12.20%), 30-34.9 kg/m2 (11.32%), and 35-39.9 kg/m2 (11.57%) decreased significantly (P < 0.01). Compared with the fetal fraction of 14.38% in the group of 18-24 years old, the fetal fraction in the maternal age group of 25-29 years old group (13.98%) (P < 0.05), 30-34 years old group (13.18%) (P < 0.01), 35-39 years old group (12.34%) (P < 0.01), and ≥ 40 years old (11.90%) group (P < 0.01) decreased significantly. CONCLUSIONS: The percentage of fetal fraction significantly increased with increase of gestational age. Decreased fetal fraction with increasing maternal BMI was found. Maternal age was also negatively related to the fetal fraction.

Noninvasive prenatal detection of hemoglobin Bart hydrops fetalis via maternal plasma dispensed with parental haplotyping using the semiconductor sequencing platform.

BACKGROUND: Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE: In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN: In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS: As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION: Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.

The impact of an mHealth app on knowledge, skills and anxiety about dressing changes: A randomized controlled trial.

AIMS: To evaluate the effectiveness of a mobile health (mHealth) application, based on self-regulation theory, on patients' knowledge of wound care, skills in changing dressings and anxiety. DESIGN: A prospective randomized controlled trial. METHODS: Seventy patients (or family members) at a 1,500-bed university hospital in Taiwan were randomized into an experimental (N = 35) or control group (N = 35) from March to December 2016. The experimental group used a mHealth application for wound care; the control group received verbal instructions and a booklet. Instruments to collect data were a wound care knowledge scale, wound care skills scale, State-Trait Anxiety Inventory, and a digital heart variability device. Data were collected at baseline, after three additional demonstrations and before discharge. The generalized estimating equation was used for statistical analysis. RESULTS: The experimental group showed significantly higher levels of wound care knowledge, improved wound care skills, lower levels of state anxiety, and lower heart rate variability than the control group after baseline data collection. CONCLUSIONS: Results support hat a mHealth application may be effective in health education. Clinicians can use the results to promote patients' wound care knowledge, enhance their wound care skills, and reduce anxiety related to dressing changes. IMPACT: Lack of wound care knowledge and skills can affect the willingness and ability to perform effective wound dressing changes, producing anxiety and having an impact on a patient's self-care after hospital discharge. mHealth applications (apps) have the potential to deliver health information in targeted and tailored ways that strengthen the self-management of diseases. mHealth app can increase wound care knowledge, improve care skills, and reduce anxiety related to wound care. mHealth app effectively supports self-monitoring of the wound healing process, self-judgement of the wound condition, and self-reaction of wound care accuracy. mHealth app provides step-by-step visual tutorials on wound care that allow patients and family caregivers to take pictures of the wounds and monitor the wound healing process. mHealth app for wound care knowledge is an effective and individualized method for learning. CLINICAL TRIAL: This study was registered by U.S. National Library of Medicine, ClinicalTrials.gov (ID: NCT03683303).

Topical tacrolimus and steroids modulate T cells in acute rejection of hand allotransplantation: Two case reports.

Acute rejection is not uncommon after vascularized composite allotransplantation. We reported the effects of adjunctive topical immunosuppressant with topical tacrolimus (Protopic®) and steroid cream (Clobetasol®) in the management of acute rejection in two hand transplantation patients. Case 1 is a 45-year-old male with distal forearm deficit 4 years ago and Case 2 is a 30-year-old male with a proximal forearm deficiency 2 years ago, respectively. Both of them suffered from occupational accident and received hand allotransplantation. Induction was performed with antithymocyte globulins and methylprednisolone. Maintenance therapy consisted of tacrolimus (FK506), mycophenolate mofetil, and prednisone. Both cases experienced acute rejection, which we treated with topical tacrolimus and Clobetasol for 2 weeks, combined with systemic immunosuppressant maintenance therapy without adding pulse-steroid therapy. Clinically, both cases recovered after adjunctive treatments. The skin biopsies showed significantly decreased perivascular lymphocyte infiltration after topical treatment. Immunohistochemical staining showed that CD3+ T-cells and CD20+ B-cells were suppressed in the recovery phase. FoxP3-positive regulatory T cells were increased after treatment. Topical tacrolimus and Clobetasol as an adjunctive treatment with maintenance systemic immunosuppressives may be useful to control acute rejection, which correlated with modulation of lymphocyte activation, especially T cells. The treatment needs further investigation with gaining more comparable data.

Association between fetal fraction at the second trimester and subsequent spontaneous preterm birth.

OBJECTIVE: To evaluate the association between the fetal fraction of cell-free DNA at the second trimester and subsequent spontaneous preterm birth. METHODS: In this retrospective cohort study, data were collected from women with singleton pregnancies who underwent noninvasive prenatal testing at 14 to 25 weeks of gestation. The eligible patients were classified into three groups according to pregnancy outcome: birth at ≥37 weeks of gestation (term group), delivery at <34 weeks of gestation (early spontaneous preterm), and delivery at 34+0 to 36+6  weeks of gestation (late spontaneous preterm). Stepwise linear regression was performed to determine the maternal characteristics associated with the fetal fraction of cell-free DNA. Logistic regression was used to determine the relationship between the fetal fraction of cell-free DNA and pregnancy outcomes by adjusting for history of preterm birth. RESULTS: A total of 8129 singleton pregnancies met the recruitment criteria. Among them, 7790 (95.83%) were in the term group, 284 (3.49%) were in the late spontaneous preterm group, and 55 (0.68%) were in the early spontaneous preterm group. The fetal fraction of cell-free DNA was negatively correlated with body mass index, maternal age, nulliparity, and history of spontaneous preterm birth; positively correlated with gestational age; and not correlated with assisted reproduction or surface antigen of hepatitis B virus (HBsAg) positivity. After adjusting for history of preterm birth, a logistic regression analysis demonstrated no statistically significant associations between the fetal fraction of cell-free DNA and spontaneous preterm birth in any of the preterm groups (<34 weeks, 34+0 to 36+6  weeks, and <37 weeks). CONCLUSION: Our preliminary study found no relationship between the fetal fraction on NIPT at the second trimester and subsequent spontaneous preterm birth.

Diagnostic Effect of the Single BP Cut-Offs for Identifying Elevated BP and Hypertension in Adolescents Aged 13-17 Years.

In contrast to the percentile-based definitions of elevated blood pressure (BP) and hypertension for children and adolescents of all ages in the 2004 fourth report, the 2017 American Academy of Pediatrics (AAP) BP guideline recommends a change to single BP cut-offs for clinical diagnosis (120/< 80-129/< 80 mmHg for elevated BP and ≥ 130/80 mmHg for hypertension) in adolescents aged 13 years and older, and it also recommends researchers using the percentile-based definitions for more precise BP classification. The aim of our study was to assess the diagnostic effect of the single BP cut-offs for identifying adolescent abnormal BP as compared to the 2017 AAP percentile table by sex, age, and height. Data were from 8287 adolescents aged 13-17 years in NHANES 1999-2016 and 1659 adolescents aged 13-17 years in NHANES III (1988-1994). Compared to the 2017 AAP percentile table, the single BP thresholds performed well for identifying elevated BP in adolescents in NHANES 1999-2016/NHANES III, with high values of area under the curve 0.93/0.95, sensitivity 86.7%/89.9%, specificity 100%/100%, positive predictive value (PPV) 100%/100%, negative predictive value (NPV) 98.2%/98.8%, and kappa coefficient 0.92/0.94. The results were similar for identifying hypertension in the two datasets, with especially high PPV 100%/100% and NPV 99.2%/99.2%. However, the sensitivity values of the simple method for identifying hypertension were not satisfactory among girls, younger adolescents, and Hispanic adolescents in both datasets. In conclusion, the single BP cut-offs in general performed similarly well for identifying abnormal BP as compared to 2017 AAP percentile table, but not well in some subgroups.

Association of risk factors for high blood pressure across 46 low- and middle-income countries: A multi-country cross-sectional analysis.

Background: Despite acknowledging the influence of various lifestyle and metabolic risk factors on hypertension, it remains uncertain to identify the primary contributors and differentiate which modifiable risk factors mediate the causal effects of hypertension. We aimed to examine the hierarchical association of eight prominent lifestyle and metabolic risk factors, along with demographic variables, with hypertension in adults and to explore the mediating effects of modifiable metabolic risk factors on hypertension. Methods: A cross-sectional study was conducted in 46 low- and middle-income countries using the World Health Organization (WHO) STEPwise approach to noncommunicable disease risk factor surveillance from 2002 to 2020. In a sample of 179 535 non-pregnant adults, we assessed the weighted population-attributable risk percentages (PAR%) for hypertension associated with eight risk factors. Additionally, we investigated the mediating role of metabolic risk factors on the effects of lifestyle risk factors on hypertension. Results: After adjusting for the sample weight in each country, 26.7% of participants had hypertension. The prevalence of hypertension was highest in those aged ≥65 years, with obesity-associated hypertension (45.7%) exceeding the rates for overweight (32.2%) and non-overweight individuals (18.2%). These eight risk factors collectively explain 83.7% of the PAR% associated with hypertension adjusted for the communal variance. Among the modifiable factors, obesity contributed to a weighted PAR% of 38.2%, while sedentary behaviour and low physical activity combined accounted for a weighted PAR% of 3.1%. Overweight/obesity played a predominant mediating role in the correlation between lifestyle risk factors and systolic and diastolic blood pressure, with the indirect effect accounting for approximately 25-64% and 13-80% of the total effect, respectively. Conclusions: These findings offer new insights into the modified risk factors associated with hypertension in adults in low- and middle-income countries, highlighting the crucial role of maintaining a normal body weight for the effective prevention and management of hypertension.

Establishment and application of a reverse dot blot assay for 13 mutations of hearing-loss genes in primary hospitals in China.

Background: Hearing loss is a common sensorineural dysfunction with a high incidence in China. Although genetic factors are important causes of hearing loss, hearing-related gene detection has not been widely adopted in China. Objective: Establishing a rapid and efficient method to simultaneously detect hotspot hearing loss gene mutations. Methods: A reverse dot blot assay combined with a flow-through hybridization technique was developed for the simultaneous detection of 13 hotspot mutations of 4 hearing loss-related genes including GJB2, GJB3, SLC26A4, and the mitochondrial gene MT-RNR1. This method involved PCR amplification systems and a hybridization platform. Results: The technique can detect 13 hotspot mutations of 4 hearing loss-related genes. And a total of 213 blood samples were used to evaluate the availability of this method. Discussion: Our reverse dot blot assay was a simple, rapid, accurate, and cost-effective method to identify hotspot mutations of 4 hearing loss-related genes in a Chinese population.

Deep metagenomic characterization of the gut virome in pregnant women with preeclampsia.

Preeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

Changes in methylation patterns of multiple genes from peripheral blood leucocytes of Alzheimer's disease patients.

BACKGROUND: Efforts aiming at identifying biomarkers and corresponding methods for early diagnosis of Alzheimer's disease (AD) might be the most appropriate strategy to initiate promising new treatments and/or prevention of AD OBJECTIVE: The aim of our study is to assess the association of DNA methylation pattern of various leucocyte genes with AD pathogenesis in order to find potential biomarkers and corresponding methods for molecular diagnosis of AD. METHODS: DNA methylation level of various genes in AD patients and normal population were compared by bisulphite sequencing PCR and methylation-specific PCR (MSP). Furthermore, real-time PCR was used to explore the effects of DNA methylation on the expression of target genes. RESULTS: Results showed significant hypermethylation of mammalian orthologue of Sir2 (SIRT1) gene in AD patients compared with normal population. Meanwhile, changes in methylation level of SIRT1 gene between different severities of AD were also found. Specific primers were designed from the SIRT1 CpG islands to differentiate AD and control group by MSP method. Besides, significant demethylation of ß-amyloid precursor protein (APP) gene was observed in AD patients, whereas no difference was observed in other AD-related genes. Moreover, significant decrease in expression of SIRT1 gene and increase in expression of APP gene were also found in AD patients. In addition, the expression level of SIRT1/APP genes was associated with the severity, but not with the age or gender, of AD patients. CONCLUSION: SIRT1 and APP might be the interesting candidate biomarkers and valuable for clinical diagnosis or treatment of AD.