Structure and dynamics of a pentameric KCTD5/CUL3/Gßγ E3 ubiquitin ligase complex.

Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3KCTD5) that ubiquitylates Gßγ and reduces Gßγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3NTD/Gß1γ2 assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5BTB/CUL3NTD and KCTD5CTD/Gßγ moieties of the structure. CRL3KCTD5 engages the E3 ligase ARIH1 to ubiquitylate Gßγ in an E3-E3 superassembly, and extension of the structure to include full-length CUL3 with RBX1 and an ARIH1~ubiquitin conjugate reveals that some conformational states position the ARIH1~ubiquitin thioester bond to within 10 Å of lysine-23 of Gß and likely represent priming complexes. Most previously described CRL/substrate structures have consisted of monovalent complexes and have involved flexible peptide substrates. The structure of the KCTD5/CUL3NTD/Gßγ complex shows that the oligomerization of a substrate receptor can generate a polyvalent E3 ligase complex and that the internal dynamics of the substrate receptor can position a structured target for ubiquitylation in a CRL3 complex.

Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein.

Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin (1), halolitoralin A (3), and a lactone pleurone (2), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1-3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A (1), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein.

Population genetic structure and demographic history of the dipterocarp species Anisoptera costata Korth revealed by microsatellite analysis.

MAIN CONCLUSION: Moderate levels of genetic diversity and differentiation of Anisoptera costata were determined. A population divergence occurred during Younger Dryas. The anthropogenic disturbance had significantly affected the genetic diversity of the species in low tropical forests. Anisoptera costata Korth, an endangered species, is mainly distributed in the lowland tropical forests of the Southeast region in Vietnam, which has not been explored for genetic diversity and demographic history. In this study, eight polymorphic microsatellite markers were used to analyze 232 wild trees of A. costata at nine different populations, representing the natural distribution range of the species in Vietnam. Genetic diversity within the populations was determined with mean values of 0.284 and 0.327 observed and expected heterozygosity, respectively, while genetic differentiation among populations was found with Weir and Cockerham index of 0.12 and Hedrick index of 1.38. These results indicated that habitat fragmentation by the anthropogenic disturbance may be the major factor for the low heterozygosity values and affected the number of alleles in all the targeted populations of A. costata in lowland tropical forests. Populations in the Central Southeast area had a higher level of genetic diversity than the populations in the Coastal and Western Southeast areas. The analysis of molecular variance showed that high genetic variation existed within populations (86.15%) compared to the variation among populations. A reduction in the population size of A. costata was determined by BOTTLENECK. Different clustering methods (Bayesian analysis, the neighbor-joining tree, and principal coordinate analysis) suggested optimal genetic clusters related to gene flow among different areas. Approximate Bayesian computation suggested that population divergence occurred during Younger Dryas. We also discussed the measures for species conservation based on these results.

Probabilities of False Alarm for Vital Sign Detection on the Basis of a Doppler Radar System.

Vital detection on the basis of Doppler radars has drawn a great deal of attention from researchers because of its high potential for applications in biomedicine, surveillance, and finding people alive under debris during natural hazards. In this research, the signal-to-noise ratio (SNR) of the remote vital-sign detection system is investigated. On the basis of different types of noise, such as phase noise, Gaussian noise, leakage noise between the transmitting and receiving antennae, and so on, the SNR of the system has first been examined. Then the research has focused on the investigation of the detection and false alarm probabilities of the system when the transmission link between the human and the radar sensor system took the Nakagami-m channel model. The analytical model for the false alarm and the detection probabilities of the system have been derived. The proposed theoretical models for the SNR and detection probability match with the simulation and measurement results. These theoretical models have the potential to be used as good references for the hardware development of the vital-sign detection radar sensor system.

Dynamic charging as a complementary approach in modern EV charging infrastructure.

Whether the future of transportation is going to be electric or not is no longer a question. Electric vehicles (EVs) offer several benefits toward global sustainability. However, without a variety of charging infrastructures that cover diverse forthcoming charging needs, the speed of vehicle electrification may be slow and limited. In this study, we investigate the synergistic benefits of traditional charging stations and an emerging alternative, i.e., wireless dynamic charging roads, focusing on their impact on the daily commute of EV users. We center our evaluation on quantifiable metrics, chiefly time and convenience, and deploy computer simulations utilizing authentic transportation datasets from New York City, USA. Our findings underscore that integrating both charging stations and charging roads can substantially alleviate detours for EV users and remarkably reduce additional charging time. Our research provides evidence to encourage researchers, EV manufacturers, urban infrastructure planners, and policymakers to explore future charging infrastructures for EVs, with a notable emphasis on wireless dynamic charging roads.

Application of DIY Electrodermal Activity Wristband in Detecting Stress and Affective Responses of Students.

This paper describes the analysis of electrodermal activity (EDA) in the context of students' scholastic activity. Taking a multidisciplinary, citizen science and maker-centric approach, low-cost, bespoken wearables, such as a mini weather station and biometric wristband, were built. To investigate both physical health as well as stress, the instruments were first validated against research grade devices. Following this, a research experiment was created and conducted in the context of students' scholastic activity. Data from this experiment were used to train machine learning models, which were then applied to interpret the relationships between the environment, health, and stress. It is hoped that analyses of EDA data will further strengthen the emerging model describing the intersections between local microclimate and physiological and neurological stress. The results suggest that temperature and air quality play an important role in students' physiological well-being, thus demonstrating the feasibility of understanding the extent of the effects of various microclimatic factors. This highlights the importance of thermal comfort and air ventilation in real-life applications to improve students' well-being. We envision our work making a significant impact by showcasing the effectiveness and feasibility of inexpensive, self-designed wearable devices for tracking microclimate and electrodermal activity (EDA). The affordability of these wearables holds promising implications for scalability and encourages crowd-sourced citizen science in the relatively unexplored domain of microclimate's influence on well-being. Embracing citizen science can then democratize learning and expedite rapid research advancements.

Retroperitoneal laparoscopic partial nephrectomy with selective renal artery clamping for renal cell carcinoma: initial outcomes.

Introduction: To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy (RLPN) with selective artery clamp (SAC) in patients with renal cell carcinoma (RCC). Methods: The authors recruited three men and two women who underwent RLPN for T1 RCC between December 2022 and May 2023 at a tertiary hospital. The median age of the patients was 32 years (range, 25-70 years). The tumour size ranged from 3 to 4.5 cm. The R.E.N.A.L scores were 4x, 5p, 8a, 5a, and 8ah. The median preoperative eGFR was 96.9 (74.3-105.2). Renal computed tomography angiography was performed before the surgery to evaluate the artery branches. The operation time, number of clamped arteries, warm ischaemic time (WIT), intraoperative blood loss, RCC type, postoperative hospital stay, changes in renal function, and complications were evaluated. The follow-up duration was 6 months. Results: The median operation time was 120 (75-150) minutes. One artery was clamped in four patients, while three were clamped in one patient. The median WIT was 22 (15-30) min, and the median blood loss was 150 (100-300) ml. No complications were recorded, and the resection margin was negative in all patients. The median decrease in eGFR was 6 (4-30%). Conclusions: RLPN with SAC for T1 RCC is safe and feasible in clinical practice.

Long-Term Safety and Efficacy of Transcatheter Microwave and Radiofrequency Denervation in a Chronic Ovine Model.

BACKGROUND: Transcatheter renal denervation (RDN) has had inconsistent efficacy and concerns for durability of denervation. We aimed to investigate long-term safety and efficacy of transcatheter microwave RDN in vivo in normotensive sheep in comparison to conventional radiofrequency ablation. METHODS AND RESULTS: Sheep underwent bilateral RDN, receiving 1 to 2 microwave ablations (maximum power of 80-120 W for 240 s-480 s) and 12 to 16 radiofrequency ablations (180 s-240 s) in the main renal artery in a paired fashion, alternating the side of treatment, euthanized at 2 weeks (acute N=15) or 5.5 months (chronic N=15), and compared with undenervated controls (N=4). Microwave RDN produced substantial circumferential perivascular injury compared with radiofrequency at both 2 weeks [area 239.8 (interquartile range [IQR] 152.0-343.4) mm2 versus 50.1 (IQR, 32.0-74.6) mm2, P <0.001; depth 16.4 (IQR, 13.9-18.9) mm versus 7.5 (IQR, 6.0-8.9) mm P <0.001] and 5.5 months [area 20.0 (IQR, 3.4-31.8) mm2 versus 5.0 (IQR, 1.4-7.3) mm2, P=0.025; depth 5.9 (IQR, 1.9-8.8) mm versus 3.1 (IQR, 1.2-4.1) mm, P=0.005] using mixed models. Renal denervation resulted in significant long-term reductions in viability of renal sympathetic nerves [58.9% reduction with microwave (P=0.01) and 45% reduction with radiofrequency (P=0.017)] and median cortical norepinephrine levels [71% reduction with microwave (P <0.001) and 72.9% reduction with radiofrequency (P <0.001)] at 5.5 months compared with undenervated controls. CONCLUSIONS: Transcatheter microwave RDN produces deep circumferential perivascular ablations without significant arterial injury to provide effective and durable RDN at 5.5 months compared with radiofrequency RDN.

The Relationship Between Smooth Endoplasmic Reticulum Clusters in Metaphase II Oocytes and Embryological and Birth Outcomes in Infertile Couples.

Background: To assess the relationship between oocytes with smooth endoplasmic reticulum cluster (SERc) and embryological and birth outcomes in infertile couples. Methods: This was a descriptive study that included 231 infertile patients undergoing in vitro fertilization (IVF) with a total of 2447 mature oocytes (MII), of which 279 oocytes with SERc(+) from 100 patients, the remaining 2168 oocytes with SERc(-). Oocytes were evaluated for the presence or absence of the SERc simultaneously with intracytoplasmic sperm injection at 200x magnification using inverted microscopy - Observe D1. Results: The mean age of patients was 32.05 ± 5.56 years. One hundred patients had at least one SERc(+) oocyte (with 279 SERc(+) and 956 SERc(-) oocytes). One hundred and thirty-one patients had 1212 SERc(-) oocytes. Fertilization outcomes and the rates of good-quality embryos on day 2 and day 5 did not differ between the SERc(+) and the SERc(-) groups. In the first frozen embryo transfer cycles, the clinical pregnancy rate in the group of patients with SERc(+) was not different with the SERc(-) group (61.1% vs 48.78%, p = 0.074, respectively). The live birth rate in the SERc(+) group was statistically significantly higher than the SERc(-) group (57.7% vs 43.9%, p = 0.045, respectively). Conclusion: The fertilization rate, the quality of embryos on days 2 and 5 from oocytes with SERc(+) are similar to those with SERc(-). The live birth rate in the patients with SERc(+) group is statistically significantly higher than the SERc(-) group. There is no difference in clinical pregnancy rate between patients with and without SERc. Therefore, the exclusion of oocytes with SERc should not be recommended.

Incoherent resonant seeding of modulation instability in optical fiber.

We report control of the spectral and noise properties of spontaneous modulation instability (MI) in optical fiber using an incoherent seed with power at the 10(-6) level relative to the pump. We sweep the seed wavelength across the MI gain band, and observe significant enhancement of MI bandwidth and improvement in the signal-to-noise ratio as the seed coincides with the MI gain peak. We also vary the seed bandwidth and find a reduced effect on the MI spectrum as the seed coherence decreases. Stochastic nonlinear Schrödinger equation simulations of spectral and noise properties are in excellent agreement with experiment.

The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection.

Background: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. Methodology: Female BALB/c mice were infected with a bioluminescent T. cruzi H1 clone for approximately 70 days, then randomly divided into groups of 15 mice each. Mice were treated with a 25mg/kg BNZ, 25µg Tc24-C4 protein/5µg E6020-SE (Vaccine), 25mg/kg BNZ followed by vaccine, or 100mg/kg BNZ (curative dose). At study endpoints we evaluated hepatomegaly, parasite burden by quantitative PCR, cellular infiltration by histology, and expression of B-cell translocation gene 2(BTG2) and Peroxisome proliferator-activated receptor alpha (PPARα) by RT-PCR. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were quantified from serum. Results: Curative BNZ treatment significantly reduced hepatomegaly, liver parasite burdens, and the quantity of cellular infiltrate, but significantly elevated serum levels of ALT, AST, and LDH. Low BNZ plus vaccine did not significantly affect hepatomegaly, parasite burdens or the quantity of cellular infiltrate, but only elevated ALT and AST. Low dose BNZ significantly decreased expression of both BTG2 and PPARα, and curative BNZ reduced expression of BTG2 while low BNZ plus vaccine had no impact. Conclusions: These data confirm toxicity associated with curative doses of BNZ and suggest that the dose sparing low BNZ plus vaccine treatment better preserves liver health.

The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection.

BACKGROUND: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. METHODOLOGY: Female BALB/c mice were infected with a bioluminescent T. cruzi H1 clone for approximately 70 days, then randomly divided into groups of 15 mice each. Mice were treated with a 25mg/kg BNZ, 25µg Tc24-C4 protein/ 5µg E6020-SE (Vaccine), 25mg/kg BNZ followed by vaccine, or 100mg/kg BNZ (curative dose). At study endpoints we evaluated hepatomegaly, parasite burden by quantitative PCR, cellular infiltration by histology, and expression of B-cell translocation gene 2(BTG2) and Peroxisome proliferator-activated receptor alpha (PPARα) by RT-PCR. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were quantified from serum. RESULTS: Curative BNZ treatment significantly reduced hepatomegaly, liver parasite burdens, and the quantity of cellular infiltrate, but significantly elevated serum levels of ALT, AST, and LDH. Low BNZ plus vaccine did not significantly affect hepatomegaly, parasite burdens or the quantity of cellular infiltrate, but only elevated ALT and AST. Low dose BNZ significantly decreased expression of both BTG2 and PPARα, and curative BNZ reduced expression of BTG2 while low BNZ plus vaccine had no impact. CONCLUSIONS: These data confirm toxicity associated with curative doses of BNZ and suggest that while dose sparing low BNZ plus vaccine treatment does not reduce parasite burdens, it better preserves liver health.

Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case-Control and Family-Based Study.

This study aims to identify potential variants in the TP63-IRF6 pathway and GREM1 for the etiology of non-syndromic orofacial cleft (NSOFC) among the Vietnamese population. By collecting 527 case-parent trios and 527 control samples, we conducted a stratified analysis based on different NSOFC phenotypes, using allelic, dominant, recessive and over-dominant models for case-control analyses, and family-based association tests for case-parent trios. Haplotype and linkage disequilibrium analyses were also conducted. IRF6 rs2235375 showed a significant association with an increased risk for non-syndromic cleft lip and palate (NSCLP) and cleft lip with or without cleft palate (NSCL/P) in the G allele, with pallele values of 0.0018 and 0.0003, respectively. Due to the recessive model (p = 0.0011) for the NSCL/P group, the reduced frequency of the GG genotype of rs2235375 was associated with a protective effect against NSCL/P. Additionally, offspring who inherited the G allele at rs2235375 had a 1.34-fold increased risk of NSCL/P compared to the C allele holders. IRF6 rs846810 and a G-G haplotype at rs2235375-rs846810 of IRF6 impacted NSCL/P, with p-values of 0.0015 and 0.0003, respectively. In conclusion, our study provided additional evidence for the association of IRF6 rs2235375 with NSCLP and NSCL/P. We also identified IRF6 rs846810 as a novel marker associated with NSCL/P, and haplotypes G-G and C-A at rs2235375-rs846810 of IRF6 associated with NSOFC.

Modal decomposition technique for multimode fibers.

We propose a new solution for modal decomposition in multimode fibers, based on a spectral and spatial imaging technique. The appearance of spurious modes in the spectral and spatial processing of the images at the output of the fiber under test when it has more than two modes is demonstrated theoretically. The new method, which allows us to identify spurious modes, is more accurate, simpler, and faster than previously reported methods. For demonstration, measurements in a standard step-index multimode fiber and a small-core microstructured fiber are carried out successfully.

Efficient four-wave mixing in an ultra-highly nonlinear suspended-core chalcogenide As38Se62 fiber.

We report a chalcogenide suspended-core fiber with ultra-high nonlinearity and low attenuation loss. The glass composition is As(38)Se(62).With a core diameter as small as 1.13 µm, a record Kerr nonlinearity of 46,000 W(-1) km(-1) is demonstrated with attenuation loss of 0.9 dB/m. Four-wave mixing is experimented by using a 1m-long chalcogenide fiber for 10 GHz and 42.7 GHz signals. Four-wave mixing efficiencies of -5.6 dB at 10 GHz and -17.5 dB at 42.7 GHz are obtained. We also observed higher orders of four-wave mixing for both repetition rates.

Normative Nasalance Values in Vietnamese With Southern Dialect: Vowel and Tone Effects.

Purpose The purpose of the current study was to examine normative nasalance values in Vietnamese adult speakers with Southern dialect and to investigate the effects of vowels and tones on nasalance. Previous studies examining nasalance have been mainly conducted with Indo-European languages. Limited information on nasalance is available in tone languages other than Chinese. Furthermore, tone and vowel effects on nasalance scores in tone languages have not been fully examined. Method Nasalance scores of various speech stimuli including passages, syllables, and prolonged vowels were obtained from Vietnamese-speaking adults with Southern dialect (M age = 23 years) using a nasometer (KayPENTAX 6450). Results The average nasalance scores of Southern Vietnamese adult speakers were 24.16%, 38.17%, and 70.03% for the oral, oral-nasal, and nasal passages, respectively. Southern Vietnamese speakers produced the highest nasalance scores on the vowel /a/, followed by /i/ and /u/. Nasalance scores of stimuli produced with the falling and restricted tone were significantly lower than those produced with the other tones. Conclusions The normative nasalance values of the current study will contribute as a reference index for the Vietnamese language. The effects of vowels and tones can also provide insight into the development of nasalance testing stimuli and for characterizing nasalance values across languages.

Optimizing Impedance Change Measurement During Radiofrequency Ablation Enables More Accurate Characterization of Lesion Formation.

OBJECTIVES: This study sought to determine whether a novel impedance thermal imaging system (ITIS) provides an impedance measurement that is better correlated with lesion dimensions than circuit impedance during radiofrequency (RF) ablation. BACKGROUND: A 5- to 10-Ω impedance drop is clinically used to corroborate an effective RF ablation lesion. However, the contribution of local tissue heating to circuit impedance change is small and dependent on the local environment of the catheter and placement of the grounding patch. METHODS: ITIS uses ablation catheter and skin electrodes to perform 4-terminal impedance measurements with separate voltage sensing and current injection electrode pairs. Seven sheep underwent endocardial ventricular irrigated RF ablation at 40 W for 60 s. ITIS impedance and circuit impedance were both measured throughout ablation. When the sheep were sacrificed, ablation lesions were cut along their long axis; the depth, width, and surface area of the cut surface were measured. RESULTS: A total of 68 RF ablations were performed, with a median depth of 3.5 mm (interquartile range [IQR]: 2.1 to 4.9 mm), width of 8.3 mm (IQR: 5.7 to 10.8 mm), and surface area of 23.8 mm2 (IQR: 9.3 to 43.0 mm2). ITIS impedance change had good correlation with lesion depth, width, and surface area (R = 0.76, R = 0.87, and R = 0.87, respectively); and superior to circuit impedance for lesion depth, width, and surface area (p = 0.0018, p = 0.0004, and p = 0.0001, respectively). CONCLUSIONS: By optimizing the current path and using 4-terminal impedance measurement during RF ablation, the contribution of tissue temperature changes to measured impedance is better standardized to provide a more reliable measure than conventional ablation circuit impedance.

Dentinogenesis Imperfecta and Caries in Osteogenesis Imperfecta among Vietnamese Children.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass, caused mainly by mutations in collagen type I encoding genes. The current study aimed to evaluate dentinogenesis imperfecta (DI), oral manifestations and caries status of OI children. Sixty-eight children (41 males, 27 females) aged from 3 to 17 years old (mean 9 ± 4.13) participated in the study. Participants were classified into three OI type groups (I-2 cases, III-31 cases and IV-35 cases). Clinical examination and an orthopantomogram were used to obtain prevalences and associations of DI, caries status, malocclusion, crossbite, open bite, eruption, impaction and missing teeth with OI. The prevalence of DI among OI patients was 47.1%, more common in OI type III than type IV. The yellow-brown discoloration type was more vulnerable to attrition than the opalescent-grey one in the primary dentition. OI seemed not to have a high risk of caries; the prevalence of caries was 69.1%. A high incidence of malocclusion, crossbite and open bite was observed. In-depth oral information would provide valuable data for better dental management in OI patients. Parents and general doctors should pay more attention to dental care to prevent caries and premature tooth loss.

Oro-Dental Health and Primary Nephrotic Syndrome among Vietnamese Children.

Primary nephrotic syndrome (PNS) is common in children, affecting the soft and hard tissues of the oral cavity. This study aimed to investigate the percentage of dental caries, gingivitis, hypertrophic gingivitis, and developmental defects of enamel (DDE) in children with PNS. The association of PNS with these diseases and oral care behavior was also assessed. A total of 407 children with PNS and 407 age- and gender-matched controls were recruited. PNS was diagnosed based on blood and urinary tests. The Simplified Oral Hygiene Index (OHI-S), the Gingival Index (GI), the Gingival Overgrowth Index (GOI), the Decayed, Missing, and Filled Teeth Index (dmft/DMFT), and DDE were collected. The PNS patients showed significantly higher scores of OHI-S, GI, and dmft, and higher proportions of dental caries and DDE than those of the controls (p < 0.001). It is necessary to establish a periodic dental protocol for PNS patients to improve their oral health status.

Family based and case-control designs reveal an association of TFAP2A in nonsyndromic cleft lip only among Vietnamese population.

AIMS: Dozens of causative genes and their mechanisms of nonsyndromic cleft lip with or without cleft palate (NSCL/P) were revealed through genome-wide association and linkage studies. Results were, however, not always replicated in different populations or methodologies. This study used case-control and family based approaches to investigate the etiology of NSCL/P and its two subtypes: nonsyndromic cleft lip only (NSCLO) and nonsyndromic cleft lip and palate (NSCLP) among the Vietnamese population. METHODS: Two hundred and seventeen NSCL/P case-parent trios (one affected child and two parents), including 105 NSCLO and 112 NSCLP were involved for a family based design; and 273 ethnic and region-matched healthy controls with no cleft history in their families were recruited for a case-control design. Three SNPs consisting of TFAP2A (rs1675414 and rs303048) and 8q24 (rs987525) were genotyped using the TaqMan SNP genotyping assay. RESULTS: TFAP2A rs1675414 was associated with NSCLO, replicated by both case-control and family based tests. Other SNPs yielded no evidence of susceptibility to NSCL/P or two subtypes. CONCLUSION: The current investigation suggests an intriguing role of TFAP2A in the etiology of NSCLO among the Vietnamese population.