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  1. Shafiee MN, Kah Teik C, Md Zain RR, Kampan N
    Horm Mol Biol Clin Investig, 2019 Aug 09;41(2).
    PMID: 31398145 DOI: 10.1515/hmbci-2019-0037
    Uterine leiomyosarcoma (LMS) is rare but primary ovarian LMS is even rarer constituting less than 0.1% of all gynecologic disorders. Neither histologic features nor immunohistochemistry could be utilized to distinguish between uterine or ovarian origin. We illustrate a clinical case of metastatic LMS to the ovary in a woman with underlying uterine fibroid presenting with anemia with heavy menses.
  2. Esther LSY, Chew KT, Rahman RA, Zainuddin AA, Hing EY, Kampan N
    Horm Mol Biol Clin Investig, 2020 Mar 13;41(2).
    PMID: 32167930 DOI: 10.1515/hmbci-2020-0001
    Intramyometrial ectopic pregnancy (IMEP) is a rare form of ectopic pregnancy. It is defined as a conceptus implanted within the myometrium and is completely surrounded by myometrium with clear separation from both the uterine cavity and tubes. IMEP possesses not only diagnostic but also therapeutic challenge. The majority of reported cases were managed by hysterectomy. Early management of unruptured IMEP using methotrexate may help to preserve fertility. We, for the first time, report a case of ruptured IMEP managed successfully using suction and curettage followed by Bakri balloon tamponade and avoiding hysterectomy. Post-procedure, the patient received two doses of intramuscular methotrexate 50 mg/m2 due to plateauing serial beta human chorionic gonadotropin (β-hCG) levels and subsequently achieved undetectable level 10 weeks post-methotrexate. She also had complete resolution of the ectopic intramyometrial mass.
  3. Mosavat M, Omar SZ, Sthanshewar P
    Horm Mol Biol Clin Investig, 2020 Mar 13;41(2).
    PMID: 32167928 DOI: 10.1515/hmbci-2019-0060
    Background Fibroblast growth factors (FGFs); FGF-21 and FGF-23, have been proposed to be associated with metabolic syndrome. However, data on the role of these peptides in gestational diabetes mellitus (GDM) are limited. Therefore, this study was designed to assess the association of serum FGF-21 and FGF-23 with the risk of GDM. Furthermore, we evaluated the circulation of these peptides in pregnancy and post-puerperium. Materials and methods Fifty-three pregnant subjects with GDM and 43 normal glucose tolerance (NGT) pregnant women participated in this study. Serum FGF-21 and FGF-23 were measured during pregnancy and post-puerperium. Results FGF-21 and FGF-23 were low in GDM compared to NGT during pregnancy. There were no significant differences in the level of these peptides post-puerperium. Using logistic regression, FGF-23 [odds ratio (OR) 0.70 (95% confidence interval [CI]: 0.50-0.96)] was inversely associated with GDM, so a 1-μg/mL decrease in FGF-23 levels was associated with a 1.4-fold increased risk of developing GDM and this remained statistically significant after adjustment for confounders [adjusted OR (aOR) 0.70 (95% CI: 0.50-0.98)]. There was no association of FGF-21 with the development of GDM risk. Conclusions Lower FGF-23 concentrations could be involved in the pathophysiology of GDM. FGF-21, even though associated with metabolic risk factors in pregnancy, may not be a fundamental factor in GDM.
  4. Basri NI, Abd Ghani NA, Mahdy ZA, Abdul Manaf MR, Mohamed Ismail NA
    Horm Mol Biol Clin Investig, 2020 Apr 17;41(3).
    PMID: 32304300 DOI: 10.1515/hmbci-2019-0069
    Background The objective was to compare the effectiveness and tolerability of mefenamic acid and celecoxib in women with primary dysmenorrhea (PD) and to compare the quality of life of study participants pre- and post-treatment. Materials and methods This was a randomized crossover clinical trial conducted among sexually inactive female adults aged 18-25 years with PD. Participants were asked to rate their pain score and answer a validated quality of life questionnaire (EQ-5D-3L) before and after consumption of each medication in two menstrual cycles. The effectiveness of celecoxib and mefenamic acid in treating PD was compared with regard to reduction in pain score and the need for medical leave and rescue therapy. Drug tolerability was determined by comparing the occurrence of side effects of both drugs. Quality of life scores pre- and post-intervention were measured and compared. Results Mefenamic acid had a comparable effect to celecoxib in relieving symptoms of PD. Both drugs were equally tolerable and showed similar impacts on quality of life. Conclusions This study demonstrated that mefenamic acid and celecoxib had similar effectiveness in improving pain score and quality of life in women with PD.
  5. Tiong YL, Ng KY, Koh RY, Ponnudurai G, Chye SM
    Horm Mol Biol Clin Investig, 2020 Jun 29;41(4).
    PMID: 32598308 DOI: 10.1515/hmbci-2020-0009
    BACKGROUND: Cardiovascular disease (CVD) is one of the major cause of mortality in diabetic patients. Evidence suggests that hyperglycemia in diabetic patients contributes to increased risk of CVD. This study is to investigate the therapeutic effects of melatonin on glucose-treated human umbilical vein endothelial cells (HUVEC) and provide insights on the underlying mechanisms.

    MATERIALS AND METHODS: Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and membrane potential was detected using 2',7'-dichlorofluorescein diacetate and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1) dye staining, respectively. While, cell apoptosis was determined by Annexin-V staining and protein expression was measured using Western blot.

    RESULTS: Our results suggested that melatonin inhibited glucose-induced ROS elevation, mitochondria dysfunction and apoptosis on HUVEC. Melatonin inhibited glucose-induced HUVEC apoptosis via PI3K/Akt signaling pathway. Activation of Akt further activated BcL-2 pathway through upregulation of Mcl-1 expression and downregulation Bax expression in order to inhibit glucose-induced HUVEC apoptosis. Besides that, melatonin promoted downregulation of oxLDL/LOX-1 in order to inhibit glucose-induced HUVEC apoptosis.

    CONCLUSIONS: In conclusion, our results suggested that melatonin exerted vasculoprotective effects against glucose-induced apoptosis in HUVEC through PI3K/Akt, Bcl-2 and oxLDL/LOX-1 signaling pathways.

  6. Chua AC, Abdul Karim AK, Tan ACC, Abu MA, Ahmad MF
    Horm Mol Biol Clin Investig, 2021 Jun 14;42(4):367-372.
    PMID: 34118795 DOI: 10.1515/hmbci-2020-0089
    OBJECTIVES: The male-factor subfertility was reported to be 30% globally; thus, the intracytoplasmic sperm injection (ICSI) procedure was implemented to improve the overall in vitro fertilization (IVF) rates. Nevertheless, at least 10% of fertilization failure still occurs. Concerning this issue, we explored the association of sperm concentration and motility with the quality of embryo development and pregnancy outcome in IVF-ICSI cycles.

    METHODS: Retrospective analysis of 109 couples with male factor were done over 14 months in a tertiary university hospital in Malaysia. The data were divided into four groups; Group I: normal sperm parameters, Group II: normal sperm concentration but reduced total sperm motility, Group III: reduced sperm concentration and motility, Group IV: reduced sperm concentration but normal sperm motility. Only fresh semen samples and fresh embryo transfers were included. The fertilization, cleavage rate, embryo quality and pregnancy outcome were assessed.

    RESULTS: Overall, group I had the highest oocytes yield and ICSI attempted; (10.12 + 6.50), whereas the lowest was in group IV; (7.00 + 2.82). Group II revealed the highest fertilization and cleavage rates; (54.14 + 25.36), (55.16 + 26.06), thus not surprisingly resulting in the highest number of good embryos and highest clinical pregnancy rates. The lowest cleavage and pregnancy rates were seen in group IV. However, all the outcomes were not statically significant (p>0.05).

    CONCLUSIONS: Similar fertilization rate and comparable pregnancy outcome was seen among couples with normal and reduced sperm concentration and motility.

  7. Ng MG, Ng KY, Koh RY, Chye SM
    Horm Mol Biol Clin Investig, 2021 Aug 06;42(4):445-461.
    PMID: 34355548 DOI: 10.1515/hmbci-2021-0009
    Leukaemia is a haematological malignancy originated from the bone marrow. Studies have shown that shift work could disrupt the melatonin secretion and eventually increase leukaemia incidence risk. Melatonin, a pineal hormone, has shown promising oncostatic properties on a wide range of cancers, including leukaemia. We first reviewed the relationship between shift work and the incidence rate of leukaemia and then discussed the role of melatonin receptors (MT1 and MT2) and their functions in leukaemia. Moreover, the connection between inflammation and leukaemia, and melatonin-induced anti-leukaemia mechanisms including anti-proliferation, apoptosis induction and immunomodulation are comprehensively discussed. Apart from that, the synergistic effects of melatonin with other anticancer compounds are also included. In short, this review article has compiled the evidence of anti-leukaemia properties displayed by melatonin and discuss its potential to act as adjunct for anti-leukaemia treatment. This review may serve as a reference for future studies or experimental research to explore the possibility of melatonin serving as a novel therapeutic agent for leukaemia.
  8. Khoo BP, Chew KT, Hing EY, Kampan N, Shafiee MN
    Horm Mol Biol Clin Investig, 2021 Aug 10;42(4):429-433.
    PMID: 34378876 DOI: 10.1515/hmbci-2021-0025
    OBJECTIVES: Endometrial cancer is the sixth most common cancer among women and recurrence of after 10 years is extremely rare.

    CASE PRESENTATION: We reported a comprehensive review of histopathology, investigations and treatment regarding a woman with distant recurrence of endometrial cancer to rectus abdominis muscle after 23 years from the primary surgery. Previous published literatures of similar case were included into the review analysis. A total of 11 similar cases had been reported. Overall, 9 (81.8%) cases were stage 1 disease and only 2 cases were classified as stage II disease. The majority, 6 (54.5%) cases were endometrial adenocarcinoma. Majority of the cases shared the similarity of low grade endometrial cancer with positive oestrogen receptor immunophynetype.

    CONCLUSIONS: Thus, the phenomenon of 'cell dormancy' was hypothesized to explain the mechanism of late recurrence for these cases.

  9. Yeoh S, Yong SL, Teoh PI, Kang M
    PMID: 34854654 DOI: 10.1515/hmbci-2021-0048
    OBJECTIVES: Choriocarcinoma after a term pregnancy is rare and can be life-threatening, especially when it perforates the uterus, resulting in massive haemoperitoneum. As uterine rupture due to choriocarcinoma is uncommonly encountered in the clinical practice, its diagnosis is often missed or delayed.

    CASE PRESENTATION: We present a case of a 41-year-old para 4 + 1 who had acute abdomen and hypovolaemic shock secondary to haemoperitoneum at three months postpartum period. The urine pregnancy test was positive, and, therefore, a provisional diagnosis of a ruptured ectopic pregnancy was made. She was managed aggressively with fluids and blood product transfusion at the emergency department to achieve haemodynamic stability. Subsequently, she underwent an emergency laparotomy where intraoperatively noted a perforation at the left posterior uterine cornu with purplish tissue spillage. A wedge resection was performed, and the histopathological examination (HPE) was reported as atypical trophoblastic cells, in which choriocarcinoma could not be ruled out. The patient then underwent a total abdominal hysterectomy three weeks later. The final HPE confirmed the diagnosis of choriocarcinoma.

    CONCLUSIONS: The clinical presentation of postpartum choriocarcinoma can be indistinguishable from a ruptured ectopic pregnancy. A high index of suspicion is crucial to allow early diagnosis.

  10. Shafiee MN, Lim WK, Poh Shwen Shi C, Mohamed Yasin IA, Azemi AF, Zakaria ML, et al.
    Horm Mol Biol Clin Investig, 2021 Aug 09;42(4):403-410.
    PMID: 34364315 DOI: 10.1515/hmbci-2021-0017
    OBJECTIVES: To determine the significance of tumour PTEN protein expression in endometrioid endometrial carcinoma (EEC) and it is correlation with tumour characteristics.

    METHODS: A total of 30 eligible archived paraffin-embedded tissue blocks from 61 EEC cases (January 2015-December 2017) were retrieved from the Histopathology Laboratory in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) following institutional ethic approval. For PTEN protein detection, immunohistochemistry (IHC) staining was performed and the data was correlated with clinicopathologic parameters.

    RESULTS: Fourteen samples (46.7%) showed positive PTEN protein expression, while 16 (53.3%) were negative. The mean age was 62.00 ± 9.51 years old, while the mean Body Mass Index (BMI) was 27.28 ± 7.16 kg/m2. There was no significant difference between age (p=0.27, 95% CI: -10.98 to 3.21) and BMI (p=0.67, 95% CI: -4.30 to 6.58) with PTEN protein expression. There were significant correlation between PTEN protein expression with myometrial invasion (p=0.010), but not with lymphovascular space invasion (p=0.743), grade (p=0.532), stage (p=0.733) and CA-125 level (p=0.47). The higher stage correlates with the presence of LVSI (p=0.002). PTEN positive associated with longer disease-free-interval (p=0.025), but not improving the overall survival (p=0.38).

    CONCLUSIONS: Positive PTEN protein expression correlates with less myometrial invasion.

  11. Harbhajan Singh JS, Ahmad MF, Abu MA, Omar MH, Abdul Karim AK
    Horm Mol Biol Clin Investig, 2021 Jul 29;42(4):389-393.
    PMID: 34323055 DOI: 10.1515/hmbci-2021-0002
    OBJECTIVES: The role of air bubbles in bracketing the embryo-containing medium in inner catheter during embryo transfer (ET) has already been established. However, the role of air bubbles in outer catheter (OC) during implantation is yet to be determined. This study aimed to compare the implantation rates between women who have undergone ET with or without ASP (Vitrolife®; Sweden), a medium use for oocyte retrieval and rinsing in OC embryo catheter. The purpose of introducing the ASP medium to the OC was to eliminate air bubbles in that space during implantation.

    METHODS: A total of 312 women were randomly divided into two groups with 156 participants each group. In Group A, ASP medium was used during ET, whereas in Group B, no ASP medium was utilized. Positive implantation was defined as serum beta-hCG level >5 mIU/mL taken on the 7th day following ET.

    RESULTS: The average age of the majority of the participants was 30-39 years and had at least 4-5 years of subfertility. The unexplained subfertility was the prominent cause of ET failure in both groups. In most of the participants in both groups, ET was done using fresh embryo cycles with good to excellent embryo grades. After the ASP medium was manipulated in the OC in both groups, the positive implantation rate was not different in both groups (p>0.05).

    CONCLUSIONS: The elimination of air bubbles in OC by using the ASP medium during ET did not confer an additional benefit nor exert a negative impact on implantation rate.

  12. Basri NI, Soon CH, Ali A, Abdul Ghani NA, Zainuddin AA
    Horm Mol Biol Clin Investig, 2021 Mar 08;42(3):325-328.
    PMID: 33675193 DOI: 10.1515/hmbci-2021-0001
    OBJECTIVES: We compared cases of phenotypic female patients who presented with male karyotype and underwent prophylactic gonadectomy.

    CASE PRESENTATION: Five patients with female phenotypes presented in early adulthood with primary amenorrhoea with varying degrees of puberty. One was tall with breast development. Another was very short with clitoromegaly and multiple co-morbidities. The other three had no secondary sexual characteristics. They were examined, after which hormonal profile, karyotyping, ultrasound examination and magnetic resonance imaging were done to assess the site of gonads. Gonadectomy was performed once their 46 XY karyotype was confirmed. Results of histopathological examination of their gonads ranged from dysgenetic gonads to having testicular tissues and malignancy.

    CONCLUSION: Female patients with 46 XY karyotypes require prophylactic gonadectomy performed at different timings depending on diagnosis due to the malignancy risk. Pre-operative assessment is essential to locate the gonads prior to surgery.

  13. Zainal N, Kampan NC, Rose IM, Ghazali R, Shafiee MN, Yussoff NH, et al.
    Horm Mol Biol Clin Investig, 2021 May 21;42(3):311-316.
    PMID: 34018382 DOI: 10.1515/hmbci-2020-0086
    OBJECTIVES: Gestational trophoblastic disease comprises of a spectrum of pregnancy-related tumours which includes complete (CHM) and partial hydatidiform moles (PHM). Accurate diagnosis and subclassification of HM subtypes are crucial as prognosis differs. Histopathological examination using haemotoxylin and eosin (H&E) staining remains the basis for diagnosing HM, with only 80% accuracy. p57kip2 is a cyclin-dependent kinase inhibitor (CDKI) protein and is strongly paternally imprinted, being expressed from maternal allele. Therefore, complete mole (CHM) with only paternal genome has nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes. This study is aimed to determine usefulness of p57kip2 immunohistochemistry (IHC) analysis in the diagnosis of HM subtypes.

    METHODS: A total of 82 archived paraffin embedded HM tissues with subtypes classified based on H&E staining - 39 (47.5%) CHM, 41 (50.0%) PHM and two (2.43%) unclassified molar pregnancy were retrieved. All tissue samples were subjected for p57kip2 IHC analysis and HM subtypes were then reclassified.

    RESULTS: A total of 66 cases (80.5%) were re-classified as CHM, 14 cases (17.1%) as PHM and two cases (2.4%) were decidual and cystic tissues. Analysis using p57kip2 immunostaining showed a diagnostic discrepancy of 33.0% from routine H&E staining and helps to improve the characterisation of the HM subtypes specifically at early gestations which have less distinctive morphologies.

    CONCLUSIONS: IHC using p57kip2 monoclonal antibody should be considered as a routine ancillary test to H&E in improving the diagnosis of HM subtypes particularly in developing countries with limited resources.

  14. Abu MA, Borhan AS, Abdul Karim AK, Ahmad MF, Mahdy ZA
    Horm Mol Biol Clin Investig, 2020 Dec 14;42(1):49-56.
    PMID: 33781008 DOI: 10.1515/hmbci-2020-0034
    OBJECTIVES: To compare the effect of Iberet Folic® and Zincofer® on haemoglobin (Hb) and serum ferritin level; and its adverse effect.

    METHODS: This randomised controlled trial conducted from January 2018 until December 2018. Pregnant women below 34 weeks of gestation, with Hb concentration less than 11 g/dL and serum ferritin level less than 12 ug/L were randomised to receive either one tablet Zincofer® or one tablet Iberet Folate® daily for four weeks. Both groups were compared in terms of effect on Hb level, serum ferritin level, and other haematological indices adverse effect related to treatment, and treatment cost.

    RESULTS: Hundred and thirty patients were recruited in this study with 68 patients in Iberet Folic group and 62 patients in Zincofer group. The change in the Hb and serum ferritin level from baseline to day 30 did not differ significantly between treatment groups. The mean (±SD) change from baseline to day 30 was 2.15 (±0.59) g/dL in the Iberet Folic group, and 1.98 (±0.49) in the Zincofer (p value = 0.08). Mean serum ferritin at day 30 was 17.2 (±3.68) ug/L and 16.7 (±4.28) ug/L with 8.44 (±3.41) and 8.55 (±3.50) difference, respectively (p = 0.86). Adverse events were comparable in between groups, with p value >0.05. GI intolerance and constipation were among the common side effects, occurred in 34.6 and 29.2% cases, respectively.

    CONCLUSIONS: Zincofer® offers equivalent efficacy and side effect profile in comparison with Iberet Folic® for the treatment of iron deficiency anaemia (IDA) during pregnancy, but with lower cost.

  15. Ngai ZN, Chok KC, Ng KY, Koh RY, Chye SM
    Horm Mol Biol Clin Investig, 2022 Dec 01;43(4):485-503.
    PMID: 35728260 DOI: 10.1515/hmbci-2022-0018
    Lung cancer is the second most common cancer and the most lethal cancer worldwide. Melatonin, an indoleamine produced in the pineal gland, shows anticancer effects on a variety of cancers, especially lung cancer. Herein, we clarify the pathophysiology of lung cancer, the association of circadian rhythm with lung, and the relationship between shift work and the incidence of lung cancer. Special focus is placed on the role of melatonin receptors in lung cancer, the relationship between inflammation and lung cancer, control of cell proliferation, apoptosis, autophagy, and immunomodulation in lung cancer by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as a comprehensive reference for the various mechanisms of action of melatonin against lung cancer, as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for lung cancer.
  16. Mat Jin N, Ahmad SM, Mohd Faizal A, Abdul Karim AKB, Abu MA
    Horm Mol Biol Clin Investig, 2022 Dec 01;43(4):469-474.
    PMID: 35545610 DOI: 10.1515/hmbci-2021-0096
    OBJECTIVES: We aim to discuss the hematological cancer cases that opted for ovarian tissue cryopreservation (OTC) as fertility preservation before the gonadotoxic chemotherapy agent.

    CASE PRESENTATION: The ovarian tissue cryopreservation (OTC) was started in August 2020 in our center. Up to now, there were four cases have been performed and included in this report. The ovarian tissue cortex was cryopreserved with cryoprotectant using Kitazato™ (Tokyo, Japan) media and fit in the closed system devices. A total of four post-OTC patients were included. The mean age was 24 years old, whereas the mean serum AMH level was 30.43 pmol/L. Most of them were diagnosed with lymphoma, except one was leukemia. All of them received additional GnRH analog following OTC as a chemoprotective agent before cancer treatment. Currently, they are recovering well and on regular follow-up with the hematological department.

    CONCLUSIONS: Although The OTC is an ultimate option for prepubertal girls, it can be proposed as a good strategy for adult cancer women who could not delay cancer therapy.

  17. Ahmad SM, Mat Jin N, Ahmad MF, Abdul Karim AK, Abu MA
    Horm Mol Biol Clin Investig, 2023 Dec 01;44(4):379-384.
    PMID: 38124670 DOI: 10.1515/hmbci-2022-0087
    OBJECTIVES: Unexplained subfertility (UEI) describes a couple whose standard subfertility workout consider acceptable but unable to conceived.

    METHODS: This retrospective study was conducted in the Advanced Reproductive Centre, UKM Hospital, Kuala Lumpur, from January 2016 to December 2019. The data of 268 UEI couples were obtained from the clinical database. Women aged 21-45 years old was included and further divided into four groups according to the female partner's age and subfertility duration: group A (age <35 years and subfertility <2 years), group B (age <35 years and subfertility >2 years), group C (age >35 years and subfertility <2 years), and group D (age >35 years and subfertility <2 years). All statistical analyses were performed using SPSS 22.0 for Windows.

    RESULTS: A total of 255 cases were included in this study. The mean age of the women was 32.9 ± 4.04 years, and the mean subfertility duration was 5.04 ± 2.9 years. A total of 51 (20 %) cases underwent timed sexual intercourse, 147 (57.6 %) cases had intrauterine insemination (IUI), whereas 57 (22.4 %) cases opted for in vitro fertilization (IVF). A total of 204 cases underwent active management (IUI/IVF), which showed a significant difference (p<0.05). Out of eight clinical pregnancies, half of them were from group B.

    CONCLUSIONS: Active management in younger women with a shorter subfertility duration revealed a better pregnancy outcome. Otherwise, individualized treatment should be considered in selecting a suitable treatment plan.

  18. Dutta S, Nie CW, Sarna A, Hari P, Sengupta P
    PMID: 38726654 DOI: 10.1515/hmbci-2023-0063
    OBJECTIVES: Digit ratio (2D:4D), as endocrine fingerprint, can indicate prenatal androgen exposure. It serves as an anatomical marker for various systemic diseases and a few studies relating it to oral health. The present study aims to evaluate the association between digit ratio and susceptibility to dental plaque formation.

    METHODS: The study was conducted on young adults aged between 18 and 25 years. Digit ratio and reproductive hormones were measured; dental plaque score and gingival index (GI) were recorded. Data were analysed using the MedCalc. v.20.

    RESULTS: Male and female participants were categorized into two groups based on their digit ratios being either above or below the calculated average (0.99 for females, 0.98 for males). Those with a digit ratio below the average had a significantly higher mean dental plaque score (p < 0.0001) than those with ratios at or above the average. However, there was no significant difference in the GI between the two groups. Reproductive hormone profiles varied significantly between the higher and lower digit ratio groups for both sexes.

    CONCLUSIONS: Digit ratio may find potential to be used as an anatomical marker to identify the susceptibility to dental plaque build-up.

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