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Chondrogenesis of adipose-derived stem cells with chondrocytes in low serum towards clinical application

Adila A Hamid, Satish Vaarman Jeyabalan, Aleza Omar, Nik Zattil Hanan Mohd Yasin, Wong TL, Liau LL, et al.

Sains Malaysiana, 2018;47:2369-2379.

Currently, fetal bovine serum (FBS) have been widely use in culture media to promote human cell proliferation. However,
the usage of FBS for cell therapy in clinical application was associated with the risk of viral and prion transmission as
well as immune rejection. To provide an option for this risk, this study was conducted to determine the effect of adipose
derived stem cells (ADSCs) co-culture with chondrocyte in promoting cell proliferation and chondrogenesis toward
FBS free condition. ADSCs co-cultured with chondrocyte at the ratio of 1:1, 2:1 and 1:2 were tested. Cell morphology
changes, cell proliferation and gene expression level of stemness (Oct4, FGF-4, Nanog) and chondrogenic (Collagen
Type II, ACP) were assessed. The results showed ADSCs in all co-culture groups changed morphology from fibroblastic
spindle to polygonal shape which resembled chondrocytes. The morphological changes were accompanied with increased
expression of chondrogenic genes; denoted chondrogenesis process. While maintaining expression of stemness genes
indicated continuation of cell proliferation. From the three co-culture groups tested; ADSCs and chondrocytes (1:1 ratio)
have been shown to exert better effects in promoting cell proliferation and chondrogenesis. In conclusion, ADSCs could
replace FBS to grow sufficient number of chondrogenic cells to repair cartilage injury in the near future. Further in vivo
study should be performed to test the effectiveness of this co-culture technique in cartilage injury repair.
The quality of life of adolescents with menstrual problems

Nur Azurah AG, Sanci L, Moore E, Grover S

J Pediatr Adolesc Gynecol, 2013 Apr;26(2):102-8.
PMID: 23337310 DOI: 10.1016/j.jpag.2012.11.004

To date, very few publications have examined the health related quality of life (HRQL) in the younger population with menstrual problems, despite their high prevalence in adolescent girls. We describe the health-related quality of life (HRQL) among adolescents with menstrual problems and identified factors that have an impact on it.
Fulltext Beneficial Effects of Probiotics on Benign Gynaecological Disorders: A Review

Norfuad FA, Mokhtar MH, Nur Azurah AG

Nutrients, 2023 Jun 13;15(12).
PMID: 37375637 DOI: 10.3390/nu15122733

Probiotics are live microorganisms that confer beneficial effects on human health when an adequate dose is administered. Recently, the use of probiotics has gained tremendous interest from the public due to its promising effects in the management of various reproductive diseases. However, the review of probiotics' benefits on benign gynaecological disorders, including vaginal infections, polycystic ovary syndrome (PCOS) and endometriosis, remains scarce. Therefore, this review is built on current knowledge on the beneficial effects of probiotics against selected benign gynaecological disorders. Recent findings point out that probiotics' supplementation in different clinical and in vivo models showed promising health effects and results in the amelioration of disease symptoms. Thus, in this review, we showed the findings of both studies performed in clinical settings and animal studies. However, current information, solely based on clinical trials or animal studies, is inadequate in communicating the excellent findings on the beneficial effects of probiotics on human health. Therefore, future clinical intervention studies are required to further elucidate the evidence of the benefits of probiotics benefits regarding these gynaecological disorders.
Dysmenorrhea in young people: Experiences from a tertiary center with a focus on conservative management

Sachedina A, Abu Bakar M, Dunford AM, Morris A, Nur Azurah AG, Grover SR

J Obstet Gynaecol Res, 2021 Jan;47(1):352-358.
PMID: 33084069 DOI: 10.1111/jog.14532

AIM: To describe the characteristics, management and outcomes of a cohort of young people with dysmenorrhea presenting to a tertiary adolescent gynecology service, managed primarily with medical interventions.
METHODS: A retrospective cohort study was conducted at the Royal Children's Hospital in Melbourne, Australia. Data were collected from medical records of patients presenting with dysmenorrhea and/or pelvic pain.
RESULTS: Of 154 patients, mean age of presentation was 15.7 years (SD = 2.2) and mean duration of pain was 14.9 months (SD = 10.8). Regular cycles were reported by 64.5%, and heavy menstrual bleeding (HMB) in 67.8%. Patients self-reporting HMB reported less pain on the day prior to menses than those not reporting HMB (P
Fulltext Maternal Mental Health following Ultrasonographic Detection of Fetal Structural Anomaly in the Midst of the COVID-19 Pandemic

Roslan NR, Mohd Fauzi MF, Wan Teng L, Nur Azurah AG

Int J Environ Res Public Health, 2021 12 07;18(24).
PMID: 34948508 DOI: 10.3390/ijerph182412900

Prenatal ultrasonographic detection of fetal structural anomaly may adversely affect maternal mental health throughout pregnancy, particularly in the current COVID-19 pandemic. This study aims to prospectively assess maternal stress, anxiety, and depression following ultrasonographic detection of fetal structural anomaly from diagnosis until delivery during the COVID-19 pandemic. A total of 141 pregnant women at a tertiary hospital who underwent detailed scans between 16 and 24 gestational weeks were included and categorized into the study (anomaly finding, n = 65) and comparison (normal finding, n = 76) groups. Self-administered questionnaires of 10-item Perceived Stress Scale (PSS-10) and Hospital Anxiety and Depression Scale (HADS) were used to assess maternal stress, anxiety, and depression at prior detection (T1), two-to-four weeks post-detection (T2), one-to-two weeks prior to delivery (T3), and one-to-two weeks post-delivery (T4). Repeated measures of analysis of variance (ANOVA) were conducted to assess time-, between-group, and time-group interaction effect. In general, maternal stress improved, but anxiety worsened, while depression persisted, over the time from T1 to T4. The average maternal stress and anxiety levels were significantly higher among groups with fetal anomaly. The maternal stress and anxiety level were significantly affected within one-to-two weeks post-detection of fetal structural anomaly. In conclusion, maternal mental health parameters were affected differently during the COVID-19 pandemic, with higher vulnerability of stress and anxiety among pregnant women with fetal structural anomaly particularly within one-to-two weeks post-detection.
Outpatient versus inpatient intravaginal misoprostol for the treatment of first trimester incomplete miscarriage: a randomised controlled trial

Ng BK, Annamalai R, Lim PS, Aqmar Suraya S, Nur Azurah AG, Muhammad Abdul Jamil MY

Arch Gynecol Obstet, 2015 Jan;291(1):105-13.
PMID: 25078052 DOI: 10.1007/s00404-014-3388-0

BACKGROUND: Study objective To assess the efficacy of outpatient misoprostol administration versus inpatient misoprostol administration for the treatment of first trimester incomplete miscarriage.
MATERIALS AND METHODS: A prospective randomised controlled trial was conducted at a tertiary hospital from May 2012 to April 2013. A total of 154 patients with first trimester incomplete miscarriage were randomised to receive misoprostol either as outpatient or inpatient. Intra-vaginal misoprostol 800 mcg was administered eight hourly to a maximum of three doses. Complete evacuation is achieved when the cervical os was closed on vaginal examination or ultrasound showed no more retained products of conception evidenced by endometrial thickness of less than 15 mm. Treatment failure was defined as failure in achieving complete evacuation on day seven hence surgical evacuation is offered.
RESULTS: Outpatient administration of misoprostol was as effective as inpatient treatment with success rate of 89.2 and 85.7 % (p = 0.520). The side effects were not significantly different between the two groups. Side effects that occurred were minor and only required symptomatic treatment. Duration of bleeding was 6.0 days in both groups (p = 0.317). Mean reduction in haemoglobin was lesser in the outpatient group (0.4 g/dl) as compared to in the inpatient group (0.6 g/dl) which was statistically significant (p = 0.048).
CONCLUSION: Medical evacuation using intra-vaginal misoprostol 800 mcg eight hourly for a maximum of three doses in an outpatient setting is as effective as in inpatient setting with tolerable side effects.

Study site: tertiary hospital
Effects of keratinocyte growth factor on skin epithelial differentiation of human amnion epithelial cells

Fatimah SS, Tan GC, Chua K, Tan AE, Nur Azurah AG, Hayati AR

Burns, 2013 Aug;39(5):905-15.
PMID: 23273814 DOI: 10.1016/j.burns.2012.10.019

The aim of the present study was to determine the effects of KGF on the differentiation of cultured human amnion epithelial cells (HAECs) towards skin keratinocyte. HAECs at passage 1 were cultured in medium HAM's F12: Dulbecco's Modified Eagles Medium (1:1) supplemented with different concentrations of KGF (0, 5, 10, 20, 30 and 50 ng/ml KGF). Dose-response of KGF on HAECs was determined by morphological assessment; growth kinetic evaluation; immunocytochemical analysis; stemness and epithelial gene expression quantification with two step real time RT-PCR. KGF promotes the proliferation of HAECs with maximal effect observed at 10 ng/ml KGF. However, KGF decreased the stemness genes expression: Oct-3/4, Sox-2, Nanog3, Rex-1, FGF-4, FZD-9 and BST-1. KGF also down-regulates epithelial genes expression: CK3, CK18, CK19, Integrin-β1, p63 and involucrin in cultured HAECs. No significant difference on the gene expression was detected for each Nestin, ABCG-2, CK1 and CK14 in KGF-treated HAECs. Immunocytochemical analysis for both control and KGF-treated HAECs demonstrated positive staining against CK14 and CK18 but negative staining against involucrin. The results suggested that KGF stimulates an early differentiation of HAECs towards epidermal cells. Differentiation of KGF-treated HAECs to corneal lineage is unfavourable. Therefore, further studies are needed to elucidate the roles of KGF in the differentiation of HAECs towards skin keratinocytes.
Update on the management of ovarian torsion in children and adolescents

Nur Azurah AG, Zainol ZW, Zainuddin AA, Lim PS, Sulaiman AS, Ng BK

World J Pediatr, 2015 Feb;11(1):35-40.
PMID: 25557598 DOI: 10.1007/s12519-014-0536-3

Ovarian torsion is commonly seen in young girls. Unfortunately it is often misdiagnosed because of its non-specific symptoms and lack of diagnostic modalities. This article focuses on the diagnostic challenge and also the changes in the management of ovarian torsion.
Oestrogen-induced epithelial-mesenchymal transition (EMT) in endometriosis: Aetiology of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome

Lih Yuan T, Sulaiman N, Nur Azurah AG, Maarof M, Rabiatul Adawiyah Razali, Yazid MD

Front Physiol, 2022;13:937988.
PMID: 36582359 DOI: 10.3389/fphys.2022.937988

Endometriosis occurs when endometrial-like tissue forms and grows outside the uterus due to oestrogen-induced epithelial-mesenchymal transition in the female reproductive tract. Factors that suppress this event could become potential therapeutic agents against disease occurrence and progression. However, an overview of these studies is still lacking. This review assessed the impact of a number factors on oestrogen-mediated epithelial-mesenchymal transition in the emergence of several diseases in the female reproductive tract, primarily endometriosis. The association between epithelial-mesenchymal transition and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome was also investigated. Oestrogen, Wnt4 and epithelial-mesenchymal transition were chosen as keywords in Scopus, PubMed, and Web of Science searches performed on 28th June 2021. Study selection was refined to cancer-irrelevant, English, original articles published between years 2011-2021. The full-text assessment was carried out for topic-related articles after title and abstract screening. Included studies were summarised and assessed for their risk of bias using the Office of Health Assessment and Translation tool. In this review, 10 articles investigating oestrogen and epithelial-mesenchymal transition in the female reproductive tract were summarised and classified into two groups: seven studies under 'factor'-modulated epithelial-mesenchymal transition and three studies under 'factor'-manipulated oestrogen-induced epithelial-mesenchymal transition. The current evidence proposes that epithelial-mesenchymal transition is one of the prime causes of reproductive-related disease. This event could be mediated by distinct stimuli, specifically oestrogen and Wnt4 aberration. The results of this review suggest that oestrogen and Wnt4 participate in epithelial-mesenchymal transition in vaginal epithelial cells in MRKH syndrome, adopting from the theories of endometriosis development, which could therefore serve as a foundation for novel target treatment, specifically related to vaginal epithelialisation, to ensure better surgical outcomes.
Fulltext Prevalence, Knowledge and Awareness of Pelvic Floor Disorder among Pregnant Women in a Tertiary Centre, Malaysia

Nur Farihan M, Ng BK, Phon SE, Nor Azlin MI, Nur Azurah AG, Lim PS

Int J Environ Res Public Health, 2022 Jul 07;19(14).
PMID: 35886170 DOI: 10.3390/ijerph19148314

Pelvic floor disorders are common and of concern, as the majority of maternity healthcare providers seldom discuss this issue with patients compared to other antenatal issues. The aim of this study is to determine the prevalence and to assess the knowledge and awareness of pelvic floor disorder (PFD) among pregnant women in a tertiary centre in Malaysia. We also aim to assess the association between women’s risk factors regarding their knowledge and awareness of pelvic floor disorder so that primary prevention strategies can be planned, initiated and implemented in the future. This is a cross-sectional study with a total of four hundred twenty-four pregnant women that were recruited over a 6-month duration from May to November 2017 in a tertiary centre in Malaysia. The Pelvic Floor Distress Inventory (PFDI-20) was used to evaluate pelvic floor distress symptoms during pregnancy, namely urinary incontinence, pelvic organ prolapse and faecal incontinence. A validated Prolapse and Incontinence Knowledge Questionnaire (PIKQ), which consists of 24 items, was used to assess respondents’ knowledge about urinary incontinence (UI) and pelvic organ prolapse (POP). A total of 450 participants were approached, but 424 participants agreed to participate, showing a response rate of 94.3%. The median age was 31.5 years old, and 33.3% were primiparity. Overall, 46.1% of pregnant women had at least one symptom of pelvic floor disorder during pregnancy. Of these, 62.3% experienced urinary incontinence, 41.1% experienced symptoms of pelvic organ prolapse, and 37.8% experienced symptoms of faecal incontinence. The overall median score of PIKQ was 12.0 (8.0, 17.0). The median score for PIKQ—UI was 7.0 (5.0, 9.0) and the median score for PIKQ—POP was 6.0 (4.0, 8.0). There were 341 (80.4%) pregnant women that had a low level of knowledge in UI, and 191 (45.0%) had a low level of knowledge in POP. Having a tertiary level of education and receiving antenatal specialist care were both associated with better proficiency in both the PIKQ—UI (p < 0.001) and PIKQ—POP (p < 0.001) subscales. Pelvic floor disorder during pregnancy was common. A knowledge of pelvic floor disorder was lacking among pregnant women in this study. Having a tertiary education and receiving antenatal specialist care were both associated with better knowledge proficiency. This study hopefully serves as a basic platform for future educational programs to bridge the knowledge gaps in PFD among pregnant women.
Fulltext Management of Menstrual Disorder in Adolescent Girls with Intellectual Disabilities: A Blessing or a Curse?

Nurkhairulnisa AI, Chew KT, Zainudin AA, Lim PS, Shafiee MN, Kampan N, et al.

Obstet Gynecol Int, 2018;2018:9795681.
PMID: 30116271 DOI: 10.1155/2018/9795681

Objective: This study aims to describe the menstrual pattern and menstrual care of girls with intellectual disabilities and to evaluate the impact of menstruation and awareness of parents/guardians on girls with intellectual disabilities.
Methodology: Parents/guardians of girls aged 9-17 years with known intellectual disabilities who attended a scheduled public forum and Paediatrics and Adolescent Gynaecology Clinic (PAC) were recruited in a questionnaire-based study.
Results: A total of 123 parents/guardians with a mean age of 41.83 ± 5.45 years completed the questionnaire. The mean age of girls with intellectual disabilities was 12.28 ± 2.78 years, and the mean menarcheal age was 11.12 ± 1.76 years. Only 53 (43.1%) parents/guardians were aware of availability of menstrual suppression. Parents/guardians with lower family income (OR = 0.00; 95% CI = 0.00-0.20), unable to manage menses (OR = 0.03; 95% CI = 0.00-0.61), and moderate severity of menses (OR = 0.01; 95% CI = 0.00-1.21), were associated with seeking medical help on menstrual suppression. The factors associated with parents/guardians requesting for sterilization were lower family income (OR = 0.02; 95% CI = 0.00-0.36) and concern about sexual abuse (OR = 0.25; 95% CI = 0.06-0.39).
Conclusion: Menstrual pattern in girls with intellectual disabilities is similar to those without disabilities. Parents/guardians' knowledge and awareness on menstrual suppression were still lacking.
Fulltext Isolation of Vaginal Epithelial Cells: In Preparation of Autologous Vaginal Tissue Lining for Congenital Absence of Vagina Patients

Lih Yuan T, Sulaiman N, Nur Azurah AG, Maarof M, Razali RA, Koh B, et al.

Int J Mol Sci, 2023 May 15;24(10).
PMID: 37240142 DOI: 10.3390/ijms24108798

Infertility is a condition affecting women who are born with an underdeveloped or absent vagina, a birth defect known as congenital absence of the vagina. It is a rare disorder where the development of the Mullerian duct is obstructed by unidentified causes. The case is seldom reported due to the low prevalence and sparse epidemiology studies worldwide. A potential solution for the disorder is neovaginal creation with in vitro cultured vaginal mucosa. Limited studies have reported its application, but none are reproducible or specific regarding the established processes for acquiring vaginal epithelial cells from vaginal biopsies. These research gaps were adequately answered with an epidemiology study of inpatient details in Hospital Canselor Tuanku Muhriz, Malaysia, established methods and outcomes of vaginal tissue processing and isolation, and characterization of vaginal epithelial cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and immunofluorescence assays. The reported evidence and speculation that the disorder arises because of a cellular transition event between epithelial and mesenchymal cells during the development of the Mullerian duct could be key in the creation of neovaginas using established culture procedures to improve surgical results and restore fertility.
Fulltext Factors associated with placenta praevia in primigravidas and its pregnancy outcome

Nur Azurah AG, Wan Zainol Z, Lim PS, Shafiee MN, Kampan N, Mohsin WS, et al.

ScientificWorldJournal, 2014;2014:270120.
PMID: 25478587 DOI: 10.1155/2014/270120

To examine the factors associated with placenta praevia in primigravidas and also compare the pregnancy outcomes between primigravidas and nonprimigravidas.
Differential osteogenic potential of human adipose-derived stem cells co-cultured with human osteoblasts on polymeric microfiber scaffolds

Rozila I, Azari P, Munirah S, Wan Safwani WK, Gan SN, Nur Azurah AG, et al.

J Biomed Mater Res A, 2016 Feb;104(2):377-87.
PMID: 26414782 DOI: 10.1002/jbm.a.35573

The osteogenic potential of human adipose-derived stem cells (HADSCs) co-cultured with human osteoblasts (HOBs) using selected HADSCs/HOBs ratios of 1:1, 2:1, and 1:2, respectively, is evaluated. The HADSCs/HOBs were seeded on electrospun three-dimensional poly[(R)-3-hydroxybutyric acid] (PHB) blended with bovine-derived hydroxyapatite (BHA). Monocultures of HADSCs and HOBs were used as control groups. The effects of PHB-BHA scaffold on cell proliferation and cell morphology were assessed by AlamarBlue assay and field emission scanning electron microscopy. Cell differentiation, cell mineralization, and osteogenic-related gene expression of co-culture HADSCs/HOBs were examined by alkaline phosphatase (ALP) assay, alizarin Red S assay, and quantitative real time PCR, respectively. The results showed that co-culture of HADSCs/HOBs, 1:1 grown into PHB-BHA promoted better cell adhesion, displayed a significant higher cell proliferation, higher production of ALP, extracellular mineralization and osteogenic-related gene expression of run-related transcription factor, bone sialoprotein, osteopontin, and osteocalcin compared to other co-culture groups. This result also suggests that the use of electrospun PHB-BHA in a co-culture HADSCs/HOBs system may serve as promising approach to facilitate osteogenic differentiation activity of HADSCs through direct cell-to-cell contact with HOBs.
Fulltext Adhesion barriers in gynecologic surgeries and cesarean section: An Asia-Pacific expert panel consensus recommendation

Tanigaki S, Batra A, Chan TF, Kang JH, Lam SK, Lim TY, et al.

Int J Gynaecol Obstet, 2025 Feb;168(2):436-448.
PMID: 39277817 DOI: 10.1002/ijgo.15903

Adhesions arising from gynecologic surgeries and cesarean sections pose substantial clinical, social, and economic challenges, leading to issues like pelvic pain, infertility, bowel obstruction, and recurring surgeries. Preventing adhesions is a pressing unmet need, hindered by difficulties in assessing postoperative adhesions and understanding barriers. To bridge adhesion prevention gaps, statements on clinical practices were synthesized to present Asia-Pacific expert perspectives on gynecologic surgery and cesarean section adhesion prevention. An expert panel of eight physicians from various healthcare settings in the Asia-Pacific region was convened and a comprehensive literature search on topics related to adhesion prevention in gynecologic surgeries and cesarean sections was performed. Information from full-text publications was used to develop draft consensus statements, with each statement assigned the highest available evidence level based on a systematic literature review and graded using the Oxford Center for Evidence-based Medicine criteria. A modified Delphi process, involving two rounds of online voting and discussions with an extended group of 109 experts, was employed to reach a consensus on six topics related to adhesion barriers. A set of 15 consensus statements were synthesized. Key topics include adhesion incidence in Asia, cesarean section complications, barrier application status, adhesion formation and prevention, absorbable barriers' effectiveness, recommendations, and future considerations. The statements provide guidance for healthcare professionals, especially in the Asia-Pacific region, to tackle the challenges posed by postoperative adhesions and improve patient outcomes. Further research is needed to enhance understanding and prevention of adhesions in this region.
Fulltext Malaysian Females With Congenital Adrenal Hyperplasia: Surgical Outcomes and Attitudes

Zainuddin AA, Grover SR, Soon CH, Nur Azurah AG, Mahdy ZA, Wu LL, et al.

Front Pediatr, 2019;7:144.
PMID: 31058121 DOI: 10.3389/fped.2019.00144

Background: Girls born with congenital adrenal hyperplasia have virilized external genitalia. There is considerable debate regarding both the outcomes of feminizing genitoplasty and timing of the surgery in this population. Objective: To investigate outcomes of females 46,XX individuals with CAH in Malaysia, the surgical outcomes of feminizing genitoplasty (FG) and their attitudes toward surgery. Study Design: This is a cross-sectional study involving the two main tertiary centers in Malaysia. All 46,XX patients with CAH and raised female, who had undergone FG were identified and invited to participate. Data on socio-demographic, medical profiles, and attitudes toward surgery were collected. A standardized evaluation of the external genitalia was undertaken including the anatomic and cosmetic evaluation by independent gynecologists. Results: Of 61 individuals identified, 59 participated-consisting of children (n = 12), adolescents (n = 29) and adults (n = 18). All but one had classical CAH (98.3%) and had undergone FG (n = 55, 93.2%) with surgery mostly undertaken by pediatric surgeons trained in DSD work (n = 44, 74.6%). Complications overall were low (20.3%), with repeat surgery rate of 9.1%. External genital examination was performed in 38 participants. Overall 36.8% had absent clitoral glands and 39.5% had a persistent urogenital sinus and in 10.5%, no vaginal orifices were seen. Poor cosmetic outcomes were present in 42.1% with 55.3% recommended for further assessment under general anesthetic. Almost half participants did not venture an opinion on FG, those who did varied from having a positive attitude toward it (18 participants) to 3 opining that it should not be done, or avoided or delayed. From the participants, 35.5% preferred FG to be done early in life compared to 44.0% of the parents. Conclusions: The reoperation rates of the feminizing genitoplasty surgeries were low however due to the anatomic and cosmetic outcomes, reassessment of the external genitalia of these CAH patients may be required once they consider becoming sexually active as they may require further treatment. Many factors such as cultural sensitivities and access to medical treatment and late diagnoses have an impact on attitudes toward FG.
Fulltext Effect of Acupressure at P6 on Nausea and Vomiting in Women with Hyperemesis Gravidarum: A Randomized Controlled Trial

Mohd Nafiah NA, Chieng WK, Zainuddin AA, Chew KT, Kalok A, Abu MA, et al.

Int J Environ Res Public Health, 2022 Sep 01;19(17).
PMID: 36078602 DOI: 10.3390/ijerph191710886

Hyperemesis gravidarum is characterized by severe nausea and vomiting. This study aims to illustrate the efficacy of acupressure at P6 in treating nausea and vomiting in hyperemesis gravidarum. This parallel randomized controlled trial was conducted from 2016-2017 in a tertiary hospital. Hospitalized women with ≤16 weeks of gestation and moderate to severe nausea and vomiting classified using a modified PUQE score were randomly assigned in a 1:1 ratio to either apply an acupressure wristband at the P6 point three times daily or to receive regular doses of intravenous antiemetics. The primary outcome was differences in modified PUQE scores among the groups. The secondary outcomes were differences in the rate of urine ketone clearance and the frequency of requiring rescue antiemetics. Ninety women were equally randomized into two groups, with no dropout. There was a statistically significant difference in the degrees of nausea and vomiting between the groups at 8, 16, and 24 hours post-admission (p8hours= 0.001, p16hours = 0.006, and p24hours = 0.001). The requirement of antiemetics and the rate of urine ketone clearance between the two groups were also statistically significant, at p = 0.001 and p = 0.02 respectively. There were no side effects in either group. The P6 acupressure was efficacious in alleviating nausea and vomiting among hyperemesis gravidarum women. The trial was retrospectively registered on ClinicalTrials.gov (NCT05175079).
Fulltext Umbilical Cord Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Modulate Skin Matrix Synthesis and Pigmentation

Kee LT, Foo JB, How CW, Nur Azurah AG, Chan HH, Mohd Yunus MH, et al.

Int J Nanomedicine, 2025;20:1561-1578.
PMID: 39931529 DOI: 10.2147/IJN.S497940

INTRODUCTION: Research has unveiled the remarkable properties of extracellular vesicles derived from mesenchymal stromal cells (MSCs), particularly in promoting wound healing, aiding re-epithelialization, revitalizing aging skin, and inhibiting hyperpigmentation. However, investigations into the potential of small extracellular vesicles from umbilical cord-derived MSCs (UC-MSC-sEVs) in reducing scarring and preventing hyperpigmentation remain limited. Therefore, this study aims to evaluate the impact of UC-MSC-sEVs on the synthesis of the skin's extracellular matrix (ECM) and pigmentation using in vitro models.
METHODS: The study investigated the impact of characterized UC-MSC-sEVs on various aspects including the proliferation, migration, antioxidant activity, and ECM gene expression of human dermal fibroblasts (HDF). Additionally, the effects of UC-MSC-sEVs on the proliferation, melanin content, and tyrosinase (TYR) activity of human melanoma cells (MNT-1) were examined. Furthermore, ex vivo models were employed to evaluate the skin permeation of PKH26-labelled UC-MSC-sEVs.
RESULTS: The findings indicated that a high concentration of UC-MSC-sEVs positively influenced the proliferation of HDF. However, no changes in cell migration rate were observed. While the expressions of collagen type 1 and type 3 remained unaffected by UC-MSC-sEVs treatment, there were dose-dependent increases in the gene expressions of fibronectin, matrix metallopeptidase (MMP) 1, and MMP 3. Furthermore, UC-MSC-sEVs treatment did not impact the antioxidative superoxide dismutase (SOD) expression in HDF. Although UC-MSC-sEVs did not alter the proliferation of MNT-1 cells, it did result in a dose-dependent reduction in melanin synthesis without affecting TYR activity. However, when it was applied topically, UC-MSC-sEVs failed to penetrate the skin barrier and remained localized within the stratum corneum layer even after 18 hours.
CONCLUSION: These results highlight the potential of UC-MSC-sEVs in stimulating HDF proliferation, regulating ECM synthesis, and reducing melanin production. This demonstrates the promising application of UC-MSC-sEVs in medical aesthetics for benefits such as scar reduction, skin rejuvenation, and skin lightening.
Fulltext The role of probiotics in improving menstrual health in women with primary dysmenorrhoea: A randomized, double-blind, placebo-controlled trial (the PERIOD study)

Zakaria IA, Mohammed Zain NA, Teik CK, Abu MA, Zainuddin AA, Abdul Aziz NH, et al.

Womens Health (Lond), 2024;20:17455057241234524.
PMID: 38444064 DOI: 10.1177/17455057241234524

BACKGROUND: Primary dysmenorrhea is associated with poorer quality of life; however, the causal mechanism remains unclear. A vast body of literature supports the use of oral probiotics for relief from the symptoms of endometriosis; however, to our knowledge, no study has prescribed probiotics for primary dysmenorrhea.
OBJECTIVE: The aim of this study is to investigate the effects of 3-month supplementation with oral probiotics on quality of life and inflammatory markers in women with primary dysmenorrhea.
DESIGN: Randomized placebo-controlled trial.
METHODS: A total of 72 patients (36 patients in each arm) were randomized to receive either oral sachets containing 5 billion colony-forming units each of Lactobacillus acidophilus BCMC (BCrobes Microbial Cells) 12130, Lactobacillus casei subsp BCMC 12313, Lactobacillus lactis BCMC 12451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum BCMC 02120, and Bifidobacterium infantis BCMC 02129 each or placebo twice daily for 3 months. Main outcome measures were visual analog scale, verbal rating scale, physical and mental health scores using Short-Form 12-Item version 2 questionnaire, frequency of nonsteroidal anti-inflammatory drug use, and changes in inflammatory markers (interleukin-6, interleukin-8, and tumor necrosis factor alpha) before and after treatment.
RESULTS: There was no significant difference in the quality of life scores between the probiotic and placebo groups. Both groups showed significant improvement in pain (visual analog scale) and severity (verbal rating scale) scores but the probiotic group had much lower nonsteroidal anti-inflammatory drug use (odds ratio: 0.69, 95% confidence interval: 0.26-1.83) and better mental health scores (mean change: 6.5, p = 0.03 versus 6.1, p = 0.08) than the placebo group. There was a significant confounding effect of nonsteroidal anti-inflammatory drug use on quality of life scores. No significant difference was found in inflammatory cytokines.
CONCLUSION: Tested oral probiotics improved mental health and potentially reduced the use of nonsteroidal anti-inflammatory drugs; however, there was no significant change in inflammatory markers. Further research with a larger sample size is needed to confirm the findings.
REGISTRATION: This study is registered under ClinicalTrials.gov (NCT04119011).
Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women

Iversen OE, Miranda MJ, Ulied A, Soerdal T, Lazarus E, Chokephaibulkit K, et al.

JAMA, 2016 12 13;316(22):2411-2421.
PMID: 27893068 DOI: 10.1001/jama.2016.17615

Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts.

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