Effect of menopausal hormonal therapy on cardiovascular risks in Korean postmenopausal women: A nationwide cohort study.

OBJECTIVE: To evaluate the association between menopausal hormonal therapy (MHT) and the risk of cardiovascular disease (CVD), according to various regimens, dosages, routes of administration and starting ages of MHT. DESIGN: A population-based cohort study using the Korean National Health Insurance Services database. SETTING: Nationwide health insurance database. POPULATION: Women who reported entering menopause at an age of ≥40 years with no history of CVD in the national health examination. METHODS: The study population comprised 1 120 705 subjects enrolled between 2002 and 2019, categorised according to MHT status (MHT group, n = 319 007; non-MHT group, n = 801 698). MAIN OUTCOME MEASURES: Incidence of CVD (a composite of myocardial infarction and stroke). RESULTS: The incidence of CVD was 59 266 (7.4%) in the non-MHT group and 17 674 (5.5%) in the MHT group. After adjusting for confounding factors, an increased risk of CVD was observed with the administration of tibolone (hazard ratio, HR 1.143, 95% CI 1.117-1.170), oral estrogen (HR 1.246, 95% CI 1.198-1.295) or transdermal estrogen (HR 1.289, 95% CI 1.066-1.558), compared with the non-MHT group; the risk was based on an increased risk of stroke. The risk trends were consistent regardless of the age of starting MHT or the physicians' specialty. Among tibolone users, a longer period from entering menopause to taking tibolone and the use of any dosage (1.25 or 2.5 mg) were linked with a higher risk of CVD, compared with non-MHT users. CONCLUSIONS: This nationwide cohort study demonstrated an increased risk of CVD, driven mainly by an increased risk of stroke, among tibolone and oral or transdermal estrogen users, compared with that of non-MHT users.

Case Report: Upper limb superficial venous thrombosis associated with oral contraceptives mimicking soft tissue mass.

Background: Venous thrombosis associated with the use of oral contraceptives (OCs) occurs mostly in the deep veins of the lower extremity. A lesion of the upper extremity is rare, and the majority of thrombotic events that occur in the superficial vein of the upper extremity are caused by intravenous catheters. We present a rare case of superficial venous thrombus on the upper extremity in a woman with a history of long-term OC use. Case presentation: A 35-year-old woman, with an 8-year history of OC use, presented with a 2-year history of painfully palpable masses on her left forearm. The lesion mimicking soft tissue mass was confirmed to be superficial venous thrombi through ultrasound and magnetic resonance imaging. Conservative treatment including non-steroidal anti-inflammatory drugs, vasoprotective agents, and aspirin was prescribed. Through consultation with the Department of Obstetrics and Gynecology, it was confirmed that the current OCs could be discontinued, and the pain was almost relieved after conservative treatment. Conclusions: If thrombotic events occur in the superficial vein of the upper extremity without intravenous catheters, detailed medical history taking and the possibility of OCs should be considered.

Relationship between myomectomy and risk of osteoporosis or fracture: A population-based cohort study.

Myomectomy, a surgery to remove multiple leiomyomas from the uterus, is a treatment option for uterine fibroids (UF) in premenopausal patients. Osteoporosis and bone fractures are known to be strongly associated with menopausal status or hormonal changes. However, no studies have discussed the association between myomectomy and osteoporosis or fractures. This study investigated the risk of osteoporosis or fractures (vertebrae, hip, and others) in Korean patients who had undergone myomectomy without bilateral oophorectomy. We used data from the 10-year claims database of the Korean National Health Insurance from January 2009 to December 2020. Data for patients who had undergone myomectomy without oophorectomy (n = 211,969) and the control group (n = 450,124) who were randomly selected from the database were extracted. The incidence and hazard ratios (HRs) of osteoporosis or fracture between the myomectomy patients and the control group were calculated. A Cox proportional hazards model was used to analyze hazard ratios and 95% confidence intervals (CI). Subgroup analyses were performed based on age. The adjusted hazard ratios for osteoporosis and total fractures were 0.934 (95% CI: 0.916-0.954, P<0.001) and 0.919 (95% CI: 0.896-0.941, P<0.001), respectively, in the myomectomy group. The adjusted hazard ratios according to fracture site were 0.857 (95% CI: 0.799-0.92, P<0.001) for vertebral fractures, 0.706 (95% CI: 0.48-1.037, P = 0.076) for hip fractures, and 0.919 (95% CI: 0.896-0.943, P<0.001) for other fractures. In conclusion, patients who have undergone myomectomy might have a decreased risk of osteoporosis or fractures.

Enhanced Photothermal Effect Assisted by Resonance Energy Transfer in Carbon/Covellite Core-Shell Nanoparticles toward a High-Performance Interfacial Water Evaporation Process.

Carbon and semiconductor nanoparticles are promising photothermal materials for various solar-driven applications. Inevitable recombination of photoinduced charge carriers in a single constituent, however, hinders the realization of a greater photothermal effect. Core-shell heterostructures utilizing the donor-acceptor pair concept with high-quality interfaces can inhibit energy loss from the radiation relaxation of excited species, thereby enhancing the photothermal effect. Here, core-shell structures composed of a covellite (CuS) shell (acceptor) and spherical carbon nanoparticle (CP) core (donor) (abbreviated as CP/CuS) are proposed to augment the photothermal conversion efficiency via the Förster resonance energy transfer (FRET) mechanism. The close proximity and spectral overlap of the donor and acceptor trigger the FRET mechanism, where the electronic excitation relaxation energy of the CP reinforces the plasmonic resonance and near-infrared absorption in CuS, resulting in boosting the overall photothermal conversion efficiency. CP/CuS core-shell coated on polyurethane (PU) foam exhibits a total solar absorption of 97.1%, leading to an elevation in surface temperature of 61.6 °C in dry conditions under simulated solar illumination at a power density of 1 kW m-2 (i.e., 1 sun). Leveraging the enhanced photothermal conversion emanated from the energy transfer effect in the core-shell structure, CP/CuS-coated PU foam achieves an evaporation rate of 1.62 kg m-2 h-1 and an energy efficiency of 93.8%. Thus, amplifying photothermal energy generation in core-shell structures via resonance energy transfer can be promising in solar energy-driven applications and thus merits further exploration.

Association between breast diseases and symptomatic uterine fibroids by using South Korean National Health Insurance database.

Both the uterus and breasts have sex hormone dependence, yet there are few studies on the association between breast disease and uterine fibroids (UFs). The purpose of this study was to investigate the incidence of benign breast disease (BBD), carcinoma in situ (CIS), and breast cancer (BC) in women treated for UFs compared to women who were not treated for UFs. This retrospective cohort study used national health insurance data from January 1st, 2011, to December 31st, 2020. We selected women between 20 and 50 years old who (1) were treated for UFs (UF group) or (2) visited medical institutions for personal health screening tests without UFs (control group). We analyzed independent variables such as age, socioeconomic status (SES), region, Charlson comorbidity index (CCI), delivery status, menopausal status, menopausal hormone therapy (MHT), endometriosis, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia based on the first date of uterine myomectomy in the UF group and the first visiting date for health screening in the non-UF group. There were 190,583 and 439,940 participants in the UF and control groups, respectively. Compared with those of the control group, the RRs of BBD, CIS, and BC were increased in the UF group. The hazard ratios (HRs) of BBD, CIS, and BC in the UF group were 1.335 (95% confidence interval (CI) 1.299-1.372), 1.796 (95% CI 1.542-2.092), and 1.3 (95% CI 1.198-1.41), respectively. When we analyzed the risk of BC according to age at inclusion, UFs group had the increased risk of BCs in all age groups in comparison with control group. Women with low SES (HR 0.514, 95% CI 0.36-0.734) and living in rural areas (HR 0.889, 95% CI 0.822-0.962) had a lower risk of BC. Our study showed that women with UFs had a higher risk of BBD, CIS, and BC than those without UFs. This result suggests that women with UFs should be more conscious of BC than those without UFs. Therefore, doctors should consider recommending regular breast self-exams, mammography, or ultrasound for the early detection of BC in women with UFs.

The increased risk of colorectal cancer in the women who underwent hysterectomy from the South Korean National Health Insurance Database.

BACKGROUND: Several population-based studies and observational studies have shown that oophorectomy is associated with an increased risk of colorectal cancer (CRC), and hormone replacement therapy has been associated with a reduction in the risk of colorectal cancer. This study was carried out to investigate whether hysterectomy, which may affect the levels of female hormones, is associated with a risk of cancer of the specific gastrointestinal tract. METHODS: This population-based retrospective cohort study was conducted using insurance data provided by the Health Insurance Review and Assessment Service (HIRA) from January 1, 2007, to December 31, 2020. The hysterectomy group included 40- to 59-year-old women who underwent hysterectomy with uterine leiomyoma or uterine endometriosis from January 1, 2011, to December 31, 2014. The control group included women aged 40 to 59 years who visited medical institutions for medical examination from January 1, 2011 to December 31, 2014. RESULTS: The hysterectomy and non-hysterectomhy groups comprised 66,204 and 89,768 subjects, respectively. The median ages in the non-hysterectomy group and hysterectomy group were 48 (range: 43-53) and 46 (range: 44-49) years, respectively. In the unadjusted results of the analysis, all colorectal cancer (CRC) increased in the hysterectomy alone group (HR 1.222, 95% confidence interval (CI) 1.016-1.47, p = 0.033), sigmoid colon cancer increased in the hysterectomy alone group (HR 1.71, 95% CI 1.073-2.724, p = 0.024), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.924, 95% CI 1.073-2.724, p = 0.002). The adjusted results showed that all CRC increased in the hysterectomy alone group (HR 1.406, 95% CI 1.057-1.871, p = 0.019), colon cancer increased in the hysterectomy alone group (HR 1.523, 95% CI 1.068-2.17, p = 0.02), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.933, 95% CI 1.131-3.302, p = 0.016). The all-cause mortality of GI cancer increased in the hysterectomy alone group (HR 3.495, 95% CI 1.347-9.07, p = 0.001). CONCLUSIONS: This study showed that the risk of all CRC increased in women who underwent hysterectomy compared with women who did not. In particular, the risk of rectal cancer was significantly higher in the women who underwent hysterectomy with adnexal surgery than in the controls. There was no association between hysterectomy and other GI cancers.

Association of Early Hysterectomy With Risk of Cardiovascular Disease in Korean Women.

Importance: Women who undergo surgical hysterectomy before natural menopause may have an earlier increase in hematocrit and storage iron levels than those who continue menstruation, thereby increasing the risk of cardiovascular disease (CVD) at ages younger than usually seen. Examining this issue may provide important implications for women's cardiovascular health to both physicians and patients. Objective: To evaluate the association of hysterectomy with the risk of incident CVD among women before age 50 years. Design, Setting, and Participants: In this Korean population-based cohort study, 135 575 women aged 40 to 49 years were evaluated from January 1, 2011, to December 31, 2014. After propensity score matching in covariates including age, socioeconomic status, region, Charlson Comorbidity Index, hypertension, diabetes, dyslipidemia, menopause, menopausal hormone therapy, and adnexal surgery before inclusion, 55 539 pairs were included in the hysterectomy and nonhysterectomy groups. Participants were followed up until December 31, 2020. Data analysis was conducted from December 20, 2021, to February 17, 2022. Main Outcomes and Measures: The primary outcome was an incidental CVD, a composite of myocardial infarction, coronary artery revascularization, and stroke. The individual components of the primary outcome were also evaluated. Results: A total of 55 539 pairs were included; median age in the combined groups was 45 (IQR, 42-47) years. During median follow-up periods in the hysterectomy group of 7.9 (IQR, 6.8-8.9) years and nonhysterectomy group of 7.9 (IQR, 6.8-8.8) years, the incidence of CVD was 115 per 100 000 person-years for the hysterectomy group and 96 per 100 000 person-years for the nonhysterectomy group. After adjusting for confounding factors, the hysterectomy group had an increased risk of CVD compared with the nonhysterectomy group (hazard ratio [HR], 1.25; 95% CI, 1.09-1.44). The incidences of myocardial infarction and coronary artery revascularization were comparable between the groups, whereas the risk of stroke was significantly higher in the hysterectomy group (HR, 1.31; 95% CI, 1.12-1.53). Even after excluding women who underwent oophorectomy, the hysterectomy group had higher risks of CVD (HR, 1.24; 95% CI, 1.06-1.44). Conclusions and Relevance: The findings of this cohort study suggest early menopause owing to hysterectomy was associated with increased risks for a composite of CVD, particularly stroke.

Risk of Gestational Diabetes and Pregnancy-Induced Hypertension with a History of Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study.

OBJECTIVE: To evaluate the risks of developing gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) in women with polycystic ovary syndrome (PCOS) using data from Korea's National Health Insurance Service. METHOD: The PCOS group comprised women aged 20 to 49 years diagnosed with PCOS between 1 January 2012, and 31 December 2020. The control group comprised women aged 20 to 49 years who visited medical institutions for health checkups during the same period. Women with any cancer within 180 days of the inclusion day were excluded from both the PCOS and control groups, as were women without a delivery record within 180 days after the inclusion day, as well as women who visited a medical institution more than once before the inclusion day due to hypertension, diabetes mellitus (DM), hyperlipidemia, DM in pregnancy, or PIH. GDM and PIH were defined as cases with at least three visits to a medical institution with a GDM diagnostic code and a PIH diagnostic code, respectively. RESULTS: Overall, 27,687 and 45,594 women with and without a history of PCOS experienced childbirth during the study period. GDM and PIH cases were significantly higher in the PCOS group than in the control group. When adjusted for age, SES, region, CCI, parity, multiple pregnancies, adnexal surgery, uterine leiomyoma, endometriosis, PIH, and GDM, an increased risk of GDM (OR = 1.719, 95% CI = 1.616-1.828) was observed among women with a history of PCOS. There was no increase in the risk of PIH among women with a history of PCOS (OR = 1.243, 95% CI = 0.940-1.644). CONCLUSION: A history of PCOS itself might increase the risk of GDM, but its relationship with PIH remains unclear. These findings would be helpful in the prenatal counseling and management of patients with PCOS-related pregnancy outcomes.

Enhancing the electrical properties of graphite nanoflake through gamma-ray irradiation.

Understanding changes in material properties through external stimuli is critical to validating the expected performance of materials as well as engineering material properties in a controlled manner. Here, we investigate a change in the c-axis electrical properties of graphite nanoflakes (GnFs) induced by gamma-ray irradiation, using conductive probe atomic force microscopy (CP-AFM). The fundamentals behind the change in their electrical properties are elucidated by analyzing the interlayer spacing, graphitization, and morphology. An increase in gamma-ray irradiation dose for GnFs leads to an exponential increase in the electrical conductance and a gradual decrease in the interlayer spacing, while accompanying indistinguishable changes in their morphology. Our experimental results suggest that the c-axis electrical conductance enhancement of GnFs with gamma-ray irradiation might be attributed to a reduction in interlayer spacing, though the created defects may also play a role. This study demonstrates that gamma-ray irradiation can be a promising route to tailor the electrical properties of GnFs.

Incidence of bowel injury during gynecologic surgery for benign indications: A nationwide cross-sectional study of cases from 2009 to 2018.

OBJECTIVE: To investigate the incidence and risk factors of intestinal injury during gynecologic surgery for benign diseases, based on a national database. METHOD: The study cohort was generated by extracting patients with operation codes for benign gynecologic diseases from the Health Insurance Review & Assessment Service National Inpatient Sample from 2009 to 2018. After analyzing the incidence of bowel injury during gynecologic surgery, a multivariate analysis was performed to identify the associated risk factors for bowel injury. RESULTS: Among 81 451 patients who underwent gynecologic surgery for benign diseases, the incidence of bowel injury was 6.14 per 1000 women. The risk of bowel injury decreased with laparoscopy (odds ratio [OR] 0.54; 95% confidence interval [CI] 0.41-0.69; P < 0.001) and increased with subtotal hysterectomy (OR 2.83; 95% CI 1.79-4.46; P < 0.001) and adnexectomy (OR 2.83; 95% CI 1.93-4.16; P < 0.001). Old age, higher Charlson comorbidity index, low socioeconomic status, and a higher clinic grade were associated with a higher risk of bowel injury. CONCLUSION: This study revealed the incidence of bowel injury during benign gynecologic surgery in a Korean national population-based cohort. The risk of bowel injury increased with open surgery, subtotal hysterectomy, and adnexectomy.

Rupture-mediated large uterine defect at 30th gestational week with protruded amniotic sac and fetal head without fetal compromise after laparoscopic electromyolysis: Case report and literature review.

BACKGROUND: We describe a case of a rupture-mediated large uterine defect, which occurred on the 30th gestation week presenting a protruding amniotic sac sac without fetal compromise after a laparoscopic electromyolysis. CASE PRESENTATION: A 28-year-old woman in her 30th week of gestation (gravida 2, para 0) presented with whole abdominal and right lower quadrant pain at Sanggye Paik Hospital. Ultrasound examination showed normal amniotic fluid and placentation but with breech presentation. She had undergone laparoscopic right ovarian cystectomy due to endometriosis 5 years earlier. Cardiotocography revealed an intermittent variable deceleration and no uterine contraction. Magnetic resonance imaging ruled out acute appendicitis. Four hours later, we observed a protrusion of the amniotic sac with the fetal head through a large uterine defect on magnetic resonance imaging, and performed emergency cesarean section. A boy was delivered without fetal compromise. During the cesarean section, multiple myometric wall defects and thinning were identified. After reconstruction of the uterine wall, the flaccid uterus bled persistently; thus, a cesarean hysterectomy was performed. Packed red cells and frozen plasma were transfused. The mother and neonate had uneventful puerperal and neonatal courses, respectively. After cesarean hysterectomy, we were informed that the mother had undergone a combined laparoscopic electromyolysis during the laparoscopic right ovarian cystectomy. Three years later, the child showed normal neural development. CONCLUSIONS: Before myomectomy or electromyolysis, patients should be informed of the possibility of uterine rupture during subsequent pregnancies. If a pregnant woman has abdominal pain, clinicians should take a detailed history of uterine surgery and consider uterine rupture. Although, fortunately, the outcomes in this case were uneventful, urgent delivery is required when uterine rupture is diagnosed.

Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: A retrospective cohort study.

OBJECTIVE: This study aimed to investigate incidence and risk for venous thromboembolism (VTE) according to primary treatment in women with ovarian cancer. METHODS: We selected 26,863 women newly diagnosed with ovarian cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and the first six months after initiation of primary treatments, incidence and risk of VTE were evaluated according to primary treatment as no treatment, surgery, radiotherapy, or chemotherapy. RESULTS: The mean follow-up period was 1285.5±6 days. The VTE incidence was highest in women who underwent chemotherapy (306 per 10,000 women). Among women who underwent surgery, VTE was highest in surgery with neoadjuvant chemotherapy (536 per 10,000 women), followed by surgery with adjuvant chemotherapy (360 per 10,000 women) and surgery alone (132 per 10,000 women). During the first 12 months, monthly incidence of VTE decreased. Compared with women with no treatment, risk of VTE significantly increased in women undergoing chemotherapy (HR 1.297; 95% CI, 1.08-1.557; P = 0.005) during the total follow-up period and decreased in women undergoing surgery (HR 0.557; 95% CI, 0.401-0.775; P<0.001) and radiotherapy (HR 0.289; 95% CI, 0.119-0.701; P = 0.006) during the first six months. Among women who underwent surgery, VTE risk significantly increased in surgery with neoadjuvant chemotherapy (HR 4.848; 95% CI, 1.86-12.632; P = 0.001) followed by surgery with adjuvant chemotherapy (HR 2.807; 95% CI, 1.757-4.485; P<0.001) compared with surgery alone during the total follow-up period and in surgery with neoadjuvant chemotherapy (HR 4.223; 95% CI, 1.37-13.022; P = 0.012) during the first six months. CONCLUSIONS: In this large Korean cohort study, incidence and risk of VTE were highest in women with ovarian cancer who underwent chemotherapy and surgery with neoadjuvant chemotherapy as a primary cancer treatment. Incidence of VTE decreased over time.

A highly robust approach to fabricate the mass-customizable mold of sharp-tipped biodegradable polymer microneedles for drug delivery.

A skin-perforable dissolving microneedle is a promising mediator for painlessly delivering active pharmaceutical compounds across the skin. All the microneedle manufacturing processes so far, however, are much sensitive to input variation and unfavorable for make-to-order approach. Here, a robust method for fabricating mass-customizable master molds is developed to prepare sharp-tipped biodegradable polymer microneedles. Our approach combines the predrying and chip casting (PCC) of an ultrathick photoresist layer with a substrateless, inclined, and rotational exposure (SIR exposure). The PCC achieves the uniform reduction of solvent across the photoresist thickness which is critically required for the formation of a sharp tip; the SIR exposure creates master molds whose geometry is easily customizable and virtually insensitive to a variation in ultraviolet (UV) exposure dose. A theoretical model for the spatiotemporal distribution of UV dose under SIR exposure is established to show the technological superiority of our method. Next, our method's applicability is proven by fabricating a set of poly(lactic-co-glycolic) acid (PLGA) microneedles and performing both porcine skin penetration test and their in vitro degradation test. Our approach is verified to be robust in manufacturing mass-customizable molds for skin-perforable dissolving microneedles and to have high compatibility with almost all existing biodegradable polymers. The findings of this study lead to both a significant growth of dissolving microneedle-mediated drug delivery and better understanding of drug release kinetics.

Sarcopenia as a Predictor of Prognosis in Early Stage Ovarian Cancer.

BACKGROUND: To identify sarcopenia as a predictive prognostic factor of ovarian cancer in terms of survival outcome in patients with early-stage ovarian cancer. METHODS: Data of Konkuk University Medical Center from March 2002 to December 2017 were reviewed retrospectively. Eighty-two patients who underwent surgery due to early-stage (International Federation of Gynecology and Obstetrics stage I/II) ovarian cancer and had computed tomography (CT) images taken at the initial diagnosis were included. The initial CT scan images were analyzed with SliceOmatic software (TomoVision). A sarcopenia cutoff value was defined as a skeletal muscle index of ≤ 38.7 cm²/m². Overall survival (OS) times were compared according to the existence of sarcopenia, and subgroup analyses were performed. RESULTS: A Kaplan-Meier analysis showed a significant survival disadvantage for patients with early-stage ovarian cancer when they had sarcopenia (P < 0.001; log-rank test). Sarcopenia remained a significant prognostic factor for OS in early-stage ovarian cancer, in a Cox proportional hazards model regression analysis (HR, 21.9; 95% CI, 2.0-199.9; P = 0.006). CONCLUSION: This study demonstrated that sarcopenia was predictive of OS in patients with early-stage ovarian cancer. Further prospective studies with a larger number of patients are warranted to determine the extent to which sarcopenia can be used as a prognostic factor in ovarian cancer.

Effect of porcine placental extract on menopausal symptoms in postmenopausal women: A prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To determine the effect of oral administration of porcine placental extract (PPE) on the menopausal symptoms of Korean women. MATERIALS AND METHODS: This study was a multicenter, randomized double-blind placebo-controlled trial. A hundred menopausal Korean women were randomly allocated either to the PPE 400 mg per day or the control group during 12 weeks of the study period. Menopausal symptoms were evaluated using the Kupperman Index (KMI). RESULTS: The KMI decreased after 12 weeks in both groups; however, the difference in the changes was not statistically significant. Among overweight or obese women whose body mass index (BMI) was 23 kg/m2 or higher, the KMI decreased more significantly in the PPE group than placebo group after 12 weeks (-18.52 ± 9.09 vs -11.40 ± 10.68, P < 0.05). Among 49 early menopausal women whose duration of menopause was less than 3 years, the KMI decreased more significantly in the PPE group after 12 weeks (-17.29 ± 9.07 vs -11.29 ± 10.68, P < 0.05). The baseline estradiol level was not statistically different between the two groups before trial, but the estradiol level of the PPE group was significantly increased at 12 weeks (11.13 ± 35.13 pg/m, P < 0.05). CONCLUSIONS: Oral administration of 400 mg PPE per day decreases menopausal symptoms in women with BMI 23 kg/m2 or higher or in early menopausal women. PPE may be considered as a short-term complementary treatment to reduce menopausal symptoms, especially in overweight or early menopausal women.

Gabapentin for the treatment of hot flushes in menopause: a meta-analysis.

OBJECTIVE: Gabapentin is used to treat vasomotor symptoms (VMS) in postmenopausal women with contraindications to hormonal therapy or who prefer alternatives. We investigated the efficacy and tolerability of gabapentin for treating menopausal hot flushes via a meta-analysis. METHODS: We searched the PubMed, MEDLINE, EMBASE, and CENTRAL databases for English-language articles published until June, 2018. The following search terms were used: "menopause," "hot flushes," "vasomotor symptoms," "gabapentin," and "non-hormonal therapy." Primary outcomes were frequency, duration, and composite score of hot flushes. Secondary outcomes were adverse effects and dropout rate. We estimated the standardized mean difference (SMD) and combined odds ratio (OR) using fixed or random-effects models, depending on study heterogeneity. Subgroup and meta-regression analyses of gabapentin dosage were performed. RESULTS: We included seven randomized controlled trials that compared single-agent gabapentin with placebo for treating hot flushes in the meta-analysis. Women who received gabapentin reported a significantly greater reduction in the frequency (SMD 2.99 [95% confidence interval 2.01-3.98], P < 0.001), duration (0.89 [0.49-1.30], P < 0.001), and composite score (2.31 [1.50-3.11], P < 0.001) of hot flushes. Adverse events were significantly more frequent among those taking gabapentin than among those taking the placebo (OR 1.58 [0.98-2.18], P < 0.001; and 1.19 [0.43-1.95], P = 0.002 for dizziness and unsteadiness, respectively). CONCLUSIONS: Gabapentin could be used to treat VMS in postmenopausal women with contraindications to hormonal therapy. Future studies should investigate the lowest effective dose of gabapentin to minimize adverse effects. : Video Summary:http://links.lww.com/MENO/A521.

Predicting the temporal wetting of porous, surfactant-added polydimethylsiloxane (PDMS).

Diverse surface/bulk treatments have been introduced to overcome the interfacial limitations of pristine (or untreated) PDMS, thus extending the possible applications of PDMS in micro/nano device development. Despite of extensive efforts, the temporal wetting change of PDMS induced by surface/bulk treatments still remains incompletely understood. We prepared 3 kinds of physicochemically treated PDMS blocks using widely used surface/bulk treatments-3D interconnected pore network formation, biocompatible surfactant (i.e., Silwet L-77) addition, and combination of both. Their wetting nature was characterized by measuring the time profile of water contact angle. A 3D interconnected pore network formation produced a time-invariant decrease in PDMS wettability; a surfactant addition increased the PDMS wettability in a time-variant way; a combination of pore network formation and surfactant addition had a combined effect. The measurement led to the successful development of a model for predicting the temporal wetting change in PDMS caused by variances in pore size and surfactant concentration. The accuracy of our model was verified by comparing experimental results with model predictions. This model will result in better understanding of polymer interface.

Bioinspired microneedle insertion for deep and precise skin penetration with low force: Why the application of mechanophysical stimuli should be considered.

A mosquito is known to precisely and easily insert its proboscis to the human skin by pressing down a labium and vibrating a fascicle bundle. Its advanced skin-piercing mechanisms indicate that skin resistance to the insertion of needle-like objects can be changed by the application of mechanophysical stimuli. Here, we characterize the effect of the application of mechanophysical stimuli on skin resistance to microneedle insertion to find clues for inserting a microneedle in a deep and precise fashion with low force. Microneedles with a diameter of 60-140µm are inserted at a velocity of 0.1-2.0mm/s to full-thickness porcine skins while either uniaxial/equibiaxial stretch of 0-20% or mechanical vibration at a frequency of 1 to 1000Hz and an amplitude of 1-10µm is applied to the skins as static or dynamic mechanophysical stimulus, respectively. The values of force and depth at two events of skin puncture and maximum penetration are measured to explore changes in skin resistance induced by the application of external stimuli. The static mechanophysical stimulus applied to the skin mainly affects the precision of microneedle insertion; the application of dynamic mechanophysical stimulus controls the value and deviation of skin resistance to microneedle insertion. The application of mechanophysical stimuli, inspired from a mosquito, therefore allows a microneedle to be deeply and easily inserted to the skin in a controlled way. The findings will have broad impacts on microneedle-mediated applications and lead to an in-depth understanding of skin biomechanics.

A Review on Quantitative Measurement of Cell Adhesion Strength.

There is an explosion of interest in characterizing cell adhesion process and the mechanochemical players that is critical to a wide range of physiological and pathological consequences. Much, however, still remains uncertain and controversial about the quantitative measurement of cell adhesion strength (i.e., cell-substratum adhesion force, cell-cell adhesion force, etc.). The main reason for this deficit is a lack of well-established and comprehensive experimental methods that quantitatively measure cell adhesion strength at cellular and even molecular levels. This leads to the need for conducting a literature review on the methods for characterizing the adhesion force of anchorage-dependent cells. In this review article, we discern and critique available techniques for measuring cell adhesion strength that is required for an adherent cell (or cells) of interest to detach from the neighboring cell or the substratum. This review focuses on recent advances in the technique for measuring cell adhesion strength to weigh up the strengths and weaknesses of each technique, together with a brief description for the biological aspects of cell adhesion process. The summary of this article might help us both to develop a standard method for measuring cell adhesion strength and to broaden and deepen our understanding of cell adhesion process.

Characterization on the Expanding Nature of Graphite in Microwave-Irradiated Exfoliation.

Much still remains uncertain and controversial about the mechanophysical parameters involved in graphite exfoliation. Here, we quantify the expansion characteristics of natural graphite in the microwave-irradiated exfoliation where KMnO4 and HNO3 are used as an oxidant and an intercalant, respectively. As a mark of the degree to which graphite becomes exfoliated, the expansion ratio of graphite is investigated as a function of mix ratio by weight of 3 ingredients (i.e., graphite, KMnO4, and HNO3), mixing time, and graphite physical properties. The findings of this study will lead to a better understanding of graphite exfoliation and make it possible to achieve the industrial-scale production of defect-free graphene.