Association between age, gender, and oral traumatic ulcerative lesions: a retrospective study.

BACKGROUND: Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. METHODS: A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. RESULTS: The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. CONCLUSION: The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.

Fanconi anemia complementation group D2 promotes sensitivity of endometrial cancer cells to chemotherapeutic agents by inhibiting the ferroptosis pathway.

BACKGROUND: Resistance can develop during treatment of advanced endometrial cancer (EC), leading to unsatisfactory results. Fanconi anemia complementation group D2 (Fancd2) has been shown to be closely related to drug resistance in cancer cells. Therefore, this study was designed to explore the correlation of Fancd2 with EC resistance and the mechanism of Fancd2. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of Fancd2 in EC tissues and cells. EC cells (Ishikawa) and paclitaxel-resistant EC cells (Ishikawa/TAX) were transfected to knock down Fancd2. In addition, the ferroptosis inhibitor Ferrostatin-1 was adopted to treat Ishikawa/TAX cells. The sensitivity of cancer cells to chemotherapeutic agents was observed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and inhibitory concentration (IC)50 was calculated. Reactive oxygen species (ROS) levels were measured by flow cytometry, the activity of malondialdehyde (MDA) and the levels of glutathione (GSH) and Fe2+ in cells were detected by corresponding kits, and protein expression of solute farrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was obtained through western blot. RESULTS: Compared with the normal tissues and endometrial epithelial cells, Fancd2 expression was significantly increased in EC tissues and Ishikawa cells, respectively. After knock-down of Fancd2, Ishikawa cells showed significantly increased sensitivity to chemotherapeutic agents. Besides, compared with Ishikawa cells, the levels of ROS, the activity of MDA, and the levels of GSH and Fe2+ were significantly decreased in Ishikawa/TAX cells, while the expression levels of SLC7A11 and GPX4 were significantly increased. Knock-down of Fancd2 significantly increased the ferroptosis levels in Ishikawa/TAX cells, but this effect could be reversed by Ferrostatin-1. CONCLUSION: Fancd2 increases drug resistance in EC cells by inhibiting the cellular ferroptosis pathway.

Comparison of the efficacy and safety of total laparoscopic hysterectomy without and with uterine manipulator combined with pelvic lymphadenectomy for early cervical cancer.

OBJECTIVE: Some studies have reported that the prognosis of total laparoscopic hysterectomy (TLH) for early-stage cervical cancer (CC) is worse than that of open surgery. And this was associated with the use of uterine manipulator or not. Therefore, this study retrospectively analyzes the efficacy and safety of TLH without uterine manipulator combined with pelvic lymphadenectomy for early-stage CC. METHODS: Fifty-eight patients with CC (stage IB1-IIA1) who received radical hysterectomy from September 2019 to January 2020 were divided into no uterine manipulator (n = 26) and uterine manipulator group (n = 32). Then, clinical characteristics were collected and intraoperative/postoperative related indicators were compared. RESULTS: Patients in the no uterine manipulator group had significantly higher operation time and blood loss than in the uterine manipulator group. Notably, there was no significant difference in hemoglobin change, blood transfusion rate, number of pelvic nodules, anal exhaust time, complications and recurrence rate between the two groups. Additionally, patients in the uterine manipulator group were prone to urinary retention (15.6%) and lymphocyst (12.5%), while the no uterine manipulator group exhibited high probability of bladder dysfunction (23.1%) and urinary retention (15.4%). Furthermore, the 1-year disease-free survival rate and the 1-year overall survival rate were not significantly different between the two groups. CONCLUSION: There was no significant difference in the efficacy and safety of TLH with or without uterine manipulator combined with pelvic lymphadenectomy in the treatment of patients with early-stage CC. However, the latter requires consideration of the negative effects of high operation time and blood loss.

A nonlinear correlation measure with applications to gene expression data.

Nonlinear correlation exists in many types of biomedical data. Several types of pairwise gene expression in humans and other organisms show nonlinear correlation across time, e.g., genes involved in human T helper (Th17) cells differentiation, which motivated this study. The proposed procedure, called Kernelized correlation (Kc), first transforms nonlinear data on the plane via a function (kernel, usually nonlinear) to a high-dimensional (Hilbert) space. Next, we plug the transformed data into a classical correlation coefficient, e.g., Pearson's correlation coefficient (r), to yield a nonlinear correlation measure. The algorithm to compute Kc is developed and the R code is provided online. In three simulated nonlinear cases, when noise in data is moderate, Kc with the RBF kernel (Kc-RBF) outperforms Pearson's r and the well-known distance correlation (dCor). However, when noise in data is low, Pearson's r and dCor perform slightly better than (equivalently to) Kc-RBF in Case 1 and 3 (in Case 2); Kendall's tau performs worse than the aforementioned measures in all cases. In Application 1 to discover genes involved in the early Th17 cell differentiation, Kc is shown to detect the nonlinear correlations of four genes with IL17A (a known marker gene), while dCor detects nonlinear correlations of two pairs, and DESeq fails in all these pairs. Next, Kc outperforms Pearson's and dCor, in estimating the nonlinear correlation of negatively correlated gene pairs in yeast cell cycle regulation. In conclusion, Kc is a simple and competent procedure to measure pairwise nonlinear correlations.

Taking account of asymptomatic infections: A modeling study of the COVID-19 outbreak on the Diamond Princess cruise ship.

The COVID-19 outbreak on the Diamond Princess (DP) cruise ship has provided empirical data to study the transmission potential of COVID-19 with the presence of pre/asymptomatic cases. We studied the changes in R0 on DP from January 21 to February 19, 2020 based on chain binomial models under two scenarios: no quarantine assuming a random mixing condition, and quarantine of passengers in cabins-passengers may get infected either by an infectious case in a shared cabin or by pre/asymptomatic crew who continued to work. Estimates of R0 at the beginning of the epidemic were 3.27 (95% CI, 3.02-3.54) and 3.78 (95% CI, 3.49-4.09) respectively for serial intervals of 5 and 6 days; and when quarantine started, with the reported asymptomatic ratio 0.505, R0 rose to 4.18 (95%CI, 3.86-4.52) and 4.73 (95%CI, 4.37-5.12) respectively for passengers who might be exposed to the virus due to pre/asymptomatic crew. Results confirm that the higher the asymptomatic ratio is, the more infectious contacts would happen. We find evidence to support a US CDC report that "a high proportion of asymptomatic infections could partially explain the high attack rate among cruise ship passengers and crew." Our study suggests that if the asymptomatic ratio is high, the conventional quarantine procedure may not be effective to stop the spread of virus.

The Seychelles Child Development Study of methyl mercury from fish consumption: analysis of subscales from the Child Behaviour Checklist at age 107 months in the main cohort.

Methyl mercury (MeHg) is neurotoxic and all fish contain at least trace amounts. Consequently, prenatal or fetal exposure occurs when pregnant women consume fish and children are exposed postnatally when they breastfeed or consume fish. However, the level of exposure at which toxicity occurs is presently unknown. Since behavioural endpoints can be sensitive indicators of toxic exposure, we administered the Child Behaviour Checklist (CBCL) to measure behaviour as part of a prospective, longitudinal, double blind study (n=779) of prenatal MeHg exposure, the Seychelles Child Development Study (SCDS). The CBCL Total T score was a primary endpoint at 66 and 107 month evaluations of the cohort and showed no association with prenatal or postnatal MeHg exposure. This paper reports the results of a secondary analysis of the CBCL subscales to see if specific aspects of behaviour might show associations. The SCDS main cohort was enrolled in 1989-90 and evaluated on five occasions through 107 months of age. The child's primary caregiver completed the CBCL at the 107 month evaluation. Prenatal exposure was determined by measuring total mercury (THg) in maternal hair growing during pregnancy and recent postnatal exposure by analysing the child's hair taken at the 107 month evaluation. Analysis included linear and nonlinear multiple regression models. For prenatal MeHg exposure, the Social Problems subscale was significantly associated and the Somatic Complaints subscale was marginally associated. Both were beneficial associations. For postnatal exposure the Thought Problems subscale was associated in an adverse direction. This secondary analysis identified a small number of subtle beneficial and adverse associations with prenatal and postnatal MeHg exposure for specific CBCL subscales. These analyses provide no evidence for an adverse effect of prenatal exposure. The adverse postnatal association is difficult to interpret because we measured only recent (about one month) exposure and no adjustment was made for the multiplicity of endpoints.

Scholastic achievement among children enrolled in the Seychelles Child Development Study.

The Seychelles Child Development Study is a longitudinal cohort study following a group of 779 children exposed prenatally to methyl mercury (MeHg) through a maternal diet high in fish. The cohort has been examined six times beginning in infancy with no consistent evidence of adverse effects. In fact, their performance resembles what would be expected from normal children of comparable ages growing up in western cultures. During a neurodevelopment assessment at 66 months, the children were tested for scholastic achievement using the Woodcock Johnson Tests of Achievement. Their reading scores were depressed relative to US norms while arithmetic scores were within normal limits. This disparity was not evident at 107 months; in fact, reading achievement scores far exceeded expected performance relative to US norms, with over 75% of the cohort obtaining scores at or above the 90th percentile. This study reports a secondary analysis of the scholastic achievement data to test the hypothesis that the results obtained in the primary analysis were probably due to the onset of the primary school curriculum between the first and second testing, and not to inherent cognitive deficits among the children at 66 months. The results suggest that a combination of reading instruction and characteristically consistent letter-sound relationships in Creole, the language spoken at home by the majority of Seychellois families, probably accounted for the high achievement scores at 107 months.

Analysis of Nonlinear Associations between Prenatal Methylmercury Exposure from Fish Consumption and Neurodevelopmental Outcomes in the Seychelles Main Cohort at 17 Years.

BACKGROUND: The Seychelles Child Development Study has been examining the relationship between prenatal methylmercury (MeHg) exposure from consuming fish during pregnancy and child development. This study re-analyzes seven outcomes in the 17 year Main Cohort data to determine if there are nonlinear or non-homogeneous (subgroup) associations that were not identified in the linear analysis. METHODS: We adopted two statistical approaches. First, we carried out an additive nonlinear analysis assuming homogeneous prenatal MeHg-outcome relationships to explore overall associations. Second, we applied the regression tree to the Woodcock-Johnson Calculation subtest (it was significantly associated in earlier analyses) and identified 4 clusters based on covariates. Then we used additive models to assess the prenatal MeHg association in each of the four clusters for all seven outcomes. This approach assumes nonlinear associations in each cluster and non-homogeneous associations between clusters. RESULTS: The additive nonlinear analysis yielded prenatal MeHg curves similar to the linear analysis. For the regression tree analysis, the curves relating prenatal MeHg to outcomes between the 4 clusters differed and some crossed at higher prenatal MeHg levels, suggesting non-homogeneity in the upper range of exposure. Additionally, some of the curves suggested a possible non-linear relationship within the range of exposure we studied. CONCLUSION: This non-linear analysis supports the findings from the linear analysis. It shows little evidence to support an adverse association of prenatal MeHg exposure through maternal consumption of fish contaminated with natural background levels. However, the tree analysis suggests that the prenatal exposure/outcome relationship may not be homogeneous across all individuals and that some subpopulations may have an adverse association in the upper range of the exposures studied. More robust data in the higher levels of exposure in this cohort are needed to confirm this finding.

[Effects of Chiropractics on Intervertebral Disk Extracell Matrix and Metabolic Enzymes in Rats with Cervical Spondylosis].

OBJECTIVE: To observe the effect of chiropractics on intervertebral disk extracell matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, cellular collagen type Ⅱ (COL-Ⅱ), tissue inhibitor 1 of metalloproteinase (TIMP-1) and extracellular matrix (ECM) in the rats with cervical spondylosis, so as to explore its mechanism underlying improvement of cervical spondylosis. METHODS: A total of 40 SD rats were randomized into a sham group, a model group, a chiropractics group and a mobic group, 8 rats in each one. The model was established by static-dynamic imbalance method. The rats in the chiropractics group were treated with chiropractic therapy for two courses, 14 times a day and 14 days as a course. The rats in the mobic group were treated with intragastric administration of mobic. The expression of MMP-1, MMP-3, MMP-13, COL-Ⅱ and TIMP-1 in the intervertebral disk tissue were detected by immunohistochemistry, and the protein expression of ECM was detected by Western blot. RESULTS: Compared with those in the sham group, the expressions of MMP-1, MMP-3, MMP-13 in the model group increased (all P<0.05), and COL-Ⅱ, TIMP-1 decreased (both P<0.05).Compared with those in the model group, the expressions of MMP-1, MMP-3, MMP-13 in the chiropractics group and the mobic group decreased (all P<0.05), and COL-Ⅱ, TIMP-1 increased (all P<0.05). Compared with that in the sham group, the expression of ECM protein in the model group decreased (P<0.05). Compared with that in the model group, the expression of ECM protein in the chiropractics group and the mobic group increased (both P<0.05). CONCLUSIONS: Chiropractics may improve the degeneration in rats with cervical spondylosis by regulating intervertebral disc ECM system and relevant metabolic enzymes.

Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors.

OBJECTIVES: Diabetic retinopathy (DR) is a common microvascular complication in both type I and type II diabetes. Several previous reports indicated the serum centration of some secretary factors were highly associated with DR. Therefore, we hypothesis regulatory SNPs (rSNPs) genotype in secretary factors may alter these gene expression and lead to DR. METHODS: At first, pyrosequencing were applying to screen the SNPs which present allele frequency different in DR and DNR. Then individual genotyping was processed by Taqman assays in Taiwanese DR and DNR patients. To evaluate the effect of SNP allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. RESULTS: We found the frequencies of the CC, CG, and GG genotype of the rs2010963 polymorphism were 15.09%, 47.14%, and 37.74% in DR and 12.90%, 19.35%, and 67.74% in DNR, respectively (p = 0.0205). The prevalence of DR was higher (p = 0.00793) in patients with the CC or CG genotype (62.26% and 32.26% for DR and DNR, respectively) compared with the patients with the GG genotype. To evaluate the effect of rs2010963-C allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. The rs2010963-C reporter showed 1.6 to 2-fold higher luciferase activity than rs2010963-G in 3 cell lines. CONCLUSION: Our data proposed rs2010963-C altered the expression level of VEGFA in different tissues. We suggested small increase but long term exposure to VEGFA may lead to DR finally.

Peri-transplant psychosocial factors and neutrophil recovery following hematopoietic stem cell transplantation.

OBJECTIVE: Multiple psychosocial factors appear to affect cancer progression in various populations; however, research investigating the relationship between psychosocial factors and outcomes following hematopoietic stem cell transplantation (HCT) is scarce. Subject to adverse immunological and psychological conditions, HCT patients may be especially vulnerable to psychosomatic health sequelae; therefore, we studied whether optimism and anxiety influence the pertinent clinical outcome of days to neutrophil engraftment (DTE). METHOD: 54 adults undergoing either autologous or allogeneic HCT completed self-report questionnaires measuring optimism and anxiety. We assessed the association between these psychosocial variables and DTE. RESULTS: Greater optimism and less anxiety were associated with the favorable outcome of fewer DTE in autologous HCT recipients, though this relationship was no longer significant when reducing the sample size to only subjects who filled out their baseline survey by the time of engraftment. CONCLUSION: Our findings are suggestive that optimism and anxiety may be associated with time to neutrophil recovery in autologous, but not allogeneic, adult HCT recipients. Further investigation in larger, more homogeneous subjects with consistent baseline sampling is warranted.

Fish consumption and prenatal methylmercury exposure: cognitive and behavioral outcomes in the main cohort at 17 years from the Seychelles child development study.

INTRODUCTION: People worldwide depend upon daily fish consumption as a major source of protein and other nutrients. Fish are high in nutrients essential for normal brain development, but they also contain methylmercury (MeHg), a neurotoxicant. Our studies in a population consuming fish daily have indicated no consistent pattern of adverse associations between prenatal MeHg and children's development. For some endpoints we found performance improved with increasing prenatal exposure to MeHg. Follow up studies indicate this association is related to the beneficial nutrients present in fish. OBJECTIVES: To determine if the absence of adverse outcomes and the presence of beneficial associations between prenatal MeHg and developmental outcomes previously reported persists into adolescence. METHODS: This study was conducted on the Main Cohort of the Seychelles Child Development Study (SCDS). We examined the association between prenatal MeHg exposure and subjects' performance at 17 years of age on 27 endpoints. The test battery included the Wisconsin Card Sorting Test (WCST), the California Verbal Learning Test (CVLT), the Woodcock-Johnson (W-J-II) Achievement Test, subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), and measures of problematic behaviors. Analyses for all endpoints were adjusted for postnatal MeHg, sex, socioeconomic status, maternal IQ, and child's age at testing and the child's IQ was added for problematic behavioral endpoints. RESULTS: Mean prenatal MeHg exposure was 6.9 ppm. There was no association between prenatal MeHg and 21 endpoints. Increasing prenatal MeHg was associated with better scores on four endpoints (higher W-J-II math calculation scores, reduced numbers of trials on the Intra-Extradimensional Shift Set of the CANTAB), fewer reports of substance use and incidents of and referrals for problematic behaviors in school. Increasing prenatal MeHg was adversely associated with one level of referrals to a school counselor. CONCLUSIONS: At age 17 years there was no consistent pattern of adverse associations present between prenatal MeHg exposure and detailed domain specific neurocognitive and behavioral testing. There continues to be evidence of improved performance on some endpoints as prenatal MeHg exposure increases in the range studied, a finding that appears to reflect the role of beneficial nutrients present in fish as demonstrated previously in younger subjects. These findings suggest that ocean fish consumption during pregnancy is important for the health and development of children and that the benefits are long lasting.

Smoking in dialysis patients: a systematic review and meta-analysis of mortality and cardiovascular morbidity.

BACKGROUND: Cigarette smoking is associated with increased cardiovascular morbidity and mortality in the general population, but the effect of smoking on these outcomes in the dialysis population is less well studied. STUDY DESIGN: Systematic review and meta-analysis of cohort studies. SETTING & POPULATION: Adults treated with long-term hemodialysis or peritoneal dialysis. SELECTION CRITERIA FOR INCLUDED STUDIES: Cohort studies of unselected dialysis patients reporting the association between smoking status and cardiovascular morbidity and/or mortality. PREDICTOR: Smoking status (determined using patient report). OUTCOMES: (1) All-cause or cardiovascular mortality; (2) incident cardiovascular events. RESULTS: We identified 34 studies that fulfilled all inclusion criteria. Of these, 26 studies provided data for smoking and mortality and 10 (n = 6,538) were included in a meta-analysis. The pooled HR for all-cause mortality in smokers compared with nonsmokers was 1.65 (95% CI, 1.26-2.14; P < 0.001). 11 studies provided data for smoking and incident cardiovascular events; 5 (pooled n = 845) were included in a meta-analysis. The pooled HR for composite cardiovascular events in smokers compared with nonsmokers was 1.01 (95% CI, 0.98-1.05; P = 0.4). LIMITATIONS: Data for these meta-analyses were heterogeneous. Few individual studies assessed smoking as the primary variable of interest. CONCLUSIONS: Active smoking is associated with a significant increase in all-cause mortality in dialysis patients, although there was no corresponding increased risk of cardiovascular events.

Randomized trial of leuprolide versus continuous oral contraceptives in the treatment of endometriosis-associated pelvic pain.

OBJECTIVE: To compare the efficacy of leuprolide and continuous oral contraceptives in the treatment of endometriosis-associated pain. DESIGN: Prospective, randomized, double-blind controlled trial. SETTING: Academic medical centers in Rochester, New York, and Boston, Massachusetts. PATIENT(S): Forty-seven women with endometriosis-associated pelvic pain. INTERVENTION(S): Forty-eight weeks of either depot leuprolide, 11.25 mg IM every 12 weeks with hormonal add-back using norethindrone acetate 5 mg orally, daily; or a generic monophasic oral contraceptive (1 mg norethindrone + 35 mg ethinyl estradiol) given daily. MAIN OUTCOME MEASURE(S): Biberoglu and Behrman (B&B) pain scores, numerical rating scores (NRS), Beck Depression Inventory (BDI), and Index of Sexual Satisfaction (ISS). RESULT(S): Based on enrollment of 47 women randomized to continuous oral contraceptives and to leuprolide, there were statistically significant declines in B&B, NRS, and BDI scores from baseline in both groups. There were no significant differences, however, in the extent of reduction in these measures between the groups. CONCLUSION(S): Leuprolide and continuous oral contraceptives appear to be equally effective in the treatment of endometriosis-associated pelvic pain.

Varying coefficient function models to explore interactions between maternal nutritional status and prenatal methylmercury toxicity in the Seychelles Child Development Nutrition Study.

Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children's development. This cohort of mother-child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children's neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development.

Vascular effects of ultrafine particles in persons with type 2 diabetes.

BACKGROUND: Diabetes confers an increased risk for cardiovascular effects of airborne particles. OBJECTIVE: We hypothesized that inhalation of elemental carbon ultrafine particles (UFP) would activate blood platelets and vascular endothelium in people with type 2 diabetes. METHODS: In a randomized, double-blind, crossover trial, 19 subjects with type 2 diabetes inhaled filtered air or 50 µg/m³ elemental carbon UFP (count median diameter, 32 nm) by mouthpiece for 2 hr at rest. We repeatedly measured markers of vascular activation, coagulation, and systemic inflammation before and after exposure. RESULTS: Compared with air, particle exposure increased platelet expression of CD40 ligand (CD40L) and the number of platelet-leukocyte conjugates 3.5 hr after exposure. Soluble CD40L decreased with UFP exposure. Plasma von Willebrand factor increased immediately after exposure. There were no effects of particles on plasma tissue factor, coagulation factors VII or IX, or D-dimer. CONCLUSIONS: Inhalation of elemental carbon UFP for 2-hr transiently activated platelets, and possibly the vascular endothelium, in people with type 2 diabetes.

Oral desipramine and topical lidocaine for vulvodynia: a randomized controlled trial.

OBJECTIVE: To estimate the efficacy of common treatments for vulvodynia: topical lidocaine monotherapy, oral desipramine monotherapy, and lidocaine-desipramine combined therapy. METHODS: A 12-week randomized, double-blinded, placebo-controlled trial was conducted on 133 vulvodynia-afflicted women assigned to four treatment arms: placebo tablets-placebo cream, desipramine tablets-placebo cream, placebo tablets-lidocaine cream, and desipramine tablets-lidocaine cream. The tampon test was selected as primary end point using a modified intention-to-treat analysis. Twelve secondary end points were also examined. At completion of the 12-week randomized phase, women were examined "open label" through 52 weeks postrandomization. RESULTS: All treatment arms reported substantial tampon-test pain reduction: 33% reduction placebo cream-placebo tablet, 20% reduction lidocaine cream-placebo tablet, 24% reduction placebo cream-desipramine tablet, and 36% reduction lidocaine cream-desipramine tablet. Compared with placebo, we found no significant difference in tampon-test pain reduction with desipramine (t=0.90; P=.37) or lidocaine (t=1.27; P=.21). Of the remaining 12 outcome measures, only the Index of Sexual Satisfaction, improved with desipramine compared with placebo (t=-2.81; P=.006). During the open-label phase, women undergoing vestibulectomy surgery reported significantly improved pain as measured by cotton swab test and the McGill Pain Scale compared with nonsurgical alternatives. CONCLUSION: Oral desipramine and topical lidocaine, as monotherapy or in combination, failed to reduce vulvodynia pain more than placebo. Placebo or placebo-independent effects are behind the substantial pain improvement seen in all treatment allocations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00276068. LEVEL OF EVIDENCE: I.

Fish consumption, mercury exposure, and their associations with scholastic achievement in the Seychelles Child Development Study.

Studies of neurodevelopmental outcomes in offspring exposed to MeHg from maternal consumption of fish have primarily measured cognitive abilities. Reported associations have been subtle and in both adverse and beneficial directions. Changes in functional outcomes such as school achievement and behavior in exposed children and adolescents have not been examined. We undertook an assessment of school success of children in the Seychelles Child Development Study (SCDS) main cohort to determine if there were any associations with either prenatal or recent postnatal MeHg exposure. The primary endpoints were Seychelles nationally standardized end-of-year examinations given when the cohort children were 9 and 17 years of age. A subgroup (n=215) from the main cohort was also examined at 9 years of age using a regional achievement test called SACMEQ. Prenatal MeHg exposure was 6.8 ppm in maternal hair; recent postnatal exposure was 6.09 ppm at 9 years and 8.0 ppm at 17 years, measured in child hair. Multiple linear regression analyses showed no pattern of associations between prenatal or postnatal exposure, and either the 9- or 17-year end-of-year examination scores. For the subgroup of 215 subjects who participated in the SACMEQ test, there were significant adverse associations between examination scores and postnatal exposure, but only for males. The average postnatal exposure level in child hair for this subgroup was significantly higher than for the overall cohort. These results are consistent with our earlier studies and support the interpretation that prenatal MeHg exposure at dosages achieved by mothers consuming a diet high in fish are not associated with adverse educational measures of scholastic achievement. The adverse association of educational measures with postnatal exposure in males is intriguing, but will need to be confirmed by further studies examining factors that influence scholastic achievement.

Efficacy of soaking in 70% isopropyl alcohol on aerobic bacterial decontamination of surgical instruments and gloves for serial mouse laparotomies.

Rodent surgeries in biomedical research facilities are often performed in series. This practice presents many challenges to maintaining aseptic technique between animals. Here, we examined using soaking in 70% isopropyl alcohol for aerobic bacterial decontamination of surgical instruments and gloves used in a series of as many as 10 mouse laparotomy surgeries. These surgeries were performed on mice that were euthanized immediately prior to the procedure. Instruments and gloves were cultured before and after each procedure to determine the presence of aerobic bacterial contamination. To assess the efficacy of the decontamination protocol, culture results were grouped by procedure and then paired (before soak and after soak) for analysis using McNemar test at an α level of 0.05. In addition, by using the Fisher exact test, this modified aseptic method was compared with strict aseptic technique, for which autoclaved instruments and sterile surgical gloves were used for each procedure. In this study, we observed that the modified aseptic technique using 70% isopropyl alcohol soaks pre- vented aerobic bacterial contamination of instruments and gloves for as many as 5 mice.

The tampon test for vulvodynia treatment outcomes research: reliability, construct validity, and responsiveness.

OBJECTIVE: A standardized tampon insertion and removal test, the Tampon Test provides an alternative to sexual intercourse pain as an outcome measure for vulvodynia research. We report upon the reliability, validity, and responsiveness to change of the Tampon Test as an outcome measure for vulvodynia clinical trials. METHODS: Outcome measures were assessed in women enrolled in the Vulvar Vestibulitis Clinical Trial, a randomized clinical trial of oral desipramine and topical lidocaine effectiveness. Reliability estimates of the Tampon Test using the Kappa statistic evaluated week-to-week measures at baseline. Tampon Test construct and discriminant validity were assessed through correlation with other outcome measures. Patients' ability to regularly perform the Tampon Test was compared with regularity of reporting intercourse pain. RESULTS: During the 2-week baseline phase, women with vulvodynia reported stable mean Tampon Test scores 4.6+/-2.6 (week -2); 4.6+/-2.7 (week -1); and 4.7+/-2.8 (week 0) with moderate week-to-week reliability (weighted Kappa 0.52). Over an 8-week phase of trial intervention, change in the Tampon Test measure significantly correlated to a number of outcome measures, including daily pain (r=0.42), intercourse pain (r=0.35), cotton swab vestibular pain (r=0.38), and the Brief Pain Inventory (r=0.49). Women with vulvodynia study participants performed the Tampon Test 96.3% of the requested time, which was twofold higher adherence than intercourse pain measurement (49.7%). CONCLUSION: The Tampon Test reflects a real life experience that is reliable, with good construct validity as shown by the breadth of correlated outcome measures. The Tampon Test is an appropriate outcome measure for vulvodynia research that can be considered for use as the primary efficacy endpoint in clinical trials of treatments for vulvodynia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00276068 LEVEL OF EVIDENCE: II.