Oral and general health conditions involved in periodontal status during pregnancy: a prospective cohort study.

PURPOSE: Pregnancy is a period in a woman's life that has important consequences on oral health, particularly for gingival health. Present study aims to identify women at higher risk of developing periodontal disease (gingivitis and periodontitis) during late pregnancy and evaluate how this condition evolves during this period. METHODS: Prospective cohort study was designed with pregnant women who were assessed during the first and third trimesters of gestation in a southern Spanish public hospital. Data regarding gingival and periodontal health, oral hygiene, and overall health status (obesity and diabetes mellitus) were collected. Reporting followed STROBE checklist. RESULTS: Significantly higher number of women had the periodontal and gingival disease in the third trimester of gestation compared with in early pregnancy. In the third trimester of gestation, 42 (28.6%) and 63 (42.9%) of women presented symptoms of periodontal disease and gingival disease, respectively. Obesity (OR 2.834; 95%CI 0.919-8.741), worse oral hygiene during the first trimester of gestation (OR: 4.031; 95%CI 2.12-7.65), and periodontal disease during early pregnancy (OR: 15.104; 95%CI 3.60-63.36) most effectively predicted periodontal disease during late pregnancy. CONCLUSIONS: Pregnancy is associated with exacerbated periodontal and gingival disease symptoms throughout the different trimesters of gestation. Obesity and oral hygiene during early pregnancy were the risk factors that most contributed to the aforementioned changes in periodontal disease.

Trend changes in the incidence of benign parotid tumours in the last 30 years in a Spanish population.

PURPOSE: To study the demographics and clinical characteristics of benign parotid tumours, focusing on the evolution of the incidence of Warthin tumour (WT) in recent years. METHODS: A retrospective observational study is designed of patients diagnosed with a benign parotid tumour in a single tertiary hospital centre, from 1994 to 2021. The evaluation of the relationship between the different variables, and the changes in tumour incidence, is carried out using an analysis of standardized residuals. RESULTS: The study evaluated 279 patients, and the total of benign parotid tumours was 291. The most frequent type of tumour was pleomorphic adenoma (PA) (52.7%), followed by WT (37.6%). WT was more frequent in men (79%), and PA in women (55.8%). Smoking history is significantly high in patients with WT (83%), as well as mid-age, compared to PA. CONCLUSIONS: It seems to be an increase in the proportion of WT compared to PA in recent years. These changes can be concerning tobacco use and older patients at diagnosis in our series.

Factors associated with oral health-related quality of life during pregnancy: a prospective observational study.

PURPOSE: To evaluate the evolution of perceived quality of life in relation to oral health during pregnancy and to determine the risk factors involved in this process. METHODS: A follow-up study was carried out with pregnant Spanish women. Two oral examinations and an oral health-related quality of life (OHRQoL) assessment, using the OHIP-14 questionnaire, were performed in the first and third trimester of pregnancy. Data on sociodemographic characteristics, medical history, O'Sullivan Test measures, oral hygiene habits, history of caries, and periodontal status of participants were collected through structured medical-dental questionnaires. RESULTS: A complete dataset comprising 246 pregnant women was available for analysis. Overall scores for negative impacts on the OHIP questionnaire were significantly higher during late pregnancy (74%). This indicated a deterioration in oral health-related quality of life amongst participants. Items describing "painful aching", "self-consciousness", "unsatisfactory diet", and "interrupted meals" showed the greatest increase between the first and third trimester of gestation. Multivariate analysis showed that pre-gestational/gestational diabetes mellitus and poor oral hygiene habits during the first trimester of gestation were directly associated with worse oral health-related quality of life during the third trimester of gestation (hyperglycemia: OR 2.86; 95% CI 1.019-8.050: p = 0.043 / oral hygiene: OR 1.33; 95% CI 0.970-1.836; p = 0.076). CONCLUSIONS: In the present research, hyperglycemia during pregnancy and poor oral hygiene habits during the first trimester of gestation led to a higher risk of poor oral quality of life during late pregnancy.

Quality assessment of fetal middle cerebral and umbilical artery Doppler images using an objective scale within an international randomized controlled trial.

OBJECTIVES: To determine the quality of Doppler images of the fetal middle cerebral artery (MCA) and umbilical artery (UA) using an objective scale, and to determine the reliability of this scale, within a multicenter randomized controlled trial (Revealed versus concealed criteria for placental insufficiency in unselected obstetric population in late pregnancy (Ratio37)). METHODS: The Ratio37 trial is an ongoing randomized, open-label, multicenter controlled study of women with a low-risk pregnancy recruited at 20 weeks. Doppler measurements of the fetal MCA and UA were performed at 37 weeks. Twenty patients from each of the six participating centers were selected randomly, with two images evaluated per patient (one each for the MCA and UA). The quality of a total of 240 images was evaluated by six experts, scored on an objective scale of six items. Inter- and intrarater reliability was assessed using the Fleiss-modified kappa statistic for ordinal scales. RESULTS: On average, 89.2% of MCA images and 85.0% of UA images were rated as being of perfect (score of 6) or almost perfect (score of 5) quality. Kappa values for intrarater reliability of quality assessment were 0.90 (95% CI, 0.88-0.92) and 0.90 (95% CI, 0.88-0.93) for the MCA and UA, respectively. The corresponding inter-rater reliability values were 0.85 (95% CI, 0.81-0.89) and 0.84 (95% CI, 0.80-0.89), respectively. CONCLUSION: The quality of MCA and UA Doppler ultrasound images can be evaluated reliably using an objective scale. Over 85% of images, which were obtained by operators from a broad range of clinical practices within a multicenter study, were rated as being of perfect or almost perfect quality. Intra- and inter-rater reliability of quality assessment was very good. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Haplotype characterization of Ceraeochrysa cubana (Hagen) and Ceraeochrysa valida (Banks) (Neuroptera: Chrysopidae) from the state of Colima, Mexico.

The larvae of Ceraeochrysa cubana and Ceraeochrysa valida, green lacewing species widely spread in Mexico, have been described as natural enemies of Diaphorina citri (Hemiptera: Liviidae), vector of the bacteria Candidatus Liberibacter spp. causing Huanglongbing disease. To develop an effective biological control program, the establishment of the genetic structure of the biocontrol agent species is mandatory. Consequently, the goal of this work was to obtain reliable DNA barcoding regions of the two species, and then by sequence analysis of the mitochondrial gene cytochrome c oxidase subunit I, evaluate the genetic structure of Mexican lime populations of C. cubana and C. valida from the state of Colima. This research produced the first barcode region of C. cubana and C. valida with morphological and molecular confirmation. The genetic parameters revealed the presence of 15 and 10 haplotypes, and haplotype diversity values of 0.889 and 0.838 for C. cubana and C. valida, respectively. The populations showed high diversity and gene flow, and AMOVA analysis demonstrated no genetic structure in the two populations. Consequently, these single populations of C. cubana and C. valida could be used as unique genetic source for mass production and release in the Mexican lime-producing state of Colima to control D. citri.

Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies.

BACKGROUND: The aim of this study was to determine the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of OPB-51602, an oral, direct signal transduction activator of transcription 3 (STAT3) inhibitor, in patients with refractory solid tumors. PATIENTS AND METHODS: Three cohorts were studied: cohort A, a sequential dose escalation of OPB-51602 administered intermittently (days 1-14 every 21 days); cohort B, an expansion cohort evaluating the dose lower than the MTD; cohort C, evaluating continuous daily dosing. RESULTS: Fifty-one patients were studied at 2, 4, and 5 mg per day dosing. The MTD was 5 mg; first-cycle dose-limiting toxicities (DLTs) were grade 3 hyponatremia in one patient, and grade 3 dehydration in another. Intermittent dosing of both 2 and 4 mg doses were tolerable, and the recommended phase II dose was 4 mg. Cohort B investigated 4 mg intermittently, whereas cohort C investigated 4 mg continuously. Common toxicities included fatigue, nausea/vomiting, diarrhea, anorexia, and early-onset peripheral neuropathy. Drug-induced pneumonitis occurred in two patients in cohort C. Continuous dosing was associated with a higher incidence of peripheral neuropathy and a lower mean relative dose intensity, compared with intermittent dosing. Steady-state pharmacokinetics was characterized by high oral clearance, mean elimination half-life ranging from 44 to 61 h, and a large terminal-phase volume of distribution. An active metabolite, OPB-51822, accumulated to a greater extent than OPB-51602. Flow cytometry of peripheral blood mononuclear cells demonstrated pSTAT3 (Tyr(705)) inhibition following exposure. Two patients achieved partial responses at 5 mg intermittently and 4 mg continuously; both had epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor exposure. CONCLUSION: OPB-51602 demonstrates promising antitumor activity, particularly in NSCLC. Its long half-life and poorer tolerability of continuous dosing, compared with intermittent dosing, suggest that less frequent dosing should be explored. CLINICALTRIALSGOV IDENTIFIER: NCT01184807.

Body fat composition impacts the hematologic toxicities and pharmacokinetics of doxorubicin in Asian breast cancer patients.

Body surface area (BSA)-based dosing leads to wide inter-individual variations in drug pharmacokinetics and pharmacodynamics, whereas body composition has been shown to be a more robust determinant of efficacy and toxicity of certain chemotherapeutic agents. We correlated various parameters of body composition with doxorubicin pharmacokinetics and hematologic toxicities in Asian patients with locally advanced or metastatic breast cancer. Our analysis included 84 patients from two studies who received pre- or post-operative single-agent doxorubicin; pharmacokinetic parameters were available for 44 patients. Body composition parameters were derived from CT cross-sectional images and population pharmacokinetic analysis was conducted using mixed-effects modeling. Higher intra-abdominal fat volume and fat ratio (intra-abdominal:total abdominal fat volume) correlated with greater incidence of grade 4 leukopenia on cycle 1 day 15 (mean intra-abdominal fat volume: 97.4 ± 46.5 cm(3) vs 63.4 ± 30.9 cm(3), p = 0.014; mean fat ratio: 0.43 ± 0.11 vs 0.33 ± 0.09, p = 0.012, grade 4 vs grade 0-3 leukopenia). On subset analysis, this relationship was maintained even in underweight patients. Concordantly, there were positive correlations between doxorubicin AUC and intra-abdominal fat volume as well as total abdominal fat volume (r (2) = 0.324 and 0.262, respectively, all p < 0.001). BSA and muscle volume did not predict for doxorubicin pharmacokinetics or toxicities. High-intra-abdominal fat volume but not BSA predicted for greater doxorubicin exposure and hematologic toxicities, suggesting that body composition is superior to BSA in determining doxorubicin pharmacokinetics and pharmacodynamics. Body composition has an emerging role in chemotherapy dose determination.

Is there a role for cervical assessment and uterine artery Doppler in the first trimester of pregnancy as a screening test for spontaneous preterm delivery?

OBJECTIVE: To evaluate the role of cervical length (CL) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks as predictors of spontaneous preterm delivery (sPTD) in a Chilean population. METHODS: This was a prospective study of asymptomatic women with singleton pregnancies attending for a nuchal translucency scan at 11+0 to 13+6 weeks' gestation and who underwent a transvaginal scan for evaluation of CL and UtA-PI. Exclusion criteria were fetal and pregnancy complications (other than sPTD) and iatrogenic delivery at<34 weeks. Measurements of CL and UtA-PI were adjusted for fetal crown-rump length and maternal characteristics and expressed as multiples of the median (MoM) of the unaffected group. Prediction of sPTD using maternal and pregnancy characteristics was studied using logistic regression analysis. RESULTS: A total of 3480 women were recruited into the study and, after application of exclusion criteria, 3310 were included in the analysis. The rate of sPTD at<34 weeks was 0.9% (n=31). A previous PTD had occurred in 7.4% of parous women. Patients with sPTD in the index pregnancy were characterized by a significantly higher prevalence of previous PTD (12.9% vs 3.7%, P<0.05). No significant difference was found in either CL or UtA-PI between pregnancies with and without subsequent sPTD. Logistic regression analysis showed that smoking and previous PTD were significantly associated with sPTD at<34 weeks. The combination of these characteristics provided a detection rate of 26% with a false-positive rate of 8%. CONCLUSIONS: Neither UtA-PI nor CL during the first trimester was shown to be a useful predictor of early sPTD. However, a combined model that includes smoking and previous PTD predicts approximately one-quarter of those women destined to deliver at<34 weeks, with a false-positive rate of 8%.

Role of the glucose tolerance test as a predictor of preeclampsia.

OBJECTIVE: To determine whether oral glucose tolerance tests (OGTT) play a role as predictors of preeclampsia (PET) in pregnant women. METHODS: A retrospective case-control study was conducted in 2,002 singleton pregnancies that had a uterine artery (UtA) Doppler at 22-25 weeks and an OGTT. The UtA Doppler and OGTT were adjusted based on maternal characteristics, and the results were expressed as multiples of the expected normal median and compared between groups. Logistic regression analysis was used to determine whether maternal characteristics, OGTT, and UtA Doppler significantly contribute to the prediction of early- (<34 weeks), intermediate- (34-37 weeks), or late-onset (>37 weeks) PET. The performance of the screening was determined by ROC curves. RESULTS: Women who developed PET were characterized by an older maternal age, an increased body mass index, and an altered UtA Doppler. The group with intermediate-onset PET was the only one associated with higher 2-hour OGTT levels compared to controls. Combined models were developed via logistic regression analysis using maternal characteristics, UtA Doppler, and OGTT to predict PET. These combined models were able to detect around 74, 42, and 21% of women who later developed early-, intermediate-, or late-onset PET, respectively, with only a 5% false-positive rate. CONCLUSIONS: This study shows that the combination of maternal characteristics, second-trimester UtA Doppler, and OGTT is a predictor of the development of PET in healthy pregnant women.

[Monitoring indicators of the program "Chile Grows with You" 2008-2011]. / Monitoreo de los indicadores del Programa "Chile Crece Contigo" 2008-2011.

OBJECTIVE: To monitor coverage and outcomes associated with the activities of the integrated protection system for early childhood Chile Grows with You (CHCC), which includes the comprehensive psychosocial development of children between 18 months and 3 years old, in each of the 29 Health Services of the country, as well as the changes observed after 4 years. MATERIAL AND METHOD: Database analysis of all local public networks in the country between 2008 and 2011 was performed. The application of the test regarding psychomotor development, prevalence of development delay and risk, participation of mothers in educational workshops, home visits and recovery rate of deficient children by age were studied. Median and observed changes of each indicator were analyzed developing a ranking based on the results observed. RESULTS: Approximately 75% of children were evaluated, with a prevalence of delay or risk of about 5% and a rate of recovery close to 50%. The participation of mothers in educational workshops increased from 7.6 to 11.0% (p<0.001) and home visits to developmentally delayed children increased 6 times between 2009 and 2011 (p<0.001). Most changes were positive, although the prevalence of developmentally delayed children under 2 years slightly increased (0.6%), and the recovery of 3 year olds decreased (-14.4%). A great variability was observed among the Health Services. CONCLUSIONS: There are some positive results in relation to psychomotor development, with significant regional differences. A lower than expected deficit rate regarding psychomotor development was observed, which implies the need to further analyze the instrument used or the conditions of application.

Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2-positive ABC patients with stable or active brain metastases (BMs); however, its efficacy in patients with HER2-low ABC with BMs is not well established yet. METHODS: DEBBRAH is a single-arm, five-cohort, phase II study evaluating T-DXd in patients with central nervous system involvement from HER2-positive and HER2-low ABC. Here, we report results from patients with heavily pretreated HER2-low ABC and active BMs, enrolled in cohorts 2 (n = 6, asymptomatic untreated BMs) and 4 (n = 6, progressing BMs after local therapy). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was intracranial objective response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for both cohorts. RESULTS: Intracranial objective response rate per RANO-BM was 50.0% [3/6 patients; 95% confidence interval (CI) 11.8% to 88.2%] and 33.3% [2/6 patients; 95% CI 4.3% to 77.7%; P = 0.033 (one-sided)] in cohorts 2 and 4, respectively. All responders had partial responses. Median time to intracranial response was 2.3 months (range, 1.5-4.0 months) and median duration of intracranial response was 7.2 months (range, 2.8-16.8 months). Median progression-free survival per RECIST v.1.1. was 5.4 months (95% CI 4.1-10.0 months). Treatment-emergent adverse events occurred in all patients included (16.7% grade 3). Three patients (25.0%) had grade 1 interstitial lung disease/pneumonitis. CONCLUSIONS: T-DXd demonstrated promising intracranial activity in pretreated HER2-low ABC patients with active BMs. Further studies are needed to validate these results in larger cohorts. This trial is registered with ClinicalTrials.gov, NCT04420598.

Flexible probe for in vivo quantification of corneal epithelium permeability through non-invasive tetrapolar impedance measurements.

Studies concerning the functional status of the corneal epithelium are of special interest due to its key role in preventing ocular surface disease and corneal infections. In particular, quantitative measurements of the epithelium permeability translayer electrical resistance (TER) have been proven as a sensitive in vitro test for evaluation of the corneal barrier function. In a recent work from the authors (Guimera et al. Biosens. Bioelectron. 31:55-61, 2012), a novel method to non-invasively assess the corneal epithelial permeability by using tetrapolar impedance measurements, based on the same TER theoretical principles, was presented and validated using a rigid sensing device. In this work, the usability of this method has been dramatically improved by using SU-8 photoresist as a substrate material. The flexibility of this novel sensing device makes no need to apply pressure on the cornea to ensure the electrical contact between the electrodes and the corneal surface. The feasibility of this flexible sensor has been evaluated in vivo by increasing the permeability of rabbit corneal epithelium. For that, different concentrations of benzalkonium chloride (BAC) solution were instilled on different rabbit corneas. The obtained results have been compared with measurements of the permeability to sodium fluorescein of different excised corneas, a well-known method used to evaluate the corneal barrier function, to demonstrate the feasibility of this novel flexible sensor for quantifying the corneal epithelium permeability in vivo in a non-invasive way.

Prediction of early and late pre-eclampsia from maternal characteristics, uterine artery Doppler and markers of vasculogenesis during first trimester of pregnancy.

OBJECTIVE: To develop a predictive model for pre-eclampsia using clinical, biochemical and ultrasound markers during the first trimester of pregnancy. METHODS: This was a nested case-control study within a pre-eclampsia screening project that involved 5367 asymptomatic pregnant women undergoing routine transvaginal uterine artery (UtA) Doppler at 11 + 0 to 13 + 6 weeks. Following exclusions, there were 70 pregnant women who later developed pre-eclampsia and 289 control patients enrolled during the first trimester who had serum or plasma samples taken at enrolment available for the purposes of this study. Of these, 17 pregnancies were diagnosed with early-onset (delivery < 34 weeks) pre-eclampsia and 53 with late-onset (delivery ≥ 34 weeks) pre-eclampsia. The lowest, highest and mean of left and right UtA pulsatility indices (PI) were calculated. Blood samples were stored at -84 °C until biochemical analysis for markers of vasculogenesis was performed. The distributions of the lowest UtA-PI and the biochemical markers were adjusted for maternal characteristics, expressed as multiples of the median (MoM), and compared between groups. Logistic regression analysis was used to evaluate if any variable was significantly associated with pre-eclampsia. RESULTS: Pregnancies that later developed pre-eclampsia were associated with higher maternal prepregnancy body mass index. An increased lowest UtA-PI was significantly associated with both early- and late-onset disease. Placental growth factor (PlGF) MoM was significantly reduced in women who later developed early- or late-onset pre-eclampsia compared with controls (median (interquartile range), 0.69 (0.33-1.46) and 1.10 (0.39-1.56), respectively, vs 1.19 (0.65-1.84), P < 0.05). Different combined models were generated by logistic regression analysis, and the detection rate with a fixed 10% false-positive rate was 47% and 29% for early- and late-onset pre-eclampsia, respectively. CONCLUSION: Pregnancies that later developed early or late pre-eclampsia were characterized by impaired placentation and an anti-angiogenic state during the first trimester of pregnancy. Regression models which include maternal characteristics, UtA Doppler and PlGF can apparently predict approximately half of pregnancies that will be complicated by early-onset pre-eclampsia. We believe more research in several areas is needed to aid in the creation of a better and more population-specific screening test for pre-eclampsia during the first trimester of pregnancy.

Prenatal exposure to androgen excess increases LH pulse amplitude during postnatal life in male sheep.

Prenatal exposure to excess testosterone has a profound impact on reproductive and metabolic functions in young and adult female sheep. Nevertheless, few studies have addressed the impact of prenatal exposure to an excess of androgens on reproductive and metabolic functions in males. The aim of the present study was to assess the impact of prenatal exposure to an excess of testosterone or dihydrotestosterone on the luteinizing hormone (LH) pulse characteristics during sexual development in male sheep. Control male sheep (C-males) and males born to mothers exposed to twice weekly injections of 30 mg testosterone or dihydrotestosterone from day 30-90 and 40 mg from day 90-120 of gestation (T-males, DHT-males) were studied at 5, 10, and 20 weeks of age, ages that represent infancy, early prepubertal, and late prepubertal stages of sexual development in this species, respectively. Patterns of LH pulsatility showed that T- and DHT-males exhibited a higher secretion of LH during the 6-h study and a higher amplitude of the LH pulses compared with C-males. Moreover, nadir of the pulses was higher in T- and DHT-males compared with C-males. Frequency of LH pulses, however, was not different within ages or between groups. These results show that males can be responsive to prenatal androgenization and suggest that treatment transiently alters the amplitude of LH pulses probably as the result of defects in the pituitary responsiveness pattern or in the gonadotropin-releasing hormone (GnRH) release pattern.