The Use of Crystal Violet Degradation Products for Ballpoint Pen Ink Manuscript Dating.

Determining the approximate dates that written documents were drawn up based on the chemical composition of the ink is not a simple process. It is very demanding in terms of legal requirements. Various studies have succeeded in dating manuscripts by analyzing the temporal evolutions of the concentrations of dyes and solvents in documents based on the original formulations of the ink pens. These analyses were carried out simultaneously by HPLC-DAD for dyes and by GC-MS for solvents. This study aims, for the first time, to evaluate novel ink compounds and the temporal evolution of the concentrations of the degradation products of the dyes used by most suppliers and which are present in almost all types of ballpoint inks, i.e., Crystal Violet (CV). CV degrades through two parallel pathways: on the one hand, it undergoes progressive demethylation until it becomes pararosaniline, and on the other, it undergoes a breakdown of the molecule obtaining, among other by-products, the compound N,N'-Dimethyl-4-aminophenol (NNAPH), that was experimentally verified using four different inks (e.g., Inoxcrom® and Sigma® brands, in blue and black). For the NNAPH compound, we observed that four of the inks under analysis displayed the same temporary behavior despite having different initial chemical compositions. These initial results show the high potential for both CV and NNAPH, together with the rest of the pararosaniline family, as age tracers for dated/old documents. These techniques may potentially open up new avenues for universal dating tools, regardless of the brands of ink employed for use in different ballpoint pen types.

Lapillus otolith shape, a useful taxonomic feature for the identification of sea catfishes (Ariidae: Siluriformes) from the north-eastern Pacific.

Otolith shape is widely used as a taxonomic feature in fish systematics. In Siluriformes, the lapillus otolith is the most relevant character for taxonomic purposes, although its discriminant potential has not been assessed quantitatively. Our study model were sea catfishes of the family Ariidae from the north-eastern Pacific as representatives of Siluriformes, a taxon with increased taxonomic complexity. The lapillus otolith shape obtained by geometric morphometrics showed high discrimination potential both at the genus and species levels with an overall classification accuracy of c. 93% (K = 0.92). Due to the strong species delimitation exhibited by lapillus otolith shape, the descriptions and identification keys provided here are the most useful materials to recognize the eight sea catfish species evaluated. The shared similarities in lapillus otolith shape among species seem to be more influenced by phylogenetic relationships than other factors such as habitat. The lapillus otolith shape is the most powerful taxonomic feature discovered so far for the identification of sea catfishes from the north-eastern Pacific.

Gestational Hypertensive Disorders and Maternal Breast Cancer Risk in a Nationwide Cohort of 40,720 Parous Women.

BACKGROUND: Preeclampsia and gestational hypertension are hypothesized to be associated with reduced maternal breast cancer risk, but the epidemiologic evidence is inconclusive. Our objective was to examine associations between gestational hypertensive disorders and breast cancer in a nationwide cohort of women with a family history of breast cancer. METHODS: Women ages 35-74 years who had a sister previously diagnosed with breast cancer, but had never had breast cancer themselves, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported diagnoses of eclampsia, preeclampsia, or gestational hypertension in each pregnancy. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between history of a gestational hypertensive disorder and incident invasive breast cancer or ductal carcinoma in situ among 40,720 parous women. We used age as the time scale and adjusted for birth cohort, race-ethnicity, and reproductive, socioeconomic, and behavioral factors. We examined effect measure modification by risk factors for gestational hypertensive disease and breast cancer and assessed possible etiologic heterogeneity across tumor characteristics. RESULTS: The prevalence of gestational hypertensive disease was 12%. During follow-up (mean = 10.9 years), 3,198 eligible women self-reported a breast cancer diagnosis. History of a gestational hypertensive disorder was not associated with breast cancer risk (HR = 1.0; 95% CI = 0.90, 1.1). We did not observe clear evidence of effect measure modification or etiologic heterogeneity. CONCLUSIONS: History of a gestational hypertensive disorder was not associated with breast cancer risk in a cohort of women with a first-degree family history of breast cancer.

Vitamin D concentrations and breast cancer incidence among Black/African American and non-Black Hispanic/Latina women.

BACKGROUND: Vitamin D may protect against breast cancer. Although Black/African American women and Hispanic/Latina women have lower circulating vitamin D levels than non-Hispanic White women, few studies have examined the association between vitamin D and breast cancer within these racial/ethnic groups. METHODS: The vitamin D-breast cancer association was evaluated using a case-cohort sample of self-identified Black/African American and non-Black Hispanic/Latina women participating in the US-wide Sister Study cohort. Circulating 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured using liquid chromatography-tandem mass spectrometry in blood samples collected at the baseline from 415 women (290 Black/African American women and 125 non-Black Hispanic/Latina women) who developed breast cancer. These were compared to concentrations in 1545 women (1084 Black/African American women and 461 Hispanic/Latina women) randomly selected from the cohort. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a mean follow-up of 9.2 years, women with circulating 25(OH)D concentrations above the clinical cut point for deficiency (20.0 ng/mL) had lower breast cancer rates than women with concentrations ≤ 20 ng/mL (HR, 0.79; 95% CI, 0.61-1.02). The inverse association was strongest among Hispanic/Latina women (HR, 0.52; 95% CI, 0.29-0.93), with a weaker association observed among Black/African American women (HR, 0.89; 95% CI, 0.68-1.18; P for heterogeneity = 0.13). There were no clear differences by menopausal status, follow-up time, estrogen receptor status, or invasiveness. Neither 24,25(OH)2 D nor the 24,25(OH)2 D to 25(OH)D ratio were independently associated with breast cancer risk. CONCLUSIONS: This prospective study supports the hypothesis that vitamin D may be protective against breast cancer incidence in women, including non-Black Hispanic/Latina and Black/African American women. LAY SUMMARY: Vitamin D may protect against breast cancer. Although women of color have lower average vitamin D levels than non-Hispanic White women, few studies have considered the role of race/ethnicity. In a sample of self-identified Black/African American and Hispanic/Latina women, we observed that vitamin D concentrations measured in blood were inversely associated with breast cancer, particularly among Latinas. These findings indicate that vitamin D may protect women against breast cancer, including those in racial/ethnic groups with low average circulating levels.

Nocardiosis in Free-Ranging Cetaceans from the Central-Eastern Atlantic Ocean and Contiguous Mediterranean Sea.

We report the pathologic features of nocardiosis in five free-ranging delphinids from the Canary Islands and Andalusia, namely four striped dolphins (Stenella coerulealba) and one bottlenose dolphin (Tursiops truncatus). All animals had a multiorgan (disseminated) pattern of infection involving suppurative to pyogranulomatous and thromboembolic lesions in two or more organs. Most affected organs were (by decreasing order) lung, pulmonary lymph nodes, liver, kidney, adrenal glands, and central nervous system. Typical intralesional and intravascular branched and filamentous bacteria were highlighted by Grocott's methenamine silver and Gram stains. Bacterial analysis including 16S rRNA gene sequencing identified Nocardia farcinica in two striped dolphins and Nocardia otitidiscaviarum in one striped dolphin and the bottlenose dolphin. All dolphins tested (n = 4) for cetacean morbillivirus were negative; one dolphin had concurrent cutaneous herpesvirosis. These results provide the first record of N. otitidiscaviarum in cetaceans, the first account of N. farcinica in free-ranging dolphins, and confirmation of nocardiosis in central eastern Atlantic Ocean. These results expand the known geographic range of nocardiosis in cetaceans.

Persistence of Risk for Type 2 Diabetes After Gestational Diabetes Mellitus.

OBJECTIVE: Gestational diabetes mellitus complicates ∼6% of pregnancies and strongly predicts subsequent type 2 diabetes. It has not been fully elucidated how risk depends on the number of affected pregnancies or how long the excess risk persists. RESEARCH DESIGN AND METHODS: We assessed reproductive histories in relation to risk of type 2 diabetes using a nationwide cohort of 50,884 women. Among participants who initially did not have diabetes, 3,370 were diagnosed with diabetes during 10 years of follow-up. We used Cox proportional hazards models that allowed risk to depend on age, cumulative number of pregnancies with gestational diabetes mellitus, and time since the most recent affected pregnancy, adjusting for BMI, educational level, and race/ethnicity. RESULTS: History of one or more pregnancies with gestational diabetes mellitus predicted elevated age-specific risk of type 2 diabetes, with a hazard ratio of 3.87 (95% CI 2.60-5.75) 6-15 years after an affected pregnancy. Risk increased steeply with multiple affected pregnancies. The age-specific associations attenuated over time after an affected pregnancy, with an estimated 24% reduction of the hazard ratio per decade. Risk remained elevated, however, for >35 years. CONCLUSIONS: Gestational diabetes mellitus predicted markedly increased rates of type 2 diabetes. Relative risk increased substantially with each additional affected pregnancy. The estimated hazard ratio declined with time after a pregnancy with gestational diabetes mellitus but remained elevated for >35 years. Women recalling a history of gestational diabetes mellitus should be screened regularly for type 2 diabetes, even late in life.

Vitamin D Supplement Use and Risk of Breast Cancer by Race-Ethnicity.

BACKGROUND: Vitamin D has anticarcinogenic properties, but a relationship between vitamin D supplement use and breast cancer is not established. Few studies have accounted for changes in supplement use over time or evaluated racial-ethnic differences. METHODS: The Sister Study is a prospective cohort of 50,884 women with 35-74 years of age who had a sister with breast cancer, but no breast cancer themselves at enrollment (2003-2009). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D supplement use and incident breast cancer (3,502 cases; median follow-up 10.5 years). RESULTS: Vitamin D supplement use was common, with 64% reporting ever use (at least once per month) in the year before enrollment. Considering supplement use over time, ever use of vitamin D supplements was not meaningfully associated with breast cancer (HR = 0.96, 95% CI = 0.88, 1.0), relative to never use. However, after adjusting for prior use, recent use of vitamin D supplements ≥1/month was inversely associated with breast cancer (HR = 0.88, 95% CI = 0.78, 1.0), relative to nonrecent use. The inverse association was stronger for ductal carcinoma in situ (HR = 0.67, 95% CI = 0.52, 0.87) than invasive breast cancer (HR = 0.94, 95% CI = 0.72, 1.1, p-for-heterogeneity = 0.02). Supplement use was less common among African American/Black (56%) and non-Black Hispanic/Latina (50%) women than non-Hispanic White women (66%), but there was limited evidence of racial-ethnic differences in HRs (p-for-heterogeneity = 0.16 for ever use, P = 0.55 for recent). CONCLUSIONS: Our findings are consistent with the hypothesis that recent vitamin D use is inversely associated with breast cancer risk.

Identifying Peripheral Neuropathy in Colour Fundus Photographs Based on Deep Learning.

The aim of this study was to develop and validate a deep learning-based system to detect peripheral neuropathy (DN) from retinal colour images in people with diabetes. Retinal images from 1561 people with diabetes were used to predictDN diagnosed on vibration perception threshold. A total of 189 had diabetic retinopathy (DR), 276 had DN, and 43 had both DR and DN. 90% of the images were used for training and validation and 10% for testing. Deep neural networks, including Squeezenet, Inception, and Densenet were utilized, and the architectures were tested with and without pre-trained weights. Random transform of images was used during training. The algorithm was trained and tested using three sets of data: all retinal images, images without DR and images with DR. Area under the ROC curve (AUC) was used to evaluate performance. The AUC to predict DN on the whole cohort was 0.8013 (±0.0257) on the validation set and 0.7097 (±0.0031) on the test set. The AUC increased to 0.8673 (±0.0088) in the presence of DR. The retinal images can be used to identify individuals with DN and provides an opportunity to educate patients about their DN status when they attend DR screening.

Development of a Robust Manufacturing Route for Molnupiravir, an Antiviral for the Treatment of COVID-19.

Herein is described the development of a large-scale manufacturing process for molnupiravir, an orally dosed antiviral that was recently demonstrated to be efficacious for the treatment of patients with COVID-19. The yield, robustness, and efficiency of each of the five steps were improved, ultimately culminating in a 1.6-fold improvement in overall yield and a dramatic increase in the overall throughput compared to the baseline process.

A phylogenetic approach to understand the evolution of reproduction in coleoid cephalopods.

A central question in the evolution of life-histories is whether organisms reproduce once or repeatedly. For cephalopods, the main differences between semelparous and iteroparous are based on ovulation pattern and spawning type. The different reproductive strategies in coleoid cephalopods could be related to the habitat in which the species dwell (coastal vs. oceanic) and/or to environmental forces, thus, both aspects should be quantitatively evaluated under an evolutionary perspective to reconstruct: (a) the ancestral ovulation type of coleoid cephalopods, and (b) the potential of correlated evolution between ovulation type versus habitat and environment. Ancestral states of ovulation type were estimated using stochastic mapping based on literature data (i.e. synchronous or asynchronous), and this information was combined with a new molecular phylogeny including 165 species. The evolutionary correlation between ovulation type, habitat, and environment was estimated by means of the Markov model comparing the rates of gain and loss. The estimates of ancestral states of ovulation type for coleoid cephalopods resulted in a high probability that Octopodiformes evolved from synchronous ovulation type, and Decapodiformes from asynchronous ovulation type. The three traits evaluated presented phylogenetic signal, although no correlation was found between habitat and ovulation type. Overall, species in stable environments showed a tendency towards synchronous ovulation type, while the asynchronous ovulation pattern was found more frequently in species that live in unstable environments, being this last trait also responsible for triggering the change of ovulation type in some species throughout evolution.

First detection of an ocellate octopus in the Revillagigedos ecoregion, a biodiversity hotspot located in the Tropical East Pacific Province.

The biodiversity of mollusks, particularly cephalopods, has not been exhaustively determined in the Revillagigedos ecoregion, which is a biodiversity hotspot for several marine groups located in the Tropical East Pacific Province. In our study, we detected and examined ocellate octopuses from Socorro and Clarion Islands, and determined their identity using morphological criteria and molecular data from two mitochondrial genes (COIII and COI). The taxon identified was Octopus oculifer, a species considered endemic to the Galapagos Archipelago. In addition, according to our analyses, O. mimus, O. hubbsorum and O. oculifer are very closely related and may represent a species complex comprised of three morphotypes. We found that the evolutionary relationships among octopuses are not determined by the presence of ocelli. This study is the first to report a clade represented by ocellate and non-ocellate species, in addition, the identity of cephalopods in the Revillagigedos was determined with analytical support.

Histopathological Differential Diagnosis of Meningoencephalitis in Cetaceans: Morbillivirus, Herpesvirus, Toxoplasma gondii, Brucella sp., and Nasitrema sp.

Infectious and inflammatory processes are among the most common causes of central nervous system involvement in stranded cetaceans. Meningitis and encephalitis are among the leading known natural causes of death in stranded cetaceans and may be caused by a wide range of pathogens. This study describes histopathological findings in post-mortem brain tissue specimens from stranded cetaceans associated with five relevant infectious agents: viruses [Cetacean Morbillivirus (CeMV) and Herpesvirus (HV); n = 29], bacteria (Brucella sp.; n = 7), protozoa (Toxoplasma gondii; n = 6), and helminths (Nasitrema sp.; n = 1). Aetiological diagnosis was established by molecular methods. Histopathologic evaluations of brain samples were performed in all the cases, and additional histochemical and/or immunohistochemical stains were carried out accordingly. Compared with those produced by other types of pathogens in our study, the characteristic features of viral meningoencephalitis (CeMV and HV) included the most severe and frequent presence of malacia, intranuclear, and/or intracytoplasmic inclusion bodies, neuronal necrosis and associated neuronophagia, syncytia and hemorrhages, predominantly in the cerebrum. The characteristic features of Brucella sp. meningoencephalitis included the most severe and frequent presence of meningitis, perivascular cuffing, cerebellitis, myelitis, polyradiculoneuritis, choroiditis, ventriculitis, vasculitis, and fibrinoid necrosis of vessels. The characteristic features of T. gondii meningoencephalitis included lymphocytic and granulomatous encephalitis, tissue cysts, microgliosis, and oedema. In the case of Nasitrema sp. infection, lesions are all that we describe since just one animal was available. The results of this study are expected to contribute, to a large extent, to a better understanding of brain-pathogen-associated lesions in cetaceans.

Retrospective Study of Fishery Interactions in Stranded Cetaceans, Canary Islands.

Estimating cetacean interactions with fishery activities is challenging. Bycatch and chronic entanglements are responsible for thousands of cetacean deaths per year globally. This study represents the first systematic approach to the postmortem investigation of fishery interactions in stranded cetaceans in the Canary Islands. We retrospectively studied 586 cases necropsied between January 2000 and December 2018. Of the cases with a known cause of death, 7.4% (32/453) were due to fishery interactions, and the Atlantic spotted dolphin (Stenella frontalis) was the most affected species [46.9% (15/32)]. Three types of fishery interactions were recognized by gross findings: bycatch [65.6% (21/32)], chronic entanglements [18.8% (6/32)], and fishermen aggression [15.6% (5/32)]. Among the bycaught cases, we differentiated the dolphins that died because of ingestion of longline hooks [23.8% (5/21)] from those that died because of fishing net entrapments [76.2% (16/21)], including dolphins that presumably died at depth due to peracute underwater entrapment (PUE) [37.5% (6/16)], dolphins that were hauled out alive and suffered additional trauma during handling [43.8% (7/16)], and those that were released alive but became stranded and died because of fishery interactions [18.7% (3/16)]. Gross and histologic findings of animals in each group were presented and compared. The histological approach confirmed gross lesions and excluded other possible causes of death. Cetaceans in good-fair body condition and shallow diving species were significantly more affected by fishery interactions, in agreement with the literature. Low rates of fishery interactions have been described, compared with other regions. However, within the last few years, sightings of entangled live whales, especially the minke whale (Balaenoptera acutorostrata) and Bryde's whale (B. edeni), have increased. This study contributes to further improvement of the evaluation of different types of fishery interactions and may facilitate the enforcement of future conservation policies to preserve cetacean populations in the Canary Islands.

Self-Reported Practices in Opioid Management of Chronic Noncancer Pain: An Updated Survey of Canadian Family Physicians.

Chronic pain affects one in five Canadians, and opioids continue to be prescribed to 12.3% of the Canadian population. A survey of family physicians was conducted in 2010 as a baseline prior to the release of the Canadian Opioid Guideline. We repeated the same survey with minor modifications to reflect the updated 2017 opioid prescribing guideline. The online survey was distributed in all provinces and territories in both English and French. There were 265 responses from May 2018 to October 2019, 55% of respondents were male, 16% had advanced training in pain management, 51% had more than 20 years in practice, 54% wrote five or fewer prescriptions of opioids per month, and 58% were confident in their skills in prescribing opioids. Of the 11 knowledge questions, only two were correctly selected by more than 80% of the respondents. Twenty-nine physicians (11%) do not prescribe opioids, and the main factor affecting their decisions were concerns about long-term adverse effects and lack of evidence for effectiveness of opioids in chronic noncancer pain. Of the 12 guideline-concordant practices, only two were performed regularly by 90% or more of the respondents: explain potential harms of long-term opioid therapy and beginning dose of less than 50 mg of morphine equivalent daily. This survey represents a small proportion of family physicians in Canada and its generalizability is limited. However, we identified a number of opioid-related and guideline-specific gaps, as well as barriers and enablers to prescribing opioids and adhering to the guideline.

Perinatal and postnatal exposures and risk of young-onset breast cancer.

BACKGROUND: Perinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer. We aimed to evaluate the association between young-onset breast cancer and perinatal exposures and to explore etiologic heterogeneity in the relationship between associated perinatal factors and estrogen receptor status of the tumor. METHODS: We addressed this in a sister-matched case-control study. Cases were women who had been diagnosed with ductal carcinoma in situ or invasive breast cancer before the age of 50. Each case had a sister control who was free of breast cancer up to the same age at which her case sister developed the disease. The factors considered were self-reported and included the mother's preeclampsia in that pregnancy, mother's smoking in that pregnancy, gestational hypertension, prenatal diethylstilbestrol use, and gestational diabetes, as well as low birth weight (less than 5.5 pounds), high birth weight (greater than 8.8 pounds), short gestational length (less than 38 completed weeks), and being breastfed or being fed soy formula. RESULTS: In conditional logistic regression analyses, high birth weight (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.07-2.36) and preeclampsia (adjusted OR = 1.92, CI 0.824-4.5162) were positively associated with risk. The association with preeclampsia was stronger when the analysis was restricted to invasive breast cancer (OR = 2.87, CI 1.08-7.59). We also used case-only analyses to assess etiologic heterogeneity for estrogen receptor (ER)-positive versus estrogen receptor-negative cancer. Women who were born to a preeclamptic pregnancy and later developed young-onset breast cancer were at increased odds for the ER-negative type (OR = 2.27; CI 1.05-4.92). CONCLUSION: These results suggest that being born to a preeclamptic pregnancy may increase risk for young-onset breast cancer, especially for the ER-negative subtype.

Seminoma in an adult striped dolphin Stenella coeruleoalba: tomographic, macroscopical, histological and immunohistochemical study.

Testicular neoplasms have been extensively described and characterized in domestic animals, but reports in wildlife species, including marine mammals, are scarce. This case report describes a testicular seminoma in an adult striped dolphin Stenella coeruleoalba stranded along the coasts of the Canary Islands. Post-mortem computerized tomography (CT) showed a prominent enlargement of the cranial pole of the right testicle, displacing the intestinal loops. Necropsy gross findings confirmed the presence of a testicular mass, bulging at the cut surface, with multiple well-delimitated whitish nodular lesions. Histologically, intratubular and diffuse neoplastic germinative cell proliferation was described. Complementary immunohistochemical assessments for vimentin and CD117 antibodies were negative. To the authors' knowledge, this is the first seminoma described in a S. coeruleoalba. We suggest that post-mortem (PM) pre-necropsy CT in dolphins is a useful tool for anatomic-guided pathology in such cases.

Changes in Opioid Prescribing Behaviors among Family Physicians Who Participated in a Weekly Tele-Mentoring Program.

A weekly tele-mentoring program was implemented in Ontario to help address the growing opioid crisis through teaching and mentoring family physicians on the management of chronic pain and opioid prescribing. This study assessed opioid prescribing behaviours among family physicians who attended the tele-mentoring program compared to two groups of Ontario family physicians who did not attend the program. We conducted a retrospective cohort study with two control groups: a matched cohort, and a random sample of 3000 family physicians in Ontario. Each physician was followed from one year before the program, which is the index date, and one year after. We examined the number and proportion of patients on any opioid, on high dose opioids, and the average daily morphine equivalent doses prescribed to each patient. We included 24 physicians who participated in the program (2760 patients), 96 matched physicians (11,117 patients) and 3000 random family doctors (374,174 patients). We found that, at baseline, the tele-mentoring group had similar number of patients on any opioid, but more patients on high dose opioids than both control groups. There was no change in the number of patients on any opioid before and after the index date, but there was a significant reduction in high-dose opioid prescriptions in the extension for community healthcare outcomes (ECHO) group, compared to a non-significant increase in the matched cohort, and a non-significant reduction in the Ontario group during the same comparable periods. Participation in the program was associated with a greater reduction in high-dose opioid prescribing.

Taxonomic assessment of species of the genus Octopus from the northeastern Pacific via morphological, molecular and morphometric analyses.

Species of the genus Octopus from the northeastern Pacific are ecologically and economically important; however, their taxonomy is confusing and has not been comprehensively assessed. In this study, we performed a taxonomic evaluation of these species considering the morphological characteristics of the original descriptions, a molecular analysis of partial COI-gene sequences, and a traditional morphometry analysis of nine body measurements. Several interesting findings were obtained with our results: for instance, we updated the diagnoses of some species by including characters such as the number of lamellae per demibranch and the presence of chromatophores in the visceral sac; we deposited partial COI-gene sequences of species that had not been incorporated into the GenBank repository; and according to the morphometric analysis, we confirmed that the lengths of arms I-IV are relevant to discriminate the species under study. The taxa evaluated were morphologically, molecularly and morphometrically well-delimited; however, features such as funnel organ shape and arm length proportions in regard to dorsal mantle length are either not included in the diagnosis of the genus Octopus or overlap with other genera. Hence, this information, combined with the results obtained from the molecular analysis, supports the generic re-assignation of two of the species evaluated.

Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study.

BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women. METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants' weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models. RESULTS: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [ΣDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years. CONCLUSIONS: Certain phthalates may contribute to short-term weight gain among postmenopausal women.