Potential therapeutic applications of mesenchymal stem cells in the oral and maxillofacial tissues.

Over the past decades, we have noted that the study of stem cells is of interest to scientists because it offers great promise for the development of cell-based therapies and establishes basic models for studying the pathogenesis of diseases, overcoming all the challenges it encounters. The majority of craniofacial tissues are derived from mesenchymal tissues, so it makes the mesenchymal stem cells (MSCs) an attractive candidate for regenerating damaged or diseased craniofacial structures. Mesenchymal stem cells (MSCs) do not have the same obstacles as embryonic stem cells. Mesenchymal stem cells can be used to conduct research and treat diseases, as they do not require embryonic destruction. MSCs possess unique properties such as self-renewal, the ability to differentiate into different cell types, and the modulation of immune cells. The present review article provided an overview of MSCs isolated from both nondental and dental tissues and highlighted the available information regarding the significant progress in both experimental and clinical trials of MSCs and their potential therapeutic application in the oral and maxillofacial regions. This review sheds light on the experimental research and clinical applications that have led to the development of new MSCs therapies for a variety of diseases. Moreover, we have highlighted the experiments that proved that MSCs are an effective tool for tissue regeneration in the oral and craniofacial regions. This could pave the way for scientists to improve the surgical methods of oral and maxillofacial and treatment of craniofacial malformations.

Functional and mental health affection (depression, anxiety, stress) among Egyptian rheumatic diseases patients during COVID-19 pandemic.

OBJECTIVE: Psychological distress caused by the SARS-CoV-2 outbreak has had deleterious effects on patients with chronic rheumatic disease, as those patients were highly susceptible for COVID-19 infection due to their chronicity, in addition to use of immunosuppressive drugs. Therefore, they underwent to more isolation than other people and develop more stress and depression. This study aimed at evaluating level of depression, anxiety, stress symptoms and physical health status in Egyptian patients with various rheumatic diseases during COVID-19 pandemic. PATIENTS AND METHODS: This is a cross-sectional study conducted in Gharbia Governorate, Egypt. It included 440 diagnosed cases of rheumatic diseases from 1st to the end of March 2021. Depression, Anxiety and Stress Scale-21 (DASS21) and RAPID3/MDHAQ test were used to assess the pandemic's psychological and functional effect on participants. RESULTS: RAPID3 test results showed that during the COVID-19 outbreak the 40% of patients had a moderate severity functional affection and 20% had high severity. DASS21 depression scoring showed mild to moderate depression (33% and 35%, respectively), while severe depression was detected in only 3.2% of cases. Moderate anxiety was reported in 49% of cases, 29% had severe anxiety while 1% showed extremely severe anxiety. Mild to moderate stress was reported in 17% and 16%, respectively. Female and cases aged more than 45 years had significantly more severe functional affection recorded by RAPID3 test, moderate stress and severe anxiety. On the other hand, severe depression was significantly higher in male and young patients younger than 45 years old. CONCLUSIONS: Rheumatic disease patients have been highly susceptible to functional affection and psychological distress related to COVID-19 pandemic. Planning and implementation of programs to enforce coping strategies for these patients are required.

Soybean-associated endophytic fungi as potential source for anti-COVID-19 metabolites supported by docking analysis.

AIMS: To identify the metabolites produced by the endophytic fungus, Aspergillus terreus and to explore the anti-viral activity of the identified metabolites against the pandemic disease COVID-19 in-silico. METHODS AND RESULTS: Herein, we reported the isolation of A. terreus, the endophytic fungus associated with soybean roots, which is then subcultured using OSMAC approach in five different culture media. Analytical analysis of media ethylacetate extracts using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) was carried out. Furthermore, the obtained LC-MS data were statistically processed with MetaboAnalyst 4.0. Molecular docking studies were performed for the dereplicated metabolites against COVID-19 main protease (Mpro ). Metabolomic profiling revealed the presence of 18 compounds belonging to different chemical classes. Quinones, polyketides and isocoumarins were the most abundant classes. Multivariate analysis revealed that potato dextrose broth and modified potato dextrose broth are the optimal media for metabolites production. Molecular docking studies declared that the metabolites, Aspergillide B1 and 3a-Hydroxy-3, 5-dihydromonacolin L showed the highest binding energy scores towards COVID-19 main protease (Mpro ) (-9·473) and (-9·386), respectively, and they interact strongly with the catalytic dyad (His41 and Cys145) amino acid residues of Mpro . CONCLUSIONS: A combination of metabolomics and in-silico approaches have allowed a shorter route to search for anti-COVID-19 natural products in a shorter time. The dereplicated metabolites, aspergillide B1 and 3α-Hydroxy-3, 5-dihydromonacolin L were found to be potent anti-COVID-19 drug candidates in the molecular docking study. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that the endophytic fungus, A. terreus can be considered as a potential source of natural bioactive products. In addition to, the possibility of developing the metabolites, aspergillide B1 and 3α-Hydroxy-3, 5-dihydromonacolin L to be used as phytopharmaceuticals for the management of COVID-19.

Residual time of sinusoidal metachronal ciliary flow of non-Newtonian fluid through ciliated walls: fertilization and implantation.

The monitoring of the ciliated walls in the uterine tube has supreme importance in enhancing the sperm to reach the egg (capacitation processes), and at peristaltic ciliary flow has a more favorable residual time along the canal when compared to the peristaltic flow. Based on the importance of this study, a mathematical simulation of this process has been carried out by studying the behavior of a non-Newtonian magnetized fluid with a Darcy flow model with an oscillating wall having an internal ciliated surface. The governing equation is formed with Eyring-Powell fluid (tubal fallopian fluid) without using any approximations and solved using the Adomian analysis method. Using the vorticity formula, the components of the velocity function, pressure gradient, and stream function are obtained. The influence of relevant parameters is explained through diagramming and discussion. We also analyzed the residue time effects on the flow parameters. The results indicate that peristaltic ciliary flow has a more favorable residual time along the canal when compared to peristaltic flow.

Effect of Disaccharide Inclusion in Vitrification and Warming Solutions on Developmental Competence of Vitrified/Warmed Germinal Vesicle Stage Buffalo Oocytes.

BACKGROUND: Cryopreservation of immature oocyte is a potential strategy for preserving the female germline, providing a non-seasonal, easily accessible source for reproduction and science. Exposure of oocytes to high concentrations of cryoprotectants during vitrification is toxic and can negatively impact the fertilization ability and development of vitrified/warmed oocytes. OBJECTIVE: 1) to evaluate the effects of exposure of buffalo germinal vesicle (GV) oocytes to different vitrification solutions (VS), either supplemented with or without sucrose, on cumulus expansion and nuclear maturation following IVM; and 2) to compare the effects of sucrose and trehalose in the warming solution on developmental competence of buffalo oocytes vitrified at the GV-stage. MATERIALS AND METHODS: Cumulus oocyte complexes (COCs) obtained at slaughter from mature buffalo ovaries were randomly assigned into five groups: control - directly subjected to IVM); VS1 group - exposed to 20% ethylene glycol (EG) + 20% glycerol (GLY) + 0.5 M sucrose; VS2 group - exposed to 20% EG + 20% GLY; VS3 group - subjected to 20% EG+20% dimethyl sulfoxide (DMSO) + 0.5 M sucrose; and VS4 group - subjected to 20% EG+20% DMSO. Following cryoprotectant dilution, viable oocytes were matured in vitro for 22 h; cumulus expansion and nuclear maturation were then evaluated (Experiment 1). COCs were vitrified by solid surface vitrification (SSV) in a solution composed of 20% EG + 20% DMSO (VS4). Following vitrification, COCs were warmed in a solution composed of either sucrose or trehalose in decreasing concentrations (1 M, 0.5 M and 0.25 M). Morphologically viable oocytes were matured, fertilized and cultured in vitro. Cleavage and blastocyst rates were evaluated at 30 h and day 7 post-insemination (p.i.), respectively (Experiment 2). RESULTS: Exposure of GV-buffalo oocytes to different cryoprotectant combinations did not significantly affect cumulus expansion following IVM. However, nuclear maturation rate (oocytes at MII) was significantly higher (P<0.05) in the groups exposed to sucrose-free vitrification solutions (VS2 and VS4) and not significantly different from the control. Compared with the control group, the cleavage and blastocyst rates were significantly (P<0.05) lower in oocytes vitrified and then warmed in a solution containing trehalose; whilst this was not the case when sucrose was present in the solution. CONCLUSION: Our results suggest that exposure of buffalo GV-oocytes to sucrose-free vitrification solutions improved nuclear maturation after IVM. Moreover, warming of vitrified buffalo oocytes in sucrose-based solution improved preimplantation development following IVM and IVF compared to trehalose based media.

Optimization of the Protocol for Cryopreservation of Arabian Stallion Spermatozoa: Effects of Centrifugation, Semen Extenders and Cryoprotectants.

BACKGROUND: Cryopreservation of Arabian stallion semen is important in order to improve the function and fertility of frozen/thawed semen in this breed. OBJECTIVE: To investigate the effects of centrifugation, type of semen extenders, and type of cryoprotectants on the quality of frozen/thawed Arabian stallion spermatozoa. MATERIALS AND METHODS: Semen samples collected from four adult Arabian stallions (one ejaculate per week for 10 consecutive weeks) were either processed directly without centrifugation (no centrifugation; NC) or subjected to centrifugation on the gel-free fraction. Centrifugation protocols were divided into six categories; 600 x g for 10 min (C1), 600 x g for 15 min (C2), 900 x g for 10 min (C3), 900 x g for 15 min (C4), 1200 x g for 10 min (C5), or 1200 x g for 15 min (C6) (Experiment 1). Two semen extenders, INRA-82 and modified Kenney's were compared (Experiment 2). Three different cryoprotectants, [namely 5% glycerol, 5% dimethylformamide (DMF) and 2.5% glycerol] plus 2.5% DMF were used (Experiment 3). Following freezing and thawing, motility, viability, plasma membrane integrity, acrosome status and viability index were evaluated. RESULTS: Centrifugation at 600 x g for 15 min before cryopreservation increased (P< 0.05) sperm motility, viability, membrane integrity and percentage of spermatozoa with intact acrosome compared to other centrifugation protocols. Dilution of Arabian stallion semen with INRA-82 before cryopreservation improved (P< 0.05) sperm quality after freezing and thawing compared to modified Kenney's extender. Supplementation of semen diluent INRA-82 with 5% DMF improved (P< 0.05) the quality of frozen/thawed Arabian stallion spermatozoa compared to 5% glycerol. CONCLUSION: These findings suggest that optimized conditions such as centrifugation, types of semen extenders and cryoprotectants play an important role in processing Arabian stallion spermatozoa for cryopreservation.

Effect of brain-derived neurotrophic factor on sperm function, oxidative stress and membrane integrity in human.

Oxidative stress has negative impacts on the clinical outcomes of assisted reproduction techniques. The brain-derived neurotrophic factor (BDNF) promotes the viability of nerve cells and is known to decrease oxidative stress and apoptosis in different cells. The aim of this study was to evaluate the effect of BDNF treatment on human sperm functions that are known to be essential for fertilisation. Our findings showed that treatment of human spermatozoa with 0.133 nM BDNF significantly increased the percentages of both total (P = 0.001) and progressive (P < 0.01) motile sperm cells compared to those observed in the nontreated (control) group. We also showed that the mean fluorescence intensity of DCFH-DA, as an indicator of intracellular reactive oxygen species, was significantly lower (P < 0.05) in spermatozoa treated with BDNF compared to the control group. Treatment of spermatozoa with BDNF significantly decreased the percentages of both dead (P = 0.001) and apoptotic-like sperm cells (P < 0.05) compared to the control group. On the other hand, BDNF treatment significantly increased the percentage of viable sperm cells compared to the control (P = 0.001). In conclusion, BDNF has protective effects against oxidative stress in spermatozoa and could improve sperm functions that are essential for sperm-egg fusion and subsequent fertilisation.

Isolation and molecular identification of Vibrio spp. by sequencing of 16S rDNA from seafood, meat and meat products in Libya.

The genus Vibrio includes several food-borne pathogens that cause a spectrum of clinical conditions including septicemia, cholera and milder forms of gastroenteritis. Several Vibrio spp. are commonly associated with food-borne transmission including Vibrio cholerae, Vibrio parahemolyticus, and Vibrio vulnificus. Microbiological analysis for enumeration and isolation of Vibrio spp. were carried out for a total of 93 samples of seafood, meat and meat products from different geographic localities in Libya (Tripoli, Regdalin, Janzour and Tobruk). Vibrio spp. were detected by conventional cultural and molecular method using PCR and sequencing of 16S rDNA. Out of the 93 cultured samples only 48 (51.6%) yielded colonies on Thiosulfate Citrate Bile Salt agar (TCBS) with culture characteristics of Vibrio spp. More than half (n=27) of processed seafood samples (n=46) yielded colonies on TCBS, while only 44.6 % of samples of meat and meat products showed colonies on TCBS. Among cultured seafood samples, the highest bacterial count was recorded in clam with a count of 3.8 ×10(4) CFU\g. Chicken burger samples showed the highest bacterial count with 6.5 ×10(4) CFU\g. Molecular analysis of the isolates obtained in this study, showed that 11 samples out of 48 (22.9%) were Vibrio spp. Vibrio parahemolyticus was isolated from camel meat for the first time. This study is an initial step to provide a baseline for future molecular research targeting Vibrio spp. foodborne illnesses. This data will be used to provide information on the magnitude of such pathogens in Libyan seafood, meat and meat products.

Effect of Cytochalasin B pretreatment on developmental potential of ovine oocytes vitrified at the germinal vesicle stage.

Oocyte cryopreservation remains a challenge in most mammalian species because of their sensitivities to chilling injuries. Relaxation of the cytoskeleton during vitrification may improve post-thaw viability and pre-implantation embryo development. The aim of this study was to investigate the effect of cytochalasin B (CB) pre-treatment before vitrification on viability, frequencies of in vitro fertilisation (IVF) and subsequent development of ovine cumulus-oocyte complexes (COCs) vitrified at the germinal vesicle (GV) stage using cryoloop. COCs obtained at slaughter were randomly divided into two groups and incubated with or without 7.5µg/mL CB for 60 min. Oocytes from each group were then vitrified using a cryoloop or used as toxicity and controls. Oocytes were then matured, fertilised, and cultured in vitro for 7 days. Viability following vitrifiaction and warming, fertilisation events following IVF and subsequent pre-implantation embryo development were evaluated. No significant differences were observed in survival rates between CB treated and non-treated oocytes in both vitrified and toxicity groups. Frequencies of fertilisation were increased in CB-vitrified group (oocytes pre-treated with CB before vitrification) than those vitrified without CB pre-treatment (57.0% vs 40.7%). Cleavage was significantly lower (P < 0.05) in vitrified and CB-vitrified oocytes at both 24 hpi (12.5% vs 9.1%) and 48 hpi (25.0% vs 16.2%) than in other groups. Based on the numbers of cleaved oocytes, (48 hpi), 16.1% and 18.8% of the cleaved embryos developed to blastocysts in both vitrified and CB-vitrified groups. These values did not differ significantly from those obtained in CB-control group (37.8%). No significant differences were observed in mean cell numbers per blastocyst between all groups. In conclusion, pre-treatment of ovine GV oocytes with cytochalasin B as cytoskeleton stabilizer before vitrification increased frequencies of in vitro fertilisation and subsequently resulted in production of good quality late stage pre-implantation embryos following IVF.

Follicular fluid composition in relation to follicular size in pregnant and non pregnant dromedary camels (Camelus dromedaries)

aim of this study was to evaluate the effects of the reproduct ive status of female dromedary camels ( pregnant vs. non - pregnant ) on the chemical composition, hormonal profile and antioxidant capacity of follicular fluid collected from different sized ovarian follicles during the breeding season . One hundred ovaries we re collected at slaughter house from fifty female dromedary camel s . The ovaries were collected in pairs from each animal and allocated into two groups according to the reproductive status of the females ; 25 pairs were obtained from pregnant females and 25 p airs were obtained from non - pregnant animals . The follicles on each ovary were categorized according to their diameter into three categories; small ( 1 - 3 mm), medium (4 - 9 mm) and large ( 10 - 20 mm). Follicular fluid (FF) aspirated from each follicle category from each pair of ovaries w as analyzed . The results showed that the average number of follicles per ovary was greater ( P < 0.05) in the ovaries obtained from non - pregnant females compared to those collected from pregnant ones ( 6.4 ± 1.2 vs . 3.6 ± 0.9, resp ectively). Progesterone concentrations were significantly higher in the follicular fluid collected from all follicle categories in pregnant animals than those obta ined from non - pregnant animals . Glucose concentration s were higher (P < 0.05) in the follicul ar fluid collected from large follicles in the non - pregnant group (64.9 ± 6.1 mg/d l ) than those obtained from the same follicle category in the pregnant ovaries (45.4 ± 4.0 mg/d l ). C oncentrations of malondialdehyde (MDA) were higher (P < 0.05) in the FF co llected from small, medium and large follicles in pregnant ovaries than non - pregnant ones . In conclusion , these data indicate that FF composition differ s according to the reproductive status of the female . In pregnant camels, the p resence of the corpus lut eum on the ovar ies could play an important role not only in the process of follicle growth and development , but also in the concentrations of biochemical metabolites and hormonal profiles in the FF of dromedary camels.

Raw cow's milk relatively inhibits quorum sensing activity of Cromobacterium violaceum in comparison to raw she-camel's milk.

Milk from different animal species has variable levels of antimicrobial factors against some of spoilage bacteria. For example, they are significantly present in higher concentration in she-camel's milk than in cattle or buffalo and they are more heat-resistant than their counterparts in cattle and buffalo. Spoilage bacteria are known to communicate with each other by release of signaling molecules, a phenomenon described as quorum sensing (QS). Some food matrices inhibit these signaling compounds. In this study we screened QS inhibitory activities in raw milk of cattle and camel. Ten samples each of fresh raw cow's milk and she-camel's milk from apparently healthy animals were screened using the bacterial model Cromobacterium violaceum. The tested cow's raw milk samples were able to inhibit the production of QS signalling molecules acyl-homoserine lactones (AHLs) produced by C. violaceum. However, she-camel's milk samples were less effective in inhibiting such AHLs. Thus, one of the factors which influence the inhibitory activity could be derived from variation in milk chemical composition, especially in the percentage of fat which is significantly higher in tested cow's milk samples (2.22±0.12) than in tested she-camel's milk samples (1.44±0.35). Natural inhibition of QS signaling by cow's milk may offer a unique means to control foodborne pathogens and reduce microbial spoilage.

Preterm prediction study: comparison of the cervical score and Bishop score for prediction of spontaneous preterm delivery.

OBJECTIVE: To prospectively compare digital cervical score with Bishop score as a predictor of spontaneous preterm delivery before 35 weeks of gestation. METHODS: Data from a cohort of 2,916 singleton pregnancies enrolled in a multicenter preterm prediction study were available. Patients underwent digital cervical examinations at 22-24 and 26-29 weeks of gestation for calculation of Bishop score and cervical score. Relationships between Bishop score, cervical score, and spontaneous preterm delivery were assessed with multivariable logistic regression analysis, McNemar test, and receiver operating characteristic (ROC) curves to identify appropriate diagnostic thresholds and predictive capability. RESULTS: One hundred twenty-seven of 2,916 patients (4.4%) undergoing cervical examination at 22-24 weeks had a spontaneous preterm delivery before 35 weeks. Eighty-four of the 2,538 (3.3%) reexamined at 26-29 weeks also had spontaneous preterm delivery. Receiver operating characteristic curves indicated that optimal diagnostic thresholds for Bishop score were at least 4 at 22-24 weeks, at least 5 at 26-29 weeks, and less than 1.5 at both examinations for cervical score. At 22-24 weeks, areas under the ROC curve favored Bishop score. At 26-29 weeks, there was no significant difference in areas under the ROC curve; however, a cervical score less than 1.5 (sensitivity 35.7%, false positive rate 4.8%) was superior to a Bishop score of 5 or more (P<.001). CONCLUSION: Both cervical evaluations are associated with spontaneous preterm delivery in a singleton population; however, predictive capabilities for spontaneous preterm delivery were modest among women with low event prevalence. Although Bishop score performed better in the mid trimester, by 26-29 weeks a cervical score less than 1.5 was a better predictor of spontaneous preterm delivery before 35 weeks than a Bishop score of at least 5.

Physical and chemical processes for removing suspended solids and phosphorus from liquid swine manure.

A physical/chemical treatment train, that included 24-hour preliminary settling followed by coagulation/flocculation and sedimentation, was tested at a laboratory bench scale to treat liquid swine manure for the removal of total suspended solids (TSS) and total phosphorus (TP). Preliminary (i.e., natural) settling time had an effect on TSS removal within only the first 24 hours. TSS removal efficiency reached 75% (TSS concentration was reduced from 5,800 to 1,450 mg 1(-1)) after 24 hours of preliminary settling. Also, as a result of the 24-hour preliminary settling, TP concentration was reduced from 533 to 318 mg 1(-1), thus leading to a TP removal efficiency of 40%. When compared to ferric chloride, alum was more effective in reducing both TSS and TP. At a 95% confidence interval, alum dose, coagulation Gt (coagulation velocity gradient * rapid-mixing time), and flocculation Gt (flocculation velocity gradient * slow-mixing time) were not significant for TSS removal while alum dose was the only significant factor for TP removal. For the 24-hour settled liquid manure that had a TP concentration in the range of 362 to 401 mg l(-1)and as alum dose increased up to 1,600 mg 1(-1), TP removal efficiency increased up to 70%. Then, the rate of increase in TP removal efficiency per increase in alum dose started to decrease and TP removal efficiency reached about 93% at an alum dose of 3,000 mg 1(-1). Sequential alum dosing improved the TSS removal efficiency while it had no effect on TP removal efficiency. The mass ratio of removed TSS/applied alum increased from about 0.38, during a one-step dosing of alum at a concentration of 1,600 mg l(-1), to about 0.58 during a two-step dosing of alum at a concentration of 1,600 mg l(-1) (i.e., 800 mg l(-1) followed by another 800 mg l(-1)).

The Preterm Prediction Study: toward a multiple-marker test for spontaneous preterm birth.

OBJECTIVE: The Preterm Prediction Study evaluated 28 potential biologic markers for spontaneous preterm birth in asymptomatic women at 23 to 24 weeks gestational age. This analysis compares those markers individually and in combination for an association with spontaneous preterm birth at <32 and <35 weeks gestational age. STUDY DESIGN: With the use of a nested case-control design from an original cohort study of 2929 women, results of tests from 50 women with a spontaneous preterm birth at <32 weeks and 127 women with a spontaneous preterm birth at <35 weeks were compared with results from matched-term control subjects. RESULTS: In the univariate analysis, the most potent markers that are associated with spontaneous preterm birth at <32 weeks by odds ratio were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and <10th percentile cervical length (odds ratio, 5.8), and in serum, >90th percentiles of alpha-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and >75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at <35 weeks were generally similar but not as strong. Univariate and multivariate logistic regression analyses demonstrated little interaction among the tests in their association with spontaneous preterm birth. Combinations of the 5 markers were evaluated for their association with <32 weeks spontaneous preterm birth. Ninety-three percent of case patients had at least 1 positive test result versus 34% of control subjects (odds ratio, 24.0; 95% CI, 6.4-93.4). Among the case patients, 59% had >or=2 positive test results versus 2.4% of control subjects (odds ratio, 56.5; 95% CI, 7.1-451.7). If a cutoff of 3 positive test results was used, 20% of case patients and none of the control subjects had positive test results (P < .002). With the use of only the 3 serum tests (alkaline phosphatase, alpha-fetoprotein, and granulocyte colony-stimulating factor), any positive test identified 81% of cases versus 22% of control subjects (odds ratio, 14.7; 95% CI, 5.0-42.7). For spontaneous preterm birth at <35 weeks gestation, any 2 positive tests identified 43% of cases and 6% of control subjects (odds ratio, 11.2; 95% CI, 4.8-26.2). CONCLUSION: Overlap among the strongest biologic markers for spontaneous preterm birth is small. This suggests that the use of tests such as maternal serum alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin test and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.

Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.

BACKGROUND: Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery. METHODS: We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation. RESULTS: Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9). CONCLUSIONS: Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.

The preterm prediction study: can low-risk women destined for spontaneous preterm birth be identified?

OBJECTIVE: Half of all preterm births occur in women without clinical risk factors. Our goal was to assess fetal fibronectin assay, Bishop score, and cervical ultrasonography as screening tests to predict which low-risk pregnancies will end in preterm birth. STUDY DESIGN: We performed a secondary analysis of data collected at 22 to 24 weeks' gestation from low-risk subjects enrolled in the Preterm Prediction Study, an observational study of risk factors for preterm birth conducted by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Analysis was limited to primigravid women and to women who did not have a history of preterm birth or spontaneous pregnancy loss at <20 weeks' gestation. Bishop score (> or =4), fetal fibronectin level (> or =50 ng/mL), and cervical length (< or =25 mm) at 24 weeks' gestation were evaluated alone and in sequence as tests to predict spontaneous delivery before 35 weeks' gestation. RESULTS: Of the 2929 subjects enrolled in the original study, 2197 (1207 primigravid women and 900 low-risk multiparous women) met criteria for this analysis. There were 64 spontaneous births before 35 weeks' gestation (3.04%). All three tests were significantly related to birth before 35 weeks' gestation (high Bishop score: relative risk, 3.6; 95% confidence interval, 2.1-6.3; fetal fibronectin detection: relative risk, 8.2; 95% confidence interval, 4.8-13.9; short cervical length: relative risk, 6.9; 95% confidence interval, 4.3-11.1). However, the sensitivities of the tests alone were low (23.4% for high Bishop score, 23.4% for fetal fibronectin detection, and 39.1% for short cervix), as were the sensitivities for Bishop score followed by cervical ultrasonography (14.1%) and fetal fibronectin assay followed by cervical scan (15.6%). CONCLUSION: In the setting of low-risk pregnancy, fetal fibronectin assay and cervical ultrasonography have low sensitivity for preterm birth before 35 weeks' gestation. Sequential screening with Bishop score or fetal fibronectin assay followed by cervical ultrasonography further decreased sensitivity to only 15% among low-risk women.

Occupational fatigue and preterm premature rupture of membranes. National Institute of Child Health and Human Development Maternal-Fetal Medicine, Units Network.

OBJECTIVE: The aim of this study was to prospectively determine the relationship between occupational fatigue and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous preterm labor, preterm premature rupture of membranes, and indicated preterm delivery. STUDY DESIGN: A total of 2929 women with singleton pregnancies at 22 to 24 weeks' gestation were enrolled in a multicenter (10 sites) Preterm Prediction Study. Patients reported the number of hours worked per week and answered specific questions designed to determine the following 5 sources of occupational fatigue described by Mamelle et al: posture, work with industrial machines, physical exertion, mental stress, and environmental stress. Fatigue was quantified (0-5 index) according to the number of these sources positively reported. Simple and Mantel-Haenszel chi2 tests were used to test the univariate association and hypothesis of a linear trend between sources of occupational fatigue and spontaneous preterm delivery. Covariables were considered by multivariate logistic regression analysis. Women who did not work outside the home were considered separately from those who worked but did not report any sources of occupational fatigue. RESULTS: Each source of occupational fatigue was independently associated with a significantly increased risk of preterm premature rupture of membranes among nulliparous women but not among multiparous women. The risk of preterm premature rupture of membranes increased (P = .002) with an increasing number of sources of occupational fatigue-not working outside the home, 2.1%; working but not reporting fatigue, 3.7%; working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%; working with 3 sources of fatigue, 5.1%; and working with 4 or 5 sources of fatigue, 7.4%. There was also a significant relationship (P = .01) between preterm premature rupture of membranes and an increasing number of hours worked per week among nulliparous women. Neither spontaneous preterm labor nor indicated preterm delivery was significantly associated with occupational fatigue among either nulliparous or multiparous women. CONCLUSION: The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at increased risk for preterm premature rupture of membranes. The relationship between preterm premature rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which nulliparous women and their employers can be advised.

The Preterm Prediction Study: association between cervical interleukin 6 concentration and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: The aim of this study was to determine the interrelationship between cervical concentration of interleukin 6 and detection of fetal fibronectin and other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with spontaneous preterm birth at <35 weeks' gestation (case patients; n = 125) and subjects matched for race, parity, and center delivered at > or = 37 weeks' gestation (n = 125; control subjects) were selected from women enrolled in the National Institute of Child Health and Human Development's Preterm Prediction Study. Interleukin 6 concentrations were determined by enzyme-linked immunosorbent assay in cervical swabs obtained at 22 weeks' to 24 weeks 6 days' gestation. Cutoffs to define an elevated interleukin 6 concentration included the 90th and 95th percentiles for control subjects (>305 and >538 pg/mL, respectively). RESULTS: The mean (+/-SD) interleukin 6 concentration was significantly higher in case patients than in control subjects (212 +/- 339 vs 111 +/- 186 pg/mL; P = .008). With either cutoff value elevated interleukin 6 concentration was significantly associated with spontaneous preterm birth (90th percentile, 20% vs 9.6%; P = .02; 95th percentile, 12% vs 4.8%; P = .04). Cervical interleukin 6 levels were highest within 4 weeks of delivery, and the trend continued until term. Elevated interleukin 6 concentration was not significantly associated with bacterial vaginosis, maternal body mass index <19.8 kg/m2, or a short cervix (< or = 25 mm), but it was significantly associated with a positive cervicovaginal fetal fibronectin test result (90th percentile, odds ratio, 5.5; 95% confidence interval, 2.6-11.9; 95th percentile, odds ratio, 5.3, 95% confidence interval, 2.1-12.9). The mean interleukin 6 concentration among women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among women with a negative fetal fibronectin test result was 130 +/- 239 pg/mL (P = .001). In a regression analysis that adjusted for risk factors significantly associated with spontaneous preterm birth in this population (positive fetal fibronectin test result, body mass index <19.8 kg/m2, vaginal bleeding in the first or second trimester, previous spontaneous preterm birth, and short cervix) elevated cervical interleukin 6 concentration was not independently associated with spontaneous preterm birth (odds ratio, 1.8; 95% confidence interval, 0.8-4.3). CONCLUSIONS: At 24 weeks' gestation cervical interleukin 6 concentration in women who subsequently had a spontaneous preterm birth at <35 weeks' gestation was significantly elevated relative to those who were delivered at term. The association was particularly strong within 4 weeks of testing. A positive fetal fibronectin test result was strongly associated with elevated cervical interleukin 6 concentration, but bacterial vaginosis was not.

The preterm prediction study: quantitative fetal fibronectin values and the prediction of spontaneous preterm birth. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: A cervicovaginal fetal fibronectin value of >/=50 ng/mL has been used to define women at risk of having a preterm birth. We evaluated the relationship between quantitative fetal fibronectin values and spontaneous preterm birth. STUDY DESIGN: Cervical and vaginal specimens for fetal fibronectin were obtained at 24, 26, 28, and 30 weeks' gestation from 2926 women. Quantitative fetal fibronectin values were calculated by using absorbances determined by enzyme-linked immunosorbent assay. The highest fetal fibronectin value (cervical or vaginal) for each woman at each visit was evaluated in relation to spontaneous preterm birth at <35 weeks' gestation. Receiver operating characteristic curves were constructed to determine the optimal cutoff point for fetal fibronectin values to predict spontaneous preterm birth at <35 weeks' gestation and within 4 weeks of testing. RESULTS: The risk of spontaneous preterm birth increased as a function of increasing fetal fibronectin values from approximately 20 to 300 ng/mL. Fetal fibronectin values > or =300 ng/mL were not associated with a further increase in spontaneous preterm birth. Examination of the receiver operating characteristic curve indicates that the optimal cutoff point for a positive fetal fibronectin test result at 24 to 30 weeks' gestation to predict spontaneous preterm birth at <35 weeks is between 45 and 60 ng/mL. CONCLUSION: Increasing levels of cervicovaginal fetal fibronectin up to 300 ng/mL are associated with an increasing risk of spontaneous preterm birth. Nevertheless, at 24 to 30 weeks, the value currently used, 50 ng of fetal fibronectin per milliliter, appears to be a reasonable cutoff point for predicting spontaneous preterm birth at <35 weeks' gestation.

Preterm delivery in women with pregestational diabetes mellitus or chronic hypertension relative to women with uncomplicated pregnancies. The National institute of Child health and Human Development Maternal- Fetal Medicine Units Network.

OBJECTIVE: The purpose of this study was to compare the rates of indicated and spontaneous preterm delivery among women with chronic hypertension or pregestational diabetes mellitus with the rates among healthy women. STUDY DESIGN: This was a secondary analysis of data from healthy women with singleton gestations enrolled in a prospective observational study for prediction of preterm delivery (control group, n = 2738), women with pregestational diabetes mellitus requiring insulin therapy (n = 461), and women with chronic hypertension (n = 761). The two latter groups were enrolled in a randomized multicenter trial for prevention of preeclampsia. The main outcome measures were rates of preterm delivery, either spontaneous (preterm labor or rupture of membranes) or indicated (for maternal or fetal reasons), and neonatal outcomes. RESULTS: The overall rates of preterm delivery were significantly higher among women with diabetes mellitus (38%) and hypertension (33.1%) than among control women (13.9%). Rates were also significantly higher for delivery at <35 weeks' gestation. Women with diabetes mellitus had significantly higher rates of both indicated preterm delivery (21.9% vs 3.4%; odds ratio, 8.1; 95% confidence interval, 6.0-10.9) and spontaneous preterm delivery (16.1% vs 10.5%; odds ratio, 1.6; 95% confidence interval, 1.2-2.2) than did women in the control group. In addition, they had significantly higher rates of both indicated preterm delivery (odds ratio, 4.8; 95% confidence interval, 3.0-7.5) and spontaneous preterm delivery (odds ratio, 2.1; 95% confidence interval, 1.4-3.0) at <35 weeks' gestation than did control women. Compared with control women those with chronic hypertension had higher rates of indicated preterm delivery at both <37 weeks' gestation (21.9% vs 3.4%; odds ratio, 8.1; 95% confidence interval, 6.2-10.6) and at <35 weeks' gestation (12.1% vs 1.6%; odds ratio, 8.2; 95% confidence interval, 5.7-11.9), but there were no differences in rates of spontaneous preterm delivery. CONCLUSION: The increased rate of preterm delivery among women with chronic hypertension relative to control women was primarily an increase in indicated preterm delivery, whereas the rates of both spontaneous and indicated preterm delivery were increased among women with pregestational diabetes mellitus.