Development and validation of a machine-learning model for prediction of shoulder dystocia.

OBJECTIVES: To develop a machine-learning (ML) model for prediction of shoulder dystocia (ShD) and to externally validate the model's predictive accuracy and potential clinical efficacy in optimizing the use of Cesarean delivery in the context of suspected macrosomia. METHODS: We used electronic health records (EHR) from the Sheba Medical Center in Israel to develop the model (derivation cohort) and EHR from the University of California San Francisco Medical Center to validate the model's accuracy and clinical efficacy (validation cohort). Subsequent to application of inclusion and exclusion criteria, the derivation cohort included 686 singleton vaginal deliveries, of which 131 were complicated by ShD, and the validation cohort included 2584 deliveries, of which 31 were complicated by ShD. For each of these deliveries, we collected maternal and neonatal delivery outcomes coupled with maternal demographics, obstetric clinical data and sonographic fetal biometry. Biometric measurements and their derived estimated fetal weight were adjusted (aEFW) according to gestational age at delivery. A ML pipeline was utilized to develop the model. RESULTS: In the derivation cohort, the ML model provided significantly better prediction than did the current clinical paradigm based on fetal weight and maternal diabetes: using nested cross-validation, the area under the receiver-operating-characteristics curve (AUC) of the model was 0.793 ± 0.041, outperforming aEFW combined with diabetes (AUC = 0.745 ± 0.044, P = 1e-16 ). The following risk modifiers had a positive beta that was > 0.02, i.e. they increased the risk of ShD: aEFW (beta = 0.164), pregestational diabetes (beta = 0.047), prior ShD (beta = 0.04), female fetal sex (beta = 0.04) and adjusted abdominal circumference (beta = 0.03). The following risk modifiers had a negative beta that was < -0.02, i.e. they were protective of ShD: adjusted biparietal diameter (beta = -0.08) and maternal height (beta = -0.03). In the validation cohort, the model outperformed aEFW combined with diabetes (AUC = 0.866 vs 0.784, P = 0.00007). Additionally, in the validation cohort, among the subgroup of 273 women carrying a fetus with aEFW ≥ 4000 g, the aEFW had no predictive power (AUC = 0.548), and the model performed significantly better (0.775, P = 0.0002). A risk-score threshold of 0.5 stratified 42.9% of deliveries to the high-risk group, which included 90.9% of ShD cases and all cases accompanied by maternal or newborn complications. A more specific threshold of 0.7 stratified only 27.5% of the deliveries to the high-risk group, which included 63.6% of ShD cases and all those accompanied by newborn complications. CONCLUSION: We developed a ML model for prediction of ShD and, in a different cohort, externally validated its performance. The model predicted ShD better than did estimated fetal weight either alone or combined with maternal diabetes, and was able to stratify the risk of ShD and neonatal injury in the context of suspected macrosomia. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Transperineal sonographic assessment of angle of progression as a predictor of successful vaginal delivery following induction of labor.

OBJECTIVES: To assess whether measurement of the angle of progression (AOP) before induction of labor (IOL) can predict successful vaginal delivery in nulliparous women. METHODS: This was a prospective, observational study of nulliparous women with a singleton term pregnancy and an indication for IOL. Transperineal sonography was used to measure the AOP before cervical ripening. Since all women enrolled had a low Bishop score, 98.6% of them were induced with either intracervical extra-amniotic balloon catheter or vaginal prostaglandin E-2. The staff in the labor ward were blinded to the AOP measurements. Clinical data were retrieved from computerized medical records. RESULTS: Of the 150 women included in the final analysis, 40 (26.7%) delivered by Cesarean section. The median AOP was narrower in women who had a Cesarean delivery than in those who delivered vaginally (90° (interquartile range (IQR), 84-94.5°) vs 98° (IQR, 90.8-105°); P < 0.001). When including only women who underwent Cesarean delivery for non-progression of labor (n = 27) in the analysis, an AOP of > 92° (derived from a receiver-operating characteristics curve) was associated with a successful vaginal delivery in 94.8% of women. Multivariate stepwise logistic regression analysis including maternal age, body mass index, gestational age, estimated fetal weight, fetal head station, indication for IOL and AOP demonstrated that only AOP was independently associated with the prediction of a successful induction. CONCLUSION: AOP may be a useful sonographic parameter for predicting successful vaginal delivery among nulliparous women at term undergoing IOL; an AOP wider than 92° is associated with a high rate of vaginal delivery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Elevations in Intra-cranial blood flow velocities following a SCUBA Dive and the Influence of Post-dive Exercise.

The effect that a SCUBA dive has on cerebral blood flow (CBF) at rest and during exercise is poorly understood. We examined the hypothesis that the altered hemodynamic parameters following a SCUBA dive will lead to differential changes in CBF at rest and during exercise. 16 divers completed a field-based study with a single dive at a depth of 18 m sea water with a 47-min bottom time. A follow-up laboratory based study was conducted - 1 week later. Intra-cranial velocities were measured with transcranial Doppler ultrasound (TCD) pre-dive, post-dive at rest and throughout incremental exercise until exhaustion. Following the dive at rest, middle cerebral artery velocity (MCAv) was elevated 15 and 30 min after surfacing (by 3.3±5.8 and 4.0±6.9 cm/s, respectively; p<0.05); posterior cerebral artery velocity (PCAv) was increased at 30 min after surfacing (by 3.0±4.5 cm/s; p<0.05). During exercise following the dive, both MCAv and PCAv increased up to 150W followed by a decrease towards baseline at 180W (p<0.05). We found no difference in CBV during exercise between field and laboratory studies (p<0.05). The novel finding of this study is the transient elevation in resting intra-cranial velocities within 30 min following a SCUBA dive.

HEART RATE VARIABILITY IN METABOLICALLY HEALTHY AND METABOLICALLY UNHEALTHY OBESE PREMENOPAUSAL WOMEN.

CONTENT: Metabolically healthy obese (MHO) individuals are characterized by absence of metabolic syndrome. The role of autonomic nervous system in metabolic profile of obese subjects has not been sufficiently investigated. OBJECTIVE: We analyzed heart rate variability (HRV) in MHO and metabolically unhealthy obese (MUO) premenopausal women. DESIGN: In 42 women metabolic profile was defined as MHO and MUO. SUBJECTS AND METHODS: For metabolic profile Wildman, IDF and HOMA-IR criteria were used. Autonomic nervous system activity was assessed by analysis of heart rate variability. RESULTS: There was no significant difference in HRV between MHO and MUO premenopausal women. In Wildman division, after adjustment for systolic blood pressure, RRNN and LF/HF were statistically different between groups (p=0.0001; p=0.029). In IDF division, adjusting for waist circumference, LF was significantly different between groups (p=0.004). In HOMA division, adjusting for HOMA, groups were different in SDNN (p=0.009), RMSSD (p=0.002), pNN50 (p=0.003), HF(p=0.002) and TP (p=0.005). CONCLUSIONS: Autonomic nervous system does not share the leading role in premenopausal women metabolic profile. The differences in HRV between MHO and MUO women depend on the metabolic health criteria. Systolic blood pressure, HOMA and waist circumference have significant effect on HRV differences between MHO and MUO premenopausal women.

Clinical and microbiological characterization of localized aggressive periodontitis: a cohort study.

BACKGROUND: Localized aggressive periodontitis (LAgP) is an infectious periodontal disease which generally affects young people. Recent data suggest the involvement of different bacterial species in different populations. The causative bacterial species in Israel has never been identified despite a high prevalence of LAgP in this population. The objectives of this study were to characterize the bacterial microbiota of periodontal pockets within an Israeli LAgP population who were also clinically assessed. METHODS: Twenty-one LAgP patients (test) and 12 chronic periodontitis patients (control) were examined. Bacterial samples were collected from periodontal pockets and analysed by both culture and polymerase chain reaction techniques. Mann-Whitney U test and chi-square test were used to compare results between the groups. RESULTS: Higher levels of Parvimonas micra (>10(6) ), Aggregatibacter actinomycetemcomitans (>10(5) ), Fusobacterium nucleatum/F. periodonticum (>10(6) ), and Tannerella forsythia (levels of 10(5) to 10(6) bacteria) were detected in the LAgP group compared to the control (p < 0.05), while levels of Porphyromonas gingivalis and Prevotella intermedia were higher in the CP group. CONCLUSIONS: The characteristic periodontal bacterial flora of LAgP patients in Israel is mainly comprised of P. micra, A. actinomycetemcomitans, F. nucleatum/F. periodonticum and T. forsythia. Similar population based studies of each population will improve the quality of treatment of LAgP when individual sampling is not possible.

Influence of graded exercise therapy on anxiety levels and health-related quality of life in chronic fatigue syndrome.

AIM: The purpose of the present study was twofold: 1) to determine to what extent graded exercise therapy (GET) improves health-related quality of life (HRQOL) and anxiety levels in patients with chronic fatigue syndrome (CFS); and 2) to correlate scores of HRQOL and anxiety levels in CFS patients. METHODS: Anxiety and HRQOL were assessed in 26 CFS patients before and after 12 weeks of GET. Anxiety was measured using the State-Trait Anxiety Inventory questionnaire (STAI) and HRQOL using the Medical Outcomes Study Short-Form questionnaire (SF-36). RESULTS: GET significantly decreased trait anxiety (STAI-T) levels in patients with CFS. Patients' scores on SF-36 following GET showed higher levels of functioning, but only the "vitality" subscale scores showed a statistically significant difference. A negative correlation was present between all eight subscales of SF-36 and anxiety levels. The strongest negative correlation for both state and trait anxiety scores (STAI-S and STAI-T) was found with the scores on the "Limitations due to emotional problems" subscale of SF-36 (r=-0.69 and r=-0.55, respectively), while the weakest negative correlation was with the "Physical functioning" subscale scores (r=-0.30 and r=-0.31, respectively). CONCLUSION: Graded exercise therapy has a positive effect on both physical and psychological state of CFS patients. GET can decrease anxiety and improve quality of life of CFS patients. CFS patients with higher state and trait anxiety levels have lower quality of life, and vice versa.

Protein-Loosing Entropathy Induced by Unique Combination of CMV and HP in an Immunocompetent Patient.

Protein-losing gastroenteropathies are characterized by an excessive loss of serum proteins into the gastrointestinal tract, resulting in hypoproteinemia (detected as hypoalbuminemia), edema, and, in some cases, pleural and pericardial effusions. Protein-losing gastroenteropathies can be caused by a diverse group of disorders and should be suspected in a patient with hypoproteinemia in whom other causes, such as malnutrition, proteinuria, and impaired liver protein synthesis, have been excluded. In this paper, we present a case of protein-losing enteropathy in a 22-year-old immunocompetent male with a coinfection of CMV and Hp.

Dapsone induced eosinophilic pneumonia.

Eosinophilic lung diseases (ELD) are a variety of several clinical entities, which may result from different etiologies, including drug treatment. Dapsone, a sulfone antibiotic widely used in leprosy (among other indications), has been described as a possible cause of ELD. We report a patient with leprosy who presented with respiratory symptoms and pulmonary infiltrates and was diagnosed as suffering from eosinophilic pneumonia. To the best of our knowledge, this is the first report in which the diagnosis of dapsone-induced eosinophilic pneumonia was supported by bronchoalveolar lavage, lung biopsy and typical response to therapy.

[Pregnancy and periodontal disease--is there a relation?].

Pregnancy complications, especially low birth weight (defined as birth weight less than 2.500 kilograms (kg)), pre-term delivery (less than 37 weeks) and pre-ecclampsia (elevated maternal blood pressure), continue to be a significant public health issue in both developed and developing countries. Recent data indicate that periodontal disease might confer risk for several systemic disorders. The relationship between periodontal diseases in pregnancy and obstetric complications has been increasingly investigated, showing inconclusive results. The purpose of this study is to review the current literature regarding the influence of periodontal status on pregnancy outcome, including the effect of periodontal treatment. Further research in this area is required, particularly with respect to the effect of population differences on this potential association between periodontal diseases and pregnancy complications as well as on the exact mechanism of this association. Since pregnancy tends to influence periodontal status, and considering the potential reported relation between periodontal disease and pregnancy complications, careful periodontal diagnosis and treatment before as well as during pregnancy is warranted.

St. John's wort (Hypericum perforatum L.) and kindling epilepsy in rabbit.

Effects of different extracts of Hypericum perforatum L. on the kindling epileptic discharges were analyzed. The experiment was carried out on Chinchilla rabbits with chronically implanted electrodes in cortical structures and hippocampus. In our study we used water, n-butanol and ether fractions (mass concentrations 0.1 g/ml) of crude ethanol extract of Hypericum perforatum. The particular extracts were given intramuscularly in single dose of 1 ml/kg BW. The bioelectric activity was registered before and after applications of each extracts. The obtained results show that the effect depends on the constituents present in particular fractions. The repression of epileptic activity was in correlation with the polarity of plant constituents. Most polar constituents that remained in water fraction exerted highest antiepileptic activity in all (100%) animals tested. Substances present in butanol fraction repressed the epileptic manifestations in 40% of animals with kindling epilepsy, whereas lipid-soluble constituents in ether fraction potentated the epileptic activity.

A novel permissive role for glucocorticoids in induction of febrile and behavioral signs of experimental herpes simplex virus encephalitis.

Herpes simplex virus type 1 (HSV-1) encephalitis may present with fever and behavioral changes, to the extent of a psychotic state and psychomotor agitation. We developed a clinically relevant experimental model of HSV-1 encephalitis and investigated host brain responses associated with its clinical signs and whether these responses depend on the presence of circulating glucocorticoids. Intracerebral inoculation of HSV-1 in rats induced fever, motor hyperactivity and aggressive behavior. In adrenalectomized rats HSV-1 failed to induce these signs, although mortality rate was identical to sham-operated rats. Hypophysectomy or blocking glucocorticoid receptors also prevented HSV-1-induced fever. Dexamethasone replacement therapy to adrenalectomized rats restored the HSV-1-induced fever and behavioral abnormalities. HSV-1 inoculation produced hyperproduction of prostaglandin E(2) by brain slices. This effect was abolished in adrenalectomized rats and was restored by dexamethasone treatment. In intact rats HSV-1 induced brain interleukin-1beta (IL-1beta) gene expression. Adrenalectomy alone caused brain IL-1beta expression, which did not increase after HSV-1 infection. Similarly, HSV-1 induced IL-1beta expression in astrocyte cultures. Removal of cortisol from the culture medium caused basal IL-1beta mRNA expression which was not increased by infection. In conclusion, fever, motor hyperactivity and aggressive behavior during experimental HSV-1 encephalitis are dependent on brain responses, including prostaglandin E(2) and IL-1beta synthesis. Circulating glucocorticoids play an essential permissive role in the induction of these host brain responses.

Periodontal changes in liver cirrhosis and post-transplantation patients. I: clinical findings.

BACKGROUND: Cyclosporin A (CsA) is widely used to prevent liver transplantation failure. CsA-induced gingival overgrowth is a common side effect. However, the effect of cirrhotic liver disease, liver transplantation, and immunosuppressive therapy on the periodontium is yet unclear. The aim of the present cross-sectional study was to examine the effect of liver cirrhosis, transplantation, and immunosuppressive therapy on the periodontium. METHODS: The experimental group (LC) consisted of 13 liver cirrhosis patients. A second experimental group (PT) included 24 patients, post-liver transplantation, receiving immunosuppressive therapy. Seventeen healthy subjects formed a control group. The Ramfjord index teeth were recorded for plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and gingival overgrowth (GO). RESULTS: Mean PI and mean GI for the LC, PT, and C groups were not statistically different (P >0.05). Mean PD for the LC (3.32+/-0.24 mm) and PT group (3.41+/-0.13 mm) was significantly higher (P = 0.0001, ANOVA) compared to the C group (2.45+/-0.16 mm). Likewise, CAL for the LC (4.89+/-0.47 mm) and PT group (4.68+/-0.47 mm) was significantly higher (P = 0.001, ANOVA) than the C group (2.78+/-0.23 mm). Patients in the PT group exhibited the greatest mean GO scores (0.88+/-0.09) compared to the LC group (0.37+/-0.07) and the C group (0.09+/-0.02). All 3 groups were significantly different from each other (P = 0.0001) despite great variability within the groups. GO in the CsA-treated patients (1.1+/-0.09) was significantly higher (P = 0.0001) than in those treated with tacrolimus (0.57+/-0.1). CONCLUSIONS: Liver cirrhosis patients demonstrated greater pocketing and attachment loss compared to healthy matched controls. These same differences were observed in patients post-transplantation. Gingival overgrowth occurred as a result of the immunosuppressive therapy with CsA, while to a lesser degree with tacrolimus. Replacement of CsA by tacrolimus in patients manifesting gingival overgrowth might be recommended whenever possible to overcome this problem.

Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4.

Oculocutaneous albinism (OCA) affects approximately 1/20,000 people worldwide. All forms of OCA exhibit generalized hypopigmentation. Reduced pigmentation during eye development results in misrouting of the optic nerves, nystagmus, alternating strabismus, and reduced visual acuity. Loss of pigmentation in the skin leads to an increased risk for skin cancer. Two common forms and one infrequent form of OCA have been described. OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for approximately 40% of OCA worldwide. OCA2 (MIM 203200), the most common form of OCA, is associated with mutations of the P gene and accounts for approximately 50% of OCA worldwide. OCA3 (MIM 203290), a rare form of OCA and also known as "rufous/red albinism," is associated with mutations in TYRP1 (encoding tyrosinase-related protein 1). Analysis of the TYR and P genes in patients with OCA suggests that other genes may be associated with OCA. We have identified the mouse underwhite gene (uw) and its human orthologue, which underlies a new form of human OCA, termed "OCA4." The encoded protein, MATP (for "membrane-associated transporter protein") is predicted to span the membrane 12 times and likely functions as a transporter.

The SMRT and N-CoR corepressors are activating cofactors for histone deacetylase 3.

Repression of gene transcription is linked to regulation of chromatin structure through deacetylation of core histone amino-terminal tails. This action is mediated by histone deacetylases (HDACs) that function within active multiprotein complexes directed to the promoters of repressed genes. In vivo, HDAC3 forms a stable complex with the SMRT corepressor. The SMRT-HDAC3 complex exhibits histone deacetylase activity, whereas recombinant HDAC3 is an inactive enzyme. Here we report that SMRT functions as an activating cofactor of HDAC3. In contrast, SMRT does not activate the class II HDAC4, with which it also interacts. Activation of HDAC3 is mediated by a deacetylase activating domain (DAD) that includes one of two SANT motifs present in SMRT. A cognate DAD is present in the related corepressor N-CoR, which can also activate HDAC3. Mutations in the DAD that abolish HDAC3 interaction also eliminate reconstitution of HDAC activity. Using purified components, the SMRT DAD is shown to be necessary and sufficient for activation of HDAC3. Moreover, the DAD is required both for HDAC3 to function enzymatically and for the major repression function of SMRT. Thus, SMRT and N-CoR do not serve merely as platforms for HDAC recruitment but function as an integral component of an active cellular HDAC3 enzyme.

Human telomerase reverse transcriptase promoter regulation in normal and malignant human ovarian epithelial cells.

The telomerase RNA-protein complex responsible for maintenance of telomeric DNA at chromosome ends, is usually inactive in most primary somatic human cells, but is specifically activated with in vitro immortalization and during tumorigenesis. Although expression of the RNA component of telomerase appears to be constitutive, the expression pattern of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is correlated with measured enzyme activity. In particular, a >80% concordance has been reported between telomerase activity and hTERT mRNA expression in ovarian tumors. Accordingly, to learn more about the mechanism regulating hTERT gene expression in ovarian carcinoma, we have performed a detailed analysis of the 5'-flanking promoter region of the hTERT gene. We have reported previously the isolation and analysis of a 5.8-kb genomic fragment containing the human hTERT gene promoter (M. Tzukerman et al., Mol. Biol. Cell, 11: 4381-4391, 2000). Deletion analysis of this promoter was carried out using transient transfection of promoter-reporter constructs in four different telomerase-expressing, ovarian carcinoma-derived cell lines, the tumorigenic properties of which have been characterized, and was compared with telomerase-negative primary human fibroblasts and nontransformed ovarian epithelial cells. These assays have shown that the hTERT promoter is inactive in telomerase-negative cells and is active in telomerase-positive cell lines. A core promoter of 283 bp upstream of the transcription initiation site (TI) was found to be sufficient for maximum promoter activity, suggesting the presence of inhibitory elements within the larger promoter sequence. Gel shift analysis of the core promoter using nuclear extracts from the ovarian and control cell lines revealed specific transcription factor binding using extracts from telomerase-positive cells. Among the binding elements, we identified two E-boxes (CACGTG) as well as a novel element (MT-box), which we identified recently in a number of differentiation systems. Site-directed mutagenesis was used to introduce mutations into this novel transcription factor binding element. These mutations significantly affect the transcriptional activity of hTERT promoter in a cell type-specific manner and suggest that the transcription factors that bind to the E-box and the novel element cooperatively function as major determinants of hTERT expression and telomerase activity in ovarian cancer. Further comparison of promoter activity, telomerase activity, and telomere length among the different ovarian cancer cells indicated that a threshold level of telomerase activity is apparently sufficient to protect telomere integrity and permit the immortal state of the different ovarian cancer cell lines.