A machine learning analysis of a "normal-like" IDH-WT diffuse glioma transcriptomic subgroup associated with prolonged survival reveals novel immune and neurotransmitter-related actionable targets.

BACKGROUND: Classification of primary central nervous system tumors according to the World Health Organization guidelines follows the integration of histologic interpretation with molecular information and aims at providing the most precise prognosis and optimal patient management. According to the cIMPACT-NOW update 3, diffuse isocitrate dehydrogenase-wild type (IDH-WT) gliomas should be graded as grade IV glioblastomas (GBM) if they possess one or more of the following molecular markers that predict aggressive clinical course: EGFR amplification, TERT promoter mutation, and whole-chromosome 7 gain combined with chromosome 10 loss. METHODS: The Cancer Genome Atlas (TCGA) glioma expression datasets were reanalyzed in order to identify novel tumor subcategories which would be considered as GBM-equivalents with the current diagnostic algorithm. Unsupervised clustering allowed the identification of previously unrecognized transcriptomic subcategories. A supervised machine learning algorithm (k-nearest neighbor model) was also used to identify gene signatures specific to some of these subcategories. RESULTS: We identified 14 IDH-WT infiltrating gliomas displaying a "normal-like" (NL) transcriptomic profile associated with a longer survival. Genes such as C5AR1 (complement receptor), SLC32A1 (vesicular gamma-aminobutyric acid transporter), MSR1 (or CD204, scavenger receptor A), and SYT5 (synaptotagmin 5) were differentially expressed and comprised in gene signatures specific to NL IDH-WT gliomas which were validated further using the Chinese Glioma Genome Atlas datasets. These gene signatures showed high discriminative power and correlation with survival. CONCLUSION: NL IDH-WT gliomas represent an infiltrating glioma subcategory with a superior prognosis which can only be detected using genome-wide analysis. Differential expression of genes potentially involved in immune checkpoint and amino acid signaling pathways is providing insight into mechanisms of gliomagenesis and could pave the way to novel treatment targets for infiltrating gliomas.

Cervical stroma apoptosis in pregnancy.

OBJECTIVE: To determine whether the percentage of apoptotic nuclei is different in cervical stroma of pregnant laboring women compared with nonpregnant women and pregnant nonlaboring women. METHODS: We took cervical stromal biopsies during cesarean delivery at the level of the lower uterine segment from ten women in active labor and 13 women before labor. In addition, we took biopsies of cervical stroma at the level of the internal cervical os from hysterectomy specimens in ten reproductive-aged women. Cryosections were then analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining. Tissue specimens were analyzed with ligation-mediated polymerase chain reaction to visualize nucleosomal ladders characteristic of apoptosis. To detect a 10% difference in the percentage of apoptotic cells per subject between study groups assuming a power of 0.90, an alpha of.05 in approximately ten subjects per group was needed. RESULTS: The median percentage of apoptotic nuclei was 0.7 (interquartile range 0.4, 1.4) for the nonpregnant group, 7.5 (interquartile range 6.6, 11.2) for the pregnant nonlaboring group, and 11.6 (interquartile range 8.3, 16.7) for the pregnant laboring group (P <.001). The percentage of apoptotic nuclei differed significantly across the three study groups. Using ligation-mediated polymerase chain reaction, nucleosomal ladders were seen in the specimens from pregnant women but not in the specimens from nonpregnant women, confirming the increase in stromal apoptosis seen with pregnancy. CONCLUSION: Apoptosis of cervical stromal cells may play a role in the remodeling of the cervix during pregnancy and contribute to cervical changes during labor.

Placental apoptosis in preeclampsia.

OBJECTIVE: To determine whether preeclampsia is associated with an increase in placental apoptosis and differential expression of mediators of apoptosis. METHODS: Placental samples from 31 preeclamptic women and 31 normotensive controls were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining. Expression of Fas, Fas ligand, Bcl-2, and Bax was assessed using immunohistochemistry. RESULTS: The median percent apoptotic nuclei was significantly higher for the study group than for the controls (0.49 versus 0.19; P =.001), as was the median percent apoptotic nuclei in the trophoblast nuclei (0.33 versus 0.09; P <.01). Fas ligand expression was significantly less and Fas expression significantly greater in the villus trophoblast among the study subjects compared with controls. There was no difference in the expression of Bax or Bcl-2 between groups. CONCLUSION: Placental apoptosis and altered expression of Fas and Fas ligand in trophoblast might influence pathogenesis or sequelae of preeclampsia.

Subcutaneous drain vs. suture in obese women undergoing cesarean delivery. A prospective, randomized trial.

OBJECTIVE: To determine if subcutaneous drain or closure of the subcutaneous layer decreases the incidence of wound complications in obese women undergoing cesarean delivery. STUDY DESIGN: Seventy-six obese women undergoing cesarean delivery and with at least 2 cm of subcutaneous fat were randomized to one of three groups: group 1 had suture closure of the subcutaneous tissue, group 2 had placement of a subcutaneous closed suction drain, and group 3 had neither suture closure nor drainage. RESULTS: Wound separation occurred in 12 (15.8%), seroma in 5 (6.6%) and infection in 3 (4%). There were no reports of wound hematoma. The overall incidence of any wound complication (infection, separation, seroma, hematoma) was higher in obese women who received neither subcutaneous suture nor drain as compared to obese women who received either subcutaneous suture closure or subcutaneous drain. The incidence of major wound complications (infection or separation) was also higher in obese women who received neither subcutaneous suture or drain compared to obese women who received either subcutaneous suture closure or subcutaneous drain. CONCLUSION: The use of closed suction drainage in the subcutaneous space may reduce the incidence of postoperative wound complications in obese women who have at least 2 cm of subcutaneous fat and undergo cesarean delivery.

Complementary and alternative medicine in pregnancy: a survey of North Carolina certified nurse-midwives.

OBJECTIVE: To determine the prevalence and types of complementary and alternative medicine therapies used by certified nurse-midwives in North Carolina. METHODS: Surveys were sent to all 120 licensed certified nurse-midwives in North Carolina requesting information concerning their recommendations for use of complementary and alternative medicine for their pregnant or postpartum patients. RESULTS: Eighty-two responses were received (68.3%). Seventy-seven (93.9%) reported recommending complementary and alternative medicine to their pregnant patients in the past year. Forty-seven (57.3%) reported recommending complementary and alternative medicine to more than 10% of patients. The percentage of nurse-midwives who recommended each type of complementary and alternative medicine was as follows: herbal therapy (73.2%), massage therapy (67.1%), chiropractic (57.3%), acupressure (52.4%), mind-body interventions (48.8%), aromatherapy (32.9%), homeopathy (30.5%), spiritual healing (23.2%), acupuncture (19.5%), and bioelectric or magnetic applications (14.6%). The 60 respondents who reported prescribing herbal therapies gave them for the following indications: nausea and vomiting, labor stimulation, perineal discomfort, lactation disorders, postpartum depression, preterm labor, postpartum hemorrhage, labor analgesia, and malpresentation. CONCLUSION: Complementary and alternative medicine, especially herbal therapy, is commonly prescribed to pregnant women by nurse-midwives in North Carolina.

Second-trimester presentation of placenta percreta.

Placenta percreta is diagnosed usually in the third trimester as massive postpartum hemorrhage when an attempt to remove the placenta reveals lack of a cleavage plane. However, placenta percreta may present in the second trimester with signs and symptoms of uterine rupture. The diagnosis of this event may be difficult because of mild abdominal discomfort often associated with normal pregnancy. We describe two cases that occurred in the second trimester with an unusual presentation. Both patients suffered considerable surgical morbidity. Other cases reported in the literature are mentioned as well. When a patient with risk factors for abnormal placentation presents with abdominal pain and/or vaginal bleeding in the second trimester of pregnancy, the diagnosis of placenta percreta should be considered. A laparotomy is indicated immediately when hemoperitoneum is suspected because uterine rupture has most likely occurred. Placenta percreta in the second trimester is a potentially life-threatening condition that warrants expeditious diagnosis to limit maternal postoperative morbidity.

Initial and repeat screening for Chlamydia trachomatis during pregnancy.

OBJECTIVES: The objective of this study is to determine the prevalence of Chlamydia trachomatis and risk factors for positive repeat tests in a high-risk population presenting for early prenatal care. METHODS: We completed a retrospective cohort study of 2,484 women who initiated prenatal care prior to 20 weeks gestation, delivered, and received testing for cervical C. trachomatis at Grady Memorial Hospital or a Grady-affiliated clinic between July 1, 1993 and December 31, 1994. We calculated adjusted odds ratios (OR) for selected risk factors for a positive initial test and for a positive subsequent test after an initial negative test. RESULTS: The prevalence of C. trachomatis was 14.8%. At initial testing, 10.4% of the women were positive. If the initial test was negative, 5.7% had a positive subsequent test; but if the initial test was positive, 32.0% had a positive subsequent test (P < 0.001). The variables significantly and independently associated with a positive initial test were black race/ethnicity, age less than 25, unmarried, and less than a high-school education (adjusted OR of 1.66, 3.53, 2.18, and 1.81, respectively). Variables significantly and independently associated with a positive subsequent test after a negative initial test were white race/ethnicity, black race/ethnicity, age less than 25, and less than a high-school education (adjusted OR 8.69, 7.77, 4.12, and 2.27, respectively). CONCLUSIONS: In our inner-city population, most pregnant women have risk factors suggesting the need to rescreen for C. trachomatis in the second half of pregnancy.

Preconceptional health care model.

During the last 10 years, there has been a movement to expand the definition of prenatal care to encompass preconceptional counseling. Major organizations throughout the world have endorsed preconceptional counseling as an integral component of care for all women contemplating pregnancy. This article will assist health care providers who interact with women of reproductive age to understand the potential benefits and limitations of preconceptional counseling and to develop an approach to that service relating to nutrition, infections, and metabolic diseases as they impact on reproductive outcome. Although there are many potential benefits of the preconception health care model, barriers to its implementation remain.

Identification, characterization, and chromosomal organization of cell division cycle genes in Caulobacter crescentus.

We report a detailed characterization of cell division cycle (cdc) genes in the differentiating gram-negative bacterium Caulobacter crescentus. A large set of temperature-sensitive cdc mutations was isolated after treatment with the chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine. Analysis of independently isolated mutants at the nonpermissive temperature identified a variety of well-defined terminal phenotypes, including long filamentous cells blocked at various stages of the cell division cycle and two unusual classes of mutants with defects in both cell growth and division. The latter strains are uniformly arrested as either short bagel-shaped coils or large predivisional cells. The polar morphology of these cdc mutants supports the hypothesis that normal cell cycle progression is directly responsible for developmental regulation in C. crescentus. Genetic and physical mapping of the conditional cdc mutations and the previously characterized dna and div mutations identified at least 21 genes that are required for normal cell cycle progression. Although most of these genes are widely scattered, the genetically linked divA, divB, and divE genes were shown by genetic complementation and physical mapping to be organized in one gene cluster at 3200 units on the chromosome. DNA sequence analysis and marker rescue experiments demonstrated that divE is the C. crescentus ftsA homolog and that the ftsZ gene maps immediately adjacent to ftsA. On the basis of these results, we suggest that the C. crescentus divA-divB-divE(ftsA)-ftsZ gene cluster corresponds to the 2-min fts gene cluster of Escherichia coli.

Chlamydia trachomatis: management in pregnancy.

Chlamydia trachomatis is a sexually transmitted disease (STD) commonly diagnosed in pregnancy. C. trachomatis has been linked to several pregnancy complications including premature rupture of membranes (PROM), preterm labor and birth, low birth weight, intrauterine growth retardation, and postpartum endometritis. Infants born to mothers through an infected birth canal are at risk for acquiring C. trachomatis pneumonitis, conjunctivitis, and nasopharyngeal infection. The standard treatment of C. trachomatis in pregnancy is erythromycin. Recently, amoxicillin and clindamycin have been added as alternative regimens for those patients intolerant of erythromycin. This paper reviews the effectiveness and tolerance of the alternative regimens compared with erythromycin and the success of antepartum treatment of chlamydia in preventing the poor pregnancy outcome and neonatal morbidity associated with C. trachomatis.

Dracunculosis of the broad ligament. A case of a "parasitic leiomyoma".

This report describes the case of a 29-year-old Nigerian woman with dracunculosis presenting as an adnexal mass. The patient had a history of two second-trimester spontaneous abortions for which she was being evaluated. During the evaluation, she was found to have multiple uterine leiomyomas and a calcified left adnexal mass by pelvic ultrasound and radiography. At laparotomy, the calcified mass was excised from the left broad ligament, and a myomectomy was performed. Histologic examination revealed a calcified, coiled guinea worm embedded in the fibrous tissue of the broad ligament. Only one other case of calcified guinea worm in the broad ligament has been reported in the literature.

Use of descriptive and experimental analyses to identify the functional properties of aberrant behavior in school settings.

We conducted descriptive and experimental analyses of aberrant behavior in school settings with 2 children with autism, using teachers as assessors. Experimental functional analyses carried out by the investigators were followed by training teachers to conduct a descriptive analysis and a classroom experimental analysis. A comparison of the assessment procedures showed that each procedure identified negative reinforcement as a maintaining variable for aberrant behavior. The teacher implemented an intervention based on the assessment with mixed results. We then replicated the initial results by having the first teacher train a second teacher to carry out the two assessment procedures. The results of these analyses were also in agreement, again identifying negative reinforcement as a variable maintaining aberrant behavior. An intervention based on negative reinforcement was then successfully implemented. These results suggest the applicability and utility of functional analyses carried out in school settings.