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Introduction: We report the rare finding of recurrent periventricular pseudocysts (PVPC) in consecutive pregnancies in 4 families and their postnatal outcome., Materials and Methods: We reviewed the databases of 3 large ultrasound units searching for the diagnosis of PVPC in 2 pregnancies of the same patient., Results: The first case of recurrent PVPC was diagnosed in 2011 and since then 3 additional families were diagnosed (8 cases of PVPC all in all). All fetuses underwent fetal MRI that confirmed the presence of frontal or frontocaudal PVPC. Amniocentesis, when performed, demonstrated a normal karyotype. Termination of pregnancy was carried out in 2 pregnancies in 2 of 4 families. The remaining 6 pregnancies ended with a term delivery, and to date all babies are developing normally., Conclusion: The rare finding of recurrent brain PVPC in consecutive pregnancies raises the possibility of a hereditary etiology as opposed to a sporadic event. As in isolated PVPC, frontocaudal 'familial PVPC' appears to carry a favorable prognosis., (© 2016 S. Karger AG, Basel.)

Introduction The aim of our study was to demonstrate the distribution of an uncomplicated third stage and to determine the optimal time for manual intervention. Risk factors for a prolonged third stage were studied. Materials and Methods Computerized data of all vaginal deliveries at our L&D unit from 2010 to 2014 were obtained. Cases of complete and spontaneous placental separation were extracted for further analysis. Cases necessitating manual removal of the placenta due to immediate postpartum hemorrhage (PPH) were also excluded. Patient demographics, obstetrical history, course of delivery, and delivery outcome were assessed, and risk factors for a prolonged third stage were analyzed. Results There were 31,226 vaginal deliveries during the study period. Of these, 25,160 deliveries met inclusion criteria. The median third-stage length was 12 minutes. Within 30 minutes 97% of the placentas separated spontaneously. Independent risk factors for a third stage > 30 minutes included older maternal age, primiparity, history of abortions, twin gestation, and intrapartum fever. Conclusion The average time for third stage is < 15 minutes with 97% occurring by 30 minutes and 100% by 60 minutes. In the absence of PPH, it is clinically prudent to perform manual removal after 30 minutes., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The aim of our study was to determine the optimal time for manual placental removal in an uncomplicated third stage while taking into consideration the risk for blood transfusion. Risk factors for postpartum blood transfusions were studied., Methods: Computerized data of all vaginal deliveries at our labor and delivery unit from 2010 to 2014 were obtained. Cases of complete and spontaneous placental separation up to 60 minutes into the third stage of labor were extracted for analysis. Patient demographics, obstetrical history, delivery course, and outcome were assessed as well as blood product requirements during the postpartum period. Receiver-operating curves (ROC) for prediction of blood transfusion during the third stage were calculated and risk factors were assessed., Results: 31,226 vaginal deliveries occurred during the study period and 28,586 deliveries culminated with complete and spontaneous placental separation, 25,160 of which met inclusion criteria. Independent risk factors for blood transfusions were primiparity, longer second and third stage length, labor induction, and maternal intrapartum fever. ROC curves showed that the optimal cutoff for the prediction of blood transfusions was 17 minutes into the third stage of labor. Waiting more than 30 minutes for placental separation increases the risk for blood transfusion more than threefold., Conclusions: A third stage longer than 17 minutes is associated with an increased risk for blood transfusion postpartum. After more than 30 minutes, the risk for blood transfusions increases more than threefold., (© 2015 Wiley Periodicals, Inc.)

Objective: Oxytocin, a nanopeptide secreted by the posterior pituitary gland, has well-established uterotonic activity. Its role in initiating the vigorous and regular contractions of the first stage of labor is still controversial. We report four cases of panhypopituitarism who had spontaneous onset of labor, undermining the role of maternal oxytocin in the first phase of labor., Study Design: Four women with no residual pituitary function conceived through ovulation induction and were treated throughout pregnancy with thyroid replacement therapy, desmopressin and glucocorticoids. In all cases pituitary function was undetectable in repeated blood tests. We report their course of pregnancy and delivery., Results: All four pregnancies progressed to term with hormonal replacement therapy. All cases went into spontaneous labor. Two women delivered vaginally unassisted by pharmacological intervention and two delivered by cesarean sections during active labor due to obstetrical indications. Three suffered postpartum hemorrhage. Lactation did not ensue in all four cases., Conclusions: Endogenous pituitary oxytocin is probably not obligatory for initiation of labor in the first phase of parturition., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To describe clinical characteristics in parturients with group A streptococcal infection and suggest preventive strategies., Methods: We performed a retrospective review of all group A streptococci cultures from women presenting with peripartum fever or abdominal tenderness between January 2008 and May 2015 in a university hospital. Records and epidemiologic investigations of patients and staff were reviewed., Results: Thirty-seven patients with group A streptococci cultures were identified, with an incidence of one identified postpartum group A streptococcal infection per 2,837 deliveries. Eighty-nine percent of infections occurred postpartum with isolates obtained mainly from the genital tract. Symptoms for group A streptococcal puerperal sepsis were high fever and abdominal tenderness, mostly appearing within 48 hours postpartum. More than one fifth of patients (n=7) developed streptococcal toxic shock syndrome often complicated by multiorgan failure, hysterectomy, and hospitalization in the intensive care unit. There were no uniform risk factors before infection. Epidemiologic investigations suggested that only 23% of infections were nosocomially acquired and that 77% were community-acquired., Conclusion: The high morbidity and the scarcity of distinct risk factors related to parturient group A streptococcal infections in the face of often community-acquired group A streptococci call for reassessing preventive strategies. These may include improved microbiological screening during pregnancy in high-prevalence areas or clinical and microbiological risk stratification in the immediate prepartum and peripartum period.

The ovary is a dynamic organ that undergoes dramatic remodeling throughout the ovulatory cycle. Maturation of the ovarian follicle, release of the oocyte in the course of ovulation as well as formation and degradation of corpus luteum involve tightly controlled remodeling of the extracellular matrix and vasculature. Ovarian tumors, regardless of their tissue of origin, dynamically interact with the ovarian microenvironment. Their activity in the tissue encompasses recruitment of host stroma and immune cells, attachment of tumor cells to mesothelial layer, degradation of the extracellular matrix and tumor cell migration. High-resolution dynamic imaging of such processes is particularly challenging for internal organs. The implementation of a novel imaging window as reported here enabled longitudinal microscopy of ovarian physiology and orthotopic tumor invasion.

In this retrospective cohort study we intended to propose a classification and preliminary management strategy for couples exhibiting total fertilization failure (TFF) in intra-cytoplasmic sperm injection (ICSI) cycles. Sixteen couples with a total of 27 cycles exhibiting TFF, age <40 and/or more than four M2 oocytes aspirated were enrolled. While TFF occurred in 4.3% of all 3723 ICSI cycles, in women younger than 40 with at least 5 M2 oocytes the TFF rate was 0.7%. Indications for ICSI were severe male factor and unexplained infertility. Of the 16 couples with TFF, 4 demonstrated a single episode of TFF, with either subsequent or former normal fertilizations, thus implying possible sporadic faulty laboratory conditions. Ten couples demonstrated repeated total or very low fertilization rates, hinting at a gamete defect not overcome by ICSI. Two couples experienced TFF in the first and only cycle performed at our unit. We conclude that initial and repeated TFF hints at severe gamete defects for which only donor gametes may prove successful while sporadic TFF events could simply imply a technical modifiable condition.

The enzyme integrase (IN) of human immunodeficiency virus type 1 (HIV-1) mediates integration of reverse transcribed viral DNA into the human genome, an essential step in the HIV-1 replication cycle. Elvitegravir (EVG) is an HIV-1 strand transfer inhibitor that binds IN and is the second drug in its class to be approved for clinical use in combination with other anti-HIV-1 medications. However, certain IN sequence mutational patterns have an effect on inhibitor binding, thereby altering the degree of IN mutant susceptibility to EVG. Employing a dataset of 115 translated IN sequences, each having a known EVG susceptibility value and consisting of a distinct set of amino acid replacements relative to the native IN, here we develop and evaluate statistical learning models for predicting the phenotypes (i.e., quantified EVG susceptibilities) of new IN mutants based solely on their genotypes (i.e., translated IN sequences). Each IN mutant is represented as a feature vector of structure-based attributes obtained via an in silico mutagenesis procedure that quantifies all anticipated IN residue-specific environmental perturbations from wild type upon mutation. Cross-validated performance based on four classification models show that balanced accuracy reaches 87%, while two regression models yield a Pearson's correlation coefficient as high as r=0.78. At the present time, the models may potentially be useful for diagnostic purposes, but only in conjunction with other tools and techniques, including experimental phenotype assays. However, as published experimental phenotypes for new IN variants become available, a larger and more diverse training set will likely lead to significantly more accurate models., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Study Objective: To evaluate the accuracy of diagnostic office hysteroscopy in the detection of abnormal uterine findings in symptomatic and asymptomatic patients and compare it with the accuracy of operative hysteroscopy., Design: A retrospective analysis of all women after operative hysteroscopy between 2010 and 2012 in our institution (Canadian Task Force classification II-2)., Setting: The department of gynecology in a tertiary referral medical center., Patients: One hundred thirty-two patients with a mean age of 48 years after diagnostic office hysteroscopy and subsequent operative hysteroscopy., Interventions: Operative hysteroscopy., Measurements and Main Results: We collected demographic and clinical data from patients' charts. The indications as well as findings of the previous diagnostic modality (transvaginal ultrasound [TVUS] and diagnostic hysteroscopy) were gathered and compared with the final tissue diagnosis obtained via operative hysteroscopy. Positive predictive values in diagnostic hysteroscopy were calculated for common pathological intrauterine findings. Forty-eight patients (37%) were menopausal, and 84 (63%) were premenopausal. The indications for hysteroscopy were abnormal uterine bleeding in 46% of patients and suspected uterine finding in 44%. A TVUS preceded the diagnostic hysteroscopy in 105 women (80%). Older female age, menopausal status, and abnormal intrauterine findings larger than 15 mm were associated with significantly greater true-positive rates on diagnostic hysteroscopy (i.e., the suspected findings on diagnostic hysteroscopy were verified by final pathology). Uterine bleeding during the interval between procedures was marginally significant and associated with greater false-positive results. Bleeding as opposed to routine evaluation of uterine cavity, interval between procedures, location of intrauterine finding, and hormone replacement therapy were not associated with greater true-positive values., Conclusion: Although diagnostic hysteroscopy is superior to TVUS in the assessment of polyps, it contributes little to TVUS when myomas and endometrial hyperplasia are suspected. Therefore, it should not be used routinely as an interface between TVUS and operative hysteroscopy when such findings such are suspected. Furthermore, in premenopausal patients with abnormal uterine bleeding between diagnostic and operative procedures and when small (<15 mm) polyps are suspected, it might be worthwhile to repeat a diagnostic procedure before operative hysteroscopy., (Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.)

Introduction: Lengthy clinical and epidemiological studies at the Research Institute of Radiation Medicine and Ecology have discovered basic patterns of long-term effects from ionizing radiation in population groups exposed to radiation risk. Methodology for calculating injury from radiation risk factors has been developed and implemented to minimize the effects of the Semipalatinsk nuclear test site (SNTS)., Material and Methods: We analyzed materials from the database of the Scientific Medical Register that were exposed to radiation as a result of SNTS. We analyzed both male and female populations of the Abay, Beskaragai and Zhanasemei, Kokpekti (control) areas of East-Kazakhstan region (EKR) from 2008-2012. These populations were split into three groups allocated by the generation. The first group represented persons born from the period of 01/01/1930-08/01/1949 and their children born from the period of 10/09/1949-12/31/1962. The second group were persons born after 01/01/1963. The third group served as the control and were persons who immigrated to these areas after 1990., Results: There was an increased incidence of cancer (21.5%, p < 0.000734), cardiovascular diseases (10.2%); respiratory problems (9.6%), gastrointestinal issues (9.1%, p < 0.00371-0.00679) in the first group. The effect of the radiation dose has not been fully stuided among the subjects in the second group.The major causes of excess mortality in the first group were neoplams (30.6%), hypertension (23.8%), and myocardial infarction (22.6%). The effects of radiation influenced mortality in the second group were 2-2.5 times lower than the first group., Conclusion: There is a correlation between the size of the radiation dose, the risk profile, and age at the moment of radiation exposure with trends of morbidity and mortality in the radiation exposed areas.

Data of 1,290,222 volunteer blood donors, in a 5-year period, was analyzed for prevalence and incidence of syphilis. Subsequent testing of donations positive in Treponema pallidum hemagglutination assay included Venereal Disease Research Laboratory and fluorescent Treponemal antibody absorption. Stepwise logistic regression model was used to identify positive syphilis serology. Prevalence of syphilis was 47 : 100,000, similar in men and women and increased significantly with age (P < 0.001). Native Israelis had the lowest prevalence rate of syphilis (21 : 100,000), while a significantly higher prevalence was found among immigrants from Africa, Eastern Europe, and South America (odds ratios of 19.0, 10.8, and 7.3, resp., P < 0.001 for each). About 33.2% of the seropositive donors had evidence of recent infection, and 66.8% had past infections. Incidence rate reached 8 : 100,000 person-years. Coinfection with HIV, HCV, and HBV was calculated as 8%, 1.88%, and 0.37% for positive donations, respectively. The data support the need to continue screening blood donors in Israel for syphilis and employ preventive measures to populations at risk, in order to improve public health, blood safety, and quality. A subsequent study to assess blood donors' knowledge, attitude, and behavior is planned. In times of global migration this information may be useful to blood services worldwide.

Objective: To establish the frequency of post-cesarean relaparotomy, identify its risk factors, indications, and operative management., Methods: This study was a retrospective matched case control study. Records of all women who underwent a cesarean section (CS) from July 2006 to March 2012 were reviewed. We identified all women who had a relaparotomy within 1 month from their CS. For each woman, two women were matched. We analyzed data regarding obstetrical history, current gestation, surgical parameters, and outcome., Results: A total of 14,637 CS were performed during this period, of these, 58 cases required a relaparotomy (0.4%). In univariate analysis, female sex and duration of CS were associated with an increased risk for relaparotomy. In multivariate analysis, multiple pregnancies, general anesthesia, duration of operation, and female sex, independently increased the risk for relaparotomy. The leading indications for relaparotomy were hemodynamic shock and subcutaneous hematoma. The most common interventions during relaparotomy were cauterization of subcutaneous vessels, and ligation of large vessels. Overall, women requiring relaparotomy received, on average, 16 units of blood products., Conclusions: This study highlights risk factors associated with post-cesarean relaparotomy. Surgeons might use this important data to identify women at risk beforehand, and thus, reduce the morbidity associated with relaparotomy.

Background: It has been suggested that Q fever infection in pregnancy is associated with various maternal and neonatal adverse outcomes, including intrauterine growth restriction, stillbirth, preterm delivery, intrauterine fetal death, and oligohydramnios., Case: We describe the cases of two pregnant women remote from term who presented with premature contractions and fever of unknown origin. During their hospitalizations, they had development of near-complete placental abruption. In both cases, immediate delivery ensued. Fever of unknown origin work-up revealed chronic Q fever infection, and polymerase chain reaction investigation of the placenta demonstrated chronic Q fever placentitis., Conclusion: Q fever placentitis may result in placental abruption remote from term. Therefore, in endemic areas, the diagnosis of Q fever requires appropriate surveillance and prenatal care.

Autosomal-recessive early-onset Parkinsonism (AREP) due to PINK1 mutations is characterized by an early-onset, slowly progressive disease, with a good response to levodopa. Psychiatric and cognitive disturbances associated with AREP have rarely been reported in the literature. We describe 2 brothers from a Jewish-Iraqi consanguineous family with a homozygous PINK1 nonsense mutation. Both patients presented with anxiety and dysphoria accompanied by a gait disturbance that developed subsequently into a clinical depression. During the course of the disease, both developed drug-induced behavioral disturbances of the hedonistic homeostatic dysregulation type and 1 had drug-induced psychosis. The first patient had been diagnosed with mild mental retardation and during the 22 years of disease had further deteriorated; the second developed frontal-type dementia at an early age, 20 years after onset. Their father had a psychiatric disorder but no Parkinsonism. This report expands the phenotypic profile of PINK1-related disease, presenting unique psychiatric and cognitive features as part of the clinical picture., ((c) 2006 Movement Disorder Society.)

Introduction: The human multidrug resistance gene ATP-binding cassette B1 (ABCB1) codes for P-glycoprotein (P-gp), an important membrane-bound efflux transporter known to confer anticancer drug resistance as well as affect the pharmacokinetics of many drugs and xenobiotics. A number of single nucleotide polymorphisms (SNPs) have been identified throughout the ABCB1 gene that may have an effect on P-gp expression levels and function. Haplotype as well as genotype analysis of SNPs is becoming increasingly important in identifying genetic variants underlying susceptibility to human disease. Three SNPs, 1236C-->T, 2677G-->T and 3435C-->T, have been repeatedly shown to predict changes in the function of P-gp. The frequencies with which these polymorphisms exist in a population have also been shown to be ethnically related., Methods: In this study, 95 individuals representative of the entire ethnic make-up of the USA were compared with 101 individuals from an Ashkenazi-Jewish population. These individuals were analyzed by genomic sequencing and polymerase chain reaction, using restriction fragment length polymorphisms, to calculate their genotype frequencies., Results: A total of 25 SNPs were located in the exons of the ABCB1 gene. All of the polymorphisms identified were in parts of the ABCB1 gene product predicted to be intracellular, and 16 appear to be novel as compared with those listed by the National Center for Biotechnological Information. Frequencies of the 1236C-->T and 2677G-->T/A/C SNPs were similar for the US and Ashkenazi populations (64.2 and 60.4%, respectively for 1236C-->T [chi2: 0.30; p < or = 1]; 55.8 and 64.4%, respectively for 2677G-->T/A/C [chi2: 1.49; p < or = 1]), but were different for 3435C-->T (24.2% for the US population and 69.3% for the Ashkenazi population [chi2: 39.927; p < or = 0.001]). The 1236T/ 2677T/3435T haplotype occurred in 23.6% (standard error: 0.013) of the Ashkenazi population., Conclusion: The SNP at location 3435C-->T plays a significant role in the ABCB1 gene. The haplotype and genotype analysis from these data may be used as a basis for studies on the relationship between ABCB1 genotypes and drug efficacy, drug toxicity, disease susceptibility or other phenotypes.

The enzymatic activity of Streptomyces griseus protease B (SGPB) was measured over pH range 8.4--11.5 using a specific new, chromophoric substrate N-succinyl-glycyl-glycyl-L-phenylalanine p-nitroanilide. It was found that the activity is dependent on ionization of a single group with apparent pK = 10.84, possibly lysine-125. Maleylation of the epsilon-amino group of this lysine was linearily associated with the loss of enzymatic activity. It is therefore suggested that the electrostatic interaction between the side chain of lysine-125 and the alpha-carboxyl group of the C-terminal tyrosine is crucial to the active conformation of the enzyme. In contrast the maleylation of the alpha-amino group of the N-terminal isoleucine was rapid but could not be correlated to the loss of activity.