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  • Abstracts from the Thirteenth Rambam Research Day, December 22, 2016

    We are proud to introduce you to the Thirteenth Rambam Research Day, now established as a key annual event at Rambam Health Care Campus (Rambam), reflecting the diverse research activities on our campus...
  • The Development of Robotic Technology in Cardiac and Vascular Interventions

    Robotic technology has been used in cardiovascular medicine for over a decade, and over that period its use has been expanded to interventional cardiology and percutaneous coronary and peripheral vascular interventions. The safety and feasibility of robotically assisted interventions has been demonstrated in multiple studies ranging from simple to complex coronary lesions, and in the treatment of ileofemoral and infrapopliteal disease. These studies have shown a reduction in operator exposure to harmful ionizing radiation, and the use of robotics has the intuitive benefit of alleviating the occupational hazard of operator orthopedic injuries. In addition to the interventional operator benefits, robotically assisted intervention has the potential also to be beneficial for patients by allowing more accurate lesion length measurement, stent placement, and patient radiation exposure; however, more investigation is required to elucidate these benefits fully.
  • The Role of Exercises in Osteoporotic Fracture Prevention and Current Care Gaps. Where Are We Now? Recent Updates

    Introduction: The primary non-pharmacological management recommended for patients with osteoporosis (OP) is exercise, but whether it should be high-force, resistive, or other means can be obscure. Objective: To describe the role of exercises in osteoporotic fracture prevention, identify effects and potential risks of high-force exercises, detect the optimal exercises to combat OP, and explore the challenges that might arise from interventions. Methods: A search on MEDLINE and Cochrane databases was conducted on the role of exercises in preventing osteoporotic fractures from 1989 onwards, leading to 40 results, including op-ed pieces, qualitative studies, randomized clinical trials (RCTs) (n=5), and RCT follow-up studies (n=1). Articles deemed relevant to the objectives were analyzed and summarized. Data on effects of vitamin D and calcium supplementation were later gathered from different sources as well. Results: High-intensity, resistive strength training provided the maximum benefit in increasing bone mineral density (BMD) levels, muscle mass, and reduction in fractures, while posture and balance exercises only improved mobility. High-force exercises did not increase fractures and were associated with increases in BMD. Interventions including exercises, vitamin D, and calcium intake had limited effect when used as single interventions, while vitamin D and calcium may potentially cause increases of cardiovascular events. Conclusion: A long-term regular exercise program designed to improve postural stability, mobility, and mechanical efficiency, alongside an increased vitamin D and dietary calcium intake, is most effective in preventing OP and reducing osteoporotic fractures.
  • Surgical Updates in the Treatment of Pelvic Organ Prolapse

    Pelvic organ prolapse affects approximately 8% of women, and the demand for pelvic organ prolapse surgery is expected to increase by nearly 50% over the next 40 years. The surgical techniques used to correct pelvic organ prolapse have evolved over the last 10 years, with multiple well-designed studies addressing the risks, outcomes, reoperation rates, and optimal surgical approaches. Here we review the most recent evidence on the route of access, concomitant procedures, and synthetic materials for augmenting the repair. Ultimately, this review highlights that there is no optimal method for correcting pelvic organ prolapse and that the risks, benefits, and approaches should be discussed in a patient-centered, goal-oriented approach to decision-making.
  • Maternal Inflammation, Fetal Brain Implications and Suggested Neuroprotection: A Summary of 10 Years of Research in Animal Models

    A growing body of evidence implicates that maternal inflammation during pregnancy is associated with increased risk of neurodevelopmental disorders in the offspring. The pathophysiological mechanisms by which maternal inflammation evokes fetal brain injury and contribute to long-term adverse neurological outcomes are not completely understood. In this review, we summarize our 10 years’ research experience on maternal inflammation and the implications upon the fetal/offspring brain. We review our findings regarding the underlying mechanisms that connects maternal inflammation and fetal brain injuries (e.g. cytokines, oxidative stress), we discuss our imaging, pathological and behavioral test results which support brain damage following maternal inflammation and finally we describe some of the therapeutic strategies which might prevent the damage.
  • The Female Urinary Microbiota/Microbiome: Clinical and Research Implications

    The changing science of the urinary microbiota and microbiome has both clinical and research implications. This review manuscript provides an overview of the state of this science, as well as a discussion of the potential for prevention, diagnosis, and treatment of human disease. The history of techniques used for clinical detection of infection are placed into context along with the modern methods of bacterial detection and identification.
  • Anovulatory Patients Demonstrate a Sharp Decline in LH Levels upon GnRH Antagonist Administration during IVF Cycles

    To evaluate the decrease in luteinizing hormone (LH) levels following gonadotropin-releasing hormone (GnRH) antagonist administration in in vitro fertilization (IVF) cycles, data were retrospectively collected from 305 consecutive IVF or intracytoplasmic sperm injection (ICSI) cycles of patients who underwent ovarian stimulation with gonadotropins and were treated with GnRH antagonist for the prevention of premature luteinization. We compared the percent change in LH concentration from stimulation start to that observed before ovulation triggering in patients with or without anovulation. Anovulatory patients were younger, with higher body mass index (BMI), and demonstrated higher ovarian reserve parameters as compared to ovulatory patients. The decline in LH concentration was almost two-fold greater in anovulatory versus ovulatory patients. Numbers of oocytes, fertilizations, cleavage stage embryos, and transferred embryos were similar; however, implantation rates were higher in anovulatory versus ovulatory patients. Older patients (age ≥39) showed a smaller decline in LH levels as compared to younger ones (age <39) and exhibited poor IVF outcomes. There is a wide range of pituitary responses to GnRH antagonists. Anovulatory patients are more susceptible to GnRH antagonists and therefore demonstrate over-suppression of the pituitary. Older patients demonstrate a reduced pituitary response to GnRH antagonists than younger ones. Cycle scheduling with estradiol pretreatment did not influence LH decline, nor IVF treatment outcomes.
  • Fear of Vaginal Penetration in the Absence of Pain as a Separate Category of Female Sexual Dysfunction: A Conceptual Overview

    Functional sexual pain disorders in women are a particular challenge to the gynecologist, inasmuch as phobic avoidance and guarding on the part of the patient lead to difficulties in the gynecological examination and diagnosis. In some such cases examination may even be impossible. Vaginismus is the commonly diagnosed etiology of such cases. This article offers an overview of vaginismus and approaches to its treatment but also examines a subset of penetration-avoidant patients who do not appear to have a pain component. We have reviewed this separate category conceptually and clinically, and propose that this case subset be separated from the diagnosis of vaginismus and designated as vaginal penetration phobia (VPP). We further propose that this category be diagnosed as one of several possible presentations of phobic disorder, under the rubric of mental health disorder, and thus be separated from gynecology. The nosological implications are raised.
  • Protective Effect of N-Acetyl-Cysteine (NAC) in Lipopolysaccharide (LPS)-Associated Inflammatory Response in Rat Neonates

    Objective: Increased inflammatory response may be associated with adverse clinical outcomes, especially in the neonatal period. The aims of this study were to determine whether N-acetyl-cysteine (NAC), an anti-inflammatory agent, attenuates the inflammatory response in young rats and to determine the most effective route of administration. Methods: Four groups of Sprague-Dawley rats (in each group four rats) were studied at 30 days of age. One hour following intraperitoneal (IP) injection of lipopolysaccharide 50 µg/kg, the rats were randomized to subcutaneous (SC), per os (PO), or intraperitoneal (IP) injection of NAC 300 mg/kg, or saline. The control group received saline injection (IP). Three hours following the N-acetyl-cysteine injection the rats were sacrificed, then serum tumor necrosis factor-α (TNF-α) and IL-6 levels were determined by ELISA. Results: Lipopolysaccharide significantly increased the neonatal serum IL-6 and TNF-α (2051.0±349 and 147.0±25.8 pg/mL, respectively; P<0.01) levels compared to 10 pg/mL in the controls. N-acetyl-cysteine administered one hour following lipopolysaccharide injection significantly attenuated the inflammatory response. Intraperitoneal administration of NAC decreased IL-6 and TNF-α concentration to 294.6 and 17.1 pg/mL, respectively, and was more effective than SC or PO administration. Conclusions: N-acetyl-cysteine attenuated the inflammatory response in the neonatal rats, and IP was the most effective administration route.
  • Prolactin-induced Subcellular Targeting of GLUT1 Glucose Transporter in Living Mammary Epithelial Cells

    Background: Studying the biological pathways involved in mammalian milk production during lactation could have many clinical implications. The mammary gland is unique in its requirement for transport of free glucose into the cell for the synthesis of lactose, the primary carbohydrate in milk. Objective: To study GLUT1 trafficking and subcellular targeting in living mammary epithelial cells (MEC) in culture. Methods: Immunocytochemistry was used to study GLUT1 hormonally regulated subcellular targeting in human MEC (HMEC). To study GLUT1 targeting and recycling in living mouse MEC (MMEC) in culture, we constructed fusion proteins of GLUT1 and green fluorescent protein (GFP) and expressed them in CIT3 MMEC. Cells were maintained in growth medium (GM), or exposed to secretion medium (SM), containing prolactin. Results: GLUT1 in HMEC localized primarily to the plasma membrane in GM. After exposure to prolactin for 4 days, GLUT1 was targeted intracellularly and demonstrated a perinuclear distribution, co-localizing with lactose synthetase. The dynamic trafficking of GFP-GLUT1 fusion proteins in CIT3 MMEC suggested a basal constitutive GLUT1 recycling pathway between an intracellular pool and the cell surface that targets most GLUT1 to the plasma membrane in GM. Upon exposure to prolactin in SM, GLUT1 was specifically targeted intracellularly within 90–110 minutes. Conclusions: Our studies suggest intracellular targeting of GLUT1 to the central vesicular transport system upon exposure to prolactin. The existence of a dynamic prolactin-induced sorting machinery for GLUT1 could be important for transport of free glucose into the Golgi for lactose synthesis during lactation.