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α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) positive allosteric modulators (AMPAkines) have a multitude of promising therapeutic properties. The pharmaceutical development of high impact AMPAkines has, however, been limited by the appearance of calcium-dependent neuronal toxicity and convulsions in vivo. Such toxicity is not observed at exceptionally high concentrations of low impact AMPAkines. Because most AMPAR are somewhat impermeable to calcium, the current study sought to examine the extent to which different mechanisms contribute to the rise in intracellular calcium in the presence of high impact ampakines. In the presence of AMPA alone, cytosolic calcium elevation is shown to be sodium-dependent. In the presence of high impact AMPAkines such as cyclothiazide (CTZ) or CX614, however, AMPAR potentiation also activates an additional mechanism that induces calcium release from endoplasmic reticular (ER) stores. The pathway that connects AMPAR to the ER system involves a Gq-protein, phospholipase Cß-mediated inositol triphosphate (InsP3) formation, and ultimately stimulation of InsP3-receptors located on the ER. The same linkage was not observed using high concentrations of the low impact AMPAkines, CX516 (Ampalex), and CX717. We also demonstrate that CX614 produces neuronal hyper-excitability at therapeutic doses, whereas the newer generation low impact AMPAkine CX1739 is safe at exceedingly high doses. Although earlier studies have demonstrated a functional linkage between AMPAR and G-proteins, this report demonstrates that in the presence of high impact AMPAkines, AMPAR also couple to a Gq-protein, which triggers a secondary calcium release from the ER and provides insight into the disparate actions of high and low impact AMPAkines.

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OBJECTIVE: A novel type of Coronavirus was identified in China in December 2019. The first cases of a form of pneumonia of unknown etiology were detected at the beginning of that month in Wuhan. The virus is believed to have emerged at the Wuhan Huanan Seafood Market, where transmission of a zoonotic pathogen to humans occurred. PATIENTS AND METHODS: Some studies conducted in China during the epidemic report small numbers of pregnant women infected with SARS-CoV-2 and some pregnancy complications in patients with COVID-19. However, they fail to document the transplacental passage of the virus from mother to fetus. RESULTS: Following the COVID-19 outbreak, guidelines for couples who are undergoing treatments of assisted reproduction have been issued by the International Federation for Fertility Societies (IFFS), the American Society for Reproductive Medicine (ASRM), the European Society of Human Reproduction and Embryology (ESHRE) and the Latin American Network of Assisted Reproduction (REDLARA). They recommend couples to discuss assisted reproduction with their doctors while those at risk or with SARS-CoV-2 should consider freezing oocytes or embryos and retransferring them later. CONCLUSIONS: Other than the US, Italy is the country with the highest number of cases (197675 positives, 26644 deaths) (updated on April 26). The Italian National Transplant Centre and the Higher Institute of Health advised on March 17 to complete the cycles already started and not to start new cycles. Phase 2 will begin on 4 May with an increase in freedom of action and fertilization treatments will start again. The Society that brings together embryologists (SIERR) has issued the guidelines to be followed when this happens.

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OBJECTIVE: To counteract the arising problem of couple infertility, having good quality gametes is increasingly important. A molecule that seems to be useful to favor this condition is myo-inositol (MI), the most common stereoisomer of the inositol family, involved as second messenger in several cell pathways (osmoregulation, chromatin remodeling, gene expression, etc.). To evaluate this possibility, a treatment with myo-inositol in idiopathic infertile couples was performed in this randomized, placebo-controlled study. PATIENTS AND METHODS: 86 couples were enrolled and randomly assigned to two groups, treated either with MI (Xyminal®, Lo.Li. Pharma Srl, Rome, Italy) or placebo suppositories, to evaluate the effects on sperm motility, cervical mucus quality and pregnancy rate. Moreover, in pregnancy cases, all routine controls on gestation progress and foetal health were performed to confirm the safety of this treatment. RESULTS: As showed in this study, MI treatment allows an increase of total sperm motility (54.42 ± 8.72) in comparison to placebo group (46.21 ± 5.33). Moreover, MI mildly improves cervical mucus quality and increases the number of pregnancies (18.60%) in comparison to the placebo group (6.97%). CONCLUSIONS: MI improves sperm motility and cervical mucus quality, increasing the probability of conception. The absence of adverse events both for the mother and the foetus confirmed the safety of this molecule in pregnancy, supporting even more its use for couples seeking pregnancy.

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OBJECTIVE: The aim of the study is to investigate the efficacy of a treatment with myoinositol plus L-tyrosine, selenium, and chromium in women with polycystic ovarian syndrome (PCOS). PATIENTS AND METHODS: One hundred and eighty-six women, with diagnosis of PCOS, were divided in four groups according to their clinical features. Phenotype A: androgen excess + ovulatory dysfunction + polycystic ovarian morphology. Phenotype B: androgen excess + ovulatory dysfunction. Phenotype C: androgen excess + polycystic ovarian morphology. Phenotype D: ovulatory dysfunction + polycystic ovarian morphology. All patients were given daily for six months a compound with 2 g myo-inositol, 0.5 mg L-Tyrosine, 0.2 mg folic acid, 55 mcg selenium, 40 mcg chromium. Hormonal assessment, BMI, Ferriman-Gallway Gallway score, HOMA index, and follicular monitoring were reported before starting the therapy, three months and six months after. RESULTS: Phenotype A showed an improvement, consistent with restored ovulation: more regular length of the menstrual cycle, detection of periovulatory follicle at ultrasound, and rising of progesterone in the luteal phase. A total of 45 patients (65.2%) ovulated after six months. In the same period glucose and HOMA index decreased. In the phenotype B, 80% of patients ovulated after six months. An improvement of the clinical and biochemical sign of hyperandrogenism was also reported. In the phenotype C, after BMI had followed the treatment for six months, it decreased in a statistically significant manner. In the phenotype D, 49 out of 82 women (59.7%) restored their regular menstrual period and ovulated. CONCLUSIONS: Our study reported how the synergistic action of myoinositol, L-tyrosine, selenium, and chromium could restore normal menstrual cycle, ovulation, and decrease weight in these patients.

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PURPOSE: Thoracic outlet syndrome includes arterial, venous or neurological symptoms. Frequently difficult to diagnose clinically, confirmatory imaging studies are usually required. The purpose of this study is to review the diagnostic work-up during management of patients with thoracic outlet syndrome and demonstrate the value of angiography in the sitting position. MATERIALS AND METHODS: Retrospective study of 81 surgical procedures for thoracic outlet syndrome, between 1997 and 2005, in 56 patients aged 17-57 years. Surgery was bilateral in 26 cases, with bilateral surgery in a single setting for 1 patient. All patients presented clinical symptoms confirmed on US, angiography, venogram or EMG. Angiography, from a transfemoral approach, was initially performed in the supine position, without and with dynamic maneuver, and in the sitting position with dynamic maneuver when needed. RESULTS: In 48 patients, supine rest angiography showed stenosis in 6% of cases and supine dynamic angiography showed stenosis in 81% of cases, with severe stenosis in only 35% of cases (stenosis>80% or arterial occlusion). Angiography in the sitting position was performed in 33 patients, showing worsening of stenosis in 91% of cases, with severe stenosis in 87%. CONCLUSION: Angiography in the sitting position with dynamic maneuver improves the sensitivity for detection of thoraci coutlet syndrome. This procedure may be considered in addition to other imaging modalities routinely used including Doppler US, CT and MRI.

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The authors report the case of a patient presenting with small bowel obstruction after a pelvic trauma with associated bladder injury. While urinary bladder and bowel injuries are frequent following this type of trauma, their association is rare. Small bowel obstruction secondary to trans-vesical incarceration of a small bowel loop at the fracture site is exceptional. CT is invaluable for diagnosis.

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Benzodiazepines remain widely used for the treatment of anxiety disorders despite prominent, often limiting side effects including sedation, muscle relaxation, and ataxia. A compound producing a robust anxiolytic action comparable to benzodiazepines, but lacking these limiting side effects at therapeutic doses (an anxioselective agent), would represent an important advance in the treatment of generalized anxiety disorder, and perhaps other anxiety disorders. Here we report that the pyrazolo[1,5-a]-pyrimidine, ocinaplon, exhibits an anxioselective profile in both preclinical procedures and in patients with generalized anxiety disorder, the most common of the anxiety disorders. In rats, ocinaplon produces significant muscle relaxation, ataxia, and sedation only at doses >25-fold higher than the minimum effective dose (3.1 mg/kg) in the Vogel "conflict" test. This anticonflict effect is blocked by flumazenil (Ro 15-1788), indicating that like benzodiazepines, ocinaplon produces an anxiolytic action through allosteric modulation of GABA(A) receptors. Nonetheless, in eight recombinant GABA(A) receptor isoforms expressed in Xenopus oocytes, the potency and efficacy of ocinaplon to potentiate GABA responses varied with subunit composition not only in an absolute sense, but also relative to the prototypical benzodiazepine, diazepam. In a double blind, placebo controlled clinical trial, a 2-week regimen of ocinaplon (total daily dose of 180-240 mg) produced statistically significant reductions in the Hamilton rating scale for anxiety scores. In this study, the incidence of benzodiazepine-like side effects (e.g., sedation, dizziness) in ocinaplon-treated patients did not differ from placebo. These findings indicate that ocinaplon represents a unique approach both for the treatment and understanding of anxiety disorders.

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BACKGROUND: Postpartum is known to be an important risk factor for stroke. Bromocriptine may induce cerebral angiopathy. CASE DESCRIPTION: We report the case of a 26-year-old postpartum woman who presented with headaches, seizures, hypertension and acute renal failure eight days after the beginning of a treatment with bromocriptine prescribed for lactation suppression. Brain MRI and MR angiogram excluded cortical vein thrombosis and revealed multiple abnormal areas of increased signal in the cortex with segmental arterial narrowings of intracranial vasculitis. The patient completely recovered within one week after drug withdrawal. Biological and radiological abnormalities were also reversible. Following the chronology bromocriptine was most likely responsible for this adverse cerebral and systemic event. CONCLUSION: Clinicians should be aware of bromocripine-related postpartum cerebral angiopathy, a rarely described but serious complication of bromocriptine used to prevent postpartum breast engorgement.

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Gastrointestinal metastasis from lung cancer is exceptional and generally asymptomatic. Other secondary localizations are often present. Metastastic dissemination may involve any portion of the gastrointestinal tract. Clinical expression is variable: dysphagia, anemia, bowel obstruction, peritonitis. Surgical treatment may be indicated in selected patients. We describe the cases of two patients who developed obstruction of the small bowel due to metastases from squamous-cell lung cancer. Bowel obstruction was in the inaugural sign in the first patient. Mesenteric metastasis was associated in the second patient.

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Intramedullary metastases from a non neurogenic cancer are relatively rare, representing approximately 1-2,1% of metastatic sites according to published autopsy reports. Their association with syrinx is extremely rare. Four cases have been described in the last 30 years. We report the case of a 60 year old female with past medical history of Peutz-Jeghers disease, who presented with clinical signs suggestive of medullary lesions of the cervical spine. MR imaging showed tumoral lesions at different levels associated with syrinx. Surgical biopsy confirmed the intramedullary lesions which, by pathology, were found to be of metastatic origin.

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BACKGROUND: The aim of the study, that is still on the way, was to evaluate the negative effects of an intrauterine device, used for more than 2 years, on future fertility of young women who due to medical or personal reasons couldn't use hormonal contraceptives. METHODS: A prospective study was started in 1987 in a group of 515 nulliparous healthy women (age 20-30) using an intrauterine device (Nova T, Schering, Multiload Cu 275 Organon) as contraceptive method. Two hundred and twentyfour women wished to become pregnant following the IUD extraction. RESULTS: Within 12 months, 221 (98.7%) of them became pregnant demonstrating the harmlessness of the contraceptive method on future fertility. All pregnancies had a normal course, except one abortion at the 8th week of gestational age. There hadn't been pregnancies during the observation period, 25 (4.8%) women requested the IUD be removed before the end of the study because of side effects. DISCUSSION: IUD did not cause a reduction in fertility or an increase in ectopic pregnancy in our group of patient.

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OBJECTIVE: To determine whether sperm aneuploidy can lead to abortion. DESIGN: Clinical study. SETTING: Couples with reproductive problems evaluated in a private diagnostic laboratory. PATIENT(S): Two men whose wives had histories of multiple abortions. INTERVENTION(S): Whole and Percoll-processed semen samples were analyzed. MAIN OUTCOME MEASURE(S): The results of fluorescence in situ hybridization. RESULT(S): Aneuploidy rates in Percoll-processed samples were higher than those found in whole specimens. Aneuploid spermatozoa also displayed greater motility. CONCLUSION(S): Sperm aneuploidy should be studied before and after Percoll capacitation in all couples with unexplained infertility.

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BACKGROUND: To analyze risk factors for ectopic pregnancy in an Italian population. METHODS: A retrospective case-control study has been carried out on 213 cases of ectopic pregnancy and 213 controls. The control subjects were women who delivered spontaneously at the same time and in the same hospital of the cases considered. RESULTS: Smoking more than 10 cigarettes/die doubles the risk of ectopic pregnancy. IUD causes an increased risk in women using this contraceptive method for less than two years. A history of abdominal surgery was associated with about a double risk of ectopic pregnancy. The risk was higher in cases of cesarean section and pelvic surgery. CONCLUSIONS: Abdominal surgery (particularly pelvic surgery and cesarean sections), use of IUD for less than two years and cigarette smoking are the risk factors found to be a cause for ectopic pregnancy in the population studied. It was not possible to evaluate the history of pelvic inflammatory disease because there were not enough data. For this reason it is suggested it will be possible in the future to compile a register data, collecting all the cases of ectopic pregnancy as a part of a prevention campaign.

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Endometrial ossification is a rare finding. Its aetiology and pathogenesis are controversial. However a history of previous abortion is usually present. It has variable clinical presentations. We report a case in which the patient presented with secondary infertility.

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Primary Fallopian tube cancer is a very un common cancer that appears between 40 and 65 years old, highly aggressive associate to a poor survival. In this work the authors explain a clinic case of primary Fallopian tube cancer in a woman of 57 years old operated for endometrial cancer. The authors display that the definitive diagnosis was possible only after the histological examination of the operating piece.

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By the analysis of the series reported by many authors, urolithiasis in pregnancy seems to be a rare, but significant pathology. The disease, potentially dramatic for the mother and fetus, appearing into a such particular physiological state like is pregnancy, suggests a reevaluation of diagnostic and therapeutic methods and better control of maternal and fetal risk. Furthermore, urolithiasis must be considered as cause of premature birth, a very severe complication of pregnancy the incidence and predisposing factors of urinary tract stones are generally the same in nonpregnant women. But any metabolic effects and the anatomical changes happen in pregnancy can have a important role on stone's formation. Signs and symptoms in urinary stone disease are: colic, flank pain, hematuria, urinary tract infection; irritative voiding, fever. The initial evaluation and treatment are again similar to those used for the non pregnant population. Radiographic studies any way must be used with caution for the risks of the ionizing radiations for the fetus. All forms of treatment with the exception of extracorporeal shock ware lithotripsy, are appropriate in the pregnant patients but naturally very useful, for the appropriate care of these patients is the coordination by the urologist, the obstetrician, the pediatrician, the radiologist and the anesthesiologist.

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BACKGROUND: In order to have an updated review of the causes for transferring patients from our Institute to Intensive Care Unit (ICU), a study has been conducted on patients admitted from 1990 to 1996. METHODS: Of the 28 women transferred, one underwent dilatation & curettage of uterine cavity after abortion, 3 had a normal delivery and 24 underwent a cesarean section. RESULTS AND CONCLUSIONS: The complications were as follows: respiratory failure (5 cases); suspected or confirmed lung embolism (1); cerebral ischemia (1); septic complications (1); cardiocirculatory complications (19 cases; 7 of them were due to DIC; 6 due to cardiocirculatory failure; 6 due to haemorrhagic shock). These patients were divided into 3 groups, those with pre-existing pathologies which worsened (2 cases); those due to deterioration of pathology arose during pregnancy (17) and, finally, complications during delivery (9). In total the cases of mortality were 7, all of them following cardiocirculatory complications.

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