Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

A Systematic Review of Outcomes and Patient Satisfaction Following Surgical and Non-surgical Treatments for Hair Loss.

INTRODUCTION: This systematic review aims to examine surgical and non-surgical treatments and identify those procedures that are most effective in terms of patient satisfaction. MATERIALS AND METHODS: A systematic review protocol was developed a priori in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. The search was conducted in accordance with the PRISMA guidelines, the Cochrane handbook. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, and Cochrane databases was performed to identify studies on hair loss causes and hair loss treatment with different surgical and non-surgical techniques RESULTS: Our search generated a total of 781 articles; 646 studies were excluded based on the content of the abstracts, and an additional 105 studies were excluded based on the content of the complete article. We performed a review of the 30 remaining studies, which had sufficient data for inclusion, and met all the aforementioned inclusion criteria. Of the 30 studies, four were about minoxidil, four about finasteride, two about dutasteride, three about phototherapy, six about platelet-rich plasma injection, four about follicular unit transplantation technique, six about follicular unit extraction technique, and one about patient satisfaction following surgical treatment without a specified surgical technique. Only three studies used a patient-reported outcome measurement. CONCLUSIONS: Our study is the first comprehensive systematic review of hair loss, looking at the problem from different points of view, and focusing on finding the best solution for the patient. In the literature, there is currently no algorithm for the management of patients who go to a plastic surgeon for a solution to the problem of hair loss. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

[Usefulness of ultrasound in the delivery room]. / Impiego degli ultrasuoni in sala parto.

The use of diagnostic ultrasound and the diffusion of the technique improved the obstetric treatment and the usefulness of ultrasound increases in the delivery room for maternal and fetal care and as method of diagnosis of some obstetric complications. The knowledge of intrapartum ultrasound imaging can be considered useful for the obstetric team, since there is evidence that ultrasound can improve the obstetric management. The mean indications are described: fetal biometry and estimated fetal weight, amniotic fluid volume, fetal situation and presentation, placental localization and anatomy, assessment of size and location of uterine leiomyomas, fetal cardiac activity, evaluation of umbilical cord and fetal cardinal movements intrapartum. Besides, the use of ultrasound is reported in obstetric and postpartum complications. Actually ultrasonography, as a non-invasive, safety and low-cost technique, offers a diagnostic method in particular conditions during labour, delivery and postpartum.

Reproducibility of the fetal cerebral vessels assessment in full and late term pregnancies.

Objective: Data concerning feasibility of the fetal cerebral Doppler examination in full term and late term pregnancy is lacking. Our purpose was to perform an evaluation of these arteries with power Doppler ultrasound, calculating the percentage of identification and measurement and the intraobserver reproducibility.Methods: This was a cross sectional study evaluating a population of 578 normally grown fetuses divided according to the week of examination. The first group included fetuses examined at week 40 (N = 323) and the second fetuses examined at week 41 (N = 255). The three major branches of the internal carotid artery (anterior, middle and posterior cerebral arteries, ACA, middle cerebral artery (MCA), posterior cerebral arteries (PCA)) and their anastomosis (A1, A2, P1, P2) were examined with power Doppler ultrasonography by three independent ultrasonographers. The proportion of vessel identified and measured was calculated and the reproducibility among the three operators was investigated.Results: The major arteries at the circle of Willis were fully identified/measured in 65/56 and 62/48% of fetuses at 40 and 41 weeks. The MCA obtained the higher percentage of identification and measurement at both periods (> 80 and >70%). The entire set of anastomosis were less frequently identified/measured at both periods (50/< 50% of cases), especially in the A2 segment. The best agreement was obtained in the MCA and the worst in the PCA-P1 segment.Conclusions: At 40 and 41 weeks, the fetal cerebral vessels, especially the MCA, are suitable for power Doppler evaluation, providing an interesting tool to evaluate fetal hemodynamics in full and late term pregnancy.

The first case of mitoxantrone exposure in early pregnancy.

Mitoxantrone is an antineoplastic agent considered a potential human teratogen because of its mechanism of action and is classified by the US Food and Drug Administration in pregnancy category risk D. In the literature there are only four cases of women exposed to the drug in late pregnancy. We report the first case of mitoxantrone therapy in the first trimester and during the pregnancy. A 41-year-old woman affected with multiple sclerosis, conceived during therapy and continued mitoxantrone until 29 weeks and 3 days of her pregnancy. She delivered by cesarean section at 39 weeks a growth restricted female baby weighing 1950g without evidence of congenital malformations.

Pediatric renal transplantation: 13 years of experience--report from the Chilean Cooperative Multicenter Group.

Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End-state renal disease etiologies were: congenital renal hypoplasia/dysplasia, chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received antibody induction. Acute rejection episodes were reported in 76 patients: 38% in LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for CD recipients. Actuarial graft survival was significantly better among those patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved from the first period (1989 to 1996) to the second period (1997 to 2002); (P = .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%, respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the time of transplantation. The Z-score height/age at 1, 3, and 5 years posttransplantation was -2.25, -2.24, and -2.5. No significant differences were observed in transplant outcomes comparing patients younger than 7 years with those older ones. In conclusion, pediatric renal transplant has been performed in Chile with acceptable morbidity. The patient and graft survivals are similar to the reported international experience. In the last period there was a significant improvement in graft survival.

Human Sertoli cells in vitro: morphological features and androgen-binding protein secretion.

Sertoli cells play a pivotal role in the regulation of spermatogenesis as they provide the anatomical basis of the blood-testis barrier. In the present paper we report some results of our studies on the ultrastructural features, the responsiveness to FSH, and the ability to secrete androgen-binding protein (ABP) of human Sertoli cells in vitro. The nucleus showed the characteristic foldings of the nuclear membrane, scattered chromatin, and a fibrillar nucleolus. In the cytoplasm Charcot-Boettcher crystals were present and active phagocytic activity was documented by the presence of vacuoles containing lipids and cellular debris. Human Sertoli cells in culture responded to FSH with a maximal rise in cAMP that was approx. 3-fold. This response to FSH is comparable to that reported for the adult rat but lower than that of the immature rat, and suggests that human as well as rat Sertoli cells could have a reduced response to FSH since sexual maturation was achieved. As no evidence has been reported on ABP secretion by human Sertoli cells in culture we evaluated the concentration of this protein in the Sertoli cell spent media. Human Sertoli cells in culture produced ABP and the response to FSH was dose-related. The Kd value of human ABP (hABP) was approx. 7.5 nM, being slightly higher than that of the rat ABP and an order of magnitude different from that of sex hormone-binding globulin (SHBG) present in human plasma. We also measured the association and dissociation rates of dihydrotestosterone-hABP complexes and the Kd/Ka ratio was very close to the value of Kd of the Scatchard analysis. The differences between hABP and SHBG may open the way to the selective measurement of ABP in many conditions of male infertility.

Transvaginal sonographic detection of embryonic-fetal abnormalities in early pregnancy.

OBJECTIVE: To estimate the detection rate of abnormalities by transvaginal ultrasound in early pregnancy. METHODS: We prospectively analyzed records of 3592 sequential pregnant women at 10-16 weeks' (singleton) gestation (mean 13 weeks and 2 days). After exclusion of 114 women, there were 3478 women in the study. Each woman underwent a transvaginal sonographic survey for fetal anomalies as well as biometric measurements. Fetuses diagnosed with malformations were followed to delivery, and those without underwent transabdominal sonography at 18-24 weeks' gestation. RESULTS: The anomaly detection rate by transvaginal ultrasound was 51.6% (33 of 64; 95% confidence interval [CI] 38.7, 64.2) in early pregnancy, and the detection rate by transvaginal ultrasound combined with second-trimester transabdominal ultrasound was 84.4% (54 of 64; 95% CI 73.1, 92.2). Cystic hygroma and fetal hydrops were the anomalies detected most frequently by transvaginal ultrasound. Low detection rates for abnormalities of the face and of the cardiac, skeletal, and urinary systems were found even when both methods were used. CONCLUSION: Transvaginal sonography appears to be an effective way to identify many congenital fetal anomalies in early pregnancy. There is a good probability of diagnosing cystic hygroma and fetal hydrops, although other abnormalities, particularly heart defects, are associated with lower detection rates.

Ultrasound diagnosis of uterine myomas and complications in pregnancy.

OBJECTIVE: To evaluate myomas for ultrasound-documented size, location, position, and relation to the placenta, and to relate these findings to complications during pregnancy, at delivery, and in the puerperium. METHODS: Among 12,708 pregnant patients who had ultrasound scans, 492 had uterine myomas. Single myomas were found in 88% of cases and multiple myomas in 12%. The myomas were evaluated for size, number, position, location, relationship to the placenta, and echogenic structure, and the outcome of pregnancy was compared to that of patients in the control group. RESULTS: A statistically significant increased incidence of threatened abortion, threatened preterm delivery, abruptio placentae, and pelvic pain was observed in patients with uterine myomas (P < .001). Abruptio placentae was particularly evident in women with myoma volumes greater than 200 cm3, submucosal location, or superimposition of the placenta. Pelvic pain was related to myoma volume greater than 200 cm3 and ultrasound findings of heterogeneous echo patterns and cystic areas. Mode of delivery, abortion, preterm birth, premature rupture of membranes, and fetal growth did not seem to be affected by the presence of myomas. Thirty-two women with uterine myomas were managed surgically. Thirteen underwent myomectomy during pregnancy. Of these, eight delivered at term and five delivered preterm after the 32nd week of gestation. None of the deliveries were associated with neonatal death. The other 19 patients had surgery at delivery. Nine myomectomies were performed at cesarean delivery. Of these, three were complicated by severe hemorrhage necessitating hysterectomy. Another nine hysterectomies were performed during cesarean and one after vaginal delivery. CONCLUSIONS: In addition to myoma size, the ultrasound evaluation of pregnant women with myomas should include position, location, relationship to the placenta, and echogenic structure. These ultrasound findings make it possible to identify women at risk for myoma-related complications and could be useful in managing the pregnancy.

Isolated mild fetal pyelectasis detected by transvaginal sonography in advanced maternal age.

OBJECTIVE: To evaluate the importance and evolution of isolated, mild fetal pyelectasis, detected in early pregnancy by high-resolution transvaginal sonography, and to determine its association with abnormal fetal karyotypes. METHODS: Transvaginal scan at 11-16 weeks' gestation and transabdominal ultrasound examinations at the time of amniocentesis (16-18 weeks) were performed in 1093 pregnant women undergoing genetic amniocentesis because of advanced maternal age. In 795 cases, transabdominal scans were repeated at 22-24 weeks. Women were excluded if they had a spontaneous abortion, chose to terminate their pregnancy, or declined amniocentesis. Each patient was screened for fetal pyelectasis, defined as an increase in anteroposterior renal pelvic diameter, using cutoff values related to various stages of pregnancy. RESULTS: Isolated fetal pyelectasis was detected at the first ultrasound examination in 56 women (5.1%) in early pregnancy, in 32 (2.9%) at the time of amniocentesis, and in 23 (2.9%) at 22-24 weeks' gestation. Two fetuses with diagnoses of mild pyelectasis at the first transvaginal ultrasound demonstrated abnormal karyotypes at amniocentesis. In one case, the pyelectasis disappeared at 22-24 weeks' gestation. CONCLUSION: This retrospective study shows that pyelectasis is more frequently detectable by high-resolution transvaginal sonography in the first half of pregnancy than in the second half. When detected in early pregnancy, the finding is frequently transient and not associated with an increased risk of abnormal fetal karyotypes.

Resting energy expenditure in young patients with cystic fibrosis receiving antibiotic therapy for acute respiratory exacerbations.

BACKGROUND: patients with cystic fibrosis commonly have severe malnutrition and growth retardation. Among possible causes of these manifestations are low caloric intake, loss of nutrients and increased resting energy expenditure. This study was designed to assess the influence of antibiotic therapy for infectious exacerbations on resting energy expenditure in young patients with cystic fibrosis. METHODS: We studied 17 patients with cystic fibrosis (mean age, 13.6 years). All were hospitalized to receive intravenous antibiotic therapy (mean duration, 2 weeks) for acute respiratory exacerbations. At the beginning of therapy and after it ended, all patients underwent blood chemical tests, anthropometrical measures, determination of body composition by bioelectrical impedance, spirometry, and indirect calorimetry. RESULTS: Antibiotic therapy led to a significant improvement in biochemical, spirometric variables and in estimated calorimetry measurements expressed in relation to fat-free mass. These findings suggest that infective exacerbations are among the causes of increased resting energy expenditure in young patients with cystic fibrosis. CONCLUSIONS: Indirect calorimetry may prove useful in the diagnosis of infective exacerbations and in monitoring the effect of antibiotic therapy in patients with cystic fibrosis.

Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis.

BACKGROUND: Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis. Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal. AIMS: To compare patients' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis. PATIENTS: Patients with pancreatic exocrine insufficiency due to cystic fibrosis. METHODS: Patients were assigned to the crossover treatment with Creon or Pancrease for 1 week and then to the alternative treatment. Patients had to follow a fixed diet (at least 2 g fat/kg) and had to assume 1000 units lipase/g fat. The evaluation parameters were: patients' preference, acceptance of therapy, stool fat excretion, stool weight, gastrointestinal symptoms, and tolerance. RESULTS AND CONCLUSIONS: Of the 33/60 patients who expressed a preference for one of the two treatments, 30 preferred Creon while only 3 patients preferred Pancrease (p<0.001). No difference between the two treatments was observed regarding stool characteristics, gastrointestinal symptoms and tolerance. The mean number of capsules taken daily was reduced by 35% with Creon. The results of this study showed a preference in favour of Creon probably due to the reduction of daily capsule intake of 35%, supporting digestion as well as Pancrease.

Drug abuse in pregnancy: fetal growth and malformations.

The influence of drug addiction in pregnancy on the fetus is in terms of malformation, ponderal and functional development and post-natal psychoneuromotor development. The Authors evaluate the incidence of this complications in 101 drug addicted pregnant patients and the results are shown below.

Benign intracranial hypertension in an older child with cystic fibrosis.

Despite having normal height and weight, a 6-year-old girl had frequent bowel movements and slight recurrent chest infections since the age of 4 years and headache for 1 year. The patient appeared healthy, but examination of the ocular fundus revealed papilledema. Cranial computed tomography appeared normal. Lumbar puncture disclosed an elevated opening cerebrospinal fluid pressure, with normal biochemical, cellular, and bacteriologic findings. Laboratory investigations indicated pathologic steatorrhea, elevated electrolytes in 3 sweat tests, and low serum levels of vitamins A and E. The diagnosis of pseudotumor cerebri in a patient with cystic fibrosis was made. After treatment with prednisone (1 mg/kg/day), pancreatic extracts, and vitamin supplements, headache and papilledema resolved and serum vitamin A and E levels subsequently became normal. Older children with cystic fibrosis rarely have benign intracranial hypertension, but when present it is often due to hypervitaminosis during correction of malnutrition. In this child, pseudotumor cerebri and associated hypovitaminosis improved after combined corticosteroid and vitamin treatment.

Transvaginal fetal biometry in early pregnancy.

OBJECTIVE: To produce reference charts for fetal size with transvaginal sonography that are potentially helpful in evaluating normal and abnormal early pregnancies. DESIGN: A prospective cross-sectional study. SUBJECTS: 1081 normal singleton pregnancies with a normal fetal karyotype or normal healthy baby at delivery, at 9-16 weeks' gestation. Measurements included crown rump length, biparietal diameter, transverse cerebellar diameter, head and abdominal circumference, mean abdominal diameter, thoracic circumference, femur length, humerus length and foot length. RESULTS: The best description of the relationship between single ultrasonographic parameters and gestational age was achieved by polynomial regression analysis. All fetal biometric parameters correlated closely with gestational age. Biparietal diameter maintained the closest correlation with gestational age (r2 = 97.15, p < 0.001; y = -0.545 - 0.06x + 0.15x2); transverse cerebellar diameter showed the poorest correlation with gestational age (r2 = 88.17, p < 0.001). Reference ranges (5 degrees and 95 degrees percentile intervals) were constructed for all biometric parameters in relation to gestational age. Mean residuals are similar for all parameters with a very low range. CONCLUSIONS: These data provide normograms for first and early second trimester fetal measurements which may be of aid in the dating of pregnancies and can be useful in the early detection of genetic disorders affecting the growth of fetal structures.

Proposal of an experimental model of fetal hydrocephalus.

There have been numerous experimental studies reported in literature that simulate congenital hydrocephalus. The various techniques that have been proposed present the obstacle of being difficult to reproduce and the results therefore, often do not match. We have proposed a new experimental model that is easily created, reproduced and that allows for precise monitoring of the hydrocephalic entity, in addiction to presenting itself as an example to follow in resolving the hydrocephalic pathology. The authors report the results relative to their case studies of 14 pregnant animals treated and they list and discuss the principal complications encountered.

Ultrasound-guided fine needle aspiration of ovarian cysts during pregnancy.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound-guided fine needle aspiration in the treatment of ovarian cysts during pregnancy. STUDY DESIGN: Nine out of twenty-nine patients between the 6th and the 16th week of gestation with unilateral ovarian cysts ranging between 65 and 540 cm3 in volume were selected for sonographically-guided fine needle aspiration. RESULTS: No complications were observed at either short or long-term follow-up; all patients delivered healthy infants at term. Clinical and sonographic post-partum follow-up was uneventful in all cases. In three cases it was necessary to repeat the procedure once and in one case twice during pregnancy. In one case a recurrent serous cyst was excised at operative laparoscopy performed 3 months after delivery. CONCLUSIONS: Ultrasound-guided fine needle aspiration was safely performed in nine patients as an alternative treatment to surgery when persistent monolateral and unilocular ovarian cysts with regular borders and completely anechoic structure are detected during pregnancy.

Uterine myoma in pregnancy: ultrasound study.

In many cases the presence of a myomatous formation in pregnancy begins its effect in a symptomless way and is revealed only by a regular sonographic control or at the time of delivery. In other cases, however, it could represent the cause of several complications, such as increased incidence of abortion extrauterine pregnancy premature breaking of the membranes, premature delivery distocia during delivery or it could itself be the site of necrotic processes. The attitude towards this type of pathology during pregnancy has often varied. The authors report their experiences regarding 408 cases of pregnancies complicated by myoma that were followed with accurate sonographic monitoring and they evaluate the incidence of the principal complications during pregnancy at the time of delivery and the eventual influence on the fetal weight at the time of birth.

The use of amniotic fluid viscosity measurements to establish fetal lung maturity.

A Haake viscosimeter was used to determine the viscosity of amniotic fluid and this value correlated with fetal lung maturity. The results were evaluated along the weeks of pregnancy and compared to those obtained using Gluck's method (lecithin/sphingomyelin ratio (L/S). Using 91 separate amniotic fluid samples, free of meconium and blood contamination, we found that the new method was quick and easy to perform. Thirty-one neonates were delivered within 48 h of the amniotic fluid sampling and the percentage of correct prediction of respiratory distress syndrome (RDS) was 71% with a mature L/S ratio and 83% with viscosity less than 1.17 cP. In cases with an immature L/S ratio (value below 2) the correct prediction of RDS was 64%; with the fluorescence polarization (FP) technique it was 91%. We conclude that the amniotic fluid FP value is a reliable index of fetal lung maturity and risk for developing RDS and has also specific technical and diagnostic advantages over the L/S ratio.

Retinal and lens damages observed in young rats undergoing protein malnutrition in selected stages of their growth.

Ocular damages of young rats undergoing protein malnutrition in selected stages of their growth have been valuated. Malnutrition was induced by a purified, hypoproteinic diet given to mothers or to newborns after their weaning. The histologic results pointed out that protein lack damages ocular structures different in embryonal origin: retina and lens. In fact, vacuolar degeneration of retinal optic fiber layer and cataract of lens were observed in experimental groups of rats. Only lens damage appeared completely reversible after a prolonged nutritional rehabilitation as for rats malnourished during fetal stage and lactation and then rehabilitated for 50 days. On the contrary retinal degeneration was still present in these animals even if some improvement could be observed.