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OBJECTIVE: Survival (> or =1 twin) after laser surgery for patients with twin-to-twin transfusion syndrome (TTTS) ranges from 65 to 93%. However, most studies are noncontrolled and retrospective, and have included a limited number of patients. The aim of this study was to perform a systematic review of outcomes after laser surgery in patients with TTTS. METHODS: We conducted database and manual searches of reference lists and pertinent journals published between 1995 and 2009 that report outcomes of laser surgery in patients with TTTS. Two authors performed the search independently of each other. There exist only two randomized controlled trials, each with fewer than 80 patients having undergone laser surgery. Uncontrolled and retrospective series were therefore considered as well. Studies had to report sufficient information on inclusive dates, stage distribution, overall neonatal survival, and neonatal survival of at least one twin. Of the 486 studies identified, we considered 19 studies. RESULTS: For each series, 95% confidence intervals (CI) were calculated. Survival was plotted against the date of publication, number of patients/series, gestational age at delivery, and proportion of advanced cases. Univariate analysis was performed to detect significant differences. Our meta-analysis, which included 1484 patients, shows 81.2% survival of at least one twin (CI: 79.1-83.2%). The average survival of at least one twin for the entire population remained within the CI of all but one series. Neither case load, nor stage distribution, nor chronological date of the study affected the survival. CONCLUSION: A systematic review of endoscopic laser surgery performed in patients with TTTS failed to show a significant impact of high caseloads, disease severity distribution, or improvements in technique. [ABSTRACT FROM AUTHOR]

In Huntington's Disease (HD) and related disorders, expansion of CAG trinucleotide repeats produces a toxic gain of function in affected neurons. Expanded huntingtin (expHTT) mRNA forms aggregates that sequester essential RNA binding proteins, dysregulating mRNA processing and translation. The physical basis of RNA aggregation has been difficult to disentangle owing to the heterogeneous structure of the CAG repeats. Here, we probe the folding and unfolding pathways of expHTT mRNA using single-molecule force spectroscopy. Whereas normal HTT mRNAs unfold reversibly and cooperatively, expHTT mRNAs with 20 or 40 CAG repeats slip and unravel non-cooperatively at low tension. Slippage of CAG base pairs is punctuated by concerted rearrangement of adjacent CCG trinucleotides, trapping partially folded structures that readily base pair with another RNA strand. We suggest that the conformational entropy of the CAG repeats, combined with stable CCG base pairs, creates a stick-slip behavior that explains the aggregation propensity of expHTT mRNA., (© 2024. The Author(s).)

RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or parentally inherited. Despite being a known frequent presentation, the fraction of monogenic NIHF cases due to RASopathies is limited in the literature. Also, the specific parental contribution of RASopathies to NIHF is not well described. Our objective was to review pooled exome sequencing (ES) diagnostic yield of RASopathies for NIHF and to determine the parental contribution of RASopathy to NIHF. We performed a systematic review of prenatal ES studies from January 1, 2000 to August 1, 2022. Thirty-six studies met inclusion criteria. Cases with RASopathy gene variants were reviewed. NIHF cases were further classified as isolated or non-isolated. Thirty-six ES studies including 46 pregnancies with NIHF and a diagnosed RASopathy were reviewed. Forty-four diagnostic variants and 2 variants of uncertain significance in 12 RASopathy genes were identified. Expanding on what was previously published, a total of 506 NIHF cases were extracted with 191 cases yielding a positive diagnosis by ES. The overall rate of RASopathy diagnosis in clinically diagnosed NIHF cases was 9% (44/506). The rate of RASopathy diagnosis among NIHF cases with positive genetic diagnosis by ES was 23% (44/191). Of the 46 cases identified, 13 (28%) variants were parentally inherited; specifically, 5/13 (38%) maternal, 3/13 (23%) paternal, 2/13 (15%) biparental, and 3/13 (23%) unspecified. Majority of NIHF cases 29/46 (63%) were isolated. Among NIHF cases with positive ES diagnoses, RASopathy diagnostic yield by ES was 23%. NIHF secondary to RASopathies was parentally inherited in 28% of cases. Most cases of NIHF due to RASopathy were isolated, with no prenatal detection of associated anomalies., (© 2023 Wiley Periodicals LLC.)

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare neurological disorder caused by the mutations in the DARS2 gene, which encodes the mitochondrial aspartyl-tRNA synthetase. The objective of this study was to understand the impact of DARS2 mutations on cell processes through evaluation of LBSL patient stem cell derived cerebral organoids and neurons. We generated human cerebral organoids (hCOs) from induced pluripotent stem cells (iPSCs) of seven LBSL patients and three healthy controls using an unguided protocol. Single cells from 70-day-old hCOs were subjected to SMART-seq2 sequencing and bioinformatic analysis to acquire high-resolution gene and transcript expression datasets. Global gene expression analysis demonstrated dysregulation of a number of genes involved in mRNA metabolism and splicing processes within LBSL hCOs. Importantly, there were distinct and divergent gene expression profiles based on the nature of the DARS2 mutation. At the transcript level, pervasive differential transcript usage and differential spliced exon events that are involved in protein translation and metabolism were identified in LBSL hCOs. Single-cell analysis of DARS2 (exon 3) showed that some LBSL cells exclusively express transcripts lacking exon 3, indicating that not all LBSL cells can benefit from the "leaky" nature common to splice site mutations. At the gene- and transcript-level, we uncovered that dysregulated RNA splicing, protein translation and metabolism may underlie at least some of the pathophysiological mechanisms in LBSL. To confirm hCO findings, iPSC-derived neurons (iNs) were generated by overexpressing Neurogenin 2 using lentiviral vector to study neuronal growth, splicing of DARS2 exon 3 and DARS2 protein expression. Live cell imaging revealed neuronal growth defects of LBSL iNs, which was consistent with the finding of downregulated expression of genes related to neuronal differentiation in LBSL hCOs. DARS2 protein was downregulated in iNs compared to iPSCs, caused by increased exclusion of exon 3. The scope and complexity of our data imply that DARS2 is potentially involved in transcription regulation beyond its canonical role of aminoacylation. Nevertheless, our work highlights transcript-level dysregulation as a critical, and relatively unexplored, mechanism linking genetic data with neurodegenerative disorders., (© 2023. Springer Nature Limited.)

Future-oriented thought is ubiquitous in humans but challenging to study in children. Adults not only think about the future but can also represent a future state of the world that differs from the present. However, behavioral tasks to assess the development of future thought have not traditionally required children to do so as most can be solved based solely on representations of the present. To overcome this limitation, we modified an existing task such that children could not simply rely on a representation of the present to succeed (i.e., the correct answer for "right now" was different than the correct answer for "tomorrow"). A sample of 117 4- to 7-year-olds (64 girls and 53 boys) from Ottawa, Canada, and surrounding area, who were predominantly European Canadian (78.6% of sample) and had a family income of over $100,000 CAN (66.1% of sample) participated. Children remembered the information required to solve our task, and there were age-related changes in performance, but only 7-year-olds made an adaptive future-oriented decision significantly more often than chance. With the task modification removed (so the correct answer for the present and the future was the same), even 4-year-olds were above chance. Our work challenges the notion that starting at age 4, children solve behavioral tasks of future thinking by acting on their representations of the future. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Two-color laser beams are instrumental in light-field control and enhancement of high-order harmonic, spectral supercontinuum, and terahertz radiation generated in gases, plasmas, and solids. We demonstrate a multi-terawatt two-color beam produced using a relativistic plasma mirror, with 110 mJ at 800 nm and 30 mJ at 400 nm. Both color components have high spatial quality and can be simultaneously focused, provided that the plasma mirror lies within a Rayleigh range of the driving fundamental beam. Favorable scaling of second-harmonic generation by plasma mirrors at relativistic intensities suggests them as an excellent tool for multi-color waveform synthesis beyond the petawatt level.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare, slowly progressive white matter disease caused by mutations in the mitochondrial aspartyl-tRNA synthetase (mt-AspRS, or DARS2). While patients show characteristic MRI T2 signal abnormalities throughout the cerebral white matter, brainstem, and spinal cord, the phenotypic spectrum is broad and a multitude of gene variants have been associated with the disease. Here, Dars2 disruption in CamKIIα-expressing cortical and hippocampal neurons results in slowly progressive increases in behavioral activity at five months, and culminating by nine months as severe brain atrophy, behavioral dysfunction, reduced corpus callosum thickness, and microglial morphology indicative of neuroinflammation. Interestingly, RNAseq based gene expression studies performed prior to the presentation of this severe phenotype reveal the upregulation of several pathways involved in immune activation, cytokine production and signaling, and defense response regulation. RNA transcript analysis demonstrates that activation of immune and cell stress pathways are initiated in advance of a behavioral phenotype and cerebral deficits. An understanding of these pathways and their contribution to significant neuronal loss in CamKII-Dars2 deficient mice may aid in deciphering mechanisms of LBSL pathology., Competing Interests: Declaration of Competing Interest AF is a paid drug safety monitoring board member for Bluebird Bio, Stealth Biotherapeutics, and a paid consultant to Calico Labs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To examine the association of low fetal fraction of cell-free DNA (cfDNA) with placental compromise and adverse perinatal outcomes., Materials and Methods: This was a retrospective cohort utilizing a sample of convenience including 639 women undergoing cfDNA screening at our institution from January 2013 to January 2017. Low fetal fraction was defined as less than the 25th percentile. Indicators of placental compromise were examined individually and as a composite outcome, including hypertensive disease of pregnancy, intrauterine growth restriction, abruption, and oligohydramnios. Neonatal outcomes, including preterm delivery, low Apgar scores, and small for gestational age, also were examined. We calculated risk ratios (RR) and 95% confidence intervals (CI)., Results: Low fetal fraction was associated with placental compromise (RR 1.6 [CI 1.1-2.2]), hypertensive disease of pregnancy (RR 1.6 [CI 1.003-2.6]), and preeclampsia with severe features (RR 3.3 [CI 1.2-8.9]). Low fetal faction was not associated with preterm delivery, low Apgar scores, or small for gestational age., Conclusions: Low fetal fraction of cfDNA among asymptomatic women may serve as a predictor of subsequent placental dysfunction and hypertensive disease., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Technological advances in genetics have resulted in an increase in the number and complexity of screening and diagnostic tests in the prenatal clinical arena. It is critical that patients are provided with appropriate counseling to enable them to make educated decisions. During this workshop session participants discussed the education, background and credentials required to provide counseling regarding prenatal genetic testing options. The participants agreed that prenatal care providers may have limited time and training to adequately address prenatal genetic testing. Telemedicine and online education may help to address this challenge. Workshop participants agreed that educational and certifying organizations should work together to develop standards for the certification and maintenance of certification processes., (Copyright © 2018. Published by Elsevier Inc.)

The use of cell-free DNA (cfDNA) for screening and diagnosis of single-gene disorders is an evolving technology, and its application at this time is limited. Invasive testing is currently recommended for the diagnosis of single-gene disorders. The limitations of cfDNA technology are most notable in clinical settings involving X-linked and autosomal recessive conditions, in part because maternal mutant alleles greatly outnumber those of fetal origin. Examples of single-gene disorders for which cfDNA has been used include skeletal dyplasias, cystic fibrosis, congenital adrenal hyperplasia, β-thalassemia, and muscular dystrophies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess the clinical utility of cell-free DNA (cfDNA)-based screening for aneuploidies offered through primary obstetrical care providers to a general pregnancy population., Methods: Patient educational materials were developed and validated and providers were trained. Serum was collected for reflexive testing of cfDNA failures. Providers and patients were surveyed concerning knowledge, decision making, and satisfaction. Pregnancy outcome was determined by active or passive ascertainment., Results: Between September 2014 and July 2015, 72 providers screened 2,691 women. The five largest participating practices increased uptake by 8 to 40%. Among 2,681 reports, 16 women (0.6%) were screen-positive for trisomy 21, 18, or 13; all saw genetic professionals. Twelve were confirmed (positive predictive value (PPV), 75%; 95% CI, 48-93%) and four were false-positives (0.15%). Of 150 failures (5.6%), 79% had a negative serum or subsequent cfDNA test; no aneuploidies were identified. Of 100 women surveyed, 99 understood that testing was optional, 96 had their questions answered, and 95 received sufficient information. Pretest information was provided by the physician/certified nurse midwife (55) or office nurse/educator (40); none was provided by genetic professionals., Conclusion: This first clinical utility study of cfDNA screening found higher uptake rates, patient understanding of basic concepts, and easy incorporation into routine obstetrical practices. There were no reported cases of aneuploidy among cfDNA test failures.Genet Med advance online publication 12 January 2017.

Counseling patients regarding the benefits, harms, and dilemmas of genetic testing is one of the greatest ethical challenges facing reproductive medicine today. With or without test results, clinicians grapple with how to communicate potential genetic risks as patients weigh their reproductive options. Here, we consider a case of a woman with a strong family history of early-onset Alzheimer's disease (EOAD). She is early in her pregnancy and unsure about learning her own genetic status. We address the ethical ramifications of each of her options, which include genetic testing, genetic counseling, and termination versus continuation of the pregnancy. Our analysis foregrounds clinicians' role in helping to ensure autonomous decision making as the patient reflects on these clinical options in light of her goals and values., (© 2017 American Medical Association. All Rights Reserved.)

Owing to vascular connections within a single placenta, monochorionic gestations present distinctive prenatal management challenges. Complications that can arise as a result of unbalanced hemodynamic exchange (twin-twin transfusion syndrome and twin anemia polycythemia sequence) and unequal placental sharing (selective fetal growth restriction) should be kept in mind while prenatal management is being planned. Because of unique monochorionic angioarchitecture, what happens to one twin can directly affect the other. Death of one twin can result in death or permanent disability of the co-twin. Early detection of these unique disease processes through frequent ultrasonographic surveillance may allow the opportunity for earlier referral, intervention, or both and potentially better outcomes. Therefore, monochorionic gestations should be managed differently than dichorionic gestations or singletons. The purpose of this document is to present in detail methods for monitoring and management of uncomplicated monochorionic gestations and to review the evidence for the roles of these methods for detection of complications in clinical practice. Finally, we present evidence-based and expert opinion-supported recommendations developed by the North American Fetal Therapy Network for the diagnosis, surveillance, and delivery of uncomplicated monochorionic gestations.

Informed consent is the process by which the treating health care provider discloses appropriate information to a competent patient so that the patient may make a voluntary choice to accept or refuse treatment. When the analysis of circulating cell free DNA (ccfDNA) became commercially available in 2011 through the Prenatal Diagnostic Laboratory at Women & Infants Hospital of Providence, Rhode Island to "high-risk" women, it provided an opportunity to examine how commercial laboratories informed potential consumers. We identified, via an internet search, four laboratories offering such testing in the United States and one in Europe. We evaluated patient educational materials (PEMs) from each using the Flesch Reading Ease method and a modified version of the Suitability Assessment of Materials (SAM) criteria. Pamphlets were also reviewed for their inclusion of content recommendations from the International Society for Prenatal Diagnosis, the National Society of Genetic Counselors, the American College of Obstetricians and Gynecologists jointly with the Society of Maternal Fetal Medicine, and the American College of Genetics and Genomics. Reading levels were typically high (10th-12th grade). None of the pamphlets met all SAM criteria evaluated nor did any pamphlet include all recommended content items. To comply with readability and content recommendations more closely, Women & Infants Hospital created a new pamphlet to which it applied the same criteria, and also subjected it to focus group assessment. These types of analyses can serve as a model for future evaluations of similar patient educational materials.

Introduction: To describe the incidence and risk factors for iatrogenic premature preterm rupture of membranes (iPPROM) after fetoscopic laser surgery for the twin-to-twin-transfusion syndrome., Materials and Methods: This is a retrospective review of all patients who have undergone fetoscopic laser surgery at a single fetal treatment center since 2000. We defined iPPROM as spontaneous rupture of membranes before the onset of labor prior to 34 weeks of gestation. The iPPROM cohort was compared to the cohort without iPPROM for several preoperative, operative, and delivery characteristics., Results: Ninety-two consecutive patients were reviewed. The overall rate of iPPROM was 18.5% (n = 17). The rates of iPPROM within 1 and 4 weeks were 5.4 and 10.9%, respectively. The median interval from surgery to delivery was significantly shorter in the iPPROM group (21 vs. 62 days, p = 0.01). The mean gestational age at delivery (27.0 vs. 31.1 weeks, p = 0.02) was lower in the iPPROM group. No other characteristics studied differed significantly between the groups., Discussion: The incidence of iPPROM was substantially lower than in recent multicenter reports; however, no risk factors of iPPROM could be identified. Whether this is related to variations in surgical or anesthetic management will require further investigation., (© 2014 S. Karger AG, Basel.)

Aims: To evaluate the early introduction of circulating cell-free (ccf) DNA testing in a prenatal diagnosis center serving a statewide population., Results: A retrospective chart review of patients at high aneuploidy risk counseled during the two 10-week periods that documents indication, risk, maternal age, insurance coverage, decisions, and reasoning behind that decision. Among the 299 included women, indication was advanced maternal age (17% with and 56% without an additional indication), positive serum screen (15%), and abnormal ultrasound (12%). Uptake increased from 10% to 17%, as did patient awareness of the test (4% to 14%). Women with lower copayments were more likely to complete testing (23% vs. 5%, p<0.001). Most women completing testing (75%) wanted to avoid an invasive procedure, while those declining cited testing would not change anything (47%), preferred diagnostic testing (16%), negative follow-up testing (20%), and cost/insurance issues (9%). One of 42 tests was positive (trisomy 21)., Conclusions: Individual patient follow-up allows us to document ccfDNA-related patient decision-making. Nearly half of the women did not want further testing and one in seven preferred immediate diagnostic testing. Patient costs were a barrier to testing that, if avoided, could increase test uptake by 50% or more.

Study Objective: To review our experience with general anesthesia in endoscopic fetal surgery for twin-to-twin transfusion syndrome (TTTS), and to compare fetomaternal outcome before and after protocol implementation., Design: Retrospective impact study., Setting: University-affiliated medical center., Measurements: Data from 85 consecutive patients who underwent endoscopic laser ablation of placenta vessels for severe TTTS were studied. Outcomes were compared in patients before (2000-2007) and after (2008-2012) a change to strict intraoperative intravenous (IV) fluid and liberal vasopressor management. Perioperative parameters (IV fluid administration, vasopressor use, maternal hemoglobin [Hb] concentration); maternal complication rate (respiratory, hemorrhagic); pregnancy outcome; and fetal and neonatal survival were recorded., Main Results: Patients in the early group (2000-2007; n = 55) received 1634 ± 949 mL of crystalloid fluid intraoperatively, compared with 485 ± 238 mL (P < 0.001; Student's t test) given to the late group (2008-2012; n = 30). Maternal pulmonary edema and any respiratory distress were seen in 5.5% and 12.7% of patients in the early group, respectively, and in none of the late group patients (P < 0.05; Chi-square analysis)., Conclusions: A significant risk of maternal respiratory complications exists after general anesthesia for endoscopic fetal surgery. Judicious fluid management significantly decreases this risk., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The identification of circulating cell-free fetal DNA in maternal plasma has led to the introduction of noninvasive prenatal tests with high sensitivity and high specificity for common aneuploidies (trisomy 13, trisomy 18, trisomy 21). A new expanded noninvasive prenatal testing panel that includes five microdeletion syndromes (22q11 deletion syndrome, cri-du-chat [5p minus], Prader Willi or Angelman syndrome, 1p36 deletion syndrome) and two aneuploidies usually associated with nonviable pregnancies (trisomy 16 and trisomy 22) is now available. This expanded panel will be performed unless an opt-out box is checked. Because these disorders are so rare, the positive predictive value is expected to be low. As with all new screening tests and technologies, the expanded panel should be appropriately studied before it is widely adopted.

Background: Genetic abnormalities have been associated with 6 to 13% of stillbirths, but the true prevalence may be higher. Unlike karyotype analysis, microarray analysis does not require live cells, and it detects small deletions and duplications called copy-number variants., Methods: The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth in five geographic catchment areas. Standardized postmortem examinations and karyotype analyses were performed. A single-nucleotide polymorphism array was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. Variants that were not identified in any of three databases of apparently unaffected persons were then classified into three groups: probably benign, clinical significance unknown, or pathogenic. We compared the results of karyotype and microarray analyses of samples obtained after delivery., Results: In our analysis of samples from 532 stillbirths, microarray analysis yielded results more often than did karyotype analysis (87.4% vs. 70.5%, P<0.001) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants, 8.3% vs. 5.8%; P=0.007). Microarray analysis also identified more genetic abnormalities among 443 antepartum stillbirths (8.8% vs. 6.5%, P=0.02) and 67 stillbirths with congenital anomalies (29.9% vs. 19.4%, P=0.008). As compared with karyotype analysis, microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9% in all stillbirths, 34.5% in antepartum stillbirths, and 53.8% in stillbirths with anomalies., Conclusions: Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

Background/purpose: Severe twin-to-twin transfusion syndrome (TTTS) leads to 80% to 100% dual mortality. Endoscopic laser coagulation of connecting vessels improves outcome to 80% survival of at least 1 twin. There is limited long-term follow-up of surviving TTTS patients. The aim of this study was to analyze gestational age-stratified, long-term morbidity in these patients., Methods: A retrospective case-control study of TTTS surviving patients (38 patients, 72% follow-up rate) from one center. Perinatal and pediatric records were reviewed, and outcomes were compared with published reports and gestational age-matched controls., Results: Forty percent (15/38) had at least 1 major sequela, all but 6 of which were fully resolved at a median follow-up of 4.4 years. There were no permanent cardiac, genitourinary, renal, or respiratory sequelae. All major complications were in patients born <29 weeks. There were no significant differences in complications between this cohort of patients and gestational age (GA)-matched control patients., Conclusions: The long-term morbidity of monochorionic twins after fetal laser surgery for severe TTTS is 13%. At a median follow-up of more than 4 years, these children fare no worse than gestational age-matched, non-operated twins and singletons. The degree of prematurity at birth is the best predictor of temporary or permanent sequela in this group of patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Endoscopic fetal surgery is most commonly used for the treatment of twin-to-twin transfusion syndrome (TTTS), but the surgical techniques can be applied to other forms of fetal surgery. We present our experience with endoscopic fetal surgery over the past 10 years. From 2000 to 2010, 70 endoscopic laser ablations of placental vessels for TTTS were performed. Median number of placental vessels ablated was four. The incidence of preterm rupture of membranes (PROM) was 6%. Overall survival was 70%, with at least one twin surviving in 82%. Tocolysis was used in 73% of patients for a median of 12 hours. The combination of an open surgical approach, Seldinger technique, and uterine plugging led to outcomes similar to other reports, with a significantly lower PROM rate. Although TTTS is the most common application of endoscopic fetal surgery, this approach is applicable for other indications. Insertion and removal of tracheal occlusion balloons for severe congenital diaphragmatic hernia are currently being performed at our institution.

The mouse sensory neocortex is reported to lack several hallmark features of topographic organization such as ocular dominance and orientation columns in primary visual cortex or fine-scale tonotopy in primary auditory cortex (AI). Here, we re-examined the question of auditory functional topography by aligning ultra-dense receptive field maps from the auditory cortex and thalamus of the mouse in vivo with the neural circuitry contained in the auditory thalamocortical slice in vitro. We observed precisely organized tonotopic maps of best frequency (BF) in the middle layers of AI and the anterior auditory field as well as in the ventral and medial divisions of the medial geniculate body (MGBv and MGBm, respectively). Tracer injections into distinct zones of the BF map in AI retrogradely labeled topographically organized MGBv projections and weaker, mixed projections from MGBm. Stimulating MGBv along the tonotopic axis in the slice produced an orderly shift of voltage-sensitive dye (VSD) signals along the AI tonotopic axis, demonstrating topography in the mouse thalamocortical circuit that is preserved in the slice. However, compared with BF maps of neuronal spiking activity, the topographic order of subthreshold VSD maps was reduced in layer IV and even further degraded in layer II/III. Therefore, the precision of AI topography varies according to the source and layer of the mapping signal. Our findings further bridge the gap between in vivo and in vitro approaches for the detailed cellular study of auditory thalamocortical circuit organization and plasticity in the genetically tractable mouse model.

Background: Endoscopic laser ablation of placental vessels is now the preferred treatment for severe feto-fetal transfusion syndrome in twin gestations, and has been well-documented in triplet gestations as well., Case: Stage IV feto-fetal transfusion syndrome was diagnosed at 20.3 weeks of gestation between two of a set of monochorionic, tetramniotic quadruplets. Endoscopic laser ablation occurred at 20.4 weeks. Feto-fetal transfusion recurred at 22 weeks between the initial donor and the two previously unaffected fetuses. Delivery occurred at 24.9 weeks. The donor and one of the corecipients died shortly after birth. The sole survivor was doing well., Conclusion: Treatment of feto-fetal transfusion syndrome in higher-order gestations is challenging because of the increased pregnancy risks, the difficult angioarchitecture and the risk of recurrence.

Objective: The objective of the study was to develop a noninvasive technique to determine hemoglobin (Hb) content through spectral analysis of diffusely reflected broadband visible illumination from individual blood vessels during endoscopic fetal surgery for twin-to-twin transfusion syndrome (TTTS)., Methods: The reflection of an incoming xenon endoscopic light source was captured through a 630-mum-diameter optic fiber coupled to a fixed grating spectrometer (2-nm resolution). A 450- to 700-nm wavelength range was used for analysis. Three data-capturing methods were studied: (1) fixed-image spectrum capture with fiber aimed at (but not touching) center of a vessel, (2) no-touch scanning perpendicular to the vessel and dynamic spectral capture, and (3) dynamic spectral capture and analysis of the reflectance spectra during brief vessel touch., Results: Eight controls (elective laparoscopic and thoracoscopic operations in children aged 1-17 years) were enrolled. Four vessels were analyzed in each case. The brief-touch technique with intensity peak analysis yielded the most reproducible results between multiple vessels in the same patient. Spectrometry was also applied to 2 TTTS patients. The (anemic) donor and (polycythemic) recipient twin fetuses could be differentiated with good correlation between vessels (arteries and vein) of the same fetus., Conclusions: It is possible to differentiate donor from recipient placental vessels by spectral analysis of the reflected light through the endoscope using a noninvasive and real-time method. This may improve the accuracy of endoscopic laser ablation of placental vessels in TTTS and may allow instant endoscopic Hb determination for laparoscopic procedures as well., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To evaluate the outcome of twin-to-twin transfusion syndrome (TTTS) treated using a combination of endoscopic fetal surgery-specific techniques and surgical restraint., Summary Background Data: TTTS is a condition of identical twins that, if progressive and left untreated, leads to 100% mortality. The best treatment option is obliteration of the intertwin placental anastomoses, but fetal surgery carries significant maternal and fetal risks. Even if successful, percutaneous endoscopic laser ablation of placental vessels (LASER) causes premature rupture of membranes (PROM) in 10% to 20% of pregnancies. Patient selection is particularly critical because the progression of the disease is unpredictable. This has prompted many to intervene early, yielding survival rates of >=1 twin of 75% to 80%., Methods: We developed a minimally invasive approach to fetal surgery, a unique membrane sealing technique and a conservative algorithm that reserves intervention for severe TTTS. Pregnancies with TTTS (stages I-IV) managed in the last 8 years were reviewed. LASER was offered in stage III/IV only., Results: Ninety-eight cases of TTTS were managed in a pediatric surgery/maternal-fetal medicine collaborative Fetal Treatment Program-39 were observed (40%) and 59 underwent LASER (60%). Survival of >= twin was seen in 82.7%, and overall survival was 69.4%. These survival rates are similar to, or better than, other comparable series with similar stage distribution (low:high stage ratio 1:1) in which all patients underwent LASER. PROM rate was 4%., Conclusions: Reserving LASER treatment for severe TTTS results in outcomes similar to, or better than, LASER for all stages. Applying fetal surgery-specific endoscopic techniques, including port-site sealing, reduces postoperative complications.

Misoprostol is a synthetic prostaglandin E(1) analogue that is used off-label for a variety of indications in the practice of obstetrics and gynecology, including medication abortion, medical management of miscarriage, induction of labor, cervical ripening before surgical procedures, and the treatment of postpartum hemorrhage. Due to its wide-ranging applications in reproductive health, misoprostol is on the World Health Organization Model List of Essential Medicines. This article briefly reviews the varied uses of misoprostol in obstetrics and gynecology.

Twin pregnancies are associated with an increase in both fetal and maternal morbidity and mortality. Health care supervision is complex, increasingly requiring care from maternal-fetal medicine specialists. This review discusses optimal twin prenatal management, which includes recognizing increased twin pregnancy risks specific to twin-types; counseling families regarding fetal complications, ranging from prematurity to cerebral palsy; screening for aneuploidy and open neural tube defects; specific twin guidelines for diagnostic testing, including chorionic villus sampling and amniocentesis; and monitoring for maternal complications., (Copyright 2009 Wiley-Liss, Inc.)

Skin diseases are the third most common cause of morbidity in returning travellers and may affect 8% of travellers during travel. Classic tropical diseases account for one quarter and the remainder are cosmopolitan diseases. The majority are of infectious origin, and of these bacterial infections are the most common and lead to the most hospitalisations. The ten most frequently encountered diagnoses comprise four classical tropical infections (cutaneous larva migrans, myiasis, tungiasis and cutaneous leishmaniasis) and six nontropical diseases (bacterial skin infections, arthropod bites, allergic reactions, scabies, animal bites and superficial fungal infections). Other notable skin problems include swimmer's itch, dengue fever presenting with a rash and rickettsial infections presenting with a rash or eschar. Delayed diagnosis, especially of tropical diseases, is common and may be reduced by improved knowledge and a systematic approach to skin problems. This involves a thorough travel specific, traveller specific and skin problem based history, combined with targeted examination and investigations. A frequency weighted differential diagnosis of the most common skin lesions is presented. An increased emphasis on preventative advice in relation to skin disease is encouraged during pre-travel consultations.