Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Right and left ventricular 24-segment sphericity index is abnormal in small-for-gestational-age fetuses.

OBJECTIVE: Fetuses with growth restriction have been reported to have an abnormal sphericity index (SI), which is indicative of the shape of the ventricular chambers of the heart. Our aim was to evaluate the SI for 24 transverse segments distributed from base to apex of the right (RV) and left (LV) ventricles to determine whether, in small-for-gestational-age (SGA) fetuses, the SI is abnormal at locations other than the basal segment. METHODS: We evaluated 30 SGA fetuses between 25 and 37 weeks of gestation. SI was computed for both ventricles by dividing the end-diastolic mid-basal-apical length by each of 24 end-diastolic transverse segmental widths, from base (Segment 1) to apex (Segment 24). For each ventricle, the Z-score and centile for the SI from each of the 24 segments were computed using the mean and SD from published equations. The 24-segment method, defining abnormal SI as values < 10th centile or > 90th centile, was compared with that of using only the basal segment by chi-square analysis to determine the number of fetuses identified with an abnormal SI. RESULTS: In 23 of the 30 (77%) SGA fetuses, at least one of the 24 transverse segments in one or both ventricles had an abnormal SI; in 17% of cases, both ventricles were affected, in 23% of cases only the RV was involved and in 37% of cases only the LV was involved. Compared with the 24-segment model, significantly fewer fetuses with an abnormal SI were identified using only basal Segment 1, from the RV base (58%, 7/12; P < 0.01) or only Segment 12, in the mid portion of the RV (50%, 6/12; P < 0.005). Combining measurements of Segment 1 and Segment 12 from the RV identified 83% of fetuses with at least one abnormal SI and was not significantly different from using the 24-segment model. Similarly, significantly fewer fetuses with an abnormal SI were identified using only LV basal Segment 1 (63%, 10/16; P < 0.006) or only Segment 12, in the mid portion of the LV (75%, 12/16; P < 0.03), when compared with the 24-segment model. Combining measurements of both LV Segment 1 and Segment 12 identified 81% (13/16) of fetuses with an abnormal SI and was not significantly different from using the 24-segment model. CONCLUSION: The 24-segment SI of RV and LV provides a comprehensive method with which to examine the shape of the ventricular chambers and identifies more SGA fetuses with an abnormal SI than are identified using only the basal segment SI. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Epistasis in natural populations of a predominantly selfing plant.

Populations of predominantly selfing plant species often show spatial genetic structure but little is known whether epistatic gene interactions are spatially structured. To detect a possible epistatic effect and a spatial scale at which it operates, we created artificial crosses between plants spanning a range of fixed distances from 1 to 400 m in three populations of wild barley. The self-pollinated and crossed progeny (F(1)) and two generations of segregated progeny (F(2) and F(3)) were tested in experimentally simulated population environments for relative performance (RP). The measured fitness traits included number of seeds, total seed weight and seed germination. For any of these traits, there was no association between RP of F(1), F(2) and F(3) plants and either pairwise kinship coefficients or crossing distance. In contrast, in all three populations, we found lower seed viability of outcrossed as compared with self-pollinated genotypes in the first generation of segregation. However, in the F(3) generation this outbreeding effect disappeared in the two populations and greatly decreased in the third population. For seed production, heterosis in F(1) and outbreeding depression in F(2) were observed only in the population with unusually high number of heterozygotes. Our findings support the view that in selfing species a spatial mosaic of various locally abundant genotypes represents not randomly fixed combinations of alleles but the co-adapted gene complexes that were sieved by selection, while heterozygotes are characteristic for the transient phase of this process, when segregation and purging of maladaptive genotypes have not yet occurred.

Fine-scale spatial genetic structure in a predominantly selfing plant: role of seed and pollen dispersal.

We present a study of fine-scale spatial genetic structure (SGS) and assess the impact of seed and pollen dispersal on the pattern of genetic diversity in the predominantly selfing Hordeum spontaneum. The study included (1) direct measurement of dispersal in a controlled environment, and (2) analyses of SGS and estimation of the ratio of pollen to seed flow in three natural populations sampled in linear transects at fixed increasing inter-plant distances. Analysis of SGS with 10 nuclear SSRs showed in all three populations a significant autocorrelation for the distance classes of 1 or 2 m and a negative linear relationship between kinship coefficients, calculated for pairs of individuals, and logarithm of geographical distance between members of the pairs. Major seed dispersal (95%) was found to be within 1.2 m from the mother plant. Pollen flow, estimated from the comparison of nuclear and chloroplast variation, was spatially limited as much as was seed dispersal, and tended to be overestimated when measured at spatial scales exceeding that of SGS. We conclude that combined effects of selfing, occasional outcrossing, localized seed dispersal and high plant density create an equilibrium between drift and gene flow in this species resulting in SGS at a very fine spatial scale.

Analysis of mycorrhizal associations formed by Cistus incanus transformed root clones with Terfezia boudieri isolates.

One clone (M-2), out of several Agrobacterium rhizogenes transformed root clones of Cistus incanus, formed ecto- or endomycorrhiza in vitro with two isolates of Terfezia boudieri collected in Israel. All other clone-fungal isolate combinations formed ectomycorrhiza. The endomycorrhiza-forming isolate secreted smaller amounts of auxin than an ectomycorrhiza-forming isolate. Addition of 2,4-dichlorophenoxyacetic acid (2,4-D) led to ectomycorrhiza formation by the M-2 clone on low P medium. Endomycorrhizas were formed by both M-2 and a control clone with the same T. boudieri isolates on high P medium with 2,4-D. The M-2 clone of C. incanus exhibited greater sensitivity to exogenous auxins (IAA and 2,4-D) than other clones, and clonal sensitivity to auxin was increased tenfold under low P conditions. Results are discussed in relation to phosphate and auxin influence on T. boudieri-C. incanus interaction.

Single uterine axial fast acquisition magnetic resonance fetal survey: is it feasible?

OBJECTIVES: To determine which non-biometric components of the ultrasound fetal survey can routinely be seen on a single fast acquisition magnetic resonance (MR) sequence aligned axial to the maternal uterus. STUDY DESIGN: The non-biometric components of the routine fetal ultrasound examination were applied retrospectively to the initial MR single-shot fast spin-echo acquisition aligned axial to the maternal uterus in the normal fetus to determine whether these parameters could be routinely evaluated. Nineteen women with anatomically normal fetuses had a total of 31 MR studies performed for fetal or maternal indications, either as part of an indicated examination or as part of a study protocol approved by the institutional review board. The images in these 31 MR studies were reviewed by two independent examiners who were blinded to the other's assessment; concordance was necessary for a component to be adequately assessed. The Wilcoxon rank sum test was used to determine the effect of gestational age and fetal lie on the ability to assess non-biometric parameters. RESULTS: Assessment was possible in 85% of the non-biometric parameters. Cord insertion, external genitalia and the four-chamber view of the heart were most problematic. In only two cases was the four-chamber view of the heart identified. Longitudinal lie allowed significantly more parameters (82%) to be evaluated than transverse lie (45%) (p < 0.003). No difference based on gestational age was found. CONCLUSION: A single fast acquisition axial MR sequence can evaluate 85% of the non-biometric components of the fetal ultrasound survey. Fetal lie is an important confounder in the ability to resolve fetal anatomy with a single MR axial uterine acquisition.

Treatment of postcatheterisation false aneurysms: ultrasound-guided compression vs ultrasound-guided thrombin injection.

OBJECTIVES: to compare the efficacy and cost-effectiveness of ultrasound-guided compression (UGC) with ultrasound-guided thrombin injection (UGTI) for treatment of postcatheterisation arterial false aneurysms (cFA). DESIGN: prospective clinical study using historical controls. MATERIALS AND METHODS: we prospectively collected data on 33 consecutive patients diagnosed with cFA larger than 1.5 cm in diameter. These were treated with UGTI. We performed a retrospective review of data on a former group of 33 consecutive historical control patients that were treated by UGC. RESULTS: the groups were similar in respect of demographic and clinical variables. Thirty patients were suitable for UGC and 33 patients were suitable for UGTI. The success rate for UGC was 26/30 (87%) compared to 33/33 (100%) for UGTI (p<0.05). Thrombosis was achieved during the first treatment session in 7/26 patients treated by UGC, compared to 26/33 in the UGTI group (p<0.0001). Four patients that failed UGC and two patients that were unsuitable for UGC required surgical repair. UGTI as compared to UGC was shorter in duration (25 vs 75 min) and required no sedation. No thromboembolic or systemic complications occurred in either group. Cost analysis revealed savings of $US 517 for each patient treated by UGTI as compared with UGC. CONCLUSIONS: in our study, UGTI is superior to UGC, and we suggest that UGTI should become the procedure of choice for the treatment of cFA.

N-acetylcysteine replenishes glutathione in HIV infection.

BACKGROUND: Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. DESIGN: Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks. SUBJECTS: HIV-infected, low GSH, CD4 T cells < 500 micro L(-1), no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors. RESULTS: Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and beta2-microglobulin levels, also increased in the NAC-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion. CONCLUSION: NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.

Rapidly progressive stroke in a young adult with very low high-density lipoprotein cholesterol.

Ischemic strokes can affect young adults (15-45 years old). Most such strokes are caused by cardioembolic events, small vessel disease, or illicit drug use, and less frequently by large vessel atherosclerosis. Large vessel cerebral atherosclerosis is usually associated with high levels of low-density lipoprotein (LDL) cholesterol, but a low level of high-density lipoprotein (HDL) is also a risk factor for ischemic strokes. The magnitude of increased risk is unclear, particularly with extremely low HDL levels found only in various genetic and inherited disorders. Advanced atherosclerosis developed in the patient in this study, with HDL of 3 mg/dL, leading to rapidly progressive stroke with a fatal outcome. The disease primarily affected the posterior circulation. The course of this case illustrates that very low HDL may be associated with advanced cerebrovascular atherosclerosis and fatal stroke, and as such should be considered in young individuals with stroke.

Rapidly progressive, acute polyradiculopathies and cranial neuropathies resulting from leptomeningeal nasal-type NK cell lymphoma.

Lymphomas may cause polyradiculopathies by several pathogenic mechanisms. However, such a presentation of a nasal-type NK (natural killer) cell lymphoma is rare. We report a previously healthy man who developed acute, axon-loss radiculopathies and cranial neuropathies. Despite the lack of a nasal or midline facial mass, cerebrospinal fluid cytologic and flow cytometric immurtophenotypic studies disclosed that the patient's rapid demise was the result of a nasal-type NK cell lymphoma with leptomeningeal involvement.

AZT toxicity and AIDS prophylaxis: is AZT beneficial for HIV+ asymptomatic persons with 500 or more T4 cells per cubic millimeter?

Analyses of the effects of prophylactic use of zidovudine (AZT) on progression to acquired immune deficiency syndrome (AIDS) in human immunodeficiency virus seropositive (HIV+) asymptomatic persons with T4 lymphocyte (CD4+) cell counts > or = 500/mm3 is reported for data obtained from two studies, the Australian European Group Collaborative Study, a multi-centered double-blind placebo-controlled clinical trial of the effects of AZT on progression to AIDS and other clinical endpoints, and the San Francisco Men's Health Study, an observational cohort. The analyses of the data of both studies demonstrate no benefit from AZT treatment in terms of progression to AIDS for those who are asymptomatic with CD4+ cell counts > or = 500/mm3. The analysis of the San Francisco study, performed with Kaplan-Meier survivorship estimates, indicates a heterogeneity in the efficacy of AZT between baseline CD4+ cell count strata, 200-499/mm3 and 500-800/mm3. Within the 200-499 stratum, 47% of those receiving AZT therapy and 62% of those not receiving AZT therapy progressed to AIDS during the study period. By contrast, within the 500-800 stratum 41% of those receiving AZT therapy and 27% of those not receiving AZT therapy progressed to AIDS during the same period. Application of the Cox proportional hazards survivorship regression model for the relative risk of progression to AIDS to these same data accounts for this heterogeneity. The model includes an interaction between AZT treatment and baseline CD4+ cell counts. The hematological toxicity of AZT, demonstrated in clinical studies and laboratory investigations, indicates a biological correlate for this interaction: the toxic effects of AZT on the more intact immune system of those with CD4+ cell counts in the 500-800/mm3 range [corrected].

Anatomy and electrophysiology of individual neurosecretory cells of an insect brain.

The structure and electrophysiological properties of individual neurosecretory cells of the pars intercerebralis, medial neurosecretory cells (MNSCs), in the brain of an insect, the cricket Teleogryllus commodus, were investigated by means of intracellular injections of the dye Lucifer Yellow and electrophysiological recordings. Action potentials recorded from these cells were of long duration, 8-50 msec. In the pars intercerebralis there are both neurosecretory cells with axons that join one of the tracts of the nervi corpori cardiaci I (NCC I) and cells without an axon or collateral that leaves the brain, local neurosecretory cells. MNSCs with axons that join NCC I and terminate in the anterior corpus cardiacum arborize extensively in the protocerebrum and to a lesser degree in the deutocerebrum. Other MNSCs have axons that pass through the corpus cardiacum and hypocerebral ganglion and join one of the oesophageal nerves. These MNSCs have sparse collateral arborizations in the protocerebrum but do have extensive terminal arborizations in the tritocerebrum. This type of cell is dye-coupled to other MNSCs. Among the local MNSCs, some have an unusual loop shape. These cells branch extensively in the protocerebrum and have massive terminal arborizations in a posterior ventromedial region of the brain. Both the long curved axons of the loop-shaped cells and their ventromedial branches are of large diameter, suitable for storage of neurosecretory material.

Quantitative measurements of centrally and retinally generated saccadic suppression in a locust movement detector neurone.

1. Chronic recordings from tethered but otherwise freely moving locusts demonstrate that the response of the descending contralateral movement detector (d.c.m.d.) neurone, an identified visual interneurone of the brain, is greatly reduced during the performance of saccades. 2. The reduction in the response of the d.c.m.d. is effected by both a centrally generated corollary discharge and the changing contrast of the image of the visual background on the retina. 3. The corollary discharge that is concomitant with a saccade reduces the d.c.m.d. response by 0 . 94 log units, and this reduction is independent of contrast frequency. 4. Changing contrast produced by relative motion of eye and background reduces the sensitivity of the d.c.m.d. neurone by 0 . 16 log units for each 10-fold increase in contrast frequency. This retinally generated reduction in sensitivity is not significantly different whether the locust performs saccades or is fixating with the visual background passively moved. The maximal reduction in the d.c.m.d. response by retinal sources is 0 . 45 log units. 5. Proprioceptive reafference does not contribute significantly to saccadic suppression of the response of the d.c.m.d. neurone.

A new auditory area of the songbird forebrain: a connection between auditory and song control centers.

Single unit microelectrode recordings followed by electrolytic lesions which mark the recording sites demonstrate that there is an auditory region of the songbird forebrain that is distinct from and superficial to field L, the primary auditory region of the telencephalon. The location of the superficial auditory area and its large cells suggest identification with HVc, the large-celled telencephalic nucleus which controls song in the canary.