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Heart Failure Reviews Nov 2021The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important... (Meta-Analysis)
Meta-Analysis Review
The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important characteristics that define the degree of cardiac remodeling in this model. A systematic review and meta-analyses were performed on studies using the TAC mouse/rat model and reporting echocardiographic outcome parameters. We included all animal studies in which a constriction around the transverse aorta and at least one of the predefined echocardiography or MRI outcome parameters were assessed. A total of 502 articles and > 3000 wild-type, untreated animals undergoing TAC were included in this study and referenced to a control group. The duration of aortic constriction correlated to the degree of adverse remodeling. However, the mouse data is strongly biased by the preferential use of male C57Bl/6 mice (66% of studies). Furthermore, mostly ketamine/xylazine anesthetics, 27G needle constriction, and silk sutures are used. Nonetheless, despite the homogeneity in experimental design, the model contained a substantial degree of heterogeneity in the functional outcome measures. When looking at study quality, only 12% reported randomization, 23% mentioned any sort of blinding, 25% adequately addressed the outcomes, and an amazingly low percentage (2%) showed sample size calculation. Meta-analyses did not detect specific study characteristics that explained the heterogeneity in the reported outcome measures, however this might be related to the strong bias towards the use of specific mouse lines, sex as well as age or to poor reporting of characteristics of study quality.
Topics: Animals; Aorta; Constriction; Echocardiography; Female; Heart Failure; Humans; Male; Mice; Mice, Inbred C57BL; Rats
PubMed: 32335789
DOI: 10.1007/s10741-020-09960-w -
Journal of Perinatology : Official... Feb 2017Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an... (Review)
Review
Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut-umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution.
Topics: Blood Component Transfusion; Constriction; Female; Humans; Infant, Newborn; Infant, Premature; Placenta; Practice Guidelines as Topic; Pregnancy; Randomized Controlled Trials as Topic; Time Factors; Umbilical Cord
PubMed: 27654493
DOI: 10.1038/jp.2016.151 -
European Journal of Pediatrics Aug 2023Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group,... (Randomized Controlled Trial)
Randomized Controlled Trial
Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate. Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia. Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Infant, Premature; Polycythemia; Aftercare; Umbilical Cord Clamping; Patient Discharge; Anemia; Iron Deficiencies; Hyperbilirubinemia, Neonatal; Constriction; Ferritins; Umbilical Cord; Delivery, Obstetric
PubMed: 37278737
DOI: 10.1007/s00431-023-05053-6 -
Clinics in Perinatology Aug 2021Keeping the umbilical cord intact after delivery facilitates transition from fetal to neonatal circulation and allows a placental transfusion of a considerable amount of... (Review)
Review
Keeping the umbilical cord intact after delivery facilitates transition from fetal to neonatal circulation and allows a placental transfusion of a considerable amount of blood. A delay of at least 3 minutes improves neurodevelopmental outcomes in term infants. Although regarded as common sense and practiced by many midwives, implementation of delayed cord clamping into practice has been unduly slow, partly because of beliefs regarding theoretic risks of jaundice and lack of understanding regarding the long-term benefits. This article provides arguments for delaying cord clamping for a minimum of 3 minutes.
Topics: Blood Transfusion; Constriction; Female; Humans; Infant, Newborn; Placenta; Pregnancy; Time Factors; Umbilical Cord
PubMed: 34353575
DOI: 10.1016/j.clp.2021.05.002 -
Archivos Argentinos de Pediatria Aug 2021For several years now, the survival of preterm infants has been increasing, which has shifted our concern to preterm infants born before 28 weeks of gestation in... (Review)
Review
For several years now, the survival of preterm infants has been increasing, which has shifted our concern to preterm infants born before 28 weeks of gestation in particular. The timing of umbilical cord clamping may lead to several disorders, especially when done early (10-15 seconds). In the last two decades, several investigations have shown the considerable benefits of delayed cord clamping (2-3 minutes). Delayed cord clamping has been practiced in obstetrics and neonatal care based on the recommendations made by scientific societies and in systematic reviews, which have provided solid evidence to support this practice in preterm infants. This review describes the most relevant articles from the last years, which strongly support the use of delayed cord clamping versus early cord clamping. In addition, this practice reduces the rate of severe disorders in preterm infants.
Topics: Constriction; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Parturition; Pregnancy; Systematic Reviews as Topic; Umbilical Cord
PubMed: 34309309
DOI: 10.5546/aap.2021.eng.e315 -
Nature Chemical Biology Sep 2022Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a is widely used for genome editing and diagnostics, so it is important to understand how...
Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a is widely used for genome editing and diagnostics, so it is important to understand how RNA-guided DNA recognition activates the cleavage of the target strand (TS) following non-target-strand (NTS) cleavage. Here we used single-molecule magnetic tweezers, gel-based assays and nanopore sequencing to explore DNA unwinding and cleavage. In addition to dynamic and heterogenous R-loop formation, we also directly observed transient double-stranded DNA unwinding downstream of the 20-bp heteroduplex and, following NTS cleavage, formation of a hyperstable 'clamped' Cas12a-DNA intermediate necessary for TS cleavage. Annealing of a 4-nucleotide 3' CRISPR RNA overhang to the unwound TS downstream of the heteroduplex inhibited clamping and slowed TS cleavage by ~16-fold. Alanine substitution of a conserved aromatic amino acid in the REC2 subdomain that normally caps the R-loop relieved this inhibition but favoured stabilisation of unwound states, suggesting that the REC2 subdomain regulates access of the 3' CRISPR RNA to downstream DNA.
Topics: CRISPR-Cas Systems; Constriction; DNA; DNA Cleavage; Gene Editing; Nucleic Acid Conformation; RNA; RNA, Guide, CRISPR-Cas Systems
PubMed: 35836018
DOI: 10.1038/s41589-022-01082-8 -
Cardiovascular Journal of AfricaClamp application is safe and widely used in the visceral organs. This raises the question: why not use clamping in orthopaedic, oncological, fracture and revision...
BACKGROUND
Clamp application is safe and widely used in the visceral organs. This raises the question: why not use clamping in orthopaedic, oncological, fracture and revision surgeries of areas where tourniquets are not suitable. This experimental animal study aimed to compare tourniquet and arterial clamp applications with regard to their histological effects and inflammatory responses on a molecular level, on the artery, vein, nerve and muscle tissue.
METHODS
Twenty-one rabbits were divided into three groups (group I: proximal femoral artery clamp; group II: proximal thigh tourniquet; and group III: control group). In the clamp group, the common femoral artery was clamped with a microvascular clamp for two hours. In the tourniquet group, a 12-inch cuff was applied to the proximal thigh for two hours at 200 mmHg. The common femoral artery, vein, nerve, rectus femoris and tibialis anterior muscles were excised and analysed in all groups.
RESULTS
Artery and vein endothelial injuries were found in the clamp and tourniquet groups (relative to the control group, ≤ 0.001 and = 0.007, respectively). However, no difference was found between the clamp and tourniquet groups regarding vessel wall injury.
CONCLUSIONS
We found there were no differences in incidence of vessel, muscle and nerve injury when comparing the tourniquet and clamp applications. For surgical procedures that are unsuited to a tourniquet, arterial clamping can be selected, resulting in close-to-tourniquet vessel injury rates but without tourniquet-related complications.
Topics: Animals; Constriction; Femoral Artery; Lower Extremity; Muscle, Skeletal; Rabbits; Tourniquets
PubMed: 34292289
DOI: 10.5830/CVJA-2021-023 -
Nature Communications Jan 2023Apical constriction is a cell shape change critical to vertebrate neural tube closure, and the contractile force required for this process is generated by actin-myosin...
Apical constriction is a cell shape change critical to vertebrate neural tube closure, and the contractile force required for this process is generated by actin-myosin networks. The signaling cue that instructs this process has remained elusive. Here, we identify Wnt4 and the transmembrane ephrinB2 protein as playing an instructive role in neural tube closure as members of a signaling complex we termed WERDS (Wnt4, EphrinB2, Ror2, Dishevelled (Dsh2), and Shroom3). Disruption of function or interaction among members of the WERDS complex results in defects of apical constriction and neural tube closure. The mechanism of action involves an interaction of ephrinB2 with the Dsh2 scaffold protein that enhances the formation of the WERDS complex, which in turn, activates Rho-associated kinase to induce apical constriction. Moreover, the ephrinB2/Dsh2 interaction promotes non-canonical Wnt signaling and shows how cross-talk between two major signal transduction pathways, Eph/ephrin and Wnt, coordinate morphogenesis of the neural tube.
Topics: Ephrin-B2; Constriction; Signal Transduction; Morphogenesis; Neural Tube
PubMed: 36670115
DOI: 10.1038/s41467-023-35991-6 -
Birth (Berkeley, Calif.) Dec 2022Umbilical cord clamp timing has implications for newborn health, which include increased iron stores up to 6 months of age. National and International cord clamping... (Review)
Review
BACKGROUND
Umbilical cord clamp timing has implications for newborn health, which include increased iron stores up to 6 months of age. National and International cord clamping guidelines differ as do health professionals' practices. The rationale for differences in cord clamping practice is unclear.
AIMS AND OBJECTIVE
Studies on the knowledge, attitudes, and practices of maternity health care professionals about cord clamp timing were synthesized. Similarities and differences between professional groups and understanding of the optimal timing of cord clamp timing for term newborns were compared.
METHODS
An integrative review was undertaken. PubMed, Scopus, MIDIRS, CINAHL, and Google Scholar were searched. Publication date limits were set between January 2007 and December 2020. Quality appraisal was undertaken using the Critical Appraisal Skills Program (CASP) tools.
RESULTS
Eighteen studies met inclusion criteria, as they included primary research studies that investigated maternity health care professionals' knowledge, attitudes, and practices about umbilical cord clamping, and were written in English. Four main subject areas were identified: a) knowledge of optimal cord clamp timing; b) attitudes and perceptions of early vs deferred cord clamping; c) cord clamping practice; and d) rationale for cord clamping practice.
CONCLUSIONS
Different attitudes and practices were identified between midwifery and medical professionals in relation to cord clamp timing together with health professional knowledge and practice gaps pertaining to optimal cord clamp timing. Contemporary evidence should inform guidelines for clinical practice and be embedded into maternity health professional curricula and professional development programs.
Topics: Humans; Infant, Newborn; Female; Pregnancy; Umbilical Cord; Umbilical Cord Clamping; Health Knowledge, Attitudes, Practice; Time Factors; Constriction; Health Personnel
PubMed: 35582849
DOI: 10.1111/birt.12647 -
ELife Apr 2022Previously we reported that Synaptotagmin-1 and Complexin synergistically clamp the SNARE assembly process to generate and maintain a pool of docked vesicles that fuse...
Previously we reported that Synaptotagmin-1 and Complexin synergistically clamp the SNARE assembly process to generate and maintain a pool of docked vesicles that fuse rapidly and synchronously upon Ca influx (Ramakrishnan et al., 2020). Here, using the same in vitro single-vesicle fusion assay, we determine the molecular details of the Complexin-mediated fusion clamp and its role in Ca-activation. We find that a delay in fusion kinetics, likely imparted by Synaptotagmin-1, is needed for Complexin to block fusion. Systematic truncation/mutational analyses reveal that continuous alpha-helical accessory-central domains of Complexin are essential for its inhibitory function and specific interaction of the accessory helix with the SNAREpins enhances this functionality. The C-terminal domain promotes clamping by locally elevating Complexin concentration through interactions with the membrane. Independent of their clamping functions, the accessory-central helical domains of Complexin also contribute to rapid Ca-synchronized vesicle release by increasing the probability of fusion from the clamped state.
Topics: Adaptor Proteins, Vesicular Transport; Calcium; Constriction; Membrane Fusion; Nerve Tissue Proteins; SNARE Proteins; Synaptic Vesicles
PubMed: 35442188
DOI: 10.7554/eLife.71938