Ultrasound-Guided Bilateral Transverses Abdominis Plane Block Versus Bilateral Quadratus Lumborum Block on Postoperative Analgesia in Women Undergoing Total Laparoscopic Hysterectomy

Background: No trials were comparing the Bilateral Quadratus lumborum (QL) block versus transverses abdominis plane (TAP) block in patients undergoing laparoscopic hysterectomy. Hence the present study compared the ultrasound-guided bilateral TAP and QL blocks in patients undergoing total laparoscopic hysterectomy and measured the pain score, rescue anesthesia requirement, adverse events, and patient satisfaction. Materials and Methods: This prospective randomized controlled open-labeled study was conducted on 140 adult female patients (ASA I-II) who were scheduled for total laparoscopic hysterectomy. Patients were randomized into two equal groups of 70 each (group TAP and group QL). Each patient received either Ultrasound-guided bilateral TAP or QL block after completion of laparoscopic hysterectomy under general anesthesia. Patients were monitored for Visual Analogue Scale (VAS) scores postoperatively, time for first analgesic requirement, and adverse effects if any. Independent t-test and Chi-square test were used for statistical analysis. Results: Group QL showed significantly better VAS scores up to 24 hr postoperatively. VAS scores were significantly higher in group TAP than in group QL at all intervals postoperatively (p<0.05), the duration of postoperative analgesia was significantly shorter in group TAP than in group QL (p<0.05), and the total analgesic requirement was lesser in group QL than group TAP (p<0.05). Time for the first request for rescue analgesia was significantly longer in the group QL than in group TAP (497.774±35.45 vs 247.55±11.71min, p<0.001), and its consumption was significantly lesser in the group QL than in group TAP (72.1428±18.328 vs 138.57±25.77mg). The time for the first analgesic demand (Tramadol) was prolonged in group QL than in group TAP (15.1± 2.12 vs 4.35 ±5 hours). The sensory level was higher in the group QL than in the group TAP with a significant difference (7.92±0.51 vs 5.97±0.35, p<0.001). Three patients (4.28%) in the group QL experienced vomiting versus 6 (8.57%) in group TAP. Patient satisfaction score was comparable between group TAP and group QL (4.78 ± 0.45 vs 4.22 ± 0.42). Conclusion: Bilateral QL block provided a better postoperative analgesia technique than bilateral TAP block in women undergoing laparoscopic hysterectomy

Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases

Contact lens rehabilitation following repaired corneal perforations

BACKGROUND: Visual outcome following repair of post-traumatic corneal perforation may not be optimal due to presence of irregular keratometric astigmatism. We performed a study to evaluate and compare rigid gas permeable contact lens and spectacles in visual rehabilitation following perforating corneal injuries. METHOD: Eyes that had undergone repair for corneal perforating injuries with or without lens aspiration were fitted rigid gas permeable contact lenses. The fitting pattern and the improvement in visual acuity by contact lens over spectacle correction were noted. RESULTS: Forty eyes of 40 patients that had undergone surgical repair of posttraumatic corneal perforations were fitted rigid gas permeable contact lenses for visual rehabilitation. Twenty-four eyes (60%) required aphakic contact lenses. The best corrected visual acuity (BCVA) of ≥ 6/18 in the snellen's acuity chart was seen in 10 (25%) eyes with spectacle correction and 37 (92.5%) eyes with the use of contact lens (p < 0.001). The best-corrected visual acuity with spectacles was 0.20 ± 0.13 while the same with contact lens was 0.58 ± 0.26. All the patients showed an improvement of ≥ 2 lines over spectacles in the snellen's acuity chart with contact lens. CONCLUSION: Rigid gas permeable contact lenses are better means of rehabilitation in eyes that have an irregular cornea due to scars caused by perforating corneal injuries

An AP Endonuclease 1–DNA Polymerase β Complex: Theoretical Prediction of Interacting Surfaces

Abasic (AP) sites in DNA arise through both endogenous and exogenous mechanisms. Since AP sites can prevent replication and transcription, the cell contains systems for their identification and repair. AP endonuclease (APEX1) cleaves the phosphodiester backbone 5′ to the AP site. The cleavage, a key step in the base excision repair pathway, is followed by nucleotide insertion and removal of the downstream deoxyribose moiety, performed most often by DNA polymerase beta (pol-β). While yeast two-hybrid studies and electrophoretic mobility shift assays provide evidence for interaction of APEX1 and pol-β, the specifics remain obscure. We describe a theoretical study designed to predict detailed interacting surfaces between APEX1 and pol-β based on published co-crystal structures of each enzyme bound to DNA. Several potentially interacting complexes were identified by sliding the protein molecules along DNA: two with pol-β located downstream of APEX1 (3′ to the damaged site) and three with pol-β located upstream of APEX1 (5′ to the damaged site). Molecular dynamics (MD) simulations, ensuring geometrical complementarity of interfaces, enabled us to predict interacting residues and calculate binding energies, which in two cases were sufficient (∼−10.0 kcal/mol) to form a stable complex and in one case a weakly interacting complex. Analysis of interface behavior during MD simulation and visual inspection of interfaces allowed us to conclude that complexes with pol-β at the 3′-side of APEX1 are those most likely to occur in vivo. Additional multiple sequence analyses of APEX1 and pol-β in related organisms identified a set of correlated mutations of specific residues at the predicted interfaces. Based on these results, we propose that pol-β in the open or closed conformation interacts and makes a stable interface with APEX1 bound to a cleaved abasic site on the 3′ side. The method described here can be used for analysis in any DNA-metabolizing pathway where weak interactions are the principal mode of cross-talk among participants and co-crystal structures of the individual components are available

Increased sensitivity for detecting malaria parasites in human umbilical cord blood using scaled-up DNA preparation

BACKGROUND: All mothers donating umbilical cord blood units to the NHS cord blood bank undergo an assessment for the likelihood of prior exposure to malaria infection. Those deemed at risk due to a history of travel to, or residence in, malaria endemic regions are screened serologically to detect anti-malaria antibodies. A positive result excludes the use of the cord blood for transplant therapy unless a risk assessment can ensure that malaria transmission is extremely unlikely. This paper details the screening of cord blood units from malaria serology positive mothers to detect malaria parasite DNA using a highly sensitive nested PCR. METHODS: Uninfected blood from a healthy volunteer was spiked with known quantities of malaria parasites and 5 millilitre and 200 microlitre aliquots were subjected to DNA extraction using QIAamp DNA maxi and DNA mini kits respectively. Nested PCR, to detect malarial SSU rRNA sequences, was performed on the purified DNA samples to determine the limit of detection for this assay with both extraction methodologies. Following assay validation, 54 cord blood units donated by mothers who were positive for anti-malaria antibodies were screened by this approach. RESULTS: When DNA was purified from 5 millilitres of blood it was possible to routinely detect as few as 50 malaria parasites per millilitre using nested PCR. This equates to a significant increase in the sensitivity of the current gold standard nucleic acid amplification technique used to detect malaria parasites (routinely performed from > 200 microlitre volumes of blood). None of the 54 donated cord blood units from serology positive mothers tested positive for malaria parasites using this scaled up DNA preparation method. CONCLUSION: Serological testing for malaria parasites may be overly conservative, leading to unnecessary rejection of cord blood donations that lack malaria parasites and which are, therefore, safe for use in stem cell therapy

Visual ecology of aphids – a critical review on the role of colours in host finding

We review the rich literature on behavioural responses of aphids (Hemiptera: Aphididae) to stimuli of different colours. Only in one species there are adequate physiological data on spectral sensitivity to explain behaviour crisply in mechanistic terms. Because of the great interest in aphid responses to coloured targets from an evolutionary, ecological and applied perspective, there is a substantial need to expand these studies to more species of aphids, and to quantify spectral properties of stimuli rigorously. We show that aphid responses to colours, at least for some species, are likely based on a specific colour opponency mechanism, with positive input from the green domain of the spectrum and negative input from the blue and/or UV region. We further demonstrate that the usual yellow preference of aphids encountered in field experiments is not a true colour preference but involves additional brightness effects. We discuss the implications for agriculture and sensory ecology, with special respect to the recent debate on autumn leaf colouration. We illustrate that recent evolutionary theories concerning aphid–tree interactions imply far-reaching assumptions on aphid responses to colours that are not likely to hold. Finally we also discuss the implications for developing and optimising strategies of aphid control and monitoring

Cardiorespiratory fitness, fatness and the acute blood pressure response to exercise in adolescence

Objective: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) areindependent contributors to cardiovascular risk, but their interrelated associationswith exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness, and the acute BP response to exercise in a large birth cohort ofadolescents.Methods: 2292 adolescents from the Avon Longitudinal Study of Parents andChildren (aged 17.8 ± 0.4 years, 38.5% male) completed a sub-maximal exercisestep test that allowed fitness (VO2 max) to be determined from workload and heart rateusing a validated equation. Exercise BP was measured immediately on test cessationand fatness calculated as the ratio of total fat mass to total body mass measured byDXA.Results: Post-exercise systolic BP decreased stepwise with tertile of fitness (146(18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142(16); 149 (18) mmHg). In separate models, fitness and fatness were associated withpost-exercise systolic BP adjusted for sex, age, height, smoking, and socioeconomicstatus (standardized β: −1.80, 95%CI: −2.64, −0.95 mmHg/SD and 4.31, 95%CI:3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in thesame model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69,5.61 mmHg/SD).Conclusion: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness mayonly be realized with more favorable body composition

Open Problems on Central Simple Algebras

We provide a survey of past research and a list of open problems regarding central simple algebras and the Brauer group over a field, intended both for experts and for beginners.Comment: v2 has some small revisions to the text. Some items are re-numbered, compared to v

Diagnosis and treatment trends in mucopolysaccharidosis I: findings from the MPS I Registry

Our objective was to assess how the diagnosis and treatment of mucopolysaccharidosis I (MPS I) have changed over time. We used data from 891 patients in the MPS I Registry, an international observational database, to analyze ages at symptom onset, diagnosis, treatment initiation, and treatment allocation (hematopoietic stem cell transplantation, enzyme replacement therapy with laronidase, both, or neither) over time for all disease phenotypes (Hurler, Hurler–Scheie, and Scheie syndromes). The interval between diagnosis and treatment has become shorter since laronidase became available in 2003 (gap during 2006–2009: Hurler—0.2 year, Hurler–Scheie—0.5 year, Scheie—1.4 years). However, the age at diagnosis has not decreased for any MPS I phenotype over time, and the interval between symptom onset and treatment initiation remains substantial for both Hurler–Scheie and Scheie patients (gap during 2006–2009, 2.42 and 6.71 years, respectively). Among transplanted patients, an increasing proportion received hematopoietic stem cells from cord blood (34 out of 64 patients by 2009) and was also treated with laronidase (42 out of 45 patients by 2009). Conclusions: Despite the availability of laronidase since 2003, the diagnosis of MPS I is still substantially delayed for patients with Hurler–Scheie and Scheie phenotypes, which can lead to a sub-optimal treatment outcome. Increased awareness of MPS I signs and symptoms by primary care providers and pediatric subspecialists is crucial to initiate early treatment and to improve the quality of life of MPS I patients