The adductor canal block has become a common analgesic technique in patients undergoing knee arthroplasty. Dispersion of local anesthetic outside the adductor canal through interfascial layers and ...blockade of smaller nerves that confer innervation to the knee could contribute to the analgesic efficacy of the adductor canal block. We studied the diffusion of local anesthetic mixed with dye after injection into the adductor canal in fresh human cadavers. In all 8 legs, injectate was found in the popliteal fossa in contact with the sciatic nerve and/or popliteal blood vessels. Interfascial spread patterns were identified.
The Microprocessor complex (DGCR8/Drosha) is required for microRNA (miRNA) biogenesis but also binds and regulates the stability of several types of cellular RNAs. Of particular interest, DGCR8 ...controls the stability of mature small nucleolar RNA (snoRNA) transcripts independently of Drosha, suggesting the existence of alternative DGCR8 complex(es) with other nucleases to process a variety of cellular RNAs. Here, we found that DGCR8 copurifies with subunits of the nuclear exosome, preferentially associating with its hRRP6-containing nucleolar form. Importantly, we demonstrate that DGCR8 is essential for the recruitment of the exosome to snoRNAs and to human telomerase RNA. In addition, we show that the DGCR8/exosome complex controls the stability of the human telomerase RNA component (hTR/TERC). Altogether, these data suggest that DGCR8 acts as an adaptor to recruit the exosome complex to structured RNAs and induce their degradation.
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•DGCR8 forms an alternative complex with the hRRP6-containing form of the exosome•DGCR8 acts as an adaptor to recruit the exosome to target structured RNAs•The DGCR8/hRRP6 complex also controls the stability of human telomerase RNA
DGCR8 is part of the Microprocessor, a complex required for miRNA biogenesis. Macias et al. report that DGCR8 forms an alternative complex with the exosome, acting as an adaptor to recruit the exosome to mature snoRNAs and human telomerase RNA for degradation.
Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid ...disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.
The analgesic efficacy reported for the adductor canal block may be related to the spread of local anesthetic outside the adductor canal.
Fifteen patients undergoing knee surgery received ...ultrasound-guided injections of local anesthetic at the level of the adductor hiatus. Sensory-motor block and spread of contrast solution were assessed.
Sensation was rated as "markedly diminished" or "absent" in the saphenous nerve distribution and "slightly diminished" in the sciatic nerve territory without motor deficits. Contrast solution was found in the popliteal fossa.
The spread of injectate to the popliteal fossa may contribute to the analgesic efficacy of adductor canal block.
The use of ultrasound to monitor needle placement and spread of local anesthetics (LA) has allowed reductions in the volume of LA required to anesthetize peripheral nerves. In the current study we ...investigated the minimal volume necessary to accomplish surgical anesthesia with interscalene brachial plexus block.
Twenty ASA physical status I-III patients, ages 18 to 75 years and scheduled for shoulder surgery under interscalene brachial plexus block, were enrolled. Using a previously validated step-up/step-down method, we determined the injection volume of 0.75% ropivacaine used for consecutive patients by the outcome of the preceding block. The starting volume was 15 mL (3 injections of 5 mL per each trunk); in the case of block failure, the volume was increased by 1 mL, whereas after successful block, the volume was reduced by 1 mL. The study was stopped upon achieving the secondary stopping rule of 10 consecutive successful interscalane blocks using 5 mL of ropivacaine 0.75%. Successful surgical anesthesia with the brachial plexus block was defined as presence of adequate motor block (motor score of ≤2 on 0 to 4 scale), absent sensation to cold and pinprick sensation within 30 minutes of injection, and absence of the need for general anesthesia for completion of surgery. Duration of sensory blockade was assessed by asking the patient to record the time of first pain sensation.
Under our study conditions, successful surgical anesthesia for arthroscopic shoulder surgery can be achieved with 5 mL of 0.75% ropivacaine, or approximately 1.7 mL per each of the 3 trunks of the brachial plexus (superior, middle, and inferior). The study was stopped after 10 consecutive successful blocks with 5 mL of LA (100%, 95% confidence interval CI: 74.1%-100%). For the group as a whole, the median (range) sensory block onset time was 5 (5-20) minutes, the median (range) motor block for the biceps was 7.5 (5-15) minutes, and for abduction 10 (5-15) minutes. The median (range) block duration was 9.9 (5-19) hours, and the mean (SD) block performance time was 8.0 ± 3.2 minutes. Mean duration of analgesia was 9.9 ± 3.7 hours. Duration of analgesia was not associated with volume of LA (r = 0.05, P = 0.83).
All patients in our study had successful surgical blocks with 5 mL of LA. However, the lower limit of the CI (calculated on the assumption of a single failure) does include the possibility of a 25% failure rate; thus studies using similar stopping rules for doses higher than 5 mL are nonetheless warranted.
Spinal anesthesia with intrathecal morphine (ITM) is a common anesthesia technique for cesarean delivery. The hypothesis was that the addition of ITM will delay micturition in women undergoing ...cesarean delivery.
Fifty-six ASA physical status I and II women scheduled to undergo elective cesarean delivery under spinal anesthesia were randomized to the PSM group (50 mg prilocaine + 2.5 mcg sufentanil + 100 mcg morphine; n = 30) or PS group (50 mg prilocaine + 2.5 mcg sufentanil; n = 24). The patients in the PS group received a bilateral transverse abdominal plane (TAP) block. The primary outcome was the effect of ITM on the time to micturition and the secondary outcome was the need for bladder re-catheterization.
The time to first urge to urinate (8 6−10 hours in the PSM group versus 6 4−6 hours in the PS group) and the time to first micturition (10 8−12 hours in the PSM group versus 6 6−8 hours in the PS group) were significantly (p < 0.001) prolonged in the PSM group. Two patients in the PSM group met the 800 mL criterium for urinary catheterization after 6 and 8 h respectively.
This study is the first randomized trial to demonstrate that the addition of ITM to the standardized mixture of prilocaine and sufentanil significantly delayed micturition.
Acquired deficiencies in platelet glycoprotein VI are rare and have not been found associated with other defects. Here we report the case of a 64-year old male patient presenting an immune GPVI ...deficiency associated to a mutation in the alpha-actinin gene and who has been treated with dual anti platelet therapy without bleeding.Introduction: Glycoprotein (GP) VI, a pluripotent receptor interacting with collagen and fibrin(ogen) is responsible for thrombus formation, growth and stability (1-4). It is co-expressed with the Fc receptor γ (FcRγ) chain (5). GPVI is not critical for haemostasis since subjects with a GPVI deficiency usually present low or even no bleeding tendency (6, 7). Acquired GPVI deficiency due to antibody-induced GPVI depletion is the most frequent finding. At least 10 patients have been described with an acquired GPVI deficiency, most often associated to immune thrombocytopenia, moderate bleeding and impaired collagen-induced platelet aggregation (7). Several mechanisms leading to the GPVI deficiency are proposed including antibody-triggered GPVI internalization and/or shedding of the extracellular domain (8, 9).We report the case of a patient presenting an acquired GPVI deficiency different from those previously described: (i) he is male whereas all previous cases were female, (ii) he is heterozygous for a mutation in α (alpha)-actinin-1 gene and (iii) he was treated with dual antiplatelet therapy with no haemorrhagic manifestation.
Brittle cornea syndrome (BCS) is a rare recessive condition characterised by extreme thinning of the cornea and sclera. BCS results from loss-of-function mutations in the poorly understood genes ...ZNF469 or PRDM5. In order to determine the function of ZNF469 and to elucidate pathogenic mechanisms, we used genome editing to recapitulate a human ZNF469 BCS mutation in the orthologous mouse gene Zfp469. Ophthalmic phenotyping showed that homozygous Zfp469 mutation causes significant central and peripheral corneal thinning arising from reduced stromal thickness. Expression of key components of the corneal stroma in primary keratocytes from Zfp469BCS/BCS mice is affected, including decreased Col1a1 and Col1a2 expression. This alters the collagen type I/collagen type V ratio and results in collagen fibrils with smaller diameter and increased fibril density in homozygous mutant corneas, correlating with decreased biomechanical strength in the cornea. Cell-derived matrices generated by primary keratocytes show reduced deposition of collagen type I, offering an in vitro model for stromal dysfunction. Work remains to determine whether modulating ZNF469 activity will have therapeutic benefit in BCS or in conditions such as keratoconus in which the cornea thins progressively. This article has an associated First Person interview with the first author of the paper.
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