The differentiation of an organism into a male or female phenotype is a critical developmental process, but the mechanisms that control this decision are remarkably evolutionarily labile. This Review discusses the wide diversity of vertebrate sex-determination mechanisms, their rapid evolution under different forms of genetic and environmental control and the over-arching principles that are shared despite this mechanistic diversity.
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Κυριακή 13 Αυγούστου 2017
Vertebrate sex determination: evolutionary plasticity of a fundamental switch
The interplay of epigenetic marks during stem cell differentiation and development
Cell state transitions during embryonic development are associated with epigenetic changes that alter chromatin structure and gene expression. Interplay between epigenetic regulatory layers can be studied using genomic technologies and embryonic stem cell cultures that reflect in vivo cell states.
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Settling the score: variant prioritization and Mendelian disease
For clinical cases of Mendelian disease that lack a genetic diagnosis, genome and exome sequencing are increasingly used for seeking the genetic cause. This Review discusses the strategies and computational tools for prioritizing the many genetic variants identified in each genome into those that are most likely to be causal for disease. The authors discuss how diverse types of biochemical, evolutionary, pedigree and clinical-phenotype information are used, and they highlight common pitfalls to be aware of for responsible variant prioritization.
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Comparison of the ability of esCCO and Volume View to measure trends in cardiac output in patients undergoing cardiac surgery
BACKGROUND: Cardiac output (CO) is a physiological variable that should be monitored during cardiac surgery. The purpose of this study was to assess the trending ability of two CO monitors, esCCO (Nihon Kohden™, Tokyo, Japan) and Volume View (VV) (Edwards Lifesciences, Irvine, USA).
METHODS: A total of 19 patients were included in the study. Before cardiopulmonary bypass (CPB), CO was measured simultaneously using both esCCO and VV devices before and after three CO-modifying manoeuvres (passive leg raise [PLR], the end expiratory occlusion test [EEOT] and positive end expiratory pressure [PEEP] at 10 cm H2O). Five CO values for esCCO and three for VV were averaged and compared during a one-minute period of time before and after each manoeuvre.
RESULTS: A total of 114 paired readings were collected. Median CO values were 4.3 L min-1 (IQR: 3.8; 5.2) and 3.8 L min-1 (IQR: 3.5; 4.5) for esCCO and VV, respectively. The precision error was 1.4% (95% CI:1.0–1.7) for esCCO and 2.2% (95% CI: 1.8–2.7) for VV. The bias between esCCO and VV values was normally distributed (P = 0.0596). Between esCCO and VV, the mean bias was +0.6 L min-1 with a Limit of Agreement (LOA) of –1.8 L min-1 and +3.0 L min-1. The concordance rate was 43% (95% CI: 29–58) between esCCO and VV.
CONCLUSION: Both single and trended measurements of CO using esCCO and VV were not in agreement. This large discrepancy leads one to the conclusion that any outcome study conducted with one of these devices cannot be applied to the other.
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Thermoregulation disorders of central origin — how to diagnose and treat
Fever is a common symptom in the Intensive Care Unit. At least half of febrile episodes are caused by infection. Excluding infectious etiology and other non-infectious causes of fever, especially in patients with central nervous system (CNS) disorders, attention should be paid to disturbances of thermoregulatory centre. In particular, subarachnoid haemorrhage, cerebral trauma, along with ischaemic or haemorrhagic stroke are strongly associated with the development of central fever. Proper, speedy diagnosis of the cause of fever makes it possible to implement preventive measures against the harmful effects of hyperthermia on the CNS and to avoid the consequences of inappropriate treatment. The aim of this review is to present the current treatment options for the management of central fever and to analyze recent recommendations for the treatment of hyperthermia, including the use of hypothermia. The recommendations of American and European associations are inconsistent, mainly due to the lack of randomized clinical trials confirming the effectiveness of such treatment. The diagnosis of central fever is still made by the exclusion of other causes. The authors of the review intended to present the characteristic features of central fever, differentiating this state from infectious fever and also analyze the presence of central fever in particular neurological diseases. It seems particularly important to establish diagnostic criteria for central fever or to find diagnostic markers. It is also necessary to conduct further randomized clinical trials evaluating the indications for treatment of hyperthermia.
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Electrical impedance tomography for diagnosis and monitoring of pulmonary function disorders in the intensive care unit — case report and review of literature
The aim of this paper is to describe the possibility of using Electrical Impedance Tomography (EIT) as a treatment monitoring tool in the ICU. It was based on case report and literature review. A 19-year-old female was admitted to ICU due to severe acute respiratory distress syndrome. Despite aggressive treatment there was no improvement. We decided to use EIT in the monitoring of treatment because of difficulties in transporting the patient to the radiology department in order to perform a control CT scan. After identifying the causing factor (Pneumocyctis jiroveci), EIT monitoring was maintained to assess the effectiveness of targeted microbial treatment. In the following days, we observed an improvement of regional ventilation of the upper and middle segments of the left lung that corresponded well with laboratory test results, especially arterial blood gas analysis. The use of Electrical Impedance Tomography enables non-invasive, bedside, continuous assessment of regional lung ventilation. It is possible to use it in both mechanically ventilated and spontaneously breathing patients. It allows efficient and dynamic monitoring of the course of the therapeutic process. Interpretation of the results is relatively easy to learn and does not require specialist knowledge. Moreover, it is possible to use EIT in those cases where other methods are of high risk or contraindicated.
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Neutrophils, NETs, NETosis — old or new factors in sepsis and septic shock?
Neutrophils are an key part of the innate immune system in the host's defences against pathogens. Circulating neutrophils are recruited at the sites of infection or sterile inflammation in response to pathogen and host-derived inflammatory mediators. In addition to phagocytosis and degranulation, neutrophils display the release of NETs in order to restrain infection. NETs are able to entrap and kill microbes, and display proinflammatory and prothrombotic properties.
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Benefits of ultrasound-guided transversus abdominis plane block for open appendectomy in children
BACKGROUND: One of the most frequently performed emergency surgical procedures in children is an appendectomy. The aim of this study was to determine the benefits of supplementing standard, general anaesthesia with the ultrasound-guided right TAP block.
METHODS: We analyzed the medical records of 90 children of both sexes, aged 4–16 years with a body mass of 16–78 kg who underwent general anaesthesia for open appendectomy. Sixty-two individuals were anaesthetized using the standard method, while 28 patients had an additional right-sided TAP block under ultrasound guidance. Subsequently these groups were divided into 2 subgroups: children under 8 years and those older. We evaluated the total consumption of opioids, intraoperative fentanyl requirement, the amount of non-opioid analgesic and antiemetic drugs used during the whole hospitalization, time to recovery of digestive track function and length of hospital stay.
RESULTS: TAP block performed under USG guidance reduced the overall consumption of opioids (0.36 vs. 0.42 mg kg-1, P = 0.048), significantly shortened time of fasting after the surgery (17 vs. 29 hours, P = 0.003) as well as reduced the need for antiemetic drugs: ondansetron were used only in 21.4% of children in the group with TAP block vs. 38.7% of children with standard protocol. Additionally, we noted that the application of the TAP block shortened the length of hospitalization (3 vs. 4 days, P = 0.045).
CONCLUSION: The application of the TAP block, as a supplementary treatment to standard general anaesthesia for open appendectomy in children is a valuable component of multimodal analgesia, which might improve the quality of life of the patient and shorten the length of hospitalization.
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Impact of absence of critical respiratory rate change on oxygen desaturation following tracheal extubation after general anaesthesia: a propensity score-matched analysis
BACKGROUND: It has been suggested that oxygen desaturation may be paradoxically related to the absence of an abnormal respiratory rate (RR) during acoustic respiratory rate (RRa) monitoring in a postoperative setting. We retrospectively compared the incidence of desaruration in patients without an abnormal RR with that in patients with an abnormal RR using propensity scorer matching. We also explored the factors contributing to oxygen desaturation without an RR monitoring alert.
METHODS: We used ≤ 8 h postoperative data of the first 935 patients. Outcomes of patients with and without critical RR changes (RR > 30 or < 8 beats per min for > 2 min) (critical RR change vs. noncritical RR change) were first compared according to oxygen desaturation levels (SpO2< 90% for > 10 s). Multivariate analysis was used to determine oxygen desaturation-associated explanatory factors.
RESULTS: Propensity score matching yielded 259 patients without critical RR changes and 259 patients with critical RR changes, respectively. Oxygen desaturation rates were higher in patients without critical RR changes [noncritical RR change vs. critical RR change: 39/220 (15.1%) vs. 16/243 (6.2%)]. An odds ratio and 95% CI for the noncritical RR change was 2.56 (1.38–4.55, P = 0.002). A critical change in the RRa was not observed in 576 patients; of these, oxygen desaturation was observed in 76 (13.2%) patients. Surgery duration (OR, 1.018 per 10 min increase; 95% CI, 1.002 to 1.035) was independently associated with oxygen desaturation without critical RR change.
CONCLUSION: Postoperative oxygen desaturation paradoxically occurred more frequently in patients without critical RR changes, whose RR was monitored by the RRa under oxygen therapy. The duration of surgery may explain the possibility of postoperative oxygen desaturation without an RRa device alert.
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Sensitivity and specificity of urinalysis samples in critically ill patients
BACKGROUND: Pre-emptive screening of urine for patients admitted to an intensive care unit can result in the misinterpretation of data and over- or under-treatment of urinary tract infection.
METHODS: Data were studied from 169 consecutive patients admitted to the neurologic or burn intensive care unit at Shands Hospital at the University of Florida. All patients had a urinary catheter in place at the time of admission. Urinalysis and urine culture were sent for analysis. Data included leukocyte esterase, urine nitrate, urine protein, pyuria or urine white blood cell count, and culture.
RESULTS: Leukocyte esterase and pyuria were the most sensitive indicators of a positive urine culture at 87.5% (95% CI: 71.3–100%) and 73.3% (95% CI: 51.0–95.7%), respectively; urine nitrate was specific at 100%. More than half of the patients (56.3%) with positive cultures did not initially receive antibiotics.
CONCLUSION: The combination of leukocyte esterase and urine nitrate provides the best indicator for the initiation of antibiotic coverage for urinary tract infection prior to culture availability.
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Evaluation of a low-cost, 3D-printed model for bronchoscopy training
BACKGROUND: Flexible bronchoscopy is a fundamental procedure in anaesthesia and critical care medicine. Although learning this procedure is a complex task, the use of simulation-based training provides significant advantages, such as enhanced patient safety. Access to bronchoscopy simulators may be limited in low-resource settings. We have developed a low-cost 3D-printed bronchoscopy training model.
METHODS: A parametric airway model was obtained from an online medical model repository and fabricated using a low-cost 3D printer. The participating physicians had no prior bronchoscopy experience. Participants received a 30-minute lecture on flexible bronchoscopy and were administered a 15-item pre-test questionnaire on bronchoscopy. Afterwards, participants were instructed to perform a series of predetermined bronchoscopy tasks on the 3D printed simulator on 4 consecutive occasions. The time needed to perform the tasks and the quality of task performance (identification of bronchial anatomy, technique, dexterity, lack of trauma) were recorded. Upon completion of the simulator tests, participants were administered the 15-item questionnaire (post-test) once again. Participant satisfaction data on the perceived usefulness and accuracy of the 3D model were collected. A statistical analysis was performed using the t-test. Data are reported as mean values (± standard deviation).
RESULTS: The time needed to complete all tasks was 152.9 ± 71.5 sec on the 1st attempt vs. 98.7 ± 40.3 sec on the 4th attempt (P = 0.03). Likewise, the quality of performance score improved from 8.3 ± 6.7 to 18.2 ± 2.5 (P < 0.0001). The average number of correct answers in the questionnaire was 6.8 ± 1.9 pre-test and 13.3 ± 3.1 post-test (P < 0.0001). Participants reported a high level of satisfaction with the perceived usefulness and accuracy of the model.
CONCLUSIONS: We developed a 3D-printed model for bronchoscopy training. This model improved trainee performance and may represent a valid, low-cost bronchoscopy training tool.
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Do bacteria isolated from ICU patients ‘ESKAPE’ antibiotic treatment? In vitro susceptibility of the Enterobacteriaceae family to tigecycline
Background: Enterobacteriaceae are currently causing the majority of healthcare-associated infections (HAI) and
simultaneously expressing increasing levels of antibiotic resistance. The purpose of this study is to assess the in vitro
sensitivity of MDR strains from the family Enterobacteriaceae to tigecycline in relation to their origin from patients
hospitalized in intensive care units (ICUs) and non-ICUs.
Methods: The study involved 156 clinically significant strains of the Enterobacteriaceae family isolated from patients
with complicated intraabdominal infections (cIAIs) and/or complicated skin and skin structure infections (cSSSIs)
hospitalized in ICUs and other surgical departments. Tigecycline MICs were determined by Etest.
Results: The highest percentage of tigecycline non-susceptible (intermediate + resistant strains) in vitro strains
among the Enterobacteriaceae species were observed for Serratia spp. 77.3%, followed by Citrobacter spp. (76.9%)
and Enterobacter spp. (70%); whereas K. pneumoniae and E. coli showed 73–73.8% tigecycline susceptibility rates.
Conclusion: Tigecycline demonstrates a high level of antimicrobial in vitro activity when tested against E. coli and
K. pneumoniae, even those with the ESBL-phenotype. Tigecycline retained activity against merely 22–30% of Enterobacter, Citrobacter and Serratia genera.
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Randomised controlled trial of analgesic effectiveness of three different techniques of single-shot interscalene brachial plexus block using 20 mL of 0.5% ropivacaine for shoulder arthroscopy
BACKGROUND: Shoulder arthroscopic procedures impose a challenge to anaesthesiologists in terms of postoperative analgesia. Proper pain management after arthroscopic procedures improves patient satisfaction and facilitates early rehabilitation.
METHODS: We performed a randomized, prospective clinical study to assess the influence of anthropometric parameters and IBPB technique on the quality of postoperative analgesia. A total of 106 randomly selected patients of ASA I–III status scheduled for elective shoulder arthroscopy. Reasons for exclusion were neurological deficit in the upper arm, allergies to amide-type local anesthetics, coagulopathy, and pregnancy.The patients received 20 mL of 0.5% ropivacaine for an ultrasound-guided interscalene brachial plexus block (IBPB) (group U), peripheral nerve stimulation (PNS)-confirmed IBPB (group N), or ultrasound-guided, PNS-confirmed IBPB (dual guidance; group NU).
RESULTS: We observed that the three groups did not differ in mean time of sensory and motor block terminations. In individual cases in each group, sensory block lasted up to 890–990 minutes, providing satisfactory long lasting postoperative analgesia in patients receiving IBPB. We observed a negative correlation between body mass index and termination of motor block (P = 0.037, Pearson's correlation coefficient) and a positive correlation between age and termination of sensory block (P = 0.0314, Pearson's correlation coefficient) in group U compared to the other two groups. We found a positive correlation between male gender and termination of motor block (P = 0.0487, Pearson's correlation coefficient) in group N compared to the other two groups.
CONCLUSION: In our study, patients received satisfactory analgesia in the postoperative period regardless of technique used, age, gender, or potentially uncommon anthropometry.
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HEPACONTROL. A program that reduces early readmissions, mortality at 60 days, and healthcare costs in decompensated cirrhosis
Decompensated cirrhosis patients have an elevated incidence of early readmission, mortality and economic burden. The aims of HEPACONTROL were to reduce early readmission and to evaluate its impact on mortality and emergency department visits.
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HEPACONTROL. A program that reduces early readmissions, mortality at 60 days, and healthcare costs in decompensated cirrhosis
Decompensated cirrhosis patients have an elevated incidence of early readmission, mortality and economic burden. The aims of HEPACONTROL were to reduce early readmission and to evaluate its impact on mortality and emergency department visits.
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FERM domain phosphorylation and endogenous 3′UTR are not essential for regulating the function and subcellular localization of polarity protein Crumbs
Source:Journal of Genetics and Genomics
Author(s): Haowei Cao, Rui Xu, Qiping Shi, Dandan Zhang, Juan Huang, Yang Hong
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Efficient generation of the mouse model with a defined point mutation through haploid cell-mediated gene-editing
Source:Journal of Genetics and Genomics
Author(s): Leixin Wei, Xiukun Wang, Suming Yang, Wen Yuan, Jinsong Li
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