Accuracy and speed of elongation in a minimal model of DNA replication.

Being a dual purpose enzyme, the DNA polymerase is responsible for elongation of the newly formed DNA strand as well as cleaving the erroneous growth in case of a misincorporation. The efficiency of replication depends on the coordination of the polymerization and exonuclease activity of DNA polymerase. Here, we propose and analyze a minimal kinetic model of DNA replication and determine exact expressions for the velocity of elongation and the accuracy of replication. We first analyze the case without exonuclease activity. In that case, accuracy is determined by a kinetic competition between stepping and unbinding, with discrimination between correct and incorrect nucleotides in both transitions. We then include exonuclease activity and ask how different modes of additional discrimination in the exonuclease pathway can improve the accuracy while limiting the detrimental effect of exonuclease on the speed of replication. In this way, we ask how the kinetic parameters of the model have to be set to coordinate the two activities of the enzyme for high accuracy and high speed. The analysis also shows that the design of a replication system does not universally have to follow the speed-accuracy trade-off rule, although it does in the biologically realized parameter range. The accuracy of the process is mainly controlled by the crucial role of stepping after erroneous incorporation, which has impact on both polymerase and exonuclease activities of DNA polymerase.

Breathing comfort associated with different modes of ventilation: a comparative study in non-intubated healthy Nepalese volunteers.

OBJECTIVE: To compare subjective experience of comfort associated with various commonly used supportive modes of mechanical ventilation for weaning in the intensive care unit (ICU). SUBJECTS AND METHODS: The study was carried out in general ICU of a community-based teaching hospital in 30 healthy adult Nepalese volunteers of either sex and 19-37 years of age. The subjects were randomly made to experience breathing via anatomical facemask through ventilator circuit with synchronized intermittent mandatory ventilation (SIMV), assisted spontaneous breathing (ASB), biphasic positive airway pressure (BiPAP), and continuous positive airway pressure (CPAP) modes of ventilation with parameters set at intermediate level of respiratory support. Subjective comfort of breathing was noted using a 10 cm visual analogue scale (VAS) with no discomfort at one end and maximum imaginable discomfort at the other. Inspiratory and expiratory experience of discomfort was also noted using a four point ranking scale (0-no discomfort, 1-mild discomfort, 2-moderate discomfort and 3-severe discomfort). In addition, presence or absence of feeling of breathlessness and inflation was also noted. RESULTS: BiPAP was the most comfortable mode of ventilation (p<0.01) on visual analogue scale. SIMV and CPAP modes were associated with higher discomfort than other modes during inspiratory and expiratory phases respectively. Breathlessness and inflation were least felt in BiPAP and SIMV modes respectively. CONCLUSION: Perception of breathing comfort can vary widely with various supportive modes of ventilation in the ICU. Hence, no single supportive mode should be used in all patients during weaning from mechanical ventilation. Key words: assisted spontaneous breathing; biphasic positive airway pressure; breathing comfort; continuous positive airway pressure; mechanical ventilation; supportive modes synchronized intermittent mandatory ventilation; weaning.

Brachial plexus block as a sole anaesthetic technique in upper extremity fracture/dislocation in children: subclavian perivascular vs parascalene approach.

OBJECTIVE: To compare parascalene approach of brachial plexus block with the classical subclavian perivascular approach as a sole anaesthetic technique in children undergoing closed manipulation for fracture/dislocation around the elbow. MATERIALS AND METHODS: Sixty children (age 6-13 years) undergoing closed manipulation for fracture/dislocation around the elbow were randomly assigned to two groups, Group I (n=30) receiving brachial plexus block using Winnie's classical subclavian perivascular approach and Group II (n=30) receiving brachial plexus block using parascalene approach described by Dalens. Time required for performing the block, onset of analgesia, sensory block to pin prick, adequacy of relaxation, complications and acceptance of the technique to the children, parents and the surgeons were compared. RESULTS: Time required for performing the block (6.3+/-2.2 min vs. 8.2+/-2.4 min), onset of subjective analgesia (4.1+/-1.6 min vs. 5.2+/-1.4 min) and onset of sensory block to pinprick (6.8+/-2.1 min vs. 8.6+/-1.7 min) were significantly shorter in Group I as compared to Group II (p<0.01). Acceptance of the techniques by the children, parents and the surgeons, and the overall success rates were high and comparable between the groups. Complications were minor and the incidence was low in both the groups except Horner's syndrome in 46.7% of patients in Group II. CONCLUSION: Parascalene approach to brachial plexus block is comparable to classical subclavian perivascular approach in safety, success rate and acceptance in children undergoing closed manipulation and reduction of fracture/dislocation around the elbow.