Position Statement of ISCCM Committee on Weaning from Mechanical Ventilator.

Background and purpose: Weaning from a mechanical ventilator is a milestone in the recovery of seriously ill patients in Intensive care. Failure to wean and re-intubation adversely affects the outcome. The method of mechanical ventilation (MV) varies between different ICUs and so does the practice of weaning. Therefore, updated guidelines based on contemporary literature are designed to guide intensivists in modern ICUs. This is the first ISCCM Consensus Statement on weaning complied by a committee on weaning. The recommendations are intended to be used by all the members of the ICU (Intensivists, Registrars, Nurses, and Respiratory Therapists). Methods: A Committee on weaning from MV, formed by the Indian Society of Critical Care Medicine (ISCCM) has formulated this statement on weaning from mechanical ventilators in intensive care units (ICUs) after a review of the literature. Literature was first circulated among expert committee members and allotted sections to each member. Sections of the statement written by sectional authors were peer-reviewed on multiple occasions through virtual meetings. After the final manuscript is accepted by all the committee members, it is submitted for peer review by central guideline committee of ISCCM. Once approved it has passed through review by the Editorial Board of IJCCM before it is published here as "ISCCM consensus statement on weaning from mechanical ventilator". As per the standard accepted for all its guidelines of ISCCM, we followed the modified grading of recommendations assessment, development and evaluation (GRADE) system to classify the quality of evidence and strength of recommendation. Cost-benefit, risk-benefit analysis, and feasibility of implementation in Indian ICUs are considered by the committee along with the strength of evidence. Type of ventilators and their modes, ICU staffing pattern, availability of critical care nurses, Respiratory therapists, and day vs night time staffing are aspects considered while recommending for or against any aspect of weaning. Result: This document makes recommendation on various aspects of weaning, namely, definition, timing, weaning criteria, method of weaning, diagnosis of failure to wean, defining difficult to wean, Use of NIV, HFOV as adjunct to weaning, role of tracheostomy in weaning, weaning in of long term ventilated patients, role of physiotherapy, mobilization in weaning, Role of nutrition in weaning, role of diaphragmatic ultrasound in weaning prediction etc. Out of 42 questions addressed; the committee provided 39 recommendations and refrained from 3 questions. Of these 39; 32 are based on evidence and 7 are based on expert opinion of the committee members. It provides 27 strong recommendations and 12 weak recommendations (suggestions). Conclusion: This guideline gives extensive review on weaning from mechanical ventilator and provides various recommendations on weaning from mechanical ventilator. Though all efforts are made to make is as updated as possible one needs to review any guideline periodically to keep it in line with upcoming concepts and standards. How to cite this article: Clerk AM, Shah RJ, Kothari J, Sodhi K, Vadi S, Bhattacharya PK, et al. Position Statement of ISCCM Committee on Weaning from Mechanical Ventilator. Indian J Crit Care Med 2024;28(S2):S233-S248.

Tissue heterogeneity of mitochondrial activity, biogenesis and mitochondrial protein gene expression in buffalo.

BACKGROUND: Cellular metabolism is most invariant process, occurring in all living organisms, which involves mitochondrial proteins from both nuclear and mitochondrial genomes. The mitochondrial DNA (mtDNA) copy number, protein-coding genes (mtPCGs) expression, and activity vary between various tissues to fulfill specific energy demands across the tissues. METHODS AND RESULTS: In present study, we investigated the OXPHOS complexes and citrate synthase activity in isolated mitochondria from various tissues of freshly slaughtered buffaloes (n = 3). Further, the evaluation of tissue-specific diversity based on the quantification of mtDNA copy numbers was performed and also comprised an expression study of 13 mtPCGs. We found that the functional activity of individual OXPHOS complex I was significantly higher in the liver compared to muscle and brain. Additionally, OXPHOS complex III and V activities was observed significantly higher levels in liver compared to heart, ovary, and brain. Similarly, CS-specific activity differs between tissues, with the ovary, kidney, and liver having significantly greater. Furthermore, we revealed the mtDNA copy number was strictly tissue-specific, with muscle and brain tissues exhibiting the highest levels. Among 13 PCGs expression analyses, mRNA abundances in all genes were differentially expressed among the different tissue. CONCLUSIONS: Overall, our results indicate the existence of a tissue-specific variation in mitochondrial activity, bioenergetics, and mtPCGs expression among various types of buffalo tissues. This study serves as a critical first stage in gathering vital comparable data about the physiological function of mitochondria in energy metabolism in distinct tissues, laying the groundwork for future mitochondrial based diagnosis and research.

Are "High-alert Medication" Used Safely in Intensive Care Units?

How to cite this article: Clerk AM. Are "High-alert Medication" Used Safely in Intensive Care Units? Indian J Crit Care Med 2023;27(12):871-872.

Arrest Outcome Consortium Registry Analysis [AOCRA 2022]: Outcome Statistics of Cardiac Arrest in Tertiary Care Hospitals in India, Analysis of Five Year Data of Indian Online Cardiac Arrest Registry, www.aocregistry.com.

Aim and background: To publish data with outcome statistics from our online cardiac arrest (CA) outcome consortium (AOC) online registry. Materials and methods: Data on cardiac arrest (CA) from tertiary care hospitals were collected on the AOC registry online portal from January 2017 to May 2022. Survival endpoints from cardiac arrest events like ROSC, and survival at hospital discharge with neurological status at discharge were analyzed and presented. Studies of demographics, the association of outcome with age, gender, bystander CPR, low and no flow times, and admission lactate were also done along with suitable statistical analysis. Results: Out of 2,235 CA, 2,121 received CPR (1,998 IHCA, 123 Out of hospital Cardiac Arrest (OHCA)) as 114 were DNR. The males-female ratio was 70:30. Average age at arrest was 58.7 years. 26% OHCA received bystander CPR but survival advantage was not significant. (with 16%, without 14% p = 0.78). Asystole (67.7%), Pulseless Electrical Activity (PEA) (25.6%), and VF/pVT (6.7%) as first rhythm significantly influence survival (4.9, 8.6 and 39.4%: p < 0.001) ROSC was achieved in 355 (16.7%), with 173 (8.2%) alive and 141 (6.6%) having good (CPC ≤ 2) neurological state at discharge. At discharge, survival as well as CPC ≤ 2 outcomes were significantly better in females. On multivariate regression analysis, first rhythm and low flow time influence survival at discharge. Admission lactate (available only in 102 OHCA) was lower in survivors than non-survivors 10.3 vs 11.5 mmol/L but the difference was not statistically significant (p = 0.397]. Conclusion: Data from our AOC registry shows poor overall survival from CA. The Female gender had a higher survival rate. Ventricular Fibrillation/Pulseless Ventricular Tachycardia (VF/pVT) as first rhythm and low flow time influence the survival to discharge (CTRI/2022/11/047140). How to cite this article: Clerk AM, Patel K, Shah BA, Prajapati D, Shah RJ, Rachhadia J, et al. Arrest Outcome Consortium Registry Analysis [AOCRA 2022]: Outcome Statistics of Cardiac Arrest in Tertiary Care Hospitals in India, Analysis of Five Year Data of Indian Online Cardiac Arrest Registry, www.aocregistry.com. Indian J Crit Care Med 2023;27(5):322-329.

Sepsis in Intensive Care Unit: Which Score Predicts Better about Outcome?

How to cite this article: Clerk AM. Sepsis in Intensive Care Unit: Which Score Predicts Better about Outcome? Indian J Crit Care Med 2022;26(10):1072-1073.

Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation.

How to cite this article: Srinivasan S, Kumar PG, Govil D, Gupta S, Kumar V, Pichamuthu K, et al. Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation. Indian J Crit Care Med 2022;26(S2):S7-S12.

Beware of Neglect of Non-COVID Patients in COVID Era.

Clerk AM. Beware of Neglect of Non-COVID Patients in COVID Era. Indian J Crit Care Med 2021;25(8):837-838.

Attempting a Change in Human Behavior in ICU in COVID Era: Handle with Care!

How to cite this article: Clerk AM. Attempting a Change in Human Behavior in ICU in COVID Era: Handle with Care! Indian J Crit Care Med 2020;24(8):626-627.

Indian Society of Critical Care Medicine Position Statement for Central Venous Catheterization and Management 2020.

BACKGROUND AND PURPOSE: Short-term central venous catheterization (CVC) is one of the commonly used invasive interventions in ICU and other patient-care areas. Practice and management of CVC is not standardized, varies widely, and need appropriate guidance. Purpose of this document is to provide a comprehensive, evidence-based and up-to-date, one document source for practice and management of central venous catheterization. These recommendations are intended to be used by critical care physicians and allied professionals involved in care of patients with central venous lines. METHODS: This position statement for central venous catheterization is framed by expert committee members under the aegis of Indian Society of Critical Care Medicine (ISCCM). Experts group exchanged and reviewed the relevant literature. During the final meeting of the experts held at the ISCCM Head Office, a consensus on all the topics was made and the recommendations for final document draft were prepared. The final document was reviewed and accepted by all expert committee members and after a process of peer-review this document is finally accepted as an official ISCCM position paper.Modified grade system was utilized to classify the quality of evidence and the strength of recommendations. The draft document thus formulated was reviewed by all committee members; further comments and suggestions were incorporated after discussion, and a final document was prepared. RESULTS: This document makes recommendations about various aspects of resource preparation, infection control, prevention of mechanical complication and surveillance related to short-term central venous catheterization. This document also provides four appendices for ready reference and use at institutional level. CONCLUSION: In this document, committee is able to make 54 different recommendations for various aspects of care, out of which 40 are strong and 14 weak recommendations. Among all of them, 42 recommendations are backed by any level of evidence, however due to paucity of data on 12 clinical questions, a consensus was reached by working committee and practice recommendations given on these topics are based on vast clinical experience of the members of this committee, which makes a useful practice point. Committee recognizes the fact that in event of new emerging evidences this document will require update, and that shall be provided in due time. ABBREVIATIONS LIST: ABHR: Alcohol-based hand rub; AICD: Automated implantable cardioverter defibrillator; BSI: Blood stream infection; C/SS: CHG/silver sulfadiazine; Cath Lab: Catheterization laboratory (Cardiac Cath Lab); CDC: Centers for Disease Control and Prevention; CFU: Colony forming unit; CHG: Chlorhexidine gluconate; CL: Central line; COMBUX: Comparison of Bedside Ultrasound with Chest X-ray (COMBUX study); CQI: Continuous quality improvement; CRBSI: Catheter-related blood stream infection; CUS: Chest ultrasonography; CVC: Central Venous Catheter; CXR: Chest X-ray; DTTP: Differential time to positivity; DVT: Deep venous thrombosis; ECG: Electrocardiography; ELVIS: Ethanol lock and risk of hemodialysis catheter infection in critically ill patients; ER: Emergency room; FDA: Food and Drug Administration; FV: Femoral vein; GWE: Guidewire exchange; HD catheter: Hemodialysis catheter; HTS: Hypertonic saline; ICP: Intracranial pressure; ICU: Intensive Care Unit; IDSA: Infectious Disease Society of America; IJV: Internal jugular vein; IPC: Indian penal code; IRR: Incidence rate ratio; ISCCM: Indian Society of Critical Care Medicine; IV: Intravenous; LCBI: Laboratory confirmed blood stream infection; M/R: Minocycline/rifampicin; MBI-LCBI: Mucosal barrier injury laboratory-confirmed bloodstream infection; MRSA: Methicillin-resistant Staphylococcus aureus; NHS: National Health Service (UK); NHSN: National Healthcare Safety Network (USA); OT: Operation Theater; PICC: Peripherally-inserted central catheter; PIV: Peripheral intravenous line; PL: Peripheral line; PVI: Povidone-iodine; RA: Right atrium; RCT: Randomized controlled trial; RR: Relative risk; SCV/SV: Subclavian vein; ScVO2: Central venous oxygen saturation; Sn: Sensitivity; SOP: Standard operating procedure; SVC: Superior vena cava; TEE: Transesophageal echocardiography; UPP: Useful Practice Points; USG: Ultrasonography; WHO: World Health Organization. HOW TO CITE THIS ARTICLE: Javeri Y, Jagathkar G, Dixit S, Chaudhary D, Zirpe KG, Mehta Y, et al. Indian Society of Critical Care Medicine Position Statement for Central Venous Catheterization and Management 2020. Indian J Crit Care Med 2020;24(Suppl 1):S6-S30.

Publication Rate of Abstracts Presented at the Society for Obstetric Anesthesia and Perinatology Annual Meetings 2010-2014.

The Society for Obstetric Anesthesia and Perinatology (SOAP) annual meeting provides a forum to present new scientific work with the goal of broader dissemination of knowledge. The objective of this study was to evaluate the proportion of research abstracts presented at SOAP meetings, from 2010 to 2014, which resulted in peer-reviewed publications. The abstract-to-publication rate was compared with the percent of abstracts presented at biomedical meetings resulting in publication, as estimated by a 2007 Cochrane Review. The SOAP abstract-to-publication rate was lower than that of the Cochrane Review (26.8% vs 44.5%, P < .0001). Future work should identify barriers to publication.

Assessment of advanced gastric cancer management in the United States.

BACKGROUND: Increasing attention is being placed on utilization of treatment for advanced malignancies. Though some suggest it is futile, recent reports have advocated noncurative surgery for advanced gastric cancer. Our objectives were to (1) assess treatment trends, (2) identify predictors of surgery, and (3) evaluate the effect of treatment on outcomes. METHODS: Patients with stage IV gastric adenocarcinoma were identified from the National Cancer Data Base (1998-2007). Patients who underwent emergent surgery were excluded. Models were developed to identify factors associated with treatment receipt and to compare adjusted overall survival by treatment group. RESULTS: Twenty-four percent (n = 22,430) of patients presented with stage IV gastric adenocarcinoma; 1.5 % (n = 414) underwent emergent surgery. Of the remaining 21,039 patients, 62.4 % underwent treatment (87.0 % chemotherapy with or without radiotherapy (C ± RT), 5.6 % surgery, 7.2 % combined surgery and C ± RT). Over the decade, surgery rates increased by 43 %, and C ± RT use increased by 16 % while receipt of no treatment decreased by 26 % (all p < 0.001). Patients who were younger, white, and insured, as well as those with distal tumors were more likely to undergo surgery. Reasons for receiving no treatment were multifactorial but were most strongly associated with advanced age and being uninsured. Median survival was longest for patients selected to undergo surgery and C ± RT (13.5 months) versus C ± RT alone (6.1 months), surgery alone (4.8 months), or no treatment (1.7 months, all p < 0.001). CONCLUSIONS: Utilization of nonemergent surgical treatment and C ± RT for metastatic gastric adenocarcinoma has increased considerably over time, especially in certain patient populations; however, the true utility and cost of these treatments remain unknown.

A role for BELLRINGER in cell wall development is supported by loss-of-function phenotypes.

BACKGROUND: Homeodomain transcription factors play critical roles in metazoan development. BELLRINGER (BLR), one such transcription factor, is involved in diverse developmental processes in Arabidopsis, acting in vascular differentiation, phyllotaxy, flower and fruit development. BLR also has a redundant role in meristem maintenance. Cell wall remodelling underpins many of these processes, and BLR has recently been shown to regulate expression of PECTIN METHYL-ESTERASE 5 (PME5), a cell wall modifying enzyme in control of phyllotaxy. We have further explored the role of BLR in plant development by analysing phenotypes and gene expression in a series of plants over-expressing BLR, and generating combinatorial mutants with blr, brevipedicellus (bp), a member of the KNOX1 family of transcription factors that has previously been shown to interact with blr, and the homeodomain transcription factor revoluta (rev), required for radial patterning of the stem. RESULTS: Plants over-expressing BLR exhibited a wide range of phenotypes. Some were defective in cell size and demonstrated misregulation of genes predominantly affecting cell wall development. Other lines with more extreme phenotypes failed to generate lateral organs, consistent with BLR repressing transcription in the shoot apex. Cell wall dynamics are also affected in blr mutant plants, and BLR has previously been shown to regulate vascular development in conjunction with BP. We found that when bp and blr were combined with rev, a set of defects was observed that were distinct from those of bp blr lines. In these triple mutants xylem development was most strikingly affected, resulting in an almost complete lack of vessels and xylem parenchyma with secondary thickening. CONCLUSIONS: Our data support a role for BLR in ordering the shoot apex and, in conjunction with BP and REV, playing a part in determining the composition and organisation of the vascular system. Microarray analysis strongly indicates that the striking vascular phenotypes of blr bp rev triple mutants and plants over-expressing BLR result from the misregulation of a suite of genes, targets of BLR in wild type plants, that determine cell size and structure in the developing vasculature.

STN Versus GPi Deep Brain Stimulation for Action and Rest Tremor in Parkinson's Disease.

OBJECTIVE: To investigate the effects of subthalamic nucleus (STN) and globus pallidus internus (GPi), deep brain stimulation (DBS) on individual action tremor/postural tremor (AT) and rest tremor (RT) in Parkinson's disease (PD). Randomized DBS studies have reported marked benefit in tremor with both GPi and STN and DBS, however, there is a paucity of information available on AT vs RT when separated by the surgical target. METHODS: We retrospectively reviewed the 1-year clinical outcome of PD patients treated with STN and GPi DBS at the University of Florida. We specifically selected patients with moderate to severe AT. Eighty-eight patients (57 STN and 31 GPi) were evaluated at 6 and 12 months for changes in AT and RT in the OFF-medication/ON stimulation state. A comparison of "response" was performed and defined as greater than or equal to a 2-point decrease in tremor score. RESULTS: STN and GPi DBS both improved AT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). The STN DBS group experienced a greater improvement in AT at 6 months compared to the GPi group (p = 0.005) but not at the 12 months follow-up (p = 0.301). Both STN and GPi DBS also improved RT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). There was no difference in RT scores between the two groups at 6 months (p = 0.23) or 12 months (p = 0.74). The STN group had a larger proportion of patients who achieved a "response" in AT at 6 months (p < 0.01), however, this finding was not present at 12 months (p = 0.23). A sub-analysis revealed that in RT, the STN group had a larger percentage of "responders" when followed through 12 months (p < 0.01). CONCLUSION: Both STN and GPi DBS reduced PD associated AT and RT at 12 months follow-up. There was no advantage of either brain target in the management of RT or AT. One nuance of the study was that STN DBS was more effective in suppressing AT in the early postoperative period, however, this effect diminished over time. Clinicians should be aware that it may take longer to achieve a similar tremor outcome when utilizing the GPi target.

EXS, a putative LRR receptor kinase, regulates male germline cell number and tapetal identity and promotes seed development in Arabidopsis.

BACKGROUND: Plant germlines arise late in development from archesporial initials in the L2 layer of the anther and ovule primordia. These cells generate a radially symmetrical array of tissues that, in the Arabidopsis anther, comprises a core of sporogenous cells (meiocytes) and the enveloping tapetum, middle cell, and endothecium layers. The putative transcription factor NZZ/SPL is required for the specification of archesporial cells, but nothing is known of how their number is regulated, or what controls cell fate in the lineages they generate. Here, we report detailed characterization of extra sporogenous cells (exs), a male sterile mutant that generates extra meiocytes but lacks tapetal and middle cell layers. RESULTS: We identified the EXS locus by map-based cloning and found it to encode a putative LRR receptor kinase. In the anther, an increased number of L2 layer cells assume an archesporial fate and divide to generate a larger number of sporogenous cells. In seeds, the exs mutation results in smaller embryonic cells, delayed embryo development, and smaller mature embryos. Consistent with the observed phenotype, EXS is expressed in the inflorescence meristem, floral apices, anthers, and in developing seeds. CONCLUSIONS: EXS regulates the number of cells that divide in the L2 layer of the anther, and thus the number of functional male archesporial initials. In the young seed, EXS affects cell size in the embryo and the rate at which it develops. The apparently contrasting roles of EXS in the anther and embryo suggest that signaling through the EXS receptor kinase is a feature of a number of regulatory pathways in Arabidopsis.

Hyperhomocysteinemic diabetic cardiomyopathy: oxidative stress, remodeling, and endothelial-myocyte uncoupling.

Accumulation of oxidized-matrix (fibrosis) between the endothelium (the endothelial cells embedded among the myocytes) and cardiomyocytes is a hallmark of diabetes mellitus and causes diastolic impairment. In diabetes mellitus, elevated levels of homocysteine activate matrix metalloproteinase and disconnect the endothelium from myocytes. Extracellular matrix functionally links the endothelium to the cardiomyocyte and is important for their synchronization. However, in diabetes mellitus, a disconnection is caused by activated metalloproteinase, with subsequent accumulation of oxidized matrix between the endothelium and myocyte. This contributes to endothelial-myocyte uncoupling and leads to impaired diastolic relaxation of the heart in diabetes mellitus. Elevated levels of homocysteine in diabetes are attributed to impaired homocysteine metabolism by glucose and insulin and decreased renal clearance. Homocysteine induces oxidative stress and is inversely related to the expression of peroxisome proliferators activated receptor (PPAR). Several lines of evidence suggest that ablation of the matrix metalloproteinase (MMP-9) gene ameliorates the endothelial-myocyte uncoupling in diabetes mellitus. Homocysteine competes for, and decreases the PPARgammaactivity. In diabetes mellitus, endothelial-myocyte uncoupling is associated with matrix metalloproteinase activation and decreased PPARgamma activity. The purpose of this review is to discuss the role of endothelial-myocyte uncoupling in diabetes mellitus and increased levels of homocysteine, causing activation of latent metalloproteinases, decreased levels of thioredoxin and peroxiredoxin, and cardiac tissue inhibitor of metalloproteinase (CIMP) in response to antagonizing PPARgamma.

Readability, content, and quality of online patient education materials on preeclampsia.

OBJECTIVE: The objective of this study was to evaluate the readability, content, and quality of patient education materials addressing preeclampsia. METHODS: Websites of U.S. obstetrics and gynecology residency programs were searched for patient education materials. Readability, content, and quality were assessed. A one-sample t-test was used to evaluate mean readability level compared with the recommended 6th grade reading level. RESULTS: Mean readability levels were higher using all indices (p < 0.001). Content was variable with good website understandability, but poor actionability. CONCLUSIONS: The mean readability was above the recommended 6th grade reading level. The content, readability, and actionability of preeclampsia patient education materials should be improved.

Gene structure and molecular analysis of Arabidopsis thaliana ALWAYS EARLY homologs.

Drosophila always early (aly) is essential for spermatogenesis, and is related to the LIN-9 protein of Caenorhabditis elegans; lin-9 is a class B Synthetic Multivulva gene (synMuvB) required for gonadal sheath development. Aly/LIN-9 have two conserved regions, called domains 1 and 2, which have been identified in homologous proteins from several multicellular eukaryotes, including the model plant Arabidopsis thaliana. We cloned and sequenced cDNAs of three different A. thaliana ALWAYS EARLY homologs (AtALY1, AtALY2 and AtALY3), analysed the expression pattern of these three genes and show that AtALY1, like Aly, is nuclear localised. We also demonstrate that the plant homologs of aly/lin-9 contain an additional N-terminal myb domain not present in the animal Aly/LIN-9 proteins, and that part of the ALY/LIN-9 conserved domain 1 in the predicted plant proteins is related to the TUDOR domain.

VAAMANA--a BEL1-like homeodomain protein, interacts with KNOX proteins BP and STM and regulates inflorescence stem growth in Arabidopsis.

Plant shoot growth depends on the activity of the shoot apical meristem (SAM), where organ primordia are initiated. In turn, the function of the SAM depends on the activities of homeodomain (HD) proteins of the knotted1-like homeobox (KNOX) class [Long et al., Nature 379 (1996) 66; Vollbrecht et al., Development 127 (2000) 3161]. In plants, KNOX proteins have been shown to interact specifically with the BEL1-like (BELL) class of homeodomain proteins [Bellaoui et al., Plant Cell 13 (2001) 2455; Muller et al., Plant 27 (2001) 13; Smith et al., Proc. Natl. Acad. Sci. USA 99 (2002) 9579], through a domain conserved between plants and animals. We have isolated a mutation in a BELL homeobox gene VAAMANA (VAN) that causes a dwarf phenotype. In addition, van inflorescence stems have clusters of cauline leaves; typically three are produced at each node. VAN interacts specifically with the class I KNOX proteins SHOOTMERISTEMLESS (STM), BREVIPEDICELLUS (BP), and KNAT6 (K6), and nuclear localisation of a VAN-GFP fusion depends on co-expression of STM or BP in tobacco leaves. This suggests that localisation of VAN, like that of the animal PBC homeodomain protein [Rieckhof et al., Cell 91 (1997) 171; Berthelsen et al., Genes Dev. 13 (1999) 946], is also regulated by interaction with a partner homeodomain protein.

The role of APACHE-II triaging in optimum management of small bowel perforations.

Small bowel perforations with peritonitis pose a serious problem to an emergency surgeon because of the lack of any uniformity of opinion regarding the optimum surgical treatment to be performed. This may be attributed to lack of any common and reliable scoring system. A prospective study to discover the utility of APACHE-II triaging in small bowel perforations was conducted over a period of 14 months on 51 patients with small bowel perforations of various aetiologies. The triaging facilitated definitive surgical treatments based on the predictive value of APACHE-II scoring. The classification of patients into three groups, effectively brought uniformity in the management. A significant reduction in mortality and cost-effective utilization of scarce intensive care unit resources were the dominant outcomes of this study conducted at a busy tertiary centre.

PAH-domain-specific interactions of the Arabidopsis transcription coregulator SIN3-LIKE1 (SNL1) with telomere-binding protein 1 and ALWAYS EARLY2 Myb-DNA binding factors.

The eukaryotic SIN3 protein is the central component of the evolutionarily conserved multisubunit SIN3 complex that has roles in regulating gene expression and genome stability. Here we characterise the structure of the SIN3 protein in higher plants through the analysis of SNL1 (SIN3-LIKE1), SNL2, SNL3, SNL4, SNL5 and SNL6, a family of six SIN3 homologues in Arabidopsis thaliana. In an Arabidopsis-protoplast beta-glucuronidase reporter gene assay, as well as in a heterologous yeast repression assay, full-length SNL1 was shown to repress transcription in a histone-deacetylase-dependent manner, demonstrating the conserved nature of SIN3 function. Yeast two-hybrid screening identified a number of DNA binding proteins each containing a single Myb domain that included the Arabidopsis ALWAYS EARLY proteins AtALY2 and AtALY3, and two telomere binding proteins AtTBP1 and AtTRP2/TRFL1 as SNL1 partners, suggesting potential functions for SNL1 in development and telomere maintenance. The interaction with telomere-binding protein 1 was found to be mediated through the well-defined paired amphipathic helix domain PAH2. In contrast, the AtALY2 interaction was mediated through the PAH3 domain of SNL1, which is structurally distinct from PAH1 and PAH2, suggesting that evolution of this domain to a more novel structural motif has occurred. These findings support a diverse role of SNL1 in the regulation of transcription and genome stability.