Evaluation of a pulse oximeter during profound hypothermia. An assessment of the Biox 3700 during induction of hypothermia before cardiac surgery in paediatric patients

The accuracy of the Ohmeda Biox 3700 pulse oximeter was evaluated in 10 paediatric patients, deliberately surface cooled to 25°C in preparation for cardiac surgery, by comparing the arterial oxygen saturation results obtained from an Ohmeda Biox 3700 and a Radiometer OSM-2 Hemoximeter. Though, there was a good correlation between the two series of results, the arterial oxygen saturation was over-estimated by the pulse oximeter compared to the OSM-2 Hemoximeter in the temperature range 36° to 30°C and under-estimated below 30°C. These differences were greatest when the initial saturations were low.     

Strategies for developing biomarkers of heart failure

BACKGROUND: Heart failure (HF) is a devastating disease with increasing prevalence in elderly populations. One-half of all patients die within 5 years of diagnosis. The annual cost of treating patients with HF in the US is more than $20 billion, which is estimated to be greater than that of myocardial infarction and all cancers combined. Given the complex pathophysiology and varied manifestations of HF, interest has intensified in developing biological markers to predict susceptibility and aid in the early diagnosis and management of this disease. METHODS: We searched Medline via Ovid for studies published during the period 1966-2003 regarding various biomarkers suggested for HF. Our review focused on developing strategies for discovering and using new biomarkers, particularly those potentially linked to pathophysiologic mechanisms. We also point out strategic advantages, limitations, and methods available for measuring each of the currently proposed markers. RESULTS: Biomarkers reviewed include those released from the heart during normal homeostasis (natriuretic peptides), those produced elsewhere that act on the heart (endogenous cardiotonic steroids and other hormones), and those released in response to tissue damage (inflammatory cytokines). The concept of using a combination of multiple markers based on diagnosis, prognosis, and acute vs chronic disease is also discussed. In view of recent advances in our understanding of molecular biochemical derangements observed during cardiac failure, we consider the concept of myocardial remodeling and the heart as part of an endocrine system as strategies. CONCLUSION: Strategically, biomarkers linked to mechanisms involved in the etiology of HF, such as dysregulation of ion transport, seem best suited for serving as early biological markers to predict and diagnose disease, select therapy, or assess progression.     

Spectrum and outcome of pancreatic trauma.

BACKGROUND AND AIMS: Pancreatic trauma is associated with high morbidity and mortality. Diagnosis is often difficult and surgery poses a formidable challenge. METHOD: Data from 17 patients of pancreatic trauma gathered from a prospectively maintained database were analysed and the following parameters were considered: mode of injury, diagnostic modalities, associated injury, grade of pancreatic trauma and management. Pancreatic trauma was graded from I through IV, as per Modified Lucas Classification. RESULTS: The median age was 39 years (range 19-61). The aetiology of pancreatic trauma was blunt abdominal trauma in 14 patients and penetrating injury in 3. Associated bowel injury was present in 4 cases (3 penetrating injury and 1 blunt trauma) and 1 case had associated vascular injury. 5 patients had grade I, 3 had grade II, 7 had grade III and 2 had grade IV pancreatic trauma. Contrast enhanced computed tomography scan was used to diagnose pancreatic trauma in all patients with blunt abdominal injury. Immediate diagnosis could be reached in only 4 (28.5%) patients. 7 patients responded to conservative treatment. Of the 10 patients who underwent surgery, 6 required it for the pancreas and the duodenum. (distal pancreatectomy with splenectomy-3, pylorus preserving pancreatoduodenectomy-1, debridement with external drainage-1, associated injuries-duodenum-1). Pancreatic fistula, recurrent pancreatitis and pseudocyst formation were seen in 3 (17.05%), 2 (11.7%) and 1 (5.4%) patient respectively. Death occurred in 4 cases (23.5%), 2 each in grades III and IV pancreatic trauma. CONCLUSIONS: Contrast enhanced computed tomography scan is a useful modality for diagnosing, grading and following up patients with pancreatic trauma. Although a majority of cases with pancreatic trauma respond to conservative treatment, patients with penetrating trauma, and associated bowel injury and higher grade pancreatic trauma require surgical intervention and are also associated with higher morbidity and mortality.     

Immunomodulatory studies of a bioactive fraction from the fruit of Prunus cerasus in BALB/c mice

In order to evaluate the role of ethyl acetate fraction (PNRS-EtOAC) obtained from the Prunus cerasus fruit in the modulation of immune responses, detailed studies were carried out using a panel of in vivo assays. Oral administration of PNRS-EtOAC (25-100 mg/kg) stimulated the IgM and IgG titre expressed in the form of hemagglutination antibody (HA) titre. Further, it elicited a dose related increase in the delayed type hypersensitivity reaction (DTH) after 24 and 48 h in BALB/c mice. Besides augmenting the humoral and cell mediated immune response, the concentration of cytokines (IFN-γ, IL-4, and TNF-α) in serum with respect to T cell interactions, i.e. the proliferation of lymphocytes were significantly increased at 50 mg/kg compared with the control. The results in these studies demonstrated the immunostimulatory effect of PNRS-EtOAC in a dose-dependent manner with respect to the macrophage activation possibly expressing the phagocytosis and nitrite production by the enhancement of TNF-α production as a mode of action.     

Overlapping pools for high-throughput targeted resequencing

Resequencing genomic DNA from pools of individuals is an effective strategy to detect new variants in targeted regions and compare them between cases and controls. There are numerous ways to assign individuals to the pools on which they are to be sequenced. The naïve, disjoint pooling scheme (many individuals to one pool) in predominant use today offers insight into allele frequencies, but does not offer the identity of an allele carrier. We present a framework for overlapping pool design, where each individual sample is resequenced in several pools (many individuals to many pools). Upon discovering a variant, the set of pools where this variant is observed reveals the identity of its carrier. We formalize the mathematical framework for such pool designs and list the requirements from such designs. We specifically address three practical concerns for pooled resequencing designs: (1) false-positives due to errors introduced during amplification and sequencing; (2) false-negatives due to undersampling particular alleles aggravated by nonuniform coverage; and consequently, (3) ambiguous identification of individual carriers in the presence of errors. We build on theory of error-correcting codes to design pools that overcome these pitfalls. We show that in practical parameters of resequencing studies, our designs guarantee high probability of unambiguous singleton carrier identification while maintaining the features of naïve pools in terms of sensitivity, specificity, and the ability to estimate allele frequencies. We demonstrate the ability of our designs in extracting rare variations using short read data from the 1000 Genomes Pilot 3 project.DNA sequencing is being revolutionized by new technologies, replacing the methods of the past decade. “Second Generation” sequencing currently offers several orders of magnitude better throughput at the same cost by massively parallel reading of short ends of genomic fragments (Mardis 2008). This enables addressing new questions in genomics, but poses novel technical challenges. Specifically, it is now feasible to obtain reliable genomic sequence along a considerable fraction of the human genome, from multiple individual samples. Such high-throughput resequencing experiments hold the promise of shifting the paradigm of human variation analysis and are the focus of this study.Connections between genetic and phenotypic variation have traditionally been studied by determining the genotype of prescribed markers. This cost-effective strategy for large-scale analysis has recently led to multiple successes in detecting trait-associated alleles in humans (Wang et al. 1998; Risch 2000). However, genotyping technologies have two fundamental drawbacks: First, they are limited to a subset of segregating variants that are predetermined and prioritized for typing; second, this subset requires the variant to have been previously discovered in the small number of individuals sequenced to date. Both of these limitations are biased toward typing of common alleles, present in at least 5% of the population. Such alleles have been well characterized by the Human Haplotype Map (The International HapMap Project 2003) and have been associated with multiple phenotypes. On the other hand, rare alleles are both underprioritized for association studies, and a large fraction of them remain undiscovered (Reich et al. 2003; Brenner 2007; Levy et al. 2007).Resequencing can fill in the last pieces of the puzzle by allowing us to discover these rare variants and type them. Particularly, regions around loci that have previously been established or suspected for involvement in disease can be resequenced across a large population to seek variation. However, finding rare variation requires the resequencing of hundreds of individuals: something considered infeasible until now. With the arrival of low-cost, high-fidelity, and high-throughput resequencing technology, however, this search is feasible, albeit expensive. Illumina''s Genome Analyzer (Gunderson et al. 2004), ABI''s SOLiD sequencer (Fu et al. 2008), 454 Life Sciences'' (Roche) Genome Sequencer FLX (Margulies et al. 2005), to name a few, are the current primary technology providers offering throughputs on the order of giga base pairs in a single run (Mardis 2008).Resequencing is typically done on targeted regions rather than the whole genome, making throughput requirements to sequence an individual much less than what is provided by a single run. A costly option is to utilize one run per individual, but in a study population of hundreds or thousands, such an approach is prohibitively expensive. In such cases, “pooled” sequence runs may be used.The central idea of pooling is to assay DNA from several individuals together on a single sequence run. Pooled Genotyping has been used to quantify previously identified variations and study allele frequency distributions (Shaw et al. 1998; Ito et al. 2003; Zeng and Lin 2005) in populations. Given an observed number of alleles and an estimate of the number of times an allelic region was sampled in the pool, it is possible to infer the frequency of the allele in the pooled individuals being studied. Pooled resequencing can be used to reach similar ends, with the added advantage of being able to identify new alleles. At least one recent work has analyzed the efficacy of pooled resequencing for complete sequence reconstruction (Hajirasouliha et al. 2008). The investigators of that work studied the problem of reconstructing multiple disjoint regions of a single genome while minimizing overlap between regions. Our work addresses the problem of identifying rare variations contained within a single region across multiple individuals.Historically, the primary trade-off of a pooled approach has been the inability to pinpoint the variant carrier from among the individuals sequenced in a pool. Retracing an observed variant back to its carrier required additional sequencing (or genotyping) of all of these individuals, one at a time. Barcoding is an upcoming experimental method that involves ligating a “signature” nucleotide string (∼5 bp) to the start of all reads belonging to an individual. These nucleotides serve as the barcode that identifies which individual a given sequenced read came from. If/when established, barcoding technology may essentially offer a more complex assay for a wetlab solution to the same problem we address through computational means.The central idea behind our overlapping pool design is that while sequencing DNA from several individuals on a single pool, we also sequence DNA from a single individual on several pools. Individuals are assigned to pools in a manner so as to create a code: a unique set of pools for each individual. This set of pools on which an individual is sequenced defines a code word, or pool signature. If a variation is observed on the signature pools of one individual and on no other, then we identify the carrier of the variation. For example, consider a study where a single proband X is part of a cohort of one hundred individuals being resequenced for the same genomic region. Out of 15 pools used by the study, assume that Xs DNA is sequenced on pools 1, 3, and 7, such that no other individual in the cohort has been sequenced on the same three pools. A variation uniquely recorded on these three pools is likely to be carried by X, and only by X. Code-based pool assays like this have been studied before. In particular, we extend and apply principles developed in other contexts of pooling, such as genotyping (Pe''er and Beckmann 2003; Beckman et al. 2006) and de-novo sequencing (Cai et al. 2001; Csuros et al. 2003).The balance of this work is organized as follows: In the Methods section, we first introduce a generic mathematical model that can be used to represent the pooled resequencing process. We develop figures of merit to evaluate a pool design''s robustness to error, and coverage under given budgetary constraints. We then propose two algorithms for pool design: logarithmic signature designs and error-correcting designs. In the Results section we compare the efficacies of our designs against each other and against current practices using synthetic data as well as real short-read data from the 1000 Genomes Pilot 3 project (www.1000genomes.org), where we quantify the abilities and trade-offs of the designs. A significant part of our analysis deals with the errors and noise introduced at various stages in the pooled resequencing process. We summarize our contributions in the Discussion section.     

Curcuma zedoaria Rosc. (white turmeric): a review of its chemical,pharmacological and ethnomedicinal properties

Objectives Curcuma zedoaria Rosc is a perennial herb found in tropical countries, such as India, Japan and Thailand. Various parts of this plant are used in Ayurveda and other folk medicines for the treatment of different ailments such as diarrhoea, cancer, flatulence and dyspepsia. This study is an attempt to compile an up‐to‐date and comprehensive review of C. zedoaria that covers its traditional and folk medicinal uses, phytochemistry and pharmacology. Key findings Research carried out using different in‐vitro and in‐vivo techniques of biological evaluation supports most of the claims. Summary This review presents the botany, chemistry, traditional uses and pharmacological data of the plant.     

Vertical Strut Ossiculoplasty: A Versatile Alternate to Conventional Techniques—A Randomized study

IntroductionVarious ossicular reconstruction materials and techniques have been described in literature using autologous ossicle, cortical bone, autologous cartilage, synthetic materials and implants like total/partial ossicular replacement prosthesis (TORP/PORP) etc., but it has always been a topic of controversy in terms of the efficacy, longevity and complications of the material or method used.Material and MethodsThis is a prospective, interventional, comparative, double-blind randomized control study which was done at a tertiary care center to compare outcomes of conventional and carved conchal cartilage (vertical strut) type III Tympanoplasty in terms of graft uptake and hearing gain. A total number of 52 cases were enrolled, randomized and allocated to 2 groups (26 each) i.e. group A (conventional type III) and group B (vertical strut technique).ResultsGraft uptake was seen in 25 (96.16%) patients in group B while it was observed in 23 (88.5%) cases in group A. Hearing gains were also better in group B.ConclusionThis study suggests that Vertical Strut technique can be studied further as it gives better gains in Air Conduction threshold and A-B Gap along with graft uptake as it provides better middle ear space and ossicular / tympanic membrane interface resulting in better hearing.     

Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction and excess

Females and males typically play different roles in survival of the species and would be expected to respond differently to food scarcity or excess. To elucidate the physiological basis of sex differences in responses to energy intake, we maintained groups of male and female rats for 6 months on diets with usual, reduced [20% and 40% caloric restriction (CR), and intermittent fasting (IF)], or elevated (high-fat/high-glucose) energy levels and measured multiple physiological variables related to reproduction, energy metabolism, and behavior. In response to 40% CR, females became emaciated, ceased cycling, underwent endocrine masculinization, exhibited a heightened stress response, increased their spontaneous activity, improved their learning and memory, and maintained elevated levels of circulating brain-derived neurotrophic factor. In contrast, males on 40% CR maintained a higher body weight than the 40% CR females and did not change their activity levels as significantly as the 40% CR females. Additionally, there was no significant change in the cognitive ability of the males on the 40% CR diet. Males and females exhibited similar responses of circulating lipids (cholesterols/triglycerides) and energy-regulating hormones (insulin, leptin, adiponectin, ghrelin) to energy restriction, with the changes being quantitatively greater in males. The high-fat/high-glucose diet had no significant effects on most variables measured but adversely affected the reproductive cycle in females. Heightened cognition and motor activity, combined with reproductive shutdown, in females may maximize the probability of their survival during periods of energy scarcity and may be an evolutionary basis for the vulnerability of women to anorexia nervosa.