A double take on bivalent promoters

Histone modifications and chromatin-associated protein complexes are crucially involved in the control of gene expression, supervising cell fate decisions and differentiation. Many promoters in embryonic stem (ES) cells harbor a distinctive histone modification signature that combines the activating histone H3 Lys 4 trimethylation (H3K4me3) mark and the repressive H3K27me3 mark. These bivalent domains are considered to poise expression of developmental genes, allowing timely activation while maintaining repression in the absence of differentiation signals. Recent advances shed light on the establishment and function of bivalent domains; however, their role in development remains controversial, not least because suitable genetic models to probe their function in developing organisms are missing. Here, we explore avenues to and from bivalency and propose that bivalent domains and associated chromatin-modifying complexes safeguard proper and robust differentiation.     

Comparative forensic analysis of reverse root canal filing and conventional method for DNA isolation from extracted teeth under different environmental conditions: A prospective study

The grinding of a whole tooth specimen has been considered the conventional method to extract genomic deoxyribonucleic acid (DNA) in forensic science. However, we have tried the less destructive reverse root canal filing (RRCF) method without disturbing the morphology of the tooth to achieve competent amplifiable DNA. A total of 27 pairs of bilateral intact extracted teeth from the same subject were used in three different simulated environmental conditions for the respective RRCF and conventional methods: (a) soil burial for six months, (b) incineration at 200º C for four minutes, and (c) immersion in water for two months. Qualitative agarose gel electrophoresis assessment and downstream amplification were performed. The results showed significantly higher mean DNA concentration for the RRCF method in all three environmental conditions (p value = 0.008) in comparison to the conventional method. However, comparable qualitative results were found in both methods for the mean DNA concentration for incinerated (159.49 ng/ml), soil (119.52 ng/ml), and water (108.60 ng/ml) samples. It was concluded that the RRCF method is better quantitively (ng/ml) and comparable in terms of quality with respect to the conventional method, with the added advantage of preservation of the tooth morphology.     

Recurrent hyperhemolytic transfusion reaction in myelodysplastic syndrome- A case based approach

We present here a case report of a 27 year old female, with myelodysplatic syndrome suspected to have recurrent hyperhemolytic transfusion reactions (HHTR). Patient was transfusion dependent for ten years and was transfused with leukodepleted and irradiated Packed Red Blood Cells (PRBC). She presented with signs and symptoms of acute intravascular hemolysis, deranged coagulation profile with post transfusion Hb lower than baseline. Post transfusion workup was uneventful. She was managed conservatively with fluid support and methylprednisolone initially. After few uneventful transfusions, patient developed second episode of HHTR with compatible unit.Immunophenotype favored an inflammatory response possibly induced by monocytic lineage. As transfusion dependent, the patient required methylprednisolone as premedication and all subsequent transfusions were uneventful.     

The development and psychometric evaluation of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients scale

BackgroundValidated measures of ward nurses' safety cultures in relation to escalations of care in deteriorating patients are lacking.ObjectivesThis study aimed to develop and evaluate the psychometric properties of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients (CARED) scale for use among ward nurses.MethodsThe study was conducted in two phases: scale development and psychometric evaluation. The scale items were developed based on a systematic literature review, informant interviews, and expert reviews (n = 15). The reliability and validity of the scale were examined by administering the scale to 617 registered nurses with retest evaluations (n = 60). The factor structure of the CARED scale was examined in a split-half analysis with exploratory and confirmatory factor analyses. The internal consistency, test–retest reliability, convergent validity, and known-group validity of the scale were also analysed.ResultsA high overall content validity index of 0.95 was obtained from the validations of 15 international experts from seven countries. A three-factor solution was identified from the final 22 items: ‘beliefs about rapid response system’, ‘fears about escalating care’, and ‘perceived confidence in responding to deteriorating patients’. The internal consistency reliability of the scale was supported with a good Cronbach's alpha value of 0.86 and a Spearman-Brown split-half coefficient of 0.87. An excellent test–retest reliability was demonstrated, with an intraclass correlation coefficient of 0.92. The convergent validity of the scale was supported with an existing validated scale. The CARED scale also demonstrated abilities to discriminate differences among the sample characteristics.ConclusionsThe final 22-item CARED scale was tested to be a reliable and valid scale in the Singaporean setting. The scale may be used in other settings to review hospitals' rapid response systems and to identify strategies to support ward nurses in the process of escalating care in deteriorating ward patients.     

Linkage of essential hypertension to chromosome 18q

We performed a genomewide scan with 904 microsatellite markers using 120 extended Icelandic families with 490 hypertensive patients. The families were identified by cross-matching a list of hypertensive patients from the Hypertension Clinic of the University Hospital (Landspitalinn) in Iceland with a genealogy database of the entire Icelandic nation. After adding 5 markers, we found linkage to chromosome 18q with an allele-sharing LOD score of 4.60 (P=2.1x 10(-6)). These results provide evidence for a novel susceptibility gene for essential hypertension on chromosome 18q and show that it is possible to study the genetics of essential hypertension without stratifying by subphenotypes.     

Interferon Gamma ELISPOT Testing as a Risk‐Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT‐01 Multicenter Study

Previous studies suggest that quantifying donor‐reactive memory T cells prior to kidney transplantation by interferon gamma enzyme‐linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation‐01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6‐ or 12‐month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell‐depleting, rabbit anti‐thymocyte globulin (ATG). Within the no‐ATG subset, IFNγELISPOT^neg subjects had higher 6‐ and 12‐month eGFRs than IFNγELISPOT^pos subjects, independent of biopsy‐proven AR, peak PRA, human leukocyte antigen mismatches, African‐American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor‐reactive memory T cells.     

Effectiveness of medical thoracoscopy and thoracoscopic talc poudrage in patients with exudative pleural effusion

INTRODUCTION

This study aimed to assess the effectiveness of medical thoracoscopy (MT) and thoracoscopic talc poudrage (TTP) in patients with exudative pleural effusion.

METHODS

We evaluated the diagnostic yields, complications and outcomes of MT and TTP in 41 consecutive patients with symptomatic pleural effusions who were planned to undergo both procedures from 1 December 2011 to 30 November 2012. Data was reviewed retrospectively and prospectively up to March 2013.

RESULTS

Among the 41 patients, 36 underwent MT with the intent of biopsy and talc pleurodesis, 2 underwent MT for pleurodesis only and 3 had failed MT. Aetiologies of pleural effusion included lung cancer (n = 14), tuberculosis (n = 9), breast cancer (n = 7), ovarian cancer (n = 2), malignant mesothelioma (n = 1), congestive cardiac failure (n = 1), peritoneal dialysis (n = 1) and hepatic hydrothorax (n = 1); pleural effusion was undiagnosed in five patients. The overall diagnostic yield of MT, and the yield in tubercular and malignant pleural effusions were 77.8%, 100.0% and 82.6%, respectively; it was inconclusive in 22.2%. Complications that occurred were self-limiting, with no procedure-related mortality. The 30-day mortality rate was 17.1%. A total of 15 patients underwent TTP. The 30-, 60- and 90-day success rates were 77.8%, 80.0% and 80.0%, respectively, with one patient having complications (i.e. empyema). The 30-day mortality was 40.0%.

CONCLUSION

MT is a safe procedure with high diagnostic yields in undiagnosed pleural effusions. TTP is an effective method to stop recurrence of pleural effusions.     

Does this patient really have chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is a condition commonly encountered by primary care practitioners. The disease should be detected in its early stages to prevent disease progression and to reduce the burden of symptoms. Early treatment also results in improved mortality and reduced morbidity. COPD should be differentiated from other similar conditions such as asthma, as the basis of treatment differs in these conditions, and misdiagnosis can lead to poorer patient outcomes. Non-pharmacological treatment such as smoking cessation and vaccinations are important in the management of COPD, while pharmacotherapy such as bronchodilators and antimuscarinics are the mainstay of therapy in COPD. Referral to a specialist is recommended when there is progression of the disease or uncertainty regarding the diagnosis.