Averting transmission: A pivotal target to manage amoebiasis

Amoebiasis is a parasitic infectious disease caused by the enteric protozoan Entamoeba histolytica, a leading basis of deaths accounted to parasites, succeeding malaria and schistosomiasis. Conventional treatment methodologies used to deal with amoebiasis mainly rely on the administration of anti‐amoebic compounds and vaccines but are often linked with substantial side‐effects on the patient. Besides, cases of development of drug resistance in protozoans have been recorded, contributing further to the reduction in the efficiency of the treatment. Loopholes in the efficacious management of the disease call for the development of novel methodologies to manage amoebiasis. A way to achieve this is by targeting the essential metabolic processes of ‘encystation’ and ‘excystation’, and the associated biomolecules, thus interrupting the biphasic life cycle of the parasite. Technologies like the CRISPR‐Cas9 system can efficiently be exploited to discover novel and essential molecules that regulate the protozoan's metabolism, while efficiently manipulating and managing the known drug targets, leading to an effective halt and forestall to the enteric infection. This review presents a perspective on these essential metabolic processes and the associated molecules that can be targeted efficaciously to prevent the transmission of amoebiasis, thus managing the disease and proving to be a fruitful endeavour.     

Heme Oxygenase-1 Regulates Myeloid Cell Trafficking in AKI

Renal ischemia-reperfusion injury is mediated by a complex cascade of events, including the immune response, that occur secondary to injury to renal epithelial cells. We tested the hypothesis that heme oxygenase-1 (HO-1) expression, which is protective in ischemia-reperfusion injury, regulates trafficking of myeloid-derived immune cells in the kidney. Age-matched male wild-type (HO-1^+/+), HO-1–knockout (HO-1^−/−), and humanized HO-1–overexpressing (HBAC) mice underwent bilateral renal ischemia for 10 minutes. Ischemia-reperfusion injury resulted in significantly worse renal structure and function and increased mortality in HO-1^−/− mice. In addition, there were more macrophages (CD45⁺ CD11b^hiF4/80^lo) and neutrophils (CD45⁺ CD11b^hi MHCII⁻ Gr-1^hi) in HO-1^−/− kidneys than in sham and HO-1^+/+ control kidneys subjected to ischemia-reperfusion. However, ischemic injury resulted in a significant decrease in the intrarenal resident dendritic cell (DC; CD45⁺MHCII⁺CD11b^loF4/80^hi) population in HO-1^−/− kidneys compared with controls. Syngeneic transplant experiments utilizing green fluorescent protein–positive HO-1^+/+ or HO-1^−/− donor kidneys and green fluorescent protein–negative HO-1^+/+ recipients confirmed increased migration of the resident DC population from HO-1^−/− donor kidneys, compared to HO-1^+/+ donor kidneys, to the peripheral lymphoid organs. This effect on renal DC migration was corroborated in myeloid-specific HO-1^−/− mice subjected to bilateral ischemia. These mice also displayed impaired renal recovery and increased fibrosis at day 7 after injury. These results highlight an important role for HO-1 in orchestrating the trafficking of myeloid cells in AKI, which may represent a key pathway for therapeutic intervention.     

A study of assessment of patient safety climate in tertiary care hospitals

Background

Medical errors are being detected with increasing frequency in healthcare environment, in many cases leading to patient harm. Measurement and improvement of patient safety climate has been identified as a strategic effort towards addressing this vital issue.

Method

Safety Attitude Questionnaire (SAQ), validated by previous research was administered to 300 respondents in three tertiary care hospitals of India, the respondents representing various categories of healthcare workers and variations in safety scale score was analyzed by various statistical tools.

Results

No variation was observed in the Patient Safety Index score among the study hospitals. However, significant variations were observed among different categories of healthcare workers across dimensions of Teamwork, Perception of Management and Stress Recognition. Multiple Regression models identified Teamwork and Perception of Management to have significant correlation with Patient Safety Index Score.

Conclusion

Patient Safety Climate can be effectively assessed and such assessment utilized for focused improvement efforts towards safety in healthcare organizations.     

Management of neonatal cholestasis: Consensus statement of the pediatric gastroenterology chapter of Indian academy of pediatrics

Justification

Neonatal cholestasis is an important cause of chronic liver disease in young children. Late referral and lack of precise etiological diagnosis are reasons for poor outcome in substantial number of cases in India. There is a need to create better awareness among the pediatricians, obstetricians and primary care physicians on early recognition, prompt evaluation and referral to regional centers.

Process

Eminent national faculty members were invited to participate in the process of forming a consensus statement. Selected members were requested to prepare guidelines on specific issues, which were reviewed by two other members. These guidelines were then incorporated into a draft statement, which was circulated to all members. A round table conference was organized; presentations, ensuing discussions, and opinions expressed by the participants were incorporated into the final draft.

Objectives

To review available published data on the subject from India and the West, to discuss current diagnostic and management practices in major centers in India, and to identify various problems in effective diagnosis and ways to improve the overall outcome. Current problems faced in different areas were discussed and possible remedial measures were identified. The ultimate aim would be to achieve results comparable to the West.

Recommendations

Early recognition, prompt evaluation and algorithm-based management will improve outcome in neonatal cholestasis. Inclusion of stool/urine color charts in well baby cards and sensitizing pediatricians about differentiating conjugated from the more common unconjugated hyperbilirubinemia are possible effective steps. Considering the need for specific expertise and the poor outcome in suboptimally managed cases, referral to regional centers is warranted.     

An integrative approach using systems biology,mutational analysis with molecular dynamics simulation to challenge the functionality of a target protein

Visceral leishmaniasis affects millions of people worldwide in areas where Leishmania donovani is endemic. The protozoan species serves a greater threat as it has gradually evolved drug resistance whereby requiring newer approaches to treat the infection. State‐of‐art techniques are mostly directed toward finding better targets extracted from the available proteome data. In light of recent computational advancements, we ascertain and validate one such target, adenylosuccinate lyase (ADSL) by implementation of in‐silico methods which led to the identification of critical amino acid residues that affects its functional attributes. Our target selection was based on comprehensive topological analysis of a knowledge‐based protein–protein interaction network. Subsequently, mutations were incorporated and the dynamic behavior of mutated and native proteins was traced using MD simulations for a total time span of 600 ns. Comparative analysis of the native and mutated structures exhibited perceptible changes in the ligand‐bound catalytic region with respect to time. The unfavorable changes in the orientations of specific catalytic residues, His118 and His196, induced by generated mutations reduce the enzyme specificity. In summary, this integrative approach is able to select a target against pathogen, identify crucial residues, and challenge its functionality through the selected mutations.     

Unconventional initiator tRNAs sustain Escherichia coli

Of all tRNAs, initiator tRNA is unique in its ability to start protein synthesis by directly binding the ribosomal P-site. This ability is believed to derive from the almost universal presence of three consecutive G-C base (3G-C) pairs in the anticodon stem of initiator tRNA. Consistent with the hypothesis, a plasmid-borne initiator tRNA with one, two, or all 3G-C pairs mutated displays negligible initiation activity when tested in a WT Escherichia coli cell. Given this, the occurrence of unconventional initiator tRNAs lacking the 3G-C pairs, as in some species of Mycoplasma and Rhizobium, is puzzling. We resolve the puzzle by showing that the poor activity of unconventional initiator tRNAs in E. coli is because of competition from a large pool of the endogenous WT initiator tRNA (possessing the 3G-C pairs). We show that E. coli can be sustained on an initiator tRNA lacking the first and third G-C pairs; thereby reducing the 3G-C rule to a mere middle G-C requirement. Two general inferences following from our findings, that the activity of a mutant gene product may depend on its abundance in the cell relative to that of the WT, and that promiscuous initiation with elongator tRNAs has the potential to enhance phenotypic diversity without affecting genomic integrity, have been discussed.