Role of PfGCN5 in nutrient sensing and transcriptional regulation in Plasmodium falciparum

Malaria is a deadly, infectious disease caused by the parasite Plasmodium, leading to millions of deathsworldwide. Plasmodium requires a coordinated pattern of sequential gene expression for surviving in bothinvertebrate and vertebrate host environments. As parasites largely depend on host resources, they also developefficient mechanisms to sense and adapt to variable nutrient conditions in the environment and modulate theirvirulence. Earlier we have shown that PfGCN5, a histone acetyltransferase, binds to the stress-responsive andvirulence-related genes in a poised state and regulates their expression under temperature and artemisinintreatment conditions in P. falciparum. In this study, we show upregulation of PfGCN5 upon nutrient stresscondition. With the help of chromatin immunoprecipitation coupled high-throughput sequencing (ChIP-seq)and transcriptomic (RNA-sequencing) analyses, we show that PfGCN5 is associated with the genes that areimportant for the maintenance of parasite cellular homeostasis upon nutrient stress condition. Furthermore, weidentified various metabolic enzymes as interacting partners of PfGCN5 by immunoprecipitation coupled withmass spectroscopy, possibly acting as a sensor of nutrient conditions in the environment. We also demonstratedthat PfGCN5 interacts and acetylates PfGAPDH in vitro. Collectively, our data provides important insights intotranscriptional deregulation upon nutrient stress condition and elucidate the role of PfGCN5 during nutrientstress condition.

Diverse presentations of phenytoin toxicity-presenile cataract, encephalopathy and peripheral neuropathy: a case series

One of the most commonly used antiepileptic drugs, phenytoin, has a narrow therapeutic index, high plasma protein binding, non-linearpharmacokinetics and inter-individual variability. It can also present with adverse drug reactions due to phenytoin toxicity with diverse presentations mimicking symptoms of other diseases thus causing diagnostic predicament. This case series reports three such cases of uncommon presentation of phenytoin toxicity like presenile cataract, fluctuating encephalopathy with diurnal variation and peripheral neuropathy. Monitoring of serum drug levels in such cases aids in confirming drug toxicity. Adverse drug reaction monitoring helps in early detection and appropriate management of drug related morbidity.

Parathyroid Carcinoma Masking Behind Primary Hyperparathyroidism: A Case Report with Review of Literature

Parathyroid carcinoma is a rare disease. It accounts for lessthan 1% of all case of primary hyperparathyroidism and isusually not detected until the time of surgery or thereafter.Preoperative staging is not available for most patients. Hence aradical excision remains the standard management. Usuallythe disease has an indolent but slowly progressive course.Most of the patients suffer due to complications ofhypercalcemia, rather than direct tumor invasion ormetastases. The management of PC is difficult in terms ofdiagnosis, treatment and follow up. Here is a case report thatproves a diagnostic challenge to both the clinicians andpathologists and is discussed below

Clinical presentation of patients with seasonal influenza and pandemic influenza A (H1N1-2009) requiring hospitalisation.

Background. A sudden increase in the number of novel influenza A virus (pH1N1-2009) infection prompted us to compare the clinical presentation and outcomes of patients infected with pH1N1-2009 and seasonal influenza A virus during the postpandemic phase. Methods. During the period August 13 to September 27, 2010, case records of 106 patients with severe influenza like illness (ILI) and respiratory complications who underwent diagnostic testing by real-time polymerase chain reaction (RT-PCR) for confirmation of pH1N1-2009 were retrospectively studied. Results. Nineteen (17.9%) patients were tested positive for pH1N1-2009 and 78 (73.6%) were tested positive for seasonal influenza A virus. The mean age of patients infected with pH1N1-2009 was 45.2±15.3 years (range of 22 to 80 years). Common presenting symptoms included fever in 17 (89.4%), cough in 16 (84.2%), myalgia in 15 (78.9%) and breathlessness in 10 (52.6%) patients. The most common comorbidities included bronchial asthma/bronchitis/chronic obstructive pulmonary disease (COPD) in 4 (21%); followed by hypertension in 3 (15.8%) and diabetes in 3 (15.8%) patients. Overall, of the 97 influenza infected patients, 9 (9.3%) needed hospitalisation to the intensive care unit (ICU); one patient with COPD died due to multi-organ failure. Conclusions. Both the pandemic and seasonal strains were found to be co-circulating in the community. Patients with severe hypoxia, hypertension, acute respiratory distress syndrome and shock required ICU care.