Pharmacological characterization of the excitatory ‘Cys‐loop’ GABA receptor family in Caenorhabditis elegans

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136449/1/bph13736.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136449/2/bph13736_am.pd

Neurological complications in patients with plasmodium vivax malaria from Karachi, Pakistan

Background: Malaria remains an endemic disease in Pakistan with an estimated healthcare burden of 1.6 million cases annually, with Plasmodium vivax accounting for 67% of reported cases. P. vivax is the most common species causing malaria outside of Africa, with approximately 13.8 million reported cases worldwide. Method: We report a series of P. vivax cases with cerebral involvement that presented at Aga Khan University Hospital, Karachi, Pakistan. Results: The majority of the patients presented with high-grade fever accompanied by projectile vomiting and abnormal behaviour, seizures, shock and unconsciousness. Seven of 801 patients with P. vivax monoinfection presented or developed cerebral complications. P. vivax infections were diagnosed based on peripheral smears and rapid diagnostic testing. Conclusion: P. vivax infection can lead to severe complications, although not with the frequency of Plasmodium falciparum infection. Current cases highlight an increasing trend of cerebral complications caused by P. vivax

Spectrum of complications and mortality of bacterial meningitis: an experience from a developing country

Objective: The aim of this study was to obtain data on predisposing factors, causative organisms and their associated mortality and complications related to acute bacterial meningitis. Methods: The chart review of all patients in whom acute bacterial meningitis was diagnosed at The Aga Khan University Hospital from January 1995 through December 2001. Results: One hundred ninety-four patients were included in study. There were 146 males and 48 females. The mean age of our study population was 41±12.3 years. One hundred and ninety (97.9%) patients had community acquired meningitis; only 4 (2.0%) patients developed meningitis nosocomially. The two most common predisposing factors were diabetes mellitus (13.9%) and otitis media (7.7%) among all 194 patients. A significant proportion of patients with complications had diabetes mellitus (24.6%, p Conclusion: Bacterial Meningitis remains a serious disease associated with substantial morbidity and mortality. Most cases are community acquired with S. Pneumoniae being the most common pathogen. Old age, diabetes mellitus, a positive culture, seizures as a complication and late stage in the disease are the important predictors of a poor outcome (JPMA 53:580;2003)

Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies

Using linkage analysis and whole-exome sequencing, Safka Brozkova et al. reveal missense mutations in the histidyl-tRNA synthetase gene in 23 patients from four families with axonal and demyelinating neuropathies of varying severity. The mutations cause loss of function in yeast complementation assays and neurotoxicity in a C. elegans mode

Highly Efficient, Rapid and Co-CRISPR-Independent Genome Editing in Caenorhabditis elegans

We describe a rapid and highly efficient method to generate point mutations in Caenorhabditis elegans using direct injection of CRISPR-Cas9 ribonucleoproteins. This versatile method does not require sensitized genetic backgrounds or co-CRISPR selection-based methods, and represents a single strategy that can be used for creating genomic point mutations, regardless of location. As proof of principle, we show that knock-in mutants more faithfully report variant-associated phenotypes as compared to transgenic overexpression. Data for nine knock-in mutants across five genes are presented that demonstrate high editing efficiencies (60%), a reduced screening workload (24 F1 progeny), and a rapid timescale (4–5 d). This optimized method simplifies genome engineering and is readily adaptable to other model systems

Percutaneous aspiration-injection-reaspiration drainage plus albendazole or mebendazole for hepatic cystic echinococcosis: a meta-analysis

Using meta-analysis methodology, we compared the clinical outcomes for 769 patients with hepatic cystic echinococcosis treated with percutaneous aspiration-injection-reaspiration (PAIR) plus albendazole or mebendazole (group 1) with 952 era-matched historical control subjects undergoing surgical intervention (group 2). The rate of clinical and parasitologic cure (P\u3c.0001) was greater in patients receiving PAIR plus chemotherapy. Disease recurrence (P\u3c.0001), major complications (anaphylaxis, biliary fistula, cyst infection, liver/intra-abdominal abscess, and sepsis; P\u3c.0001), minor complications (P\u3c.0001), and death (P\u3c.0824) occurred more frequently among surgical control subjects. Fever (P\u3c.002) and minor allergic reactions subjects (P\u3c.0001) were more common among PAIR-treated subjects. The mean durations of hospital stay were 2.4 days for group 1 and 15.0 days for group 2 (P\u3c.001). Compared with surgery, PAIR plus chemotherapy is associated with greater clinical and parasitologic efficacy; lower rates of morbidity, mortality, and disease recurrence; and shorter hospital stays

Emerging drug--resistance and guidelines for treatment of malaria

The increasing prevalence of multi-resistant Plasmodium falciparum malaria worldwide is a serious public health threat to the global control of malaria, especially in poor countries like Pakistan. In many countries choloroquine-resistance is a huge problem, accounting for more than 90% of malaria cases. In Pakistan, resistance to choloroquin is on the rise and reported in up to 16- 62% of Plasmodium falciparum. four to 25% of Plasmodium falciparum also reported to be resistant to sulfadoxine-pyrimethamine and several cases of delayed parasite clearance have been observed in patients with Plasmodium falciparum malaria treated with quinine. In this article we have introduced the concept of artemisinin- based combination therapy (ACT) and emphasize the use of empiric combination therapy for all patients with Plasmodium falciparum malaria to prevent development of drug resistance and to obtain additive and synergistic killing of parasite