Emergence of Extended Spectrum β-lactamases producing Escherichia coli among urinary tract infected patients from tertiary hospital in Nepal

Escherichia coli, a growing health concern, produces extended spectrum β-lactamases (ESBL), which are causing public health onset infections in multiple countries. Geographical variations in the distribution and prevalence of ESBL-synthesizing E. coli have been observed, with India reporting the largest proportion (61%). The worldwide dissemination of ESBL-producing bacteria, along with the restricted availability of effective treatments, could exacerbate antibiotic resistance. The identification of ESBL synthesizing E. coli is crucial for its characterisation and epidemiology in specific geographical regions. In Nepal, a developing nation, research shows a high prevalence of antibiotic-resistant bacteria, particularly the ESBL strain. Our study aimed to identify ESBL-producing E. coli from patients with urinary tract complications from a tertiary hospital in Nepal. Out of 125 E. coli isolates, 15.6% were female and 1.2% male. The highest resistance was detected for ampicillin, cefazolin, cefotaxime, and ceftazidime, while less resistance was observed against nitrofurantoin, gentamicin, and imipenem. The study found that 51 (40.8%) E. coli isolates produced ESBLs, indicating a higher level of ESBL production among urinary tract infection patients

Cytokines induce effector T-helper cells during invasive aspergillosis; what we have learned about T-helper cells?

Invasive aspergillosis caused by Aspergillus species (Aspergillus fumigatus, A. flavus and A. terreus) is life-threatening infections in immunocompromised patients. Understanding the innate and adaptive immune response particularly T-helper cells (TH-cells) against these Aspergillus species and how the different sub-set of TH-cells are regulated by differentiating cytokines at primary target organ site like lung, kidney and brain is of great significance to human health. This review focuses on presentation of Aspergillus through Antigen presenting cells (APCs) to the naive CD4+ T-cells in the host. The production of differentiating/effector cytokines that activate following TH-cells e.g., TH1, TH2, TH9 and TH17 has been reported in association or alone in allergic or invasive aspergillosis. Chemokines (CXCL1, CXCL2, CCL1 and CCL20) and their receptors associated to these TH-cells have also been observed in invasive aspergillosis. Thus, further study of these TH-cells in invasive aspergillosis and other elements of adaptive immune response with Aspergillus species are required in order to have a better understanding of host response for safer and effective therapeutic outcome

Structural and Biophysical Studies on Two Promoter Recognition Domains of the Extra-cytoplasmic Function σ Factor σC from Mycobacterium tuberculosis

σ factors are transcriptional regulatory proteins that bind to the RNA polymerase and dictate gene expression. The extracytoplasmic function σ factors (ECF) govern the environment dependent regulation of transcription. ECF σ factors have two domains σ(2) and σ(4) that recognize the −10 and −35 promoter elements. However, unlike the primary σ factor σ(A), the ECF σ factors lack σ(3), a region that helps in the recognition of the extended −10 element and σ(1.1), a domain involved in the auto-inhibition of σ(A) in the absence of core RNA polymerase. Mycobacterium tuberculosis σ(C) is an ECF σ factor that is essential for the pathogenesis and virulence of M. tuberculosis in the mouse and guinea pig models of infection. However, unlike other ECF σ factors, σ(C) does not appear to have a regulatory anti-σ factor located in the same operon. We also note that Mycobacterium tuberculosis σ(C) differs from the canonical ECF σ factors as it has an N-terminal domain comprising of 126 amino acids that precedes the σ(C)(2) and σ(C)(4) domains. In an effort to understand the regulatory mechanism of this protein, the crystal structures of the σ(C)(2) and σ(C)(4) domains of σ(C) were determined. These promoter recognition domains are structurally similar to the corresponding domains of σ(A) despite the low sequence similarity. Fluorescence experiments using the intrinsic tryptophan residues of σ(C)(2) as well as surface plasmon resonance measurements reveal that the σ(C)(2) and σ(C)(4) domains interact with each other. Mutational analysis suggests that the Pribnow box binding region of σ(C)(2) is involved in this inter-domain interaction. Interaction between the promoter recognition domains in M. tuberculosis σ(C) are thus likely to regulate the activity of this protein even in the absence of an anti-σ factor

Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC).

<p>Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC)</p

Molecular, pathological, radiological, and immune profiling of non-brainstem pediatric high-grade glioma from the HERBY phase II randomized trial

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8+ tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term ‘‘HGG’’ in the pediatric population