Reduced Glycolysis and Cytotoxicity in Staphylococcus aureus Isolates from Chronic Rhinosinusitis as Strategies for Host Adaptation.

Chronic rhinosinusitis (CRS) is a multifactorial infection of the nasal cavity and sinuses. In this study, nasal swabs from control donors (N = 128) and patients with CRS (N = 246) were analysed. Culture methods and metagenomics revealed no obvious differences in the composition of the bacterial communities between the two groups. However, at the functional level, several metabolic pathways were significantly enriched in the CRS group compared to the control group. Pathways such as carbohydrate transport metabolism, ATP synthesis, cofactors and vitamins, photosynthesis and transcription were highly enriched in CRS. In contrast, pathways related to lipid metabolism were more representative in the control microbiome. As S. aureus is one of the main species found in the nasal cavity, staphylococcal isolates from control and CRS samples were analysed by microarray and functional assays. Although no significant genetic differences were detected by microarray, S. aureus from CRS induced less cytotoxicity to lung cells and lower rates of glycolysis in host cells than control isolates. These results suggest the differential modulation of staphylococcal virulence by the environment created by other microorganisms and their interactions with host cells in control and CRS samples. These changes were reflected in the differential expression of cytokines and in the expression of Agr, the most important quorum-sensing regulator of virulence in S. aureus. In addition, the CRS isolates remained stable in their cytotoxicity, whereas the cytotoxic activity of S. aureus isolated from control subjects decreased over time during in vitro passage. These results suggest that host factors influence the virulence of S. aureus and promote its adaptation to the nasal environment during CRS.

Comparison Of Knowledge Among Millennials Studying In Non-Medical Universities Regarding Premarital And Prenatal Thalassemia Screening Policies In Pakistan.

Thalassemia awareness among the youth is vital for policy- making to reduce the disease burden in our country. A descriptive cross-sectional study was conducted via simple random sampling technique for which data was collected from May 2020 to May 2021 through Google forms. Results showed that out of a total of 394 non-medical university students, the majority, i.e. 265 (67.3%), were not aware of prenatal screening. Majority, i.e. 117 (29.7%), agreed that the couple should be screened before marriage, and 190 (48.2%) strongly agreed, while 46 (11.7%) had no knowledge. Students, however, believed premarital screening was either unavailable, not possible, or expensive. Other reasons included custom and culture of arranged marriages and religious reasons. The query that if both the parents are carriers and the foetus has thalassemia major should they have an abortion, showed mixed results. The key to controlling thalassemia is awareness of future parents.

Double-edged sword role of miRNA-633 and miRNA-181 in human cancers.

Understanding the function and mode of operation of microRNAs (miRNAs) in cancer is of growing interest. The short non-coding RNAs known as miRNAs, which target mRNA in multicellular organisms, are described as controlling essential cellular processes. The miR-181 family and miR-633 are well-known miRNAs that play a key role in the development and metastasis of tumor cells. They may facilitate either tumor-suppressive or oncogenic function in malignant cells, according to mounting evidence. Metastatic cells that are closely linked to cancer cell migration, invasion, and angiogenesis can be identified by abnormal levels of miR-181 and miR-633. Numerous studies have demonstrated their capacity to control drug resistance, cell growth, apoptosis, and the epithelial-mesenchymal transition (EMT) and metastasis process. Interestingly, the levels of miR-181 and miR-633 and their potential target genes in the basic cellular process can vary depending on the type of cancer cells and their gene expression profile. Such miRNAs' interactions with other non-coding RNAs such as long non-coding RNAs and circular RNAs can influence tumor behaviors. Herein, we concentrated on the multifaceted roles of miR-181 and miR-633 and potential targets in human tumorigenesis, ranging from cell growth and metastasis to drug resistance.

Large-scale genetic characterization of the model sulfate-reducing bacterium, Desulfovibrio vulgaris Hildenborough.

Sulfate-reducing bacteria (SRB) are obligate anaerobes that can couple their growth to the reduction of sulfate. Despite the importance of SRB to global nutrient cycles and their damage to the petroleum industry, our molecular understanding of their physiology remains limited. To systematically provide new insights into SRB biology, we generated a randomly barcoded transposon mutant library in the model SRB Desulfovibrio vulgaris Hildenborough (DvH) and used this genome-wide resource to assay the importance of its genes under a range of metabolic and stress conditions. In addition to defining the essential gene set of DvH, we identified a conditional phenotype for 1,137 non-essential genes. Through examination of these conditional phenotypes, we were able to make a number of novel insights into our molecular understanding of DvH, including how this bacterium synthesizes vitamins. For example, we identified DVU0867 as an atypical L-aspartate decarboxylase required for the synthesis of pantothenic acid, provided the first experimental evidence that biotin synthesis in DvH occurs via a specialized acyl carrier protein and without methyl esters, and demonstrated that the uncharacterized dehydrogenase DVU0826:DVU0827 is necessary for the synthesis of pyridoxal phosphate. In addition, we used the mutant fitness data to identify genes involved in the assimilation of diverse nitrogen sources and gained insights into the mechanism of inhibition of chlorate and molybdate. Our large-scale fitness dataset and RB-TnSeq mutant library are community-wide resources that can be used to generate further testable hypotheses into the gene functions of this environmentally and industrially important group of bacteria.

ECG Classification Using an Optimal Temporal Convolutional Network for Remote Health Monitoring.

Increased life expectancy in most countries is a result of continuous improvements at all levels, starting from medicine and public health services, environmental and personal hygiene to the use of the most advanced technologies by healthcare providers. Despite these significant improvements, especially at the technological level in the last few decades, the overall access to healthcare services and medical facilities worldwide is not equally distributed. Indeed, the end beneficiary of these most advanced healthcare services and technologies on a daily basis are mostly residents of big cities, whereas the residents of rural areas, even in developed countries, have major difficulties accessing even basic medical services. This may lead to huge deficiencies in timely medical advice and assistance and may even cause death in some cases. Remote healthcare is considered a serious candidate for facilitating access to health services for all; thus, by using the most advanced technologies, providing at the same time high quality diagnosis and ease of implementation and use. ECG analysis and related cardiac diagnosis techniques are the basic healthcare methods providing rapid insights in potential health issues through simple visualization and interpretation by clinicians or by automatic detection of potential cardiac anomalies. In this paper, we propose a novel machine learning (ML) architecture for the ECG classification regarding five heart diseases based on temporal convolution networks (TCN). The proposed design, which implements a dilated causal one-dimensional convolution on the input heartbeat signals, seems to be outperforming all existing ML methods with an accuracy of 96.12% and an F1 score of 84.13%, using a reduced number of parameters (10.2 K). Such results make the proposed TCN architecture a good candidate for low power consumption hardware platforms, and thus its potential use in low cost embedded devices for remote health monitoring.

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis.

Invasive mucormycosis (IM) is a life-threatening infection caused by the fungal order Mucorales, its diagnosis is often delayed, and mortality rates range from 40-80% due to its rapid progression. Individuals suffering from hematological malignancies, diabetes mellitus, organ transplantations, and most recently COVID-19 are particularly susceptible to infection by Mucorales. Given the increase in the occurrence of these diseases, mucormycosis has emerged as one of the most common fungal infections in the last years. However, little is known about the host immune response to Mucorales. Therefore, we characterized the interaction among L. corymbifera-one of the most common causative agents of IM-and human monocytes, which are specialized phagocytes that play an instrumental role in the modulation of the inflammatory response against several pathogenic fungi. This study covered four relevant aspects of the host-pathogen interaction: i) The recognition of L. corymbifera by human monocytes. ii) The intracellular fate of L. corymbifera. iii) The inflammatory response by human monocytes against the most common causative agents of mucormycosis. iv) The main activated Pattern-Recognition Receptors (PRRs) inflammatory signaling cascades in response to L. corymbifera. Here, we demonstrate that L. corymbifera exhibits resistance to intracellular killing over 24 hours, does not germinate, and inflicts minimal damage to the host cell. Nonetheless, viable fungal spores of L. corymbifera induced early production of the pro-inflammatory cytokine IL-1ß, and late release of TNF-α and IL-6 by human monocytes. Moreover, we revealed that IL-1ß production predominantly depends on Toll-like receptors (TLRs) priming, especially via TLR4, while TNF-α is secreted via C-type lectin receptors (CTLs), and IL-6 is produced by synergistic activation of TLRs and CTLs. All these signaling pathways lead to the activation of NF-kB, a transcription factor that not only regulates the inflammatory response but also the apoptotic fate of monocytes during infection with L. corymbifera. Collectively, our findings provide new insights into the host-pathogen interactions, which may serve for future therapies to enhance the host inflammatory response to L. corymbifera.

Anticancer activity of milk fat rich in conjugated linoleic acid against Ehrlich ascites carcinoma cells in female Swiss albino mice.

BACKGROUND AND AIM: The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. MATERIALS AND METHODS: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106/0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. RESULTS: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. CONCLUSION: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Very rare electrocardiograph abnormalities in meningitis: a case report.

Osborn waves are produced when the J point deviates from baseline. While there are many known causes of Osborn waves, hypothermia remains the most common. We report electrocardiographic changes with Osborn wave in a 32-year-old woman with fatal meningoencephalitis, potentially reversible, probably non-ischaemic myocardial dysfunction may occur in association with acute non cardiac illnesses, such as brain injuries or severe infections. The mechanisms of the electrocardiography (ECG) abnormalities in this disease are unclear.

The Use of Probiotic with ORS and ORS Only in Children with Acute Diarrhea.

OBJECTIVE: To compare the mean number of stools per day in children treated with combination of probiotic (lactobacillus rhamnosus) with ORS and ORS only in acute diarrhea. STUDY DESIGN: Randomised control trial. PLACE AND DURATION OF STUDY: Department of Pediatric Medicine, PNS Shifa Hospital, from February to July, 2017. METHODOLOGY: A total of 80 children with acute watery diarrhea were randomly divided into two groups. Forty patients in first group were given probiotic with ORS and 40 patients in second group (control) were given ORS only. All children were monitored from 0 day (inclusion day) to next 5 days. Demographic data was collected regarding age, gender, weight and frequency of loose stools. Dehydration status was also assessed at the time of admission by the attending physician. Data was collected through a structured proforma. RESULTS: The average age of the children was 24.3 ±18.65 months. There were 47 (58.8%) males and 33 (41.3%) females. Mean number of stools was significantly low in those patients who were treated with combination of probiotic (lactobacillus rhamnosus) with ORS than those who were treated with ORS only in acute diarrhea (3.25 ±1.13 vs. 4.13 ±0.79; p<0.001). CONCLUSION: Probiotics are found to be significantly more effective in reducing the stool frequency in acute diarrhea.

Genomes OnLine Database (GOLD) v.6: data updates and feature enhancements.

The Genomes Online Database (GOLD) (https://gold.jgi.doe.gov) is a manually curated data management system that catalogs sequencing projects with associated metadata from around the world. In the current version of GOLD (v.6), all projects are organized based on a four level classification system in the form of a Study, Organism (for isolates) or Biosample (for environmental samples), Sequencing Project and Analysis Project. Currently, GOLD provides information for 26 117 Studies, 239 100 Organisms, 15 887 Biosamples, 97 212 Sequencing Projects and 78 579 Analysis Projects. These are integrated with over 312 metadata fields from which 58 are controlled vocabularies with 2067 terms. The web interface facilitates submission of a diverse range of Sequencing Projects (such as isolate genome, single-cell genome, metagenome, metatranscriptome) and complex Analysis Projects (such as genome from metagenome, or combined assembly from multiple Sequencing Projects). GOLD provides a seamless interface with the Integrated Microbial Genomes (IMG) system and supports and promotes the Genomic Standards Consortium (GSC) Minimum Information standards. This paper describes the data updates and additional features added during the last two years.