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Infectious Diseases (London, England) Jun 2024This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for...
OBJECTIVES
This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis.
METHODS
Data have been prospectively collected for the period1977-2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5-1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin.
RESULTS
In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone ( = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone ( = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone ( = 0.000).
CONCLUSIONS
A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients.
PubMed: 38922314
DOI: 10.1080/23744235.2024.2370967 -
Metabolites May 2024Coronary artery disease (CAD) and atherosclerosis pose significant global health challenges, with intricate molecular changes influencing disease progression....
Coronary artery disease (CAD) and atherosclerosis pose significant global health challenges, with intricate molecular changes influencing disease progression. Hypercholesterolemia (HC), hypertension (HT), and diabetes are key contributors to CAD development. Metabolomics, with its comprehensive analysis of metabolites, offers a unique perspective on cardiovascular diseases. This study leveraged metabolomics profiling to investigate the progression of CAD, focusing on the interplay of hypercholesterolemia, hypertension, and diabetes. We performed a metabolomic analysis on 221 participants from four different groups: (I) healthy individuals, (II) individuals with hypercholesterolemia (HC), (III) individuals with both HC and hypertension (HT) or diabetes, and (IV) patients with self-reported coronary artery disease (CAD). Utilizing data from the Qatar Biobank, we combined clinical information, metabolomic profiling, and statistical analyses to identify key metabolites associated with CAD risk. Our data identified distinct metabolite profiles across the study groups, indicating changes in carbohydrate and lipid metabolism linked to CAD risk. Specifically, levels of mannitol/sorbitol, mannose, glucose, and ribitol increased, while pregnenediol sulfate, oleoylcarnitine, and quinolinate decreased with higher CAD risk. These findings suggest a significant role of sugar, steroid, and fatty acid metabolism in CAD progression and point to the need for further research on the correlation between quinolinate levels and CAD risk, potentially guiding targeted treatments for atherosclerosis. This study provides novel insights into the metabolomic changes associated with CAD progression, emphasizing the potential of metabolites as predictive biomarkers.
PubMed: 38921428
DOI: 10.3390/metabo14060292 -
Neurosurgery Jun 2024
PubMed: 38920384
DOI: 10.1227/neu.0000000000003089 -
Neurosurgery Jun 2024
PubMed: 38920363
DOI: 10.1227/neu.0000000000003088 -
Scientific Reports Jun 2024Mastitis is considered one of the most widespread infectious disease of cattle and buffaloes, affecting dairy herds. The current study aimed to characterize the...
Mastitis is considered one of the most widespread infectious disease of cattle and buffaloes, affecting dairy herds. The current study aimed to characterize the Staphylococcus aureus isolates recovered from subclinical mastitis animals in Pothohar region of the country. A total of 278 milk samples from 17 different dairy farms around two districts of the Pothohar region, Islamabad and Rawalpindi, were collected and screened for sub clinical mastitis using California Mastitis Test. Positive milk samples were processed for isolation of Staphylococcus aureus using mannitol salt agar. The recovered isolates were analyzed for their antimicrobial susceptibility and virulence genes using disc diffusion and PCR respectively. 62.2% samples were positive for subclinical mastitis and in total 70 Staphylococcus aureus isolates were recovered. 21% of these isolates were determined to be methicillin resistant, carrying the mecA gene. S. aureus isolates recovered during the study were resistant to all first line therapeutic antibiotics and in total 52% isolates were multidrug resistant. SCCmec typing revealed MRSA SCCmec types IV and V, indicating potential community-acquired MRSA (CA-MRSA) transmission. Virulence profiling revealed high prevalence of key genes associated with adhesion, toxin production, and immune evasion, such as hla, hlb, clfA, clfB and cap5. Furthermore, the Panton-Valentine leukocidin (PVL) toxin, that is often associated with recurrent skin and soft tissue infections, was present in 5.7% of isolates. In conclusion, the increased prevalence of MRSA in bovine mastitis is highlighted by this study, which also reveals a variety of virulence factors in S. aureus and emphasizes the significance of appropriate antibiotic therapy in combating this economically burdensome disease.
Topics: Animals; Cattle; Mastitis, Bovine; Female; Staphylococcal Infections; Pakistan; Virulence; Anti-Bacterial Agents; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Virulence Factors; Microbial Sensitivity Tests; Milk; Bacterial Proteins
PubMed: 38914650
DOI: 10.1038/s41598-024-65448-9 -
Cureus May 2024Background A major development in noninvasive imaging modalities, computed tomographic enterography (CTE) has a number of benefits over conventional computed tomography...
Background A major development in noninvasive imaging modalities, computed tomographic enterography (CTE) has a number of benefits over conventional computed tomography (CT) and capsule endoscopy. Through the utilization of multidetector computed tomography (MDCT) technology, CTE expedites the assessment of small bowel diseases, especially in those segments that are not accessible through traditional endoscopy. This study's main goal is to thoroughly evaluate CTE's diagnostic accuracy for a range of small intestinal conditions. Methodology In this investigation, which is a prospective observational study, 40 patients, 25 men and 15 women, with suspected small intestinal disorders and ages ranging from 10 to 70 underwent CTE. To evaluate diagnosis accuracy, a combination of clinical symptoms, imaging data, and histopathological/ultrasonography findings were evaluated. Throughout the research procedure, ethical issues and statistical analysis were incorporated to guarantee validity and adherence to ethical norms. Results The most frequent findings on CTE were bowel thickening and mucosal hyperenhancement, which were seen in 25 (62.5%) and 20 (50%) of the patients, respectively. The majority of patients (65%) exhibited both the ileal and jejunal loops to be adequately distended in grade III. In 35% of the patients, grade II distensibility of the ileal and jejunal loops was seen. Conclusion When it comes to accurately detecting small intestinal disorders, CTE is superior. It evaluates extraintestinal, mural, and intraluminal diseases with efficacy, particularly in places that are difficult to reach. It is essential for directing clinical decisions because of its capacity to assess disease activity prior to endoscopy and see consequences.
PubMed: 38910779
DOI: 10.7759/cureus.60915 -
International Journal of Pharmaceutics Jun 2024Labrafac™ MC60 (glycerol monocaprylocaprate) is a lipid-based excipient used in oral formulations as a solubiliser. Due to the high proportions of established...
Labrafac™ MC60 (glycerol monocaprylocaprate) is a lipid-based excipient used in oral formulations as a solubiliser. Due to the high proportions of established permeability enhancers, caprylate (C) and caprate (C), in Labrafac™ MC60, we hypothesised that it might behave as an intestinal permeation enhancer. We therefore evaluated this using two paracellular markers (ex vivo) and insulin (in vivo) as model molecules. Ex vivo studies were conducted in isolated muscle-stripped rat colonic mucosae mounted in Ussing chambers. Apical addition of Labrafac™ MC60 (8, 12, and 16 mg/ml) enhanced the apparent permeability coefficients (P) of [C] mannitol and FITC-dextran 4 kDa (FD4) across colonic mucosae. Similar effects were observed in isolated jejunal mucosae, but at higher concentrations (40 mg/ml). The enhancing capacity of Labrafac™ MC60 was transient due to reversibility of reductions in transepithelial electrical resistance (TEER) upon wash-out and effects on fluxes were molecular weight-dependent (MW) as suggested by fluxes of a set of high MW FITC-dextrans. The permeability enhancing effects of Labrafac™ MC60 ex vivo were maintained in the presence of simulated intestinal fluids, FaSSIF and FaSSCoF, in both jejunal and colonic mucosae, respectively. Following intra-intestinal regional instillations to rats, the relative bioavailability of 50 IU/kg insulin ad-mixed with Labrafac™ MC60 was 5 % in jejunum (40 mg/ml) and 6 % in colon (8 mg/ml). When Labrafac™ MC60 was combined with PEG-60 hydrogenated castor oil (1 % v/v), this further increased the bioavailability of insulin to 8 % in jejunum. Absorption enhancement was also maintained in the presence of FaSSIF in jejunal instillations. Histology after 120 min exposure to Labrafac™ MC60 in vivo for both jejunum and colon was similar to untreated control. Labrafac™ MC60 therefore acts as a non-damaging intestinal permeation enhancer for macromolecules and can be considered as another excipient in screening programmes to develop orally administered macromolecules.
PubMed: 38909926
DOI: 10.1016/j.ijpharm.2024.124353 -
Journal of Cardiothoracic Surgery Jun 2024Systematic evaluation of the safety of del Nido cardioplegia compared to cold blood cardioplegia in adult cardiac surgery. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Systematic evaluation of the safety of del Nido cardioplegia compared to cold blood cardioplegia in adult cardiac surgery.
METHODS
We systematically searched PubMed, EMbase, The Cochrane Library and ClinicalTrials.gov for randomized clinical trials (published by 14 January 2024) comparing del Nido cardioplegia to cold blood cardioplegia in adult. Our main endpoints were myocardial injury markers and clinical outcomes. We assessed pooled data by use of a random-effects model or a fixed-effects model.
RESULTS
A total of 10 studies were identified, incorporating 889 patients who received del Nido cardioplegia and 907 patients who received cold blood cardioplegia. The meta-analysis results showed that compared with the cold blood cardioplegia, the del Nido cardioplegia had less volume of cardioplegia, higher rate of spontaneous rhythm recovery after cross clamp release, lower levels of postoperative cardiac troponin T and creatinine kinase-myocardial band, all of which were statistically significant. However, there was no statistically significant difference in postoperative troponin I and postoperative left ventricular ejection fraction. The clinical outcomes including mechanical ventilation time, intensive care unit stay time, hospital stay time, postoperative stroke, postoperative new-onset atrial fibrillation, postoperative heart failure requiring intra-aortic balloon pump mechanical circulation support, and in-hospital mortality of both are comparable.
CONCLUSION
Existing evidence suggests that del Nido cardioplegia reduced volume of cardioplegia administration and attempts of defibrillation. The superior postoperative results in CTnT and CK-MB may provide a direction for further research on improvement of the composition of cardioplegia.
Topics: Humans; Heart Arrest, Induced; Randomized Controlled Trials as Topic; Cardiac Surgical Procedures; Cardioplegic Solutions; Adult; Potassium Chloride; Mannitol; Lidocaine; Solutions; Electrolytes; Magnesium Sulfate; Sodium Bicarbonate
PubMed: 38909234
DOI: 10.1186/s13019-024-02846-0 -
ELife Jun 2024Soil-free assays that induce water stress are routinely used to investigate drought responses in the plant . Due to their ease of use, the research community often...
Soil-free assays that induce water stress are routinely used to investigate drought responses in the plant . Due to their ease of use, the research community often relies on polyethylene glycol (PEG), mannitol, and salt (NaCl) treatments to reduce the water potential of agar media, and thus induce drought conditions in the laboratory. However, while these types of stress can create phenotypes that resemble those of water deficit experienced by soil-grown plants, it remains unclear how these treatments compare at the transcriptional level. Here, we demonstrate that these different methods of lowering water potential elicit both shared and distinct transcriptional responses in shoot and root tissue. When we compared these transcriptional responses to those found in roots subject to vermiculite drying, we discovered many genes induced by vermiculite drying were repressed by low water potential treatments on agar plates (and vice versa). Additionally, we also tested another method for lowering water potential of agar media. By increasing the nutrient content and tensile strength of agar, we show the 'hard agar' (HA) treatment can be leveraged as a high-throughput assay to investigate natural variation in growth responses to low water potential.
Topics: Arabidopsis; Water; Transcriptome; Plant Roots; Gene Expression Regulation, Plant; High-Throughput Screening Assays; Droughts; Plant Shoots; Gene Expression Profiling
PubMed: 38904663
DOI: 10.7554/eLife.84747 -
Molecular & Cellular Proteomics : MCP Jun 2024Osmotic stress significantly hampers plant growth and crop yields, emphasizing the need for a thorough comprehension of the underlying molecular responses. Previous...
Osmotic stress significantly hampers plant growth and crop yields, emphasizing the need for a thorough comprehension of the underlying molecular responses. Previous research has demonstrated that osmotic stress rapidly induces calcium influx and signaling, along with the activation of a specific subset of protein kinases, notably the Raf-SnRK2 kinase cascades within minutes. However, the intricate interplay between calcium signaling and the activation of RAF-SnRK2 kinase cascades remains elusive. Here in this study, we discovered that Raf-like protein (RAF) kinases undergo hyperphosphorylation in response to osmotic shocks. Intriguingly, treatment with the calcium chelator EGTA robustly activates RAF-SnRK2 cascades, mirroring the effects of osmotic treatment. Utilizing high-throughput DIA-based phosphoproteomics, we unveiled the global impact of EGTA on protein phosphorylation. Beyond the activation of RAFs and sucrose non-fermenting-1-related protein kinase 2s (SnRK2s), EGTA treatment also activates mitogen-activated protein kinase (MAPKs) cascades, Calcium-dependent protein kinases (CDPKs), and receptor-like protein kinases, etc. Through overlapping assays, we identified potential roles of mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) and receptor-like protein kinases in the osmotic-stress-induced activation of RAF-SnRK2 cascades. Our findings illuminate the regulation of phosphorylation and cellular events by Ca signaling, offering insights into the (exocellular) Ca deprivation during early hyperosmolality sensing and signaling.
PubMed: 38901673
DOI: 10.1016/j.mcpro.2024.100804