Degree of Cure, Microstructures, and Properties of Carbon/Epoxy Composites Processed via Frontal Polymerization.

The frontal polymerization (FP) of carbon/epoxy (C/Ep) composites is investigated, considering FP as a viable route for the additive manufacturing (AM) of thermoset composites. Neat epoxy (Ep) resin-, short carbon fiber (SCF)-, and continuous carbon fiber (CCF)-reinforced composites are considered in this study. The evolution of the exothermic reaction temperature, polymerization frontal velocity, degree of cure, microstructures, effects of fiber concentration, fracture surface, and thermal and mechanical properties are investigated. The results show that exothermic reaction temperatures range between 110 °C and 153 °C, while the initial excitation temperatures range from 150 °C to 270 °C. It is observed that a higher fiber content increases cure time and decreases average frontal velocity, particularly in low SCF concentrations. This occurs because resin content, which predominantly drives the exothermic reaction, decreases with increased fiber content. The FP velocities of neat Ep resin- and SCF-reinforced composites are seen to be 0.58 and 0.50 mm/s, respectively. The maximum FP velocity (0.64 mm/s) is observed in CCF/Ep composites. The degree of cure (αc) is observed to be in the range of 70% to 85% in FP-processed composites. Such a range of αc is significantly low in comparison to traditional composites processed through a long cure cycle. The glass transition temperature (Tg) of neat epoxy resin is seen to be approximately 154 °C, and it reduces slightly to a lower value (149 °C) for SCF-reinforced composites. The microstructures show significantly high void contents (12%) and large internal cracks. These internal cracks are initiated due to high thermal residual stress developed during curing for non-uniform temperature distribution. The tensile properties of FP-cured samples are seen to be inferior in comparison to autoclave-processed neat epoxy. This occurs mostly due to the presence of large void contents, internal cracks, and a poor degree of cure. Finally, a highly efficient and controlled FP method is desirable to achieve a defect-free microstructure with improved mechanical and thermal properties.

Practice of standardization of CLSI M45 A3 antimicrobial susceptibility testing of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in Guangdong Province 2017-2021.

The concentration of antimicrobial agents in environments like water and food has increased rapidly, which led to a rapid increase in antimicrobial resistance levels in the environment. Monitoring of bacterial resistance levels is considered as a necessary means to control the bacterial resistance. Reference standards are critical for antimicrobial susceptibility testing. CLSI M45 A3 standard defines pathogenic microorganisms that cause infections less frequently than those covered by CLSI M02, M07, and M100 as Infrequently Isolated or Fastidious Bacteria and specifies antimicrobial susceptibility testing methods. Our study investigated the epidemiology and antimicrobial susceptibility testing data of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in 70 hospitals in Guangdong Province between 2017 and 2021. We defined testing methods other than those specified in CLSI M45 A3 as "Non-Standardized." The proportion of standardized antimicrobial susceptibility testing for penicillin increased significantly (Corynebacterium spp. 17.4% vs. 50.0% p < 0.05; Micrococcus spp. 50.0% vs. 77.8% p < 0.05; Abiotrophia spp. and Granulicatella spp. 21.4% vs. 90.9% p < 0.001), while for cefotaxime (Corynebacterium spp. 0.0% vs. 45.2% p < 0.05; Abiotrophia spp. and Granulicatella spp. 0.0% vs. 14.3% p = 0.515) and vancomycin increased finitely. Non-standardized methods were used for all other antimicrobials. Due to limitations in the economic and medical environment, some clinical laboratories are unable to fully comply with CLSI M45 A3 standard. We recommend that CLSI should add breakpoints for disk diffusion method to improve the standardization of antimicrobial susceptibility testing.

Development of a Simple Method to Detect the Carbapenemase-Producing Genes blaNDM, blaOXA-48-like, blaIMP, blaKPC, and blaVIM Using a LAMP Method with Lateral Flow DNA Chromatography.

Infections by carbapenemase-producing Enterobacterales constitute a global public health threat. The rapid and efficient diagnosis of Enterobacterales infection is critical for prompt treatment and infection control, especially in hospital settings. We developed a novel loop-mediated isothermal amplification (LAMP) method combined with DNA chromatography to identify five major groups of carbapenemase-producing genes (blaNDM, blaOXA-48-like, blaIMP, blaKPC, and blaVIM). This method uses DNA-DNA hybridization-based detection in which LAMP products can be easily visualized as colored lines. No specific technical expertise, expensive equipment, or special facilities are required for this method, allowing its broad application. Here, 73 bacteria collections including strains with carbapenemase-producing genes were tested. Compared to sequencing results, LAMP DNA chromatography for five carbapenemase-producing genes had a sensitivity and specificity of 100% and >97%, respectively. This newly developed method can be a valuable rapid diagnostic test to guide appropriate treatments and infection control measures, especially in resource-limited settings.

Neuroendocrine hyperplasia of infancy; a rare form of childhood interstitial lung disease: a case report.

Interstitial lung disease in infancy is rare. In this case report, we discuss the case of a six-week-old male infant who presented with persistent tachypnoea, retraction and mild hypoxaemia corrected by low-dose supplemental oxygen since the age of 2 weeks. Birth history was unremarkable. Routine workup was done which turned out to be non-contributory. The child received multiple rounds of antibiotics along with bronchodilators and corticosteroids. There was no evidence of severe gastroesophageal reflux. Computed tomography of chest showed ground glass appearance, which was especially prominent in the right middle lobe and lingula ,and accompanied with air trapping. He was managed with mild respiratory supportive care, without positive pressure ventilation and nutritional management. He was discharged home, with instructions for in clinic follow up. A distinctive topographical picture and typical clinical symptoms were consistent with neuroendocrine hyperplasia of infancy (NEHI), which has a favourable prognosis. A high index of suspicion may enable a timely diagnosis. Adequate long-term respiratory and nutritional management without lung biopsy improves the outcome.

Impact of the First Wave of COVID-19 on PICU Admissions in Pakistan.

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The Efficacy of Phage Therapy in a Murine Model of Pseudomonas aeruginosa Pneumonia and Sepsis.

The emergence of multi-drug resistant Pseudomonas aeruginosa necessitates the search for treatment options other than antibiotic use. The use of bacteriophages is currently being considered as an alternative to antibiotics for the treatment of bacterial infections. A number of bacteriophages were introduced to treat pneumonia in past reports. However, there are still lack of knowledge regarding the dosages, application time, mechanism and safety of phage therapy against P. aeruginosa pneumonia. We used the bacteriophage KPP10 against P. aeruginosa strain D4-induced pneumonia mouse models and observed their outcomes in comparison to control models. We found that the nasal inhalation of highly concentrated KPP10 (MOI = 80) significantly improved survival rate in pneumonia models (P < 0.01). The number of viable bacteria in both lungs and in serum were significantly decreased (P < 0.01) in phage-treated mice in comparison to the control mice. Pathological examination showed that phage-treated group had significantly reduced bleeding, inflammatory cell infiltration, and mucus secretion in lung interstitium. We also measured inflammatory cytokine levels in the serum and lung homogenates of mice. In phage-treated models, serum TNFα, IL-1ß, and IFN-γ levels were significantly lower (P < 0.05, P < 0.01, and P < 0.05, respectively) than those in the control models. In the lung homogenate, the mean IL-1ß level in phage-treated models was significantly lower (P < 0.05) than that of the control group. We confirmed the presence of phage in blood and lungs, and evaluated the safety of bacteriophage use in living models since bacteriophage mediated bacterial lysis arise concern of endotoxic shock. The study results suggest that phage therapy can potentially be used in treating lung infections caused by Pseudomonas aeruginosa.

Abstract to publication conversion in pediatric critical care medicine in Pakistan.

BACKGROUND: To determine the rate of conversion of abstracts presented at conferences into full-text articles published in peer-reviewed journals in the field of pediatric critical care medicine (PCCM) in a developing country. METHODS: We retrospectively reviewed PCCM abstracts from Pakistan presented at national and international pediatric and critical care conferences over 10 years (January 2010 to March 2020). Data included abstract characteristics, such as presentation (poster/oral), presenter (fellow/resident), time of meeting (month and year), type of meeting, study design and topic; and publication characteristics, such as journal name, time (month and year) and first author. The primary outcome was publication rate of PCCM abstracts presented in meetings and time (months) from presentation to publication. RESULTS: A total of 79 PCCM abstracts were presented in 20 meetings during the study period. There were 65 poster presentations (82.28%), of which 63 (79.74%) were presented at international critical care conferences and all presenters were PCCM fellows. In total, 64 (81%) abstracts were descriptive observational studies (retrospective: 50, 63.29%) and prospective (14, 17.72%). Only one was an interventional randomized controlled trial. The publication rate of PCCM abstracts was 63.3% (50/79) and the mean time to publication was 12.39±13.61 months. The publication rate was significantly correlated to the year of publication (P<0.001). CONCLUSIONS: The PCCM abstract publication rate and mean time from presentation to publication was 63.3% and 12.39±13.61 months, respectively, in a developing country.

High-Speed Quenching Probe-Polymerase Chain Reaction Assay for the Rapid Detection of Carbapenemase-Producing Gene Using GENECUBE: A Fully Automatic Gene Analyzer.

BACKGROUND: The prevalence of carbapenemase-producing organisms (CPOs) globally poses a public health threat; however, detecting carbapenemases is a challenge because of their variety. METHODS: GENECUBE, a fully automated gene analyzer, detects a target gene in a short time and simultaneously detects its single nucleotide polymorphism. We used this property to develop for the first time a rapid assay for detecting CPOs from cultured bacteria using GENECUBE. The original primer-probe sets were used to detect blaKPC, blaIMP, blaVIM, blaNDM, and blaOXA-48-like from 149 CPOs (nine types) and 61 non-CPOs. RESULTS: The sensitivity, specificity, and positive and negative predictions of the GENECUBE assay were 100%. This assay detected carbapenemase single-producers and carbapenemase co-producers with 100% accuracy. The time required for detects of four types of carbapenemase at one run was about 30 min, but it took about 1 h to detect all five types. In addition, this assay performed the rapid detection and classification of blaOXA-48, blaOXA-181, blaOXA-232, and blaOXA-244 simultaneously. CONCLUSIONS: The GENECUBE assay is a promising tool for controlling the spread of CPOs and helping to select accurate and rapid antibiotic therapies.

CRISPR-Cas9: A Promising Genome Editing Therapeutic Tool for Alzheimer's Disease-A Narrative Review.

Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative disorder characterized by cognitive deficiency and development of amyloid-ß (Aß) plaques and neurofibrillary tangles, comprising hyperphosphorylated tau. The number of patients with AD is alarmingly increasing worldwide; currently, at least 50 million people are thought to be living with AD. The mutations or alterations in amyloid-ß precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes are known to be associated with the pathophysiology of AD. Effective medication for AD is still elusive and many gene-targeted clinical trials have failed to meet the expected efficiency standards. The genome editing tool clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 has been emerging as a powerful technology to correct anomalous genetic functions and is now widely applied to the study of AD. This simple yet powerful tool for editing genes showed the huge potential to correct the unwanted mutations in AD-associated genes such as APP, PSEN1, and PSEN2. So, it has opened a new door for the development of empirical AD models, diagnostic approaches, and therapeutic lines in studying the complexity of the nervous system ranging from different cell types (in vitro) to animals (in vivo). This review was undertaken to study the related mechanisms and likely applications of CRISPR-Cas9 as an effective therapeutic tool in treating AD.

Unexpected effect of probiotics by Lactococcus lactis subsp. lactis against colitis induced by dextran sulfate sodium in mice.

Ulcerative colitis (UC) is a representative intestinal chronic inflammatory disease whose incidence is rapidly increasing worldwide. It was previously shown that some specific probiotics help to guard against UC. In this study, we analyzed the effect of Lactococcus lactis subsp. lactis JCM5805 (L. lactis), which has been put to practical use as a probiotic, on the pathogenesis of UC using a dextran sulfate sodium-induced colitis mouse model. Survival rate, length, and histopathological parameters of the colon were elucidated. Further, the concentrations of inflammatory cytokines in serum were measured. As a result, the oral administration of high-dose L. lactis showed significant decreases in survival rate and colon length. Histopathological analysis showed that a bleeding appearance was observed in the L. lactis group, and the histology scores in the L. lactis group were significantly higher than those in the normal saline group. Furthermore, the levels of interferon gamma, tumor necrosis factor alpha, and interleukin-6 were significantly elevated in the L. lactis group. These results support that high-dose administration of L. lactis deteriorates intestinal inflammation and suggest that the careful selection of probiotics strains and administration dose is important for improving colitis including UC.

Characteristics of Carbapenemase-Producing Klebsiella pneumoniae Isolated in the Intensive Care Unit of the Largest Tertiary Hospital in Bangladesh.

For addressing the issue of antimicrobial drug resistance in developing countries, it is important to investigate the characteristics of carbapenemase-producing organisms. We aimed to genetically characterize a carbapenemase-producing Klebsiella pneumoniae (CPKP) isolated in the intensive care unit of a tertiary hospital in Bangladesh. The number of CPKP isolates were 43/145 (30%), of which pandrug-resistant (PDR) strains were 14%. These carbapenemases were New Delhi metallo-beta-lactamase (NDM)-1 (53%), NDM-5 (14%), oxacillinase (OXA)-181 (12%), OXA-232 (10%), NDM-5 + OXA-181 (5%), and NDM-5 + OXA-232 (2%). Many CPKP isolates harbored a variety of resistance genes, and the prevalence of 16S rRNA methyltransferase was particularly high (91%). The 43 CPKP isolates were classified into 14 different sequence types (STs), and the common STs were ST34 (26%), ST147 (16%), ST11 (9%), ST14 (9%), ST25 (7%), and ST231 (7%). In this study, PDR strains were of three types, ST147, ST231, and ST14, and their PDR rates were 57, 33, and 25%, respectively. The spread of the antimicrobial drug resistance of CPKP in Bangladesh was identified. In particular, the emergence of PDR is problem, and there may be its spread as a superbug of antimicrobial treatment.

Characteristics of Resistance Mechanisms and Molecular Epidemiology of Fluoroquinolone-Nonsusceptible Salmonella enterica Serovar Typhi and Paratyphi A Isolates from a Tertiary Hospital in Dhaka, Bangladesh.

The aim of this study was to characterize the fluoroquinolone (FQ) resistance mechanism of Salmonella enterica serovar Typhi and Paratyphi A in Bangladesh. Salmonella Typhi isolates were classified into sequence type (ST) 1, ST2, and ST2209 and Salmonella Paratyphi A isolates were classified into ST85 and ST129. The most common STs of the FQ-nonsusceptible strain were ST1 (44.4%) and ST129 (66.6%). Thirty-nine percent of Salmonella Typhi isolates were multidrug resistant, and these were all ST1, which is the type prevalent in the Indian subcontinent. Although plasmid-mediated quinolone resistance genes were not detected in any of the tested strains, single and double mutations were identified in the quinolone resistance-determining region (QRDR). The most common QRDR mutation was GyrA_Ser83Phe (66.7% for Salmonella Typhi and 100% for Salmonella Paratyphi A). Treatment with an efflux pump inhibitor resulted in susceptibility of the strains to levofloxacin. All isolates demonstrated 100% susceptibility to ceftriaxone, azithromycin, and carbapenem. Our results suggest that mutations in gyrase A and enhancement of efflux pump activity are responsible for the resistance to FQs; in particular, the AcrAB-TolC efflux pump may be an important resistance factor for levofloxacin. To control the spread of FQ-nonsusceptible Salmonella Typhi, intensive surveillance in endemic areas, including Bangladesh, and effective infection control are necessary.

Drug Targeting and Biomarkers in Head and Neck Cancers: Insights from Systems Biology Analyses.

The head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, but robust biomarkers and diagnostics are still not available. This study provides in-depth insights from systems biology analyses to identify molecular biomarker signatures to inform systematic drug targeting in HNSCC. Gene expression profiles from tumors and normal tissues of 22 patients with histological confirmation of nonmetastatic HNSCC were subjected to integrative analyses with genome-scale biomolecular networks (i.e., protein-protein interaction and transcriptional and post-transcriptional regulatory networks). We aimed to discover molecular signatures at RNA and protein levels, which could serve as potential drug targets for therapeutic innovation in the future. Eleven proteins, 5 transcription factors, and 20 microRNAs (miRNAs) came into prominence as potential drug targets. The differential expression profiles of these reporter biomolecules were cross-validated by independent RNA-Seq and miRNA-Seq datasets, and risk discrimination performance of the reporter biomolecules, BLNK, CCL2, E4F1, FOSL1, ISG15, MMP9, MYCN, MYH11, miR-1252, miR-29b, miR-29c, miR-3610, miR-431, and miR-523, was also evaluated. Using the transcriptome guided drug repositioning tool, geneXpharma, several candidate drugs were repurposed, including antineoplastic agents (e.g., gemcitabine and irinotecan), antidiabetics (e.g., rosiglitazone), dermatological agents (e.g., clocortolone and acitretin), and antipsychotics (e.g., risperidone), and binding affinities of the drugs to their potential targets were assessed using molecular docking analyses. The molecular signatures and repurposed drugs presented in this study warrant further attention for experimental studies since they offer significant potential as biomarkers and candidate therapeutics for precision medicine approaches to clinical management of HNSCC.

Outcome Of Traumatic Brain Injury In Children By Using Rotterdam Score On Computed Tomography.

BACKGROUND: The Rotterdam Score (RS) on CT head is a new evolving clinical tool as a predictor of mortality in Traumatic Brain Injury (TBI). The objective of this study is to assess the outcome of children with TBI admitted in paediatric intensive care unit (PICU) of a tertiary-care, university hospital by using RS. METHODS: This was a prospective observational study conducted on children (age: 1mo -16yr) with TBI admitted in PICU of Aga Khan University Hospital from 2013 to 2016. RS on CT was calculated by a radiologist. All patients were managed according to according to Paediatric Brain Trauma Foundation Guidelines 2012.Demographic data, clinical variables and outcomes were recorded. Logistic regression analysis was applied to assess the association between outcome and R.. RESULTS: Ninety-two cases were enrolled during four years. The median age was 77 months (3 months to 16 years) and 73 (79%) were male. The main cause of injury was RTA (60.9%) followed by fall (39.1%). Sixty-two patients (67%) had a post-resuscitation GCS of 8 or less. 54% (51) patients were managed conservatively. The RS of 1, 2, 3, 4 and 5 were present in 19, 36,19,15 and 3 patients. The mean RS was 2.4. The higher mortality rate was observed in high RS. The RS was significantly associated with mortality (OR 1.75, 95% CI 1.03-2.95; p<0.04). CONCLUSIONS: Rotterdam Score on CT head can be used to predict mortality in paediatric patients with TBI.

Ultrasonographic optic nerve sheath diameter Measurement for raised intracranial pressure in a Tertiary care centre of a developing country.

BACKGROUND: Intracranial hypertension is not an uncommon life-threatening syndrome, caused by a variety of non-neurological and neurological illnesses, and quick diagnosis, timely treatment of Raised Intracranial Pressure (ICP) is associated with improved outcome. Our aim of study was to determine ultrasonographic measurement of Optic nerve sheath diameter (ONSD) for raised ICP. METHODS: Prospective case series done in Emergency and Paediatric critical care unit of Aga Khan University Hospital. ONSD measurement in millimetres was done by placing linear probe of ultrasound on eye ball. RESULTS: Forty-eight patients were included in study with mean age of 7.5±5.0 years with 21/48 (43.8%) between 1-8 years and 19/48 (39.6%) >8 years with 32/48 (66.7%) were male. Non-traumatic coma was most common diagnosis 41/48 (85.4%) with infectious cause being most common while Traumatic brain injury constitutes 7/48 (14.6%). Ct scan brain was done in 39/48 (81.3%) while MRI brain in rest of patients. Raised ICP was found in 83.33% (40/48) patients with Ultrasonographic ONSD measurement as compared to CT scan/MRI 14/48 (29.2%). 85% of patients, showed ultrasonographic ONSD measurement suggestive of Raised ICP with GCS ≤12. Mean ONSD with signs of raised ICP in infants 4.64 (±0.48), in 1-10 years 6.44 (±0.65), and in adolescent >10 years 6.28 (±0.62) ONSD respectively with ROC Curve showing Area Under Curve (AUC) 0.814 ( 95% CI, 0.692-0.936). CONCLUSIONS: We identified threshold of Ultrasonographic ONSD measurement in infants >4.0 mm, in children 1-10 yrs >4.71 mm, in adolescent >10 yrs >5.43 mm for raised ICP with sensitivity and specificity of 100% and 60-66.7% respectively. 85% of patients showed raised ICP with Ultrasonographic ONSD measurement with GCS ≤12.

Robust suppression of cardiac energy catabolism with marked accumulation of energy substrates during lipopolysaccharide-induced cardiac dysfunction in mice.

BACKGROUND: Myocardial contractile dysfunction in sepsis has been attributed mainly to increased inflammatory cytokines, insulin resistance, and impaired oxidative phosphorylation of fatty acids (FAs). However, precise molecular mechanisms underlying the cardiac dysfunction in sepsis remain to be determined. We previously reported major shift in myocardial energy substrates from FAs to glucose, and increased hepatic ketogenesis in mice lacking fatty acid-binding protein 4 (FABP4) and FABP5 (DKO). PURPOSE: We sought to determine whether a shift of energy substrates from FAs to glucose and increased availability of ketone bodies are beneficial or detrimental to cardiac function under the septic condition. METHODS: Lipopolysaccharide (LPS, 10mg/kg) was intraperitoneally injected into wild-type (WT) and DKO mice. Twelve hours after injection, cardiac function was assessed by echocardiography and serum and hearts were collected for further analyses. RESULTS: Cardiac contractile function was more deteriorated by LPS injection in DKO mice than WT mice despite comparable changes in pro-inflammatory cytokine production. LPS injection reduced myocardial uptake of FA tracer by 30% in both types of mice, while uptake of the glucose tracer did not significantly change in either group of mice in sepsis. Storage of glycogen and triacylglycerol in hearts was remarkably increased by LPS injection in both mice. Metabolome analysis revealed that LPS-induced suppression of pool size in the TCA cycle was more enhanced in DKO hearts. A tracing study with 13C6-glucose further revealed that LPS injection substantially reduced glucose-derived metabolites in the TCA cycle and related amino acids in DKO hearts. Consistent with these findings, glucose oxidation in vitro was similarly and markedly reduced in both mice. Serum concentration of ß-hydroxybutyrate and cardiac expression of genes associated with ketolysis were reduced in septic mice. CONCLUSIONS: Our study demonstrated that LPS-induced cardiac contractile dysfunction is associated with the robust suppression of catabolism of energy substrates including FAs, glucose and ketone bodies and accumulation of glycogen and triacylglycerol in the heart. Thus, a fuel shift from FAs to glucose and/or ketone bodies may be detrimental rather than protective under septic conditions.

Clinical Profile and Short-Term Outcome of Pediatric Hyperleukocytic Acute Leukemia from a Developing Country.

This study was conducted to determine the frequency, clinical profile, and short-term outcome of children with hyperleukocytosis at two pediatric oncology centers in Karachi. Of a total 1,045 patients, 13.97% (n=146) patients had hyperleukocytosis. Majority (61.7%, n=90) were under 10 years of age and 76% (n=146) were male. The symptom duration before diagnosis was more than 30 days in 49.3% (n=72). The median WBC count was 181 x109/L(IQR=130.45298.3) and extreme hyperleukocytosis (>200 x109/L) was observed in 44.5% (n=65) patients. Majority (94.5%, n=138) of patients were diagnosed with acute lymphoblastic leukemia. One or more complications developed in 78% (n=114) of cases. Clinical and laboratory tumor lysis syndrome (TLS) was observed in 17.1% (n=25) and 39% (n=57) patients, respectively. Pulmonary and neurological complications related to leukostasis were noted in 9.5% (n=14) and 27.3% (n=40) of cases, respectively. Infectious complications occurred in 23.2% (n=34) patients. The case-specific mortality was 20.5% (n=30). No mortality was related to early complications of hyperleukocytosis.

Administration of colistin sulfate in endotoxic model at slow and sustained fashion may reverse shock without causing nephrotoxicity in its optimal concentration.

OBJECTIVES: Despite of proven LPS neutralizing activity, intravenous polymyxin use was waned due to experience of associated nephrotoxicity. But, increasing resistance to all available antibiotics has necessitated their resurgence and the prodrug of colistin sulfate (CS), known as colistin-methanesulfonate (CMS), is increasingly used as the only therapeutic option in many infections. Currently available CMS employ very different dose definitions and thus because of complex pharmacokinetics/pharmacodynamics information and short half-life, this drug use remains confusing. We aimed to expose CS in endotoxic shock models by micro-osmotic pump and evaluated its effectiveness. METHODS: We used micro-osmotic pumps to deliver either sterile saline or CS at different dosages ranging from 0.25mg/day to 7mg/day for consecutive 3days in LPS (8mg/kg body weight) induced endotoxic mice and observed their outcome twice daily for a week to determine the survival rate. Serum pro-inflammatory cytokine levels and apoptosis in renal tissues in these models were evaluated. RESULTS: We showed endotoxic shock was reversed and all mice survived with a CS administration at a dosage of 2mg/day for 3 days, in comparison to survival rate with saline administration (p≤0.0001) in endotoxic models. CS infusion in shock models using micro-osmotic pump ameliorated rising of serum TNF-α, IL-12p70 and IL-6 levels. Nephrotoxicity was evident only with a higher dosage, but not with a lower dosage which was optimum to control endotoxic shock in models. CONCLUSIONS: These results highlighted that an optimal dosage of CS effectively improved outcome in endotoxic shock models without causing nephrotoxicity when administered at a slow and sustained manner. And a higher CS dosage administration was nephrotoxic and fatal. Thus this study bought an opportunity to consider future investigations with CS administration in murine Gram-negative bacterial infections in a novel way.

Implementation of Ventilator Bundle in Pediatric Intensive Care Unit of a Developing Country.

The aim of this study was to assess the frequency of VAP(ventilator associated pneumonia) after strict implementation of ventilator bundle in PICU. Medical records of all children (age 1 month - 16 years) were retrospectively reviewed, who were on mechanical ventilation (MV) for more than 48 hours and received all key components of "ventilator bundle" from January 2012 to December 2014. Out of 1050, 565 (54%) patients were enrolled. The mean age was 4.02 SD 4.29 years and 62 (69%) were male. The indications of MV were respiratory illness (54%), neurological illness (31%), shock (9%), and postoperative care (6%). The mean duration of MV was 7.05 SD 5.4 days. Only 4 patients (0.7%) developed VAP. The incidence-density of VAP was 1.6 per 1000 ventilator days. The strict implementation of simple, inexpensive interventions (ventilator bundle) in care of mechanically ventilated children can decrease significantly VAP even in resource-limited country.