Risk Factors of Central Line-Associated Bloodstream Infection (CLABSI): A Prospective Study From a Paediatric Intensive Care Unit in South India.

Background Central line-associated bloodstream infection (CLABSI) is the most common hospital-acquired infection. However, studies evaluating the factors associated with the risk of CLABSI in pediatric intensive care units (PICU) were limited in India. Objective The objective of our study is to evaluate the association of factors and the etiology causing CLABSI. Study design This is a hospital-based single-center prospective study conducted in the pediatric intensive care unit (PICU) of our tertiary care hospital spanning one year. Participants Children aged between two months to 15 years admitted in the PICU for more than 48 hours with central venous catheterization were included. Pearson's chi-squared test with Yates' continuity correction and logistic regression with odds ratio were calculated by R statistical software (R Foundation for Statistical Computing, Vienna, Austria) and a p-value less than 0.05 was considered statistically significant. Results Our analysis showed that factors such as young age (2-12 months), high pediatric risk of mortality (PRISM III) score (> 15), leukocytosis, neutrophilia, anemia, change of central venous catheter, duration of catheterization (>7 days), exposure to blood products, use of steroids, inotropes, and prophylactic antibiotics were significantly associated with increased risk of CLABSIs with an odds ratio of 4.53, 4.54, 2.91, 4.56, 4.76, 3.74, 2.49, 2.41, 7.22, 6.77 and 5.16 respectively (p<0.05). Further, factors such as older age (>12 months) and low PRISM III score (≤ 15) significantly reduce the risk of CLABSIs by 83.64% and 69.14% respectively (p<0.05). Conclusion In conclusion, our results revealed that factors such as young age, high PRISM III score, leukocytosis, neutrophilia, anemia, change of central venous catheter, duration of catheterization (> 7 days), exposure to blood products during the hospital stay, use of steroids, inotropes, and prophylactic antibiotics were identified as risk factors for CLABSI.

Investigation of Autonomic Dysfunction in Alzheimer's Disease-A Computational Model-Based Approach.

(1) Background and Objective: Alzheimer's disease (AD) is commonly accompanied by autonomic dysfunction. Investigating autonomic dysfunction's occurrence patterns and severity may aid in making a distinction between different dementia subtypes, as cardiac autonomic dysfunction and AD severity are correlated. Heart rate variability (HRV) allows for a non-invasive assessment of the autonomic nervous system (ANS). AD is characterized by cholinergic depletion. A computational model of ANS based on the kinetics of acetylcholine and norepinephrine is used to simulate HRV for various autonomic states. The model has the flexibility to suitably modulate the concentration of acetylcholine corresponding to different autonomic states. (2) Methods: Twenty clinically plausible AD patients are compared to 20 age- and gender-matched healthy controls using HRV measures. Statistical analysis is performed to identify the HRV parameters that vary significantly in AD. By modulating the acetylcholine concentration in a controlled manner, different autonomic states of Alzheimer's disease are simulated using the ANS model. (3) Results: In patients with AD, there is a significant decrease in vagal activity, sympathovagal imbalance with a dominant sympathetic activity, and change in the time domain, frequency domain, and nonlinear HRV characteristics. Simulated HRV features corresponding to 10 progressive states of AD are presented. (4) Conclusions: There is a significant difference in the HRV features during AD. As cholinergic depletion and autonomic dysfunction have a common neurological basis, autonomic function assessment can help in diagnosis and assessment of AD. Quantitative models may help in better comprehending the pathophysiology of the disease and assessment of its progress.

Exophiala dermatitidis as a cause of central line associated bloodstream infection in an infant: Case report and literature review / Exophiala dermatitidis como causante de infección del torrente sanguíneo asociada a catéter central en un lactante: reporte de un caso y revisión de la literatura

BACKGROUND: Exophiala dermatitidis is a dematiaceous fungus known to cause superficial, subcutaneous, cutaneous and deep seated infections, and rarely central line associated bloodstream infection (CLABSI). A case of CLABSI due to E. dermatitidis in an infant is described. CASE REPORT: Clinical and laboratory data were extracted from patient's chart and laboratory records. The isolate was identified as E. dermatitidis by phenotypic characterization and sequencing of the ITS and LSU regions of the ribosomal DNA. Medline search was done to review all cases of CLABSI due to E. dermatitidis. Among the azoles tested, posaconazole (0.06mg/l), voriconazole (0.03mg/l) and itraconazole (0.03mg/l) showed very low MICs when compared to fluconazole (4mg/l). CONCLUSIONS: As we did not found in the literature any case of CLABSI due to E. dermatitidis in an infant, we report the first one. Sequencing is a mandatory method for accurately identifying this species. Prompt removal of the central line, followed by a treatment with amphotericin B or an azole, seems to be the most effective treatment

ANTECEDENTES: Exophiala dermatitidis es un hongo dematiáceo conocido por causar infecciones superficiales, subcutáneas, cutáneas y profundas, y rara vez infección del torrente sanguíneo asociada a catéter central (central line associated bloodstream infection [CLABSI]). Se describe un caso de CLABSI debido a E. dermatitidis en un bebé. CASO CLÍNICO: Los datos del paciente se extrajeron de la historia clínica y de los registros de laboratorio. El aislamiento se identificó como E. dermatitidis mediante caracterización fenotípica y la secuenciación de las regiones ITS y LSU del ADN ribosómico. Se realizó una búsqueda en Medline para revisar todos los casos de CLABSI debidos a E. dermatitidis. Entre los azoles evaluados, el posaconazol (0,06mg/l), el voriconazol (0,03mg/l) y el itraconazol (0,03mg/l) mostraron valores de MIC muy bajos en comparación con el fluconazol (4mg/l). CONCLUSIONES: Tras la revisión de todo lo publicado en la literatura, presentamos el primer caso de CLABSI debido a E. dermatitidis en un lactante. La secuenciación es necesaria para identificar con precisión esta especie. La retirada inmediata del catéter venoso central seguida de un tratamiento con anfotericina B o un azol es el tratamiento más efectivo

Exophiala dermatitidis as a cause of central line associated bloodstream infection in an infant: Case report and literature review.

BACKGROUND: Exophiala dermatitidis is a dematiaceous fungus known to cause superficial, subcutaneous, cutaneous and deep seated infections, and rarely central line associated bloodstream infection (CLABSI). A case of CLABSI due to E. dermatitidis in an infant is described. CASE REPORT: Clinical and laboratory data were extracted from patient's chart and laboratory records. The isolate was identified as E. dermatitidis by phenotypic characterization and sequencing of the ITS and LSU regions of the ribosomal DNA. Medline search was done to review all cases of CLABSI due to E. dermatitidis. Among the azoles tested, posaconazole (0.06mg/l), voriconazole (0.03mg/l) and itraconazole (0.03mg/l) showed very low MICs when compared to fluconazole (4mg/l) CONCLUSIONS: As we did not found in the literature any case of CLABSI due to E. dermatitidis in an infant, we report the first one. Sequencing is a mandatory method for accurately identifying this species. Prompt removal of the central line, followed by a treatment with amphotericin B or an azole, seems to be the most effective treatment.

Plasma of Acute Lymphoblastic Leukemia Patients React to the Culture of a Mycovirus Containing Aspergillus flavus.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is also seen in adults. Currently, no plasma-based test for the detection of ALL is available. We have cultured the home of a patient with ALL and isolated a mycovirus containing Aspergillus flavus. This culture was subjected to electron microscopy, purification, and mass spectrometry. Using enzyme-linked immunosorbent assay technique, plasma of patients with ALL and long-term survivors of this disease were tested for antibodies, utilizing supernatant of the culture of this organism. The results were compared with 3 groups of controls, including healthy individuals, patients with sickle cell disease, and solid tumors. Using electron microscopy, the isolated A. flavus contained mycovirus particles. In chemical analysis, this organism did not produce any aflatoxin. Using an enzyme-linked immunosorbent assay technique, the supernatant of the culture of the mycovirus containing A. flavus could differentiate ALL patients from each group of controls (P<0.001). These studies provide a new technique for the detection of ALL and may add information for future research regarding leukemogenesis.

Synthesis of Hollow Nanotubes of Zn2SiO4 or SiO2: Mechanistic Understanding and Uranium Adsorption Behavior.

We report a facile synthesis of Zn2SiO4 nanotubes using a two-step process consisting of a wet-chemical synthesis of core-shell ZnO@SiO2 nanorods followed by thermal annealing. While annealing in air leads to the formation of hollow Zn2SiO4, annealing under reducing atmosphere leads to the formation of SiO2 nanotubes. We rationalize the formation of the silicate phase at temperatures much lower than the temperatures reported in the literature based on the porous nature of the silica shell on the ZnO nanorods. We present results from in situ transmission electron microscopy experiments to clearly show void nucleation at the interface between ZnO and the silica shell and the growth of the silicate phase by the Kirkendall effect. The porous nature of the silica shell is also responsible for the etching of the ZnO leading to the formation of silica nanotubes under reducing conditions. Both the hollow silica and silicate nanotubes exhibit good uranium sorption at different ranges of pH making them possible candidates for nuclear waste management.

Nicotine-mediated invasion and migration of non-small cell lung carcinoma cells by modulating STMN3 and GSPT1 genes in an ID1-dependent manner.

BACKGROUND: Inhibitor of DNA binding/Differentiation 1 (ID1) is a helix loop helix transcription factor that lacks the basic DNA binding domain. Over-expression of ID1 has been correlated with a variety of human cancers; our earlier studies had shown that reported ID1 is induced by nicotine or EGF stimulation of non-small cell lung cancer (NSCLC) cells and its down regulation abrogates cell proliferation, invasion and migration. Here we made attempts to identify downstream targets of ID1 that mediate these effects. METHODS: A microarray analysis was done on two different NSCLC cell lines (A549 and H1650) that were transfected with a siRNA to ID1 or a control, non-targeting siRNA. Cells were stimulated with nicotine and genes that were differentially expressed upon nicotine stimulation and ID1 depletion were analyzed to identify potential downstream targets of ID1. The prospective role of the identified genes was validated by RT-PCR. Additional functional assays were conducted to assess the role of these genes in nicotine induced proliferation, invasion and migration. Experiments were also conducted to elucidate the role of ID1, which does not bind to DNA directly, affects the expression of these genes at transcriptional level. RESULTS: A microarray analysis showed multiple genes are affected by the depletion of ID1; we focused on two of them: Stathmin-like3 (STMN3), a microtubule destabilizing protein, and GSPT1, a protein involved in translation termination; these proteins were induced by both nicotine and EGF in an ID1 dependent fashion. Overexpression of ID1 in two different cell lines induced STMN3 and GSPT1 at the transcriptional level, while depletion of ID1 reduced their expression. STMN3 and GSPT1 were found to facilitate the proliferation, invasion and migration of NSCLC cells in response to nAChR activation. Attempts made to assess how ID1, which is a transcriptional repressor, induces these genes showed that ID1 down regulates the expression of two transcriptional co-repressors, NRSF and ZBP89, involved in the repression of these genes. CONCLUSIONS: Collectively, our data suggests that nicotine and EGF induce genes such as STMN3 and GSPT1 to promote the proliferation, invasion and migration of NSCLC, thus enhancing their tumorigenic properties. These studies thus reveal a central role for ID1 and its downstream targets in facilitating lung cancer progression.

ID1 facilitates the growth and metastasis of non-small cell lung cancer in response to nicotinic acetylcholine receptor and epidermal growth factor receptor signaling.

Expression of ID1 (inhibitor of differentiation) has been correlated with the progression of a variety of cancers, but little information is available on its role in non-small cell lung cancer (NSCLC). Here we show that ID1 is induced by nicotinic acetylcholine receptor (nAChR) and epidermal growth factor receptor (EGFR) signaling in a panel of NSCLC cell lines and primary cells from the lung. ID1 induction was Src dependent and mediated through the α7 subunit of nAChR; transfection of K-Ras or EGFR to primary cells induced ID1. ID1 depletion prevented nicotine- and EGF-induced proliferation, migration, and invasion of NSCLC cells and angiogenic tubule formation of human microvascular endothelial cells from lungs (HMEC-Ls). ID1 could induce the expression of mesenchymal markers such as vimentin and fibronectin by downregulating ZBP-89, a zinc finger repressor protein. ID1 levels were elevated in tumors from mice that were exposed to nicotine. Further, human lung tissue microarrays (TMAs) showed elevated levels of ID1 in NSCLC samples, with maximal levels in metastatic lung cancers. Quantitative reverse transcription-PCR (RT-PCR) performed on patient lung tumors showed that ID1 levels were elevated in advanced stages of NSCLC and correlated with elevated expression of vimentin and fibronectin, irrespective of smoking history.

Water hyacinth as carbon source for the production of cellulase by Trichoderma reesei.

Water hyacinth (Eichhornia crassipes), an aquatic weed common to the subtropic/tropical regions, was utilized as an inexpensive lignocellulosic substrate for production of cellulase by Trichoderma reesei. The effects of process parameters like substrate pretreatment, substrate concentration, initial medium pH, mode of inoculation, and incubation temperature on cellulase production were investigated. Under optimal conditions, a maximal cellulase activity of 0.22 +/- 0.04 IU/ml (approximately 73.3 IU/g cellulose) was recorded at the end of 15-day incubation period. Specific activity of the enzyme was 6.25 IU/mg protein. Hydrolysis of 1% substrate (water hyacinth) using crude enzyme dosage of 1.2 IU/g water hyacinth showed 28.7% saccharification in 1 h. The observations in present study indicate that saccharification of cellulose from water hyacinth was significantly higher by laboratory-produced cellulase than the commercial blend.

Hypercalcemia and metastatic calcification in a neonate with subcutaneous fat necrosis.

We report a 30-day-old baby with subcutaneous fat necrosis and symptomatic hypercalcemia, who developed metastatic calcification in the subcutaneous tissue, kidneys, pericardium and brain. The baby also had anemia, hypertriglyceridemia and hypercholesterolemia. He was managed with intravenous saline, furosemide, oral steroids and bisphosphonates and improved with treatment.

Recurrent abdominal pain due to hereditary angioedema.

Recurrent abdominal pain is a common problem in children that may need invasive procedures for diagnosis. Hereditary angioedema (HAE) is rarely considered in the differential diagnosis. Here it is reported a girl with HAE, who presented initially as recurrent abdominal pain without cutaneous manifestations. Each episode was managed elsewhere as an acute surgical emergency and an exploratory laparotomy was planned. Diagnosis was confirmed by quantitative assay of C1 inhibitor. On detailed evaluation, many members of her family were affected.

SIADH complicating deep neck abscess in infancy.

Symptomatic hyponatremia due to syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in infancy is seen usually with pneumonia and meningitis and its association with deep neck abscess is not documented. Recognition and appropriate management of this complication is important to prevent mortality and long-term neurological morbidity. We report a 3-month-old infant with parapharyngeal abscess presenting with altered sensorium and recurrent seizures as a result of hyponatremia due to SIADH. The clinical course and outcome is described. Limitation of imaging modalities in an infant with airway compromise is discussed.

Thrombocytopenia in hepatitis A--an atypical presentation.

Acute hepatitis due to hepatitis A virus (HAV) is usually a benign self-limiting disease during childhood. Autoimmune manifestations are rare with acute HAV, especially in children. We report an 8-year-old boy with severe thrombocytopenia as an initial manifestation of acute HAV infection. Bone marrow examination suggested peripheral destruction of platelets. His clinical course was complicated by persistent severe thrombocytopenia and progressive cholestasis requiring prednisolone therapy.