Early Neonatal Presentation and Neuroimaging of Parechovirus Meningoencephalitis in a Preterm Baby: A Case Report.

Neonatal meningoencephalitis caused by human parechovirus infection is being increasingly recognized in recent literature. While most cases are postnatally acquired, intrauterine infection is rare, presents early and has a more severe impact on brain health and development. We discuss here an infant born preterm at 34 weeks gestational age, with neonatal course remarkable for severe encephalopathy presenting on day 2 of life due to human parechovirus meningoencephalitis transmitted in utero. Early magnetic resonance brain imaging detected extensive white matter injury and subsequently evolved into multicystic leukoencephalopathy. Posthospital discharge, infant was noted to have early neurodevelopmental impairment at 4 months corrected age.

Biochemical Characterization of Laccase from Spirulina CPCC-695 and Their Role in Estrone Degradation.

The addition of exogenous endocrine disrupting compounds (EDCs) like estrone, in the food chain through the aquatic system, disrupts steroid biosynthesis and metabolism by altering either the genomic or non-genomic pathway that eventually results in various diseases. Thus, bioremediation of these compounds is urgently required to prevent their addition and persistence in the environment. Enzymatic degradation has proven to be a knight in shining armour as it is safe and generates no toxic products. The multicopper oxidases (E.C. 1.10.3.2 benzenediol: oxygen oxidoreductase), laccase with the potential to degrade both phenolic and non-phenolic substrates has recently gained attention. In this study, the laccase was purified, characterized, and used to study estrone degradation. The culture filtrate (crude laccase) was concentrated and precipitated using cold-acetone and dialyzed against tris buffer (50 mM) giving a four-fold partially purified form, with 45.56% yield and 204.14 U/mg as specific activity and a single peak at 250-300 nm. The partially purified laccase was approximately 80 kDa as estimated by SDS-PAGE preferred ABTS as substrate. Both crude and partially purified laccase showed maximum activity at pH 3.0, 40 °C, and 4 mM ABTS. Kinetic constants (Km, Vmax) of crude and partially purified laccase were found to be 0.83 mM; 494.31 mM/min, and 0.58 mM; 480.54 mM/min respectively. Iron sulphate and sodium azide inhibited laccase maximally. Crude and partially purified laccase degradation efficiency was 87.55 and 91.35% respectively. Spirulina CPCC-695 laccase with efficient estrone degradation ability renders them promising candidates for EDCs bioremediation.

Diminished TMEM100 Expression in a Newborn With Acinar Dysplasia and a Novel TBX4 Variant: A Case Report.

Acinar dysplasia (AcDys) of the lung is a rare lethal developmental disorder in neonates characterized by severe respiratory failure and pulmonary arterial hypertension refractory to treatment. Recently, abnormalities of TBX4-FGF10-FGFR2-TMEM100 signaling regulating lung development have been reported in patients with AcDys due to heterozygous single-nucleotide variants or copy-number variant deletions involving TBX4, FGF10, or FGFR2. Here, we describe a female neonate who died at 4 hours of life due to severe respiratory distress related to AcDys diagnosed by postmortem histopathologic evaluation. Genomic analyses revealed a novel deleterious heterozygous missense variant c.728A>C (p.Asn243Thr) in TBX4 that arose de novo on paternal chromosome 17. We also identified 6 candidate hypomorphic rare variants in the TBX4 enhancer in trans to TBX4 coding variant. Gene expression analyses of proband's lung tissue showed a significant reduction of TMEM100 expression with near absence of TMEM100 within the endothelium of arteries and capillaries by immunohistochemistry. These results support the pathogenicity of the detected TBX4 variant and provide further evidence that disrupted signaling between TBX4 and TMEM100 may contribute to severe lung phenotypes in humans, including AcDys.

Exogenous salicylic acid mediated herbicide (Paraquat) resistance in cyanobacterial biofertilizer Microchaete sp. NCCU-342.

Paddy field farming remains the dominant form of growing rice in modern times as the rice is the staple food for over half the world's population and is closely associated with food security and political stability of many countries. Record increase in rice production have been observed since the start of the Green Revolution. India is one of the largest paddy producer and exporter in the world. However, constant use of chemical herbicide like paraquat had shown adverse impact on the rice yield. Non-target organisms of the habitat including cyanobacterial paddy biofertilizer face the herbicide toxicity and are unable to perform efficiently their role as biofertilizer. Therefore, in the present study, an attempt has been made to enhance the paraquat resistance in rice biofertilizer (Microchaete sp. NCCU-342) by exogenous addition of salicylic acid. Paraquat showed toxicity in Microchaete sp. NCCU-342 in a dose-dependent manner. Concentration of paraquat >1.0 µM exhibited lethal effect since the beginning. Through successive narrow range experiment, LD50 value of paraquat was obtained as 0.6 µM. Biomass exposed to paraquat (LD50 value) and salicylic acid (0.3 mM) showed mitigation in free radical production (2.20 % MDA and 1.69 % H2O2) and enhancement in the activity of the antioxidant enzymes activity, i.e. SOD, CAT, APX (137.76 %, 87.45 %, 118 %, respectively) and osmolytes (3.8 % proline and 21.51% sucrose). Thus, for sustainable agricultural practice, especially for paddy field cyanobacterial biofertilizer, application of salicylic acid or organism with higher salicylic acid production ability may be an alternative to overcome the paraquat toxicity.

Biosynthesis, characterization and biomedical potential of Arthrospira indica SOSA-4 mediated SeNPs.

The use of aqueous cyanobacterial extracts for selenium nanoparticle (SeNP) synthesis is considered green, cost-effective, and eco-friendly technology that is more advanced than physical and chemical methods. In the current study, an aqueous extract of Arthrospira indica SOSA-4 was used as a reducing and stabilizing agent for the green synthesis of SeNPs. The UV-Visible absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-Ray diffraction, Raman spectroscopy, Atomic force microscopy (AFM), Scanning electron microscopy-Energy Dispersive X-Ray spectroscopy(SEM-EDX), and Transmission electron microscopy (TEM) were performed to characterize the biosynthesized SeNPs. Gas chromatography-Mass spectrometry (GC-MS) was also performed to know the composition of the cyanobacterial extract. SEM, TEM, and AFM showed the average size of SeNPs to be 8.5 nm, 9 nm, and 8.7 nm respectively. FT-IR analysis demonstrated the presence of functional groups on the SeNPs that acted as stabilizing agents. XRD pattern and Raman spectroscopy showed the amorphous nature of SeNPs. Synthesized SeNPs showed significant antioxidant activity in DPPH, FRAP, SOR, and ABTS assay. SeNPs showed good anti-microbial activity against Staphylococcus aureus, Escherichia coli, Candida albicans, Candida glabrata, and Candida tropicalis and good anti-cancer activity in MTT assay, Trypan assay, and Flow cytometry analysis against MCF-7, SiHa, and SW480 cell lines. Non-toxicity of SeNPs against normal cell line (HEK-293) was an additional property that affirmed its potential as a bio-compatible nanomaterial.

Experiences of a Regional Quality Improvement Collaborative to Reduce Unplanned Extubations in the Neonatal Intensive Care Unit.

BACKGROUND: Unplanned extubations (UEs) occur frequently in the neonatal intensive care unit (NICU). These events can be associated with serious short-term and long-term morbidities and increased healthcare costs. Most quality improvement (QI) initiatives focused on UE prevention have concentrated efforts within individual NICUs. METHODS: We formed a regional QI collaborative involving the four regional perinatal center (RPC) NICUs in upstate New York to reduce UEs. The collaborative promoted shared learning and targeted interventions specific to UE classification at each center. RESULTS: There were 1167 UEs overall during the four-year project. Following implementation of one or more PDSA cycles, the combined UE rate decreased by 32% from 3.7 to 2.5 per 100 ventilator days across the collaborative. A special cause variation was observed for the subtype of UEs involving removed endotracheal tubes (rETTs), but not for dislodged endotracheal tubes (dETTs). The center-specific UE rates varied; only two centers observed significant improvement. CONCLUSIONS: A collaborative approach promoted knowledge sharing and fostered an overall improvement, although the individual centers' successes varied. Frequent communication and shared learning experiences benefited all the participants, but local care practices and varying degrees of QI experience affected each center's ability to successfully implement potentially better practices to prevent UEs.

Synthesis, purification and characterization of Plectonema derived AgNPs with elucidation of the role of protein in nanoparticle stabilization.

Driven by the need to biosynthesize alternate biomedical agents to prevent and treat infection, silver nanoparticles have surfaced as a promising avenue. Cyanobacteria-derived nanomaterial synthesis is of substantive interest as it offers an eco-friendly, cost-effective, sustainable, and biocompatible route for further development. In the present study optimal conditions for synthesis of silver nanoparticles (AgNPs) were 1 : 9 v/v [cell extract: AgNO3 (1 mM)], pH 7.4, and 30 °C reaction temperatures. Synthesis of nanoparticles was monitored by UV-vis spectrophotometry and the maximum absorbance was observed at a wavelength of 420 nm. SEM with EDX analysis confirmed 96.85% silver by weight which revealed the purity of AgNPs. TEM & XRD analysis exhibited a particle size of ∼12 nm with crystalline nature. FTIR analysis confirmed the presence of possible biomolecules involved in the synthesis and stabilization of AgNPs. Decapping of AgNPs followed by SDS-PAGE, LCMS and MALDI TOF analysis elucidates the proteinaceous nature of the capping and stabilizing agent. Cyanobacterial-derived capped AgNPs showed more cytotoxicicity towards a non-small cell lung cancer (A549) cell line, free radical scavenger and an antimicrobial than de-capped AgNPs. In addition they showed significant synergistic characteristics with antibiotics and fungicides. The test revealed that the capped AgNPs were biocompatible with good anti-inflammatory properties. The blend of antimicrobial and biocompatible properties, coupled with their intrinsic "green" and facile synthesis, made these biogenic nanoparticles particularly attractive for future applications in nanomedicine.

Mitigative effect of biosynthesized SeNPs on cyanobacteria under paraquat toxicity.

Increasing population has resulted in increased food demand. Pesticides like paraquat (PQ) have been used indiscriminately to increase the growth and yield of crops. However, this has adversely affected a wide spectrum of non-target organisms like cyanobacteria that are used as a bio-fertilizer in the rice field. In the present study, biogenic- Gloeocaspa gelatinosa NCCU -430 mediated selenium nanoparticles (SeNPs) were synthesized and characterized using different techniques including UV-Visible spectroscopy, XRD, FTIR, TEM and SEM-EDX for their use as PQ toxicity mitigator in cyanobacterial biofertilizer (Anabaena variabilis NCCU-442). Therefore, a comparative study was performed among control, PQ, SeNPs and SeNPs+PQ to check the efficacy of SeNPs in mitigation of PQ induced toxicity. Supplementation of SeNPs in PQ treated culture enhanced antioxidant enzymes activity i.e., SOD (7.55%), CAT (57.94%), APX (17.45%) and GR (14.72%) as compared to only PQ treated culture. The outcomes of the present study suggested that SeNPs can ameliorate the PQ induced stress that may be used in sustainable rice cultivation needed for filing the gap between requirement and supply.

Developing Medical Technologies for Low-Resource Settings: Lessons From a Wireless Wearable Vital Signs Monitor-neoGuard.

The neoGuard™ technology is a wireless wearable vital signs monitor attached to a patient's forehead to continuously measure oxygen saturation, pulse rate, respiratory rate and temperature. Developed with feedback from more than 400 health workers, primarily in East Africa, the product has been designed to meet the unique constraints of low-resource settings. This perspective piece by the innovators of neoGuard™ and some of their key partners examines the complicated journey of taking a medical technology from concept through clinical validation and finally to market. By shedding light on some of the most critical steps and common challenges encountered along the pathway to commercialization, the authors hope that their experiences will provide some valuable insights to other aspiring innovators in this space.

Biomedical potential of Anabaena variabilis NCCU-441 based Selenium nanoparticles and their comparison with commercial nanoparticles.

Selenium nanoparticles (SeNPs) are gaining importance in the field of medicines due to their high surface area and unique properties than their other forms of selenium. In this study, biogenic selenium nanoparticles (B-SeNPs) were synthesized using cyanobacteria and their bioactivities (antioxidant, antimicrobial, anticancer and biocompatibility) were determined for comparison with commercially available chemically synthesized selenium nanoparticles (C-SeNPs). Color change of reaction mixture from sky blue to orange-red indicated the synthesis of biogenic SeNPs (B-SeNPs). UV-Vis spectra of the reaction mixture exhibited peak at 266 nm. During optimization, 30 °C of temperature, 24 h of time and 1:2 concentration ratio of sodium selenite and cell extract represented the best condition for SeNPs synthesis. Various functional groups and biochemical compounds present in the aqueous extract of Anabaena variabilis NCCU-441, which may have possibly influenced the reduction process of SeNPs were identified by FT-IR spectrum and GC-MS. The synthesized cyanobacterial SeNPs were orange red in color, spherical in shape, 10.8 nm in size and amorphous in nature. The B-SeNPs showed better anti-oxidant (DPPH, FRAP, SOR and ABTS assays), anti-microbial (antibacterial and antifungal) and anti-cancer activitities along with its biocompatibility in comparison to C-SeNPs suggesting higher probability of their biomedical application.

Cyanobacteria as a bioreactor for synthesis of silver nanoparticles-an effect of different reaction conditions on the size of nanoparticles and their dye decolorization ability.

The green synthesis of metallic nanoparticles has paved the way for improving and protecting the environment by decreasing the use of toxic chemicals and eliminating biological risks in biomedical applications. Biological synthesis of metal nanoparticles is gaining more importance due to simplicity, rapid rate of synthesis and eco-friendliness. In the present investigation cyanobacterial (Microchaete NCCU-342) cell free aqueous extract has been used for optimizing biosynthesis of silver nanoparticles (AgNP). The optimized reaction parameters for efficient synthesis of AgNP were: biomass quantity of 80 µg/ml, pH 5.5, 60 °C temperature, duration of 60 min UV light exposure and 1 mM AgNO3 concentration. AgNP was characterized by UV-Visible Spectrophotometery, Transmission Electron Microscopy and Dynamic light scattering. The smallest nanoparticles (obtained from biomass parameter were spherical, polydisperessed and in the range of 60-80 nm) were characterized further in a degradation study of azo dye methyl red. Degradation of methyl red within 2 h was more with AgNP (84.60%) as compared to cyanobacterial extract (49.80%).

Monitoring Gas Exchange During Hypothermia for Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: Therapeutic hypothermia is standard of care in management of moderate/severe hypoxic-ischemic encephalopathy. Persistent pulmonary hypertension of the newborn is associated with hypoxic-ischemic encephalopathy and is exacerbated by hypoxemia and hypercarbia. Gas exchange is assessed by arterial blood gas analysis (with/without correction for body temperature), pulse oximetry, and end-tidal CO2. DESIGN: A retrospective chart review. SETTINGS: Regional perinatal center in Western New York. PATIENTS: Fifty-eight ventilated neonates with indwelling arterial catheter on therapeutic hypothermia. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: We compared pulse oximetry, PaO2, end-tidal CO2, and PaCO2 during hypothermia and normothermia in neonates with hypoxic-ischemic encephalopathy using 1,240 arterial blood gases with simultaneously documented pulse oximetry. During hypothermia, pulse oximetry 92-98% was associated with significantly lower temperature-corrected PaO2 (51 mmHg; interquartile range, 43-51) compared with normothermia (71 mmHg; interquartile range, 61-85). Throughout the range of pulse oximetry values, geometric mean PaO2 was about 23% (95% CI, 19-27%) lower during hypothermia compared with normothermia. In contrast, end-tidal CO2 accurately assessed temperature-corrected PaCO2 during normothermia and hypothermia. CONCLUSIONS: Hypothermia shifts oxygen-hemoglobin dissociation curve to the left resulting in lower PaO2 for pulse oximetry. Monitoring oxygenation with arterial blood gas uncorrected for body temperature and pulse oximetry may underestimate hypoxemia in hypoxic-ischemic encephalopathy infants during whole-body hypothermia, while end-tidal CO2 reliably correlates with temperature-corrected PaCO2.

Optimal Duration of Continuous Video-Electroencephalography in Term Infants With Hypoxic-Ischemic Encephalopathy and Therapeutic Hypothermia.

Continuous video-electroencephalography (EEG) is an important diagnostic and prognostic tool in newborns with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia. The optimal duration of continuous video-EEG during whole-body hypothermia is not known. We conducted a retrospective study of 35 neonates with hypoxic-ischemic encephalopathy undergoing whole-body hypothermia with continuous video-EEG. EEG ictal changes were detected in 9/35 infants (26%). Of these 9 infants, the seizures were initially observed within 30 minutes of EEG monitoring in 6 (67%), within 24 hours in 2 (22%), and during rewarming in 1 infant (11%). No new seizures were detected between 24-72 hours of therapeutic hypothermia. Background suppression was detected in 14 infants (40%) by 24 hours. In neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia, continuous video-EEG has the highest diagnostic yield within the first 24 hours and during the rewarming phase. In the absence of prior seizures or antiepileptic therapy, limiting continuous video-EEG to these periods in resource-limited settings may reduce cost during therapeutic hypothermia.