Broad-Spectrum Supramolecularly Reloadable Antimicrobial Coatings.

Antimicrobial surfaces limit the spread of infectious diseases. To date, there is no antimicrobial coating that has widespread use because of short-lived and limited spectrum efficacy, poor resistance to organic material, and/or cost. Here, we present a paint based on waterborne latex particles that is supramolecularly associated with quaternary ammonium compounds (QACs). The optimal supramolecular pairing was first determined by immobilizing selected ions on self-assembled monolayers exposing different groups. The QAC surface loading density was then increased by using polymer brushes. These concepts were adopted to develop inexpensive paints to be applied on many different surfaces. The paint could be employed for healthcare and food production applications. Its slow release of QAC allows for long-lasting antimicrobial action, even in the presence of organic material. Its efficacy lasts for more than 90 washes, and importantly, once lost, it can readily be restored by spraying an aqueous solution of the QAC. We mainly tested cetyltrimethylammonium as QAC as it is already used in consumer care products. Our antimicrobial paint is broad spectrum as it showed excellent antimicrobial efficiency against four bacteria and four viruses.

Beyond the limiting gap length: peripheral nerve regeneration through implantable nerve guidance conduits.

Peripheral nerve damage results in the loss of sensorimotor and autonomic functions, which is a significant burden to patients. Furthermore, nerve injuries greater than the limiting gap length require surgical repair. Although autografts are the preferred clinical choice, their usage is impeded by their limited availability, dimensional mismatch, and the sacrifice of another functional donor nerve. Accordingly, nerve guidance conduits, which are tubular scaffolds engineered to provide a biomimetic environment for nerve regeneration, have emerged as alternatives to autografts. Consequently, a few nerve guidance conduits have received clinical approval for the repair of short-mid nerve gaps but failed to regenerate limiting gap damage, which represents the bottleneck of this technology. Thus, it is still necessary to optimize the morphology and constituent materials of conduits. This review summarizes the recent advances in nerve conduit technology. Several manufacturing techniques and conduit designs are discussed, with emphasis on the structural improvement of simple hollow tubes, additive manufacturing techniques, and decellularized grafts. The main objective of this review is to provide a critical overview of nerve guidance conduit technology to support regeneration in long nerve defects, promote future developments, and speed up its clinical translation as a reliable alternative to autografts.

Webbed Neck Deformity Reconstruction in Patients with Turner Syndrome: Technical Considerations in Treating Congenital Pterygium Colli.

Importance: Present an excellent outcome for a rare pterygium colli reconstruction. Objective: Establish techniques that have yielded a successful aesthetic and functional outcome for a patient with pterygium colli in a procedure that lacks consensus. Design, Setting, and Participants: Surgical pearls-description of considerations for a successful reconstruction. An academic practice. Pediatric patient with Turner's syndrome who underwent neck and auricular reconstruction.

A Novel RNPC3 Gene Variant Expands the Phenotype in Patients with Congenital Hypopituitarism and Neuropathy.

INTRODUCTION: Pathogenic biallelic RNPC3 variants cause congenital hypopituitarism (CH) with congenital cataracts, neuropathy, developmental delay/intellectual disability, primary ovarian insufficiency, and pituitary hypoplasia. Here, we aimed to evaluate the clinical and molecular characteristics of 2 patients with CH and neuropathy. MATERIALS AND METHODS: Proband was evaluated by clinical, laboratory, and radiological exams, followed by exome sequencing (ES). Clinical investigation of an affected sibling and variant segregation in the family was performed by Sanger sequencing. A three-dimensional protein model study was conducted to predict the effect of the variant on the function of the RNPC3 peptide. RESULTS: Proband was a 16-month-old girl who was referred for the evaluation of failure to thrive. Her height, weight, and head circumference were 55.8 cm (-7.6 SDS), 6.5 kg (-3.6 SDS), and 41.8 cm (-3.82), respectively. She had a developmental delay and intellectual disability. Central hypothyroidism, growth hormone, and prolactin deficiencies were identified, and MRI revealed pituitary hypoplasia. Electroneuromyography performed for the gait abnormality revealed peripheral neuropathy. A homozygous novel variant c.484C>T/p.(Pro162Ser) in the RNPC3 was detected in the ES. Her brother had the same genotype, and he similarly had pituitary hormone deficiencies with polyneuropathy. CONCLUSION: Expanding our knowledge of the spectrum of RNPC3 variants, and apprehending clinical and molecular data of additional cases, is decisive for accurate diagnosis and genetic counseling.

The effect of High-Dose Vitamin C Treatment for Acute Respiratory Failure Due to Coronavirus Disease Pneumonia on Mortality and Length of Intensive Care Stay: A Retrospective Cohort Study.

Objectives: In our study, we aimed to determine the effect of vitamin C on short-term mortality and length of intensive care unit (ICU) stay in patients with coronavirus disease (COVID-19) followed up in the ICU. Methods: The patients who received and those who did not receive the high-dose intravenous vitamin C protocol were assigned to the treatment and control groups, respectively. The primary study findings in both groups were length of ICU stay and short-term mortality, while the secondary findings were vasopressor and invasive mechanical ventilation requirements and change in sequential organ failure assessment score from the 0 to the 96th hour. Results: Thirty-eight patients were included in the treatment group and 40 were included in the control group. The mortality rates were 44% and 60% in the treatment and control groups, respectively; however, the difference between the groups was not statistically significant (p>0.05). The median length of ICU stay in both groups was 10 days (p>0.05). No significant differences in the invasive mechanical ventilation and vasopressor requirements were found between the groups (p>0.05). Conclusion: Consequently, the high-dose vitamin C therapy in the patients with acute respiratory failure due to COVID-19 pneumonia did not reduce the length of ICU stay, mortality, and invasive mechanical ventilation and vasopressor reqirements.

Shear Wave Elastography in Patients with Spinal Muscular Atrophy Types 2 and 3.

INTRODUCTION: This study aimed to investigate selective muscle involvement by shear wave elastography (SWE) in patients with spinal muscular atrophy (SMA) types 2 and 3 and to compare SWE values with magnetic resonance imaging (MRI) in demonstrating muscle involvement. METHODS: Seventeen patients with SMA types 2 and3 were included in the study. SWE was used to evaluate stiffness of the upper and lower extremities and paraspinal muscles. Involvement of the paraspinal muscles was evaluated using 1.5-T MRI. RESULTS: Among the upper extremity muscles, SWE values were the highest for the triceps brachii; however, no significant difference was noted (p = 0.23). In post hoc analysis, a significant difference was observed between triceps brachii and biceps brachii (p = 0.003). Patients with a longer disease duration have the highest SWE values for the triceps brachii (r = 0.67, p = 0.003). Among the lower extremity muscles, SWE values for the iliopsoas were significantly higher than the gluteus maximus (p < 0.001). A positive correlation was found between SWE values and MRI scores of paraspinal muscles (r = 0.49, p = 0.045; r = 0.67, p = 0.003). CONCLUSION: This is the first study to report muscle involvement assessed by SWE in patients with SMA types 2 and 3. Our findings are similar to the presence of selective muscle involvement demonstrated in previous studies, and also SWE and MRI values were similar. SWE is an alternative noninvasive practical method that can be used to demonstrate muscle involvement in patients with SMA, to understand the pathogenesis of segmental involvement, and to guide future treatments or to monitor the effectiveness of existing new treatment options.

Lignin: A Sustainable Antiviral Coating Material.

Transmission of viruses through contact with contaminated surfaces is an important pathway for the spread of infections. Antiviral surface coatings are useful to minimize such risks. Current state-of-the-art approaches toward antiviral surface coatings either involve metal-based materials or complex synthetic polymers. These approaches, however, even if successful, will have to face great challenges when it comes to large-scale applications and their environmental sustainability. Here, an antiviral surface coating was prepared by spin-coating lignin, a natural biomass residue of the paper production industry. We show effective inactivation of herpes simplex virus type 2 (>99% after 30 min) on a surface coating that is low-cost and environmentally sustainable. The antiviral mechanism of the lignin surface was investigated and is attributed to reactive oxygen species generated upon oxidation of lignin phenols. This mechanism does not consume the surface coating (as opposed to the release of a specific antiviral agent) and does not require regeneration. The coating is stable in ambient conditions, as demonstrated in a 6 month aging study that did not reveal any decrease in antiviral activity. This research suggests that natural compounds may be used for the development of affordable and sustainable antiviral coatings.

Effect of early awake prone positioning application on prognosis in patients with acute respiratory failure due to COVID-19 pneumonia: a retrospective observational study.

BACKGROUND: We evaluated the effect of early awake prone position administration on oxygenation and intubation requirements and short-term mortality in patients with acute respiratory failure due to coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This is an observational-cohort study. Patients receiving mask oxygen therapy in our intensive care units because of acute respiratory failure due to COVID-19 pneumonia were included. The Awake Prone Position (APP) group consisted of patients who were applied awake prone position, whereas non-APP group consisted of patients who were not applied awake prone position. PaCO2, PaO2, pH, SpO2 values and PaO2/FiO2 ratios were recorded at the beginning and 24th hour. Demographic data, comorbidities, intubation requirements, ventilator-free days, length of intensive care unit stay and short-term mortality of the patients were recorded. RESULTS: The data of total 225 patients were examined, and 48 patients who met our study criteria were included. At the 24th hour, the median SpO2 value of the APP group was 95%, the median PaO2 value was 82 mmHg, whereas the SpO2 value of the non-APP group was 90% and the PaO2 value was 66 mmHg. (p = 0.001, p = 0.002). There was no statistically significant difference between the groups in length of intensive care unit stay and ventilator-free days, but short-term mortality and intubation requirements was lower in the APP group (p = 0.020, p = 0.001) CONCLUSION: Awake prone position application in patients receiving non-rebreather mask oxygen therapy for respiratory failure due to COVID-19 pneumonia improves oxygenation and decreases the intubation requirements and mortality.

Anxiety and burnout in anesthetists and intensive care unit nurses during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: This study aimed to measure the levels of anxiety and burnout among healthcare workers, including attending physicians, residents, and nurses in intensive care units during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This is a cross-sectional survey analysis of healthcare workers in our institution. Data were collected on demographic variables, COVID-19 symptoms and test, disease status, anxiety level (assessed by the Beck Anxiety Inventory), and burnout level (measured by the Maslach Burnout Inventory). Subscales of the burnout inventory were evaluated separately. RESULTS: A total of 104 participants completed the survey. Attending physicians, residents, and nurses constituted 25%, 33.7%, and 41.3% of the cohort, respectively. In comparison to untested participants, those tested for COVID-19 had a lower mean age (p = 0.02), higher emotional exhaustion and depersonalization scores (p = 0.001, 0.004, respectively), and lower personal accomplishment scores (p = 0.004). Furthermore, moderate to severe anxiety was observed more frequently in tested participants than untested ones (p = 0.022). Moderate or severe anxiety was seen in 23.1% of the attending physicians, 54.3% of the residents, and 48.8% of the nurses (p = 0.038). Emotional exhaustion, personal accomplishment, and depersonalization scores differed depending on the position of the healthcare workers (p = 0.034, 0.001, 0.004, respectively). CONCLUSION: This study revealed higher levels of anxiety and burnout in younger healthcare workers and those tested for COVID-19, which mainly included residents and nurses. The reasons for these observations should be further investigated to protect their mental health.

Clinically isolated syndrome and multiple sclerosis in children: a single center study.

BACKGROUND AND OBJECTIVES: This study was conducted to determine the differences in clinical and radiological features at the first demyelinating event in children with clinically isolated syndrome (CIS) and multiple sclerosis (MS). METHODS: This was a single center retrospective cohort study of the children with CIS followed-up at Istanbul University Faculty of Medicine, Department of Pediatric Neurology, between 2010 and 2018. Children with CIS who were assessed at 3, 6, 12 and 24 months following their first identified demyelinating event were included. Demographic data, mode of presentation and the presence of the oligoclonal band in the cerebrospinal fluid (CSF) were abstracted from the medical records. Magnetic resonance imaging of the brain and spinal cord was analyzed for the location, number, size and gadolinium enhancement of the lesions. RESULTS: A total of 51 patients` data was assessed, 38 patients at a mean age of 12.3 years were enrolled in the study. Twenty-seven children (71%) evolved into clinically definite MS after a mean follow-up of 11 months. Older age at first demyelinating event and the presence of the oligoclonal band in CSF were tended to be more common in patients with MS than patients with CIS (p < 0.05). The increased number of T2-hyperintense lesion and the presence of the lesion in periventricular, infratentorial and corpus callosum were associated with a tendency for development of MS (p < 0.05). CONCLUSION: Older age at first demyelinating event, the presence of the oligoclonal band in CSF, the number and localization of T2-hyperintense lesion were associated with a tendency for development of MS.

Electro-Viscoelastic Migration under Simultaneously Applied Microfluidic Pressure-Driven Flow and Electric Field.

Under the simultaneous use of pressure-driven flow and DC electric field, migration of particles inside microfluidic channels exhibits intricate focusing dynamics. Available experimental and analytical studies fall short in giving a thorough explanation to particle equilibrium states. Also, the understanding is so far limited to the results based on Newtonian and neutral viscoelastic carrier fluids. Hence, a holistic approach is taken in this study to elaborate the interplay of governing electrophoretic and slip-induced/elastic/shear gradient lift forces. First, we carried out experimental studies on particle migration in Newtonian, neutral viscoelastic, and polyelectrolyte viscoelastic media to provide a comprehensive understanding of particle migration. The experiments with the viscoelastic media led to contradictory results with the existing explanations. Then, we introduced the Electro-Viscoelastic Migration (EVM) theory to give a unifying explanation to particle migration in Newtonian and viscoelastic solutions. Confocal imaging with fluorescent-labeled polymer solutions was used to explore the underlying migration behavior. A surprising outcome of our results is the formation of cross-sectionally nonuniform viscoelasticity that may have unique applications in microfluidic particle focusing.

Evaluation of the prognostic factors in school age children who experienced neonatal seizures.

BACKGROUND: This prospective study aimed to evaluate long-term neurodevelopmental outcomes and risk factors of the previously reported cohort, at their school age. METHOD: We included neonates whose seizures were directly observed by the child neurologist or neonatologist based on clinical observations. They were assessed for cognitive and neurological outcomes at the age of 9-11 years. The test battery included a neurological examination, the Wechsler Intelligence Scale for Children-Revised (WISC-R) test, and patients with the diagnosis of cerebral palsy (CP) were graded according to the Gross Motor Function Classification System (GMFCS). The primary outcome of this study was to determine risk factors for the long-term prognosis of neonatal seizures. RESULTS: For the long-term follow-up, 97 out of 112 patients of the initial cohort were available (86.6%). We found that 40 patients (41%) have the normal prognosis, 22 patients (22.7%) have the diagnosis of CP, and 30 patients (30.9%) were diagnosed as having epilepsy. Twelve out of 22 patients with CP had the diagnosis of epilepsy. The WISC-R full-scale IQ scores were <55 points in 27 patients (27.8%) and were >85 points in 40 patients (41.2%). According to GMFCS, 10 patients were classified as levels 1-2, and 12 patients were classified as levels 3-5. In multivariate regression analyses, 5-min APGAR score <6 was found to be an independent risk factor for CP, and 5-min APGAR score <6 and neonatal status epilepticus were independent risk factors for epilepsy. CONCLUSIONS: This prospective cohort study reveals that abnormal school age outcome after neonatal seizures are significantly related to 5-min APGAR score <6 and neonatal status epilepticus.

Water-dispersible glycosylated poly(2,5'-thienylene)porphyrin-based nanoparticles for antibacterial photodynamic therapy.

Here we report the preparation of water-dispersible glycosylated poly(2,5'-thienylene)porphyrin based nanoparticles by a nanoprecipitation method and demonstrate the application of these nanoparticles in antibacterial photodynamic therapy. The diameter of the nanoparticles is in the range of 50-80 nm and the resulting nanoparticles are stable in water without precipitation at least for a month. They have high singlet oxygen efficiency and display light-triggered biocidal activity against both Gram negative bacteria (Escherichia coli, E. coli) and Gram positive bacteria (Bacillus subtilis, B. subtilis). Upon white light irradiation for 10 min with a flux of 22 mW cm-2 of the E. coli suspension incubated with NPs (18 µg mL-1), a killing efficiency of 99% is achieved, whereas in the dark the effect is recorded as only around 8%.

Cucurbit[7]uril-Anchored Porphyrin-Based Multifunctional Molecular Platform for Photodynamic Antimicrobial and Cancer Therapy.

Here we report a photoactive supramolecular assembly that is multifunctional and constructed by covalently linking four receptor molecules (cucurbit[7]uril) to a porphyrin derivative with suitable linkers. While this molecular platform serves very efficiently as a light-triggered broad-spectrum antibacterial agent, owing to its negligible dark cytotoxicity and the presence of host molecules (CB7), it can also be utilized as a vehicle to carry drug molecules for a combined chemo and photodynamic cancer therapy.

Efficacy of Stiripentol and the Clinical Outcome in Dravet Syndrome.

Dravet syndrome is a rare and progressive epileptic encephalopathy of infancy. Stiripentol reduces the seizure frequency in patients with Dravet syndrome. We evaluated the clinical characteristics of patients with Dravet syndrome and their response to stiripentol. We retrospectively collected the data of 21 patients (11 females; mean age, 8.2 years, range: 5.4-15 years) with Dravet syndrome who were treated with stiripentol in our outpatient clinic between June 2016 and June 2017. Patients with seizure reduction ≥50% were considered responders. Most of our patients had severe (47%) or moderate (33%) cognitive disabilities, although 14% had mild cognitive disability. There was a significant difference in both status epilepticus and age between the groups with normal/mild versus severe/moderate neurocognitive prognoses. Of the patients, 85.7% were using stiripentol. The mean duration of stiripentol use was 41.2 months (range: 24-64 months). In 12 patients (57%), the seizure frequency decreased by more than 50%, and 2 of them were seizure-free. Status epilepticus was not recorded after stiripentol treatment in 8 of 11 patients with status epilepticus. Despite the small sample size, our results suggest that stiripentol has a favorable efficacy. In addition, considering the absence of status epilepticus after treatment and the negative effects of status epilepticus on cognitive development, early treatment should be initiated in SD patients, for whom disease control is difficult.

Efficacy of rufinamide in childhood refractory epilepsy.

Yildiz EP, Hizli Z, Bektas G, Ulak-Özkan M, Tatli B, Aydinli N, Çaliskan M, Özmen M. Efficacy of rufinamide in childhood refractory epilepsy. Turk J Pediatr 2018; 60: 238-243. Rufinamide has been used as a new antiepileptic drug in the treatment of drug-resistant epilepsy, in recent years. The objective of this study was to evaluate the reliability of rufinamide and its impact on seizure frequency in patients diagnosed with drug-resistant epilepsy, where seizures could not be controlled with `classical` antiepileptic drugs. We retrospectively reviewed the data of epileptic patients who were followed up between January 2004 and December 2014 in the Pediatric Neurology Department. Patients who were diagnosed with `drug resistant epilepsy` and treated with rufinamide were evaluated. Decrease in seizure frequency and drug side effects were assessed as parameters. A total of 38 patients (14 girls, 24 boys) with a mean age of 8.5 (range, 3.5-17) years were included in the study. The mean follow-up duration was 25.5 (23-29.5) months, while the mean maximal dose of rufinamide was 32.5 (28-42) mg/kg/day. Response to treatment was assessed by the reduction in frequency of seizures. The decrease was < 50% (essentially unresponsive to treatment) in 20 patients and 50­99% in 8 patients. Ten patients (26.3%) remained seizure-free. The response rate for tonic seizures was 50%. In drop/attacks seizures, this ratio was found as 73%, which was quite high. Patients with myoclonic and tonic-clonic seizures did not significantly benefit from rufinamide. The rate of patients with Lennox-Gestaut syndrome (LGS) who responded very well (reduction in seizure frequency > 50%) was 55.5%. In the LGS group, patients with drop/attacks showed the best response to treatment. Rufinamide was not effective in two patients diagnosed with Dravet syndrome. Rufinamide can be safely used in pediatric patients who use multiple antiepileptic drugs and are unresponsive to the treatment. It was seen to be effective especially in patients diagnosed with LGS and drop/attacks types of seizures.

Vanishing white matter disease with a novel EIF2B5 mutation: A 10-year follow-up.

BACKGROUND: Vanishing white matter disease is a heterogeneous disorder caused by mutation in one of the five genes encoding subunits of the eukaryotic initiation factor eIF2B. It is a heterogeneous disorder due to phenotypic variation and a clear genotype-phenotype correlation could not be established so far. We describe a novel mutation in the EIF2B5 gene by analyzing the clinical phenotype and the progression of brain lesions for 10 years. CASE: A novel mutation in the EIF2B5 gene was detected in the heterozygous state; c.1688G > A (p. Arg563Gln) mutation in exon 12, accompanied by a previously detected c.806G > A (p. Arg269Gln) mutation in exon 6, leading to substitution of arginine for a glutamine. This compound heterozygous mutation was associated with disease onset at early childhood and relatively slow progression of neurological deterioration. In contrast to previous findings indicated the association of c.806G > A mutation and peripheral neuropathy in patients with vanishing white matter disease, electromyography of our case was normal. The corpus callosum inner rim was the affected area at early stages, which may be remarkable for early diagnosis of vanishing white matter disease. Serial follow-up magnetic resonance imaging revealed the white matter signal abnormality, subsequently cystic degeneration and decrease in white matter volume. CONCLUSION: The novel mutation c.1688G > A in compound heterozygous state leads to intermediate phenotype of the vanishing white matter disease. In the early stages of the disease the signal abnormality in the corpus callosum inner rim might be remarkable.