Tocilizumab challenge: A series of cytokine storm therapy experiences in hospitalized COVID-19 pneumonia patients

To recognize the period of exaggerated cytokine response in patients with coronavirus disease 2019 (COVID-19) pneumonia, and to describe the clinical outcomes of using tocilizumab as a treatment option. The data of 12 adult COVID-19 pneumonia patients who were followed in the inpatient clinics of Biruni University Medical Faculty Hospital (Istanbul, Turkey) were retrospectively analyzed. Diagnostic tests, laboratory examinations, clinical findings, and computed tomography of the thorax imaging results were evaluated. A dramatic laboratory and clinical improvement was observed in 83% (10 out of 12) of patients after tocilizumab. In 17% (2 out of 12) of our patients, short-term ventilator support was required in the intensive care unit. The longest hospital stay was 18 days. However, in the end, all of our patients were discharged home with good health. Although arterial oxygen saturations (87.58 ± 3.12%) dropped in room air in the pre-tocilizumab period, post-tocilizumab they normalized in all patients (94.42 ± 1%). None of them had fever after tocilizumab treatment and the levels of C-reactive protein (13.08 ± 12.89) were almost within normal limits. Eosinophil values were quite low at the time of diagnosis (10 ± 17.06), but increased significantly post-tocilizumab (155.33 ± 192.69). There is currently no proven treatment for COVID-19 induced by novel coronavirus SARS-CoV-2. Based on our experience with twelve adult COVID-19 pneumonia patients, we can say that tocilizumab, an IL-6 inhibitor, is more beneficial in preventing the damage caused by excessive cytokine response in the body if administered at the right time and provides clinical and radiological recovery.     

Equilibrium and Kinetics Characteristics of Copper (II) Sorption onto Gyttja

The sorption characteristics of gyttja to remove copper (Cu²⁺) ions from aqueous solutions were satisfactorily described with the Freundlich, Langmuir and Dubinin–Redushckevich (D–R) models. The sorption capacity (q _max) of gyttja was 11.76 mg g⁻¹. The D–R model indicated that the sorption of Cu²⁺ by gyttja was almost taken place by chemisorption. Thermodynamic parameters such as change in free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) suggested that the adsorption process of Cu²⁺ by gyttja was feasible, spontaneous and endothermic in nature. Kinetic examination of the equilibrium data showed that the sorption processes of Cu²⁺ ions followed well pseudo-second-order kinetics model.     

Prevalence of Nocturnal Enuresis and Related Factors in Children Aged 5-13 in Istanbul

Objective

Enuresis is a health problem frequently encountered in childhood. This study was carried out in two socio-demographically different districts of the province of Istanbul, for the purpose of determining the relationship between the prevalence of primary nocturnal enuresis and certain demographic characteristics.

Methods

The study design is a cross-sectional carried out on 420 children (5 to 13 yr old) through random sampling. The research was conducted at two health centers in two different districts in the province of Istanbul. Data was collected with a questionnaire created by the researchers. Diagnosis of enuresis considered nocturnal voiding twice a week for at least three consecutive months.

Findings

Enuresis was a complaint expressed by 16.2% of the cases in the study group; 8.3% reported intermittent bedwetting. The data collected in the two districts pointed to a significant difference in terms of the frequency of enuresis in favor of the district where socio-demographic features were inferior (P<0.005). When family histories were explored in cases of children with enuresis, it was found that the mothers of 76.2% had the problem of enuresis while 14.9% had enuretic fathers. Thus statistically, the presence of enuresis in the family history was seen to have had a markedly significant impact on the occurrence of enuresis in the child (P<0.001).

Conclusion

It was concluded that familial predisposition to the condition constituted a more significant risk factor for enuresis compared to socio-demographic or economic characteristics.     

Enteral nutrition is feasible in pediatric stem cell transplantation patients

We aimed to demonstrate whether enteral nutrition (EN) is feasible in daily practice of hematopoietic stem cell transplantation (HSCT).Nutritional records of 100 patients were evaluated. Patients with poor oral intake were fed by EN with tube. A total of 79 patients required nutritional support. Of them, 71 were fed by EN only. Five were fed by EN plus parenteral nutrition (PN),three were fed by PN only. Median duration of EN was 21 days. In the EN only group, 68% gained or maintained their weight. EN should be considered as a feasible option for nutrition support in children undergoing HSCT. Pediatr Blood Cancer 2012; 59: 1327–1329. © 2012 Wiley Periodicals, Inc.     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

Physiological differences between neurons in layer 2 and layer 3 of primary visual cortex (V1) of alert macaque monkeys

The physiological literature does not distinguish between the superficial layers 2 and 3 of the primary visual cortex even though these two layers differ in their cytoarchitecture and anatomical connections. To distinguish layer 2 from layer 3, we have analysed the response characteristics of neurons recorded during microelectrode penetrations perpendicular to the cortical surface. Extracellular responses of single neurons to sweeping bars were recorded while macaque monkeys performed a fixation task. Data were analysed from penetrations where cells could be localized to specific depths in the cortex. Although the most superficial cells (depth, 145–371 μm; presumably layer 2) responded preferentially to particular stimulus orientations, they were less selective than cells encountered immediately beneath them (depth, 386–696 μm; presumably layer 3). Layer 2 cells had smaller spikes, higher levels of ongoing activity, larger receptive field activating regions, and less finely tuned selectivity for stimulus orientation and length than layer 3 cells. Direction selectivity was found only in layer 3. These data suggest that layer 3 is involved in generating and transmitting precise, localized information about image features, while the lesser selectivity of layer 2 cells may participate in top-down influences from higher cortical areas, as well as modulatory influences from subcortical brain regions.     

Tikhonov regularized solutions for improvement of signal-to-noise ratio in case of auditory-evoked potentials

In the present study, standard Tikhonov regularization (STR) Technique and the subspace regularization (SR) method have been applied to remove the additive EEG noise on average auditory-evoked potential (EP) signals. In methodological manner, the difference between these methods is the formation of regularization matrices which are used to solve the weighted problem of EP estimation. Those methods are compared to ensemble averaging (EA) with respect to signal-to-noise-ratio (SNR) improvement in experimental studies, simulations and pseudo-simulations. The results of tests no superiority of the SR in comparison to STR has been observed. In addition, the STR is found to be less computational complex. Moreover, results support the theoretical fact that the STR was introduced to be optimum for smooth solutions whereas the SR allows sharp variations in solutions. Thus, the STR is found to be more useful in removing the noise with the average signal remaining.     

Analysis of UV-stimulated recombination in the Drosophila SMART assay

The UV component of solar radiation is classified into UVA (320-400 nm), UVB (290-320 nm), and UVC (200-290 nm). Although all three types of UV light are capable of damaging biological systems, the earth's atmosphere filters out UVC, and a portion of UVB. In this study, we evaluated the induction of mutation and recombination by different wavelengths of UV light in the wing spot test of Drosophila melanogaster (Somatic Mutation and Recombination Test, SMART). Third-instar larvae that were trans-heterozygous for the third chromosome recessive markers, multiple wing hairs (mwh) and flare-3 (flr(3)), were exposed to different doses of UVA (at 365 nm), UVB (at 312 nm) or UVC (at 254 nm), and transferred to standard Drosophila culture medium. Feeding ended with pupation of the surviving larvae, and the genetic changes induced in the somatic cells of the wing's imaginal discs lead to the formation of mutant clones on the wing blade. Point mutation, chromosome breakage, and mitotic recombination produce single spots, while twin spots are produced only by mitotic recombination. Exposure to 500-4,000 J/cm(2) UVA did not increase the frequency of mutant spots. UVB doses of 200, 250, 300, 350, and 400 J/cm(2) increased the frequency of all categories of spots, indicating that UVB was potentially both mutagenic and recombinogenic. Assays run in balancer-heterozygous flies (which are insensitive to recombination) indicated that the fraction of mutants in trans-heterozygous flies due to recombination increased from 48.57% at 200 J/cm(2) UVB to 98.30% at 400 J/cm(2) UVB. While 140-480 J/cm(2) of UVC was not genotoxic, UVC produced a strong toxic response at doses higher than 140 J/cm(2). The results of this study indicate that UVB was much more active than UVC or UVA in the SMART assay, and that UVB was highly recombinogenic.