SARS-CoV-2 infection in Spanish children with chronic kidney pathologies.

BACKGROUND: There is little information about Coronavirus Disease 2019 (COVID-19) in children with underlying chronic renal pathologies. CASES REPORT: From March until April 15, 2020, 16 children with chronic renal pathologies were diagnosed with COVID-19 in Spain. Of these, 6 had end-stage kidney disease (ESKD) (3 transplant recipients and 3 on chronic hemodialysis). The severity of symptoms was mild in all the patients, with little radiological involvement. Three patients were asymptomatic. Fever and upper respiratory symptoms were the most frequent findings. Basal glomerular filtration worsened in 3 patients; however, recovery was rapidly achieved with rehydration and drug dose adjustment. In 2 patients diagnosed with steroid-dependent nephrotic syndrome, COVID-19 provoked a disease relapse. None required oxygen therapy, and 7 could be managed as outpatients. CONCLUSIONS: COVID-19 disease appears to have a similar clinical course in children with underlying chronic renal pathologies, even in immunosuppressed cases, as in healthy children of the same age; however, special attention must be paid to fluid management and drug dose adjustment.

Colour differences in Caucasian and Oriental women's faces illuminated by white light-emitting diode sources.

OBJECTIVE: To provide an approach to facial contrast, analysing CIELAB colour differences (ΔEab,10∗) and its components in women's faces from two different ethnic groups, illuminated by modern white light-emitting diodes (LEDs) or traditional illuminants recommended by the International Commission on Illumination (CIE). METHODS: We performed spectrophotometric measurements of spectral reflectance factors on forehead and cheek of 87 young healthy women (50 Caucasians and 37 Orientals), plus five commercial red lipsticks. We considered a set of 10 white LED illuminants, representative of technologies currently available on the market, plus eight main illuminants currently recommended by the CIE, representative of conventional incandescent, daylight and fluorescent light sources. Under each of these 18 illuminants, we analysed the magnitude and components of ΔEab,10∗ between Caucasian and Oriental women (considering cheek and forehead), as well as for cheek-forehead and cheek-lipsticks in Caucasian and Oriental women. Colour-inconstancy indices for cheek, forehead and lipsticks were computed, assuming D65 and A as reference illuminants. RESULTS: ΔEab,10∗ between forehead and cheek were quantitatively and qualitatively different in Orientals and Caucasians, but discrepancies with respect to average values for 18 illuminants were small (1.5% and 5.0% for Orientals and Caucasians, respectively). ΔEab,10∗ between Caucasians and Orientals were also quantitatively and qualitatively different both for forehead and cheek, and discrepancies with respect to average values were again small (1.0% and 3.9% for forehead and cheek, respectively). ΔEab,10∗ between lipsticks and cheek were at least two times higher than those between forehead and cheek. Regarding ΔEab,10∗ between lipsticks and cheeks, discrepancies with respect to average values were in the range 1.5-12.3%, although higher values of up to 54.2% were found for a white RGB LED. This white RGB LED provided the highest average colour-inconstancy indices: 17.1 and 11.5 CIELAB units, under reference illuminants D65 and A, respectively. CONCLUSION: Colour contrasts in women's faces under CIE standard illuminants for outdoor and indoor conditions may be strongly altered using specific white LEDs. More research needs to be performed on the impact of spectral power distribution of light sources with high colour rendering indices on visual colour appearance of cosmetic products.

DRESS-syndrome on sulfasalazine and naproxen treatment for juvenile idiopathic arthritis and reactivation of human herpevirus 6 in an 11-year-old Caucasian boy.

DRESS-syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is a severe drug-induced hypersensitivity syndrome characterized by diffuse maculopapular rash, lymphadenopathy, multivisceral involvement, eosinophilia and atypical lymphocytes with a mortality rate of 10-40% (Seminars in Cutaneous Medicine and Surgery, 1, 250). It is described in adults treated with aromatic antiepileptics and less frequently with sulphonamides, and non-steroidal anti-inflammatory drugs (Clinics in Dermatology, 23, 171; Pediatrics, 108, 485). We report on an 11-year-old Caucasian boy hospitalized with a skin eruption, lymphadenopathy, acute hepatitis, renal tubular involvement, haematological abnormalities and human-herpevirus-6 reactivation, treated with sulfasalazine and naproxen for juvenile idiopathic arthritis (JIA). This is the first report in children with rheumatic disease and highlights the possibility of sulfasalazine and naproxen-induced-DRESS-syndrome in children with JIA.

Colourimetric characterisation of disposable optical sensors from spectroradiometric measurements.

Spectroradiometric measurements of reflectance and CIELAB hue-angle, were tested for K(I) determination using disposable optical sensors based on ion exchange mechanism. The linearisation of the sigmoidal response function, using a logistic regression, increases the linear range noticeably to 7.65 x 10(-8)-1.5 M and 1.22 x 10(-7)-1.5 M for CIELAB hue-angle and reflectance, respectively. The trueness of both procedures was demonstrated comparing it with results obtained by a DAD spectrophotometer used as a reference measurement procedure. The usefulness of the procedure was checked by analysing K(I) in different types of waters and beverages. Additionally, we studied the possible visual discrimination for the whole potassium range tested, obtaining the possibility of discriminating twelve groups of concentrations.

Retroviral vectors: new applications for an old tool.

Retroviral vectors (RVs) have been used for stable gene transfer into mammalian cells for more than 20 years. The most popular RVs are those derived from the Moloney murine leukaemia virus (MoMLV). One of their main limitations is their inability to transduce noncycling cells. However, they have a relatively simple genome and structure, are easy to use, and are relatively safe for in vivo applications. For the last two decades, the artificial evolution of RVs has paralleled evolution in their applications, which now include those as diverse as the generation of transgenic animals, the stable delivery of small interfering RNA (siRNA) and gene therapy clinical trials. Recent reports of two successful gene therapy clinical trials in patients with severe immunodeficiency disease in France and Italy, and the development of T-cell acute leukaemia in two of 10 children participating in one of these clinical trials, demonstrate the great potential of RVs, but also some potential risks which may be intrinsically associated with their use. Basic aspects of RVs and vector production were reviewed in detail in a previous supplement of this journal. This article will first summarize some general aspects of retroviruses and RVs. Thereafter, recent developments in gene therapy using RVs, novel applications such as stable RNA interference and some other recent issues related to retroviral integration, including clonality studies after haematopoietic stem cell transplantation, retroviral tagging and insertional oncogenesis will be discussed.

A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival.

The role of DNA methylation and of the maintenance DNA methyltransferase Dnmt1 in the epigenetic regulation of developmental stage- and cell lineage-specific gene expression in vivo is uncertain. This is addressed here through the generation of mice in which Dnmt1 was inactivated by Cre/loxP-mediated deletion at sequential stages of T cell development. Deletion of Dnmt1 in early double-negative thymocytes led to impaired survival of TCRalphabeta(+) cells and the generation of atypical CD8(+)TCRgammadelta(+) cells. Deletion of Dnmt1 in double-positive thymocytes impaired activation-induced proliferation but differentially enhanced cytokine mRNA expression by naive peripheral T cells. We conclude that Dnmt1 and DNA methylation are required for the proper expression of certain genes that define fate and determine function in T cells.

Carrier-mediated enhancement of cognate T cell help: the basis for enhanced immunogenicity of meningococcal outer membrane protein polysaccharide conjugate vaccine.

Haemophilus influenzae type b capsular polysaccharide (PRP) conjugate vaccines, which are thought to induce T cell-dependent antibody production, induce protective responses after a single dose in individuals under 15 months of age. However, multiple doses of these vaccines are required to induce protective antibody responses in infants, with the exception of PRP conjugated to meningococcal outer membrane proteins (OMPC), which does so after a single dose. The basis for this difference is not fully understood, although others have proposed that OMPC and porins, the major protein component of OMPC, act as adjuvants or mitogens. In this report OMPC is shown to enhance CD40 ligand-mediated, T cell-dependent antibody production in mice. This paralleled the induction by OMPC of CD86, CD80 and CD40 costimulatory molecules on human neonatal and murine B cells and of Th1 cytokines. Neither porins nor lipopolysaccharide fully reproduced the effects of OMPC. These studies indicate that OMPC acts both as carrier and adjuvant, and thereby enhances T cell-dependent antibody responses in human infants.

Membranous nephropathy associated with hepatitis B in Spanish children.

AIM: To examine retrospectively long-term evolution and treatment of pediatric membranous nephropathy (MN) cases associated with hepatitis B (HB) in the hospital "La Paz". MATERIAL AND METHODS: The clinical records of 12 children diagnosed with HB-associated MN in our hospital between 1970 and 1996. RESULTS: All patients were positive for hepatitis B surface antigen (HBsAg); 6 were tested for hepatitis Be antigen (HBeAg) and were also positive. At onset, all of them had proteinuria (8 in nephrotic range), 6 had microscopic hematuria and 4 macroscopic hematuria. Seven of 8 children who started with a nephrotic syndrome received steroids and all of them were steroid-resistant. After 9.95 +/- 5.88 years of follow-up, renal function remained normal and proteinuria and hematuria have disappeared in all of them. A family study for hepatitis B was carried out in 8 cases and 7 of them were positive. Only in one case vertical transmission was demonstrated; this patient remained HBeAg positive. In 7 patients, hepatic biopsy was performed: 3 had a chronic active hepatitis, 3 a persistent chronic hepatitis and one a residual acute hepatitis. CONCLUSIONS: Membranous nephropathy is a rare pediatric disease in our area and most of the cases are related to hepatitis B (HB). The outcome was excellent with and without treatment but all of them remained HBsAg positive.

Towards a colorimetric characterization of the human iris.

We propose a new approach to the quantitative determination of the iris colour through the spectroradiometric measurement of a set of 72 artificial irises under controlled illumination and geometry. The spread of these samples in the CIELAB colour space indicates no clearly distinguished groups within the set analysed. Colour measurements for different points of these irises and for the overall irises (pupil and specular image of the light source included) are well correlated. Complementary colour measurements were also performed for the irises of 25 ocular prostheses and 40 real observers. All these colour measurements appear to be quite consistent, the average standard deviation of any of the three a*, b*, L* co-ordinates being lower than 1.0 units. In a visual experiment where 11 normal observers matched the 25 ocular prostheses using the 72 artificial irises, the results indicate that a simple criterion based on the lowest colour-difference agreed with the observers' judgements in only 18% of the cases. This result suggests that, although colour appears to be a major parameter in the overall characterization of the human iris, additional factors such as patterns or textures should also be considered.

Usefulness of cathode ray tube color displays in chromaticity-discrimination experiments.

Chromatic-discrimination thresholds have been determined by use of a CRT color monitor that simulates aperture and object observation modes. The results were compared with earlier ones [Appl. Opt. 35, 176 (1996)] that were obtained under the same experimental observation conditions with different devices. The differences found between the results obtained with the CRT monitor and with visual colorimeters are of the order of magnitude of interobserver variability (9%). However, greater differences were found between results for CRT monitors and for illuminated samples, which could be attributed to suboptimal distribution of the samples in color space. The current results support the usefulness of CRT color monitors in new chromatic-discrimination experiments.

Cutting edge: CD40 ligand is a limiting factor in the humoral response to T cell-dependent antigens.

CD40 ligand (CD40L) plays a crucial role in T cell-dependent B cell responses, but whether its abundance is a limiting factor in their development is unclear. This question was addressed in transgenic mice expressing the murine CD40L gene under the control of the IL-2-promoter (CD40Ltg+). The fraction of activated T cells from the CD40Ltg+ mice with detectable levels of surface CD40L was modestly greater (1.1- to 2-fold) than littermate controls and paralleled an approximately 1.8-fold increase in CD40L mRNA abundance. In response to trinitrophenol (TNP)-keyhole limpet hemocyanin and tetanus/diphtheria vaccine, CD40Ltg+ mice developed higher titers of high-affinity IgG and IgG1 Ab than wild-type mice. In contrast, the Ab response of CD40Ltg+ and control mice was similar in response to the T-independent Ag TNP-Ficoll. These results suggest that a modest increment in expression of CD40L accelerates the development of T-dependent responses, and that CD40L plays a limiting role in the induction of high-affinity Ab and Ab-class switching.

Dopamine beta-hydroxylase deficiency impairs cellular immunity.

Norepinephrine, released from sympathetic neurons, and epinephrine, released from the adrenal medulla, participate in a number of physiological processes including those that facilitate adaptation to stressful conditions. The thymus, spleen, and lymph nodes are richly innervated by the sympathetic nervous system, and catecholamines are thought to modulate the immune response. However, the importance of this modulatory role in vivo remains uncertain. We addressed this question genetically by using mice that lack dopamine beta-hydroxylase (dbh-/- mice). dbh-/- mice cannot produce norepinephrine or epinephrine, but produce dopamine instead. When housed in specific pathogen-free conditions, dbh-/- mice had normal numbers of blood leukocytes, and normal T and B cell development and in vitro function. However, when challenged in vivo by infection with the intracellular pathogens Listeria monocytogenes or Mycobacterium tuberculosis, dbh-/- mice were more susceptible to infection, exhibited extreme thymic involution, and had impaired T cell function, including Th1 cytokine production. When immunized with trinitrophenyl-keyhole limpet hemocyanin, dbh-/- mice produced less Th1 cytokine-dependent-IgG2a antitrinitrophenyl antibody. These results indicate that physiological catecholamine production is not required for normal development of the immune system, but plays an important role in the modulation of T cell-mediated immunity to infection and immunization.

Absorbable screws through the greater trochanter do not disturb physeal growth: rabbit experiments.

We studied the effect of implantation of self-reinforced polyglycolic acid (SR-PGA) screws through the greater trochanter in rabbits. 15 rabbits aged 10 weeks had an SR-PGA screw inserted through the left trochanter physis. A similar drilling was made through the right greater trochanter without screw implantation. The animals were assigned to 3 groups of 5, and were killed after 1, 2 or 3 months. Radiographs of both femurs were obtained monthly and the articulo-trochanteric distance and the neck-shaft angle were measured. After killing the animals, a histological study was performed. The drilling on the right trochanter generated a bony bridge in all the animals. The SR-PGA screws did not give rise to an epiphysiodesis. The progressive peripheral degradation of the implants gave rise to the formation of only modest bridges, which were smaller in size than those observed in the control trochanter. Our findings suggest that absorbable PGA screws implanted through a growth plate cause only minor bone formation and no epiphyseodesis.

Soft tissue behavior during limb lengthening: an experimental study in lambs.

The effect of femoral elongation on skeletal muscle, nerves, and vessels was studied. Three groups of five lambs were used. After the intervention, the animals were killed at 2, 3, and 4 months. A left femoral elongation of 6 cm was practiced on all of them by means of callotasis, with a distraction rate of 0.5 mm every 12 hours. The femoral elongation process was evaluated by monthly x-ray films. The nucleic acid and protein levels in the muscular tissue were quantified at the level of the elongation focus and in the control extremity. The motor conduction velocity of the sciatic nerve was measured in both posterior limbs before the intervention and immediately before the lambs were killed. The arterial blood flow of both subsequent extremities was measured at the moment of death. A histological study of quadriceps muscle, sciatic nerves, artery, and subsequent femoral vein were examined histologically at the level of the elongation focus of both extremities. After elongation, no significant differences were observed in the muscle protein and nucleic acid levels with respect to the control extremity. No significant changes of the nerve conduction velocity were observed in any animal among the different groups. The arterial blood flow of the elongated extremity showed a progressive increase, reaching its maximum value 1 month after the distraction had terminated, with subsequent normalization. This increase of the blood flow was also observed in the control extremity, suggesting a possible systemic effect. The histological study revealed a comparative thickening of the endomysium and perimysium in the elongated muscle tissue, present at the end of the distraction and which was later normalized. No histological changes of the nerve stems undergoing distraction were observed either. During elongation, the arteries showed minimal histological changes. On the other hand, the veins showed areas of endothelial damage accompanied by thrombosis phenomena, especially at the end of the distraction period. The vascular morphology presented progressive normalization after the distraction phase.

Performance of a color indicator in a disinfecting solution for the maintenance of soft contact lenses.

An experimental study of Allergan's Oxysept Comfort system was performed by measuring the slight reddish hue that appears in the disinfecting solution, indicating to the users that their lenses are again ready to be worn. The temporal evolution of the color of the solution has been measured under standardized conditions and analyzed in the CIELAB system, from the perspective of the typical threshold discrimination of the human eye. Color differences between neutralized and non-neutralized solutions occurred in an appropriate direction of the color space to enhance discrimination and were clearly perceptible by normal observers (greater than 9.7 +/- 1.2 CIELAB units). Colorimetric analyses have been used to draw conclusions regarding observers with defective color vision. The color of the solution changes abruptly, approximately 25 min after the neutralization process begins, and remains nearly constant after about 60 min, this agreeing well with the temporal evolution of the hydrogen peroxide concentration.

Chromaticity-discrimination thresholds with aperture and object colors: experimental results and predictions of some recent color-difference formulas.

Threshold-discrimination ellipses were obtained by three normal observers, at five color centers, by the use of two experimental devices, which provided light-surface colors, and the same method and experimental conditions. The ellipses obtained for each center in both devices were quite similar when the sample distributions were appropriate and slightly smaller for object color than for aperture color. The ellipses predicted by three recent color-difference formulas based on the CIE uniform color space (CIELAB) were compared with those experimentally obtained by us as well as by other researchers who analyzed a greater number of color centers. The color-difference formula proposed by the CIE Technical Committee 1-29 [Color Res. Appl. 18, 137 (1993)] provides the best prediction of the semiaxis relationship for all the experimental datasets used, confirming their good performance in previous works [Appl. Opt. 33, 8069 (1993)], although the differences with respect to the experimental results are higher than those attributable to the interobserver variability.

Isolation and characterization of a gene encoding a Chlamydia pneumoniae 76-kilodalton protein containing a species-specific epitope.

Chlamydia pneumoniae is a human respiratory pathogen. Unlike the other two Chlamydia species, no species-specific antigen has been defined for C. pneumoniae. An immunoreactive clone containing a 0.8-kb fragment was isolated from a C. pneumoniae (AR-39) genomic library by using anti-C. pneumoniae rabbit immune serum. By Southern hybridization analysis of chromosomal digests of the different Chlamydia spp., the 0.8-kb fragment was shown to react specifically with C. pneumoniae. Subcloning of this fragment into the pGEX-1 lambda T expression vector resulted in the expression of a 62-kDa fusion protein. This fusion protein as well as the cleaved C. pneumoniae peptide were recognized by anti-C. pneumoniae rabbit immune serum, while the glutathione S-transferase moiety was not recognized. The fusion protein was used to produce monospecific rabbit antiserum. This antiserum was shown to react with a 76-kDa protein in all C. pneumoniae isolates tested, specifically recognize C. pneumoniae inclusions in tissue culture, and neutralize infectivity of C. pneumoniae in cell culture. No reactivity was observed with Chlamydia trachomatis or Chlamydia psittaci. To isolate the entire coding sequence of the 76-kDa protein, two partially overlapping fragments of C. pneumoniae DNA, a 3.2-kb HindIII fragment and a 1.2-kb PvuII fragment, were isolated, cloned, and sequenced. No significant sequence similarity was found with any previously reported nucleotide or amino acid sequence of the other Chlamydia species. This C. pneumoniae protein containing a species-specific epitope could play a role in pathogenesis and may be useful as a diagnostic tool.

Uniformity of some recent color metrics tested with an accurate color-difference tolerance dataset.

The Rochester Institute of Technology-Dupont dataset [Color Res. Appl. 16, 297-316 (1991)] has been used to analyze the uniformity of seven color metrics, developed after CIELUV and CIELAB, with methods similar to those previously applied to several other classical datasets [J. Opt. Soc. Am. A 9, 1247-1253 (1992)]. Significant performance improvements over CIELAB were found with several CIELAB-based metrics, mainly with the model recently proposed by Commission Internationale de L'Eclairage Technical Committee 1-29 [Color Res. Appl. 18, 137-139 (1993)]. Several significant differences found between some pairs of metrics became insignificant when we selected from the Rochester Institute of Technology-Dupont dataset pairs of samples with only chromaticity differences.