Management of congenital ichthyoses: European guidelines of care, part two.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.

Management of congenital ichthyoses: European guidelines of care, part one.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert-based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.

The role of drought on wheat yield interannual variability in the Iberian Peninsula from 1929 to 2012.

The production of wheat in the Iberian Peninsula is strongly affected by climate conditions being particularly vulnerable to interannual changes in precipitation and long-term trends of both rainfall and evapotranspiration. Recent trends in precipitation and temperature point to an increase in dryness in this territory, thus highlighting the need to understand the dependence of wheat yield on climate conditions. The present work aims at studying the relation between wheat yields and drought events in the Iberian Peninsula, using a multiscalar drought index, the standardized precipitation evapotranspiration index (SPEI), at various timescales. The effects of the occurrence of dry episodes on wheat yields were analyzed, on regional spatial scale for two subperiods (1929-1985 and 1986-2012). The results show that in western areas, wheat yield is positively affected by dryer conditions, whereas the opposite happens in eastern areas. The winter months have a bigger influence in the west while the east is more dependent on the spring and summer months. Moreover, in the period of 1986-2012, the simultaneous occurrence of low-yield anomalies and dry events reaches values close to 100 % over many provinces. Results suggest that May and June have a strong control on wheat yield, namely, for longer timescales (9 to 12 months). A shift in the dependence of wheat yields on climatic droughts is evidenced by the increase in the area with positive correlation and the decrease in area with negative correlation between wheat yields and SPEI, probably due to the increase of dry events.

Micro-CT evaluation of calcium hydroxide removal through passive ultrasonic irrigation associated with or without an additional instrument.

AIM: To use computerized microtomography (micro-CT) to evaluate the efficacy of passive ultrasonic irrigation (PUI), with or without an additional file (F5), in removing calcium hydroxide medication. METHODOLOGY: The root canals of single-rooted human teeth were prepared with a ProTaper(®) F4 file (Dentsply Maillefer) and filled with calcium hydroxide/propylene glycol 400 paste. After 30 days of storage under 100% humidity, the teeth were divided into four groups (n = 8) according to the removal technique: passive ultrasonic irrigation (PUI) only, additional file only (file F5), PUI + additional file and master apical file only (F4, control). The specimens were scanned (SkyScan 1174, resolution: 14.36 µm) after chemomechanical preparation, 30 days after the application of Ca(OH)2 paste and following its removal. The percentage of medicament remaining was calculated in terms of total canal volume and medicament volume after storage, based on microtomographic images. Data were analysed using three-way anova/Tukey's test or Kruskal-Wallis/Student-Newman-Keuls test (alpha: 5%). RESULTS: The use of PUI resulted in lower Ca(OH)2 residue volumes (3.7%) compared to when PUI was not used (6.4%; P < 0.001). The use of the additional file did not significantly influence the percentage of remaining Ca(OH)2 . The percentage of Ca(OH)2 residue was greater in the apical region (6.4%) than in the cervical region (3.8%; P < 0.01). CONCLUSIONS: The use of PUI resulted in more effective Ca(OH)2 paste removal relative to the control regardless of the use of the additional file. The apical region had the highest residue volumes in all techniques.

Water loss at normal enamel histological points during air drying at room temperature.

This in vitro study aimed to quantify water loss at histological points in ground sections of normal enamel during air drying at room temperature (25°C) and relative humidity of 50%. From each of 10 ground sections of erupted permanent human normal enamel, three histological points (n = 30) located at 100, 300 and 500 µm from enamel surface and along a transversal following prisms paths were characterized regarding the mineral, organic and water volumes. Water loss during air drying was from 0 to 48 h. Drying occurred with both falling and constant-drying rates, and drying stabilization times (Teq ) ranged from 0.5 to 11 h with a mean 0.26 (±0.12)% weight loss. In some samples (n = 5; 15 points), Teq increased as a function of the distance from the enamel surface, and drying occurred at an apparent diffusion rate of 3.47 × 10⁻8 cm² s⁻¹. Our data provide evidence of air drying resulting in air replacing enamel's loosely bound water in prisms sheaths following a unidirectional water diffusion rate of 3.47 × 10⁻8 cm² s⁻¹ (from the original enamel surface inward), not necessarily resulting in water evaporating directly into air, with important implications for transport processes and optical and mechanical properties.

Efficacy and safety of secukinumab for the treatment of severe ABCA12 deficiency-related ichthyosis in a child.

Background: Patients with severe autosomal recessive congenital ichthyosis (ARCI) show a T helper 17/interleukin 17 (Th17/IL17) skewing in their skin and serum, resembling the inflammatory profile of psoriatic patients. Secukinumab, an IL-17A inhibitor, has shown clinical efficacy in patients with moderate-to-severe plaque psoriasis. Aims: To test the clinical efficacy and safety of secukinumab in a paediatric patient with ATP-binding cassette subfamily A member 12 deficiency-related severe erythrodermic ARCI. Materials & Methods: 6-months therapeutic trial. During the first 4-weeks induction period, the patient received weekly subcutaneous injections of 150 mg secukinumab (five injections in total). During the following 20-weeks maintenance period, the patient was given a subcutaneous injection of 150 mg secukinumab every 4 weeks. Result & Discussion: After the 6-months therapy period, there was a 48% reduction from the baseline Ichthyosis-Area-Severity-Index (-Erythema/-Scaling) score. The treatment was well tolerated. Moreover, cytokine analysis revealed a reduction of keratinocyte-derived proinflammatory cytokines and an abrogation of Th17-skewing during therapy. Conclusion: Further studies are needed to evaluate the effects of the use of IL-17A inhibition in ARCI patients.

Benign growing mass of the digit presenting as an ulcerated mass - case report and review of the literature.

A 68 year-old female presents with an ulcerated mass of the 5th digit, with rapid growth during the previous month to surgery. The mass was excised and covered with a 4th dorsal metacarpal artery perforator flap. The histologic analysis was compatible with the diagnosis of fibro-osseous pseudotumor of the digit.

Twenty-first century droughts have not increasingly exacerbated fire season severity in the Brazilian Amazon.

Biomass burning in the Brazilian Amazon is modulated by climate factors, such as droughts, and by human factors, such as deforestation, and land management activities. The increase in forest fires during drought years has led to the hypothesis that fire activity decoupled from deforestation during the twenty-first century. However, assessment of the hypothesis relied on an incorrect active fire dataset, which led to an underestimation of the decreasing trend in fire activity and to an inflated rank for year 2015 in terms of active fire counts. The recent correction of that database warrants a reassessment of the relationships between deforestation and fire. Contrasting with earlier findings, we show that the exacerbating effect of drought on fire season severity did not increase from 2003 to 2015 and that the record-breaking dry conditions of 2015 had the least impact on fire season of all twenty-first century severe droughts. Overall, our results for the same period used in the study that originated the fire-deforestation decoupling hypothesis (2003-2015) show that decoupling was clearly weaker than initially proposed. Extension of the study period up to 2019, and novel analysis of trends in fire types and fire intensity strengthened this conclusion. Therefore, the role of deforestation as a driver of fire activity in the region should not be underestimated and must be taken into account when implementing measures to protect the Amazon forest.

Erythropoietin production by distal nephron in normal and familial amyloidotic adult human kidneys.

BACKGROUND/AIM: the kidney is the major site of erythropoietin production. Many efforts have been made to identify renal erythropoietin-producing cells. Previous studies showed conflicting results, but the predominant localization reported was the peritubular interstitial and tubular epithelial cells. This study was conducted to identify the erythropoietin-producing cells in renal biopsies from 10 cadaveric donors and 45 patients with familial amyloidosis ATTR V30M, thirteen of them with anemia. Familial amyloidosis Type I (FAP-I) is a genetic disorder caused by a transthyretin (TTR) protein variant presenting a single amino acid substitution of methionine for valine at position 30 of the polypeptide chain (TTR V30M). Anemia in FAP-I is associated with inappropriately low serum erythropoietin levels. METHODS: erythropoietin expression was detected by in situ hybridization (ISH) and confirmed by laser capture microdissection followed by PCR. Renal segments were identified by immunohistochemistry. RESULTS: erythropoietin was mainly expressed by epithelial distal tubular cells and collecting tubules and additionally, in a few biopsies, by glomerular cells. A similar expression pattern was observed in donors and FAP-I patients. No increased mRNA erythropoietin expression was found in anemic patients, all of them presenting only a slight expression in medulla and cortex. CONCLUSIONS: these results suggest the distal nephron as the major site of erythropoietin production, and support the notion that an inappropriate erythropoietin production is the cause of anemia in familial amyloidosis ATTR V30M.

Collaborative monitoring of chlorine flavours in drinking water.

Sensory data have always been used by concerned citizens to evaluate environmental variables within volunteer monitoring initiatives. The work presented in this paper intends to explore the possibility of using human sensory data as a source of information to monitor environmental quality variables within a public participation context. A case study that uses untrained citizens to monitor chlorine flavour of tap water is presented. Two collaborative monitoring tests were developed: (1) the one-sample one-trial test and (2) the Chlorine@Home test. The tests intended to address the participatory context required by collaborative monitoring initiatives. The development of the collaborative tests was supported by two tests that were designed for a laboratory context and explored sensory methodologies. The sensory tests implemented were: (1) the paired comparison test, (2) the forced-choice triangle test (ASTM Method E679-04). The collaborative experiments showed that the ability to detect chlorine flavours on a participatory context was independent on chlorine concentrations. The use of sensors by citizens may be a way to increase the credibility of the information. Nevertheless, this case study suggested that more research should be carried out to explore ways to involve citizens while increasing data reliability.

Effects of thyroid hormone administration and estrogen deficiency on bone mass of female rats.

To investigate the effects of thyroxine (T4) administration on bone mass, five 81-day-old female rats were treated with T4 (25 microg of T4/100 g of body weight [bw]/day), and bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) 28 days later. The BMD values for the total skeleton, femoral, and tibial subsegments were lower than in controls (p < or = 0.05). The lumbar spine (L2-L5) was not significantly affected by T4 treatment. Next, thirty-seven 211 +/- 1.5 (mean +/- SEM)-day-old female rats were divided into six groups as follows: (1) control; (2) ovariectomized (OVX); (3) 1xT4 (approximately 1.0 microg of T4/100 g of bw/day; approximately physiological replacement dose); (4) OVX + 1xT4; (5) 2xT4 (approximately 2.0 microg of T4/100 g of bw/day); (6) OVX + 2xT4. DXA scans were performed at days 0 and 85. Control rats showed a generalized BMD increase, as opposed to a decrease in OVX rats. The trabecular bone volume of the fifth lumbar vertebra was also lower in OVX rats than in controls (p < 0.05). The 1xT4 treatment had no effect on BMD of intact rats, while treatment with 2xT4 impaired the expected BMD increase. Unexpectedly, the OVX + 1xT4 group presented a generalized BMD increase that was significant for the total skeleton, L2-L5, and femoral subsegments (p < 0.05), comparable to controls. Treating OVX animals with 2xT4 did not potentiate the osteopenic effects of estrogen deficiency, nor did it reverse the osteopenic effects of OVX. In conclusion, treatment with high doses of T4 caused BMD to decrease substantially, particularly at the femur, whereas near physiological doses of T4 prevented bone loss associated with OVX, and regardless of bone type (trabecular or cortical), the skeleton site seems to be a more important determinant of the effects of thyroid hormone on bone mass.

Morphometric dual-energy X-ray absorptiometry of the spine: report of a large series and correlation with axial bone mineral density.

We studied vertebral morphometry and its relation to bone mineral density (BMD) in normal Brazilian women (n = 605). All women (age 22-97 years) were ambulatory and healthy. A lateral spine scan was done for morphometric X-ray absorptiometry using an imaging densitometer. In 429 of these women, BMD of the spine and proximal femur also were measured using dual-energy X-ray absorptiometry. All women were white with mean (+/- 1 SD) age of 53.7 (+/- 9.5) years. About 21% of the women over 50 years had a T score for spine BMD lower than -2.5 SD, and 7% had a femoral neck BMD below this osteoporosis threshold. Vertebral heights (anterior, HA; middle, HM; and posterior, HP) and ratios (HA/HP and HM/HP) were assessed. There was no systematic difference between younger (20-49 years) and older (50+ years) women in heights or ratios. The vertebral heights were normalized for those observed in each individual case for the L2-L4 sequence. This normalization was adequate for all vertebral heights; the Z score averaged about +0.1. The average Z score for HA/HP was +0.01, but that for the HM/HP was -0.72, indicating that the latter ratio might differ from the reference population used (white American and European women). We observed a small positive correlation between vertebral heights and spine or femur BMD, but this was due entirely to the influence of body size on BMD. On a group basis, the HM/HP showed a significant association with axial BMD; the 1 SD difference between the lowest and highest quartile was associated with a difference of 8-15% (0.5-1.0 SD) in axial BMD.

Thyroid hormone stimulation of osteocalcin gene expression in ROS 17/2.8 cells is mediated by transcriptional and post-transcriptional mechanisms.

We investigated the mechanism of thyroid hormone regulation of osteocalcin (OC) gene expression in osteoblast-like cells (ROS 17/2.8). Treatment with tri-iodothyronine (T3) (10(-8) M) increased OC mRNA levels by approximately 3-fold after 24 h and reached a maximum, approximately 5.4-fold, after 48 h. The mRNA levels of other bone-specific genes, alkaline phosphatase and osteopontin, were not affected by T3 treatment. Interestingly, T3 induction of OC mRNA varied according to cell density: approximately 4-fold at approximately 1x10(5) cells/dish and 1.5-fold at 40-60x10(5) cells/dish. The magnitude of OC mRNA induction by T3 was approximately 40% lower than induction by 1,25 dihydroxyvitamin D3 (1,25D3) alone, and the combination of T3+1,25D3 did not further stimulate OC mRNA levels. T3 induction of OC mRNA was not affected by treatment with cycloheximide (10 microg/ml) for 5 h indicating that new protein synthesis is not required for the response. To study the half-life of OC mRNA, ROS 17/2.8 cells were incubated with actinomycin D. The basal half-life of OC mRNA (means+/-s.e.m.) was 6.4+/-0.2 h which was increased significantly with either T3 or 1,25D3 treatment to 10.9+/-0.6 h and 13.5+/-0.4 h respectively. T3 modestly up-regulated the rate of OC gene transcription (1.7+/-0.2-fold) as determined by run-off assay. T3 did not induce a reporter construct containing the rat OC gene (rOC) 5'-flanking region (to -1750 bp) or the previously described rOC vitamin D response element, when transfected into ROS 17/2.8 cells. In conclusion, T3 up-regulates the OC mRNA expression in ROS 17/2.8 cells in a dose-, time- and cell confluence-dependent fashion, and does so by transcriptional and post-transcriptional mechanisms. The greater T3 induction of OC expression in ROS 17/2.8 cells at low cell density is consistent with findings of thyroid hormone action on bone development.

Deleteriuos effects of immobilization upon rat skeletal muscle: role of creatine supplementation.

AIM: The aim of the study was to investigate the impact of creatine feeding (5 g kg(-1) body weight day(-1)) upon the deleterious adaptations in skeletal muscle induced by immobilization. METHODS: Male Wistar rats were submitted to hind limb immobilization together with three dietary manipulations: control, supplemented with creatine for 7 days (along with immobilization) and supplemented with creatine for 14 days (7 days before immobilization and together with immobilization). Muscle weight (wet/dry) was determined in the soleus (SOL) and gastrocnemius (GAS). The analysis of lean mass was performed by DEXA and myosin heavy chain (MHC) distribution by SDS-PAGE. RESULTS: After 14 days of creatine loading, immobilized SOL and GAS total creatine content were increased by 25% and 18%, respectively. Regardless of dietary manipulation, the immobilization protocol induced a decrease in the weight of SOL and GAS (P < 0.001). However, creatine feeding for 14 days minimized mass loss in the SOL and GAS (P < 0.05). Our findings also indicate that creatine supplementation maximizes the expected slow-to-fast MHC shift driven by immobilization (P < 0.05). CONCLUSIONS: Previous creatine supplementation attenuates muscle wasting induced by immobilization. This effect is associated with the increment of intramuscular creatine content.

Influence of body composition on the bone mass of postmenopausal women.

AIMS: To investigate the influence of body weight (BW), fat mass (FM) and lean mass (LM) on the bone mineral density (BMD) of several areas of the skeleton. PARTICIPANTS: Sixty one white postmenopausal women (50.1 +/- 4.8 years). MEASUREMENTS: Measurement of BMD by dual energy x-ray absorptiometry. The results were analyzed by linear regression and the slopes of each curve were compared. RESULTS: The results showed that the correlations between BW, FM and LM to BMD were positive, whilst the correlations between age and years since menopause to BMD were negative. LM was the main factor that influence BMD in almost all areas. CONCLUSIONS: FM and LM present a positive effect on BMD, although LM is the main determinant of bone mass. Moreover, higher values of LM and FM present a protective effect against the reduction of BMD combined with menopause. Therefore postmenopausal women with low BW, especially low LM, present serious risk for developing osteoporosis.

[Vertebral and femoral bone mineral density of 724 caucasian Brazilian women: influence of age and body weight]. / Densidade mineral óssea vertebral e femoral de 724 mulheres brancas brasileiras: influência da idade e do peso corporal.

OBJECTIVE: To study the vertebral (L2-L4) and femoral (neck) bone mineral density (BMD) of normal white women. MATERIAL AND METHOD: We measured the BMD of 724 women (40-79 kg; 20-69 years-age) by dual-energy X-ray absorptiometry. Data were analysed as a function of age and body weight (BW). RESULTS: Thinner women (40-49 kg) attained maximal vertebral and femoral BMD (mBMD) at ages between 30-39 years, while heavier women (60-79 kg) already had the mBMD by the age of 20. At the femur, there was a significant mBMD-BW correlation (r = 0.97; p < 0.001; slope = 0.72%/kg). At the spine, only the 40-49 Kg women exhibited lower mBMD when compared to the others (p < 0.001). The decrease of the vertebral BMD was more intense (-8.3 vs. -5.7%/decade) and started earlier (fourth vs. fifth decade) in women weighting 40-59 kg, as compared to those weighting 60-79 kg. The decrease of the femoral BMD was initiated just after mBMD was achieved and, at the age of 69, heavier women showed a decrease that was 5.3% lower than those weighting 40-49 kg. The vertebral BMD of the Brazilian women was practically the same as reported for a North-American population. CONCLUSIONS: (i) Vertebral and femoral BMD of this Brazilian population varied with age similarly to other white female populations; (ii) provided that appropriate corrections are made for BW, the BMD of Brazilian women is comparable to the BMD of North-Americans; and (iii) the BW is important both in acquisition and decline of bone mass, as it influences the relation BMD-age.

Evanescent wave DNA-aptamer biosensor based on long period gratings for the specific recognition of E. coli outer membrane proteins.

An evanescent wave fiber optic sensor for detection of Escherichia coli (E. coli) outer membranes proteins (EcOMPs) using long period gratings (LPGs) as a refractometric platform is presented. The sensing probes were attained by the functionalization of LPGs inscribed in single mode fiber using two different methods of immobilization; electrostatic assembly and covalent binding. The resulting label-free configuration enabled the specific recognition of EcOMPs in water by monitoring the resonance wavelength shift due to refractive index changes induced by binding events. The sensors displayed linear responses in the range of 0.1 nM to 10 nM EcOMPs with sensitivities of -0.1563±0.005 nm decade(-1) [EcOMP, M] (electrostatic method) and -0.1597±0.004 nm decade(-1) [EcOMP, M] (covalent method). The devices could be regenerated (under low pH conditions) with a deviation less than 0.1% for at least three subsequent detection events. The sensors were also applied to spiked environmental water samples.