Search

This study aims to integrate an open-source software capable of estimating hydrodynamic forces solely from kinematic data with a full-body biomechanical model of the human body to enable inverse dynamic analyses of swimmers. To demonstrate the methodology, intersegmental forces and joint torques of the lower limbs were computed for a six-beat front crawl swimming motion, acquired at LABIOMEP-UP. The hydrodynamic forces obtained compare well with existing numerical literature. The intersegmental forces and joint torques obtained increase from distal to proximal joints. Overall, the results are consistent with the limited literature on swimming biomechanics, which provides confidence in the presented methodology.

Soil moisture is a key factor for mercury (Hg) emission from soil. Despite its significance for Hg emissions, the effect of soil moisture on Hg flux and fractions has not been thoroughly investigated. The objective of this study was to elucidate the influences of soil moisture and temperature on Hg fluxes from soils and Hg fractions. A kinetic study was performed to measure Hg emission fluxes of six soil samples under different temperature (T) (15 °C, 20 °C, 25 °C, 30 °C, and 35 °C) and moisture conditions (0%, 10%, and 20% added water). The results showed that the Hg fluxes increased with increases in T and soil moisture. A linear correlation was found between ln (Hg emission flux) and 1/T for the six soil samples at different moisture contents (R

Vancomycin is associated with nephrotoxicity; however, the influence of the number of combined nephrotoxic agents on the incidence of vancomycin nephrotoxicity has not been clarified. We investigated patient backgrounds in 148 inpatients who received vancomycin treatment. The patients were divided into nephrotoxicity (n=35) and non-nephrotoxicity (n=113) groups. A comparison of the patient backgrounds in the two groups revealed significant differences in weight, changes in serum creatinine before vancomycin administration, blood urea nitrogen to serum creatinine ratio, length of vancomycin therapy, vancomycin trough concentration, and number of combined nephrotoxic agents. Multiple logistic regression analysis using these six factors as autonomous variables showed that the highest vancomycin trough concentration (odds ratio, 1.080; 95% confidence interval, 1.030-1.140; p = 0.003) and the number of combined nephrotoxic agents (odds ratio, 1.590; 95% confidence interval, 1.120-2.260; p = 0.010) were significantly related to nephrotoxicity.

Background Liver stiffness is reported to be associated with right atrial pressure and worse prognosis of heart failure. Fibrosis-4 (FIB4) index (age (years) × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)) is known as a useful and simple marker for evaluating liver stiffness. However, the association between FIB4 index and prognosis in heart failure with preserved ejection fraction (HFpEF) was not elucidated. Purpose This study aimed to clarity the association between FIB4 index and right ventricular (RV) function and major adverse cardiac events (MACE) of HFpEF. Method From February 2012 to December 2015, 132 subjects diagnosed as HFpEF after hospitalization of acute decompensation were enrolled (79 years, 59 male). Subjects performed thoracic surgery or percutaneous coronary intervention within half a year and died before discharge were excluded. All subjects were measured FIB4 index and tricuspid annular plane systolic excursion (TAPSE) to assess RV function before discharge. In addition, patients were classified into two groups: high-(≥3.01, n=52) and low-FIB4 index groups ( Results Patient with high-FIB4 index were older and higher level of blood pressure. There was no difference in prevalence rates of history of liver disease. In multivariate Linear regression analysis, FIB4 index was significantly association with TAPSE independently confounding factors. Kaplan-Meier analysis showed that patients with high-FIB4 index experienced more CV events during the 1734 days of follow-up (42.3% vs 26.2%, p=0.028) (figure). Kaplan-Meier curve freedom from MACE Conclusions FIB4 index is associated with RV dysfunction and a high risk of future CV event of HFpEF.

Dental stem cells are potential cells for use in tissue engineering, including dental tissue, nerve, and bone regeneration. Multifactorial potential including high proliferation rate, multidifferentiation ability, easy accessibility, high viability, and ease to be induced to distinct cell lineages, make the dental stem cells an attractive cell source. Several types of dental stem cells are described: dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, dental follicle progenitor cells, and periodontal ligament stem cells. An overview and biological properties of these cell populations are provided in this article.

Long-term outcomes of allogeneic hematopoietic cell transplantation with intensified myeloablative conditioning for refractory myeloid malignancy

BACKGROUND Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear. AIMS To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR). METHODS A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24). RESULTS Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70-4.18) kPa and 2.80 (2.40-3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7-3.4)% and 1.9 (1.3-2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF

The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that is associated with epileptogenesis. In mice, Szt2 is abundantly expressed in the central nervous system. Recently, biallelic SZT2 mutations were found in 7 patients (from 5 families) presenting with epileptic encephalopathy with dysmorphic features and/or non-syndromic intellectual disabilities. In this study, we identified by whole-exome sequencing compound heterozygous SZT2 mutations in 3 patients with early-onset epileptic encephalopathies. Six novel SZT2 mutations were found, including 3 truncating, 1 splice site and 2 missense mutations. The splice-site mutation resulted in skipping of exon 20 and was associated with a premature stop codon. All individuals presented with seizures, severe developmental delay and intellectual disabilities with high variability. Brain MRIs revealed a characteristic thick and short corpus callosum or a persistent cavum septum pellucidum in each of the 2 cases. Interestingly, in the third case, born to consanguineous parents, had unexpected compound heterozygous missense mutations. She showed microcephaly despite the other case and previous ones presenting with macrocephaly, suggesting that SZT2 mutations might affect head size.

BCL11A encodes a zinc finger protein that is highly expressed in hematopoietic tissues and the brain, and that is known to function as a transcriptional repressor of fetal hemoglobin (HbF). Recently, de novo variants in BCL11A have been reported in individuals with intellectual disability syndrome without epilepsy. In this study, we performed whole-exome sequencing of 302 patients with epileptic encephalopathies (EEs), and identified 2 novel BCL11A variants, c.577delC (p.His193Metfs*3) and c.2351AC (p.Lys784Thr). Both the patients shared major physical features characteristic of BCL11A-related intellectual disability syndrome, suggesting that characteristic physical features and the persistence of HbF should lead clinicians to suspect EEs caused by BCL11A pathogenic variants. Patient 1, with a frameshift variant, presented with Lennox-Gastaut syndrome, which expands the phenotypic spectrum of BCL11A haploinsufficiency. Patient 2, with a p.Lys784Thr variant, presented with West syndrome followed by drug-resistant focal seizures and more severe developmental disability. These 2 newly described patients contribute to delineating the associated, yet uncertain phenotypic characteristics of BCL11A disease-causing variants.

Coffin-Siris syndrome (CSS) is a congenital disorder characterized by intellectual disability, growth deficiency, microcephaly, coarse facial features, and hypoplastic or absent fifth fingernails and/or toenails. We previously reported that five genes are mutated in CSS, all of which encode subunits of the switch/sucrose non-fermenting (SWI/SNF) ATP-dependent chromatin-remodeling complex: SMARCB1, SMARCA4, SMARCE1, ARID1A, and ARID1B. In this study, we examined 49 newly recruited CSS-suspected patients, and re-examined three patients who did not show any mutations (using high-resolution melting analysis) in the previous study, by whole-exome sequencing or targeted resequencing. We found that SMARCB1, SMARCA4, or ARID1B were mutated in 20 patients. By examining available parental samples, we ascertained that 17 occurred de novo. All mutations in SMARCB1 and SMARCA4 were non-truncating (missense or in-frame deletion) whereas those in ARID1B were all truncating (nonsense or frameshift deletion/insertion) in this study as in our previous study. Our data further support that CSS is a SWI/SNF complex disorder.

Objectives We have previously demonstrated that dental pulp stem cells (DPSCs) isolated from mature teeth by granulocyte colony-stimulating factor (G-CSF)-induced mobilization method can enhance angiogenesis/vasculogenesis and improve pulp regeneration when compared with colony-derived DPSCs. However, the efficacy of this method in immature teeth with root-formative stage has never been investigated. Therefore, the aim of this study was to examine the stemness, biological characteristics, and regeneration potential in mobilized DPSCs compared with colony-derived DPSCs from immature teeth. Materials and methods Mobilized DPSCs isolated from immature teeth were compared to colony-derived DPSCs using methods including flow cytometry, migration assays, mRNA expression of angiogenic/neurotrophic factor, and induced differentiation assays. They were also compared in trophic effects of the secretome. Regeneration potential was further compared in an ectopic tooth transplantation model. Results Mobilized DPSCs had higher migration ability and expressed more angiogenic/neurotrophic factors than DPSCs. The mobilized DPSC secretome produced a higher stimulatory effect on migration, immunomodulation, anti-apoptosis, endothelial differentiation, and neurite extension. In addition, vascularization and pulp regeneration potential were higher in mobilized DPSCs than in DPSCs. Conclusions G-CSF-induced mobilization method enhances regeneration potential of colony-derived DPSCs from immature teeth.

Mutations in SPATA5 have recently been shown to result in a phenotype of microcephaly, intellectual disability, seizures, and hearing loss in childhood. Our aim in this report is to delineate the SPATA5 syndrome as a clinical entity, including the facial appearance, neurophysiological, and neuroimaging findings. Using whole-exome sequencing and Sanger sequencing, we identified three children with SPATA5 mutations from two families. Two siblings carried compound heterozygous mutations, c.989_991del (p.Thr330del) and c.2130_2133del (p.Glu711Profs*21), and the third child had c.967TA (p.Phe323Ile) and c.2146GC (p.Ala716Pro) mutations. The three patients manifested microcephaly, psychomotor retardation, hypotonus or hypertonus, and bilateral hearing loss from early infancy. Common facies were a depressed nasal bridge/ridge, broad eyebrows, and retrognathia. Epileptic spasms or tonic seizures emerged at 6-12 months of age. Interictal electroencephalography showed multifocal spikes and bursts of asynchronous diffuse spike-wave complexes. Augmented amplitudes of visually evoked potentials were detected in two patients. Magnetic resonance imaging revealed hypomyelination, thin corpus callosum, and progressive cerebral atrophy. Blood copper levels were also elevated or close to the upper normal levels in these children. Clinical delineation of the SPATA5-related encephalopathy should improve diagnosis, facilitating further clinical and molecular investigation.

Genetic reversion is the phenomenon of spontaneous gene correction by which gene function is partially or completely rescued. However, it is unknown whether this mechanism always correctly repairs mutations, or is prone to error. We investigated a family of three boys with intellectual disability, and among them we identified two different mutations in KDM5C, located at Xp11.22, using whole-exome sequencing. Two affected boys have c.633delG and the other has c.631delC. We also confirmed de novo germline (c.631delC) and low-prevalence somatic (c.633delG) mutations in their mother. The two mutations are present on the same maternal haplotype, suggesting that a postzygotic somatic mutation or a reversion error occurred at an early embryonic stage in the mother, leading to switched KDM5C mutations in the affected siblings. This event is extremely unlikely to arise spontaneously (with an estimated probability of 0.39-7.5 × 10(-28) ), thus a possible reversion error is proposed here to explain this event. This study provides evidence for reversion error as a novel mechanism for the generation of somatic mutations in human diseases.

Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine and its exaggerated production has been implicated in acute, chronic and autoimmune inflammatory diseases. Proteinaceous and non-proteinaceous anti-TNF-α agents have been developed to reduce its circulating levels either by neutralizing, binding or inhibiting the de novo synthesis with the aim of achieving desirable therapeutic effects. In the present study, we compared the effects of a protein-based anti-TNF-α drug, etanercept, and a non-protein-based anti-TNF-α small molecule, 5-ethyl-1-phenyl-2-(1H) pyridone (5-EPP), on the LPS-stimulated secretion of TNF-α in the medium and TNF-α associated with the THP-1 cells in vitro. Both drugs had marked concentration-dependent inhibitory effects on the LPS-stimulated secretion of TNF-α. However, their effects on the LPS-stimulated cell-associated TNF-α were diametrically opposed to each other. For instance, etanercept further increased the level by up to 12-fold, whereas 5-EPP inhibited the level in a dose dependent manner. In addition, 5-EPP caused a significant reduction in the elevated level of cell associated TNF-α caused by LPS + etanercept. The differences in the levels of cell-associated TNF-α as reported in the present study may partly explain the adverse effects of some protein-based anti-TNF-α drugs including etanercept as opposed to a non-protein-based anti-TNF-α drug such as pirfenidone, a structural analogue of 5-EPP, for treatment of some TNF-α mediated diseases. It was concluded from the findings of this study that drugs which elevate the levels of cell associated-TNF-α will potentially have more adverse events even after reducing the secreted levels of TNF-α than the drugs which reduce both the secreted and cell-associated TNF-α levels.

In order to assess the effect of marine and terrestrial environmental change in the last decades on the sedimentation environment in Ariake Bay, we collected three sediment cores. The concentrations of natural and anthropogenic radionuclides, major elements, and rare-earth elements were measured using gamma-spectrometry and neutron activation analysis. Vertical distributions of both radionuclides and sedimentation rates, determined using Cs-137 and Pb-210ex dating methods, varied significantly among the sites.

The S100P protein stimulates cell proliferation and survival, thereby contributing to tumor progression. The purpose of this study was to evaluate S100P expression in the three subtypes of mucinous cystic tumors, cystadenomas, borderline tumors, and adenocarcinomas. The authors examined nuclear S100P expression in 60 mucinous ovarian tumor specimens, including 24 specimens of mucinous cystadenoma, 15 of borderline tumors, and 21 of adenocarcinomas. Immunohistochemistry revealed S100P expression followed one of three patterns: (1) Expressed in most nuclei of mucinous epithelial cells, (2) sporadic (spotted or patchy) expression, or (3) absent or rarely expressed in the nuclei of mucinous epithelial cells. Most adenomas showed the first expression pattern, and borderline tumors often showed a patchy expression pattern. Adenocarcinomas generally demonstrated absence of S100P expression. These data suggest that S100P is a useful histological marker to differentiate between benign, borderline, and malignant mucinous tumors of the ovary.

In end-stage renal disease patients, various abnormalities of bone mineral metabolism adversely affect mortality. Hyperphosphatemia is known to adversely affect mortality and quality of life in chronic kidney disease patients and has been shown to be involved not only in the onset and progression of secondary hyperparathyroidism but also in vascular calcification. Thus, hyperphosphatemia is the main treatment target indicated in several guidelines for chronic kidney disease-mineral and bone disorder treatment. Phosphate binders are typically required for the management of hyperphosphatemia because dietary phosphorus restriction and phosphorus removal by hemodialysis alone are insufficient. We are able to prescribe five phosphate binders (calcium carbonate, sevelamer HCl, lanthanum carbonate (LaC), bixalomer, and ferric citrate) to Japanese hemodialysis patients. LaC is the most powerful noncalcium-containing phosphate binder for the treatment of hyperphosphatemia. In this chapter, we discuss the efficacy and safety of LaC, the safety of which has been under debate. In particular, we consider its toxic effects on the skeletal system. LaC is effective for hyperphosphatemia treatment in end-stage renal failure patients. It has been shown to be able to decrease serum fibroblast growth factor-23 levels. This result suggests that it may have beneficial effects on the cardiovascular system in patients undergoing renal replacement therapy. However, the effects of LaC remain obscure. Further investigations are required. No negative effects of LaC on bone metabolism or bone morphometry have been reported, but long-term clinical data are needed.

The effects of hydrogen charge on cyclic stress-strain properties, slip band morphology and crack behaviour of annealed medium carbon steels (JIS-S45C) were studied. The total strain range of the stress-strain hysteresis loop in the hydrogen-charged specimen was smaller than that in the uncharged specimen. Localized slip bands were observed in the hydrogen-charged specimen, while the slip bands were widely and uniformly distributed in the uncharged specimen. It is presumed that the decrease in the total strain range of the hysteresis loop is due to the slip localization caused by the hydrogen charge and cyclic loading. The sites of fatigue crack initiation were mostly at grain boundaries in the uncharged specimen. The sites of crack initiation in the hydrogen-charged specimen were not only at grain boundaries but also at slip bands inside ferrite grains. These results imply that hydrogen enhances dislocation mobility along slip bands and results in slip localization. These slip bands then attract hydrogen. This mechanism of hydrogen - slip band interaction may play an important role in the hydrogen- influenced metal fatigue.

Prognoses in cases of uterine cervical squamous cell carcinoma treated with radiotherapy were investigated in association with immunohistochemical expression of an angiogenic factor, thymidine phosphorylase (TP). Forty-six cases of uterine cervical squamous cell carcinoma mainly treated with radiotherapy during 1992–2001 at our clinic were studied. All were diagnosed as stages IIB to IVA. Paraffin-embedded biopsy specimens excised before radiotherapy were stained immunohistochemically using anti-TP monoclonal antibody. The extent of staining in both tumor and interstitial cells was graded as (−), (±), (+), and (2+). Specimens with TP expression levels of (2+) and (+) were regarded as positively stained and those with TP expression levels of (±) and (−) as negatively stained. The efficacy of radiotherapy in both groups was analyzed by the Kaplan–Meier method. With tumor cells, 5-year survival rates for the positive (n = 38) and negative (n = 8) staining groups were 73.9% and 42.9%, respectively; the rate being significantly higher for the TP-positive group (log rank, P = 0.0096). Contrarily, with staining for interstitial cells, the 5-year survival rates for the positive (n = 20) and negative (n = 26) staining groups were 74.1% and 64.6%, respectively, with no significant difference (log rank, P = 0.406). The efficacy of radiotherapy in the group with positive staining of tumor cells was significantly better than in the negative staining group. Immunohistochemical expression of TP in tumor cells is suggested as a useful prognostic factor for uterine cervical squamous cell carcinomas treated with radiotherapy. Choosing therapy for individual cases by referring to factors including TP expression should contribute to an improved prognosis.

Cyclin D1 is a target molecule transcriptionally activated by aberrant beta-catenin in Wnt signalling. Thyroid papillary microcarcinoma (PMC) may be considered a precursor of papillary thyroid cancer (PTC). Ki67 is widely used as a proliferation marker. The aim of this study was to determine whether cyclin D1 overexpression is involved in early thyroid carcinogenesis.Thirty-five cases of PMC were examined immunohistochemically, including 11 cases less than 5 mm (PMC5) and 24 cases more than 5 mm (PMC5), and 18 PTC cases (size 11-15 mm). Cyclin D1 expression was significantly lower in PMC5 than in PMC5, while there was no significant difference between PMC5 and PTC. Statistical analysis revealed significant correlations between cyclin D1 labelling index (LI) and Ki67 LI (P = 0.0272)/cytoplasmic beta-catenin expression (P0.001) in PMC and PTC. Four of five PMC5 cases with lymph node (LN) metastases displayed a high cyclin D1 LI and strong cytoplasmic beta-catenin expression.Cyclin D1 overexpression and correlation with aberrant beta-catenin expression were demonstrated in PMC. Cyclin D1 expression was significantly associated with tumour size and LN metastases in PMC. Cyclin D1 may be up-regulated at an early stage of thyroid carcinogenesis and promote tumour growth and metastatic potency in PMC through activation of the Wnt/beta-catenin pathway.

Aspiration of foreign bodies is extremely rare in adults, but it may occur during the course of dental treatment and become a serious problem for the patient. A case of a 77-year old man with chronic cough after dental treatment and unrecognised aspiration of an implant is presented. The implant remained unidentified for three years as an endobronchial foreign body of the lower lobe bronchus. A bronchoscopic removal failed and surgery was indicated for lobectomy of the right lower lobe because of chronic pneumonia. A review of prevention, signs and symptoms, management and documentation of the complications is presented.

Objectives: To investigate the efficacies of two different triple-therapy regimens (standard versus low doses), and the influence of cytochrome P450 enzyme (CYP) genetic polymorphism on these efficacies, in Japanese patients undergoing Helicobacter pylori eradication treatment. Methods: All patients received 1 week of triple therapy. Patients in group A (low-dose regimen) received omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day; patients in group B (standard-dose regimen) received omeprazole 40 mg/day + amoxicillin 2000 mg/day + clarithromycin 1000 mg/day. Results: A total of 225 patients (113 in group A and 112 in group B) were randomised to one of the two triple-therapy regimens. The eradication rates were 78.8% (89/113 patients; 95% CI 70.1, 85.9) in group A and 83.0% (93/112 patients; 95% CI 74.8, 89.5) in group B. Genetic polymorphism of CYP2C19, a major metabolic enzyme of omeprazole, did not affect eradication rates, while susceptibility to clarithromycin greatly affected the success of eradication. The cumulative ulcer relapse rate at 24 weeks after endoscopically documented ulcer healing (30 weeks after completion of the drug regimen) was 8.3% for group A and 12.5% for group B (log rank test: p = 0.6248). However, comparison of the cumulative relapse rate of 6.7% in patients after successful H. pylori eradication with the relapse rate of 27.3% in those who failed H. pylori eradication revealed a significant difference in the remission-time curve (log rank test: p = 0.0047). This finding suggested the existence of a relationship between H. pylori eradication failure and ulcer relapse. Both drug regimens were well tolerated. Endoscopically proven reflux esophagitis developed in about 10% of patients after eradication, but was not clinically significant. Conclusions: One week of triple therapy with a low-dose regimen provides adequate H. pylori eradication in Japanese patients. CYP genetic polymorphism is of minimal clinical significance with both triple-therapy regimens.

This paper describes a robotic-head system as a multimodal communication device for human-robot interaction, and the system's potential application in home environments. Most robotic systems for natural user interaction have facial expressions, since facial expressiveness is regarded as a key component to developing personal attachment along with prosodic expressiveness. In the first part of the paper is the description of our robotic head system Character Robot Face (CRF). A deformation approach and a parametric normalization scheme are proposed to produce facial expressions of nonhuman face models with high recognition rates. In the second half of the paper, CRF is endowed with artificial emotions and assigned tasks conceivable in home environments. A coordination mechanism between the robot's mood (an activated emotion) and its task is proposed so that the robot can, by referring to the emotion-task history, select a task depending on its current mood if there is no explicit task command from the user. When the robot performs a task, a particular emotion value gets boosted according to the same emotion-task history so that the emotion is more likely to be activated.

Emphysema is characterised by a loss of alveolar structure, as reflected in elastic recoil and gas exchange. As fibroblasts play a key role in the maintenance of structure, the current authors hypothesised that their proliferation might be constitutively impaired in lung emphysema. Using explant cultures, lung fibroblasts were obtained from resected lungs of 10 patients with emphysema (median forced expiratory volume in one second (FEV1) 40% predicted) and 10 control patients (FEV1, 95% pred). The doubling time (DT) was measured over 4 days under standard conditions (10% foetal calf serum) prior and after cryopreservation. Additionally, in seven samples per group the total population doubling level (PDL) was determined. In emphysema, mean+/-sem DT was 33.6+/-2.8 h compared with 24.8+/-1.4 h in controls. The differences in DT were preserved after cryopreservation. Groups also differed in the initial slope of the PDL plot during long-term culture (up to 35 days). However, the median (range) maximum PDL did not differ significantly between groups (13.8 (7.4-22.6) versus 20.2 (11.2-25.5)). The current authors, therefore, suggest that the reduced proliferation rate in vitro of lung fibroblasts from patients with emphysema reflects a persistent, intrinsic failure of cellular replacement and maintenance in this disease, possibly in relation to pre-term aging.