Retrospective evaluation of the orthodontic treatment needs in primary school children with Robin sequence following Tübingen palatal plate therapy in infancy.

INTRODUCTION: The aim of this study was to investigate the orthodontic treatment needs (OTN) of children with RS treated with the TPP in infancy compared to age- and sex-matched controls. METHODS: The aim of this study was to investigate the orthodontic treatment needs (OTN) of children with RS treated with the TPP in infancy compared to age- and sex-matched controls. RESULTS: In 21 children with RS (n = 23; 19 non-syndromic, 4 syndromic; average age 9.9 years) showed high OTN, which was significantly higher than in controls (n = 21). The latter of 9 controls had minor OTN, followed by 8 participants with borderline OTN. Regarding the intraoral picture, patients with RS had an increased open bite tendency. Without considering the presence of a cleft palate, 16 children with RS had high or very high OTN, compared to 4 of controls. CONCLUSIONS: Patients with RS have significantly higher OTN than healthy controls, independent of cleft occurrence. RS is associated with dental anomalies and special skeletal growth patterns, both increasing malocclusion and negatively affecting dentoalveolar growth. This should raise awareness for identifying these needs and provide a comprehensive orthodontic treatment, where functional rehabilitation should be favored over aesthetic results.

Fatty acid composition of adipose tissue at term indicates deficiency of arachidonic and docosahexaenoic acid and excessive linoleic acid supply in preterm infants.

BACKGROUND: Arachidonic (ARA) and docosahexaenoic acid (DHA) are constitutive to membrane phospholipids, and essential for brain and overall development. ARA/DHA pools in term infants (TI) are built during the third trimester, stored as adipose tissue triglycerides and predominantly distributed via plasma phosphatidylcholine (PC). In preterm infants (PTI), placental ARA/DHA supply is replaced by linoleic-acid (LA)-enriched nutrition. This study aimed to investigate the impact of PTI nutrition, compared to placental supply, on fatty acid composition in adipose tissue and blood. METHODS: Prospective observational study (4/2017-3/2019) in 12 PTI and 3 PTI with enterostomy (PTI/E) (gestational age (GA) < 32 weeks) with surgical intervention at term (± 6 weeks) and 14 TI (GA ≥ 34 weeks, surgical intervention < 2 weeks postnatally). PTI/E were analyzed descriptively only. PC and triglyceride fatty acids were analyzed with tandem mass spectrometry and gas chromatography, respectively. Results were compared between TI and PTI with Wilcoxon Test and shown as median [25th percentile-75th percentile] mol%. RESULTS: PTI had less ARA in adipose tissue TG (0.77[0.67-0.87]% vs. 1.04[0.95-1.14]%, p = 0.0003) and plasma PC (20.7[18.7-22.8]% vs. 28.3[22.7-33.5]%, p = 0.011) than TI. PTI also had less DHA in adipose tissue TG (0.6[0.4-0.8]% vs. 1.1[0.8-1.4]%, p = 0.006) and plasma PC (6.4[5.6-7.1]% vs. 8.4[7.8-13.1]%, p = 0.002). LA was increased in PTI's adipose tissue TG (10.0[8.8-12.3]% vs. 3.0[2.5-3.6]%, p < 0.0001) and plasma PC (48.4[44.6-49.6]% vs. 30.6[24.9-35.6]%, p = 0.0002). Similar differences were observed in erythrocyte PC. CONCLUSION: In PTI, LA is increased and ARA/DHA decreased in adipose tissue, plasma and erythrocyte lipids as proxies for other tissues, likely caused by PTI nutrition. This may contribute to impaired PTI development.

Technical note on introducing a digital workflow for newborns with craniofacial anomalies based on intraoral scans - part II: 3D printed Tübingen palatal plate prototype for newborns with Robin sequence.

BACKGROUND: Orthodontic treatment of newborns and infants with Robin-Sequence using the Tübingen Palatal Plate (TPP) is a complex procedure that could benefit from simplification through digitalization. The design of the velar extension (spur) and the palatal base determines the success of the treatment. Therefore, a prototype must be produced and inserted under endoscopic supervision in order to determine the appropriate shape, length and position of the spur. This technical note demonstrates a fully digital workflow for the design and manufacturing of a functional TPP prototype, based on an intraoral scan. This prototype can be altered and individualized digitally for each patient. After the shape and position of the spur have been optimized, the prototype is duplicated using a silicone mold. Then the definitive TPP is manufactured and inserted. We aim to present a workflow which facilitates the fitting procedure and does not require a conventional impression or a physical model to create the appliance. METHODS: As described in part I of this series, the intraoral scan is performed using the 3Shape TRIOS3 scanner and its corresponding acquisition software. The virtual model is rendered in the 3Shape ortho appliance designer and the base of the palatal plate is designed in the 3Shape dental designer. The palatal plate and the virtual model are then imported into Autodesk Meshmixer and a standardized spur is positioned and merged with the base. The TPP is exported in Standard Tessellation Language (STL) format and manufactured on a W2P Solflex 170 DLP printer using VOCO VPrint Splint material (MDR Class IIa). RESULTS: Based on an intraoral scan, the TPP prototype could be successfully manufactured and proved suitable for the patients' treatment. CONCLUSION: The new digital workflow for the design of the TPP can been successfully implemented into daily clinical routine in our facility. Patients could be alleviated from having to undergo conventional impression procedures and fitting of the TPP could be facilitated by producing multiple functional prototypes for endoscopic evaluation. Through rapid prototyping, the expenditure of the fitting process was reduced, which makes the TPP therapy more efficient and accessible to a wider range of clinicians.

Technical note on introducing a digital workflow for newborns with craniofacial anomalies based on intraoral scans - part I: 3D printed and milled palatal stimulation plate for trisomy 21.

BACKGROUND: Advanced digital workflows in orthodontics and dentistry often require a combination of different software solutions to create patient appliances, which may be a complex and time-consuming process. The main objective of this technical note is to discuss treatment of craniofacial anomalies using digital technologies. We present a fully digital, linear workflow for manufacturing palatal plates for infants with craniofacial anomalies based on intraoral scanning. Switching to intraoral scanning in infant care is advantageous as taking conventional impressions carries the risk of impression material aspiration and/or infections caused by material remaining in the oronasal cavity. MATERIAL AND METHODS: The fully digital linear workflow presented in this technical note can be used to design and manufacture palatal plates for cleft palate patients as well as infants with functional disorders. We describe the workflow implemented in an infant with trisomy 21. The maxilla was registered using a digital scanner and a stimulation plate was created using dental CAD software and an individual impression tray module on a virtual model. Plates were manufactured using both additive and subtractive methods. Methacrylate based light curing resin and Poly-Ether-Ether-Ketone were the materials used. RESULTS: The palatal area was successfully scanned to create a virtual model. The plates fitted well onto the palatal area. Manual post-processing was necessary to optimize a functional ridge along the vestibular fold and remove support structures from the additively manufactured plate as well as the milled plate produced from a blank. The additively manufactured plate fitted better than the milled one. CONCLUSION: Implementing a fully digital linear workflow into clinical routine for treatment of neonates and infants with craniofacial disorders is feasible. The software solution presented here is suitable for this purpose and does not require additional software for the design. This is the key advantage of this workflow, which makes digital treatment accessible to all clinicians who want to deal with digital technology. Whether additive or subtractive manufacturing is preferred depends on the appliance material of choice and influences the fit of the appliance.

Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period.

Preterm delivery is the leading cause of perinatal morbidity and mortality. Among the most important complications in preterm infants are peri- or postnatal infections. Myeloid-derived suppressor cells (MDSC) are myeloid cells with suppressive activity on other immune cells. Emerging evidence suggests that granulocytic MDSC (GR-MDSC) play a pivotal role in mediating maternal-fetal tolerance. The role of MDSC for postnatal immune-regulation in neonates is incompletely understood. Until the present time, nothing was known about expression of MDSC in preterm infants. In the present pilot study, we quantified GR-MDSC counts in cord blood and peripheral blood of preterm infants born between 23 + 0 and 36 + 6 weeks of gestation (WOG) during the first 3 months of life and analysed the effect of perinatal infections. We show that GR-MDSC are increased in cord blood independent of gestational age and remain elevated in peripheral blood of preterm infants during the neonatal period. After day 28 they drop to nearly adult levels. In case of perinatal or postnatal infection, GR-MDSC accumulate further and correlate with inflammatory markers C-reactive protein (CRP) and white blood cell counts (WBC). Our results point towards a role of GR-MDSC for immune-regulation in preterm infants and render them as a potential target for cell-based therapy of infections in these patients.

Acoustics of snoring and automatic snore sound detection in children.

OBJECTIVE: Acoustic analyses of snoring sounds have been used to objectively assess snoring and applied in various clinical problems for adult patients. Such studies require highly automatized tools to analyze the sound recordings of the whole night's sleep, in order to extract clinically relevant snore- related statistics. The existing techniques and software used for adults are not efficiently applicable to snoring sounds in children, basically because of different acoustic signal properties. In this paper, we present a broad range of acoustic characteristics of snoring sounds in children (N = 38) in comparison to adult (N = 30) patients. APPROACH: Acoustic characteristics of the signals were calculated, including frequency domain representations, spectrogram-based characteristics, spectral envelope analysis, formant structures and loudness of the snoring sounds. MAIN RESULTS: We observed significant differences in spectral features, formant structures and loudness of the snoring signals of children compared to adults that may arise from the diversity of the upper airway anatomy as the principal determinant of the snore sound generation mechanism. Furthermore, based on the specific audio features of snoring children, we proposed a novel algorithm for the automatic detection of snoring sounds from ambient acoustic data specifically in a pediatric population. The respiratory sounds were recorded using a pair of microphones and a multi-channel data acquisition system simultaneously with full-night polysomnography during sleep. Brief sound chunks of 0.5 s were classified as either belonging to a snoring event or not with a multi-layer perceptron, which was trained in a supervised fashion using stochastic gradient descent on a large hand-labeled dataset using frequency domain features. SIGNIFICANCE: The method proposed here has been used to extract snore-related statistics that can be calculated from the detected snore episodes for the whole night's sleep, including number of snore episodes (total snoring time), ratio of snore to whole sleep time, variation of snoring rate, regularity of snoring episodes in time and amplitude and snore loudness. These statistics will ultimately serve as a clinical tool providing information for the objective evaluation of snoring for several clinical applications.

Cardiorespiratory events in preterm infants: etiology and monitoring technologies.

Every year, an estimated 15 million infants are born prematurely (<37 weeks gestation) with premature birth rates ranging from 5 to 18% across 184 countries. Although there are a multitude of reasons for this high rate of preterm birth, once birth occurs, a major challenge of infant care includes the stabilization of respiration and oxygenation. Clinical care of this vulnerable infant population continues to improve, yet there are major areas that have yet to be resolved including the identification of optimal respiratory support modalities and oxygen saturation targets, and reduction of associated short- and long-term morbidities. As intermittent hypoxemia is a consequence of immature respiratory control and resultant apnea superimposed upon an immature lung, improvements in clinical care must include a thorough knowledge of premature lung development and pathophysiology that is unique to premature birth. In Part 1 of a two-part review, we summarize early lung development and diagnostic methods for cardiorespiratory monitoring.

Cardiorespiratory events in preterm infants: interventions and consequences.

Stabilization of respiration and oxygenation continues to be one of the main challenges in clinical care of the neonate. Despite aggressive respiratory support including mechanical ventilation, continuous positive airway pressure, oxygen and caffeine therapy to reduce apnea and accompanying intermittent hypoxemia, the incidence of intermittent hypoxemia events continues to increase during the first few months of life. Even with improvements in clinical care, standards for oxygen saturation targeting and modes of respiratory support have yet to be identified in this vulnerable infant cohort. In addition, we are only beginning to explore the association between the incidence and pattern of cardiorespiratory events during early postnatal life and both short- and long-term morbidity including retinopathy of prematurity, growth, sleep-disordered breathing and neurodevelopmental impairment. Part 1 of this review included a summary of lung development and diagnostic methods of cardiorespiratory monitoring. In Part 2 we focus on clinical interventions and the short- and long-term consequences of cardiorespiratory events in preterm infants.

Healthy term and moderately preterm infants have similar cerebral oxygen saturation and cerebral blood flow volumes during early post-natal transition.

AIM: This pilot study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants. METHODS: The cohort comprised 16 preterm infants and seven full-term infants with mean gestational ages of 34 and 39 weeks, respectively. Longitudinal measurements were conducted during the first three days after birth. Regional cerebral oxygen saturation was determined bilaterally by frequency domain near-infrared spectroscopy. Flow volumes were determined in internal carotid and vertebral arteries by multiplying the time-averaged velocity by the cross-sectional area: cerebral blood flow volume was calculated as the sum of flow volumes and adjusted for brain weight. RESULTS: Brain weight-adjusted cerebral blood flow volumes and regional cerebral oxygen saturation were similar in preterm and term infants. Regional cerebral oxygen saturation did not correlate with brain weight-adjusted cerebral blood flow volume. Right and left brain weight-adjusted internal carotid flow volumes did not correlate with right and left regional cerebral oxygen saturation. CONCLUSION: Our findings suggest that during the first three days after birth there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both healthy term and moderately preterm infants.

[Snoring in children. Algorithm for diagnostic approach]. / Schnarchen bei Kindern. Algorithmus zum diagnostischen Vorgehen.

BACKGROUND: Snoring in children is a prevalent symptom and may be an indicator of obstructive sleep apnoea. Despite its importance, there is no national guideline on its appropriate management. OBJECTIVE: To provide recommendations for the management of snoring in children and adolescents treated in a primary care setting. METHODS: A total of 16 national paediatric sleep experts were included in a Delphi process and formulated recommendations in the form of a step-wise work-up procedure. RESULTS: The following 8 steps were developed: (1) Identification of true cases of habitual snoring. (2) Identification of high-risk patients who should undergo polysomnography in a sleep laboratory. (3) Identification of mild cases that may be treated with anti-inflammatory medication. (4) Identification of cases that should be referred to an otorhinolaryngologist for potential surgery. (5) Performance of polysomnography in cases that remain unclear despite steps 3 and 4 to rule out obstructive sleep apnoea. (6) Reconsideration of surgery in cases with moderate to severe obstructive sleep apnoea. (7) Identification of severe sleep apnoea cases requiring continuous positive airway pressure therapy. (8) Identification of cases suitable for orthodontic treatment, craniofacial surgery or speech therapy. CONCLUSION: This guideline should help to improve the management of snoring children and adolescents in Germany.

[Medicinal treatment of breathing disorders in adenotonsillar hyperplasia]. / Medikamentöse Behandlung von Atmungsstörungen bei adenotonsillärer Hyperplasie.

BACKGROUND: Adenotonsillar hyperplasia (ATH) can lead to severe breathing disorders, such as impaired nasal breathing, mouth breathing, snoring and obstructive sleep apnea. In such cases ATH should be treated mostly by performing adenoidectomy and/or adenotonsillectomy. There is increasing evidence that anti-inflammatory medication (AIM) is effective in treating ATH-related breathing disorders. OBJECTIVES: The aim of this study was to provide evidence and recommendations for the use of AIM in the treatment of ATH-related breathing disorders. METHODS: In this study 12 national pediatric sleep experts were included into a Delphi process and formulated indications and recommendations. RESULTS: The use of AIM in the treatment of ATH-related breathing disorders is sufficiently supported by the results of randomized controlled trials and systematic reviews. Nasal beclometason and nasal mometason have been studied for the treatment of enlarged adenoids and nasal fluticason and oral montelukast for the treatment of obstructive sleep apnea. The use of AIM for first-line treatment should be restricted to selected indications, such as a characteristic patient age and exclusion of an acute upper respiratory tract infection. Evidence-based recommendations are given concerning indications, dosage, treatment duration and correct administration of AIM. CONCLUSIONS: Anti-inflammatory medications are simple and effective alternatives for the treatment of ATH-related breathing disorders. These guidelines are intended to promote the use of AIM by pediatricians in ambulatory care settings.

Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses.

Neonates show an impaired anti-microbial host defence, but the underlying immune mechanisms are not understood fully. Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell subset characterized by their capacity to suppress T cell immunity. In this study we demonstrate that a distinct MDSC subset with a neutrophilic/granulocytic phenotype (Gr-MDSCs) is highly increased in cord blood compared to peripheral blood of children and adults. Functionally, cord blood isolated Gr-MDSCs suppressed T cell proliferation efficiently as well as T helper type 1 (Th1), Th2 and Th17 cytokine secretion. Beyond T cells, cord blood Gr-MDSCs controlled natural killer (NK) cell cytotoxicity in a cell contact-dependent manner. These studies establish neutrophilic Gr-MDSCs as a novel immunosuppressive cell subset that controls innate (NK) and adaptive (T cell) immune responses in neonates. Increased MDSC activity in cord blood might serve as key fetomaternal immunosuppressive mechanism impairing neonatal host defence. Gr-MDSCs in cord blood might therefore represent a therapeutic target in neonatal infections.

A historic cohort study on accelerated advancement of enteral feeding volumes in very premature infants.

BACKGROUND: The optimal rate of enteral feeding (EF) advancement in very low birth weight infants is under debate. OBJECTIVES: To evaluate the effects of accelerated EF advancement on the time to full enteral feeds, on early postnatal growth as well as on the frequency of necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) in very premature infants. METHODS: In a retrospective single-center historic cohort study, infants with a gestational age <32 weeks at birth and birth weight <1,500 g, born between January 1, 2006, and December 31, 2007 (n = 136), were compared with infants born between January 1, 2010, and December 31, 2010 (n = 88). In 2006/2007, enteral feeds were initiated on day 1 with 10-15 ml/kg/day and advanced by 15-20 ml/kg/day. In 2010, enteral feeds were initiated with 20 ml/kg/day on day 1 and advanced by 25-30 ml/kg/day. Full enteral feeds were defined as ≥ 140 ml/kg/day. Data are presented as median (P25-P75). RESULTS: The time to establish full enteral feeds was shorter in 2010: 8 (7-11) days in 2006/2007 versus 6 (5-9) days in 2010. The incidences of NEC and FIP were 2.7 and 4.1% in 2006/2007 and 3.3 and 2.2% in 2010, respectively. Weight gain was not affected by the rate of EF advancement. Higher parenteral protein intake during week 1 in 2006/2007 was associated with better head circumference growth. CONCLUSIONS: The new approach was associated with a significantly shorter period to establish full enteral feeds. No difference in the incidence of FIP or NEC was observed; however, the study was underpowered to detect small but possibly important differences.

[Pierre Robin Sequence: interdisciplinary treatment after prenatal diagnosis]. / Pierre Robin Sequenz: Pränatale Diagnostik und interdisziplinäre Therapie.

BACKGROUND: Pierre Robin Sequence (PRS) is characterised by mandibular micrognathia and/or retrognathia, glossoptosis and upper airway obstruction (UAO). In severe cases, UAO and cyanosis occur immediately after birth and endoscopic intubation may become necessary. Therefore, prenatal diagnosis with referral to a specialized department is important. METHOD: A non-invasive interdisciplinary treatment protocol is presented. The postnatal adjustment of the preepiglottic baton plate (PEBP) as early as possible is essential in this concept. EVIDENCE: In a randomised cross-over trial with 11 patients with isolated PRS, the PEBP was found to reduce the apnoea index significantly and to be superior to a conventional palatal plate. An uncontrolled longitudinal study indicated that the UAO had normalised 3 months after discharge; all infants showed adequate weight gain with bottle feeding. In a comparative study with 34 healthy children and 34 children with isolated PRS, no significant differences in cognitive outcome was found. CONCLUSIONS: Interdisciplinary co-operation between prenatal care, neonatology and orthodontics is a pre-requisite for optimal postnatal therapy. Complications of UAO can be avoided by early and adequate treatment, resulting in good results for feeding, speech and facial profile. Invasive surgical treatment options like tongue-lip-adhesion, mandibular extension or distraction should be obsolete.

Acute scrotum in a neonate caused by renal vein thrombosis.

The authors report on a rare case of neonatal scrotal oedema occurring concurrently with pain upon palpation of the spermatic cord on the first day of life. An ultrasound examination showed poor perfusion of the left testicle and a thrombosis of the left renal vein; intraoperative exploration indicated necrosis of the left testicle without signs of torsion. Gorged vessels with paravasal bleeding were found in the spermatic cord. The authors hypothesise that necrosis of the testicle may result from haemorrhagic infarction caused by renal venous thrombosis. Acute scrotal discolouration with pain upon palpation in neonates is usually attributed to testicular torsion. The authors report a case where these symptoms had a different cause.

Are recommended phototherapy thresholds safe enough for extremely low birth weight (ELBW) infants? A report on 2 ELBW infants with kernicterus despite only moderate hyperbilirubinemia.

Two extremely low birth weight (ELBW) infants developed characteristic signs of kernicterus at 4 and 8 months corrected age despite only moderate neonatal hyperbilirubinemia (peak serum bilirubin <10 g/dl) and phototherapy being applied according to current guidelines. Both girls were from twin pregnancies and had fetal complications (donor in a twin-twin transfusion syndrome and acardius-acranius malformation in the second twin, respectively), connatal anemia (initial hematocrit 30%), and mild acidosis after birth. They had been neurologically normal at discharge except for abnormal otoacustic emissions (OAE). At the time kernicterus was diagnosed, both infants were nearly deaf, showed severe psychomotor retardation with dystonic features and had marked bilateral hyperintensities in the globus pallidum on MRI. Based on these and similar cases from the literature, we question whether current phototherapy guidelines are appropriate for high-risk ELBW infants. Lower thresholds may be preferable, at least if additional risk factors, such as anemia, are present.

Survey of practices regarding utilization of inhaled steroids in 223 German neonatal units.

BACKGROUND: No survey has been published in recent years which primarily focuses on the prescription of inhaled corticosteroids in neonatal practice. Thus, the utilization rate of inhaled corticosteroids is unknown. OBJECTIVES: To elucidate the current utilization rate of inhaled corticosteroids in the prevention and therapy of bronchopulmonary dysplasia (BPD). METHODS: We developed an 18-item questionnaire that was distributed in March 2009, via electronic mail, to the pediatricians-in-chief of all the 343 German pediatric hospitals with a neonatal unit (all levels of neonatal care). We sent electronic reminders after 4 and 8 weeks. RESULTS: 223 hospitals (65%) returned the questionnaire. Of these, 102 (46%) administered inhaled corticosteroids to premature infants either as prophylaxis or treatment for BPD. Predominantly, treatment with inhaled steroids was seen as a 'rescue therapy' and used only if other therapeutic approaches had failed. Of the hospitals not administering inhaled steroids, the most frequently stated reason was 'insufficient robust evidence to support benefit of therapy' (57%). In the majority of hospitals (81%), the active substance of choice was budesonide. CONCLUSIONS: Of the responders, approximately 50% administer inhaled corticosteroids to premature infants either as a prophylaxis or treatment for BPD. Lack of beneficial evidence was the main reason for not administering inhaled steroids in about half of the units which took this approach. Future trials should address this discrepancy by aiming to establish a clear benefit-risk ratio of inhaled corticosteroids.

Population prevalence of obstructive sleep apnoea in a community of German third graders.

We aimed to estimate the population prevalence of obstructive sleep apnoea (OSA) in an urban community of German third graders (age range 7.3-12.4 yrs) and the diagnostic test accuracy of two OSA screening methods. Using a cross-sectional study design with a multi-stage sampling strategy, 27 out of 59 primary schools within the city limits of Hanover, Germany, were selected. 1,144 third graders were screened for symptoms and signs of OSA using questionnaires and nocturnal home pulse oximetry. 183 children underwent abbreviated nocturnal home polysomnography (OSA definition: apnoea/hypopnoea index ≥1) and 22 were diagnosed to suffer from OSA. In general, sensitivity for both screening methods was low (<0.6), while specificity was moderately high (mostly >0.7). Independent predictors for OSA were body mass index, history of allergy, a composite questionnaire score, and two oximetry-based criteria. Based on these variables and logistic regression, a prediction model (accuracy; 95% confidence interval: 0.86; 0.71-0.94) was constructed and applied to children who had not successfully undergone polysomnography. This resulted in nine additional OSA cases and an overall design-adjusted population prevalence (95% confidence interval) of 2.8% (1.5-4.1%). Clinical and oximetry findings may be helpful for screening and predicting OSA in primary school children.