[PREFERENCES OF PARENTS FOR PEDIATRIC INPATIENT WARD PHYSICIAN'S ATTIRE].

BACKGROUND: The preferred attire for physicians has not been defined to date. In Israel, where casual attire is acceptable in most circumstances, patients' preferences have not yet been systematically evaluated. METHODS: This is a cross-sectional study that was designed to evaluate parents' preferences for physicians' attire in a pediatric inpatient ward. A volunteer was dressed in four types of clothes sets: elegant attire, sportive attire, careless attire and scrubs - all of which were displayed, with or without a white coat. Parents were asked whether or not they felt the physician was an important component of the medical encounter; they were also asked to choose the picture of the doctor they preferred to care for their child. RESULTS: A total of 250 parents participated in the study; 68% of the parents believe that the physician's attire is an important component of the medical encounter; 41% of the parents preferred the doctor to wear scrubs with a white coat, 22% preferred scrubs without a white coat. Careless attire was the least preferred attire. CONCLUSIONS: The physicians' attire was important for most of the participants. We recommend that doctors in inpatient wards wear scrubs.

Intermittent inhaled tobramycin and systemic cytokines response in CF patients with Pseudomonas aeruginosa.

INTRODUCTION: CF pulmonary guidelines recommend alternate therapy (one month on, one month off) with inhaled tobramycin for chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF). Tobramycin-inhaled powder (TIP™) is increasingly replacing time-consuming nebulizer therapy. It is unclear whether laboratory parameters change during the month off period compared with the month on therapy. PURPOSE: Our aim was to assess whether spirometry, lung clearance index and circulating inflammatory markers differ between on/off treatment periods. MATERIALS AND METHODS: A prospective pilot study evaluating CF patients treated with TIP, on two consecutive months (on/off) therapy. The evaluations were performed at the end of a month off therapy (1-2 days before the initiation of TIP) and after 28 days of treatment with TIP (1-2 days after the end of the treatment cycle). RESULTS: Nineteen CF patients (10 males) with a mean age of 18.7±9.7 years and BMI (body mass index) of 19.62±3.53 kg/m2 were evaluated. After a month off treatment with TIP, spirometry parameters and lung clearance index remained unchanged. IL-6 increased significantly (p=0.022) off treatment. There was a non-significant change in the other inflammatory cytokines off therapy [hs-CRP, IL-8,TNF-α, α1-antitrypsin (α1AT) and neutrophilic elastase]. CONCLUSIONS: The results of lung function parameters support the relative stability of CF patients during the month off therapy; however, the difference in serum IL-6 raises the possibility of ongoing higher degrees of inflammation during the month off therapy with TIP. The small sample size and the multiple parameters evaluated preclude firm conclusions; therefore, larger multicenter studies are needed to assess the on/off treatment strategy.

Factors Associated with Recurrence of Tracheoesophageal Fistula.

BACKGROUND: Recurrence of tracheoesophageal fistula (TEF) is reported in 8-20% patients. Factors that may influence recurrence of fistula beyond the postoperative period are not clear. OBJECTIVES: To evaluate possible factors associated with recurrence of TEF beyond the immediate postoperative period. METHODS: A single center, retrospective comparison of patients with and without recurrence of TEF was conducted. Medical records of patients previously operated for TEF who were followed in our pediatric pulmonary institute between January 2007 and December 2016 were reviewed. RESULTS: The medical records of 74/77 patients previously operated for TEF were evaluated. Nine patients (12%) had a recurrence of TEF and 65 did not. These groups had similar age and gender distribution and similar prevalence of VACTERL association. In addition, they had similar length of atretic gap, rates of thoracoscopic surgery, rates of prolonged need for respiratory assistance post-surgery, and frequency of gastrointestinal symptoms. Notably, the patients who had recurrent TEF had significantly more hospitalizations for respiratory symptoms (P = 0.011) and significantly more episodes of clinical bronchiolitis per patient (P < 0.0001). In addition, the patients with recurrent TEF had significantly more episodes of positive polymerase chain reaction for viruses (P = 0.009). CONCLUSIONS: Hospitalizations for respiratory symptoms as well as clinical and/or viral bronchiolitis are associated with recurrence of TEF. Even though cause and effect cannot be established, these patients should undergo meticulous evaluation for the possibility of recurrence of TEF.

Lung Clearance Index (LCI) in Patients with Bronchiolitis Obliterans: A Preliminary Report and Comparison to Cystic Fibrosis Patients.

INTRODUCTION: Bronchiolitis obliterans (BO) is a chronic airway disease following an insult to the lower respiratory tract. Lung clearance index (LCI) measures ventilation inhomogeneity and has been studied in cystic fibrosis (CF). We aimed to evaluate LCI in BO and to compare it to LCI in CF patients. METHODS: LCI was measured in BO patients, compared to CF patients, and correlated with spirometry and CT findings. RESULTS: Twenty BO patients and 26 CF patients (with similar mean age and BMI) underwent evaluation. FEV1 % and FEF25-75 % predicted were significantly lower in the BO group (60.5 ± 17.8 vs. 72.7 ± 20.7, p = 0.041, and 42.8 ± 22.8 vs. 66.4 ± 37.4, p = 0.017, respectively). In both groups, LCI was inversely correlated with FVC %, FEV1 %, and FEF25-75 % predicted. LCI  % was slightly higher (190.4 ± 63.5 vs. 164.9 ± 39.4, p = 0.1) and FRC gas % (measured by multiple breath washout) was significantly higher in the BO group (92.5 ± 35.9 vs. 71.3 ± 18, p = 0.014). The strength of statistical association between the lower FEF25-75 % values and the higher LCI values was stronger in BO patients. CONCLUSIONS: Similar to CF, LCI may provide estimation of ventilation inhomogeneity in BO. The results indicate greater small airway involvement and air trapping in BO. Further prospective longitudinal studies evaluating the correlation of LCI measurements with multiple clinical and physiological parameters should be performed to assess the clinical benefit of LCI measurement in BO.

Evaluation of high-sensitivity serum CRP levels compared to markers of airway inflammation and allergy as predictors of methacholine bronchial hyper-responsiveness in children.

BACKGROUND: Bronchial hyper-responsiveness assessed by the methacholine challenge test (MCT) may aid in the diagnosis of asthma, while a negative MCT can help in excluding the diagnosis. Laboratory measures that predict the results of MCT are expected to reduce the number of procedures. We evaluated the capacity of serum high-sensitivity C-reactive protein (hs-CRP) to predict positive or negative MCT in school-aged children and compared it to a marker of airway inflammation, fractional exhaled nitric oxide (FeNO), and markers of allergic sensitization, immune globulin E (IgE) and peripheral blood eosinophils. PATIENTS AND METHODS: Children aged 6-18 years referred for MCT were included in the study. The results of the MCT were compared to hs-CRP levels and FeNO levels, IgE, and peripheral blood eosinophil counts. RESULTS: Of the 131 children assessed, 63 (48 %) patients had positive MCTs (Group I), and 68 (52 %) had negative MCTs (Group II). The best cut-off values to predict a positive MCT by receiver-operating characteristic curves were: 23 ppb for FeNO, 120 IU/mL for IgE, and 500/mL for eosinophils; no cut-off value was found for hs-CRP. The odds ratio for a positive MCT with the above cut-off points were 2.43 (1.05-5.61) for FeNO, 2.4 (1.01-5.74) for IgE, 3.32 (1.13-9.75) for eosinophils, and NS for hs-CRP. No correlation was found between hs-CRP and FeNO, IgE, or eosinophil levels. CONCLUSIONS: hs-CRP levels were not helpful, while FeNO, IgE, and eosinophils were useful in the prediction of methacholine bronchial hyper-responsiveness in our group of children.

Parents' attitudes toward oral rehydration therapy in children with mild-to-moderate dehydration.

OBJECTIVE: According to current guidelines, the first line of treatment for mild-to-moderate dehydration is oral rehydration; the second line is rehydration through a nasogastric tube. Both methods are widely underused. This study was conducted to evaluate parents' attitudes towards rehydration methods used in pediatric emergency departments. DESIGN: 100 questionnaires were distributed to parents of children who visited emergency room due to gastroenteritis and suspected dehydration. RESULTS: 75 of the parents expected their child to get IV fluids. 49 of them would refuse to consider oral rehydration. 75 of the parents would refuse to consider insertion of nasogastric tube. Parents whose children were previously treated intravenously tended to be less likely to agree to oral treatment. Parents were more prone to decline oral rehydration if the main measurement of dehydration was the child's clinical appearance, clinical appearance with vomiting, or child's refusal to drink and were more likely to agree if the main measurement was diarrhea, diarrhea with clinical appearance, or clinical personnel opinion. CONCLUSIONS: This is the first study to examine parents' expectations. We found that in the majority of cases, parents' expectations contradict current guidelines. Efforts should be taken to educate parents in order to allow full implementation of the guidelines.

Chronic valproic acid intoxication.

Valproic acid intoxication may be associated with cerebral, cardiovascular, respiratory, gastrointestinal, and hematologic complications. We report a case of a 7-year-old girl, epilepsy-treated chronically with valproic acid, sulthiame, and clonazepam, who presented to the emergency room because of a global deterioration during the preceding 2 months, including poorer feeding and worsened general responsiveness. The girl was later diagnosed to have chronic valproic acid intoxication.

Do newborn infants of Ethiopian origin spit up more than other newborn infants?

BACKGROUND: Ethnic differences in the incidence of spitting up have not been reported. The nursing team at our well-baby nursery observed that newborn infants of Ethiopian origin appeared to spit up more than the others. OBJECTIVE: To determine whether there are such ethnic differences and what, if anything, is their clinical relevance. METHODS: Of the 3663 enrolled infants born at the Hillel Yaffe Medical Center during the 12 month study period, 55 were of Ethiopian origin and their medical records were retrospectively surveyed. The retrieved data were compared with those of 167 randomly selected non-Ethiopian newborns (controls). Exclusion criteria were preterm delivery, admission to the neonatal intensive care unit, and congenital birth defects. RESULTS: Newborn infants of Ethiopian origin spit up 57% more than control infants. The difference in the number of spit ups was more obvious when only the infants who spit up were compared (2.3 +/- 1.7 Ethiopian newborns vs. 1.5 +/- 0.9 controls, P=0.002), although the percentage of infants who spit up was the same in the two groups. There was no difference in weight gain, days of hospitalization, bilirubin levels or nutrition type between the groups. CONCLUSIONS: Infants of Ethiopian origin spit up more than the control newborn infants of non-Ethiopian origin, while other clinical parameters were similar. In the absence of other pathological signs, spitting up is a non-relevant clinical condition.

The effect of nose clip on exercise-induced bronchoconstriction in adolescents.

BACKGROUND: Oral breathing is considered to increase hyper-responsiveness of the airways. Data on the need for nose clip (NC) during exercise challenge test (ECT) in children and adolescents is scarce. Ouraim was to evaluate the role of NC during ECT in children and adolescents. METHODS: A prospective, cohort study; children referred for ECT were evaluated on two separate visits, with and without a NC. Demographic, clinical data and measurements of lung functions were recorded. Allergy and asthma control were evaluated by Total Nasal Symptoms Score (TNSS) and Asthma Control Test (ACT) questionnaires. RESULTS: Sixty children and adolescents (mean age 16.7 ± 1.1 years, 38% Female,) performed ECT with NC and 48 (80%) completed visit 2 (ECT without NC), 8.7 ± 7.9 days after visit 1. Following exercise, 29/48 patients (60.4%) with NC had a decline of ≥12% in forced expiratory volume in the first second (FEV1 ) (positive ECT) compared to only 16/48 (33.3%) positive tests without NC (p = 0.0008). Test result was changed in 14 patients from positive ECT (with NC) to negative ECT (no NC) and in only one patient from negative to positive. The use of NC resulted in greater FEV1 decline (median 16.3% predicted, IQR 6.0-19.1% predicted vs. median 4.5% predicted, IQR 1.6-18.4% predicted, p = 0.0001), and better FEV1 increase after bronchodil at or inhalation compared to ECT without NC. Higher TNSS scores did not predict higher probability to positive ECT. CONCLUSIONS: The use of NC during ECT increases detection rate of exercise induced bronchoconstriction during ECT in the pediatric population. These findings strengthen the recommendation of nasal blockage during ECT in children and adolescents.

Pediatric negative pressure pulmonary edema: Case series and review of the literature.

INTRODUCTION: Negative pressure pulmonary edema (NPPE) is a potentially life-threatening complication that develops rapidly following acute upper airway obstruction. The condition is rare, dramatic but resolves quickly. Prompt recognition and appropriate supportive treatment may prevent unnecessary investigations and iatrogenic complications. METHODS: We describe a spectrum of etiologies and clinical manifestation of pediatric NPPE in our center and review of previous publications. CONCLUSION: The etiology for the development of NPPE in children has shifted over the years. Although dramatic in presentation, this type of pulmonary edema often resolves quickly with minimal support.

The association between Attention-Deficit-Hyperactivity-Disorder (ADHD) symptoms and disease severity in people with Cystic Fibrosis (pwCF).

BACKGROUND: The hallmarks of Cystic fibrosis (CF), chronic infection and inflammation, require intensive daily treatment to maintain and improve quality of life and outcome. The incidence of Attention Deficit/Hyperactivity Disorder (ADHD) is increased in chronic inflammatory diseases. Previous studies suggested that the prevalence of ADHD in people with CF (pwCF) is higher than in the general population. The objective of this study was to evaluate the association between ADHD symptoms and parameters of CF disease severity, measured by demographic and clinical data. METHODS: Based on our previous study, the results of ADHD questionnaires and the MOXOCPT (continuous performance task) from 143 pwCF (7-68 years old) were analyzed and linked to patient data such as forced expiratory volume in 1 second (FEV1)%predicted, body mass index (BMI), number of pulmonary exacerbations, days of antibiotic (Abx) treatment and serum inflammatory markers. RESULTS: A positive correlation between FEV1 and ADHD questionnaire's score (p = 0.046) was observed in the children's group. Furthermore, BMI, white blood cells (WBC) count, and days of Abx treatment showed a positive correlation with some of the MOXOCPT parameters. CONCLUSION: There is an association between ADHD symptoms and some parameters of CF disease severity. These results highlight the need for an early diagnosis of ADHD in pwCF, which have the potential to improve their ability to deal with the burden of their disease and consequently their quality of life. Additional research is needed to understand the full spectrum of ADHD pathophysiology and the relationship with chronic inflammatory diseases such as CF.

Late better than early elective term Cesarean section.

AIM: Caesarean section (CS) deliveries have increased, mostly because of patient/obstetrician preference. Although CS decreases the risk of delivery-related injuries, it increases the risk for respiratory and neurological complications. Complication rates are reportedly higher for elective CSs for term infants performed at 37-38 gestational weeks than later. We investigated this difference in an Israeli cohort. METHODS: Data on all births in our medical centre during 2007-2009 were reviewed. Those on elective CSs for term infants were retrieved and divided into 'early' (37-38 gestational weeks) or 'late' (week 39 or later) groups whose epidemiological and outcome characteristics were compared. RESULT: Of the 12,276 births, 596 were early and 454 were late elective CSs. There were no differences in gender, ethnicity, Apgar score or length of hospital stay. Twenty-six infants from the early group and 11 infants from the late group were transferred to the neonatal intensive care unit. Within them, compared with all elective CSs, the morbidity rate was higher for the former infants than for the latter. CONCLUSION: Morbidity was higher among infants who were delivered at 37-38 gestational weeks by elective CS. We recommend postponing elective CSs to ≥39 weeks.

[Asymptomatic classical hereditary xanthinuria type 1].

We report on a girl who was diagnosed with classical hereditary xanthinuria due to an incidental finding of extremely low Levels of uric acid in the blood. The girl is compLetely asymptomatic. Hereditary xanthinuria is a rare autosomal recessive disease that usually causes early urolithiasis but may cause rheumatoid arthritis-like disease and even be associated with defects in the formation of bone, hair and teeth. In Israel it has mostly been described in patients of Bedouin origin. Throughout the world, only about 150 cases have been described; about two thirds of these patients were asymptomatic. Since the clinical presentation and age of symptom appearance are diverse, the case raises questions as to the required follow-up of these patients and as to whether a low oxalate diet should be initiated.

Reversible Bronchial Obstruction in Primary Ciliary Dyskinesia.

BACKGROUND: Inhaled bronchodilators are frequently used among patients with primary ciliary dyskinesia (PCD), although neither the effectiveness nor the prevalence of their use is known, due to the paucity of relevant studies. METHODS: This is a retrospective analysis of pre- and post-bronchodilator spirometry results, of patients with PCD from two centers. Correlations were examined of bronchodilator response, with asthma and atopy markers. RESULTS: Of 115 patients, 46 (40%) completed spirometry pre- and post-bronchodilation. Of these, 26 (56.5%) demonstrated reversible airway obstruction (increase in %FEV1 predicted ≥ 10%). Obstruction reversibility was not found to be associated with a family history of asthma, blood eosinophil level, elevated IgE, or atopy symptoms. Of the 46 patients who completed bronchodilator spirometry, 29 (63%) were regularly using bronchodilators and inhaled corticosteroids. CONCLUSIONS: More than half of patients with PCD presented with reversible airway obstruction, without any correlation to markers of personal or familial atopy. Inhaled bronchodilators and corticosteroid therapies are commonly used for treating PCD. Evaluating bronchodilator response should be considered, and its effectiveness should be further studied.

Functional capacity and quality of life in patients with vascular ring.

BACKGROUND: Vascular rings are congenital anomalies of the aortic arch that compress the trachea and esophagus and may require corrective surgery. Data about the long-term effects of vascular rings are scarce. We aimed to evaluate the long-term cardiorespiratory, exercise capacity, and quality of life of vascular ring patients. METHODS: A single center prospective study evaluating spirometry, echocardiography, six-minute walk test (6MWT), cardiopulmonary exercise testing (CPET), and quality of life questionnaire (SF36) in patients with a diagnosis of vascular ring, with or without corrective surgery. RESULTS: Twenty-seven patients participated (11.9 ± 6 years, 52% males). The most common diagnosis was double aortic arch (16 patients, 59%). Nineteen patients had corrective surgery (O) and 8 did not (NO). Pulmonary function tests were within normal range in both groups (FEV1 % predicted O = 87.6 ± 16.5, NO = 83 ± 10.8%). However, 11/27 had abnormal FEV1 , 5 had abnormal FVC, and 13 (48%) had flattening of the expiratory curve. 6MWD and oxygen uptake were similarly mildly reduced in both groups; (6MWD O = 80.1 ± 10.7% predicted, NO = 74.1 ± 10.9% and oxygen uptake O = 78.5 ± 23.2% predicted, NO = 73.4 ± 14.3%). Peak O2 pulse (V̇O2 /HR% predicted) was mildly reduced in the NO group (O = 88.4 ± 17.3%, NO = 75.8 ± 16.2%). Echocardiogram and SF36 scores were normal in all patients. CONCLUSIONS: Long-term evaluation of patients born with vascular rings revealed mild pulmonary impairment, reduction in 6MWD, and oxygen uptake. The NO group had also mild reduced peak O2 pulse. Larger, long-term studies assessing functional parameters in operated and non-operated patients are needed to assess disease/surgery limitation in patients with vascular rings. Clinical trial registration number: NCT04781738.

Factors associated with complicated pneumonia in children.

INTRODUCTION: Community acquired pneumonia (CAP) is a leading cause of morbidity in children, despite advances in health care and anti-pneumococcal vaccine. Complicated pneumonia accounts for a significant burden with prolonged hospitalization. Finding risk factors for complicated pneumonia may help in tailoring management. We aimed to identify risk factors for developing complicated pneumonia and need for intervention. METHODS: A retrospective single tertiary center study. Children admitted with a diagnosis of CAP and/or complicated pneumonia (parapneumonic effusion, empyema, necrotizing pneumonia, and lung abscess) on January 2001-March 2020 were included. Demographic, clinical, and laboratory parameters were collected using MDclone, a data acquisition tool. Risk factors for complicated pneumonia (on admission or during hospitalization) and risk for intervention were analyzed. RESULTS: A total of 6778 children with pneumonia were included; 323 arrived at the Emergency Department with complicated pneumonia while 232 developed a complication during hospitalization. Risk factors for complicated pneumonia (on admission or during hospitalization) were Arab ethnicity, cardiac disease, increased age, and CRP and low O2 Sat (OR = 2.236 p < .001, OR = 4.376 p < .001, OR = 1.131 p < .001, OR = 1.065 p < .001 and OR = 0.959 p = .029, respectively). O2 Sat was lower, while fever and CRP were higher in patients with complicated pneumonia requiring intervention. CONCLUSIONS: Identifying children at risk for complicated pneumonia may help in decision-making in the Emergency Department and during hospitalization. The increased risk of the Arab population for complicated pneumonia requires further understanding. Addressing the underlying socioeconomic and ethnic health inequities may help to decrease the disease burden in this population.

Reverse butterfly pattern image with eosinophilia: Effective treatment with benralizumab-A case report.

A 16-year-old adolescent presented with dry cough, fever, weight loss, night sweats, exercise intolerance, and eosinophilia. Computed tomography showed consolidations with "reverse butterfly" pattern. He responded well to corticosteroids but had frequent relapses. He became steroid dependent and developed steroid related morbidity. Benralizumab was prescribed with complete resolution of eosinophilia and lung infiltrates with no adverse effect.

Short- and long-term effects of fluticasone furoate/vilanterol in exercising asthmatic adolescents: A randomized and open label trial.

PURPOSE: Relvar® (fluticasone furoate [FF]/vilanterol [VI]) is a once-daily inhaler with bronchodilator effect lasting 24 h. Our aim was to investigate the short- and long-term effects of FF/VI on exercise-induced asthma (EIA) in adolescents. METHODS: Ninety-three adolescent asthmatics aged 12-18 years were referred for evaluation of EIA. Following a positive exercise challenge test (ECT), 22/44 were allocated to a single administration of salbutamol (400 µg) and 22/44 to FF/VI (92/22 µg) in a double-blind method. Thirty-five subjects were reassessed by repeat ECT 30-60 days of FF/VI. RESULTS: Median FEV1 change post-ECT at baseline was -22.8% predicted (interquartile range [IQR] -26.1 and -18.0) for salbutamol and -21.0 (IQR -30.7 and -16.8) for FF/VI. Following bronchodilator, FEV1 improved similarly in both groups. Repeat ECT following 30-60 days of FF/VI resulted in negative ECT in 33/35 subjects; the median decrease in FEV1 of these 35 subjects was 22.6% predicted (IQR 29-18) before, and 4.6% predicted (IQR 8.7-2.5) after 30-60 days of FF/VI treatment (p < 0.0001). CONCLUSIONS: FF/VI is effective in reversing EIA after 15 min in adolescents and in protecting EIA after 30-60 days in adolescents. Larger studies are needed to assess the effect of FF/VI on EIA.

Understanding the interplay between factors that influence bone mineral density in CF.

BACKGROUND AND OBJECTIVES: Multiple factors affect bone mineral density (BMD) in cystic fibrosis (CF). Our aim was to perform comprehensive analyses of parameters potentially contributing to BMD. METHODS: A prospective single-center study assessing BMD, and correlations with multiple parameters including pancreatic status, lung functions, 6-minute walk test (6MWT), clinical score (modified Shwachman-Kulczycki [SK] score), vitamin D, nutritional intake, hand grip strength (HGS), habitual physical activity (smart watches), and quality of life (SF-36 questionnaire). RESULTS: Forty CF patients, mean age 18.3 ± 8.1 years, forced expiratory volume in 1 second 74.7% ± 17.9% predicted. Fifteen (37.5%) and 11 (27.5%) had osteopenia and osteoporosis, respectively. BMD was similar in pancreatic sufficient (pancreatic sufficient [PS], n = 15) and insufficient (pancreatic insufficient [PI], n = 25); median hip z score -1.5 ((-2.7)-(+0.2)) vs -1.5 ((-3.5)-(+0.7)), P = .79; spine -0.8 ((-2.2)-(+2)) vs -1.2 ((-4.4)-(+1.5)), P = .39 in PS vs PI, respectively. BMD correlated with HGS (r = .72, P < .001 hip; r = .52, P = .001 spine) and fat-free mass index (r = .81, P < .001 hip; r = .63, P < .001 spine). BMD z score correlated weakly with SK score and moderately with SF-36 general health. Data from smart watches, nutrition questionnaires, and 6MWT did not correlate with BMD. In a multivariate model, age and SK score predicted spine z score BMD. CONCLUSIONS: A substantial number of CF patients have low BMD. Similar rates in PS and PI suggest that other factors, such as disease severity, may contribute to low BMD. SK and age, which can easily be obtained even with limited resources, were the best predictors of low BMD. Further larger multicenter studies are warranted to evaluate the contribution of multifactorial etiologies to low BMD in CF.