scholarly journals Disseminate Recurrent Folliculitis and Hidradenitis Suppurativa Are Associated Conditions: Results From a Retrospective Study of 131 Patients With Down Syndrome and a Cohort of 12,351 Pediatric Controls

2019 ◽  
pp. 187-194 ◽  
Author(s):  
Andrea Sechi ◽  
Alba Guglielmo ◽  
Annalisa Patrizi ◽  
Francesco Savoia ◽  
Guido Cocchi ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Hidradenitis Suppurativa ◽  
Control Group ◽  
Pilosebaceous Unit ◽  
Cutaneous Manifestations ◽  
Regional Center ◽  
Wide Range ◽  
Associated Conditions ◽  
The Mean

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent skin disease of the pilosebaceous unit characterized by protean manifestations. Several studies have found an increased incidence and earlier presentation of this disease in patients carrying trisomy 21. Patients with Down syndrome (DS) have a higher risk of developing a wide range of cutaneous manifestations, including HS and chronic folliculitis. Recently, disseminate recurrent folliculitis (DRF) has been reported as an atypical monosymptomatic feature of HS at its onset. Objective: To assess the prevalence of HS and DRF by comparing a cohort of patients carrying trisomy 21 vs pediatric controls. Methods: A retrospective 2-year monocentric clinical study was performed by collecting clinical data of 131 patients with DS, aged 4-36 years, followed at the Dermatology Unit and Down Syndrome Regional Center of Bologna University. Data were matched with those coming from 12,351 pediatric controls. Results: In DS patients, DRF and HS showed a prevalence of, respectively, 6.8% and 24.4%, while 5.3% of patients presented both diseases. In the control group the prevalence for HS+ and DRF+ was 0.5% and 1.2%, respectively, with a 0.14% of overlap cases. The association between HS and DRF proved to be statistically significant in both groups (P < 0.05). In the DS cohort the mean age of symptoms onset was 15.67 (SD: 2.29) years for HS and 13.11 (SD: 4.93) years for DRF. Buttocks were the most frequently affected body area for DRF followed by the inguinocrural area, while in HS buttocks were less frequently involved than groins and upper thighs. Conclusions: Because of the later onset of HS, patients with DRF at an early age should be monitored for the possible onset of HS in the apocrine-bearing areas.

Hidradenitis suppurativa: Wie die Partner von Betroffenen psychosozial beeinträchtigt werden

2021 ◽  
pp. 1-3
Author(s):  
Uwe Gieler
Keyword(s):  
Disease Severity ◽  
Social Life ◽  
Hidradenitis Suppurativa ◽  
Life Quality ◽  
Psychosocial Burden ◽  
Wide Range ◽  
The Family ◽  
The Mean ◽  
Moderate Effect

<b>Background</b>: Hidradenitis suppurativa is a debilitating disease related to a great psychosocial burden in affected patients and subsequently also people around them. Patients’ partners as caregivers may indirectly experience wide range of devastating effects of the disease on their emotional and social life. <b>Objective:</b> The purpose of this study was to determine the QoL impairment in HS patients’ partners and to identify its aspects that are affected the most. Correlation between QoL burden and disease severity, duration, sex, age and smoking was also assessed. <b>Methods:</b> A total of 50 HS sufferers were assessed according to disease severity and their partners’ QoL was determined using the Family Dermatology Life Quality Index questionnaire. <b>Results:</b> The mean FDLQI for patients’ partners was 8.7 ± 6.8 points, indicating generally a moderate effect of HS on their life. Quality of partners’ life correlated significantly with disease severity but no correlation was found according to other factors. <b>Conclusion:</b> Hidradenitis suppurativa is a highly psychologically devastating disease not only for patients but also for their partners. It occurred to diminish partners’ QoL mostly by increasing daily expenditure but also other problems were often reported. Clinicians should be aware of these psychosocial implications, in order to provide optimal therapy of HS affected families by a multidisciplinary specialized management addressing both, patients and their cohabitants simultaneously.

THE CUT-OFF POINT IN SUB-CLINICAL OBSESSIVE-COMPULSIVE RESEARCH

2000 ◽  
Vol 28 (3) ◽  
pp. 225-233 ◽  
Author(s):  
David Mataix-Cols ◽  
Julio Vallejo ◽  
Miquel Sànchez-Turet
Keyword(s):  
Selection Criteria ◽  
Methodological Issue ◽  
Theoretical Models ◽  
Control Group ◽  
Personality Measures ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Wide Range ◽  
The Mean ◽  
Selection Of

The question of which cut-off point would be more appropriate in the selection of sub-clinical obsessive-compulsive (OC) samples is an important methodological issue that has not been formally addressed, hence prompting the current study. Three groups of sub-clinical OC subjects, scoring 1, 1.5, and 2 standard deviations (SD) above the mean on the Padua Inventory, and a matched non-OC control group, were compared on various clinical and personality measures. As expected, the three sub-clinical groups had higher scores than the non-OC group on measures of OC symptoms (including obsessional slowness), depression, anxiety, and on personality measures of neuroticism, psychoticism, and obsessional traits. However, no significant differences were observed between the three sub-clinical groups on most measures, although the 2 SD group had higher scores on neuroticism and obsessional personality traits. It is concluded that a wide range of selection criteria can yield similar results that are interpretable within the current theoretical models of Obsessive-Compulsive Disorder (OCD). It is suggested that subjects with a diagnosis of OCD should be carefully excluded from sub-clinical studies. [A Spanish abstract follows the references.]

Down Syndrome from a Neurodevelopmental Perspective

2016 ◽  
Author(s):  
Hana D’Souza ◽  
Jamie Edgin ◽  
Annette Karmiloff-Smith
Keyword(s):  
Down Syndrome ◽  
Individual Differences ◽  
Trisomy 21 ◽  
Genetic Disorder ◽  
Developmental Time ◽  
Receptive Vocabulary ◽  
Chromosome 21 ◽  
Typically Developing ◽  
Altered Expression ◽  
Wide Range

This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Psychology. Please check back later for the full article. Down syndrome (DS; trisomy 21) is the most common genetic disorder associated with intellectual disability. It occurs in one out of every 700 to 1,000 live births. DS is caused by trisomy of human chromosome 21, which results in the altered expression of over 300 genes. This neurodevelopmental syndrome is characterized by distinctive facial dysmorphology and an uneven cognitive phenotype including relative strengths and weaknesses. Relative strengths include visual processing, receptive vocabulary, and social-emotional functioning (though performance in these domains generally falls below the level expected for typically developing individuals). Relative weaknesses include verbal working memory, expressive language, and motor ability. However, the phenotype of individuals with DS is far from homogeneous, and a wide range of individual differences is present at every level of description. On the genetic level, the trisomy can occur through different mechanisms at distinct developmental time points, and the expression of trisomy 21 may be modulated by different genes across individuals. On the level of the brain, individual differences in brain structure and/or function correlate with variation in cognition and behavior, including communication skills. Large individual differences can also be observed on the cognitive level. For example, while some toddlers with DS are nonverbal, others reach expressive vocabulary levels close to those of typically developing children. A wide range of individual differences has also been reported in other areas, including the motor domain, sleep, parent-child interaction, and medical and psychiatric comorbidities. In order to understand a neurodevelopmental syndrome such as DS, it is crucial to consider individual variations at multiple levels of description and the interactions between them over developmental time. A more complex, dynamic view that goes beyond a description of DS as a homogenous group is thus required.

scholarly journals Polymorphisms of the MTHFR Gene in Mothers of Children with Trisomy 21 (Down Syndrome) in a Polish Population

2019 ◽  
Author(s):  
Paulina Czechowicz ◽  
Malgorzata Malodobra-Mazur ◽  
Karolina Cukierska ◽  
Arleta Lebioda ◽  
Anna Jonkisz ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Venous Blood ◽  
Mthfr Gene ◽  
Chromosome 21 ◽  
Test Material ◽  
Control Group ◽  
Polish Population ◽  
Nucleotide Polymorphisms ◽  
Cellular Mechanisms

Abstract Background: Down Syndrome (DS) is the most frequent cause of intellectual disability. In 95% of cases, it is caused by simple trisomy of chromosome 21 resulting from nondisjunction of chromosomes in meiotic division. Currently, the molecular and cellular mechanisms responsible for the phenomenon of nondisjunction are unknown. In this paper, we evaluated the incidence of five single-nucleotide polymorphisms (SNPs) of the MTHFR gene in a population of Polish mothers who had given birth to children with trisomy 21 in comparison with a control group of women with healthy offspring. Methods: The test material comprised venous blood collected from mothers who had given birth to a child with Down syndrome (study group, n = 130) as well as from women who had given birth to children without trisomy 21 (control group, n = 88). DNA was isolated using a kit manufactured by Qiagen. Amplification was carried out using a Qiagen Multiplex PCR Kit (Qiagen); genotyping was performed using SNaPshot Genotyping MasterMix (Applied Biosystems). Results: No statistically significant differences were observed in the frequency of genotypes between the examined groups in terms of the polymorphisms of the MTHFR gene. Conclusions: In the studied Polish population, no relationship was found between the occurrence of particular genotypes of the MTHFR gene, i.e. 677CT, 1298AC, rs3737964, rs4846048, and rs1994798, in women and the birth of children with trisomy 21. The results contradict the validity of research on polymorphisms of the MTHFR gene as potential predisposing factors for the occurrence of trisomy 21 in children.

Prevalence of Aspirin Resistance among Jordanian Patients with Cardiovascular Disease

2017 ◽  
Vol 9 (02) ◽  
Author(s):  
Eman Elayeh ◽  
Mohammad Mohammad ◽  
Mohammad Fararjeh ◽  
Eman Abu-Rish ◽  
Islam Hamad ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Aspirin Resistance ◽  
University Hospital ◽  
Control Group ◽  
P Value ◽  
Clinical Predictors ◽  
Number Of Patients ◽  
Wide Range ◽  
Urinary Levels ◽  
The Mean

Introduction: Despite the wide range of aspirin indications, there is a considerable amount of patients do not respond to aspirin, who also are referred to as aspirin non-responders or aspirin resistant patients. Aims and objectives: This study was carried out to prospectively evaluate the prevalence of aspirin resistance in Jordanian patients with cardiovascular disease and further clarify the clinical predictors of aspirin resistance. Materials and methods: Biochemical aspirin response was assessed based on the measurements of urinary11-dehydro thromboxane B2 (11-dhTxB2) levels using FDA approved diagnostic kit. Patients taking aspirin (75-325mg) for at least 7 days were prospectively enrolled from all stable cardiac patients presenting at Jordan University hospital outpatient clinics. Results: Eighty six (86) patients were enrolled in this study. Another twenty four healthy individuals were enrolled to function as a control group. The mean urinary levels of 11- dhTxB2/creatinine were significantly lower almost 3- times in patients in the primary and secondary aspirin prevention group compared with the control group (1567.58 vs. 4236.19 pg/mg, p-value >0.005). Thirty-one patients were found to be aspirin resistant with a prevalence of 36%. Conclusion: Our findings of aspirin resistance are particularly important given the large number of patients using this medication for prevention of atherothrombotic events. These results indicate that aspirin resistance should be diagnosed so that individuals with no response to aspirin can receive an alternative or an additional antiplatelet therapy.

Changes in the responsiveness of parabrachial neurons in the arthritic rat: an electrophysiological study

1996 ◽  
Vol 76 (6) ◽  
pp. 4113-4126 ◽  
Author(s):  
N. Matsumoto ◽  
H. Bester ◽  
L. Menendez ◽  
J. M. Besson ◽  
J. F. Bernard
Keyword(s):  
Spontaneous Activity ◽  
Receptive Fields ◽  
Maximum Response ◽  
Oxygen Mixture ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Response Curves ◽  
Stimulus Response ◽  
Wide Range ◽  
The Mean

1. Rats rendered polyarthritic by injection of Mycobacterium butyricum into the tail were used as a model for the study of “chronic pain”. In such rats, anesthetized with halothane in a nitrous oxide-oxygen mixture, spontaneous activity and responses of parabrachial (PB) neurons to somatic stimulations were studied in comparison with those in a control group of healthy animals processed under the same experimental conditions. 2. The size of the somatic receptive field of PB neurons was similar in both arthritic and control groups. In the control group 13%, 55%, and 32% of the receptive fields were small, medium, and large, respectively. Similarly, in the arthritic group, 10%, 60%, and 30% of the receptive fields were small, medium, and large, respectively. 3. The spontaneous activity was significantly (P < 0.001) increased in the arthritic rats (0.1 < 3 < 16 Hz, n = 31; 10th percentile < median < 90th percentile) in comparison with the healthy rats (0.03 < 0.3 < 5 Hz, n = 22). 4. The sensitivity to mechanical stimuli was markedly increased in arthritic compared with healthy rats: 1) although PB neurons in normal rats never responded to innocuous stimuli, several PB neurons in arthritic rats responded to touch and/or joint movement; 2) the mean mechanical threshold decreased from 15.8 N/cm2 in normal rats to 5.9 N/cm2 in arthritic rats; 3) the mean pressure evoking 50% of the maximum response decreased from 34 N/cm2 in normal rats to 21 N/cm2 in arthritic rats; and 4) the intensity of the maximum response increased from 15.7 Hz in normal rats to 26.3 Hz in arthritic rats. 5. The mechanical encoding properties were clearly modified in arthritic rats compared with healthy rats. In this latter group, the PB neurons exhibited a clear capacity to encode mechanical stimuli in the noxious range: 1) the stimulus-response curves were always positive and monotonic until 48 N/cm2; and 2) the slope of the mean curve increased progressively from 2 to 8 N/cm2 before reaching a roughly linear maximum for a wide range of pressure (8-64 N/cm2) and plateauing beyond. In the arthritic rat, the PB neurons also encoded mechanical stimuli, but clearly from a lower pressure range: the slope of the mean curve was maximum and remained steep from the lowest pressure tested (1 N/cm2) up to 16 N/cm2; afterward the slope decreased progressively from 16 to 64 N/cm2 before plateauing. 6. The sensitivity to heat stimuli was only weakly modified. The thermal threshold was weakly, but significantly, increased from 44 degrees C in the normal rat to 45.8 degrees C in the arthritic rat. Other parameters for thermal modality were not changed, with the mean stimulus-response curves being similar in both arthritic and normal groups. 7. In conclusion, these experiments demonstrate that the activity of PB neurons is clearly changed in arthritic rats. These changes are reminiscent of some behavioral and electrophysiological modifications observed during arthritis. Considering the current literature, it is hypothesized that the PB relay could be responsible, at least in part, for several affective-emotional, behavioral, autonomic, and energy metabolism changes observed in arthritic rats.

scholarly journals Down Syndrome and Thyroid Gland

2006 ◽  
Vol 6 (3) ◽  
pp. 38-42 ◽  
Author(s):  
Mensuda Hasanhodžić ◽  
Husref Tahirović ◽  
Ljerka Lukinac
Keyword(s):  
Down Syndrome ◽  
Thyroid Function ◽  
Trisomy 21 ◽  
Thyroid Dysfunction ◽  
Clinical Symptoms ◽  
Screening Program ◽  
Mental Deficiency ◽  
Control Group ◽  
Adequate Treatment ◽  
Mental Fitness

Down Syndrome (DS) or trisomy 21 (T21) is the most frequent and the best known malformation syndrome associated with mental deficiency that appears in human,. Average incidence of this syndrome is about 1:700 newborns. Numerous researchers noted thyroid disorders in people with Down Syndrome but, clinical symptoms of thyroid dysfunction are difficult to separate from DS phenotype. The aim of this study was to examine the thyroid function in the patients with DS. Our results confirmed higher frequency of thyroid dysfunction in DS patients. Higher values of TSH were found in 60,34% of the examined DS patients, which is significantly higher value comparing with the control group (p<0,01). Compensated hypothyroidism was established in 27,92% of the examined DS patients, and most of those (63,23%) were younger than 6 years. The conclusions emphasize the necessity of implementation of thyroid function screening program in persons with DS, and the need for adequate treatment of its dysfunction. Thus, the symptoms of the disease would be alleviated and better physical and mental fitness ensured.

scholarly journals Cutaneous Manifestations of Thyroid Hormone Disorder

2019 ◽  
Vol 17 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Karuna Singh Sijapati ◽  
Arpana Rijal ◽  
Sudha Agrawal ◽  
Dhan Keshar Khadka ◽  
Robin Maskey
Keyword(s):  
Thyroid Hormone ◽  
Clinical Signs ◽  
Control Group ◽  
Major Health Problem ◽  
Cutaneous Manifestations ◽  
Major Health ◽  
Skin Changes ◽  
Normal Individuals ◽  
Nail Changes ◽  
Wide Range

Introduction: Thyroid hormone disorder (THD), a major health problem, is associated with a wide range of diseases. One of the organs, which  shows this wide range of clinical signs is the skin. Some dermatological findings may be the first symptoms of THD. Therefore, this study was planned to determine various cutaneous manifestations of THD that can be used as a diagnostic marker for THD. In Nepal due to lack of awareness, thyroid diseases may go unnoticed .So, cutaneous manifestations help in early diagnosis and treatment of THD. Objectives: To identify cutaneous manifestations of THD and to evaluate dermatological manifestations specific for THD.  Materials and methods: Seventy six patients with diagnosis of THD attending endocrine clinic of Internal Medicine Department in BPKIHS, Dharan were consecutively assessed for cutaneous changes by detailed history and clinical examination. As a control group, 26 age and  sex matched individuals without THD were included to assess frequency of cutaneous manifestation in normal individuals.  Results: Fifty five (72.3%) cases and 4(15.4%) control had skin changes. This observation was statistically significant with OR-14.4(95% CI4.43 – 46.78) and p<0.001.Hair changes (OR-2.100, 95% CI 0.647-6.821 and p=0.210) and nail changes (OR-1.818, 95% CI 0.371-8.902 and p=0.726) had no statistically significant association with THD. Conclusion: THD may present as or be associated with many changes in skin, hair and nails.

scholarly journals AB0087 FEATURES OF ANTIPHOSPHOLIPID ANTIBODIES SPECTRUM IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1343.1-1344
Author(s):  
N. Bashlakova ◽  
T. Tyabut ◽  
A. Buglova ◽  
A. Trushyna
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Disease Duration ◽  
Control Group ◽  
Frequency Of Occurrence ◽  
Igm Antibodies ◽  
Wide Range ◽  
The Mean

Background:Currently, some data have been accumulated on the participation of antiphospholipid antibodies (aPL) in the development of thrombotic complications in patients with autoimmune rheumatic diseases (ARD), in particular, in patients with systemic lupus erythematosus (SLE). The most studied aPL in this pathology are IgG and IgM antibodies to cardiolipin (aCL), anti-β2-glycoprotein 1 antibodies (aβ2-GP 1), lupus anticoagulant (LA). The participation of IgG and IgM antibodies to prothrombin (aPT) and to annexin V (aAnV), antibodies to oxidized low density lipoproteins (aOxLDL) in hypercoagulation and the development of thrombosis is also discussed. However, the studies focusing on the investigation of aPL in patients with rheumatoid arthritis (RA) are few.Objectives:To estimate the levels and the frequency of occurrence of aPL in patients with RA in comparison to the SLE patients and the control group.Methods:The study included 85 female patients with ARD (RA (n=45), mean age 43,0 (33,0; 52,0) years old, disease duration 9,0 (5,0; 13,0) years, disease activity (DAS28= 5,37 (4,69; 5,89) points) and SLE (n=40), mean age 33,5 (27,5; 44,5) years old, disease duration 8,0 (5,0; 14,5) years, disease activity SLEDAI-2K 7,0 (4,0; 11,5) points). Fifty four healthy women (mean age 38,5 (35,0; 46,0) years old) formed the control group.The levels of antiphospholipid antibodies (IgG/IgM aCL, aβ2-GP 1, aAnV and aPT, aOxLDL) were determined with ELISA according to the instruction of a manufacturer. LA was determined by one-stage clotting assay using reagents for screening and confirmation (Technoclot LA Screen and Technoclot LA Confirm, Austria).Results:The frequency of occurrence of elevated levels of all investigated aPL in patients with RA was similar to SLE patients and was revealed in 57,8% of cases for IgG/IgM aCL, 44,4% for IgG/IgM aβ2-GP-1, 26,7% for IgG/IgM aAnV, 8,9% for aPT, 52,6% for LA, 64,4% for aOxLDL. The patients with SLE had an increased levels of IgG/IgM aCL in 60,0% of cases, IgG/IgM aβ2-GP-1 in 57,5%, IgG/IgM aAnV in 15,0%, IgG/IgM aPT in 17,5%, high levels of LA in 68,8%, of IgG aOxLDL – in 80,0% of cases. The control group had a high levels of IgG/IgM aCL in 1,8%, IgG/IgM aβ2-GP-1 in 3,7%, IgG/IgM aAnV in 5,6%, IgG/IgM aPT in 1,8%, high levels of IgG aOxLDL – in 42,6% of cases. None of the controls had an increased level of LA. The frequency of occurrence of elevated levels of aPL and their mean levels in both groups of patients with ARD was higher as compare to the control group (р<0,05).The mean levels of IgG aβ2-GP-1, LA, aOxLDL in SLE patients and mean levels of LA, aOxLDL in RA patients were above standard values but were similar in both groups. Moreover, the mean levels of IgG aCL, IgM aβ2-GP-1, IgG/IgM aAnV and aPT were comparable in patients with SLE and RA. However, the mean levels of IgM aCL in RA patients was higher than in SLE patients. This may indicate an increased autoimmune activity.Simultaneous elevation in four types of aPL levels was observed in 4,4% patients with RA, in 2,5% - with SLE; simultaneous elevation in three types of aPL was reveled in 11,1% patients with RA, in 17,5% - with SLE; two types of aPL were increased in 35,6% patients with RA and 27,5% - with SLE. Only one type of elevated aPL levels (12,9%) was indentified in the control group.Conclusion:Thus, patients with RA are characterized by a wide range of aPL. Qualitative and quantitative changes in the levels and types of autoantibodies in patients with RA have been established similar to those in SLE patients.In patients with autoimmune rheumatic pathology, the presence of simultaneously elevated several types of aPL have been proved.Disclosure of Interests:None declared

scholarly journals Comparison of COVID-19 and Non-COVID-19 Pneumonia in Down Syndrome

2021 ◽  
Vol 10 (16) ◽  
pp. 3748
Author(s):  
Diego Real de Asua ◽  
Miguel A. Mayer ◽  
María del Carmen Ortega ◽  
Jose M. Borrel ◽  
Teresa de Jesús Bermejo ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Cohort Study ◽  
Trisomy 21 ◽  
Retrospective Cohort ◽  
Mortality Rates ◽  
Research Society ◽  
Clinical Database ◽  
Increased Risk ◽  
The Mean ◽  
Disease Specific

Whether the increased risk for coronavirus disease 2019 (COVID-19) hospitalization and death observed in Down syndrome (DS) are disease specific or also occur in individuals with DS and non-COVID-19 pneumonias is unknown. This retrospective cohort study compared COVID-19 cases in persons with DS hospitalized in Spain reported to the Trisomy 21 Research Society COVID-19 survey (n = 86) with admissions for non-COVID-19 pneumonias from a retrospective clinical database of the Spanish Ministry of Health (n = 2832 patients). In-hospital mortality rates were significantly higher for COVID-19 patients (26.7% vs. 9.4%), especially among individuals over 40 and patients with obesity, dementia, and/or epilepsy. The mean length of stay of deceased patients with COVID-19 was significantly shorter than in those with non-COVID-19 pneumonias. The rate of admission to an ICU in patients with DS and COVID-19 (4.3%) was significantly lower than that reported for the general population with COVID-19. Our findings confirm that acute SARS-CoV-2 infection leads to higher mortality than non-COVID-19 pneumonias in individuals with DS, especially among adults over 40 and those with specific comorbidities. However, differences in access to respiratory support might also account for some of the heightened mortality of individuals with DS with COVID-19.

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