Serum parathyroid hormone and active vitamin D in chronic periodontitis.

OBJECTIVES: To study the association between periodontitis and serum parathyroid hormone (PTH) and the response of PTH to periodontal therapy in type 1 diabetic patients (T1DM). We also investigated the PTH-1,25(OH)2 D axis in the T1DM group. METHODS: Periodontal health status was recorded in 54 periodontitis patients and 30 periodontally healthy controls (case-control data). Data were also collected from patients with type 1 diabetes mellitus at the baseline (n = 76) and after periodontal therapy (intervention data) (n = 53). RESULTS: Periodontitis was not associated with serum PTH in the case-control data or at the baseline of the intervention data. A post-therapy increase in serum PTH was found in 61% of the T1DM patients; in patients with moderate or severe periodontitis (n = 26) the average increase was 0.6 pmol/l (p = 0.016) and in patients with no or mild periodontitis (n = 27) 0.2 pmol/l (p = 0.250). In 47% of the T1DM patients, an increase in PTH was associated with an increase in serum 1,25(OH)2 D. CONCLUSION: An association between serum PTH and periodontal infection was found only after periodontal therapy in T1DM patients. This post-treatment response in serum PTH may partly explain the previously reported increase in serum 1,25(OH)2 D.

Serum osteoprotegerin and periodontal destruction in subjects with type 1 diabetes mellitus.

AIM: Besides their role in bone metabolism, receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) are also known to be associated with inflammation. We explored associations between the extent/severity of periodontitis and circulating levels of sRANKL and OPG and their ratio using a cross-sectional study design. SUBJECTS & METHODS: The extent of periodontal inflammation and tissue destruction and the serum levels of sRANKL (pg/ml) and OPG (pg/ml) were determined in 80 subjects with type 1 diabetes mellitus (T1DM). Plaque-, age-, gender-, smoking-, HbA1c- and body mass index-adjusted associations between periodontal parameters and serum sRANKL, OPG and their ratio were studied using multiple linear regression analysis. RESULTS: Adjusted regression analyses of all the subjects indicated a significant positive association between AL ≥ 4 mm and severity of periodontitis and the level of serum OPG. A major drop in the strength and statistical significance of the above association was observed when the analyses included only non-smokers. Serum sRANKL level and sRANKL/OPG ratio were not associated with periodontitis. CONCLUSION: Our observations suggest that serum OPG may be an indicator of periodontal tissue destruction in T1DM.

Ten-year natural course of habitual snoring and restless legs syndrome in a population aged 61-63 years at the baseline.

PURPOSE: We investigated the prevalence, natural course, and associated risk factors of habitual snoring (HS) and restless legs syndrome (RLS) over a period of 10 years among an aging population from their early sixties to their seventies. METHODS: A population-based follow-up study among all persons born in 1935 and living in the city of Oulu in northern Finland was conducted. In this study, we examined subjects who had participated in two subsequent surveys conducted in 1996-1998 and 2007-2008. The data were gathered by questionnaires, as well as by laboratory and clinical measurements. RESULTS: Altogether 457 (55%) of the 838 eligible subjects participated in both surveys. The prevalence of both RLS and HS decreased during the 10 years from 21% to 15% and from 26% to 19%, respectively. Half of those who snored in 1996-1998 stopped snoring in 10 years time, and half of those who suffered from restless legs at least three times per week in 1996-1998 suffered from this syndrome never or less than once a week in 2007-2008. The 10-year incidence of new cases of both HS and RLS was 7%. Male gender predicted best the incidence of new HS in 10 years, while the Zung sum score as a marker of depressive symptoms and waist circumference predicted RLS. CONCLUSIONS: Overall, the prevalence of both HS and RLS seems to diminish during aging. The causes behind this still remain unknown and should be investigated with more sophisticated methods.

Heredity of food allergies in an unselected child population: an epidemiological survey from Finland.

The heredity of food allergies (FA) has not previously been addressed in a large unselected child population. Our target population comprised all children born from April 2001 to March 2006 resident in one province of South-East Finland (n c. 6000), as identified from the national population register. In a questionnaire survey conducted in 2005-2006, data were obtained on allergic manifestations (FA symptoms, atopic rash, allergic asthma, hay fever/pollen allergy, or animal allergy) in the biologic parents of 3800 children (64% of the total). Concurrently with the survey but independently of it, results of specific immunoglobulin E antibodies (sIgE), skin prick tests (SPT), and open food challenges (OFC) in the offspring were collected from patient records throughout the province. Up to the age of 4 yr, the incidences of any positive FA test, a positive SPT or sIgE for food items, and a positive OFC in these children were threefold higher if both parents reported having an allergic manifestation and twofold higher if either mother or father had such a manifestation when compared with children whose parents did not report any of these conditions. The estimated risk of any positive FA test increased by a factor of 1.3 (95% CI 1.2-1.4) for each additional allergic manifestation in the parents. Positive FA tests in the offspring were relatively strongly associated with the reports of allergic phenotypes and the number of these phenotypes in their biologic parents.

Real-life epidemiology of food allergy testing in Finnish children.

BACKGROUND: The cumulative incidence of parental-reported symptoms of food allergy (FA) during the first years of life is estimated to exceed 30%. However, the occurrence and determinants of FA testing in a general child population have remained unknown. METHODS: The study population comprised all 5920 children aged 0-4 yr in the province of South Karelia, Finland, identified from the nationwide population register. The study included a questionnaire survey and a retrospective collection of FA test results (skin prick tests, IgE antibodies, or open food challenges) from the patient records of the entire study population. The questionnaire and patient record data were linked together on an individual basis with the parents' permission. RESULTS: A total of 5849 FA tests had been performed on 961 children. By the age of 4 yr, the cumulative incidence of FA testing was 18% for any food item; 17% for essential items (milk, egg, cereals) and 9% for other food items. Essential food items had been tested in 90% of children who reportedly had a physician-diagnosed FA for these. The incidence of testing was 30% higher in boys than in girls and twofold higher among the offspring whose either or both parents reportedly had some allergic manifestation. CONCLUSIONS: A large proportion of children are subjected to FA testing in their early years. This result shows the need to evaluate the financial burden of FA testing and to improve current testing practices.

Serum high-density lipoprotein cholesterol level associated with the extent of periodontal inflammation in type 1 diabetic subjects.

AIM: High-density lipoprotein (HDL) cholesterol is known for its anti-inflammatory and antioxidant activities in protection against cardiovascular diseases. We investigated whether a protective association also exists between serum HDL and periodontal inflammation in type 1 diabetic subjects (T1DM). METHODS: Plaque and periodontal inflammation (bleeding and PD ≥ 4 mm) were examined in 80 subjects with T1DM. The serum levels of glycosylated haemoglobin (HbA1c, %) and HDL (mmol/l) were determined. Adjusted associations between inflammation and serum HDL were analysed using linear regression analysis. To study the linearity of the association, the subjects were categorized into HDL tertiles (I-III). RESULTS: A statistically significant negative association was observed between serum HDL level and the extent of bleeding and PD ≥ 4 mm. Subjects in HDL tertiles II and III (high HDL) presented significantly fewer inflamed sites when compared with the subjects in tertile I (low HDL), whereas no significant difference in the number of inflamed sites was observed between tertiles II and III. CONCLUSIONS: Based on the finding of a negative association between serum HDL and periodontal inflammation, HDL may be considered a marker of susceptibility to periodontal inflammation. A longitudinal study is needed to verify possible causal relationship between serum HDL and inflammation.

Serum interleukin-6 may modulate periodontal inflammation in type 1 diabetic subjects.

AIMS: To evaluate the associations between serum inflammatory biomarkers and periodontal inflammation in subjects with type 1 diabetes mellitus (T1DM). Our hypothesis was that local host responses may be modulated by the serum inflammatory mediators. MATERIAL AND METHODS: Plaque, bleeding on probing and probing pocket depth (PD) were examined in 80 T1DM subjects at the baseline and in 58 subjects 8 weeks after periodontal therapy. The levels of glycosylated haemoglobin, serum interleukin (IL)-6, ultrasensitive C-reactive protein and the lipid profile were measured at the baseline and after therapy. Stratification of the sample separately by smoking and body mass index (BMI) was performed. Adjusted associations between the levels of systemic biomarkers and periodontal parameters were studied using multiple regression models. RESULTS: The level of serum IL-6 was associated with the extent of bleeding and PD≥4 mm at the baseline in non-smokers and in subjects with BMI≤26 kg/m(2). These associations were also evident after periodontal therapy. Subjects with a high after-therapy IL-6 level presented poorer periodontal healing than those with a low level. CONCLUSIONS: The observed associations may be considered to be suggestive of a modulatory effect of IL-6 on host responses in T1DM subjects.

SKARP--A population-based cohort study of childhood food-associated symptoms perceived by parents and food allergies diagnosed by physicians: design, methods and participation.

BACKGROUND: Few epidemiological studies exist on food-associated symptoms and allergies in large unselected child populations. AIMS: To describe the design, methods and participation rate of the South Karelian Allergy Research Project (SKARP), a population-based epidemiological study on food-associated symptoms and physician-diagnosed food allergies. METHODS: The study population of 5,973 children born between 2001 and 2006 and resident in the province of South Karelia, Finland, was identified from the nationwide population register. The parents received a questionnaire to be returned at their child's annual visit to the child health clinic, where supplementary interviews were performed. Results of allergy tests (skin prick tests, immunoglobulin E antibodies and open food challenges) performed on participants and non-participants were collected from the relevant health care units in the area. RESULTS: Participation rates in the questionnaire study were 54% (644/1,194) among the parents of neonates and 69% (3308/4,779) among those of the children aged 1 to 4 years. Cooperation with the child health clinics and mailing of a reminder questionnaire improved participation by 8 and 10 percentage points, respectively. The final participation rate seemed to be unaffected by whether the child had or had not been tested for suspected allergy. CONCLUSIONS: A reasonably good participation rate and almost complete coverage of allergy tests were achieved thanks to successful cooperation with the child health clinics and test laboratories. This baseline study forms a representative database to estimate the occurrence of food-associated symptoms, physician-diagnosed food allergies and allergy testing in the general population.

Occurrence of parent-reported food hypersensitivities and food allergies among children aged 1-4 yr.

Food allergies (FAs) and hypersensitivities (FHSs) have rarely been studied in large unselected child populations. This population-based cross-sectional survey estimated the occurrence of FHS as perceived by parents and that of FA diagnosed by a physician among children aged 1-4 yr in south-eastern Finland. Before the scheduled annual follow-up visit to the local child health clinic, the parents of children who were born between 1 April, 2001 and 31 March, 2005, and living in the Province of South Karelia (data from Finnish Population Register) were mailed a questionnaire containing items on the child's background, physician-diagnosed FAs and FHSs perceived by the parents. The questionnaires were returned during the visit. Three thousand three hundred and eight (69%) out of the 4779 questionnaires were returned. The lifetime prevalence of physician-diagnosed FAs was 9%. In an additional 21%, FHSs were perceived by the parents only. In a further 19% at least one food item had been eliminated from the diet without any perception of symptoms, this proportion having a downward trend by age. Physician-diagnosed FAs were more common in boys than in girls. Cow's milk was the most commonly reported cause of food-associated symptoms (13% of all children). One-third of the children aged 1-4 yr suffered from food-associated symptoms, and in an additional fifth at least one food item had been eliminated from their diet, implying that every other child had possibly been subjected to some form of elimination diet.

Resolution of periodontal inflammation does not guarantee improved glycemic control in type 1 diabetic subjects.

OBJECTIVE: The aim of this study was to find out if periodontal therapy has any effect on glycemic control of type 1 diabetes mellitus (DM). SUBJECTS AND METHODS: The periodontal health status of 65 type 1 diabetic subjects was assessed at the baseline and 8 weeks after completion of periodontal therapy. Glycemic control was assessed on both visits by measuring the percentage of glycosylated haemoglobin (GHbA1c). The change in HbA1c (DeltaHbA1c) was assessed by using both a positive or negative change >or=0.5% and any change in HbA1c. RESULTS: The mean HbA1c level (+/-SD) of the whole study group was 8.6% (+/-1.5) at the baseline and 8.5% (+/-1.5) after treatment. Glycemic control improved during the study period in 23 subjects (35%) and worsened in 18 subjects (28%). Approximately 78% of the bleeding sites and 87% of the sites with probing depth >or=4 mm presented healing. DeltaHbA1c associated significantly with baseline HbA1c but not with baseline periodontal health status or periodontal healing. CONCLUSION: Regardless of a significant resolution of periodontal infection, a great majority of the subjects did not present any improvement in their glycemic control.

IL-6(-174) genotype associated with the extent of periodontal disease in type 1 diabetic subjects.

AIM: The aim of this study was to investigate whether genetic polymorphism in certain cytokine and receptor molecule genes and diabetic status associate with the extent of periodontal disease in type 1 diabetes mellitus (DM). MATERIAL AND METHODS: Eighty patients with type 1 DM participated. Visible plaque, bleeding on probing (BOP), probing pocket depth (PD) and attachment level (AL) were examined clinically and glycosylated haemoglobin (HbA1c) levels were used to assess the glycemic control of DM. CD-14, IL-6, TNF-alpha, IL-10, IL-1alpha, IL-1beta and TLR-4 gene polymorphisms were studied using the polymerase chain reaction (PCR). RESULTS: The 3-year HbA1c was good (<7.5%) in 16%, acceptable (7.5-8.5%) in 36% and poor (>8.5%) in 48% of the subjects. IL-6(-174) genotype and 3-year GHbA1c associated significantly with BOP and PD>or=4 mm, subjects with the GG genotype of the IL-6(-174) exhibiting more severe periodontal disease than those with the GC/CC genotype. After stratification by IL-6 genotype, associations between the extent of periodontal disease and 3-year HbA1c levels remained significant in subjects carrying the GC/CC but not the GG genotype. CONCLUSIONS: In addition to the HbA1c level, the IL-6(-174) genotype is a significant susceptibility factor for periodontal disease among type 1 diabetics.

Coffee consumption and mortality in a 14-year follow-up of an elderly northern Finnish population.

The present study assessed the relationship between coffee consumption and mortality in a home-dwelling elderly population. A population-based cohort of 817 men and women born in 1920 or earlier and living in northern Finland provided complete data on daily coffee consumption and other variables at the baseline examination in 1991-1992. Deaths were monitored through to the end of 2005 by national death certificates, resulting in 6960 person-years of follow-up. Hazard rate ratios for mortality by daily coffee intake were estimated by Poisson regression models adjusted for some known predictors of mortality. During 14.5 years of follow-up, 623 deaths occurred. The total mortality rate was inversely related to the number of cups (average volume, 125 ml) of coffee consumed daily. After adjustment for age, sub-period of follow-up, sex, marital status, basic educational level, previous occupational group, current smoking, BMI, history of myocardial infarction, self-rated health and presence of diabetes, cognitive impairment or physical disability, the estimated relative risk reduction of total mortality per an increment of one more cup of coffee per d reported at baseline was 4 (95% CI 0, 8) %. The observed associations between coffee consumption and mortality from CVD, cancer, and other or unknown causes, respectively, were qualitatively similar to that of total mortality but the estimates were less precise. The effect of coffee consumption at baseline appeared to attenuate after 10 years since the start of follow-up. The present study provides evidence for daily (caffeine-containing) coffee intake being inversely associated with mortality in the elderly.

Diabetes and impaired glucose metabolism is associated with more cold-related cardiorespiratory symptoms.

AIMS: Diabetes and impaired glucose metabolism cause metabolic, neural and circulatory disturbances that may predispose to adverse cooling and related symptoms during the cold season. This study assessed the prevalence of cold-related cardiorespiratory symptoms in the general population according to glycaemic status. METHODS: The study population consisted of 2436 men and 2708 women aged 45-74years who participated in the National FINRISK cold sub-studies in 2002 and 2007. A questionnaire assessed cold-related symptoms (respiratory, cardiac, peripheral circulation). Glycaemic status was determined based on fasting blood glucose, oral glucose tolerance tests or reported diagnosis of diabetes and categorized into normal glucose metabolism, impaired fasting blood glucose, impaired glucose tolerance, screening-detected type 2 diabetes and type 2 diabetes. RESULTS: Type 2 diabetes was associated with increased odds for cold-related dyspnoea [Adjusted OR 1.72 (95% CI, 1.28-2.30)], chest pain [2.10 (1.32-3.34)] and respiratory symptoms [1.85 (1.44-2.38)] compared with normal glucose metabolism. Screened type 2 diabetes showed increased OR for cold-related dyspnoea [1.36 (1.04-1.77)], cough [1.41 (1.06-1.87)] and cardiac symptoms [1.51 (1.04-2.20)]. Worsening of glycaemic status was associated with increased odds for cold-related dyspnoea (from 1.16 in impaired fasting glucose to 1.72 in type 2 diabetes, P=0.000), cough (1.02-1.27, P=0.032), chest pain (1.28-2.10, P=0.006), arrhythmias (0.87-1.74, P=0.020), cardiac (1.11-1.99, P=0.000), respiratory (1.14-1.84, P=0.000) and all symptoms (1.05-1.66, P=0.003). CONCLUSIONS: Subjects with diabetes and pre-diabetes experience more cold-related cardiorespiratory symptoms and need instructions for proper protection from cold weather to reduce adverse health effects.

Association of insulin resistance linked diseases and hair loss in elderly men. Finnish population-based study.

Previous investigations have shown an association of androgenetic alopecia (AGA) with insulin resistance related disorders such as ischemic heart disease. An association between AGA and anthropometric abnormalities linked with insulin resistance and heredity in women aged 63 years has also been shown. We therefore compared 63-year-old men with AGA and ones with normal hair status for insulin resistance linked parameters. A population of 245 men aged 63 years, who were participants in a population-based cross-sectional study in the City of Oulu, underwent a medical check-up including assessment of hair status on the Hamilton-Norwood scale and determination of anthropometric measures, blood pressure, fasting glucose and serum lipids. Fifty eight per cent of the men reported extensive hair loss (grade III-VII). Hypertension and the use of antihypertensive drugs were common among men with AGA (61% vs. 45% and 50% vs. 26%, respectively). The rates of diabetes and hyperinsulinemia (21% vs. 12% and 61% vs. 49%) were higher among men with AGA compared to those with normal hair status but no difference was seen in other factors. Our findings show that AGA is common among Finnish men aged 63 years but that it is also associated with insulin linked disturbances, such as hypertension and diabetes. Such men developing AGA might benefit from attention in medical check-up.

Ten-year mortality and glucose tolerance status in an elderly Finnish population.

The aim of this study was to determine the 10-year mortality rate of an elderly population aged 70 years or over (n=379) with reference to glucose tolerance status, taking into account other determinants of excess mortality. The baseline examination during 1991-1992 included a postal questionnaire, a physical examination and a 2h OGTT, which was classified according to both the 1985 WHO criteria and the 1999 WHO criteria. Follow-up was continued until death or until 31 December 2001. 66% of men and 51% of women died within 10 years. In men, the cumulative mortalities were 84% for previously diagnosed diabetes, 67% for undiagnosed diabetes, 67% for impaired glucose tolerance (IGT) and 60% for normal glucose tolerance (NGT). The corresponding percentages for women were 76, 52, 49, and 40%. Male gender, poor self-rated health and previously diagnosed diabetes were the most powerful predictors of mortality. When adjustments were made for age, gender, BMI, cardiovascular disease, hypertension, physical exercise and self-rated health, the estimated relative mortality rate was 2.0 (95% CI 1.5-2.7) among previously diagnosed diabetic subjects, 1.3 (CI 0.8-2.2) among undiagnosed diabetic subjects and 1.1 (0.8-1.5) among IGT subjects compared to NGT subjects. These relative mortalities were higher in women than in men. When abnormal glucose tolerance was pooled into one category, the OR for excess mortality was 1.4 (95% CI 1.1-1.9).

The relationship of glucose tolerance to sleep disorders and daytime sleepiness.

The purpose of the study was to find out if snoring, sleep apnea and daytime sleepiness are independent indices of obesity related to type two diabetes (T2D), and whether depression is independently associated with features of sleep apnea. A population-based cohort study was conducted among 593 subjects (245 men and 348 women) born in 1935 and living in Oulu in 1996-1998. Glucose status was determined with a standard 2h oral glucose tolerance test, and sleeping disorders were recorded on the Epworth sleepiness scale (ESS) and in a questionnaire of five questions about sleeping and snoring. Depression was measured by the Zung self-rated depression scale. Insulin sensitivity was measured by quantitative insulin sensitivity check index. Habitual snoring was more common in diabetic subjects than in subjects with impaired glucose regulation (IGR) or normal glucose tolerance (NGT). All sleep disorders associated with neck circumference, waist circumference and body mass index (BMI). There was also a relationship between impaired insulin sensitivity and habitual snoring in bivariate analysis. In multiple logistic regression analysis, depression associated independently with daytime sleepiness (OR 3.00, 95% CI 1.40-6.46). Type 2 diabetes (T2D) (OR 1.93, 95% CI 1.04-3.57) and smoking (OR 1.69, 95% CI 1.00-2.84) associated independently with habitual snoring. BMI (OR 1.20, 95% CI 1.09-1.34) and male gender (OR 2.61, 95% CI 1.05-6.72) associated independently with sleep apnea. In a multiple regression model, BMI, neck circumference and habitual snoring associated independently with T2D. Habitual snoring was associated with T2D and impaired insulin sensitivity. Daytime sleepiness seemed to be linked with depression but not with using sleep medication, IGR and T2D.

Health-related quality of life and physical well-being among a 63-year-old cohort of women with androgenetic alopecia; a Finnish population-based study.

BACKGROUND: The aim of this study was to assess the possible associations between female androgenetic alopecia (AGA), insulin resistance and health-related quality of life (HRQOL)-linked factors in women. We hypothesized that not only the mental aspects but also certain physical aspect of women's health, such as insulin resistance, have an important role in the determination of HRQOL among women with hair loss. METHODS: A population-based cohort of 330 healthy women aged 63 years, who participated in this study in the City of Oulu in Northern Finland, underwent a medical check-up including assessment of hair status on Ludwig's scale. Background data were collected with a standard questionnaire including a validated RAND 36-Item Health Survey (RAND-36) questionnaire. RESULTS: 105 (31%) women with AGA and 225 (69%) controls completed the RAND-36 questionnaire. The women with AGA were more insulin-resistant than the women with normal hair (QUICKI 0.337 vs. 0.346, p = 0.012). Impaired glucose regulation (IGR) was more prevalent among the former than the latter group (39% vs. 25%). The mean RAND-36 scores were significantly lower on the dimensions of physical functioning, role limitation due to physical health and general health, but not on the mental or social dimensions, among the women with AGA compared with the controls. In multivariate logistic regression analyses with the lowest quintiles of the HRQOL dimensions as the dependent variables and AGA, depression, marital status, education and IGR or QUICKI as independent variables, AGA was independently associated with role limitations due to physical health (2.2, 95% CI 1.20-4.05, 2.45 95% CI 1.32-4.55, respectively). CONCLUSION: In women aged 63 years, AGA was associated with role limitations due to physical health. Furthermore, the prevalence rates of IGR and insulin resistance measured by QUICKI were higher among the women with hair loss than those with normal hair.

Serum 1,25(OH)D level increases after elimination of periodontal inflammation in T1DM subjects.

OBJECTIVES: The aim of the present study was to investigate associations between serum concentrations of vitamin D metabolites, 25-hydroxyvitamin D [25(OH)D], and its active form, 1,25-dihydroxyvitamin D [1,25(OH)D], and the severity of chronic periodontitis. SUBJECTS AND DESIGN: Presence of dental plaque, probing pocket depth (PD), and attachment level in 80 type 1 diabetes mellitus subjects were recorded. The serum levels of 25(OH)D, 1,25(OH)D, ultrasensitive C-reactive protein, IL-6, TNF-α, high-density lipoprotein cholesterol, and glycosylated hemoglobin (percentage) were determined. Multivariate regression models were used to explore the associations between serum 25(OH)D (nanomoles per liter) and 1,25(OH)D (picomoles per liter) levels and periodontal health status. INTERVENTION: Antiinfective periodontal therapies were delivered and the clinical examination and laboratory analyses were repeated 8 weeks after the therapies. RESULTS: A statistically significant association was found between the serum level of 1,25(OH)D (odds ratio 1.06, 95% confidence interval 1.02-1.11) and periodontal health at the baseline; subjects with a high level were more likely to belong to the group of no or mild periodontitis. The serum level of 1,25(OH)D showed a statistically significant increase after antiinfective periodontal therapy in both no or mild (P = .001) and moderate or severe periodontitis (P < .001) subjects. The association between serum 25(OH)D level and periodontal health was negligible. CONCLUSION: This study has shown a significant positive association between the serum 1,25(OH)D level and periodontal health status. To what extent this association is causal in nature remains to be confirmed.