Effect of procalcitonin on the severity and prognostic value of elderly patients with a severe infection of oral and maxillofacial space.

This study aimed to investigate the effect on the severity and prognostic value of serum procalcitonin for elderly patients with oral and maxillofacial infections. We divided 163 elderly patients with severe oral and maxillofacial infection into survival and death groups according to the prognosis between June 2015 and May 2021, measured serum procalcitonin by enzyme-linked immunosorbent assay on the 1st, 2nd, 3rd, 5th, and 7th day after admission for the dynamic changes of serum procalcitonin level, collected the general physiological and biochemical indexes for the scores of acute physiology and general chronic condition, compared the correlation between serum procalcitonin, mean platelet count and APACHE score, analyzed the prognostic value of serum procalcitonin levels at different time after admission by ROC curve. The serum procalcitonin level increased significantly in both groups after admission, sharply increased at first and then rapidly decreased in the survival group, and continued to rise or declined slowly with fluctuation of high level in the death group. There was a negative correlation between serum procalcitonin level and mean platelet count (r = -0.698, P < .05) and a positive correlation between serum procalcitonin and APACHE II (R = 0.803, P < .05). The ROC curve showed that the serum procalcitonin level had little value on the first day and great value on the third day in predicting the prognosis of elderly patients with severe oral and maxillofacial infection (PCT1d = 0.539, PCT3d = 0.875, P < .05). The serum procalcitonin level is correlated with the severity of the disease in elderly patients with severe oral and maxillofacial space infection. Dynamic observation of it is helpful for the prognosis judgment of patients. After admission, serum procalcitonin level on the third day has a great value for the prognosis judgment of elderly patients with severe oral and maxillofacial space infection.

Case Report: Severe Dental Abscess Complications in Rural Sierra Leone.

Prevalence data on severe dental infections is scarce, particularly for low-income countries. Patients with dental abscess complications who presented from September 2020 until December 2020 in two hospitals in Tonkolili District, Sierra Leone, were included into this case series. We report on a total of 20 patients, median age 28 years, with severe complications of dental abscesses, with a mortality rate of 45%. This case series illustrates the severity of the dire consequences of the absence of access to basic dental and oral healthcare.

Poor oral health and mortality in geriatric patients admitted to an acute hospital: an observational study.

BACKGROUND: Poor oral health at hospital admission is a potential higher mortality risk predictor. We aimed to determine in-hospital mortality by assessing poor oral health using a validated tool. METHODS: A retrospective observational study was conducted in an acute care hospital, and 624 consecutive geriatric patients were included. Patients were divided into three groups according to oral health, stratified by the Oral Health Assessment Tool (OHAT) scores. Nutritional status, daily living activities, cognitive impairment, and comorbidities were collected as covariates. Univariate and multivariate analyses were performed to identify the relationship between oral health and survival. RESULTS: The mean age was 83.8 ± 7.9 years, and 41% were males. Groups with an OHAT score equivalent to 0, 1-2, and ≥ 3 comprised 213, 206, and 205 patients, and 11 (5.2%), 13 (6.3%), and 37 (18.0%) of those patients died in the hospital, respectively. Patients in the OHAT score ≥ 3 group had higher mortality than those in the other groups (log-rank test: p = 0.012 for the OHAT = 0 group; p = 0.010 for the OHAT = 1-2 group after Bonferroni corrections). Patients in the OHAT score ≥ 3 group continued to have poor survival even after adjusting for confounders in the Cox's regression analysis (hazard ratio: 2.514, 95% confidence interval: 1.220-5.183, p = 0.012). CONCLUSION: In geriatric patients, poor oral health at hospital admission was an independent in-hospital mortality predictor. Future studies on oral care intervention stratified by oral health conditions are warranted.

Dissociations of oral foci of infections with infectious complications and survival after haematopoietic stem cell transplantation.

INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) recipients are at increased risk for severe infections. This study examined the associations of common oral infections with survival and infectious complications in HSCT recipients. MATERIALS AND METHODS: All autologous and allogeneic HSCT recipients transplanted in the University Hospital of Basel, Switzerland, between 2008 and 2016 and referred to oral infection control pre-HSCT were included in this retrospective case-control study. All patients had a clinical and a panoramic radiological dental examination taken immediately prior to HSCT. Presence of acute or chronic oral foci of infections, decayed, missing or filled tooth index (DMFT) and radiological attachment loss (RAL) were examined. Survival and infections of the subjects were followed up for 6 months post-HSCT. RESULTS: Altogether 341 allogeneic and 125 autologous HSCT recipients were included in the study. Within 6 months post-HSCT, 47 (14%) of the allogeneic and 4 (3%) of the autologous recipients died. Oral foci of infections (acute or chronic), DMFT or periodontitis pre-HSCT were not associated with survival 6 months post-HSCT. Oral foci of infections were also not associated with hospital treated infectious diseases or blood culture positive bacteremia during the 6 month follow-up period. Untreated oral foci of infections were not associated with survival or severe infectious complications within 6 months post-HSCT. CONCLUSION: The results of this study suggest that radical dental interventions to chronic oral infections could be postponed until post-HSCT.

Oral mucosal lesions and risk of all-cause and cardiovascular mortality in people treated with long-term haemodialysis: The ORAL-D multinational cohort study.

BACKGROUND: Chronic kidney disease is a risk factor for oral diseases, which may be associated with premature death. We evaluated the risk of all-cause and cardiovascular mortality associated with oral mucosal lesions in adults with kidney failure treated with long-term haemodialysis. METHODS: Oral mucosal lesions (herpes, ulceration, neoformation, white lesion, red lesion, oral candidiasis, geographical tongue, petechial lesions, and fissured tongue) were evaluated within the Oral Diseases in Haemodialysis (ORAL-D) study, a multinational cohort study of 4726 haemodialysis adults. We conducted cox regression analyses adjusted for demographic and clinical variables to evaluate the association with all-cause and cardiovascular mortality. RESULTS: Overall, 4205 adults (mean age 61.6 ± 15.6 years) underwent oral mucosal examination with 40% affected by at least one lesion. The prevalence of oral lesions was (in order of frequency): oral herpes 0.5%, mucosal ulceration 1.7%, neoformation 2.0%, white lesion 3.5%, red lesion 4.0%, oral candidiasis 4.6%, geographical tongue 4.9%, petechial lesions 7.9%, and fissured tongue 10.7%. During median follow-up of 3.5 years, 2114 patients died (1013 due to cardiovascular disease). No association was observed between any individual oral lesion and all-cause or cardiovascular mortality when adjusted for comorbidities, except for oral candidiasis, which was associated with all-cause mortality (adjusted hazard ratio 1.37, 95% CI 1.00 to 1.86) and cardiovascular mortality (adjusted hazard ratio 1.64, 95% CI 1.09 to 2.46). CONCLUSION: Oral mucosal lesions are prevalent in haemodialysis patients. Oral candidiasis appears to be a risk factor for death due to cardiovascular diseases.

Oral health in relation to all-cause mortality: the IPC cohort study.

We evaluated the association between oral health and mortality. The study population comprised 76,188 subjects aged 16-89 years at recruitment. The mean follow-up time was 3.4 ± 2.4 years. Subjects with a personal medical history of cancer or cardiovascular disease and death by casualty were excluded from the analysis. A full-mouth clinical examination was performed in order to assess dental plaque, dental calculus and gingival inflammation. The number of teeth and functional masticatory units <5 were recorded. Causes of death were ascertained from death certificates. Mortality risk was evaluated using Cox regression model with propensity score calibrated for each oral exposure. All-cause mortality risk were raised with dental plaque, gingival inflammation, >10 missing teeth and functional masticatory units <5. All-cancer mortality was positively associated with dental plaque and gingival inflammation. Non-cardiovascular and non-cancer mortality were also positively associated with high dental plaque (HR = 3.30, [95% CI: 1.76-6.17]), high gingival inflammation (HR = 2.86, [95% CI: 1.71-4.79]), >10 missing teeth (HR = 2.31, [95% CI: 1.40-3.82]) and functional masticatory units <5 (HR = 2.40 [95% CI 1.55-3.73]). Moreover, when ≥3 oral diseases were cumulated in the model, the risk increased for all-cause mortality (HR = 3.39, [95% CI: 2.51-5.42]), all-cancer mortality (HR = 3.59, [95% CI: 1.23-10.05]) and non-cardiovascular and non-cancer mortality (HR = 4.71, [95% CI: 1.74-12.7]). The present study indicates a postive linear association between oral health and mortality.

Oral Health and Mortality in Patients With Chronic Kidney Disease.

BACKGROUND: Factors related to mortality of patients with chronic kidney disease (CKD) were investigated to find out whether oral disease inflammatory burden or different etiology (diabetes nephropathy vs. other etiologies) of CKD could be associated with mortality. METHODS: This prospective cohort study comprised 144 adults at the predialysis stage. Clinical oral and radiologic examination was made from 2000 to 2005. Patients were followed up until August 2015 (complete follow-up time: 157 months). Cause of death could be verified from 62 of 65 patients. Clinical health data were combined with mortality records obtained from the Finland national statistics database. Number of teeth, total dental index (TDI), and periodontal inflammatory burden index were calculated to describe degree of oral inflammation. RESULTS: Primary causes of death were cardiovascular diseases, infection, and cancer. There was a statistically significant difference in survival between diabetic nephropathy (23.8%) and other patients with CKD (59.9%; log-rank test P <0.001). A Cox regression model showed fewer teeth, higher age, and diabetes mellitus were statistically significant independent risk factors for death. Deceased patients had fewer teeth (P <0.001) and higher TDI (P <0.05). CONCLUSIONS: Risk of death was higher among patients with diabetic nephropathy. The deceased had fewer teeth and more oral infections. However, indices used failed to show independent association with survival.

[Non-communicable disease and their significance for dental medicine]. / Nicht übertragbare Krankheiten und ihre Bedeutung für die Zahnmedizin.

Non-communicable diseases (NCDs), such as cardiovascular diseases, chronic respiratory diseases, cancers, and diabetes mellitus, are responsible for most deaths worldwide. In view of the rising prevalence and the long-term consequences of NCDs, their prevention is a public health priority. Dentistry plays an important role in this endeavor. Since oral and general diseases share common risk factors (e.g., poor oral hygiene, unhealthy diet, alcohol abuse, tobacco consumption, distress), preventive measures may target both oral diseases (e.g., dental caries, periodontal diseases, oral tumors) and medical NCDs. Consequently, dental medicine assumes an important medical and social role, which has been recognized by the World Health Organization and the General Assembly of the United Nations. To fulfill its mission successfully, consideration of the principles of evidence-based dentistry is a prerequisite. At the same time, the new development provides dentistry with the opportunity to critically reflect on its current and future orientation.

[Social inequalities in the occurrence of chronic diseases]. / Soziale Ungleichheiten beim Auftreten chronischer Krankheiten.

The risks of the occurrence of most chronic diseases are unequally distributed. The highest risks occur in men and women with the lowest incomes, the lowest educational qualifications, and in occupations with the lowest decision latitude. Education, occupational position, and income as indicators of socio-economic position differ with regard to their latent content and can thus not be considered to be interchangeable. The relative magnitudes of their effects differ according to the diseases considered, but all three are not available in all studies. After an explanation of the latent content of the most frequently used indicators of social differentiation, health inequalities are considered by using four groups of chronic illnesses: oral, type 2 diabetes, cardiovascular diseases, and cancers. The description is not designed to be an exhaustive assessment of the available empirical findings, but rather a representative presentation of the results and the explanatory value of education, occupation and income.

Associations between oral complications and days to death in palliative care patients.

PURPOSE: Adverse oral symptoms gradually appear in advanced cancer patients as the disease progresses. We retrospectively investigated the associations between the incidence of oral problems and the days to death (DTD) in patients receiving palliative care. METHODS: The dental assessment sheets and medical charts of 105 patients who had been admitted into the palliative care unit at our hospital were examined. Case data included evaluations of organic and functional oral conditions at the time of admission for all patients. The cohort was divided into two groups according to the DTD as the short group (<28 days from the time of dental assessment until death) and the long group (≥28 days). We compared the incidences of organic and functional oral problems between these groups. RESULTS: Dry mouth, tongue inflammation, and bleeding spots were significantly more frequent in the short group than in the long group (78 vs. 54% for dry mouth, 67 vs. 46% for tongue inflammation, 35 vs. 14% for bleeding spots, respectively; p < 0.05). Tongue coating and candidiasis were comparable between the two groups. Dysphagia was significantly more common in the short group (43%) than in the long group (20%) (p = 0.01), as was assistance with oral health care (76 vs. 50%) (p = 0.01). CONCLUSIONS: Our findings suggest that, during palliative care, oral complications appear more frequently when the DTD period is shorter. These symptoms may be useful indicators when deciding on the proper timing of intensive oral care intervention to decrease oral problems and pain in terminally ill patients.

Oral disease in adults treated with hemodialysis: prevalence, predictors, and association with mortality and adverse cardiovascular events: the rationale and design of the ORAL Diseases in hemodialysis (ORAL-D) study, a prospective, multinational, longitudinal, observational, cohort study.

BACKGROUND: People with end-stage kidney disease treated with dialysis experience high rates of premature death that are at least 30-fold that of the general population, and have markedly impaired quality of life. Despite this, interventions that lower risk factors for mortality (including antiplatelet agents, epoetins, lipid lowering, vitamin D compounds, or dialysis dose) have not been shown to improve clinical outcomes for this population. Although mortality outcomes may be improving overall, additional modifiable determinants of health in people treated with dialysis need to be identified and evaluated. Oral disease is highly prevalent in the general population and represents a potential and preventable cause of poor health in dialysis patients. Oral disease may be increased in patients treated with dialysis due to their lower uptake of public dental services, as well as increased malnutrition and inflammation, although available exploratory data are limited by small sample sizes and few studies evaluating links between oral health and clinical outcomes for this group, including mortality and cardiovascular disease. Recent data suggest periodontitis may be associated with mortality in dialysis patients and well-designed, larger studies are now required. METHODS/DESIGN: The ORAL Diseases in hemodialysis (ORAL-D) study is a multinational, prospective (minimum follow-up 12 months) study. Participants comprise consecutive adults treated with long-term in-center hemodialysis. Between July 2010 and February 2012, we recruited 4500 dialysis patients from randomly selected outpatient dialysis clinics in Europe within a collaborative network of dialysis clinics administered by a dialysis provider, Diaverum, in Europe (France, Hungary, Italy, Poland, Portugal, and Spain) and South America (Argentina). At baseline, dental surgeons with training in periodontology systematically assessed the prevalence and characteristics of oral disease (dental, periodontal, mucosal, and salivary) in all participants. Oral hygiene habits and thirst were evaluated using self-administered questionnaires. Data for hospitalizations and mortality (total and cause-specific) according to baseline oral health status will be collected once a year until 2022. DISCUSSION: This large study will estimate the prevalence, characteristics and correlations of oral disease and clinical outcomes (mortality and hospitalization) in adults treated with dialysis. We will further evaluate any association between periodontitis and risk of premature death in dialysis patients that has been suggested by existing research. The results from this study should provide powerful new data to guide strategies for future interventional studies for preventative and curative oral disease strategies in adults who have end-stage kidney disease.

[Smokeless tobacco]. / Tabac non fumé

Use of smokeless tobacco (ST) (chewing tobacco and snuff) can lead to a number of consequences detrimental to health. ST rapidly delivers high doses of nicotine, which can lead to dependence and is also a source of carcinogenic nitrosamines. Changes usually develop in the mouth area where the ST is most often placed. Non-malignant oral lesions include leuko-oedema, hyperkeratotic lesions of the oral mucosa and localised periodontal disease. Oral premalignant lesions are leukoplakia, erythroplakia, submucosal fibrosis and lichen planus. Betel chewing, with or without tobacco, may increase the incidence of oral cancer. There is conflicting evidence with regard to snuff users about the risk of oral and gastro-oesophageal cancer. ST use is a risk factor for pancreatic cancer and may increase the risk of fatal myocardial infarction and ischemic stroke. During pregnancy, ST is associated with an increase in pre-eclampsia, preterm delivery and stillbirth. Nicotine replacement therapy and bupropion reduce withdrawal symptoms and tobacco craving during ST cessation. However, they have not been shown to help long-term abstinence. Information concerning the potential hazards of ST products should be incorporated into educational programmes to discourage its use and to help users to quit. Smokeless tobacco is not recommended to help smoking cessation.

Oral health profile of cirrhotic patients awaiting liver transplantation in the Brazilian Northeast.

BACKGROUND: Infections are a frequent cause of morbidity and mortality among postoperative liver transplant (OLT) patients and a leading cause of decompensated chronic liver disease (CLD) among patients awaiting the procedure. Oral lesions that are frequently observed in subjects with CLD may represent foci for systemic infections before and after OLT. AIMS: To evaluate the oral health profile of patients with CLD awaiting OLT. METHODS: One hundred thirty one patients including 100 males of overall mean age 49.5 ± 10.8 years with CLD were listed for OLT and examined for oral health status according to a established protocol. RESULTS: One hundred thirty (99%) patients were partially edentulous; 66 (51%) had chewing difficulties; and 63 (48%) experienced reduced salivary flow. With respect to periodontal disease and oral infections, 68 (25%) had periodontitis, 63 (48%) had periapical lesion, 64 (49%) had abscesses, and 59 (45%) had root fragments. Loss of follow-up was observed in 21 subjects. Among the 110 other patients, 63 (57%) underwent dental treatments with complications in only two cases. Interestingly, mortality was significantly lower among treated (31%) versus nontreated patient (79%; P<.001). CONCLUSIONS: Poor oral health status observed in most CLD patients may represent a source of systemic infections before and after OLT. Treatment of such lesions was feasible in the majority of the patients and seemed to be associated with a reduction in mortality.

Oral disease and subsequent cardiovascular disease in people with type 2 diabetes: a prospective cohort study based on the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial.

AIMS/HYPOTHESIS: While there are plausible biological mechanisms linking oral health with cardiovascular disease (CVD) and mortality rates, no study, to our knowledge, has examined this association in a representative population of people with type 2 diabetes. METHODS: We used the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study, a large, detailed, randomised controlled trial among a general population of individuals with type 2 diabetes. For the purposes of the present analyses, data from the trial are used within a prospective cohort study design. A total of 10,958 men and women, aged 55 to 88 years and with type 2 diabetes, participated in a baseline medical examination, during which they counted their number of natural teeth and reported the number of days that their gums had bled over the preceding year. Study members were followed up for mortality and morbidity over 5 years. RESULTS: After controlling for a range of potential confounding factors, the group with no teeth had a markedly increased risk of death due to all causes (HR 1.48, 95% CI 1.24-1.78), CVD (1.35, 1.05-1.74) and non-CVD (1.64, 1.26-2.13), relative to the group with the most teeth (≥22 teeth). Frequency of bleeding gums was not associated with any of the outcomes of interest. There was no suggestion that treatment group or sex modified these relationships. CONCLUSIONS/INTERPRETATION: In people with type 2 diabetes, oral disease, as indexed by fewer teeth, was related to an increased risk of death from all causes and of death due to CVD and non-CVD.

Longitudinal study of the prevalence and prognostic implications of oral manifestations in romanian children infected with human immunodeficiency virus type 1.

OBJECTIVE: We evaluated the prevalence and predictive value for human immunodeficiency virus (HIV) disease progression of oral manifestations in Romanian children. METHODS: A nonrandom sample of 238 HIV-infected children was followed prospectively between 1998 and 2001 at the Romanian-American Children's Center in Constanta, Romania. Study subjects underwent comprehensive annual oral examinations. Oral manifestations of interest, demographic data and other selected medical information were recorded at baseline and at each subsequent visit. Descriptive statistics and survival analysis methods were used in the study. A level of statistical significance of alpha = 0.05 was used. RESULTS: The study subjects' mean age was 9.9 +/- 1.2 (SD) years. The most common oral lesions were gingivitis (49%), parotid enlargement (13%) and oral candidiasis (11%). Oral candidiasis was associated with progression to acquired immunodeficiency syndrome or death (whichever occurred first) (log rank P = 0.03) and with death (log rank P < 0.001). Oral hairy leukoplakia also was associated with progression to death (log rank P = 0.001). The risk of dying was 3.43 (95% confidence interval, 1.86-6.34; P < 0.001) for children who had oral candidiasis at baseline and 4.62 (95% confidence interval, 1.67-12.77; P = 0.003) for those who had oral hairy leukoplakia. CONCLUSIONS: Oral manifestations occur commonly among HIV-infected Romanian children. Oral candidiasis and oral hairy leukoplakia were positive predictors of HIV disease progression.

Relationship between self-assessed masticatory disability and 9-year mortality in a cohort of community-residing elderly people.

OBJECTIVES: To examine the relationship between self-assessed masticatory disability and mortality. DESIGN: Prospective. SETTING: Community based. PARTICIPANTS: Total of 1,405 randomly selected people aged 65 and older living in Settsu, Osaka Prefecture, in October 1992. MEASUREMENTS: Data on health status as indicated by disability scores, history of health management, self-assessed masticatory ability, and psychosocial conditions were collected by means of interviews during home visits at the time of enrollment. Nine-year follow-up was completed for 1,245 (88.6%; 398 deceased and 847 alive). RESULTS: Self-assessed masticatory disability was significantly associated with being 75 and older, having overall disability, not using dental health checks or general health checks, not participating in social activities, not feeling that life is worth living (no ikigai), and finding relationships with people difficult. As for the association between self-assessed masticatory disability and mortality, the estimated survival rate for those with self-assessed masticatory disability was lower than that for those without for each group stratified by sex and age (65-74 and >or=75), and the equality of survival curves according to self-assessed masticatory disability was significant for each group. After controlling for potential predictors of mortality, self-assessed masticatory disability remained as a significant predictor of mortality (adjusted hazard ratio=1.63, 95% confidence interval=1.30-2.03, P<.001). CONCLUSION: These results indicate that self-assessed masticatory disability may be associated with a greater risk of mortality in community-residing elderly people.

Acquired immunodeficiency syndrome-related oral and/or cutaneous histoplasmosis: a descriptive and comparative study of 21 cases in French Guiana.

BACKGROUND: Oral or cutaneous acquired immunodeficiency syndrome (AIDS)-related histoplasmosis is a rare presentation of disseminated histoplasmosis. OBJECTIVE: To describe this clinical presentation and to compare it with other forms of AIDS-related disseminated histoplasmosis. METHODS: A cross-sectional study of patients with AIDS-related disseminated histoplasmosis was performed. CD4 counts and survival were compared between patients with oral or cutaneous histoplasmosis and patients with nonmucocutaneous disseminated histoplasmosis. RESULTS: The mean CD4 lymphocyte count was lower in patients with mucocutaneous lesions than in patients with nonmucocutaneous disseminated histoplasmosis (29 vs. 72/mm3, P = 0.002). The proportion of survivors 1 month after diagnosis did not differ significantly between the two groups (13/21 vs. 32/45, P = 0.4). At 6 months, the proportion of survivors was significantly lower for patients with mucocutaneous lesions (6/21 vs. 22/39, P = 0.03). CONCLUSIONS: These results suggest that mucocutaneous lesions occur at a later stage of human immunodeficiency virus infection, but are not, in themselves, associated with a higher level of mortality. The excess mortality at 6 months reflects deaths from other complications of severe immunodepression. This study confirms the polymorphism of mucocutaneous lesions, emphasizing the need for systematic testing for Histoplasma in all cases of mucocutaneous lesions in AIDS patients.

Discovery of a novel murine keratin 6 (K6) isoform explains the absence of hair and nail defects in mice deficient for K6a and K6b.

The murine genome is known to have two keratin 6 (K6) genes, mouse K6 (MK6)a and MK6b. These genes display a complex expression pattern with constitutive expression in the epithelia of oral mucosa, hair follicles, and nail beds. We generated mice deficient for both genes through embryonic stem cell technology. The majority of MK6a/b-/- mice die of starvation within the first two weeks of life. This is due to a localized disintegration of the dorsal tongue epithelium, which results in the build up of a plaque of cell debris that severely impairs feeding. However, approximately 25% of MK6a/b-/- mice survive to adulthood. Remarkably, the surviving MK6a/b-/- mice have normal hair and nails. To our surprise, we discovered MK6 staining both in the hair follicle and the nail bed of MK6a/b-/- mice, indicating the presence of a third MK6 gene. We cloned this previously unknown murine keratin gene and found it to be highly homologous to human K6hf, which is expressed in hair follicles. We therefore termed this gene MK6 hair follicle (MK6hf). The presence of MK6hf in the MK6a/b-/- follicles and nails offers an explanation for the absence of hair and nail defects in MK6a/b-/- animals.