Effect of expiratory muscle strength training on voice and speech: An exploratory study in persons with Parkinson's disease or multiple sclerosis.

PURPOSE: This study explored how respiration, voice, and speech were affected following expiratory muscle strength training (EMST) and maintenance training in persons with Parkinson's disease (PD) or multiple sclerosis (MS). METHOD: Nine participants with PD and six with MS participated in a randomised study, where the effects of EMST, sham, and maintenance treatment were investigated. Outcome measures included maximum expiratory pressure (MEP); maximum phonation time (MPT); intelligibility; verbal diadochokinesis (DDK); speech rate; a self-report form on voice, speech, and communication; and open questions about how the participants experienced the intervention. Group comparisons were performed within and between groups. RESULT: The PD and the MS groups both improved significantly in MEP, and this improvement remained after 3 months of maintenance EMST. An improvement was also seen in DDK. Post-EMST, 33% of the PD group and 80% of the MS group reported a positive effect on communication. CONCLUSION: The results of this study support previous evidence that EMST has positive effects on expiratory pressure in persons with PD or MS, but its effect on voice and speech remains unclear. Since subjective reports of the intervention and effects on communication were predominantly positive, further research is needed on larger groups to explore appropriate outcome measures.

Orofacial dysfunction after stroke-A multidisciplinary approach.

OBJECTIVE: This paper describes the study protocol in an ongoing clinical trial evaluating oral screen training as part of a post-stroke rehabilitation programme. Baseline data were related to four domains: dysphagia, lip function, masticatory performance and patient-related outcome measures (PROM). BACKGROUND: Stroke is one of the most common causes of disability-adjusted life years, and dysphagia is a common remaining problem after stroke. Rehabilitation using oral screen training has been suggested to improve swallowing, but evidence is still insufficient. MATERIALS AND METHODS: Patients diagnosed with stroke with persisting objective and/or subjective swallowing dysfunction after primary rehabilitation were assessed for eligibility. In total, 25 patients were included. Objective function was assessed by swallowing capacity test (SCT), lip force and masticatory performance, subjective function by EAT-10 and NOT-S and PROM by LiSat-11 and ESAS. RESULTS: Baseline data presented a heterogeneous pattern with no significant association between objective and subjective dysfunction. Most of the participants (20/25) showed impaired swallowing capacity in SCT, and 23/24 revealed orofacial dysfunction according to NOT-S. The most common subjective item reported was chewing and swallowing problems (19/24). CONCLUSION: The heterogenous findings in the included tests and the lack of correlations emphasise the importance of multidisciplinary approaches to identify objective and subjective orofacial post-stroke dysfunction in clinical practice to be able to offer evidence-based individualised care. The included participants were representative of stroke patients with dysphagia, which supports proceeding with the planned intervention.

Free from Dysphagia? A Test Battery to Differentiate Between Mild and No Dysphagia.

Assessing mild oropharyngeal dysphagia (OD) raises the question where to draw the line between normal and pathological swallowing. There is a lack of clinical test methods appropriate in the subacute phase of recovery from dysphagia following stroke and other brain injuries. The aim of this pilot study was to investigate the diagnostic accuracy of a new test battery, called the Swallow Battery (SwaB), in relation to Fiberoptic Endoscopic Evaluation of Swallowing (FEES). SwaB consists of the validated tests Repetitive Saliva Swallowing Test (RSST), Timed Water Swallowing Test (TWST) and parts of the Test of Masticating and Swallowing Solids (ToMaSS). Nineteen adult patients with acquired brain injury who were enrolled in a rehabilitation programme underwent the SwaB and a FEES, both resulting in a pass or fail outcome. The pass or fail results were based on RSST's and TWST's suggested cutoffs, normative values of ToMaSS and on established rating scales used for FEES. The SwaB's ability to predict FEES results was 74% according to a binary logistic regression analysis, with a 92% correct prediction of fail results and 33% correct prediction of pass results. The ToMaSS was sensitive to small changes in eating ability, failing 13 out of 19 patients using 95% CI normative values as cutoff, including patients with a passed FEES. Alternative cutoffs were therefore suggested, depending on purpose of dysphagia assessment. The results of this study indicate that the SwaB may be a useful tool when assessing mild dysphagia following brain injury. Further studies of SwaB's validity and clinical utility are suggested.

Self-Reported Changes in Cognition, Communication and Swallowing in Multiple Sclerosis: Data from the Swedish Multiple Sclerosis Registry and from a National Survey.

PURPOSE: The aim of this study was to investigate self-reported cognition, speech, communication and swallowing changes in a large sample of individuals with multiple sclerosis (MS) in Sweden. A second aim was to update information about speech and language pathology (SLP) services received by people with MS (pwMS). METHOD: Self-ratings of cognition, speech/communication and swallowing registered by pwMS between 2012 and 2018 were retrieved from the Swedish MS Registry. In addition, more detailed information about speech, communication, swallowing and provision of SLP services was collected using an online survey distributed via a national patient organization. RESULTS: In total, entries from 5,289 pwMS were retrieved from the MS Registry. Nearly two thirds of the respondents reported that cognition was affected to some degree, whereas approximately one third perceived some difficulties with speech/communication. A smaller group reported swallowing problems. The majority of those who reported problems with speech/communication also reported problems with cognition. Among the 440 individuals who responded to the MS survey, word-finding difficulties were the most frequently self-reported problem related to communication, and the second most common problem was getting off topic. In all, close to four out of five respondents experienced at least one symptom related to speech and communication, such as speech-related fatigue or imprecise articulation. Swallowing difficulties were reported by one out of four respondents in the MS survey. As a result of their speech difficulties, up to one in three experienced changes in professional or social roles and participation. A limited number of respondents had received SLP services, the most common intervention being voice training. CONCLUSIONS: In MS, changes associated with cognition as well as speech/communication are frequent, cognitive-linguistic symptoms being the most common. Swallowing difficulties are also relatively prevalent. Access to SLP services seems to be insufficient compared to prevalence of perceived symptoms. Considering that the majority of pwMS are part of the working-age population, access to SLP services must be more highly prioritized and must address cognitive-linguistic problems as well as voice, speech and swallowing dysfunction.

Assessment of speech impairment in patients with Parkinson's disease from acoustic quantifications of oral diadochokinetic sequences.

This investigation aimed at determining whether an acoustic quantification of the oral diadochokinetic (DDK) task may be used to predict the perceived level of speech impairment when speakers with Parkinson's disease (PD) are reading a standard passage. DDK sequences with repeated [pa], [ta], and [ka] syllables were collected from 108 recordings (68 unique speakers with PD), along with recordings of the speakers reading a standardized text. The passage readings were assessed in five dimensions individually by four speech-language pathologists in a blinded and randomized procedure. The 46 acoustic DDK measures were merged with the perceptual ratings of read speech in the same recording session. Ordinal regression models were trained repeatedly on 80% of ratings and acoustic DDK predictors per dimension in 10-folds, and evaluated in testing data. The models developed from [ka] sequences achieved the best performance overall in predicting the clinicians' ratings of passage readings. The developed [pa] and [ta] models showed a much lower performance across all dimensions. The addition of samples with severe impairments and further automation of the procedure is required for the models to be used for screening purposes by non-expert clinical staff.

Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden.

Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.

Assessment of voice, speech and communication changes associated with cervical spinal cord injury.

BACKGROUND: Respiratory muscle impairment following cervical spinal cord injury (CSCI) may lead to reduced voice function, although the individual variation is large. Voice problems in this population may not always receive attention since individuals with CSCI face other, more acute and life-threatening issues that need/receive attention. Currently there is no consensus on the tasks suitable to identify the specific voice impairments and functional voice changes experienced by individuals with CSCI. AIMS: To examine which voice/speech tasks identify the specific voice and communication changes associated with CSCI, habitual and maximum speech performance of a group with CSCI was compared with that of a healthy control group (CG), and the findings were related to respiratory function and to self-reported voice problems. METHODS & PROCEDURES: Respiratory, aerodynamic, acoustic and self-reported voice data from 19 individuals (nine women and 10 men, aged 23-59 years, heights = 153-192 cm) with CSCI (levels C3-C7) were compared with data from a CG consisting of 19 carefully matched non-injured people (nine women and 10 men, aged 19-59 years, heights = 152-187 cm). OUTCOMES & RESULTS: Despite considerable variability of performance, highly significant differences between the group with CSCI and the CG were found in maximum phonation time, maximum duration of breath phrases, maximum sound pressure level and maximum voice area in voice-range profiles (all p = .000). Subglottal pressure was lower and phonatory stability was reduced in some of the individuals with CSCI, but differences between the groups were not statistically significant. Six of 19 had voice handicap index (VHI) scores above 20 (the cut-off for voice disorder). Individuals with a vital capacity below 50% of the expected for an equivalent reference individual performed significantly worse than participants with more normal vital capacity. Completeness and level of injury seemed to impact vocal function in some individuals. CONCLUSIONS & IMPLICATIONS: A combination of maximum performance speech tasks, respiratory tasks and self-reported information on voice problems help to identify individuals with reduced voice function following CSCI. Early identification of individuals with voice changes post-CSCI, and introducing appropriate rehabilitation strategies, may help to minimize development of maladaptive voice behaviours such as vocal strain, which can lead to further impairments and limitations to communication participation.

Perceptual Detection of Subtle Dysphonic Traits in Individuals with Cervical Spinal Cord Injury Using an Audience Response Systems Approach.

OBJECTIVES: Reduced respiratory function following lower cervical spinal cord injuries (CSCIs) may indirectly result in vocal dysfunction. Although self-reports indicate voice change and limitations following CSCI, earlier efforts using global perceptual ratings to distinguish speakers with CSCI from noninjured speakers have not been very successful. We investigate the use of an audience response system-based approach to distinguish speakers with CSCI from noninjured speakers, and explore whether specific vocal traits can be identified as characteristic for speakers with CSCI. METHODS: Fourteen speech-language pathologists participated in a web-based perceptual task, where their overt reactions to vocal dysfunction were registered during the continuous playback of recordings of 36 speakers (18 with CSCI, and 18 matched controls). Dysphonic events were identified through manual perceptual analysis, to allow the exploration of connections between dysphonic events and listener reactions. RESULTS: More dysphonic events, and more listener reactions, were registered for speakers with CSCI than for noninjured speakers. Strain (particularly in phrase-final position) and creak (particularly in nonphrase-final position) distinguish speakers with CSCI from noninjured speakers. CONCLUSIONS: For the identification of intermittent and subtle signs of vocal dysfunction, an approach where the temporal distribution of symptoms is registered offers a viable means to distinguish speakers affected by voice dysfunction from non-affected speakers. In speakers with CSCI, clinicians should listen for presence of final strain and nonfinal creak, and pay attention to self-reported voice function and voice problems, to identify individuals in need for clinical assessment and intervention.

Speech and Communication Changes Reported by People with Parkinson's Disease.

BACKGROUND: Changes in communicative functions are common in Parkinson's disease (PD), but there are only limited data provided by individuals with PD on how these changes are perceived, what their consequences are, and what type of intervention is provided. AIM: To present self-reported information about speech and communication, the impact on communicative participation, and the amount and type of speech-language pathology services received by people with PD. METHODS: Respondents with PD recruited via the Swedish Parkinson's Disease Society filled out a questionnaire accessed via a Web link or provided in a paper version. RESULTS: Of 188 respondents, 92.5% reported at least one symptom related to communication; the most common symptoms were weak voice, word-finding difficulties, imprecise articulation, and getting off topic in conversation. The speech and communication problems resulted in restricted communicative participation for between a quarter and a third of the respondents, and their speech caused embarrassment sometimes or more often to more than half. Forty-five percent of the respondents had received speech-language pathology services. CONCLUSIONS: Most respondents reported both speech and language symptoms, and many experienced restricted communicative participation. Access to speech-language pathology services is still inadequate. Services should also address cognitive/linguistic aspects to meet the needs of people with PD.

Treatment for dysphagia (swallowing difficulties) in hereditary ataxia.

BACKGROUND: Hereditary ataxias are a heterogeneous group of disorders resulting in progressive inco-ordination. Swallowing impairment, also known as dysphagia, is a common and potentially life threatening sequel of disease progression. The incidence and nature of dysphagia in these conditions is largely unknown. The loss of an effective and safe swallow can dramatically affect the health and well-being of an individual. Remediation of difficulties of eating and drinking is an important goal in the clinical care of people with hereditary ataxia. OBJECTIVES: To assess the effects of interventions for swallowing impairment (dysphagia) in people with hereditary ataxias. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, PsycINFO, and the Education Resources Information Center (ERIC) on 14 September 2015. We also searched Linguistics and Language Behavior Abstracts (LLBA), Dissertation Abstracts, and Trials Registries on 24 September 2015. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) and quasi-RCTs that compared treatments for hereditary ataxia with placebo or no treatment. We only included studies measuring dysphagia. DATA COLLECTION AND ANALYSIS: Three review authors (ES, KJ, MK) independently screened all titles and abstracts. In the event of any disagreement or uncertainty over the inclusion of a particular paper, the review authors planned to meet and reach consensus. MAIN RESULTS: We identified no RCTs from the 519 titles and abstracts screened. We excluded papers primarily for not including participants with a hereditary ataxia (that is, being focused on other neurological conditions), being theoretical reviews rather than intervention studies, or being neither randomised nor quasi-randomised trials.We identified five papers of various design that described treatment for dysphagia, or improvement to swallow as a by-product of treatment, in people with hereditary ataxia. None of these studies were RCTs or quasi-RCTs. AUTHORS' CONCLUSIONS: There is an absence of any significant evidence supporting the use of any dysphagia intervention in hereditary ataxia. The lack of evidence highlights the critical need for well-controlled treatment trials in the field.

Evaluation of a new PVC-free catheter material for intermittent catheterization: a prospective, randomized, crossover study.

OBJECTIVE: Polyvinyl chloride (PVC) is commonly used as a catheter material in catheters for clean intermittent catheterization (CIC) but, owing mainly to environmental concerns, a PVC-free material has been proposed. The objective of this study was to compare patients' tolerability for catheters made of PVC and a newly developed PVC-free material. MATERIAL AND METHODS: This was a prospective, randomized, crossover study in 104 male patients with maintained urethra sensibility who practised CIC. The patients evaluated in a randomized order a PVC and a PVC-free LoFric® catheter after 1 week's use of each. The material properties and tolerability, i.e. reported perceived discomfort, of each catheter were compared and adverse events documented. RESULTS: Twenty-nine (28%) and 15 (14%) patients reported discomfort when using the PVC catheter and the PVC-free LoFric catheter, respectively. A comparison showed that five patients (5%) reported discomfort with the PVC-free and not with the PVC catheter, and 19 patients (18%) reported discomfort with the PVC and not with the PVC-free catheter (p = 0.0066). Forty patients reported a total of 91 adverse events, of which the most common were discomfort in terms of pain, a burning sensation and bleeding. CONCLUSIONS: Generally low discomfort rates were reported in the study population, suggesting a high tolerance for CIC with catheters of both the PVC and the PVC-free materials. The lowest discomfort was, however, found when CIC was performed using the PVC-free LoFric catheter.

Effects of glossopharyngeal breathing on speech and respiration in multiple sclerosis: a case report.

This case report describes the effects of glossopharyngeal breathing on respiration and speech in a patient with tetraplegia due to multiple sclerosis. Glossopharyngeal breathing is a technique where air is insufflated with the glossopharyngeal muscles, to increase vital capacity. Results from follow-up assessments up to 20 months after intervention showed that (1) the patient's speech and respiratory function with glossopharyngeal breathing improved over time, (2) the patient's respiratory function without glossopharyngeal breathing deteriorated over time (possibly because of a severe cold), and (3) at each assessment, the patient's speech and respiratory function was better with glossopharyngeal breathing than without it.

Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development.

During development, pancreatic endocrine cells are specified within the pancreatic epithelium. They subsequently delaminate out of the epithelium and cluster in the mesenchyme to form the islets of Langerhans. Neurogenin3 (Ngn3) is a transcription factor required for the differentiation of all endocrine cells and we investigated its role in their delamination. We observed in the mouse pancreas that most Ngn3-positive cells have lost contact with the lumen of the epithelium, showing that the delamination from the progenitor layer is initiated in endocrine progenitors. Subsequently, in both mouse and chick newly born endocrine cells at the periphery of the epithelium strongly decrease E-cadherin, break-down the basal lamina and cluster into islets of Langerhans. Repression of E-cadherin is sufficient to promote delamination from the epithelium. We further demonstrate that Ngn3 indirectly controls Snail2 protein expression post-transcriptionally to repress E-cadherin. In the chick embryo, Ngn3 independently controls epithelium delamination and differentiation programs.

Infection with Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus t034.

Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA), sequence type 398 is believed to be of animal origin. We report 2 cases of infection due to PVL-positive MRSA, spa type t034, in patients in Sweden who had had no animal contact.

Temporal control of neurogenin3 activity in pancreas progenitors reveals competence windows for the generation of different endocrine cell types.

All pancreatic endocrine cells, producing glucagon, insulin, somatostatin, or PP, differentiate from Pdx1+ progenitors that transiently express Neurogenin3. To understand whether the competence of pancreatic progenitors changes over time, we generated transgenic mice expressing a tamoxifen-inducible Ngn3 fusion protein under the control of the pdx1 promoter and backcrossed the transgene into the ngn3(-/-) background, devoid of endogenous endocrine cells. Early activation of Ngn3-ER(TM) almost exclusively induced glucagon+ cells, while depleting the pool of pancreas progenitors. As from E11.5, Pdx1+ progenitors became competent to differentiate into insulin+ and PP+ cells. Somatostatin+ cells were generated from E14.5, while the competence to make glucagon+ cells was dramatically decreased. Hence, pancreas progenitors, similar to retinal or cortical progenitors, go through competence states that each allow the generation of a subset of cell types. We further show that the progenitors acquire competence to generate late-born cells in a mechanism that is intrinsic to the epithelium.

The transcription factor SREBP-1c is instrumental in the development of beta-cell dysfunction.

Accumulation of lipids in non-adipose tissues is often associated with Type 2 diabetes and its complications. Elevated expression of the lipogenic transcription factor, sterol regulatory element binding protein-1c (SREBP-1c), has been demonstrated in islets and liver of diabetic animals. To elucidate the molecular mechanisms underlying SREBP-1c-induced beta-cell dysfunction, we employed the Tet-On inducible system to achieve tightly controlled and conditional expression of the nuclear active form of SREBP-1c (naSREBP-1c) in INS-1 cells. Controlled expression of naSREBP-1c induced massive accumulation of lipid droplets and blunted nutrient-stimulated insulin secretion in INS-1 cells. K(+)-evoked insulin exocytosis was unaltered. Quantification of the gene expression profile in this INS-1 stable clone revealed that naSREBP-1c induced beta-cell dysfunction by targeting multiple genes dedicated to carbohydrate metabolism, lipid biosynthesis, cell growth, and apoptosis. naSREBP-1c elicits cell growth-arrest and eventually apoptosis. We also found that the SREBP-1c processing in beta-cells was irresponsive to acute stimulation of glucose and insulin, which was distinct from that in lipogenic tissues. However, 2-day exposure to these agents promoted SREBP-1c processing. Therefore, the SREBP-1c maturation could be implicated in the pathogenesis of beta-cell glucolipotoxicity.

Experimental models of transcription factor-associated maturity-onset diabetes of the young.

Six monogenic forms of maturity-onset diabetes of the young (MODY) have been identified to date. Except for MODY2 (glucokinase), all other MODY subtypes have been linked to transcription factors. We have established a MODY3 transgenic model through the beta-cell-targeted expression of dominant-negative HNF-1alpha either constitutively (rat insulin II promoter) or conditionally (Tet-On system). The animals display either overt diabetes or glucose intolerance. Decreased insulin secretion and reduced pancreatic insulin content contribute to the hyperglycemic state. The conditional approach in INS-1 cells helped to define new molecular targets of hepatocyte nuclear factor (HNF)-1alpha. In the cellular system, nutrient-induced insulin secretion was abolished because of impaired glucose metabolism. Conditional suppression of HNF-4alpha, the MODY1 gene, showed a similar phenotype in INS-1 cells to HNF-1alpha. The existence of a regulatory circuit between HNF-4alpha and HNF-1alpha is confirmed in these cell models. The MODY4 gene, IPF-1 (insulin promoter factor-1)/PDX-1 (pancreas duodenum homeobox-1), controls not only the transcription of insulin but also expression of enzymes involved in its processing. Suppression of Pdx-1 function in INS-1 cells does not alter glucose metabolism but rather inhibits insulin release by impairing steps distal to the generation of mitochondrial coupling factors. The presented experimental models are important tools for the elucidation of the beta-cell pathogenesis in MODY syndromes.

Long-term oxygen therapy and quality of life in elderly patients hospitalised due to severe exacerbation of COPD. A 1 year follow-up study.

The aim of this study was (1) to evaluate the effects of long-term oxygen treatment (LTOT) in elderly patients with severe exacerbations of chronic obstructive pulmonary disease (COPD) and hypoxaemia, (2) to study the health-related quality of life (QOL) during hospital stay and at follow-up, (3) to study the safety of an oxygen withdrawal test performed a few days after admission to hospital and the possibility to predict the future need for LTOT from that test. Patients > 70 years with COPD-exacerbations with hypoxaemia were included after 5-7 days treatment in hospital. Inclusion was based on results of a standardised oxygen withdrawal test. After 1, 3, 6 and 12 months a new oxygen withdrawal test was performed. Health-related QOL was evaluated with SF-36 and the St George's Respiratory Questionnaire at inclusion and after 3,6 and 12 months. Forty-seven patients were screened for participation and 29 patients, mean age 79 years, participated in the study. Only one patient could not tolerate the oxygen withdrawal test. Eighteen patients survived to the follow-up after 12 months, 8/19 women and 2/10 men died. After 1 month LTOTwas needed (PaO2 without oxygen was < or = 75 k Pa) in only 6/20 patients. The effect of LTOT could therefore not be studied. Most components of SF-36 were very low at inclusion, but tended to increase after 3 months and were among the surviving patients after 12 months similar to that of healthy people of the same age for psychic well being and functioning. Especially, the symptom score of the SGRQ improved after 3 months. In conclusion, the future need for LTOT cannot be judged after a few days treatment in hospital due to exacerbations with hypoxaemia in elderly patients with COPD. A standardised oxygen withdrawal test can be safely done. Health-related QOL is low in patients during the stay in hospital, but improves after returning home.

[Swedish physicians smoke least in all the world. A new study of smoking habits and attitudes to tobacco]. / Svenska läkare röker minst i världen. Ny studie av tobaksvanor och attityder till tobak.

Since 1969, studies of Swedish doctors' tobacco habits and attitudes have been carried out regularly every fifth year. The present investigation was made in 2001 in the form of a questionnaire distributed to a random sample of 5% of Swedish doctors (n = 1,367). The response rate was 80%. The proportion of daily smokers was 6%, a figure that had not changed since 1996. More doctors had never smoked (44% compared with 38% in 1996). Most smokers were found among psychiatrists and surgeons (10%). The use of oral snuff had increased to 16% among male and 5% among female doctors (compared with 9% and 3% in 1996). About 50% of the doctors believed that the use of snuff increased the risk of hypertension, angina pectoris, myocardial infarction and oral cancer. Protection of health was the main reason for not smoking (98%). An overall majority (92%) of doctors advise patients with lung diseases and pregnant women not to smoke, and only a few (16%) never give advice about smoking cessation to smokers with non-smoking related diseases. Many doctors do not allow smoking in their homes (69%) and ask for smoke free hotel rooms (82%). The doctor as a role model for patients was regarded as important by 71%. The number of smokers in the general Swedish population was as low as 19% in 2001, achieving the WHO goal for the year 2000. The low, unchanged level of 6% of doctors who smoke daily indicates that it might be possible to achieve a target level of 5-10% among the general population. The slowly increasing use of snuff requires further studies.

Foxa2 (HNF3beta ) controls multiple genes implicated in metabolism-secretion coupling of glucose-induced insulin release.

The transcription factor Foxa2 is implicated in blood glucose homeostasis. Conditional expression of Foxa2 or its dominant-negative mutant DN-Foxa2 in INS-1 cells reveals that Foxa2 regulates the expression of genes important for glucose sensing in pancreatic beta-cells. Overexpression of Foxa2 results in blunted glucose-stimulated insulin secretion, whereas induction of DN-Foxa2 causes a left shift of glucose-induced insulin release. The mRNA levels of GLUT2 and glucokinase are drastically decreased after induction of Foxa2. In contrast, loss of Foxa2 function leads to up-regulation of hexokinase (HK) I and II and glucokinase (HK-IV) mRNA expression. The glucokinase and the low K(m) hexokinase activities as well as glycolysis are increased proportionally. In addition, induction of DN-Foxa2 also reduces the expression of beta-cell K(ATP) channel subunits Sur1 and Kir6.2 by 70%. Furthermore, in contrast to previous reports, induction of Foxa2 causes pronounced decreases in the HNF4alpha and HNF1alpha mRNA levels. Foxa2 fails to regulate the expression of Pdx1 transcripts. The expression of insulin and islet amyloid polypeptide is markedly suppressed after induction of Foxa2, while the glucagon mRNA levels are significantly increased. Conversely, Foxa2 is required for glucagon expression in these INS-1-derived cells. These results suggest that Foxa2 is a vital transcription factor evolved to control the expression of genes essential for maintaining beta-cell glucose sensing and glucose homeostasis.