Identification of runs of homozygosity affecting female fertility and milk production traits in Finnish Ayrshire cattle.

Inbreeding gives rise to continuous lengths of homozygous genotypes called runs of homozygosity (ROH) that occur when identical haplotypes are inherited from both parents. ROHs are enriched for deleterious recessive alleles and can therefore be linked to inbreeding depression, defined as decreased phenotypic performance of the animals. However, not all ROHs within a region are expected to have harmful effects on the trait of interest. We aimed to identify ROHs that unfavourably affect female fertility and milk production traits in the Finnish Ayrshire population. The estimated effect of ROHs with the highest statistical significance varied between parities from 9 to 17 days longer intervals from calving to first insemination, from 13 to 38 days longer intervals from first to last insemination and from 0.3 to 1.0 more insemination per conception. Similarly, for milk production traits ROHs were associated with a reduction of 208 kg for milk yield, 7 kg for protein yield and 16 kg for fat yield. We also found regions where ROHs displayed unfavourable effects across multiple traits. Our findings can be exploited for more efficient control of inbreeding depression, for example by minimizing the occurrence of unfavourable haplotypes as homozygous state in breeding programmes.

Estimation of intrachromosomal inbreeding depression on female fertility using runs of homozygosity in Finnish Ayrshire cattle.

Inbreeding increases homozygosity, which in turn increases the frequency of harmful recessive alleles, resulting in inbreeding depression. Inbreeding depression on fertility reduces the profitability of dairy farming by decreasing the lifetime milk production of cows and by increasing insemination and veterinary costs. Continuous homozygous segments, called runs of homozygosity (ROH), are currently considered to provide an effective measure of genomic inbreeding. The aim of this study was to estimate the effect of increased intrachromosomal homozygosity for female fertility in the Finnish Ayrshire population using ROH and haplotype analysis. Genotypes were obtained from 13,712 females with the Illumina BovineLD v.2 BeadChip low-density panel (Illumina Inc., San Diego, CA) and imputed to 50K density. After quality control, 40,554 single nucleotide polymorphisms remained for the analysis. Phenotypic data consisted of records for nonreturn rate, intervals from first to last insemination (IFL), and intervals from calving to first insemination. The raw phenotypic values were preadjusted for systematic effects before statistical analyses. The ROH-based inbreeding coefficients (FROH) were used as covariates in the mixed model equation to estimate the association between inbreeding and inbreeding depression on female fertility. First, we estimated the effect of increased chromosomal FROH. We detected significant inbreeding depression on IFL. Based on our results, a 10% increase in FROH on chromosomes 2, 18, and 22 were associated with IFL of heifers lengthening by 1.6, 0.9, and 0.7 d, respectively. Similarly, a 10% increase in FROH on chromosome 15 was associated with IFL of second-parity cows increasing by 2.3 d. Next, we located the regions within the chromosomes showing inbreeding depression. Our analysis revealed regions near the beginning of chromosome 2 and toward the ends of chromosomes 15, 18, and 22 that were associated with inbreeding depression on IFL. Last, we performed a haplotype analysis for the detected regions. The most promising haplotypes of each region were associated with IFL of heifers increasing by 4.4, 3.2, and 4.1 d on chromosomes 2, 18, and 22, respectively. The haplotype on chromosome 15 associated with IFL of second-parity cows increasing by 7.6 d. Overall, the breeding program requires inbreeding control, as increased genomic inbreeding in our study was associated with reduced reproductive ability in Finnish Ayrshire cattle.

Estimation of inbreeding depression on female fertility in the Finnish Ayrshire population.

Single nucleotide polymorphism (SNP) data enable the estimation of inbreeding at the genome level. In this study, we estimated inbreeding levels for 19,075 Finnish Ayrshire cows genotyped with a low-density SNP panel (8K). The genotypes were imputed to 50K density, and after quality control, 39,144 SNPs remained for the analysis. Inbreeding coefficients were estimated for each animal based on the percentage of homozygous SNPs (FPH ), runs of homozygosity (FROH ) and pedigree (FPED ). Phenotypic records were available for 13,712 animals including non-return rate (NRR), number of inseminations (AIS) and interval from first to last insemination (IFL) for heifers and up to three parities for cows, as well as interval from calving to first insemination (ICF) for cows. Average FPED was 0.02, FROH 0.06 and FPH 0.63. A correlation of 0.71 was found between FPED and FROH , 0.66 between FPED and FPH and 0.94 between FROH and FPH . Pedigree-based inbreeding coefficients did not show inbreeding depression in any of the traits. However, when FROH or FPH was used as a covariate, significant inbreeding depression was observed; a 10% increase in FROH was associated with 5 days longer IFL0 and IFL1, 2 weeks longer IFL3 and 3 days longer ICF2 compared to non-inbred cows.

Sleeping difficulties and health-related quality of life in Parkinson's disease.

OBJECTIVE: Various sleep-related symptoms occur in Parkinson's disease (PD). Their occurrence with health-related quality of life (HRQL), comorbid sleep disorders, and other comorbidities was studied. METHODS: Altogether, 1447 randomly selected patients with Parkinson's disease, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, sleep disorders, and comorbidities were included. RESULTS: The response rate was 59.0%, and of these, 80% had answered to all questions that were used in the analyses (N=684). Occurrence of long sleep was found in 26.2% of the subjects, short sleep in 32.5%, poor sleep in 21.2%, sleep deprivation in 33.8%, disrupted sleep in 47.4%, and difficulties to fall asleep in 12.2%, respectively. Poor self-rated health and poor quality of life occurred in 44.4% and in 43.3% of all participants. In the logistic regression, age and gender differentially predicted long sleep and sleep deprivation, such that older age and being male were positively associated with long sleep but negatively associated with the report of sleep deprivation. Depression, subjective negative stress, and fatigue occurred with long sleep. On the other hand, poor sleep and excessive daytime sleepiness occurred with short sleep and sleep deprivation. CONCLUSIONS: The sleep difficulties in PD are frequent. The long sleeping patients have depression, stress, and fatigue.

Education-corrected CERAD identifies MCI and dementia in Parkinson's disease.

OBJECTIVES: This study examined whether controlling for educational background in the CERAD cognitive screening battery would affect the likelihood of patients with Parkinson's disease to fulfill criteria for mild cognitive impairment (PD-MCI) and dementia (PDD). MATERIALS & METHODS: One-hundred seventeen patients with PD were studied. Cognitive impairment was determined as two subtest scores falling below either the standard cutoff scores or education-corrected cutoff scores. The presence of dementia was determined by clinical interview or Clinical Dementia Rating. Patients were then classified as PD-MCI and PDD according to cognitive test performance and presence/absence of dementia. RESULTS: The number of cognitively impaired patients (PD-MCI or PDD) was significantly higher when education-controlled cutoff scores were used (62.5% vs 38%). Correspondingly, the number of false negatives (demented PD patients performing normally in CERAD) was significantly lower when education-corrected cutoff scores were used (4% vs 10%). CONCLUSIONS: Controlling for education increases the sensitivity of the CERAD for PD-MCI and PDD.

CERAD test performance and cognitive impairment in Parkinson's disease.

OBJECTIVES: Many patients with Parkinson's disease (PD) develop mild cognitive impairment (PD-MCI) and dementia (PDD). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neurocognitive test battery was originally developed to identify early Alzheimer's disease, but it has become a widely used screening instrument also for other types of dementia. The aim of the study was to examine differences in CERAD test performances between cognitively intact and impaired PD patients. MATERIALS AND METHODS: Eighty-eight PD patients participating in a rehabilitation course were studied. The Clinical Dementia Rating (CDR) was used to assess cognitive impairment. Sixty-six patients were cognitively intact and 22 had cognitive impairment (≥1 in two or more domains or a sum of boxes score of ≥3). The Finnish CERAD test battery was used to measure cognitive functions in seven different domains (language functions, verbal learning, visuospatial functions, delayed recall, memory consolidation, recognition memory, and executive functions). RESULTS: There were significant differences between the cognitively intact and impaired patients in six CERAD subtests (wordlist learning sum, wordlist delayed recall, constructional praxis recall, clock drawing, verbal fluency and constructional praxis copy) when controlling for covariates (disease duration, motor symptoms, age, and education). No differences were observed in memory consolidation scores. CONCLUSIONS: The results indicate that mild cognitive impairment in PD is related to deficits in memory, executive functions, and visuospatial functions. The memory deficit is non-amnestic and does not entail accelerated forgetting. CERAD shows promise in identifying PD patients with cognitive impairment and increased risk of dementia.

Apathy is associated with activities of daily living ability in Parkinson's disease.

BACKGROUND: Neuropsychiatric symptoms and impairment in performing activities of daily living (ADL) in patients with Parkinson's disease (PD) are strong predictors of the overall caregiver burden and they increase the risk for nursing home admission of the patients. The purpose of the present study was to assess the association of neuropsychiatric symptoms and ADL functions in PD. METHODS: A total of 73 community-dwelling PD patients were studied. The mean age of the patient group was 65 years and the mean disease duration was 9 years. The Neuropsychiatric Inventory was used to measure neuropsychiatric symptoms, and ADL abilities were measured by the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. RESULTS: The prevalence of neuropsychiatric symptoms in patients with PD was 73%. The most common symptoms were depression, anxiety, irritability, apathy and agitation. ADL ability correlated significantly with apathy (p < 0.002) even when adjusted for motor symptoms. CONCLUSION: Apathy was significantly associated with ADL in PD. The result indicates that more attention should be paid to identifying apathy and targeting therapeutic interventions.

Sleep-related disorders in carpal tunnel syndrome.

INTRODUCTION: Patients with carpal tunnel syndrome (CTS) often wake up at night due to pain and numbness of affected fingers and hand. We studied the sleep disorder caused by CTS. SUBJECTS AND METHODS: 34 consecutive patients referred for operative treatment of CTS answered to a sleep questionnaire and the results were compared to a stratified random sample of 1600 Finns aged 36-50 year, whose response rate to the mailed questionnaires was 75.2% (n = 1186). Six CTS patients underwent a polygraphic sleep study before and after operative treatment of CTS. RESULTS: CTS patients reported suffering from poor sleep quality, fragmentary sleep and daytime sleepiness more often than controls. Before operative treatment of CTS there were more nocturnal body movements (p < 0.01) and awakenings lasted longer (p < 0.05) than after operation. During preoperative sleep studies no drop in median nerve conduction was detected during awakenings. CONCLUSIONS: Patients with CTS suffer from fragmentary sleep. Although patients reported waking up for the pain or numbness of hands no impairment in median and ulnar nerve conduction could be observed during these awakenings. Operative treatment of hand entrapment significantly reduced the number of nocturnal movements.

Significance of electrical brain activity in brain-stem death.

A 46-year-old man was diagnosed clinically brain dead after sustaining head trauma. The patient was in deep coma, brain nerves were unresponsive and spontaneous breathing was absent. However, EEG showed well preserved activity, but no reactivity to external stimuli. EEG activity disappeared within 40 h. BAEP were highly abnormal, flash-VEP as recorded 3 h after the diagnosis of brain stem death was of high amplitude but of simplified form. The neurophysiological findings revealed that the main reason for deep coma was brain stem damage while cortical activity was still present. This condition raises ethical questions when brain death is diagnosed clinically prior to removal of organs for transplantation.

Natural evolution of snoring: a 5-year follow-up study.

INTRODUCTION: The natural evolution of snoring was studied in a middle-aged population in Finland. MATERIAL AND METHODS: A questionnaire was mailed to a stratified random sample of 1600 people aged 36-50 years in 1985 with a response rate of 75.2%; 53% of them completed also the 5-year-follow-up questionnaire. Clinical examinations (N = 36) and whole-night polygraphic recordings (N = 22) were made to habitual (every or almost every night) snorers and daily sleepy persons. RESULTS: A total of 626 persons completed the 5-year-follow-up questionnaire. The prevalence of habitual snoring among men was 28.3-43.8% and among women 6.3-18.8%, increasing with age. Sleepiness was common: doze-off at the wheel was reported by 23% of snorers and traffic accidents because of sleepiness by 4.5%. Hypertension was clearly more common (p = 0.002) among habitual snorers, but the self-reported rates of strokes and coronary heart disease were not increased in this study. None of the snorers had been investigated because of their snoring or sleepiness during the five years. In polygraphic recordings 11/22 showed an oxygen desaturation index (ODI4) more than 5/h; active treatment was started for 8 of them. The observed prevalence of sleep apnea syndrome with ODI4 > 10 was 1.1% in this study. CONCLUSIONS: Snorers, even with clear sleepiness, are passive in seeking help for their symptoms. Physicians should actively diagnose this treatable condition impairing the quality of life and increasing the risk of traffic accidents and vascular diseases.

Evaluation of Sleep Expert--a computer-aided decision support system for sleep disorders.

Sleep Expert--a medical decision support system--is a prototype program, with knowledge based on the International Classification of Sleep Disorders (1990). The goal of this project was to evaluate Sleep Expert. In the evaluation project the knowledge of the program was first validated. Three physicians, experts in sleep disorders, were asked to choose 10 typical patient cases with sleep disorders, and to write a description. They also made a diagnosis for each case. Next, each expert made a diagnosis of the cases supplied by the other experts. They were not given the original diagnosis. The 'right diagnosis' (so-called majority agreement) was determined from the three diagnoses. Then the diagnosis of each expert was compared with the 'right diagnosis'. Two physicians, not experts in sleep disorders, were asked to make a diagnosis by using Sleep Expert. Compared to the 'right diagnosis' the diagnoses of each user (non-expert physician) were correct to 63 and 70% of cases, which is quite a good result, although it does not reach the level of the expert physicians (> or = 87%). The functionality of Sleep Expert was studied by using a limited inquiry. On the basis of the user inquiry Sleep Expert provided a useful clinical tool for non-experts.

Daytime sleepiness: a risk factor in community life.

The prevalence of daytime sleepiness and background factors associated with it were investigated in a study carried out at the UKK Institute. The inquiry took the form of a questionnaire mailed to 1600 people of middle age. Daytime sleepiness was found to be associated with disturbed night sleep. Women were more tired than men, but men slept more frequently during the day. Those suffering from tiredness complained of poor health more than other respondents. Traffic accidents and other mishaps attributable to tiredness had occurred in 1.3% of cases, and almost 5% of male respondents had dozed off while driving at least five times in their lives. The findings indicate a need for increased attention to disturbance of sleep and daytime sleepiness in routine health screening.