Genome-wide association study suggests genetic candidate loci of insulin dysregulation in Finnhorses.

Equine metabolic syndrome (EMS) is a common welfare problem in horses worldwide. It is characterized by insulin dysregulation (ID), predisposition to laminitis and often obesity. EMS is multifactorial by nature, with both the environment and genetics contributing to the phenotype. Environmental factors, such as feeding and exercise, can be controlled, thus forming the basis for treatment and prevention. Genetic factors, by contrast, are less well-known and not easily controllable. The aim of this study was to identify potential genetic loci influencing ID/EMS in Finnhorses. A single-breed (Finnhorse) case-control genome-wide association study (GWAS) of ID was conducted with controls that included age-appropriate non-ID horses. ID status was determined with an oral sugar test (OST) for fasted horses. Seventy-one Finnhorses participated (n = 34 ID, n = 37 control). DNA samples (hair roots) were genotyped for 65 157 single-nucleotide polymorphisms (SNPs) with the Illumina Equine SNP70 BeadChip, and these data were analysed for association and FST outliers with genomic tools. P-values that exceeded the suggestive threshold (P = 1.00 ×10-5) were found in SNP BIEC2_383954 (P = 3.45 ×10-6) in chromosome 17 and SNP BIEC2_312374 (P = 1.89 ×10-5) in chromosome 15. Hierarchical and Bayesian FST outlier tests also detected these SNPs. Potential candidate genes associated with the ID close to SNP BIEC2_383954, with functions in carbohydrate metabolism, were Arginine and Glutamate Rich 1 (ARGLU1) and Ephrin-B2 (EFNB2).

Exposure to persistent organic pollutants and sperm sex chromosome ratio in men from the Faroe Islands.

People in the Arctic as well as fishermen on the polluted Swedish east coast are highly exposed to persistent organic pollutants (POPs). These compounds have been shown to affect the sperm Y:X chromosome ratio. In present study, the aim was to investigate whether polychlorinated biphenyl (PCB) congeners and 1,1,-dichloro-2,2,-bis(p-chlorophenyl)ethane (p,p'-DDE) influence sperm sex chromosome ratio in Faroese men, and whether these men differ regarding Y:X ratio compared to Greenland Inuit and Swedish fishermen. The study population (n=449) consisted of young men from the general population (n=276) as well as proven fertile men (n=173). The Y:X ratio was assessed by fluorescent in situ hybridization. Serum concentrations of POPs were measured using gas chromatography. Associations between POP concentrations and Y:X ratio were calculated using linear and non-linear regression models as well as trend analysis and pairwise comparison of exposure data categorized into quartiles. The selected POPs were associated with Y:X ratio in fertile Faroese men, but not in the total population; p,p'-DDE (95% CI for B=-0.005 to -0.001, p=0.005) and ΣPCB (95% CI for B=-0.005 to -0.001, p=0.012). Since p,p'-DDE and ΣPCB correlated significantly (r=0.927, p<0.001), the results involving the exposure variables can be regarded as a single finding. The Y:X ratio for the total Faroese population was 0.500±0.018, which was statistically significantly lower than in both Inuit and Swedish fishermen (0.512 for both). In conclusion, Faroese men presented with lower Y:X ratio than Greenland Inuit and Swedish fishermen. Although no direct health effects are expected due to the lower Faroese Y:X ratio, it could be indicative of adverse effects on the reproductive system.

Identification and evaluation of Peruvian plants used to treat malaria and leishmaniasis.

Households in eleven geographically and ethnically distinct areas in Loreto, Peru, were interviewed about their knowledge and use of plants, for the treatment of malaria and leishmaniasis. The survey resulted in 988 use records representing 118 plant-taxa for malaria and 289 use-records representing 85 plant-taxa for leishmaniasis. In both cases the 10 most frequently reported taxa accounted for about half of all the use-records. Plant material was collected and extracts were screened for in vitro inhibition of Plasmodium and Leishmania parasites. In the case of Plasmodium, extracts of 11 of the 13 most frequently reported plants showed significant growth inhibitory activity, while only a few plant extracts inhibited the growth of Leishmania parasites.

Colonisation and diversification of the blue tits (Parus caeruleus teneriffae-group) in the Canary Islands.

The blue tit (Parus caeruleus teneriffae group) is proposed to have colonised the Canary Islands from North Africa according to an east-to-west stepping stone model, and today, the species group is divided into four subspecies, differing in morphological, acoustic, and ecological characters. This colonisation hypothesis was tested and the population structure between and within the islands studied using mitochondrial DNA sequences of the non-coding and relatively fast evolving control region. Our results suggest that one of the central islands, Tenerife, was colonised first and the other islands from there. Three of the presently recognised four subspecies are monophyletic, exception being the subspecies teneriffae, which consists of two monophyletic groups, the one including birds of Tenerife and La Gomera and the other birds of Gran Canaria. The Gran Canarian birds are well differentiated from birds of the other islands and should be given a subspecies status. In addition, the teneriffae subspecies group is clearly distinct from the European caeruleus group, and therefore the blue tit assemblage should be divided into two species.

Effects of acupuncture and care interventions on the outcome of inflammatory symptoms of the breast in lactating women.

OBJECTIVES: To compare modes of care and treatment for lactating women with inflammatory symptoms of the breast, with special focus on the use of acupuncture. METHOD: Eighty-eight mothers were randomized into three treatment groups. All three groups were given advice regarding emptying of the breasts and care in the form of comfort interventions. Acupuncture was included in the treatment regime for two of the groups. A severity index was created by adding together scores for signs and symptoms: breast tension, erythema and pain. FINDINGS: Mothers in all groups expressed relative satisfaction with the breastfeeding situation despite considerable discomfort. There was no significant difference between the groups for the number of mothers requiring more than three contact days for recovery nor for their severity index scores on day 3. These findings must be interpreted with care but may suggest that care interventions play as great a part in the recovery of these women as acupuncture treatment or the use of oxytocin spray. Antibiotic therapy was used in 9% of the study population, which is in contrast to other studies. PROPOSED FUTURE ACTION: Based on these results, a new study has been designed to test the hypothesis that acupuncture hastens recovery from inflammatory processes in the lactating breast and approximately 200 mothers will be randomized in a new expanded study.

Genomic organization of the human COL3A1 and COL5A2 genes: COL5A2 has evolved differently than the other minor fibrillar collagen genes.

We report here on the complete structure of the human COL3A1 and COL5A2 genes. Collagens III and V, together with collagens I, II and XI make up the group of fibrillar collagens, all of which share a similar structure and function; however, despite the similar size of the major triple-helical domain, the number of exons coding for the domain differs between the genes for the major fibrillar collagens characterized so far (I, II, and III) and the minor ones (V and XI). The main triple-helical domain being encoded by 49-50 exons, including the junction exons, in the COL5A1, COL11A1 and COL11A2 genes, but by 43-44 exons in the genes for the major fibrillar collagens. Characterization of the genomic structure of the COL3A1 gene confirmed its association with the major fibrillar collagen genes, but surprisingly, the genomic organization of the COL5A2 gene was found to be similar to that of the COL3A1 gene. We also confirmed that the two genes are located in tail-to-tail orientation with an intergenic distance of approximately 22 kb. Phylogenetic analysis suggested that they have evolved from a common ancestor gene. Analysis of the genomic sequences identified a novel single nucleotide polymorphism and a novel dinucleotide repeat. These polymorphisms should be useful for linkage analysis of the Ehlers-Danlos syndrome and related disorders.

The economic importance of products extracted from Amazonian flood plain forests.

Rural people in the Peruvian Amazon practice agriculture and extract a wide range of products from natural forests, rivers and lakes. Their diversified livelihood system includes fish, game, and plant products. In 2 flood-plain villages, data for one year have been collected to compare the economy of local agriculture with the economy of extracted forest products for subsistence as well as for commerce. The study includes both fauna (game and fish) and flora (timber as well as nontimber). The results show that extracted forest products for subsistence, especially fish, are a main factor in the local economy. The daily net income from extraction activities exceeds both income from cultivation and the normal daily wages for unskilled workers, emphasizing the need for thorough socioeconomic investigations before any alternative land-use option is implemented. The average value per ha of natural forest used for extraction is in the order of USD 13 yr-1, and the average extraction area is 113 ha household-1. When yield from agriculture is included in the calculations, the total per ha value of current extraction and agricultural activities increases to USD 21 yr-1.

Absolute configuration and antiprotozoal activity of minquartynoic acid.

Minquartynoic acid (1) was isolated as an antimalarial and antileishmanial constituent of the Peruvian tree Minquartia guianensis and its absolute configuration at C-17 established to be (+)-S through conversion to the known (+)-(S)-17-hydroxystearic acid (2) and confirmed using Mosher's method.

A simple and efficient separation of the curcumins, the antiprotozoal constituents of Curcuma longa.

A simple and efficient method for the separation of the three phenolic diketones, curcumin 1, demethoxycurcumin 2, and bis-demethoxycurcumin 3, isolated from the rhizomes of Curcuma longa has been developed. The method is of general applicability for the separation of compounds containing acidic and chelating groups and is amenable to large scale separations. The curcumins 1-3 show moderate activity against Plasmodium falciparum (IC50: 3.5, 4.2 and 3.0 micrograms/ml) and Leishmania major (IC50: 7.8, 14.1 and 21.5 micrograms/ml) respectively.

Equipment for drug release testing of medicated chewing gums.

An apparatus was specially designed and constructed for release testing of medicated chewing gums. The adjustable instrumental settings such as temperature, chewing frequency, chewing time, volume of test medium, distance between the jaws and twisting angle increased the versatility of the apparatus. Selection of the test medium was also an important parameter. Each sample was kneaded mechanically in separate test chambers and the drug release was followed by sampling and HPLC analysis. Different gum formulations were tested and the obtained results demonstrated satisfactory release curves for a variety of formulations and active ingredients. The tested gum formulations comprised nicotine, meclizine, dimenhydrinate and xylitol. The apparatus proved to be suitable in product control of commercial batches but also a useful tool in the research and development of medicated gum formulations.

The colonization history and present-day population structure of the european great tit (Parus major major)

The colonization history and present-day population structure of the European subspecies of the great tit Parus major major were studied using mitochondrial control region sequences. One major haplotype was found in all but one of the eight sampled populations from Spain to northern Finland. The other haplotypes differed from the common one by just a few substitutions; the overall nucleotide diversity was 0.00187 and haplotype diversity 0.8633. No population structuring was detected. The mismatch distribution followed the expected distribution of an expanding population. The estimated time to the most recent common ancestor coincides with the last glacial period. The results suggest that P. m. major survived the last glacial period in a single isolated refuge probably by the Mediterranean Sea. This was followed by rapid colonization of the European continent and population growth. The most recent range expansion northwards is still occurring. Gene flow between the sampled populations is extensive. It is aided by juvenile dispersal, long-distance movements of juvenile flocks and partial migration in the northern parts of the great tit's range.

Mitochondrial control region polymorphism reveal high amount of gene flow in Fennoscandian willow tits (Parus montanus borealis).

We studied the genetic variability and differentiation of two Fennoscandian willow tit (Parus montanus borealis) populations located ca. 1000 km apart in Finland and Sweden by using the control region sequences of the mitochondrial DNA. Individual variation in the control region was extensive since all the 13 Finnish and the 12 Swedish individuals had unique haplotypes and the mean pairwise genetic distance resulted in 0.0052 (range 0.0008-0.0109). In the minimum spanning network connecting the genotypes, the two populations were completely intermingled. The mismatch distribution of the combined data set was very close to expected distribution of an expanding population. This result was supported by a significantly negative Tajima's D value. The sequence data indicate that (1) the long-term effective population size of the breeding willow tits has been large (122,000 and 110,000 females for the Finnish and the Swedish populations, respectively); and that (2) the gene exchange between distant localities is/has been extensive. Dispersal area for the Finnish females was estimated to be about 19,000-30,000 km2 and for the Swedish, 22,000-28,000 km2. Thus, the whole Fennoscandian population can be regarded as one panmictic unit, without any subdivisions to local demes. The amount of gene flow is remarkable because the willow tit has been considered a highly sedentary species. Provided that adult birds are site-tenacious, the gene flow must occur through juvenile summer dispersal, or irruptive autumn invasions, or both.

A comparative study of breast feeding after traditional postnatal hospital care and early discharge.

OBJECTIVE: To provide quality assurance for the care plan and working structure within the early discharge unit at the Women's Clinic, Central Hospital, Helsingborg, Sweden. DESIGN: Survey, using postal questionnaire. SETTING: The Women's Clinic, Central Hospital, Helsingborg, Sweden. PARTICIPANTS: 304 women with babies of six months of age, delivered at the Central Hospital, Helsingborg, between September and December 1993 and who, together with their baby, met the criteria for early discharge. Early discharge is generally defined in Sweden as discharge before 72 hours postpartum. MEASUREMENTS AND FINDINGS: Of the participants 41% chose early discharge (ED) and 59% chose traditional hospital care (THC). Four groups were studied for breast feeding frequency - THC primiparae, ED primiparae, THC multiparae and ED multiparae. Further division was made for breast feeding at 2, 4 and 6 months of age. The four main groups were examined for demographic differences. A difference was found in education level; early discharge mothers had a lower level of education than THC mothers. No significant difference was found for the frequency or duration of breast feeding between the early discharge and the traditional hospital care groups, despite the higher education level in the traditional hospital care group. IMPLICATIONS FOR PRACTICE: A possible explanation for this finding is that a care plan aimed at supporting the individual's responsibility and participation, providing relevant knowledge and a subliminal communication of trust in the competence of parent and child, is of particular significance for women with less education. The presence and participation of the baby's father at an early stage may also be a factor.

Mutated human androgen receptor gene detected in a prostatic cancer patient is also activated by estradiol.

Androgens are necessary for the development of prostatic cancer. The mechanisms by which the originally androgen-dependent prostatic cancer cells are relieved of the requirement to use androgen for their growth are largely unknown. The human prostatic cancer cell line LNCaP has been shown to contain a point mutation in the human androgen receptor gene (hAR), suggesting that changes in the hAR may contribute to the abnormal hormone response of prostatic cells. To search for point mutations in the hAR, we used single strand conformation polymorphism analysis and a polymerase chain reaction direct sequencing method to screen 23 prostatic cancer specimens from untreated patients, 6 prostatic cancer specimens from treated patients, and 11 benign prostatic hyperplasia specimens. One mutation was identified in DNA isolated from prostatic cancer tissue, and the mutation was also detected in the leukocyte DNA of the patient and his offspring. The mutation changed codon 726 in exon E from arginine to leucine and was a germ line mutation. The mutation we found in exon E of the hAR gene does not alter the ligand binding specificity of the AR, but the mutated receptor was activated by estradiol to a significantly greater extent than the wild-type receptor. The AR gene mutation described in this study might be one explanation for the altered biological activity of prostatic cancer.

Pharmacokinetics of different epidural sites of morphine administration.

In order to determine the rate and degree of redistribution of morphine within the cerebrospinal fluid (CSF), and whether it was affected by the site of and volume of the injection, morphine was given to 23 elderly patients undergoing thoracotomy - in 10 ml saline in the lumbar epidural interspace (n = 5), in 10 ml saline in the thoracic epidural interspace (n = 5), in 2 ml saline in the thoracic interspace (n = 8) and in 10 ml saline in the lumbar epidural interspace (n = 5). The plasma concentration of morphine in all patients was comparable and was much lower than in the CSF. The CSF morphine concentration, measured as the area under the CSF concentration curve (AUC), the maximal CSF concentration (Cmax) and the time to reach maximal CSF concentration (tmax), varied between the four groups. The variation was related to the site of the injection; the AUC and Cmax were lower and tmax appeared later after thoracic than lumbar injection. Lumbar CSF morphine concentrations were further reduced by thoracic epidural injection of morphine in a small as compared to a large volume. The permeability of the dura to morphine was not influenced by the volume used. The results show that morphine is not homogeneously distributed within the CSF. The availability of morphine to CSF from the epidural space is not altered by the injection volume, but the drug remains more localized in CSF after epidural injection of morphine in a small volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of oral theophylline poisoning.

Two patients, 15 and 20 years old, were admitted after an overdose of theophylline in a slow-release preparation. The gradual occurrence of clinical symptoms reflected the slow gastrointestinal absorption of the drug, and therefore active treatment was not started until 10 and 12 hours after intake, respectively. Peak s-concentrations were 275 and 1295 mumol/l, respectively. One patient was treated with hemoperfusion only, whereas the more severely intoxicated patient was treated with combined hemoperfusion and hemodialysis. Only about 0.2 g theophylline was eliminated by hemodialysis in this patient compared to a calculated amount of 6.9 g by hemoperfusion. Severely theophylline-intoxicated patients should be treated with supportive therapy and hemoperfusion.