Three genes expressing Kunitz domains in the epididymis are related to genes of WFDC-type protease inhibitors and semen coagulum proteins in spite of lacking similarity between their protein products

<p>Abstract</p> <p>Background</p> <p>We have previously identified a locus on human chromosome 20q13.1, encompassing related genes of postulated WFDC-type protease inhibitors and semen coagulum proteins. Three of the genes with WFDC motif also coded for the Kunitz-type protease inhibitor motif. In this report, we have reinvestigated the locus for homologous genes encoding Kunitz motif only. The identified genes have been analyzed with respect to structure, expression and function.</p> <p>Results</p> <p>We identified three novel genes; <it>SPINT3, SPINT4 </it>and <it>SPINT5</it>, and the structure of their transcripts were determined by sequencing of DNA generated by rapid amplification of cDNA ends. Each gene encodes a Kunitz domain preceded by a typical signal peptide sequence, which indicates that the proteins of 7.6, 8.7, and 9.7 kDa are secreted. Analysis of transcripts in 26 tissues showed that the genes predominantly are expressed in the epididymis. The recombinantly produced proteins could not inhibit the amidolytic activity of trypsin, chymotrypsin, plasmin, thrombin, coagulation factor Xa, elastase, urokinase and prostate specific antigen, whereas similarly made bovine pancreatic trypsin inhibitor (BPTI) had the same bioactivity as the protein isolated from bovine pancreas.</p> <p>Conclusions</p> <p>The similar organization, chromosomal location and site of expression, suggests that the novel genes are homologous with the genes of WFDC-type protease inhibitors and semen coagulum proteins, despite the lack of similarity in primary structure of their protein products. Their restricted expression to the epididymis suggests that they could be important for male reproduction. The recombinantly produced proteins are presumably bioactive, as demonstrated with similarly made BPTI, but may have a narrower spectrum of inhibition, as indicated by the lacking activity against eight proteases with differing specificity. Another possibility is that they have lost the protease inhibiting properties, which is typical of Kunitz domains, in favor of hitherto unknown functions.</p

Leisure repertoire among persons with a spinal cord injury: Interests, performance, and well-being

Objective: To explore and describe the leisure repertoire of persons with traumatic spinal cord injury (SCI) and how the repertoire is related to interest, performance, and well-being. Design: Cross-sectional study. Setting: A total of 97 persons with traumatic SCI were recruited from the non-profit national organization, RG Active Rehabilitation in Sweden. Outcome measure: Data were collected through a two-part postal survey. The first comprised of questions investigating socio-demographic variables and injury characteristics; the second part included an interest checklist with 20 areas of leisure activities. Results: The participants were mostly interested in, performed, and experienced well-being from social and culture activities and TV/DVD/movies. The areas of leisure activities in which they had most likely experienced changes after the SCI were outdoor activities, exercise, and gardening. Sex, age, and to some extent, time since injury were related to interest, performance, well-being, and changed performance. Conclusions: The results provided an explanation and limited description of a changed leisure repertoire among persons after a traumatic SCI. The study showed that sex, age, and time since injury were more closely related to the choice of leisure activities to include in the leisure repertoire than the level of injury. This knowledge can be of importance when professionals in the field of rehabilitation are planning and implementing interventions concerning leisure activities for persons with SCI

Kaasasündinud N-glükosüülimise haigused Eestis

Väitekirja elektrooniline versioon ei sisalda publikatsiooneKaasasündinud glükosüülimise haigused (KGH) moodustavad kiirelt areneva ainevahetushaiguste grupi ning on põhjustatud valkude ja lipiididega seotud glükaanide häirunud sünteesist. Erinevad valkude N-glükosüülimise haigused on enim diagnoositavad KGH-d ja PMM2-CDG on kõige sagedasem N-glükosüülimise haigus. KGH sümptomid on mittespetsiifilised ja multisüsteemsed. Valikmeetod KGH skriinimiseks on seerumi transferriini isoelektriline fokuseerimine (IEF). Käesoleva uuringu eesmärk oli juurutada Eestis KGH diagnostikaks transferriini IEF ja hinnata kolme aasta jooksul N-glükosüülimise haiguste esinemist meie patsientide hulgas. Kuuel patsiendil 1230-st esines KGH skriiningul positiivne tulemus, mis leidis molekulaarse kinnituse. Esmalt näitasime, et kõige sagedasem KGH Eestis on PMM2-CDG, mida diagnoositi neljal patsiendil kahest perekonnast. Ühe pere lastel väljendub haigus kerge neuroloogilise vormina, kuid normaalse kognitiivse arenguga, mida PMM2-CDG patsientide hulgas esineb harva. Eesti PMM2-CDG patsientidel oli kõige sagedasem variant PMM2 geenis p.Val131Met. Teiseks, esitasime tulemused PMM2-CDG eeldatava sageduse kohta, kasutades Tartu Ülikooli Eesti Geenivaramu andmeid. Leidsime viis erinevat PMM2 heterosügootset mutatsiooni. Kõige sagedasem geenivariant on p.Arg141His kandlussagedusega 1/224. p.Val131Met kandlussagedus on 1/449. Eeldatav PMM2-CDG sagedus Eestis on 1/77,000. Kolmandaks, kirjeldasime patsienti KGH alatüübiga SLC35A2-CDG ning võrdlesime tema fenotüüpi ja genotüüpi 14 rahvusvahelise patsiendi kliiniliste andmetega. Patsientidele on iseloomulik mittespetsiifiline neuroloogiline haigus üldise arengu hilistumise, lihashüpotoonia, krampide ning epileptilise entsefalopaatiaga, düsmorfsed tunnused ja lühike kasv. Lisaks võib transferriini IEF olla vale-negatiivne. Neljandaks, kirjeldasime multisüsteemsete kliiniliste sümptomitega ning uue, seni kirjeldamata KGH alatüübiga patsienti, kellel on KGH alatüübi põhjuseks tõenäoliselt haiguspõhjuslik homosügootne muutus STX5 geenis. Käesolev uuring näitas, et Eesti patsientide puhul on transferriini IEF on tulemuslik meetod KGH diagnostikas. Skriiningu rakendamine võimaldas lisada uusi kliinilisi ja epidemioloogilisi andmeid erinevate teadaolevate ning uue KGH alatüübi kohta.Congenital disorders of glycosylation (CDG) are an expanding group of inherited metabolic diseases caused by impaired synthesis and attachment of glycans on proteins and lipids. Disorders affecting the N-glycosylation pathway form the most common CDG subgroup, and the most common N-glycosylation disorder is PMM2-CDG. The symptoms of different CDG are often non-specific and multisystem. Serum transferrin isoelectric focusing (Tf IEF) is a routine method to screen CDG. The aim of this study was to implement Tf IEF in Estonian clinical practice and to study the presence of N-glycosylation defects among Estonian patients in a three-year screening period. Altogether, positive CDG screening with subsequent molecular confirmation was detected in six patients among 1230 subjects screened. First, the most frequent CDG in Estonia is PMM2-CDG as we diagnosed this disorder in four patients from two families. In one family, the siblings show a mild neurological phenotype with normal-borderline cognitive development, which has previously been seldom described. Among PMM2-CDG patients, the most common variant in PMM2 gene is p.Val131Met. Second, we reported the expected frequency of PMM2-CDG based on the Estonian population data. In this cohort, we identified five different heterozygous variants in PMM2 gene. The most frequent variant is p.Arg141His with carrier frequency 1/224. The carrier frequency for p.Val131Met based on the Estonian population data is 1/449. The expected frequency of PMM2-CDG is 1/77,000. Third, we described a patient with SLC35A2-CDG and compared his phenotype-genotype with 14 international SLC35A2-CDG patients. This type of CDG presents as a non-specific neurological syndrome with global developmental delay, hypotonia, seizures and epileptic encephalopathy, together with dysmorphic features and short stature. In addition, Tf IEF can show a normal profile. Fourth, we presented a patient with multisystem clinical CDG features and a novel type II CDG likely caused by homozygous variant in STX5. In conclusion, Tf IEF proved to be an effective method to detect CDG among Estonian patients. Our results led to many findings, which have helped to add new clinical and epidemiological data about different known types of CDG, but also to expand the group of CDG by the discovery of a new type of CDG

Elderly disabled persons in the home setting : aspects of activities in daily life

The overall aim of this thesis was to explore and describe elderly disabled persons' activities in daily life in the home environment from an occupational perspective and, secondly to describe occupational therapy interventions provided to elderly disabled persons in their home setting. Study I explored and described elderly persons' performance in ADL, and occupational therapy interventions provided. Most of the participants wanted to engage in more activities than they were judged to have the capacity and/or environmental support for. Hobby activities outside/inside the home, taking a bath or shower, washing clothes, and cooking were activities presenting significant problems. Participants who received occupational therapy experienced problems regarding self-care. Assessment and assistive devices were the most common occupational therapy interventions provided in the study. Study II focused on participants from study I that had an elevator in their housing and their need for mobility support in the environment. Social contacts in the home and weekly shopping were activities where no major difference could be seen between those elderly persons who needed assistance using the elevator and those who managed the elevator alone. Mobility was not only related to a person's bodily function but also to social support from the environment. Study III explored and described occupational therapy intervention patterns over two periods. Treatment/training, prevention in everyday activities and information/consultation increased from period I to period 2, while interventions concerning assistive devices decreased. Treatment/training during both periods concerning leisure/recreation activities, whilst interventions concerned consultation seemed to be changing over time from focusing on clients to relatives and home help staff. Study IV aimed at uncovering and interpreting elderly disabled persons' experiences, values and meanings of being engaged in daily occupations. Themes related to participation against the odds, retreat from occupation, the need for an invitation from others, and personal meanings related to capacities for occupations were uncovered. The findings suggest that for occupational therapy it is important to distinguish between when a person has made a conscious choice to withdraw from occupational life and when a person, for example, has to few occupational choices. Study V described and evaluated a clinical attempt to change occupational therapy practice when reporting clients between occupational therapists in the chain of care. The ADL taxonomy was used as an instrument for transferring the information. It was seen as useful for this purpose but there was still a need for reporting clients orally. Aspects of temporality, structure, professionalism and the instrument's usefulness overall influenced the transfer of information. Systematic discharge planning schemes, written and formally structured information, feedback loop for communication, and collaboration with the clients and their families in the discharge process are suggested as guidelines for the transfer of information. Implications of the studies for occupational therapy for elderly disabled persons in the home setting are proposed in the discussion section

Äldres rehabiliteringsbehov i hemmiljö

Upprättat; 2001; 20131113 (andbra

Rural crime novels - the new home district literature? : Analysis of three detective series from Sandhamn, Kiruna and Öland

During the last years the number of Swedish detective stories which take place in the province outside the big cities has increased enormously. In this study I have analysed the novels by the three authors Viveca Sten, Åsa Larsson and Johan Theorin to investigate the connection between the milieu and the story and in what way it is involved in the crime riddle. They all keep to the formula of the classical detective story but represent different variations within this formula. In spite of the differences in their stories the basic pattern is the same. As their protagonists the authors are emotionally connected to the place in the novels. This connection it strengthen by the authors themselves as well as the publishing companies when introducing them on the market. The protagonists have lived elsewhere and are getting back into the place. They return to houses where an older generation has lived, take over the furniture and the tools. The history of the place and the living there in old days are referred to in separate parts or by an elderly person who has lived in the place all the time and know everything about it. How people lived long ago is also often told in backlashes which in the end are connected to the murder in which the protagonist is engaged. The motives of the crimes are timeless in these novels. The three authors describe a nostalgic longing back to the place as it once was. It is a sort of new romanticism in a timeless world

Attention difficulties and physical dysfunction common in children with complex congenital malformations : a study of preschool children with VACTERL association

AIM: Knowledge on the neurodevelopmental and physical function in children with vertebral defects, anorectal malformations, cardiac defects, tracheo-oesophageal fistula, renal and limb malformations (VACTERL) is scarce. We evaluated Swedish preschool children with VACTERL and identified whether they would need extra support in school. METHODS: From 2015 to 2017, we recruited children aged 5-7 with VACTERL association from the paediatric surgical centre at the University Children's Hospital at Uppsala. Neurodevelopmental function was assessed by age-appropriate intelligence and visual and auditory attention tests, and the children's behaviour and attention were observed by an experienced psychologist. Physical function was evaluated through parental interviews and examinations. Data on patient characteristics, including any surgery and anaesthesia, were extracted from medical records. RESULTS: Of the 13 eligible families, 10 agreed to participate. Intelligence was within the normal range for all children, but attention difficulties were found in eight of the children, requiring adjustments at school, and two of these were later diagnosed with attention deficit hyperactivity disorder. All children had physical dysfunctions that affected their daily nutrition, bowel or bladder functions. CONCLUSION: Attention difficulties and physical dysfunction were common in Swedish preschool children aged 5-7 with VACTERL and they would need support and adjustments when they started school

“To Work Just Like Anyone Else”—A Narrative from a Man Aging with Spinal Cord Injury

People aging with spinal cord injury (SCI) develop medical problems commonly associated with the aging process at a younger age than the general population. However, research about how the life story changes and how meaning will be experienced in occupations is lacking. The aim was to describe and offer an explanation of how a man experienced meaning in everyday occupations while aging with an SCI. Four narrative interviews were performed over a four-year period, with a man in his fifties, who lived with SCI for 39 years. The narrative analysis generated an overall plot, named “To Work Just Like Anyone Else,” and gives a picture of his experiences, thoughts, and reflections about meaning in occupations, from when he became injured to the present, and in relation to his future. His life story is characterized by secondary health complications, and his experiences of negotiating with the aging body and making choices to continue working. Further, how occupational risk factors, e.g., imbalance, alienation, and deprivation, occur as a result of lack of rehabilitation and support from social systems is addressed. Future research should explore how rehabilitation and social systems can support people aging with SCI to experience meaning in everyday occupations and to have balance in everyday life

Irish Traveller Children's Play: A Scoping Review

Irish Traveller children, an ethnic indigenous minoritized community in Ireland are identified in Ireland’s play policy as at higher risk of exclusion from realising their right to play, alongside a reported absence of research on indigenous children’s play. This scoping review aimed to identify the breadth and scope of available research on representations of Irish Traveller children’s play and the factors influencing play opportunities. Applying the updated Joanna Briggs Institute methodological guidance, a systematic search was completed of nine databases. Thirty-five peer reviewed studies met the inclusion criteria, descriptive study information was charted and summarised and enabling and restricting factors influencing Irish Traveller children’s play were identified using an existing conceptual model. The scoping review findings revealed a limited focus within research on Irish Traveller children’s play. Included studies however, provided evidence of; the importance of feeling a sense of belonging and safety to enable Irish Traveller children’s access to preferred play opportunities, involving real life activities, physical play outdoors and play with others; Irish Traveller parents value and facilitation of play; and the significant restricting influence of racism on Irish Traveller children’s play .Limited knowledge on Irish Traveller children’s own perspectives on play and the need to address racism as a restricting influence on play in school and community environments are considered in relation to practice and further research. Discourses representing Irish Traveller children as marginalised, were problematized as reflective of culturist assumptions, and a shift towards understanding the situated nature of Irish Traveller children’s play, as a capability is proposed.License fulltext: CC BY</p

Cross-Cultural Validity of the German Version of the Pediatric Evulation of Disabiity Inventory (PEDI-G) : a Rasch Model Application

Godkänd; 2016; 20160629 (andbra