A mutation creating an upstream translation initiation codon in SLC22A5 5′UTR is a frequent cause of primary carnitine deficiency

Primary carnitine deficiency is caused by a defect in the active cellular uptake of carnitine by Na⁺‐dependent organic cation transporter novel 2 (OCTN2). Genetic diagnostic yield for this metabolic disorder has been relatively low, suggesting that disease‐causing variants are missed. We Sanger sequenced the 5′ untranslated region (UTR) of SLC22A5 in individuals with possible primary carnitine deficiency in whom no or only one mutant allele had been found. We identified a novel 5′‐UTR c.‐149G>A variant which we characterized by expression studies with reporter constructs in HeLa cells and by carnitine‐transport measurements in fibroblasts using a newly developed sensitive assay based on tandem mass spectrometry. This variant, which we identified in 57 of 236 individuals of our cohort, introduces a functional upstream out‐of‐frame translation initiation codon. We show that the codon suppresses translation from the wild‐type ATG of SLC22A5, resulting in reduced OCTN2 protein levels and concomitantly lower transport activity. With an allele frequency of 24.2% the c.‐149G>A variant is the most frequent cause of primary carnitine deficiency in our cohort and may explain other reported cases with an incomplete genetic diagnosis. Individuals carrying this variant should be clinically re‐evaluated and monitored to determine if this variant has clinical consequences.     

Nurses’ perceptions towards the delivery and feasibility of a behaviour change intervention to enhance physical activity in patients at risk for cardiovascular disease in primary care: a qualitative study

Background

Self-management support is widely accepted for the management of chronic conditions. Self-management often requires behaviour change in patients, in which primary care nurses play a pivotal role. To support patients in changing their behaviour, the structured behaviour change Activate intervention was developed. This intervention aims to enhance physical activity in patients at risk for cardiovascular disease in primary care as well as to enhance nurses’ role in supporting these patients. This study aimed to evaluate nurses’ perceptions towards the delivery and feasibility of the Activate intervention.

Methods

A qualitative study nested within a cluster-randomised controlled trial using semistructured interviews was conducted and thematically analysed. Fourteen nurses who delivered the Activate intervention participated.

Results

Three key themes emerged concerning nurses’ perceptions of delivering the intervention: nurses’ engagement towards delivering the intervention; acquiring knowledge and skills; and dealing with adherence to the consultation structure. Three key themes were identified concerning the feasibility of the intervention: expectations towards the use of the intervention in routine practice; perceptions towards the feasibility of the training programme; and enabling personal development.

Conclusions

Delivering a behaviour change intervention is challenged by the complexity of changing nurses’ consultation style, including acquiring corresponding knowledge and skills. The findings have increased the understanding of the effectiveness of the Activate trial and will guide the development and evaluation of future behaviour change interventions delivered by nurses in primary care.

Trial registration

ClinicalTrials.gov NCT02725203.

     

Bone formation following implantation of bone biomaterials into extraction sites

BACKGROUND: Adequate bone volume is imperative for the osseointegration of endosseous implants, but postextraction resorption and remodeling may challenge implant placement. The use of bone biomaterials has been advocated to fill extraction sites and to enhance primary implant stability during osseointegration. The objective of the case series was to evaluate bone formation histologically and biomechanically in extraction sites following implantation of three commercially available bone biomaterials to compare their ability to allow guided bone regeneration. METHODS: Thirty-six periodontally involved teeth were extracted from eight healthy non-smoking subjects. At least two bone biomaterials, a synthetic sponge based on polylactic-polyglycolic acid technology (FIS), bovine porous bone mineral (BPBM), or a natural coral derivative physically and chemically transformed into a calcium carbonate ceramic (COR), and one non-grafted control were applied to the extraction sockets within each subject and were covered by an expanded polytetrafluoroethylene device. The devices were removed after 2 months, and trephine biopsies were obtained from each site 4 months later. At that time, endosseous implants were placed in 25 of the sites, and healing abutments were placed; measurements were taken 4 to 6 months later with an electronic mobility testing device. RESULTS: The percentage of residual biomaterial was 5.6% +/- 8.9% for FIS (P <0.001), 20.2% +/- 17.0% for BPBM (P <0.05), and 12.0% +/- 16.4% for COR (P <0.001). The amount of residual biomaterial after 6 months showed a significant relationship with the insertion torque measurements during the first third of implant insertion (P <0.05) and with values of the electronic mobility testing device at the abutment connection (P = 0.05). Histologically, new bone apposition was seen on BPBM particles. FIS sites showed similar ingrowth of blood vessels and osteocytes as empty controls. CONCLUSION: All sites revealed good primary stability at implant insertion and proper implant rigidity at abutment placement, indicating that early implant osseointegration was not influenced by the application of bone biomaterials used in this study.     

Excisional biopsy of suspected benign soft tissue tumors of the upper extremity: correlation between preoperative diagnosis and actual pathology

Background

Tumors of the upper extremity are common and mostly benign. However, the prevalence of discordant diagnosis of a solid hand tumor is less studied. The objectives of this retrospective study were (1) to determine the proportion of patients with a different (discrepant or discordant) pathological diagnosis compared to the preoperative diagnosis, (2) to determine the prevalence of the types of pathologies encountered at excisional biopsy for suspected benign tumors, and (3) to determine the types of tumors diagnosed when the surgeon does not make a preoperative diagnosis.

Methods

One hundred and eighty-two suspected benign soft tissue tumors of the upper extremity with a preoperative diagnosis other than ganglion cyst were excised by one of three surgeons over a 10-year period. A preoperative diagnosis was applied for 125 tumors. No preoperative imaging was used.

Results

Only 26 of the 125 tumors (21 %) with a preoperative diagnosis were discrepant. The tumors that were most likely to have a discrepant diagnosis were vascular tumors (32 %) and other less common benign tumors (33 %). Among the entire cohort of 182 tumors, lipomas (19 %), giant cell tumors of tendon sheath (GCTTS; 19 %), and vascular tumors (16 %) were the most frequent pathological diagnoses. Among the 57 tumors that did not have a preoperative diagnosis, most were vascular tumors (23 %), fibromas (14 %), and GCTTS (11 %). One tumor without a preoperative diagnosis was a malignant tumor, but we consider this unusual and possibly spurious.

Conclusions

A hand surgeon’s preoperative diagnosis without imaging is usually correct prior to excision of a mass in the hand. Discrepant diagnoses are usually benign and do not alter treatment. Level of evidence: Prognostic II     

Health related quality of life in parents of six to eight year old children with Down syndrome

Raising a child with Down syndrome (DS) has been found to be associated with lowered health related quality of life (HRQoL) in the domains cognitive functioning, social functioning, daily activities and vitality. We aimed to explore which socio-demographics, child functioning and psychosocial variables were related to these HRQoL domains in parents of children with DS. Parents of 98 children with DS completed the TNO-AZL adult quality of life questionnaire (TAAQOL) and a questionnaire assessing socio-demographic, child functioning and psychosocial predictors. Using multiple linear regression analyses for each category of predictors, we selected relevant predictors for the final models. The final multiple linear regression models revealed that cognitive functioning was best predicted by the sleep of the child (β = .29, p < .01) and by the parent having given up a hobby (β = ?.29, p < .01), social functioning by the quality of the partner relation (β = .34, p < .001), daily activities by the parent having to care for an ill friend or family member (β = ?.31, p < .01), and vitality by the parent having enough personal time (β = .32, p < .01). Overall, psychosocial variables rather than socio-demographics or child functioning showed most consistent and powerful relations to the HRQoL domains of cognitive functioning, social functioning, daily activities and vitality. These psychosocial variables mainly related to social support and time pressure. Systematic screening of parents to detect problems timely, and interventions targeting the supportive network and the demands in time are recommended.