Experiences of rehabilitation services from the perspective of older adults with dual sensory loss - a qualitative study.

PURPOSE: To describe the rehabilitation service experiences of older adults with dual sensory loss (DSL). METHODS: Twenty older adults aged ≥65 years with DSL participated in semistructured interviews. Inductive qualitative content analysis was conducted. RESULTS: The participants' experiences were classified into three main categories: 1. Maintaining and regaining function included experiences regarding interventions compensating for loss of function and medical corrections; 2. Mastering the situation described the individuals' competence of DSL, skills acquisition and taking control; and 3. Delivery of rehabilitation services included experiences of encounters with professionals, their attitudes and the organizational impact on accessibility and collaboration. CONCLUSIONS: It was important for participants to regain function and compensate for loss in function and to meet others in group rehabilitation. The professionals' attitudes were an important factor that affected the participants' approach to rehabilitation services. Rehabilitation services mainly focused on either VL or HL, not DSL. Based on the participants' experiences, the rehabilitation services seemed to contribute to the older adults' well-being, participation in activities and life roles, which is consistent with the WHO's definition of healthy ageing. The findings can contribute to the development of rehabilitation services for older adults with DSL to meet the diversity of these individuals' needs.

Prevalence, diagnoses and rehabilitation services related to severe dual sensory loss (DSL) in older persons: a cross-sectional study based on medical records.

OBJECTIVE: To estimate the prevalence of severe dual sensory loss (DSL) among older persons (aged ≥65 years) in the Swedish population, to identify the diagnoses that cause severe DSL, and to identify rehabilitation services in which the participants have been involved. DESIGN: A cross-sectional design was applied. Medical records from Audiological, Low Vision, and Vision clinics from two Swedish counties were used. STUDY SAMPLE: 1257 adults, aged ≥65 years with severe hearing loss (HL) (≥70 dB HL) were included, whereof 101 had decimal visual acuity ≤0.3. RESULTS: Based on the population size in the two counties (≥65 years, n = 127,638), the prevalence of severe DSL was approximately 0.08% in the population. Within the group having DSL (n = 101), 61% were women and 71% were aged ≥85 years. Common diagnoses were cataract and/or age-related macular degeneration (AMD) in combination with HL. The rehabilitation services offered were mainly hearing aids and various magnifiers. CONCLUSIONS: The study confirmed previous results, indicating that the prevalence of severe DSL increases with age and that sensorineural HL and cataract, AMD or glaucoma coexist. The identified rehabilitation services mainly focussed on either vision loss or HL but not on severe DSL as a complex health condition.

Spatiotemporal mapping of RNA editing in the developing mouse brain using in situ sequencing reveals regional and cell-type-specific regulation.

BACKGROUND: Adenosine-to-inosine (A-to-I) RNA editing is a process that contributes to the diversification of proteins that has been shown to be essential for neurotransmission and other neuronal functions. However, the spatiotemporal and diversification properties of RNA editing in the brain are largely unknown. Here, we applied in situ sequencing to distinguish between edited and unedited transcripts in distinct regions of the mouse brain at four developmental stages, and investigate the diversity of the RNA landscape. RESULTS: We analyzed RNA editing at codon-altering sites using in situ sequencing at single-cell resolution, in combination with the detection of individual ADAR enzymes and specific cell type marker transcripts. This approach revealed cell-type-specific regulation of RNA editing of a set of transcripts, and developmental and regional variation in editing levels for many of the targeted sites. We found increasing editing diversity throughout development, which arises through regional- and cell type-specific regulation of ADAR enzymes and target transcripts. CONCLUSIONS: Our single-cell in situ sequencing method has proved useful to study the complex landscape of RNA editing and our results indicate that this complexity arises due to distinct mechanisms of regulating individual RNA editing sites, acting both regionally and in specific cell types.

Automatic registration of 2D histological sections to 3D microCT volumes: Trabecular bone.

Histomorphometry and microCT are the two dominant imaging techniques to study bone structure and quality to evaluate repair, regeneration, and disease. These two methods are complementary; where histology provides highly resolved tissue properties on a cellular level in 2D, microCT provides spatial information of bone micro-structure in 3D. For this reason, both of these modalities are commonly used in bone studies. As it is not trivial to combine the images of these two modalities, the two methods are typically applied to different specimens within a study. However, we believe that applying both imaging modalities to the same specimen with a suitable fusion strategy may further strengthen the value of each modality. Therefore, we propose a registration method to align 2D histology slices with a 3D microCT volume, without any prior knowledge of the sectioning direction. In a preprocessing step, bone is extracted from both images. Then, we use a strategy for initializing potential locations, and an iterative approach for searching for an ideal fitting plane using Radon-based rigid transforms and feature-based affine alignments. The algorithm was tested and validated with simulated and real data. For the latter, microCT images of trabecular bone with 76 corresponding histological sections acquired from decalcified and calcified specimens were used. The registration resulted in 94.7% acceptable solutions as defined by a registration orientation error of less than 3°. Average registration accuracy of the acceptable results was 0.6°, leading to a target registration error for our method of 106.3µm, computed based on landmarks annotated by an observer. This corresponds roughly to 10pixels in the images; although, the relation to actual visible structures that provide the features to register, is arguably more relevant.

Spatial sexual dimorphism of X and Y homolog gene expression in the human central nervous system during early male development.

BACKGROUND: Renewed attention has been directed to the functions of the Y chromosome in the central nervous system during early human male development, due to the recent proposed involvement in neurodevelopmental diseases. PCDH11Y and NLGN4Y are of special interest because they belong to gene families involved in cell fate determination and formation of dendrites and axon. METHODS: We used RNA sequencing, immunocytochemistry and a padlock probing and rolling circle amplification strategy, to distinguish the expression of X and Y homologs in situ in the human brain for the first time. To minimize influence of androgens on the sex differences in the brain, we focused our investigation to human embryos at 8-11 weeks post-gestation. RESULTS: We found that the X- and Y-encoded genes are expressed in specific and heterogeneous cellular sub-populations of both glial and neuronal origins. More importantly, we found differential distribution patterns of X and Y homologs in the male developing central nervous system. CONCLUSIONS: This study has visualized the spatial distribution of PCDH11X/Y and NLGN4X/Y in human developing nervous tissue. The observed spatial distribution patterns suggest the existence of an additional layer of complexity in the development of the male CNS.

Percutaneous Closure in Transfemoral Aortic Valve Implantation: A Single-Centre Experience.

PURPOSE: To report the experience of a percutaneous closure device used for transfemoral transcatheter aortic valve implantation (TAVI) in an unselected patient and operator population. MATERIALS AND METHODS: Eighty-two consecutive patients (32 women, 50 men) who underwent transfemoral TAVI between September 2009 and February 2014 at our hospital were retrospectively reviewed for percutaneous closure device (PCD) failure, vascular complications, and bleeding. The diameter and calcification of the common femoral artery (CFA) and the thickness of the subcutaneous fat layer in the groin were assessed on computed tomography images. RESULTS: The incidences of PCD failure and minor and major vascular complications were 19.5% (n = 16/82), 19.5% (n = 16/82), and 7% (n = 6/82) respectively. 8.5% (n = 7/82) had a minor perioperative bleeding, 6% (n = 5/82) had a major bleeding, and none had any life-threatening bleeding. When PCD failed, haemostasis was obtained with fascia suturing, covered stent placement, or with surgical cutdown. Thirty-day mortality and 1-year all-cause mortality were 8.5% (n = 7/82) and 19.5% (n = 16/82), respectively. In a multiple regression analysis, the CFA diameter and the presence of severe calcification were independently related to PCD failure (correlation coefficient = -0.24, p = 0.027 and correlation coefficient = 0.23, p = 0.036, respectively). CONCLUSION: PCD failure was related to a small CFA diameter and to a severely calcified CFA. Failure could largely be managed with minimally invasive techniques such as covered stents or fascia suturing.

No difference in small bowel microbiota between patients with irritable bowel syndrome and healthy controls.

Several studies have indicated that colonic microbiota may exhibit important differences between patients with irritable bowel syndrome (IBS) and healthy controls. Less is known about the microbiota of the small bowel. We used massive parallel sequencing to explore the composition of small bowel mucosa-associated microbiota in patients with IBS and healthy controls. We analysed capsule biopsies from the jejunum of 35 patients (26 females) with IBS aged 18-(36)-57 years and 16 healthy volunteers (11 females) aged 20-(32)-48 years. Sequences were analysed based on taxonomic classification. The phyla with the highest total abundance across all samples were: Firmicutes (43%), Proteobacteria (23%), Bacteroidetes (15%), Actinobacteria (9.3%) and Fusobacteria (7.0%). The most abundant genera were: Streptococcus (19%), Veillonella (13%), Prevotella (12%), Rothia (6.4%), Haemophilus (5.7%), Actinobacillus (5.5%), Escherichia (4.6%) and Fusobacterium (4.3%). We found no difference among major phyla or genera between patients with IBS and controls. We identified a cluster of samples in the small bowel microbiota dominated by Prevotella, which may represent a common enterotype of the upper small intestine. The remaining samples formed a gradient, dominated by Streptococcus at one end and Escherichia at the other.

Human enterovirus species B in ileocecal Crohn's disease.

OBJECTIVES: Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency of NOD2 mutations. Recent findings implicate a role of NOD2 and another CD susceptibility gene, ATG16L1, in the host response against single-stranded RNA (ssRNA) viruses. However, the role of viruses in CD is unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA viruses with dual tropism both for the intestinal epithelium and the nervous system, could play a role in ICD. METHODS: We used immunohistochemistry and in situ hybridization to study the general presence of HEV-B and the presence of the two HEV-B subspecies, Coxsackie B virus (CBV) and Echovirus, in ileocecal resections from 9 children with advanced, stricturing ICD and 6 patients with volvulus, and in intestinal biopsies from 15 CD patients at the time of diagnosis. RESULTS: All patients with ICD had disease-associated polymorphisms in NOD2 or ATG16L1. Positive staining for HEV-B was detected both in the mucosa and in myenteric nerve ganglia in all ICD patients, but in none of the volvulus patients. Expression of the cellular receptor for CBV, CAR, was detected in nerve cell ganglia. CONCLUSIONS: The common presence of HEV-B in the mucosa and enteric nervous system of ICD patients in this small cohort is a novel finding that warrants further investigation to analyze whether HEV-B has a role in disease onset or progress. The presence of CAR in myenteric nerve cell ganglia provides a possible route of entry for CBV into the enteric nervous system.

In situ detection of individual mRNA molecules and protein complexes or post-translational modifications using padlock probes combined with the in situ proximity ligation assay.

Analysis at the single-cell level is essential for the understanding of cellular responses in heterogeneous cell populations, but it has been difficult to perform because of the strict requirements put on detection methods with regard to selectivity and sensitivity (i.e., owing to the cross-reactivity of probes and limited signal amplification). Here we describe a 1.5-d protocol for enumerating and genotyping mRNA molecules in situ while simultaneously obtaining information on protein interactions or post-translational modifications; this is achieved by combining padlock probes with in situ proximity ligation assays (in situ PLA). In addition, we provide an example of how to design padlock probes and how to optimize staining conditions for fixed cells and tissue sections. Both padlock probes and in situ PLA provide the ability to directly visualize single molecules by standard microscopy in fixed cells or tissue sections, and these methods may thus be valuable for both research and diagnostic purposes.