A potential LINC complex

Apicomplexan parasites include some of the most important pathogens, such as Plasmodium spp., the causative agent of malaria, or Toxoplasma gondii, the causative agent of toxoplasmosis. As obligate intracellular parasites, Apicomplexa invade host cells in an active process, where they replicate within a parasitophorous vacuole, followed by egress and lysis of the host cell. T. gondii parasites use a unique mode of cell division called endodyogeny, in which two daughter cells form within the mother parasite. Connections between the nucleus and the cytoskeleton are important for positioning and division of the nucleus. In most eukaryotes, the LINC complex (Linker of Nucleoskeleton and Cytoskeleton) spans the outer and inner nuclear membranes and connects the nucleus to the cytoskeleton. In opisthokonts, it is composed of KASH domain proteins and SUN domain proteins. Given that the nucleus is positioned at the posterior pole of T. gondii, it can be speculated that apicomplexan parasites must have a similar mechanism that integrates the nucleus and the cytoskeleton. Here, three UNC family proteins were identified in the genome of the apicomplexan parasite T.gondii. While the UNC-50 protein TgUNC1 localised to the Golgi and appeared to be not essential for the parasite, the SUN domain protein TgSLP2 showed a diffuse pattern throughout the parasite. The second SUN domain protein, TgSLP1, was expressed in a cell-cycle dependent manner, localised close to the mitotic spindle and conditional knockout of TgSLP1 leads to failure of nuclear division and loss of centrocone integrity

Downbeat nystagmus: aetiology and comorbidity in 117 patients

Objectives: Downbeat nystagmus (DBN) is the most common form of acquired involuntary ocular oscillation overriding fixation. According to previous studies, the cause of DBN is unsolved in up to 44% of cases. We reviewed 117 patients to establish whether analysis of a large collective and improved diagnostic means would reduce the number of cases with ``idiopathic DBN'' and thus change the aetiological spectrum.Methods: The medical records of all patients diagnosed with DBN in our Neurological Dizziness Unit between 1992 and 2006 were reviewed. In the final analysis, only those with documented cranial MRI were included. Their workup comprised a detailed history, standardised neurological, neuro-otological and neuro-ophthalmological examination, and further laboratory tests.Results: In 62% (n = 72) of patients the aetiology was identified (``secondary DBN''), the most frequent causes being cerebellar degeneration (n = 23) and cerebellar ischaemia (n = 10). In 38% (n = 45), no cause was found (``idiopathic DBN''). A major finding was the high comorbidity of both idiopathic and secondary DBN with bilateral vestibulopathy (36%) and the association with polyneuropathy and cerebellar ataxia even without cerebellar pathology on MRI.Conclusions: Idiopathic DBN remains common despite improved diagnostic techniques. Our findings allow the classification of ``idiopathic DBN'' into three subgroups: ``pure'' DBN (n = 17); ``cerebellar'' DBN (ie, DBN plus further cerebellar signs in the absence of cerebellar pathology on MRI; n = 6); and a ``syndromatic'' form of DBN associated with at least two of the following: bilateral vestibulopathy, cerebellar signs and peripheral neuropathy (n = 16). The latter may be caused by multisystem neurodegeneration

The SUN-like protein TgSLP1 is essential for nuclear division in the apicomplexan parasite Toxoplasma gondii

Connections between the nucleus and the cytoskeleton are important for positioning and division of the nucleus. In most eukaryotes, the linker of nucleoskeleton and cytoskeleton (LINC) complex spans the outer and inner nuclear membranes and connects the nucleus to the cytoskeleton. In opisthokonts, it is composed of Klarsicht, ANC-1 and Syne homology (KASH) domain proteins and Sad1 and UNC-84 (SUN) domain proteins. Given that the nucleus is positioned at the posterior pole of Toxoplasma gondii, we speculated that apicomplexan parasites must have a similar mechanism that integrates the nucleus and the cytoskeleton. Here, we identified three UNC family proteins in the genome of the apicomplexan parasite T. gondii. Whereas the UNC-50 protein TgUNC1 localised to the Golgi and appeared to be not essential for the parasite, the SUN domain protein TgSLP2 showed a diffuse pattern throughout the parasite. The second SUN domain protein, TgSLP1, was expressed in a cell cycle-dependent manner and was localised close to the mitotic spindle and, more detailed, at the kinetochore. We demonstrate that conditional knockout of TgSLP1 leads to failure of nuclear division and loss of centrocone integrity

Use of professional home care in persons with spinal cord injury in Switzerland: a cross-sectional study

BACKGROUND Persons with spinal cord injury (SCI) living in the community often require care. The boundaries between professional home care and informal care are blurred, and it is unclear who the typical user of home care is. The objective of this study was to describe the characteristics of persons with SCI using professional home care in Switzerland, determine the frequency of home care visits, and investigate the association of sociodemographic factors, SCI-specific characteristics, secondary health conditions, and functional independence with the use of home care. METHODS We used cross-sectional data from the 2017 community survey of the Swiss Spinal Cord Injury Cohort Study (SwiSCI). Out of 3,959 eligible individuals 1294 completed the questionnaire and were included in the analysis (response rate 33%). Using descriptive statistics, differences between home care users and non-users as well as the frequency of home care visits were investigated. The association between sociodemographic factors, SCI-specific characteristics, secondary health conditions, functional independence and the use of home care was analyzed using multivariable logistic regression. Multiple imputation was used to account for missing data. RESULTS Of 1,294 participants, 280 (22%) used professional home care. The median weekly professional home care duration was 6 h (Q1 = 2, Q3 = 12). More home care was used in persons with lower functional independence (Odds ratio (OR) 0.30 per 10 unit decrease in the Spinal Cord Independence Measure, 95%-Confidence interval (CI) 0.24-0.37), fewer secondary health conditions (OR 0.96 per unit Spinal Cord Injury Secondary Conditions Scale, 95%-CI 0.94-0.99), tetraplegia (OR 2.77, 95%-CI 1.92-4.00), women (OR 2.42, 95%-CI 1.70-3.43), higher age (OR 1.22 per 10 years increase, 95%-CI 1.06-1.39), living alone (OR 2.48, 95%-CI 1.53-4.03), and those receiving support from an informal caregiver (OR 1.88, 95%-CI 1.27-2.77). CONCLUSIONS This is the first study to examine the use of professional home care from the perspective of persons with SCI in Switzerland. Lower functional independence strongly predicts increased home care use. The findings showed that professional home care complements informal care and is more likely to be used by individuals with SCI who live alone, have tetraplegia, and are female

Assessing real-world vaccine effectiveness against severe forms of SARS-CoV-2 infection: an observational study from routine surveillance data in Switzerland.

BACKGROUND In Switzerland, SARS-CoV-2 vaccination campaigns started in early 2021. Vaccine coverage reached 65% of the population in December 2021, mostly with mRNA vaccines from Moderna and Pfizer-BioNtech. Simultaneously, the proportion of vaccinated among COVID-19-related hospitalisations and deaths rose, creating some confusion in the general population. We aimed to assess vaccine effectiveness against severe forms of SARS-CoV-2 infection using routine surveillance data on the vaccination status of COVID-19-related hospitalisations and deaths, and data on vaccine coverage in Switzerland. METHODS We considered all routine surveillance data on COVID-19-related hospitalisations and deaths received at the Swiss Federal Office of Public Health from 1 July to 1 December 2021. We estimated the relative risk of COVID-19-related hospitalisation or death for not fully vaccinated compared with fully vaccinated individuals, adjusted for the dynamics of vaccine coverage over time, by age and location. We stratified the analysis by age group and by calendar month. We assessed variations in the relative risk of hospitalisation associated with the time since vaccination. RESULTS We included a total of 5948 COVID-19-related hospitalisations of which 1245 (21%) were fully vaccinated patients, and a total of 739 deaths of which 259 (35%) were fully vaccinated. We found that the relative risk of COVID-19 related hospitalisation was 12.5 (95% confidence interval [CI] 11.7-13.4) times higher for not fully vaccinated than for fully vaccinated individuals. This translates into a vaccine effectiveness against hospitalisation of 92.0% (95% CI 91.4-92.5%). Vaccine effectiveness against death was estimated to be 90.3% (95% CI 88.6-91.8%). Effectiveness appeared to be comparatively lower in age groups over 70 and during the months of October and November 2021. We also found evidence of a decrease in vaccine effectiveness against hospitalisation for individuals vaccinated for 25 weeks or more, but this decrease appeared only in age groups below 70. CONCLUSIONS The observed proportions of vaccinated among COVD-19-related hospitalisations and deaths in Switzerland were compatible with a high effectiveness of mRNA vaccines from Moderna and Pfizer-BioNtech against hospitalisation and death in all age groups. Effectiveness appears comparatively lower in older age groups, suggesting the importance of booster vaccinations. We found inconclusive evidence that vaccine effectiveness wanes over time. Repeated analyses will be able to better assess waning and the effect of boosters

No Association between Clinical Periodontal Conditions and Microbiological Findings on Driveline of Patients with Left-Ventricular Assist Devices (LVAD)

The aim of this retrospective study was to investigate whether there would be an association between periodontal disease parameters and positive bacterial findings at the driveline of patients with a left ventricular assist device (LVAD). Patients with an LVAD, who underwent a full oral and microbiological examination between 2016 and 2018, were included. During oral examination, periodontitis severity (stage and grade) and the periodontal inflamed surface area (PISA) were evaluated. A microbiological analysis was performed from swabs of the driveline, whereby different bacterial species were cultivated and analyzed. A total of 73 patients were included in the current study. The majority of participants (80.8%) had at least one positive bacterial finding during the study period. Most patients had a periodontitis stage of III-IV (80.9%). The determined PISA of the total group was 284.78 ± 352.29 mm2. No associations were found between the periodontal disease parameters and the bacterial findings in general, the bacterial findings on the day of oral examination or the bacterial findings 12 months prior to/after the oral examination (p > 0.05). Periodontitis is not associated with cultivated microbiological findings at the driveline of patients with an LVAD and thus appears not to be a risk indicator for driveline colonization. Nevertheless, the high periodontal burden in LVAD patients underlines the need for their improved periodontal care

Insufficient Oral Behaviour and the High Need for Periodontal Treatment in Patients with Heart Insufficiency and after Heart Transplantation: A Need for Special Care Programs?

Background: The aim of this cross-sectional study was the assessment of dental behaviour and oral health condition of heart transplant recipients (HTx) in comparison to patients with heart insufficiency (HI). Methods: Patients attending the Department for Cardiac Surgery, Leipzig Heart Center, Germany were recruited. Standardized questionnaires regarding dental behaviour and periodontal complaints were applied. A dental (decayed-, missing- and filled-teeth index) and periodontal examination (periodontal probing depth (PPD) and clinical attachment loss (CAL)) was performed. Based on the oral findings, dental and periodontal treatment need was determined. Statistics: T-test, Mann-Whitney U test, Chi-square test, and Fisher-test (p < 0.05). Results: A total of 201 patients (HTx: 112, HI: 89) were included. HTx patients were significantly more often allocated to dentists (p < 0.01). Furthermore, the HTx patients rated feeling informed appropriately about oral health more often (p < 0.01). HTx patients used interdental cleaning (p < 0.01) and mouth rinse (p = 0.02) more often than HI patients. No differences between groups were present regarding dental status and periodontitis severity (p > 0.05). Periodontal treatment need was high, showing prevalence of 79.5% (HTx) and 87.6% (HI, p = 0.14), respectively. Conclusions: Both groups show insufficient oral behaviour and a high need for periodontal treatment. Special care programs for HTx candidates and recipients appear recommendable

Organisational Health Services Research in Germany:A Scoping Review of Conference Abstracts

Background Health Services Research (HSR) is a growing field in Germany, in which Organisational Health Services Research (OHSR) has emerged as a subfield. The aim of this scoping review was to provide an overview of the field of OHSR within HSR in Germany and to map systematically original contributions by describing the organisational setting, the research design, the research objectives and the theoretical underpinning.Methods A scoping review examined published abstracts from the 19th German Conference on Health Services Research 2020. Abstracts were included if (1) health care organisations, subunits or organisational processes were mentioned as research objects, and (2) if at least one out of five research perspectives from a recent German definition of OHSR was addressed. After intensive pilot screenings within a group of nine researchers, all abstracts were screened independently in three review teams with three researchers each, and data from included abstracts were extracted using content analysis based on a self-developed detailed coding scheme.Results Out of n=468 identified abstracts in German (84%) or English (16%) language, n=138 (29.5%) abstracts were included. The majority of included abstracts addressed acute care in hospitals (34.8%), reported results from observational studies (59.4%) and collected primary data (69.6%). There was a slightly higher use of quantitative (32.6%) than qualitative (24.6%) research methods with a considerable number of studies using more than one method (31.9%). An explicit reference to theory was made in 7.2% and 17.4% used the term ‘organisation’ or related terms explicitly in their abstract.Discussion This review provides a systematic but preliminary overview of the scope to which HSR in Germany addresses OHSR. The organisational perspective is considered extensively in HSR abstracts, but mostly implicitly. The research is reported largely free of theory which can reduce their explanatory power. Therefore, a research agenda, more awareness as well as education and better conceptualisation of OHSR topics within German HSR are needed

Swiss Recommendations for Cutaneous Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer in Switzerland and worldwide. Most BCCs can be treated in a curative setting. However, patients can develop locally destructive and, rarely, metastatic tumors that require a different treatment approach. The clinical subtype of individual lesions provides prognostic information and influences management decisions. Surgical excision, topical therapies, and radiotherapy are highly effective in the majority of subtypes as well as in low- and high-risk diseases. For patients with low-risk diseases and superficial tumors not amenable to surgery, several nonsurgical alternatives are available. Systemic therapy is indicated for high-risk BCCs, which are not amenable to either surgery or radiotherapy. Hedgehog pathway inhibitors (HHI) are currently approved. Other therapeutic options such as immune checkpoint inhibitors show promising results in clinical trials. This first version of Swiss recommendations for diagnosis and management of BCC was prepared through extensive literature review and an advisory board consensus of expert dermatologists and oncologists in Switzerland. The present guidelines recommend therapies based on a multidisciplinary team approach and rate of recurrence for individual lesions. Based on the risk of recurrence, two distinct groups have been identified: low-risk (easy-to-treat) and high-risk (difficult-to-treat) tumors. Based on these classifications, evidence-based recommendations of available therapies are presented herein