Morphological and Functional Aspects and Quality of Life in Patients with Achromatopsia

(1) Background: Achromatopsia is a rare disease of which the natural course and impact on life are still unknown to this date. We aimed to assess the morphological, functional characteristics, and quality of life in a large sample size of patients with achromatopsia. (2) A total of 94 achromats were included in this retrospective cohort study. Sixty-four were patients of the Department of Ophthalmology, Saarland University Medical Centre in Homburg/Saar, Germany, between 2008 and 2021. Thirty further participants with achromatopsia from the national support group were included using an online questionnaire, which is available under ‘Supplementary data’. Statistical analysis was performed using SPSS Version 25; (3) The 94 patients (37 males (39.4%) and 57 females (60.6%)) showed a mean age of 24.23 ± 18.53 years. Visual acuity was stable (SD ± 0.22 logMAR at 1.0 logMAR) over a time of observation from 2008 to 2021. Edge filter glasses were the most used optical aids, while enlarged reading glasses were the most used low vision aids. (4) Conclusions: Our findings give an insight into describing the natural process and the quality of life of achromatopsia. The results demonstrate that achromatopsia is a predominantly stationary disease. The individual prescription of edge filters and low-vision aids is essential following a personalised fitting

Prediction of cardiac worsening through to cardiogenic shock in patients with acute heart failure

Aims: Acute heart failure (AHF) can result in worsening of heart failure (WHF), cardiogenic shock (CS), or death. Risk factors for these adverse outcomes are not well characterized. This study aimed to identify predictors for WHF or new‐onset CS in patients hospitalized for AHF. Methods and results: Prospective cohort study enrolling consecutive patients with AHF admitted to a large tertiary care centre with follow‐up until death or discharge. WHF was defined by the RELAX‐AHF‐2 criteria. CS was defined as SCAI stages B–E. Potential predictors were assessed by fitting logistic regression models adjusted for age and sex. N = 233 patients were enrolled, median age was 78 years, and 80 were women (35.9%). Ischaemic cardiomyopathy was present in 82 patients (40.8%). Overall, 96 (44.2%) developed WHF and 18 (9.7%) CS. In‐hospital death (8/223, 3.6%) was related to both events (WHF: OR 6.64, 95% CI 1.21–36.55, P = 0.03; CS: OR 38.27, 95% CI 6.32–231.81, P < 0.001). Chronic kidney disease (OR 2.20, 95% CI 1.25–3.93, P = 0.007), logarithmized serum creatinine (OR 2.90, 95% CI 1.51–5.82, P = 0.002), cystatin c (OR 1.86, 95% CI 1.27–2.77, P = 0.002), tricuspid valve regurgitation (OR 2.08, 95% CI 1.11–3.94, P = 0.023) and logarithmized pro‐adrenomedullin (OR 3.01, 95% CI 1.75–5.38, P < 0.001) were significant predictors of WHF. Chronic kidney disease (OR 3.17, 95% CI 1.16–9.58, P = 0.03), cystatin c (OR 1.88, 95% CI 1.00–3.53, P = 0.045), logarithmized pro‐adrenomedullin (OR 2.90, 95% CI 1.19–7.19, P = 0.019), and tricuspid valve regurgitation (OR 10.44, 95% CI 2.61–70.00, P = 0.003) were significantly with new‐onset CS. Conclusions: Half of patients admitted with AHF experience WHF or new‐onset CS. Chronic kidney disease, tricuspid valve regurgitation, and elevated pro‐adrenomedullin concentrations predict these events. They could potentially serve as early warning signs for further deterioration in AHF patients

The replisome-coupled E3 ubiquitin ligase Rtt101Mms22 counteracts Mrc1 function to tolerate genotoxic stress

Faithful DNA replication and repair requires the activity of cullin 4-based E3 ubiquitin ligases (CRL4), but the underlying mechanisms remain poorly understood. The budding yeast Cul4 homologue, Rtt101, in complex with the linker Mms1 and the putative substrate adaptor Mms22 promotes progression of replication forks through damaged DNA. Here we characterized the interactome of Mms22 and found that the Rtt101Mms22 ligase associates with the replisome progression complex during S-phase via the amino-terminal WD40 domain of Ctf4. Moreover, genetic screening for suppressors of the genotoxic sensitivity of rtt101Δ cells identified a cluster of replication proteins, among them a component of the fork protection complex, Mrc1. In contrast to rtt101Δ and mms22Δ cells, mrc1Δ rtt101Δ and mrc1Δ mms22Δ double mutants complete DNA replication upon replication stress by facilitating the repair/restart of stalled replication forks using a Rad52-dependent mechanism. Our results suggest that the Rtt101Mms22 E3 ligase does not induce Mrc1 degradation, but specifically counteracts Mrc1's replicative function, possibly by modulating its interaction with the CMG (Cdc45-MCM-GINS) complex at stalled forks.</p

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Oral abstracts 1: SpondyloarthropathiesO1. Detecting axial spondyloarthritis amongst primary care back pain referrals

Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn's disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interes

Formalization and evaluation of memory-based listening experiments

Which acoustic features of the audio signal make music memorable and recognizable is still debated. One restricting factor in music research has been the lack of externally valid data. To overcome this, gamified experiments such as musical memory have been introduced. However, to keep track of all variables of interest and be able to model latent cognitive processes a formal account for these games is needed. This report therefore introduces a formal representation of the states and transitions in our version of the solitaire audio matching pairs game. These formalizations give us the possibility to talk about different states in the game, can be used to track how players progress through the game and might allow us to find mappings between different game outcomes and the underlying cognitive processes.  </p

Optic pit maculopathy: incidence and clinical course

Ziel: Ziel dieser Fallserie ist es, den klinischen Verlauf von Patienten mit GrubenpapillenMakulopathie zu untersuchen. Methoden: Es wurde die Krankenakten aller Patienten ausgewertet, bei denen in den letzten 10 Jahren eine Grubenpapille diagnostiziert wurde. Eine GrubenpapillenMakulopathie wurde diagnostiziert, wenn sich lokalisierte intraretinale oder/und subretinale Flüssigkeit vom Sehnerv zur Makula ausgebreitet hatte. Zu den Zielgrößen gehörten Veränderungen der bestkorrigierten Sehschärfe (BCVA), der zentralen Netzhautdicke (RT), der nasalen parafovealen und perifovealen RT. Ergebnisse: Bei 18 Patienten (9 weiblich, 9 männlich, Durchschnittsalter: 33 ± 23 Jahre) wurde eine Grubenpapille diagnostiziert. Bei 6 Patienten (33,3 %) lag eine Ansammlung von Netzhautflüssigkeit vor (1 intraretinal, 1 subretinal, 4 intra- und subretinal). Eine Pars-plana-Vitrektomie mit Entfernung der peripapillären Glaskörpertraktion und ILM-Peeling wurde bei 5 Patienten indiziert und bei 4 Patienten durchgeführt. Ein Patient unterzog sich stattdessen einer Nano-Puls-Laserbehandlung. Die Patienten mit Grubenpapillen-Makulopathie waren im Durchschnitt 47 ± 16 Jahre alt. Die mittlere bestkorrigierte Sehschärfe (BCVA) (dezimal) der Patientengruppe verbesserte sich von 0,3 ± 0,2 vor der Behandlung auf 0,5 ± 0,2 3 Monate nach der Behandlung (p= 0,03). Bei allen Patienten mit Grubenpapillen-Makulopathie, die mit Pars-plana-Vitrektomie behandelt wurden, verbesserte sich der Visus. Die mittlere zentrale Netzhautdicke (RT) sank von 796 ± 214 vor der Behandlung auf 324 ± 57 3 Monate nach der Behandlung (p= 0,005). Die mittlere nasale parafoveale RT sank von 683 ± 87 vor der Behandlung auf 372 ± 41 (p= 0,0003), und die mittlere nasale perifoveale RT sank von 547 ± 89 vor der Behandlung auf 360 ± 48 (p= 0,007). Bei 4 Augen war nach einem mittleren Followup von 3 Monaten eine vollständig trockene Makula erreicht. Bei der langfristigen Verlaufskontrolle (2,5 ± 1,2 Jahre) trat an den vitrektomierten Augen kein Rezidiv auf. Schlussfolgerung: In dieser Fallserie wurde festgestellt, dass bei mehr als einem Drittel der Patienten mit Grubenpapillen eine Makulopathie auftritt, die wahrscheinlich durch eine Disruption des Kuhnt-Intermediärgewebes verursacht wird. In allen Fällen war eine interventionelle Therapie indiziert, 4 davon wurden operiert und führte zu einer signifikanten Verbesserung der Funktion und der anatomischen Netzhautstrukturen.Purpose: The aim of this case series was to investigate the clinical course of patients with optic pit maculopathy. Methods: The medical records of all patients diagnosed with optic pit maculopathy in the past 10 years were reviewed. Optic pit maculopathy was diagnosed when localized intraretinal or/and subretinal fluid spread from the optic nerve to the macula. Outcome measures included changes in best corrected visual acuity (BCVA), central retinal thickness (RT) as well as nasal parafoveal and perifoveal RT. Results: An optic disc pit was detected in 18 patients (9 female, 9 male, mean age: 33 ± 23 years). Retinal fluid accumulation was present in 6 (33.3%) of the patients (1 intraretinal, 1 subretinal, 4 intraretinal and subretinal). Pars plana vitrectomy with removal of peripapillary vitreous traction and peeling of the internal limiting membrane (ILM) was indicated in 5 patients and was performed in 4 patients. One patient underwent nanopulse laser treatment instead. The patients with optic pit maculopathy were 47 ± 16 years old. In this group of patients, mean BCVA (decimal) improved from 0.3 ± 0.2 before treatment to 0.5 ± 0.2 3 months after treatment (p= 0.03). Visual acuity improved in all patients with optic disc pit maculopathy after pars plana vitrectomy. The mean central RT decreased from 796 ± 214 before treatment to 324 ± 57 3 months after treatment (p= 0.005). The mean nasal parafoveal RT decreased from 683 ± 87 before treatment to 372 ± 41 (p= 0.0003) and the mean nasal perifoveal RT decreased from 547 ± 89 before treatment to 360 ± 48 (p= 0.007). A completely dry macula was achieved in 4 eyes after a mean follow-up of 3 months. At long-term follow-up (2.5 ± 1.2 years), no recurrence occurred in the vitrectomized eyes. Conclusion: This case series showed that more than one third of the patients had optic pit maculopathy presumably caused by disruption of the Kuhnt intermediate tissue. Interventional treatment was indicated in all cases, of which 4 were surgically treated and resulted in significant improvement of function and anatomical retinal structures

Mutationsabhängige Mechanismen und deren Bedeutung für zielgerichtete Behandlungsstrategien am Beispiel von Bestrophin 1 und den Bestrophinopathien

Bestrophin 1 (BEST1) encodes an integral membrane protein localized in the basolateral aspect of the retinal pigment epithelium. Mutations in BEST1 are associated with distinct retinal dystrophies, the so-called "bestrophinopathies", often causing visual impairment, even in early childhood. The clinical entities of the bestrophinopathies can be distinguished by phenotypic characteristics and mode of inheritance of the respective gene defect. While the autosomal dominant inheritance pattern with one altered copy of BEST1 is common, heterozygous carriers of the autosomal recessive bestrophinopathy are generally but not consistently symptom-free. This review highlights the significance of understanding the underlying molecular mechanisms that contribute to disease pathogenesis of autosomal dominant and autosomal recessive bestrophinopathies. This knowledge is deemed crucial and needs to be considered in future planning of treatment strategies