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Vertical reading training (VRTr) increases reading speed (RS) significantly in patients with hemianopic field defects (HFD). We ask, how eye movements (EM) contribute to this improvement and whether EM-behavior is affected by the side of HFD. Twenty-one patients, randomly assigned to VRTr or horizontal RTr, trained reading single lines from a screen at home, for 4 weeks. In the clinic, we recorded EM while reading short sentences aloud from a screen before training (T1), directly (T2) and 4 weeks afterwards (T3). RS-screen was correlated with RS during reading printed paragraphs (RS-print) to assess the transfer to everyday life. RS-screen and RS-print correlated positively (horizontal: r > 0.8, vertical: r > 0.9) at all times. Vertical RS did not exceed horizontal RS. We found significant negative correlations of EM-variables and RS-print: in right-HFD with the number of forward saccades (T1: r =  − 0.79, T2: r =  − 0.94), in left-HFD with the steps during return sweeps (T1: r =  − 0.83, T2: r =  − 0.56). Training effects remained stable at T3. EM-improvement was specific for the RTr and the side of the HFD: in right-HFD fewer forward saccades after VRTr, in left-HFD fewer steps during return sweeps after HRTr. RTr on a screen transfers to reading printed text in real-life situations. Trial registration: The study was retrospectively registered in the German Clinical Trials register: DRKS-ID: DRKS00018843, March 13th, 2020.

BackgroundAge-related macular degeneration (AMD) causes reading impairment, reduced quality of life (QoL), and secondary depression. We have shown that support with magnifying aids improved reading speed (RS), emotional and cognitive status, and QoL. The present study investigates whether additional reading training (RT) (after adapting to appropriate visual aids) can further improve vision rehabilitation.MethodsPatients with dry AMD were randomly assigned to 2 groups. The primary RT group (P-RTG, n = 25) trained with sequentially presented text (RSVP), and the control group (CG, n = 12) performed placebo training (crossword puzzles) and later crossed over to RT, so that altogether 37 participants performed reading training. Patients trained at home on a PC for 6 weeks. RS was assessed during reading printed paragraphs of text aloud. Using a scanning laser ophthalmoscope, we examined fixation stability and preferred retinal locus (PRL) for fixating a cross, as well as PRL and eye movements during reading single words. We assessed emotional status by Montgomery–Åsberg Depression Rating Scale (MADRS), cognitive status by dementia detection test (DemTect) and QoL by Impact of Vision Impairment (IVI) profile. Visual acuity and magnification requirement were examined by standard procedures. All variables were measured before and after placebo training, before and after RT, and after 6 weeks without training (follow-up).ResultsRS improved significantly in the P-RTG during RT, but not in the CG during placebo training. The effect remained stable at follow-up. Fixation performance and eye movement variables did not change. Emotional status (MADRS) improved in P-RTG during RT and showed a significant difference of the change of scores between the 2 groups.Complete IVI scores improved significantly during RT and remained stable.ConclusionThe results indicate that patients with AMD, who already use magnifying aids, benefit from additional RT and that it can contribute in preventing depression and improve QoL.Trial registrationThe study was registered at the German Clinical Trials Register (DRKS00015609).

HypothesisPatients with hemianopic field defects (HFD) might benefit from reading text in vertical orientation if they place the text in the seeing hemifield along the vertical midline.MethodsWe assigned 21 patients with HFD randomly to either vertical or horizontal reading training. They trained reading single lines of texts from a computer screen at home for 2 × 30 min/day, 5 days/week, for 4 weeks. The main outcome variable was reading speed (RS) during reading standardized paragraphs of printed text (IReST) aloud. RS was assessed before training (T1), directly after training (T2) and 4 weeks later (T3). Quality of life (QoL) was assessed by Impact of Visual Impairment (IVI) questionnaire.ResultsVertical training improved RS in the vertical direction significantly. Only patients with right HFD benefited. Horizontal training improved RS in horizontal diection significantly, but much more in patients with left than in those with right HFD. Both effects remained stable at T3. RS during training at the computer improved highly significantly and correlated strongly with RS of printed text (Pearson r= > 0.9). QoL: Vertical training showed a statistically significant improvement in the complete IVI-score, patients with right HFD in the emotional IVI-score.ConclusionsThe improvements of RS were specific for the training. The stable effect indicates that the patients can apply the newly learned strategies to everyday life. The side of the HFD plays an essential role: Left-HFD patients benefitted from horizontal training, right-HFD patients from vertical training. However, the vertical RS did not reach the level of horizontal RS.The study was registered in the German Clinical Trials register (DRKS-ID: DRKS00018843).

Involvement of the central nervous system has important therapeutic implications in acute leukaemia. Because the identification of blast cells in cerebrospinal fluid (CSF) is often difficult, there is a need for sensitive markers of leukaemic infiltration. Since the shed form of L-selectin (sL-selectin) is frequently increased in acute leukaemia (sL-selectin* leukaemia), we examined whether assay of sL-selectin in CSF could improve our ability to detect such meningeal involvement. CSF sL-selectin was significantly (p<0·001) higher in 15 patients with sL-selectin + meningeal leukaemia (median 60 ng/mL, range 34-150) than in 20 patients with acute leukaemia without meningeal involvement (12 ng/mL, 1-39) or 88 control patients (14 ng/mL, 0-37). Serial measurements of sL-selectin in patients with sL-selectin + leukaemic meningitis showed increased CSF concentrations of the cleaved receptor in 4 patients with therapy-resistant meningeal leukaemia and sustained normal concentrations in 9 patients in remission. Our results suggest that CSF sL-selectin may be a useful marker in the detection of meningeal involvement by blast cells in patients with sL-selectin + leukaemia.

Recent publications have demonstrated neural plasticity in adult amblyopes subjected to psychophysical training based on perceptual learning. The purpose of this case report is to present rarely available prospective data of visual acuity development in a strabismic amblyope undergoing psychophysical training and pleoptic treatment after loss of function of the non-amblyopic eye. The design is a prospective, observational and interventional case report. Visual acuity was tested monthly, with constant optical correction. The 60-year-old female patient participated in a psychophysical training implemented in our laboratory, and in pleoptic treatment. Slow functional improvement of the amblyopic eye was observed during a period of 10 months, both in the tests used for training and in visual acuity: single optotypes increased by 4 chart lines, crowded optotypes by 2-3 lines. To our knowledge, this is the first report of the new approach of perceptual learning in an adult amblyope after loss of vision in the contralateral eye. Our results represent further evidence that the visual system of adult amblyopes preserves a certain degree of neural plasticity, whether spontaneous or enhanced by training. Furthermore, that plasticity in adults is limited, and early diagnosis and treatment of amblyopia must remain the primary goal.

This paper draws on qualitative research using focus groups involving 38 general practitioners (GPs). It explores their attitudes and feelings about (over-)medicalisation. Our main findings were that GPs had a complex representation of (over-)medicalisation, composed of many professional, social, technological, economic and relational issues. This representation led GPs to feel uncomfortable. They felt pressure from all sides, which led them to question their social roles and responsibilities. We identified four main GP-driven proposals to deal with (over-)medicalisation: (1) focusing on the communication in doctor–patient relationships; (2) grounding practices in evidence-based medicine; (3) relying on clinical skills, experience and intuition; and (4) promoting training, leadership bodies and social movements. Drawing on these proposals, we identify and discuss five paradigms that underpin GPs’ attitudes toward (over-)medicalisation: underlying social factors, preventing medicalisation, managing uncertainties, sharing medical decision-making and thinking about care as a rationale. We suggest that these paradigms constitute a defensive posture against GPs’ uncomfortable feelings. All five defensive paradigms were identified in our focus groups, echoing contemporary political debates on public health. This non-exhaustive framework forms the outline of what we call ordinary defensive medicine . GPs’ uncomfortable feelings are the origin of their defensive solutions and the manifestation of their vulnerability. This professional vulnerability can be shared with the patient’s vulnerability. In our view, this creates an opportunity to rediscover patient–doctor relationships and examine patients’ and doctors’ vulnerabilities together. “There are many cases in which—though the signs of a confusion of tongues between the patient and his doctor are painfully present—there is apparently no open controversy. Some of these cases demonstrate the working of two other, often interlinked, factors. One is the patient’s increasing anxiety and despair, resulting in more and more fervently clamouring demands for help. Often the doctor’s response is guilt feelings and despair that his most conscientious, most carefully devised examinations do not seem to throw real light on the patient’s “illness”, that his most erudite, most modern, most circumspect therapy does not bring real relief.” (Balint M. The Doctor, His Patient and the Illness. New York: International Universities; 2005. [1957].) “Theories about care put an unprecedented emphasis on vulnerability—taking up that challenge to transform what really counts in today’s hospitals implies letting colleagues inside previously closely guarded professional boundaries” (2, our translation).

Clathrin-mediated endocytosis in budding yeast requires the formation of a dynamic actin network that produces the force to invaginate the plasma membrane against the intracellular turgor pressure. The type-I myosins Myo3 and Myo5 are important for endocytic membrane reshaping, but mechanistic details of their function remain scarce. Here, we studied the function of Myo3 and Myo5 during endocytosis using quantitative live-cell imaging and genetic perturbations. We show that the type-I myosins promote, in a dose-dependent way, the growth and expansion of the actin network, which controls the speed of membrane and coat internalization. We found that this myosin-activity is independent of the actin nucleation promoting activity of myosins, and cannot be compensated for by increasing actin nucleation. Our results suggest a new mechanism for type-I myosins to produce force by promoting actin filament polymerization.

Anelloviruses are ubiquitous in humans and represent a major component of the human virome. Its best-known representative is Torque teno virus (i.e., the Alphatorquevirus genus), which is considered a potential immunity biomarker. Recent metagenomic investigations revealed not only the extraordinary genomic diversity of anellovirus sequences, but also that co-detection of genera, genotypes, or species seems to be the rule in humans. SCANellome was developed to represent a user-friendly tool to analyze the primate (both human and non-human) anellovirus composition at the genus, species, and genotype level from metagenomics data based on an up-to-date database. This SCANellome update includes >900 additional reference sequences from GenBank. Using a clustering at 90% identity, the FASTA database was updated and generated 134 new representative sequences. Based on ORF1, the analysis of these new sequences indicates the presence of 206 potential new species, including four nonhuman primates, and adds four new non-human primate species which will be the subject of a proposal to the International Committee on Taxonomy of Viruses (ICTV). In addition, SCANellome V2 provides now the user with an interactive up-to-date phylogenetic analysis (of ORF1) to show the distribution among the 12 human and nonhuman primate genera of these new potential species. Finally, the Anelloviridae taxonomy was updated to rename species names in binomial format as required by the ICTV.

Anelloviruses are extremely prevalent in the human population and are considered to be commensal parts of the human virome. The best-known member in humans is the Torque teno virus. Recent metagenomic next-generation sequencing investigations have helped reveal the considerable number of species and genotypes from the same genus that can be co-detected within a single individual and that this diversity increases as a function of age during the first months/years of life. As a result, to date, the bioinformatics analysis of this genetic diversity remains complex and constraining for researchers. Here, we present SCANellome, a user-friendly tool to investigate the anellome composition at the genus, species, and genotype levels of samples from metagenomics data generated by the Illumina and Nanopore platforms. SCANellome is based on an in-house up-to-date database that includes all human and non-human primate anellovirus reference sequences available on GenBank and meets the latest classification criteria established by the International Committee on Taxonomy of Viruses.

This study is based on zircon U-Pb ages of 12 volcanic ash layers and volcanogenic sandstones from two deep water sections with conformable and continuous formational Permian–Triassic boundaries (PTBs) in the Nanpanjiang Basin (South China). Our dates of single, thermally annealed and chemically abraded zircons bracket the PTB in Dongpan and Penglaitan and provide the basis for a first proof-of-concept study utilizing a Bayesian chronology model comparing the three sections of Dongpan, Penglaitan and the Global Stratotype Section and Point (GSSP) at Meishan. Our Bayesian modeling demonstrates that the formational boundaries in Dongpan (251.939 ± 0.030 Ma), Penglaitan (251.984 ± 0.031 Ma) and Meishan (251.956 ± 0.035 Ma) are synchronous within analytical uncertainty of  ∼  40 ka. It also provides quantitative evidence that the ages of the paleontologically defined boundaries, based on conodont unitary association zones in Meishan and on macrofaunas in Dongpan, are identical and coincide with the age of the formational boundaries. The age model also confirms the extreme condensation around the PTB in Meishan, which distorts the projection of any stratigraphic points or intervals onto other more expanded sections by means of Bayesian age–depth models. Dongpan and Penglaitan possess significantly higher sediment accumulation rates and thus offer a greater potential for high-resolution studies of environmental proxies and correlations around the PTB than Meishan. This study highlights the power of high-resolution radio-isotopic ages that allow a robust intercalibration of patterns of biotic changes and fluctuating environmental proxies and will help recognizing their global, regional or local significance.