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Key Clinical Message Recurrent depression with psychotic features is an atypical presentation of neurosyphilis. This case emphasizes the polymorphic clinical presentation of neurosyphilis and how it mimics affective disorders with psychotic symptoms.

Patients with schizophrenia often have cognitive impairments that contribute to diminished psychosocial functioning. Cognitive remediation therapy (CRT) has proven efficacy and is recommended by evidence-based treatment guidelines. Important moderators of efficacy include integration of CRT into a psychiatric rehabilitation concept and patient attendance at a sufficient number of therapy sessions. These conditions can probably best be met in an outpatient setting; however, outpatient treatment is prone to higher rates of treatment discontinuation and outpatient settings are not as well protected as inpatient ones and less closely supervised.The present study investigated the feasibility of outpatient CRT in schizophrenia over a six-month period. Adherence to scheduled sessions and safety parameters were assessed in 177 patients with schizophrenia randomly assigned to one of two matched CRT programs.Results showed that 58.8 % of participants completed the CRT (>80 % of scheduled sessions) and 72.9 % completed at least half the sessions. Predictor analysis revealed a high verbal intelligence quotient as favorable for good adherence, but this factor had only low general predictive power. During the six-month treatment phase, serious adverse events occurred in 15.8 % (28/177) of the patients, which is a comparable rate to that reported in the literature.Our findings support the feasibility of six-month outpatient CRT in schizophrenia in terms of adherence to scheduled sessions and safety. Trial registration number: NCT02678858, DRKS00010033.

BackgroundAlthough clinically effective treatment is available for schizophrenia, recovery often is still hampered by persistent poor psychosocial functioning, which in turn is limited by impairments in neurocognition, social cognition, and social behavioral skills. Although cognitive remediation has shown general efficacy in improving cognition and social functioning, effects still need to be improved and replicated in appropriately powered, methodologically rigorous randomized controlled trials (RCTs). Existing evidence indicates that effects can most likely be optimized by combining treatment approaches to simultaneously address both social cognitive and social behavioral processes.ObjectivesTo assess whether Integrated Social Cognitive and Behavioral Skill Therapy (ISST) is more efficacious in improving functional outcome in schizophrenia than the active control treatment Neurocognitive Remediation Therapy (NCRT).MethodsThe present study is a multicenter, prospective, rater-blinded, two-arm RCT being conducted at six academic study sites in Germany. A sample of 180 at least partly remitted patients with schizophrenia are randomly assigned to either ISST or NCRT. ISST is a compensatory, strategy-based program that targets social cognitive processes and social behavioral skills. NCRT comprises mainly drill and practice-oriented neurocognitive training. Both treatments consist of 18 sessions over 6 months, and participants are subsequently followed up for another 6 months. The primary outcome is all-cause discontinuation over the 12-month study period; psychosocial functioning, quality of life, neurocognitive and social cognitive performance, and clinical symptoms are assessed as secondary outcomes at baseline before randomization (V1), at the end of the six-month treatment period (V6), and at the six-month follow-up (V12).DiscussionThis RCT is part of the German Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments (ESPRIT) research network, which aims at using innovative treatments to enhance prevention and recovery in patients with schizophrenia. Because this study is one of the largest and methodologically most rigorous RCTs on the efficacy of cognitive remediation approaches in schizophrenia, it will not only help to identify the optimal treatment options for improving psychosocial functioning and thus recovery in patients but also allow conclusions to be drawn about factors influencing and mediating the effects of cognitive remediation in these patients.Trial RegistrationClinicalTrials.gov NCT 02678858, German Study Register DRKS 00010033

Abstract. Introduction:. Small fiber pathology may be involved in the pathophysiology of pain in women with fibromyalgia syndrome (FMS). Objectives:. This prospective single-center case-control study provides detailed pain phenotyping and small fiber pathology data in a cohort of men with FMS on a morphological and functional level. Methods:. Forty-two men with FMS underwent a comprehensive pain-related interview and neurological examination, a questionnaire and neurophysiological assessment, and specialized small fiber tests: skin punch biopsy, quantitative sensory testing including C-tactile afferents, and corneal confocal microscopy. Data were compared with those of healthy male controls. Results:. Men with FMS reported generalized and permanent pain with additional pain attacks and a mostly pressing pain character. Intraepidermal nerve fiber density was reduced at ≥1 biopsy site in 35 of 42 (83%) men with FMS (controls: 32/65, 49%). Compared with male controls, men with FMS had elevated cold (P < 0.05) and warm detection thresholds (P < 0.001) and an increased mechanical pain threshold (P < 0.05) as well as an impairment of C-tactile afferents (P < 0.05). Corneal nerve fiber density was lower in male patients with FMS vs healthy men (P < 0.01). Male FMS patients with pathological skin innervation at ≥1 biopsy site compared with those with normal skin innervation had a higher clinical Widespread Pain Index (P < 0.05) indicating an association between the severity of cutaneous denervation and symptom load. Conclusion:. We show a distinct pain phenotype and small nerve fiber dysfunction and pathology in male patients with FMS. These findings may have implications for the diagnosis and management of men with FMS.

Belantamab mafodotin (belantamab) is a first-in-class anti-BCMA antibody-drug conjugate approved for the treatment of triple-class refractory multiple myeloma. It provides a unique therapeutic option for patients ineligible for CAR-T and bispecific antibody therapy, and/or patients progressing on anti-CD38 treatment where CAR-T and bispecifics might be kept in reserve. Wider use of the drug can be challenged by its distinct ocular side effect profile, including corneal microcysts and keratopathy. While dose reduction has been the most effective way to reduce these toxicities, the underlying mechanism of this BCMA off-target effect remains to be characterized. In this study, we provide the first evidence for soluble BCMA (sBCMA) in lacrimal fluid and report on its correlation with tumor burden in myeloma patients. We confirm that corneal cells do not express BCMA, and show that sBCMA-belantamab complexes may rather be internalized by corneal epithelial cells through receptor-ligand independent pinocytosis. Using an hTcEpi corneal cell-line model, we show that the pinocytosis inhibitor EIPA significantly reduces belantamab-specific cell killing. As a proof of concept, we provide detailed patient profiles demonstrating that, after belantamab-induced cell killing, sBCMA is released into circulation, followed by a delayed increase of sBCMA in the tear fluid and subsequent onset of keratopathy. Based on the proposed mechanism, pinocytosis-induced keratopathy can be prevented by lowering the entry of sBCMA into the lacrimal fluid. Future therapeutic concepts may therefore consist of belantamab-free debulking therapy prior to belantamab consolidation and/or concomitant use of gamma-secretase inhibition as currently evaluated for belantamab and nirogacestat in ongoing studies.

Purpose: Fusarium keratitis is a severe infection of the anterior eye, frequently leading to keratoplasty or surgical removal of the affected eye. A major risk factor for infection is the use of contact lenses. Inadequate hygiene precautions and mold-growth permissive storage fluids are important risk factors for fungal keratitis. The aim of this study was to comparatively analyze contact lens storage fluids disinfection efficacy against Fusarium species. Methods: Eleven commercially available storage fluids were tested. The storage fluids were classified according to their active ingredients myristamidopropyldimethylamine (Aldox), polyhexanide and hydrogen peroxide. Efficacy was tested against isolates belonging to the Fusarium solani and Fusarium oxysporum species complexes as the most common agents of mould keratitis. Tests were carried out based on DIN EN ISO 14729. Results: All Aldox and hydrogen peroxide (H2O2) based fluids were effective against Fusarium spp., while the majority of polyhexanide based storage fluids showed only limited or no antifungal effects. Efficacy of polyhexanide could be restored by the addition of the pH-regulating agent tromethamine - an additive component in one commercially available product. Conclusions: In summary, the use of Aldox- or hydrogen peroxide-based storage fluids may reduce the risk of Fusarium keratitis, while polyhexanide-based agents largely lack efficacy against Fusarium.

Abstract In vitro culture and generation of highly specialized goblet cells is still a major challenge in conjunctival 3D in vitro equivalents. A model comprising all physiological factors, including mucus-secreting goblet cells has the potential to act as a new platform for studies on conjunctival diseases. We isolated primary conjunctival epithelial cells and fibroblasts from human biopsies. 3D models were generated from either epithelial layers or a combination of those with a connective tissue equivalent. Epithelial models were investigated for marker expression and barrier function. Full-thickness models were analyzed for goblet cell morphology and marker expression via immunofluorescence and quantitative real-time PCR. Simple epithelial models cultured at the air–liquid interface showed stratified multi-layer epithelia with pathologic keratinization and without goblet cell formation. The combination with a connective tissue equivalent to generate a full-thickness model led to the formation of a non-keratinized stratified multi-layer epithelium and induced goblet cell differentiation. In our model, a high resemblance to natural conjunctiva was achieved by the combination of conjunctival epithelial cells with fibroblasts embedded in a collagen-hydrogel as connective tissue equivalent. In the future, our conjunctival in vitro equivalent enables the investigation of goblet cell differentiation, conjunctival pathologies as well as drug testing.

The United Nations (UN) 2030 Agenda and Sustainable Development highlights the value of the Sustainable Development Goals (SDGs) in enabling societal progress. Contemporary society needs to consider sustainable development in a broader context where equity, diversity, and inclusion are integral to design of educational systems. Education can act as a disruptor that brings change to existing economic growth models misaligned with the needs and demands of modern society. As we transition to economic models that are more attuned to the needs of global society and planet, access to education, natural resources, and human talent is crucial for sustaining development, and allowing societies to continue advancing. However, it is imperative to deliberate on the necessity of adopting an alternative perspective on economic growth and its facilitation while adhering to the principles of sustainability. Inclusive, diverse, and transdisciplinary education can help to enhance quality learning, social equity, and resilience in nations, fostering intellectual empowerment, lifelong learning values, and a cohesive society. The prominence of education and its partners, training, and awareness has been recurrently underscored in UN assemblies, illuminating its capacity to address concerns such as climate change, violations of human rights, and degradation of the environment. Conversely, minimal headway in this realm indicates enduring and formidable hurdles obstructing the progress of education. Broadening the reach of education is fundamental for supporting an improved future. Although the expansion of educational opportunities is applauded, it is insufficient if the requirements of global economies are not considered. A thriving community requires substantial investment, and the capability of world economies to bring about change through capital investment is finite and dependent on access to scarce resources and their level of economic development. In addition, the fact that education has become an unattainable luxury good contributes to the widening gaps and distinctions between wealthier and less affluent nations. As such, there is a need to critically introspect on the role that education plays in driving sustainable development.

The world's economies face acute anthropocentric challenges. We are witnessing significant structural disruption, driven by an urgent need to redress a historical focus on unchecked economic growth and unequal access to resources, requiring seismic transformations of our economic, social, and educational systems. Debate about sustainable development is becoming less controversial. Yet, many countries still struggle to commit to action. Whist political leaders engage in commendable discussion on sustainable practices, impacts range from rhetoric to constrained solutions. Our socio-economic and environmental challenges require collective effort, as we witness a contestation of development models that omit environmental preservation, lack inclusivity and compromise future generations. In this context, in which we seek alternative models that are more applicable to reality, education emerges as a driving force for change. Education already plays a role in the design of the socio-political economy. So, thoughtfully designed, it can help to define our understanding of sustainability beyond political and economic selection of goals and self-serving dimensions. Given transformative character, education can help to bridge the need for an inclusive and sustainable economic development model. Through an economic lens, this paper offers critical and reflective insights into how education can contribute to the necessary transformation for the achievement of the UN Sustainable Development Goals (SDGs). We argue that, with the right changes, education and economic development can be synergistic in pursuit of circularity, thereby meeting the requirements for just and equitable access, and preventing the depletion of natural resources needed for a thriving and flourishing humanity.

We present a case of Kluyveromyces marxianus keratitis nine months after Descemet's membrane endothelial keratoplasty (DMEK) in a patient with Fuchs endothelial disease. Endothelial scraping revealed this rare yeast infection at the interface between graft and host cornea. Immediate antifungal treatment with intracameral and corneal intrastromal injections of voriconazole and amphotericin B remained unsuccessful, requiring penetrating keratoplasty. This case highlights the challenging management of keratomycosis in patients with endothelial grafts.

Abstract Background Health care workers have an increased risk of being infected with Methicillin-resistant Staphylococcus aureus (MRSA), though little information is available about how prevalent (dormant) MRSA colonization is among health care workers. The aim of this study was to estimate the prevalence and predictors of MRSA carriage in a non-outbreak setting in a university hospital in Germany. Methods The entire staff of a university hospital heart center for cardiologic maximum medical care and cardiac surgery were invited to participate in a cross-sectional study (N = 575). The sampled population included health care workers as well as employees with no close patient contact. A questionnaire concerning personal and occupational risk factors as well as lifestyle and demographic factors was applied and nasal swabs were taken. In total 180 persons (31.3%) participated in the study. Results The majority of study participants had close contact to patients at work (n = 149, 82.8%). Thereof, about one-third had contact to MRSA-patients (n = 53, 35.6%), and most reported wearing protective clothing (n = 44, 83.0%). None of the administrative staff tested positive for MRSA and only one in 149 persons (0.7%, CI 0.00–0.02) with close patient contact carried MRSA (strain CC1-MRSA-IV). This person had close contact to patients with MRSA, less than 1 year of work experience, and had been treated with antibiotics within the last 12 months. Conclusion The results of our study suggest low point prevalence rates of MRSA colonization in health care workers in a non-outbreak setting.

Background and aims: Small fiber neuropathy (SFN) is increasingly suspected in patients with pain of uncertain origin, and making the diagnosis remains a challenge lacking a diagnostic gold standard. Methods: In this case–control study, we prospectively recruited 86 patients with a medical history and clinical phenotype suggestive of SFN. Patients underwent neurological examination, quantitative sensory testing (QST), and distal and proximal skin punch biopsy, and were tested for pain-associated gene loci. Fifty-five of these patients additionally underwent pain-related evoked potentials (PREP), corneal confocal microscopy (CCM), and a quantitative sudomotor axon reflex test (QSART). Results: Abnormal distal intraepidermal nerve fiber density (IENFD) (60/86, 70%) and neurological examination (53/86, 62%) most frequently reflected small fiber disease. Adding CCM and/or PREP further increased the number of patients with small fiber impairment to 47/55 (85%). Genetic testing revealed potentially pathogenic gene variants in 14/86 (16%) index patients. QST, QSART, and proximal IENFD were of lower impact. Conclusion: We propose to diagnose SFN primarily based on the results of neurological examination and distal IENFD, with more detailed phenotyping in specialized centers.

Fungal eye infections can lead to loss of vision and blindness. The disease is most prevalent in the tropics, although case numbers in moderate climates are increasing as well. This study aimed to determine the dominating filamentous fungi causing eye infections in Germany and their antifungal susceptibility profiles in order to improve treatment, including cases with unidentified pathogenic fungi. As such, we studied all filamentous fungi isolated from the eye or associated materials that were sent to the NRZMyk between 2014 and 2020. All strains were molecularly identified and antifungal susceptibility testing according to the EUCAST protocol was performed for common species. In total, 242 strains of 66 species were received. Fusarium was the dominating genus, followed by Aspergillus, Purpureocillium, Alternaria, and Scedosporium. The most prevalent species in eye samples were Fusarium petroliphilum, F. keratoplasticum, and F. solani of the Fusarium solani species complex. The spectrum of species comprises less susceptible taxa for amphotericin B, natamycin, and azoles, including voriconazole. Natamycin is effective for most species but not for Aspergillus flavus or Purpureocillium spp. Some strains of F. solani show MICs higher than 16 mg/L. Our data underline the importance of species identification for correct treatment.

Primary open-angle glaucoma (POAG) is a leading cause of blindness due to chronic degeneration of retinal ganglion cells and their optic nerve axons. It is associated with disturbed regulation of intraocular pressure, elevated intraocular levels of TGF-β2, aberrant extracellular matrix (ECM) deposition and increased outflow resistance in the trabecular meshwork (TM). The mechanisms underlying these changes are not fully understood. Cell-matrix interactions have a decisive role in TM maintenance and it has been suggested that TGF-β-induced inhibition of matrix metalloproteases may drive aberrant ECM deposition in POAG. Invadopodia and podosomes (invadosomes) are distinct sites of cell-matrix interaction and localized matrix-metalloprotease (MMP) activity. Here, we report on the effects of TGF-β2 on invadosomes in human trabecular meshwork cells. Human TM (HTM) cells were derived from donor tissue and pretreated with vehicle or TGF-β2 (2 ng/ml) for 3d. Invadosomes were studied in ECM degradation assays, protein expression and MMP-2 activity were assessed by western blot and zymography and ECM protein transcription was detected by RT-qPCR. HTM cells spontaneously formed podosomes and invadopodia as detected by colocalization of Grb2 or Nck1 to sites of gelatinolysis. Pretreatment with TGF-β2 enhanced invadosomal proteolysis and zymographic MMP-2 activity as well as MMP-2, TIMP-2 and PAI-1 levels in HTM cell culture supernatants. Rho-kinase inhibition by H1152 blocked the effects of TGF-β2. Concomitant transcription of fibronectin and collagens-1, -4 and -6 was increased by TGF-β2 and fibrillar fibronectin deposits were observed in areas of invadosomal ECM remodelling. In contrast to a current hypothesis, our data indicate that TGF-β2 induces an active ECM remodelling process in TM cells, characterized by concurrent increases in localized ECM digestion and ECM expression, rather than a mere buildup of material due to a lack of degradation. Invadosomal cell adhesion and signaling may thus have a role in POAG pathophysiology.