[Diagnostics and management of patients with inherited retinal diseases in Germany : Results of a nationwide survey of university and non-university eye departments and specialized practices].

Background: Inherited retinal diseases (IRDs) refer to a heterogeneous group of rare disorders that potentially lead to blindness. Emerging therapeutic options have led to a growing interest in IRDs; however, there are insufficient systematic studies on IRDs in Germany characterizing the demographics and management in clinical practice.

Objective: To characterize the care for IRD patients in Germany, to assess the applied diagnostics, the use of databases and the implementation of education in ophthalmic genetics.

Loneliness and diurnal cortisol levels during COVID-19 lockdown: the roles of living situation, relationship status and relationship quality.

Loneliness and social isolation have become increasing concerns during COVID-19 lockdown through neuroendocrine stress-reactions, physical and mental health problems. We investigated living situation, relationship status and quality as potential moderators for trait and state loneliness and salivary cortisol levels (hormonal stress-responses) in healthy adults during the first lockdown in Germany. N = 1242 participants (mean age = 36.

Lonely in the Dark: Trauma Memory and Sex-Specific Dysregulation of Amygdala Reactivity to Fear Signals.

Loneliness exacerbates psychological distress and increases the risk of psychopathology after trauma exposure. However, it is still unclear whether a lack of social connectedness affects trauma-related intrusions and the neural processing of fear signals. Moreover, it is uncertain, whether loneliness plays a different role in women and men.

Insula reactivity mediates subjective isolation stress in alexithymia.

The risk for developing stress-related disorders is elevated in individuals with high alexithymia, a personality trait characterized by impaired emotional awareness and interpersonal relating. However, it is still unclear how alexithymia alters perceived psychosocial stress and which neurobiological substrates are mechanistically involved. To address this question, we examined freshmen during transition to university, given that this period entails psychosocial stress and frequently initiates psychopathology.

The intestinal microbiome, weight, and metabolic changes in women treated by adjuvant chemotherapy for breast and gynecological malignancies.

Background: Adjuvant chemotherapy induces weight gain, glucose intolerance, and hypertension in about a third of women. The mechanisms underlying these events have not been defined. This study assessed the association between the microbiome and weight gain in patients treated with adjuvant chemotherapy for breast and gynecological cancers.

10 Hz tACS Over Somatosensory Cortex Does Not Modulate Supra-Threshold Tactile Temporal Discrimination in Humans.

Perception of physical identical stimuli can differ over time depending on the brain state. One marker of this brain state can be neuronal oscillations in the alpha band (8-12 Hz). A previous study showed that the power of prestimulus alpha oscillations in the contralateral somatosensory area negatively correlate with the ability to temporally discriminate between two subsequent tactile suprathreshold stimuli.

Sepsis recognition in the emergency department - impact on quality of care and outcome?

Background: Appropriate and timely recognition of sepsis is a prerequisite for starting goal-directed therapy bundles. We analyzed the appropriateness of sepsis recognition and documentation with regard to adequacy of therapy and outcome in an internal medicine emergency department (ED).

Methods: This study included 487 consecutive patients ≥18 years of age who presented to a university hospital ED during a 4-week period.

Identification, Synthesis, and Field Tests of the Sex Pheromone of Margarodes prieskaensis (Jakubski).

Here, we report the identification and synthesis of the sex pheromone of female Margarodes prieskaensis (Jakubski), and the attractiveness of the synthetic pheromone to males in field trapping tests. Volatile organic compounds were collected from virgin females using a sample enrichment probe (SEP). Analyses by gas chromatography coupled to mass spectrometry revealed the presence of only two constituents.

Application of Synthetic Peptide Arrays To Uncover Cyclic Di-GMP Binding Motifs.

Unlabelled: High levels of the universal bacterial second messenger cyclic di-GMP (c-di-GMP) promote the establishment of surface-attached growth in many bacteria. Not only can c-di-GMP bind to nucleic acids and directly control gene expression, but it also binds to a diverse array of proteins of specialized functions and orchestrates their activity. Since its development in the early 1990s, the synthetic peptide array technique has become a powerful tool for high-throughput approaches and was successfully applied to investigate the binding specificity of protein-ligand interactions.

A chemical proteomics approach to identify c-di-GMP binding proteins in Pseudomonas aeruginosa.

In many bacteria, high levels of the ubiquitous second messenger c-di-GMP have been demonstrated to suppress motility and to promote the establishment of surface-adherent biofilm communities. While molecular mechanisms underlying the synthesis and degradation of c-di-GMP have been comprehensively characterized, little is known about how c-di-GMP mediates its regulatory effects. In this study, we have established a chemical proteomics approach to identify c-di-GMP interacting proteins in the opportunistic pathogen Pseudomonas aeruginosa.

Bis-(3',5')-cyclic dimeric adenosine monophosphate: strong Th1/Th2/Th17 promoting mucosal adjuvant.

New effective adjuvants are required to improve the performance of subunit vaccines. Here, we showed that bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP), a second messenger molecule in bacteria and archaea, exerts strong adjuvant activities when delivered by mucosal route. In vitro studies showed that c-di-AMP was able to both stimulate pre-activated murine macrophages and promote the activation and maturation of dendritic cells of murine and human origin.

Electrophysiological indices of discrimination of long-duration, phonetically similar vowels in children with typical and atypical language development.

Purpose: The authors investigated the neurophysiological bases of vowel perception in children with specific language impairment (SLI) compared with typical language development (TLD) controls using 250-ms phonetically similar vowels. In a previous study, children with SLI showed a poor neurophysiological response (the mismatch negativity [MMN]) to 50-ms versions of these vowels, regardless of whether attention was directed to (attend) or away (passive) from the auditory modality (V. Shafer, M.

The member of the cyclic di-nucleotide family bis-(3', 5')-cyclic dimeric inosine monophosphate exerts potent activity as mucosal adjuvant.

Here we demonstrated that bis-(3',5')-cyclic dimeric inosine monophosphate (c-di-IMP) exhibits potent adjuvant properties. BALB/c or C57BL/6 mice were immunized with the model antigens beta-galactosidase (beta-Gal) or Ovalbumin (OVA) alone or co-administered with c-di-IMP by the intranasal route. Animals receiving c-di-IMP showed significantly higher anti-beta-Gal or OVA immunoglobulin G titres (IgG) in sera than those vaccinated with beta-Gal or OVA alone.

Quantitative determination of cyclic diguanosine monophosphate concentrations in nucleotide extracts of bacteria by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry.

The physiological response to small molecules (secondary messengers) is the outcome of a delicate equilibrium between biosynthesis and degradation of the signal. Cyclic diguanosine monophosphate (c-di-GMP) is a novel secondary messenger present in many bacteria. It has a complex cellular metabolism whereby usually more than one enzyme synthesizing and degrading c-di-GMP is encoded by a bacterial genome.

Pseudomonas aeruginosa cupA-encoded fimbriae expression is regulated by a GGDEF and EAL domain-dependent modulation of the intracellular level of cyclic diguanylate.

Cyclic-diguanylate (c-di-GMP) is a widespread bacterial signal molecule that plays a major role in the modulation of cellular surface components, such as exopolysaccharides and fimbriae, and in the establishment of a sessile life style. Here, we report that intracellular c-di-GMP levels influence cupA-encoded fimbriae expression in Pseudomonas aeruginosa. In an autoaggregative P.

A pegylated derivative of alpha-galactosylceramide exhibits improved biological properties.

The glycolipid alpha-galactosylceramide (alphaGalCer) has immunomodulatory properties, which have been exploited to combat cancer, chronic inflammatory diseases, and infections. However, its poor solubility makes alphaGalCer a suboptimal compound for in vivo applications. In this study, a pegylated derivative of alphaGalCer is characterized, which exhibits improved physical and biological properties.

The bacterial second messenger cdiGMP exhibits promising activity as a mucosal adjuvant.

The development of mucosal adjuvants is still a critical need in vaccinology. In the present work, we show that bis(3',5')-cyclic dimeric GMP (cdiGMP), a second messenger that modulates cell surface properties of several microorganisms, exerts potent activity as a mucosal adjuvant. BALB/c mice were immunized intranasally with the model antigen beta-galactosidase (beta-Gal) coadministered with cdiGMP.

Neurophysiological indices of attention to speech in children with specific language impairment.

Objective: The aim was to determine whether children with specific language impairment (SLI) differed from children with typical language development (TLD) in their allocation of attention to speech sounds.

Methods: Event-related potentials were recorded to non-target speech sounds in two tasks (passive-watch a video and attend to target tones among speech sounds) in two experiments, one using 50-ms duration vowels and the second using 250-ms vowels. The difference in ERPs across tasks was examined in the latency range of the early negative difference wave (Nd) found in adults.

Total synthesis and biological evaluation of (-)-pectinatone employing a methyl-branched wax ester as key building block.

Unnatural (-)-pectinatone ((-)-3) was prepared in five steps starting from the highly methyl-branched wax ester 4, employing bromination of the ester enolate and subsequent base-induced elimination to the enoate 6 as the key step. Both (-)-3 and the amides 8b and 8c, which were isolated as by-products in the reaction sequence, displayed antimicrobial activity and cytotoxicity.

The bacterial second messenger cyclic diGMP exhibits potent adjuvant properties.

The identification of new adjuvants is a critical need in vaccinology. In this work, it is demonstrated that bis-(3',5')-cyclic dimeric guanosine monophosphate (cdiGMP) exhibits potent adjuvant properties. Subcutaneous co-administration of cdiGMP with beta-galactosidase (beta-Gal) to mice resulted in the elicitation of significantly higher antigen-specific serum IgG titres than in animals receiving beta-Gal alone.

Comparison of the supramolecular structures of two glyco lipids with chiral and nonchiral methyl-branched alkyl chains from natural sources.

Two alkyl glycosides with the same type of disaccharide headgroups (melibiose) and different methyl-branched alkyl chains, short chiral [(2R,4R,6R,8R)-2,4,6,8-tetramethyldecyl, extracted from an animal source] and long nonchiral (3,7,11,15-tetramethylhexadecyl, from a plant source), were synthesized. The supramolecular aggregate structure formed in dilute solutions was investigated by small-angle neutron scattering and surface tension measurements. The lyotropic phase diagram was studied by differential scanning calorimetry and water penetration scans.

Hierarchical involvement of various GGDEF domain proteins in rdar morphotype development of Salmonella enterica serovar Typhimurium.

GGDEF and EAL domain proteins are involved in the turnover of the novel secondary messenger cyclic-di(3'-->5')-guanylic acid (c-di-GMP) in many bacteria. In this work the role of the 12 GGDEF domain proteins encoded by the Salmonella enterica serovar Typhimurium (S. Typhimurium) chromosome in rdar morphotype development was investigated.

Selective hydroxylation of highly branched fatty acids and their derivatives by CYP102A1 from Bacillus megaterium.

Highly branched fatty acids, the main components of the preen-gland waxes of the domestic goose and the Muscovy duck, and their derivatives are promising chiral precursors for the synthesis of macrolide antibiotics. The key step in the utilisation of these compounds is their regioselective hydroxylation, which cannot be achieved in a classical chemical approach. Three P450 monooxygenases, CYP102A1, CYP102A2 and CYP102A3, demonstrating high turnover numbers in the hydroxylation of iso and anteiso fatty acids (>400 min(-1)), were tested for their activity towards these substrates.

Neurophysiological indexes of speech processing deficits in children with specific language impairment.

We used neurophysiological and behavioral measures to examine whether children with specific language impairment (SLI) have deficits in automatic processing of brief, phonetically similar vowels, and whether attention plays a role in such deficits. The neurophysiological measure mismatch negativity (MMN) was used as an index of discrimination in two tasks; one in which children ignored the auditory stimuli and watched a silent video and a second in which they attended to the auditory modality. Children with SLI showed good behavioral discrimination, but significantly poorer behavioral identification of the brief vowels than the children with typical language development (TLD).