Search Results (18)

Background: Parental satisfaction is an important factor in the evaluation of early intervention programs but is rarely investigated. The Muenster Parental Program (MPP) is a short, evidence-based early intervention program that focuses on parental responsiveness. It is a family-centered intervention for parents of infants aged 3–18 months who have recently been diagnosed with hearing loss and fitted with hearing devices, including prior to or following cochlear implant surgery. Objective: We aim to receive feedback from parents regarding the process and outcomes of their participation in the MPP. Method: Following their participation, all participants of the MPP were asked to complete an evaluation questionnaire. This article reports feedback from the first 52 participants (44 mothers, 7 fathers, and 1 godmother). Their infants (N = 45) had moderate to complete hearing loss, they were aged 2–20 months, and 40% of them had an additional disease, disorder, and/or developmental delay. Results: Parents reported high levels of satisfaction with the content, didactics, setting, and individual benefits of the intervention, and a high recommendation rate (92%). The aspects most appreciated were meeting other affected parents and the concrete individual support of parent–child communication, including video feedback. Almost all parents (96%) reported a change in their communication style with their child. This confirms the results of a previous controlled intervention study on the enhancement of parental responsiveness via the MPP. Conclusions: This evaluation of the MPP from a parental point of view has revealed equally high satisfaction with the content, setting, and didactics amongst all parents regardless of any potentially influential parent or child variables. The MPP is well suited to a wide range of close caregivers’ needs despite the known diversity of children with hearing loss and their parents or families. Full article

Phonological developmental speech sound disorders (pDSSD) in childhood are often associated with later difficulties in literacy acquisition. The present study is a follow-up of the randomized controlled trial (RCT) on the effectiveness of PhonoSens, a treatment for pDSSD that focuses on improving auditory self-monitoring skills and categorial perception of phoneme contrasts, which could have a positive impact on later spelling development. Our study examines the spelling abilities of 26 German-speaking children (15 girls, 11 boys; mean age 10.1 years, range 9.3–11.2 years) 3–6 years after their successful completion of the PhonoSens treatment. Spelling assessment revealed that only 3 out of 26 participants developed a spelling disorder. In the overall population of fourth-graders, one in five children showed a spelling deficit; in another study of elementary school children, with resolved pDSSD, 18 of 32 children had a spelling deficit. Thus, the applied pDSSD treatment method appears to be associated with positive spelling development. Multiple regression analysis revealed that among the potentially predictive factors for German-speaking children with resolved pDSSD to develop later spelling difficulties, parental educational level and family risk for developmental language disorder (DLD) had an impact on children’s spelling abilities; gender and the child’s phonological memory had not. Full article

Background: Vocal fold polyps (VFP) are a common cause of voice disorders and laryngeal discomfort. They are usually treated by behavioral voice therapy (VT) or phonosurgery, or a combination (CT) of both. However, the superiority of either of these treatments has not been clearly established. Methods: Three databases were searched from inception to October 2022 and a manual search was performed. All clinical trials of VFP treatment were included that reported at least auditory–perceptual judgment, aerodynamics, acoustics, and the patient-perceived handicap. Results: We identified 31 eligible studies (VT: n = 47–194; phonosurgery: n = 404–1039; CT: n = 237–350). All treatment approaches were highly effective, with large effect sizes (d > 0.8) and significant improvements in almost all voice parameters (p-values < 0.05). Phonosurgery reduced roughness and NHR, and the emotional and functional subscales of the VHI-30 were the most compared to behavioral voice therapy and combined treatment (p-values < 0.001). Combined treatment improved hoarseness, jitter, shimmer, MPT, and the physical subscale of the VHI-30 more than phonosurgery and behavioral voice therapy (p-values < 0.001). Conclusions: All three treatment approaches were effective in eliminating vocal fold polyps or their negative sequelae, with phonosurgery and combined treatment providing the greatest improvement. These results may inform future treatment decisions for patients with vocal fold polyps. Full article

Home monitoring examinations offer diagnostic and economic advantages compared to inpatient monitoring. In addition, these technical solutions support the preservation of health care in rural areas in the absence of local care providers. The acceptance of patients is crucial for the implementation of home monitoring concepts. The present research assesses the preference for a health service that is to be introduced, namely an EEG home-monitoring of neurological outpatients—using a mobile, dry-electrode EEG (electroencephalography) system—in comparison to the traditional long-time EEG examination in a hospital. Results of a representative study for Germany (n = 421) reveal a preference for home monitoring. Importantly, this preference is partially driven by a video explaining the home monitoring system. We subsequently analyzed factors that influence the behavioral intention (BI) to use the new EEG system, drawing on an extended Unified Theory of Acceptance and Use of Technology (UTAUT) model. The strongest positive predictor of BI is the belief that EEG home-monitoring will improve health quality, while computer anxiety and effort expectancy represent the strongest barriers. Furthermore, we find the UTAUT model’s behavioral intention construct to predict the patients’ decision for or against home monitoring more strongly than any other patient’s characteristic such as gender, health condition, or age, underlying the model’s usefulness. Full article

The pyrolytic conversion of lignocellulosic biomass into fuels and chemicals is a promising option for the valorization of agricultural and forestry residues. However, technological developments are still needed to maximize product recovery and carbon fixation of the pyrolysis process. The pyrolysis aqueous condensate (PAC), a pyrolysis by-product, has a high water content and is highly toxic, hampering its use. The anaerobic digestion of PAC from different biomasses has been proven a viable technology for PAC valorization and detoxification, but its toxicity limits the methanogenic potential. Alternatively, methanation or VFA production from syngas by anaerobic mixed cultures are technologies of scientific interest. This study investigates the potential of a two-stage process to convert the carbon and energy in syngas and PAC into L-malate. PAC and syngas were co-fermented by two mixed cultures at 37 and 55 °C, identifying kinetic inhibitions and the effects of increasing PAC concentrations on the product pool. The media from selected mixed culture fermentations were then inoculated with Aspergillus oryzae for L-malate production. The results show that mixed cultures can perform simultaneous syngas fermentation and PAC detoxification. While PAC concentrations above 2% completely inhibited methanogenesis, CO consumption was inhibited at PAC concentrations above 5%, regardless of the temperature. In fermentations where PAC inhibited methanation, the mixed cultures channelled the carbon and electrons from syngas and PAC to volatile fatty acids or acetate/H₂ production, depending on the incubation temperature. Substantial detoxification of PAC was observed under PAC concentrations up to 10% independently of the rates of syngas metabolism. PAC detoxification enabled the further valorization of the acetate produced via syngas and PAC fermentations into L-malate, achieving yields up to 0.17 mM/mM. These results are promising for the development of an integrated process that simultaneously detoxifies and recovers value from gaseous and aqueous waste streams originating from pyrolysis. Full article

Our study aimed to assess the applicability of miR-486 in combination with soluble GP88 protein as a diagnostic and/or predictive biomarker for prostate cancer (PCa) patients. miR-486 and GP88 levels in serum samples from 136 patients undergoing MRI-guided biopsy of the prostate were assessed by qRT–PCR and ELISA, respectively. Of these, 86 patients received a histologically confirmed diagnosis of PCa. Neither marker showed an association with the diagnosis of cancer. PCa patients were separated based on (i) treatment into patients with active surveillance or patients with any type of curative treatment and (ii) age into elderly (>68 years) patients and younger patients (≤68 years). In elderly patients (N = 41) with the intention of curative treatment at optimized cut-off values, significantly higher GP88 levels (p = 0.018) and lower miR-486 levels (p = 0.014) were observed. The total PSA level and ISUP biopsy grade were used in a baseline model for predicting definitive therapy. The baseline model exhibited an area under the curve (AUC) of 0.783 (p = 0.005). The addition of the serum biomarkers miR-486 and GP88 to the baseline model yielded an improved model with an AUC of 0.808 (p = 0.002). Altogether, combined miR-486 and GP88 serum levels are associated with and are therefore suggested as supportive biomarkers for therapy decisions, particularly in elderly PCa patients. Full article

Glomerulonephritis (GN) comprises a group of immune-mediated kidney diseases affecting glomeruli and the tubulointerstitium. Glomerular crescent formation is a histopathological characteristic of severe forms of GN, also referred to as crescentic GN (cGN). Based on histological findings, cGN includes anti-neutrophil cytoplasmic antibody (ANCA)-associated GN, a severe form of ANCA-associated vasculitis, lupus nephritis associated with systemic lupus erythematosus, Goodpasture’s disease, and IgA nephropathy. The immunopathogenesis of cGN is associated with activation of CD4⁺ and CD8⁺ T cells, which particularly accumulate in the periglomerular and tubulointerstitial space but also infiltrate glomeruli. Clinical observations and functional studies in pre-clinical animal models provide evidence for a pathogenic role of Th1 and Th17 cell-mediated immune responses in cGN. Emerging evidence further argues that CD8⁺ T cells have a role in disease pathology and the mechanisms of activation and function of recently identified tissue-resident CD4⁺ and CD8⁺ T cells in cGN are currently under investigation. This review summarizes the mechanisms of pathogenic T-cell responses leading to glomerular damage and renal inflammation in cGN. Advanced knowledge of the underlying immune mechanisms involved with cGN will enable the identification of novel therapeutic targets for the replacement or reduction in standard immunosuppressive therapy or the treatment of refractory disease. Full article

Immune-mediated glomerular diseases are characterized by infiltration of T cells, which accumulate in the periglomerular space and tubulointerstitium in close contact to proximal and distal tubuli. Recent studies described proximal tubular epithelial cells (PTECs) as renal non-professional antigen-presenting cells that stimulate CD4⁺ T-cell activation. Whether PTECs have the potential to induce activation of CD8⁺ T cells is less clear. In this study, we aimed to investigate the capacity of PTECs for antigen cross-presentation thereby modulating CD8⁺ T-cell responses. We showed that PTECs expressed proteins associated with cross-presentation, internalized soluble antigen via mannose receptor-mediated endocytosis, and generated antigenic peptides by proteasomal degradation. PTECs induced an antigen-dependent CD8⁺ T-cell activation in the presence of soluble antigen in vitro. PTEC-activated CD8⁺ T cells expressed granzyme B, and exerted a cytotoxic function by killing target cells. In murine lupus nephritis, CD8⁺ T cells localized in close contact to proximal tubuli. We determined enhanced apoptosis in tubular cells and particularly PTECs up-regulated expression of cleaved caspase-3. Interestingly, induction of apoptosis in the inflamed kidney was reduced in the absence of CD8⁺ T cells. Thus, PTECs have the capacity for antigen cross-presentation thereby inducing cytotoxic CD8⁺ T cells in vitro, which may contribute to the pathology of immune-mediated glomerulonephritis. Full article

There is substantial evidence that newborn hearing screening (NHS) reduces the negative sequelae of permanent childhood hearing loss (PCHL) if performed in programs that aim to screen all newborns in a region or nation (often referred to as Universal Newborn Hearing Screening or UNHS). The World Health Organization (WHO) has called in two resolutions for the implementation of such programs and for the collection of large-scale data. To assess the global status of NHS programs we surveyed individuals potentially involved with newborn and infant hearing screening (NIHS) in 196 countries/territories (in the following text referred to as countries). Replies were returned from 158 countries. The results indicated that 38% of the world’s newborns and infants had no or minimal hearing screening and 33% screened at least 85% of the babies (hereafter referred to as UNHS). Hearing screening programs varied considerably in quality, data acquisition, and accessibility of services for children with PCHL. In this article, we summarize the main results of the survey in the context of several recent WHO publications, particularly the World Report on Hearing, which defined advances in the implementation of NHS programs in the Member States as one of three key indicators of worldwide progress in ear and hearing care (EHC). Full article

Background: The treatment of functional speech sound disorders (SSDs) in children is often lengthy, ill-defined, and without satisfactory evidence of success; effectiveness studies on SSDs are rare. This randomized controlled trial evaluates the effectiveness of the integrated SSD treatment program PhonoSens, which focuses on integrating phonological and phonetic processing according to the Integrated Psycholinguistic Model of Speech Processing (IPMSP). Methods: Thirty-two German-speaking children aged from 3.5 to 5.5 years (median 4.6) with functional SSD were randomly assigned to a treatment or a wait-list control group with 16 children each. All children in the treatment group and, after an average waiting period of 6 months, 12 children in the control group underwent PhonoSens treatment. Results: The treatment group showed more percent correct consonants (PCC) and a greater reduction in phonological processes after 15 therapy sessions than the wait-list control group, both with large effect sizes (Cohen’s d = 0.89 and 1.04). All 28 children treated achieved normal phonological abilities: 21 before entering school and 7 during first grade. The average number of treatment sessions was 28; the average treatment duration was 11.5 months. Conclusion: IPMSP-aligned therapy is effective in the treatment of SSD and is well adaptable for languages other than German. Full article

Unlike conventional yeasts, several oleaginous yeasts, including Saitozyma podzolica DSM 27192, possess the innate ability to grow and produce biochemicals from plant-derived lignocellulosic components such as hexose and pentose sugars. To elucidate the genetic basis of S. podzolica growth and lipid production on glucose and xylose, we performed comparative temporal transcriptome analysis using RNA-seq method. Approximately 3.4 and 22.2% of the 10,670 expressed genes were differentially (FDR < 0.05, and log2FC > 1.5) expressed under batch and fed batch modes, respectively. Our analysis revealed that a higher number of sugar transporter genes were significantly overrepresented in xylose relative to glucose-grown cultures. Given the low homology between proteins encoded by most of these genes and those of the well-characterised transporters, it is plausible to conclude that S. podzolica possesses a cache of putatively novel sugar transporters. The analysis also suggests that S. podzolica potentially channels carbon flux from xylose via both the non-oxidative pentose phosphate and potentially via the first steps of the Weimberg pathways to yield xylonic acid. However, only the ATP citrate lyase (ACL) gene showed significant upregulation among the essential oleaginous pathway genes under nitrogen limitation in xylose compared to glucose cultivation. Combined, these findings pave the way toward the design of strategies or the engineering of efficient biomass hydrolysate utilization in S. podzolica for the production of various biochemicals. Full article

Obesity is a major risk factor for developing cancer, with obesity-induced immune changes and inflammation in breast (BC) and colorectal cancer (CRC) providing a potential link between the two. This study investigates systemic effects of obesity on adaptive and innate immune cells in healthy and tumour-bearing mice. Immune cells from lean and obese mice were phenotyped prior to implantation of either BC (C57mg and EO771.LMB) or CRC (MC38) cells as tumour models. Tumour growth rate, tumour-infiltrating lymphocytes (TIL) and peripheral blood immune cell populations were compared between obese and lean mice. In vitro studies showed that naïve obese mice had higher levels of myeloid cells in the bone marrow and bone marrow-derived dendritic cells expressed lower levels of activation markers compared to cells from their lean counterparts. In the tumour setting, BC tumours grew faster in obese mice than in lean mice and lower numbers of TILs as well as higher frequency of exhausted T cells were observed. Data from peripheral blood showed lower levels of myeloid cells in tumour-bearing obese mice. This study highlights that systemic changes to the immune system are relevant for tumour burden and provides a potential mechanism behind the effects of obesity on cancer development and progression in patients. Full article

Cardiorespiratory fitness (CRF) represents a strong predictor of all-cause mortality and is strongly influenced by regular physical activity (PA). However, the biological mechanisms involved in the body’s adaptation to PA remain to be fully elucidated. The aim of this study was to systematically examine the relationship between CRF and plasma metabolite patterns in 252 healthy adults from the cross-sectional Karlsruhe Metabolomics and Nutrition (KarMeN) study. CRF was determined by measuring the peak oxygen uptake during incremental exercise. Fasting plasma samples were analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry coupled to one- or two-dimensional gas chromatography or liquid chromatography. Based on this multi-platform metabolomics approach, 427 plasma analytes were detected. Bi- and multivariate association analyses, adjusted for age and menopausal status, showed that CRF was linked to specific sets of metabolites primarily indicative of lipid metabolism. However, CRF-related metabolite patterns largely differed between sexes. While several phosphatidylcholines were linked to CRF in females, single lyso-phosphatidylcholines and sphingomyelins were associated with CRF in males. When controlling for further assessed clinical and phenotypical parameters, sex-specific CRF tended to be correlated with a smaller number of metabolites linked to lipid, amino acid, or xenobiotics-related metabolism. Interestingly, sex-specific CRF explanation models could be improved when including selected plasma analytes in addition to clinical and phenotypical variables. In summary, this study revealed sex-related differences in CRF-associated plasma metabolite patterns and proved known associations between CRF and risk factors for cardiometabolic diseases such as fat mass, visceral adipose tissue mass, or blood triglycerides in metabolically healthy individuals. Our findings indicate that covariates like sex and, especially, body composition have to be considered when studying blood metabolic markers related to CRF. Full article

Cancer is one of the leading causes of morbidity and mortality worldwide. Traditional treatments include surgery, chemotherapy and radiation therapy, and more recently targeted therapies including immunotherapy are becoming routine care for some cancers. Immunotherapy aims to upregulate the patient’s own immune system, enabling it to destroy cancerous cells. Obesity is a metabolic disorder characterized by significant weight that is an important contributor to many different diseases, including cancers. Obesity impacts the immune system and causes, among other things, a state of chronic low-grade inflammation. This is hypothesized to impact the efficacy of the immunotherapies. This review discusses the effects of obesity on the immune system and cancer immunotherapy, including the current evidence on the effect of obesity on immune checkpoint blockade, something which currently published reviews on this topic have not delved into. Data from several studies show that even though obesity causes a state of chronic low-grade inflammation with reductions in effector immune populations, it has a beneficial effect on patient survival following anti-PD-1/PD-L1 and anti-CTLA-4 treatment. However, research in this field is just emerging and further work is needed to expand our understanding of which cancer patients are likely to benefit from immunotherapy. Full article

In contrast to CRISPR/Cas9 nucleases, CRISPR base editors (BE) and prime editors (PE) enable predefined nucleotide exchanges in genomic sequences without generating DNA double strand breaks. Here, we employed BE and PE mRNAs in conjunction with chemically synthesized sgRNAs and pegRNAs for efficient editing of human induced pluripotent stem cells (iPSC). Whereas we were unable to correct a disease-causing mutation in patient derived iPSCs using a CRISPR/Cas9 nuclease approach, we corrected the mutation back to wild type with high efficiency utilizing an adenine BE. We also used adenine and cytosine BEs to introduce nine different cancer associated TP53 mutations into human iPSCs with up to 90% efficiency, generating a panel of cell lines to investigate the biology of these mutations in an isogenic background. Finally, we pioneered the use of prime editing in human iPSCs, opening this important cell type for the precise modification of nucleotides not addressable by BEs and to multiple nucleotide exchanges. These approaches eliminate the necessity of deriving disease specific iPSCs from human donors and allows the comparison of different disease-causing mutations in isogenic genetic backgrounds. Full article