Dealing with an uncertain future: a survey study on what patients with chronic kidney disease actually want to know.

Background: Prognostic uncertainty is a recurring theme among patients with chronic kidney disease (CKD). We developed a survey to explore whether CKD patients want to know more about their future, and if so, which topics they prioritize. In addition, we explored differences between several subgroups. Methods: A survey was constructed and tested in collaboration with the Dutch Kidney Patients Association. The survey consisted of three parts: (i) demographics, (ii) considerations about the future, and (iii) prognostic information. The survey was distributed among CKD patients (all stages) through patient associations and via healthcare professionals in two Dutch hospitals. Descriptive statistics were used to summarize the results. All results were stratified by population, sex, and age. Results: A total of 163 patients (45 CKD, 26 dialysis, and 92 kidney transplantation) participated in the survey. The mean age was 63.9 (SD 12.0) and 48.5% was male. Most patients think about their future with CKD occasionally (56.4%) or often (35.0%). Nearly half of the patients (49.7%) discuss the future with their nephrologist, some (19.6%) do not but would like to, and 20 (15.3%) prefer not to. Most patients (73.6%) want more prognostic information, regardless of it being positive or negative. Key topics to receive prognostic information about were laboratory values, symptoms, and physical well-being. Dialysis patients prioritized mental over physical well-being. CKD patients without kidney replacement therapy (KRT) indicated thinking about, and discussing their future more regularly than KRT patients. Conclusions: Patients with CKD contemplate their future regularly and express interest in receiving prognostic information on a variety of topics. One in five patients currently do not discuss their future with CKD with their nephrologist, despite wanting to do so. These findings underline the need to tailor prognostic information provision to patients' preferences, advocating more attention to this subject both in research and clinical practice.

FLOW: Flow dysfunction of hemodialysis vascular access: A randomized controlled trial on the effectiveness of surveillance of arteriovenous fistulas and grafts.

INTRODUCTION: It is assumed that identification and correction of asymptomatic stenoses in the vascular access circuit will prevent thrombosis that would require urgent intervention to continue hemodialysis treatment. However, the evidence base for this assumption is limited. Recent international clinical practice guidelines reach different conclusions on the use of surveillance for vascular access flow dysfunction and recommend further research to inform clinical practice. METHODS: The FLOW trial is a double-blind, multicenter, randomized controlled trial with a 1:1 individual participant treatment allocation ratio over two study arms. In the intervention group, only symptomatic vascular access stenoses detected by clinical monitoring are treated, whereas in the comparison group asymptomatic stenoses detected by surveillance using monthly dilution flow measurements are treated as well. Hemodialysis patients with a functional arteriovenous vascular access are enrolled. The primary outcome is the access-related intervention rate that will be analyzed using a general linear model with Poisson distribution. Secondary outcomes include patient satisfaction, access-related serious adverse events, and quality of the surveillance process. A cost effectiveness analysis and budget impact analysis will also be conducted. The study requires 828 patient-years of follow-up in 417 participants to detect a difference of 0.25 access-related interventions per year between study groups. DISCUSSION: As one of the largest randomized controlled trials assessing the clinical impact of vascular access surveillance using a strong double-blinded study design, we believe the FLOW trial will provide much-needed evidence to improve vascular access care for hemodialysis patients.

Choosing conservative care in advanced chronic kidney disease: a scoping review of patients' perspectives.

BACKGROUND: Conservative care (CC) is a viable treatment option for some patients with kidney failure. Choosing between dialysis and CC can be a complex decision in which involvement of patients is desirable. Gaining insight into the experiences and preferences of patients regarding this decision-making process is an important initial step to improve care. We aimed to identify what is known about the perspective of patients regarding decision-making when considering CC. METHODS: PubMed, EMBASE and Cochrane databases were systematically searched on 23 February 2023 for qualitative and quantitative studies on patient-reported experiences on decision-making about CC. Data were analysed thematically. RESULTS: Twenty articles were included. We identified three major themes: creating awareness about disease and treatment choice, decision support and motivation to choose CC. Patients were often not aware of the option to choose CC. Patients felt supported by their loved ones during the decision-making process, although they perceived they made the final decision to choose CC themselves. Some patients felt pressured by their healthcare professional to choose dialysis. Reported reasons to choose CC were maintaining quality of life, treatment burden of dialysis, cost and the desire not to be a burden to others. In general, patients were satisfied with their decision for CC. CONCLUSIONS: By focussing on the perspective of patients, we identified a wide range of patient experiences and preferences regarding the decision-making process. These findings can help to improve the complex decision-making process between dialysis and CC and to provide patient-centred care.

Exploring Patients' Perceptions About Chronic Kidney Disease and Their Treatment: A Qualitative Study.

BACKGROUND: Unhelpful illness perceptions can be changed by means of interventions and can lead to improved outcomes. However, little is known about illness perceptions in patients with chronic kidney disease (CKD) prior to kidney failure, and no tools exist in nephrology care to identify and support patients with unhelpful illness perceptions. Therefore, this study aims to: (1) identify meaningful and modifiable illness perceptions in patients with CKD prior to kidney failure; and (2) explore needs and requirements for identifying and supporting patients with unhelpful illness perceptions in nephrology care from patients' and healthcare professionals' perspectives. METHODS: Individual semi-structured interviews were conducted with purposive heterogeneous samples of Dutch patients with CKD (n = 17) and professionals (n = 10). Transcripts were analysed using a hybrid inductive and deductive approach: identified themes from the thematic analysis were hereafter organized according to Common-Sense Model of Self-Regulation principles. RESULTS: Illness perceptions considered most meaningful are related to the seriousness (illness identity, consequences, emotional response and illness concern) and manageability (illness coherence, personal control and treatment control) of CKD. Over time, patients developed more unhelpful seriousness-related illness perceptions and more helpful manageability-related illness perceptions, caused by: CKD diagnosis, disease progression, healthcare support and approaching kidney replacement therapy. Implementing tools to identify and discuss patients' illness perceptions was considered important, after which support for patients with unhelpful illness perceptions should be offered. Special attention should be paid towards structurally embedding psychosocial educational support for patients and caregivers to deal with CKD-related symptoms, consequences, emotions and concerns about the future. CONCLUSIONS: Several meaningful and modifiable illness perceptions do not change for the better by means of nephrology care. This underlines the need to identify and openly discuss illness perceptions and to support patients with unhelpful illness perceptions. Future studies should investigate whether implementing illness perception-based tools will indeed improve outcomes in CKD.

Differences in mental health status during the COVID-19 pandemic between patients undergoing in-center hemodialysis and peritoneal dialysis.

BACKGROUND: The mental health of dialysis patients during the COVID-19 pandemic may have been modulated by dialysis modality. Studies comparing mental health of in-center hemodialysis and peritoneal dialysis patients during the first 2 years of the pandemic are lacking. METHODS: We conducted repeated cross-sectional and multivariable regression analyses to compare the mental health of in-center hemodialysis and peritoneal dialysis patients from March 2019 until August 2021 using data from the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes. The study period was divided into one pre-pandemic and six 3-month pandemic periods (period 1-period 6). Mental health was assessed with the Mental Component Summary score of the 12-item Short Form health survey and mental symptoms of the Dialysis Symptom Index. RESULTS: We included 1274 patients (968 on in-center hemodialysis and 306 on peritoneal dialysis). Mental Component Summary scores did not differ between in-center hemodialysis and peritoneal dialysis patients. In contrast, in-center hemodialysis patients more often reported nervousness during period 3 (27% vs 15%, P = 0.04), irritability and anxiety during period 3 (31% vs 18%, P = 0.03, 26% vs. 9%, P = 0.002, respectively) and period 4 (34% vs 22%, P = 0.04, 22% vs 11%, P = 0.03, respectively), and sadness in period 4 (38% vs 26%, P = 0.04) and period 5 (37% vs 22%, P = 0.009). Dialysis modality was independently associated with mental symptoms. CONCLUSIONS: In-center hemodialysis patients more often experienced mental symptoms compared to peritoneal dialysis patients from September 2020 to June 2021, which corresponds to the second lockdown of the COVID-19 pandemic. Mental health-related quality-of-life did not differ between in-center hemodialysis and peritoneal dialysis patients. TRIAL REGISTRATION NUMBER: Netherlands Trial Register NL6519, date of registration: 22 August, 2017.

Health professionals' attitudes towards acupuncture/acupressure for post-operative nausea and vomiting: a survey and implications for implementation.

PURPOSE: Level 1 evidence supports the use of acupuncture/acupressure (A/A) to manage post-operative nausea and vomiting (PONV). This study aimed to survey healthcare professionals' attitudes towards A/A, influencing factors and barriers to implementing this effective non-drug intervention into peri-operative care. METHODS: A validated, anonymous survey with 43 questions was emailed or distributed as a hard copy at meetings to anaesthetists, midwives, nurses, obstetricians, gynaecologists and surgeons at a public hospital in Australia. Descriptive data were presented. Influencing factors were explored using chi-square analysis. Multinomial logistical regression was used to identify the influences of confounding factors. RESULTS: A total of 155 completed surveys were returned, reflecting a response rate of 32%. The majority of participants were female (69%), nurses/midwives (61%) and aged between 20 and 50 years old (76%). Eighty-three percent of respondents considered A/A 'clearly alternative' medicine or 'neither mainstream nor alternative'. Eighty-one percent would encourage patients to use acupressure for PONV if it was offered at the hospital. Previous personal use of A/A was the key factor influencing attitudes and openness to clinical use. The key barriers to implementation were perceived lack of evidence and lack of qualified providers and time. CONCLUSION: Hospital-based healthcare professionals strongly supported the evidence-based use of A/A for PONV despite considering the therapy to be non-mainstream and having limited A/A education or history of personal use, providing a positive context for an acupressure implementation study. Significant gaps in training and a desire to learn were identified.

Diagnostic outcomes of bone marrow aspirate and trephine biopsies performed at a hospital in KwaZulu-Natal, South Africa.

BACKGROUND: Bone marrow aspiration and trephine biopsy (BMAT) are widely performed in adults to evaluate haematological and malignant conditions. However, the diagnostic yield from the procedure in unselected patients in the South African public sector has not previously been described. OBJECTIVES: We identified the main indications and most common diagnoses encountered for BMAT and described the demographic and blood profiles of patients, including HIV-positive patients, who had undergone the procedure at a tertiary hospital in KwaZulu-Natal. METHODS: We retrospectively reviewed laboratory data from January 2016 to December 2016 for all patients aged ≥ 13 years who underwent the procedure and stratified findings by demographic data. RESULTS: Among 120 BMAT biopsies studied, 80 (67%) cases were performed to evaluate suspected malignancy and a further 40 (33%) cases for non-malignant indications. The main indications for bone marrow examination were: cytopenias 38 (32%), lymphoma 35 (29%), leukaemia 21 (18%), and multiple myeloma 17 (14%). BMAT results revealed that 60 cases (50%) were malignant in origin, 30 cases (25%) were non-malignant and 30 cases (25%) were classified as normal. The common diagnoses were: leukaemia, 24 (20%); multiple myeloma, 16 (13%) and lymphoma, 13 (11%). Cases aged ≥ 50 years were more likely to have a malignant diagnosis (odds ratio: 5.8 (95% confidence interval: 2.2-17.1) p-value < 0.001). CONCLUSION: The diagnostic yield of BMAT was high, with significant abnormalities detected in three quarters of cases. Haematological malignancy was the more common diagnosis. Increasing age was associated with an increase in reporting of haematology malignancy.

Diagnostic outcomes of bone marrow aspirate and trephine biopsies performed at a hospital in KwaZulu-Natal, South Africa

Background: Bone marrow aspiration and trephine biopsy (BMAT) are widely performed in adults to evaluate haematological and malignant conditions. However, the diagnostic yield from the procedure in unselected patients in the South African public sector has not previously been described. Objectives: We identified the main indications and most common diagnoses encountered for BMAT and described the demographic and blood profiles of patients, including HIV-positive patients, who had undergone the procedure at a tertiary hospital in KwaZulu-Natal.Methods: We retrospectively reviewed laboratory data from January 2016 to December 2016n for all patients aged ≥ 13 years who underwent the procedure and stratified findings by demographic data.Results: Among 120 BMAT biopsies studied, 80 (67%) cases were performed to evaluate suspected malignancy and a further 40 (33%) cases for non-malignant indications. The main indications for bone marrow examination were: cytopenias 38 (32%), lymphoma 35 (29%), leukaemia 21 (18%), and multiple myeloma 17 (14%). BMAT results revealed that 60 cases (50%) were malignant in origin, 30 cases (25%) were non-malignant and 30 cases (25%) were classified as normal. The common diagnoses were: leukaemia, 24 (20%); multiple myeloma, 16 (13%) and lymphoma, 13 (11%). Cases aged ≥ 50 years were more likely to have a malignant diagnosis (odds ratio: 5.8 (95% confidence interval: 2.2­17.1)bp-value < 0.001). Conclusion: The diagnostic yield of BMAT was high, with significant abnormalities detected in three quarters of cases. Haematological malignancy was the more common diagnosis. Increasing age was associated with an increase in reporting of haematology malignancy

Older patients' experiences with a shared decision-making process on choosing dialysis or conservative care for advanced chronic kidney disease: a survey study.

BACKGROUND: Many older patients approaching end-stage kidney disease have to decide whether to go for dialysis or non-dialytic conservative care (CC). Shared decision-making is recommended to align the treatment plan with the patient's preferences and values. Little is known about older patients' experiences with shared decision-making on dialysis or CC. METHODS: We performed a survey study, in collaboration with the Dutch Kidney Patients Association, in 99 patients aged ≥70 years who had chosen dialysis (n = 75) or CC (n = 24) after a shared decision-making process involving an experienced multidisciplinary team. RESULTS: Patients stated to be overall satisfied with the shared decision-making process (% with score 6-10 on 11-point Likert scale, dialysis versus CC: 93% vs. 91%, P = 0.06), and treatment decision (87% vs. 91%, P = 0.03). However, patients also reported negative experiences, especially those who had chosen dialysis. Such negative experiences were related to the timing, informing, and level of decision-making being shared. More patients who selected dialysis indicated to have felt forced to make a decision, mostly due to the circumstances, such as their deteriorating health or kidney function, or by their nephrologist (31% vs. 5%, P = 0.01). Also, patients who selected dialysis mentioned a perceived lack of choice as most common reason for choosing dialysis, and 55% considered their own opinion as most important rather than their nephrologists' or relatives' opinion compared to 90% of the patients who had chosen CC (P = 0.02). A subset of patients who had chosen dialysis still doubted their treatment decision compared to no patient who had chosen CC (17% vs. 0%, P = 0.03). CONCLUSIONS: Older patients reported contrasting experiences with shared decision-making on dialysis or CC. Despite high overall satisfaction, the underlying negative experiences illustrate important but modifiable barriers to an optimal shared decision-making process.

A matched case-control study comparing udder health, production and fertility parameters in dairy farms before and after the eradication of Bovine Virus Diarrhoea in Switzerland.

An obligatory eradication programme for Bovine Virus Diarrhoea (BVD) was implemented in Switzerland in 2008. Between 2008 and 2012, all bovines were tested for antigen or antibodies against BVDV. By the year 2012, eradication was completed in the majority of farms. A decrease of the prevalence of persistently infected (PI) newborn calves was observed from 1.4% in 2008 to <0.02% in 2012. The objective of the present study was to assess the effects of BVD eradication on different parameters of animal health, production and fertility in Swiss dairy herds which had completed the eradication programme. A matched case-control study was carried out using data from two periods, before (Period 1) and after (Period 2) the active phase of eradication. Case farms had at least two PI animals detected before or during the eradication; controls were BVD-free and matched for region, herd size and use of alpine pasture. A total of 110 farmers (55 pairs) were recruited. During a phone interview, a questionnaire about farm characteristics, animal health and appreciation of the BVD eradication programme was filled in. Breeding data and milk test day records were also analyzed. Parameters were first compared between (i) case and control herds before eradication, and (ii) Period 1 and Period 2 for case herds only. Milk yield (MY), bulk milk somatic cell count (BMSCC), prevalence of subclinical mastitis (SCM), and non-return rate (NRR) showed a p-value<0.25 in at least one of the univariable comparisons and were thus further analyzed with a multilevel mixed-effects model to account for repeated measures over time. In order to assess whether changes in health status over time were due to BVD eradication, an interaction variable between period and group (case-control) was created (IA). Except for MY, the IA was significant for all parameters modelled. Despite an overall p-value of 0.27, case herds tended to have a higher MY after eradication (ß=0.53, p=0.050). For BMSCC and SCM, case herds had higher values than controls in both periods; udder health was significantly improved in control herds and it remained stable in case herds, with a slight decrease of BMSCC (ß=-0.19, p=0.010). Finally, among fertility parameters, NRR showed a general improvement but it was significant only in control herds (ß=0.29, p=0.019). Even though the effects of the eradication programme measured in this study were less pronounced than expected, 73% of the participants of this study had a positive attitude towards the campaign.

Nurse Research Rounds: In the Spirit of Inquiry.

Nurses deliver a point-of-care service to patients. The nursing staff work extensive schedules and do not have time to research a clinical question to help support patient care. This article describes the implementation of the first research service that supports evidence-based practice at Georgia's second largest hospital. Inspired by a similar service at a children's hospital in 2014, the first year of nurse research rounds provides clinicians a new research service in their clinical setting.

Pseudo-immortalization of postnatal cochlear progenitor cells yields a scalable cell line capable of transcriptionally regulating mature hair cell genes.

The mammalian cochlea is a highly specialized organ within the inner ear. Sensory hair cells (HC) in the cochlea detect and transduce sound waves into electrical impulses that are sent to the brain. Studies of the molecular pathways regulating HC formation are hindered by the very sparse nature of HCs, where only ~3300 are found within an entire mouse cochlea. Current cell lines mimic certain aspects of HCs but lack terminal HC marker expression. Here we successfully "pseudo-immortalized" cochlear progenitor cells using the "conditional reprogramming" technique. These cells, termed "Conditionally Reprogrammed Otic Stem Cells" (CR-OSC), are able to bypass the senescence inherent to cochlear progenitor cells without genetic alterations, allowing for the generation of over 15 million cells from a single cochlea. These cells can be differentiated and up-regulate both early and terminal differentiation genes associated with HCs, including the terminal HC differentiation marker prestin. CR-OSCs also respond to known HC cues, including upregulation of HC genes in response to Atoh1 overexpression, and upregulation of prestin expression after thyroid hormone application. Overall, we describe the creation of a HC line capable of regulated expression of HC genes that can easily be recreated in any laboratory from any mouse of interest.

In Vivo Cochlear Hair Cell Generation and Survival by Coactivation of ß-Catenin and Atoh1.

The mammalian cochlea exhibit minimal spontaneous regeneration, and loss of sensory hair cells (HCs) results in permanent hearing loss. In nonmammalian vertebrates, spontaneous HC regeneration occurs through both proliferation and differentiation of surrounding supporting cells (SCs). HC regeneration in postnatal mammalian cochleae in vivo remains limited by the small HC number and subsequent death of regenerated HCs. Here, we describe in vivo generation of 10-fold more new HCs in the mouse cochlea than previously reported, most of which survive to adulthood. We achieved this by combining the expression of a constitutively active form of ß-catenin (a canonical Wnt activator) with ectopic expression of Atoh1 (a HC fate determination factor) in neonatal Lgr5+ cells (the presumed SC and HC progenitors of the postnatal mouse cochlea), and discovered synergistic increases in proliferation and differentiation. The new HCs were predominantly located near the endogenous inner HCs, expressed early HC differentiation markers, and were innervated despite incomplete alignment of presynaptic and postsynaptic markers. Surprisingly, genetic tracing revealed that only a subset of Lgr5+ cells that lie medial to the inner HCs respond to this combination, highlighting a previously unknown heterogeneity that exists among Lgr5+ cells. Together, our data indicate that ß-catenin and Atoh1 mediate synergistic effects on both proliferation and differentiation of a subset of neonatal cochlear Lgr5+ cells, thus overcoming major limitations of HC regeneration in postnatal mouse cochleae in vivo. These results provide a basis for combinatorial therapeutics for hearing restoration. SIGNIFICANCE STATEMENT: Hearing loss in humans from aging, noise exposure, or ototoxic drugs (i.e., cisplatin or some antibiotics) is permanent and affects every segments of the population, worldwide. However, birds, frog, and fish have the ability to recover hearing, and recent studies have focused on understanding and applying what we have learned from them for restoring hearing in humans. However, studies have been hampered by low efficiency, limited cell numbers, and subsequent death of these newly generated auditory cells. Here, we describe a combinatorial approach, which results in the generation of auditory cells in greater numbers than previously reported, with most of them surviving to adult ages in vivo. These results provide a basis for combinatorial therapeutics for hearing restoration efforts.

Failed Reverse Total Shoulder Arthroplasty Caused by Recurrent Candida glabrata Infection with Prior Serratia marcescens Coinfection.

This report describes a 58-year-old insulin-dependent diabetic male patient who initially sustained a proximal humerus fracture from a fall. The fracture fixation failed and then was converted to a humeral hemiarthroplasty, which became infected with Candida glabrata and Serratia marcescens. After these infections were believed to be cured with antibacterial and antifungal treatments and two-stage irrigation and debridement, he underwent conversion to a reverse total shoulder arthroplasty. Unfortunately, the C. glabrata infection recurred and, nearly 1.5 years after implantation of the reverse total shoulder, he had a resection arthroplasty (removal of all implants and cement). His surgical and pharmacologic treatment concluded with (1) placement of a tobramycin-impregnated cement spacer also loaded with amphotericin B, with no plan for revision arthroplasty (i.e., the spacer was chronically retained), and (2) chronic use of daily oral fluconazole. We located only three reported cases of Candida species causing infection in shoulder arthroplasties (two C. albicans, one C. parapsilosis). To our knowledge, a total shoulder arthroplasty infected with C. glabrata has not been reported, nor has a case of a C. glabrata and S. marcescens periprosthetic coinfection in any joint. In addition, it is well known that S. marcescens infections are uncommon in periprosthetic joint infections.

CHD7 and retinoic acid signaling cooperate to regulate neural stem cell and inner ear development in mouse models of CHARGE syndrome.

CHARGE syndrome is a multiple congenital anomaly disorder that leads to life-threatening birth defects, such as choanal atresia and cardiac malformations as well as multiple sensory impairments, that affect hearing, vision, olfaction and balance. CHARGE is caused by heterozygous mutations in CHD7, which encodes an ATP-dependent chromatin remodeling enzyme. Identification of the mechanisms underlying neurological and sensory defects in CHARGE is a first step toward developing treatments for CHARGE individuals. Here, we used mouse models of Chd7 deficiency to explore the function of CHD7 in the development of the subventricular zone (SVZ) neural stem cell niche and inner ear, structures that are important for olfactory bulb neurogenesis and hearing and balance, respectively. We found that loss of Chd7 results in cell-autonomous proliferative, neurogenic and self-renewal defects in the perinatal and mature mouse SVZ stem cell niche. Modulation of retinoic acid (RA) signaling prevented in vivo inner ear and in vitro neural stem cell defects caused by Chd7 deficiency. Our findings demonstrate critical, cooperative roles for RA and CHD7 in SVZ neural stem cell function and inner ear development, suggesting that altered RA signaling may be an effective method for treating Chd7 deficiency.

Epigenetic regulation in the inner ear and its potential roles in development, protection, and regeneration.

The burgeoning field of epigenetics is beginning to make a significant impact on our understanding of tissue development, maintenance, and function. Epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues that direct cell-type specific gene networks. The inner ear is comprised of highly specialized cell types with identical genomes that originate from a single totipotent zygote. During inner ear development specific combinations of transcription factors and epigenetic modifiers must function in a coordinated manner to establish and maintain cellular identity. These epigenetic regulatory mechanisms contribute to the maintenance of distinct chromatin states and cell-type specific gene expression patterns. In this review, we highlight emerging paradigms for epigenetic modifications related to inner ear development, and how epigenetics may have a significant role in hearing loss, protection, and regeneration.

Epigenetic alterations by NuRD and PRC2 in the neonatal mouse cochlea.

Mammalian cochlear supporting cells remain quiescent at postnatal ages and age-dependent changes in supporting cell proliferative capacity are evident. Ectopic Atoh1 expression in neonatal supporting cells converts only a small percentage of these cells into hair cell-like cells. Despite tremendous potential for therapeutics, cellular reprogramming in the mammalian inner ear remains a slow inefficient process that requires weeks, with most cells failing to reprogram. Cellular reprogramming studies in other tissues have shown that epigenetic inhibitors can significantly improve reprogramming efficiency. Very little is known about epigenetic regulation in the mammalian inner ear, and almost nothing is known about the histone modifications. Histone modifications are vital for proper transcriptional regulation, and aberrant histone modifications can cause defects in the regulation of genes required for normal tissue development and maintenance. Our data indicate that cofactors of repressive complexes such as NuRD and PRC2 are present in the neonatal organ of Corti. These NuRD cofactors are present throughout most of the organ of Corti from E18.5 until P4. By P6, these NuRD cofactors are mostly undetectable by immunofluorescence and completely lost by P7, but are detectable again at P8 and continue to be present through P21. The PRC2 enzymatic subunit, EZH2 is also highly present from E18.5 to P0 in the organ of Corti, but lost between P2 and P4. However, EZH2 staining is evident again throughout the organ of Corti by P6 and persists through P21. Our data provide evidence that HDACs, DNA methyltransferases, histone methyltransferases, and histone demethylases are expressed postnatally within the organ of Corti, and may be targets for drug inhibition to increase the capacity, speed, and efficiency of reprogramming a supporting cell into a hair cell.

Analysis of the variation in meat inspection of pigs using variance partitioning.

According to legal regulations, all slaughtered pigs in the European Union are subject to routine meat inspection at the slaughterhouses. The resulting post-mortem findings are valuable indicators that help improve slaughterhouse and farm management and can be used to establish a feedback system regarding animal health. A sufficiently high quality of meat inspection is therefore imperative, which implies that the results of the inspection must not depend on the person carrying out the examination. The objective of the study at hand is the estimation of the amount of variation in these post-mortem findings that can be attributed to the official meat inspectors. In order to reduce the influence of the heterogeneity in the health state of the pigs, the variation due to the farms of origin was considered in the statistical model as well. The analyzed meat inspection data were recorded by 12 official meat inspectors under real working conditions at an Austrian slaughterhouse. Logistic Multilevel Models with cross-classified random effects were applied to 20 post-mortem findings. On the basis of these models, variance partitioning coefficients (VPCs) were used to estimate the amount of variation in the probabilities of these findings due to meat inspector and farm levels. The estimated VPCs suggest that especially meat inspection of blood aspiration, scalding water lungs, skin lesions and hepatitis can be deemed as not sufficiently standardized. Hardly any variation in meat inspection could be identified for other post-mortem findings, such as pericarditis, peritonitis, arthritis and milkspots.

Effectiveness of a polyamide film releasing lactic acid on the growth of E. coli O157:H7, Enterobacteriaceae and Total Aerobic Count on vacuum-packed beef.

The suitability of a polyamide 6 monolayer film containing lactic acid for use as an antimicrobial package for fresh beef cuts was studied. The release of lactic acid in an aqueous environment was immediate (within 1h) and was from approx. 55 µg lactic acid/cm(2) film at 0-8°C to approx. 67 µg lactic acid/cm(2) film at 12-20°C. Beef was contaminated with an Escherichia coli O157:H7 isolate with known minimum inhibitory concentration against lactic acid (0.09% v/v), then wrapped with the lactic-acid polyamide film and vacuum packaged. During storage at 12°C, the numbers of E. coli were 1 log unit lower than that of a control (untreated polyamide film) and decreased by an additional 1 log during storage for 14 days.