Continuous Multidisciplinary Care for Patients With Orofacial Clefts—Should the Follow-up Interval Depend on the Cleft Entity?

Objective: The multidisciplinary follow-up of patients with cleft lip with or without palate (CL/P) is organized differently in specialized centers worldwide. The aim of this study was to evaluate the different treatment needs of patients with different manifestations of CL/P and to potentially adapt the frequency and timing of checkup examinations accordingly. Design:We retrospectively analyzed the data of all patients attending the CL/P consultation hour at a tertiary care center between June 2005 and August 2020 (n=1126). We defined 3 groups of cleft entities: (1) isolated clefts of lip or lip and alveolus (CL/A), (2) isolated clefts of the hard and/or soft palate, and (3) complete clefts of lip, alveolus and palate (CLP). Timing and type of therapy recommendations given by the specialists of different disciplines were analyzed for statistical differences. Results: Patients with CLP made up the largest group (n=537), followed by patients with cleft of the soft palate (n=371) and CL ±A (n=218). There were significant differences between the groups with regard to type and frequency of treatment recommendations. A therapy was recommended in a high proportion of examinations in all groups at all ages. Conclusion: Although there are differences between cleft entities, the treatment need of patients with orofacial clefts is generally high during the growth period. Patients with CL/A showed a similarly high treatment demand and should be monitored closely. A close follow-up for patients with diagnosis of CL/P is crucial and measures should be taken to increase participation in followup appointments

Reducing office workers' sitting time: rationale and study design for the Stand Up Victoria cluster randomized trial

Background: Excessive time spent in sedentary behaviours (sitting or lying with low energy expenditure) is associated with an increased risk for type 2 diabetes, cardiovascular disease and some cancers. Desk-based office workers typically accumulate high amounts of daily sitting time, often in prolonged unbroken bouts. The Stand Up Victoria study aims to determine whether a 3-month multi-component intervention in the office setting reduces workplace sitting, particularly prolonged, unbroken sitting time, and results in improvements in cardio-metabolic biomarkers and work-related outcomes, compared to usual practice

Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size

Stem cells reside in a specialized niche that regulates their abundance and fate. Components of the niche have generally been defined in terms of cells and signaling pathways. We define a role for a matrix glycoprotein, osteopontin (OPN), as a constraining factor on hematopoietic stem cells within the bone marrow microenvironment. Osteoblasts that participate in the niche produce varying amounts of OPN in response to stimulation. Using studies that combine OPN-deficient mice and exogenous OPN, we demonstrate that OPN modifies primitive hematopoietic cell number and function in a stem cell–nonautonomous manner. The OPN-null microenvironment was sufficient to increase the number of stem cells associated with increased stromal Jagged1 and Angiopoietin-1 expression and reduced primitive hematopoietic cell apoptosis. The activation of the stem cell microenvironment with parathyroid hormone induced a superphysiologic increase in stem cells in the absence of OPN. Therefore, OPN is a negative regulatory element of the stem cell niche that limits the size of the stem cell pool and may provide a mechanism for restricting excess stem cell expansion under conditions of niche stimulation

How is neck dissection performed in Oral and Maxillofacial Surgery? Results of a representative nationwide survey among university and non-university hospitals in Germany

Introduction Neck dissection (ND) is a surgical procedure addressing cervical lymph nodes and metastases in patients with oral squamous cell carcinoma (OSCC). The aim of this study was to analyze clinical decisions regarding indications and variations of ND in Oral and Maxillofacial Surgery (OMFS) in Germany. Material and methods A nationwide survey of the German Association of Oral and Maxillofacial Surgery was performed using dynamic online questionnaires including 38 questions. Data about oncological centers, case numbers, and staging procedures were collected. Relevant aspects, such as inclusion of level IIb and levels IV and V to ND, uni- vs. bilateral ND, and the influence of extra-nodal extension (ENE) of metastases on extension of ND were evaluated. Results Eighty-four OMFS of university and non-university hospitals participated in the study (responding rate 21.4%). Sixty-six (78.57%) stated to work at certified cancer centers and 53.57% of the hospitals treated between 50 and 100 OSCC cases per year. CT and/or MRI of the head and neck was performed in most of the staging procedures. Level IIb was included by 71 (93.42%) of the participants in selective ND. Levels IV and V were included by 53 (69.74%) in node-positive neck. In solitary ipsilateral metastases (ENE−), 49 participants (62.82%) stated to perform exclusively an ipsilateral ND and 40 (51.95%) stated to perform only an ipsilateral ND in ENE+. Conclusion This study demonstrated a high rate of certified cancer centers in Germany showing differences regarding staging procedures, indications, and extension of ND, especially in increasingly complex cases. Clinical relevance Clinical decisions regarding ND are dependent on case-individual aspects and must be decided individually

Balancing competing needs in kidney transplantation: does an allocation system prioritizing children affect the renal transplant function?

Children often merit priority in access to deceased donor kidneys by organ-sharing organizations. We report the impact of the new Swiss Organ Allocation System (SOAS) introduced in 2007, offering all kidney allografts from deceased donors <60 years preferentially to children. The retrospective cohort study included all paediatric transplant patients (<20 years of age) before (n = 19) and after (n = 32) the new SOAS (from 2001 to 2014). Estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio (UPC), need for antihypertensive medication, waiting times to kidney transplantation (KTX), number of pre-emptive transplantations and rejections, and the proportion of living donor transplants were considered as outcome parameters. Patients after the new SOAS had significantly better eGFRs 2 years after KTX (Mean Difference, MD = 25.7 ml/min/1.73 m(2) , P = 0.025), lower UPC ratios (Median Difference, MeD = -14.5 g/mol, P = 0.004), decreased waiting times to KTX (MeD = -97 days, P = 0.021) and a higher proportion of pre-emptive transplantations (Odds Ratio = 9.4, 95% CI = 1.1-80.3, P = 0.018), while the need for antihypertensive medication, number of rejections and living donor transplantations remained stable. The new SOAS is associated with improved short-term clinical outcomes and more rapid access to KTX. Despite lacking long-term research, the study results should encourage other policy makers to adopt the SOAS approach

Determinants of Kidney Failure in Primary Hyperoxaluria Type 1:Findings of the European Hyperoxaluria Consortium

INTRODUCTION: Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G&gt;A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies. METHODS: In this retrospective study of 932 patients with PH1 included in the OxalEurope registry, we analyzed genotype-phenotype correlations as well as the impact of nephrocalcinosis, urolithiasis, and urinary oxalate and glycolate excretion on the development of kidney failure, using survival and mixed model analyses.RESULTS: The risk of developing kidney failure was the highest for 175 vitamin-B6 unresponsive ("null") homozygotes and lowest for 155 patients with c.508G&gt;A and c.454T&gt;A (p.Phe152Ile) variants, with a median age of onset of kidney failure of 7.8 and 31.8 years, respectively. Fifty patients with c.731T&gt;C (p.Ile244Thr) homozygote variants had better kidney survival than null homozygotes ( P = 0.003). Poor outcomes were found in patients with other potentially vitamin B6-responsive variants. Nephrocalcinosis increased the risk of kidney failure significantly (hazard ratio [HR] 3.17 [2.03-4.94], P &lt; 0.001). Urinary oxalate and glycolate measurements were available in 620 and 579 twenty-four-hour urine collections from 117 and 87 patients, respectively. Urinary oxalate excretion, unlike glycolate, was higher in patients who subsequently developed kidney failure ( P = 0.034). However, the 41% intraindividual variation of urinary oxalate resulted in wide confidence intervals. CONCLUSION: In conclusion, homozygosity for AGXT null variants and nephrocalcinosis were the strongest determinants for kidney failure in PH1. </p

Heterologous Expression of Membrane Proteins: Choosing the Appropriate Host

International audienceBACKGROUND: Membrane proteins are the targets of 50% of drugs, although they only represent 1% of total cellular proteins. The first major bottleneck on the route to their functional and structural characterisation is their overexpression; and simply choosing the right system can involve many months of trial and error. This work is intended as a guide to where to start when faced with heterologous expression of a membrane protein. METHODOLOGY/PRINCIPAL FINDINGS: The expression of 20 membrane proteins, both peripheral and integral, in three prokaryotic (E. coli, L. lactis, R. sphaeroides) and three eukaryotic (A. thaliana, N. benthamiana, Sf9 insect cells) hosts was tested. The proteins tested were of various origins (bacteria, plants and mammals), functions (transporters, receptors, enzymes) and topologies (between 0 and 13 transmembrane segments). The Gateway system was used to clone all 20 genes into appropriate vectors for the hosts to be tested. Culture conditions were optimised for each host, and specific strategies were tested, such as the use of Mistic fusions in E. coli. 17 of the 20 proteins were produced at adequate yields for functional and, in some cases, structural studies. We have formulated general recommendations to assist with choosing an appropriate system based on our observations of protein behaviour in the different hosts. CONCLUSIONS/SIGNIFICANCE: Most of the methods presented here can be quite easily implemented in other laboratories. The results highlight certain factors that should be considered when selecting an expression host. The decision aide provided should help both newcomers and old-hands to select the best system for their favourite membrane protein