Morbidity and long-term outcome of surgery for renal hyperparathyroidism: results from a prospective cohort.

PURPOSES: Surgery remains an important treatment option for renal hyperparathyroidism (rHPT). The number of long-term outcome studies of parathyroidectomy is limited. METHODS: All consecutive patients with a parathyroidectomy for rHPT between 09/2009 and 04/2021 in a Belgian tertiary referral hospital were prospectively enrolled. The main outcomes were (long-term) cured proportion and postoperative morbidity (hypocalcemia, recurrent laryngeal nerve (RLN) palsy, re-intervention for bleeding, and wound morbidity). RESULTS: Sixty patients with a median age of 57 years were analyzed, including 23 patients before kidney transplantation, 23 patients without kidney transplantation, and 14 patients after kidney transplantation. Median time to transplant was 15 (6-24) months after parathyroidectomy. Morbidity was low with only two non-urgent returns to theatre (wound infection and non-compressive hematoma), two temporary RLN paralyses, and no 30-day mortality. Length of hospital stay was longer in patients with parathyroidectomy before kidney transplant, due to a more severe and prolonged need for calcium supplementation. After a median follow-up of 63 months, 37 patients (62%) were still alive, and 11 patients (18%) developed a recurrence. CONCLUSIONS: This single-surgeon, single-center cohort with long-term follow-up confirms the safety and excellent 'cure' proportions of surgery for rHPT but stretches the importance of long-term follow-up.

In situ Synthesis of Supramolecular Polymers: Finding the Right Conditions when Combining Covalent and Non-Covalent Synthesis.

The combination of covalent and non-covalent synthesis is omnipresent in nature and potentially enables access to new materials. Yet, the fundamental principles that govern such a synthesis are barely understood. Here, we demonstrate how even simple reaction mixtures behave surprisingly complex when covalent reactions are coupled to self-assembly processes. Specifically, we study the reaction behavior of a system in which the in situ formation of discotic benzene-1,3,5-tricarboxamide (BTA) monomers is linked to an intertwined non-covalent reaction network including self-assembly into helical BTA polymers. This system shows an unexpected phase-separation behavior in which an interplay of reactant/product concentrations, side-products and solvent purity determines the system composition. We envision that these insights can bring us one step closer to how to design the synthesis of systems in a combined covalent/non-covalent fashion.

Culex torrentium mosquitoes from Germany are negative for Wolbachia.

Wolbachia (Rickettsiales: Anaplasmataceae) infects a wide range of arthropods, including several mosquito species. The bacterium is known to induce a plethora of phenotypes in its host, examples being the reproductive phenotype cytoplasmic incompatibility or resistance against infection with arboviruses. The latter is especially relevant when assessing the vector competence of mosquito species for emerging arboviruses. Thus, knowledge of Wolbachia infection status is important for the assessment of vector competence. To facilitate Wolbachia screening in mosquito populations, a quantitative polymerase chain reaction (qPCR) assay was developed to enable high-throughput analysis of mosquito samples. Using this assay, the Wolbachia infection status of the two most common Culex mosquito species in Germany, Culex pipiens biotype pipiens Linnaeus (Diptera: Culicidae) and Culex torrentium Martini (Diptera: Culicidae), was assessed. About 93% of all tested C. pipiens biotype pipiens individuals were positive for Wolbachia, whereas none of the C. torrentium samples was found to be infected. Furthermore, other applications of the qPCR assay were explored by assessing a potential link between the levels of Wolbachia and West Nile virus (WNV) infections in German C. pipiens biotype pipiens mosquitoes. No relationship was found between the two variables, indicating that a Wolbachia-induced antiviral phenotype in this mosquito population is not exclusively attributable to the general level of bacterial infection.

Optical techniques for perfusion monitoring of the gastric tube after esophagectomy: a review of technologies and thresholds.

Anastomotic leakage is one of the most severe complications after esophageal resection with gastric tube reconstruction. Impaired perfusion of the gastric fundus is seen as the main contributing factor for this complication. Optical modalities show potential in recognizing compromised perfusion in real time, when ischemia is still reversible. This review provides an overview of optical techniques with the aim to evaluate the (1) quantitative measurement of change in perfusion in gastric tube reconstruction and (2) to test which parameters are the most predictive for anastomotic leakage.A Pubmed, MEDLINE, and Embase search was performed and articles on laser Doppler flowmetry (LDF), near-infrared spectroscopy (NIRS), laser speckle contrast imaging (LSCI), fluorescence imaging (FI), sidestream darkfield microscopy (SDF), and optical coherence tomography (OCT) regarding blood flow in gastric tube surgery were reviewed. Two independent reviewers critically appraised articles and extracted the data: Primary outcome was quantitative measure of perfusion change; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters.Thirty-three articles (including 973 patients and 73 animals) were selected for data extraction, quality assessment, and risk of bias (QUADAS-2). LDF, NIRS, LSCI, and FI were investigated in gastric tube surgery; all had a medium level of evidence. IDEAL stage ranges from 1 to 3. Most articles were found on LDF (n = 12), which is able to measure perfusion in arbitrary perfusion units with a significant lower amount in tissue with necrosis development and on FI (n = 12). With FI blood flow routes could be observed and flow was qualitative evaluated in rapid, slow, or low flow. NIRS uses mucosal oxygen saturation and hemoglobin concentration as perfusion parameters. With LSCI, a decrease of perfusion units is observed toward the gastric fundus intraoperatively. The perfusion units (LDF, LSCI), although arbitrary and not absolute values, and low flow or length of demarcation to the anastomosis (FI) both seem predictive values for necrosis intraoperatively. SDF and OCT are able to measure microvascular flow, intraoperative prediction of necrosis is not yet described.Optical techniques aim to improve perfusion monitoring by real-time, high-resolution, and high-contrast measurements and could therefore be valuable in intraoperative perfusion mapping. LDF and LSCI use perfusion units, and are therefore subjective in interpretation. FI visualizes influx directly, but needs a quantitative parameter for interpretation during surgery.

Effect of ephedrine on gastric conduit perfusion measured by laser speckle contrast imaging after esophagectomy: a prospective in vivo cohort study.

Compromised perfusion due to ligation of arteries and veins in esophagectomy with gastric tube reconstruction often (5-20%) results in necrosis and anastomotic leakage, which relate to high morbidity and mortality (3-4%). Ephedrine is used widely in anesthesia to treat intraoperative hypotension and may improve perfusion by the increase of cardiac output and mean arterial pressure (MAP). This study tests the effect of ephedrine on perfusion of the future anastomotic site of the gastric conduit, measured by laser speckle contrast imaging (LSCI). This prospective, observational, in vivo pilot study includes 26 patients undergoing esophagectomy with gastric tube reconstruction from October 2015 to June 2016 in the Academic Medical Center (Amsterdam). Perfusion of the gastric conduit was measured with LSCI directly after reconstruction and after an increase of MAP by ephedrine 5 mg. Perfusion was quantified in flux (laser speckle perfusion units, LSPU) in four perfusion locations, from good perfusion (base of the gastric tube) toward decreased perfusion (fundus). Intrapatient differences before and after ephedrine in terms flux were statistically tested for significance with a paired t-test. LSCI was feasible to image gastric microcirculation in all patients. Flux (LSPU) was significantly higher in the base of the gastric tube (791 ± 442) compared to the fundus (328 ± 187) (P < 0.001). After administration of ephedrine, flux increased significantly in the fundus (P < 0.05) measured intrapatients. Three patients developed anastomotic leakage. In these patients, the difference between measured flux in the fundus compared to the base of the gastric tube was high. This study presents the effect of ephedrine on perfusion of the gastric tissue measured with LSCI in terms of flux (LSPU) after esophagectomy with gastric tube reconstruction. We show a small but significant difference between flux measured before and after administration of ephedrine in the future anastomotic tissue (313 ± 178 vs. 397 ± 290). We also show a significant decrease of flux toward the fundus.

SNP g.1007A>G within the porcine DNAL4 gene affects sperm motility traits and percentage of midpiece abnormalities.

The flagellar beating of a spermatozoa's axoneme is caused by the varying activation and inactivation of dynein molecules. Dynein, axonemal, light chain 4 (DNAL4) is a functional candidate gene for sperm motility as it encodes a small subunit of the dyneins. We resequenced the porcine DNAL4 using three artificial insemination (AI) boars each with high (>68%) or low (<60%) motility, and detected 23 SNP. These were then genotyped for 82 AI boars. Using spermatological records, significantly negative genetic correlations between ejaculate volume (VOL) and the further spermatological parameters concentration (CONC) (r = -.43), motility of undiluted semen (MOTUD) (r = -.09), motility after 24 h (MOT1) (r = -.17) and after 48 hr (MOT2) (r = -.23) were estimated. Significantly positive correlations existed between CONC and MOT1 (r = .07) as well as MOT2 (r = .10), between MOTUD and MOT1 (r = .33), between MOTUD and MOT2 (r = .36), and finally between MOT1 and MOT2 (r = .70). Significantly negatively correlated were all motility traits with the parameters abnormal acrosome (AA) (MOTUD r = -.06; MOT1 r = -.08, and MOT2 r = -.1) and presence of cytoplasmic droplet (CD) (MOTUD r = -.07; MOT1 r = -.08; MOT2 r = -.07). Association analyses (single marker regression model; SMR) propose that SNP g.1007A>G, located in the second intron, reduces motility significantly (MOTUD -4.59%; MOT1 -10.33%; MOT2 -19.37%). According to the dominant-recessive model (DRM), genotype AA is always superior compared to genotypes AG and GG (i.e. MOTUD 67.67%, 64.16% and 53.91%; MOT1 54.17%, 43.75% and 28.44%; MOT2 44.12%, 24.91% and 4.97%). The average effect of gene substitution (g.1007A>G) on abnormal midpiece (AM) was 0.71%, the genotypic values-as expressed by LSmeans-were 0.1 (AA) and 0.81 (AG).

Identification of new TRIP12 variants and detailed clinical evaluation of individuals with non-syndromic intellectual disability with or without autism.

The ubiquitin pathway is an enzymatic cascade including activating E1, conjugating E2, and ligating E3 enzymes, which governs protein degradation and sorting. It is crucial for many physiological processes. Compromised function of members of the ubiquitin pathway leads to a wide range of human diseases, such as cancer, neurodegenerative diseases, and neurodevelopmental disorders. Mutations in the thyroid hormone receptor interactor 12 (TRIP12) gene (OMIM 604506), which encodes an E3 ligase in the ubiquitin pathway, have been associated with autism spectrum disorder (ASD). In addition to autistic features, TRIP12 mutation carriers showed intellectual disability (ID). More recently, TRIP12 was postulated as a novel candidate gene for intellectual disability in a meta-analysis of published ID cohorts. However, detailed clinical information characterizing the phenotype of these individuals was not provided. In this study, we present seven novel individuals with private TRIP12 mutations including two splice site mutations, one nonsense mutation, three missense mutations, and one translocation case with a breakpoint in intron 1 of the TRIP12 gene and clinically review four previously published cases. The TRIP12 mutation-positive individuals presented with mild to moderate ID (10/11) or learning disability [intelligence quotient (IQ) 76 in one individual], ASD (8/11) and some of them with unspecific craniofacial dysmorphism and other anomalies. In this study, we provide detailed clinical information of 11 TRIP12 mutation-positive individuals and thereby expand the clinical spectrum of the TRIP12 gene in non-syndromic intellectual disability with or without ASD.

Determinants of lifestyle behavior change to prevent type 2 diabetes in high-risk individuals.

BACKGROUND: Although there are many effective lifestyle interventions for type 2 diabetes (T2DM) prevention, insight into effective intervention pathways, especially of long-term interventions, is often lacking. This study aims to provide insight into the effective intervention pathways of the SLIMMER diabetes prevention intervention using mediation analyses. METHODS: In total, 240 participants at increased risk of T2DM were included in the analyses over 18 months. The intervention was a combined lifestyle intervention with a dietary and a physical activity (PA) component. The primary and secondary outcomes were change in fasting insulin (pmol/L) and change in body weight (kg) after 18 months, respectively. Firstly, in a multiple mediator model, we investigated whether significant changes in these outcomes were mediated by changes in dietary and PA behavior. Secondly, in multiple single mediator models, we investigated whether changes in dietary and PA behavior were mediated by changes in behavioral determinants and the participants' psychological profile. The mediation analyses used linear regression models, where significance of indirect effects was calculated with bootstrapping. RESULTS: The effect of the intervention on decreased fasting insulin was 40% mediated by change in dietary and PA behavior, where dietary behavior was an independent mediator of the association (34%). The effect of the intervention on decreased body weight was 20% mediated by change in dietary and PA behavior, where PA behavior was an independent mediator (17%). The intervention significantly changed intake of fruit, fat from bread spread, and fiber from bread. Change in fruit intake was mediated by change in action control (combination of consciousness, self-control, and effort), motivation, self-efficacy, intention, and skills. Change in fat intake was mediated by change in action control and psychological profile. No mediators could be identified for change in fiber intake. The change in PA behavior was mediated by change in action control, motivation, and psychological profile. CONCLUSION: The effect of the SLIMMER intervention on fasting insulin and body weight was mediated by changes in dietary and PA behavior, in distinct ways. These results indicate that changing dietary as well as PA behavior is important in T2DM prevention.

Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440 treatments in 100 patients.

OBJECTIVE: Frey's syndrome is characterised as sweating, redness and warmth of the parotideal area and is often treated with botulinum toxin A. The objective of this retrospective study was to prove whether the toxin dosage and time-to-treatment intervals change after repeated botulinum toxin injections. STUDY DESIGN/METHODS: The charts of patients, who were treated for Frey's syndrome during the last 16 years, were assessed. Three brands of botulinum toxin A were available for therapy. The Minor test was used to confirm the sweating before each treatment and to determine the toxin dosage. Constant amount of botulinum toxin was injected per cm2 of the affected area. Patients consulted our department for the next treatment as soon as they felt disturbed by recurring sweating and when the sweating was objectively evident in the Minor test. Time intervals between treatments and injected toxin dosages were assessed. RESULTS: In total, 100 patients received 440 treatments in 16 years. Repeated injections, median 4.0, were carried out in 70.5% of patients. Median time interval to the first injection was 2.8 years. Median time interval between treatments was 12.0 months and showed to be steady (anova, P = .49, F = 1.01). CONCLUSION: Duration of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with no significantly different time intervals between treatments. The extent of the sweating area did not vary significantly after repeated treatments and required a constant dose of botulinum toxin A.

Reliability of Eustachian tube function measurements in a hypobaric and hyperbaric pressure chamber.

OBJECTIVES: Measurement of the Eustachian tube (ET) function is a challenge. The demand for a precise and meaningful diagnostic tool increases-especially because more and more operative therapies are being offered without objective evidence. The measurement of the ET function by continuous impedance recording in a pressure chamber is an established method, although the reliability of the measurements is still unclear. METHODS: Twenty-five participants (50 ears) were exposed to phases of compression and decompression in a hypo- and hyperbaric pressure chamber. The ET function reflecting parameters-ET opening pressure (ETOP), ET opening duration (ETOD) and ET opening frequency (ETOF)-were determined under exactly the same preconditions three times in a row. The intraclass correlation coefficient (ICC) and Bland and Altman plot were used to assess test-retest reliability. RESULTS: ICCs revealed a high correlation for ETOP and ETOF in phases of decompression (passive equalisation) as well as ETOD and ETOP in phases of compression (active induced equalisation). Very high correlation could be shown for ETOD in decompression and ETOF in compression phases. The Bland and Altman graphs could show that measurements provide results within a 95 % confidence interval in compression and decompression phases. CONCLUSIONS: We conclude that measurements in a pressure chamber are a very valuable tool in terms of estimating the ET opening and closing function. Measurements show some variance comparing participants, but provide reliable results within a 95 % confidence interval in retest. This study is the basis for enabling efficacy measurements of ET treatment modalities.

[The pressure-equalizing function of the Eustachian tube : Evaluation in a hypo-/hyperbaric pressure chamber]. / Druckausgleichende Funktion der Eustachischen Röhre : Evaluation in einer hypo-/hyperbaren Druckkammer.

BACKGROUND: The Eustachian tube connects the tympanic cavity (cavum tympani) and the nasopharynx, and enables pressure equalization between the middle ear and ambient pressure. Functional pressure compensation is very important for flying and diving in particular, due to non-physiologically large pressure differences. OBJECTIVE: Evaluation of the pressure-equalizing function of the Eustachian tube is still a clinical challenge. This review article evaluates the existing data. METHODS: Based on a selective literature search, different methods for evaluation of tube function are presented and evaluated, with special reference to evaluation of the pressure-equalizing function in a hypo-/hyperbaric pressure chamber. RESULTS: The pressure chamber enables the dynamics of active and passive pressure compensation to be provoked and also permits accurate measurement of pressures in the millibar range. CONCLUSION: A pressure chamber seems to be suitable to evaluate Eustachian tube function and therapeutic approaches to tube dysfunction. Further studies are needed to assess the value of the pressure chamber in combination with other functional tests.

De novo loss-of-function mutations in X-linked SMC1A cause severe ID and therapy-resistant epilepsy in females: expanding the phenotypic spectrum.

De novo missense mutations and in-frame coding deletions in the X-linked gene SMC1A (structural maintenance of chromosomes 1A), encoding part of the cohesin complex, are known to cause Cornelia de Lange syndrome in both males and females. For a long time, loss-of-function (LoF) mutations in SMC1A were considered incompatible with life, as such mutations had not been reported in neither male nor female patients. However, recently, the authors and others reported LoF mutations in females with intellectual disability (ID) and epilepsy. Here we present the detailed phenotype of two females with de novo LoF mutations in SMC1A, including a de novo mutation of single base deletion [c.2364del, p.(Asn788Lysfs*10)], predicted to result in a frameshift, and a de novo deletion of exon 16, resulting in an out-of-frame mRNA splice product [p.(Leu808Argfs*6)]. By combining our patients with the other recently reported females carrying SMC1A LoF mutations, we ascertained a phenotypic spectrum of (severe) ID, therapy-resistant epilepsy, absence/delay of speech, hypotonia and small hands and feet. Our data show the existence of a novel phenotypic entity - distinct from CdLS - and caused by de novo SMC1A LoF mutations.

The effect of a lollipop on vocally disruptive behavior in a patient with frontotemporal dementia: a case-study.

A problematic and disturbing behavior which can develop in people with dementia, is vocally disruptive behavior (VDB). To date, the study of VDB is underdeveloped and with only a limited knowledge base. Medications commonly used in VDB have limited benefits and specific risks in patients with dementia. This report details the case of a patient with frontotemporal dementia with VDB, which responded very well by providing a lollipop. Subsequently, we pose theory-based hypotheses in order to try to explain the beneficial effect of this intervention. This may contribute to a better understanding of VDB and possible treatment strategies.

Mesenchymal stromal/stem cells promote intestinal epithelium regeneration after chemotherapy-induced damage.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for leukemia and a range of non-malignant disorders. The success of the therapy is hampered by occurrence of acute graft-versus-host disease (aGvHD); an inflammatory response damaging recipient organs, with gut, liver, and skin being the most susceptible. Intestinal GvHD injury is often a life-threatening complication in patients unresponsive to steroid treatment. Allogeneic mesenchymal stromal/stem cell (MSC) infusions are a promising potential treatment for steroid-resistant aGvHD. Data from our institution and others demonstrate rescue of approximately 40-50% of aGvHD patients with MSCs in Phase I, II studies and minor side effects. Although promising, better understanding of MSC mode of action and patient response to MSC-based therapy is essential to improve this lifesaving treatment. METHODS: Single cell human small intestine organoids were embedded in Matrigel, grown for 5 days and treated with busulfan for 48 h. Organoids damaged by treatment with busulfan or control organoids were co-cultured with 5000, 10,000, and 50,000 MSCs for 24 h, 48 h or 7 days and the analyses such as surface area determination, proliferation and apoptosis assessment, RNA sequencing and proteomics were performed. RESULTS: Here, we developed a 3D co-culture model of human small intestinal organoids and MSCs, which allows to study the regenerative effects of MSCs on intestinal epithelium in a more physiologically relevant setting than existing in vitro systems. Using this model we mimicked chemotherapy-mediated damage of the intestinal epithelium. The treatment with busulfan, the chemotherapeutic commonly used as conditioning regiment before the HSCT, affected pathways regulating epithelial to mesenchymal transition, proliferation, and apoptosis in small intestinal organoids, as shown by transcriptomic and proteomic analysis. The co-culture of busulfan-treated intestinal organoids with MSCs reversed the effects of busulfan on the transcriptome and proteome of intestinal epithelium, which we also confirmed by functional evaluation of proliferation and apoptosis. CONCLUSIONS: Collectively, we demonstrate that our in vitro co-culture system is a new valuable tool to facilitate the investigation of the molecular mechanisms behind the therapeutic effects of MSCs on damaged intestinal epithelium. This could benefit further optimization of the use of MSCs in HSCT patients.

Evaluation of colour vision impairment during acute hypobaric hypoxia in aviation medicine: a randomized controlled trial.

The digitization of aircraft cockpits places high demands on the colour vision of pilots. The present study investigates colour vision changes upon acute exposure to hypobaric hypoxia. The digital Waggoner Computerized Color Vision Test and the Waggoner D-15 were performed by 54 healthy volunteers in a decompression chamber. Respective altitude levels were sea level, 10,000 or 15,000 ft for exposure periods of 15 and 60 min, respectively. As for 60 min of exposure a significant decrease in colour perception was found between subjects at 15,000 ft as compared to the control group as well as between subjects at 15,000 ft as compared to subjects at 10,000 ft. No significant difference was found in the comparison within the 15,000 ft groups across time points pre-, peri-, and post-exposure. Thus, pilots appear to experience only minor colour vision impairment up to an exposure altitude of 15,000 ft over 60 min of exposure.

Central-line-associated bloodstream infection burden among Dutch neonatal intensive care units.

BACKGROUND: The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives. AIM: To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs). METHODS: Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500 g admitted to all nine Dutch NICUs over a two-year surveillance period (2019-2020) were analysed. Variations in baseline characteristics, CLABSI incidence per 1000 central-line days, pathogen distribution and CLABSI care bundles were evaluated. Multi-variable logistic mixed-modelling was used to identify significant predictors for CLABSI. RESULTS: A total of 1699 (58%) neonates received a central line, in which 160 CLABSI episodes were recorded. Coagulase-negative staphylococci were the most common infecting organisms of all CLABSI episodes (N=100, 63%). An almost six-fold difference in the CLABSI incidence between participating units was found (2.91-16.14 per 1000 line-days). Logistic mixed-modelling revealed longer central line dwell-time (adjusted odds ratio (aOR):1.08, P<0.001), umbilical lines (aOR:1.85, P=0.03) and single rooms (aOR:3.63, P=0.02) to be significant predictors of CLABSI. Variations in bundle elements included intravenous tubing care and antibiotic prophylaxis. CONCLUSIONS: CLABSI remains a common problem in preterm infants in The Netherlands, with substantial variation in incidence between centres. Being the largest collection of data on the burden of neonatal CLABSI in The Netherlands, this epidemiological overview provides a solid foundation for the development of a collaborative platform for continuous surveillance, ideally leading to refinement of national evidence-based guidelines. Future efforts should focus on ensuring availability and extraction of routine patient data in aggregated formats.

What parents find important in the support of a child with profound intellectual and multiple disabilities.

BACKGROUND: The importance of a partnership between parents and professionals in the support of children with disabilities is widely acknowledged and is one of the key elements of 'family-centred care'. To what extent family-centred principles are also applied to the support of persons with profound intellectual and multiple disabilities (PIMD) is not yet known. AIM: The purpose of this exploratory study was to examine what parents with a child with PIMD find important in the support of their child. In addition, we examined which child or parent characteristics influence these parental opinions. METHOD: In total, 100 parents completed an adapted version of the Measure of Processes of Care. Mean unweighted and weighted scale scores were computed. Non-parametric tests were used to examine differences in ratings due to child (gender, age, type and number of additional disabilities, type of services used and duration of service use) and parent characteristics (gender, involvement with support and educational level). RESULTS: Parents rated situations related to 'Respectful and Supportive Care' and 'Enabling and Partnership' with averages of 7.07 and 6.87 respectively on a scale from 1 to 10. They were generally satisfied with the services provided, expressed in a mean score of 6.88 overall. The age of the child significantly affected the scores for 'Providing Specific Information about the Child'. Parents of children in the '6-12 years' age group gave significantly higher scores on this scale than did parents of children in the '≥17 years' age group (U = 288, r = -0.34). CONCLUSION: This study shows that parents with children with PIMD find family-centred principles in the professional support of their children important. Although the majority of parents are satisfied with the support provided for their children, a substantial minority of the parents indicated that they did not receive the support they find important.

Localisation of the Fanconi anaemia complementation group A gene to chromosome 16q24.3.

Fanconi anaemia (FA) is an autosomal recessive disorder associated with diverse developmental abnormalities, bone-marrow failure and predisposition to cancer. FA cells show increased chromosome breakage and hypersensitivity to DNA cross-linking agents such as diepoxybutane and mitomycin C. Somatic-cell hybridisation analysis of FA cell lines has demonstrated the existence of at least five complementation groups (FA-A to FA-E), the most common of which is FA-A. This genetic heterogeneity has been a major obstacle to the positional cloning of FA genes by classical linkage analysis. The FAC gene was cloned by functional complementation, and localised to chromosome 9q22.3 (ref. 2), but this approach has thus far failed to yield the genes for the other complementation groups. We have established a panel of families classified as FA-A by complementation analysis, and used them to search for the FAA gene by linkage analysis. We excluded the previous assignment by linkage of an FA gene to chromosome 20q, and obtained conclusive evidence for linkage of FAA to microsatellite markers on chromosome 16q24.3. Strong evidence of allelic association with the disease was detected with the marker D16S303 in the Afrikaner population of South Africa, indicating the presence of a founder effect.

Influence of transition from open bay units to single room units in a neonatal intensive care unit on hospital transmission of multi-drug-resistant Enterobacterales.

BACKGROUND: It was shown previously that changing the design of a hospital neonatal intensive care unit (NICU) from open bay units (OBUs) to single room units (SRUs) was not associated with a reduction in Gram-negative multi-drug-resistant organism (MDRO) colonization rates. It was therefore hypothesized that colonization mainly occurs vertically, or through parents and healthcare workers, and not through environmental factors, and that transition to SRUs would not decrease the number of clusters of MDROs with an epidemiological link. To investigate this, core-genome multi-locus sequence typing (cgMLST) was applied on MDROs cultured from infants at the study hospital. METHODS: This retrospective cohort study included all infants carrying MDROs admitted to the NICU of a tertiary care academic hospital 2 years prior to the transition from OBUs to SRUs in May 2017, and 1.5 years after the transition (2018-2020). RESULTS: In total, 55 infants were diagnosed with MDRO carriership. Isolates were available from 49 infants for cgMLST. In the OBU period, one cluster involving four of 20 (20%) infants was identified, and in the SRU period, four clusters involving nine of 29 (31%) infants were identified. It was possible to make an epidemiological link in all four SRU MDRO clusters, but this was not possible for the OBU cluster. In the latter case, transmission from an environmental source on the ward seemed likely. CONCLUSION: After transition to SRUs, there was no decrease in the number of clusters of MDROs with an epidemiological link, suggesting that nursing infants in an NICU with an SRU design is not, in itself, protective against the acquisition of MDROs.

Assessing the agreement between the pneumatic and the flow-centrifuge method for estimating xylem safety in temperate diffuse-porous tree species.

The increasing frequency of global change-type droughts has created a need for fast, accurate and widely applicable techniques for estimating xylem embolism resistance to improve forecasts of future forest changes. We used data from 12 diffuse-porous temperate tree species covering a wide range of xylem safety to compare the pneumatic and flow-centrifuge method, two rapid methods used for constructing xylem vulnerability curves. We evaluated the agreement between parameters estimated with both methods and the sensitivity of pneumatic measurements to the duration of air discharge (AD) measurements. There was close agreement between xylem water potentials at 50% air discharged (PAD), estimated with the Pneumatron, and 50% loss of hydraulic conductivity (PLC), estimated with the flow-centrifuge method (mean signed deviation: 0.12 MPa, Pearson correlation: 0.96 after 15 s of gas extraction). However, the relationship between the estimated slopes was more variable, resulting in lower agreement in the xylem water potential at 12% and 88% PAD/PLC. The agreement between the two methods was not affected by species-specific vessel length distributions. All pneumatic parameters were sensitive to AD time. Overall agreement was highest at relatively short AD times, with an optimum at 16 s. Our results highlight the value of the Pneumatron as an easy and reliable tool to estimate 50% embolism thresholds for a wide range of diffuse-porous temperate angiosperms. Further, our study provides a set of useful metrics for methodological comparisons of vulnerability curves in terms of systematic and random deviations, as well as overall agreement.