Capsular type K54 of Klebsiella pneumoniae is associated with hypervirulence and we sought to discover the basis for this among isolates submitted to the UK reference laboratory between 2012 and ...2017. Isolates were typed by variable number tandem repeat analysis, and capsular type and virulence elements sought by PCR. The most prevalent type found (15/31 isolates) corresponded to clonal group (CG) 29 and included five representatives carrying rmpA, rmpA2 (regulators of mucoid phenotype), iutA and iroD (from the aerobactin and salmochelin siderophore clusters) associated with virulence plasmids. These included isolate KpvK54, recovered from pus. The remaining isolates did not carry a virulence plasmid. We also noted 11 further related isolates, including NCTC 9159, not of capsular type K54, but nevertheless sometimes associated with sepsis and abscesses. Whole-genome sequencing showed that KpvK54 carried a large virulence plasmid and an ICEKp3-like structure carrying the yersiniabactin cluster, absent in NCTC 9159. Comparative chromosomal analysis with an additional four genomes showed that KpvK54 shared further genes with K1-ST23 hypervirulent isolates, and with LS358, a K54-ST29 isolate from liver abscess puncture fluid. While CG29 isolates displayed varying degrees of virulence, some, especially those with the virulence plasmid (all K54), were clearly associated with hypervirulence.
Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and ...social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction.
Background:
LHX4 encodes a member of the LIM-homeodomain family of transcription factors that is required for normal development of the pituitary gland. To date, only incompletely penetrant ...heterozygous mutations in LHX4 have been described in patients with variable combined pituitary hormone deficiencies.
Objective/Hypothesis:
To report a unique family with a novel recessive variant in LHX4 associated with a lethal form of congenital hypopituitarism that was identified through screening a total of 97 patients.
Method:
We screened 97 unrelated patients with combined pituitary hormone deficiency, including 65% with an ectopic posterior pituitary, for variants in the LHX4 gene using Sanger sequencing. Control databases (1000 Genomes, dbSNP, Exome Variant Server, ExAC Browser) were consulted upon identification of variants.
Results:
We identified the first novel homozygous missense variant (c.377C>T, p.T126M) in two deceased male patients of Pakistani origin with severe panhypopituitarism associated with anterior pituitary aplasia and posterior pituitary ectopia. Both were born small for gestational age with a small phallus, undescended testes, and mid-facial hypoplasia. The parents' first-born child was a female with mid-facial hypoplasia (DNA was unavailable). Despite rapid commencement of hydrocortisone and T4 in the brothers, all three children died within the first week of life. The LHX4(p.T126M) variant is located within the LIM2 domain, in a highly conserved location. The absence of homozygosity for the variant in over 65 000 controls suggests that it is likely to be responsible for the phenotype.
Conclusion:
We report, for the first time to our knowledge, a novel homozygous mutation in LHX4 associated with a lethal phenotype, implying that recessive mutations in LHX4 may be incompatible with life.
Summary Background Stenotrophomonas maltophilia causes opportunistic infections and remains a problem pathogen on intensive care unit (ICU) due to its multidrug resistance. Aim An outbreak of ...S. maltophilia on ICU is described in order to highlight the risk from contaminated devices for supply of drinking water. Methods The outbreak was investigated by a combination of epidemiology, environmental sampling and molecular typing. Findings From 2009 to 2011 isolates of S. maltophilia from 23 patients were found to belong to only two genotypes by contrast with isolates from 52 other patients during this period, which represented distinct strains. The monthly incidence for all S. maltophilia strains ranged from 0 to 11% and for the two outbreak strains from 0 to 9%. Admission and weekly pharyngeal screening on ICU showed that the outbreak strains were acquired on ICU (range: 3–90 days). The majority of isolates (74%) were from the respiratory tract. Only two of 12 (17%) colonized intubated patients developed pneumonia. Environmental sampling found the two outbreak strains in two sinks and in the drinking water of the cooling unit in the ICU kitchen. S. maltophilia had formed a biofilm in the flexible tube from the carbon filter to the chiller and from the latter to the tap at the kitchen sink. This cooled water was used for providing drinking water and mouth care to ICU patients. The outbreak strains disappeared after removal of the water-cooler and the monthly incidence fell to <2% of ICU admissions. Conclusion This outbreak report highlights the risk from biofilms in devices that supply drinking water for ICU patients.
Representatives (n = 31) of outbreak strains of Acinetobacter baumannii from five countries fell into three clear groups, designated Groups 1–3, based on their ompA (outer-membrane protein A), csuE ...(part of a pilus assembly system required for biofilm formation) and blaOXA-51-like (the intrinsic carbapenemase gene in A. baumannii) gene sequences. With the exception of the closely related alleles within the Group 1 clonal complex, alleles at each locus were highly distinct from each other, with a minimum of 14 nucleotide differences between any two alleles. Isolates within a group shared the same combination of alleles at the three loci, providing compelling evidence that the outbreak strains investigated belonged to three clonal lineages. These corresponded to the previously identified European clones I–III. Sequence differences among the alleles were used to design multiplex PCRs to rapidly assign isolates belonging to particular genotypes to sequence groups. In the UK, genotypes belonging to the Group 1 clonal complex have been particularly successful, accounting for the vast majority of isolates referred from hospitals experiencing problems with Acinetobacter.
Summary Background In December 2011 and early 2012 four neonates died from Pseudomonas aeruginosa bacteraemia in hospitals in Northern Ireland. Aim To assess whether P. aeruginosa was associated with ...the neonatal unit taps and whether waterborne isolates were consistent with patient isolates. Methods Thirty taps and eight flow straighteners from the relevant hospitals were categorized and dismantled into 494 components and assessed for aerobic colony and P. aeruginosa counts using non-selective and selective agars. P. aeruginosa isolates were typed by variable number tandem repeat (VNTR) analysis. Selected tap components were subjected to epifluorescence and scanning electron microscopy to visualize biofilm. Findings The highest P. aeruginosa counts were from the flow straighteners, metal support collars and the tap bodies surrounding these two components. Complex flow straighteners had a significantly higher P. aeruginosa count than other types of flow straighteners ( P < 0.05). Highest aerobic colony counts were associated with integrated mixers and solenoids ( P < 0.05), but there was not a strong correlation ( r = 0.33) between the aerobic colony counts and P. aeruginosa counts. Representative P. aeruginosa tap isolates from two hospital neonatal units had VNTR profiles consistent with strains from the tap water and infected neonates. Conclusion P. aeruginosa was predominantly found in biofilms in flow straighteners and associated components in the tap outlets and was a possible source of the infections observed. Healthcare providers should be aware that water outlets can be a source of P. aeruginosa contamination and should take steps to reduce such contamination, monitor it and have strategies to minimize risk to susceptible patients.
To get a better overview of atmosphere-driven mass changes at the 79N Glacier (Nioghalvfjerdsfjorden Glacier), the largest outlet glacier of the northeast Greenland ice stream, the surface mass ...balance (SMB) is modeled by linking the COupled Snowpack and Ice surface energy and mass-balance model in PYthon (COSIPY) with the output of a regional atmospheric model (Polar WRF) for the years 2014–2018. After a manual model optimization, the model produces reliable results when compared to observations in the region and to values from the literature. High spatial resolution (1 km) simulations reveal strong interannual variability of the SMB. Stronger surface melting increased the ablation and runoff in years with high mass loss (2016 and 2017) whereas in other years (2015 and 2018) melting and refreezing inside the snowpack dominated the mass balance (MB). A cooler regional climate with higher snowfall-driven accumulation, higher albedo and reduced surface melt in the ablation period of 2018 resulted in a positive SMB in 2018, however, the annual total MB remained negative. The results suggest a promising new dataset for gaining more insights into mass-balance processes and their contribution to the acceleration of glacier retreat in northeast Greenland.
Repeat numbers at nine variable-number tandem-repeat (VNTR) loci were determined for 177 isolates of Pseudomonas aeruginosa representing 77 strains distinguished by pulsed-field gel electrophoresis ...(PFGE). Eight loci provided for discrimination similar to that provided by PFGE, with variation at the ninth locus (ms61) sometimes allowing discrimination within a PFGE-defined type. The Liverpool and Midlands 1 strains, which are common among patients with cystic fibrosis in the UK, could be unambiguously identified by their characteristic VNTR profiles. In rare cases, the repeat number at the ninth locus alone provided discrimination among isolates that were distinct according to PFGE. In each case, the two isolates shared the same blaOXA-50-like allele and belonged to the same oprD sequence type group, supporting the VNTR results in suggesting that they are similar.
Pseudomonas aeruginosa healthcare outbreaks can be time consuming and difficult to investigate. Guidance does not specify which typing technique is most practical for decision-making.
To explore the ...usefulness of whole-genome sequencing (WGS) in the investigation of a P. aeruginosa outbreak, describing how it compares with pulsed-field gel electrophoresis (PFGE) and variable number tandem repeat (VNTR) analysis.
Six patient isolates and six environmental samples from an intensive care unit (ICU) positive for P. aeruginosa over two years underwent VNTR, PFGE and WGS.
VNTR and PFGE were required to fully determine the potential source of infection and rule out others. WGS results unambiguously distinguished linked isolates, giving greater assurance of the transmission route between wash-hand basin water and two patients, supporting the control measures employed.
WGS provided detailed information without the need for further typing. When allied to epidemiological information, WGS can be used to understand outbreak situations rapidly and with certainty. Implementation of WGS in real-time would be a major advance in day-to-day practice. It could become a standard of care as it becomes more widespread due to its reproducibility and lower costs.
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