The efficacy of a simulated tunnel washer process on removal and destruction of Clostridioides difficile spores from health care textiles.

BACKGROUND: Research on reducing Clostridioides difficile spore contamination of textiles via laundering is needed. We evaluated the sporicidal properties of 5 laundry chemicals and then determined the ability of a peracetic acid (PAA) laundry cycle to inactivate and/or remove spores from cotton swatches during a simulated tunnel washer (TW) process. METHODS: In phase I, spore-inoculated swatches were immersed in alkaline detergent, sodium hypochlorite, hydrogen peroxide, or PAA for 8 minutes. In phase II, inoculated swatches were passed through a simulated 24-minute TW process employing 5 wash liquids. Spore survivors on swatches and in test chemical fluids in both studies were enumerated using standard microbiologic assay methods. RESULTS: In phase I, hypochlorite solutions achieved >5 log10 spore reductions on swatches and >3 log10 reductions for wash solutions. PAA achieved minimal spore reduction in the wash solution (0.26 log10). In phase II, the PAA equilibrium-containing process achieved a >5 log10 spore reduction on swatches. In wash solution tests, the cumulative spore reduction peaked at >3.08 log10 in the final module. CONCLUSIONS: Sodium hypochlorite as a laundry additive is sporicidal. The cumulative effects of a TW process, coupled with a PAA bleach agent at neutral pH, may render textiles essentially free of C difficile spore contamination.

Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS.

BACKGROUND: Astrocytes regulate neuronal function, synaptic formation and maintenance partly through secreted extracellular vesicles (EVs). In amyotrophic lateral sclerosis (ALS) astrocytes display a toxic phenotype that contributes to motor neuron (MN) degeneration. METHODS: We used human induced astrocytes (iAstrocytes) from 3 ALS patients carrying C9orf72 mutations and 3 non-affected donors to investigate the role of astrocyte-derived EVs (ADEVs) in ALS astrocyte toxicity. ADEVs were isolated from iAstrocyte conditioned medium via ultracentrifugation and resuspended in fresh astrocyte medium before testing ADEV impact on HB9-GFP+ mouse motor neurons (Hb9-GFP+ MN). We used post-mortem brain and spinal cord tissue from 3 sporadic ALS and 3 non-ALS cases for PCR analysis. FINDINGS: We report that EV formation and miRNA cargo are dysregulated in C9ORF72-ALS iAstrocytes and this affects neurite network maintenance and MN survival in vitro. In particular, we have identified downregulation of miR-494-3p, a negative regulator of semaphorin 3A (SEMA3A) and other targets involved in axonal maintenance. We show here that by restoring miR-494-3p levels through expression of an engineered miRNA mimic we can downregulate Sema3A levels in MNs and increases MN survival in vitro. Consistently, we also report lower levels of mir-494-3p in cortico-spinal tract tissue isolated from sporadic ALS donors, thus supporting the pathological importance of this pathway in MNs and its therapeutic potential. INTERPRETATION: ALS ADEVs and their miRNA cargo are involved in MN death in ALS and we have identified miR-494-3p as a potential therapeutic target. FUNDING: Thierry Latran Fondation and Academy of Medical Sciences.

Prognosis prediction with two calculations of Palliative Prognostic Index: further prospective validation in hospice cancer patients with multicentre study.

OBJECTIVES: In palliative care settings, predicting prognosis is important for patients and clinicians. The Palliative Prognostic Index (PPI), a prognostic tool calculated using clinical indices alone has been validated within cancer population. This study was to further test the discriminatory ability of the PPI (ie, its ability to determine whether a subject will live more or less than a certain amount of time) in a larger sample but with a palliative care context and to compare predictions at two different points in time. METHODS: Multicentre, prospective, observational study in 10 inpatient hospices in the UK. The PPI score was calculated on the day of admission (PPI1) and again once on days 3-5 of inpatient stay (PPI2). Patients were followed up for 6 weeks or until death, whichever was earlier. RESULTS: Of the 1164 patients included in the study, 962 had both scores available. The results from PPI2 showed improved sensitivity, specificity, positive predictive value and negative predictive value compared with PPI1. For PPI1versus PPI2, area under receiver operator character curve (ROC) for <21 days were 0.73 versus 0.82 and for ≥42 days prediction 0.72 versus 0.80. The median survival days for patients with PPI1 ≤4, 4.5-6 and >6 were 38 (31 to 44), 17 (14 to 19) and 5 (4 to 7). CONCLUSION: This study showed improved discriminatory ability using the PPI score calculated between day 3and day5 of admission compared with that calculated on admission. This study further validated PPI as a prognostic tool within a palliative care population and showed recording at two time points improved accuracy.

A new paradigm in the treatment of kerions: treat the inflammation.

Kerions result from a massive delayed-type hypersensitivity reaction to a dermatophyte. Treatment traditionally has been directed primarily toward the dermatophyte. The authors propose, however, that inflammation should be the initial target oftreatment. Clinical findings and treatment outcomes for two patients with kerions, treated with short courses of anti-inflammatory agents, are presented. Earlier studies showing minimal effects with corticosteroid treatment of kerions may have had design flaws. The anti-inflammatory treatment of kerions is both safe and effective and permits the duration of therapy to be shortened dramatically.

Microbiome analysis of dairy cows fed pasture or total mixed ration diets.

Understanding rumen microbial ecology is essential for the development of feed systems designed to improve livestock productivity, health and for methane mitigation strategies from cattle. Although rumen microbial communities have been studied previously, few studies have applied next-generation sequencing technologies to that ecosystem. The aim of this study was to characterize changes in microbial community structure arising from feeding dairy cows two widely used diets: pasture and total mixed ration (TMR). Bacterial, archaeal and protozoal communities were characterized by terminal restriction fragment length polymorphism of the amplified SSU rRNA gene and statistical analysis showed that bacterial and archaeal communities were significantly affected by diet, whereas no effect was observed for the protozoal community. Deep amplicon sequencing of the 16S rRNA gene revealed significant differences in the bacterial communities between the diets and between rumen solid and liquid content. At the family level, some important groups of rumen bacteria were clearly associated with specific diets, including the higher abundance of the Fibrobacteraceae in TMR solid samples and members of the propionate-producing Veillonelaceae in pasture samples. This study will be relevant to the study of rumen microbial ecology and livestock feed management.

Custom formed orthoses in cycling.

To assess the effects of currently used prescribed in-shoe custom foot orthoses (CFOs) on a number of biomechanical variables during the power phase of cycling, including: hip adduction, knee abduction and tibial internal rotation. Before and after cross-over study recording subjects' biomechanical variables with and without their CFOs. Twelve competitive cyclists, currently using prescribed in-shoe CFOs, performed two exercise bouts on a stationary trainer, with 3-dimensional data recorded on an 8 camera Vicon Mx system. 2-way ANOVA statistical analysis of Null vs Orthotic condition, and left leg vs right leg. No systematic effects from the CFOs were seen. A trend towards reduced tibial internal rotation range of movement was found (P<0.072). Significant subject-specific effects from the CFOs were seen (P<0.05). Three distinct patterns of knee movement were observed. All subjects had significant left to right leg differences. CFOs do not produce systematic effects on cycling biomechanics. Significant subject-specific biomechanical effects can be produced by CFOs utilizing rearfoot and/or forefoot wedges. An individualised approach to orthotic prescription, and attention to the forefoot-rearfoot relationship, is recommended.

Amazonian anthrosols support similar microbial communities that differ distinctly from those extant in adjacent, unmodified soils of the same mineralogy.

We compared the microbial community composition in soils from the Brazilian Amazon with two contrasting histories; anthrosols and their adjacent non-anthrosol soils of the same mineralogy. The anthrosols, also known as the Amazonian Dark Earths or terra preta, were managed by the indigenous pre-Colombian Indians between 500 and 8,700 years before present and are characterized by unusually high cation exchange capacity, phosphorus (P), and calcium (Ca) contents, and soil carbon pools that contain a high proportion of incompletely combusted biomass as biochar or black carbon (BC). We sampled paired anthrosol and unmodified soils from four locations in the Manaus, Brazil, region that differed in their current land use and soil type. Community DNA was extracted from sampled soils and characterized by use of denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism. DNA bands of interest from Bacteria and Archaea DGGE gels were cloned and sequenced. In cluster analyses of the DNA fingerprints, microbial communities from the anthrosols grouped together regardless of current land use or soil type and were distinct from those in their respective, paired adjacent soils. For the Archaea, the anthrosol communities diverged from the adjacent soils by over 90%. A greater overall richness was observed for Bacteria sequences as compared with those of the Archaea. Most of the sequences obtained were novel and matched those in databases at less than 98% similarity. Several sequences obtained only from the anthrosols grouped at 93% similarity with the Verrucomicrobia, a genus commonly found in rice paddies in the tropics. Sequences closely related to Proteobacteria and Cyanobacteria sp. were recovered only from adjacent soil samples. Sequences related to Pseudomonas, Acidobacteria, and Flexibacter sp. were recovered from both anthrosols and adjacent soils. The strong similarities among the microbial communities present in the anthrosols for both the Bacteria and Archaea suggests that the microbial community composition in these soils is controlled more strongly by their historical soil management than by soil type or current land use. The anthrosols had consistently higher concentrations of incompletely combusted organic black carbon material (BC), higher soil pH, and higher concentrations of P and Ca compared to their respective adjacent soils. Such characteristics may help to explain the longevity and distinctiveness of the anthrosols in the Amazonian landscape and guide us in recreating soils with sustained high fertility in otherwise nutrient-poor soils in modern times.

Nanowire transistors without junctions.

All existing transistors are based on the use of semiconductor junctions formed by introducing dopant atoms into the semiconductor material. As the distance between junctions in modern devices drops below 10 nm, extraordinarily high doping concentration gradients become necessary. Because of the laws of diffusion and the statistical nature of the distribution of the doping atoms, such junctions represent an increasingly difficult fabrication challenge for the semiconductor industry. Here, we propose and demonstrate a new type of transistor in which there are no junctions and no doping concentration gradients. These devices have full CMOS functionality and are made using silicon nanowires. They have near-ideal subthreshold slope, extremely low leakage currents, and less degradation of mobility with gate voltage and temperature than classical transistors.

Body fat distribution and metabolic variables in patients with neonatal progeroid syndrome.

Neonatal progeroid syndrome (NPS), also known as Wiedemann-Rautenstrauch Syndrome, is a rare autosomal recessive disorder characterized by accelerated aging and lipodystrophy from birth. Affected children have extreme intrauterine growth retardation, poor postnatal weight gain, and characteristic facial dysmorphic features such as a triangular shape, pinched nose, pseudohydrocephalus with wide fontanelles and prominent subcutaneous (sc) veins. Generalized loss of sc fat has been reported as a cardinal feature; however, the pattern of fat loss and its association with insulin resistance and its metabolic complications have not been systematically studied. The aim of the current study was to examine body fat distribution and body composition in two girls with NPS using anthropometric measures, whole-body magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DEXA), and to assess metabolic complications such as hyperinsulinemia and dyslipidemia. Both the girls (aged 17 years and 10 years, respectively) had generalized paucity of sc fat on physical examination. However, measurements of skin-fold thickness revealed that sc fat was decreased over the extremities, but preserved over the chest and abdomen. MRI studies confirmed the presence of normal amounts of sc truncal fat, and marked loss of fat from the face and distal extremities. Striking fat loss was also noted in the paravertebral and lateral gluteal regions. Interestingly, body composition analysis with DEXA scan revealed a marked reduction in both the fat and lean tissue mass. Fasting glucose, lipids and insulin levels were not elevated. We conclude that patients with NPS do not have generalized lipodystrophy as previously reported, but fat loss is confined to the face, distal extremities, and possibly the paravertebral and lateral gluteal regions. Metabolic abnormalities related to insulin resistance are also uncommon in this condition.

A monolithic silicon based integrated signal generation and detection system for monitoring DNA hybridisation.

The aim of this work was to develop an integrated solution to DNA hybridisation monitoring for diagnostics on a monolithic silicon platform. A fabrication process was developed incorporating a gold initiation electrode patterned directly onto a PIN photodiode detector. Patterned interdigitated type electrodes exhibited the smallest reduction in photodiode sensitivity, therefore these were chosen as the ECL initiator design. A novel DNA hybridisation assay was developed based on the displacement of a partially mismatched complementary strand by a perfectly matched labelled complementary strand. Pre-hybridised thiolated oligonucleotide and unlabelled 25% mismatched oligonucleotide were assembled on the gold initiation electrode. On addition of the labelled perfectly complementary oligonucleotide, the mismatched strands were displaced and a signal was generated. The sensitivity of the photodiode to light emitted at 620 nm, the ruthenium emission wavelength, was determined and subsequently, the diode current response to light generated by flow addition of ruthenium solution was found to be measurable to a concentration of 10 fM. Pre-hybridised duplex DNA, consisting of thiolated oligonucleotide and ruthenium labelled complementary oligonucleotide, was assembled on the gold initiation electrode. The difference between the current measured during flow of buffer and the ECL co-reactant TPA was three orders of magnitude, indicating that DNA assembled on the surface comprised sufficient ruthenium to generate a measurable signal. Finally, the displacement of unlabelled partial mismatch oligonucleotide from the sensor surface was monitored on addition of the ruthenium labelled perfectly complementary oligonucleotide in TPA flow and the measured photodiode current response was up to 50 times greater.

Underwater detectibility of a lighting system on a helicopter escape exit.

BACKGROUND: When a helicopter ditches into water, it immediately inverts due to the weight of the engines and then fills with water. Locating the emergency exit for escape under such conditions is a difficult task. A new lighting system for an escape exit has been developed that illuminates on contact with water. The detectibility of the lighting was investigated under varying conditions of ambient illumination, water turbidity, and viewing distance. METHOD: A total of 288 underwater detection trials were carried out by 9 subjects with an illuminated hatch placed at 2 distances (1.5 m and 3.1 m), under 2 ambient illuminations (bright: > 3000 lux and dark: < 0.1 lux), and in 2 conditions of water turbidity. The water temperature was 12 degrees C for all conditions. RESULTS: At 1.5 m, the lighting system was detectable in less than 1.5 s by all subjects in both clear and turbid water and under both bright and dark conditions. At 3.1 m, the lights were detectable in both clear and turbid water under the dark condition and in clear water under the bright condition. However, the lighting was not reliably detected in turbid water under bright condition. CONCLUSIONS: The system met original design requirements in terms of detectibility at 1.5 m. The detection time was always under 1.5 s. It could also be detected at 3.1 m in clear and turbid water, under dark conditions. However, the detectibility at 3.1 m in turbid water, under bright condition was less reliable.