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PubMed1979

Effects of intraperitoneal nitroprusside on peritoneal clearances in man with variations of dose, frequency of administration and dwell times.

Clinical studies with intraperitoneal nitroprusside were designed to examine drug effects on peritoneal clearances as a function of dose, frequency of administration and dwell times. Increases in clearances and protein losses were seen with 1 mg of nitroprusside per liter of dialysis solution, with progressively greater effects up to maximum doses of 4.5 mg/1. Maximum effects were seen at the high dose after 3 or more consecutive exchanges. Clearance effects promptly returned toward control during postdrug exchanges and, in some studies, even during alternate exchanges. Proportional effects on solute clearances appeared independent of dwell time, supporting previous studies suggesting area permeability alterations. Series of 12 or more consecutive exchanges showed little change in blood pressure. Increases in serum thiocyanate were not detected after multiple exchanges. Dialysate cell counts showed no evidence of chemical irritation.

Biological Transport↗

PubMed2025

Mechanisms of enhanced or impaired DNA target selectivity driven by protein dimerization.

Successful DNA transcription demands coordination between proteins that bind DNA while simultaneously binding to one another to form dimers or higher-order complexes. For proteins with numerous DNA targets throughout the genome, measurements that report on their dwell time or occupancy thus represent a convolution over a population interacting with specific DNA, nonspecific DNA, or protein partners on DNA. Dimerization is known to add contacts that can help a single protein to stably bind DNA. However, we show here that dimerization can also impair measured dwell times and occupancy on target sequences because the population redistributes across DNA. We combine mass-action kinetic models of pairwise reversible reactions between proteins and DNA with theory and spatial stochastic simulations to isolate the role of dimerization on observed DNA dwell times, occupancy, and spatial distribution of proteins on DNA. Three key themes emerge: (i) Protein-protein interactions, in addition to protein-DNA interactions, can localize a protein to DNA, and relative binding rates can thus widely tune dwell times. (ii) Dimensional reduction achieved through nonspecific binding and subsequent 1D diffusion controls the order-of-magnitude of enhancements despite nucleosome barriers. (iii) Dimerization enhances selectivity for locally clustered targets and often impairs binding to widely-spaced targets by sequestration. Compared with ChIP-seq data, our model explains how the distribution of the essential GAF protein throughout the genome is highly selective for clustered targets due to protein interactions. This model framework predicts when even weak dimerization can redistribute and stabilize proteins on DNA as a necessary part of transcription.

DNA binding↗

PubMed2026

Altered EEG microstate dynamics reflect depressive symptoms in temporal lobe epilepsy.

BACKGROUND: Depressive symptoms are a common and disabling comorbidity in temporal lobe epilepsy (TLE), yet the neural mechanisms linking seizure networks to affective symptoms remain unclear. Although limbic network dysfunction has been implicated in both epilepsy and depressive disorders, it is unknown whether the time-varying dynamics of large-scale electrophysiological brain states reflect depressive symptom severity in TLE. In this study, we examined whether EEG microstate dynamics capture network alterations associated with depressive symptoms in individuals with unilateral TLE. METHODS: We analyzed resting-state, visually normal scalp EEG from 26 individuals with unilateral TLE. EEG microstates were identified by clustering global field power peaks into four canonical classes, with electrode positions mirrored to align the ictal hemisphere across subjects. Microstate dwell time, fractional occupancy, global transition entropy, and Markov transition probabilities were quantified and related to Beck Depression Inventory-II (BDI) scores. RESULTS: Individuals with high depressive symptoms (BDI ≥ 13; N = 12) exhibited longer mean dwell time in the ictal hemisphere-aligned microstate compared with individuals with low depressive symptom burden (BDI < 13; N = 14). Across subjects, dwell time in this microstate correlated with depressive symptom severity (r = 0.57, p = 0.002). TLE individuals with higher depressive symptoms exhibited reduced global transition entropy (p = 0.02), which also correlated with depressive symptom severity (r = -0.54, p = 0.004), indicating decreased flexibility of microstate transitions. Despite similar fractional occupancy of this state between groups, individuals with higher depressive symptoms were less likely to transition into the ictal hemisphere-aligned microstate from non-ictal or posterior configurations. Once engaged, however, the ictal-aligned microstate showed increased persistence, indicating prolonged stabilization of this network configuration. CONCLUSION: Higher depressive symptom burden in unilateral TLE is associated with increased temporal rigidity of the ictal hemisphere-aligned brain microstate, reflecting impaired disengagement of epileptogenic network configurations. These findings suggest that depressive symptoms in TLE may be associated with epilepsy-related disruptions in large-scale neural dynamics.

Humans↗

PubMed2026

Leveraging ONT move table values for signal aware variant calling.

Oxford Nanopore Technologies (ONT) sequencing enables long-range haplotype phasing and contiguous genome assembly but still exhibits elevated error rates that challenge small variant calling, particularly for insertions and deletions (Indels). While raw electrical signals contain rich information, existing signal-aware methods require computationally intensive processing of large signal files. Here, we present Clair3 v2, a method that leverages the ONT move table-a lightweight byproduct of basecalling that maps signal events to nucleotide positions-to improve variant calling accuracy. Clair3 v2 builds upon Clair3 and integrates signal-level dwelling time to significantly enhance variant calling performance. We also propose a genome position based circular buffer to incorporate dwelling time with minimal computational overhead. Benchmarking across six Genome in a Bottle samples demonstrates substantial improvements in variant calling accuracy. With HAC basecalling, Clair3 v2 achieves a mean SNP F1-score of 97.69% at 10 × depth (compared to 96.45% for baseline Clair3), and Indel F1 scores improved from 64.27% to 76.70%, while gains persisted at higher depths. The benefits were most pronounced for longer Indels and in complex genomic regions, where Indel F1 scores in long homopolymer regions improved from 14.3% to 45.2%. Benchmark results across various basecalling modes, samples, and coverage settings outperformed Clair3 baselines and other methods, including DeepVariant and Dorado Variant, and demonstrate the significant benefits of Clair3 v2. Furthermore, Clair3 v2 incurs negligible runtime compared to standard Clair3, making it practical for routine use.

Sequence Analysis, DNA↗

PubMedDate not supplied

Visual scanning, pattern recognition and decision-making in pulmonary nodule detection.

Eye movements were recorded while four subjects searched a set of 60 films, 24 normal and 36 abnormal for pulmonary nodules. Error rates, scanning patterns and the dwell time of fixation clusters on normal and nodule-containing areas of the film were studied. Using the assumption that prolonged dwell time indicates intensive processing of visual data, a model was developed for nodule detection that includes four steps: orientation, scanning, pattern recognition and decision-making. False-negative errors were divided into three classes: scanning errors, recognition errors and decision-making errors. Of 20 false-negative errors, 30% were considered scanning, 25% recognition and 45% decision-making.

Decision Making↗

PubMed2026

Effectiveness of chlorhexidine gluconate-impregnated dressings in preventing central line-associated bloodstream infection in a paediatric intensive care unit: A randomised controlled trial.

OBJECTIVES: To compare the effectiveness and dermatological safety of chlorhexidine gluconate (CHG)-impregnated dressings versus conventional transparent dressings in preventing central line-associated bloodstream infection (CLABSI) in paediatric patients admitted to a PICU. METHODS: A single-blind, randomised controlled trial with a 1:1 allocation ratio was conducted in a tertiary PICU. A total of 250 paediatric patients with a central venous catheter were included (125 per group). Patient characteristics, catheter-related variables, catheter dwell time and skin alterations were recorded. The primary outcome was CLABSI, defined according to CDC/NHSN criteria. Bivariate analyses and multivariable logistic regression were performed, including clinically relevant covariates related to catheter exposure, dressing type, and vaccination status. The trial was registered at ClinicalTrials.gov (NCT07175116). RESULTS: CLABSI incidence was significantly lower in the CHG group compared with the conventional dressing group (2.4% vs. 18.4%; p < 0.001). In multivariable analysis, CHG-impregnated dressings were independently associated with reduced CLABSI risk (OR = 0.15; 95% CI: 0.04-0.58). Longer catheter dwell time (OR = 1.13 per day; 95% CI: 1.04-1.22) and absence of complete vaccination (OR = 8.68; 95% CI: 2.48-30.47) were also associated with increased infection risk. Incomplete vaccination showed a similar trend without reaching statistical significance (OR = 6.48; 95% CI: 0.95-44.20). Skin alterations were more frequent in the CHG group (16.8% vs. 11.2%), predominantly in younger infants. CONCLUSIONS: CHG-impregnated dressings were associated with a significant reduction in CLABSI incidence in critically ill paediatric patients, although their use was linked to a modest increase in mild skin reactions. IMPLICATIONS FOR CLINICAL PRACTICE: CHG-impregnated dressings may be considered as part of a multifaceted infection prevention strategy, alongside appropriate catheter management, minimisation of catheter manipulation and proactive skin monitoring, with cautious and individualised use in infants.

Humans↗

PubMed1978

Application and evaluation of limited mass monitoring with a gas chromatograph mass spectrometer computer system.

The technique of scanning a preselected set of ions employing a combined gas chromatography mass spectrometer computer system has been investigated to ascertain the advantages and disadvantages of such a procedure. This technique allows one to determine gas chromatographic retention data with with a high degree of precision and accuracy, in rapid temperature programming operation, due to shortening of the mas spectral scanning interval. Signal-to-noise ratio in ion abundance recordings can be enhanced by increasing the dwell time for as many as 100 ions without lenghtening the scanning interval. The utility of such an approach was demonstrated by analysis of complex mixtures isolated form human urine and cerebrospinal fluid.

Carboxylic Acids↗

PubMed1979

Peritoneal clearance of creatinine and inulin during dialysis in dogs: effect of splanchnic vasodilators.

The peritoneal clearance of creatinine and inulin during isotonic peritoneal dialysis was studied in dogs before and after the administration of two vasodilators: isoproterenol and glucagon. One-liter exchanges with 15-min dwell times were used. Blood flow in the superior mesenteric artery was recorded with an electromagnetic flow probe and used as an index for total splanchnic flow. Intravenous isoproterenol (2.4 microgram/min) increased blood flow by 88%, but did not alter peritoneal clearance. When isoproterenol was given i.p. (0.5 microgram/ml dialysis fluid), blood flow increased by 81%, and inulin clearance rose by 26.8% (2.06 +/- 0.18 to 2.61 +/- 0.23 ml/min; P less than 0.05). Creatinine clearance increased by 17.5%, from 10.94 +/- 0.32 to 12.85 +/- 0.34 ml/min (P less than 0.05). When blood flow was returned to control levels with a clamp, clearances also returned to control levels. Glucagon given i.p. (1.0 microgram/ml) had no effect on any measured variable. Glucagon given i.v. at 10 microgram/min caused blood flow to rise by 81% and inulin clearance to rise by 25% from 1.88 +/- 0.16 to 2.35 +/- 0.19 ml/min (P less than 0.05). Cp, inulin clearance remained at control levels. Vasodilators seem to exercise two effects in augmenting clearance of small and middle-sized molecules: a direct permeability effect and a blood-flow related effect, possibly in increasing the surface area available for exchange and/or increasing permeability of the capillary endothelium.

Animals↗

PubMed1979

Relative determination of W-values for alpha particles in tissue-equivalent and other gases.

W (the average energy to form an ion pair) for 5.4 MeV 241Am alpha particles in a Rossi-type tissue-equivalent (TE) gas, argon and methane was determined to an accuracy better than 0.2% using a new automated data handling system. A vibrating reed electrometer and current digitiser were used to measure the current produced by completely stopping the alpha particles in a large cylindrical ionisation chamber. A multichannel analyser, operating in a slow multiscaler mode, was used to store pulses from the current digitiser. The dwell time, of the order of 60 min per channel, was selected with an external timer gate. Current measurements were made at reduced pressures (200 Torr) to reduce ion recombination. The average current, over many repeated measurements, was compared to the current produced in nitrogen and its previously published W-value of 36.39+/-0.04 eV per ion pair. The resulting W-values were, in eV per ion pair, 26.29+/-0.05 for argon, 29.08+/-0.03 for methane and 30.72+/-0.04 for TE gas, which had an analysed composition of 64.6% methane, 32.4% CO2 and 2.7% nitrogen. Although the methane and argon values agree within 0.1% with previously published values, the value for TE is 1.2% lower than the single previously reported value.

Alpha Particles↗

PubMed2026

Ribosome dynamics at the conserved PGP motif governs 2A peptide-bond-skipping efficiency.

Viral 2A oligopeptides drive an unusual ribosome recoding event in which peptide-bond formation fails at a conserved PG↓P motif, producing two discrete proteins without canonical termination. Despite decades of study, the molecular basis of 2A-mediated peptide-bond skipping remains poorly understood. Here, we combine quantitative 2A reporters with high-resolution ribosome profiling to interrogate ribosome dynamics at the core 2A sequences. We identify a pausing event at the terminal proline codon of the PGP motif that functions as a kinetic decision point: ribosome dwell time at this site inversely correlates with skipping efficiency. Increasing nascent chain flexibility by inserting linkers immediately upstream of the 2A sequence reduces ribosome occupancy at the terminal proline codon and enhances peptide-bond skipping. Strikingly, amino acid repeats positioned distally upstream also modulate 2A activity, indicating long-range coupling between nascent chain properties outside of the ribosome and the peptidyl transferase center inside the ribosome. In particular, hydrophobic residues potently suppress skipping, an effect that can be rescued by extending flexible segments within the peptide exit tunnel. Together, our findings support a model in which nascent chain features-beyond the core 2A motif-dynamically tune ribosomal recoding efficiency through co-translational feedback into the catalytic center.

Ribosomes↗

PubMed1978

Augmented peritoneal mass transport with intraperitoneal nitroprusside.

Lightly restrained, alert New Zealand white rabbits underwent peritoneal dialysis by percutaneous instillation of standard dialysis solution with or without intraperitoneal nitroprusside. Corrected to a mean intraperitoneal dwell time of 36 minutes, mean clearances of creatinine and urea were 0.74 and 0.90 ml/kg/min in six rabbits. With intraperitoneal nitroprusside, 1.13 mg/kg clearances increased to 1.13 and 1.30 ml/kg/min (p less than 0.01) respectively. The 53% increment in creatinine clearance maintained the ratio clearance larger/smaller solute suggesting increased peritoneal permeability and/or area. Lower nitroprusside doses were less effective and not significantly above control. Nitroprusside also increased clearances during hypertonic peritoneal dialysis, but had no effect on osmotically induced water flux. Lavage studies demonstrated a persistent effect of nitroprusside after a single exposure and a sustained effect with repeated use.

Animals↗

PubMed1979

Equilibration of peritoneal dialysis solutions during long-dwell exchanges.

There is an increasing interest in CAPD for the treatment of chronic uremia. This technique uses long-dwell peritoneal exchanges lasting 4 hr or more. We have determined equilibration curves for multiple solutes during long exchanges with commercially available 1.5% and 4.25% dextrose dialysis solutions. For small solutes, rates of change of D/P ratios fall off dramatically after 3 hr of dwell time. For larger solutes, D/P ratios change more linearly. Some concentration gradients for net removal by diffusion persist well beyond 4 hr for all but the most highly diffusible solutes. Previously reported net sieving of sodium and chloride during hypertonic exchanges is still evident after many hours.

Adult↗

PubMed1979

[A morphological and functional analysis of the extent of cartilage coverage in the human hip joint].

The extension and the shape of the cartilage surface of 30 human femora and acetabula were measured. The results were considered and discussed as the response of the articular cartilage to the specific stress on this joint. 3 kinds of cartilage distribution were found on the femoral head; these shapes were understood as the consequence of the position and the dwelling time of the actual cartilage stimulating area. The largest extention of the cartilage was found in the ventrolateral direction and the smallest in medial direction. The cartilage margin of the "A" type was regulary curved. The "B" type has an inlet towards the fovea capitis. This inlet reaches in the "C" type to the fovea as an area free of cartilage. The acetabula could not be divided into types with different cartilage distribution because of the great similarity in shape. Therefore we computed an average acetabulum. The largest extension of the facies lunata was found 15 degrees in front of the roof of the acetabulas as seen in x-ray pictures. The cornu anterius is always narrower than the cornu posterius. The outer margin of the osseous acetabulum does not reach the equator, it lies on a latitude of 11.5 degrees. The incisura acetabuli is inclined against the vertical line with 18.3 degrees. The width of the facies lunata can be considered as a result of mechanical stress. The different extensions of the cartilage of both joint components in ventro-lateral direction seems to be the consequence of different extensions of movement. The area of movement of the caput femoris is larger than the area of the acetabulum.

Acetabulum↗

PubMed1979

Mites in house dust in the Stockholm area.

Today there is no doubt that mites (and especially species within the Pyroglyphidae family: Dermatophagoides pteronyssinus and Dermatophagoides farinae) are an important agent in dust allergies. The author reports on a study of the occurrence of mites in house dust in the environment of allergic persons in the Stockholm area. 201 private homes, 13 farmers' houses and two hospitals have been studied. In 12% of the homes several different types of mite were found in dust in relatively small numbers, while pyroglyphids occurred in only 1.5% of the dwellings. The frequency of mites in dust from farmers' homes was three times higher and that of pyroglyphids ten times higher than in other dwellings. Mites were most often found in floor dust and very infrequently in bed dust. All hospital beds were free from mites; in floor-dust samples from a hospital for long-term therapy several species of mite were found. The author draws the conclusion that the conditions of climate and humidity within the geographical area studied are adverse to the development of an allergologically significant mite population in indoor dust, but that small numbers may spread from potted plants, work premises and outdoor flora.

Allergens↗

PubMed1979

Photoreactivating enzyme in the blind cave fish, Anoptichthys jordani.

1. Exposure of cells to ultraviolet light induces molecular changes in DNA which may lead to cellular death. 2. One product, pyrimidine dimers, is reversed during subsequent exposure to visible light by photoreactivating enzyme. 3. Photoreactivating enzyme has been recorded in different organisms, but inconsistencies in its distribution suggest it may have other functions. 4. We have found photoreactivating enzyme in the blind cave dwelling fish, Anoptichthys jordani. 5. Sufficient time has elapsed in the cave environment to allow loss of features of importance to epigean fish, including the eyes and pigmentation. 6. The continued presence of the enzyme indicates that it may have other functions.

Adaptation, Physiological↗

PubMed1978

Speed of retrieval from long-term memory in relation to age, familiarity, and datedness of information.

The time required to name four groups of pictures was measured in 83 community dwelling males (18-70 years of age). One group consisted of objects used 50 to 70 years ago (unique dated exemplars), and another consisted of objects unique to contemporary times (unique contemporary exemplars). For comparison, other pictures of contemporary and dated objects commonly used in both periods were employed. There were three major findings. One, the familiarity of the pictured object is the major determinant of the time required to retrieve its name. Older subjects named the dated unique objects that were relatively more familiar to them more rapidly than did younger adults, while the reverse was true for contemporary unique objects. No age difference in the speed of naming common contemporary objects was found. Two, the overall age-related difference in naming latency was attributed to perceptual-motor aspects of the task. Three, the physical features as well as the familiarity of the object contributed to the speed of retrieval of the object's name.

Adolescent↗

PubMed1978

Assessment of airborne radon daughter concentrations in dwellings in Great Britain.

Calculations of the activity concentration of RaA (218Po) in the air within living rooms and in the outside air were made at 87 dwellings in England and Scotland. From these measurements together with a determination of the ventilation rate existing in the room at the time of the measurements, the rate at which 222Rn is emanating from room surfaces into room air in pCil-1 h-1, can be calculated. For the dwellings studied the mean emanation rate is 0.54 pCil-1 h-1 and on the basis of a mean ventilation rate of one room change per hour throughout the year and assuming an occupancy factor of 0.8 the population exposure rate for the population of Great Britain to the short-lived daughters of 222Rn is estimated to be 0.15 Working Level Months per year.

Air Pollution, Radioactive↗

PubMed1977

The course of Hymenolepis nana infections in thymus-deficient mice.

The kinetics of infection with Hymenolepis nana was examined in normal thymus-deficient mice. Following inoculation with 5 cyticercoids, the number of adult lumen-dwelling H. nana in congenitally thymus-deficient (nude) mice ultimately was at least 75 times the maximum infection intensity of normal thymus-bearing mice or thymus-reconstituted nude mice. Similar results were obtained following inoculation of H. nana eggs into nude mice; although thymus-bearing mice eliminated their infections, nude mice harbored more than 1,000 adult worms throughout the 7 weeks of the experiments. These data show that in mice, immunity is not generated against H. nana in the absence of thymus function. The data also confirm and establish the requirement of cysticercoid development in the intestinal mucosa for stimulation of a protective immune response against H. nana.

Animals↗