Serum vancomycin levels predict the short-term adverse outcomes of peritoneal dialysis–associated peritonitis

Background: The role of monitoring serum vancomycin levels during treatment of peritoneal dialysis (PD)–associated peritonitis is controversial. Substantial inter-individual variability may result in suboptimal serum levels despite similar dosing of vancomycin. The published predictors of suboptimal serum vancomycin levels remain limited. Methods: Data were retrospectively collected from 541 patients on continuous ambulatory peritoneal dialysis between 1 January 2018 and 31 December 312019. For gram-positive cocci and culture-negative peritonitis, we adopted a vancomycin administration and monitoring protocol. Short-term adverse outcomes of PD-associated peritonitis, including transfer to haemodialysis, death, persistent infection beyond planned therapy duration and relapse, were observed. The association between trough serum vancomycin levels and short-term adverse outcomes was evaluated. Results: Intraperitoneal vancomycin was used in 61 gram-positive cocci or culture-negative peritonitis episodes in 56 patients. Fourteen episodes of short-term adverse outcomes occurred in 12 patients, whose average trough serum vancomycin levels on day 5 of treatment were significantly lower than those who didn’t experience any adverse outcomes (8.4 ± 1.7 vs 12.5 ± 4.3 mg/L, p = 0.003). In gram-positive cocci or culture-negative peritonitis patients, those with higher day 5 trough serum vancomycin levels had a lower risk of short-term adverse outcomes (odds ratio: 0.6, 95% confidence interval: 0.4 to 0.9, p = 0.011). Receiver operating charecteristic curve (ROC) analyses showed that the day 5 trough serum vancomycin levels diagnostic threshold value for short-term adverse outcomes was 10.1 mg/L. After adjustments for gender, exchange volume and residual kidney function (RKF), baseline higher peritoneal transport was associated with a suboptimal (<10.1 mg/L) day 5 serum vancomycin level. Conclusions: Serum vancomycin levels are correlated with short-term adverse outcomes of PD-associated peritonitis, and higher peritoneal solute transport status is associated with suboptimal trough serum vancomycin levels on day 5.

Impact of Indian and East Asian summer monsoons on the diurnal temperature range of the low-latitude highlands of China in the rainy season

This study investigates the impact of the Indian and East Asian summer monsoons on the diurnal temperature range (DTR) in the low-latitude highlands of China (CLLH) based on in-situ DTR observations, ERA5 reanalysis data, and numerical simulations. Diagnoses indicate that the DTR in the CLLH shows a significant positive correlation with the Indian summer monsoon (ISM), while a negative correlation with the East Asian summer monsoon (EASM). When a strengthened ISM occurs with a weakened EASM, an anomalous anticyclonic circulation with downward motion is excited over the CLLH. This anomalous circulation pattern increases the DTR in the rainy season by reducing the medium and high cloud cover in the CLLH. When a weakened ISM with a strengthened EASM decreases the DTR over the CLLH in the rainy season. Numerical experiments help to verify this crucial physical process linking the variability of the ISM and EASM with the DTR in the CLLH. The model results further indicate that the covariability of ISM and EASM contributes most to the variability of the rainy season DTR in the CLLH, followed by the individual variability of the EASM, and the smallest contribution to the rainy season DTR in the CLLH is the individual variability of the ISM.

From Intricacy to Conciseness: A Progressive Transfer Strategy for EEG-Based Cross-Subject Emotion Recognition

Emotion plays a significant role in human daily activities, and it can be effectively recognized from EEG signals. However, individual variability limits the generalization of emotion classifiers across subjects. Domain adaptation (DA) is a reliable method to solve the issue. Due to the nonstationarity of EEG, the inferior-quality source domain data bring negative transfer in DA procedures. To solve this problem, an auto-augmentation joint distribution adaptation (AA-JDA) method and a burden-lightened and source-preferred JDA (BLSP-JDA) approach are proposed in this paper. The methods are based on a novel transfer idea, learning the specific knowledge of the target domain from the samples that are appropriate for transfer, which reduces the difficulty of transfer between two domains. On multiple emotion databases, our model shows state-of-the-art performance.

Comparing the electrophysiological effects of traumatic noise exposure between rodents

Noise-induced hearing deficits are important health problems in the industrialized world. As the underlying physiological dysfunctions are not well understood, research in suitable animal models is urgently needed. Three rodent species (Mongolian gerbil, rat and mouse) were studied to compare the temporal dynamics of noise-induced hearing loss after identical procedures of noise exposure. Auditory brainstem responses (ABRs) were measured before, during and up to eight weeks after noise exposure for threshold determination and ABR waveform analysis. Trauma induction with stepwise increasing sound pressure level was interrupted by five interspersed ABR measurements. Comparing short- and long-term dynamics underlying the following noise-induced hearing loss revealed diverging time courses between the three species. Hearing loss occurred early on during noise exposure in all three rodent species at or above trauma frequency. Initial noise level (105 dB SPL) was most effective in rats while the delayed level-increase to 115 dB SPL affected mice much stronger. Induced temporary threshold shifts in rats and mice were larger in animals with lower pre-trauma ABR thresholds. The increase in activity (gain) along the auditory pathway was derived by comparing the amplitudes of short- and long-latency ABR waveform components. Directly after trauma, significant effects were found for rats (decreasing gain) and mice (increasing gain) while gerbils revealed high individual variability in gain changes. Taken together, our comparative study revealed pronounced species-specific differences in the development of noise-induced hearing loss and the related processing along the auditory pathway.

Variation and Variability in Drosophila Grooming Behavior

Behavioral differences can be observed between species or populations (variation) or between individuals in a genetically similar population (variability). Here, we investigate genetic differences as a possible source of variation and variability in Drosophila grooming. Grooming confers survival and social benefits. Grooming features of five Drosophila species exposed to a dust irritant were analyzed. Aspects of grooming behavior, such as anterior to posterior progression, were conserved between and within species. However, significant differences in activity levels, proportion of time spent in different cleaning movements, and grooming syntax were identified between species. All species tested showed individual variability in the order and duration of action sequences. Genetic diversity was not found to correlate with grooming variability within a species: melanogaster flies bred to increase or decrease genetic heterogeneity exhibited similar variability in grooming syntax. Individual flies observed on consecutive days also showed grooming sequence variability. Standardization of sensory input using optogenetics reduced but did not eliminate this variability. In aggregate, these data suggest that sequence variability may be a conserved feature of grooming behavior itself. These results also demonstrate that large genetic differences result in distinguishable grooming phenotypes (variation), but that genetic heterogeneity within a population does not necessarily correspond to an increase in the range of grooming behavior (variability).

Multi-Omics Study of The Salivary Modulation of The Rumen Microbiome

Ruminants are able to produce large quantities of saliva which enter into the rumen. Although previous research has indicated that salivary immunoglobulins can partially modulate the rumen microbial activity, the role of the salivary components other than ions on the rumen microbial ecosystem has not been thoroughly investigated in ruminants. A total of 16 semi-continuous in vitro cultures were used to incubate rumen fluid from 4 donor goats inoculated with autoclaved saliva (AUT) as negative control, saliva from the same rumen fluid donor (OWN) as positive control, and either GOAT or SHEEP saliva as experimental interventions. Fermentation was monitored throughout the 7 days of incubation and the prokaryotic communities and metabolome were analysed at day 7 of incubation. Characterization of the salivas used prior to incubation showed a high degree of individual variability in terms of the salivary metabolites and proteins, including immunoglobulins. The prokaryotic community composition in AUT incubators was the most divergent across treatments, suggesting a modulatory effect of active salivary components, which were not affected in the other treatments (OWN, GOAT and SHEEP). The differences across treatments in microbial diversity were mostly caused by a greater abundance of Proteobacteria and Rikenellacea and lower of Prevotellaceae, a key rumen bacterium with greater abundance in GOAT and SHEEP treatments. These results suggest that specific salivary components contribute to host-associated role in selecting the rumen commensal microbiota and its activity.

Missense variants in the TNFA epitopes and their effects on interaction with therapeutic antibodies—in silico analysis

Background Tumor necrosis factor alpha (TNFA) is an important cytokine that influences multiple biological processes. It is one of the key mediators of acute and chronic systemic inflammatory reactions and plays a central role in several autoimmune diseases. A number of approved monoclonal antibodies (mAbs) are widely used to subside these autoimmune diseases. However, there is a high rate of non-responsiveness to treatments with these mAbs. Therefore, it is important to be able to predict responses of the patients in an individualistic manner to these therapeutic antibodies before administration. In the present study, we used in silico tools to explore the effects of missense variants in the respective epitopes of four therapeutic anti-TNFA mAbs—adalimumab (ADA), certolizumab pegol (CZP), golimumab (GLM), and infliximab (IFX)—on their interactions with TNFA. Results The binding affinities of CZP and ADA to corresponding epitopes appear to be reduced by four (TNFAR131Q, TNFAE135G, TNFAR138Q, and TNFAR138W) and two (TNFAG66C and TNFAG66S) variants, respectively. The binding of GLM and IFX appears to be affected by TNFAR141S and TNFAR138W, respectively. TNFAG66C and TNFAG66S may be associated with autoimmune diseases, whereas TNFAE135G, TNFAR138W, and TNFAR141S may be pathogenic per se. Conclusion These variants may contribute to the observed inter-individual variability in response to anti-TNFA mAbs treatments and be used as markers to predict responses, and thus optimize therapeutic benefits to the patients.

Quadriceps Muscle Fatigue Reduces Extension and Flexion Power During Maximal Cycling

Purpose: To investigate how quadriceps muscle fatigue affects power production over the extension and flexion phases and muscle activation during maximal cycling.Methods: Ten participants performed 10-s maximal cycling efforts without fatigue and after 120 bilateral maximal concentric contractions of the quadriceps muscles. Extension power, flexion power and electromyographic (EMG) activity were compared between maximal cycling trials. We also investigated the associations between changes in quadriceps force during isometric maximal voluntary contractions (IMVC) and power output (flexion and extension) during maximal cycling, in addition to inter-individual variability in muscle activation and pedal force profiles.Results: Quadriceps IMVC (−52 ± 21%, P = 0.002), voluntary activation (−24 ± 14%, P &lt; 0.001) and resting twitch amplitude (−45 ± 19%, P = 0.002) were reduced following the fatiguing task, whereas vastus lateralis (P = 0.58) and vastus medialis (P = 0.15) M-wave amplitudes were unchanged. The reductions in extension power (−15 ± 8%, P &lt; 0.001) and flexion power (−24 ± 18%, P &lt; 0.001) recorded during maximal cycling with fatigue of the quadriceps were dissociated from the decreases in quadriceps IMVC. Peak EMG decreased across all muscles while inter-individual variability in pedal force and EMG profiles increased during maximal cycling with quadriceps fatigue.Conclusion: Quadriceps fatigue induced by voluntary contractions led to reduced activation of all lower limb muscles, increased inter-individual variability and decreased power production during maximal cycling. Interestingly, power production was further reduced over the flexion phase (24%) than the extension phase (15%), likely due to larger levels of peripheral fatigue developed in RF muscle and/or a higher contribution of the quadriceps muscle to flexion power production compared to extension power during maximal cycling.

Individual variability in patterns and dynamics of fecal gluten immunogenic peptides excretion after low gluten intake

Purpose Determination of Gluten Immunogenic Peptides (GIP) in feces is a direct tool for gluten exposure detection. The sensitivity of GIP detection methods for cases of unintentional low gluten intakes is unknown. We studied the interindividual variability in the kinetic of excretion under homogeneously controlled dietary conditions, and the sensitivity of fecal GIP tests after low amounts of punctual gluten ingestions. Methods Participants (n = 20) followed the same gluten-free menu for 12 days in which two separated doses of gluten (50 mg and 2 g) were ingested and all the depositions were collected. GIP from stool samples were analyzed by ELISA and lateral flow immunoassay (LFIA) tests. Results Most participants had detectable GIP after 50 mg and 2 g gluten ingestions using ELISA test (72.2% and 95%, respectively), whereas the LFIA test showed less sensitivity (22.2% and 80%, respectively). GIP were detected at higher either frequency or concentration in the range of 12–36 h after 50 mg intake, and 12–84 h after 2 g consumption. Considering this period, diagnostic sensitivity of GIP detection after a single 50 mg ingestion may be significatively increased analyzing three stool samples per individual. High variability among participants was found in the time and amount of GIP excretion; however, some individuals showed common patterns for both gluten intakes. Conclusion Sporadic gluten exposure detection may require several fecal samples to achieve level of sensitivity above 90%. Interindividual variability in the dynamic of GIP excretion may suggest patterns of gluten metabolism.

Importance of using a pharmacogenetic approach to predict individual pharmacokinetics and safety profile of apixaban

In recent years, there has been a trend towards increased prescribing of direct-acting oral anticoagulants (DOACs) due to favourable pharmacokinetics and pharmacodynamics without the need for regular coagulation monitoring. However, recent studies have documented individual variability in plasma DOAC levels. DOAC pharmacogenetics is a relatively new area of research. There is a need to understand the role of pharmacogenetics in the adaptation of anticoagulant therapy according to a patient’s genetic characteristics. This scientific review of current data on the impact of different gene polymorphisms on apixaban pharmacokinetics broadens the understanding of the clinical relevance of genotyping for treatment efficacy and safety.