Double-blind Experiment Research Articles

A Double-Blind Randomized Controlled Trial Comparing Intrathecal 0.5% Isobaric Levobupivacaine With Fentanyl to 0.5% Isobaric Ropivacaine With Fentanyl for Elective Cesarean Section.

Background This study was planned to compare the onset and duration of action and the levels of sensory and motor blocksof 0.5% isobaric levobupivacaine with fentanyl to 0.5% isobaric ropivacaine with fentanyl addition in subarachnoid block in elective cesarean cases. Materials and methods This hospital-based randomized interventional controlled study was conducted in a tertiary care facilityin Jaipur. Sixty women who planned for elective lower-segment cesarean section, with more than 37 weeks of gestational period during the study period, were included in our study. These women were randomly divided into two study groups, using sealed opaque envelopes, and double blinding was ensured. In group L, women received 0.5% isobaric levobupivacaine with fentanyl, and in group R,0.5% isobaric ropivacaine with fentanylwas given. Results The mean time for sensory and motor block onset was significantly lower in group L than in group R (p<0.05). The mean time for two-segment regression for sensory block was significantly higher in group L than in group R (p<0.05). The mean duration of total motor blockade (B0) was significantly higher in group L compared to group R. The differences in the mean duration of total motor blockade were statistically significant (p<0.05).The mean change in mean arterial pressure (MAP) in group L was significantly higher than in group R (p<0.05). Conclusion This study provides valuable insights into the comparative effects of 0.5% isobaric levobupivacaine with fentanyl and 0.5% isobaric ropivacaine with fentanyl for spinal anesthesia in cesarean sections. Both anesthetic agents were well-tolerated, with no severe complications or side effects observed in either group. While levobupivacaine offers an early onset of action, ropivacaine demonstrates a more favorable hemodynamic profile with an early regression of motor block. Ropivacaine may be a suitable alternative to levobupivacaine for spinal anesthesia in cesarean sections, particularly in patients with unstable hemodynamics. Further research is necessary to investigate the long-term effects of these agents and to optimize their use in different patient populations.

Functional and structural polypharmacology of indazole-based privileged ligands to tackle the undruggability of membrane transporters.

Despite the significant roles of solute carrier (SLC) and ATP-binding cassette (ABC) transporters in human health and disease, most remain poorly characterized as intrinsic and/or xenobiotic ligands are unknown, rendering them as 'undruggable'. Polypharmacology, defined as the simultaneous engagement of multiple targets by a single ligand, offers a promising avenue for discovering novel lead compounds addressing these emerging pharmacological challenges - a major focus in contemporary medicinal chemistry. While common structural motifs among phylogenetically diverse proteins have been proposed to underlie polypharmacology through the concept of 'multitarget binding sites', a comprehensive analysis of these functional and structural aspects from a medicinal chemistry perspective has yet to be undertaken. In our study, we synthesized 65 distinct indazole derivatives and evaluated their activity across a broad biological assessment platform encompassing 17 specific and polyspecific SLC and ABC transporters. Notably, ten indazoles exhibited cross-target activity against challenging transporter targets associated with neurodegeneration (ABCA1), metabolic reprogramming (MCT4), and cancer multidrug resistance (ABCC10). Furthermore, molecular blind docking experiments and advanced binding site analyses revealed, for the first time, conserved binding motifs across monocarboxylate transporters (MCTs), organic anion transporting polypeptides (OATPs), organic cation transporters (OCTs), and ABC transporters, characterized by specific and recurring residues of tyrosine, phenylalanine, serine, and threonine. These findings highlight not only the potential of polypharmacology in drug discovery but also provide insights into the structural underpinnings of ligand binding across membrane transporters.

In silico identification of Nipah virus protein inhibitors from secondary metabolites of medicinal plants using a high-throughput virtual screening approach.

The Nipah virus (NiV), a highly pathogenic zoonotic virus of the Paramyxoviridae family, poses significant threats with its alarming mortality rates and pandemic potential. Despite historical cases, effective therapeutics remain elusive, prompting urgent exploration of potential antivirals. In this study, a structure-based virtual screening approach was employed to evaluate 690 metabolites sourced from ten medicinal plants (Allium sativum, Andrographis paniculata, Cocos nucifera, Euphorbia hirta, Euphorbia neriifolia, Moringa oreifera, Ocimum basilicum, Piper nigrum, Vitex negundo, and Zingiber officinale) for their antiviral activity against Nipah virus proteins. Through targeted and blind docking experiments, forty-three (43) compounds were found to exhibit high binding affinities (≤ -8 Kcal mol-1) and validated site-specificity. Subsequent analysis of the ADMET properties of these compounds, along with off-target docking to swine receptors, six (6) compounds with profiles akin to approved drugs and minimal off-target binding were identified. Stability screening via 100 ns and 300 ns molecular dynamics simulations identified two (2) of the six compounds that demonstrated sustained dynamic stability over an extended duration, coupled with favorable binding energies from MM-(GB/PB)SA calculations and biologically significant binding modes and residue interactions. Betulinic acid and CID 118716357 exhibited significant potential as inhibitors of Nipah virus fusion (F) glycoprotein trimer by targeting the oligomerization sites used to form the functional hexamer-of-trimer assembly. Coupled with their dynamic stability and favorable ADMET profiles in both human and swine conditions, these findings make them good candidates for subsequent invitro testing and further biological screening in the quest for potent antiviral drugs targeting Nipah virus proteins.

COMPONENT CONSISTENCY AS ONE OF THE ASPECTS OF GERMAN-UKRAINIAN SPECIALIZED TRANSLATION QUALITY ASSURANCE

This empirical-theoretical inquiry aims to identify, describe, and propose solutions to address incon- sistent reproduction of derived terms containing recurring components in German-Ukrainian legal trans- lation. The study is grounded in translation-oriented terminology and seeks to establish new criteria for translation quality assessment. The manifold objectives encompass: 1) undertaking a scientific investiga- tion to demonstrate the problematical nature of intratextual term consistency in translation; 2) scrutinizing potential impacts of prospective translation regulating instruments on providing terminology consistency; 3) adducing extensive illustrations of adherence to the intratextual term component consistency principle while translating German legal texts into Ukrainian. The research proposes four heuristic hypotheses: 1) Term component inconsistency in translation sig- nificantly reduces translation quality, potentially leading to partial information loss or distortion, which af- fects the translation dominant. 2) Maintaining consistency in how term components are translated is cru- cial for ensuring high-quality specialized translations, especially in fields like legal translation. 3) Implicitly formulated quality requirements for specialized translation can induce strategic terminological-discursive errors, regardless of the translator’s professional experience or status, which can be attributed to trans- lator’s unconscious decisions. 4) Specialized lexicographic reference works, while functioning as translation regulating instruments, exhibit both general and component inconsistencies. Therefore, they can only serve as aids for exercising the translator’s term selection and decision-making competence. The comprehensively formulated methodology encompasses a blind translator experiment incorpo- rating three participants of disparate professional experience and status (two Ukrainian translation agen- cies and one translation studies master’s student), meticulous comparative intralingual and interlingual analysis of source and target texts, induction/deduction approach to identify recurrent translational phe- nomena, morphosemantic analysis to determine the internal semantic structure of legal terms, derivation analysis to explicate term-formation processes, and contrastive lexicographic analysis to assess the poten- tial of existing terminological records to ensure the term component consistency. The methodology pro- posed in the article allowed to examine invariant properties of the object (legal terms in both languages) under study from various translation-oriented terminology perspectives. An in-depth approach to consideration of intratextual terminology heterogeneity, which contradicts the re- quirements of current international standards for translation quality assurance, has led to the distinction of term component consistency and term component inconsistency in translation. It is established that recurring strate- gic terminological- discursive mistakes at the text level of multiple translations result from translation instructors/ scholars not sufficiently attending to the problematic issue. The overlooked translation quality criterion has led even experienced and well-regarded experiment participants to inadvertently make unconscious mistakes. Concurrently, the contrastive analysis of German-Ukrainian specialized dictionaries evinced their lim- itations in ensuring component consistency, spotlighting the indispensability of the translator’s role in up- holding this benchmark. The proposed glossary with verified equivalents for the terminological field of Ger- man “Unterhalt” demonstrates the potential for consistent translation of derived terms into Ukrainian. The extensive empirical evidence and elucidation of a novel translation studies method (viz., blind translator experiment) along with newly discovered concepts (inter alia term selection competence) ren- der this inquiry a worthwhile contribution toward enhancing German-Ukrainian legal translation quality. Ultimately, this is a commendable study advancing the field of translation-oriented terminology and con- tributing to the harmonization of German-Ukrainian terminological capital. Future research prospects include developing and describing a microstrategy to ensure intratextual term component consistency and investigating the influences of explicit translation regulating instruments on specialized translation quality.

The Video Manipulation Effect (VME): A quantification of the possible impact that the ordering of YouTube videos might have on opinions and voting preferences.

Recent research has identified a number of powerful new forms of influence that the internet and related technologies have made possible. Randomized, controlled experiments have shown, for example, that when results generated by search engines are presented to undecided voters, if those search results favor one political candidate over another, the opinions and voting preferences of those voters can shift dramatically-by up to 80% in some demographic groups. The present study employed a YouTube simulator to identify and quantify another powerful form of influence that the internet has made possible, which we have labeled the Video Manipulation Effect (VME). In two randomized, controlled, counterbalanced, double-blind experiments with a total of 1,463 politically-diverse, eligible US voters, we show that when a sequence of videos displayed by the simulator is biased to favor one political candidate, and especially when the "up-next" video suggested by the simulator favors that candidate, both the opinions and voting preferences of undecided voters shift dramatically toward that candidate. Voting preferences shifted by between 51.5% and 65.6% overall, and by more than 75% in some demographic groups. We also tested a method for masking the bias in video sequences so that awareness of bias was greatly reduced. In 2018, a YouTube official revealed that 70% of the time people spend watching videos on the site, they are watching content that has been suggested by the company's recommender algorithms. If the findings in the present study largely apply to YouTube, this popular video platform might have unprecedented power to impact thinking and behavior worldwide.

Effects of near-infrared radiation in ambient lighting on cognitive performance, emotion, and heart rate variability

Although sunlight contains approximately equal amounts of near-infrared radiation (NIR) and visible light, NIR is absent from most present-day electric lighting systems and is filtered by energy-efficient windows. However, NIR is biologically active and is commonly applied in targeted photobiomodulation treatments for a range of cognitive, emotional, and physical conditions. Given the removal of NIR from indoor illumination, it is critical to understand how ambient NIR may influence psychological and physical health, and whether reduced exposure to NIR in indoor environments could because for concern. In a preregistered within-subjects double-blind experiment, acute effects of NIR and far-red wavelengths in ambient illumination on cognition, emotional state and cardiovascular health were examined in a sample of 151 university students (117 females, 34 males). During a 2-h laboratory session, participants were monitored at rest and while engaged in cognitively demanding tasks across two counterbalanced lighting conditions. Both included 3500 K white light generated by a light-emitting diode (LED) system, while one additionally included LEDs with peak wavelengths in the NIR (875 nm, 960 nm) and far-red (735 nm) spectrum. The addition of NIR and far-red to the ambient lighting showed beneficial effects on resting high-frequency heart rate variability (HF-HRV), HF-HRV responses to cognitive demand, and feelings of pleasure, but reduced performance on a visual search task. These findings reveal that the absence of NIR from architectural lighting influences humans at a psychological and physiological level, with implications for health and well-being that need to be balanced with energy-saving considerations.

Bioelectrical stimulation therapy for muscle injuries in aerobics athletes

This article aims to explore the recovery effect of the bioelectrical stimulation therapy on muscle injuries in aerobics athletes. Non-invasive medical techniques are adopted to activate muscle tissue through electrical currents, promoting muscle contraction ability and functional recovery. This article selects 100 aerobics athletes with muscle injuries through questionnaire surveys and interviews. The Modulo Plus electrical stimulation device is used, and personalized treatment plans are set. Muscle changes before and after treatment are monitored using electromyography and ultrasound technology. In the single-blind experiment, in the fourth week, the pain score of the experimental group decreases to 2.4 points; the functional recovery score increases to 75.2 points; the flexibility measurement reaches 19.2 cm. In the case-control study, the bioelectrical stimulation therapy cures all athletes in the sixth week, exceeding the conventional therapy’s 35 patients, and has a lower recurrence rate. In the cohort study, athletes who use the bioelectrical stimulation therapy for a long time have a shorter average recovery time of 15.3 days and a recurrence rate of 16%. In the muscle recovery experiment, in the eighth week after treatment, the electromyographic activity level of the experimental group increases to 58.6 μV; the muscle thickness increases to 4.3 mm; the echo intensity increases to 63.1 dB; the fatigue characteristic score drops to 2.1. These data indicate that the bioelectrical stimulation therapy has significant effects in reducing pain, promoting functional recovery, improving flexibility, shortening recovery time, and reducing recurrence rates and pain scores, thereby providing an effective treatment option for the recovery of muscle injuries in aerobics athletes.

Lightening the mind with audiovisual stimulation as an accessible alternative to breath-focused meditation for mood and cognitive enhancement

In this randomized, controlled, and double-blind experiment with a relatively large sample (n = 262), a novel technique of audiovisual stimulation (AVS) was demonstrated to substantially improve self-reported mood states by reducing several negative affects, including anxiety and depression, and enhancing performance on mood-sensitive cognitive tasks. Most of the AVS effects were highly similar whether binaural beats were present or not and regardless of the duration of experience. Remarkably, the mood benefits from AVS closely aligned with those achieved through breath-focused meditation with additional evidence that a brief AVS exposure of approximately five minutes may be sufficient or even optimal for improving mood to a comparable or greater degree than meditation sessions of equal or longer durations (11–22 min). These exciting findings position AVS as a promising avenue for mood and cognition enhancement and a potentially more accessible “plug-and-play” alternative to meditation, which is especially relevant considering the high attrition rates commonly observed in meditation practices.

Poly-ether-ether-ketone (PEEK) versus dead-soft coaxial bonded retainers: a randomized clinical trial. Part 1. Stability, retainer failure, and participant satisfaction.

Poly-ether-ether-ketone (PEEK) was introduced in dentistry as an alternative to metal alloys. To assess the effectiveness of PEEK-fixed retainers in preserving the stability of mandibular anterior and participant satisfaction as compared to the Dead-soft coaxial fixed retainer (DSC). A single-centre, two-arm parallel groups randomized clinical trial. The patients treated with pre-adjusted orthodontic appliances who have a Little's Irregularity Index (LII) ≤ 0.5mm have been enrolled in the trial. PEEK retainers were prepared to round 0.8mm wire by computer-aided design and manufacturing, and the DSC wire was carefully adapted to the lingual surface of the lower anterior teeth. The primary outcome was the stability of lower anterior teeth as assessed by LII, while the secondary outcomes were changes in occlusal parameters, retainer failure, and patient satisfaction. The data were collected at the debonding stage (T0), 1 month (T1), 3 months (T3), and 6 months (T6) after starting the trial, except for patient's satisfaction, which was recorded using an electronic form at T1 and T6. Single blinding of participants. A total of 46 participants with an age range of 12-28 years old were randomly allocated to the two groups (n = 23 in each). Only one participant dropped out; therefore, 45 participants were analysed. The DSC group showed a significant increase in LII at T3. Both retainer groups had comparable occlusal measurements, failure frequency, and survival time, with no significant difference. The patients in the DSC group reported a statistically significant perception of change in the position of their teeth compared to those in the PEEK group. No harmful effects have been reported. Limited follow-up duration and the inability to blind the operator due to the nature of the intervention. After 6-month retention, the PEEK retainer was equally effective to DSC retainers in maintaining the teeth alignment, with no significant differences regarding the failure frequency, survival rate, and general patient satisfaction. https://register.clinicaltrials.gov. (NCT05557136).

Effects of natural reduced water on cognitive functions in older adults: A RCT study

Oxidative stress and diabetes increase the risk of cognitive decline and dementia. Natural reduced water contains active hydrogen (hydrogen radicals), eliminates reactive oxygen species, and has antidiabetic effects. However, whether natural reduced water affects human cognitive function is unknown. Therefore, we implemented a double-blind intervention experiment in which participants consumed 1 L of natural reduced water or tap water daily for 6 months. The participants were healthy older adults living in Japan. The intervention group showed significant improvements in cognitive functions of attention function (p < 0.01) and short-term memory (p < 0.05). These results indicate that the continuous intake of natural reduced water improves several cognitive functions.

Measurement report: The Fifth International Workshop on Ice Nucleation phase 1 (FIN-01): intercomparison of single-particle mass spectrometers

Abstract. Knowledge of the chemical composition and mixing state of aerosols at a single-particle level is critical for gaining insights into atmospheric processes. One common tool to make these measurements is single-particle mass spectrometry. There remains a need to compare the performance of different single-particle mass spectrometers (SPMSs). An intercomparison of SPMSs was conducted at the Aerosol Interaction and Dynamics in the Atmosphere (AIDA) chamber at the Karlsruhe Institute of Technology (KIT) in November 2014, as part of the first phase of the Fifth International Workshop on Ice Nucleation (FIN-01). In this paper we compare size distributions and mass spectra of atmospherically relevant particle types measured by five SPMSs. These include different minerals, desert and soil dusts, soot, bioaerosol (Snomax; protein granule), secondary organic aerosol (SOA), and SOA-coated mineral particles. Most SPMSs reported similar vacuum aerodynamic diameter (dva) within typical instrumental ranges from ∼100–200 nm (lower limit) to ∼2–3 µm (upper limit). In general, all SPMSs exhibited a wide dynamic range (up to ∼103) and high signal-to-noise ratio (up to ∼104) in mass spectra. Common spectral features with small diversities in mass spectra were found with high average Pearson's correlation coefficients, i.e., for average positive spectra ravg-pos=0.74 ± 0.12 and average negative spectra ravg-neg=0.67 ± 0.22. We found that instrument-specific detection efficiency (DE) was more dependent on particle size than particle type, and particle identification favored the use of bipolar, rather than monopolar, instruments. Particle classification from “blind experiments” showed that all instruments differentiated SOA, soot, and soil dust and detected subtle changes in the particle internal mixing but had difficulties differentiating among specific mineral types and dusts. This study helps to further understand the capabilities and limitations of the single-particle mass spectrometry technique in general and the specific performance of the instrument in characterizing atmospheric aerosol particles.

Poly-Ether-Ether-Ketone versus dead-soft coaxial bonded retainers: a randomized clinical trial. Part 2: periodontal health and microbial biofilm assessment.

Retainers have the potential to detrimentally impact periodontal health and contribute to tooth decay. To investigate periodontal health and bacterial biofilm related to Poly-Ether-Ether-Ketone (PEEK) fixed retainers as compared to Dead-soft coaxial fixed retainer (DSC). A two-arm parallel groups single-centre randomized clinical trial. The trial included patients whose orthodontic treatment was completed and required retainers. Participants were randomly assigned into two retainer groups: PEEK retainers, prepared by computer-aided design and manufacturing into 0.8mm wire form, and DSC retainers. The objectives included assessing periodontal health through plaque accumulation index (PI), bleeding on probing (BOP), periodontal pocket depth (PPD), gingival index (GI), calculus index (CI), and alveolar bone height (ABH) assessment. Biofilm assessment involved bacteriological screening of aerobic, facultative anaerobic, mutans streptococci, and lactobacilli. The periodontal indices and microbiological screening as well as were assessed at the debonding stage (T0), 1-month (T1), 3-month (T3), and 6-month (T6) after the commencement of the trial, except for the ABH, which was recorded using periapical radiograph at T0 and T6. Single blinding of participants in addition to the bacteriological specialist. Initially, the trial enrolled 46 participants, aged between 12 and 28 years, and were randomly assigned to two groups, with 23 participants in each group. Subsequently, one participant withdrew from the trial, resulting in a total of 45 participants whose data were analysed. Assessment of the periodontal indices, excluding the CI (P = .480), revealed statistically but not clinically significant differences between groups after 6-month of retention (P = .016 of PI, P = .020 of BOP, P = .05 of PPD, and P = .01 of GI). There was slight plaque accumulation, normal PPD (approximately 1mm), healthy to mild gingivitis with a GI of less than 1 and BOP was around 10%. Concerning the ABH, there was a noticeable reduction in its score after 6 months, particularly in the PEEK group, although the difference was not statistically significant (P = .102). Furthermore, the bacteriological viable count did not show any significant difference between the groups during the recall visits. There have been no reported negative consequences. Blinding the assessor of periodontal indices was not feasible due to the nature of the intervention. The trial follow-up duration was limited. Both the PEEK and DSC retainers have comparable impacts on periodontal health and bacterial accumulation and composition during the retention period. NCT05557136.

Physiology-inspired bifocal fronto-parietal tACS for working memory enhancement

Aging populations face significant cognitive challenges, particularly in working memory (WM). Transcranial alternating current stimulation (tACS) offer promising avenues for cognitive enhancement, especially when inspired by brain physiology. This study (NCT04986787) explores the effect of multifocal tACS on WM performance in healthy older adults, focusing on fronto-parietal network modulation. Individualized physiology-inspired tACS applied to the fronto-parietal network was investigated in two blinded cross-over experiments. The first experiment involved monofocal/bifocal theta-tACS to the fronto-parietal network, while in the second experiment cross-frequency theta-gamma interactions between these regions were explored. Participants have done online WM tasks under the stimulation conditions. Network connectivity was assessed via rs-fMRI and multichannel electroencephalography. Prefrontal monofocal theta tACS modestly improved WM accuracy over sham (d = 0.30). Fronto-parietal stimulation enhanced WM task processing speed, with the strongest effects for bifocal in-phase theta tACS (d = 0.41). Cross-frequency stimulations modestly boosted processing speed with or without impairing task accuracy depending on the stimulation protocol. This research adds to the understanding of physiology-inspired brain stimulation for cognitive enhancement in older subjects.

Intranasal atomized dexmedetomidine alone or in combination with ketamine or midazolam to sedate healthy dogs

A prospective, randomized, blinded experiment was conducted to compare the effects of intranasal (IN) dexmedetomidine (Dex, 10 µg/kg; n=12) alone or combined with midazolam (DexM, 0.3 mg/kg; n=12) or ketamine (DexK, 2 mg/kg; n=12) in healthy dogs. Ease of administration (EA1), total administration time (TAT), time for first (TA1) and second nostril administration (TA2), and adverse events during atomization were recorded. Two days later, EA2 was assessed by IN atomization of injectable water as an additional outcome variable. Onset of sedation was evaluated, along with behavioral scores and physiological parameters from T0 (baseline) to T120. Statistical analyses included Chi-square, one-way ANOVA or Kruskal-Wallis, repeated measures or Friedman’s ANOVA, and Wilcoxon’s tests. Significance was p≤0.05.Onset of sedation was 12.9 ± 4.1, 18.2 ± 7.5, and 9.9 ± 4.3 mins (mean ± SD) for Dex, DexM, and DexK, respectively. Onset was shorter in DexK compared to DexM (p=0.002), explaining the lower behavioral scores in DexM at T15. All dogs in Dex and DexK reached adequate sedation, with peak sedation occurring at T30, while some dogs in DexM never reached adequate sedation and this group peaked at T45. Adverse events such as saliva drooling and pawing at the nose were significantly higher in DexM and DexK, explaining their differences in TA2, TAT, and EA1 comparing to Dex. EA2 was also higher in Dex compared to DexM and DexK. In conclusion, Dex was better tolerated in dogs and DexK showed faster and more profound sedative effects. Due to paradoxical excitement, unpredictable sedation, and nasal irritation, DexM is not recommended.

Caffeine and modafinil modulate the effects of sleep deprivation on thalamic resting-state functional connectivity: A double-blind pilot study

BackgroundStudies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. MethodsA double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. ResultsThe subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. ConclusionsAfter 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.

Common viral infections inhibit egg laying in honey bee queens and are linked to premature supersedure

With their long lives and extreme reproductive output, social insect queens have escaped the classic trade-off between fecundity and lifespan, but evidence for a trade-off between fecundity and immunity has been inconclusive. This is in part because pathogenic effects are seldom decoupled from effects of immune induction. We conducted parallel, blind virus infection experiments in the laboratory and in the field to interrogate the idea of a reproductive immunity trade-off in honey bee (Apis mellifera) queens and to better understand how these ubiquitous stressors affect honey bee queen health. We found that queens injected with infectious virus had smaller ovaries and were less likely to recommence egg-laying than controls, while queens injected with UV-inactivated virus displayed an intermediate phenotype. In the field, heavily infected queens had smaller ovaries and infection was a meaningful predictor of whether supersedure cells were observed in the colony. Immune responses in queens receiving live virus were similar to queens receiving inactivated virus, and several of the same immune proteins were negatively associated with ovary mass in the field. This work supports the hypothesized relationship between virus infection and symptoms associated with queen failure and suggests that a reproductive-immunity trade-off is partially, but not wholly responsible for these effects.

Transcutaneous cervical vagus nerve stimulation enhances second-language vocabulary acquisition while simultaneously mitigating fatigue and promoting focus

Transcutaneous vagus nerve stimulation (tVNS) is a promising technique for enhancing cognitive performance and skill acquisition. Yet, its efficacy for enhancing learning rate and long-term retention in an ecologically valid learning environment has not been demonstrated. We conducted two double-blind sham-controlled experiments examining the efficacy of auricular tVNS (taVNS: Experiment (1) and cervical tVNS (tcVNS: Experiment (2), on a 5 day second-language vocabulary acquisition protocol among highly selected career linguists at the US Department of Defense’s premier language school. tcVNS produced accelerated recall performance during training (Day 2–4), benefits of which were maintained across a 24 h retention interval with no stimulation at the final test. Consistent with prior work, tcVNS also produced fatigue-mitigating and focus-promoting effects as measured by the Air Force Research Laboratory Mood Questionnaire. Based on the current and the previous findings supporting tVNS’ efficacy on performance, training enhancement, and fatigue mitigation, we believe tcVNS to be an effective learning acceleration tool that can be utilized at language-teaching and other institutions focused on intensive training of cognitive skills.

Seeing the Truth About Double Blinding.

Randomized clinical trials provide reassurances that confounding factors are balanced at baseline whereas blinding is essential to assure the balance of extraneous factors thereafter. This article provides a three-part taxonomy of pitfalls that can arise because of inadequate blinding in clinical trials. We introduce a cautionary framework for readers interpreting a blinded randomized trial for evidence-based medicine. Each pitfall is illustrated with a relevant example of a potential bias resulting from knowledge of group assignment. Several pitfalls occur during the conduct of the study including inadequate blinding of the intervention group, control group, or responsible clinicians. Additional pitfalls relate to data analysis including unsubstantiated assertions of blinding and subverted tests for blinding. Further pitfalls arise due to surrounding oversight including unblinding of research ethics boards and scientific reviewers. These caveats are sources of misunderstanding when observing the apparent connection between a clinical intervention and patient outcomes. An awareness of specific pitfalls might help advance the interpretation and application of blinded randomized clinical trials to inform evidence-based medical care.

Intravesical bupivacaine in reducing catheter-related bladder discomfort and lower urinary tract symptoms after transurethral surgery: A randomized controlled trial.

The objectives of this study were to investigate the efficacy and safety of intravesical bupivacaine instillation in reducing catheter-related bladder discomfort (CRBD) and lower urinary tract symptoms (LUTS) after transurethral surgery. The study enrolled 100 American Society of Anesthesiologists (ASA) grade I-III patients aged ≥18 years undergoing transurethral resection of the prostate or transurethral resection of the bladder tumor, randomly assigned to Group B (intravesical bupivacaine) or Group S (saline). Double blinding was employed. Independent variables included demographics, surgery type, ASA grade, and intervention details. Dependent variables comprised CRBD severity, Patient Perception of Bladder Condition (PPBC), Pelvic Pain Urgency Frequency (PUF), Visual Analog Scale (VAS) for pain, need for additional analgesics, and International Prostate Symptom Score (IPSS). SPSS version 19 was used for analysis with a significance level of P < 0.05. Side effects such as hematuria were also recorded. Group B reported significantly lower "moderate" CRBD immediately (2% vs. 40%, P < 0.001) and at 12 h (0% vs. 18%, P = 0.003) post-instillation compared to Group S and also required fewer additional analgesics (4% vs. 46%). The PPBC at catheter removal also favored Group B (P = 0.003) and day 1 (P < 0.001). The PUF scores were also significantly lower in Group B at catheter removal (P = 0.001) and at day 1 (P = 0.028). The IPSS was also significantly lower in the Group B on day 1 (P = 0.003) and 7 (P = 0.001). The VAS scores also favored the Group B consistently and although the side effects were higher in Group B but this was not statistically significant. Intravesical bupivacaine administration has the potential to alleviate CRBD and postoperative LUTS following lower urinary tract transurethral electrosurgery. The study's findings underscore the importance of personalized pain management strategies in optimizing the patient comfort during the postoperative recovery.

Use of Placebo in Urologic Oncology Randomized Controlled Trials.

Use of placebo in oncology randomized controlled trials (RCT) is ethically controversial. Placebo may introduce bias, as toxicity profiles of treatment arms can inadvertently unblind subjects and investigators. We investigated the use of placebo in urologic oncology RCTs, hypothesizing that most placebo-controlled trials are effectively unblinded, either explicitly with open-label design or implicitly due to large differences in adverse events (AE) or oncologic outcomes. Urologic oncology RCTs utilizing placebo were identified via ClinicalTrials.gov. Interventional prostate, bladder/urothelial, and renal cancer trials from 2014 to 2024 were included. Subject incompletion, all-cause mortality, AE rates, and serious AE (SAE) rates were identified and compared between placebo and active arms using χ2 and Fisher's exact tests. Sixty studies met inclusion criteria and included 66 placebo arms with 12,918 subjects and 81 active arms with 16,098 subjects. There was no significant difference in incompletion rates between placebo and active arms. Subjects enrolled in active arms reported statistically significant higher SAE and AE rates compared to those in placebo arms across the majority of physiological domains, including 18/24 domains for SAEs and 13/24 for AEs. This relationship persisted in sensitivity analyses where unblinded trials were excluded. In urologic oncology placebo-controlled RCTs, active arms are associated with significantly higher rates of AEs and SAEs compared with placebo arms. These findings indicate a strong possibility that true blinding is not possible in oncology RCTs, even with optimal study design, and serve to better inform future clinical trial design and implementation challenges in employing placebo control.