High-performance liquid chromatography of HIV protease inhibitors in human biological matrices

Methods for HPLC analysis of protease inhibitors (PIs) in human biological matrices were reviewed. Assays have been developed for analysis of single PIs or for simultaneous measurement of multiple PIs in plasma-serum, saliva, cerebrospinal fluid and semen. Liquid-liquid extraction was most often applied for sample pretreatment, but solid-phase extraction and protein precipitation were used as well. Reversed-phase or ion-pair chromatography have been used to separate PIs. Detection of PIs should be sensitive enough for quantitation of plasma concentrations below trough levels of single PIs, or below proposed therapeutic thresholds for PIs. The large majority of assays employs UV detection. As the potential for interferences is large, the selectivity of every method should be evaluated properly. The available high-performance liquid chromatography (HPLC) methods have been applied in clinical pharmacokinetic studies and for therapeutic drug monitoring of PIs. Participation in an interlaboratory quality control program is recommended for every laboratory engaged in the bioanalysis of PIs.     

Golf Performance Enhancement and Real-Life Neurofeedback Training Using Personalized Event-Locked EEG Profiles

Background. This study reports on a new method for golf performance enhancement employing personalized real-life neurofeedback during golf putting.

Method. Participants (n = 6) received an assessment and three real-life neurofeedback training sessions. In the assessment, a personal event-locked electroencephalographic (EEG) profile at FPz was determined for successful versus unsuccessful putts. Target frequency bands and amplitudes marking optimal prefrontal brain state were derived from the profile by two raters. The training sessions consisted of four series of 80 putts in an ABAB design. The feedback in the second and fourth series was administered in the form of a continuous NoGo tone, whereas in the first and third series no feedback was provided. This tone was terminated only when the participants EEG met the assessment-defined criteria. In the feedback series, participants were instructed to perform the putt only after the NoGo tone had ceased.

Results. From the personalized event-locked EEG profiles, individual training protocols were established. The interrater reliability was 91%. The overall percentage of successful putts was significantly larger in the second and fourth series (feedback) of training compared to the first and third series (no feedback). Furthermore, most participants improved their performance with feedback on their personalized EEG profile, with 25% on average.

Conclusions. This study demonstrates that the “zone” or the optimal mental state for golf putting shows clear recognizable personalized patterns. The learning effects suggest that this real-life approach to neurofeedback improves learning speed, probably by tapping into learning associated with contextual conditioning rather than operant conditioning, indicating perspectives for clinical applications.     

Layer-specific diffusion weighted imaging in human primary visual cortex in vitro

One of the most prominent characteristics of the human neocortex is its laminated structure. The first person to observe this was Francesco Gennari in the second half the 18th century: in the middle of the depth of primary visual cortex, myelinated fibres are so abundant that he could observe them with bare eyes as a white line. Because of its saliency, the stria of Gennari has a rich history in cyto- and myeloarchitectural research as well as in magnetic resonance (MR) microscopy. In the present paper we show for the first time the layered structure of the human neocortex with ex vivo diffusion weighted imaging (DWI). To achieve the necessary spatial and angular resolution, primary visual cortex samples were scanned on an 11.7 T small-animal MR system to characterize the diffusion properties of the cortical laminae and the stria of Gennari in particular. The results demonstrated that fractional anisotropy varied over cortical depth, showing reduced anisotropy in the stria of Gennari, the inner band of Baillarger and the deepest layer of the cortex. Orientation density functions showed multiple components in the stria of Gennari and deeper layers of the cortex. Potential applications of layer-specific diffusion imaging include characterization of clinical abnormalities, cortical mapping and (intra)cortical tractography. We conclude that future high-resolution in vivo cortical DWI investigations should take into account the layer-specificity of the diffusion properties.     

BCG-induced trained immunity in NK cells: Role for non-specific protection to infection

Adaptive features of innate immunity, also termed ‘trained immunity’, have recently been shown to characterize monocytes of BCG vaccinated healthy volunteers. Trained immunity leads to increased cytokine production in response to non-related pathogens via epigenetic reprogramming of monocytes. Recently, memory-like properties were also observed in NK cells during viral infections, but it is unknown if memory properties of NK cells contribute to trained immunity due to BCG vaccination.     

Testing the effects on information use by older versus younger women of modality and narration style in a hospital report card

BackgroundHospital report cards (HRCs) are usually presented in a textual and factual format, likely hampering information processing.ObjectiveThis study aimed to investigate the effects of audiovisual and narrative information in HRCs on user responses, and to test differences between older and younger women.DesignA 2 (modality [textual vs. audiovisual]) × 3 (narration style [factual vs. process narrative vs. experience narrative]) online experiment was conducted. Information about breast cancer care was used as a case example. Age (younger [<65] vs. older [≥65]) was included as a potential effect modifier.Setting and ParticipantsA total of 631 disease‐naïve women (M _age = 56.06) completed an online survey. The outcomes were perceived cognitive load, satisfaction, comprehension, information recall and decisional conflict. Data were analysed using AN(C)OVAs.ResultsAudiovisual (vs. textual) information resulted in higher information satisfaction across age groups, but was associated with lower comprehension in older women. An experience narrative (vs. factual information) increased satisfaction with attractiveness and emotional support of the information only in older women. A three‐way interaction effect was found, suggesting that older women were most satisfied with the comprehensibility of audiovisual factual or textual process narrative information. Younger women were most satisfied with the comprehensibility of audiovisual process narrative or textual factual information.Discussion and ConclusionAudiovisual and narrative information in an HRC showed beneficial effects on satisfaction measures. In particular, audiovisual information could be incorporated into HRCs to increase satisfaction with information.Public ContributionLay persons helped in optimizing the visuals used in the stimulus materials by checking for clarity.     

Factors which influence the rate of receiving a routine second newborn screening test in Washington State

This study was conducted to determine whether newborns from different ethnic and socioeconomic groups in Washington State are equally likely to have a routine second newborn screening (NBS) test and if there are identifiable factors associated with not having a second test. For many years, the standard of care for NBS in Washington has been that newborns should receive a routine second screening test at age 7–10 days. However, data collected by State Department of Health (DOH) staff for the past several years indicate that only about 80% of newborns receive a routine second NBS test. The data presented here suggest that identifiable factors (i.e., barriers) exist in accessing a routine second NBS test in Washington. Increased educational efforts targeting certain high-risk infants, their parents/caretakers, and primary care providers are apparently needed to ensure equal access to a routine second test. © 1995 Wiley-Liss, Inc.     

Rats assess costs and benefits according to an internal standard

Variation in effort to obtain rewards is a fact of mammalian everyday life. In this study, we assess how rats scale variable costs and benefits. Different groups of rats were trained in a T-maze to discriminate a high (three or five sugar pellets) from a low reward (one sugar pellet) arm. Subsequently barriers were introduced at the high and low reward side such that the overall long-term pay-off of the high reward arm finally became lower than that of the low reward arm. The data show that under different regimes of costs (climbing barriers) and benefits (number of rewards) of the two arms rats appear to shift their behaviour towards the better side according to a constant relative cost-benefit ratio between the arms. Such a ratio allows them to deal with variation in the (physical appearance of) costs and benefits and choose the best long-term option.     

Implementation,participation and satisfaction rates of a web-based decision support tool for patients with metastatic colorectal cancer

ObjectiveTo examine implementation and patients’ and providers’ participation and satisfaction of a newly developed decision support tool (DST) for patients with metastatic colorectal cancer (mCRC) in palliative setting.MethodsOur DST consisted of a consultation sheet and web-based tailored information for mCRC treatment options. We conducted an implementation trajectory in 11 Dutch hospitals and evaluated implementation, participation and satisfaction rates.ResultsImplementation rates fluctuated between 3 and 72 handed out (median:23) consultation sheets per hospital with patients’ login rates between 36% and 83% (median:57%). The majority of patients (68%) had (intermediate)-high participation scores. The median time spent using the DST was 38 min (IQR:18–56) and was highest for questions concerning patients’ perspective (5 min). Seventy-six% of patients were (very) satisfied. The provider DST rating was 7.8 (scale 1–10) and participation ranged between 25 and 100%. Remaining implementation thresholds included providers’ treatment preferences, resistance against shared decision-making and (over)confidence in shared decision-making concepts already in use.ConclusionWe implemented a DST with sufficient patient and oncologist satisfaction and high patient participation, but participation differed considerably between hospitals suggesting unequal adoption of our tool.Practice implicationsRequirements for structural implementation are to overcome remaining thresholds and increase awareness for additional decision support.     

The Effect of A Geriatric Assessment on Treatment Decisions for Patients with Lung Cancer

Background

Decision-making for older patients with lung cancer can be complex and challenging. A geriatric assessment (GA) may be helpful and is increasingly being used since 2005 when SIOG advised to incorporate this in standard work-up for the elderly with cancer. Our aim was to evaluate the value of a geriatric assessment in decision-making for patients with lung cancer.

Methods

Between January 2014 and April 2016, data on patients with lung cancer from two teaching hospitals in the Netherlands were entered in a prospective database. Outcome of geriatric assessment, non-oncologic interventions, and suggested adaptations of oncologic treatment proposals were evaluated.

Results

83 patients (median age 79 years) were analyzed with a geriatric assessment, of which 59% were treated with a curative intent. Half of the patients were classified as ECOG PS 0 or 1. The majority of the patients (78%) suffered from geriatric impairments and 43% (n?=?35) of the patients suffered from three or more geriatric impairments (out of eight analyzed domains). Nutritional status was most frequently impaired (52%). Previously undiagnosed impairments were identified in 58% of the patients, and non-oncologic interventions were advised for 43%. For 33% of patients, adaptations of the oncologic treatment were proposed. Patients with higher number of geriatric impairments more often were advised a reduced or less intensive treatment (p?<?0.001).

Conclusion

A geriatric assessment uncovers previously unknown health impairments and provides important guidance for tailored treatment decisions in patients with lung cancer. More research on GA-stratified treatment decisions is needed.