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Menaquinones (MK) are hydrophobic molecules that consist of a naphthoquinone headgroup and a repeating isoprenyl side chain and are cofactors used in bacterial electron transport systems to generate cellular energy. We have previously demonstrated that the folded conformation of truncated MK homologues, MK-1 and MK-2, in both solution and reverse micelle microemulsions depended on environment. There is little information on how MKs associate with phospholipids in a model membrane system and how MKs affect phospholipid organization. In this manuscript, we used a combination of Langmuir monolayer studies and molecular dynamics (MD) simulations to probe these questions on truncated MK homologues, MK-1 through MK-4 within a model membrane. We observed that truncated MKs reside farther away from the interfacial water than ubiquinones are are located closer to the phospholipid tails. We also observed that phospholipid packing does not change at physiological pressure in the presence of truncated MKs, though a difference in phospholipid packing has been observed in the presence of ubiquinones. We found through MD simulations that for truncated MKs, the folded conformation varied, but MKs location and association with the bilayer remained unchanged at physiological conditions regardless of side chain length. Combined, this manuscript provides fundamental information, both experimental and computational, on the location, association, and conformation of truncated MK homologues in model membrane environments relevant to bacterial energy production.

We sought to determine if 28 days of probiotic supplementation influenced the plasma amino acid (AA) response to acute whey protein feeding. METHODS: Twenty-two recreationally active men (n = 11; 24.3 ± 3.2 yrs; 89.3 ± 7.2 kg) and women (n = 11; 23.0 ± 2.8 yrs; 70.2 ± 15.2 kg) participated in this double-blind, placebo-controlled, randomized study. Before (PRE) and after 28 days of supplementation (POST), participants reported to the lab following a 10-hr fast and provided a resting blood draw (0 min), then subsequently consumed 25 g of whey protein. Blood samples were collected at 15-min intervals for 2 h post-consumption (15–120 min) and later analyzed for plasma leucine, branched-chain AA (BCAA), essential AA (EAA), and total AA (TAA). Participants received a probiotic (PROB) consisting of 1 x10-9 colony forming units (CFU) Bacillus subtilis DE111 (n = 11) or a maltodextrin placebo (PL) (n = 11) for 28 days. Plasma AA response and area under the curve (AUC) values were analyzed via repeated measures analysis of variance. RESULTS: Our analysis indicated no significant (p < 0.05) differential responses for plasma leucine, BCAA, EAA, or TAA between PROB and PL from PRE to POST. AUC analysis revealed no group × time interaction for plasma leucine (p = 0.524), BCAA (p = 0.345), EAA (p = 0.512), and TAA (p = 0.712). CONCLUSION: These data indicate that 28 days of Bacillus subtilis DE111 does not affect plasma AA appearance following acute whey protein ingestion.

This double-blind study examined effects of a protease enzyme blend (Prohydrolase®) added to whey protein on post-resistance exercise aminoacidemia and intramuscular anabolic signaling were investigated in ten resistance-trained males. Participants completed 4 sets of 8–10 repetitions in the leg press and leg extension exercises at 75% of 1-repetition maximum. Participants then consumed either 250 mg of Prohydrolase® + 26 g of whey protein (PW), 26 g whey alone (W), or non-nutritive control (CON) in counterbalanced order. Blood samples were obtained prior to exercise (baseline) and then immediately-post (IP), 30-, 60-, 90-, 120-, and 180-min post-exercise. Muscle biopsies were taken at baseline, 1-h (1H), and 3-h (3H) post-exercise. Phosphorylation of AKTSer437 was decreased (3H only: p < 0.001), mTORSer2448 was increased (1H: p = 0.025; 3H: p = 0.009), and p70S6KThr412 remained unchanged similarly for each condition. Plasma leucine, branch-chained amino acids, and essential amino acid concentrations for PW were significantly higher than CON (p < 0.05) at 30 min and similar to W. Compared to IP, PW was the only treatment with elevated plasma leucine levels at 30 min (p = 0.007; ∆ = 57.8 mmol/L, 95% Confidence Interval (CI): 20.0, 95.6) and EAA levels at 180 min (p = 0.003; ∆ = 179.1 mmol/L, 95% CI: 77.5, 280.7). Area under the curve amino acid analysis revealed no differences between PW and W. While no different than W, these data indicate that PW was the only group to produce elevated amino acid concentrations 30-min and 180-min post-ingestion.

Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.

Objective:Evidence suggests that the most consistent cognitive impairment found in individuals experiencing posttraumatic stress disorder symptomology is verbal memory impairment (Johnsen & Asbjornsen, 2008). More specifically, research has shown that patients with PTSD perform poorer on verbal memory tasks relating to logical (story) memory than on word memory tasks, such as CVLT-III (Barrera-Valencia et al., 2017). While recent literature accounts for memory impairments related to PTSD, less is known about this relationship for individuals with mere trauma exposure compared to individuals without trauma exposure. The present research aims to determine if there is a significant impact on WMS-LM when compared to CVLT-III for individuals in a community sample that have been exposed to a traumatic event in their lifetime.Participants and Methods:One hundred nineteen patients presented to a community-based practice for neuropsychological evaluation. Patients were screened for trauma exposure during a clinical interview. Immediate and long delay trials of Wechsler Memory Scale IV Logical Memory (WMS-LM) were used to examine structured learning and memory and the California Verbal Learning Test (CVLT-II) immediate and long delay recalls were used to examine unstructured learning and memory. Out of the 119 patients, 36 patients reported trauma exposure. Twenty-five were diagnosed as “normal,” 62 were diagnosed with mild cognitive impairment, and 32 were diagnosed with dementia. A one-way MANOVA was conducted to examine the relationship across the multiple dependent variables.Results:There was a statistically significant difference in immediate recall in memory based on exposure to trauma, F (2, 116) = 3.28, p < .05; Wilk’s A = 0.947, partial n2 = .53, such that individuals with trauma exposure performed better. For long delay recall performance, there was a similar trend though it did not reach statistical significance F (2, 114) = 3.03, p = .052; Wilk’s A = 0.949, partial n2 = .51.Conclusions:Data showed that patients who reported trauma exposure scored significantly higher on immediate recall performance on CVLT and WMS-LM than those who did not report trauma exposure. Although research suggests that patients who were exposed to trauma often experience cognitive deficits on verbal memory tasks, evidence also shows that trauma exposure can lead to higher immediate recall performance in memory related to attentional allocation modeling (Hayes et al., 2012).

Introduction: Blood pressure (BP) monitoring is an essential component of sepsis management. The Surviving Sepsis Guidelines recommend invasive arterial BP (IABP) monitoring, although the benefits over non-invasive BP (NIBP) monitoring are unclear. This study investigated discrepancies between IABP and NIBP measurement and their clinical significance. We hypothesized that IABP monitoring would be associated with changes in management among patients with sepsis requiring vasopressors. Methods: We performed a retrospective study of adult patients admitted to the critical care resuscitation unit at a quaternary medical center between January 1–December 31, 2017. We included patients with sepsis conditions AND IABP monitoring. We defined a clinically significant BP discrepancy (BPD) between NIBP and IABP measurement as a difference of > 10 millimeters of mercury (mm Hg) AND change of BP management to maintain mean arterial pressure ≥ 65 mm Hg. Results: We analyzed 127 patients. Among 57 (45%) requiring vasopressors, 9 (16%) patients had a clinically significant BPD vs 2 patients (3% odds ratio [OR] 6.4; 95% CI: 1.2-30; P = 0.01) without vasopressors. In multivariable logistic regression, higher Sequential Organ Failure Assessment (SOFA) score (OR 1.33; 95% CI: 1.02-1.73; P = 0.03) and serum lactate (OR 1.27; 95% CI: 1.003-1.60, P = 0.04) were associated with increased likelihood of clinically significant BPD. There were no complications (95% CI: 0-0.02) from arterial catheter insertions. Conclusion: Among our population of septic patients, the use of vasopressors was associated with increased odds of a clinically significant blood pressure discrepancy between IABP and NIBP measurement. Additionally, higher SOFA score and serum lactate were associated with higher likelihood of clinically significant blood pressure discrepancy. Further studies are needed to confirm our observations and investigate the benefits vs the risk of harm of IABP monitoring in patients with sepsis.

Indian rhesus macaques are vaccinated with simian immunodeficiency virus (SIV)-restricted CD8 + T-cell epitopes, and these vaccinated animals are shown to mediate elite control of virus replication. Making more of natural resistance to HIV Indian rhesus macaques expressing the Mamu-B * 08 molecule, which has important structural similarities to the human leukocyte antigen class I molecule HLA-B * 27, show a degree of control over the highly pathogenic SIVmac239 virus. This system provides a model for the rare cases in which people with HIV achieve 'elite control' over the virus. Here, David Watkins and colleagues show that vaccine-induced CD8 + T cells narrowly directed against three immunodominant T-cell epitopes bound by Mamu-B * 08 (Vif RL8, Vif RL9 and Nef RL10) can control the replication of SIVmac239 in Mamu-B * 08 + macaques. This work could provide pointers to the development of vaccines capable of achieving long-term control over HIV. Developing a vaccine for human immunodeficiency virus (HIV) may be aided by a complete understanding of those rare cases in which some HIV-infected individuals control replication of the virus 1 , 2 , 3 . Most of these elite controllers express the histocompatibility alleles HLA-B*57 or HLA-B*27 (ref. 3 ). These alleles remain by far the most robust associations with low concentrations of plasma virus 4 , 5 , yet the mechanism of control in these individuals is not entirely clear. Here we vaccinate Indian rhesus macaques that express Mamu-B*08 , an animal model for HLA-B*27-mediated elite control 6 , with three Mamu-B*08-restricted CD8 + T-cell epitopes, and demonstrate that these vaccinated animals control replication of the highly pathogenic clonal simian immunodeficiency virus (SIV) mac239 virus. High frequencies of CD8 + T cells against these Vif and Nef epitopes in the blood, lymph nodes and colon were associated with viral control. Moreover, the frequency of the CD8 + T-cell response against the Nef RL10 epitope (Nef amino acids 137–146) correlated significantly with reduced acute phase viraemia. Finally, two of the eight vaccinees lost control of viral replication in the chronic phase, concomitant with escape in all three targeted epitopes, further implicating these three CD8 + T-cell responses in the control of viral replication. Our findings indicate that narrowly targeted vaccine-induced virus-specific CD8 + T-cell responses can control replication of the AIDS virus.

Objective:Neuropsychological measures of verbal fluency help detect cognitive decline and neuropathology. The discrepancy between semantic verbal fluency and phonemic verbal fluency is commonly utilized to differentiate between cortical and subcortical processes. Understanding how other factors influence a patient’s verbal fluency scores is vital in informing clinical interpretation of neuropsychological test data. This study aimed to investigate how educational attainment and crystalized verbal skills (i.e., word reading and vocabulary) influence verbal fluency performance among a clinical sample of patients seen for neuropsychological evaluation services at a community-based outpatient neurology clinic.Participants and Methods:We utilized data from N=26 patients [mean age = 50.5 (SD = 22.0), 31% female, mean education = 13.5 (SD = 2.3)] who completed neuropsychological evaluations as part of their clinical care at an outpatient neurology clinic. Participants were included in this study if they had complete data for all variables of interest. We used Pearson correlation analyses to investigate associations between each predictor variable of interest (years of education, WRAT-5 Reading, WASI-2 Vocabulary) and age-norm corrected D-KEFS Verbal Fluency scores. Prior to analysis, all variables were converted to z-scores.Results:We found that years of education (r = 0.49, p = 0.01) and vocabulary (r = 0.41, p = 0.04) were significantly positively correlated with category fluency performance. Reading was also positively correlated with category fluency at trend level, but this association was not statistically significant (r = 0.36, p = 0.07). We found that vocabulary (r = 0.47, p = 0.02) and reading (r = 0.51, p = 0.007) were significantly positively correlated with phonemic fluency performance, while the association between education and phonemic verbal fluency performance was not significant (r = 0.27, p = 0.18).Conclusions:Our results suggest that educational attainment and crystalized verbal skills are positively associated with verbal fluency performance, though the degree of influence of these individual factors may differ for category fluency vs phonemic fluency performance. Our results have implications for the clinical practice of neuropsychology. Namely, appreciating a patient’s educational attainment and crystalized verbal skills can help guide clinical interpretation of whether or not a patient’s verbal fluency test scores reflect a decline from their baseline. This may be particularly important to consider among patients with high educational attainment or high premorbid verbal skills, as a subtle decline in their verbal fluency abilities may not be appreciated if relying only on age-based norms for interpretation. This is clinically relevant including when assessing for the early stages of neurodegenerative disorders (e.g., Alzheimer’s disease, Primary Progressive Aphasia) or for subtle changes associated with stroke or brain injury.

Examining ways to support persons with dementia and their caregivers to help minimize the disease's impact on individuals, families, and society is critical. One emerging avenue for support is technology (eg, smartphones and smart homes). Given the increasing presence of technology in caregiving, it is pertinent to appreciate whether and how technology can be most useful to a care partner's everyday life. This study aims to further understand care partner technology use, attitudes, and the potential role of off-the-shelf technologies (eg, smartphones and smart homes) in supporting caregiving from the perspective of care partners for persons with dementia. We conducted a telephone cross-sectional survey using random digit dialing with 67 self-identified care partners of persons with dementia across one Canadian province. Participants were asked about attitudes toward technology, barriers to and facilitators for technology use, technology use with caregiving, and demographic information. Eight open-ended questions were analyzed using content analysis; 2 closed-ended questions about comfort with and helpfulness of technology (rated on a scale of 1 to 10) were analyzed with frequencies. From these data, an in-depth semistructured interview was created, and 10 (15%) randomly sampled care partners from the initial collection of 67 care partners were interviewed approximately 1 year later, with responses analyzed using content analysis. Frequency analysis rated on a scale of 1 to 10 suggested that care partners were comfortable with technology (wearable technology mean 7.94, SD 2.02; smart home technology mean 6.94, SD 2.09), although they rated the helpfulness of technology less strongly (mean 5.02, SD 2.85). Qualitatively, care partners described using technology for functional tasks and some caregiving. Barriers to technology use included cost, lack of knowledge, security or privacy concerns, and undesirable features of technology. Facilitators included access to support and the presence of desirable features. Some care partners described merging technology with caregiving and reported subsequent benefits. Others stated that technology could not be adopted for caregiving due to the degree of impairment, fear of negative consequences for the person living with dementia, or due to incongruity with the caregiving philosophy. Furthermore, care partners noted that their technology use either increased or was unchanged as they moved through the COVID-19 pandemic. The 2 analyses were conducted separately, but there was notable overlap in the data, suggesting temporal stability of identified content. Both analyses suggested care partners' relative comfort with technology and its use, but other care partners noted concerns about integrating technology and caregiving. Care partners' reports of increased technology use throughout the COVID-19 pandemic may also suggest that the pandemic impacted their perceptions of the usefulness of technology, being influenced by the requirements of their reality. Future investigations should examine how to support care partners in adopting relevant technology.