Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer.

Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment.

Physical Fitness Among Adolescents Who are Hispanic With Overweight or Obesity.

PURPOSE: To describe cardiorespiratory, strength, muscular endurance, and flexibility fitness outcomes in a sample of adolescents who are Hispanic aged 11 to 15 years with overweight or obesity, stratified by age and sex. METHODS: The sample included 280 adolescents (mean age: 13.0 ± 0.83 years, mean body mass index percentile: 94.6). Anthropometric measures included height, weight, body mass index percentile, and waist and hip circumference. Fitness measures included handgrip strength, sit-ups in 60 seconds, sit-and-reach test, and 6-minute walk test. We report mean scores for each fitness outcome measure and correlation coefficients with anthropometric measures. RESULTS: Mean handgrip was 23.7 ± 6.48 kg, sit-and-reach test was 25.3 ± 8.13 cm, average sit-ups in 60 seconds were 19.4 ± 9.28, and 6-minute walk distance was 1960 ± 271 ft. Males outperformed females in all tests except sit-and-reach test. DISCUSSION: Compared with published fitness values of healthy weight adolescents, our sample of adolescents who are Hispanic with overweight/obesity living in southern Florida is unconditioned in terms of cardiorespiratory fitness, strength, muscular endurance, and flexibility.

Bariatric Surgery and Risk of Death in Persons With Chronic Kidney Disease.

OBJECTIVE: A retrospective cohort study investigated the association between having surgery and risk of mortality for up to 5 years and if this association was modified by incident ESRD during the follow-up period. Summary of Background Data: Mortality risk in individuals with pre-dialysis CKD is high and few effective treatment options are available. Whether bariatric surgery can improve survival in people with CKD is unclear. METHODS: Patients with class II and III obesity and pre-dialysis CKD stages 3-5 who underwent bariatric surgery between January 1, 2006 and September 30, 2015 (n = 802) were matched to patients who did not have surgery (n = 4933). Mortality was obtained from state death records and ESRD was identified through state-based or healthcare system-based registries. Cox regression models were used to investigate the association between bariatric surgery and risk of mortality and if this was moderated by incident ESRD during the follow-up period. RESULTS: Patients were primarily women (79%), non-Hispanic White (72%), under 65 years old (64%), who had a body mass index > 40kg/m 2 (59%), diabetes (67%), and hypertension (89%). After adjusting for incident ESRD, bariatric surgery was associated with a 79% lower 5-year risk of mortality compared to matched controls (hazard ratio = 0.21; 95% confidence interval: 0.14-0.32; P < 0.001). Incident ESRD did not moderate the observed association between surgery and mortality (hazard ratio = 1.59; 95% confidence interval: 0.31-8.23; P =0.58). CONCLUSIONS: Bariatric surgery is associated with a reduction in mortality in pre-dialysis patients regardless of developing ESRD. These findings are significant because patients with CKD are at relatively high risk for death with few efficacious interventions available to improve survival.

HIV-related drivers of sexual compulsivity and sexuality in sexual minority men who use methamphetamine.

Although co-occurring methamphetamine (meth) use and HIV amplify the risk for neuropsychiatric comorbidities, the underlying neuroimmune mechanisms are not well characterized. We examined whether a detectable viral load and dysregulated metabolism of amino acid precursors for neurotransmitters predicted subsequent levels of sexual compulsivity and sexual sensation seeking. This 15-month longitudinal study enrolled 110 sexual minority men (SMM) living with HIV who had biologically confirmed meth use (i.e., reactive urine or hair toxicology results). Peripheral venous blood samples collected at baseline, 6 months, 12 months, and 15 months were used to measure a detectable viral load (> 40 copies/mL), the kynurenine/tryptophan (K/T) ratio, and the phenylalanine/tyrosine (P/T) ratio. The K/T and P/T ratios index dysregulated serotonin and catecholamine (e.g., dopamine) synthesis, respectively. In a cross-lagged panel model, a detectable viral load at 6 months predicted greater sexual compulsivity at 12 months after adjusting for prior levels of sexual compulsivity and recent stimulant use (ß = 0.26, p = 0.046). A greater P/T ratio at baseline predicted decreased sexual sensation seeking at 6 months (ß = - 0.25, p = 0.004) after adjusting for baseline sexual sensation seeking and recent stimulant use. Taken together, HIV replication and dysregulated catecholamine synthesis could potentiate sexual compulsivity while decreasing sexual pleasure in SMM who use meth.

Psychological and physical intimate partner violence and sexual risk behavior among South African couples: a dyadic analysis.

This study aimed to examine intimate partner violence (IPV) as it relates to both partners' perceptions of IPV and sexual behaviors, considering how their IPV might be interdependent within the relationship dynamics. The sample consisted of 713 female-male dyads in which women were pregnant and living with HIV in rural South Africa. Using an actor-partner interdependence model (APIM), we examined the interdependent influence of psychological and physical IPV on men by their female partners and psychological and physical IPV on women by their male partners on sexual risk behavior. The APIM model found there were no actor (b = -0.06, SE = 0.05, p = .221) or partner (b = -1.2, SE = 0.06, p = .056) effects contributing to protected sex by female IPV victimization. In contrast, significant actor (b = -0.28, SE = 0.06, p < .001) and partner (b = -0.29, SE = 0.06, p < .001) effects for protection were related to male IPV victimization. The model also found that the covariate of female HIV disclosure was associated with both male (b = 0.5, SE = 0.12, p < .001) and female protected sexual intercourse (b = 0.58, SE = 0.1, p < .001). Female HIV disclosure was related to an increased likelihood of protected sex by both male and female partners. As male partners reported more IPV victimization, the likelihood of protected sex between male and female partners decreased.Trial registration: ClinicalTrials.gov identifier: NCT02085356.

Symptom burden profiles in men with advanced prostate cancer undergoing androgen deprivation therapy.

To identify symptom burden profiles among men with advanced prostate cancer undergoing androgen-deprivation therapy and examine their association with baseline sociodemographic and medical characteristics and psychosocial outcomes over time. Latent profile analysis was employed to identify distinct groups based on the Expanded Prostate Index Composite and the McGill Pain Questionnaire at baseline. Psychosocial outcomes were assessed at baseline, 6- and 12-month follow-ups. Three profiles emerged: "high symptom burden," "high sexual bother," and "low symptom burden." Men with "high symptom burden" were younger and exhibited higher baseline levels of depression, stress, cancer-specific distress, and anxiety than men in the other two groups. However, men with "high symptom burden" also demonstrated improvement in these psychosocial outcomes over time. Men with advanced prostate cancer who experience multiple co-occurring symptoms demonstrate worse psychosocial adjustment. Patients with substantial symptom burden, and specifically young men, may benefit from prompt referral to supportive care services.

Five-year Longitudinal Cohort Study of Reinterventions After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass.

OBJECTIVE: To compare the long-term risks of reintervention following sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in a large surgical cohort. BACKGROUND: The use of SG has increased dramatically relative to RYGB for the treatment of obesity. However, long-term risks following SG compared with RYGB have not been adequately defined in a large population-based study. METHODS: A retrospective longitudinal cohort study of all adult health-plan members undergoing SG or RYGB for obesity in a multistate integrated health care system from January 2005 through September 2015. The risks of nutritional, endoscopic, radiologic, and surgical reintervention as well as the overall risk of any reinterventions at 1, 3, and 5 years were identified using diagnosis and procedure codes from comprehensive electronic medical records. RESULTS: The study included 15,319 patients who underwent SG and 19,954 patients who underwent RYGB with a follow-up of 79.2%. The overall risk of any reintervention at 5 years was 21.3% for SG and 28.3% for RYGB (P < 0.0001). After adjustment, SG was associated with fewer reinterventions through 5 years than RYGB (hazard ratio, 0.78; 95% confidence interval, 0.74-0.84). When comparing subcategories, SG also had a lower risk of nutritional, endoscopic, radiologic, and surgical reinterventions when examined versus RYGB. The findings for risks of reinterventions were consistent across clinical subgroups. CONCLUSION: SG has significantly lower risk of reintervention in all categories studied when compared with RYGB at 5-year follow-up. The long-term safety profile of LSG compared with RYGB should be an essential part of the discussion in patient-centered decision making when choosing between bariatric procedure options.

Influence of Male Partners on HIV Disclosure Among South African Women in a Cluster Randomized PMTCT Intervention.

Disclosure of HIV serostatus is beneficial for women, their partners, and their infants as it enables women to actively participate in preventative care (Hodgson et al. in PLoS ONE 9(11):e111421, 2014; Odiachi et al. in Reprod Health 15(1):36, 2018). Therefore, it is important that interventions addressing HIV prevention include elements that foster disclosure of HIV to partners. This study conducted in South Africa utilizes the "Protect Your Family" (PYF) behavioral intervention and compares Prevention of Mother to Child Transmission (PMTCT) among women participating in the program versus those in a control program. Within both groups, male partners were either present or not present for the intervention. The purpose of this study was to examine differential disclosure over time for individuals in the different conditions and partner involvement. A firth logistic regression revealed an interaction in the experimental condition with male partners participating (b = - 2.84, SE = 1.56, p = .012), in which female participants were less likely to disclose their HIV status over time. Findings from this study illustrate that additional efforts are needed to empower women to disclose their HIV status.

RESUMEN: Revelar su estado serológico del VIH a sus parejas es beneficioso para las mujeres, sus parejas y sus bebés, ya que les permite a las mujeres participar activamente en atención preventiva (Hodgson et al. in PLoS ONE 9(11):e111421, 2014; Odiachi et al. in Reprod Health 15(1):36, 2018). Por lo tanto, es importante que las intervenciones que aborden la prevención del VIH incluyan elementos que fomenten la revelación del estado serológico del VIH de las mujeres a sus parejas. Este estudio realizado en Sudáfrica utiliza la intervención conductual "Protege a tu familia" (PYF por sus siglas en Ingles) y compara la prevención de la transmisión de madre a hijo (PMTCT por sus siglas en Ingles) entre mujeres que participaron en el programa y las que participaron en un programa de control. Dentro de ambos grupos, los compañeros masculinos estuvieron presentes o no presentes para la intervención. El propósito de este estudio fue examinar la revelación diferente a lo largo del tiempo para individuos en diferentes condiciones y participación de pareja. Una regresión logística reveló de Firth una interacción en la condición experimental con la participación de parejas masculinas (b = − 2.84, SE = 1.56, p = .012), en las cuales las participantes femeninas tenían menos probabilidades de revelar su estado de VIH a lo largo del tiempo. Los resultados de este estudio ilustran que se necesitan esfuerzos adicionales para motivar a las mujeres a revelar su estado de VIH.

Bariatric Surgical Alterations in Tolerability, Enjoyment and Cravings in the Diet (BSATED) instrument: A new scale to measure food preferences following bariatric surgery.

Bariatric surgery is associated with changing food preferences, but it is not known whether these changes differ by type of operation or are associated with weight loss. The current study presents validation results for a new 27-item scale, Bariatric Surgical Alterations in Tolerability, Enjoyment and Cravings in the Diet (BSATED). This scale measured enjoyment, craving, and intolerance changes for nine food and beverage categories common to dietary habits in the Southern California region of the U.S. one year following bariatric surgery in the Bariatric Experience Long Term (BELONG) study. Validation of BSATED was done using exploratory factor analyses, construct validity with other conceptually related survey instruments, and criterion validity using hypothesized differences for operation type and percent total weight loss (%TWL) at 12-18 months after surgery. Participants (n = 999) were 86% female, 41% non-Hispanic White, with a mean age of 43.1 ± 11.3 years and a body mass index (BMI) of 43.4 ± 6.8 kg/m2 at the time of surgery. Participants reported less enjoyment and craving for high-fat meats (62%), grains (54%), candy and other desserts (e.g. candy bars, chocolate, ice cream) (52%), and sweet baked goods (48%) 12 months after surgery. These changes were more common among participants undergoing Roux-en-Y gastric bypass (RYGB) compared to those receiving sleeve gastrectomy (SG). Participants who reported decreased enjoyment and craving for foods and beverages that post-bariatric patients are counseled to reduce or avoid had greater %TWL at 12-18 months following surgery (p < .001 and p = .003 respectively). The foods and beverages in BSATED that post-bariatric patients are counseled to reduce or avoid could be used to understand how changes in enjoyment, craving and tolerability of these foods/beverages contribute to weight loss following surgery.

Psychometric properties of an abbreviated Childhood Family Mealtime Questionnaire among overweight and obese Hispanic adolescents.

The current family mealtime literature shows that assessments of the mealtime environment are typically self-report, yet few studies discuss validation techniques or report using validated scales. As such, the current analysis was conducted to validate one of the only published measures to assess the mealtime environment from the adolescent perspective. Specifically, the Childhood Family Mealtime Questionnaire (CFMQ) was evaluated in a sample of 280 overweight and obese Hispanic adolescents to address the need for a validated measure of the family mealtime environment in a demographic that is disproportionately affected by the current obesity epidemic. Results of exploratory and confirmatory factor analyses to evaluate the optimal factor structure, reliability, and validity for a revised, abbreviated CFMQ are presented here. The concurrent validity of the CFMQ was evaluated using correlations between the factor structures and the previously used, culturally appropriate comparable measure of family functioning. Correlations were also computed between factor scores and obesogenic outcomes (fruit and vegetable intake, added sugar intake, and physical activity). Analyses produced a revised, abbreviated version that includes 22 items (reduced from a total of 69 items) and consists of the following 4 factors: family mealtime communication (5 items), family mealtime stress (7 items), appearance weight control (5 items), and mealtime structure (6 items). Cronbach's alphas are reported for reliability. When examining CFMQ concurrent validity with the family functioning latent variable, results showed the family mealtime communication subscale ranked highest. Additionally, the family mealtime communication subscale was associated with all three obesogenic outcomes. This abbreviated CFMQ may be a useful tool for those studying family mealtime environments and their influence on obesity and its associated lifestyle behaviors.

Strategies in the transfer of varying grades of vitrified-warmed blastocysts in women aged over 35 years: A propensity-matched analysis.

AIM: For in vitro fertilization, the optimal number of blastocysts to transfer according to blastocyst grade has not been well established, especially with respect to vitrified-warmed blastocyst transfer (VBT) in women aged over 35 years. This study aimed to compare the pregnancy and neonatal outcomes for three different VBT methods with variable numbers and qualities of blastocysts in women aged over 35 years. METHODS: All VBT cycles were categorized into three groups according to blastocyst grade: GG (two good-quality blastocysts transferred), GP (one good-quality blastocyst transferred with one of poor quality) and GS (one good-quality blastocyst transferred). Blastocysts graded greater than or equal to 3BB were considered good quality. We conducted three 1:1 propensity score-matched analyses (GG vs GS, GP vs GS and GG vs GP) to compare the clinical pregnancy rate (CPR), live birth rate (LBR), multiple pregnancy rate (MPR), preterm birth rate and low birthweight rate. RESULTS: Compared to GS, GG had higher CPR and LBR; however, MPR was also higher with GG. There were no significant differences, except implantation rate and MPR between GP and GS. Although implantation rate and CPR with GG were higher than those with GP, there were no significant differences in LBR and MPR. CONCLUSION: To reduce high MPR after double blastocyst transfer methods, single good-quality blastocyst transfers are recommended in the VBT of women aged over 35 years. Transferring a good blastocyst with a poor one should be avoided because it confers no advantage.

Proteolysis of virulence regulator ToxR is associated with entry of Vibrio cholerae into a dormant state.

Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI), a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP) in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human host. In this study, we show that ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline pH, a condition that occurs during the stationary phase of growth. This process involves the site-2 protease RseP (YaeL), and is dependent upon the RpoE-mediated periplasmic stress response, as deletion mutants for the genes encoding these two proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We determined that the loss of ToxR, genetically or by proteolysis, is associated with entry of V. cholerae into a dormant state in which the bacterium is normally found in the aquatic environment called viable but nonculturable (VBNC). Strains that can proteolyze ToxR, or do not encode it, lose culturability, experience a change in morphology associated with cells in VBNC, yet remain viable under nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot proteolyze ToxR remain culturable and maintain the morphology of cells in an active state of growth. Overall, our findings provide a link between the proteolysis of a virulence regulator and the entry of a pathogen into an environmentally persistent state.

The impact of race and ethnicity on rates of return to psychotherapy for depression.

BACKGROUND: There are many limitations with the evidence base for the role of race and ethnicity in continuation of psychotherapy for depression. METHODS: The study sample consisted of 242,765 patients ≥ 18 years old from six healthcare systems in the Mental Health Research Network (MHRN) who had a new episode of psychotherapy treatment for depression between 1/1/2010 and 12/31/2013. Data were from electronic medical records and organized in a Virtual Data Warehouse (VDW). The odds of racial and ethnic minority patients returning for a second psychotherapy visit within 45 days of the initial session were examined using multilevel regression. RESULTS: The sample was primarily middle aged (68%, 30-64 years old), female (68.5%), and non-Hispanic white (50.7%), had commercial insurance (81.4%), and a low comorbidity burden (68.8% had no major comorbidities). Return rates within 45 days of the first psychotherapy visit were 47.6%. Compared to their non-Hispanic white counterparts, racial and ethnic minority patients were somewhat less likely to return to psychotherapy for a second visit (adjusted odds ratios [aORs] ranged from 0.80 to 0.90). Healthcare system was a much stronger predictor of return rates (aORs ranged from 0.89 to 5.53), while providers accounted for 21.1% of the variance in return rates. CONCLUSIONS: Provider and healthcare system variation were stronger predictors of patient return to psychotherapy than race and ethnicity. More research is needed to understand why providers and healthcare systems determine psychotherapy return rates for patients of all racial and ethnic groups.

The Leukocyte Esterase Strip Test has Practical Value for Diagnosing Periprosthetic Joint Infection After Total Knee Arthroplasty: A Multicenter Study.

BACKGROUND: Leukocyte esterase (LE) was recently reported to be an accurate marker for diagnosing periprosthetic joint infection (PJI) as defined by the Musculoskeletal Infection Society (MSIS) criteria. However, the diagnostic value of the LE test for PJI after total knee arthroplasty (TKA), the reliability of the subjective visual interpretation of the LE test, and the correlation between the LE test results and the current MSIS criteria remain unclear. METHODS: This study prospectively enrolled 60 patients undergoing revision TKA for either PJI or aseptic failure. Serological marker, synovial fluid, and histological analyses were performed in all cases. The PJI group comprised 38 cases that met the MSIS criteria and the other 22 cases formed the aseptic group. All the LE tests were interpreted using both visual judgment and automated colorimetric reader. RESULTS: When "++" results were considered to indicate a positive PJI, the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were 84, 100, 100, 79, and 90%, respectively. The visual interpretation agreed with the automated colorimetric reader in 90% of cases (Cronbach α = 0.894). The grade of the LE test was strongly correlated with the synovial white blood cell count (ρ = 0.695) and polymorphonuclear leukocyte percentage (ρ = 0.638) and moderately correlated with the serum C-reactive protein and erythrocyte sedimentation rate. CONCLUSION: The LE test has high diagnostic value for diagnosing PJI after TKA. Subjective visual interpretation of the LE test was reliable and valid for the current battery of PJI diagnostic tests according to the MSIS criteria.

Intraoperative anaphylaxis to neuromuscular blocking agents: the incidence over 9 years at two tertiary hospitals in South Korea: A retrospective observational study.

BACKGROUND: Intraoperative anaphylaxis to neuromuscular blocking agents (NMBAs) is a rare event that is unpredictable and potentially life threatening. Most of the previous reports on such intraoperative anaphylaxis used market share surveys or self-reported data to estimate the incidence. OBJECTIVE: To determine the incidences of intraoperative anaphylaxis to NMBAs using electronic medical records. DESIGN: A retrospective observational study. SETTING: Two tertiary hospitals in South Korea. PATIENTS: This study involved patients exposed to NMBAs during anaesthesia between 1 January 2005 and 31 May 2014. Nineteen episodes were deemed to be intraoperative anaphylaxis to NMBAs. MAIN OUTCOME MEASURES: We calculated the incidences of intraoperative anaphylaxis to NMBAs. Exposure to the agents was determined from intraoperative records maintained in an electronic medical recording system. An anaphylactic reaction was determined from both clinical signs and the results of skin tests. RESULTS: Over 9 years, 729 429 patients were exposed to NMBA, the most frequently used being rocuronium [425 047 (58.3%)] and vecuronium [274 801 (37.7%)]. The overall incidence of intraoperative anaphylaxis was 2.6 per 100 000 (19 cases), and was higher with rocuronium (16 cases, 3.8 per 100 000) than with vecuronium (two cases, 0.7 cases per 100 000), P = 0.014. Comparing the first 3 years with the last 6 years, the incidence of intraoperative rocuronium anaphylaxis appeared to increase 1.4-fold (P = 0.006). CONCLUSION: Among commonly used NMBAs, rocuronium appears to have the highest incidence of anaphylaxis. Our findings suggest that future prospective investigation for NMBA-induced anaphylaxis should use internationally agreed skin test protocols.

A 24-48 h fed Amblyomma americanum tick saliva immuno-proteome.

BACKGROUND: Multiple tick saliva proteins, the majority of which are unknown, confer tick resistance in repeatedly infested animals. The objective of this study was to identify the 24-48 h fed Amblyomma americanum tick saliva immuno-proteome. The 24-48 h tick-feeding phase is critical to tick parasitism as it precedes important events in tick biology, blood meal feeding and disease agent transmission. Fed male, 24 and 96 h fed female phage display cDNA expression libraries were biopanned using rabbit antibodies to 24 and 48 h fed A. americanum female tick saliva proteins. Biopanned immuno-cDNA libraries were subjected to next generation sequencing, de novo assembly, and bioinformatic analysis. RESULTS: More than 800 transcripts that code for 24-48 h fed A. americanum immuno-proteins are described. Of the 895 immuno-proteins, 52% (464/895) were provisionally identified based on matches in GenBank. Of these, ~19% (86/464) show high level of identity to other tick hypothetical proteins, and the rest include putative proteases (serine, cysteine, leukotriene A-4 hydrolase, carboxypeptidases, and metalloproteases), protease inhibitors (serine and cysteine protease inhibitors, tick carboxypeptidase inhibitor), and transporters and/or ligand binding proteins (histamine binding/lipocalin, fatty acid binding, calreticulin, hemelipoprotein, IgG binding protein, ferritin, insulin-like growth factor binding proteins, and evasin). Others include enzymes (glutathione transferase, cytochrome oxidase, protein disulfide isomerase), ribosomal proteins, and those of miscellaneous functions (histamine release factor, selenoproteins, tetraspanin, defensin, heat shock proteins). CONCLUSIONS: Data here demonstrate that A. americanum secretes a complex cocktail of immunogenic tick saliva proteins during the first 24-48 h of feeding. Of significance, previously validated immunogenic tick saliva proteins including AV422 protein, calreticulin, histamine release factor, histamine binding/lipocalins, selenoproteins, and paramyosin were identified in this screen, supporting the specificity of the approach in this study. While descriptive, this study opens opportunities for in-depth tick feeding physiology studies.

Analysis of LhcSR3, a protein essential for feedback de-excitation in the green alga Chlamydomonas reinhardtii.

In photosynthetic organisms, feedback dissipation of excess absorbed light energy balances harvesting of light with metabolic energy consumption. This mechanism prevents photodamage caused by reactive oxygen species produced by the reaction of chlorophyll (Chl) triplet states with O2. Plants have been found to perform the heat dissipation in specific proteins, binding Chls and carotenoids (Cars), that belong to the Lhc family, while triggering of the process is performed by the PsbS subunit, needed for lumenal pH detection. PsbS is not found in algae, suggesting important differences in energy-dependent quenching (qE) machinery. Consistent with this suggestion, a different Lhc-like gene product, called LhcSR3 (formerly known as LI818) has been found to be essential for qE in Chlamydomonas reinhardtii. In this work, we report the production of two recombinant LhcSR isoforms from C. reinhardtii and their biochemical and spectroscopic characterization. We found the following: (i) LhcSR isoforms are Chl a/b- and xanthophyll-binding proteins, contrary to higher plant PsbS; (ii) the LhcSR3 isoform, accumulating in high light, is a strong quencher of Chl excited states, exhibiting a very fast fluorescence decay, with lifetimes below 100 ps, capable of dissipating excitation energy from neighbor antenna proteins; (iii) the LhcSR3 isoform is highly active in the transient formation of Car radical cation, a species proposed to act as a quencher in the heat dissipation process. Remarkably, the radical cation signal is detected at wavelengths corresponding to the Car lutein, rather than to zeaxanthin, implying that the latter, predominant in plants, is not essential; (iv) LhcSR3 is responsive to low pH, the trigger of non-photochemical quenching, since it binds the non-photochemical quenching inhibitor dicyclohexylcarbodiimide, and increases its energy dissipation properties upon acidification. This is the first report of an isolated Lhc protein constitutively active in energy dissipation in its purified form, opening the way to detailed molecular analysis. Owing to its protonatable residues and constitutive excitation energy dissipation, this protein appears to merge both pH-sensing and energy-quenching functions, accomplished respectively by PsbS and monomeric Lhcb proteins in plants.

Differences in cardiovascular and hypothalamic-pituitary-adrenal axis functions between high-altitude visitors and natives during a trek on the Annapurna circuit.

OBJECTIVE: Differences in the cardiovascular and hypothalamic-pituitary-adrenal (HPA) axis functions at high altitudes (HAs) between visitors to and natives of HA were examined. METHODS: The cardiovascular functions and peripheral oxygen saturation (SPO2) were monitored, and the cortisol awakening response (CAR) and nighttime cortisol concentration (NCC), as indices of the HPA axis function, were determined in 25 trekkers and 21 Sherpas during an Annapurna circuit trek. RESULTS: SPO2 decreased less in the Sherpas than in the trekkers at HAs (3,540, 3,800, and 4,800 m). Blood pressure and heart rate in the Sherpas changed concurrently during the trek; however, a tachycardic response occurred without changes in blood pressure in the trekkers at HAs. The CAR and NCC at HAs in the trekkers differed from those observed at 1,100 m and those observed at HAs in the Sherpas. The trekkers exhibited an elevated morning cortisol level at 3,540 and 3,800 m, a heightened CAR at 4,800 m, and an elevated NCC at 3,800 m. Alteration of the CAR resulted in an increase in the integrated volume of cortisol released within the first hour after awakening (CARauc) in the trekkers. The changes in SPO2 occurred concurrently with the changes in the CARauc and the heart rate in the trekkers. CONCLUSIONS: The alterations of CAR occurred at HAs where blood pressure levels reached a peak plateau, which is associated with an increase in heart rate at HAs in the trekkers. The CAR was unaltered in the Sherpas during the trek.