The synthesis of solid supports carrying base labile linkers to generate 3'-phosphate oligonucleotides.

Oligonucleotides carrying 3'-terminal phosphates and conjugates are important tools in molecular biology and diagnostic purposes. We described the preparation of solid supports carrying the base labile linker 4-((2-hydroxyethyl)sulfonyl)benzamide for the solid-phase synthesis of 3'-phosphorylated oligonucleotides. These supports are fully compatible with the phosphoramidite chemistry yielding the desired 3'-phosphate oligonucleotides in excellent yields. The use of mild deprotection conditions allows the generation of partially protected DNA fragments.

Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala.

Astrocytes release gliotransmitters via connexin 43 (Cx43) hemichannels into neighboring synapses, which can modulate synaptic activity and are necessary for fear memory consolidation. However, the gliotransmitters released, and their mechanisms of action remain elusive. Here, we report that fear conditioning training elevated Cx43 hemichannel activity in astrocytes from the basolateral amygdala (BLA). The selective blockade of Cx43 hemichannels by microinfusion of TAT-Cx43L2 peptide into the BLA induced memory deficits 1 and 24 h after training, without affecting learning. The memory impairments were prevented by the co-injection of glutamate and D-serine, but not by the injection of either alone, suggesting a role for NMDA receptors (NMDAR). The incubation with TAT-Cx43L2 decreased NMDAR-mediated currents in BLA slices, effect that was also prevented by the addition of glutamate and D-serine. NMDARs in primary neuronal cultures were unaffected by TAT-Cx43L2, ruling out direct effects of the peptide on NMDARs. Finally, we show that D-serine permeates through purified Cx43 hemichannels reconstituted in liposomes. We propose that the release of glutamate and D-serine from astrocytes through Cx43 hemichannels is necessary for the activation of post-synaptic NMDARs during training, to allow for the formation of short-term and subsequent long-term memory, but not for learning per se.

Resonant Fragmentation of the Water Cation by Electron Impact: a Wave-Packet Study.

We have investigated the dissociation of a resonant state that can be formed in low energy electron scattering from H2 O+ . We have chosen the second triplet resonance above the B ˜ 2 A ' ${{{\tilde{\rm {B}}}}\;^2 {\rm{A{^\prime}}}}$ ( B ˜ 2 B 2 ) ${{\rm{(\tilde{B}}}\;^2 {\rm{B}}_2 )}$ state of H2 O+ whose autoionization mainly produces H2 O+ ( X ˜ 2 A ' ' ${{{\tilde{\rm {X}}}}\;^2 {\rm{A{^\prime}{^\prime}}}}$ ). We have considered both dissociation of the resonant state itself, dissociative recombination (DR), or the dissociation of the H2 O+ cation after autodetachment, dissociative excitation (DE). The time-evolution of a wave packet on the potential energy surfaces of the resonance and cationic states shows, for the initial conditions studied, that the probability for DR is about 38 % while the probability for DE is negligible.

H2O˙+ and OH+ reactivity versus furan: experimental low energy absolute cross sections for modeling radiation damage.

Radiotherapy is one of the most widespread and efficient strategies to fight malignant tumors. Despite its broad application, the mechanisms of radiation-DNA interaction are still under investigation. Theoretical models to predict the effects of a particular delivered dose are still in their infancy due to the difficulty of simulating a real cell environment, as well as the inclusion of a large variety of secondary processes. This work reports the first experimental study of the ion-molecule reactions of the H2O˙+ and OH+ ions, produced by photoionization with synchrotron radiation, with a furan (c-C4H4O) molecule, a template for deoxyribose sugar in DNA. The present experiments, performed as a function of the collision energy of the ions and the tunable photoionization energy, provide key parameters for the theoretical modelling of the effect of radiation dose, like the absolute cross sections for producing protonated furan (furanH+) and a radical cation (furan˙+), the most abundant products, which can amount up to 200 Å2 at very low collision energies (<1.0 eV). The experimental results show that furanH+ is more fragile, indicating how the protonation of the sugar component of the DNA may favor its dissociation with possible major radiosensitizing effects. Moreover, the ring opening of furanH+ isomers and the potential energy surface of the most important fragmentation channels have been explored by molecular dynamics simulations and quantum chemistry calculations. The results show that, in the most stable isomer of furanH+, the ring opening occurs via a low energy pathway with carbon-oxygen bond cleavage, followed by the loss of neutral carbon monoxide and the formation of the allyl cation CH2CHCH2+, which instead is not observed in the fragmentation of furan˙+. At higher energies the ring opening through the carbon-carbon bond is accompanied by the loss of formaldehyde, producing HCCCH2+, the most intense fragment ion detected in the experiments. This work highlights the importance of the secondary processes, like the ion-molecule reactions at low energies in the radiation damage due to their very large cross sections, and it aims to provide benchmark data for the development of suitable models to approach this low collision energy range.

Gas-phase formation of glycolonitrile in the interstellar medium.

Our automated reaction discovery program, AutoMeKin, has been utilized to investigate the formation of glycolonitrile (HOCH2CN) in the gas phase under the low temperatures of the interstellar medium (ISM). The feasibility of a proposed pathway depends on the absence of barriers above the energy of reactants and the availability of the suggested precursors in the ISM. Based on these criteria, several radical-radical reactions and a radical-molecule reaction have been identified as viable formation routes in the ISM. Among the radical-radical reactions, OH + CH2CN appears to be the most relevant, considering the energy of the radicals and its ability to produce glycolonitrile in a single step. However, our analysis reveals that this reaction produces hydrogen isocyanide (HNC) and formaldehyde (CH2O), with rate coefficients ranging from (7.3-11.5) × 10-10 cm3 molecule-1 s-1 across the temperature range of 10-150 K. Furthermore, the identification of this remarkably efficient pathway for HNC elimination from glycolonitrile significantly broadens the possibilities for any radical-radical mechanism proposed in our research to be considered as a feasible pathway for the formation of HNC in the ISM. This finding is particularly interesing given the persistently unexplained overabundance of hydrogen isocyanide in the ISM. Among the radical-molecule reactions investigated, the most promising one is OH + CH2CHNH, which forms glycolonitrile and atomic hydrogen with rate coefficients in the range (0.3-6.6) × 10-10 cm3 molecule-1 s-1 within the 10-150 K temperature range. Our calculations indicate that the formation of both hydrogen isocyanide and glycolonitrile is efficient under the harsh conditions of the ISM.

Iodine Intake Based on a Survey from a Cohort of Women at Their Third Trimester of Pregnancy from the Bosque County Chile.

Adequate iodine nutrition is fundamental for all humans and is critical during pregnancy and lactation due to iodine forms part of the structure of thyroid hormones (THs) and it is required for THs function. Iodine is a scarce micronutrient that must be obtained from the diet. Sufficient iodine can be found in the nature from seafood and given it is not frequently consumed by Chileans, public health policies state that table salt in Chile must be iodized. Health plans must be monitored to determine if the intake of iodine is being appropriated and the population has not fallen in deficiency or excess. The aim of this work was to evaluate iodine intake in 26 women at the third trimester of pregnancy. Pregnant women are resident from El Bosque a low-income County located in Santiago de Chile. These Chilean pregnant women were recruited by nutritionist at the Centros de Salud familiar (CESFAM). A 24 h dietary recall (24 h-DR) was applied to them to evaluate iodine intake. Samples of urine and blood were taken by health professionals to analyze parameters of thyroid function and to measure urine iodine concentration (UIC). The survey analysis showed that the iodine consumption in these pregnant women derived mainly from salt, bread and milk and not from seafood. The survey analysis indicated that iodine intake was above the requirements for pregnant women. However, the average UIC indicated that iodine intake was adequate, suggesting the need to find a better parameter to determine iodine intake in pregnant women.

Transforming entomology to adapt to global concerns: 2021 student debates.

The 2021 Student Debates of the Entomological Society of America (ESA) were held at the Annual Meeting in Denver, CO. The event was organized by the Student Debates Subcommittee (SDS) of the Student Affairs Committee (SAC). The theme of the 2021 Student Debates was "Transforming Entomology to Adapt to Global Concerns", with 3 topics. Each topic had an unbiased introduction and 2 teams. The debate topics were (i) Nonnative insect introduction is an ethical approach for counteracting proliferation and overpopulation of consumers, (ii) What is the best technology to control undesirable insect pests in urban and agricultural settings? and (iii) Compared to other solutions, like plant-based diets, insect farming is the best method to address rising human global food and nutrient supply demands. Unbiased introduction speakers and teams had approximately 6 months to prepare for their presentations.

Charge Transfer and Electron Production in Proton Collisions with Uracil: A Classical and Semiclassical Study.

Cross sections for charge transfer and ionization in proton-uracil collisions are studied, for collision energies 0.05

LDPE Transformation by Exposure to Sequential Low-Pressure Plasma and TiO2/UV Photocatalysis.

Low-density polyethylene (LDPE) sheets (3.0 ± 0.1 cm) received sequential treatment, first by the action of direct-current low-pressure plasma (DC-LPP) with a 100% oxygen partial pressure, 3.0 × 10-2 mbar pressure, 600 V DC tension, 5.6 cm distance, 6-min treatment. Then, sheets were submitted to TiO2 photocatalysis at UV radiation at 254 nm (TiO2/UV) with a pH value of 4.5 ± 0.2 and a TiO2 concentration of 1 gL-1. We achieved a complementary effect on the transformation of LDPE films. With the first treatment, ablation was generated, which increased hydrophilicity. With the second treatment, the cavities appeared. The changes in the LDPE sheets' hydrophobicity were measured using the static contact angle (SCA) technique. The photocatalytic degradation curve at 400 h revealed that the DC-LPP photocatalysis sequential process decreased SCA by 82°. This was achieved by the incorporation of polar groups, which increased hydrophilicity, roughness, and rigidity by 12 and 38%, respectively. These sequential processes could be employed for LDPE and other material biodegradation pretreatment.

Patient exposure and diagnostic reference levels in operating rooms: a multi-centric retrospective study in over 150 private and public French clinics.

To investigate patient exposure in operating rooms and establish Diagnostic Reference Levels (DRLs), fifteen different procedures and nearly 4500 surgeries performed between January 2017 and December 2019 at over 150 different private (79% of data) and public (21% of data) French clinics were recorded. Collected information include the used C-arm equipment, exposure parameters (kVp, mAs, Fluoroscopy Time - FT and Air Kerma-Area Product - PKA) and patient Body Mass Index (BMI) whenever available. Multi-centric DRLs were derived as the 75th percentile of the median exposure data collected in more than 10 different hospitals. For the less frequent procedures, DRLs were determined as the 75th percentile of pooled exposure data with a minimum of 4 centres and 100 patients. Patient exposure proved to be significantly different among the centres. Highest DRLs were found for Abdominal Aortic Aneurysm Endoprosthesis (18 min, 81 Gy cm2), Iliac Angioplasty (6 min, 24 Gy cm2) and Flutter Ablation surgeries (17 min, 14 Gy cm2). In opposition, lowest DRLs were obtained for Hallux Valgus (0.4 min, 0.04 Gy cm2), Hand/Wrist Fracture (0.6 min, 0.16 Gy cm2), and Venous Access Device Implantation surgeries (0.3 min, 0.36 Gy cm2). Similar exposure levels are registered in private clinics and public hospitals. Multi-centric DRLs for fifteen surgical procedures including six new reference values were established to help optimise patients' radiation protection.

Alkalinized Lidocaine Preloaded Endotracheal Tube Cuffs Reduce Emergence Cough After Brief Surgery: A Prospective Randomized Trial.

BACKGROUND: Alkalinized lidocaine in the endotracheal tube (ETT) cuff decreases the incidence of cough and throat pain on emergence after surgery lasting more than 2 hours. However, alkalinized lidocaine needs 60-120 minutes to cross the ETT cuff membrane; therefore, its usefulness in shorter duration surgery is unknown. This prospective double-blind randomized controlled trial tested the hypothesis that alkalinized lidocaine would reduce the incidence of emergence cough after surgeries lasting <120 minutes. METHODS: After local ethics board approval, American Society of Anesthesiologists I-III patients consented to be randomized into 1 of 2 groups receiving either alkalinized lidocaine (group AL) or saline (group S) to inflate the ETT cuff. Cuffs were prefilled >90 minutes before intubation with either 2 mL of 2% lidocaine and 8 mL of 8.4% bicarbonate (group AL) or 10 mL of normal saline (group S). Cuffs were emptied immediately before intubation. After intubation, either 2 mL of 2% lidocaine (AL) or 2 mL of saline (S) were injected into the cuff. Additional 8.4% bicarbonate (AL) or saline (S) was injected into the cuff until there was no air leak. Anesthesia was maintained using desflurane, rocuronium, and either fentanyl or sufentanil to maintain vital signs within 20% of baseline values. Opioids administered in prophylaxis of extubation cough were proscribed. A standardized "no touch" emergence technique was used. A blinded assessor noted any cough above 0.2 minimum alveolar concentration (MAC) of expired desflurane. At 0.2 MAC, once every 30 seconds, the patient was instructed to open his eyes and extubation occurred once a directed response was noted. RESULTS: A total of 213 patients were randomized and 100 patients in each group completed the experimental protocol. The incidence of extubation cough in group AL was 12%, significantly lower (1-sided P = .045) than the 22% incidence in group S. The 1-tailed risk ratio for cough in group AL was 0.55 (0-0.94, P = .045). Total amount of opioids administered (P = .194), ETT cuff preloading times (P = .259), and extubation times (P = .331) were not significantly different between groups. The average duration of surgery was 59 ± 28 minutes in group AL and 52 ± 29 minutes in group S (P = .057). CONCLUSIONS: Alkalinized lidocaine in the ETT cuff significantly decreased general anesthesia emergence cough after surgeries with an average duration of slightly <1 hour.

Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes.

Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1ß, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.

Association of OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 polymorphisms with clinical phenotype among women with fibromyalgia.

To investigate the association between three selected pain polymorphisms and clinical, functional, sensory-related, psychophysical, psychological or cognitive variables in a sample of women with fibromyalgia (FMS). One hundred twenty-three (n = 123) women with FMS completed demographic (age, height, weight), clinical (years with pain, intensity of pain at rest and during daily living activities), functional (quality of life, physical function), sensory-related (sensitization-associated and neuropathic-associated symptoms), psychophysical (pressure pain thresholds), psychological (sleep quality, depressive and anxiety level) and cognitive (pain catastrophizing, kinesiophobia) variables. Those three genotypes of the OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 single nucleotide polymorphisms were obtained by polymerase chain reactions from no-stimulated whole saliva collection. No significant differences in demographic, clinical, functional, sensory-related, psychophysical, psychological and cognitive variables according to OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680 genotype were identified in our sample of women with FMS. A multilevel analysis did not either reveal any significant gene-to-gene interaction between OPRM1 rs1799971 x HTR1B rs6296, OPRM1 rs1799971 x COMT rs4680 and HTR1B rs6296 x COMT rs4680 for any of the investigated outcomes. This study revealed that three single nucleotide polymorphisms, OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680, mostly associated with chronic pain were not involved in phenotyping features of FMS. Potential gene-to-gene interaction and their association with clinical phenotype in women with FMS should be further investigated in future studies including large sample sizes.

The Anti-Müllerian Hormone as Endocrine and Molecular Marker Associated with Reproductive Performance in Holstein Dairy Cows Exposed to Heat Stress.

Anti-Müllerian hormone (AMH) is proposed as a biomarker for fertility in cattle, yet this associative relationship appears to be influenced by heat stress (HS). The objective was to test serum AMH and AMH-related single nucleotide polymorphisms (SNPs) as markers potentially predictive of reproductive traits in dairy cows experiencing HS. The study included 300 Holstein cows that were genotyped using BovineSNP50 (54,000 SNP). A genome-wide association study was then executed. Nine intragenic SNPs within the pathways that influence the AMH gene were found important with multiple comparisons adjustment tests (p < 1.09 × 10-6). A further validation study was performed in an independent Holstein cattle population, which was divided into moderate (MH; n = 152) and severe heat-stressed (SH; n = 128) groups and then subjected to a summer reproductive management program. Serum AMH was confirmed as a predictor of fertility measures (p < 0.05) in MH but not in the SH group. Cows were genotyped, which revealed four SNPs as predictive markers for serum AMH (p < 0.01), reproductive traits (p < 0.01), and additional physiological variables (p < 0.05). These SNPs were in the genes AMH, IGFBP1, LGR5, and TLR4. In conclusion, serum AMH concentrations and AMH polymorphisms are proposed as predictive markers that can be used in conjunction with genomic breeding value approaches to improve reproductive performance in Holstein cows exposed to summer HS conditions.

Comparison of the efficacy of cisplatin and carboplatin in combination with etoposide in firstline treatment of extensive-stage small cell lung cancer in real-world practice in the Czech Republic - a retrospective analysis of patients from the LUCAS project.

BACKGROUND: Patients with extensive-stage small-cell lung cancer (ES-SCLC) have a poor prognosis. The standard palliative treatment for four decades has been chemotherapy as a combination of etoposide with carboplatin or cisplatin, and in recent years, immunotherapy in addition. AIMS: To determine whether there is a difference in the efficacy of palliative chemotherapy as cisplatin or carboplatin in combination with etoposide in patients with ES-SCLC in real-world practice in the Czech Republic. METHODS: This was a retrospective analysis of a cohort of 348 patients from the LUCAS project with ES-SCLC. 79 were treated with etoposide plus cisplatin and 265 were treated with etoposide plus carboplatin. Kaplan-Meier curves and the Cox regression model were used for analysis. RESULTS: No statistically significant difference in median overall survival (mOS) or median progression free survival (mPFS) was found between groups or between patients grouped according to age and performance status (PS) in mOS. The Cox regression result was similar. CONCLUSION: This study shows that cisplatin and carboplatin do not differ in efficacy in a given indication, thus when choosing a treatment, the physician should consider the expected toxicity in a particular patient, assessing the patient's general condition and comorbidities.

2023 White Paper on Recent Issues in Bioanalysis: EU IVDR 2017/746 Implementation/Impact, IVD/CDx/CLIA Approved Assays, High Dimensional Cytometry, Multiplexing Technologies, LBA Tissue Analysis, Vaccine Study Endpoints, Cell-Based Assays for Biomarkers, Cell Therapy and Vaccines (PART 2 - Recommendations on Development & Validation of Biomarkers, IVD, CDx, Cell-Based, Flow Cytometry, Ligand-Binding and Enzyme Assays; Advanced Critical Reagents Strategies).

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on 19-23 June 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication (Part 2) covers the recommendations on Biomarkers, IVD/CDx, LBA and Cell-Based Assays. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 9 and 7 (2024), respectively.

Sleep disturbance, distress, and quality of life in ovarian cancer patients during the first year after diagnosis.

BACKGROUND: Sleep disturbance is a common clinical complaint of oncology patients and contributes to substantial morbidity. However, because most sleep studies have been cross-sectional, associations between sleep quality and distress in patients with ovarian cancer over time remain unclear. This prospective longitudinal study examined rates of sleep disturbance; contributions of depression, anxiety, and medication use in sleep disturbance; and associations between sleep quality and quality of life (QOL) during the first year after diagnosis among women with ovarian cancer. METHODS: Women with a pelvic mass completed measures of sleep quality, depression, anxiety, and QOL before surgery. Those diagnosed with primary epithelial ovarian, fallopian tube, or peritoneal cancer repeated surveys at 6 months and 1 year after diagnosis. Mixed modeling was used to examine trajectories of psychosocial measures over time, as well as associations between changes in distress and sleep quality. Relationships between changes in sleep and QOL were also examined. RESULTS: The majority of patients reported disturbed global sleep (Pittsburgh Sleep Quality Index > 5) at all 3 time points. Medications for sleep and pain were associated with worse sleep at all time points. Greater increases in depression were associated with increased disturbances in sleep quality over time (P < .04). Worsening sleep was also associated with declines in QOL over time (P < .001). CONCLUSIONS: Sleep disturbance is common and persistent in women with ovarian cancer, and is linked to depressive symptoms and QOL. Pharmacologic treatment does not appear to adequately address this problem. Results highlight the need for ongoing screening and intervention for sleep disturbance in this population.

Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability.

Elevations in the pro-inflammatory cytokine interleukin-6 (IL-6) and alterations in the anti-inflammatory hormone cortisol have been reported in a variety of cancers. IL-6 has prognostic significance in ovarian cancer and cortisol has been associated with fatigue, disability, and vegetative depression in ovarian cancer patients prior to surgery. Ovarian cancer patients undergoing primary treatment completed psychological self-report measures and collected salivary cortisol and plasma IL-6 prior to surgery, at 6 months, and at 1 year. Patients included in this study had completed chemotherapy and had no evidence of disease recurrence. At 6 months, patients showed significant reductions in nocturnal cortisol secretion, plasma IL-6, and a more normalized diurnal cortisol rhythm, changes that were maintained at 1 year. The reductions in IL-6 and nocturnal cortisol were associated with declines in self-reported fatigue, vegetative depression, and disability. These findings suggest that primary treatment for ovarian cancer reduces the inflammatory response. Moreover, patients who have not developed recurrent disease by 1 year appear to maintain more normalized levels of cortisol and IL-6. Improvement in fatigue and vegetative depression is associated with the normalization of IL-6 and cortisol, a pattern which may be relevant for improvements in overall quality of life for ovarian cancer patients.

Non-cancer life stressors contribute to impaired quality of life in ovarian cancer patients.

OBJECTIVES: Diagnosis and treatment for a life threatening illness such as cancer are known to be psychologically impactful. However, little is known about the influence that non-cancer life stressors have on the quality of life (QOL) of ovarian cancer patients. The goal of the present study was to examine associations between non-cancer life stressors and QOL in 123 women with invasive epithelial ovarian cancer who were followed prospectively and longitudinally for one year. METHODS: Mixed models for repeated measures were used to examine the relationship between life stressors and QOL pre-surgery and one year later, while adjusting for age, cancer stage, depressive symptoms, anxiety, and chemotherapy status (at one year). Prospective associations between QOL pre-surgery and one-year QOL were also examined. RESULTS: Number and severity of life stressors were unrelated to QOL of participants before surgery. At one year, however, participants experiencing a greater number of life stressors reported poorer concurrent physical well-being (PWB) (p=0.015), functional well-being (FWB) (p<0.0001), social well-being (SWB) (p=0.0003), and total QOL (p<0.0001). Similar effects were found for life event severity. Finally, experiencing a greater number of life stressors pre-surgery predicted poorer overall QOL one year post-diagnosis (p<0.0001). CONCLUSIONS: Non-cancer life stressors can substantially impact long-term QOL of ovarian cancer patients, adjusting for medical variables such as chemotherapy and cancer stage, thus highlighting the importance of evaluating the stress burden of patients in ongoing cancer care.

[Prevalence of Gilbert syndrome and its genetic determinants in Chile]. / Prevalencia de síndrome de Gilbert y sus determinantes genéticas en población chilena.

BACKGROUND: In Europeans the TATA box TA7 repeat promoter variant in the UGT1A1 gene (UGT1A1*28) is the major determinant of bilirubin levels. AIM: To study the prevalence of Gilbert Syndrome (GS) and its genetic determinants in Chile. MATERIAL AND METHODS: Three different studies were conducted. The prevalence of GS in Chile was assessed in 991 subjects with normal liver tests (ALT and GGT) from the 2nd National Health Survey. We defined GS as a total bilirubin (TB) between 1.4-5mg/dL. The second study assessed the genotype prevalence of SNP rs6742078 (in LD with UGT1A1*28) and rs4149056 in 500 DNA samples of non-related Hispanics. Finally, a case-control study was designed to assess the phenotype-genotype correlation. UGT1A1*28 and rs4149056 variants were determined by direct sequencing and allelic discrimination assays (TaqMan), respectively. RESULTS: Prevalence of GS in the general Chilean population was 2.6% (4.5% in males and 0.5% in female). No correlation with age, educational level or home location was found. Genotypes for UGT1A1*28 (TA6/6 50.5%, TA6/7 37.8%, TA7/7 11.7%) and rs4149056 (TT 74.1%, CT 22.8%, and CC 3.1%) variants were similar to Europeans. In the case-control study, most patients with GS were homozygotes for UGT1A1*28 (TA7/7, 74%). Of note, 44% of patients with intermediate TB levels were also TA7/7, compared to 7% in normal subjects. SLCO1B1 genotype was not correlated with TB levels. CONCLUSIONS: While the prevalence of GS was lower in Chile compared to Europeans (~5%), the prevalence of UGT1A1*28 homozygotes was similar (~12%). In Chilean Hispanics, the UGT1A1*28 variant explain 75% of GS phenotype.