Mild Negative Effects Research Articles

In vitro effects of antidepressants on human sperm function.

Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically, especially among the young and people of reproductive age, which consequently leads to an increase in antidepressant consumption. Antidepressants are associated with sexual dysfunction in both men and women; however, their role in male fertility has been scarcely studied. Fluoxetine and sertraline, two serotonin reuptake inhibitors (SSRIs), are among the most prescribed antidepressants worldwide. To determine their possible effects, human sperm cells were exposed to either sertraline or fluoxetine at concentrations previously found in blood and seminal fluid of patients undergoing treatment. Spermatozoa were incubated for up to 24 h at 37°C and 5% CO2, and important functional parameters such as sperm motility, viability, mitochondrial membrane potential, cellular reactive oxygen species (ROS) production, chromatin/DNA integrity, acrosome status, and tyrosine phosphorylation were assessed. At low levels, fluoxetine consistently decreased progressive motility throughout time while promoting fluctuations in ROS levels and sperm capacitation. Nevertheless, it did not affect viability, mitochondrial membrane potential, acrosome reaction nor chromatin/DNA integrity. Sertraline, on the other hand, had little to nonsignificant impact at low doses, but affected almost all tested parameters at supratherapeutic concentrations. Altogether, our results suggest that both antidepressants may impair sperm function, possibly through different mechanisms of action, but fluoxetine is the only exhibiting mild negative effects at doses found in vivo.

Wolbachia strains wMel and wAlbB differentially affect Aedes aegypti traits related to fecundity.

Two Wolbachia strains, wMel and wAlbB, have been transinfected into Aedes aegypti mosquitoes for population replacement with the aim of reducing dengue transmission. Epidemiological data from various endemic sites suggest a pronounced decrease in dengue transmission after implementing this strategy. In this study, we investigated the impact of the Wolbachia strains wMel and wAlbB on Ae. aegypti fitness in a common genetic background. We found that Ae. aegypti females infected with the wMel strain exhibited several significant differences compared with those infected with the wAlbB strain. Specifically, wMel-infected females laid significantly fewer eggs, ingested a lower amount of blood, had a reduced egg production rate, and exhibited a decreased Wolbachia density at a later age compared with mosquitoes infected with the wAlbB strain. Conversely, the wAlbB strain showed only mild negative effects when compared with Wolbachia-uninfected specimens. These differential effects on Ae. aegypti fitness following infection with either wMel or wAlbB may have important implications for the success of population replacement strategies in invading native Ae. aegypti populations in endemic settings. Further research is needed to better understand the underlying mechanisms responsible for these differences in fitness effects and their potential impact on the long-term efficacy of Wolbachia-based dengue control programs.IMPORTANCEThe transmission of arboviruses such as dengue, Zika, and chikungunya is on the rise globally. Among the most promising strategies to reduce arbovirus burden is the release of one out of two strains of Wolbachia-infected Aedes aegypti: wMel and wAlbB. One critical aspect of whether this approach will succeed involves the fitness cost of either Wolbachia strains on mosquito life history traits. For instance, we found that wMel-infected Ae. aegypti females laid significantly fewer eggs, ingested a lower amount of blood, had a reduced egg production rate, and exhibited a decreased Wolbachia density at a later age compared with mosquitoes infected with the wAlbB strain. Conversely, the wAlbB strain showed only mild negative effects when compared with Wolbachia-uninfected specimens. These differential effects on mosquito fitness following infection with either wMel or wAlbB may have important implications for the success of population replacement strategies in invading native Ae. aegypti populations.

Transcriptional profile of ribosome-associated quality control components and their associated phenotypes in mammalian cells

During protein synthesis, organisms detect translation defects that induce ribosome stalling and result in protein aggregation. The Ribosome-associated Quality Control (RQC) complex, comprising TCF25, LTN1, and NEMF, is responsible for identifying incomplete protein products from unproductive translation events, targeting them for degradation. Although RQC disruption causes adverse effects on vertebrate neurons, data regarding mRNA/protein expression and regulation across tissues are lacking. Employing high-throughput methods, we analyzed public datasets to explore RQC gene expression and phenotypes. Our findings revealed widespread expression of RQC components in human tissues; however, silencing of RQC yielded only mild negative effects on cell growth. Notably, TCF25 exhibited elevated mRNA levels that were not reflected in the protein content. We experimentally demonstrated that this disparity arose from post-translational protein degradation by the proteasome. Additionally, we observed that cellular aging marginally influenced RQC expression, leading to reduced mRNA levels in specific tissues. Our results suggest the necessity of RQC expression in all mammalian tissues. Nevertheless, when RQC falters, alternative mechanisms seem to compensate, ensuring cell survival under nonstress conditions.

P-299 Impact of endometriosis on responsiveness to ovarian hyperstimulation and embryo development: quantitative and qualitative aspects

Abstract Study question The present study was designed to better elucidate if endometriosis may affect follicologenesis and embryo development within a cycle of ovarian hyperstimulation for IVF (In Vitro Fertilization). Summary answer Endometriosis women showed fewer oocytes retrieved and a higher rate of unexpected poor response albeit number of patients without good quality embryos was similar. What is known already The pathogenetic mechanisms explaining the association between endometriosis and infertility are not fully explained. Pelvic adhesions and inflammation may play a role but other detrimental effects are presumably involved. They include reduced ovarian reserve, altered oocyte competence, impaired endometrial receptivity and association with other conditions affecting fertility such as adenomyosis. To note, even if in vitro fertilization is expected to overcome the pelvic detrimental milieu, the success rate of the procedure is lower in women with endometriosis. Study design, size, duration We designed a clinical retrospective study in order to analyse the impact of the disease on ovarian hyperstimulation and embryo development. Women were selected among those undergoing IVF cycles between January 2014 and December 2020. The primary outcome was the number of women without top quality embryos. Secondary outcomes included the rate of unexpected poor response (retrieval of ≤ 3 oocytes), cumulative clinical pregnancy rate and cumulative birth rate. Participants/materials, setting, methods Our study was performed at the Infertility Unit of the Fondazione IRCSS Ca’ Granda Ospedale Maggiore Policlinico of Milan. We included 496 subjects with a good ovarian reserve as demonstrated by serum Anti-mullerian hormone (AMH) > 1,1 ng/ml. Two hundreds and forty-eight women with endometriosis were identified and matched with two hundreds and forty-eight women without the disease according to age, pharmacological regimen, study period and AMH levels. Main results and the role of chance The number of women without good quality embryos did not differ between exposed and unexposed subjects (16% vs 16%, p = 1.00). The adjusted OR was 0.85 (95%CI: 0.51-1.44, p = 0.56). The clinical pregnancy rate and the live birth rate were also similar. We observed a lower number of oocytes retrieved and a higher rate of unexpected poor response (23% vs 13%, p = 0.005) in women with endometriosis. At subgroup analysis, the higher rate of unexpected poor responders persisted only in previously operated women (27% vs 13%, p = 0.02). Limitations, reasons for caution The evaluation of embryo quality was only based on morphological criteria. The histological diagnosis of endometriosis was lacking in unoperated women (128 subjects). Finally, our conclusions concern ovarian hyperstimulation and may not be extrapolated to natural reproductive processes. Wider implications of the findings Despite being generally reassuring, our findings do not completely exclude some mild negative effects on folliculogenesis. Effects demonstrated could be due to anatomical distortions of the pelvis causing an inefficient response of the ovarian parenchyma to hyperstimulation. We cannot exclude that the post-surgical healing process may alter local vascular supply. Trial registration number NA

Modulation of the DA1 pathway in maize shows that translatability of information from Arabidopsis to crops is complex

Modern agriculture is struggling to meet the increasing food, silage and raw material demands due to the rapid growth of population and climate change. In Arabidopsis, DA1 and DAR1 are proteases that negatively regulate cell proliferation and control organ size. DA1 and DAR1 are activated by ubiquitination catalyzed by the E3 ligase BIG BROTHER (BB). Here, we characterized the DA1, DAR1 and BB gene families in maize and analyzed whether perturbation of these genes regulates organ size similar to what was observed in Arabidopsis. We generated da1_dar1a_dar1b triple CRISPR maize mutants and bb1_bb2 double mutants. Detailed phenotypic analysis showed that the size of leaf, stem, cob, and seed was not consistently enlarged in these mutants. Also overexpression of a dominant-negative DA1R333K allele, resembling the da1-1 allele of Arabidopsis which has larger leaves and seeds, did not alter the maize phenotype. The mild negative effects on plant height of the DA1R333K_bb1_bb2 mutant indicate that the genes in the DA1 pathway may control organ size in maize, albeit less obvious than in Arabidopsis.

Effects of Water Stress/Rewatering on Leaf Photosynthetic Characteristics and Grain Yield of Foxtail Millet

Foxtail millet behaves strong drought resistance, but its photosynthesis process and grain yield are restricted by drought. The effects of water stress/rewatering on photosynthetic characteristics and yield of foxtail millet are studied through field water control experiment at booting and flowering stage and grain filling stage. The restraint factor on photosynthesis rate and the follow-up impact on grain yield are expounded, which may provide guidance for foxtail millet grain yield assessment and field water management under drought condition. The results are as follows: Water stress can lead to the decrease of photosynthetic rate and grain yield of characterized by larger decrease amplitude with the increase of stress intensity and duration, and increasing water use efficiency is the main survival strategy. The effect of water stress/rewatering on foxtail millet yield at grain filling stage is more obvious than that at booting and flowering stage, characterized by 22.1% production loss under 14-day mild water stress and 47.1% for FH-21 treatment group. After rewatering, photosynthesis performs compensation effect, and the photosynthetic capacity is recovered to some extent. The recovery of photosynthesis ability is lower when the the water stress intensity is stronger and the water stress duration is longer, and the recovery of photosynthetic capacity at grain filling stage is weaker than that at booting and flowering stage. Under mild and short duration water stress, the decrease of photosynthetic rate is mainly determined by stomatal factors, and the non-stomatal restriction gradually becomes the main cause for the decrease of photosynthetic rate with the increase of water stress intensity and the extension of duration. Mild negative effects of water stress on grain yield for 7 and 14 days, and severe effects for 7 days can be partially offset by the compensating effect after rewatering to some extent at booting and flowering stage, so the final effect on grain yield is not significant. In comparison, the effect of water stress on photosynthetic rate is larger, and the recovery of photosynthetic is not as good after rewatering at the grain filling stage. The formation of grain yield is more sensitive to water stress at the grain filling stage, for the closer synergistic relationship between photosynthetic rate and ultimate grain yield. The results reveal that a mild or short-term water deficit can be made up by rewatering, when the water use efficiency and photosynthesis rate will rise, and stable foxtail millet grain yield can be obtained. This can improve sustainable development by allowing deficit irrigation and water-saving agricultural practices. These critical information for optimizing water management practices is beneficial for foxtail millet sustainable development, particularly under warmer and drier climate in the future in the northern China.

Interactions of circulating estradiol and progesterone on changes in endometrial area and pituitary responsiveness to GnRH†.

Changes in circulating progesterone (P4) and estradiol (E2) during proestrus produce dynamic changes in endometrial function and pituitary release of gonadotropins. Independent and combined effects of P4 and E2 on endometrium and pituitary were evaluated. In a preliminary study, an exogenous hormone model of proestrus was created by removal of corpus luteum and follicles ≥5mm followed by gradual removal of intravaginal P4 implants during 18h and treatment with increasing doses of estradiol benzoate during 48h to mimic proestrus using high E2 (n=9) or low E2 (n=9). Decreased P4, increased E2, and increased endometrial area (EA) simulated proestrus in high-E2 cows and this was used subsequently. The main experiment used a 2×2 factorial design with: high E2 and low P4 (n=11); high E2 and high P4 (n=11); low E2 and high P4 (n=11); low E2 and low P4 (n=10). At 48h, gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle stimulating hormone (FSH) release was determined. Variables were analyzed using PROCMIXED of Statistical Analysis System. The EA increased dramatically during 48h only in high-E2 and low-P4 cows. For FSH, high-E2 cows had greater area under the curve (AUC) and FSH peak after GnRH than low E2, with mild negative effects of high P4. For LH, concentration at peak and AUC were 2-fold greater in high E2 compared to low-E2 groups, with low P4 also 2-fold greater than high-P4 groups. Thus, maximal changes in uterus and pituitary during proestrus depend on both low P4 and high E2, but different physiologic responses are regulated differently by E2 and P4. Changes in endometrium depend on low P4 and high E2, whereas GnRH-induced FSH secretion primarily depends on high E2, and GnRH-induced LH secretion is independently increased by high E2 or reduced by high P4.

Sow environment during gestation: part II. Influence on piglet physiology and tissue maturity at birth

Sow environment during gestation can generate maternal stress which could alter foetal development. The effects of two group-housing systems for gestating sows on piglet morphological and physiological traits at birth were investigated. During gestation, sows were reared in a conventional system on a slatted floor (C, 18 sows), demonstrated as being stressful for sows or in an enriched system in larger pens and on deep straw bedding (E, 19 sows). On gestation day 105, sows were transferred into identical individual farrowing crates on a slatted floor. Farrowing was supervised to allow sampling from piglets at birth. In each litter, one male piglet of average birth weight was euthanized immediately after birth to study organ development and tissue traits. Blood samples were collected from 6 or 7 piglets per litter at birth and 2 piglets per litter at 4 days of lactation (DL4). At birth, mean piglet BW did not differ between groups (P > 0.10); however, the percentage of light (<1.2 kg) and heavy (⩾2 kg) piglets was greater and lower, respectively, in C than in E litters (P < 0.01). Plasma concentrations of cortisol, IGF-I, T4, T3, lactate, NEFA, fructose and albumin did not differ (P > 0.10) between C and E piglets, but the insulin to glucose ratio was greater (P = 0.02) in C than in E piglets. Compared with E piglets, C piglets had a lighter gut at birth (P = 0.01) and their glycogen content in longissimus muscle was lower (P < 0.01). In this muscle, messenger RNA levels of PAX7, a marker of satellite cells and of PPARGC1A, a transcriptional coactivator involved in mitochondriogenesis and mitochondrial energy metabolism, were greater (P < 0.05), whereas the expression level of PRDX6, a gene playing a role in antioxidant pathway, was lower (P = 0.03) in C than in E piglets. Other studied genes involved in myogenesis did not differ between C and E piglets. No system effect was observed on target genes in liver and subcutaneous adipose tissue. On DL4, C piglets exhibited a lower plasma antioxidant capacity than E piglets (P = 0.002). In conclusion, exposure of sows to a stressful environment during gestation had mild negative effects on the maturity of piglets at birth.

Effects of ethanolic extracts of leaf, seed and fruit of Datura metel L. on kidney function of male albino rats

Effects of ethanolic extracts of leaf, seed and fruit of Datura metel on kidney function of male albino rats was investigated in this study. The result showed a non-significant (p > 0.05) increase of urea concentration in groups 2 and 3 administered low (300 mg/kg bw) and high (600 mg/kg bw) dose of leaf extract respectively and a non-significant (p > 0.05) decrease in all groups administered the seed and fruit extracts compared with normal control (group 1). Creatinine increased significantly (p < 0.05) in groups 4 and 7 administered low dose (300 mg/kg bw) of seed extract and high dose (600 mg/kg bw) of fruit extract respectively, but increased non-significantly in other groups (2, 3, 5 & 6) compared with normal control. Sodium, potassium and bicarbonate concentrations increased non-significantly (p > 0.05) in all groups administered the various extracts, except in group 4 in which sodium reduced non-significantly (p > 0.05) compared with normal control. Chloride increased significantly (p < 0.05) in group 5 and non-significantly (p > 0.05) in groups 3, 6 and 7, but reduced non-significantly (p > 0.05) in group 4 compared with normal control. The administration of some of the extracts in comparison with the normal control in histology of the animals show glomerular extrusion and glomerular collapse with resultant increased urinary space, dilated tubules, vacuolations in some epithelial lining of most of the tubules in the medulla and inflammatory cellular infiltration at some peritubular regions. The results showed that some parts of Datura metel posed mild negative effects, while some parts could possess nephroprotective potential by regulating the kidney function of male albino rats.

Effects of Maternal Deprivation and Complex Housing on Rat Social Behavior in Adolescence and Adulthood.

Early life context and stressful experiences are known to increase the risk of developing psychiatric disorders later in life, including disorders with deficits in the social domain. Our study aimed to investigate the influence of early life environment on social behavior in a well-controlled animal model. To this end we tested the effects of maternal deprivation (MD) on rat social play behavior in adolescence and social interaction in adulthood. Additionally, we provided a stimulating environment during adolescence (complex housing) as a potential intervention to diminish the effects of early life stress. Male and female Wistar rats were deprived from their mother for 24 h on postnatal day 3 (PND 3) or were left undisturbed. Complex housing started 5 days after weaning and consisted of housing 10 same-sex conspecifics in large, two-floor MarlauTM cages until the end of the study. Social play behavior in adolescence was tested under different conditions (3 h vs. 24 h social isolation prior to testing). Maternally deprived males – but not females – showed a longer latency to play and a decreased total amount of social play behavior, after a 24 h isolation period. In adulthood, social discrimination was impaired in deprived male and female rats in the three-chamber social approach task. Complex housing did not moderate the effects of MD, but in itself induced a strong behavioral phenotype. Both complex housed males and females hardly displayed any play behavior after a 3 h isolation period. However, after 24 h of isolation, these animals showed shorter latencies to engage in social play behavior. Only complex housed males truly showed more social play behavior here, while showing less social interest in adulthood. We conclude that MD has mild negative effects on social behavior in adolescence and adulthood, which are not counteracted by complex housing. Complex housing induces a specific phenotype associated with rapid habituation; a lack of social play after short isolation periods, while increasing play behavior after a prolonged period of isolation in adolescence, and less social interest, paired with intact social discrimination in adulthood. In both early life settings, males seem to be more influenced by the early life environment compared to females.

Twenty-Seven-Year Follow-Up of Vietnam Air War USAF POWs and Matched Controls Not Captured: A Qualitative Study

Objective: To provide a follow up of a 1976 study of the impact of captivity on U.S. Air Force (USAF) POWs and USAF Controls matched for time in Southeast Asia, military rank and aircraft crew position. Method: Qualitative study of replies to open ended questions of positive and negative changes due to their captivity/combat experiences made by participants (POWs and Controls) who replied in both 1976 and in 2003. Results: Both groups acknowledged positive and negative effects of the experiences in 1976. In 1976 and 2003 the POWs mainly reported negative effects on career and family domains but positive effects of individual development and growth. Controls reported mild negative effects on family in 1976, and benefits to their careers and sense of self in both 1976 and 2003. Conclusion: Captivity during the Vietnam War for USAF included two types of extreme duress which were the incarceration itself; and the repatriation experience which entailed re-assimilation despite loss of occupation and disrupted families. Despite these obstacles, POWs exhibited substantial resilience in achieving self-growth and how they regarded themselves psychologically in comparison to their matched control fellow aviators who while also suffering a lesser separation from family, tended to prosper in their careers and were proud of their accomplishments. Long term separation from work, family and friends and the inability to return to their families and careers with the effectiveness demanded by their ambition were a more devastating ongoing consequence of their captivity than the immediate suffering of their imprisonment.

Long-run Effect of the Global Financial Crisis on Singapore's Tourism and the Economy

This study employs recent Singaporean tourism survey data, the updated Singaporean input–output tables and a computable general equilibrium model to gauge the long-run effects of the 2008 global financial crisis and selected policy responses. The simulation results suggest that the global financial crisis has had mild negative long-run effects on the overall development of Singapore's economy, and that the GST deduction policy ought to offset this negative effect.

Night Shifts in Emergency Medicine: The American Board of Emergency Medicine Longitudinal Study of Emergency Physicians

BackgroundNight shift work is an integral component of the practice of emergency medicine (EM). Previous studies have demonstrated the challenges of night shift work to health and well being among health care providers. ObjectiveThis study was undertaken to describe the self-reported experience of emergency physicians regarding night shift work with respect to quality of life and career satisfaction. MethodsThe 2008 American Board of Emergency Medicine (ABEM) Longitudinal Study of Emergency Physicians (LSEP) was administered by mail to 1003 ABEM diplomates. ResultsAmong 819 participants in the 2008 LSEP Physician Survey, most participants responded that night shift work negatively influenced job satisfaction with a moderate or major negative influence (58%; n = 467/800). Forty-three percent of participants indicated that night shifts had caused them to think about leaving EM (n = 344/809). Most participants responded that working night shifts has had mild negative effects (51%; n = 407/800) or major negative effects (9%; n = 68) on their health. Respondents were asked to describe how working night shifts has affected their health. Common themes included fatigue (36%), poor quality of sleep (35%), mood decrement/irritability (29%), and health maintenance challenges (19%). Among participants in the 2008 LSEP Retired Physician Survey, night shifts were a factor in the decision to retire for 56% of participants. ConclusionsEmergency physicians report negative impacts of night shift work, including fatigue, poor quality of sleep, mood decrement, irritability, and health challenges. Night shifts have a negative influence on job satisfaction and can be a factor in the decision to retire.

Maize Physiological Responses to Heat Stress and Hormonal Plant Growth Regulators Related to Ethylene Metabolism

ABSTRACTHormonal plant growth regulators (HPGRs) have been evaluated in field grown maize (Zea mays L.), but never as a tool for prevention or mitigation of heat stress. We analyzed grain yield determination of maize crops exposed to contrasting temperature regimes (nonheated control plots [TC]; heated plots [TH]) and the application of HPGRs associated with ethylene metabolism (ethephon [ETH]; MCP [1‐MCP]). Heating extended over daytime hours between V11 and tasseling (VT), and products were sprayed immediately before (V11) and/or during (V16) heating. Plants treated with ETH always had reduced height (10–21%) and leaf area (3–10%), but these trends usually had no effect on light interception during treatment period. Biomass production was markedly affected by heating, but a significant interaction effect (P &lt; 0.01) indicated that HPGRs caused (i) no effect among TH plots, and (ii) a decrease (13–19% for ETH and 3.8–9.4% for MCP) among TC plots. The interaction effect computed for grain yield highlighted that ETH had mild negative effects (≤ 18%) among TC plots and large positive effects among TH plots (up to 73%), whereas MCP had no effect among the former and mild positive (V16) or negative (V11) effects among the latter. Variations in grain yield were due to variations in kernel numbers (r2 ≥ 0.92), which were explained by ear growth rate around flowering (r2 ≥ 0.97). Timely application of HPGRs was critical for improving biomass allocation to the ear (ETH) and having adequate blockage of ethylene receptors (MCP).

Transpersonal Effects of Exposure to Shamanic Use of Khoomei (Tuvan Throat Singing): Preliminary Evaluations from Training Seminars

Khoomei is a Tuvan Siberian shamanic practice involving overtone throat singing. One hundred eighty-one Western participants completed questionnaires after attending Khoomei seminars, asking about the following: motivation of people to learn shamanic throat singing; self-perception at the levels of body, energy, and mind before-and-after the seminar; feelings and sensations from practicing throat singing; transpersonal experience during throat singing; experience of inner vibrations from listening to the singing; and general state and feelings after seminar. In general, most participants reported many benefits from attending the seminars, although a few reported mild negative effects (e.g., dizziness and sadness). Of particular interest are the many transpersonal experiences reported (e.g., freedom from body limits and extending mind limits).

In situ remediation of contaminated sediments using carbonaceous materials

Carbonaceous materials (CM), such as activated carbons or biochars, have been shown to significantly reduce porewater concentrations and risks by binding hydrophobic organic compounds (HOCs) present in aquatic sediments. In the present study, the authors review the current state-of-the-art use of CM as an extensive method for sediment remediation, covering both technical and ecological angles. The review addresses how factors such as CM type, particle size and dosage, sediment characteristics, and properties of contaminants affect the effectiveness of CM amendment to immobilize HOCs in aquatic sediments. The authors also review the extent to which CM may reduce bioaccumulation and toxicity of HOCs and whether CM itself has negative effects on benthic species and communities. The review is based on literature and datasets from laboratory as well as field trials with CM amendments. The presence of phases such as natural black carbon, oil, or organic matter in the sediment reduces the effectiveness of CM amendments. Carbonaceous material additions appear to improve the habitat quality for benthic organisms by reducing bioavailable HOC concentrations and toxicity in sediment. The negative effects of CM itself on benthic species, if any, have been shown to be mild. The beneficial effects of reducing toxicity at low CM concentrations most probably outweigh the mild negative effects observed at higher CM concentrations.

Preventive effect of risedronate on bone loss and frailty fractures in elderly women treated with anastrozole for early breast cancer

The aim of this study was to assess the effect of adjuvant anastrozole, alone or associated with risedronate, on BMD and bone fracture risk in women more than 70 years old with hormone receptor-positive early breast cancer (EBC). In a group of 51 elderly women (aged 76.4 ± 5.0 years) considered for adjuvant aromatase inhibitors for EBC, 24 patients with T-scores ≥ -2 and no prevalent fractures received anastrozole 1 mg/day (group A), and 27 patients with T-scores < -2, or with T-scores ≥ -2 and prevalent fractures (group B), received anastrozole (1 mg/day) plus risedronate (35 mg/week). Both groups received supplementation with 1 g calcium carbonate and 800 IU vitamin D per day. Differences in BMD and frailty fractures were evaluated after 1 and 2 years. In group A, significant decreases in BMD were observed in the lumbar spine (Δ BMD, -0.030 ± 0.04 g/cm², P < 0.05), femoral neck (Δ BMD, -0.029 ± 0.05 g/cm², P < 0.05), and trochanter (Δ BMD, -0.026 ± 0.03 g/cm², P < 0.01) after 2 years. The greatest percent reduction in height (Hpr) emerged in the thoracic spine (3.6 ± 2.4%, P < 0.01), although only one incident vertebral fracture was observed. In group B, BMD increased in the lumbar spine (Δ BMD, 0.038 ± 0.04, P < 0.001), although no significant changes were seen in the hip regions. The decline in Hpr was negligible (about 1%). No incident fractures were observed at follow-up. In conclusion, anastrozole treatment for EBC in elderly women seems to have only mild negative effects on the femoral bone. Risedronate makes the use of anastrozole safer, even for osteopenic or osteoporotic elderly patients.

Cognitive effects of pregabalin in healthy volunteers

Antiepileptic drugs (AEDs) can be associated with neurotoxic side effects including cognitive dysfunction, a problem of considerable importance given the usual long-term course of treatment. Pregabalin is a relatively new AED widely used for the treatment of seizures and some types of chronic pain including fibromyalgia. We measured the cognitive effects of 12 weeks of pregabalin in healthy volunteers. Thirty-two healthy volunteers were randomized in a double-blind parallel study to receive pregabalin or placebo (1:1). Pregabalin was titrated over 8 weeks to 600 mg/d. At baseline, and after 12 weeks of treatment, all subjects underwent cognitive testing. Test-retest changes in all cognitive and subjective measures were Z scored against test-retest regressions previously developed from 90 healthy volunteers. Z scores from the placebo and pregabalin groups were compared using Wilcoxon tests. Thirty subjects completed the study (94%). Three of 6 target cognitive measures (Digit Symbol, Stroop, Controlled Oral Word Association) revealed significant test-retest differences between the pregabalin and placebo groups, all showing negative effects with pregabalin (p < 0.05). These cognitive effects were paralleled by complaints on the Portland Neurotoxicity Scale, a subjective measure of neurotoxicity (p < 0.01). At conventional doses and titration, pregabalin induced mild negative cognitive effects and neurotoxicity complaints in healthy volunteers. These effects are one factor to be considered in the selection and monitoring of chronic AED therapy. Class of Evidence: This study provides Class I evidence that pregabalin 300 mg BID negatively impacts cognition on some tasks in healthy volunteers.

Positive Affect, Negative Affect, and Negative Effects During a Phenomenological Hypnotic Assessment Within a Substance Abuse Population

Positive and negative affect generated while using the Phenomenology of Consciousness - Hypnotic Assessment Procedure (PCI-HAP) on a sample of drug and alcohol users were predicted using several variables. The results were then cross-validated on a second, smaller sample. The results suggest that, although some negative affect was reported, the PCI-HAP was more likely to generate positive, rather than negative, affect. Positive affect was related to the vividness of a suggested hypnotic dream during hypnosis and also hypnotic depth; these findings were replicated upon cross-validation. Although negative affect correlated with the Dissociative Experiences Scale scores and falling asleep, these results did not replicate upon cross-validation. Mild transient negative effects (e.g., headache) were reported by about 10% of the participants in a smaller, second sample. Implications of the results are discussed.

Preliminary effects of pagoclone, a partial GABAA agonist, on neuropsychological performance

Pagoclone is a novel cyclopyrrolone that acts as a partial GABA(A) receptor agonist. Preclinical studies suggest that pagoclone may have clinical utility as an anxiolytic agent, as well as a reduced incidence of side-effects. The present study was conducted to determine whether pagoclone would affect healthy individuals' performances on neuropsychological measures as a function of dose within the projected therapeutic range. Twelve healthy adult subjects were randomly assigned to dosage groups in a 3-way crossover study. Participants were administered neuropsychological measures six hours following dosing on Day 1 and Day 6 of administration of the drug. Dose effects were noted on measures of alertness, learning, and memory and movement time. Significant effects were also noted on measures of alertness, learning and memory, information processing and psychomotor speed. Overall, the results of this small, preliminary study do not support a finding of behavioral toxicity for these doses of pagoclone. Rather, a pattern was found of transient and mild negative effects on learning and memory scores at the highest dose administered, though these changes were small and no longer evident by the sixth day of use.