Incidence, characteristics and clinical profile of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with pre-existing primary immune thrombocytopenia (ITP) in Spain.

Infections are one of the well-known precipitating factors for relapses in patients with immune thrombocytopenia (ITP). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can sometimes lead to or be associated with thrombocytopenia due to an increase in peripheral platelet destruction from inflammatory hyperactivation. Currently, we do not know if SARS-CoV-2 infection modifies the natural evolution of chronic or persistent ITP or if previous immunosuppression of patients with ITP influences the incidence and severity of coronavirus disease 2019 (COVID-19) in this group. The present study was an observational, multicentre, national series of 32 adult patients with pre-existing ITP and subsequent SARS-CoV-2 infection, collected by the Spanish ITP Group [Grupo Español de Trombocitopenia Inmune (GEPTI)].

Simultaneous Analysis of Seven Biomarkers of Oxidative Damage to Lipids, Proteins, and DNA in Urine.

The determination of oxidative stress biomarkers (OSBs) is useful for the assessment of health status and progress of diseases in humans. Whereas previous methods for the determination of OSBs in urine were focused on a single marker, in this study, we present a method for simultaneous determination of biomarkers of oxidative damage to lipids, proteins, and DNA. 2,4-Dinitrophenylhydrazine (DNPH) derivatization followed by solid phase extraction (SPE) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) allowed the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), o- o'-dityrosine (diY), malondialdehyde (MDA), and four F2-isoprostane isomers: 8-iso-prostaglandinF2α (8-PGF2α), 11ß-prostaglandinF2α (11-PGF2α), 15( R)-prostaglandinF2α (15-PGF2α), and 8-iso,15( R)-prostaglandinF2α (8,15-PGF2α) in urine. Derivatization with DNPH and SPE was optimized to yield greater sensitivity and selectivity for the analysis of target chemicals. The limits of detection of target analytes in urine were below 30 pg mL-1. The assay intra- and interday variability was below 16% of the relative standard deviation, and the recoveries of target chemicals spiked into synthetic urine were near 100%. The method was applied to the analysis of 21 real urine samples, and the analytes were found at a detection frequency of 85% for 8-PGF2α and 15-PGF2α, 71% for 11-PGF2α, 81% for 8,15-PGF2α, and 100% for diY, 8-OHdG, and MDA. This method offers simultaneous determination of multiple OSBs of different molecular origin in urine samples selectively with high accuracy and precision.

Molecular Bases Determining Daptomycin Resistance-Mediated Resensitization to ß-Lactams (Seesaw Effect) in Methicillin-Resistant Staphylococcus aureus.

Antimicrobial resistance is recognized as one of the principal threats to public health worldwide, yet the problem is increasing. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most difficult to treat in clinical settings due to the resistance of MRSA to nearly all available antibiotics. The cyclic anionic lipopeptide antibiotic daptomycin (DAP) is the clinical mainstay of anti-MRSA therapy. The decreased susceptibility to DAP (DAP resistance [DAPr]) reported in MRSA is frequently accompanied by a paradoxical decrease in ß-lactam resistance, a process known as the "seesaw effect." Despite the observed discordance in resistance phenotypes, the combination of DAP and ß-lactams has been proven to be clinically effective for the prevention and treatment of infections due to DAPr MRSA strains. However, the mechanisms underlying the interactions between DAP and ß-lactams are largely unknown. In the study described here, we studied the role of mprF with DAP-induced mutations in ß-lactam sensitization and its involvement in the effective killing by the DAP-oxacillin (OXA) combination. DAP-OXA-mediated effects resulted in cell wall perturbations, including changes in peptidoglycan insertion, penicillin-binding protein 2 (PBP 2) delocalization, and reduced membrane amounts of PBP 2a, despite the increased transcription of mecA through mec regulatory elements. We have found that the VraSR sensor-regulator is a key component of DAP resistance, triggering mutated mprF-mediated cell membrane (CM) modifications that result in impairment of PrsA location and chaperone functions, both of which are essential for PBP 2a maturation, the key determinant of ß-lactam resistance. These observations provide for the first time evidence that synergistic effects between DAP and ß-lactams involve PrsA posttranscriptional regulation of CM-associated PBP 2a.

Gender Differences in Patients with Fibromyalgia Undergoing Cognitive-Behavioral Therapy for Insomnia: Preliminary Data.

UNLABELLED: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome that significantly affects patients' quality of life. Its main symptoms are pain, fatigue, and sleep disturbances. AIM: The aim of this study was to assess the efficacy of cognitive-behavioral therapy for insomnia (CBT-I) in men and women with FM and compare sleep and clinical features between both genders. METHODS: Fifteen women and 13 men were selected to participate in nine weekly CBT-I sessions that involved completing several self-reported questionnaires at pretreatment, post-treatment, and follow-up. Patients were recruited from the Rheumatology Service and Pain Unit of Hospital and a fibromyalgia association. Group psychotherapy was performed at clinical unit of the Faculty of Psychology. RESULTS: Both groups showed significant clinical and statistical improvements in sleep quality and the main symptoms associated with FM (ie, pain intensity, fatigue, anxiety, pain catastrophizing, and pain-related anxiety). Differential treatment responsiveness between sexes was observed. Male group exhibited significant changes at post-treatment in sleep disturbances and pain-related anxiety and catastrophizing. The female group showed post-treatment improvements in sleep latency, general fatigue, and depression, which persisted at follow-up. CONCLUSIONS: Differential responses to treatment between men and women were observed in some sleep- and pain-related variables. Outcomes show the needed to design different treatments for men and women with FM is discussed.

Selective sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: results of the GEICAM 2005-07 study.

INTRODUCTION: A controversial aspect of breast cancer management is the use of sentinel lymph node biopsy (SLNB) in patients requiring neoadjuvant chemotherapy (NCT). This paper discusses the detection rate (DT) and false negatives (FN) of SLNB after NCT to investigate the influence of initial nodal disease and the protocols applied. METHODS: Prospective observational multicenter study in women with breast cancer, treated with NCT and SLNB post-NCT with subsequent lymphadenectomy. DT and FN rates were calculated, both overall and depending on the initial nodal status or the use of diagnostic protocols pre-SLNB. RESULTS: No differences in DT between initial node-negative cases and positive cases were found (89.8 vs. 84.4%, P=.437). Significant differences were found (94.1 vs. 56.5%, P=0,002) in the negative predictive value, which was lower when there was initial lymph node positivity, and a higher rate of FN, not significant (18.2 vs. 43.5%, P=.252) in the same cases. The axillary study before SLNB and after the NCT, significantly decreased the rate of FN in patients with initial involvement (55.6 vs 12.5, P=0,009). CONCLUSIONS: NCT means less DT and a higher rate of FN in subsequent SLNB, especially if there is initial nodal involvement. The use of protocols in axillary evaluation after administering the NCT and before BSGC, decreases the FN rate in these patients.

Development and Validation of a Highly Sensitive Multiplex Immunoassay for SARS-CoV-2 Humoral Response Monitorization: A Study of the Antibody Response in COVID-19 Patients with Different Clinical Profiles during the First and Second Waves in Cadiz, Spain.

There is still a long way ahead regarding the COVID-19 pandemic, since emerging waves remain a daunting challenge to the healthcare system. For this reason, the development of new preventive tools and therapeutic strategies to deal with the disease have been necessary, among which serological assays have played a key role in the control of COVID-19 outbreaks and vaccine development. Here, we have developed and evaluated an immunoassay capable of simultaneously detecting multiple IgG antibodies against different SARS-CoV-2 antigens through the use of Bio-PlexTM technology. Additionally, we have analyzed the antibody response in COVID-19 patients with different clinical profiles in Cadiz, Spain. The multiplex immunoassay presented is a high-throughput and robust immune response monitoring tool capable of concurrently detecting anti-S1, anti-NC and anti-RBD IgG antibodies in serum with a very high sensitivity (94.34-97.96%) and specificity (91.84-100%). Therefore, the immunoassay proposed herein may be a useful monitoring tool for individual humoral immunity against SARS-CoV-2, as well as for epidemiological surveillance. In addition, we show the values of antibodies against multiple SARS-CoV-2 antigens and their correlation with the different clinical profiles of unvaccinated COVID-19 patients in Cadiz, Spain, during the first and second waves of the pandemic.

Buccopharyngeal route administered high polyphenolic olive oil and COVID-19: A pilot clinical trial.

INTRODUCTION: Waning immunity after vaccination justifies the need for additional effective COVID-19 treatments. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate mucosal immunity, which can prevent SARS-CoV-2 main immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections using an enteral route, which point to potential effects on time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID-19. SUMMARY: This pilot clinical trial investigated the effect of buccopharyngeal administered high polyphenolic olive oil on COVID-19 incidence, duration, and severity. IMPORTANCE: Waning immunity after vaccination justifies the need of further research for additional effective treatments for COVID-19. OBJECTIVE: Immunomodulation of local immune response at the buccopharyngeal mucosa could hypothetically activate mucosal immunity, which would in turn difficult SARS-CoV-2 immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections, using an enteral route, which suggest potential shortening of time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Double blind, randomized pilot clinical trial conducted at a single site, Talavera de la Reina, Spain. Potential study participants were identified by simple random sampling from the epidemiological database of contact patients recently diagnosed of COVID-19 during the study period. A total of 88 adult participants were enrolled and 84 completed the 3-month study, conducted between July 1, 2021 and August 31, 2022. INTERVENTION: Participants were randomized to receive oromucosal administered high polyphenolic olive oil, 2 mL twice a day for 3 months or no treatment. MAIN OUTCOME AND MEASURES: Primary outcomes were incidence, duration, and severity of COVID-19 after intervention. RESULTS: There were no differences in incidence between both groups but there were significant differences in duration, the median time to resolution of symptoms was 3 days in the high polyphenolic olive oil group compared with 7 days in the no-treatment group. Although time to resolution is directly related to severity, this study did not find any differences in severity. CONCLUSION AND RELEVANCE: Among full-vaccinated adults recent infected with COVID-19, a daily intake of tiny quantities of oromucosal administered high polyphenolic olive oil before infection significantly improved the time to symptom resolution. This finding strongly support the appropriateness of further deep research on the use of oromucosal administered high polyphenolic olive oil as an effective immune strategy against COVID-19.

Lead bone toxicity in growing rats exposed to chronic intermittent hypoxia.

Lead chronic intoxication under hypoxic conditions revealed growth retardation in growing rats and damages on femoral and mandibular bones that predispose to fractures. These findings aimed us to investigate if bone material and geometric properties, bone mass in terms of histomorphometry or antioxidant capacity are also impaired in such experimental model. Combined treatments significantly reduced hemimandible cross sectional geometry and intrinsic stiffness (-16% and -34%); tibia and hemimandible bone volume (-45% and -40%) and growth plate cartilage thickness (-19%). These results show a previously unreported toxic effect of lead on mandible however, longer studies should be necessary to evaluate if an adaptation of bone architecture to maintain structural properties may occur and if the oxidative stress can be identified as the primary contributory agent in the pathogenesis of lead poisoning.

Ischemic preconditioning of the graft for intestinal transplantation in rats.

To test the hypothesis that two modalities of IPC should decrease acute rejection and BT after SBTx in rats. Orthotopic allogenic SBTx was performed from Wistar to BN. IPC was performed by 2 ' and 5 ' superior mesenteric artery clamping, following 2-min and 5-min reperfusion before graft cooling and retrieving. Donor-recipient sets were randomly allocated to five groups: IPC2m4d, IPC2m7d, IPC5min7d, and the control groups for the two end points; ctrl4d and ctrl7d. IRI, rejection, and BT were assessed after four or seven days depending on the groups. Measured variables included: histology, leukocyte activation by tissue MPO determination, and proinflammatory cytokines (IL-b and TNF-α) to assess inflammatory response. Leukocyte activation was significantly reduced in IPC2m7d in comparison with Ctrl and IPC5min7d. Rejection tended to be lower in IPC2min7d. Cytokine levels were contradictory and not consistent with histology. Finally, BT was less frequent in IPC2min4d group but this benefit was missed in animals with rejection (7d). Inflammatory response (MPO) was reduced and rejection tended to be lower after in IPC2m7d. Bacterial translocation was reduced in IPC2min4d but the benefit was missed at day 7.

Endothelial KCa 1.1 and KCa 3.1 channels mediate rat intrarenal artery endothelium-derived hyperpolarization response.

AIM: Endothelium-derived hyperpolarization (EDH)-mediated response plays an essential role in the control of kidney preglomerular circulation, but the identity of the K+ channels involved in this response is still controversial. We hypothesized that large- (KCa 1.1), intermediate- (KCa 3.1) and small (KCa 2.3) -conductance Ca2+ -activated K+ (KCa ) channels are expressed in the endothelium of the preglomerular circulation and participate in the EDH-mediated response. METHODS: We study the functional expression of different K+ channels in non-cultured, freshly isolated native endothelial cells (ECs) of rat intrarenal arteries using immunofluorescence and the patch-clamp technique. We correlate this with vasorelaxant responses ex vivo using wire myography. RESULTS: Immunofluorescence revealed the expression of KCa 1.1, KCa 3.1 and KCa 2.3 channels in ECs. Under voltage-clamp conditions, acetylcholine induced a marked increase in the outward currents in these cells, sensitive to the blockade of KCa 1.1, KCa 3.1 and KCa 2.3 channels respectively. Isometric myography experiments, under conditions of endothelial nitric oxide synthase and cyclooxygenase inhibition, showed that blockade either of KCa 1.1 or KCa 3.1 channels was able to reduce the endothelium-derived vasorelaxation of isolated interlobar arteries, while their combined blockade completely abolished it. In contrast, blockade of KCa 2.3 channels did not reduce this vasorelaxant response, despite being functionally expressed in the endothelial cells. CONCLUSION: This study shows that KCa 1.1 and KCa 3.1 channels are functionally expressed at the renal vascular endothelium and play a central role in the EDH-mediated relaxation of kidney preglomerular arteries, which is important in the control of renal blood flow and glomerular filtration rate.

Biochemical characterization of recombinant UDP-sugar pyrophosphorylase and galactinol synthase from Brachypodium distachyon.

Raffinose (Raf) protects plant cells during seed desiccation and under different abiotic stress conditions. The biosynthesis of Raf starts with the production of UDP-galactose by UDP-sugar pyrophosphorylase (USPPase) and continues with the synthesis of galactinol by galactinol synthase (GolSase). Galactinol is then used by Raf synthase to produce Raf. In this work, we report the biochemical characterization of USPPase (BdiUSPPase) and GolSase 1 (BdiGolSase1) from Brachypodium distachyon. The catalytic efficiency of BdiUSPPase was similar with galactose 1-phosphate and glucose 1-phosphate, but 5- to 17-fold lower with other sugar 1-phosphates. The catalytic efficiency of BdiGolSase1 with UDP-galactose was three orders of magnitude higher than with UDP-glucose. A structural model of BdiGolSase1 allowed us to determine the residues putatively involved in the binding of substrates. Among these, we found that Cys261 lies within the putative catalytic pocket. BdiGolSase1 was inactivated by oxidation with diamide and H2O2. The activity of the diamide-oxidized enzyme was recovered by reduction with dithiothreitol or E. coli thioredoxin, suggesting that BdiGolSase1 is redox-regulated.

Efficacy of newly generated short antimicrobial cationic lipopeptides against methicillin-resistant Staphylococcus aureus (MRSA).

INTRODUCTION: Infection caused by methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) is a serious clinical challenge and research to develop new antimicrobials is imperative. METHODS: This study investigated the in vitro and in vivo efficacy of the short cationic dialkyl lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2. The antibacterial efficacy of (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 was evaluated in representative clinical methicillin-susceptible S. aureus and MRSA strains by both in vitro (MIC, time-kill curve) and in vivo (wax worms model) approaches. RESULTS: These studies revealed that both (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 have rapid bactericidal activity, with a decrease of > 3 log10 colony forming units (CFU)/mL achieved in the first 6 hours of treatment. Furthermore, (C10)2-KKKK-NH2 performed similarly to daptomycin, with a sustained bacterial killing after 24 hours. Wax worms infected and treated with these lipopeptides showed a decreased survival rate of 90% to 50% within the first day of treatment. Scanning electron microscopy determined that the effect of the short lipopeptides in S. aureus was associated with important morphological structural changes that may suggest cell membrane perturbation. CONCLUSION: These findings suggest that the short lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 may be potential new options for treating MRSA infections.

Prevalence of metabolic syndrome in scholars from Bucaramanga, Colombia: a population-based study.

BACKGROUND: Obesity and metabolic syndrome are strongly associated with type 2 diabetes mellitus and cardiovascular diseases, thus the increasing trend in their prevalence among children and adolescents from developing countries requires a further understanding of their epidemiology and determinants. METHODS AND DESIGN: A cross-sectional study was designed to determine the prevalence of metabolic syndrome among 6-10 year-old children from Bucaramanga, Colombia. A two-stage random-cluster (neighborhoods, houses) sampling process was performed based on local city maps and local statistics. The study involves a domiciliary survey; including a comprehensive socio-demographic, nutritional and physical activity characterization of the children that participated in the study, followed by a complete clinical examination; including blood pressure, anthropometry, lipid profile determination, fasting glucose and insulin levels. The prevalence of metabolic syndrome will be determined using definitions and specific percentile cut-off points for this population. Finally, the association between components of metabolic syndrome and higher degrees of insulin resistance will be analyzed through a multivariable logistic regression model. This study protocol was designed in compliance with the Helsinki declaration and approved by the local ethics board. Consent was obtained from the children and their parents/guardians. DISCUSSION: A complete description of the environmental and non-environmental factors underlying the burden of metabolic syndrome in children from a developing country like Colombia will provide policy makers, health care providers and educators from similar settings with an opportunity to guide primary and secondary preventive initiatives at both individual and community levels. Moreover, this description may give an insight into the pathophysiological mechanisms mediating the development of cardio-metabolic diseases early in life.

Sleep quality, clinical and psychological manifestations in women with systemic lupus erythematosus.

AIM: Sleep problems are a common complaint in systemic lupus erythematosus (SLE) patients. We analyzed sleep quality with subjective and objective measures in a sample with SLE and its possible relationships with the main manifestations of the disease. METHODS: Twenty-one women with SLE and 20 healthy women participated in the study. All participants were evaluated with actigraphy for a week and they completed self-report instruments of sleep quality, quality of life, fatigue, anxiety, depression and perceived stress. Comparison analyses between the two groups were done using Chi-square and Student's t-tests. The association between sleep quality and the remaining variables was explored using Pearson correlation coefficients. RESULTS: SLE patients had higher fragmentation index in the actigraphic analysis and a perception of poorer sleep quality, more fatigue, anxiety and depression than the control group. Bivariate analyses showed that the perception of more sleep disturbance and daytime dysfunction was associated with a lower health-related quality of life, more fatigue, emotional discomfort and more perceived stress. Also, the fragmentation index in the actigraphy was significantly related to the perception of poorer quality of sleep. CONCLUSION: SLE women had a poorer sleep quality (objective and subjective). These alterations could play a modulatory role in clinical and psychological manifestations of the disease and affect the quality of life in this population. More research is needed to clarify these relations and to determine the potential benefits of interventions directed to improve sleep in the clinical managing of the patients with SLE.

Enhanced erythropoietin production during hypobaric hypoxia in mice under treatments to keep the erythrocyte mass from rising: implications for the adaptive role of polycythemia.

Stress erythropoiesis is usually considered as a compensatory effort to counteract tissue hypoxia. Its homeostatic importance in anemic hypoxia has not been questioned, but researchers, clinicians, and mountain climbers have had second thoughts on polycythemia as to its appropriateness for hypoxic or altitude hypoxia (HA). Therefore, polycythemia, one of the responses to HA seen in nongenetically adapted mammals, could or could not be considered beneficial. The present study was thus performed to obtain further information on the importance of HA polycythemia on acclimation of mice to HA. To this end, the development of polycythemia was prevented by experimental manipulations (administration of 20 mg/kg/d of the hemolytic drug phenylhydrazine or removal of 0.225 mL/d of blood), and the degree of tissue hypoxia was evaluated from plasma erythropoietin (pEPO) concentration, as determined by immunoassay, in adult female mice exposed to air maintained at 506 mbar (380 mmHg) in a simulated HA (SHA) chamber during at least 23.5 h/d for 9 d. Plasma EPO concentration in those treated hypoxic mice whose hematocrit values remained almost unchanged was between 5.55 and 7.89 times higher (depending on the experimental designs) than in control hypoxic mice allowed to develop HA polycythemia. These results, plus the finding of an inverse relationship between the hematocrit value and pEPO concentration in both the polycythemic and normocythemic SHA-exposed mice indicate that HA polycythemia is highly effective in ameliorating tissue hypoxia under SHA conditions, thus giving support to the concept of the important role of the increased hemoglobin mass in nongenetically adapted animals, whereas a left-shifted oxyhemoglobin dissociation curve confers a good degree of adaptation to HA in genetically adapted animals.

Evidence from catch-up growth and hoarding behavior of rats that exposure to hypobaric air lowers the body-mass set point.

The depression of body growth rate and the reduction of body mass for chronological age and gender in growing experimental animals exposed to hypobaric air (simulated high altitude = SHA) have been associated with hypophagia because of reduced appetite. Catch-up growth during protein recovery after a short period of protein restriction only occurs if food intake becomes super-normal, which should not be possible under hypoxic conditions if the set-point for appetite is adjusted by the level of SHA. The present investigation was designed to test the hypothesis that growth retardation during exposure to SHA is due to an alteration of the neural mechanism for setting body mass size rather than a primary alteration of the central set-point for appetite. One group of female rats aged 35 d were exposed to SHA (5460m) in a SHA chamber for 27 d (HX rats). Other group was maintained under local barometric pressure conditions (NX rats). One half of both NX and HX rats were fed a protein-free diet for the initial 9 d of the experimental period. From this time on, they were fed a diet containing 20% protein, as were the remaining rats of both groups during the entire experimental period. The growth rates of both mass and length of the body were significantly depressed in well-nourished rats exposed to SHA during the entire observation period when compared to normoxic ones. At its end, body mass and body length were 24% and 21% less in HX than in NX rats. Growth rates were negatively affected by protein restriction in both NX and HX rats. During protein recovery, they reached supernormal values in response to supernormal levels of energy intake that allowed a complete catch-up of both body mass and length. The finding that energy intake during the period of protein rehabilitation in HX rats previously stunted by protein restriction was markedly higher than in HX control ones at equal levels of hypoxia demonstrates that the degree of hypoxia does not determine directly the degree of appetite and energy intake. Furthermore, the finding that catch-up growth in the stunted HX rats returns the animal only to the stunted size appropriate for the hypoxic animal supports the hypothesis that hypoxia lowers the set-point for body mass size, which is reached by inhibition of appetite. Confirmation of the hypothesis was done by assessment of the set-point of body mass by the behavioral method of the weight threshold to hoard food. It was lowered by 17.0% in HX rats.

Men and women with fibromyalgia: Relation between attentional function and clinical symptoms.

OBJECTIVES: This study was the first to explore whether individuals with fibromyalgia (FM) have different cognitive alterations (i.e., in alertness, orienting, and executive control) depending on their sex. We also analysed possible gender differences in the relationships between cognitive functioning and some of the main symptoms of FM. DESIGN: Cross-sectional study. METHODS: Two clinical groups with FM (n = 58 women and n = 20 men) and two healthy control groups (n = 21 women and n = 27 men) aged between 30 and 60 years old participated in this study. Pain intensity, sleep disturbance, depression, anxiety, pain catastrophizing, and daily functioning were evaluated with self-report measures. Attentional function was assessed with the ANT-I task (Attentional Network Test-Interactions). RESULTS: Mixed ANOVAs showed impairment in vigilance and executive control in both male and female patients with FM compared with controls. Control men were faster than control women, but FM eliminated sex differences. In addition, attention deficit was associated with worse daily functioning in women but not in men with FM. Emotional distress and sleep disruption seemed to contribute differently to these cognitive alterations in both sexes. CONCLUSIONS: Therapy strategies aimed at reducing emotional distress and sleep disruption are likely to improve cognitive function by enhancing vigilance. Therapies aimed at reducing emotional distress seem to improve attentional function more in women than in men; those aimed at improving sleep quality are likely to reduce a vigilance/alertness deficit in women and executive problems in men.

Enhanced hypoxia-stimulated erythropoietin production in mice with depression of erythropoiesis induced by hyperoxia.

Current evidence suggests that a modulatory action on O(2)-dependent EPO secretion is exerted by the erythroid/precursor cell population in the erythropoietic organs through a negative feedback system. The hypothesis is based on studies of stimulated-EPO secretion performed in mice in whom the erythropoietic rates were either enhanced or depressed in the presence of normal plasma EPO half-lives. Since erythropoietic depression was elicited by cyclophosphamide administration, which could have altered EPO production directly, the aim of the present investigation was to estimate hypoxia-stimulated EPO secretion in a mouse model of functional depressed erythropoiesis induced by exposure to normobaric hyperoxia. Females CF#1 mice aged 70 d were divided into control (C) and experimental (E) groups. The former was maintained in plastic cages in a normal environment, while the latter was placed in an environment of 60% O(2)/40% N(2) in an 85-dm(3) atmospheric chamber with air flow of 1 L/min. Erythropoiesis was evaluated by either 24-h RBC-(59)Fe uptake or iron kinetics performed 3 h after IV injection of a tracer dose of (59)Fe. Both indexes of the red cell production rate were significantly depressed in E mice. Plasma disappearance of exogenous EPO in C mice, as well as in E mice exposed to hyperoxia for 4 d, was estimated by injecting (125)I-rHuEPO intravenously. Linear regression analysis indicated that neither the differences between the slopes of both curves nor the Y-intercepts were significant. Hypobaric hypoxemia was used as stimulus for EPO production. Plasma immuno-EPO titer after a 4-h exposure to hypobaric air was 73% higher in mice with hyperoxia-induced hypoerythropoiesis than in control mice with normal erythropoiesis. Data support the concept that the rate of erythropoiesis, perhaps through the number of the erythroid progenitor/precursor cell population, modulates O(2)-dependent EPO secretion.

Failure of polycythemia-induced increase in arterial oxygen content to suppress the anorexic effect of simulated high altitude in the adult rat.

The anorexic effect of exposure to high altitude may be related to the reduction in the arterial oxygen content (Ca(O2)) induced by hypoxemia and possibly the associated decreased convective oxygen transport (COT). This study was then performed to evaluate the effects of either transfusion-induced polycythemia or previous acclimation to hypobaria with endogenously induced polycythemia on the anorexic effect of simulated high altitude (SHA) in adult female rats. Food consumption, expressed in g/d/100 g body weight, was reduced by 40% in rats exposed to 506 mbar for 4 d, as compared to control rats maintained in room air. Transfusion polycythemia, which significantly increased hematocrit, hemoglobin concentration, Ca(O2), and COT, did not change the anorexic response to the exposure to hypobaric air. Depression of food intake during exposure to SHA also occurred in rats fasted during 31 h before exposure and allowed to eat ad libitum for 2 h during exposure. Body mass loss was similar in 48-h fasted rats that were either hypoxic or normoxic. Body mass loss was similar in normoxic and hypoxic rats, the former eating the amount of food freely eaten by the latter. Hypoxia-acclimated rats with endogenously induced polycythemia taken to SHA again had diminished food intake and lost body mass at rates that were very close to those found in nonacclimated ones. Exposure to SHA also led to a decrease in food consumption, body weight, and plasma leptin in adult female mice. Analysis of data suggest that body mass loss that accompanies SHA-induced hypoxia is due to hypophagia and that experimental manipulation of the blood oxygen transport capacity cannot ameliorate it. Leptin does not appear to be an inducer of the anorexic response to hypoxia, at least in mice and rats.

The impact of pain on anxiety and depression is mediated by objective and subjective sleep characteristics in fibromyalgia patients.

OBJECTIVES: Pain is the cardinal feature in fibromyalgia syndrome (FM) and increases the risk of anxiety and depression. Patients with FM frequently report sleep disturbances as well. Sleep may mediate the association between pain and emotional symptoms, an idea which has been scarcely studied. The objective of this study was to uncover the role of subjective and objective sleep characteristics as mediators of the relationship between pain and anxiety and depression in FM. MATERIALS AND METHODS: Fifty-five female with FM (mean age, 47.62 ± 7.64 y) were assessed to obtain self-reported measures of pain, sleep quality, anxiety and depression levels, and self-efficacy to cope with pain. An ambulatory polysomnographic recording was performed to assess sleep architecture. RESULTS: Subjective poor sleep quality was found in all participtants. Pain correlated with subjective and objective sleep parameters, self-efficacy, anxiety, and, marginally, with depression. The mediated regression analysis suggested that the best models to explain the impact of pain on anxiety and depression included, as mediators, subjective sleep quality, objective sleep efficiency, and self-efficacy (these models explained 34% of the variance), with objective sleep efficiency being the mediator with the highest influence (P<0.05). DISCUSSION: These findings show a high prevalence of sleep problems in individuals with FM and suggest that they play a role in the relationship between pain and anxiety and depression. In fact, the impact of chronic pain on the later emotional variables was mediated not only by self-efficacy but also by subjective sleep quality and, especially, by objective sleep efficiency.