Extreme solar storms and the quest for exact dating with radiocarbon.

Radiocarbon (14C) is essential for creating chronologies to study the timings and drivers of pivotal events in human history and the Earth system over the past 55,000 years. It is also a fundamental proxy for investigating solar processes, including the potential of the Sun for extreme activity. Until now, fluctuations in past atmospheric 14C levels have limited the dating precision possible using radiocarbon. However, the discovery of solar super-storms known as extreme solar particle events (ESPEs) has driven a series of advances with the potential to transform the calendar-age precision of radiocarbon dating. Organic materials containing unique 14C ESPE signatures can now be dated to annual precision. In parallel, the search for further storms using high-precision annual 14C measurements has revealed fine-scaled variations that can be used to improve calendar-age precision, even in periods that lack ESPEs. Furthermore, the newly identified 14C fluctuations provide unprecedented insight into solar variability and the carbon cycle. Here, we review the current state of knowledge and share our insights into these rapidly developing, diverse research fields. We identify links between radiocarbon, archaeology, solar physics and Earth science to stimulate transdisciplinary collaboration, and we propose how researchers can take advantage of these recent developments.

Psychology research in women's soccer: a scoping review.

Previous research suggests that psychological factors play an important role in trying to explain and predict the participation, performance, and health of player and practitioners in soccer. However, most previous works have focused on specific research questions and included samples from male populations. As part of a larger Fédération Internationale de Football Association (FIFA) project aiming to steer women's soccer research, our purpose with this scoping review was to give an overview of the current state of psychology-related research within women's soccer. We searched five electronic databases up to April 2023, from which 280 original peer-reviewed articles met the inclusion criteria. Included records were inductively coded into 75 specific research topics and nine broader research categories. Population characteristics within each topic and category, and overall publication trends, were identified. The results revealed a growth in research attention, with notable increases in publication rates around the international competitions years, over the last two decades. While a notable number of abstracts did not report sufficient details about population age and/or playing levels, senior elite players were identified as the most common population studied. Most studies examined several topics from different research categories, with research focusing on emotions, moods and/or environmental factors, and the specific the topics of anxiety, stress, and coach behavior, receiving most research attention. Our study provides an informative mapping of all psychology-related research activity within women's soccer, which will enhance researchers' understanding of the current quantity of literature within this complex, heterogeneous, and growing area of research.

Radiocarbon: A key tracer for studying Earth's dynamo, climate system, carbon cycle, and Sun.

Radiocarbon (14C), as a consequence of its production in the atmosphere and subsequent dispersal through the carbon cycle, is a key tracer for studying the Earth system. Knowledge of past 14C levels improves our understanding of climate processes, the Sun, the geodynamo, and the carbon cycle. Recently updated radiocarbon calibration curves (IntCal20, SHCal20, and Marine20) provide unprecedented accuracy in our estimates of 14C levels back to the limit of the 14C technique (~55,000 years ago). Such improved detail creates new opportunities to probe the Earth and climate system more reliably and at finer scale. We summarize the advances that have underpinned this revised set of radiocarbon calibration curves, survey the broad scientific landscape where additional detail on past 14C provides insight, and identify open challenges for the future.

Modeling Obesity in Norway (The MOON Study): A Decision-Analytic Approach-Prevalence, Costs, and Years of Life Lost.

BACKGROUND: Limited knowledge exists on the expected long-term effects and cost-effectiveness of initiatives aiming to reduce the burden of obesity. AIM: To develop a Norwegian obesity-focused disease-simulation model: the MOON model. MATERIAL AND METHODS: We developed a Markov model and simulated a Norwegian birth cohort's movement between the health states "normal weight,""overweight,""obese 1,""obese 2," and "dead" using a lifetime perspective. Model input was estimated using longitudinal data from health surveys and real-world data (RWD) from local and national registers (N = 99,348). The model is deterministic and probabilistic and stratified by gender. Model validity was assessed by estimating the cohort's expected prevalence, health care costs, and mortality related to overweight and obesity. RESULTS: Throughout the cohort's life, the prevalence of overweight increased steadily and stabilized at 45% at 45 y of age. The number of obese 1 and 2 individuals peaked at age 75 y, when 44% of women and 35% of men were obese. The incremental costs per person associated with obesity was highest in older ages and, when accumulated over the lifetime, higher among women (€12,118, €9,495-€15,047) than men (€6,646, €5,252-€10,900). On average, obesity shortened the life expectancy of women/men in the whole cohort by 1.31/1.08 y. The life expectancy for normal-weight women/men at age 30 was 83.31/80.31. The life expectancy was reduced by 1.05/0.65 y if the individual was overweight, obese (2.87/2.71 y), or obese 2 (4.06/4.83 y). CONCLUSION: The high expected prevalence of obesity in the future will lead to substantial health care costs and large losses in life-years. This underscores the need to implement interventions to reduce the burden of obesity; the MOON model will enable economic evaluations for a wide range of interventions.

Data from the ERA-EDTA Registry were examined for trends in excess mortality in European adults on kidney replacement therapy.

The objective of this study was to investigate whether the improvement in survival seen in patients on kidney replacement therapy reflects the enhanced survival of the general population. Patient and general population statistics were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and the World Health Organization databases, respectively. Relative survival models were composed to examine trends over time in all-cause and cause-specific excess mortality, stratified by age and modality of kidney replacement therapy, and adjusted for sex, primary kidney disease and country. In total, 280,075 adult patients started kidney replacement therapy between 2002 and 2015. The excess mortality risk in these patients decreased by 16% per five years (relative excess mortality risk (RER) 0.84; 95% confidence interval 0.83-0.84). This reflected a 14% risk reduction in dialysis patients (RER 0.86; 0.85-0.86), and a 16% increase in kidney transplant recipients (RER 1.16; 1.07-1.26). Patients on dialysis showed a decrease in excess mortality risk of 28% per five years for atheromatous cardiovascular disease as the cause of death (RER 0.72; 0.70-0.74), 10% for non-atheromatous cardiovascular disease (RER 0.90; 0.88-0.92) and 10% for infections (RER 0.90; 0.87-0.92). Kidney transplant recipients showed stable excess mortality risks for most causes of death, although it did worsen in some subgroups. Thus, the increase in survival in patients on kidney replacement therapy is not only due to enhanced survival in the general population, but also due to improved survival in the patient population, primarily in dialysis patients.

Pretreatment and gaseous radiocarbon dating of 40-100 mg archaeological bone.

Radiocarbon dating archaeological bone typically requires 300-1000 mg material using standard protocols. We report the results of reducing sample size at both the pretreatment and 14C measurement stages for eight archaeological bones spanning the radiocarbon timescale at different levels of preservation. We adapted our standard collagen extraction protocol specifically for <100 mg bone material. Collagen was extracted at least twice (from 37-100 mg material) from each bone. Collagen aliquots containing <100 µg carbon were measured in replicate using the gas ion source of the AixMICADAS. The effect of sample size reduction in the EA-GIS-AMS system was explored by measuring 14C of collagen containing either ca. 30 µg carbon or ca. 90 µg carbon. The gas dates were compared to standard-sized graphite dates extracted from large amounts (500-700 mg) of bone material pretreated with our standard protocol. The results reported here demonstrate that we are able to reproduce accurate radiocarbon dates from <100 mg archaeological bone material back to 40,000 BP.

The relationship between maximum heart rate in a cardiorespiratory fitness test and in a maximum heart rate test.

OBJECTIVES: It is suggested that individuals will not reach their heart rate maximum (HRmax) at an incremental cardiorespiratory fitness (CRF) test and commonly five beats per minute (bpm) are added to the highest heart rate (HR) reached. To our knowledge, there is not sufficient data justifying such estimation. Our aim was to assess whether individuals reached HRmax in an incremental CRF test to exhaustion. DESIGN AND METHODS: Fifty-one males and 57 females (aged 22-70 years) completed both an incremental CRF test (gradual increase in speed and/or inclination until volitional exhaustion) and a test designed to reach HRmax (with repeated work bouts at high intensity before maximal exertion) ≥48h apart. We investigated the relationship between the highest HR in the two tests using hierarchical linear regression analysis, with HRmax from the HRmax test as a dependent variable, and the highest HR reached at the CRF test (HRcrf), whether maximum oxygen uptake was reached on the CRF test, CRF, sex and age as independent variables. RESULTS: HRmax was 2.2 (95% confidence interval, 1.5-2.9) bpm higher in the test designed to reach HRmax than in the CRF test (p<0.001). Only HRcrf significantly predicted HRmax, with no contribution of the other variables in the model. HRmax was predicted from the highest HR reached in an incremental CRF test by multiplying HRcrf with 0.967, and adding 8.197 (HRmax=8.197+[0.967×HRcrf]) beats/min. CONCLUSION: Non-athletes reached close to HRmax in a standard CRF test.

A study of coach-team perceptual distance concerning the coach-created motivational climate in youth sport.

The purpose of this study was to examine whether coach-team perceptual distance regarding the coach-created motivational climate related to achievement goal orientations and affective responses. To this end, we used polynomial regression analysis with response surface methodology. The sample consisted of 1359 youth soccer players (57.8% male; Mage  = 11.81 years, SD = 1.18), belonging to 87 different teams (Msize  = 16.47), and 87 coaches (94.6% male, Mage  = 42 years, SD = 5.67). Results showed that team perceptions of a coach-created mastery climate were positively related to team-rated task goal orientation and enjoyment, whereas team perceptions of a coach-created performance climate were positively related to team-rated ego goal orientation and anxiety, and negatively related to team-rated enjoyment. When the coach and the team were in perceptual agreement, the outcomes increased as both coach and team perceptions of the climate increased. In situations of perceptual disagreement, the most negative effects were seen when the coach held a more favorable perception of the motivational climate compared to the team. The findings highlight the importance of perceptual agreement between the coach and his/her team, contributing to the literature focusing on the effects of the coach-created motivational climate.

The impact of wearable motion sensing technology on physical activity in older adults.

BACKGROUND AND PURPOSE: Physical activity provides substantial health benefits. Older adults are less physically active than the rest of the population, and interventions that promote physical activity are needed. In this meta-analysis, we investigate how different wearable activity trackers (pedometers and accelerometers) may impact physical activity levels in older adults. METHODS: We searched MEDLINE, Embase and CINAHL for randomized controlled trials including participants that were ≥65 years, using wearable activity trackers with the intent of increasing physical activity. Studies whose comparator groups were engaged in active or inactive interventions, such as continued a physical therapy program or goal-setting counseling, were not excluded simply for implementing co-interventions. We used random-effects models to produce standardized mean differences (SMDs) for physical activity outcomes. Heterogeneity was measured using I2. RESULTS: Nine studies met the eligibility criteria: Four using accelerometers, four using pedometers, and one comparing accelerometers and pedometers, for a total number of 939 participants. Using pooled data, we found a statistically significant effect of using accelerometers (SMD = 0.43 (95%CI 0.19-0.68), I2 = 1.6%, p = 0.298), but not by using pedometers (SMD = 0.17 (95%CI -0.08-0.43), I2 = 37.7%, p = 0.174) for increasing physical activity levels. DISCUSSION AND CONCLUSIONS: In this study, we found that accelerometers, alone or in combination with other co-interventions, increased physical activity in older adults however pedometers were not found to increase physical activity. The high risk of bias found in most studies limits these findings. High quality studies that isolate the effects of accelerometers on physical activity changes are needed.

High-Frequency of Computer Tomography and Surgery for Abdominal Pain After Roux-en-Y Gastric Bypass.

INTRODUCTION: Acute, intermittent, and chronic abdominal pain is a common complaint after Roux-en-Y gastric bypass (RYGB). OBJECTIVES: The aim of the study was to evaluate the use of medical imaging and the need for surgery treating abdominal pain after RYGB in a cohort with long-term follow-up. METHODS: Data from 569 patients who underwent RYGB as the primary bariatric procedure at a public hospital in Norway between April 2004 and June 2011 were prospectively registered in a local quality registry for bariatric surgery. All abdominal imaging and abdominal surgical procedures were registered until August 2017. RESULTS: Mean follow-up was 100 months (61-159). During the observation period, 22% had one CT, 9% had two CTs, 4% had three CTs, and 5% had four or more CTs for abdominal pain. Twenty-two percent underwent abdominal surgery, as 16% had one and 6% had two or more operations and gynecological procedures excluded. The purpose of operation was postoperative complications (1.4%), suspected internal herniation (9.3%), cholecystectomy (9.3%), appendectomy (2.3%), hernias (3.2%), and perforated ulcer in the gastrojejunal anastomosis (0.7%). Mean time interval was 42 ± 27 months from RYGB to cholecystectomy and 51 ± 26 months for suspected IH. CONCLUSION: With a mean follow-up period of more than 8 years after RYGB, 40% of the patients suffered from abdominal pain, needing one or more CT scans. The need for surgery treating suspected internal hernia and cholecystectomy was equal, at 9.3% for both procedures, but the mean time from RYGB to operation was shorter for cholecystectomies.

Higher Drop in Speed during a Repeated Sprint Test in Soccer Players Reporting Former Hamstring Strain Injury.

Aim: Hamstring strain injury is common in soccer. The aim of this study was to evaluate the physical capacity of players who have and have not suffered from hamstring strain injury in a sample of semi-professional and professional Norwegian soccer players in order to evaluate characteristics and to identify possible indications of insufficient rehabilitation. Method: Seventy-five semi-professional and professional soccer players (19 ± 3 years) playing at the second and third level in the Norwegian league participated in the study. All players answered a questionnaire, including one question about hamstring strain injury (yes/no) during the previous 2 years. They also performed a 40 m maximal sprint test, a repeated sprint test (8 × 20 m), a countermovement jump, a maximal oxygen consumption (VO2max) test, strength tests and flexibility tests. Independent sample t-tests were used to evaluate differences in the physical capacity of the players who had suffered from hamstring strain injury and those who had not. Mixed between-within subject's analyses of variance was used to compare changes in speed during the repeated sprint test between groups. Results: Players who reported hamstring strain injury during the previous two years (16%) had a significantly higher drop in speed (0.07 vs. 0.02 s, p = 0.007) during the repeated sprint test, compared to players reporting no previous hamstring strain injury. In addition, there was a significant interaction (groups × time) (F = 3.22, p = 0.002), showing that speed in the two groups changed differently during the repeated sprint test. There were no significant differences in relations to age, weight, height, body fat, linear speed, countermovement jump height, leg strength, VO2max, or hamstring flexibility between the groups. Conclusion: Soccer players who reported hamstring strain injury during the previous 2 years showed significant higher drop in speed during the repeated sprint test compared to players with no hamstring strain injury. The maximal speed, leg strength, ability to produce maximal power, endurance capacity, and hamstring flexibility was similar for both groups. Thus, a repeated sprint test consisting of 8 × 20 m could be used as a field-based diagnostic tool to identify players in need of reconditioning programs to ensure complete post-injury rehabilitation.

PQRST - a unique aide-memoire for capnography interpretation during cardiac arrest.

The use of capnography is recommended during resuscitation. By implementing the mnemonic "PQRST", rescuers have a ready-made checklist to help them achieve the full potential of capnography. This approach can facilitate efforts to both reduce the hands-off time and individualize the treatment, which can lead to improved survival for our patients.

Factors complicating interpretation of capnography during advanced life support in cardiac arrest--a clinical retrospective study in 575 patients.

BACKGROUND: End tidal carbon dioxide (ETCO(2)) monitoring during advanced life support (ALS) using capnography, is recommended in the latest international guidelines. However, several factors might complicate capnography interpretation during ALS. How the cause of cardiac arrest, initial rhythm, bystander cardiopulmonary resuscitation (CPR) and time impact on the ETCO(2) values are not completely clear. Thus, we wanted to explore this in out-of-hospital cardiac arrested (OHCA) patients. METHODS: The study was carried out by the Emergency Medical Service of Haukeland University Hospital, Bergen, Norway. All non-traumatic OHCAs treated by our service between January 2004 and December 2009 were included. Capnography was routinely used in the study, and these data were retrospectively reviewed together with Utstein data and other clinical information. RESULTS: Our service treated 918 OHCA patients, and capnography data were present in 575 patients. Capnography distinguished well between patients with or without return of spontaneous circulation (ROSC) for any initial rhythm and cause of the arrest (p<0.001). Cardiac arrests with a respiratory cause had significantly higher levels of ETCO(2) compared to primary cardiac causes (p<0.001). Bystander CPR affected ETCO(2)-recordings, and the ETCO(2) levels declined with time. CONCLUSIONS: Capnography is a useful tool to optimise and individualise ALS in cardiac arrested patients. Confounding factors including cause of cardiac arrest, initial rhythm, bystander CPR and time from cardiac arrest until quantitative capnography had an impact on the ETCO(2) values, thereby complicating and limiting prognostic interpretation of capnography during ALS.

Repeated magnetic resonance imaging and cerebral performance after cardiac arrest--a pilot study.

AIM OF THE STUDY: Prognostication may be difficult in comatose cardiac arrest survivors. Magnetic resonance imaging (MRI) is potentially useful in the prediction of neurological outcome, and it may detect acute ischemia at an early stage. In a pilot setting we determined the prevalence and development of cerebral ischemia using serial MRI examinations and neurological assessment. METHODS: Ten witnessed out-of-hospital cardiac arrest patients were included. MRI was carried out approximately 2h after admission to the hospital, repeated after 24h of therapeutic hypothermia and 96 h after the arrest. The images were assessed for development of acute ischemic lesions. Neurophysiological and cognitive tests as well as a self-reported quality-of-life questionnaire, Short Form-36 (SF-36), were administered minimum 12 months after discharge. RESULTS: None of the patients had acute cerebral ischemia on MRI at admission. Three patients developed ischemic lesions after therapeutic hypothermia. There was a change in the apparent diffusion coefficient, which significantly correlated with the temperature (p < 0.001). The neurophysiological tests appeared normal. The patients scored significantly better on SF 36 than the controls as regards both bodily pain (p = 0.023) and mental health (p = 0.016). CONCLUSIONS: MRI performed in an early phase after cardiac arrest has limitations, as MRI performed after 24 and 96 h revealed ischemic lesions not detectable on admission. ADC was related to the core temperature, and not to the volume distributed intravenously. Follow-up neurophysiologic tests and self-reported quality of life were good.

Emergency intraosseous access in a helicopter emergency medical service: a retrospective study.

BACKGROUND: Intraosseous access (IO) is a method for providing vascular access in out-of-hospital resuscitation of critically ill and injured patients when traditional intravenous access is difficult or impossible. Different intraosseous techniques have been used by our Helicopter Emergency Medical Services (HEMS) since 2003. Few articles document IO use by HEMS physicians. The aim of this study was to evaluate the use of intraosseous access in pre-hospital emergency situations handled by our HEMS. METHODS: We reviewed all medical records from the period May 2003 to April 2010, and compared three different techniques: Bone Injection Gun (B.I.G® - Waismed), manual bone marrow aspiration needle (Inter V - Medical Device Technologies) and EZ-IO® (Vidacare), used on both adults and paediatric patients. RESULTS: During this seven-year period, 78 insertion attempts were made on 70 patients. Overall success rates were 50% using the manual needle, 55% using the Bone Injection Gun, and 96% using the EZ-IO®. Rates of success on first attempt were significantly higher using the EZ-IO® compared to the manual needle/Bone Injection Gun (p < 0.01/p < 0.001). Fifteen failures were due to insertion-related problems (19.2%), with four technical problems (5.1%) and three extravasations (3.8%) being the most frequent causes. Intraosseous access was primarily used in connection with 53 patients in cardiac arrest (75.7%), including traumatic arrest, drowning and SIDS. Other diagnoses were seven patients with multi-trauma (10.0%), five with seizures/epilepsy (7.1%), three with respiratory failure (4.3%) and two others (2.9%). Nearly one third of all insertions (n = 22) were made in patients younger than two years. No cases of osteomyelitis or other serious complications were documented on the follow-up. CONCLUSIONS: Newer intraosseous techniques may enable faster and more reliable vascular access, and this can lower the threshold for intraosseous access on both adult and paediatric patients in critical situations. We believe that all emergency services that handle critically ill or injured paediatric and adult patients should be familiar with intraosseous techniques.

Capillary leakage in post-cardiac arrest survivors during therapeutic hypothermia - a prospective, randomised study.

BACKGROUND: Fluids are often given liberally after the return of spontaneous circulation. However, the optimal fluid regimen in survivors of cardiac arrest is unknown. Recent studies indicate an increased fluid requirement in post-cardiac arrest patients. During hypothermia, animal studies report extravasation in several organs, including the brain. We investigated two fluid strategies to determine whether the choice of fluid would influence fluid requirements, capillary leakage and oedema formation. METHODS: 19 survivors with witnessed cardiac arrest of primary cardiac origin were allocated to either 7.2% hypertonic saline with 6% poly (O-2-hydroxyethyl) starch solution (HH) or standard fluid therapy (Ringer's Acetate and saline 9 mg/ml) (control). The patients were treated with the randomised fluid immediately after admission and continued for 24 hours of therapeutic hypothermia. RESULTS: During the first 24 hours, the HH patients required significantly less i.v. fluid than the control patients (4750 ml versus 8010 ml, p = 0.019) with comparable use of vasopressors. Systemic vascular resistance was significantly reduced from 0 to 24 hours (p = 0.014), with no difference between the groups. Colloid osmotic pressure (COP) in serum and interstitial fluid (p < 0.001 and p = 0.014 respectively) decreased as a function of time in both groups, with a more pronounced reduction in interstitial COP in the crystalloid group. Magnetic resonance imaging of the brain did not reveal vasogenic oedema. CONCLUSIONS: Post-cardiac arrest patients have high fluid requirements during therapeutic hypothermia, probably due to increased extravasation. The use of HH reduced the fluid requirement significantly. However, the lack of brain oedema in both groups suggests no superior fluid regimen. Cardiac index was significantly improved in the group treated with crystalloids. Although we do not associate HH with the renal failures that developed, caution should be taken when using hypertonic starch solutions in these patients. TRIAL REGISTRATION: NCT00347477.

Insulin-requiring diabetes in rural Ethiopia: should we reopen the case for malnutrition-related diabetes?

AIMS/HYPOTHESIS: We evaluated the incidence of insulin-requiring diabetes in a rural area of sub-Saharan Africa. METHODS: Health surveillance data from a chronic disease programme in two zones of Ethiopia, Gondar and Jimma, were studied. The two zones have a population of more than 5,000,000 people. RESULTS: In Gondar Zone (1995-2008) and Jimma Zone (2002-2008) 2,280 patients presented with diabetes, of whom 1,029 (45%) required insulin for glycaemic control at diagnosis. The annual incidence of insulin-requiring diabetes was 2.1 (95% CI 2.0-2.2) per 100,000 and was twice as high in men (2.9 per 100,000) as in women (1.4 per 100,000). In both sexes incidence rates peaked at the age of 25 to 29 years. Incidence rates in the urban areas of Gondar and Jimma were five times higher than in the surrounding rural areas. Patients with insulin-requiring diabetes from rural and urban areas had a very low BMI and most were subsistence farmers or unemployed. CONCLUSIONS/INTERPRETATION: The typical patient with diabetes in rural Ethiopia is an impoverished, young adult male with severe symptoms requiring insulin for glycaemic control. The low incidence rates in rural compared with urban areas suggest that many cases of this disease remain undiagnosed. The disease phenotype encountered in this area of Africa is very different from the classical type 1 diabetes seen in the West and most closely resembles previous descriptions of malnutrition-related diabetes, a category not recognised in the current WHO Diabetes Classification. We believe that the case for this condition should be reopened.

High-risk papillomavirus infection is associated with altered antibody responses in genital tract: non-specific responses in HPV infection.

In order to gain more information about local humoral immune responses to HPV infection, we quantified IgG, IgM, secretory-IgA (S-IgA), and total-IgA by ELISA, and lysozyme and lactoferrin by TR-IFMA, in cervical and cervicovaginal secretions of 40 healthy women and 28 high-risk HPV infected patients (11 were HPV16+). IgG, total-IgA, and S-IgA concentrations in cervicovaginal secretions (p < 0.0001) and high IgG and total-IgA concentrations (p < 0.001 and p < 0.01, respectively) in endocervical secretions were significantly higher in HPV+ patients than in the healthy group. Since the S-IgA/total-IgA ratio was significantly lower in cervicovaginal (7.5%) and endocervical secretions (36.5%) in HPV+ women compared to the control group (p < 0.003 and p < 0.001, respectively), HPV could be responsible for an increase in local production of non-secretory IgA (monomeric and dimeric forms). IgG and total-IgA concentrations in cervicovaginal and endocervical secretions fell in the same general percentage range in both HPV16+ and HPV+ groups (80% and 15%, respectively). However, the S-IgA/total-IgA ratio was much lower in HPV16+ than in HPV+ women, in both cervicovaginal secretions (3.4%) (p < 0.003) and in endocervical secretions (23.3%) (p < 0.001). Innate immunity proteins and local S-IgA response could not stop the spread of HPV infection in spite of high lysozyme and lactoferrin concentrations. HPV16+ disturbed the local humoral immune system, which could partly explain its low clearance.

Nonspecific secretory immunity in HIV-infected patients with oral candidiasis.

Buccal and digestive tract opportunistic infections occur frequently in patients infected by HIV. In this study, we measured lysozyme (Lz), lactoferrin (Lf), total IgA (T-IgA), and secretory IgA (S-IgA) levels to investigate nonspecific secretory immunity in HIV-infected patients with oral candidiasis. Serum, saliva, and stool samples were analyzed by time-resolved immunofluorometric assay for Lz and Lf levels and by enzyme-linked immunosorbent assay for T-IgA and S-IgA levels. Mean salivary Lf and T-IgA levels (66.50 mg/L and 0.10 g/L, respectively) and mean fecal Lf, T-IgA, and S-IgA outputs (0.87, 54.0, and 43.6 mg/d, respectively) were significantly higher in HIV-infected patients with oropharyngeal candidiasis than in HIV-infected patients without oropharyngeal candidiasis and healthy subjects. There was a modification in the molecular form rate, with a high increase in S-IgA and monomeric IgA transudation from the plasmatic compartment into salivary and digestive fluids and an increase in salivary Lf local synthesis by polymorphonuclear neutrophils. HIV infection appears to be associated with dysregulation of some of the nonspecific immune factors at the mucosal surface. Despite high saliva concentrations and high intestinal output, innate immunity was not able to stop yeast expansion in HIV-infected patients.

Validation of a high sensitive immunoenzymatic assay to establish the origin of immunoglobulins in female genital secretions.

Several studies were carried out to characterize the humoral immune response on mucosal genital surfaces. However, the results obtained so far were particularly conflicting due to the absence of validation methods. The aim of this study was to develop and validate a quantitative ELISA method, which is sensitive and reproducible, to measure immunoglobulin and secretory immunoglobulin concentrations in various biological fluids. This quantitative, sensitive (detection limit = 1 microg/L) and reproducible (coefficient of variation < 15%) method could be of interest to study the effects of viral infections on mucosal non-specific immune response in genital tract. To explore the humoral response, serum, saliva, vaginal secretions, and cervicovaginal secretions from 18 women, 20-45 years old, were evaluated for total-IgA, secretory IgA, IgM, and IgG. Albumin level was also evaluated by immuno-nephelometry. The secretion rates of immunoglobulins were measured by calculating their relative coefficients of excretion by reference to albumin. Despite large individual variations, median immunoglobulin levels were higher in the endocervical secretions than in the cervicovaginal secretions. When we compared the rates of immunoglobulins in genital fluids, IgG prevalence was higher (80%) in cervicovaginal and endocervical secretions than IgA prevalence (12%). In contrast, digestive mucosal secretions, such as saliva, contained mostly IgA (80%). In cervicovaginal and endocervical secretions, IgG and IgM originated mainly from serum, whereas a local synthesis provided total-IgA and secretory IgA. These results allowed us to raise a possible hypothesis for the origin of immunoglobulins in the genital tract. They illustrated the peculiar feature of the female reproductive tract and the difficulty for this tissue to contribute in the mucosal associated lymphoid tissue. The low secretory-IgA and total-IgA levels could explain the particular sensitivity of the vagina and the cervix to infections.