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Poultry litter is a valuable source of nutrients for crop production, but its use in agriculture can lead to environmental and public health concerns due to the presence of pollutants, antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs). We compared the effect of different on-farm poultry litter composting processes on physicochemical, biological, and toxicological parameters, as well as on the occurrence of antibiotics and resistant Escherichia coli. The composting treatments consisted of passively-aerated piles C:N = 19 (PAC 19 ), mechanically-aerated piles C:N = 19 (MAC 19 ), and mechanically-aerated piles C:N = 30 (MAC 30 ). Poultry litter composting led to a significant reduction of antibiotic residues, enteroparasites and antibiotic resistant E. coli. The conditions of the process, such as extra C source and mechanical aeration influence the quality of the final product. MAC 19 is a low-cost effective method to reduce the potential risks associated with poultry litter use in agriculture and produce good quality compost., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: The last nationwide evaluation of abortion education in undergraduate medical schools was conducted by Espey et al. more than 15 years ago. To better understand what medical schools are teaching medical students about abortion care, we conducted a brief assessment of abortion education and training at U.S. medical schools., Study Design: In April 2019, the study team emailed a three-item survey to the obstetrics and gynecology clerkship directors at Association of American Medical Colleges-accredited U.S. allopathic medical schools (n = 143). The multiple-choice survey assessed the availability and type of reproductive health education students had during their preclinical and clinical experiences., Results: Ninety-one (64%) medical schools responded. Fifty-four (59%) schools reported abortion education as part of their preclinical curriculum, with 26 (29%) dedicating at least one lecture to abortion education. Sixty-seven (74%) institutions provided a clinical abortion experience for students, with 24 (26%) indicating students had to arrange participation on their own. Nine programs (10%) reported offering no formal abortion education., Conclusions: While the availability of abortion education has increased since the last nationwide survey in 2005, discrepancies in the education offered persist, and many medical students remain without access to this training., Implications: Although abortion plays an essential role in women's health services, discrepancies in training opportunities limit abortion education in U.S. medical schools. Gaps in the education of medical students may have downstream effects on the availability of doctors who are trained in providing medically-safe abortions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Poultry waste has been used as fertilizer to avoid soil degradation caused by the long-term application of chemical fertilizer. However, few studies have evaluated field conditions where livestock wastes have been used for extended periods of time. In this study, physicochemical parameters, metabarcoding of the 16S rRNA gene, and ecotoxicity indexes were used for the characterization of chicken manure and poultry litter to examine the effect of their application to agricultural soils for 10 years. Poultry wastes showed high concentrations of nutrients and increased electrical conductivity leading to phytotoxic effects on seeds. The bacterial communities were dominated by typical members of the gastrointestinal tract, noting the presence of pathogenic bacteria. Soils subjected to poultry manure applications showed statistically higher values of total and extractable phosphorous, increasing the risk of eutrophication. Moreover, while the soil bacterial community remained dominated by the ones related to the biogeochemical cycles of nutrients and plant growth promotion, losses of alpha diversity were observed on treated soils. Altogether, our work would contribute to understand the effects of common local agricultural practices and support the adoption of the waste treatment process in compliance with environmental sustainability guidelines., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mining activity has degraded large extensions of soil and its waste is composed of metals, anthropogenic chemicals, and sterile rocks. The use of native species in the recovery of polluted soils improves the conditions for the emergence of other species, tending to a process of ecosystem restoration. The objective of this study was to evaluate the bioaccumulation of metal(loid)s in four species of native plants and the effect of their distribution and bioavailability in soil with waste from an abandoned gold mine. Soil samples were taken from two sites in La Planta, San Juan, Argentina: Site 1 and Site 2 (mining waste and reference soil, respectively). In Site 1, vegetative organ samples were taken from Larrea cuneifolia, Bulnesia retama, Plectrocarpa tetracantha, and Prosopis flexuosa. The concentration of metal(loid)s in soil from Site 1 were Zn > As > Cu > Cd, reaching values of 7123, 6516, 240 and 76 mg kg -1 , respectively. The contamination indices were among the highest categories of contamination for all four metal(loid)s. The spatial interpolation analysis showed the effect of the vegetation as the lowest concentration of metal(loid)s were found in rhizospheric soil. The maximum concentrations of As, Cu, Cd and Zn found in vegetative organs were 371, 461, 28, and 1331 mg kg -1 , respectively. L. cuneifolia and B. retama presented high concentrations of Cu and Zn. The most concentrated metal(loid)s in P. tetracantha and P. flexuosa were Zn, As and Cu. Cd was the least concentrated metal in all four species. The values of BAF and TF were greater than one for all four species. In conclusion, the different phytoextraction capacities and the adaptations to arid environments of these four species are an advantage for future phytoremediation strategies. Their application contributes to the ecological restoration and risk reduction, allowing the recovery of ecosystem services., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abandoned mines with untreated waste cause environmental pollution. The complex mixture of mining waste includes high metal content, anthropogenic chemicals and sterile rocks. Adverse effects of contaminated soils have been widely assessed by the use of plants. The aim of this study was to assess the chronic toxicity of a contaminated soil by waste from an abandoned gold mine on Lactuca sativa and its relationship with the bioavailability and bioaccumulation of Zn, Cu and Pb. Soil samples were taken from the site of mining waste stacking and a reference site in La Planta (Argentina). Contamination indices were calculated and acute and chronic exposures on L. sativa were carried out. Phytotoxicity indices, morphological and biochemical parameters, and concentrations of Zn, Cu and Pb in pseudo total and bioavailable soil fractions and in plant tissue were determined. Concentration- and time-dependent toxicity effects were observed, especially on plant width, fresh aerial biomass, leaf area and percentage of plants with completely necrotic aerial biomass. High levels of Zn (1453.3 ± 220.3 μg g -1 ) were found in plant tissue compared to Pb (277.2 ± 18.0 μg g -1 ) and Cu (255.3 ± 25.6 μg g -1 ). Toxicological endpoints correlated with metal uptake and mining waste concentration. In addition, bioaccumulation factors correlated with mobilisable and water soluble fractions. The concentration of Pb in aerial biomass surpassed the permissible concentrations in leaf vegetables, even at the reference site, indicating that lettuce crop consumption could be risky for the local population's health. This study demonstrated a strong relationship between metal bioavailability, toxicity endpoints and bioaccumulation, contributing with novel information to future ecotoxicological risk assessments and remediation plans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The egg industry has increased its production worldwide during the last decades. Several waste management strategies have been proposed to treat large volumes of poultry manure. Composting and anaerobic digestion are the main stabilization processes used. However, there are disagreements on the criteria for applying raw and treated poultry manure to the soil. We studied the relationship between physicochemical, toxicological, microbiological, parasitological, and metabarcoding parameters of raw and treated poultry manure (compost and digestate). Subsequently, we evaluated the mineralization of C, N and P, and the effects of amended soil on horticultural and ornamental crops. Compost and digestate presented better general conditions than poultry manure for use as organic soil amendments. The highest pathogenic microorganism content (total and fecal coliforms, Escherichia coli, and Salmonella spp.) was recorded for poultry manure. Multivariate analyses allowed associating a lower phytotoxicity with compost and a higher microbial diversity with digestate. Therefore, only compost presented stability and maturity conditions. We found high released CO 2 -C, N loss, and P accumulation in soil amended with a high dose of poultry manure during mineralization. However, high doses of poultry manure and digestate increased the biomass production in the valorization assay. We recommend the soil application of stabilized and mature poultry manure-derived amendments, which reduce the negative impacts on the environment and promote more sustainable practices in agricultural systems., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The effects of 17α-ethinylestradiol (EE 2 ) on sex ratio, gonopodium morphology, and gonadal histology of C. decemmaculatus were assessed by a full-lifecycle exposure experiment. Newborn fish were waterborne exposed to 30, 100, and 300 ng EE 2 /L for 90 d, using 50 fish per treatment. Additionally, in December of 2016, a field survey was conducted on a C. decemmaculatus population inhabiting the Girado Creek downstream of the Chascomus city wastewater effluent discharge. After 90 d of exposure, EE 2 was able to histologically skew the sex ratio toward females and inhibit the full gonopodium development since the lowest tested concentration (LOEC = 30 ng/L). At higher concentrations, EE 2 was toxic, inducing mortality in a concentration-dependent fashion (90 d-LC 50  = 109.9 ng/L) and altering the gonadal histoarchitecture, causing neither testes nor ovaries discernible histologically (LOEC = 100 ng/L). In addition, a novel response, perianal hyperpigmentation, was discovered been induced by the EE 2 exposure in a concentration-dependent fashion (90 d-EC 50  = 39.3 ng/L). A higher proportion of females and perianal hyperpigmentation were observed in wild fish collected from the Girado Creek. The major reached conclusions are: i) EE 2 induce different effects on the sexual traits of C. decemmaculatus when exposed from early-life or adult stages. ii) The most sensitive effects observed in the laboratory occur in a creek receiving wastewater effluent. iii) The perianal hyperpigmentation comes-up as a promising biomarker of exposure to estrogenic compounds., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: In-hospital administration of tranexamic acid after injury improves outcomes in patients at risk for hemorrhage. Data demonstrating the benefit and safety of the pragmatic use of tranexamic acid in the prehospital phase of care are lacking for these patients., Objective: To assess the effectiveness and safety of tranexamic acid administered before hospitalization compared with placebo in injured patients at risk for hemorrhage., Design, Setting, and Participants: This pragmatic, phase 3, multicenter, double-blind, placebo-controlled, superiority randomized clinical trial included injured patients with prehospital hypotension (systolic blood pressure ≤90 mm Hg) or tachycardia (heart rate ≥110/min) before arrival at 1 of 4 US level 1 trauma centers, within an estimated 2 hours of injury, from May 1, 2015, through October 31, 2019., Interventions: Patients received 1 g of tranexamic acid before hospitalization (447 patients) or placebo (456 patients) infused for 10 minutes in 100 mL of saline. The randomization scheme used prehospital and in-hospital phase assignments, and patients administered tranexamic acid were allocated to abbreviated, standard, and repeat bolus dosing regimens on trauma center arrival., Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality., Results: In all, 927 patients (mean [SD] age, 42 [18] years; 686 [74.0%] male) were eligible for prehospital enrollment (460 randomized to tranexamic acid intervention; 467 to placebo intervention). After exclusions, the intention-to-treat study cohort comprised 903 patients: 447 in the tranexamic acid arm and 456 in the placebo arm. Mortality at 30 days was 8.1% in patients receiving tranexamic acid compared with 9.9% in patients receiving placebo (difference, -1.8%; 95% CI, -5.6% to 1.9%; P = .17). Results of Cox proportional hazards regression analysis, accounting for site, verified that randomization to tranexamic acid was not associated with a significant reduction in 30-day mortality (hazard ratio, 0.81; 95% CI, 0.59-1.11, P = .18). Prespecified dosing regimens and post-hoc subgroup analyses found that prehospital tranexamic acid were associated with significantly lower 30-day mortality. When comparing tranexamic acid effect stratified by time to treatment and qualifying shock severity in a post hoc comparison, 30-day mortality was lower when tranexamic acid was administered within 1 hour of injury (4.6% vs 7.6%; difference, -3.0%; 95% CI, -5.7% to -0.3%; P < .002). Patients with severe shock (systolic blood pressure ≤70 mm Hg) who received tranexamic acid demonstrated lower 30-day mortality compared with placebo (18.5% vs 35.5%; difference, -17%; 95% CI, -25.8% to -8.1%; P < .003)., Conclusions and Relevance: In injured patients at risk for hemorrhage, tranexamic acid administered before hospitalization did not result in significantly lower 30-day mortality. The prehospital administration of tranexamic acid after injury did not result in a higher incidence of thrombotic complications or adverse events. Tranexamic acid given to injured patients at risk for hemorrhage in the prehospital setting is safe and associated with survival benefit in specific subgroups of patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02086500.

Pulp and paper mill wastewater (PPMWW) contains high concentrations of recalcitrant compounds that cause toxicity to organisms. Advanced oxidation processes (AOPs) have the ability to degrade these compounds and reduce overall toxicity. Physicochemical characterization and Lactuca sativa toxicity test were conducted to compare the effectiveness of two post-treatments: UV/H 2 O 2 and photo-Fenton. A comparison of four phytotoxicity indexes was carried out. PPMWW from a Brazilian treatment plant was characterized by high values of phenols, color, integrated spectral area (ISA), and chemical oxygen demand (COD), and caused significant inhibition to seedling development. The use of both post-treatments allowed the removal of over 75% of phenols, color, ISA, and COD. Although UV/H 2 O 2 was more effective in removing phenols and ISA, photo-Fenton better reduced phytotoxicity. The most sensitive phytotoxicity indexes were RGIC 0.8 and GIC 80% , whereas SGC 0 , REC -0.25 and REC -0.50 better showed the effectiveness of the post-treatments. We suggest the combined use of two phytotoxicity indexes: one that evaluates the effects on seed germination and, another, on root elongation, e.g., SGC 0 and RGIC 0.8 . Additionally, we recommend the use of ISA for monitoring programs of wastewater treatments because it is a cost-effective approach that allows narrowing down the search and identification of compounds present in complex mixtures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: A ball-tip holmium laser fiber (TracTip; Boston Scientific) has been developed to theoretically reduce damaging friction forces generated within a ureteroscope working channel. We compared the insertional forces and damage with a ureteroscope inner lining when inserting standard flat-tip and ball-tip laser fibers., Materials and Methods: A standard ureteroscope channel liner was placed in a 3D-printed plastic mold. Molds were created at four angles of deflection (30°, 45°, 90°, and 180°) with a 1 cm radius of curvature. New 200 μm ball-tip (TracTip; Boston Scientific) and 200 μm flat-tip (Flexiva; Boston Scientific) laser fibers were advanced through the liner using a stage controller. A strain gauge was used to measure force required for insertion. Each fiber was passed 600 times at each angle of deflection. The ureteroscope liner was changed every 150 passes. Leak testing was performed every 50 passes or when the insertional force increased significantly to assess damage to the liner., Results: At all deflection angles, the average insertional force was significantly lower with the ball-tip laser fibers compared with flat-tip laser fibers (p < 0.001). All trials with the ball-tip lasers were completed at each angle without any leaks. Two of four trials using flat-tip fibers at 45° deflection caused liner leaks (at 91 and 114 passes). At 90° deflection, all flat-tip trials caused liner leaks on first pass. The 180° trials could not physically be completed with the flat-tip laser fiber. Within the flat- and ball-tip groups, an increasing amount of force was needed to pass the fiber as the degree of deflection increased (p < 0.001)., Conclusions: The ball-tip holmium laser fiber can be safely passed through a deflected ureteroscope without causing liner perforation. The standard flat-tip fiber requires greater insertion force at all angles and can cause the ureteroscope liner to leak if it is deflected 45° or more.

Poultry manure (PM) can contain ammonium and ammonia nitrogen, which may inhibit the anaerobic process. The aim of this work was to evaluate the performance of anaerobic digestion of PM co-digested with fruit and vegetable waste. Two semi-continuous bench scale (19L) stirred tank reactors were used. The operating conditions were: 34.5 °C, 2 gVS/L.d (organic load rate), 28 d of hydraulic retention time and 100 revolutions per m (1 h × 3 times by day) for the agitation. The reactors were fed PM and a mixture of PM and fruit and vegetable waste (FVW) at equal proportions (based on wet weight). The performance of the anaerobic process was assessed through biogas and methane yields, reduction of organic matter, release of nitrogen compounds and the monitoring of stability indicators (pH, volatile fatty acids (VFA), total (TA) and partial (PA) alkalinity). Moreover, the digestate quality was evaluated to determine potential risk and benefits from its application as biofertilizer. Toxicity was assessed using Daphnia magna immobilization tests. Results showed that biogas and methane yields from PM-FVW were 31% and 32% higher than PM alone, respectively. Values of organic matter, pH, alpha (PA/TA) and VFA revealed that stability was approached in PM and PM-FVW. The co-digestion of PM with FVW led to the highest methane and biogas yields, lower FAN and TAN concentrations, and a better digestate quality compared to mono-digestion of this manure., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: After a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduce the risk of downstream complications from hemorrhage and shock. Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the prehospital setting., Methods: To determine the efficacy and safety of prehospital administration of thawed plasma in injured patients who are at risk for hemorrhagic shock, we conducted a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial that compared the administration of thawed plasma with standard-care resuscitation during air medical transport. The primary outcome was mortality at 30 days., Results: A total of 501 patients were evaluated: 230 patients received plasma (plasma group) and 271 received standard-care resuscitation (standard-care group). Mortality at 30 days was significantly lower in the plasma group than in the standard-care group (23.2% vs. 33.0%; difference, -9.8 percentage points; 95% confidence interval, -18.6 to -1.0%; P=0.03). A similar treatment effect was observed across nine prespecified subgroups (heterogeneity chi-square test, 12.21; P=0.79). Kaplan-Meier curves showed an early separation of the two treatment groups that began 3 hours after randomization and persisted until 30 days after randomization (log-rank chi-square test, 5.70; P=0.02). The median prothrombin-time ratio was lower in the plasma group than in the standard-care group (1.2 [interquartile range, 1.1 to 1.4] vs. 1.3 [interquartile range, 1.1 to 1.6], P<0.001) after the patients' arrival at the trauma center. No significant differences between the two groups were noted with respect to multiorgan failure, acute lung injury-acute respiratory distress syndrome, nosocomial infections, or allergic or transfusion-related reactions., Conclusions: In injured patients at risk for hemorrhagic shock, the prehospital administration of thawed plasma was safe and resulted in lower 30-day mortality and a lower median prothrombin-time ratio than standard-care resuscitation. (Funded by the U.S. Army Medical Research and Materiel Command; PAMPer ClinicalTrials.gov number, NCT01818427 .).

This study aimed to describe the demographic characteristics, hospital utilizations, patterns of inpatient surgical management, and the overall state/regional variation in surgery rate among patients with disorders of sex development (DSD). We analyzed the Nationwide Inpatient Sample from 2001 to 2012 for patients younger than 21 years. DSD-related diagnoses and procedures were identified via International Classification of Diseases, Ninth Revision (ICD-9) codes. We identified a total of 43,968 DSD-related admissions. Of these, 73.4% of the admissions were designated as female and 642 (1.9%) were inpatient surgical admissions. Among neonates, less than 1% underwent any type of genital surgery. Nonsurgical admissions were associated with longer length of stay and higher cost. There was no significant regional variation in the rate of DSD surgeries, but we observed higher concentrations of DSD surgeries in states associated with tertiary referral centers.

Context: Acromegaly is characterized by growth hormone (GH) and insulinlike growth factor-1 (IGF-1) hypersecretion, and GH and IGF-1 play important roles in regulating body composition and glucose homeostasis., Objective: The purpose of our study was to investigate body composition including ectopic lipids, measures of glucose homeostasis, and gonadal steroids in patients with active acromegaly compared with age-, body mass index (BMI)-, and sex-matched controls and to determine changes in these parameters after biochemical control of acromegaly., Design: Cross-sectional study of 20 patients with active acromegaly and 20 healthy matched controls. Prospective study of 16 patients before and after biochemical control of acromegaly., Main Outcome Measures: Body composition including ectopic lipids by magnetic resonance imaging/proton magnetic resonance spectroscopy; measures of glucose homeostasis by an oral glucose tolerance test; gonadal steroids., Results: Patients with active acromegaly had lower mean intrahepatic lipid (IHL) and higher mean fasting insulin and insulin area under the curve (AUC) values than controls. Men with acromegaly had lower mean total testosterone, sex hormone-binding globulin, and estradiol values than male controls. After therapy, homeostasis model assessment of insulin resistance, fasting insulin level, and insulin AUC decreased despite an increase in IHL and abdominal and thigh adipose tissues and a decrease in muscle mass., Conclusions: Patients with acromegaly were characterized by insulin resistance and hyperinsulinemia but lower IHL compared with age-, BMI-, and sex-matched healthy controls. Biochemical control of acromegaly improved insulin resistance but led to a less favorable anthropometric phenotype with increased IHL and abdominal adiposity and decreased muscle mass., (Copyright © 2017 Endocrine Society)

Background: This study uses publicly available data to analyze the total number of elective, potentially deferrable operative procedures involving infants <6 months of age in the United States. We investigated the factors associated with the performance of these procedures in this population., Methods: The State Ambulatory Surgery Database was used to identify patients in California, North Carolina, New York, and Utah during the years of 2007-2010 who were younger than 6 months of age at the time that they underwent outpatient (ambulatory) surgery. Operations that could reasonably be postponed until 6 months of age were classified as potentially deferrable procedures. Hernia repairs were analyzed separately from other deferrable procedures. Primary outcomes included the total number of elective procedures and the number and rates of potentially deferrable procedures per state per year in this population., Results: Over the study period, a total of 27,540 procedures were identified as meeting inclusion criteria; of those, 7832 (28%) were classified as potentially deferrable, 4315 of which were hernia repairs. The average rates of potentially deferrable nonhernia procedures in California, North Carolina, New York, and Utah were 8.3, 43.8, 30.0, and 11.7 per 10,000 person-years, respectively. In multivariable analysis, private insurance (odds ratio [OR] = 1.36), self-pay status (OR = 1.50), and treatment in a different state (OR = 0.48-3.16) were independent predictors of a potentially deferrable procedure being performed on an infant younger than 6 months., Conclusions: Potentially deferrable procedures are still performed in infants <6 months of age. There appears to be significant variation in timing of these procedures among states. Insurance status and geography may be independent predictors of a procedure being potentially deferrable.

The aim of the present study was to assess the responses of the gonopodium morphology and the gonadal and liver histology of adult male Cnesterodon decemmaculatus to sublethal long-term exposure concentrations of 17α-ethinylestradiol (EE2). Two experiments were conducted exposing the fish to waterborne concentrations of EE2 ranging from 20 ng/L to 200 ng/L for 8 wk, 12 wk, and 16 wk. Intersex gonads were observed after 8 wk and 16 wk in fish exposed to 200 ng EE2/L and 100 ng EE2/L, respectively. Oocytes' development from testis germ cells and replacement of the efferent duct periodic acid-Schiff-positive secretion surrounding spermatozeugmata by parenchymal tissue and duct structure alterations were the major observed changes in the gonads. In contrast, no response was observed in the gonopodium morphology. Liver histology was also altered, showing increasing steatosis, single-cell necrosis to generalized necrosis, and disruption of acinar organization from 100 ng EE2/L to 200 ng EE2/L. In summary, the present results showed that although EE2 was not able to alter the morphology of a developed gonopodium, it was capable of inducing development of testicular oocytes in adult male C. decemmaculatus at environmentally relevant concentrations. Thus, externally normal but intersex C. decemmaculatus males would be expected in the wastewater-receiving streams that the species inhabits. According to the literature, the present study would be the first indicating estrogen-induced intersex in adult male poeciliid. Environ Toxicol Chem 2017;36:1738-1745. © 2016 SETAC., (© 2016 SETAC.)

Objective: Minimally invasive surgery (MIS) techniques are anecdotally reported to be increasingly used, but little objective data supports this. Our objective was to assess trends in MIS utilization across various procedures in pediatric urology and to compare postoperative complication rates between MIS and open procedures., Methods: We analyzed the 1998-2012 Nationwide Inpatient Sample. We identified children (<18 years old) undergoing open and MIS inpatient procedures and any in-hospital post-operative complications that occurred during that postoperative hospitalization. We utilized propensity score matching and multivariable logistic regression to adjust for confounding factors., Results: We identified 163,838 weighted encounters in the "overall cohort," 70,273 of which were at centers performing more than five MIS procedures over the years studied. Use of MIS techniques increased significantly over time for several procedures, most prominently for nephrectomy (Fig.). The overall rate of complications was lower in patients undergoing MIS compared with open surgery (6% vs. 11%, p < 0.001). Specialized centers had a significantly lower overall rate of complications than unspecialized centers (9% vs. 12%, p < 0.001). Within specialized centers, MIS had lower complication rates than open procedures (7% vs. 9%, p < 0.001); this finding was consistent even after adjusting for other factors (OR 0.71, p = 0.02)., Discussion: Limitations include that these data may not be generalizable to encounters not in the sample pool. As a large, retrospective, administrative database, NIS may be affected by miscoding bias - rendering our analysis sensitive to the accuracy of procedure coding in NIS. Although the accuracy level of NIS is high for an administrative database, it is possible at least some portion of our cohort may be incorrectly coded. Further, the NSQIP complications we identified may represent associated comorbidities and not true postoperative complications, as NIS does not provide temporal relationships between different diagnosis codes. Despite these limitations, we note that the NIS database is rigorously monitored and audited for coding accuracy and, therefore, represents a reasonably reliable panorama of the characteristics of an inpatient surgical cohort. However, it is important to note that the choice of operative modality is, undoubtedly, multifactorial and patient/setting-specific., Conclusions: There is increasing use of MIS for pediatric urology procedures, although utilization rates vary among procedures. MIS was associated with a lower postoperative complication rate than for open procedures. Higher-volume MIS centers have a lower complication rate than lower-volume centers., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objectives: The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies., Methods: A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1., Results: Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m 2 . Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2-4 vs. 0-1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels., Conclusions: Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets., Competing Interests: Guarantor of the article: Karen K. Miller, MD. Specific author contributions: L.E.D., M.A.B., K.E.C., and K.K.M. contributed to study design. K.E.C., S.A.O., and L.E.D. contributed to data collection. J.M. performed all pathology review. L.E.D., K.E.C., M.A.B., B.J.Y., and J.C.S. performed statistical analysis and data interpretation. L.E.D., K.E.C., M.S., and K.K.M. contributed to writing the manuscript. All authors reviewed and approved the manuscript before submission. Financial support: This work was supported by National Institutes of Health grants R01 HL 077674, K24 HL092902, K23 RR023090, K23 DK099422, and T32 DK007028, as well as the Harvard Clinical and Translational Science Center (CTSC) grant UL1 RR025758. Potential competing interests: None.

Introduction: Increased case volumes and training are associated with better surgical outcomes. However, the impact of pediatric urology sub-specialization on perioperative complication rates is unknown., Objectives: To determine the presence and magnitude of difference in rates of common postoperative complications for elective pediatric urology procedures between specialization levels of urologic surgeons. The Nationwide Inpatient Sample (NIS), a nationally representative administrative database, was used., Study Design: The NIS (1998-2009) was retrospectively reviewed for pediatric (≤18 years) admissions, using ICD-9-CM codes to identify urologic surgeries and National Surgical Quality Improvement Program (NSQIP) inpatient postoperative complications. Degree of pediatric sub-specialization was calculated using a Pediatric Proportion Index (PPI), defined as the ratio of children to total patients operated on by each provider. The providers were grouped into PPI quartiles: Q1, 0-25% specialization; Q2, 25-50%; Q3, 50-75%; Q4, 75-100%. Weighted multivariate analysis was performed to test for associations between PPI and surgical complications., Results: A total of 71,479 weighted inpatient admissions were identified. Patient age decreased with increasing specialization: Q1, 7.9 vs Q2, 4.8 vs Q3, 4.8 vs Q4, 4.6 years, P < 0.01). Specialization was not associated with race (P > 0.20), gender (P > 0.50), or comorbidity scores (P = 0.10). Mortality (1.5% vs 0.2% vs 0.3% vs 0.4%, P < 0.01) and complication rates (15.5% vs 11.7% vs 9.6% vs 10.9%, P < 0.0001) both decreased with increasing specialization. Patients treated by more highly specialized surgeons incurred slightly higher costs (Q2, +4%; Q3, +1%; Q4 + 2%) but experienced shorter length of hospital stay (Q2, -5%; Q3, -10%; Q4, -3%) compared with the least specialized providers. A greater proportion of patients treated by Q1 and Q3 specialized urologists had CCS ≥2 than those seen by Q2 or Q4 urologists (12.5% and 12.2%, respectively vs 8.4% and 10.9%, respectively, P = 0.04). Adjusting for confounding effects, increased pediatric specialization was associated with decreased postoperative complications: Q2 OR 0.78, CI 0.58-1.05; Q3 OR 0.60, CI 0.44-0.84; Q4 OR 0.70, CI 0.58-0.84; P < 0.01., Discussion: Providers with proportionally higher volumes of pediatric patients achieved better postoperative outcomes than their less sub-specialized counterparts. This may have arisen from increased exposure to pediatric anatomy and physiology, and greater familiarity with pediatric techniques., Limitation: The NIS admission-based retrospective design did not enable assessment of long-term outcomes, repeated admissions, or to track a particular patient across time. The study was similarly limited in evaluating the effect of pre-surgical referral patterns on patient distributions., Conclusions: Increased pediatric sub-specialization among urologists was associated with a decreased risk of mortality and surgical complications in children undergoing inpatient urologic procedures., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To identify longitudinal trends of economic impact and resource utilization for management of pediatric urolithiasis using national databases., Methods: We analyzed the 2006-2012 Nationwide Emergency Department Sample and Nationwide Inpatient Sample. We used ICD-9 (International Classification of Diseases) codes to identify patients (≤18 years) diagnosed with urolithiasis. Diagnostic imaging and surgeries were identified using ICD-9 and Current Procedural Technology codes. We abstracted demographic, imaging, procedure, and charge data. Weighted descriptive statistics were calculated to describe the population's demographics and economic expenditures by clinical setting and year., Results: In total, 45,333 inpatient admissions (68% females) and 234,559 emergency department encounters (63% females) were identified. Most patients (84%) were teenagers and the southern region of the United States was the most common geographic region for all encounters (44%). There was no significant trend in number of urolithiasis encounters over the period studied. Utilization of all imaging techniques increased; in particular, computed tomography was used in 23% of encounters in 2006 and 40% in 2012 (P < .0001). The mean charge per emergency department visit increased by 60% from $3645 in 2006 to $5827 in 2012 (P < .0001). The mean charge increased for inpatient admissions by 102%, from $16,399 in 2006 to $33,205 in 2012 (P < .0001). Total charges increased 72% over the study period from $230 million in 2006 to $395 million in 2012 (P < .0001), outpacing medical inflation over the same period., Conclusion: Charges for pediatric urolithiasis management increased by 65% from 2006 to 2012 despite stable frequency of patient encounters. The utilization of computerized tomography in pediatric urolithiasis increased as well., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Both raw and composted poultry manure is applied as soil amendment. The aims of this study were: (1) to develop phytotoxicity indexes for organic wastes and composts, and (2) to assess the correlation among phytotoxicity indexes, ecotoxicological endpoints and stability and physicochemical parameters during passive composting of poultry manure. Six 2-m(3) composting piles were constructed and four parameter groups (physicochemical and microbiological parameters, ecotoxicological endpoints, and biological activity) were determined at four sampling times during 92days. Extracts were used to carry out acute toxicity tests on Daphnia magna, Lactuca sativa and Raphanus sativus. Composting decreased average toxicity 22.8% for the 3 species and D. magna was the most sensitive species. The static respiration index decreased from 1.12 to 0.46mgO2gOMh(-1) whilst organic matter reduced by 64.1% at the end of the process. Escherichia coli colonies remained higher than values recommended by international guidelines. The D. magna immobilization test allowed the assessment of possible leachate or run-off toxicity. The new phytotoxicity indexes (RGIC0.8 and GIC80%), proposed in this study, as well as salinity, proved to be good maturity indicators. Hence, these phytotoxicity indexes could be implemented in monitoring strategies as useful ecotoxicological tools. Multivariate analyses demonstrated positive correlations between ecotoxicological endpoints (low toxicity) and biological activity (stability). These two parameter groups were associated at the final sampling time and showed negative correlations with several physicochemical parameters (organic and inorganic contents). The final poultry manure compost was rendered stable, but immature and, thus, unsuitable for soil amending., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Intimate partner violence often begins during the courtship stage of romantic relationships. Although some relationships dissolve as a result of aggression, other relationships remain intact, increasing the risk for escalated violence. The present study identified factors predictive of individual differences in emerging adults' commitment to physically aggressive or sexually coercive dating relationships. Specifically, Rusbult's Investment Model of romantic relationships (e.g., investment, satisfaction, quality of alternatives, and commitment) was applied to a longitudinal sample of 148 young adult women who reported experiencing aggression or coercion from their current partners. To further explain commitment within aggressive or coercive dating relationships, rejection sensitivity and anxious and avoidant romantic relational styles were included as predictors of the Investment Model variables. A more avoidant romantic style indirectly predicted commitment through relationship satisfaction and investment. Both commitment and rejection sensitivity significantly predicted continuing an aggressive or coercive relationship 6 months later. The present study improves our understanding of the processes involved in relationship commitment. Continuing to understand these processes will inform interventions that seek to help women who have decided to end aggressive or coercive dating relationships.

Although children with social phobia (SP) and selective mutism (SM) present similarly in a clinical setting, it remains unclear whether children with SM are unable to speak due to overwhelming anxiety, or whether withholding speech functions as an avoidance mechanism. A total of 35 children (ages 5-12 years) with either SM (n = 10), SP (n = 11), or no diagnosis (n = 14) participated in the current study. Measurements included clinician, child, and parent ratings as well as behavioral observations and psychophysiological measures. Independent evaluators and clinicians rated children with SM as more severely impaired, more anxious, and less socially effective, but the groups did not differ in self- or parent-reported anxiety. Psychophysiological measures indicated that children in the SM group experienced less arousal than other children during social interaction tasks. The authors postulate that lack of speech may serve as an avoidance mechanism and thus account for this lack of arousal.

Investigators have identified a number of factors that increase the risk for experiencing sexual coercion, but as yet little is known about how sexual coercion in turn affects these risk factors. Using a sample of 110 adolescents, the current study examined the hypothesis that, after an incident of sexual coercion, adolescents would exhibit increases in several behaviors known to increase risk for victimization. As predicted, after experiencing sexual coercion, adolescents reported increased externalizing symptoms, more frequent sexual intercourse and a greater total number of intercourse partners. Finally, alcohol use, drug use, and problems related to substance use increased. These findings suggest the presence of a feedback loop, in which the experience of sexual coercion leads to an intensification of the factors that initially contributed risk for coercion.

Effluents generated during the process of anaerobic digestion should be treated before their disposal into the environment. The aim of this study was evaluating the effectiveness of the effluent treatment system from an anaerobic bioreactor, assessing the toxicity reduction with the Lactuca sativa seed germination and root elongation inhibition test. Three sampling points were selected along the effluent treatment system: inflow into the first treatment pond, outflow from the third pond and recirculated flow to the bioreactor. Effluent dilutions tested for each sampling point were 25% and 50% (v/v), undiluted sample and controls. The pH, conductivity, temperature, dissolved oxygen, BOD₅ and COD were measured. The decrease in the organic and inorganic loads was correlated with a reduction in the phytotoxicity. The use of the seed toxicity test allows evaluating the quality and effectiveness of the studied effluent treatment system., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Measurement of Stereopsis forms an important part of the clinical assessment of patients with disorders of ocular motility. The introduction of a real depth distance stereoacuity test (FD2) was evaluated in clinical practice and to what extent the introduction affected clinical management. Seventy-three patients under evaluation before and following the introduction of the test were included. Combined thresholds were measured at near using the Frisby and TNO test and at distance using the FD2. Fifty healthy controls were included. Forty-five patients demonstrated Stereopsis using the FD2 and 23 of these had a change in their management based in part on their responses using the FD2. Patients with evidence of Stereopsis using the FD2 were significantly more likely to have change in their management than expected from the whole sample (P = .02). The introduction of a real depth distance stereoacuity test into clinical practice contributed to a change in management when used in conjunction with other tests. The usefulness of the FD2 is limited by its range at 6 m. Use at closer distances necessitates the calculation of binocular threshold from the combined and monocular threshold.

Social Effectiveness Therapy for Children (SET-C) is a comprehensive behavioral treatment combining social skills training, peer generalization experiences, and individualized in vivo exposure for the treatment of social phobia in youth. SET-C results in positive treatment outcome and its effects are maintained at least 3 years later. In this investigation, maintenance of treatment gains 3, 4, and 5 years later was examined using a multidimensional assessment strategy consisting of self-report, parental report, clinician ratings, and direct behavioral assessment. Furthermore, the overall functioning of adolescents treated with SET-C 5 years earlier was compared with that of a group of adolescents who never suffered from psychological disorders. All posttreatment gains were maintained 5 years later, and the general functioning of SET-C treatment responders was not significantly different from those who never had a disorder. The data indicate that SET-C results in long-term positive effects for youth suffering from social phobia.

Marked increases in anxiety-like responses to stress occur during pregnancy. Considerable evidence indicates that the basolateral region of the amygdala (BLA) plays an important role in mediating these types of responses. Given the crucial inhibitory influence of GABA on excitatory glutamatergic activity in the BLA, we hypothesized that decreased GABAergic activity in this region may underlie the increased anxiety associated with pregnancy. In vivo microdialysis was used to sample extracellular GABA before and after 30 min of restraint stress. While there was no detectable effect of restraint on extracellular GABA concentrations, basal GABA levels were significantly decreased in pregnant rats compared with either virgin females or males. We suggest that the alterations in anxiety-like behavior that occur during pregnancy may be associated with decreased basal GABA in the BLA.

Mitochondrial dysfunction and oxidative stress are implicated in the pathological changes observed in the diabetic central nervous system. In this study, using the streptozotocin-induced diabetic rat model we document for the first time the over-expression of a mitochondrial specific stress protein (chaperonin 60) in the CA1/CA3 regions of the diabetic hippocampus in the absence of neurodegeneration. The increase in expression of chaperonin 60 was not observed in the cohort treated with insulin, suggesting that the observed effect was not due to streptozotocin per se but due to the hyperglycaemic state induced by the diabetic state. The expression of chaperonin 60 was also positively correlated with a marker of mitochondrial oxidative stress (manganese superoxide dismutase). We suggest that chaperonin 60 could be an early event marker of mitochondrial dysfunction in the diabetic central nervous system and indeed be neuroprotective in the early stages of hyperglycaemic-induced oxidative stress.

Pretreatment attrition, the systematic self-exclusion of potential participants during the recruitment phase of a study, poses a significant threat to the external validity of randomized clinical trials. Very little is known about the factors that contribute to pretreatment attrition, especially among families seeking treatment for a child. The current study assessed pretreatment attrition in a randomized clinical trial of behavior therapy, fluoxetine, and placebo for child and adolescent social phobia. Reluctance toward medication treatment accounted for 44.7% of study refusals and was disproportionately common among ethnic minority families. Parents were particularly worried about the potential for side effects or physical/psychological dependency upon the medication. Results are discussed in terms of the implications for external validity in future psychopharmacological clinical trials.

Identifying the central nervous system sites of action of anaesthetics is important for understanding the link between their molecular actions and clinical effects. The aim of the present pilot study was to compare the anaesthetic effect of bilateral microinjections of propofol and thiopentone (both 200 microg/microl, in Intralipid and 0.9% saline respectively) into a recently discovered anaesthetic-sensitive region in the rat brainstem, the "mesopontine tegmental anaesthetic area" (MPTA). Microinjections (1 microl per side) were made into the MPTA of fifteen male Sprague-Dawley rats. The effect of each agent on spontaneous behaviour, postural control and nociceptive responsiveness was subjectively assessed according to established criteria. The main finding was that thiopentone induced an "anaesthesia-like" state, including complete atonia and loss of righting ability, in 20% of the subjects. Overall, thiopentone significantly reduced postural control and had a moderate antinociceptive effect compared to saline microinjections (P < 0.01 and 0.05, respectively, Wilcoxon test). In contrast, propofol did not induce "anaesthesia" in any animal tested, although a similar antinociceptive effect to that of thiopentone was observed (P < 0.05, Wilcoxon test). In summary, propofol and thiopentone have different effects when microinjected into the MPTA. While both agents reduced reflex withdrawal to a nociceptive stimulus, only thiopentone induced an "anaesthesia-like" state.

Pregnancy and lactation are accompanied by behavioral changes that include altered responses to stress. Previous exposure to a stressor can also modulate subsequent stress-related behavior, and this effect is at least partly mediated by the reproductive hormone, estrogen. In this study, we sought to determine if the stress-related behavior of rats that had been exposed to a cat would vary with reproductive status. After exposure to a cat or a nonstress control procedure, pregnant, lactating, virgin female or male rats received two acoustic startle test sessions on consecutive days, followed 4 days later by testing on an elevated plus maze. Startle amplitudes tended to increase across trials in all groups, but were differentially enhanced in nonstressed pregnant and lactating rats. A 5-min exposure to a cat eliminated the enhanced responding in these two groups. The cat exposure attenuated startle stimulus-evoked freezing only in the pregnant rats and produced differential plus maze performance in this group. Cat exposure produced no differential effects in virgin females or males. These results suggest that reproductive state can influence the impact of a stressor on subsequent behavior, but does so in a rather complex way.

The activity of 378 single neurons was recorded from areas of the parahippocampal region (PHR), including the perirhinal and lateral entorhinal cortex, as well as the subiculum, in rats performing an odor-guided delayed nonmatching-to-sample task. Nearly every neuron fired in association with some trial event, and every identifiable trial event or behavior was encoded by neuronal activity in the PHR. The greatest proportion of cells was active during odor sampling, and for many cells, activity during this period was odor selective. In addition, odor memory coding was reflected in two general ways. First, a substantial proportion of cells showed odor-selective activity throughout or at the end of the memory delay period. Second, odor-responsive cells showed odor-selective enhancement or suppression of activity during stimulus repetition in the recognition phase of the task. These data, combined with evidence that the PHR is critical for maintaining odor memories in animals performing the same task, indicate that this cortical region mediates the encoding of specific memory cues, maintains stimulus representations, and supports specific match-nonmatch judgments critical to recognition memory. By contrast, hippocampal neurons do not demonstrate evoked or maintained stimulus-specific codings, and hippocampal damage results in little if any decrement in performance on this task. Thus it becomes increasingly clear that the parahippocampal cortex can support recognition memory independent of the distinct memory functions of the hippocampus itself.

The anteroventral periventricular nucleus (AVPV) of the preoptic region represents an essential component of neural pathways regulating gonadotropin secretion, and contains sexually dimorphic populations of neurons that express dynorphin or enkephalin. In the present study we used in situ hybridization to measure prodynorphin (PDYN) and proenkephalin (PENK) mRNA in the AVPV of intact animals killed on each day of the cycle. Levels of PDYN mRNA were lowest in animals killed on the afternoon of proestrus and then increased by over 60% by the morning of the following day. Expression of PENK mRNA was generally stable during the cycle, but a small yet significant reduction was detected on proestrus relative to levels of PENK mRNA in animals killed on the day of diestrus. In addition, we used double in situ hybridization to demonstrate that the majority of PDYN mRNA-containing neurons express both estrogen (50%) and progesterone receptor (85%) mRNAs. Only one quarter of the PENK-containing neurons also co-express estrogen receptor mRNA, and fewer than 10% of the PENK mRNA neurons express PR mRNA. Thus, the differential expression of PDYN and PENK during the cycle generally correlates with distinct differences in the degree of colocalization of ER and PR mRNA in PDYN and PENK mRNA-containing neurons in the AVPV.

Previous studies demonstrated that, following opsonization with normal human serum (NHS), phagocytes bind greater numbers of small-capsule Cryptococcus neoformans cells than yeast cells with large capsules. The present study tested the hypothesis that suboptimal deposition of opsonic C3 fragments contributes to this disparity. C neoformans was grown under conditions promoting large or small capsules and was incubated at various concentrations in NHS. At low concentrations of yeast cells (125 cells per microl of NHS), the deposition of C3 fragments per unit of capsule volume and the binding of yeast cells to cultured human monocytes were similar for yeast cells having large and small capsules. However, at higher cell concentrations, large-capsule cells exhibited suboptimal coating with C3 fragments and markedly diminished monocyte binding compared with small-capsule cells. Thus, the inverse correlation between capsule size and phagocyte binding can be overcome by conditions promoting optimal C3 deposition.

Ruptured intracranial aneurysms are the usual cause of acute subarachnoid hemorrhage (SAH). Noncontrast CT is the primary imaging procedure of choice for establishing the diagnosis of SAH. Conventional contrast angiography is the gold standard for establishing the presence of intracranial aneurysms, but CT and MRI have supplementary roles. The pathogenesis, presentation, and imaging of SAH and intracranial aneurysms are discussed.

Amygdala central nucleus (CNA) lesions were used to test the hypothesis that stimulus-evoked heart rate changes can reflect the development of fear during acoustic startle testing. A 120-dB white noise startle stimulus produced freezing as well as phasic heart rate accelerations and decelerations, and an abrupt decrease in tonic heart rate, in sham-operated rats. These responses were all significantly reduced in CNA-lesioned rats. In contrast, an 87-dB stimulus elicited only significant phasic decelerations that were similarly attenuated by the CNA lesions. In a follow-up experiment, the CNA lesions also attenuated phasic cardiac decelerations evoked by a conditioned stimulus-like, 85-dB pure tone. The results support the contention (B. J. Young & R.N. Leaton, 1994) that heart rate changes can reflect fear conditioned during acoustic startle testing and, in addition, suggest that the amygdala mediates responses to nonsignal acoustic stimuli.

The present study examined the extent to which heart rate changes evoked by acoustic startle stimuli are affected by the development of fear during startle testing. The phasic heart rate responses of rats elicited by a 120-dB startle stimulus were characterized by decelerations that habituated across trials and accelerations that developed across trials in a manner that paralleled the development of freezing behavior. A 92-dB stimulus evoked little freezing or tachycardia, yet evoked decelerations of similar magnitude to the 120-dB stimulus. Pharmacological blockade of autonomic activity was used to uncouple freezing from the heart rate accelerations and to show that the accelerations were not an artifact of the habituating decelerations. These results indicate that heart rate responses to nonsignal stimuli depend critically on a rat's previous experience with those stimuli.

Serum obtained from normal human subjects contains antibodies reactive in an enzyme-linked immunosorbent assay with the glucuronoxylomannan (GXM) of Cryptococcus neoformans. The frequency of occurrence of class-specific antibodies among normal subjects was 28% for immunoglobulin G (IgG), 98% for IgM, and 3% for IgA. Anti-GXM antibodies with kappa light chains occurred in 98% of normal subjects, while the occurrence of lambda light chains was 28%. Each of five subjects with high levels of anti-GXM IgG antibodies had readily detectable antibodies of the IgG2 isotype; two of the five subjects had readily detectable IgG1 antibody. An examination of sera from human immunodeficiency virus-infected patients showed that human immunodeficiency virus infection was accompanied by a significant decrease in the occurrence of IgM antibodies and anti-GXM antibodies with kappa light chains; these decreases occurred early in infection when CD4 counts were still > or = 500 cells per microliter. A slight but not statistically significant decrease in the occurrence of anti-GXM IgG antibodies was seen only in patients with CD4 levels of < 200 cells per microliter. Sera from normal subjects with high levels of anti-GXM IgG antibodies were examined to identify any contribution of the antibodies to complement activation or to opsonization of the yeast cells. An analysis of the kinetics for activation and binding of C3 to the yeast cell showed no pattern of quantitative or qualitative differences between sera with high or low levels of anti-GXM IgG antibodies. Phagocytosis studies showed that the naturally occurring IgG antibodies did not contribute to opsonization of the yeast cells.

Meningococcal infections can present in diverse clinical forms ranging from fulminant, occult, chronic meningococcaemia to meningitis. Rare presentations may include conjunctivitis, sinusitis, pneumonia, pericarditis, arthritis, and osteomyelitis. We present a very unusual case of meningococcaemia presented as an endophthalmitis.

Incubation of encapsulated and nonencapsulated Cryptococcus neoformans in normal human serum (NHS) leads to activation and binding of potentially opsonic fragments of complement component C3 to the yeast cells. Analysis of the molecular forms of C3 after incubation of encapsulated cryptococci in NHS showed that the percentage of bound C3 occurring as iC3b approached 100% after 8 min. The percentage of bound C3 occurring as iC3b on nonencapsulated cryptococci never exceeded 70%, even after 60 min of incubation in NHS. Conversion of C3b to iC3b was assessed further by incubating C3b-coated cryptococci for various times with a mixture of complement factors H and I at 40% of their respective physiological concentrations. Most, if not all, of the C3b on encapsulated cryptococci was converted to iC3b at a single fast rate. Conversion of C3b to iC3b on nonencapsulated cryptococci did not follow a single rate constant and appeared to have a fast and a slow component. Studies of the requirements for factors H and I in cleavage of C3b to iC3b showed steep dose-response curves for both factors in the case of encapsulated cryptococci and shallow curves with C3b bound to nonencapsulated cryptococci. Taken together, our results indicate that C3b molecules bound to encapsulated cryptococci have a uniformly high susceptibility to conversion to iC3b by factors H and I. In contrast, a significant portion of the C3b bound to nonencapsulated cryptococci is very resistant to conversion to iC3b by factors H and I.

Incubation of encapsulated cells of Cryptococcus neoformans in normal human serum leads to activation of the alternative complement pathway and deposition of opsonic fragments of C3 into the capsule. We determined whether the variation in capsular structure that occurs among the four major cryptococcal serotypes was reflected in the kinetics for activation and binding of C3. We also examined the effects on activation kinetics of de-O-acetylation or periodate oxidation of the capsule. Binding kinetics were characterized in terms of the time required to deposit 5% of the maximal amount of C3 on the yeast (t5%), the first-order rate constant for amplification of C3 deposition (k'), and the maximum amount of C3 that could be deposited in the capsule (C3max). Our results showed that variations in the capsular structure that characterized each serotype had no significant influence on C3max but that the rate of C3 deposition depended significantly on the serotype. C3 accumulated at a higher rate on cells of serotypes A and D than on cells of serotypes B and C. There was a significant correlation between capsular volume and C3max, although the relationship was not linear. Periodate treatment of encapsulated cryptococci of all four serotypes led to decapsulation. Periodate-oxidized encapsulated cells displayed kinetics for activation and binding of C3 that were identical to kinetics observed with nonencapsulated cryptococci. Finally, de-O-acetylation led to a significant but relatively minor increase in C3max.