Soft-tissue mineralization of bullfrog larvae (Rana catesbeiana) at a wastewater treatment facility.
Bullfrog tadpoles (Rana catesbeiana) from a wastewater treatment facility were identified with severe lesions consisting of large, up to 1-cm in diameter, mineralized nodules protruding from the tail or gular region. Sectioning of formalin-fixed specimens revealed more extensive mineralization involving the vertebrae or muscles of the head and tail. Nodules examined microscopically were not associated with parasitic or infectious agents. Large nodules consisted of mineralized aggregates surrounded by a margin of granulomatous inflammation. Individual connective-tissue fibers and muscle cells were mineralized at some foci. The nodules consisted entirely of calcium phosphate, and the lesions appeared to be novel. Total serum-calcium concentrations of tadpoles and calcium concentrations in water samples did not differ significantly with increasing distance from the discharge site. Affected tadpoles had elevated cholecalciferol (25-OH-vitamin D3) levels. Effluent from this wastewater treatment facility is divided into 3 streams, each passing through a separate series of wetlands allowing for replicated evaluation of tadpoles with increasing distance from the proximate inputs of treated wastewater. The prevalence of lesions was correlated with proximity of cells to the initial wastewater discharge site, and 28.5% of bullfrog larvae in the first cells had lesions. None were affected in the fifth cells. Southern leopard frog larvae (Rana sphenocephala), the only other species affected, had a much lower prevalence of lesions (<1%) than bullfrog tadpoles and were only affected in the first cells. To date, the primary cause of elevated cholecalciferol is undetermined, but it appears to be remediated by passage of water through the wetlands.


Repetitive Exposure of IL-17 Into the Murine Air Pouch Favors the Recruitment of Inflammatory Monocytes and the Release of IL-16 and TREM-1 in the Inflammatory Fluids.
The infiltration of Th17 cells in tissues and organs during the development of many autoimmune diseases is considered a key step toward the establishment of chronic inflammation. Indeed, the localized and prolonged release of IL-17 in specific tissues has been associated with an increased severity of the inflammatory response that remains sustained over time. The cellular and molecular mechanisms behind these effects are far from being clear. In this study we investigated the effects of two repetitive administration of recombinant IL-17 into the murine air pouch to simulate a scenario where IL-17 is released over time in a pre-inflamed tissue. Consistent with our previous observations, mice receiving a single dose of IL-17 showed a transitory influx of neutrophils into the air pouch that peaked at 24 h and declined at 48 h. Conversely, mice receiving a double dose of the cytokine-one at time 0 and the second after 24 h-showed a more dramatic inflammatory response with almost 2-fold increase in the number of infiltrated leukocytes and significant higher levels of TNF-α and IL-6 in the inflammatory fluids. Further analysis of the exacerbated inflammatory response of double-injected IL-17 mice showed a unique cellular and biochemical profile with inflammatory monocytes as the second main population emigrating to the pouch and IL-16 and TREM-1 as the most upregulated cytokines found in the inflammatory fluids. Most interestingly, mice receiving a double injection of IL-1β did not show any change in the cellular or biochemical inflammatory response compared to those receiving a single injection or just vehicle. Collectively these results shed some light on the function of IL-17 as pro-inflammatory cytokine and provide possible novel ways to target therapeutically the pathogenic effects of IL-17 in autoimmune conditions.


Calcium channel currents in pars intermedia cells of the rat pituitary gland. Kinetic properties and washout during intracellular dialysis.
Ca channel currents in primary cultured pars intermedia cells were studied using whole-cell recording with patch pipettes. Experiments were carried out at 18-21 degrees C in cells internally dialyzed with K-free, EGTA-containing solutions and in the presence of 10 mM Ca or 10 mM Ba in the external solution. Ca and Ba currents depended on the activity of two main populations of channels, SD and FD. With Ca as the charge carrier, these two populations differed in their closing time constants at -80 mV (SD, 1.8 ms; FD, 110 microseconds), apparent activation levels (SD, -40 mV; FD, -5 mV), half-maximal activation levels (SD, +5 to +10 mV; FD, +20 to +25 mV), half-times of activation at +20 mV (SD, 2.5-3.5 ms; FD, 1.0-1.3 ms), and time courses of inactivation (SD, fast; FD, slow). Functional FD channels were almost completely lost within 20-25 min of breaking into a cell, whereas SD channels retained most of their functional activity. In addition, the conductance-voltage curve for FD channels shifted approximately 15 mV toward more negative membrane potentials within 11-14 min under whole-cell recording. At that time, 60-70% of the FD channel maximum conductance was lost. However, the conductance-voltage curve for SD channels shifted less than 5 mV within 25 min. The addition of 3 mM MgATP and 40 microM GTP to the internal solution slowed down the loss of FD channels and prevented the shift in their activation curve. It was also found that the amplitude of the current carried by FD channels tends to increase as a function of the age of the culture, with no obvious changes in the kinetic properties of the channels or in SD channel activity.


Web-Based Service Provision of HIV, Viral Hepatitis, and Sexually Transmitted Infection Prevention, Testing, Linkage, and Treatment for Key Populations: Systematic Review and Meta-analysis.
Despite the growth of web-based interventions for HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) for key populations, the evidence for the effectiveness of these interventions has not been reported. This study aimed to inform the World Health Organization guidelines for HIV, VH, and STI prevention, diagnosis, and treatment services for key populations by systematically reviewing the effectiveness, values and preferences, and costs of web-based outreach, web-based case management, and targeted web-based health information for key populations (men who have sex with men, sex workers, people who inject drugs, trans and gender-diverse people, and people in prisons and other closed settings). We searched CINAHL, PsycINFO, PubMed, and Embase in May 2021 for peer-reviewed studies; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials (RCTs) and observational studies. We assessed the risk of bias using the Cochrane Collaboration tool for RCTs and the Evidence Project and Risk of Bias in Non-randomized Studies of Interventions tools for non-RCTs. Values and preferences and cost data were summarized descriptively. Of 2711 records identified, we included 13 (0.48%) articles in the effectiveness review (3/13, 23% for web-based outreach; 7/13, 54% for web-based case management; and 3/13, 23% for targeted web-based health information), 15 (0.55%) articles in the values and preferences review, and 1 (0.04%) article in the costs review. Nearly all studies were conducted among men who have sex with men in the United States. These articles provided evidence that web-based approaches are as effective as face-to-face services in terms of reaching new people, use of HIV, VH, and STI prevention services, and linkage to and retention in HIV care. A meta-analysis of 2 RCTs among men who have sex with men in China found increased HIV testing after web-based outreach (relative risk 1.39, 95% CI 1.21-1.60). Among men who have sex with men in the United States, such interventions were considered feasible and acceptable. One cost study among Canadian men who have sex with men found that syphilis testing campaign advertisements had the lowest cost-per-click ratio on hookup platforms compared with more traditional social media platforms. Web-based services for HIV, VH, and STIs may be a feasible and acceptable approach to expanding services to key populations with similar outcomes as standard of care, but more research is needed in low-resource settings, among key populations other than men who have sex with men, and for infections other than HIV (ie, VH and STIs).


Autosomal dominant optic atrophy plus due to the novel OPA1 variant c.1463G>C.
OPA1 variants most frequently manifest phenotypically with pure autosomal dominant optic atrophy (ADOA) or with ADOA plus. The most frequent abnormalities in ADOA plus in addition to the optic nerve affection include hypoacusis, migraine, myopathy, and neuropathy. Hypertelorism and atrophy of the acoustic nerve have not been reported. The patient is a 48yo Caucasian female with slowly progressive, visual impairment since childhood, bilateral hypoacusis since age 10y, and classical migraine since age 20y. The family history was positive for diabetes (father, mother) and visual impairment (daughter). Clinical examination revealed hypertelorism, visual impairment, hypoacusis, tinnitus, weakness for elbow flexion and finger straddling, and generally reduced tendon reflexes. MRI of the cerebrum was non-informative but hypoplasia of the acoustic nerve bilaterally was described. Visually-evoked potentials revealed markedly prolonged P100-latencies bilaterally. Acoustically-evoked potentials were distorted with poor reproducibility and prolonged latencies. Muscle biopsy revealed reduced activities of complexes I, II, and IV. Genetic work-up revealed the novel variant c.1463G>C in the OPA1 gene. This case provides novel information regarding the genotype of ADOA plus. The novel OPA1 variant c.1463G>C not only manifests with visual impairment, hypoacusis, migraine, and myopathy, but also with hypertelorisms and acoustic nerve atrophy.


Tobacco screening and cessation efforts by dental providers: A quality measure evaluation.
The purpose of this study was to adapt, test, and evaluate the implementation of a primary care "Preventive care and Screening" meaningful use quality measure for tobacco use, in dental institutions. We determined the percentage of dental patients screened for tobacco use, and the percentage of tobacco users who received cessation counseling. We implemented the dental quality measure (DQM), in three dental schools and a large dental accountable care organization. An automated electronic health record (EHR) query identified patients 18 years and older who were screened for tobacco use one or more times within 24 months, and who received cessation counseling intervention if identified as a tobacco user. We evaluated EHR query performance with a manual review of a subsample of charts. Across all four sites, in the reporting calendar year of 2015, a total of 143,675 patients met the inclusion criteria for the study. Within 24 months, including 2014 and 2015 calendar years, percentages of tobacco screening ranged from 79.7 to 99.9 percent, while cessation intervention percentages varied from 1 to 81 percent among sites. By employing DQM research methodology, we identified intervention gaps in clinical practice. We demonstrated the successful implementation of a DQM to evaluate screening rates for tobacco use and cessation intervention. There is substantial variation in the cessation intervention rates across sites, and these results are a call for action for the dental profession to employ tobacco evidence-based cessation strategies to improve oral health and general health outcomes.


Indirect hemagglutination test for chlamydial antibodies.
An indirect hemagglutination (IHA) test is described for chlamydial antibodies in psittacosis diagnostic sera; for this test tanned sheep erythrocytes sensitized with a deoxycholate extract of Chlamydia psittaci grown in Vero cell monolayers were used. Adaptation of the IHA test to the Microtiter system decreased sensitivity; nevertheless, the Microtiter-IHA test was more sensitive than the complement fixation test. Lymphogranuloma venereum antibodies also were detected by using antigen extracted from C. psittaci.


Urea peroxide solution in the treatment of gingivitis in orthodontics.
A 3-month study was conducted to determine the effect of a 10 per cent urea peroxide solution on gingivitis and oral debris accumulation in orthodontic patients. Sixty fullybanded children (thirty-two girls, twenty-eight boys) 10 to 17 years of age were randomly placed into two groups of thirty members. The treatment group was assigned the use of the test solution and given normal oral hygiene instructions. The control group was given only the normal oral hygiene instructions. The subjects' gingival status was evaluated by means of the gingival index (GI) of O'Leary. The accumulation of oral debris was monitored by means of the oral debris index (ODI) of Greene and Vermillion as modified by Womack. Subjects were scored at the start of the study and approximately 1 and 3 months thereafter. Analysis of variance of the GI and ODI scores revealed significant treatment effects (p = 0.0013 and p = 0.0051, respectively), which substantiated the clinical observations. Rinsing with the test solution in conjunction with toothbrushing appears useful as an oral hygiene measure for orthodontic patients. No adverse reactions were experienced by any of the patients using the test solutions.


How to bootstrap a human communication system.
How might a human communication system be bootstrapped in the absence of conventional language? We argue that motivated signs play an important role (i.e., signs that are linked to meaning by structural resemblance or by natural association). An experimental study is then reported in which participants try to communicate a range of pre-specified items to a partner using repeated non-linguistic vocalization, repeated gesture, or repeated non-linguistic vocalization plus gesture (but without using their existing language system). Gesture proved more effective (measured by communication success) and more efficient (measured by the time taken to communicate) than non-linguistic vocalization across a range of item categories (emotion, object, and action). Combining gesture and vocalization did not improve performance beyond gesture alone. We experimentally demonstrate that gesture is a more effective means of bootstrapping a human communication system. We argue that gesture outperforms non-linguistic vocalization because it lends itself more naturally to the production of motivated signs.


Neurological Monitoring and Complications of Pediatric Extracorporeal Membrane Oxygenation Support.
Extracorporeal membrane oxygenation is extracorporeal life support for life-threatening cardiopulmonary failure. Since its introduction, the use of extracorporeal membrane oxygenation has expanded to patients with more complex comorbidities without change in patient mortality rates. Although many patients survive, significant neurological complications like seizures, ischemic strokes, and intracranial hemorrhage can occur during extracorporeal membrane oxygenation care. The risks of these complications often add to the complexity of decision-making surrounding extracorporeal membrane oxygenation support. In this review, we discuss the pathophysiology and incidence of neurological complications in children supported on extracorporeal membrane oxygenation, factors influencing the incidence of these complications, commonly used neurological monitoring modalities, and outcomes for this complex patient population. We discuss the current literature on the use of electroencephalography for both seizure detection and monitoring of background electroencephalographic changes, in addition to the use of less commonly used imaging modalities like transcranial Doppler. We summarize the knowledge gaps and the lack of clinical consensus guidelines for managing these potentially life-changing neurological complications. Finally, we discuss future work to further understand the pathophysiology of extracorporeal membrane oxygenation-related neurological complications.


Dietary sugars versus glucose tablets for first-aid treatment of symptomatic hypoglycaemia in awake patients with diabetes: a systematic review and meta-analysis.
While glucose tablets have been advocated for treating symptomatic hypoglycaemia in awake patients, dietary sugars may be more convenient. We performed a systematic review to compare the impact of these treatment options on the relief of symptomatic hypoglycaemia, time to resolution of symptoms, blood glucose levels, complications and hospital length of stay. We searched PubMed, Embase and the Cochrane Library through 28 June 2016 and assessed the quality of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Reference lists from a subset of the resulting articles were mined for additional, potentially eligible papers. We calculated the risk ratio (RR) of each treatment option for the preselected outcomes of interest. Of the 1774 identified papers, four studies met the inclusion criteria; three randomised controlled trials totalling 502 hypoglycaemic events treated with dietary sugars and 223 with glucose tablets and one observational study with 13 events treated with dietary sugars and 9 with glucose tablets. The dietary forms of sugar included sucrose, fructose, orange juice, jelly beans, Mentos, cornstarch hydrolysate, Skittles and milk. In the pooled analysis, patients treated with dietary sugars had a lower resolution of symptoms 15 min after treatment compared with glucose tablets (RR 0.89, 95% CI 0.83 to 0.95). When compared with dietary sugars, glucose tablets result in a higher rate of relief of symptomatic hypoglycaemia 15 min after ingestion and should be considered first, if available, when treating symptomatic hypoglycaemia in awake patients.


Prescribing trend in cardiovascular patients at Ethiopian university hospital: The number of medications and implication on the clinical improvement.
Investigating the prescribing trend is important to improve rational prescribing. This study aimed at assessing the cardiovascular drug use, pattern, and its impact on clinical outcome. A cross-sectional study was employed in the outpatient department of chronic illness clinic of Gondar University specialized hospital, Ethiopia from 15 January 2017 to 15 March 2017. The independent variables were sociodemographic, medication, and other clinical information while cardiovascular disease improvement is the outcome variable. Binary logistic regression was used to test the association between the independent variables and the outcome variable. Kaplan Meier curve was used to analyze the clinical improvement while the Log-rank test was employed to compare the clinical outcome with the number of medications. Eight hundred thirty-three cardiovascular patient medical records were included in the final analysis. The majority (62.5%) of patients were females and more than 61% were above 50 years of age. Diuretics monotherapy accounted for a third (33.6%) of cardiovascular drug use, followed by combination therapy of angiotensin convertase enzyme inhibitors with Diuretics (21.8%) and calcium channel blockers with diuretics (8.3%). Cardiovascular patients followed for 72 months found to have a good level of clinical improvement on combination medication (Log Rank of 28.9, P = 0.000). In this study, diuretics monotherapy or in combination with angiotensin convertase enzyme inhibitors were found to be the frequently prescribed drugs in cardiovascular patients. Combination therapy has an implication for good cardiovascular improvement on long term follow-up. It seems clinicians were restricted to certain cardiovascular medications while plenty of choices are available from the diverse classes of cardiovascular drugs.


Effect of anti-histone acetyltransferase activity from Rosa rugosa Thunb. (Rosaceae) extracts on androgen receptor-mediated transcriptional regulation.
Rosa rugosa Thunb. (Rosaceae) has been traditionally used for treatments of diabetes, chronic inflammatory diseases, pain, and anticancer in Korea. We investigate the inhibitory effect of histone acetyltransferase activity from the methanol extract of stems of Rosa rugosa on androgen receptor-mediated transcriptional regulation. For the present study, Rosa rugosa methanol extract (RRME) was obtained from stem part of Rosa rugosa using methanol extraction. Histone acetyltransferase assay were performed to measure the inhibitory effect on acetylation, reporter assay, real-time PCR and ChIP assay were performed to measure androgen receptor-mediated transcriptional regulation, and MTT test were performed to measure cell viability. RRME inhibited both p300 and CBP (60-70% at 100 microg/ml) activity. We show RRME mediates agonist-dependent androgen receptor (AR) activation and suppresses antagonist-dependent inhibition. RRME treatment also decreased transcription of AR regulated genes and also reduced histone H3 and AR acetylation in the promoters of prostate-specific antigen (PSA) and beta-2-microglobulin (B2M). Finally, RRME treatment reduced the growth of LNCaP, a human prostate cancer cell line. These results demonstrate RRME is a potent HAT inhibitor, which reduced AR and histone acetylation leading to decreased AR-mediated transcription and reduced LNCaP cell growth.


Integrated nutrient management (INM) for sustaining crop productivity and reducing environmental impact: a review.
The increasing food demands of a growing human population and the need for an environmentally friendly strategy for sustainable agricultural development require significant attention when addressing the issue of enhancing crop productivity. Here we discuss the role of integrated nutrient management (INM) in resolving these concerns, which has been proposed as a promising strategy for addressing such challenges. INM has multifaceted potential for the improvement of plant performance and resource efficiency while also enabling the protection of the environment and resource quality. This review examines the concepts, objectives, procedures and principles of INM. A comprehensive literature search revealed that INM enhances crop yields by 8-150% compared with conventional practices, increases water-use efficiency, and the economic returns to farmers, while improving grain quality and soil health and sustainability. Model simulation and fate assessment further reveal that reactive nitrogen (N) losses and GHG (greenhouse gas) emissions are reduced substantially under advanced INM practices. Lower inputs of chemical fertilizer and therefore lower human and environmental costs (such as intensity of land use, N use, reactive N losses and GHG emissions) were achieved under advanced INM practices without compromising crop yields. Various approaches and perspectives for further development of INM in the near future are also proposed and discussed. Strong and convincing evidence indicates that INM practice could be an innovative and environmentally friendly strategy for sustainable agriculture worldwide.


Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma.
Glioma is the most common brain neoplasm with a poor prognosis. Circular RNA (circRNA) and their associated competing endogenous RNA (ceRNA) network play critical roles in the pathogenesis of glioma. However, the alteration of the circRNA-miRNA-mRNA regulatory network and its correlation with glioma therapy haven't been systematically analyzed. With GEO, GEPIA2, circBank, CSCD, CircInteractome, mirWalk 2.0, and mirDIP 4.1, we constructed a circRNA-miRNA-mRNA network in glioma. LASSO regression and multivariate Cox regression analysis established a hub mRNA signature to assess the prognosis. GSVA was used to estimate the immune infiltration level. Potential anti-glioma drugs were forecasted using the cMap database and evaluated with GSEA using GEO data. A ceRNA network of seven circRNAs (hsa_circ_0030788/0034182/0000227/ 0018086/0000229/0036592/0002765), 15 miRNAs(hsa-miR-1200/1205/1248/ 1303/3925-5p/5693/581/586/599/607/640/647/6867-5p/767-3p/935), and 46 mRNAs (including 11 hub genes of ARHGAP11A, DRP2, HNRNPA3, IGFBP5, IP6K2, KLF10, KPNA4, NRP2, PAIP1, RCN1, and SEMA5A) was constructed. Functional enrichment showed they influenced majority of the hallmarks of tumors. Eleven hub genes were proven to be decent prognostic signatures for glioma in both TCGA and CGGA datasets. Forty-six LASSO regression significant genes were closely related to immune infiltration. Finally, five compounds (fulvestrant, tanespimycin, mifepristone, tretinoin, and harman) were predicted as potential treatments for glioma. Among them, mifepristone and tretinoin were proven to inhibit the cell cycle and DNA repair in glioma. This study highlights the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identifies novel therapeutic options for glioma.


Toward general experimentation and discovery in conditioned laboratory and complementary and alternative medicine spaces: part v. Data on 10 different sites using a robust new type of subtle energy detector.
The earlier experimental papers in this series dealt with replication of our DeltapH = +1 IIED (intention imprinted electrical device) experiment carried out in Minnesota. This work was replicated at 3-IIED sites and 7 control sites in the United States and Europe that demonstrated room temperature information entanglement between the macroscopic sized ( approximately 10(3) to 10(4) cubic feet volume) IIED sites and non-IIED-sites (control sites) over distances separated by up to 5000 to 6000 miles. During these studies, we discovered how to gain a quantitative measure of the elevation of the thermodynamic free energy per unit volume, deltaG*(H)+, above our normal U(1) electromagnetic gauge symmetry state, for the aqueous H(+) ion in these " conditioned" spaces. In simpler language, what this means is that one can now continuously monitor a complementary and alternative medicine (CAM) office space, research space, or clinic space to gain a continuous record of (1) How much the space has been elevated or depleted in thermodynamic free energy, relative to our normal physical reality, by the processes occurring there; (2) how much the biofields of the practitioners and patients are perturbing the collective subtle energy field of these spaces; and (3) the monitoring of specific IIEDs imprinted for aiding the healing process of patients with specific pathologies under study or treatment. It allows CAM practitioners to investigate and utilize "information medicined", to evaluate the subtle energy component of various psychotronic devices, and to evaluate the efficacy of various subtle energy potentization processes for various supplements, remedies, and other materials. This paper contributes several key things to this growing body of work: (1) it develops a quantitative theoretical picture for the determination of deltaG*(H)+ from pH measurements in partially "conditioned"spaces; (2) it provides experimental, deltaG*(H)+ data for all 10 sites of the overall experimental system, (3) it provides deltaG*(H)+ data for measurements carried out in small CAM facilities and at a 1-week-long healing workshop facility; and (4) it illustrates a potential biofeedback tool to assist both individual humans and coherently coupled groups of humans to significantly enhance their evolutionary progress to Adept, Master, and perhaps even Avatar levels of performance in the world.


c-Myc promoter activation in medulloblastoma.
%The c-myc oncogene is commonly activated in medulloblastoma. Genomic amplification is a well-documented cause of c-myc activation but does not account for all cases of c-myc activation. In this study, we sought other means by which c-myc is overexpressed in medulloblastoma. Twelve medulloblastoma or PNET cell lines were screened for c-myc genomic amplification, mRNA levels, and protein levels. Two medulloblastoma lines, D283 Med and D721 Med, were identified that expressed c-myc mRNA and protein at high levels without genomic amplification. The c-myc gene's regulatory sequences were normal in those cell lines. However, specific regions of the promoter, independent of the beta-catenin binding sites, were responsible for activation as revealed by promoter assays and site-directed mutagenesis. Transcriptional activation by a beta-catenin-independent pathway is therefore a likely mechanism for c-myc overexpression in a subset of medulloblastomas.


Results of surgery in general surgical patients receiving warfarin: retrospective analysis of 61 patients.
The aim of this study is to investigate postoperative complications, mortality rates, and to determine the factors affecting mortality on the patients receiving warfarin therapy preoperatively, as well as comparing the results obtained from emergency and elective surgeries. Surgical outcomes of 61 patients on long-term oral anticoagulation with warfarin who underwent surgery in our center were retrospectively reviewed over an 8-year period. Thirty-three (54.1%) patients were female, with a mean age of 53 years. Mitral valve replacement (62.3%) was the most frequent indication for chronic anticoagulation therapy. Twelve out of 61 (19.2%) patients underwent emergency surgery; 59 (96.7%) operations were classified as major surgery. We did not observe any thromboembolic events on patients receiving our bridging therapy protocol. Cardiopulmonary dysfunction (CPD; 19.7%) and hemorrhage (16.4%) were the most encountered postoperative complications. Presence of CPD, bleeding, endocarditis, and mortality were statistically significant for emergency surgeries when compared with the results obtained from elective surgeries. There were 5 (8.2%) deaths observed during follow-up. It was found that advanced age, prolonged duration of operations, and presence of CPD had a statistically significant effect on mortality (P < 0.05). The patients receiving oral anticoagulant had high postoperative complication and mortality rates. This case was more evident in emergency surgeries. It is recommendable that as mortality is more apparent in the patients who undergo emergency surgeries-being older, having long duration of operations as well as CPD. Therefore during the postoperative follow-up process, the patients should be closely monitored.


Gaseous and Particulate Emissions from Diesel Engines at Idle and under Load: Comparison of Biodiesel Blend and Ultralow Sulfur Diesel Fuels.
Diesel exhaust emissions have been reported for a number of engine operating strategies, after-treatment technologies, and fuels. However, information is limited regarding emissions of many pollutants during idling and when biodiesel fuels are used. This study investigates regulated and unregulated emissions from both light-duty passenger car (1.7 L) and medium-duty (6.4 L) diesel engines at idle and load and compares a biodiesel blend (B20) to conventional ultralow sulfur diesel (ULSD) fuel. Exhaust aftertreatment devices included a diesel oxidation catalyst (DOC) and a diesel particle filter (DPF). For the 1.7 L engine under load without a DOC, B20 reduced brake-specific emissions of particulate matter (PM), elemental carbon (EC), nonmethane hydrocarbons (NMHCs), and most volatile organic compounds (VOCs) compared to ULSD; however, formaldehyde brake-specific emissions increased. With a DOC and high load, B20 increased brake-specific emissions of NMHC, nitrogen oxides (NOx), formaldehyde, naphthalene, and several other VOCs. For the 6.4 L engine under load, B20 reduced brake-specific emissions of PM2.5, EC, formaldehyde, and most VOCs; however, NOx brake-specific emissions increased. When idling, the effects of fuel type were different: B20 increased NMHC, PM2.5, EC, formaldehyde, benzene, and other VOC emission rates from both engines, and changes were sometimes large, e.g., PM2.5 increased by 60% for the 6.4 L/2004 calibration engine, and benzene by 40% for the 1.7 L engine with the DOC, possibly reflecting incomplete combustion and unburned fuel. Diesel exhaust emissions depended on the fuel type and engine load (idle versus loaded). The higher emissions found when using B20 are especially important given the recent attention to exposures from idling vehicles and the health significance of PM2.5. The emission profiles demonstrate the effects of fuel type, engine calibration, and emission control system, and they can be used as source profiles for apportionment, inventory, and exposure purposes.


Structural mechanism of HP1α-dependent transcriptional repression and chromatin compaction.
Heterochromatin protein 1 (HP1) plays a central role in establishing and maintaining constitutive heterochromatin. However, the mechanisms underlying HP1-nucleosome interactions and their contributions to heterochromatin functions remain elusive. In this study, we employed a multidisciplinary approach to unravel the interactions between human HP1α and nucleosomes. We have elucidated the cryo-EM structure of an HP1α dimer bound to an H2A.Z nucleosome, revealing that the HP1α dimer interfaces with nucleosomes at two distinct sites. The primary binding site is located at the N-terminus of histone H3, specifically at the trimethylated K9 (K9me3) region, while a novel secondary binding site is situated near histone H2B, close to nucleosome superhelical location 4 (SHL4). Our biochemical data further demonstrates that HP1α binding influences the dynamics of DNA on the nucleosome. It promotes DNA unwrapping near the nucleosome entry and exit sites while concurrently restricting DNA accessibility in the vicinity of SHL4. This study offers a model that explains how HP1α functions in heterochromatin maintenance and gene silencing, particularly in the context of H3K9me-dependent mechanisms. Additionally, it sheds light on the H3K9me-independent role of HP1 in responding to DNA damage.


NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder.
The NOTCH4 gene is located at 6p21.3, a site which several studies have shown to have significant linkage with schizophrenia. Recently, an exceptionally strong association was reported between NOTCH4 gene polymorphisms and schizophrenia in British patients. We re-examined their findings using a Japanese population. We genotyped three kinds of polymorphisms, SNP1 in the 5' flanking region, SNP2 in the promoter region and CTG repeats in exon 1 of the NOTCH4 gene of schizophrenics (N=188), patients with schizoaffective disorder (N=39) and controls (N=143). Genotypic distributions and allelic frequencies of SNP1, SNP2 and CTG repeats of the NOTCH4 gene did not show significant associations with schizophrenia or schizoaffective disorder. Neither they showed association with schizophrenia subcategories, hebephrenic and paranoid type schizophrenia, nor with subgroups of schizophrenia with and without positive family history of psychoses. The present study found that the NOTCH4 gene does not confer susceptibility to schizophrenia and schizoaffective disorders, at least in Japanese subjects, in contrast to the findings in British subjects.


Transient expression of neuropeptide W in postnatal mouse hypothalamus--a putative regulator of energy homeostasis.
Neuropeptide B and W (NPB and NPW) are cognate peptide ligands for NPBWR1 (GPR7), a G protein-coupled receptor. In rodents, they have been implicated in the regulation of energy homeostasis, neuroendocrine/autonomic responses, and social interactions. Although localization of these peptides and their receptors in adult rodent brain has been well documented, their expression in mouse brain during development is unknown. Here we demonstrate the transient expression of NPW mRNA in the dorsomedial hypothalamus (DMH) of postnatal mouse brain and its co-localization with neuropeptide Y (NPY) mRNA. Neurons expressing both NPW and NPY mRNAs begin to emerge in the DMH at about postnatal day 0 (P-0) through P-3. Their expression is highest around P-14, declines after P-21, and by P-28 only a faint expression of NPW and NPY mRNA remains. In P-18 brains, we detected NPW neurons in the region spanning the subincertal nucleus (SubI), the lateral hypothalamic (LH) perifornical (PF) areas, and the DMH, where the highest expression of NPW mRNA was observed. The majority of these postnatal hypothalamic NPW neurons co-express NPY mRNA. A cross of NPW-iCre knock-in mice with a Cre-dependent tdTomato reporter line revealed that more than half of the reporter-positive neurons in the adult DMH, which mature from the transiently NPW-expressing neurons, are sensitive to peripherally administrated leptin. These data suggest that the DMH neurons that transiently co-express NPW and NPY in the peri-weaning period might play a role in regulating energy homeostasis during postnatal development.


Analysis of the electroencephalographic activity during the Necker cube reversals by means of the wavelet transform.
In previous studies, a perceptual switching related potential was obtained during the observation of a multistable dynamic reversal pattern, where the averaging of the single responses was triggered by subjects pressing a button. The present methodological study aims to increase the signal quality of perceptual switching related potentials considering the dependence of the measurement method on the reaction time of the subject, which may vary significantly during a session, leading to low-amplitude waveform in the averaged event-related-potential (ERP). To overcome this problem in measuring the electrophysiological correlate of an internal event, a pattern selection method based on the wavelet transform (WT) is proposed to choose a subset of single ERPs with more homogenous latencies. Nine subjects observed a Necker cube and were instructed to press the button immediately after perceptual switching. A slow, low-amplitude positive wave with frontocentral amplitude maxima was observed around 250 ms prior to the button press. After the application of a 5 octave WT on single sweeps, the time-frequency coefficients obtained in each octave were averaged across trials. The most dominant feature representing the averaged ERP was the delta (0.5-4 Hz) coefficient occurring between 250 and 125 ms before the button press. By averaging the subset of the single sweeps containing this property, a sharpening and significant amplitude increase of the response peak was observed.


Trends in HIV prevalence among homosexual and bisexual men in eastern Australian states.
In Australia, HIV notification rates in homosexual men, previously much higher in New South Wales, have become similar across the eastern states. We examined whether trends in HIV prevalence in community-based samples of homosexual men were consistent with the trends in HIV notifications. We examined data on self-reported HIV status from annual cross-sectional, self-completed anonymous surveys of homosexual men conducted between 1998 and 2006 in Sydney, Melbourne and Brisbane. Men were recruited at gay community venues, clinics and large gay community events. We calculated age-specific and age-standardised HIV prevalence rates. Comparisons of HIV prevalence between the three cities and across time were carried out using age-specific rates, and using logistic regression, controlling for age. Men recruited from clinics had a much higher prevalence of HIV (P < 0.001) and were excluded from further analyses. Among the 50 239 completed questionnaires obtained at non-clinic sites, there was a marked decline in aged-standardised HIV prevalence in Sydney (from 14.2 to 8.98%, P < 0.001), a small decline in Brisbane (from 8.51 to 6.94%, P = 0.012) and no change in Melbourne (from 8.35 to 8.06%, P = 0.848). There were significant declines in men aged less than 50 years in Sydney, and in men aged less than 30 years in Brisbane. In Melbourne there was no significant trend in HIV at any age. HIV prevalence among young homosexual men has declined in Sydney, and these data suggest that HIV incidence among homosexual men is now similar in the eastern state capitals of Australia.


Matching isotopic distributions from metabolically labeled samples.
In recent years stable isotopic labeling has become a standard approach for quantitative proteomic analyses. Among the many available isotopic labeling strategies, metabolic labeling is attractive for the excellent internal control it provides. However, analysis of data from metabolic labeling experiments can be complicated because the spacing between labeled and unlabeled forms of each peptide depends on its sequence, and is thus variable from analyte to analyte. As a result, one generally needs to know the sequence of a peptide to identify its matching isotopic distributions in an automated fashion. In some experimental situations it would be necessary or desirable to match pairs of labeled and unlabeled peaks from peptides of unknown sequence. This article addresses this largely overlooked problem in the analysis of quantitative mass spectrometry data by presenting an algorithm that not only identifies isotopic distributions within a mass spectrum, but also annotates matches between natural abundance light isotopic distributions and their metabolically labeled counterparts. This algorithm is designed in two stages: first we annotate the isotopic peaks using a modified version of the IDM algorithm described last year; then we use a probabilistic classifier that is supplemented by dynamic programming to find the metabolically labeled matched isotopic pairs. Such a method is needed for high-throughput quantitative proteomic metabolomic experiments measured via mass spectrometry. The primary result of this article is that the dynamic programming approach performs well given perfect isotopic distribution annotations. Our algorithm achieves a true positive rate of 99% and a false positive rate of 1% using perfect isotopic distribution annotations. When the isotopic distributions are annotated given 'expert' selected peaks, the same algorithm gets a true positive rate of 77% and a false positive rate of 1%. Finally, when annotating using machine selected peaks, which may contain noise, the dynamic programming algorithm gives a true positive rate of 36% and a false positive rate of 1%. It is important to mention that these rates arise from the requirement of exact annotations of both the light and heavy isotopic distributions. In our evaluations, a match is considered 'entirely incorrect' if it is missing even one peak or containing an extraneous peak. If we only require that the 'monoisotopic' peaks exist within the two matched distributions, our algorithm obtains a positive rate of 45% and a false positive rate of 1% on the 'machine' selected data. Changes to the algorithm's scoring function and training example generation improves our 'monoisotopic' peak score true positive rate to 65% while obtaining a false positive rate of 2%. All results were obtained within 10-fold cross-validation of 41 mass spectra with a mass-to-charge range of 800-4000 m/z. There are a total of 713 isotopic distributions and 255 matched isotopic pairs that are hand-annotated for this study. Programs are available via http://www.cs.wisc.edu/~mcilwain/IDM/.


The association between active tobacco use during pregnancy and growth outcomes of children under five years of age: a systematic review and meta-analysis.
Despite considerable global efforts to reduce growth faltering in early childhood, rates of stunting remain high in many regions of the world. Current interventions primarily target nutrition-specific risk factors, but these have proven insufficient. The objective of this study was to synthesize the evidence on the relationship between active tobacco use during pregnancy and growth outcomes in children under five years of age. In this systematic review and meta-analysis, six online databases were searched to identify studies published from January 1, 1980, through October 31, 2016, examining the association between active tobacco use during pregnancy and small-for-gestational age (SGA), length/height, and/or head circumference. Ecological studies were not included. A meta-analysis was conducted, and subgroup analyses were carried out to explore the effect of tobacco dosage. Among 13,189 studies identified, 210 were eligible for inclusion in the systematic review, and 124 in the meta-analysis. Active tobacco use during pregnancy was associated with significantly higher rates of SGA (pooled adjusted odds ratio [AORs] = 1.95; 95% confidence interval [CI]: 1.76, 2.16), shorter length (pooled weighted mean difference [WMD] = 0.43; 95% CI: 0.41, 0.44), and smaller head circumference (pooled WMD = 0.27; 95% CI: 0.25, 0.29) at birth. In addition, a dose-response effect was evident for all growth outcomes. Tobacco use during pregnancy may represent a major preventable cause of impaired child growth and development.


Public estimates of cancer frequency: cancer incidence perceptions mirror distorted media depictions.
Compared with incidence rates, certain cancers are over- or underrepresented in news coverage. Past content analytic research has consistently documented these news distortions, but no study has examined whether they are related to public perception of cancer incidence. Adults (N = 400) completed a survey with questions about perceived cancer incidence, news consumption, and attention to health news. Cancer incidence perceptions paralleled previously documented news distortions. Overrepresented cancers were overestimated (e.g., blood, head/brain) and underrepresented cancers were underestimated (e.g., male reproductive, lymphatic, thyroid, and bladder). Self-reported news consumption was related to perceptual distortions such that heavier consumers were more likely to demonstrate distorted perceptions of four cancers (bladder, blood, breast, and kidney). Distortions in risk perception and news coverage also mirrored discrepancies in federal funding for cancer research. Health care professionals, journalists, and the public should be educated about these distortions to reduce or mitigate potential negative effects on health behavior and decision making.


Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1.
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.


Lipid-mediated a-factor interactions with artificial membranes.
Our understanding of the cellular export of a-factor and its interaction with the receptor do not yet allow for a description of the phenomena on a molecular level. Synthesis of a-factor analogs and biophysical studies of the lipopeptides in the presence of artificial membranes provide insights which can be analyzed with respect to the biological potency of the molecules. It is through the study of the interaction of the lipopeptides with membranes at varying levels of complexity that we will be able to develop a molecular description of the biological processes.


Mitochondrial fission factor Drp1 maintains oocyte quality via dynamic rearrangement of multiple organelles.
Mitochondria are dynamic organelles that change their morphology by active fusion and fission in response to cellular signaling and differentiation. The in vivo role of mitochondrial fission in mammals has been examined by using tissue-specific knockout (KO) mice of the mitochondria fission-regulating GTPase Drp1, as well as analyzing a human patient harboring a point mutation in Drp1, showing that Drp1 is essential for embryonic and neonatal development and neuronal function. During oocyte maturation and aging, structures of various membrane organelles including mitochondria and the endoplasmic reticulum (ER) are changed dynamically, and their organelle aggregation is related to germ cell formation and epigenetic regulation. However, the underlying molecular mechanisms of organelle dynamics during the development and aging of oocytes have not been well understood. Here, we analyzed oocyte-specific mitochondrial fission factor Drp1-deficient mice and found that mitochondrial fission is essential for follicular maturation and ovulation in an age-dependent manner. Mitochondria were highly aggregated with other organelles, such as the ER and secretory vesicles, in KO oocyte, which resulted in impaired Ca(2+) signaling, intercellular communication via secretion, and meiotic resumption. We further found that oocytes from aged mice displayed reduced Drp1-dependent mitochondrial fission and defective organelle morphogenesis, similar to Drp1 KO oocytes. On the basis of these findings, it appears that mitochondrial fission maintains the competency of oocytes via multiorganelle rearrangement.


Thoracic aortic aneurysm--subtle but serious: a case report.
A case is reported of a 55-yr-old man complaining of interscapular pain, lethargy, anorexia with weight loss and shallowness of breath following a recent traumatic blow to the abdomen. Radiographs revealed a marked and extensive aneurysm of the thoracic aorta. The importance of performing X-ray studies of the thoracic region is emphasized for all cases where histories of recent or past significant chest trauma is suspected and with older patients having hypertension and atherosclerotic heart disease.


Design and in vitro pharmacology of a selective gamma-aminobutyric acidC receptor antagonist.
In mammals, receptors for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) are divided into three pharmacological classes, which are denoted GABAA, GABAB, and GABAC. GABAC receptors are defined by their insensitivity to the GABAA receptor antagonist bicuculline and the GABAB receptor agonist (-)-baclofen. GABAC receptors probably are a heterogeneous group of proteins. The most extensively studied mammalian GABAC receptors are those found in neurons of the outer retina. These receptors are GABA-gated Cl- channels comprised of p subunits, of which there are two subtypes. The physiological functions served by GABAC receptors are largely unknown; to determine the functions, it would be useful to have GABAC-selective ligands. In a previous study, we found that isoguvacine, a GABAA-selective agonist, and 3-aminopropyl-(methyl)phosphinic acid (3-APMPA), a GABAB-selective agonist, show affinity for retinal GABAC receptors. In particular, 3-APMPA is an antagonist with low micromolar potency (Kb approximately 1 microM). Here, we report the synthesis and pharmacological characterization of (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA), a hybrid of isoguvacine and 3-APMPA designed to retain affinity for GABAC receptors but not to interact with GABAA or GABAB receptors. Electrical assays show that TPMPA is a competitive antagonist of cloned human mu 1 GABAC receptors expressed in Xenopus laevis oocytes (Kb approximately 2 microM). TPMPA is > 100-fold weaker as an inhibitor of rat brain GABAA receptors expressed in oocytes (Kb approximately 320 microM) and has only weak agonist activity on GABAB receptors assayed in rat hippocampal slices (EC50 approximately 500 microM). TPMPA should be a useful pharmacological probe with which to investigate GABAC receptor function in the outer retina and in any other areas of the nervous system in which these types of receptor are present.


Early Postinjury Screen Time and Concussion Recovery.
To determine the association between early screen time (7-10 days postinjury) and postconcussion symptom severity in children and adolescents with concussion, as compared to those with orthopedic injury (OI). This was a planned secondary analysis of a prospective longitudinal cohort study. Participants were 633 children and adolescents with acute concussion and 334 with OI aged 8 to 16, recruited from 5 Canadian pediatric emergency departments. Postconcussion symptoms were measured using the Health and Behavior Inventory at 7 to 10 days, weekly for 3 months, and biweekly from 3 to 6 months postinjury. Screen time was measured by using the Healthy Lifestyle Behavior Questionnaire. Generalized least squares models were fit for 4 Health and Behavior Inventory outcomes (self- and parent-reported cognitive and somatic symptoms), with predictors including screen time, covariates associated with concussion recovery, and 2 3-way interactions (self- and parent-reported screen time with group and time postinjury). Screen time was a significant but nonlinear moderator of group differences in postconcussion symptom severity for parent-reported somatic (P = .01) and self-reported cognitive symptoms (P = .03). Low and high screen time were both associated with relatively more severe symptoms in the concussion group compared to the OI group during the first 30 days postinjury but not after 30 days. Other risk factors and health behaviors had stronger associations with symptom severity than screen time. The association of early screen time with postconcussion symptoms is not linear. Recommending moderation in screen time may be the best approach to clinical management.


Specificity of glucose transport in Trypanosoma brucei. Effective inhibition by phloretin and cytochalasin B.
Glucose transport in the bloodstream form of the protozoan parasite Trypanosoma brucei was characterized by enzymatically measuring the D-glucose uptake. Uptake kinetics showed a concentration-dependent saturable process, typical for a carrier-mediated transport system, with an apparent Km = 0.49 +/- 0.14 mM and Vmax = 252 +/- 43 nmol.min-1.mg cell protein-1 (equal to 2.25 x 10(8) trypanosomes). The specificity of glucose transport was investigated by inhibitor studies. Glucose uptake was shown to be sodium independent; neither the Na+/K(+)-ATPase inhibitor ouabain (1 mM) nor the ionophor monensin (1 microM) inhibited uptake. Transport was also unaffected by the H(+)-ATPase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD; 20 microM) and the uncoupler carbonylcyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP; 1 microM). However, highly significant inhibition was obtained with both phloretin (82% at 0.13 mM; Ki = 64 microM) and cytochalasin B (77% at 0.3 mM; Ki = 0.44 mM), and partial inhibition with phlorizin (14% at 0.5 mM; Ki = 3.0 mM). In each case, inhibition was noncompetitive, partially reversible (45%) for phloretin and completely reversible for cytochalasin B and phlorizin. Measurement of the temperature-dependent glucose uptake between 25 degrees C and 37 degrees C resulted in a temperature quotient of Q10 = 1.97 +/- 0.02 and an activation energy of Ea = 52.12 +/- 1.00 kJ/mol for glucose uptake. We conclude that glucose uptake in T. brucei bloodstream forms occurs via a facilitated diffusion system, clearly distinguished from the human erythrocyte-type glucose transporter with about a 10-fold higher affinity for glucose and about a 1000-fold decreased sensitivity to the inhibitor cytochalasin B.


Robotic lobectomy for lung cancer: initial experience of a single institution in Korea.
Robotic surgery is known to have several advantages including magnified three-dimensional vision and angulation of the surgical instruments. To evaluate the feasibility and efficiency of robotic lobectomy in the treatment of lung cancer, we analyzed the outcomes of our initial experiences with robotic lobectomy at a single institution in Korea. Eighty-seven patients with lung cancer underwent robotic lobectomy (robotic group: 34 patients) and video-assisted thoracic surgery (VATS) lobectomy (VATS group: 53 patients) between 2011 and 2016 at our hospital. The medical records of these patients were retrospectively analyzed. The operation times of the two groups were significantly different (robotic group, 293±74 min; VATS group, 201±62 min; P<0.01). Intraoperative blood loss occurred more in the robotic group than in the VATS group (robotic group, 403±197 mL; VATS group, 298±188 mL; P=0.018). The numbers of lymph nodes dissected in the two groups were significantly different (robotic group, 22±12; VATS group, 14±7; P<0.01). There was no intraoperative mortality in both groups. Despite the initial difficulties, robotic lobectomy for lung cancer was a safe and feasible procedure with no operative mortality. If operation time and intraoperative blood loss improve as the learning curve progresses, robotic surgery may overcome the limitations of VATS in lung cancer surgery.


Hemilaminectomy approach combined with in situ restoration of vertebral laminae for thoracic intraspinal tumors.
This study aims to evaluate the hemilaminectomy approach and in situ restoration of vertebral laminae in microsurgery for thoracic intraspinal tumors. Sixteen patients with thoracic intraspinal tumors, consisting of 6 males and 10 females with a mean age of 47.5±16.4 years ranging from 21 to 71 years, underwent surgical treatment with hemilaminectomy approach and in situ restoration of vertebral laminae. All patients were followed up after surgery for 12 to 30 months, involving Frankel grade, spinal instability, and deformity. Mean operation time was 119.5±23.0 minutes. Laminotomy was performed with one vertebral plate in 2 cases, two vertebral plates in 12 cases, and three vertebral plates in 2 cases. Postoperative three-dimensional CT scanning revealed a stable bony reconstruction, and no cerebrospinal fluid leakage or subcutaneous hydrops. Surgical pathology was consistent with preoperative MRI diagnosis. With respect to neurological status, the percentage of good Frankel scale was markedly improved from 37.5% on admission to 81.3% at follow-up (p < 0.05). None of the subjects showed spinal deformity or instability. In situ restoration of vertebral laminae maximally preserves the spinal integrity and stability, and reduces postoperative complications including cerebrospinal fluid leakage, pseudomeningocele, spinal deformity, and instability.


Service delivery point and individual characteristics associated with the adoption of modern contraceptive: A multi-country longitudinal analysis.
Women who start using contraception ("adopters") are a key population for family planning goals, but little is known about characteristics that predict the adoption of contraception as opposed to current use. We used prospective data from women and facilities for five countries, (Democratic Republic of Congo, India, Kenya, Nigeria, and Burkina Faso) and identified baseline characteristics that predicted adoption of modern contraception in the short term. We used data from the Performance Monitoring for Action (PMA) Agile Project. PMA Agile administered service delivery point (SDP) client exit interview (CEI) surveys in urban sites of these five countries. Female clients responding to the CEI were asked for phone numbers that were used for a phone follow-up survey approximately four months later. For our analysis, we used data from the SDP and CEI baseline surveys, and the phone follow up to compare women who start using contraception during this period with those who remain non-users. We used characteristics of the facility and the woman at baseline to predict her contraception adoption in the future. Discussing FP with a partner at baseline was associated with greater odds of adoption in DRC (OR 2.34; 95% CI 0.97-5.66), India (OR 2.27; 95% CI 1.05-4.93), and Kenya (OR 1.65; 95% CI 1.16-2.35). Women who discussed family planning with any staff member at the health facility had 1.72 greater odds (95% CI 1.13-2.67) of becoming an adopter in Nigeria. The odds of adoption were lower in Nigerian facilities that had a stockout (OR 0.66 95% CI 0.44-1.00) at baseline. Other characteristics associated with contraception adoption across settings were education, age, wealth, parity, and marital status. Characteristics of both the woman and the health facility were associated with adoption of modern contraception in the future. Some characteristics, like discussing family planning with a spouse, education, and parity, were associated with contraceptive adoption across settings. Other characteristics that predict contraceptive use, such as health facility measures, varied across countries.


Diversity and genetic characterization of orthohantavirus from small mammals and humans during 2012-2022 in Hubei Province, Central China.
Hemorrhagic fever with renal syndrome (HFRS) is a significant public health problem in Hubei Province, China, where a novel strain of orthohantavirus, HV004, was reported in 2012. However, no systematic study has investigated the prevalence and variation of orthohantavirus in rodents and humans. Herein, 2137 small mammals were collected from ten HFRS epidemic areas in Hubei Province from 2012 to 2022, and 143 serum samples from patients with suspected hemorrhagic fever were collected from two hospitals from 2017 to 2021. Orthohantavirus RNA was recovered from 134 lung tissue samples from five rodent species, with a 6.27 % prevalence, and orthohantavirus was detected in serum samples from 25 patients. Genetic analyses revealed that orthohantavirus hantanense (HTNV), orthohantavirus seoulense (SEOV), and orthohantavirus dabieshanense (DBSV) are co-circulating in rodents in Hubei, and HTNV and SEOV were identified in patient serum. Phylogenetic analysis showed that most of the HTNV sequences were clustered with HV004, indicating that HV004-like orthohantavirus was the main HNTV subtype in rodents. Two genetic reassortments and six recombination events were observed in Hubei orthohantaviruses. In summary, this study identified the diversity of orthohantaviruses circulating in Hubei over the past decade, with the HV004-like subtype being the main genotype in rodents and patients. These findings highlight the need for continued attention and focus on orthohantaviruses, especially concerning newly identified strains.


Longitudinal relationships between cognition and functioning over 2 years in euthymic patients with bipolar disorder: a cross-lagged panel model approach with the FACE-BD cohort.
Longitudinal studies of the relationship between cognition and functioning in bipolar disorder are scarce, although cognition is thought to be a key determinant of functioning. The causal structure between cognition and psychosocial functioning in bipolar disorder is unknown. We sought to examine the direction of causality between cognitive performance and functional outcome over 2 years in a large cohort of euthymic patients with bipolar disorder. The sample consisted of 272 adults diagnosed with bipolar disorder who were euthymic at baseline, 12 and 24 months. All participants were recruited via the FondaMental Advanced Centers of Expertise in Bipolar Disorders. We used a battery of tests, assessing six domains of cognition at baseline and 24 months. Residual depressive symptoms and psychosocial functioning were measured at baseline and 12 and 24 months. The possible causal structure between cognition and psychosocial functioning was investigated with cross-lagged panel models with residual depressive symptoms as a covariate. The analyses support a causal model in which cognition moderately predicts and is causally primary to functional outcome 1 year later, whereas psychosocial functioning does not predict later cognitive performance. Subthreshold depressive symptoms concurrently affected functioning at each time of measure. Our results are compatible with an upward causal effect of cognition on functional outcome in euthymic patients with bipolar disorder. Neuropsychological assessment may help specify individual prognoses. Further studies are warranted to confirm this causal link and evaluate cognitive remediation, before or simultaneously with functional remediation, as an intervention to improve functional outcome.


Medico-legal perspectives on sudden cardiac death in young athletes.
Sudden cardiac death (SCD) in a young athlete represents a dramatic event, and an increasing number of medico-legal cases have addressed this topic. In addition to representing an ethical and medico-legal responsibility, prevention of SCD is directly correlated with accurate eligibility/disqualification decisions, with an inappropriate pronouncement in either direction potentially leading to legal controversy. This review summarizes the common causes of SCD in young athletes, divided into structural (hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, congenital coronary artery anomalies, etc.), electrical (Brugada, congenital LQT, Wolf-Parkinson-White syndrome, etc.), and acquired cardiac abnormalities (myocarditis, etc.). In addition, the roles of hereditary cardiac anomalies in SCD in athletes and the effects of a positive result on them and their families are discussed. The medico-legal relevance of pre-participation screening is analyzed, and recommendations from the American Heart Association and European Society of Cardiology are compared. Finally, the main issues concerning the differentiation between physiologic cardiac adaptation in athletes and pathologic findings and, thereby, definition of the so-called gray zone, which is based on exact knowledge of the mechanism of cardiac remodeling including structural or functional adaptions, will be addressed.


Performance characteristics and validation of the Opioid-Related Symptom Distress Scale for evaluation of analgesic side effects after orthopedic surgery.
The Opioid-Related Symptom Distress Scale (ORSDS) is a 4-point scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS is the average of 12 symptom-specific scores. The ORSDS was validated for outpatient laparoscopic cholecystectomy (under general anesthesia) by assessment of internal consistency, content validity, construct validity, principal components analysis, known group validity, responsiveness, and opioid dose dependency. Additional validation studies were suggested. We investigated performance characteristics and validity of the ORSDS for postoperative analgesia after 4 types of anesthetic and analgesic regimens. The ORSDS and validation questions were administered to 4 groups of 50 orthopedic patients. Peripheral nerve blockade (Peripheral) was performed for distal upper extremity surgery; neuraxial anesthesia (Neuraxial) was performed for anterior cruciate ligament reconstruction; combined spinal-epidural anesthesia/femoral nerve block/epidural analgesia (Regional) was performed for total knee arthroplasty; and general anesthesia/IV opioids (GA) was performed for posterior lumbar spine fusion. All patients also received oral opioid analgesics. Median composite ORSDS scores on postoperative day 1 were 0.19 (Peripheral), 0.52 (Neuraxial), 0.51 (Regional), and 0.94 (GA). The following symptoms had median symptom-specific ORSDS scores >0: Neuraxial = drowsiness, dry mouth; Regional = dizziness, dry mouth; GA = nausea, fatigue, dizziness, drowsiness, dry mouth. Problematic symptoms (symptoms for which at least 25%of patients reported symptom-specific ORSDS scores >1) were: all groups = drowsiness, dry mouth, fatigue; Neuraxial = nausea, dizziness, itchiness; Regional = nausea, dizziness, itchiness; GA = difficulty concentrating, headache, nausea, dizziness, itchiness. High symptom-specific ORSDS scores were associated with clinically meaningful adverse events. In some cases, relevant ORSDS scores were related to activity level, patient satisfaction, and nausea and vomiting measures. Many components occurred in correlated clusters. Responsiveness statistics (the ability of an instrument to detect changes once they have occurred) were high for nausea and vomiting. Linear regression analysis indicated that opioid use was associated with composite ORSDS scores for Peripheral, Regional, and GA. Validity of the ORSDS was supported by predetermined validation criteria, including measures of internal consistency, content validity, construct validity, principal components analysis, known group validity, responsiveness, and correlation with opioid intake. The ORSDS is a valid tool for assessment of opioid side effects after orthopedic surgery, and can be used in clinical trials involving a wide variety of anesthetic and analgesic regimens.


Microscopic observation of multispecies biofilm of various structures on whey concentration membranes.
The objective of this study was to evaluate biofilm formation on polyamide reverse osmosis (RO) whey concentration membranes. Biofilms were observed with scanning electron and fluorescence microscopy. For scanning electron microscopy, pieces of 6-, 12-, and 14-mo-old membranes were allowed to air dry at room temperature (22 degrees C) for 24h followed by sputter coating with a 5-nm layer of gold and microscopic observations. Scanning electron microscopy images revealed that the hydrophilic layer, used to prevent membrane plugging, was not evenly distributed on the surface. Although this hydrophilic layer seemed to prevent the attachment of proteins, it supported biofilm formation. Three different structures of multispecies biofilm were observed on the retentate side of the membrane: 1) a mono layer, 2) a 3-dimensional structure of a dense matrix of extracellular polymeric substances where different types of bacterial cells were embedded, and 3) cell aggregates. In some of the biofilms, a smooth layer (shell) covered cell aggregates. In the 6-mo-old membranes, part of the shell layer was broken off. Biofilms as observed on the RO membrane were described as having a hill-and-valley type of structure, with hills showing a mushroom-like appearance and valleys comprising dense matrices of extracellular polymers with embedded bacterial cells. Fluorescence microscopy showed live cells on the surface of the biofilm. It is concluded that both cells in the deep layers of biofilm and surface cells may resist cleaning and sanitation. The extent of biofilm formation and the presence of live cells on RO membranes after regular clean in place cycles indicate the need for a more effective cleaning regimen customized for dairy separation systems.


Temporal and spatial regulation of the expression of BAD2, a MAP kinase phosphatase, during seizure, kindling, and long-term potentiation.
Recent studies indicate that stimulation of NMDA receptors in cultured hippocampal cells activates MAP kinase. Although the pathway whereby MAP kinase is activated has been been characterized, little is known about the mechanisms that shut off MAP kinase. In the course of analyzing several immediate-early genes identified previously by differential screen as inducible by seizure activity, we found that one of them, BAD2, encodes dual purpose, threonine/tyrosine phosphates with specific activity directed against MAP kinase (MKP-1). In situ hybridization of BAD2 demonstrates that stimuli that produce seizure, kindling, and long-term potentiation cause a rapid increase in BAD2 mRNA (within 0.5-1 hr after stimulation) that has, in each case, a distinctive pattern of expression in the brain. In these regions, the induction of a MAP kinase-specific phosphatase may provide a negative feedback control associated with long-term synaptic changes.


Variation in base composition underlies functional and evolutionary divergence in non-LTR retrotransposons.
Non-LTR retrotransposons often exhibit base composition that is markedly different from the nucleotide content of their host's gene. For instance, the mammalian L1 element is AT-rich with a strong A bias on the positive strand, which results in a reduced transcription. It is plausible that the A-richness of mammalian L1 is a self-regulatory mechanism reflecting a trade-off between transposition efficiency and the deleterious effect of L1 on its host. We examined if the A-richness of L1 is a general feature of non-LTR retrotransposons or if different clades of elements have evolved different nucleotide content. We also investigated if elements belonging to the same clade evolved towards different base composition in different genomes or if elements from different clades evolved towards similar base composition in the same genome. We found that non-LTR retrotransposons differ in base composition among clades within the same host but also that elements belonging to the same clade differ in base composition among hosts. We showed that nucleotide content remains constant within the same host over extended period of evolutionary time, despite mutational patterns that should drive nucleotide content away from the observed base composition. Our results suggest that base composition is evolving under selection and may be reflective of the long-term co-evolution between non-LTR retrotransposons and their host. Finally, the coexistence of elements with drastically different base composition suggests that these elements may be using different strategies to persist and multiply in the genome of their host.


[American cutaneous leishmaniasis in the Federal District].
In the present study, we report 11 cases of mucocutaneous leishmaniasis (MCL) in patients living in the Federal District who had not left their area of residence for a period ranging from six months to two years before the onset of the disease. Six of the eleven patients live in the suburban town of Planaltina. All showed a positive Leishmanin intradermal reaction. Ten of them presented the parasite in their lesions. Leishmania (V) braziliensi was identified in the lesions of two patients by the monoclonal antibody method. Nine patients were treated with pentavalent antimoy and two with pentamidine. Relapse occurred in two cases after treatment with antimony. In view of the detection of vectors and infected patients in the Federal District, it is probable that Leishmania infection is occurring in Brasilia and its suburban areas.


The course of stage III melanoma in accordance with the severity of node involvement.
Objectives: Pathological stage III melanoma patients have variable clinical presentation and outcome when divided by substages, and the number of metastatic lymph nodes is the most significant independent factor. We aimed to determine the clinical features and natural course of node positive melanoma, such as first relapse and final outcome, and other factors influencing them. Methods: A total of 362 node positive melanoma patients were included in the study and reviewed retrospectively. Results: Cases were as follows: N1 (56.6%); N2 (27.1%); and N3 (16.3%). Lymphovascular invasion was found significant among node positive subtypes; it was predominant in patients with involvement of two or more nodes (p < .05). The majority of the relapses were locoregional alone (43.4%) and distant alone (31.3%). The lung/pleura was the most frequently metastasized site (32.1%). Time to relapse was the longest for N1 (20.8 months) (p < .05). Five and 10 year relapse-free survival (RFS) rates were 40% and 38%, respectively. Nodular histopathology, ulcerated lesion and higher mitotic rates carried worse RFS for all patients and also for N1. Five- and 10 year overall survival (OS) rates were 49% and 40%, respectively. Older age, nodular histopathology, higher mitotic rates and relapse of disease (p = .001) were the independent variables that were inversely correlated with OS for all patients. Conclusion: Comparative analyses of node positive melanoma suggested that there was not only a remarkable heterogeneity in the recurrence and survival rates but also a distinctive pattern among independent prognostic indicators in accordance with the severity of nodal involvement.


Topical application of tacrolimus prevents epidural fibrosis in a rat postlaminectomy model: histopathological and ultrastructural analysis.
Postlaminectomy epidural fibrosis is the formation of scar tissue over the dura mater following posterior spinal surgery. This devastating complication is responsible for the substantial amount of failed back syndromes. MATERIAL and Twenty male Wistar-Albino rats each weighing 350-400 grams were used. Following L3-L5 laminectomy, the rats were randomly divided into 2 groups, with 10 rats in each group. In the control group, only a laminectomy was performed. In the drug group, 5 mg/ml tacrolimus was topically applied with a cotton pad soaked with the drug solution for 5 minutes. The animals were killed on the 30th postoperative day injecting a lethal dose (250 mg/kg) of pentobarbital and the involved dural segments were removed for histopathological and ultrastructural evaluations. Epidural scar thickness and the density were significantly lower in the animals treated with tacrolimus than those of the control group. Promising evidence regarding the anti-scar potential of tacrolimus merits further research to optimize the dosage and the usage of the drug.


Targeting Value-Driven Quality Improvement for Laparoscopic Cholecystectomy in Michigan.
The purpose of this study was to evaluate complete episode expenditures for laparoscopic cholecystectomy, a common and lower-risk operation, to characterize novel targets for value-based quality improvement. Despite enthusiasm for improving the overall value of surgical care, most efforts have focused on high-risk inpatient surgery. We identified 19,213 patients undergoing elective laparoscopic cholecystectomy from 2012 to 2015 using data from Medicare and a large private payer. We calculated price-standardized payments for the entire surgical episode of care and stratified patients by surgeon. We used linear regression to risk- and reliability-adjusted expenditures for patient characteristics, diagnoses, and the use of additional procedures. Fully adjusted total episode costs varied 2.4-fold across surgeons ($7922-$17,500). After grouping surgeons by adjusted total episode payments, each component of the total episode was more expensive for patients treated by the most expensive versus the least expensive quartile of surgeons. For example, payments for physician services were higher for the most expensive surgeons [$1932, 95% confidence interval (CI) $1844-$2021] compared to least expensive surgeons ($1592, 95% CI $1450-$1701, P < 0.01). Overall differences were driven by higher rates of complications (10% vs. 5%) and readmissions (14% vs. 8%), and lower rates of ambulatory procedures (77% vs. 56%) for surgeons with the highest versus lowest expenditures. Projections showed that a 10% increase ambulatory operations would yield $3.6 million in annual savings for beneficiaries. Episode payments for laparoscopic cholecystectomy vary widely across surgeons. Although improvements in several domains would reduce expenditures, efforts to expand ambulatory surgical practices may result in the largest savings to beneficiaries in Michigan.


Alteration of cerebrovascular haemodynamic patterns due to atrial fibrillation: an in silico investigation.
There has recently been growing evidence that atrial fibrillation (AF), the most common cardiac arrhythmia, is independently associated with the risk of dementia. This represents a very recent frontier with high social impact for the number of individuals involved and for the expected increase in AF incidence in the next 40 years. Although a number of potential haemodynamic processes, such as microembolisms, altered cerebral blood flow, hypoperfusion and microbleeds, arise as connecting links between the two pathologies, the causal mechanisms are far from clear. An in silico approach is proposed that combines in sequence two lumped-parameter schemes, for the cardiovascular system and the cerebral circulation. The systemic arterial pressure is obtained from the cardiovascular system and used as the input for the cerebral circulation, with the aim of studying the role of AF on the cerebral haemodynamics with respect to normal sinus rhythm (NSR), over a 5000 beat recording. In particular, the alteration of the haemodynamic (pressure and flow rate) patterns in the microcirculation during AF is analysed by means of different statistical tools, from correlation coefficients to autocorrelation functions, crossing times, extreme values analysis and multivariate linear regression models. A remarkable signal alteration, such as a reduction in signal correlation (NSR, about 3 s; AF, less than 1 s) and increased probability (up to three to four times higher in AF than in NSR) of extreme value events, emerges for the peripheral brain circulation. The described scenario offers a number of plausible cause-effect mechanisms that might explain the occurrence of critical events and the haemodynamic links relating to AF and dementia.


Oxidative stress and DNA lesions: the role of 8-oxoguanine lesions in Trypanosoma cruzi cell viability.
The main consequence of oxidative stress is the formation of DNA lesions, which can result in genomic instability and lead to cell death. Guanine is the base that is most susceptible to oxidation, due to its low redox potential, and 8-oxoguanine (8-oxoG) is the most common lesion. These characteristics make 8-oxoG a good cellular biomarker to indicate the extent of oxidative stress. If not repaired, 8-oxoG can pair with adenine and cause a G:C to T:A transversion. When 8-oxoG is inserted during DNA replication, it could generate double-strand breaks, which makes this lesion particularly deleterious. Trypanosoma cruzi needs to address various oxidative stress situations, such as the mammalian intracellular environment and the triatomine insect gut where it replicates. We focused on the MutT enzyme, which is responsible for removing 8-oxoG from the nucleotide pool. To investigate the importance of 8-oxoG during parasite infection of mammalian cells, we characterized the MutT gene in T. cruzi (TcMTH) and generated T. cruzi parasites heterologously expressing Escherichia coli MutT or overexpressing the TcMTH enzyme. In the epimastigote form, the recombinant and wild-type parasites displayed similar growth in normal conditions, but the MutT-expressing cells were more resistant to hydrogen peroxide treatment. The recombinant parasite also displayed significantly increased growth after 48 hours of infection in fibroblasts and macrophages when compared to wild-type cells, as well as increased parasitemia in Swiss mice. In addition, we demonstrated, using western blotting experiments, that MutT heterologous expression can influence the parasite antioxidant enzyme protein levels. These results indicate the importance of the 8-oxoG repair system for cell viability.


Fluorescence correlation spectroscopy, a tool to investigate supramolecular dynamics: inclusion complexes of pyronines with cyclodextrin.
The control of supramolecular systems requires a thorough understanding of their dynamics on a molecular level. We present fluorescence correlation spectroscopy (FCS) as a powerful spectroscopic tool to study supramolecular dynamics with single molecule sensitivity. The formation of a supramolecular complex between beta-cyclodextrin (beta-CD) as host and pyronines Y (PY) and B (PB) as guests is studied by FCS. Global target analysis of full correlation curves with a newly derived theoretical model yields in a single experiment the fluorescence lifetimes and the diffusion coefficients of free and complexed guests and the rate constants describing the complexation dynamics. These data give insight into the recently published surprising fact that the association equilibrium constant of beta-CD with PY is much lower than that with the much bulkier guest PB. FCS shows that the stability of the complexes is dictated by the dissociation and not by the association process. The association rate constants are very similar for both guests and among the highest reported for this type of systems, although much lower than the diffusion-controlled collision rate constant. A two-step model including the formation of an encounter complex allows one to identify the unimolecular inclusion reaction as the rate-limiting step. Simulations indicate that this step may be controlled by geometrical and orientational requirements. These depend on critical molecular dimensions which are only weakly affected by the different alkyl substituents of PY and PB. Diffusion coefficients of PY and PB, of their complexes, and of rhodamine 110 are given and compared to those of similar molecules.


Selection, constraint, and the evolution of coloration in African starlings.
Colorful plumage plays a prominent role in the evolution of birds, influencing communication (sexual/social selection), and crypsis (natural selection). Comparative studies have focused primarily on these selective pressures, but the mechanisms underlying color production can also be important by constraining the color gamut upon which selection acts. Iridescence is particularly interesting to study the interaction between selection and color-producing mechanisms because a broad range of colors can be produced with a shared template, and innovations to this template further expand this by increasing the parameters interacting to produce colors. We examine the patterns of ornamentation and dichromatism evolution in African starlings, a group remarkably diverse in color production mechanisms, social systems, and ecologies. We find that the presence of iridescence is ancestral to the group, being predominantly lost in females and cooperative breeders, as well as species with less labile templates. Color-producing mechanisms interact and are the main predictors of plumage ornamentation and elaboration, with little influence of selective pressures in their evolution. Dichromatism, however is influenced by social system and the loss of iridescence. Our results show the importance of considering both selection and constraints, and the different roles that they may have, in the evolution of ornamentation and dimorphism.


Meta-Analysis of the Associations of p-Cresyl Sulfate (PCS) and Indoxyl Sulfate (IS) with Cardiovascular Events and All-Cause Mortality in Patients with Chronic Renal Failure.
Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are protein-bound uremic toxins that increase in the sera of patients with chronic kidney disease (CKD), and are not effectively removed by dialysis. The purpose of this meta-analysis was to investigate the relationships of PCS and IS with cardiovascular events and all-cause mortality in patients with CKD stage 3 and above. Medline, Cochrane, and EMBASE databases were searched until January 1, 2014 with combinations of the following keywords: chronic renal failure, end-stage kidney disease, uremic toxin, uremic retention, indoxyl sulfate, p-cresyl sulfate. Inclusion criteria were: 1) Patients with stage 1 to 5 CKD; 2) Prospective study; 3) Randomized controlled trial; 4) English language publication. The associations between serum levels of PCS and IS and the risks of all-cause mortality and cardiovascular events were the primary outcome measures. Of 155 articles initially identified, 10 prospective and one cross-sectional study with a total 1,572 patients were included. Free PCS was significantly associated with all-cause mortality among patients with chronic renal failure (pooled OR = 1.16, 95% CI = 1.03 to 1.30, P = 0.013). An elevated free IS level was also significantly associated with increased risk of all-cause mortality (pooled OR = 1.10, 95% CI = 1.03 to 1.17, P = 0.003). An elevated free PCS level was significantly associated with an increased risk of cardiovascular events among patients with chronic renal failure (pooled OR = 1.28, 95% CI = 1.10 to 1.50, P = 0.002), while free IS was not significantly associated with risk of cardiovascular events (pooled OR = 1.05, 95% CI = 0.98 to 1.13, P = 0.196). Elevated levels of PCS and IS are associated with increased mortality in patients with CKD, while PCS, but not IS, is associated with an increased risk of cardiovascular events.


Radical polymerization initiated by Bergman cyclization.
The diradical generated by the Bergman cyclization of 3,4-benzocyclodec-3-ene-1,5-diyne is shown to initiate the radical polymerization of several monomers. Methacrylates are polymerized to high molecular weight by the diradical initiator much more efficiently than other monomers. The relation between the rate of polymerization and the degree of polymerization indicates that the polymer primarily propagates as a monoradical. This monoradical growth is in agreement with established theory predicting that diradical initiators can produce high polymer only through chain transfer followed by monoradical growth due to the rapid intramolecular termination of short diradical chains. In agreement with this mechanism, the polymerization rate of acrylonitrile initiated by the diradical is shown to increase by more than 20-fold upon addition of a chain transfer agent. Small molecule products consistent with intramolecular termination of diradical oligomers were isolated, and the structures of these molecules suggest how the diradical self-terminates in the absence of chain transfer.


The increasing complexity of arbovirus serology: An in-depth systematic review on cross-reactivity.
Diagnosis of arbovirus infection or exposure by antibody testing is becoming increasingly difficult due to global expansion of arboviruses, which induce antibodies that may (cross-)react in serological assays. We provide a systematic review of the current knowledge and knowledge gaps in differential arbovirus serology. The search included Medline, Embase and Web of Science databases and identified 911 publications which were reduced to 102 after exclusion of studies not providing data on possible cross-reactivity or studies that did not meet the inclusion criteria regarding confirmation of virus exposure of reference population sets. Using a scoring system to further assess quality of studies, we show that the majority of the selected papers (N = 102) provides insufficient detail to support conclusions on specificity of serological outcomes with regards to elucidating antibody cross-reactivity. Along with the lack of standardization of assays, metadata such as time of illness onset, vaccination, infection and travel history, age and specificity of serological methods were most frequently missing. Given the critical role of serology for diagnosis and surveillance of arbovirus infections, better standards for reporting, as well as the development of more (standardized) specific serological assays that allow discrimination between exposures to multiple different arboviruses, are a large global unmet need.


Prevalence of endotoxemia in healthy postparturient dairy cows and cows with abomasal volvulus or left displaced abomasum.
Left displaced abomasum (LDA) and abomasal volvulus (AV) occur most commonly in postparturient dairy cows. Our main hypothesis was that endotoxemia occurred more frequently in the peripheral blood of cows with LDA or AV than in healthy cows because increased luminal pressure in AV or LDA, or the presence of a hemorrhagic strangulating obstruction in AV, may have injured the abomasal mucosa, thereby facilitating translocation of luminal endotoxin into the circulation. Therefore, our main objective was to compare the prevalence and magnitude of endotoxemia in healthy postparturient cows with the prevalence and magnitude of endotoxemia in cows with AV and LDA. We examined 60 adult dairy cows in early lactation that were diagnosed with AV (n = 15) or LDA (n = 15) or were healthy on physical examination (control group, n = 30). Jugular venous blood was obtained from cows in all 3 groups, and right gastroepiploic venous blood was obtained during surgical correction of AV and LDA immediately after repositioning of the abomasum. Platelet-rich plasma endotoxin concentrations were measured with a chromogenic limulus amoebocyte lysate assay. Endotoxin was detected in jugular vein plasma in 50% (15/30) of control cows; however, the prevalence of endotoxemia was significantly lower (P < .05) in cows with AV (7%, 1/15) or LDA (20%, 3/15). Endotoxin was detected simultaneously in right gastroepiploic and jugular vein plasma in only 1 cow with LDA and 0 cows with AV. Contrary to our hypothesis, we conclude that endotoxemia is infrequently present in postparturient dairy cows with AV or LDA.


Racial differences in mortality in older adults: factors beyond socioeconomic status.
Little is known about the simultaneous effect of socioeconomic status (SES), psychosocial, and health-related factors on race differences in mortality in older adults. This study examined the association between race and mortality and the role of SES, health insurance, psychosocial factors, behavioral factors, and health-related factors in explaining these differences. Data consisted of 2,938 adults participating in the Health, Aging and Body Composition study. Mortality was assessed over 8 years. SES differences accounted for 60% of the racial differences in all-cause mortality; behavioral factors and self-rated health further reduced the disparity. The racial differences in coronary heart disease mortality were completely explained by SES. Health insurance and behavioral factors accounted for some, but not all, of the race differences in cancer mortality. Race-related risk factors for mortality may differ by the underlying cause of mortality.


QT variability index in patients with systemic sclerosis.
Systemic sclerosis (SSc) may affect the heart with microvascular dysfunction and lead to an early cardiac death, but the association between certain repolarization indexes and SSc heart disease remains controversial. Our goal was to evaluate a previously unstudied marker of repolarization dynamics, i.e., QT variability, in patients with SSc and to assess its prognostic implications. A total of 17 patients with SSc and 21 healthy controls were included into this prospective study. Electrocardiograms were conducted under strict standards. The QT variability index (QTVI), normalized QT variability (QTVN), and power spectral analysis of QT dynamics, considered as markers of ventricular arrhythmias in a number of other disorders, were determined using designated computer software. There was no significant difference in demographic and cardiac important clinical parameters between the groups. Also, the mean QTVI, QTVN, and power spectral analysis parameters were comparable between the patients with SSc and control subjects. At baseline, the QTVI values of 1 patient with SSc, who experienced ventricular arrhythmia prior to inclusion in the study, were considerably higher compared to other patients with SSc. None of the remaining patients with SSc or the control subjects developed arrhythmia during the follow-up of 8 years. Higher than normal QTVI may be found in the minority of patients with SSc. The prognostic significance of this finding is unknown, but it may entail an increased risk of ventricular arrhythmias. Therefore, the value of QTVI as a tool for arrhythmia risk stratification in SSc merits further research.


Photographs of Daily Activities-Youth English: validating a targeted assessment of worry and anticipated pain.
PHODA is an electronic measure that individualizes and guides treatment for individuals with chronic pain. Implicit in its design is recognition that pain-related fear is a driving force that impedes treatment progress. With this tool, patients visually rate their expectations about the harmful consequences of specific movements. This study aimed to (1) develop and validate PHODA-Youth English (PHODA-YE) and (2) evaluate the potential impact of PHODA-YE assessment on treatment outcomes. Participants were 195 youth, age 8 to 20 years, who presented to an outpatient pain clinic for evaluation (n = 99), or enrolled at the Pediatric Pain Rehabilitation Center (PPRC) intensive program (PPRC; n = 96). All patients completed the PHODA-YE along with measures of emotional functioning and disability. Patients in the PPRC completed the measure at both admission and discharge. After eliminating infrequently endorsed and poorly loading items, factor analytic procedures yielded a 4-subscale, 50-item measure with strong internal consistency (from 0.92 to 0.97 across subscales). Fear, avoidance, and functional disability were strongly associated with PHODA-YE scores, supporting construct validity. Within the PPRC sample, PHODA-YE was sensitive to changes over time in relation to functional improvements. Across the PPRC sample, patients found it helpful to complete the PHODA and target feared activities. Altogether, the PHODA-YE is a valid and concrete assessment tool that rapidly identifies specific activities and movements that elicit fearful responses from patients.


A vascular bed-specific pathway.
The endothelial nitric oxide synthase (eNOS) gene is induced by a variety of extracellular signals under both in vitro and in vivo conditions. To gain insight into the mechanisms underlying environmental regulation of eNos expression, transgenic mice were generated with the 1,600-bp 5' flanking region of the human eNos promoter coupled to the coding region of the LacZ gene. In multiple independent lines of mice, transgene expression was detected within the endothelium of the brain, heart, skeletal muscle, and aorta. beta-galactosidase activity was consistently absent in the vascular beds of the liver, kidney, and spleen. In stable transfection assays of murine endothelial progenitor cells, the 1,600-bp promoter region was selectively induced by conditioned media from cardiac myocytes, skeletal myocytes, and brain astrocytes. Cardiac myocyte-mediated induction was partly abrogated by neutralizing anti-platelet-derived growth factor (PDGF) antibodies. In addition, promoter activity was upregulated by PDGF-AB. Analysis of promoter deletions revealed that a PDGF response element lies between -744 and -1,600 relative to the start site of transcription, whereas a PDGF-independent cardiac myocyte response element is present within the first 166 bp of the 5' flanking region. Taken together, these results suggest that the eNos gene is regulated in the cardiac endothelium by both a PDGF-dependent and PDGF-independent microvascular bed-specific signaling pathway.