Predictors and consequences of multiple persistent postmastectomy pains.
Persistent postmastectomy pain is quite common and has been classified into several distinct types. Few studies, however, have investigated either the predictors or functional impact of multiple types of post mastectomy pain. In this investigation, 278 women, who were, on average, several years post mastectomy, completed questionnaires assessing pain, pain-related physical function, and psychosocial distress. We assessed three distinct categories of postmastectomy pain: phantom breast pain, scar pain, and other mastectomy-related pain. Each of the three types of postmastectomy pain was strongly related to one another (i.e., women reporting one type of pain were more likely to report the other types as well). In general, the more types of postmastectomy pain a woman reported, the greater the degree of disability and distress. Collectively, the presence of "other mastectomy-related pain" was a stronger unique predictor of disability and distress than were the other two categories of pain. Interestingly, demographic and surgical factors, including time since surgery, were not consistent predictors of pain or function. The findings suggest that the assessment of postmastectomy pain should include formal evaluation of multiple types of pain, with additional attention paid to the category of "other mastectomy-related pains," and that the number of types of pain reported by women after surgery may be important in predicting functional outcomes.


A novel system for reducing leaching from formulations of anionic herbicides: clay-liposomes.
A new approach was developed for reducing leaching of herbicides and contamination of groundwater. Liposome-clay formulations of the anionic herbicides sulfometuron and sulfosulfuron were designed for slow release by incorporating the herbicide in positively charged vesicles of didodecyldimethylammonium (DDAB), which were adsorbed on the negatively charged clay, montmorillonite. Freeze fracture electron microscopy demonstrated the existence of DDAB vesicles and aggregated structures on external clay surfaces. X-ray diffraction results for DDAB with montmorillonite imply the existence of DDAB bilayers with an oblique orientation to the basal plane within the clay interlayer space at adsorbed amounts beyond the cation exchange capacity of the clay. Adding DDAB with sulfometuron or sulfosulfuron to montmorillonite yielded 95% or 83% adsorption of the herbicide at optimal ratios. Liposome-clay formulations exhibited slow release of the herbicides in water. Analytical measurements in soil columns demonstrated 2-10-fold reduction in leaching of the herbicides from liposome-clay formulations in comparison with commercial formulations. Percents of root growth inhibition of a test plant in the upper soil depths were severalfold higher for the liposome-clay formulations than for the commercial ones. Consequently, liposome-clay formulations of anionic herbicides can solve environmental and economical problems by reducing their leaching.


Feasibility of rigid 3D image registration of high-resolution peripheral quantitative computed tomography images of healing distal radius fractures.
For accurate analysis of bone formation and resorption during fracture healing, correct registration of follow-up onto baseline image is required. A per-fragment approach could improve alignment compared to standard registration based on the whole fractured region. In this exploratory study, we tested the effect of fragment size and displacement on a per-fragment registration, and compared the results of this per-fragment registration to the results of the standard registration in two stable fractures and one unstable fracture. To test the effect of fragment size and displacement, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of three unfractured radii were divided into subvolumes. Different displacements in x-, y, or z-direction or rotations around each axis were applied, and each subvolume was registered onto the initial volume to realign it. Next, registration of follow-up onto baseline scan was performed in two stable and one unstable fracture. After coarsely aligning the follow-up onto the baseline scan, a more accurate registration was performed of the whole fracture, i.e. the standard registration, and of each fracture fragment separately, i.e. per-fragment registration. Alignment was checked using overlay images showing baseline, follow-up and overlap between these scans, and by comparing correlation coefficients between the standard and per-fragment registration. Generally, subvolumes as small as 300 mm3 that were displaced up to 0.82 mm in x- or y-, or up to 1.64 mm in z-direction could be realigned correctly. For the fragments of all fractures, correlation coefficients were higher after per-fragment registration compared to standard registration. Most improvement was found in the unstable fracture and one fragment of the unstable fracture did not align correctly. This exploratory study showed that image registration of individual subvolumes, such as fracture fragments, is feasible in both stable and unstable fractures, and leads to better alignment of these fragments compared to an approach that is based on registration using the whole fractured region. This result is promising for additional analysis of bone formation and resorption in HR-pQCT studies on fracture healing.


Supercritical fluid technology as a strategy for nifedipine solid dispersions formulation: In vitro and in vivo evaluation.
Supercritical fluid technology (SFT) is an insufficiently investigated approach for the production of solid dispersions, it is environmentally acceptable and has a high potential for application in the pharmaceutical industry. The aim of this work was to formulate and characterize nifedipine solid dispersions (SDs) produced by the SFT and compare the results with ones obtained by the classical solvent based kneading method. The following in vitro tests were conducted: assay and yield, solvent residues, solid state characterization (FTIR, DSC, XRD), flowability, hygroscopicity, solubility, dissolution and stability. Additionally, bioavailability was examined on an animal model (Wistar rats). The formulation selection for in vivo study was performed using the multilevel categoric experimental design and the health risk assessment. Solid state characterization revealed that formulation obtained by the SFT method and higher ratio of polymer (1:5) have had nifedipine in completely amorphous form. Polymer ratio and method of SDs preparation do influence the investigation characteristics. Dissolution rate was fastest in SDs prepared by the SFT and higher polymer ration (1:5). In vivo data of selected SDs prepared by the kneading (ratio 1:1) and the SFT (ratio 1:5) showed alteration in pharmacokinetic profile after i.v. and p.o. application.


Natural history of asymptomatic coronary arteriographic lesions in diabetic patients with end-stage renal disease.
Arteriosclerotic heart disease is a major cause of death in insulin-requiring juvenile diabetic patients treated for end-stage renal disease. Eleven consecutive diabetic patients without clinical evidence of coronary artery disease underwent complete cardiac evaluations, including coronary arteriography, as part of transplant recipient work-ups. Seven were women and four were men; their mean age was 32 (21 to 50 years). Angiographically, every patient had multifocal atherosclerotic coronary disease. Four of seven patients tested had positive-stress electrocardiograms. In this group of patients followed for a mean of 19.8 months, eight died. Of these deaths, six were due to coronary heart disease and another due to a stroke. In two patients who became clinically symptomatic, serial angiograms revealed progressive disease of the coronary circulation; in one case, despite normal renal allograft function and serum lipid levels. The mode of end-stage renal disease treatment, serum lipids or blood pressure control could not be linked to mortality. It is concluded that arteriosclerotic heart disease is common in diabetic patients with end-stage renal disease even when angina is absent. The natural history in this high risk population is an important consideration in the selection of patients for end-stage renal disease treatment.


Fish oil blocks azoxymethane-induced rat colon tumorigenesis by increasing cell differentiation and apoptosis rather than decreasing cell proliferation.
The purpose of this study was to determine whether the protective effect of fish oil against colon carcinogenesis is due to decreased proliferation, increased differentiation and/or increased apoptosis. Male Sprague Dawley rats (n = 260) were fed one of two oils (corn or fish) and two fibers (pectin or cellulose), plus or minus the carcinogen azoxymethane (AOM). Rats were killed at wk 18 (n = 80) or 36 (n = 180) for cytokinetic measurements. In vivo cell proliferation was measured by incorporation of bromodeoxyuridine into DNA, differentiation by binding of Dolichos biflorus agglutinin and apoptosis by immunoperoxidase detection of digoxigenin labeled genomic DNA. Fish oil resulted in a lower adenocarcinoma incidence (56.1 vs. 70.3%) compared with corn oil. There was no effect of fat or fiber on number of proliferative cells/crypt column in either the proximal or distal colon. In contrast, fish oil resulted in a greater degree of differentiation compared with corn oil in both colonic sites. In addition, fish oil resulted in a higher number of apoptotic cells/crypt column in both the proximal and distal colon as compared with corn oil. AOM treatment increased the ratio of proliferative cells/crypt column to apoptotic cells/crypt column in both the proximal and distal colon compared with saline controls. Fish oil, however, resulted in a lower ratio in both sites in the colon as compared with corn oil. These results suggest that an increase in apoptosis and differentiation, rather than a decrease in proliferation, accounts for the protective effect of fish oil against experimentally induced colon tumorigenesis.


SARS-CoV-2 Transmission Dynamics in Households With Children, Los Angeles, California.
Objectives: Studies of household transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) focused on households with children are limited. We investigated household secondary attack rate (SAR), transmission dynamics, and contributing factors in households with children. Materials and Methods: In this prospective case-ascertained study in Los Angeles County, California, all households members were enrolled if ≥1 member tested positive for SARS-CoV-2 by polymerase chain reaction (PCR). Nasopharyngeal PCRs, serology, and symptom data were obtained over multiple visits. Results: A total of 489 individuals in 105 households were enrolled from June to December 2020. The majority (77.3%) reported a household annual income of <$50,000, and most (92.9%) were of Hispanic/Latinx ethnicity. Children <18 years old accounted for 46.9% index cases, of whom 45.3% were asymptomatic. Household index cases were predominantly children during low community transmission and adults during the high community transmission period (χ2 = 7.647, p = 0.0036. The mean household SAR was 77.0% (95% CI: 69.4-84.6%). Child and adult index cases both efficiently transmitted SARS-CoV-2 within households [81.9%, (95% CI: 72.1-91.9%) vs. 72.4% (95% CI: 59.8-85.1%), p = 0.23]. Household income and pets were significantly associated with higher SAR in the multivariable analysis of household factors (p = 0.0013 and 0.004, respectively). Conclusions: The SAR in households with children in an urban setting with a large ethnic minority population is much higher than previously described. Children play important roles as index cases. SAR was disproportionately impacted by household income. Vaccination and public health efforts need special focus on children and vulnerable communities to help mitigate SARS-CoV-2 spread.


A Lewis Base Nucleofugality Parameter, NFB, and Its Application in an Analysis of MIDA-Boronate Hydrolysis Kinetics.
The kinetics of quinuclidine displacement of BH3 from a wide range of Lewis base borane adducts have been measured. Parameterization of these rates has enabled the development of a nucleofugality scale (NFB), shown to quantify and predict the leaving group ability of a range of other Lewis bases. Additivity observed across a number of series R'3-nRnX (X = P, N; R' = aryl, alkyl) has allowed the formulation of related substituent parameters (nfPB, nfAB), providing a means of calculating NFB values for a range of Lewis bases that extends far beyond those experimentally derived. The utility of the nucleofugality parameter is explored by the correlation of the substituent parameter nfPB with the hydrolyses rates of a series of alkyl and aryl MIDA boronates under neutral conditions. This has allowed the identification of MIDA boronates with heteroatoms proximal to the reacting center, showing unusual kinetic lability or stability to hydrolysis.


Protein G: a powerful tool for binding and detection of monoclonal and polyclonal antibodies.
Protein G is an immunoglobulin (IgG)-binding bacterial cell wall protein recently isolated from group G streptococci. We have investigated the avidity of protein G for various monoclonal and polyclonal Ig of the IgG class, and compared it with the binding properties of protein A, the staphylococcal Fc-binding protein. Radiolabeled Ig were mixed with Sepharose-coupled protein G or protein A, and the amounts of radioactivity bound to the matrix-coupled bacterial proteins were determined. The avidity was found to be greater for protein G than for protein A for all examined Ig. Protein G bound all tested monoclonal IgG from mouse IgG1, IgG2a, and IgG3, and rat IgG2a, IgG2b, and IgG2c. In addition, polyclonal IgG from man, cow, rabbit, goat, rat, and mouse bound to protein G, whereas chicken IgG did not. The binding property of protein G was additionally exploited in the Western blot assay, in which iodine-labeled protein G was used successfully for the detection of a rat monoclonal antibody against ovalbumin, and for the detection of rabbit and goat polyclonal whole antisera against human urinary proteins. In these experimental situations, protein G was found to be a powerful reagent for the detection of IgG, and consequently the antigen against which these antibodies are directed.


Dexmedetomidine alleviates renal tubular ferroptosis in sepsis-associated AKI by KEAP1 regulating the degradation of GPX4.
Sepsis-associated acute kidney injury (SA-AKI) has a high mortality rate and lacks effective targeted treatment. We applied lipopolysaccharides-induced injury models in human and mouse renal tubular epithelial cells, and at the same time, we selected a commonly used sedative drug, dexmedetomidine, to investigate its potential for renal protection. We found a significant increase in the expression level of HSP90, and the interaction with glutathione peroxidase 4 (GPX4) led to autophagic degradation of GPX4, triggering ferroptosis. Dexmedetomidine reduced the degradation of GPX4 by increasing the binding of KEAP1 and HSP90 in the cytoplasm. Therefore, lipid peroxidation and ferroptosis were reduced. Similarly, dexmedetomidine showed renal protective effects in C57BL/6J male mice with SA-AKI induced by cecal ligation. Our study reveals a new mechanism of renal tubular epithelial cell ferroptosis in SA-AKI treated with dexmedetomidine.


[Immediate and late outcomes of surgical treatment in patients with tumor-simulating pulmonary tuberculosis].
The specific features and outcomes of surgical treatment were analyzed in 122 newly detected patients with pulmonary tuberculomas without prior specific therapy. Postoperative complications developed in 4.1% of the patients undergone surgery, recurrent tuberculosis was observed in 1.6%. Early surgical interventions in this group of patients were found to reduce the time of treatment and working rehabilitation. A value of intraoperative rapid cytological verification of diagnosis was shown while choosing the adequate volume of lung resection in difficult diagnostic cases.


Structure of LRRK1 and mechanisms of autoinhibition and activation.
Leucine Rich Repeat Kinase 1 and 2 (LRRK1 and LRRK2) are homologs in the ROCO family of proteins in humans. Despite their shared domain architecture and involvement in intracellular trafficking, their disease associations are strikingly different: LRRK2 is involved in familial Parkinson's disease while LRRK1 is linked to bone diseases. Furthermore, Parkinson's disease-linked mutations in LRRK2 are typically autosomal dominant gain-of-function while those in LRRK1 are autosomal recessive loss-of-function. Here, to understand these differences, we solved cryo-EM structures of LRRK1 in its monomeric and dimeric forms. Both differ from the corresponding LRRK2 structures. Unlike LRRK2, which is sterically autoinhibited as a monomer, LRRK1 is sterically autoinhibited in a dimer-dependent manner. LRRK1 has an additional level of autoinhibition that prevents activation of the kinase and is absent in LRRK2. Finally, we place the structural signatures of LRRK1 and LRRK2 in the context of the evolution of the LRRK family of proteins.


Effects of hyperglycemia on the TGF-β pathway in trabecular meshwork cells.
Hyperglycemia, which can lead to apoptosis, hypertrophy, fibrosis, and induces hyperinflammation in diabetic vascular complications due to oxidative stress. In order to elucidate the potential dual roles and regulatory signal transduction of TGF-β1 and TGF-β2 in human trabecular meshwork cells (HTMCs), we established an oxidative cell model in HTMCs using 5.5, 25, 50, and 100 mM d-glucose-supplemented media and characterized the TGF-β-related oxidative stress pathway. Further analysis was conducted to investigate oxidative damage and protein alterations in the HTMC caused by the signal transduction. This was done through a series of qualitative cell function studies, such as cell viability/apoptosis analysis, intracellular reactive oxygen species (ROS) detection, analysis of calcium release concentration, immunoblot analysis to detect the related protein expression alteration, and analysis of cell fibrosis to study the effect of different severities of hyperglycemia. Also, we illustrated the role of TGF-β1/2 in oxidative stress-induced injury by shRNA-mediated knockdown or stimulation with recombinant human TGF-β1 protein (rhTGF-β1). Results from the protein expression analysis showed that p-JNK, p-p38, p-AKT, and related SMAD family members were upregulated in HTMCs under hyperglycemia. In the cell functional assays, HTMCs treated with rhTGFβ-1 (1 ng/mL) under hyperglycemic conditions showed higher proliferation rates and lower ROS and calcium levels. To summarize, mechanistic analyses in HTMCs showed that hyperglycemia-induced oxidative stress activated TGF-β1 along with its associated pathway. While at low concentrations, TGF-β1 protects cells from antioxidation, whereas at high concentrations, it accumulates in the extracellular matrix, causing further HTMC dysfunction.


The Retentive Strength of Laser-Sintered Cobalt-Chromium-Based Crowns after Pretreatment with a Desensitizing Paste Containing 8% Arginine and Calcium Carbonate.
The retention of laser-sintered cobalt-chromium (Co-Cr)-based crowns were examined after dentin pretreatment with desensitizing paste containing 8% arginine and calcium carbonate (DP-ACC). Forty lower first molars were prepared using a standardized protocol. The Co-Cr crowns were produced using selective laser melting. The teeth were either pretreated with the desensitizing paste or not pretreated. After one week, each group was cemented with glass ionomer cement (GIC) or zinc phosphate cement (ZPC). Surface areas of the teeth were measured before cementation. After aging, a universal testing machine was used to test the retentive strength of the cemented crown-tooth assemblies. The debonded surfaces of the teeth and crowns were examined at 2.7× magnification. Pretreating the dentin surfaces with the desensitizing paste before cementation with GIC or ZPC did not affect the retention of the Co-Cr crowns. The retention of the GIC group (6.04 ± 1.10 MPa) was significantly higher than that of the ZPC group (2.75 ± 1.25 MPa). The predominant failure mode for the ZPC and the nontreated GIC group was adhesive cement-dentin failure; for the treated GIC group, it was adhesive cement-crown failure. The desensitizing paste can be safely used to reduce post-cementation sensitivity without reducing the retentive strength of Co-Cr crowns cemented with GIC or ZPC.


Differential regulation of B/K protein expression in proximal and distal tubules of rat kidneys with ischemia-reperfusion injury.
Brain/kidney (B/K) protein is a novel double C2-like-domain protein that is highly expressed in rat brain and kidney, but its cellular localization and functional role in the kidney are still undetermined. We examined the cellular localization of B/K protein in the rat kidney under normal and ischemic conditions. Ischemia-reperfusion (I/R) injury was induced by clamping both renal arteries for 45 min, and animals were killed at 1 and 6 h and 1, 2, 3, 5, 7, 14, and 28 days after the reperfusion. Kidney tissues were processed for immunohistochemistry and immunoblot analyses using rabbit anti-B/K polyclonal antibodies. In control kidneys, B/K protein was expressed primarily in distal tubules including the thick ascending limb, distal convoluted and connecting tubules, and collecting duct. Notably, B/K protein was also expressed in the straight portion (S3 segment), but not in the S1 or S2, of proximal tubules, and podocytes of the glomerulus. In rat kidneys with I/R injury, expression of B/K protein was differentially regulated according to the anatomic location. In distal tubules, overall expression of B/K protein was markedly decreased. On the other hand, I/R injury significantly increased B/K protein expression in the S3 segment of the outer medulla as well as in the rat proximal tubular epithelial cell line NRK-52E in vitro. Furthermore, B/K protein was strongly expressed in many exfoliated cells in the lumen and urine. These findings suggest that B/K protein is closely associated with cell death in proximal tubules, which are vulnerable to I/R injury in the kidney.


Predictors of Rectourethral Fistula Formation After Primary Whole-Gland Cryoablation for Prostate Cancer: Results from the Cryo On-Line Database Registry.
To define the incidence and risk factors associated with rectourethral fistula (RUF) formation following primary whole-gland cryosurgery using a multicenter centralized registry. The Cryo On-Line Data (COLD) registry was queried for men undergoing primary whole-gland cryotherapy between 1990 and 2014 who developed a RUF. Patient factors and disease parameters were correlated with RUF using chi-square and the t-test. Variables with p < 0.25 were entered into a binary logistic regression with stepwise backward elimination to determine the factors associated with RUF formation. A total of 4102 men underwent primary whole-gland cryotherapy in the COLD registry at the time of analysis. Postoperative RUF was documented in 50 out of 4102 cases (1.2%). Patients with RUF had similar demographic data, prostate volume, preoperative prostate-specific antigen level, and clinical stage in comparison to those without fistula. On both univariate and multivariate analyses, postoperative urinary retention (odds ratio [OR]: 6.30; confidence interval [95% CI] 3.43-11.58, p < 0.001), preoperative Gleason score of ≥7 (OR: 1.92; 95% CI 1.08-3.43, p = 0.027), and preoperative incontinence (OR: 2.95; 95% CI 1.12-7.76, p = 0.028) were the most significant risk factors associated with RUF formation. Primary whole-gland cryotherapy for prostate cancer is associated with a historically low rate (1.2%) of postoperative RUF formation. The rate decreased further to 0.55% over the last several years, suggesting better patient selection and technical improvement. Postoperative urinary retention, Gleason score ≥7, and preoperative urinary incontinence were the key demographic, clinical, and pathologic features associated with RUF formation in this study.


[Characteristics of transcapillary fluid exchange in working skeletal muscles perfused in various ways].
Acute experiments in cats revealed by means of volumometry of extracorporeal blood flow that the exchange surface of the microcirculation bed in working skeletal muscles increased irrespective of whether they were perfused under constant pressure or in constant blood flow. Capillary hydrostatic pressure depended on the perfusion mode: it decreased in conditions of stabilized blood expenditure through muscles, and increased in constant pressure perfusion. An increase of the capillary filtration coefficient is considered from the standpoint of dilatory effect of metabolites on precapillary sphincters. Changes of pre-and postcapillary resistance take part in shifts of fluid movement in the muscle during contraction.


From Testing to Decision-Making: A Data-Driven Analytics COVID-19 Response.
In March 2020, NorthShore University Health System laboratories mobilized to develop and validate polymerase chain reaction based testing for detection of SARS-CoV-2. Using laboratory data, NorthShore University Health System created the Data Coronavirus Analytics Research Team to track activities affected by SARS-CoV-2 across the organization. Operational leaders used data insights and predictions from Data Coronavirus Analytics Research Team to redeploy critical care resources across the hospital system, and real-time data were used daily to make adjustments to staffing and supply decisions. Geographical data were used to triage patients to other hospitals in our system when COVID-19 detected pavilions were at capacity. Additionally, one of the consequences of COVID-19 was the inability for patients to receive elective care leading to extended periods of pain and uncertainty about a disease or treatment. After shutting down elective surgeries beginning in March of 2020, NorthShore University Health System set a recovery goal to achieve 80% of our historical volumes by October 1, 2020. Using the Data Coronavirus Analytics Research Team, our operational and clinical teams were able to achieve 89% of our historical volumes a month ahead of schedule, allowing rapid recovery of surgical volume and financial stability. The Data Coronavirus Analytics Research Team also was used to demonstrate that the accelerated recovery period had no negative impact with regard to iatrogenic COVID-19 infection and did not result in increased deep vein thrombosis, pulmonary embolisms, or cerebrovascular accident. These achievements demonstrate how a coordinated and transparent data-driven effort that was built upon a robust laboratory testing capability was essential to the operational response and recovery from the COVID-19 crisis.


Differences in energy and nutritional content of menu items served by popular UK chain restaurants with versus without voluntary menu labelling: A cross-sectional study.
Poor diet is a leading driver of obesity and morbidity. One possible contributor is increased consumption of foods from out of home establishments, which tend to be high in energy density and portion size. A number of out of home establishments voluntarily provide consumers with nutritional information through menu labelling. The aim of this study was to determine whether there are differences in the energy and nutritional content of menu items served by popular UK restaurants with versus without voluntary menu labelling. We identified the 100 most popular UK restaurant chains by sales and searched their websites for energy and nutritional information on items served in March-April 2018. We established whether or not restaurants provided voluntary menu labelling by telephoning head offices, visiting outlets and sourcing up-to-date copies of menus. We used linear regression to compare the energy content of menu items served by restaurants with versus without menu labelling, adjusting for clustering at the restaurant level. Of 100 restaurants, 42 provided some form of energy and nutritional information online. Of these, 13 (31%) voluntarily provided menu labelling. A total of 10,782 menu items were identified, of which total energy and nutritional information was available for 9605 (89%). Items from restaurants with menu labelling had 45% less fat (beta coefficient 0.55; 95% CI 0.32 to 0.96) and 60% less salt (beta coefficient 0.40; 95% CI 0.18 to 0.92). The data were cross-sectional, so the direction of causation could not be determined. Menu labelling is associated with serving items with less fat and salt in popular UK chain restaurants. Mandatory menu labelling may encourage reformulation of items served by restaurants. This could lead to public health benefits.


Long-term outcomes of Fine Needle Diathermy for established corneal neovascularisation.
Corneal neovascularisation (CoNV) can lead to significant ocular comorbidity with reduction in vision and cosmesis. A number of techniques have been described to reduce CoNV, but these can be expensive. Our study aimed to determine the safety, efficacy and long-term outcomes of fine needle diathermy (FND) for CoNV. A 5-year retrospective study identified all cases of FND. Indications, intraoperative complications, and postoperative visual acuity, after treatment and retreatments, were documented, along with the procedure time. Evidence of regression and number of retreatments were identified. 56 eyes from 52 patients underwent FND for CoNV. The main indications included herpes simplex keratitis (HSK) (53%, n=25) and microbial keratitis/peripheral ulcerative keratitis (13%, n=6). Pretreatment acuity was significantly correlated with extent of CoNV (p=0.044). One complication was noted during the procedure-an intrastromal and subconjunctival haemorrhage (rate 2%). 68.1% of patients demonstrated regression at first follow-up (mean 6.9 weeks), and 89.3% (n=42) showed regression with two or less treatments. Mean post-FND acuity was 0.72 (range -0.2-3.0) vs 0.82 (-0.2-3.0) preprocedure (p=0.08). VA improved in the HSK subgroup (p=0.012). Mean follow-up was 18.9 months (range 1-56 months). In the largest case series reported, FND appears to be a safe and effective technique in the long term to induce regression of CoNV, with significant improvement in the VA of patients with HSK.


Identification of a cytoplasmic motif in the erythropoietin receptor required for receptor internalization.
Erythropoietin (EPO) promotes the viability, proliferation and differentiation of mammalian erythroid progenitor cells via its specific cell surface receptor. The EPO receptor (EPO-R) is a member of the cytokine receptor superfamily and is comprised of one identified subunit which homodimerizes upon ligand binding. To study the role of the intracellular domain of the EPO-R in the endocytosis of EPO, we compared the rate and extent of 125I-EPO endocytosis by wild type (wt) EPO-R and five cytoplasmically truncated EPO-Rs: 1-251 EPO-R, 1-257 EPO-R, 1-267 EPO-R, 1-276 EPO-R and 1-306 EPO-R which contain 4, 10, 20, 29 or 59 amino acids of the cytoplasmic domain, respectively. We also studied an EPO-R mutant (PB) which lacks amino acid residues 281-300 of the cytoplasmic domain. The experiments were conducted in COS 7 cells transfected with the EPO-R cDNAs and in Ba/F3 cells stably expressing the wt EPO-R, 1-251 or 1-257 EPO-R. Cells expressing wt EPO-R, PB EPO-R (delta281-300), 1-276 EPO-R or 1-306 EPO-R internalized approximately 50% of 125I-EPO bound to the cell surface, while cells expressing 1-251, 1-257 or 1-267 EPO-R internalized only 25% of the bound 125I-EPO. The steady-state expression levels of these latter receptors on the cell surface were typically 2-5-fold higher than wt EPO-R. Our data indicate that amino acid residues 267-276 (FEGLFTTHK) of the EPO-R cytoplasmic domain may have a role in receptor internalization. Metabolic labeling experiments suggest that in transiently transfected COS 7 cells most of the wt EPO-R and 1-257 EPO-Rs do not exit the ER and may be degraded there. The half-life of both receptors was essentially similar and was in the range of 1 h. In Ba/F3 cells the mature Golgi processed 1-257 EPO-R was more stable than the corresponding form of the wt EPO-R, possibly contributing to its higher cell surface expression.


Oral Lesions in Kidney Transplant Recipients
Permanent immunosuppression is necessary to prevent rejection after kidney transplantation. However, it may predispose patients to different conditions and diseases including oral lesions. The most common benign oral lesions in kidney transplant recipients are gingival hyperplasia, oral candidiasis, hairy leukoplakia and saburral tongue. Oral form of Kaposi sarcoma, although rarely, can also be seen in kidney transplant patients. In this review, we present the incidence, etiology, clinical findings, diagnosis and treatment options for these lesions. For kidney transplant recipients,it is important to maintain good oral hygiene and care, as well as regular professional control by the dentist. This approach can reduce the number and severity of oral lesions.


Renaturation of DNA by a Saccharomyces cerevisiae protein that catalyzes homologous pairing and strand exchange.
A protein from mitotic Saccharomyces cerevisiae cells that catalyzes homologous pairing and strand exchange was analyzed for the ability to catalyze other related reactions. The protein was capable of renaturing complementary single-stranded DNA as evidenced by S1 nuclease assays and analysis of the reaction products by agarose gel electrophoresis and electron microscopy. Incubation of the yeast protein with complementary single-stranded DNA resulted in the rapid formation of large aggregates which did not enter agarose gels. These aggregates contained many branched structures consisting of both single-stranded and double-stranded DNA. These reactions required stoichiometric amounts of protein but showed no ATP requirement. The protein formed stable complexes with both single-stranded and double-stranded DNA, showing a higher affinity for single-stranded DNA. The binding to single-stranded DNA resulted in the formation of large protein:DNA aggregates. These aggregates were also formed in strand-exchange reactions and contained both substrate and product DNAs. These results demonstrate that the S. cerevisiae strand-exchange protein shares additional properties with the Escherichia coli recA protein which, by analogy, gives further indication that it might be implicated in homologous recombination.


The DISC Predictive Scales (DPS): efficiently screening for diagnoses.
To derive and test a series of brief diagnosis-specific scales to identify subjects who are at high probability of meeting diagnostic criteria and those who may safely be spared more extensive diagnostic inquiry. Secondary data analysis of a large epidemiological data set (n = 1,286) produced a series of gate and contingent items for each diagnosis. Findings were replicated in a second retrospective analysis from a residential care sample (n = 884). The DISC Predictive Scales (DPS) were then used prospectively as a self-report questionnaire in two studies, in which parents (n = 128) and/or adolescents (n = 208) had subsequent diagnostic interviewing with the Diagnostic Interview Schedule for Children or the Schedule for Affective Disorders and Schizophrenia for School-Age Children. All analyses showed that gate item selection was valid and that any missed cases were due solely to inconsistent reports on the same questions. Screening performance of the full scales was shown to be good, and substantial reductions in scale length were not associated with significant changes in discriminatory power. The DPS can accurately determine subjects who can safely be spared further diagnostic inquiry in any diagnostic area. This has the potential to speed up structured diagnostic interviewing considerably. The full DPS can be used to screen accurately for cases of specific DSM-III-R disorders.


Treatment with basic fibroblast growth factor-incorporated gelatin hydrogel does not exacerbate mechanical allodynia after spinal cord contusion injury in rats.
Besides stimulating angiogenesis or cell survival, basic fibroblast growth factor (bFGF) has the potential for protecting neurons in the injured spinal cord. To investigate the effects of a sustained-release system of bFGF from gelatin hydrogel (GH) in a rat spinal cord contusion model. Adult female Sprague-Dawley rats were subjected to a spinal cord contusion injury at the T10 vertebral level using an IH impactor (200 kdyn). One week after contusion, GH containing bFGF (20 µg) was injected into the lesion epicenter (bFGF - GH group). The GH-only group was designated as the control. Locomotor recovery was assessed over 9 weeks by Basso, Beattie, Bresnahan rating scale, along with inclined plane and Rota-rod testing. Sensory abnormalities in the hind paws of all the rats were evaluated at 5, 7, and 9 weeks. There were no significant differences in any of the motor assessments at any time point between the bFGF - GH group and the control GH group. The control GH group showed significantly more mechanical allodynia than did the group prior to injury. In contrast, the bFGF - GH group showed no statistically significant changes of mechanical withdrawal thresholds compared with pre-injury. Our findings suggest that bFGF-incorporated GH could have therapeutic potential for alleviating mechanical allodynia following spinal cord injury.


Quality assessment of Red Yeast Rice by fingerprint and fingerprint-effect relationship combined with antioxidant activity.
Red Yeast Rice (RYR) is an important functional food ingredient that plays a critical role in promoting dietary guidance and maintaining health. To ensure its quality, four key compounds were quantified, and both HPLC fingerprint and electrochemical fingerprint (ECFP) were applied to assess quality. Additionally, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•) scavenging test and ECFP were applied to assay the total antioxidant activity, with ascorbic acid as the positive control. The results showed that the holistic quality of samples was divided into 4 grades based on HPLC fingerprint analysis by the comprehensive linear quantitative fingerprint method. Additionally, the area of the total peak (Atp) in ECFP was found to be linearly correlated with the antioxidant activity (R > 0.99). A further fingerprint-efficacy relationship analysis determined the significant contributions to the antioxidant activity of peaks 20-Daidzein, 21-Glycitein, and 24-Genistein. Overall, this study suggested a comprehensive and reliable approach to the quality assessment of RYR.


High-optical-quality blends of anionic polymethine salts and polycarbonate with enhanced third-order non-linearities for silicon-organic hybrid devices.
A series of anionic polymethine dyes with different aromatic counterions are prepared to improve their compatibility as guests in an amorphous polycarbonate host. When they are used as the cladding material for silicon hybrid slot waveguides, four-wave mixing wavelength conversion and two-photon absorption-based optical-power modulation are observed. Such guest-host materials may be attractive candidates for all-optical signal-processing applications.


Effect of Sunlight Radiation on the Growth and Chemical Constituents of Salvia plebeia R.Br.
This study investigated the chemical composition changes of Salvia plebeia R.Br. cultivated under different light sources, including florescent light and sunlight. The plants were exposed to fluorescent light for four months and sunlight and then examined for the next 5-7 months. Plants were harvested monthly during the seven months, and we examined whether the difference in light source affected the phenolic and flavonoid contents and antioxidant activity. A simple and reliable HPLC method using a PAH C18 column was applied for the quantitative analysis of two triterpenoids from the S. plebeia groups. Oleanolic acid (OA) and ursolic acid (UA) showed good linearity (R² > 0.9999) within the test ranges (0.005-0.05 mg/mL), and the average percentage recoveries of the OA and UA were 95.1-104.8% and 97.2-107.1%, respectively. The intra- and inter-day relative standard deviations (RSDs) were less than 2.0%. After exposure to sunlight, the phenolic contents, including rosmarinic acid, showed a reduced tendency, whereas the flavonoid contents, including homoplantaginin and luteolin 7-glucoside, were increased. The content of the triterpenoids also showed an increased tendency under sunlight irradiation, but the variance was not larger than those of the phenolic and flavonoid contents. Among experimental groups, the group harvested at six months, having been exposed to sunlight for two months, showed the most potent antioxidant activity. Therefore, these results showed that the chemical composition and antioxidant activities of S. plebeia R.Br. was affected from environmental culture conditions, such as light source. Our studies will be useful for the development of functional materials using S. plebeia R.Br.


Development of mass cytometry methods for bacterial discrimination.
Fluorescent flow cytometry has become the method of choice for interrogation of bacterial populations at the single-cell level. However, limitations of this technique include issues of dynamic range, spectral overlap, photobleaching, and overall low signal intensity due to the small size of bacteria. The recent development of mass cytometry allows single-cell analysis with the resolution of inductively coupled plasma mass spectrometry, facilitating multiparametric analysis. Using a combination of a metal-based membrane stain and lectins conjugated to lanthanide-chelating polymers, we demonstrate that individual Escherichia coli cells can be differentiated based on their cell surface polysaccharides using mass cytometry. The model E. coli system involves evaluation of three different surface polysaccharides using element-tagged concanavalin A and wheat germ agglutinin lectins. Finally, this technique enabled experiments designed to follow the export of O-antigen substituted lipopolysaccharide in a conditional mutant. These studies revealed that the culture responds as a uniform population and that lipopolysaccharide export is approximately 10 times faster than the logarithmic bacterial doubling time.


Characterization of the anti-inflammatory Lactobacillus reuteri BM36301 and its probiotic benefits on aged mice.
The gut microbiota is playing more important roles in host immune regulation than was initially expected. Since many benefits of microbes are highly strain-specific and their mechanistic details remain largely elusive, further identification of new probiotic bacteria with immunoregulatory potentials is of great interest. We have screened our collection of probiotic lactic acid bacteria (LAB) for their efficacy in modulating host immune response. Some LAB are characterized by suppression of TNF-α induction when LAB culture supernatants are added to THP-1 cells, demonstrating the LAB's anti-inflammatory potential. These suppressive materials were not inactivated by heat or trypsin. On the other hand, treatment of THP-1 directly with live bacterial cells identified a group of pro-inflammatory LAB, which stimulated significant production of TNF-α. Among those, we chose the Lactobacillus reuteri BM36301 as an anti-inflammatory strain and the L. reuteri BM36304 as a pro-inflammatory strain, and further studied their in vivo effects. We supplied C57BL/6 mice with these bacteria in drinking water while feeding them a standard diet for 20 weeks. Interestingly, these L. reuteri strains evoked different consequences depending on the gender of the mice. That is, males treated with anti-inflammatory BM36301 experienced less weight gain and higher testosterone level; females treated with BM36301 maintained lower serum TNF-α as well as healthy skin with active folliculogenesis and hair growth. Furthermore, while males treated with pro-inflammatory BM36304 developed higher serum levels of TNF-α and insulin, in contrast females did not experience such effects from this bacteria strain. The L. reuteri BM36301 was selected as an anti-inflammatory strain in vitro. It helped mice maintain healthy conditions as they aged. These findings propose the L. reuteri BM36301 as a potential probiotic strain to improve various aspects of aging issues.


Breast cancer cell CD200 expression regulates immune response to EMT6 tumor cells in mice.
CD200 has been characterized as an important immunoregulatory molecule, increased expression of which can lead to decreased transplant rejection, autoimmunity, and allergic disease. Elevated CD200 expression has been reported to be associated with poor prognosis in a number of human malignancies. We have found that cells of the transplantable EMT6 mouse breast cancer line growing in vitro express low levels of CD200, but levels increase markedly during growth in immunocompetent mice. Similar increased in vivo expression does not occur in NOD-SCID.IL-2(gammar-/-) mice or mice with generalized over-expression of a CD200 transgene. In both mice, tumor growth occurs faster. Altered CD200 expression in control versus transgenic mice is accompanied by reproducible changes in tumor-infiltrating host cells, and altered cell composition in lymph nodes draining the tumor (DLN). Neutralization of expressed CD200 by anti-CD200mAbs leads to decreased tumor growth in immunocompetent mice, with improved detection of cytotoxic anti-tumor immune cells in DLN. Finally, we report that tumor growth in vivo can be monitored by levels of soluble CD200 (sCD200) in serum of tumor-bearing animals.


The role of cytomegalovirus serostatus on outcome of hematopoietic stem cell transplantation.
The aim of this review is to discuss recent developments regarding the impact of cytomegalovirus (CMV) serological status of hematopoietic stem cell transplantation recipients and their donors on transplant outcome. CMV seropositivity of the recipient is still a negative factor for transplant outcome. The use of a CMV seropositive donor has a negative impact on survival in patients receiving unrelated but not human leukocyte antigen-identical sibling grafts. In CMV seropositive patients, the donor serological status influences outcome in patients receiving unrelated donor grafts after myeloablative but not reduced-intensity conditioning. Early CMV replication reduces the risk for leukemia relapse but does not improve survival. The use of leukocyte depleted blood products is sufficient to prevent primary CMV infection. Despite major advances in management of CMV infections, CMV serologic status remains an important risk factor for transplant-related complications and mortality after allogeneic hematopoietic stem cell transplantation.


Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study.
Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, β-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.


N-acyl migration in ceramides.
Upon exposure of truncated ceramides, such as N-acetyl-sphingenine, and long-chain ceramides to moderate acidic conditions, three derivatives are formed. Two of them turned out to be O-acylated sphingenine, 1-O- and 3-O-acyl-sphingenine, and the other was identified as sphingenine. Truncated dihydroceramides (e.g., N-acetyl- and N-hexanoyl-sphinganine) also show this type of rearrangement, which is therefore not related to the presence of the allylic hydroxy group or to the length of the N-acyl chain. Of particular concern is the fact that the O-acylated compounds, which can be considered sphingoid base analogs, can be formed in chloroform or chloroform-methanol mixtures upon storage. For long-term storage, methanol or dichloromethane is the preferred solvent. A procedure to document the presence/formation of such O-acylated sphingoid bases in ceramide solutions in the picomole range, based on reversed-phase chromatography after derivatization of their amino group with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, is presented.


Characterizing Spatial and Energetic Distributions of Trap States Toward Highly Efficient Perovskite Photovoltaics.
Due to their greater opt electric performance, perovskite photovoltaics (PVs) present huge potential to be commercialized. Perovskite PV's high theoretical efficiency expands the available development area. The passivation of defects in perovskite films is crucial for approaching the theoretical limit. In addition to creating efficient passivation techniques, it is essential to direct the passivation approach by getting precise and real-time information on the trap states through measurements. Therefore, it is necessary to establish quantitative characterization methods for the trap states in energy and 3D spaces. The authors cover the characterization of the spatial and energy distributions of trap states in this article with an eye toward high-efficiency perovskite photovoltaics. After going over the strategies that have been created for characterizing and evaluating trap states, the authors will concentrate on how to direct the creative development of characterization techniques for trap states assessment and highlight the opportunities and challenges of future development. The 3D space and energy distribution mappings of trap states are anticipated to be realized. The review will give key guiding importance for further approaching the theoretical efficiency of perovskite photovoltaics, offering some future research direction and technological assistance for the development of appropriate targeted passivation technologies.


Healing of Preterm Ruptured Fetal Membranes.
Preterm premature rupture of membrane (pPROM) is associated with 30-40% of preterm births. Infection is considered a leading cause of pPROM due to increased levels of proinflammatory cytokines in amniotic fluid. Only 30%, however, are positive for microbial organisms by amniotic fluid culture. Interestingly, in some pregnancies complicated by preterm premature rupture of membranes (pPROM), membranes heal spontaneously and pregnancy continues until term. Here, we investigated mechanisms of amnion healing. Using a preclinical mouse model, we found that small ruptures of the fetal membrane closed within 72 h whereas healing of large ruptures was only 40%. Small rupture induced transient upregulation of cytokines whereas large ruptures elicited sustained upregulation of proinflammatory cytokines in the fetal membranes. Fetal macrophages from amniotic fluid were recruited to the wounded amnion where macrophage adhesion molecules were highly expressed. Recruited macrophages released limited and well-localized amounts of IL-1β and TNF which facilitated epithelial-mesenchymal transition (EMT) and epithelial cell migration. Arg1 + macrophages dominated within 24 h. Migration and healing of the amnion mesenchymal compartment, however, remained compromised. These findings provide novel insights regarding unique healing mechanisms of amnion.


CD62L(neg)CD38⁺ expression on circulating CD4⁺ T cells identifies mucosally differentiated cells in protein fed mice and in human celiac disease patients and controls.
The aim of this study was to identify new markers of mucosal T cells to monitor ongoing intestinal immune responses in peripheral blood. Expression of cell-surface markers was studied in mice on ovalbumin (OVA)-specific T cells in the gut-draining mesenteric lymph nodes (MLN) after OVA feed. The effect of the local mucosal mediators retinoic acid (RA) and transforming growth factor-β (TGF-β) on the induction of a mucosal phenotype was determined in in vitro T-cell differentiation assays with murine and human T cells. Tetramer stainings were performed to study gluten-specific T cells in the circulation of patients with celiac disease, a chronic small-intestinal inflammation. In mice, proliferating T cells in MLN were CD62L(neg)CD38(+) during both tolerance induction and abrogation of intestinal homeostasis. This mucosal CD62L(neg)CD38(+) T-cell phenotype was efficiently induced by RA and TGF-β in mice, whereas for human CD4(+) T cells RA alone was sufficient. The CD4(+)CD62L(neg)CD38(+) T-cell phenotype could be used to identify T cells with mucosal origin in human peripheral blood, as expression of the gut-homing chemokine receptor CCR9 and β(7) integrin were highly enriched in this subset whereas expression of cutaneous leukocyte-associated antigen was almost absent. Tetramer staining revealed that gluten-specific T cells appearing in blood of treated celiac disease patients after oral gluten challenge were predominantly CD4(+)CD62L(neg)CD38(+). The total percentage of circulating CD62L(neg)CD38(+) of CD4 T cells was not an indicator of intestinal inflammation as percentages did not differ between pediatric celiac disease patients, inflammatory bowel disease patients and respective controls. However, the phenotypic selection of mucosal T cells allowed cytokine profiling as upon restimulation of CD62L(neg)CD38(+) cells interleukin-10 (IL-10) and interferon-γ (IFN-γ) transcripts were readily detected in circulating mucosal T cells. By selecting for CD62L(neg)CD38(+) expression that comprises 5-10% of the cells within the total CD4(+) T-cell pool we are able to highly enrich for effector T cells with specificity for mucosal antigens. This is of pivotal importance for functional studies as this purification enhances the sensitivity of cytokine detection and cellular activation.


Increased flow and shear stress enhance in vivo transforming growth factor-beta1 after experimental arterial injury.
We have previously demonstrated that high-flow (HF) conditions inhibit experimental intimal hyperplasia. We hypothesized that such flow conditions may alter transforming growth factor-beta1 (TGF-beta1) after mural injury. The right common carotid artery (CCA) was balloon-injured in 54 New Zealand White male rabbits. Flow was thereafter preserved (normal flow [NF]), reduced by partial outflow occlusion (low flow [LF]), or increased by ligation of the left CCA (HF). Four sham-operated animals served as uninjured controls. Mean blood flow and pressure in the right CCA were measured before and after flow modulation and before euthanasia (3, 7, and 14 days). TGF-beta1 mRNA and protein levels in the right CCA were determined by Northern and ELISA analyses at each time point. At 7 and 14 days, intimal hyperplasia was quantified, and the transmural localization of TGF-beta1 was determined by immunohistochemical analysis. Mean flow was reduced from 22+/-1 to 10+/-3 mL/min in the LF group and increased to 34+/-2 mL/min in the HF group (P<0.001). Blood pressure was not different among the flow groups for all time points. Wall shear stress was markedly decreased in the LF group to 14+/-4 dyne/cm(2) and increased in the HF group to 63+/-6 dyne/cm(2) at 7 days compared with values in uninjured controls (39+/-2 dyne/cm(2), P<0.001) and the NF group (44+/-7 dyne/cm(2), P<0.001). At 14 days, wall shear stress was similar among the flow groups. The intima-to-media ratio was 5- and 2-fold greater in the LF group than in the HF and NF groups at 14 days. mRNA levels for TGF-beta1 and its active ligand were increased in the HF group by at least 2- and 3-fold, respectively, at 3 and 7 days compared with levels in uninjured controls and the LF group (P<0.05) but were not different among the flow groups at 14 days. TGF-beta1 preferentially localized in the abluminal vascular smooth muscle cells of the HF arterial segments. Flow- and shear-mediated release of TGF-beta1 may therefore play a role in abrogating the proliferative and migratory response of vascular smooth muscle cells in the early stages after mural injury.


A center-based approach to a transplant employment program.
The return to work after transplantation has been actively discussed in the transplant community for years. However, despite the desire for transplant practitioners to have recipients return to being healthy, contributing members of society as well as return to work, practitioners often passively support the sick role. We discovered that patients who are returning to work after transplantation may have been out of the work force for several years, and require assistance that we as healthcare providers were unable or untrained to provide. An employment specialist was added to the transplant staff and became a vital part of our attempts to create a proactive employment atmosphere and enhance our patients' quality of life. Adding an advocate for employment in our center has also facilitated the shift in our thinking and approach to care from the sick role to one of rehabilitation and from reactive to proactive. This change in attitude has assisted in empowering our recipients to feel as if they can truly resume a normal life.


Stimulation of uric acid release from the perfused rat liver by platelet activating factor or potassium.
The stimulation of hepatic glycogenolysis by platelet activating factor (AGEPC) or increased perfusate potassium concentration ([K+]o), but not phenylephrine, causes a transient increase in uric acid release into the effluent perfusate of perfused rat livers. Uric acid was identified in chromatograms of perfusate samples using reversed-phase h.p.l.c., which show a peak which co-elutes with authentic uric acid, and by the fact that the A293 of perfusate samples decreases in the presence of uricase. Uric acid release is dose-dependent with respect to both AGEPC and [K+]o, and is blocked completely by prior exposure of the perfused liver to 5 mM-allopurinol, a specific inhibitor of xanthine oxidase (XOD). Allopurinol inhibits the increase in portal vein pressure induced by AGEPC, increased [K+]o or phenylephrine; the inhibitory effect increases with increasing concentrations of the agents. Also, allopurinol inhibits the second phase of O2 uptake and glucose release characteristic of concentrations of AGEPC or increased [K+]o equal to or greater than their reported half-maximal concentration for glucose release. The ratio of xanthine dehydrogenase (XDH) to XOD activity in extracts of freeze-clamped perfused livers is not affected by treatment of the livers with AGEPC or increased [K+]o. The results suggest that uric acid production may be an indicator of ischaemia within localized hepatic sinusoids, and that allopurinol partially protects the hepatocyte from the effects of AGEPC or increased [K+]o by inhibiting XOD-dependent superoxide production. We propose that the second phase of the glycogenolytic response to these agents results from ischaemia and subsequent reperfusion. Activation of XOD in vivo and hence O2-derived free radical production may be involved in the response of the liver to vasoactive agonists under a variety of pathophysiological conditions.


Complicated urethral rupture and scrotal urethrostomy in a Bongo antelope (Tragelaphus eurycerus isaaci).
A 4-yr-old, 300-kg male Bongo antelope presented a fluctuant swelling on the ventral abdomen surrounding the penis, which was confirmed later as compatible with urethral rupture. Initial treatment included broad-spectrum antibiotic and radical surgical debridement. Total prepuce and partial penile amputation with orchidectomy was performed and normal micturition was restored. At a later stage, when the extent of the lesion was controlled, a permanent scrotal urethrostomy was performed. Complete healing by second intention was achieved 2 mo after the last surgery. Although the outcome was very good, considering the extent and severity of the tissue damage, prompt permanent urethrostomy when urethral rupture was first suspected would have prevented deterioration of the condition and prevented the need for extensive surgery.


Craniectomy: an aggressive treatment approach in severe encephalitis.
Focal encephalitis may be associated with brain edema, which is often fatal. The control of intracranial pressure (ICP) is therefore crucial for further therapeutic strategies in space-occupying edema following encephalitis. However, aggressive treatment strategies such as hemicraniectomy have not been described in a larger series of patients. We describe the clinical course and outcome in six patients who developed severe brain edema associated with acute encephalitis. All received maximum medical treatment for elevated ICP, but with signs of brainstem compression emerging, hemicraniectomy was performed to control ICP. All patients had a very severe encephalitic syndrome and were treated over the course of weeks in the neurocritical care unit (NCCU). However, all patients recovered almost completely and showed only mild or no neurologic deficit when reexamined after 4 months to 3 years. Hemicraniectomy should be considered in patients with severe brain edema following encephalitis as a potentially lifesaving therapeutic measure. Moreover, the initial neurologic deficit seems to have no impact on the long-term clinical outcome.


SARS-CoV-2 Infection Rates Following Use of Regular Compared With Defective Respirators When Caring for COVID-19 Patients: A Retrospective Follow-up Study.
There is strong observational evidence that respirators are highly effective in protecting the users from being infected with Middle East respiratory syndrome and severe acute respiratory syndrome coronavirus (SARS-CoV), but the evidence for SARS-CoV-2 during daily work is limited. This study utilized a subset of healthcare workers' temporary use of a new brand respirator with frequent defects when caring for coronavirus disease 2019 (COVID-19) patients to assess the protective effect of regular respirators against SARS-CoV-2 infection. We retrospectively followed 463 participants wearing a regular respirator and 168 wearing the new brand respirator day-by-day when caring for COVID-19 patients until testing polymerase chain reaction positive for SARS-CoV-2 between 27th December 2020 and 14th January 2021. We observed seven and eight incident SARS-CoV-2-infected cases. This corresponded with daily infection rates of 0.2 and 0.5%, an incidence rate ratio of 0.4 [95% confidence interval (CI) 0.1; 1.0], and an incidence rate difference of 0.3% (95% CI -0.1; 0.8) when comparing a regular with the new brand respirator. We regard the new brand respirator a sham intervention, and this study thus provides further evidence for the protective effect of respirators when exposed to SARS-CoV-2 virus.


A coherent feed-forward loop drives vascular regeneration in damaged aerial organs of plants growing in a normal developmental context.
Aerial organs of plants, being highly prone to local injuries, require tissue restoration to ensure their survival. However, knowledge of the underlying mechanism is sparse. In this study, we mimicked natural injuries in growing leaves and stems to study the reunion between mechanically disconnected tissues. We show that PLETHORA (PLT) and AINTEGUMENTA (ANT) genes, which encode stem cell-promoting factors, are activated and contribute to vascular regeneration in response to these injuries. PLT proteins bind to and activate the CUC2 promoter. PLT proteins and CUC2 regulate the transcription of the local auxin biosynthesis gene YUC4 in a coherent feed-forward loop, and this process is necessary to drive vascular regeneration. In the absence of this PLT-mediated regeneration response, leaf ground tissue cells can neither acquire the early vascular identity marker ATHB8, nor properly polarise auxin transporters to specify new venation paths. The PLT-CUC2 module is required for vascular regeneration, but is dispensable for midvein formation in leaves. We reveal the mechanisms of vascular regeneration in plants and distinguish between the wound-repair ability of the tissue and its formation during normal development.


Estimation of genetically effective breeding numbers using a rejection algorithm approach.
Polygynous mating results in nonrandom sampling of the adult male gamete pool in each generation, thereby increasing the rate of genetic drift. In principle, genetic paternity analysis can be used to infer the effective number of breeding males (Nebm). However, this requires genetic data from an exhaustive sample of candidate males. Here we describe a new approach to estimate Nebm using a rejection algorithm in association with three statistics: Euclidean distance between the frequency distributions of maternally and paternally inherited alleles, average number of paternally inherited alleles and average gene diversity of paternally inherited alleles. We quantify the relationship between these statistics and Nebm using an individual-based simulation model in which the male mating system varied continuously between random mating and extreme polygyny. We evaluate this method using genetic data from a natural population of highly polygynous fruit bats (Cynopterous sphinx). Using data in the form of mother-offspring genotypes, we demonstrate that estimates of Nebm are very similar to independent estimates based on a direct paternity analysis that included data on candidate males. Our method also permits an evaluation of uncertainty in estimates of Nebm and thus facilitates inferences about the mating system from genetic data. Finally, we investigate the sensitivity of our method to sample size, model assumptions, adult population size and the mating system. These analyses demonstrate that the rejection algorithm provides accurate estimates of Nebm across a broad range of demographic scenarios, except when the true Nebm is high.


A virus-like agent associated with neurofibromatosis in damselfish.
Damselfish neurofibromatosis (DNF) is a transmissible disease involving neurofibromas and chromatophoromas affecting bicolor damselfish Stegastes partitus on Florida reefs. Analysis of genomic DNA by Southern blotting techniques demonstrated the presence of a group of extrachromosomal DNAs in tumors from fish affected with DNF but not in healthy individuals. Cell lines obtained from tumors contained identical DNAs and were shown to be tumorigenic in vivo, while lines established from healthy fish did not contain such DNA and were not tumorigenic. These DNA patterns were also observed in experimentally induced tumors. A DNase resistant component of this DNA was isolated from both tumor cells and conditioned media of tumor cell lines suggesting that these sequences were encapsulated in viral particles. These data support the hypothesis that one or more of these extrachromosomal DNA forms is the genome of an unusual virus and that this virus is the etiologic agent of DNF. We have tentatively termed this agent the damselfish virus-like agent (DVLA).


Acute tobacco smoke-induced airways inflammation in spontaneously hypertensive rats.
Common laboratory rats and mice fail to develop persistent, progressive pulmonary inflammation found in chronic obstructive pulmonary disease as a result of tobacco smoke exposure. We hypothesized that spontaneously hypertensive rats would be more susceptible than normal Wistar Kyoto rats to acute tobacco smoke-induced pulmonary inflammation due to impaired apoptosis. Spontaneously hypertensive rats display systemic oxidative stress, inflammation, hypercoagulation, and immunosupression, similar to humans with chronic obstructive pulmonary disease. Male spontaneously hypertensive rats and Wistar Kyoto rats were exposed whole-body to tobacco smoke (total particulate concentration 75-85 mg/m(3)) or filtered air for 6 h/day for 2 or 15 days (3 days/wk). Tobacco smoke caused an increase in bronchoalveolar lavage fluid neutrophils at both time points in each strain. Significantly more neutrophils were noted in spontaneously hypertensive rats at 15 days compared to Wistar Kyoto rats. There was a trend of increase for macrophages in spontaneously hypertensive rats at both time points (significant at 2 days). TUNEL assay detected apoptotic cells in bronchoalveolar lavage fluid and lung tissue sections. The number of apoptotic neutrophils in airway walls and bronchoalveolar lavage fluid increased at 2 days in both strains, but at 15 days the effect was much lower in spontaneously hypertensive rats than in Wistar Kyoto rats. Tobacco smoke induces a greater inflammatory response associated with lower apoptotic neutrophils in the lungs of spontaneously hypertensive rats compared to Wistar Kyoto rats. The spontaneously hypertensive rat may be a more relevant animal model of acute tobacco smoke-induced airway inflammation than other laboratory rats.


Higher Concentrations of Bacterial Enveloped Virus Phi6 Can Protect the Virus from Environmental Decay.
Phage Phi6 is an enveloped virus considered a possible nonpathogenic surrogate for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viral pathogens in transmission studies. Larger input amounts of bacteriophage Phi6 are shown to delay and protect the phage from environmental decay, both when the phages are dried in plastic tubes and when they are stored in saline solution at 4°C. In contrast, when bacteriophage Phi6 is placed in LB (Luria-Bertani) growth medium (instead of saline) prior to placement on the plastic surface, the influence of the starting concentration on viral recovery is negligible. Protection is reflected in the phage half-lives at higher concentrations being longer than the half-lives at lower concentrations. Because experiments supporting the possibility of fomite transmission of SARS-CoV-2 and other viruses rely upon the survival of infectious virus following inoculation onto various surfaces, large initial amounts of input virus on a surface may generate artificially inflated survival times compared to realistic lower levels of virus that a subject would normally encounter. This is not only because there are extra half-lives to go through at higher concentrations but also because the half-lives themselves are extended at higher virus concentrations. It is important to design surface drying experiments for pathogens with realistic levels of input virus and to consider the role of the carrier and matrix if the results are to be clinically relevant. IMPORTANCE During the coronavirus disease 2019 (COVID-19) pandemic, much attention has been paid to the environmental decay of SARS-CoV-2 due to the proposed transmission of the virus via fomites. However, published experiments have commenced with inocula with very high virus titers, an experimental design not representative of real-life conditions. The study described here evaluated the impact of the initial virus titer on the environmental decay of an enveloped virus, using a nonpathogenic surrogate for the transmission of SARS-CoV-2, enveloped bacteriophage Phi6. We establish that higher concentrations of virus can protect the virus from environmental decay, depending on conditions. This has important implications for stability studies of SARS-CoV-2 and other viruses. Our results point to a limitation in the fundamental methodology that has been used to attribute fomite transmission for almost all respiratory viruses.


Polycyclic aromatic hydrocarbons-aromatic DNA adducts in cord blood and behavior scores in New York city children.
Airborne polycyclic aromatic hydrocarbons (PAH) are widespread urban pollutants that can bind to DNA to form PAH-DNA adducts. Prenatal PAH exposure measured by personal monitoring has been linked to cognitive deficits in childhood in a prospective study conducted by the Columbia Center for Children's Environmental Health. We measured PAH-DNA and other bulky aromatic adducts in umbilical cord white blood cells using the 32P-postlabeling assay to determine the association between this molecular dosimeter and behavioral/attention problems in childhood. Children born to nonsmoking African-American and Dominican women residing in New York City (NYC) were followed from in utero to 7-8 years of age. At two time points before 8 years of age (mean ages, 4.8 years and 7 years), child behavior was assessed using the Child Behavior Checklist (CBCL). To estimate and test the association between adducts and behavioral outcomes, both CBCL continuous raw scores and dichotomized T-scores were analyzed. Higher cord adducts were associated with higher symptom scores of Anxious/Depressed at 4.8 years and Attention Problems at 4.8 and 7 years, and with Diagnostic and Statistical Manual of Mental Disorders, 4th edition-oriented Anxiety Problems at 4.8 years. These results suggest that PAH exposure, measured by DNA adducts, may adversely affect child behavior, potentially affecting school performance.


Transmission Versus Truth, Imitation Versus Innovation: What Children Can Do That Large Language and Language-and-Vision Models Cannot (Yet).
Much discussion about large language models and language-and-vision models has focused on whether these models are intelligent agents. We present an alternative perspective. First, we argue that these artificial intelligence (AI) models are cultural technologies that enhance cultural transmission and are efficient and powerful imitation engines. Second, we explore what AI models can tell us about imitation and innovation by testing whether they can be used to discover new tools and novel causal structures and contrasting their responses with those of human children. Our work serves as a first step in determining which particular representations and competences, as well as which kinds of knowledge or skills, can be derived from particular learning techniques and data. In particular, we explore which kinds of cognitive capacities can be enabled by statistical analysis of large-scale linguistic data. Critically, our findings suggest that machines may need more than large-scale language and image data to allow the kinds of innovation that a small child can produce.


Assigning Defined Daily/Course Doses for Antimicrobials in Turkeys to Enable a Cross-Country Quantification and Comparison of Antimicrobial Use.
Antimicrobial resistance (AMR) threatens our public health and is mainly driven by antimicrobial usage (AMU). For this reason the World Health Organization calls for detailed monitoring of AMU over all animal sectors involved. Therefore, we aimed to quantify AMU on turkey farms. First, turkey-specific Defined Daily Dose (DDDturkey) was determined. These were compared to the broiler alternative from the European Surveillance of Veterinary Antimicrobial Consumption (DDDvet), that mention DDDvet as a proxy for other poultry species. DDDturkey ranged from being 81.5% smaller to 48.5% larger compared to its DDDvet alternative for broilers. Second, antimicrobial treatments were registered on 60 turkey farms divided over France, Germany and Spain between 2014 and 2016 (20 flocks per country). Afterwards, AMU was quantified using treatment incidence (TI) per 100 days. TI expresses the percentage of the rearing period that the turkeys were treated with a standard dose of antimicrobials. Minimum, median and maximum TI at flock level and based on DDDturkey = 0.0, 10.0 and 65.7, respectively. Yet, a huge variation in amounts of antimicrobials used at flock level was observed, both within and between countries. Seven farms (12%) did not use any antimicrobials. Aminopenicillins, polymyxins, and fluoroquinolones were responsible for 72.2% of total AMU. The proportion of treating farms peaked on week five of the production cycle (41.7%), and 79.4% of the total AMU was administered in the first half of production. To conclude, not all DDDvet values for broilers can be applied to turkeys. Additionally, the results of AMU show potential for reducing and improving AMU on turkey farms, especially concerning the usage of critically important antimicrobials.


Evolution of allosteric regulation in chorismate mutases from early plants.
Plants, fungi, and bacteria synthesize the aromatic amino acids: l-phenylalanine, l-tyrosine, and l-tryptophan. Chorismate mutase catalyzes the branch point reaction of phenylalanine and tyrosine biosynthesis to generate prephenate. In Arabidopsis thaliana, there are two plastid-localized chorismate mutases that are allosterically regulated (AtCM1 and AtCM3) and one cytosolic isoform (AtCM2) that is unregulated. Previous analysis of plant chorismate mutases suggested that the enzymes from early plants (i.e. bryophytes/moss, lycophytes, and basal angiosperms) formed a clade distinct from the isoforms found in flowering plants; however, no biochemical information on these enzymes is available. To understand the evolution of allosteric regulation in plant chorismate mutases, we analyzed a basal lineage of plant enzymes homologous to AtCM1 based on sequence similarity. The chorismate mutases from the moss/bryophyte Physcomitrella patens (PpCM1 and PpCM2), the lycophyte Selaginella moellendorffii (SmCM), and the basal angiosperm Amborella trichopoda (AmtCM1 and AmtCM2) were characterized biochemically. Tryptophan was a positive effector for each of the five enzymes examined. Histidine was a weak positive effector for PpCM1 and AmtCM1. Neither tyrosine nor phenylalanine altered the activity of SmCM; however, tyrosine was a negative regulator of the other four enzymes. Phenylalanine down-regulates both moss enzymes and AmtCM2. The 2.0 Å X-ray crystal structure of PpCM1 in complex with the tryptophan identified the allosteric effector site and reveals structural differences between the R- (more active) and T-state (less active) forms of plant chorismate mutases. Molecular insight into the basal plant chorismate mutases guides our understanding of the evolution of allosteric regulation in these enzymes.


Gold nanoparticle size and shape influence on osteogenesis of mesenchymal stem cells.
Gold nanoparticles (AuNPs) have been extensively explored for biomedical applications due to their advantages of facile synthesis and surface functionalization. Previous studies have suggested that AuNPs can induce differentiation of stem cells into osteoblasts. However, how the size and shape of AuNPs affect the differentiation response of stem cells has not been elucidated. In this work, a series of bovine serum albumin (BSA)-coated Au nanospheres, Au nanostars and Au nanorods with different diameters of 40, 70 and 110 nm were synthesized and their effects on osteogenic differentiation of human mesenchymal stem cells (hMSCs) were investigated. All the AuNPs showed good cytocompatibility and did not influence proliferation of hMSCs at the studied concentrations. Osteogenic differentiation of hMSCs was dependent on the size and shape of AuNPs. Sphere-40, sphere-70 and rod-70 significantly increased the alkaline phosphatase (ALP) activity and calcium deposition of cells while rod-40 reduced the ALP activity and calcium deposition. Gene profiling revealed that the expression of osteogenic marker genes was down-regulated after incubation with rod-40. However, up-regulation of these genes was found in the sphere-40, sphere-70 and rod-70 treatment. Moreover, it was found that the size and shape of AuNPs affected the osteogenic differentiation of hMSCs through regulating the activation of Yes-associated protein (YAP). These results indicate that the size and shape of AuNPs had an influence on the osteogenic differentiation of hMSCs, which should provide useful guidance for the preparation of AuNPs with defined size and shape for their biomedical applications.


SadB is required for the transition from reversible to irreversible attachment during biofilm formation by Pseudomonas aeruginosa PA14.
Current models of biofilm formation by Pseudomonas aeruginosa propose that (i) planktonic cells become surface associated in a monolayer, (ii) surface-associated cells form microcolonies by clonal growth and/or aggregation, (iii) microcolonies transition to a mature biofilm comprised of exopolysaccharide-encased macrocolonies, and (iv) cells exit the mature biofilm and reenter the planktonic state. Here we report a new class of P. aeruginosa biofilm mutant that defines the transition from reversible to irreversible attachment and is thus required for monolayer formation. The transposon insertion carried by the sadB199 mutant was mapped to open reading frame PA5346 of P. aeruginosa PA14 and encodes a protein of unknown function. Complementation analysis and phage-mediated transduction demonstrated that the transposon insertion in PA5346 was the cause of the biofilm-defective phenotype. Examination of flow cell-grown biofilms showed that the sadB199 mutant could initiate surface attachment but failed to form microcolonies despite being proficient in both twitching and swimming motility. Closer examination of early attachment revealed an increased number of the sadB199 mutant cells arrested at reversible attachment, functionally defined as adherence via the cell pole. A positive correlation among biofilm formation, irreversible attachment, and SadB level was demonstrated, and furthermore, RpoN and FleR appear to negatively affect SadB levels. Fractionation studies showed that the SadB protein is localized to the cytoplasm, and with the use of GPS-linker scanning mutagenesis, the C-terminal portion of SadB was shown to be dispensable for function, whereas the two putative domains of unknown function and the linker region spanning these domains were required for function. We discuss the results presented here in the context of microbial development as it applies to biofilm formation.


Visual acuity and macular hole size after unsuccessful macular hole closure.
To evaluate the visual acuity, change in macular hole size, and change in subretinal fluid cuff size after unsuccessful macular hole closure. Forty-two consecutive eyes with macular hole and unsuccessful surgery for macular hole were studied. Preoperative and postoperative best-corrected visual acuities were tested according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, and changes were compared. Preoperative and postoperative fundus photographs were analyzed on a photograph documenter for changes in diameter of the macular hole and surrounding subretinal fluid cuff. Mean visual acuity decreased from 20/133 preoperatively to 20/154 postoperatively (mean loss, 0.79 ETDRS line). Mean diameter of the macular hole enlarged 22%; mean diameter of the visible surrounding subretinal fluid cuff enlarged 36%. A decrease in best-corrected visual acuity postoperatively was correlated with better preoperative visual acuity, earlier macular hole stage, and shorter duration. Enlargement in the diameter of the macular hole and fluid cuff did not correlate with better preoperative best-corrected visual acuity, earlier macular hole stage, or shorter duration. In 23 eyes that had failed previous surgery, macular hole surgery was anatomically successful in 17 (65%) (mean improvement, 3.7 ETDRS lines; mean best-corrected final visual acuity, 20/74). After macular hole surgery, anatomically unsuccessful closure of the hole correlates with small enlargements in the diameter of the macular hole and its surrounding subretinal fluid cuff, and with a slight decrease in visual acuity. Macular hole closure after repeat surgery improves visual acuity outcome in the majority of retreated eyes.


Development of novel sophorolipids with improved cytotoxic activity toward MDA-MB-231 breast cancer cells.
Sophorolipids (SLs) are glycolipid biosurfactants, produced as a mixture of several compounds by some nonpathogenic yeast. In the current study, separation of individual SLs from mixtures with further evaluation of their surface properties and biologic activity on MDA-MB-321 breast cancer cell line were investigated. SLs were biosynthesized by Starmerella bombicola in a culture media supplemented with borage oil. A reverse-phase flash chromatography method with an automated system coupled with a prepacked cartridge was used to separate and purify the main SLs. Compositional analysis of SLs was performed by high-performance liquid chromatography with electrospray ionization mass spectrometry and tandem mass spectrometry. The following diacetylated lactonic SLs were isolated and purified: C18:0, C18:1, C18:2, and C18:3. The critical micelle concentration (CMC) and surface tension at CMC (γCMC ) of the purified SLs showed an increase with the number of double bonds. High cytotoxic effect against MDA-MB-231 cells was observed with C18:0 and C18:1 lactonic SLs. The cytotoxic effects of C18:3 lactonic SL on cancerous cells were for the first time studied. This cytotoxic effect was considerably higher than the promoted by acidic SLs; however, it induced a lower effect than the previously mentioned SLs, C18:0 and C18:1. To our knowledge, for the first time, C18:1 lactonic SL, in selected concentrations, proved to be able to inhibit MDA-MB-231 cell migration without compromising cell viability and to increase intracellular reactive oxygen species.


[Basic research on the use of mosquito spiroplasmas in the control of the major tropical diseases transmitted by mosquitoes].
An increasing number of experimental findings suggest that Spiroplasma taiwanense (Class Mollicutes) has considerable potential for inclusion in integrated mosquito vector control programmes. These experimental findings are outlined in conjunction with preferred strategies for its eventual use as a biological control agent.


Analysis of failure in medical abortion.
Medical abortion opens a new choice to women wishing to terminate a pregnancy. Increasingly, providers in the developing and developed world will begin to offer this option. Yet, the nomenclature and concepts used for measuring failure of surgical abortion are not directly adaptable because of important differences inherent in the method and in the way it is offered in a given setting. We propose that failures in medical abortion should be defined as a surgical intervention (whether vacuum aspiration or dilatation and curettage) performed for any reason. Such instances may be further classified into three types: user choice interventions, provider choice or error interventions, and true drug failures requiring intervention. Further description and examples of each type are given.


Reciprocal effects of thyroxine and triiodothyronine on their deiodination by rat tissues in vitro.
The reciprocal effects of loading doses of thyroxine (T4) or triiodothyronine (T3) on the deiodination of their 125iodine-labelled isotopes by rat muscle and liver homogenates were studied. In 21 experiments muscle homogenates deiodinated a mean 45.0% of a tracer dose of [125I]T4 and 18.0% of [125I]T3. On addition of graded amounts of nonradioactive T4 or T3 the percentual deiodination of both labelled hormones progressively declined. This effect was significantly greater in homogenates incubated with non-radioactive T4, thus reflecting a stronger affinity of this hormone for muscle deiodinating sites. This correlate with the greater displacment of [125I]T3 as revealed by the percentage of recovered labelled hormone. In 18 experiments liver homogenates deiodinated a mean 14.6% of a tracer amount of [125I]T4 and 8.5% of [125I]T3. The addition of a T4- or a T3-load was followed by a smaller decrease in percentual deiodination of both labelled hormones as compared to muscle homogenates. Unlike the effects observed in muscle, the breakdown of [125I]T4 and [125I]T3 by liver homogenates was equally affected by similar amounts of stable T4 or T3. It is concluded that in the present in vitro system T4 and T3 share cellular sites of deiodination in rat muscle and liver and that, at least in muscle, which constitutes over one-half of the rat body weight T4 appears to be preferentially deiodinated.


Prevalence and correlates of depression in a rural adult population in Northwest India.
Mental disorders are showing a discerning upward trend globally and it is projected that by 2030, depression would be the leading cause of disease burden globally. Depression has not only confined the developed world but is increasingly seen as a major public health problem in the developing world too. A stratified two-stage design was used to conduct a house-to-house survey in selected villages among consenting eligible members of the family. A three-part questionnaire, with the first part eliciting sociodemographic information was used. Patient Health Questionnaire (PHQ-9), the second part of the questionnaire was used to screen those positive for depression and Beck's Depression Inventory (BDI-II). The third part was used for rating the depression. Data thus collected was analyzed and Chi-square test was used as test of significance. The prevalence of depression was found to be 8.94% (73/816). Beck's Depression Inventory (BDI- II) for rating the depression revealed that mild depression was present in nearly half of the cases (47.95%), while 39.7% and 9.5% of the cases had moderate and severe depression, respectively. Among the various variables, literacy level, marital status, alcohol intake, chronic illness, and socioeconomic status were significantly associated with the depression. Prevalence of depression to the tune of 8.94% in rural adults seems to be a cause of concern for the health planners. Prevention and treatment of depression must be taken on priority and as a challenge by the health professionals.


Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma.
Adipocyte differentiation is an important component of obesity and other metabolic diseases. This process is strongly inhibited by many mitogens and oncogenes. Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and reduction of its transcriptional activity. Expression of PPARgamma with a nonphosphorylatable mutation at this site (serine-112) yielded cells with increased sensitivity to ligand-induced adipogenesis and resistance to inhibition of differentiation by mitogens. These results indicate that covalent modification of PPARgamma by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage.


Raising household saving: does financial education work?
This article highlights the prevalence and economic outcomes of financial illiteracy among American households, and reviews previous research that examines how improving financial literacy affects household saving. Analysis of the research literature suggests that previous financial literacy efforts have yielded mixed results. Evidence suggests that interventions provided for employees in the workplace have helped increase household saving, but estimates of the magnitude of the impact vary widely. For financial education initiatives targeted to other groups, the evidence is much more ambiguous, suggesting a need for more econometrically rigorous evaluations.


The merozoite surface protein 1 complex is a platform for binding to human erythrocytes by Plasmodium falciparum.
Plasmodium falciparum is the causative agent of the most severe form of malaria in humans. The merozoite, an extracellular stage of the parasite lifecycle, invades erythrocytes in which they develop. The most abundant protein on the surface of merozoites is merozoite surface protein 1 (MSP1), which consists of four processed fragments. Studies indicate that MSP1 interacts with other peripheral merozoite surface proteins to form a large complex. Successful invasion of merozoites into host erythrocytes is dependent on this protein complex; however, the identity of all components and its function remain largely unknown. We have shown that the peripheral merozoite surface proteins MSPDBL1 and MSPDBL2 are part of the large MSP1 complex. Using surface plasmon resonance, we determined the binding affinities of MSPDBL1 and MSPDBL2 to MSP1 to be in the range of 2-4 × 10(-7) m. Both proteins bound to three of the four proteolytically cleaved fragments of MSP1 (p42, p38, and p83). In addition, MSPDBL1 and MSPDBL2, but not MSP1, bound directly to human erythrocytes. This demonstrates that the MSP1 complex acts as a platform for display of MSPDBL1 and MSPDBL2 on the merozoite surface for binding to receptors on the erythrocyte and invasion.


Loss of neurons from the external cuneate nucleus of the ageing mouse brain.
The number of neurons in the ASH/TO mouse external cuneate nucleus was examined at 6, 15, 22, 25, 28 and 31 months of age. There is a highly significant decrease in the number of neurons between 6 and 31 months of age. Neuron loss begins at 15 months when degenerating neurons are first found in the nucleus and becomes more rapid with increasing age. It is suggested that neuronal loss is due to anterograde transneuronal degeneration following a loss of primary proprioceptive neurons, first from the spinal roots and later from the brainstem.


Lessons From the West Africa Ebola Epidemic: A Systematic Review of Epidemiological and Social and Behavioral Science Research Priorities.
This systematic literature review compared the epidemiological (EPI) research and the qualitative social and behavioral science (SBS) research published during the West Africa Ebola virus disease (EVD) epidemic. Beginning with an initial capture of over 2000 articles, we extracted 236 EPI and 171 SBS studies to examine how disciplinary priorities affected research conducted during the EVD response, with implications for epidemic response effectiveness. Building on this research, we set forth a roadmap for the closer integration of EPI and SBS research in all aspects of epidemic preparedness and response that incorporates the lessons of the West Africa EVD outbreak. Key priorities include the following: (1) developing the capacity to systematically quantify qualitative sociocultural variables; (2) establishing interdisciplinary collaborations to improve "risk segmentation" practices; (3) creating and prepositioning qualitative indicators and composite sociocultural indexes for rapid deployment in outbreaks; (4) integrating novel systems with community resources; (5) developing new techniques for modeling social mobilization and community engagement; (6) prioritizing good data and complex analyses early in emergencies; and (7) learning from past experiences. Our findings support a program of action that situates data collection and analysis in real-time, recursive, integrated efforts to move community attitudes, behaviors, and responses into epidemiological research. We offer recommendations to improve coordinated, multidisciplinary approaches to health emergencies.


Purine-nucleoside phosphorylase from Salmonella typhimurium and Escherichia coli. Initial velocity kinetics, ligand banding, and reaction mechanism.
Purine nucleoside phosphorylase from Salmonella typhimurium has been subjected to kinetic analysis i.e. determination of initial velocity patterns and product inhibition studies. The kinetic results suggest that the enzyme works by a sequential reaction mechanism, where the nucleoside, phosphate, and pentose 1-phosphate are all able to bind to the free enzyme, whereas it appears that the purine base binds after addition of the pentose 1-phosphate. The proposed mechanism is confirmed by substrate binding studies. In addition to the enzyme-substrate complexes suggested by the kinetics, the binding studies revealed a 'dead end' complex, consisting of enzyme, phosphate, and purine base. Similar binding experiments were carried out using the enzyme from Escherichia coli. The results suggest that this enzyme works by an identical reaction mechanism. The binding data are in agreement with the presence of six binding sites per native enzyme molecule, one binding site per subunit, for each ligand. Both enzymes show normal Michaelis-Menten kinetics for their substrates with the exception of phosphate, for which the double-reciprocal plots are concave down. This behaviour is seen in both binding and velocity curves, and most likely is a result of negative cooperativity in the binding of phosphate to the enzyme.