Antisperm antibodies and testicular blood flow after inguinal hernia mesh repair.
Testicular flow studies after hernia mesh repair mostly showed different outcomes. The reason of infertility in some men after hernia repair is immunological factors. Aim of the study was to investigate the influence of mesh hernia repair on antisperm antibodies production and testicular blood flow and a connection among these parameters. A prospective interventional longitudinal cohort study was made on 82 male patients without exclusion criteria who had an inguinal hernia. Patients underwent laparoscopic TAPP or open tension-free hernia repair. Vascular ultrasound and antisperm antibodies were measured in the preoperative and postoperative periods. Main outcome measures were resistive index (RI), peak systolic velocity (PSV) cm/s, and end-diastolic velocity (EDV) cm/s in testicular blood flow measurement and the quantitative value of antisperm antibodies (ASA) in serum (IU/ml). ASA significantly increased postoperatively only in patients who underwent open tension-free hernia repair (p < 0.001). ASA stayed in normal range in all patients except the one with postoperative complication. Friedman analysis showed significant change of the RI only on intratesticular (p < 0.001) and capsular artery level (0.02) in patients who underwent laparoscopic technique. PSV significantly changed on intratesticular (p < 0.001) and capsular artery level (p = 0.015) in the laparoscopic hernia repair. PSV showed significant change on intratesticular (p < 0.001) and testicular artery levels (p < 0.001) in the open tension-free hernia repair. EDV showed significant change only on testicular artery level (p = 0.032) in the patients who had open tension-free hernia repair. These blood flow parameters significantly increased in the early postoperative period and returned on basal value in the late postoperative period. Parameters of flow did not show any significant correlation with ASA. Mesh hernia repairs without complication caused only a transitory change in testicular blood flow and no clinical significant autoimmune reaction.


The Impact of Eye-gaze Controlled Computer on Communication and Functional Independence in Children and Young People with Complex Needs - A Multicenter Intervention Study.
Children and young people with complex needs (severe motor impairments and without speech) have few opportunities to use alternative devices for communication. Eye-gaze controlled computers (EGCCs) might provide individuals with complex needs increased opportunities for communication and participation in society. To investigate the impact of EGCCs on communication, functional independence and participation in activities in children and young people with complex needs. A multicenter intervention study during seven months, measuring outcomes with or without EGCC at four time points, was conducted in Sweden, Dubai, and in USA. Seventeen participants (aged 3-26 years, diagnosis e.g. cerebral palsy, Rett syndrome) were provided with EGCC and services from an Assistive Technology center to implement EGCC in school and/or at home. Participants significantly increased their expressive communication skills and functional independence with EGCC compared to baseline. All but one (16 of 17) increased their activity repertoire and computer use with EGCC. With EGCC, participation in computer activities averaged 4.1 performed activities (e.g. communication, play), with a duration of 70 minutes/day and a frequency of 76% of days. The study strengthened the research evidence that EGCC can be an effective intervention in daily life for children and young people with complex needs. Communication and independence, common goals of intervention, were shown to be relevant EGCC outcomes.


[A relationship between the breakpoint of the bcr gene and some hematologic parameters in patients with chronic myelogenous leukemia].
We examined the hybrid bcr/abl mRNA present in 59 patients with chronic myeloid leukemia, using the reverse transcription method and polymerase chain reaction. Bcr/abl gene was found in 98% of patients. 60% of patients had b3a2 type of translocation, 40% type b2a2. Patients with b3a2 type had higher platelet count at diagnosis presentation than patients with b2a2. Other hematological data were similar in both groups.


Efficacy of rituximab treatment in chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis.
Current standard treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has been proved effective, but it is poorly effective in refractory patients and unclear for anti-IgG4 antibody-associated CIDP. Rituximab is a B cell-depleting monoclonal antibody. It has been applied as one of the management strategies in CIDP, but its efficacy is unknown. To perform a systematic review and a meta-analysis of the efficacy of rituximab treatment in CIDP patients. Through searches in MEDLINE, PubMed, EMBASE, BIOSOS, Web of Science, and Cochrane library on March 31st, 2021, 15 studies were identified. Patients' characteristics, treatment regime and outcome measure were extracted. Ninety-six patients in 15 studies were included. The pooled estimate of responsiveness was 75% (95% CI 72-78%). The standard mean difference (SMD) of Inflammatory Neuropathy Cause and Treatment (INCAT) disability score improvement was 1.7 (95% CI 1.0-2.3, p value < 0.0001) and the Medical Research Council (MRC) score for muscle power is 1.3 (95% CI - 2.6 to - 0.1, p value 0.04). All of the anti-IgG4 antibody-positive patients showed excellent responses to rituximab treatment. Rituximab was effective in the treatment in CIDP patients, especially in anti-IgG4 antibody-positive patients. Randomized clinical trials are needed to determine the effectiveness and safety of rituximab in CIDP patients.


Whitening Efficacy of 3% Carbamide Peroxide Gel Activated by Lactoperoxidase.
The aim of this clinical study was to evaluate the effectiveness of a whitening toothpaste containing 3% carbamide peroxide and lactoperoxidase. Materials and methods. Participants were instructed to brush their teeth using an enzymatic-activated dentifrice following a particular procedure for three weeks. Color was recorded before and after treatment using a VITA Easyshade spectrophotometer. Differences in L ∗ (tooth color lightness), a ∗ (displacement along the red-green axis), and b ∗ (displacement along the yellow-blue axis) were measured before and after treatment using the paired t and the Wilcoxon signed-rank tests. Color changes (Δ E ) were calculated using the obtained measurements. Thirty-four volunteers were included. Δ E was 4.03. For the set of 348 teeth, a greater tendency towards green (lower a ∗ ) and blue (lower b ∗ ) was observed (p < 0.05). There were no significant differences in lightness after treatment. Mandibular central incisors showed a greater tendency towards green (lower a ∗ ) and blue (lower b ∗ ). Bleaching effectiveness was observed in both the upper and lower central incisors and in the lateral mandibular incisors. Based on these results, it may be concluded that brushing with an enzymatic-activated dentifrice is effective for whitening teeth.


A Reagentless, Screen-Printed Amperometric Biosensor for the Determination of Glutamate in Food and Clinical Applications.
A reagentless biosensor has been successfully developed to measure glutamate in food and clinical samples. The enzyme, glutamate dehydrogenase (GLDH) and the cofactor, nicotinamide adenine dinucleotide (NAD+) are fully integrated onto the surface of a Meldola's Blue screen-printed carbon electrode (MB-SPCE). The biological components are immobilized by utilizing unpurified multi-walled carbon nanotubes (MWCNT's) mixed with the biopolymer chitosan (CHIT), which are drop-coated onto the surface of the MB-SPCE in a layer-by-layer fashion. Meldola's Blue mediator is also incorporated into the biosensor cocktail in order to increase and facilitate electron shuttling between the reaction layers and the surface of the electrode. The loadings of each component are optimized by using amperometry in stirred solution at a low fixed potential of +0.1 V. The optimum temperature and pH are also determined using this technique. Quantification of glutamate in real samples is performed using the method of standard addition. The method of standard addition involves the addition of a sample containing an unknown concentration of glutamate, followed by additions of known concentrations of glutamate to a buffered solution in the cell. The currents generated by each addition are then plotted and the resulting line is extrapolated in order to determine the concentration of glutamate in the sample (Pemberton et al., Biosens Bioelectron 24:1246-1252, 2009). This layer-by-layer approach holds promise as a generic platform for the fabrication of reagentless biosensors.


Characterization of a human chromosome 22 enriched bacterial artificial chromosome sublibrary.
Selection of chromosomal sublibraries from total human genomic libraries is critical for chromosome-based physical mapping approaches. We have previously reported a method of screening total human genomic library using flow sorted chromosomal DNA as a hybridization probe and selection of a human chromosome 22-enriched sublibrary from a total human bacterial artificial chromosome (BAC) library (Nucleic Acids Res 1995; 23: 1838-39). We describe here further details of the method of construction as well as characterization of the chromosome 22-enriched sublibrary thus constructed. Nearly 40% of the BAC clones that have been mapped by fluorescence in situ hybridization (FISH) analysis were localized to chromosome 22. By screening the sublibrary using chromosome 22-specific hybridization probes, we estimated that the sublibrary represents at least 2.5 x coverage of chromosome 22. This is in good agreement with the results from FISH mapping experiments. FISH map data also indicate that chromosome 22-specific BACs in the sublibrary represent all the subregions of chromosome 22.


Five-year follow up of a low glycaemic index dietary randomised controlled trial in pregnancy-no long-term maternal effects of a dietary intervention.
To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post-intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes. Randomised control trial of low glycaemic index (GI) diet in pregnancy with longitudinal follow up to 5 years post-intervention. Dublin, Ireland (2007-2016). In all, 403 women of 759 (53.1%) were followed up at 5 years. A total of 370 (intervention n = 188; control n = 182) were included in this analysis. Fasting glucose was measured at 13 and 28 weeks' gestation and HbA1c (mmol/mol) at 5-year follow up. Weight retention (kg) from early pregnancy to 5 years post-intervention was calculated. Dietary intakes, anthropometry, and lifestyle factors were measured in pregnancy and 5 years post-intervention. Multiple linear regression models, controlling for confounders, were used for analysis. Maternal diet, HbA1c, and weight retention at 5 years post-intervention. There was no difference between the intervention and control at 5 years post-intervention for any long-term maternal outcomes measured. HbA1c at 5 years post-intervention was associated with early-pregnancy fasting glucose (B 1.70, 95% CI 0.36-3.04) and parity ≥3 (B 1.04, 95% CI 0.09-1.99). Weight retention was associated with change in well-being from pregnancy to 5 years (B -0.06, 95% CI -0.11 to -0.02), gestational weight gain (B 0.19, 95% CI 0.00-0.38), and GI (B 0.26, 95% CI 0.06-0.46) at 5 years. The ROLO low-GI dietary intervention in pregnancy had no impact on maternal dietary intakes, HbA1c or body composition 5 years post-intervention. Maternal factors and lifestyle behaviours in pregnancy have long-term effects on glucose metabolism and weight retention up to 5 years later. Pregnancy factors are associated with maternal glucose metabolism and weight retention 5 years later-findings from the ROLO Study.


European radiographers' challenges from mammography education and clinical practice - an integrative review.
This study aims to identify European radiographers' challenges in clinical performance in mammography and the main areas of mammography that require more and better training. An extensive search was performed to identify relevant studies focused on clinical practice, education and training in mammography published between January 2010 and December 2015 in the English language. The data were analysed by using deductive thematic analysis. A total of 27 full text articles were read, evaluating their quality. Sixteen articles out of 27 were finally selected for this integrative review. The main challenges of radiographers' mammography education/training can be divided into three groups: training needs, challenges related to radiographers, and challenges related to the organization of education. The most common challenges of clinical performance in mammography among European radiographers involved technical performance, the quality of practices, and patient-centeredness. The introduction of harmonized mammography guidelines across Europe may serve as an evidence-based tool to be implemented in practice and education. However, the variability in human and material resources as well as the different cultural contexts should be considered during this process. • Radiographers' awareness of their professional identity and enhancing multiprofessional cooperation in mammography. • Radiographers' responsibilities regarding image quality (IQ) and optimal breast imaging performance. • Patient-centred mammography services focusing on the psychosocial needs of the patient. • Challenges: positioning, QC-testing, IQ-assessment, optimization of breast compression, communication, teamwork, and patient-centred care. • Introduction of evidence-based guidelines in Europe to harmonize mammography practice and education.


The Roles of Insulin-Like Growth Factor Binding Protein Family in Development and Diseases.
The insulin-like growth factor (IGF) system comprises ligands of IGF-I/II, IGF receptors (IGFR), IGF binding proteins (IGFBPs), and IGFBP hydrolases. The IGF system plays multiple roles during various disease development as IGFs are widely involved in cell proliferation and differentiation through regulating DNA transcription. Meanwhile, IGFBPs, which are mainly synthesized in the liver, can bind to IGFs and perform two different functions: either inhibition of IGFs by forming inactive compounds with IGF or enhancement of the function of IGFs by strengthening the IGF-IGFR interaction. Interestingly, IGFBPs may have wider functions through IGF-independent mechanisms. Studies have shown that IGFBPs play important roles in cardiovascular disease, tumor progression, fetal growth, and neuro-nutrition. In this review, we emphasize that different IGFBP family members have common or unique functions in numerous diseases; moreover, IGFBPs may serve as biomarkers for disease diagnosis and prediction.


Medial Patellofemoral Ligament Reconstruction With Growth Modulation in Children With Patellar Instability and Genu Valgum.
Patellar instability is common in the second decade, and genu valgum is a risk factor for patellar instability. In skeletally immature patients, genu valgum can be gradually corrected using less-invasive, well-established, growth-modulation techniques. For skeletally immature patients with patellar instability and genu valgum, it would be desirable to address both instability and deformity. We describe our technique of physeal-respecting medial patellofemoral ligament reconstruction in skeletally immature patients using hamstring autograft and simultaneous transphyseal screw hemiepiphysiodesis to gradually correct genu valgum. The medial patellofemoral ligament reconstruction technique features posteromedial hamstring graft harvest, single patellar tunnel fixation without implant, and femoral attachment just below the distal femoral physis. The technique of growth modulation features percutaneous insertion of a single transphyseal screw through the distal medial femoral physis without interference with medial patellofemoral ligament graft placement. Our preliminary results have been encouraging with successful correction of genu valgum and satisfactory patellar stabilization without growth disturbances.


Temporal focus and time spatialization across cultures.
The temporal focus hypothesis (TFH) proposes that whether the past or the future is conceptualized as being located in front depends on temporal focus: the balance of attention paid to the past (tradition) and the future (progress). How general is the TFH, and to what extent can cultures and subcultures be placed on a single line relating time spatialization and temporal focus in spite of stark differences in language, religion, history, and economic development? Data from 10 Western (sub)cultural groups (N = 1198,) were used to derive a linear model relating aggregated temporal focus and proportion of future-in-front responses. This model then successfully fitted 10 independently collected (sub)cultural groups in China and Vietnam (N = 899). Further analysis of the whole data set (N = 2,097) showed that the group-level relation arose at the individual level and allowed precise quantification of its influence. Finally, in an effort to apply the model to all relevant published data sets, we included recent data from Britain and South Africa: The former, but not the latter, fitted the model well. Temporal focus is a central factor that shapes how people around the world think of time in spatial terms.


Oxygen dependence of oxidative stress. Rate of NADPH supply for maintaining the GSH pool during hypoxia.
NADPH supply for oxidized glutathione (GSSG) reduction was studied in hepatocytes under different steady-state O2 concentrations with controlled infusions of diamide, a thiol oxidant. When bis-chloro-nitrosourea (BCNU) was used to inhibit GSSG reductase, the rate of GSH depletion approximated the rate of diamide infusion, showing that diamide reacted preferentially with GSH under these experimental conditions. Under aerobic conditions without BCNU treatment, the GSH and NADPH pools were largely unaffected and little diamide accumulation or protein thiol oxidation occurred with diamide infusion rates up to 5.3 nmol/10(6) cells per min. However, at greater infusion rates, GSH and NADPH decreased, diamide and GSSG concentrations increased, and protein thiols were oxidized. This critical infusion rate was easily discernible and provided a convenient means to assess the capacity of cells to reduce GSSG as a function of O2 concentration. As the O2 concentration was decreased below 15 microM, the critical infusion rate decreased from the aerobic value of 5.3 to less than 2 nmol/10(6) cells per min in anoxic cells; half-maximal change occurred at 5 microM O2. Although cells could not maintain normal thiol and NADPH pools at infusion rates above the critical value, analysis of the rates of thiol depletion showed that the maximal NADPH supply rate for GSSG reduction under aerobic conditions was 7-8 nmol/10(6) cells per min and was affected by hypoxia to the same degree as the critical value. Thus, hypoxia and anoxia impair the capability of cells to supply NADPH for the reduction of thiol oxidants. This could be an important factor in the sensitivity of hypoxic and ischemic tissues to oxidative injury.


[The role of comprehensive examination and laparoscopy in the surgical treatment of tubal pregnancy].
A total of 253 patients were examined and operated on for ectopic pregnancy. Eight-six patients were operated on through a laparoscopic access (group 1) and 167 through a laparotomic access (group 2). The authors assess the diagnostic value of echography, measurement of b-subunit of chorionic gonadotrophin, puncture of the abdominal cavity through the posterior vaginal vault, and of histologic examination of scrapings off the endometrium in a complex of examinations of patients with ectopic pregnancy. The results demonstrated the advantages of the laparoscopic access over laparotomy as involving lesser bleeding to the abdominal cavity and no evident adhesions.


Multimorbid Patterns and Cognitive Performance in the Presence of Informative Dropout Among Community-Dwelling Taiwanese Older Adults.
Longitudinal studies among older adults often feature elevated dropout rates and multiple chronic conditions. How Taiwanese multimorbid patterns relate to different cognitive domains remains unclear. This study aims to identify sex-specific multimorbid patterns and associate them with cognitive performance while modeling the risk for dropout. A prospective cohort study (2011-19) in Taiwan recruited 449 Taiwanese older adults without dementia. Global and domain-specific cognition were assessed biennially. We used exploratory factor analysis to identify baseline sex-specific multimorbid patterns of 19 self-reported chronic conditions. We utilized a joint model incorporating longitudinal and time-to-dropout data to examine the association between multimorbid patterns and cognitive performance accounting for the informative dropout via the shared random effect. At the end of the study, 324 participants (72.1%) remained in the cohort, with an average annual attrition rate of 5.5%. We found that advanced age, low levels of physical activities, and poor cognition at baseline were associated with increased dropout risks. Besides, 6 multimorbid patterns were identified, labeled Mental, Renal-vascular, and Cancer-urinary patterns in men, and Mental, Cardiometabolic, and Cancer-endocrine patterns in women. For men, as the follow-up time increased, the Mental pattern was associated with poor global cognition and attention; the Renal-vascular pattern was associated with poor executive function. For women, the Mental pattern was associated with poor memory; as follow-up time increased, and Cardiometabolic patterns were related to poor memory. Sex-specific multimorbid patterns identified in the Taiwanese older population showed differences (notably Renal-vascular pattern in men) from patterns found in Western countries and were differentially associated with cognitive impairment over time. When informative dropout is suspected, appropriate statistical methods should be applied.


In vitro uptake and immune functionality of digested Rosemary extract delivered through food grade vehicles.
The digestion, absorption, uptake and bioavailability of a rosemary supercritical fluid extract encapsulated in oil in water emulsion were studied. Two emulsions with opposite surface charge were prepared, containing 7% canola oil, and either 2% lactoferrin or whey protein isolate. When absorption and uptake of carnosic acid and carnosol were followed on Caco-2 cell monolayers, there were no differences with protein type. However, when co-cultures of HT-29 MTX were employed, the presence of mucus caused a higher retention of carnosic acid in the apical layer for lactoferrin emulsions. The immune activity of the bioavailable fractions collected from cell absorption experiments was tested ex vivo on murine splenocytes. Although transport through the intestinal barrier models was low, the bioavailable fractions showed a significant effect on splenocytes proliferation. These results demonstrated the potential of using rosemary supercritical extract through protein stabilized oil in water emulsions, as a food with immunomodulatory functionality.


Construction of 3D human distal femoral surface models using a 3D statistical deformable model.
Construction of 3D geometric surface models of human knee joint is always a challenge in biomedical engineering. This study introduced an improved statistical shape model (SSM) method that only uses 2D images of a joint to predict the 3D joint surface model. The SSM was constructed using 40 distal femur models of human knees. In this paper, a series validation and parametric analysis suggested that more than 25 distal femur models are needed to construct the SSM; each distal femur should be described using at least 3000 nodes in space; and two 2D fluoroscopic images taken in 45° directions should be used for the 3D surface shape prediction. Using this SSM method, ten independent distal femurs from 10 independent living subjects were predicted using their 2D plane fluoroscopic images. The predicted models were compared to their native 3D distal femur models constructed using their 3D MR images. The results demonstrated that using two fluoroscopic images of the knee, the overall difference between the predicted distal femur surface and the MR image-based surface was 0.16±1.16 mm. These data indicated that the SSM method could be a powerful method for construction of 3D surface geometries of the distal femur.


Stress shielding around radial head prostheses.
Stress shielding is known to occur around rigidly fixed implants. We hypothesized that stress shielding around radial head prostheses is common but nonprogressive. In this study, we present a classification scheme to support our radiographic observations. We reviewed charts and radiographs of 86 cases from 79 patients with radial head implants from both primary and revision surgeries between 1999 and 2009. Exclusion criteria included infection, loosening, or follow-up of less than 12 months. We classified stress shielding as: I, cortical thinning; II, partially (IIa) or circumferentially (IIb) exposed stem; and III, impending mechanical failure. Of 26 well-fixed stems, 17 (63%) demonstrated stress shielding: I = 2, II = 15 (IIa = 12, IIb = 3), and III = 0. We saw stress shielding with all stem types: cemented or noncemented; long or short; and straight, curved, or tapered. The only significant difference was that stems implanted into the radial shaft had less stress shielding than stems implanted into the neck or tuberosity (P = .03). The average follow-up was 33 months (range, 13-70 mo). Stress shielding was detectable by an average of 11 months (range, 1-15 mo). The pattern of bone loss was similar in 16 of 17 cases (94%), starting on the outer periosteal cortex. The 3 cases with circumferential exposure of the stem (stage IIb) averaged 2.6 mm (range, 1-4 mm) of exposed stem. Stress shielding never extended to the bicipital tuberosity, and there were no cases of impending mechanical failure. Stress shielding around radial head prostheses is common, regardless of stem design. However, it is typically minor, nonprogressive, and of questionable clinical consequence. Therapeutic IV.


Four-Tier Pathologic Tumor Regression Grading System Predicts the Clinical Outcome in Patients Who Undergo Surgical Resection for Locally Advanced Pancreatic Cancer after Neoadjuvant Chemotherapy.
Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response. We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems. One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333). The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.


Construction and application of nano ZnO/eugenol@yam starch/microcrystalline cellulose active antibacterial film.
The goal of this study was to develop new biocomposite films that can better protect and prolong the shelf life of food. Here, a ZnO: eugenol@yam starch/microcrystalline cellulose (ZnO:Eu@SC) antibacterial active film was constructed. Because of the advantages of metal oxides and plant essential oils, codoping with these can effectively improve the physicochemical and functional properties of composite films. The addition of an appropriate amount of nano-ZnO improved the compactness and thermostability, reduced the moisture sensitivity, and enhanced the mechanical and barrier properties of the film. ZnO:Eu@SC exhibited good controlled release of nano-ZnO and Eu in food simulants. Nano-ZnO and Eu release was controlled by two mechanisms: diffusion (primary) and swelling (secondary). After loading Eu, the antimicrobial activity of ZnO:Eu@SC was significantly enhanced, resulting in a synergistic antibacterial effect. Z4:Eu@SC film extended the pork shelf life by 100 % (25 °C). In humus, the ZnO:Eu@SC film was effectively degraded into fragments. Therefore, the ZnO:Eu@SC film has excellent potential in food active packaging.


RuCu Nanosheets with Ultrahigh Nanozyme Activity for Chemodynamic Therapy.
Nanoenzymes have been widely explored for chemodynamic therapy (CDT) in cancer treatment. However, poor catalytic efficiency of nanoenzymes, especially in the tumor microenvironment with insufficient H2 O2 and mild acidity, limits the effect of CDT. Herein, a new ultrathin RuCu nanosheet (NS) based nanoenzyme which has a large specific surface area and abundant channels and defects is developed. The RuCu NSs show superb catalytic efficiency for the oxidation of peroxidase substrate H2 O2 at a wide range of pH and their catalytic efficiency (kcat /Km = 177.2 m-1 s-1 ) is about 14.9 times higher than that of the single-atom catalyst FeN3 P. Besides being an efficient nanozyme as peroxidase, the RuCu NSs possess other two enzyme activities, not only disproportionating superoxide anion to produce H2 O2 but also consuming glutathione to keep a high concentration of H2 O2 in the tumor microenvironment for Fenton reaction. With these advantages, the RuCu NSs exhibit good performance to kill cancer cells and inhibit tumor growth in mice, demonstrating a promising potential as new CDT reagent.


Comparison of the ability of adult and pediatric trauma scores to predict pediatric outcome following major trauma.
The Pediatric Trauma Score (PTS) has been identified as the only accurate and adequate means of predicting outcome in pediatric trauma. In answer to the increasing number of trauma patients arriving at local hospitals, the ability of the adult Trauma Score (TS) to predict pediatric trauma outcome was tested. Of the total 2,604 pediatric trauma cases in the North Carolina State Trauma Registry, 441 had both a PTS and TS available for analysis. The primary measures of outcome were emergency department and hospital dispositions. Logistic regression demonstrated that TS (R2 = 0.50) was a stronger predictor of pediatric outcome and PTS (R2 = 0.35) for emergency department disposition and TS (R2 = 0.63) with PTS (R2 = 0.51) for hospital disposition. The correlation between TS and PTS was high (R = 0.8). Stepwise discriminant analysis demonstrated that TS was the stronger predictor of outcome and the PTS added only 9% (partial R2 = 0.09) more accuracy to TS for emergency department disposition and only 6% (partial R2 = 0.06) for hospital disposition. The results of this research demonstrate that TS is a useful method of predicting outcome in pediatric trauma. The use of both scores for each patient does not increase the predictive value of the scores.


Arthroscopically assisted retrodrade intramedullary fixation for fractures of the distal femur: technique, indications and results.
The purpose of this study is to present our experience with the technique, the problems and the potential pitfalls of arthroscopically assisted retrograde femoral nailing for supracondylar femoral fractures. In a 2-year period, nine patients (seven women, two men, average age 72 years) with supracondylar femoral fractures were treated in our department with a retrograde nailing under arthroscopic control. The mean operative time was 63.8 min (42-84 min) and the mean follow up period was 34.5 months (ranged 12-52). Solid union of the fracture was achieved in all patients without additional intervention, in 14 weeks (range 12-18). There was no malalignment (more than 5 degrees in any plane) or implant failure. In conclusion we believe that the arthroscopically assisted technique is a very good method to treat supracondylar fractures of the femur. It has very low morbidity since the knee is not opened through the operation, and the surgeon has the ability to inspect the joint for any additional damage. It is very helpful in multitrauma patients and in young patients, where the precision of the entry point is critical. However, we do not recommend the technique in intraarticular fractures because the reduction is difficult and the fixation is performed with safety only under direct vision.


Aerobic marine bacteria can use H2 for growth.
Molecular hydrogen (H2) and carbon monoxide (CO) are ubiquitously available in the Earth's oceans, yet their low dissolved concentrations seemed unlikely to support microbial growth. Lappan, Shelley, Islam et al. now report that dissolved H2 supports the growth of diverse aerobic marine bacteria in the oceans.


Synthesis and in vitro evaluation of antitumor activity of spiro[indolo[2,1-b]quinazoline-pyrano[2,3-d]pyrimidine] and spiro[indolo[2,1-b]quinazoline-pyrido[2,3-d]pyrimidine] derivatives by using 2D and 3D cell culture models.
Cancer as one of the biggest human health problems remains unsolved. The identification of novel platforms with the highest efficacy and low toxicity is a big challenge among interested researchers. In this regard, we are interested to synthesis and evaluate antitumor activity of spiro[indolo[2,1-b]quinazoline-pyrano[2,3-d]pyrimidine] and spiro[indolo[2,1-b]quinazoline-pyrido[2,3-d]pyrimidine] derivatives. The spiro heterocycles were synthesized via four-component reaction of isatoic anhydride, isatins, malononitrile, and some CH-acids including barbituric acid/thiobarbituric acid and 4(6)-aminouracil in CH2Cl2 under reflux condition. The significant features of this process are short reaction time, easy purification without chromatographic process, and high yields which make it attractive. Next, we employed 2D and 3D cell culture models to evaluate biological activity of our compounds. Our results showed that among our seven products (4a-g), the compounds 4a and 4e are the best with 50% growth inhibitory concentration (IC50) value lower than etoposide. Our results support this idea that the compounds 4a and 4e may be potential for drug designing in cancer therapy. However, more experiments will be required to find possible side effects of related compounds in vivo.


Distributed sensor and actuator networks for closed-loop bioelectronic medicine.
Designing implantable bioelectronic systems that continuously monitor physiological functions and simultaneously provide personalized therapeutic solutions for patients remains a persistent challenge across many applications ranging from neural systems to bioelectronic organs. Closed-loop systems typically consist of three functional blocks, namely, sensors, signal processors and actuators. An effective system, that can provide the necessary therapeutics, tailored to individual physiological factors requires a distributed network of sensors and actuators. While significant progress has been made, closed-loop systems still face many challenges before they can truly be considered as long-term solutions for many diseases. In this review, we consider three important criteria where materials play a critical role to enable implantable closed-loop systems: Specificity, Biocompatibility and Connectivity. We look at the progress made in each of these fields with respect to a specific application and outline the challenges in creating bioelectronic technologies for the future.


Chemical Modification of Phage-Displayed Helix-Loop-Helix Peptides to Construct Kinase-Focused Libraries.
Conformationally constrained peptides hold promise as molecular tools in chemical biology and as a new modality in drug discovery. The construction and screening of a target-focused library could be a promising approach for the generation of de novo ligands or inhibitors against target proteins. Here, we have prepared a protein kinase-focused library by chemically modifying helix-loop-helix (HLH) peptides displayed on phage and subsequently tethered to adenosine. The library was screened against aurora kinase A (AurA). The selected HLH peptide Bip-3 retained the α-helical structure and bound to AurA with a KD value of 13.7 μM. Bip-3 and the adenosine-tethered peptide Bip-3-Adc provided IC50 values of 103 μM and 7.7 μM, respectively, suggesting that Bip-3-Adc bivalently inhibited AurA. In addition, the selectivity of Bip-3-Adc to several protein kinases was tested, and was highest against AurA. These results demonstrate that chemical modification can enable the construction of a kinase-focused library of phage-displayed HLH peptides.


Communicating and understanding pain: Limitations of pain scales for patients with sickle cell disorder and other painful conditions.
Pain communication in healthcare is challenging. We examine use of pain scales to communicate pain severity via a case study of people with sickle cell disorder (SCD). We show how pain communication involves complex social interactions between patients, healthcare professionals and significant others - none of which are included in pain ratings. Failure to account for relational aspects of pain may cause problems for any patient. For SCD, mutual distrust shapes pain communication, further complicating clinical assessments. Moreover, SCD pain is particularly severe, making ratings hard to interpret compared with ratings from non-SCD patients, potentially exacerbating problems in managing pain relief.


JAG2/Notch2 inhibits intervertebral disc degeneration by modulating cell proliferation, apoptosis, and extracellular matrix.
Intervertebral disc degeneration (IVDD)-related disorders are the major causes of low back pain. A previous study suggested that Notch activation serves as a protective mechanism and is a part of the compensatory response that maintains the necessary resident nucleus pulposus (NP) cell proliferation to replace lost or non-functional cells. However, the exact mechanism remains to be determined. In this study, we aimed to investigate the role of JAG2/Notch2 in NP cell proliferation and apoptosis. Recombinant JAG2 or Notch2, Hes1, and Hey2 siRNAs were used to activate or inhibit Notch signaling. Cell proliferation, apoptosis, cell cycle regulatory factors, and pathways associated with Notch-mediated proliferation were examined. In vivo experiments involving an intradiscal injection of Sprague-Dawley rats were performed. Recombinant JAG2 induced Notch2 and Hes1/Hey2 expression together with NP cell proliferation. Downregulation of Notch2/Hes1/Hey2 induced G0/G1 phase cell cycle arrest in NP cells. Moreover, Notch2 mediated NP cell proliferation by regulating cyclin D1 and by activating PI3K/Akt and Wnt/β-catenin signaling. Furthermore, Notch signaling inhibited TNF-α-promoted NP cell apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Finally, we found that intradiscal injection of JAG2 alleviated IVDD and that sh-Notch2 aggravated IVDD in a rat model. These results indicated that JAG2/Notch2 inhibited IVDD by modulating cell proliferation, apoptosis, and extracellular matrix. The JAG2/Notch2 axis regulated NP cell proliferation via PI3K/Akt and Wnt/β-catenin signaling and inhibited TNF-α-induced apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. The current and previous results shed light on the therapeutic implications of targeting the JAG2/Notch2 axis to inhibit or reverse IVDD.


Final report of the Bawnmore Personal Development Programme: staff attitudes and sexuality programme development in an Irish service organisation for people with mental handicap.
In this paper, issues on sexuality and mental handicap are reviewed, and recognition of the growing importance of sex education to integration is noted. The development of a sex education programme and staff training provided within a service organisation, with some involvement from other services within an Irish setting, are described, and their evaluation is reported. Attitudes towards involvement prove of particular interest, and factors influencing continuation or discontinuation are identified. The need for attitude change among staff and administration towards the priority given to sex education is highlighted, and a need for structural change in staffing arrangements to facilitate such education is indicated. Failure to recognise sexuality as a research issue in evaluating the success of integration efforts is noted, and such research is recommended as a top priority for the future.


Thermodynamic inconsistency disproves the Suga-Sagawa theory of cardiac energetics.
The theory proposed by Suga and Sagawa, encompassing the concepts of 'time-varying elastance', 'pressure-volume area' and 'isoefficiency', has been widely applied in cardiac research - albeit not without contention. In this Review, we commence with a brief history of striated muscle energetics as a prelude to re-visiting the Suga-Sagawa Theory. We conclude our discussion by including recent insights into the fundamental flaw underlying the metabolic component of the Theory.


Biceps Tenoscopy: Arthroscopic Evaluation of the Extra-articular Portion of the Long Head of Biceps Tendon.
The recent literature shows that imaging modalities, physical examination tests, and glenohumeral arthroscopy all have low sensitivities and specificities with respect to the diagnosis of the long head of biceps tendon pathology. Biceps tenoscopy is a strategy that aims to reduce the rate of missed diagnoses by improving visualization of the extra-articular part of the tendon. This is an area of predilection of pathology that is not adequately visualized with conventional arthroscopic techniques. This technical note presents the surgical technique for biceps tenoscopy.


Towards nano-physiology of insects with atomic force microscopy.
Little study of insects with modern nanotechnology tools has been done so far. Here we use one of such tool, atomic force microscopy (AFM) to study surface oscillations of the ladybird beetles (Hippodamia convergens) measured in different parts of the insect at picometer level. This allows us to record a much broader spectral range of possible surface vibrations (up to several kHz) than the previously studied oscillations due to breathing, heartbeat cycles, coelopulses, etc. (up to 5-10Hz). Here we demonstrate three different ways with which one can identify the origins of the observed peaks - by physical positioning the probe near a specific organ, and by using biological or chemical stimuli. We report on identification of high frequency peaks associated with H. convergens heart, spiracular closer muscles, and oscillations associated with muscles activated while drinking. The method, being a relatively non-invasive technique providing a new type of information, may be useful in developing "nanophysiology" of insects.


Mapping Brazilian Expansion Risk Levels of Mango Weevil (Sternochetus mangiferae Fabricius) Based on MaxEnt.
The mango weevil, Sternochetus mangiferae (Fabricius) (Curculionidae), pest present in Brazil and is restricted to some municipalities in the Rio de Janeiro State. This curculionid attacks the mango crop exclusively and puts mango production globally at risk, especially those destined for export. Using ecological modeling tools, this study is the first to map the potential risk of S. mangiferae in Brazil. We aimed to identify the potential distribution of this pest in Brazilian states, drawing up thematic maps of regions that present suitable and unsuitable climatic conditions for the establishment of the pest using the MaxEnt ecological niche model. The average annual temperature, the annual precipitation, the average daytime temperature range, and the annual temperature range were the variables that contributed most to the selected model. The MaxEnt model predicted highly suitable areas for S. mangiferae throughout the Brazilian coast, especially on the northeast coast. The region responsible for more than 50% of mango production in Brazil, the São Francisco Valley, was classified by the model with suitability for the pest; it can impacts exportations due to the imposition of phytosanitary barriers. This information can be used in strategies to prevent the introduction and establishment of this pest in new areas and monitor programs in areas with recent occurrence. In addition, the model results can be used in future research plans on S. mangiferae in worldwide modeling studies and climate change scenarios.


Inhibition of transcription at radiation-induced nuclear foci of phosphorylated histone H2AX in mammalian cells.
Double-strand DNA breaks (DSBs) induced by ionizing radiation can be visualized in human cells using antibodies against Ser-139 phosphorylated histone H2AX (gamma-H2AX). Large gamma-H2AX foci are seen in the nucleus fixed 1 hour after irradiation and their number corresponds to the number of DSBs, allowing analysis of these genome lesions after low doses. We estimated whether transcription is affected in chromatin domains containing gamma-H2AX by following in vivo incorporation of 5-bromouridine triphosphate (BrUTP) loaded by cell scratching (run-on assay). We found that BrUTP incorporation is strongly suppressed at gamma-H2AX foci, suggesting that H2AX phosphorylation inhibits transcription. This is not caused by preferential association of gamma-H2AX foci with constitutive or facultative heterochromatin, which was visualized in irradiated cells using antibodies against histone H3 trimethylated at lysine-9 (H3-K9m3) or histone H3 trimethylated at lysine-27 (H3-K27m3). Apparently, formation of gamma-H2AX induces changes of chromatin that inhibit assembly of transcription complexes without heterochromatin formation. Inhibition of transcription by phosphorylation of histone H2AX can decrease chromatin movement at DSBs and frequency of misjoining of DNA ends.


Expression of stem cell factor and its receptor c-Kit during the development of intrahepatic cholangiocarcinoma.
Stem cell factor (SCF) and its receptor, c-Kit, constitute an important signal transduction system with proliferative and anti-apoptotic functions. Besides regulating hemopoietic stem cell proliferation and liver regeneration, it has been implicated in the regulation of human malignancies. However, the cellular expression of the SCF-c-Kit gene system in the liver during cholangiocarcinogenesis has not been studied to date. The protein- and mRNA-expression levels of SCF and c-Kit genes were examined in normal rat liver, in isolated normal rat liver cells and in a thioacetamide-induced rat model of intrahepatic cholangiocarcinoma (CC). Immunohistochemical analysis of the normal liver showed that SCF is expressed in the wall of the hepatic artery and in some cells, which were located along the sinusoids, although it was absent from hepatocytes and biliary epithelial cells. The mRNA analysis of isolated normal liver cell populations revealed a co-expression of SCF- and c-Kit-mRNA in sinusoidal endothelial cells and in Kupffer cells, whereas passaged and cultured liver myofibroblasts (MFs) expressed only SCF. Low levels of the SCF- and c-Kit-mRNA expression could be detected in isolated hepatocytes of the normal liver. Immunohistochemical analysis of the CC tissue showed SCF positivity in proliferating biliary cells (CK-19(+)), in macrophages (ED-1(+)) and in MFs (alpha-smooth-muscle-actin, alpha-SMA(+)) of the tumoral microenvironment. c-Kit-positivity could be detected on hepatocytes of the regenerating nodules and on the proliferating bile ducts of CC. Compared with the normal liver tissue, SCF-mRNA from the CC tissue was upregulated up to 20-fold, whereas c-Kit-mRNA was upregulated up to fivefold. These data indicate that several cell populations may become able to express SCF and/or c-Kit during cholangiocarcinogenesis. Therefore, the SCF-c-Kit system may contribute to tumor development, for instance, by inducing proliferation of hepatocytes and of biliary cells and by acting as a surviving factor for CC cells.


[Study of the possibilities of contamination and transmission by the mosquitoes Culex pipiens f. molestus Fors, a pathogen of West Nile fever].
Experimental studies have demonstrated that the mosquitoes Cx. p. f. molestus fed with virus-containing suspensions, by using an artificial membrane and hygroscopic surface, are infected in 60 to 100% cases and transmit the accepted pathogen of West Nile fever (WNF) to newborn albino mice on blood sucking. The mosquitoes of this species maybe involved in the spread of the pathogen of WNF during its epidemic outbreaks.


Opinions of UK specialists about terminology, diagnosis, and treatment of atypical facial pain: a survey.
There are few robust, evidence-based data about what constitutes the diagnosis of atypical facial pain and how it is best treated. We therefore aimed to find out the current opinion of those on specialist lists in the United Kingdom (UK) on whether they use the term atypical facial pain, how they reach their diagnosis, and what treatment they offer. We sent out questionnaires to 240 specialists randomly selected from the UK lists of those most likely to deal with atypical facial pain (oral and maxillofacial surgeons, oral medical specialists, ear nose and throat surgeons, anaesthetists, psychiatrists and neurologists). We divided the replies according to whether the specialists were medically or dentally based. Of the 209 valid questionnaires, 143 were returned (a response rate of 68%); 127 of the 143 used the term atypical facial pain, the others used various other terms. The two groups used significantly different criteria, mainly to exclude other conditions to achieve a diagnosis. About half used haematological tests and most used radiographic investigations routinely, and there were no significant differences among the specialities. No unified pattern of referral between different units was found. Treatment was mainly by antidepressant and anticonvulsant drugs, and counselling.


Fixed dilated pupil after penetrating keratoplasty for macular corneal dystrophy and keratoconus.
To identify predisposed eyes, risk factors, and protective measures and to evaluate methods of treatment for fixed dilated pupil after penetrating keratoplasty (PKP) for macular corneal dystrophy (MCD) and keratoconus. Retrospective observational case series. A retrospective review was conducted of the charts of 195 patients who had PKP for MCD and of 1800 patients who had PKP for keratoconus at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia. The review included an evaluation of the preoperative and intraoperative data and the postoperative course. In addition, clinical examinations at the last visit and photographs of the cornea, pupil, iris, and lens were analyzed. Twenty-one eyes of 18 patients had fixed dilated pupil after PKP; 15 eyes of 12 patients had MCD, and six eyes of six patients had keratoconus. A rise in intraocular pressure (IOP) during the procedure was seen in five patients (23.8%). Fixed dilated pupil was documented on the first and second postoperative days and the second postoperative week in 17 (80.9%), one (4.8%), and three (14.3%) eyes, respectively. Six eyes (28.6%) of six patients had severe eye inflammation. Only one eye (4.8%) regained partial reactivity of the pupil on follow-up visits. Seven eyes (33.3%) experienced lens changes; nine eyes (42.8%) had elevated IOP on the first postoperative day, and none of the eyes had chronic glaucoma. Inflammatory and multifactorial pathologic condition can cause fixed pupil after PKP. Atropine use, keratoconus, and high IOP are not constant findings in this syndrome. Awareness of the risk factors of fixed dilated pupil will help prevent against its occurrence.


Significance of pre and post-implant MELD-XI score on survival in children undergoing VAD implantation.
Derangements in liver and renal function often accompany end-stage heart failure. We sought to assess the utility of an objective risk assessment tool, the Model for End-stage Liver Disease eXcluding INR (MELD-XI), to identify pediatric patients at increased risk for adverse outcomes post-ventricular assist device (VAD) implantation. The Pedimacs database was queried for all pediatric patients who underwent VAD implantation from September 19, 2012 to December 31, 2019. Pre-implant and early (1-week) post-implant MELD-XI scores were used to stratify patients into low, intermediate and high score cohorts. Comparison of pre-implant characteristics and post-implant outcomes were conducted across groups. Multiphase parametric hazard modeling was utilized to identify independent predictors of post-implant mortality. A total of 742 patients had a calculable MELD-XI score pre-implant. When stratified by MELD-XI scores pre-implant, patients in the high MELD-XI score cohort (score >13.6) had inferior survival and increased bleeding, renal dysfunction and respiratory failure post-implant compared to intermediate and low score cohorts. Risk factors for mortality post-VAD implantation were: increasing MELD-XI scores (HR 1.1 per 1 unit rise), Pedimacs profile 1 (HR 1.6), congenital heart disease (HR 2.3) and being on a percutaneous VAD (HR 2.7). Importantly, MELD-XI score was a better predictor of post-VAD implant mortality than bilirubin or creatinine alone, neither of which were significant in the final model. Patients with increasing or continued high MELD-XI scores early post-implant had the worst survival. The MELD-XI is an easily calculated score that serves as a promising risk assessment tool in identifying children at risk for poor outcomes post VAD implantation.


Complete Genome Sequence Data of Four Burkholderia glumae Strains Isolated from Rice Fields in the United States.
Bacterial panicle blight caused by Burkholderia glumae is a major disease in rice production worldwide. Currently, only a few whole-genome sequences of B. glumae strains isolated in the United States are available. Here, we report the complete genome sequence of four B. glumae strains, including three virulent strains (336gr-1, 411gr-6, and 957856-41-c) and the nonpathogenic strain B. glumae 257sh-1, which were isolated from rice fields in Louisiana (336gr-1, 957856-41-c, and 257sh-1) and Arkansas (411gr-6). The whole-genome sequence data of B. glumae strains will contribute to investigations of the molecular mechanism underlying bacterial pathogenicity and virulence to rice plants.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


MRSA dynamic circulation between the community and the hospital setting: New insights from a cohort study.
Dissemination of methicillin-resistant-Staphylococcus aureus/(MRSA) is a worldwide concern both in hospitals [healthcare-associated-(HA)-MRSA] and communities [community-associated-(CA)-MRSA]. Knowledge on when and where MRSA colonization is acquired and what clones are involved is necessary, to focus efforts for prevention of hospital-acquired MRSA-infections. A prospective/longitudinal cohort study was performed in eight Argentina hospitals (Cordoba/ October-December/2014). Surveillance cultures for MRSA (nose-throat-inguinal) were obtained on admission and at discharge. MRSA strains were genetically typed as CA-MRSAG and HA-MRSAG genotypes. Overall, 1419 patients were screened and 534 stayed at hospital for ≥3 days. S. aureus admission prevalence was 30.9% and 4.2% for MRSA. Overall MRSA acquisition rate was 2.3/1000 patient-days-at-risk with a MRSA acquisition prevalence of 1.96% (95%CI: 1.0%-3.4%); 3.2% of patients were discharged back to community with MRSA. CA-MRSAG accounted for 84.6% of imported, 100.0% of hospital-acquired and 94% of discharged MRSA strains. Most imported and acquired MRSA strains belonged to two major epidemic CA-MRSA clones spread in Argentina: PFGEtypeI-ST5-IVa-t311-PVL+ and PFGEtypeN/ST30-IVc-t019-PVL+. CA-MRSA clones, particularly ST5-IV-PVL+ and ST30-IV-PVL+, with main reservoir in the community, not only enter but also are truly acquired within hospital, causing healthcare-associated-hospital-onset infections, having a transmission capacity greater or similar than HA-MRSAG. This information is essential to develop appropriate MRSA infection prevention-control programs, considering hospital and community.


Knowledge translation in child welfare-improving educational outcomes for children at risk: study protocol for a hybrid randomized controlled pragmatic trial.
In Norway, a disproportionately high number of children receiving Child Welfare Services (CWS) struggle academically and drop out of school. Academic attainment is one of the strongest protective factors against societal marginalization. The present study is part of a knowledge translation project in collaboration with local CWS with the aim to develop, implement, and evaluate Enhanced Academic Support (EAS) for primary school children in CWS. The study is a mixed-methods hybrid type 2 randomized, controlled pragmatic trial. The participants are approximately 120 children whose families receive support measures from three child welfare agencies in and around Oslo, Norway, and practitioners from these agencies. Families are randomly assigned to either the EAS condition or "business as usual" support. Primary outcomes are math and reading skills, parental involvement in school, and intervention fidelity. Questionnaires and academic tests are administered at baseline, post-intervention (after 6 months), and at follow-up (after 12 months). Implementation drivers are assessed before and after the trial period, and intervention fidelity is monitored during the trial through checklists and structured telephone interviews. Semi-structured interviews and focus groups are conducted after the trial. This hybrid study has two implications. (1) The effects of providing EAS to children in child welfare will be investigated. The study also explores how each core component of the intervention and the use of specific adaptations, implementation drivers, and other important child-level covariates moderate the overall effects. The results can provide valuable knowledge about how to deliver precise and effective academic support to increase academic skills and prevent dropout. In turn, this can promote academic completion and well-being, outcomes that are beneficial for both children and society at large. (2) The study also evaluates the feasibility of applying an Integrated Knowledge Translation model designed to develop, implement, and evaluate research-supported practice in health, care, and welfare services in less time than is usually the case. If deemed successful, this model will provide an efficient collaborative approach to translate the best available evidence into effective evidence-based practice, applicable in effectiveness research and quality improvement efforts. ISRCTN, ISRCTN38968073 . Registered on 18 September 2017. https://doi.org/10.1186/ISRCTN38968073 .


Globally engaged nursing education: an academic program framework.
This paper presents a model for designing, providing, and evaluating global experiential education, both local and internationally. A literature review was conducted to identify studies and models of global nursing education experiences in the scientific indexed literature and the gray literature on the Internet published by professional associations. Key elements of the model developed include institutional and program mission and goals, global health core content, program characteristics, student characteristics, reflection, and perspective transformation. These factors combine to address the range of interweaving factors that need to be considered in providing well-designed global health offerings. The framework is offered for use in developing global experiences and in conducting studies to advance our understanding of what and how students learn and are transformed from participation in global education.


Consolidation of particle beds and packing of chromatographic columns.
A variety of complementary evidence reviewed here demonstrates that the packing of chromatographic columns is heterogeneous. It is denser and less well organized close to the column wall than in the center of the column. The mechanism of particle consolidation under stress explains the origin of this phenomenon and provides a fundamental justification to what is known in column chromatography as "the wall effect".


Anti-lymphoproliferative activity of brown adipose tissue of hibernating ground squirrels is mainly caused by AMP.
A fraction with mol wt < 1 kDa was obtained from the brown fat of hibernating ground squirrels (Citellus undulatus) by means of delipidization, acid extraction, ultracentrifugation and ultrafiltration. This fraction suppressed the proliferation of mouse lymph node cells under standard mitogenic stimuli for T lymphocytes. In contrast, the fraction with mol wt < 1 kDa obtained from the brown fat of active ground squirrels in spring did not display such activity. Further HPLC purification of the biologically active fraction and chemical and structural analysis of its most potent antilymphoproliferative component revealed that this is adenosine 5'-monophosphate (AMP). These data lend support to the notion that in hibernating mammals AMP originating, at least partly, from the brown fat down-regulates the seasonally-dependent proliferation of the thymus.


Glia, neurons, and axon pathfinding during optic chiasm development.
The importance of vision in the behavior of animals, from invertebrates to primates, has led to a good deal of interest in how projection neurons in the retina make specific connections with targets in the brain. Recent research has focused on the cellular interactions occurring between retinal ganglion cell (RGC) axons and specific glial and neuronal populations in the embryonic brain during formation of the mouse optic chiasm. These interactions appear to be involved both in determining the position of the optic chiasm on the ventral diencephalon (presumptive hypothalamus) and in ipsilateral and contralateral RGC axon pathfinding, development events fundamental to binocular vision in the adult animal.


A cluster of gram-negative bloodstream infections in Connecticut hemodialysis patients associated with contaminated wall boxes and prime buckets.
Maintenance hemodialysis (HD) patients are at increased risk of bloodstream infections (BSI). We investigated a cluster of Delftia acidovorans infections among patients undergoing HD at an outpatient unit (Facility A). A case was defined as a Facility A HD patient with ≥1 culture positive for D acidovorans between February 1 and April 30, 2018. An investigation included review of patient records, facility policies, practice observations, and environmental cultures. The cluster included 2 patients with confirmed D acidovorans BSI. Both patients had recently been dialyzed at Station #2, where a wall box culture yielded D acidovorans. One patient also had a BSI due to Enterobacter asburiae, which was recovered from several other wall boxes and saline prime buckets (SPB). Observations revealed leakage of wastewater from wall boxes onto the floor, and that SPBs were not always disinfected and dried appropriately before reuse. Multiple deficiencies in hand hygiene and station disinfection were observed. No deficiencies in water treatment practices were identified, and water cultures were negative for the observed pathogens. The cluster of D acidovorans infections was most likely due to indirect exposures to contaminated wall boxes and possibly SPBs due to poor hand hygiene and station disinfection.


Reproductive Outcomes after Laparoscopic Myomectomy: Conventional versus Barbed Suture.
To study the reproductive outcomes after laparoscopic myomectomy comparing conventional (nonbarbed) suture with barbed suture used for myometrial defect closure. Monocentric retrospective cohort study with prospective follow-up survey for reproductive outcomes conducted in April and May 2020. Tertiary care center (center for advanced gynecologic laparoscopy and infertility). Women who underwent laparoscopic myomectomy for uterine leiomyomas from January 2004 to December 2017. Laparoscopic myomectomy with closure of the myometrium using either conventional (nonbarbed suture) or barbed suture and follow-up survey regarding reproductive outcomes. The outcomes measured included the rate of conception, pregnancy complications, mode of delivery, and perioperative complications for both kinds of suture materials used. Of the 399 women who underwent laparoscopic myomectomy, 343 satisfied the inclusion criteria and were followed up; 235 patients responded. A total of 120 patients were included in the nonbarbed group (group A), and 115 patients were included in the barbed group (group B). A total of 182 (group A: 97 vs group B: 85; p = .204) women had actively sought pregnancy postoperatively, of whom 93 (51.09%) in total and 51 (54.8%) in group A vs 42 (45.1%) in group B reported at least 1 pregnancy with no significant difference in the incidence rate ratios between the 2 groups. Of the recorded pregnancies84.9% (group A: 88.2% vs group B: 80.9%) live births, 6.4% (group A: 5.8% vs group B: 7.1%) had first-trimester miscarriages, 2.1% (group A: 1.9% vs group B: 2.3%) had an ectopic pregnancy, and 6 were ongoing pregnancies at the time of the study analysis, which were compared statistically between both study groups. Pregnancy-related complications were noted in 12 of the 93 pregnant women (12.9%), which were comparable in both groups. No case of uterine rupture was reported. Our study supports good reproductive outcomes in women after laparoscopic myomectomy with barbed sutures. Furthermore, the inclusion of nonbarbed sutures as a control group in our study reinforces that barbed sutures in myomectomy are as safe as, and an easier alternative to, conventional sutures without affecting pregnancy outcomes.


Effects of ionizing radiation on surface properties of current restorative dental materials.
To investigate the impact of radiotherapy on surface properties of restorative dental materials. A conventional resin composite-CRC (Aura Enamel), a bulk-fill resin composite-BFRC (Aura Bulk-fill), a conventional glass ionomer cement-CGIC (Riva self cure), and a resin-modified glass ionomer cement-RMGIC (Riva light cure) were tested. Forty disc-shaped samples from each material (8 mm diameter × 2 mm thickness) (n = 10) were produced according to manufacturer directions and then stored in water distilled for 24 h. Surface wettability (water contact angle), Vickers microhardness, and micromorphology through scanning electron microscopy (SEM) before and after exposition to ionizing radiation (60 Gy) were obtained. The data were statistically evaluated using the two-way ANOVA and Tukey posthoc test (p < 0.05). Baseline and post-radiation values of contact angles were statistically similar for CRC, BFRC, and RMGIC, whilst post-radiation values of contact angles were statistically lower than baseline ones for CGIC. Exposition to ionizing radiation statistically increased the microhardness of CRC, and statistically decreased the microhardness of CGIC. The surface micromorphology of all materials was changed post-radiation. Exposure to ionizing radiation negatively affected the conventional glass ionomer tested, while did not alter or improved surface properties testing of the resin composites and the resin-modified glass ionomer cement tested.


The in vitro development of the pentastomid Porocephalus crotali from the infective instar to the adult stage.
The in vitro development of the pentastomid Porocephalus crotali from the infective, seventh (VII) instar, dissected from the tissues of rat intermediate hosts, to the adult male (X) and female (XI) instars, normally resident in the lung of rattlesnake definitive hosts, is described. The culture medium comprised washed human blood cells, resuspended in bovine serum (50:50, v/v), with 20% minimum essential medium and antibiotics. Two batches of approximately 100 pentastomids, maintained at a density of 2 worms/ml, were cultured in 500 ml bottles in an atmosphere of 5% CO2 in air at 28 degrees C. Culture bottles were rotated slowly on a Rollacell system and the medium was replenished every 2-3 days. Growth was monitored at various intervals by weighing worms, measuring cast cuticles with attached moulted hooks recovered from the medium, and by dissecting worms for measurements of various organ systems. Three moults separated the infective and adult male instar, whereas 4 moults were necessary in the case of females. In both cultures natural mortality was about 10% over a 160-day period, by which time 33-51% of females and 62-70% of males had reached the terminal instar. Some males attained full sexual maturity with seminal vesicles loaded with viable sperm: such males were indistinguishable from males recovered from naturally infected rattlesnakes. However, females never achieved full size, even after 200 days, and although copulation did not occur in vitro, some females became patent.


Analysis of the mitogenic effects of toxic shock toxin on human peripheral blood mononuclear cells in vitro.
It has been shown previously that the staphylococcal enterotoxins A and B are T-cell mitogens and also cause inhibition of murine plaque-forming cells generated in vitro. Similarly, toxic shock toxin, a 24,000-MW protein produced by toxic shock-associated strains of Staphylococcus aureus, is mitogenic and inhibits the generation of both murine and rabbit plaque-forming cells. In this study, an analysis of the T-cell response to toxic shock toxin was performed. Human peripheral blood mononuclear cells responded to toxic shock toxin over a broad dosage range (1 ng/ml to 5 micrograms/ml) with maximum proliferation at day 4 (96 hr) of culture. Heat treatment (100 degrees C for 60 min) of toxic shock toxin attenuated its mitogenic effects by only a small amount, and this attenuation could be reversed with increasing concentration of the toxin. By cytofluorography, both untreated and toxic shock toxin-treated small lymphocytes manifested normal percentages of OKT3+, OKT11+, OKT4+, OKT8+, HLA/DR+, and Leu-7+ cells. However, toxic shock toxin-induced blasts were 99% OKT11+ and expressed the receptor for interleukin 2 (89%-100% TAC+). Approximately 85% of the blasts were OKT4+, and 25% of the blasts were OKT8+. Proliferation of purified, double-rosetted T cells was enhanced monotonically by the addition of irradiated "non-T" cells. Irradiated, monocyte-enriched non-T cells were 2.5 times more potent than unfractionated non-T cells in producing quantitatively similar proliferation by toxic shock toxin-stimulated, autologous T cells. In addition, preincubation of non-T cells for 24 hr with toxic shock toxin, followed by extensive washing and irradiation, induced substantial proliferation by unexposed, autologous T cells. These data show that toxic shock toxin is mitogenic for T cells and requires accessory cells for maximal activity. Further, this substance appears to induce both a subset of OKT4+ (Class II MHC-restricted) and OKT8+ (Class I MHC-restricted) blasts.


Influence of Sn4+ ion on band gap tailoring, optical, structural and dielectric behaviors of ZnO nanoparticles.
II-VI semiconductors are being attracted due to excellent optical and electronic behaviors when they utilize for device fabrication. Among II-VI semiconductors, Zinc oxide finds cutting-edge results for various applications with a lack of toxicity. Sn4+ ion incorporated ZnO nanoparticles have been synthesized using a soft chemical route and characterized for the investigation of properties like structural, morphological, elemental, optical and dielectric responses. The prepared ZnO had a hexagonal structure and the particles size reduces by the influence of Sn4+ ion: this reduction rate increases for the increase of doping ratio. The average particles size was estimated within 24-34 nm. TEM, HRTEM and SEM results corroborate the structural aspects noticed using XRPD study. UV-vis study results showed that a blue shift on the optical band gap was received for high doping concentration (10 at.%) of Sn4+. PL peaks were observed in the UV region for 0 at.% and 2 at.% Sn4+ doped ZnO nanoparticles, and the peak position was shifted from UV to violet and blue region for 10 at.% Sn4+ doped ZnO nanoparticles. The dielectric permittivity was reduced due to the addition of Sn4+ ions. The AC conductivity was increased for higher doping concentrations. The Sn4+ ion incorporated ZnO nanoparticles shall be useful for various applications including LED fabrication for blue emission and also it is suitable to act as a buffer material in solar panel.


Why does age at HIV infection correlate with set point viral load? An evolutionary hypothesis.
Set-point viral load (SPVL) correlates with the age at which people acquire HIV. Although immunosenescence may seem like a parsimonious explanation for this, it does not easily explain the observation that the relationship between age and SPVL attenuates when accounting for source partner SPVL. Here we propose an alternative explanation that encompasses this latter finding: that decreasing risk of acquisition with older age generates a selection bottleneck that selects for more virulent strains with age. We adapted a previously published model of HIV transmission and evolution (EvoNetHIV), parameterized here for men who have sex with men (MSM). We conducted a series of simulation experiments that vary seven behavioral or clinical parameters that affect exposure risk as people age. We conducted regressions to determine the mean increase in SPVL per 10-year increase in seroconversion age, with and without source SPVL in the model. All runs generated significant relationships between seroconversion age and SPVL when not including source SPVL. All saw attenuated relationships, most to near 0, with source SPVL included. Four of our behavioral measures (relational duration, age-related homophily, coital frequency, and mean age at relationship formation) had clear effects on this relationship, all in the hypothesized direction. Combining multiple forms of behavioral heterogeneity yielded an increase of 0.056 log10 copies/mL SPVL per 10-year increase in seroconversion age, nearly as large as that seen in two empirical studies of age-SPVL correlations in MSM. The higher virulence of HIV among those infected later in life may be partly explained by a combination of selective bottlenecks and behavioral heterogeneity by age. Variation in the strength of this effect across populations may be in part due to different behavioral, epidemiological and clinical conditions, and not require assumptions about differences in patterns of immunosenescence among populations.


Proton translocation driven by ATP hydrolysis in V-ATPases.
The vacuolar H(+)-ATPases (or V-ATPases) are a family of ATP-dependent proton pumps responsible for acidification of intracellular compartments and, in certain cases, proton transport across the plasma membrane of eukaryotic cells. They are multisubunit complexes composed of a peripheral domain (V(1)) responsible for ATP hydrolysis and an integral domain (V(0)) responsible for proton translocation. Based upon their structural similarity to the F(1)F(0) ATP synthases, the V-ATPases are thought to operate by a rotary mechanism in which ATP hydrolysis in V(1) drives rotation of a ring of proteolipid subunits in V(0). This review is focused on the current structural knowledge of the V-ATPases as it relates to the mechanism of ATP-driven proton translocation.


Annual atrial tachyarrhythmia burden determined by device interrogation in patients with cardiac implanted electronic devices is associated with a risk of ischaemic stroke independent of known risk factors.
This study evaluated the risk of non-fatal ischaemic stroke associated with increased long-term cumulative duration of atrial tachycardia (AT). We retrospectively reviewed the records of 260 patients with cardiovascular implantable electronic devices capable of monitoring AT. Patients were separated into zero, low and high AT burden groups. The cut-off point between low and high AT burden was defined by the median value of AT burden in the non-zero AT burden groups (5% in 1 year, about 18 days annually). The primary outcome was non-fatal ischaemic stroke. The mean patient age was 63.3 ± 13.7 years, the average follow-up was 7.0 years and 10 patients had strokes. Multivariate analysis showed only hypertension and a diagnosis of atrial fibrillation (AF) were associated with stroke. The risk of stroke in patients with hypertension was 12.57-fold higher than in those without hypertension, and was 20.81-fold higher in patients with paroxysmal AF and 162.59-fold higher in patients with chronic AF than in those without AF. Kaplan-Meier analysis showed that stroke-free survival was significantly different in the three AT burden groups (P = 0.002, long-rank test); the rate was greatest in the zero AT burden group, followed by the low AT burden group and was lowest in the high AT burden group. Patients who accumulated an AT duration exceeding 5% (18 days) of the total time in any of the 1-year periods are more likely to have an ischaemic stroke than those who have a low or zero AT burden.


Do maternal demographics and prenatal history impact the efficacy of betamethasone therapy for threatened preterm labor?
Betamethasone (BMZ) is used to accelerate fetal lung maturation in women with threatened preterm birth, but its efficacy is variable and limited by the lack of patient individualization in its dosing and administration. To determine sources of variability and potential opportunities for individualization of therapy, the objective of this study was to evaluate maternal factors associated with development of neonatal respiratory distress syndrome (RDS) in a cohort of women who received betamethasone. This study prospectively enrolled women, gestational ages 23-34 weeks, who received betamethasone for threatened preterm birth. Maternal demographics, prenatal history, and neonatal outcomes were abstracted from hospital records. RDS was the primary outcome. Associations between RDS diagnosis and maternal demographics, prenatal history, and betamethasone dosing were evaluated in a case-control analysis and multivariable regression adjusted for gestational age at delivery. Secondary analyses limited the cohort to women who delivered within 1 or 2 weeks of betamethasone dosing. Of 209 deliveries, 90 (43 %) resulted in neonatal RDS. Within the overall cohort and controlling for gestational age at birth, RDS was only associated with cesarean births compared to vaginal births (adjusted OR 1.17 [1.06-1.29]). Route of delivery was also the only significant factor related to RDS in the 83 neonates delivered within 7 days of BMZ dosing. However, among 101 deliveries within 14 days of betamethasone dosing and controlling for gestational age at birth, women who experienced preterm premature rupture of membranes (PPROM) had lower RDS rates than those without PPROM (57.9 % vs. 80.2 %, adjusted OR 0.81 [0.67-0.99]). Maternal age, BMI, race, and ethnicity were not associated with RDS in the regression models. Of maternal characteristics analyzed, only delivery by cesarean was associated with neonatal RDS after antenatal betamethasone use.


Plasma amyloid beta level changes in aged mice with cognitive dysfunction following sevoflurane exposure.
Previous studies have stated that cognitive impairment induced by anesthetics was associated with amyloid beta (Aβ). However, few researchers have investigated the transport of Aβ inside and outside of the brain. We attempted to probe the effects of sevoflurane on cognitive functions, the plasma Aβ, and transporters of Aβ in aged mice. The receptor for advanced glycation end-products (RAGE) is an Aβ influx protein, and Low-density lipoprotein receptor-related protein-1 (LRP-1) is an Aβ efflux protein. Aged mice were divided into the control group and the sevoflurane group. The mice were exposed to 100% oxygen or 2.5% sevoflurane for 2 h. The abilities of spatial learning and memory in mice were tested using the Morris water maze. Aβ concentrations of plasma were measured with enzyme-linked immunosorbent assay kits. The RAGE and LRP-1 gene levels in the brain were assessed with quantitative polymerase chain reaction, and the protein levels were determined by western blot analysis. The locations of RAGE in the brain were confirmed via immunofluorescence. In the sevoflurane group mice, the escape latency was increased on the 5th day of training, and the time spent in the target quadrant was decreased on the 7th day after anesthesia. Sevoflurane reduced the concentration of plasma Aβ1-40. In addition, sevoflurane increased both gene and protein levels of RAGE in the brain, and increased RAGE proteins co-localized with the hippocampal vascular endothelial cells. RAGE over-expression in the hippocampal vascular endothelial cells possibly resulted in the excessive transport of the plasma Aβ1-40 into the brain after treatment with sevoflurane, which was associated with sevoflurane-induced cognitive dysfunction in aged mice.


[Leiomyosarcoma of the renal capsule: ultrasonographic and angiographic appearances: a case report (author's transl)].
A 70-year-old patient presented with general ill-health, and a mass in the right hypochondrium which was found to be a leiomyosarcoma of the renal capsule. Ultrasonography demonstrated the retroperitoneal origin of the tumor and its lack of relation with the right kidney. Arteriography showed the right renal capsule origin of the mass, with partial invasion of the inferior vena cava. Operation confirmed the angiographic findings, particularly the independent nature of the mass i relation to the kidney and the excretory pathways.


The turnover of skeletal muscle glycogen phosphorylase studied using the cofactor, pyridoxal phosphate, as a specific label.
The turnover of glycogen phosphorylase has been measured using the cofactor, pyridoxal phosphate, as a label specific for this enzyme in skeletal muscle. Radiolabelled pyridoxine administered in vivo is incorporated into a protein-bound fraction in skeletal muscle, shown by several criteria to be equivalent to glycogen phosphorylase. This pool of radiolabel disappears slowly with a half-life of 11.9 days, taken to be a good estimate of the intracellular half-life of the enzyme. The use of the cofactor in this fashion minimises overestimation of half-life that results from reincorporation of the label. Further, premature dissociation of the cofactor from native enzyme, which would lead to underestimation of half-life, is unlikely. At the level of sensitivity given by this method there was little evidence for the appearance of pyridoxal phosphate-labelled degradation intermediates of the enzyme.


Effects of different household cooking methods on the biological properties of Chinese yam.
Yam (Dioscorea opposite Thunb) is used as a staple food and a traditional medicine in China. This study investigated the effects of different household cooking methods on the bioactive components (phenolic compounds, diosgenin and allantoin) and their bioaccessibility as well as the biological properties (antioxidant activity, hypoglycemic activity, anti-angiotensin I-converting enzyme (ACE) or anti-acetylcholinesterase (AChE)) of Chinese yam using an in vitro simulated digestion model. The results demonstrated that cooking caused significant losses of total soluble phenolic compounds (lowest loss of 20% for boiling at atmospheric pressure) and diosgenin content (lowest loss of 27.37% for microwaving) but no changes in the allantoin content. The cooking methods affected the bioaccessibility of the bioactive components differently. Normal steaming resulted in the highest amount of bioaccessible phenolic compounds (71.21%) and allantoin (79.07%), whereas high-pressure boiling in the highest content of diosgenin (75.58%). The concentration of bioactive components in the digesta fluid was correlated with the antioxidant activity and enzymatic inhibitory activities. Overall, household cooking processes allow the biological activity of yam to be retained by changing the profile of bioactive components potentially available for intestinal absorption. Thus, a household cooking method such as normal pressure steaming appeared to be most suitable for achieving the expected health benefits of yam.


Newer antidepressants and other nonhormonal agents for the treatment of hot flashes.
The reluctance to use estrogen in breast cancer survivors with hot flashes has extended to its use in healthy women since the 2002 publication of the Women's Health Initiative study. This article reviews the clinical development of nonhormonal agents as alternatives to hormonal therapy for the management of hot flashes.


Hyponatraemia Associated with the Use of Quetiapine: Case Report.
Hyponatraemia is the most common electrolyte disturbance in the elderly. It can be asymptomatic or produce a spectrum of symptoms, particularly in the central nervous system, such as altered state of consciousness, lethargy, headache, seizures and gait disturbances, all of which are a common reason for consultation in this population. This condition has a high impact on the functionality of the patient given the need for multiple hospital stays, as well as on mortality. Its aetiology is multifactorial and its most common causes include low salt intake, chronic diseases such as kidney disease and heart failure, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is commonly caused by the chronic use of certain drugs, such as antidepressants, diuretics and antipsychotics, which are the most forgotten in clinical practice. The following clinical case presents the diagnostic approach of hyponatraemia and the importance of the medical history as a key tool to detect the aetiology of this clinical entity.


[Analysis of reproductive parameters in mare herds of the chief and state stud farms at Marbach and Schwaiganger].
The paper analyses different parameters of fertility in mares of different breeds. Totally 2794 cycles of the years 1973 to 1985 have been investigated.


The changing composition of urinary calculi in Southern Thailand over the past 14 years.
A worldwide increased incidence of urolithiasis has been observed over the past few decades. Insight into the composition of these stones can lead to enhanced medical treatment and outcomes. The objective of this study was to examine the distribution and chemical composition of urinary calculi in Southern Thailand over the past decade. An analysis was conducted on 2611 urinary calculi submitted to the Stone Analysis Laboratory, Songklanagarind Hospital, a single stone analysis laboratory in Southern Thailand. The analysis was performed from 2007 to 2020 using Fourier-transform infrared spectroscopy. The demographic results were described using descriptive statistical analyses, and the Chi-square test for trends was performed to identify changes in urinary calculi composition. The patients' demographic data revealed a male-to-female ratio of 2.2:1; the most common age group of affected men was 50-69 years, whereas the most common age group of affected women was 40-59 years. The most common components found in the calculi were uric acid (30.6%), mixed calcium oxalate with calcium phosphate (29.2%), and calcium oxalate (26.7%). We noted a trend of increasing uric acid calculi for 14 years (P = 0.00493), whereas the trend for the other major components was decreasing. The most common component of urinary calculi analyzed in Southern Thailand was uric acid, with a significant rising trend in proportion in the past decade; the trend of other major components, such as mixed calcium oxalate-calcium phosphate and calcium oxalate, decreased.


Melatonin modulates rat myotube-acetylcholine receptors by inhibiting calmodulin.
Melatonin, the pineal gland hormone, modulates alpha-bungarotoxin sensitive nicotinic acetylcholine receptors in sympathetic nerve terminals, cerebellum and chick retina imposing a diurnal variation in functional responses [Markus, R.P., Zago, W.M., Carneiro, R.C., 1996. Melatonin modulation of presynaptic nicotinic acetylcholine receptors in the rat vas deferens. J. Pharmacol. Exp. Ther. 279, 18-22; Markus, R.P., Santos, J.M., Zago, W., Reno, L.A., 2003. Melatonin nocturnal surge modulates nicotinic receptors and nicotine-induced [3HI] glutamate release in rat cerebellum slices. J. Pharmacol. Exp. Ther. 305, 525-530; Sampaio, L.F.S., Hamassaki-Britto, D.E., Markus, R.P., 2005. Influence of melatonin on the development of functional nicotinic acetylcholine receptors in cultured chick retinal cells. Braz. J. Med. Biol. Res. 38, 603-613]. Here we show that in rat myotubes forskolin and melatonin reduced the number of nicotinic acetylcholine receptors expressed in plasma membrane. In addition, these cells expressed melatonin MT1 receptors, which are known to be coupled to G(i)-protein. However, the pharmacological profile of melatonin analogs regarding the reduction in cyclic AMP accumulation and number of nicotinic acetylcholine receptors did not point to a mechanism mediated by activation of G(i)-protein coupled receptors. On the other hand, calmidazolium, a classical inhibitor of calmodulin, reduced in a similar manner both effects. Considering that one isoform of adenylyl cyclase present in rat myotubes is regulated by Ca2+/calmodulin, we propose that melatonin modulates the number of nicotinic acetylcholine receptors via reduction in cyclic AMP accumulation.


Excitable dynamics of Physarum polycephalum plasmodial nodes under chemotaxis.
Recent results show that the chemotactic response of uni-cellular decentralized systems such as amoeboid and mammalian cells, is excitable. The same observation has not yet been reported for multi-nucleated decentralized biological systems. Here we present experimental results that shows the Physarum polycephalum plasmodial nodes spatio-temporal chemotactic dynamics as an excitable response. We found a highly optimized signal synthesis method wherein the Physarum nodes employ two intensity thresholds to properly navigate the chemoattractant field and generate corresponding spike dynamics in the node count. The node spike dynamics was found to correspond to the polarized-depolarized transition in the Physarum polycephalum morphology. Validation of our experimental observations via Brownian lattice simulations yields the same quantitative results with our experiments.


Direct derivation of the crystalline fraction of highly potent active pharmaceutical ingredients by X-ray powder diffraction.
Direct derivation (DD) is a novel Powder X-ray diffraction quantification method based on intensity-composition equation, which can determine the weight fraction of individual phases in a mixture of components by chemical formulas . The DD method was applied to determine crystallinity degree of binary mixtures containing amorphous hydroxypropyl methylcellulose and crystalline monohydrate α-lactose in weight percentage ≤ 15% w/w. Three different scenarios were considered: a) the unit cell parameters of the crystalline phases are available b) the unit cell parameters are unknown but the patterns of pure crystalline and amorphous references are available and c) only the mixtures' patterns are available. Relative errors in scenarios a and b were comparable and reasonable (<20%), while in c, the crystalline degree was clearly underestimated evidencing the importance of determining the maximum number of crystalline reflections This can be easily achieved when the unit cell parameters and/or the patterns of pure references are available. To simulate the quantification of high potent API, the method was evaluated considering the scenario b, in samples covered by Kapton® film as containment system. In this case, an accurate quantification was achieved by subtracting the film signal from the observed pattern.


Convulsions in pregnancy in related gorillas.
Two related gorillas, the second the granddaughter of the first, had pregnancies complicated by convulsions and edema. They may have suffered from eclampsia, indicating that this is not an exclusively human disease and that in gorillas, as in humans, there is a familial factor.


Introduction to Special Issue: Interventions to Modify Psychological Well-Being and Population Health.
Psychological ill-being is on the rise, with 1 in 5 Americans suffering from a mental disorder in any given year. Additional evidence demonstrates that psychological well-being has also decreased over time. These trends are particularly worrisome given the substantial and growing body of evidence demonstrating that psychological ill-being (e.g., depression, anxiety, anger) is associated with an elevated risk of developing chronic diseases and premature mortality, while aspects of psychological well-being (e.g., positive affect, sense of purpose and meaning, life satisfaction) are independently associated with improved physical health outcomes. An underexplored but promising approach to enhancing both psychological and physical health is through developing a set of tools that specifically target psychological well-being (often referred to as positive psychological interventions (PPIs) although many interventions developed outside the field of positive psychology also achieve these goals). Such interventions hold promise as a strategy for improving population health. However, critical knowledge gaps hold us back, and we have not yet developed a robust set of intervention strategies that can improve psychological well-being in meaningful, durable, and scalable ways that would also have downstream effects on physical health. The goal of this special issue is to help address these knowledge gaps by bringing together current conceptual frameworks, critical examination of key constructs, and novel empirical evidence needed to identify and examine interventions that can modify psychological well-being, particularly those that have the potential to be scaled at the population level and with durable effects.


Improved preparative enzymatic glycosylation of vancomycin aglycon and analogues.
Modifications to the enzymatic glycosylation of vancomycin and its residue 4 thioamide analogue are detailed that significantly reduce the enzyme loading and amount of glycosyl donor needed for each glycosylation reaction, provide a streamlined synthesis and replacement for the synthetic UDP-vancosamine glycosyl donor to improve both access and storage stability, and permit a single-pot, two-step conversion of the aglycons to the fully glycosylated synthetic glycopeptides now conducted at higher concentrations. The improvements are exemplified with the two-step, one-pot glycosylation of [Ψ[C(=S)NH]Tpg4]vancomycin aglycon (92%) conducted on a 400 mg scale (2 mg to 1 g scales) and vancomycin aglycon itself (5 mg scale, 84%).


Genetics of diabetic retinopathy.
Diabetic retinopathy (DR) is a polygenic disorder. Twin studies and familial aggregation studies have documented clear familial clustering. Heritability has been estimated to be as high as 27 % for any DR and 52 % for proliferative diabetic retinopathy (PDR), an advanced form of the disease. Linkage analyses, candidate gene association studies and genome-wide association studies (GWAS) performed to date have not identified any widely reproducible risk loci for DR. Combined analysis of the data from multiple GWAS is emerging as an important next step to explain the unaccounted heritability. Key factors to future discovery of the genetic underpinnings of DR are precise DR ascertainment, a focus on the more heritable disease forms such as PDR, stringent selection of control participants with regards to duration of diabetes, and methods that allow combination of existing datasets from different ethnicities to achieve sufficient sample sizes to detect variants with modest effect sizes.


Live cell imaging of paxillin in rolling neutrophils by dual-color quantitative dynamic footprinting.
Neutrophil recruitment to sites of inflammation involves P-selectin-dependent rolling. qDF is a useful tool to visualize the topography of the neutrophil footprint as it interacts with the substrate. However, elucidating the role of specific proteins in addition to topography requires simultaneous visualization of two fluorochromes. To validate DqDF, mouse neutrophils were labeled with the membrane dyes DiO and DiI and perfused into microchannels coated with P-selectin-Fc. Footprints of rolling neutrophils were recorded as two separate images, one for each fluorochrome. To assess the localization of the cytoskeletal protein paxillin, we applied DqDF to DiO-stained neutrophils of mice expressing an mCherry-paxillin fusion protein. The footprint topographies obtained from DiO and DiI in the plasma membrane were identical. The z-coordinates of the microvilli tips obtained with the two fluorochromes in the footprint were also identical. Paxillin was found to be localized to some, but not all ridges in the neutrophil footprint. Our data suggest that the spectral properties of the fluorochrome do not affect the results. DqDF will be useful for simultaneous visualization of two fluorochromes in the footprint of rolling cells.