Unfolded protein response signature unveils novel insights into breast cancer prognosis and tumor microenvironment.
The critical role of the unfolded protein response (UPR) in tumorigenesis is widely acknowledged, yet the precise molecular mechanisms underlying its contribution to breast cancer (BC) have not been fully elucidated. The present study aimed to comprehensively explore the expression characteristics and prognostic significance of UPR-related genes in breast cancer METHODS: The transcriptome and clinical data of breast cancer were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. Differential expression analysis was conducted on UPR-related genes, and the resulting genes were employed for consensus clustering analysis. A breast cancer prognosis risk model was constructed using univariate, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression analyses. Difference in survival outcomes between groups were analyzed Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curve was used to assess predictive performance. The relationship between the risk model and clinical-pathological characteristics, immune infiltration, immunotherapy response, and drug sensitivity was assessed. Differential expression analysis identified 10 UPR-related genes that were differentially expressed in breast cancer. Using the expression matrix of these genes, two molecular subtypes of breast cancer were characterized, which displayed significant differences in prognostic and immune infiltration characteristics. Drawing from the gene expression profiles that distinguish between the molecular subtypes, a prognostic risk scoring model comprising eight genes was developed. This model stratified BC patients from both the training and validation cohorts into high-risk and low-risk groups. Patients in the low-risk group had better prognoses, while those with advanced clinical stage and T stage exhibited higher risk scores. The high- and low-risk groups exhibited notable disparities in immune cell infiltration and the expression of multiple immune checkpoint-related genes. Additionally, the low-risk group demonstrated elevated immunophenoscore, Merck18, CD274, and CAF scores compared to the high-risk group, along with a lesser sensitivity to chemotherapy drugs. These results suggest that patients within the low-risk group may potentially benefit more from immunotherapy and chemotherapy interventions. This study developed a novel UPR-derived risk signature, which could robustly predict the survival outcome, immune microenvironment, and chemotherapy response of patients with breast cancer.


Effects of mild wintering conditions on body mass and corticosterone levels in a temperate reptile, the aspic viper (Vipera aspis).
Temperate ectotherms are expected to benefit from climate change (e.g., increased activity time), but the impacts of climate warming during the winter have mostly been overlooked. Milder winters are expected to decrease body condition upon emergence, and thus to affect crucial life-history traits, such as survival and reproduction. Mild winter temperature could also trigger a state of chronic physiological stress due to inadequate thermal conditions that preclude both dormancy and activity. We tested these hypotheses on a typical temperate ectothermic vertebrate, the aspic viper (Vipera aspis). We simulated different wintering conditions for three groups of aspic vipers (cold: ~6 °C, mild: ~14 °C and no wintering: ~24 °C) during a one month long period. We found that mild wintering conditions induced a marked decrease in body condition, and provoked an alteration of some hormonal mechanisms involved in emergence. Such effects are likely to bear ultimate consequences on reproduction, and thus population persistence. We emphasize that future studies should incorporate the critical, albeit neglected, winter season when assessing the potential impacts of global changes on ectotherms.


Absence of genotoxic activity of refined smoke flavor (RSF) in two bacterial short-term tests.
The genotoxic activities of refined smoke flavor (RSF) produced in Poland and used in food processing were investigated in 2 bacterial short-term tests. Its mutagenic activity was examined in the Salmonella/histidine plate assay and its SOS-inducing capacity in the SOS Chromotest both without and with 'activation' by a rat liver homogenate. No genotoxic activity was detected using these 2 bacterial tests.


A school- and community-based intervention to promote healthy lifestyle and prevent type 2 diabetes in vulnerable families across Europe: design and implementation of the Feel4Diabetes-study.
To describe the design of the Feel4Diabetes-intervention and the baseline characteristics of the study sample. School- and community-based intervention with cluster-randomized design, aiming to promote healthy lifestyle and tackle obesity and obesity-related metabolic risk factors for the prevention of type 2 diabetes among families from vulnerable population groups. The intervention was implemented in 2016-2018 and included: (i) the 'all-families' component, provided to all children and their families via a school- and community-based intervention; and (ii) an additional component, the 'high-risk families' component, provided to high-risk families for diabetes as identified with a discrete manner by the FINDRISC questionnaire, which comprised seven counselling sessions (2016-2017) and a text-messaging intervention (2017-2018) delivered by trained health professionals in out-of-school settings. Although the intervention was adjusted to local needs and contextual circumstances, standardized protocols and procedures were used across all countries for the process, impact, outcome and cost-effectiveness evaluation of the intervention. Primary schools and municipalities in six European countries. Families (primary-school children, their parents and grandparents) were recruited from the overall population in low/middle-income countries (Bulgaria, Hungary), from low socio-economic areas in high-income countries (Belgium, Finland) and from countries under austerity measures (Greece, Spain). The Feel4Diabetes-intervention reached 30 309 families from 236 primary schools. In total, 20 442 families were screened and 12 193 'all families' and 2230 'high-risk families' were measured at baseline. The Feel4Diabetes-intervention is expected to provide evidence-based results and key learnings that could guide the design and scaling-up of affordable and potentially cost-effective population-based interventions for the prevention of type 2 diabetes.


Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga.
To assess therapeutic efficacy of sulfadoxine-pyrimethamine (SP) in treatment of uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga, South Africa. Tonga district with a population of 116,418 and subject to seasonal malaria, with an average annual incidence of 3,200 cases. One hundred and nineteen malaria patients presenting to a sentinel surveillance clinic and recruited according to World Health Organisation (WHO) criteria. Patients satisfying WHO inclusion criteria were treated with a single oral dose of SP and the response of infection to treatment in each patient was routinely monitored clinically and parasitologically on days 1, 2, 3, 7, 14, 21, 28 and 42 post-treatment. One hundred and ten patients completed follow-up to day 42 or evidence of clinical or parasitological failure. The cure rate at day 42 was 93.6% (103/110). Two patients (1.8%, RII) were early treatment failures on day 3, while recrudescence (4.5%, RI) occurred in 5 patients on day 28 (N = 3) and on day 42 (N = 2). In Mpumalanga P. falciparum remains sensitive to SP, with no significant difference between the baseline cure rate (94.5%) and the cure rate in the present study (93.6%).


Detection of Transglutaminase 2 conformational changes in living cell.
Transglutaminase 2 (TG2) is a ubiquitous Ca(2+)-dependent protein cross-linking enzyme that is implicated in a variety of biological disorders. In in vitro experiments when Ca(2+) concentration was increased TG2 changed its conformation and was able to cross-link other proteins via formation of an isopeptide bond. However the mechanisms that regulate TG2 transamidation activity in cells are still unknown. In this study we have developed FRET-based method for monitoring TG2 conformation changes and, probably, cross-linking activity in living cells. Using this approach we have showed that a significant amount of TG2 within the cell is accumulated in perinuclear endosomes and has a cross-linking inactive conformation, while TG2 that is located beneath the cell membrane has a transamidation active conformation. After the induction of apoptosis cytoplasmic TG2 changed its conformation and activates while, TG2 in endosomes retained transamidation inactive conformation even at late stages of apoptosis.


Upper-arm anthropometry: an alternative indicator of nutritional health to body mass index in unilateral lower-extremity amputees?
To evaluate the utility of body mass index (BMI) and corrected-arm-muscle area (CAMA) as measures of nutritional health for lower-limb amputees attending prosthetics clinics. Cross-sectional study. Prosthetics clinic in Australia. Unilateral lower-extremity amputees (N=58; age range, 21-91y; 37 transtibial, 21 transfemoral) attending a regional prosthetics clinic between May and November 2003. Not applicable. Weight (without prosthesis), corrected and uncorrected for the amputated limb was used with height estimated from knee height to calculate corrected BMI (cBMI) and uncorrected BMI (uBMI). CAMA was calculated using the mean of triplicate mid-upper-arm circumference (MUAC) and triceps skinfold thickness (TST) measurements. The Mini Nutritional Assessment (MNA) and Assessment of Quality of Life were administered according to recommended protocols. The Pearson correlation was used to determine the strength and significance of associations between variables, and bivariate regression analyses were performed to determine whether an association existed between the nutritional variables (BMI, CAMA, MNA) and quality of life (QOL). There were no statistically significant differences in the measures of nutritional health according to site (transtibial, transfemoral) of amputation. MUAC, TST, and CAMA all showed moderate to high positive correlations (r range, .541-.782) with both cBMI and uBMI. The strength of the relationship between the MNA and cBMI/uBMI was weaker (r=.383, r=.380, respectively) but remained positive and statistically significant (P=.003). QOL was not associated with cBMI or uBMI but was related to CAMA (beta=-.132; P=.030) and MNA (beta=-.561; P=.017). For persons with unilateral lower-extremity amputation, measurement of upper-arm anthropometry may be a more useful indicator of nutritional health and its consequences than BMI.


Exploring the impacts of heavy metals on spatial variations of sediment-associated bacterial communities.
One of the fundamental objectives in modern ecology is to decipher how bacterial communities in natural environment respond to anthropogenic activities. In recent times consequences of marine pollution, especially with heavy metals (HMs) have received increasing attention. However, insights into the response of bacterial communities to HMs in coastal sediments of India remain scarce. Here, we analyzed HMs content in three areas, along the southern coastal region of India. Based on the calculated pollution indices viz., enrichment factor (EF), contamination factor (CF), geo-accumulation index (Igeo) and sediment quality guidelines (SQGs), the studied areas were classified as uncontaminated, moderately contaminated and significantly contaminated. To explore the response of bacterial community to HMs, sediment-associated microbiota was investigated using high-throughput 16S rRNA gene amplicon sequencing. The obtained metataxonomic results revealed that bacterial diversity and community composition varied considerably in significantly contaminated area than moderately contaminated and uncontaminated areas. Proportion of bacterial classes was higher for Gammaproteobacteria, Betaproteobacteria and Actinobacteria, but lower for Alphaproteobacteria and Flavobacteriia in significantly contaminated area. Also, samples of significantly contaminated area were dominated by well-documented metal-resistant bacterial genera such as Ralstonia and Arthrobacter. Canonical correspondence analysis (CCA) showed that spatial variability of bacterial community composition was strongly correlated with HMs content such as Chromium, Cadmium and Nickel. Further analysis using PICRUSt programme indicated that the predictive functional profile also varied considerably in significantly contaminated area. By linking HMs with bacterial compositional variations, the present study highlights the likely influence of HMs in shaping sedimentary microbiota of coastal regions.


Fulvic acid enhanced peroxymonosulfate activation over Co-Fe binary metals for efficient degradation of emerging bisphenols.
Bisphenol F (BPF) and bisphenol S (BPS) are emerging bisphenols, which have become the main substitutes for bisphenol A (BPA) in industrial production and are also considered as new environmental pollution challenges. Thus, the necessity for an effective approach to remove BPF and BPS is essential. In this study, fulvic acid (FA) was used to modify Co-Fe binary metals (CFO) for peroxymonosulfate (PMS) activation. The characterization results demonstrated that CFO changed significantly in morphology after compounding with FA, with smaller particle size and 5.6 times larger specific surface area, greatly increasing the active sites of catalyst; Moreover, humic acid-like compounds increased the surface functional groups of CFO, especially phenolic hydroxyl, which could effectively prolong the PMS activation. The concentration of all reactive species, such as SO4•-, •OH, O2•-, and 1O2 increased in FA@CFO/PMS system. As a result, the degradation efficiency of CFO for both BPF and BPS was significantly improved after compounding FA, which also had a wide range of pH applications. The degradation pathways of both BPF and BPS were proposed based on liquid chromatography-mass spectrometry (LC-MS) analysis and the density functional theory (DFT) calculations. Our findings are expected to provide new strategies and methods for remediation of environmental pollution caused by emerging bisphenols.


Electric field-enhanced coupled with metal-free peroxymonosulfate activactor: The selective oxidation of nonradical species-dominated system.
Nowadays metal-free persulfate-based advanced oxidation processes (AOPs) have been intensively investigated, however, the catalysts are often too complex to fully consider their application potential. Conventional AOPs usually suffer from severe interference in real water matrix, thus, selective oxidation is practically and scientifically challenging as it could avoid unnecessary inputs of energy and possible secondary pollutants. In this study, a remarkably synergistic effect was achieved when conventional amorphous boron/peroxymonosulfate (Boron/PMS, 0.67 × 10-2 min-1) system was combined with electrolysis (E-Boron/PMS, 1.54 × 10-2 min-1) to degrade sulfamethoxazole (SMX). Evidenced by selectively quenching tests with kinetic evaluation, electron paramagnetic resonance (EPR), solvent-exchange experiment and electrochemical analysis, the dominated reactive oxygen species in E-Boron/PMS system tended to be 1O2, instead of the •OH and SO4•-. Mechanistic study unveiled that 1O2 was generated via accelerated PMS self-decomposition, triggered by interface alkalization and hydroxyl radicals transfer at the cathode interface. 1O2 is considered to be selective to the electron-rich organic compounds, thus E-Boron/PMS system was superior to conventional radical-dominated system (Boron/PMS) for SMX removal in the co-presence of common inorganic anions, showing the great merits of selective oxidation in nonradical system. These findings provided new insights into effective and selective oxidation of SMX via E-Boron/PMS system, which shed new light on the development of nonradical system.


Use of 0.3% triclosan (Bacti-Stat) to eradicate an outbreak of methicillin-resistant Staphylococcus aureus in a neonatal nursery.
Once established in an institution, methicillin-resistant Staphylococcus aureus (MRSA) outbreaks have proved difficult to eradicate, despite intensive infection control measures. This report describes the nosocomial infection with MRSA of 22 male infants in a neonatal nursery during a 7-month period and the infection control procedures that effectively brought this outbreak under control and eliminated recurrence for more than 3 1/2 years. After a single index case of bullous impetigo caused by MRSA in a neonate discharged from the nursery 2 weeks previously, an additional 18 cases of MRSA skin infections were clustered in a 7-week period. Aggressive infection control measures were instituted, including changes in umbilical cord care, circumcision procedures, diapers, handwashing, gloves, gowns, linens, disinfection, placement in cohorts of neonates and staff, surveillance, and monitoring. These measures were not effective in slowing the outbreak. The single additional measure of changing handwashing and bathing soap to a preparation containing 0.3% triclosan (Bacti-Stat) was associated with the immediate termination of the acute phase of the MRSA outbreak. The nursery has remained free of MRSA for more than 3 1/2 years, attesting to the success of our program.


What can we learn from cancer of unknown primary in canine oncology?
Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumors that lack an identifiable primary site despite an extensive diagnostic work-up. It is a well-recognized entity that is characterized by early dissemination, aggressive clinical course, unpredictable metastatic pattern, intrinsic treatment resistance, and a dismal prognosis. Despite the molecular diagnostic workup and personalized therapy, the expected improvements in the diagnosis and treatment of CUP have not been achieved. Comparative oncology has a promising role in the exchange of knowledge and practices between humans and canines. Therefore, we intended to review the literature reporting on CUP in dogs in order to identify some interesting parallels and unique results that could be transposed to in-human research.


Effect of different interset rest intervals on mean velocity during the squat and bench press exercises.
This study aimed to compare the effect of three interset rest intervals (1, 3, and 5 minutes) on (I) mean velocity during a resistance training session conducted in a Smith machine with the squat and bench press exercises, and (II) the pre- and post-exercise force-velocity relationship. Fifteen male university students completed three sessions (i.e., Rest 1', Rest 3', and Rest 5') consisting of three sets of five repetitions against the 10RM load during the squat and bench press exercises. The force-velocity relationship (maximal values of force [F0], velocity [v0], and power [Pmax]) was evaluated at the beginning and at the end of each session with the countermovement jump and bench press throw exercises. During training, mean velocity was slower in sets 2 and 3 of the Rest 1' protocol compared to Rest 3' and Rest 5', but no significant differences were present between Rest 3' and Rest 5'. After training, there was a significant decrease in F0 (p = 0.017) and Pmax (p = 0.010), but not in v0 (p = 0.259). These results support the Rest 3' as the most time-efficient protocol, among those analysed, for the maintenance of high mean velocities during training sessions not leading to failure.


Inbreeding load and inbreeding depression estimated from lifetime reproductive success in a small, dispersal-limited population.
The fitness consequences of inbreeding and the individual behaviors that prevent its detrimental effects can be challenging to document in wild populations. Here, we use field and molecular data from a 17-year study of banner-tailed kangaroo rats (Dipodomys spectabilis) to quantify the relationship between inbreeding, mate kinship, and lifetime reproductive success. Using a pedigree that was reconstructed using genetic and field data within a Bayesian framework (median probability of parental assignment = 0.92, mean pedigree depth = 6 generations), we estimated both inbreeding coefficients and kinship between individuals that produced offspring (mean inbreeding coefficient = 0.07, mean mate kinship = 0.08). We also used the pedigree, in combination with census data, to generate a series of fitness estimates, ranging from survival to reproductive maturity to lifetime reproductive success. We found that the population's inbreeding load was low to moderate (0.98-4.66 haploid lethal equivalents) and increased with the time frame over which fitness was estimated (lowest for survival to maturity, highest for adult-to-adult reproductive success). Fitness decreased with increasing inbreeding coefficients. For example, lifetime reproductive success was reduced by 24% for individuals with inbreeding coefficients greater than twice the population mean. Within full sibling pairs, the sibling with less-related mates produced an average of 30% more offspring over its lifetime. These data further illustrate that inbreeding can have a negative effect on lifetime reproductive success.


Intraocular Pressure Measurement Using Ocular Response Analyzer, Dynamic Contour Tonometer, and Scheimpflug Analyzer Corvis ST.
To compare intraocular pressure (IOP) measurements with Goldmann applanation tonometry (GAT), ocular response analyzer (ORA), dynamic contour tonometer (DCT), and Corvis ST (CST) in healthy subjects. In a prospective, observational study, IOP measurements with GAT (GAT-IOPc), ORA (IOPcc), DCT (DCT-IOP), and CST (bIOP) were performed and analyzed in 94 healthy subjects. Mean age of the participants was 45.6 ± 17.2 years (range 18 to 81 years). Mean GAT-IOPc was 12.9 ± 2.4 mmHg, mean DCT-IOP was 16.1 ± 2.6 mmHg, and mean IOPcc was 15.6 ± 3.3 mmHg. DCT-IOP and IOPcc were significantly higher than GAT-IOPc (P < 0.001). Mean bIOP was 13.5 ± 2.4 mmHg that was slightly higher but not significantly different from GAT-IOPc (P=0.146). Correlation analysis of IOP values and central corneal thickness (CCT) revealed a negative correlation between GAT-IOPc and CCT (r = -0.347; P=0.001). However, IOPcc, DCT-IOP, and bIOP showed no significant correlation to CCT. Only bIOP revealed a weak but significant age dependency (r = 0.321, P=0.002). All tonometry devices showed a good agreement of biomechanical corrected IOP values with GAT-IOPc. As no influence of CCT on IOPcc, DCT-IOP, and bIOP was detectable, the used correction algorithms appear to be appropriate in these tonometers in the clinical setting. The highest agreement was found between GAT-IOPc and bIOP. However, bIOP weakly correlated with participants' age. Further studies are needed to elucidate the role of bIOP for IOP measurement.


Serum erythropoietic activity in acute anemia--an animal model.
Serum erythropoietic activity and reticulocyte response to anemia were investigated using a rabbit model. In hemolytic anemia, induced by injections of phenylhydrazine on Day 0 the hemoglobin reached a nadir (mean, 6.23 g/dl) on Day 4 when SEA was maximal (mean, 765 mU/ml). In animals venesected on Day 0 and Day 1 to produce anemia of equal severity, the SEA was maximal (mean 235 mU/ml) on Day 2. In both groups the reticulocyte response peaked on Day 7--at 34% for the hemolytic group and 21% for the venesected group. The 2,3-diphosphoglycerate, measured on Day 4, was significantly reduced in the PHZ-treated group. In the venesected group the 2,3-DPG increased between Day 0 and Day 4. There were no concurrent changes in acid-base balance. These results imply that the degree of anemia is only one of the factors which influence the level of circulating SEA.


New anti-malarial compounds from database searching.
In a serendipitous result, pharmacophores generated for the database searching for new non-nucleoside inhibitors of the HIV-1 reverse transcriptase enzyme unearthed 12 new lead compounds which were active against the Plasmodium falciparum strain of malaria.


The association between allergy and sinusitis: a cross-sectional study based on NHANES 2005-2006.
The relationship between allergies and sinusitis, though extensively studied, remains poorly defined. While several studies proposed a cause-and-effect relationship between allergy and chronic sinusitis, several others reported the lack of any existing association. This study aimed to investigate the relationship between allergy and sinusitis. We conducted a cross-sectional study using a representative sample of the US population from the National Health and Nutrition Examination Survey 2005‒2006 (n = 7244). A self-reported allergy questionnaire and total and allergen-specific IgE levels were used for analysis. Participants were divided into positive and negative allergy symptoms groups (PAS, NAS, respectively) to eliminate the influence of allergy symptoms on the apparent incidence of sinusitis. Pearson's chi-square test and the linear regression analysis using Durbin Watson test were used for statistical analysis. Sinusitis incidence in the PAS group (22.4%; 521/2327) was significantly higher than that in the NAS group (7.1%; 348/4917) [odds ratios (OR) = 3.788, 95% confidence interval (CI) 3.272‒4.384, P < 0.001]. sinusitis incidence in non-sensitized and sensitized groups was not statistically different. After controlling for allergy symptoms, there was a negative correlation between sensitization status and the occurrence of sinusitis in the PAS group (OR = 1.407, 95% CI 1.156‒1.711, P < 0.01). Increase in serum total IgE levels correlated with decrease in incidence of sinusitis in both PAS and NAS groups. sinusitis incidence was significantly reduced in the PAS group in participants sensitized to allergens such as cockroaches, ragweed, ryegrass, Bermuda grass, oak, birch, and thistle. Allergy is related to sinusitis incidence. It is likely that sensitization status could reduce the incidence of sinusitis, albeit in an antigen-specific manner.


Flattening the curve of mental ill-health: the importance of primary prevention in managing the mental health impacts of COVID-19.
The COVID-19 pandemic is one the biggest challenges the global community has faced this century. The threat of the virus coupled with the impacts of the social and economic shut-down measures required to slow its spread, appear to be impacting on people's mental health and wellbeing. Over the weeks, months and years ahead it is likely that many countries will experience a 'wave' of COVID-19 related mental disorders as a result of an increase in risk factors linked to the pandemic such as social isolation; unemployment; housing and income stress; intimate partner violence; work-related trauma; and grief and loss. The 'two-pronged' approach used to deal with COVID-19, provides an excellent blueprint for managing its mental health impacts as well. Nations must focus on preventing the occurrence of new-onset cases of mental disorders as well as strengthening their mental healthcare response to support people who become mentally unwell. A focus on primary prevention is particularly important to 'flatten the curve' and avoid a surge in incidence of mental disorders stemming from the COVID-19 pandemic. Evidence-based interventions designed to prevent common disorders are already available and should be scaled-up. These interventions include parenting programs, social and emotional learning programs, self-care strategies, and workplace mental wellbeing programs, among others.


Predictors of postoperative complications of tension band wiring techniques for patella fracture: A retrospective multicenter (TRON group) study.
The relationship between postoperative complications and operative techniques of tension band wiring (TBW) is not well studied. We aimed to evaluate the incidence of implant breakage, implant migration, and loss of reduction in patellar fractures treated with TBW and identify radiographic factors associated with these postoperative complications. This multicenter (named, TRON group) retrospective study included 224 patients who underwent open reduction and internal fixation of patella fractures using TBW from January 2016 to December 2020. Radiographic findings were evaluated by experienced orthopedic surgeons, and radiographic outcomes were assessed for K-wire migration, implant breakage, and loss of reduction. Logistic regression analysis was performed to identify radiographic factors associated with postoperative complications. Implant migration occurred in 44 cases (19.6%), with bending of a single K-wire end identified as a significant risk factor (OR: 12.90; 95% CI: 4.99-33.30; P < 0.001). Implant breakage occurred in 43 cases (19.2%), with a large patella-tension band ratio (OR: 291.0; 95% CI: 19.60-4330; P < 0.001) and a wide distance between K-wires (OR: 1.15; 95% CI: 1.060-1.250; P = 0.001) identified as significant risk factors. Loss of reduction occurred in 5 cases (2.0%), but no significant risk factors were identified. This study highlights the importance of bending both ends of the K-wires and proper placement of the tension band and K-wires in reducing postoperative complications in patellar fractures treated with TBW. Further research is needed to better understand the risk factors associated with loss of reduction.


Visco-elasto-plastic modeling of small intestinal submucosa (SIS) for application as a vascular graft.
In developing new tissue engineered for vascular grafts, the mechanical properties of the material and its evolution once implanted are of utmost importance because they determine the regeneration of the vessel and the blood flow through the conduit. In fact, compliance mismatch is considered the main determinant of graft failure. In this research, we analyze the dynamic properties of the small intestinal submucosa (SIS), and propose and validate a constitutive model to fit the material's behavior. A uniaxial creep and recovery test was performed on SIS tubes to find the constitutive parameters. The model was composed by an elastic element in series with two Kelvin-Voigt solid elements and a plastic slider. The first elastic component was defined using Mooney-Rivlin strain energy function, while the plastic component was defined using a third-degree polynomial function of the plastic stress. The viscoelastic behavior was defined using the creep compliance formulation for the Kelvin-Voigt model. The parameters for the plastic and non-linear elastic elements followed a normal distribution, while the spring and dashpot constants of the visco-elastic element had a linear dependence on the load applied. The constitutive model was then used to simulate the SIS under the geometrical and pressure conditions found in native vessels for 1000 cycles at a frequency of 60 cycles per minute. From the cases simulated, performance curve charts were obtained in terms of the compliance of the material. These curve charts can be used as a predictive tool of the graft's behavior based on its geometry.


Author Correction: Hormones induce the formation of luminal-derived basal cells in the mammary gland.
In the initial published version of this article, there was a mistake in one author name (Jingsong Li). The correct name should be "Jinsong Li". This correction does not affect the description of the results or the conclusions of this work.


Ultrasound-guided fine-needle aspiration for retrojugular lymph nodes in the neck.
No study on ultrasound-guided fine-needle aspiration (US-FNA) for the diagnosis of retrojugular lymph node has been reported. The present study aimed to introduce US-FNA techniques for retrojugular lymph node and to evaluate their efficacy. Of the 788 patients who underwent US-FNA of the cervical lymph node, 41 patients underwent US-FNAs of retrojugular lymph node and were included in this study. The adequacy and efficacy of US-FNA of retrojugular lymph node and related complications during or after the procedure were assessed. Of the 41 patients, 35 (85.4%) were adequately diagnosed in cytological analysis; four predominantly cystic lymph nodes were identified. Based on cytohistopathology results, thyroglobulin measurement, tuberculosis polymerase chain reaction, and sonographic follow-up, malignant (n = 26) and benign (n = 15) lymph nodes were confirmed. When six lymph nodes with inadequate cytology were classified as benign and malignant, the sensitivity, specificity, positive and negative predictive values, and accuracy of US-FNA in differentiating malignant from benign lesions were 69.2% and 92.3%, 100% and 100%, 100% and 100%, 65.2% and 88.2%, and 80.5% and 95.1%, respectively. No substantial complications related to the US-FNA procedure were observed. The present US-FNA method may be helpful for the diagnosis of retrojugular lymph node.


Recent studies of T7 RNA polymerase mechanism.
Bacteriophage T7 RNA polymerase (T7 RNAP) is known to be one of the simplest enzymes catalyzing RNA synthesis. In contrast to most RNA polymerases known, this enzyme consists of one subunit and is able to carry out transcription in the absence of additional protein factors. Owing to its molecular properties, the enzyme is widely used for synthesis of specific transcripts, as well as being a suitable model for studying the mechanisms of transcription. In this minireview the recent data on the structure and mechanism of T7 RNAP, including enzyme-promoter interactions, principal stages of transcription, and the results of functional studies are discussed.


Proteomics provides insights into the inhibition of Chinese hamster V79 cell proliferation in the deep underground environment.
As resources in the shallow depths of the earth exhausted, people will spend extended periods of time in the deep underground space. However, little is known about the deep underground environment affecting the health of organisms. Hence, we established both deep underground laboratory (DUGL) and above ground laboratory (AGL) to investigate the effect of environmental factors on organisms. Six environmental parameters were monitored in the DUGL and AGL. Growth curves were recorded and tandem mass tag (TMT) proteomics analysis were performed to explore the proliferative ability and differentially abundant proteins (DAPs) in V79 cells (a cell line widely used in biological study in DUGLs) cultured in the DUGL and AGL. Parallel Reaction Monitoring was conducted to verify the TMT results. γ ray dose rate showed the most detectable difference between the two laboratories, whereby γ ray dose rate was significantly lower in the DUGL compared to the AGL. V79 cell proliferation was slower in the DUGL. Quantitative proteomics detected 980 DAPs (absolute fold change ≥ 1.2, p < 0.05) between V79 cells cultured in the DUGL and AGL. Of these, 576 proteins were up-regulated and 404 proteins were down-regulated in V79 cells cultured in the DUGL. KEGG pathway analysis revealed that seven pathways (e.g. ribosome, RNA transport and oxidative phosphorylation) were significantly enriched. These data suggest that proliferation of V79 cells was inhibited in the DUGL, likely because cells were exposed to reduced background radiation. The apparent changes in the proteome profile may have induced cellular changes that delayed proliferation but enhanced survival, rendering V79 cells adaptable to the changing environment.


Electron microscopic development of neuroglia in epiretinal portion of post-natal rabbits.
The development of epiretinal and optic nerve neuroglial cells has been studied ultrastructurally in 1-20-day post-natal rabbits. Two morphologically distinct neuroglial cells were observed, a dense "spider" type which is present from day one and a light-staining "crab" type of cell which appears on the 4th day in the epiretinal strip. "Crab" cells myelinate many axons and mature into typical dense oligodendrocytes. "Spider" cells have ultrastructural features of both astrocyte and oligodendrocyte and each cell also myelinates many axons. Many of these cells attach their processes to basement membrane of blood vessels and mature into a typical astrocyte. In 10-15-day-old animals these cells may be located at a distance of 15 micrometer or more from the axon which they enwrap. Most of these processes are sufficiently fine and tortuous to obscure the continuity in single thin sections from adult animals.


Restoration of a phosphaturic response to parathyroid hormone in the immature rat.
Recent studies have shown that immature rats display a diminished sensitivity to the phosphaturic effects of parathyroid hormone (PTH), and that the responsiveness to PTH increases with age. The attenuated phosphaturia may reflect an inability of the neonate to respond to the hormone because of functional immaturity of the developing kidney. Alternatively, PTH may actually inhibit tubular phosphate reabsorption in the neonate but, due to other phosphate conservation mechanisms, no phosphaturia occurs. Our objective was to determine whether a phosphaturic response to PTH would be elicited in immature rats during infusion of moderate amounts of phosphate (Pi). Clearance experiments were performed on 26 acutely thyroparathyroidectomized immature Wistar rats (3-5 wk of age) fed a normal Pi diet (0.63%). In response to infusion of either Pi (1 mumol/min.100 g) (group I) or PTH (8.3 ng/min.100 g) (group II) alone, the fractional excretion of phosphate rose minimally (from 0.01 +/- 0.01% to 4.9 +/- 1.9% and from 0.12 +/- 0.12% to 2.9 +/- 1.4% for groups I and II, respectively). However, when Pi and PTH were combined either Pi first followed by PTH (group III) or PTH first followed by Pi (group IV), the fractional excretion of Pi rose dramatically (from 0.01 +/- 0.01 to 21.8 +/- 3.5% and from 0.04 +/- 0.04 to 27.7 +/- 3.3% for groups III and IV, respectively). A significant increase in urinary cAMP excretion occurred during infusion of PTH even when Pi excretion was minimal, but there was no further increase in urinary cAMP during the combined infusion of Pi and PTH.(ABSTRACT TRUNCATED AT 250 WORDS)


Preoperative pelvic floor muscle exercise does not reduce the rate of postprostatectomy incontinence: evidence from a meta-analysis and a systematic review.
A growing number of researches suggested that preoperative pelvic floor muscle exercise (PFME) was beneficial for urinary incontinence (UI) after a prostatectomy. However, these studies are debatable and inconclusive. Hence, this article aimed to determine whether PFME improves UI after a radical prostatectomy (RP). PubMed, Embase, Medline and Cochrane Library were searched for articles published from 2014 to October 2019 based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). This study was evaluated based on the Oxford Evidence-Based Medicine Center. A total of 1,269 subjects (experimental group: 628, control group: 641) in 18 studies met the inclusion criteria. In 18 studies, enough quantitative data on postoperative incontinence were available for meta-analysis. UI was analyzed at 1, 3, 6 and 12 months and all comparative studies were pooled using fixed and random effects models. Contour-enhanced funnel plots were used to assess publication bias. Pooled data revealed a total of 1,269 UI patients that underwent preoperative PFME, including PFME (N=628, 49.48%) and control group (N=641, 50.51%). There was no significant difference in the postoperative incontinence rates at 1 month (RR: 0.85, 95% CI: 0.66-1.09, P=0.031, I2=62.4%), 6 weeks (RR: 0.95, 95% CI: 0.85-1.05, P=0.618, I2=0.0%), 3 months (RR: 0.92, 95% CI: 0.63-1.34, P=0.000, I2=83.2%), 6 months (RR: 0.86, 95% CI: 0.69-1.08, P=0.364, I2=8.4%) or 12 months (RR: 0.83, 95% CI: 0.47-1.47, P=0.596, I2=0.0%) after operation. Contrary to previous work, the results presented here indicated that preoperative PFME protocols did not reduce the rate of UI. Further high-quality randomized controlled trials are necessary in the future to verify these findings.


On-site calibration method based on stepwise solid-phase microextraction.
A stepwise solid-phase microextraction (SPME) method was developed for on-site calibration of SPME for volatile organic compounds analysis. In this approach, a 75-microm Carboxen-polydimethylsiloxane coated fibre was loaded with a prior to exposure to samples of interest Extraction time for the target analytes can be controlled independently from that of the standard, and the response factors for the target analytes can be adjusted accordingly. A good reproducibility of the response factors for BTEXs (benzene, toluene, ethylbenzene and xylenes) was obtained with stepwise SPME. Satisfactory results were obtained by using this method for quantitative analysis of BTEXs in the air of a gas station when tetrachloroethylene was used as a standard. The introduction of standard via the stepwise SPME procedure makes SPME more useful in field applications. It can be used to detect leaks, contaminations and losses from loading of a standard onto a fibre to introduction of the fibre to an analytical instrument. However, this method cannot be used for compensation of sample matrix effects.


[Application of bionano optical mapping for the diagnosis of a 16p11.2-p12.2 microdeletion].
To delineate chromosomal aberration caused by structural chromosomal abnormalities with bionano optical mapping. Chromosomal karyotyping, bionano optical mapping and copy number variation sequencing (CNV-seq) were used to delineate the chromosomal aberration carried by a patient. The patient was found to have an anomalous chromosome 16 by karyotyping analysis, which was verified by bionano optical mapping and CNV-seq as loss of heterozygosity at 16p11.2-p12.2. Bionano optical mapping has provided a novel tool for the detection and diagnosis of structural chromosomal aberrations.


Thresholds of heavy-metal toxicity in cuttings of European black poplar (Populus nigra L.) determined according to antioxidant status of fine roots and morphometrical disorders.
The effects of increasing concentrations of polluted soils collected from two different stands in the direct neighbourhood of a copper smelter were studied by analyzing the activity of lipid peroxidation and antioxidant enzymes in the fine roots of cuttings of black poplar (Populus nigra L.). Morphological parameters of affected and unaffected plants were compared and concentrations of heavy metals in their fine roots were estimated. Copper and lead were the major pollutants, and their threshold concentrations were determined on the basis of positive or negative impact on shoots and root growth, morphological disorders of the roots (thickening, decreasing of fine roots volume), stimulation or inhibition of the most important antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), guaiacol and ascorbate peroxidases (GPOX, APOX) and glutathione reductase (GR) as well as increasing MDA concentration. Finally, three thresholds of Cu and Pb concentrations resulting in increasing toxicity against plants were proposed, splitting the ranges of the non toxic presence of these metals into soil (Cu<100 ppm, Pb<30 ppm), full tolerance (Cu 100-220 ppm, Pb 30-70 ppm), limited tolerance (Cu 220-650 ppm, Pb 70-200 ppm) and breakdown of tolerance (Cu>650 ppm, Pb>200 ppm).


Differential induction of innate defense antimicrobial peptides in primary nasal epithelial cells upon stimulation with inflammatory cytokines, Th17 cytokines or bacterial conditioned medium from Staphylococcus aureus isolates.
To date it is incompletely understood why half of the human population is intrinsically resistant to Staphylococcus aureus colonization whereas the other half is intermittently or permanently colonized. Nasal colonization represents the primary niche for S. aureus. We therefore investigated whether primary nasal epithelial cells (HNEC) express antimicrobial peptides (AMPs) upon stimulation by inflammatory cytokines or bacterial conditioned medium (BCM) of different colonizing and invasive staphylococci. Stimulation with classical cytokines (IL-1β, TNF-α, IFN-γ) potently induced hBD-3 and RNase7 in HNEC. Th17 cytokines (IL-17A, IL-17F, IL-22) yielded comparably weak hBD-3 and RNase7 induction and no synergistic effects with classical cytokines. BCM of S. aureus and Staphylococcus epidermidis isolates moderately induced hBD3 and RNase7 mRNA expression without significant differences when comparing colonizing vs. invasive isolates. Our results indicate that HNEC contribute to the innate defense by secretion of an AMP-containing chemical defense shield along the nasal mucosa i.e. within the primary colonization niche of S. aureus. Further studies are needed to investigate whether a deficient AMP expression in the nasal mucosa may be related to different S. aureus carrier states. AMPs or AMP-inducing agents may be promising candidates for future topical decolonization regimens that aim to prevent invasive S. aureus infections.


Hemodynamic management and surgical site infection: Network meta-analysis of randomized controlled trials.
To investigate which hemodynamic management strategy is most effective in reducing surgical site infection (SSI). Network meta-analysis of randomized controlled trials. Perioperative setting. Surgical patients. Usual care vs. optimized hemodynamic management, including goal-directed hemodynamic therapy (GDHT) and liberal/restrictive fluid therapy. The primary outcome was SSI arising within postoperative 30 days. The secondary outcomes included postoperative respiratory and urinary system infectious complications and sepsis/septic shock. The effect and ranking were assessed using network meta-analysis and the surface under the cumulative ranking curve (SUCRA) scores, respectively. We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science for eligible randomized controlled trials from inception to October 11, 2019. Fifty-three eligible studies reported SSI and comprised of 56 GDHT groups (patients, n = 4205) and 51 usual care groups (patients, n = 3895). Comparing with usual care, GDHTs aimed at intravascular volume and stroke volume optimization (odds ratio (OR), 0.28 [95% credible interval (CrI), 0.13 to 0.56]; moderate quality), stroke volume and cardiac output optimization (OR, 0.34 [95% CrI, 0.16 to 0.70]; moderate quality), and intravascular volume and cardiac output optimization (OR, 0.51 [95% CrI, 0.24 to 0.99]; low quality) significantly reduced SSI. GDHT strategy aimed at intravascular volume and stroke volume optimization was likely most effective (SUCRA = 80%). Certain GDHTs significantly reduced respiratory infectious complications; however, no GDHT significantly reduced urinary infectious complications and sepsis/septic shock. GDHT strategy aimed at intravascular volume, stroke volume, and cardiac output optimization was likely most effective for reducing respiratory infectious complications (SUCRA = 88%). Different hemodynamic managements exert different effectiveness for SSI reduction. GDHTs aimed at intravascular volume, stroke volume, and cardiac output optimization are likely most effective based on the overall evidence.


The indirect corticopontine pathway relays perioral sensory signals to the cerebellum via the mesodiencephalic junction.
In the cerebro-cerebellar loop, outputs from the cerebral cortex are thought to be transmitted via monosynaptic corticopontine gray (PG) pathways and subsequently relayed to the cerebellum. However, it is unclear whether this pathway is used constitutively for cerebro-cerebellar transduction. We examined perioral sensory pathways by unit recording from Purkinje cells in ketamine/xylazine-anesthetized mice. Infraorbital nerve stimulations enhanced simple spikes (SSs) with short and long latencies (first and second peaks), followed by SS inhibition. The second peak and SS inhibition were suppressed by muscimol (a GABAA agonist) injections into not only the PG but also the mesodiencephalic junction (MDJ). The pathway from the secondary somatosensory area (SII) to the MDJ, but not the cortico-PG pathway, transmitted the second peak signals. SS inhibition was processed in the SII and primary motor area. Thus, the indirect cortico-PG pathway, via the MDJ, is recruited for perioral sensory transduction.


Effect of cyclic nucleotides, isoproterenol and cholera toxin on DNA synthesis triggered by mitogens.
The effect of cyclic nucleotides, isoproterenol and cholera toxin on phytohaemagglutinin (PHA), concanavalin A (Con A) and anti-allotype-induced rabbit lymphoid cell proliferation was examined. Cholera toxin in concentrations ranging from 10(-8) microgram to 1 microgram per culture inhibited DNA synthesis, triggered by PHA, Con A and nocardia water-soluble mitogen (NWSM). It had the opposite effect on stimulation with antibodies directed against allotypic specificities of the immunoglobulin light chains: over the entire range of tested concentrations, cholera toxin stimulated DNA synthesis triggered by antibodies to Ab4, Ab5, Ab9 and to Aa1 allotypic specificities. Relatively high concentrations of dibutyryl adenosine 3':5'-cyclic monophosphate (cAMP) and isoproterenol (10(-3) M) inhibited mitogen-stimulated thymidine incorporation; lower concentrations (10(-9) M) had an enhancing effect. A similar enhancing effect was observed when high (10(-3) M) concentrations of dibutyryl guanosine 3':5'-cyclic monophosphate (cGMP) were used.


Role of vaccinations and prophylaxis in rheumatic diseases.
Targeted strategies for reducing the increased risk of infection in patients with autoimmune rheumatic diseases include vaccinations as well as antibiotic prophylaxis in selected patients. However, there are still issues under debate: Is vaccination in patients with rheumatic diseases immunogenic? Is it safe? What is the impact of immunosuppressive drugs on vaccine immunogenicity and safety? Does vaccination cause disease flares? In which cases is prophylaxis against Pneumocystis jirovecii required? This review addresses these important questions to which clinicians and researchers still do not have definite answers. The first part includes immunization recommendations and reviews current data on vaccine efficacy and safety in patients with rheumatic diseases. The second part discusses prophylaxis for Pneumocystis pneumonia.


Low-noise operation (-1 40 dB/Hz) in close-coupled Nd:YVO(4) second-harmonic lasers pumped by single-mode laser diodes.
Very-low-noise operation (as low as -140 dB/Hz) of close-coupled Nd:YVO(4) lasers is reported. This low noise level has been attained by controlling the spectra of the pumping laser diodes into the single longitudinal mode by suppressing mode hopping. The small-packaged second-harmonic laser (Φ12 × 16 mm) showed highly stabilized 530 nm/6 mW operations with a relative intensity noise of -140 dB/Hz.


Cultured retinal pigment epithelial cells from RCS rats express an increased calcium conductance compared with cells from non-dystrophic rats.
The Royal College of Surgeon (RCS) rats suffer from a retinal dystrophy that is caused by a malfunction of the retinal pigment epithelium (RPE). We compared the membrane currents of cultured RPE cells from non-dystrophic and RCS rats by using the whole-cell configuration of the patch-clamp technique. Cultured RPE cells from RCS rats showed voltage-dependent, barium- and 4-aminopyridine-sensitive outward currents, which had characteristics of the delayed-rectifier and voltage-dependent, barium- and 4-aminopyridine-sensitive inward currents, which had characteristics of the inward rectifier. Differences between RPE cells from RCS rats and normal rats were as follows. (a) Cultured RCS rat RPE cells showed a resting potential and an activation threshold for the voltage-dependent outward current significantly more positive than that found in cells from non-dystrophic rats. (b) In the presence of 10 mM barium, the voltage-dependent outward current was reduced in both types of cells; in cells from RCS rats, an additional voltage-dependent inward current was observed. (c) This additional inward current had characteristics of L-type calcium channels and was reduced by verapamil (30 microM) and diltiazem (30 microM). In summary, we conclude that the membrane conductances of RPE cells from normal and RCS rats are dominated by potassium conductances. In contrast to cells from non-dystrophic rats, cells of RCS rats expressed an increased membrane conductance for calcium.


Impaired selection of IgA and intestinal dysbiosis associated with PD-1-deficiency.
A major function of immunoglobulin A (IgA) is to maintain balanced bacterial communities in the gut. We have previously shown that diversification of IgA upon somatic hypermutation (SHM) is critical for IgA function yet the principles governing the selection of IgA in the gut have remained elusive. Here we discuss recent progress in understanding this process as revealed by our studies in mice that lack the inhibitory co-receptor programmed cell death-1 (PD-1). We found that PD-1 affects the dynamics of germinal center (GC) B cells by controlling the number and the nature of T helper cells in the Peyer's patches (PPs). Deregulation of the T cell compartment impacts the selection of IgA plasma cells leading to gut dysbiosis. When the PD-1-dependent checkpoint is missing, gut bacteria go beyond the mucosal barrier and induce systemic GCs that can generate antibodies with auto-reactive properties.


Schwannoma of the Fourth Ventricle: The Eighth Case Report.
We report an uncommon case of a surgical resection of a fourth ventricle tumor in an adult that proved to be a schwannoma. A 53-year-old man presented with a 1.5-year history of gait unsteadiness and vertigo and a few-week history of headache, emesis, and neurogenic dysphagia. A brain magnetic resonance imaging revealed a large, heterogeneously contrast enhancing mass located within the fourth ventricle, compressing the brainstem and causing supratentorial ventricle enlargement. A suboccipital craniotomy and a telovelar approach were performed to resect the tumor. The ventricular system was repermeabilized at the end of the operation. A postoperative magnetic resonance imaging confirmed complete tumor removal. There was an initial worsening of the preoperative deficits, which progressively improved. The tumor was classified as a fourth ventricle schwannoma. There has been no evidence of tumor recurrence during the 6 years of follow-up. At present, the patient is ambulatory and reports an intermittent diplopia on conjugated gaze. This case report intends to reveal the eighth case of a fourth ventricle schwannoma since 1957. Schwannomas of the fourth ventricle are infrequent but should be accounted in the differential diagnosis of space-occupying lesions in this location. Gross total resection might be the definite treatment of these tumors if deemed possible.


Testing assumptions implicit in the use of the 15-second rule as an early predictor of whether an in-vehicle device produces unacceptable levels of distraction.
Given the proliferation of in-vehicle technologies, techniques must be developed to ensure devices do not produce unacceptable levels of distraction. One approach is to use static time on task (e.g., the 15-second rule). However, this practice makes three critical assumptions: (1) static time on task predicts time on task while driving; (2) time on task measured in a hazard-free environment predicts time on task when drivers expect hazards; (3) time on task predicts perceived distraction, collisions, and driving errors. To test these assumptions, two tasks were compared in 32 drivers using a driving simulator. The tasks were manipulating controls of a radio/tape deck and dialling a hand-held cellular phone. Static time on task underestimated dynamic time on task, though the differences between tasks were roughly consistent across testing conditions, with the cellular task taking more time. Participants who expected hazards required slightly more time on task than those who did not, but the effect was only marginal (p=0.09) and consistent across tasks. Finally, the device with higher static time on task also produced significantly more lane deviations and perceived interference, though the predicted pattern of results did not emerge for collisions and hazard response time.


Immobilization of cellulase on iron tolerant Pseudomonas stutzeri biosynthesized photocatalytically active magnetic nanoparticles for increased thermal stability.
Bacteria mediated synthesis of magnetic nanoparticles (MNPs) for biotechnological applications is an important area of nanotechnology. This study demonstrates the use of iron tolerant bacterium for synthesis of MNPs for cellulase immobilization and photocatalytic activity. The enrichment, isolation, screening and molecular identification led to the selection of Pseudomonas stutzeri KDP_M2 with high degree of iron tolerance. The synthesis parameters such as 1 mM ferric quinate, pH 9 and 96 h static incubation were found optimum for maximum yield of 210 mg/L. The characterization using various techniques indicated that MNPs were Hematite (Fe2O3) with particle size between 10 and 20 nm. Further, vibrating sample magnetometer and thermogravimetric analyses demonstrated the superparamagnetic nature with high thermal stability. The MNPs were found an excellent support for immobilization of industrially important cellulase with 96.5% binding efficiency. The immobilization which was confirmed by Fourier transform infrared spectroscopy indicated that immobilization did not reduce the cellulase activity, rather enhanced the thermal stability and operational temperature range of cellulase. The immobilized cellulase showed maximum cellulolytic activity at pH 4.6 and retained 80% activity upto 3rd cycle of reuse, therefore, can be utilized repeatedly at acidic conditions.The monitoring the photocatalytic activity showed rapid degradation of methyl violet and methylene blue within initial 10 min. of reaction.


Hierarchical assembly of a homochiral triple concentric helical system in a novel 3D supramolecular metal-organic framework: synthesis, crystal structure, and SHG properties.
The hierarchical assembly of a homochiral triple concentric helical system in a novel 3D metal-organic framework with SHG activity has been observed. The result also provides a better understanding of host-guest chemistry and the process of water transport in biological systems.


[A case of sarcoidosis with primary symptoms of lymphadenopathy of the submandibular nodes presented various skin lesions].
The lungs, eyes and skin are affected in most cases of sarcoidosis. We encountered a rare case of sarcoidosis which presented extensive lymphadenopathy, various skin lesions, lesions in the thoracic cavity with bilateral pleural effusion, eosinophilia (43% in the periphery blood).


Testicular sperm aspiration has a poor effect in predicting micro-TESE outcomes in NOA patients with AZFc deletion.
Testicular sperm aspiration (TESA) is widely used in the diagnosis and management of nonobstructive azoospermia. However, its ability for predicting microdissection testicular sperm extraction in nonobstructive azoospermia (NOA) patients with AZFc deletion remains uncertain. To investigate whether TESA affected the sperm retrieval rate (SRR) in NOA patients with AZFc deletion, a retrospective analysis of the clinical data of NOA patients with AZFc deletion who underwent microdissection testicular sperm extraction (micro-TESE) was conducted. The effects of age, testicular volume, follicle-stimulating hormone (FSH) levels, luteinizing hormone (LH) levels, testosterone (T) levels and TESA on the SRR were analyzed in this group of patients. A total of 181 individuals had their sperm successfully collected and underwent micro-TESE, with an SRR of 67.4%. The patients were separated into two groups based on their micro-TESE results (sperm acquisition and nonsperm acquisition), with no significant variations in age, testicular volume, FSH levels, LH levels, or T levels between the two groups. There was no significant difference in the SRR between any of the groups into which patients were classified based on reproductive hormone reference value ranges. Binary logistic regression was used to explore the absence of significant effects of age, testicular volume, FSH levels, LH levels, and T levels on sperm acquisition in patients undergoing micro-TESE. In the preoperative testicular diagnostic biopsy group, the sperm acquisition and nonsperm acquisition groups had SRRs of 90.1% and 65.1%, respectively. More significantly, there was no significant difference in the SRR between the negative preoperative testicular diagnostic biopsy group and the nonpreoperative testicular diagnostic biopsy group (65.1 vs. 63.8%, p = 0.855). There is a high probability of successful sperm acquisition in the testis of men undergoing micro-TESE. In this group of patients, age, testicular volume, FSH levels, LH levels, and T levels may have little bearing on the micro-TESE outcome. In patients whose preoperative TESA revealed the absence of sperm, the probability of obtaining sperm by micro-TESE remained high (65.1%); negative TESA results appeared to not influence the SRR (63.8%) in patients undergoing micro-TESE.


Molecular characterization and substrate specificity of nitrobenzene dioxygenase from Comamonas sp. strain JS765.
Comamonas sp. strain JS765 can grow with nitrobenzene as the sole source of carbon, nitrogen, and energy. We report here the sequence of the genes encoding nitrobenzene dioxygenase (NBDO), which catalyzes the first step in the degradation of nitrobenzene by strain JS765. The components of NBDO were designated Reductase(NBZ), Ferredoxin(NBZ), Oxygenase(NBZalpha), and Oxygenase(NBZbeta), with the gene designations nbzAa, nbzAb, nbzAc, and nbzAd, respectively. Sequence analysis showed that the components of NBDO have a high level of homology with the naphthalene family of Rieske nonheme iron oxygenases, in particular, 2-nitrotoluene dioxygenase from Pseudomonas sp. strain JS42. The enzyme oxidizes a wide range of substrates, and relative reaction rates with partially purified Oxygenase(NBZ) revealed a preference for 3-nitrotoluene, which was shown to be a growth substrate for JS765. NBDO is the first member of the naphthalene family of Rieske nonheme iron oxygenases reported to oxidize all of the isomers of mono- and dinitrotoluenes with the concomitant release of nitrite.


Synthesis and in vivo activity of MK2 and MK2 substrate-selective p38alpha(MAPK) inhibitors in Werner syndrome cells.
A benzopyranopyridine inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2) is prepared rapidly and efficiently in one step using microwave dielectric heating, whereas a substrate-selective p38 MAPK inhibitor was prepared using conventional heating techniques. The former had MK2 inhibitory activity above 2.5 microM concentration, whereas the latter showed no MK2 inhibition at 10 microM. However, rather than rescuing the reduced cellular growth rate and aged morphology of hTERT-immortalised WS dermal fibroblasts, both induce a state resembling stress-induced cellular senescence, suggesting that these inhibitors may have limited therapeutic use.


Stromal stem cells (CFU-f) in yolk sac, liver, spleen and bone marrow of pre- and postnatal mice.
Our results demonstrate that in yolk sac, liver, spleen and femoral bone marrow of mice at ages ranging between 11 d of gestation and adult life, important changes in the stromal stem cell population (CFU-f assay) occur which are correlated with haemopoiesis. In the liver, spleen and bone marrow, high numbers of CFU-f precede high haemopoietic stem cell values. As haemopoiesis starts in the spleen, CFU-f numbers in fetal liver are low. Similarly, CFU-f numbers decrease in the spleen as bone marrow haemopoiesis starts. This suggests the existence of a migration stream of stromal stem cells. In spleen and bone marrow, CFU-f numbers decrease towards adult life as these organs maintain a stable haemopoietic activity.


A haemoglobin switching activity modulates hereditary persistence of fetal haemoglobin.
During human development there is a switch from fetal to adult haemoglobin formation, reflecting the differential expression of fetal (G gamma and A gamma) and adult (beta and delta) globin genes. Mutations that inhibit this switch produce variants of the syndrome of hereditary persistence of fetal haemoglobin (HPFH). Adult heterozygotes for these mutants produce 15-30% fetal haemoglobin (HbF) in their red cells. The general assumption is that the mutations result in a permanent switching on of gamma-globin genes. Here, however, we show that fetal globin expression can be turned off in cultures of HPFH cells by an uncharacterized factor in fetal sheep serum. This is the first demonstration that mutations affecting the developmental expression of globin genes can be modulated by exogenous factors. The findings raise the possibility that the phenotype of HPFH is not simply the direct result of mutations in or around globin genes but the consequence of the mutations on the interaction of globin genes with trans-acting regulatory factors.


Differential expression of the cellular src gene during vertebrate development.
Cellular genes that are homologous to the transforming genes of certain RNA tumor viruses are suspected to play a functional role during normal developmental processes. To investigate this further, we are studying the expression of the cellular homolog of the Rous sarcoma virus transforming gene (c-src) during embryogenesis of fish, frog, and chicken by quantitative determination of the activity of the c-src encoded protein kinase (pp60c-src). The kinase activity from embryos of fish, frog, and chicken displays the same enzymatic characteristics as the kinase from adult animals: It phosphorylates only tyrosine residues in protein substrates, and its activity is relatively insensitive to inhibition by the diadenosine nucleotide Ap4A. During the course of development, the varying kinase activity level reflects differential expression of the c-src gene product. The kinase activity is low during early development, increases dramatically during organogenesis, and decreases thereafter to the level found in adult animals. The kinase activity displays an organ specificity, with brain showing the highest activity in embryos as well as in adults. Muscle, however, shows high activities during organogenesis, but no or barely detectable activity in adult animals. Our data suggest, therefore, that the c-src gene product plays more of a role in differentiation than in proliferation processes during embryogenesis, and that it may act as a pleiotropic effector.


Application of Pd-Catalyzed Cross-Coupling Reactions in the Synthesis of 5,5-Dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles that Inhibit ALK5 Kinase.
C-H activation of position 3 of a substituted pyrazole ring catalyzed by palladium(II) was straightforward and convenient for arylated or heteroarylated 5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles. Moreover, we introduced simple protection of the nitrogen in the pyridin-2-yl directing group, which otherwise does not allow a cross-coupling reaction, by transformation to the N-oxide. Selected final products were reasonably selective ALK5 kinase inhibitors.


Prenatal ultrasound and magnetic resonance imaging findings of a hypovascular epignathus with a favorable prognosis.
Epignathus of a fetus is an extremely rare type of an oropharyngeal teratoma that commonly arises from the palate and often grows in the prenatal period, leading to polyhydramnios due to difficulty in swallowing before birth and a high mortality due to the airway obstruction after birth. We report here a very rare case of a fetus with an epignathus decreasing in size naturally in the prenatal period with a favorable prognosis. In contrast to previously reported cases of epignathus that grew rapidly in the prenatal period, color Doppler fetal ultrasound showed a hypovascular tumor in our case. Moreover, histopathologic examination revealed an epignathus with necrotic areas inside. Based on our experience, a hypovascular epignathus demonstrated by color Doppler fetal ultrasound may be an indicator of a favorable prognosis.


Increasing readiness to decide and strengthening behavioral intentions: evaluating the impact of a web-based patient decision aid for breast cancer treatment options (BresDex: www.bresdex.com).
To undertake a quantitative evaluation of a theory-based, interactive online decision aid (BresDex) to support women choosing surgery for early breast cancer (Stage I and II), based on observations of its use in practice. Observational cohort study. Website log-files collected data on the use of BresDex. Online questionnaires assessed knowledge about breast cancer and treatment options, degree to which women were deliberating about their options, and surgery intentions, pre- and post-BresDex. Readiness to make a decision significantly increased after using BresDex (p<.001), although there was no significant improvement in knowledge. Participants that were 'less ready' to make a decision before using BresDex, spent a longer time using BresDex (p<.05). Significant associations between surgery intentions and choices were observed (p<.001), with the majority of participants going on to have BCS. Greater length of time spent on BresDex was associated with stronger intentions to have BCS (p<.05). The use of BresDex appears to facilitate readiness to make a decision for surgery, helping to strengthen surgery intentions. BresDex may prove a useful adjunct to the support provided by the clinical team for women facing surgery for early breast cancer.


Subepithelial hemorrhages and erosions of human stomach.
Subepithelial hemorrhages and erosions of the stomach are being studied extensively in experimental animal models but have not been well-characterized in humans. The definitions of these hemorrhagic and erosive lesions are not uniform and are often further confused by being labeled with the blanket term "gastritis." We define these lesions from an endoscopic perspective, describe the clinical settings in which they occur, and provide endoscopic-histologic correlations, where available.


Tafamidis.
In November 2011, tafamidis (Vyndaqel; Pfizer), a small molecule that inhibits the dissociation of transthyretin tetramers, was granted marketing authorization by the European Commission for the treatment of transthyretin amyloidosis in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral neurological impairment.


Transcription elongation factors OsSPT4 and OsSPT5 are essential for rice growth and development and act with APO2.
The transcription elongation factor SPT4/SPT5 complex is essential for rice vegetative and reproductive growth and that OsSPT5-1, with its interactor APO2, is involved in multiple phytohormone pathways. The SPT4/SPT5 complex is a transcription elongation factor that regulates the processivity of transcription elongation. However, our understanding of the role of SPT4/SPT5 complex in developmental regulation remains limited. Here, we identified three SPT4/SPT5 genes (OsSPT4, OsSPT5-1, and OsSPT5-2) in rice, and investigated their roles in vegetative and reproductive growth. These genes are highly conserved with their orthologs in other species. OsSPT4 and OsSPT5-1 are widely expressed in various tissues. By contrast, OsSPT5-2 is expressed at a relatively low level, which could cause osspt5-2 null mutants have no phenotypes. Loss-of-function mutants of OsSPT4 and OsSPT5-1 could not be obtained; their heterozygotes showed severe reproductive growth defects. An incomplete mutant line (osspt5-1#12) displayed gibberellin-related dwarfed defects and a weak root system at an early vegetative phase, and a short life cycle in different planting environments. Furthermore, OsSPT5-1 interacts with the transcription factor ABERRANT PANICLE ORGANIZATION 2 (APO2) and plays a similar role in regulating the growth of rice shoots. RNA sequencing analysis verified that OsSPT5-1 is involved in multiple phytohormone pathways, including gibberellin, auxin, and cytokinin. Therefore, the SPT4/SPT5 complex is essential for both vegetative and reproductive growth in rice.


Activation of the H+-ATPase in the plasma membrane of cells of Saccharomyces cerevisiae grown under mild copper stress.
Cells of Saccharomyces cerevisiae exhibited a more active plasma membrane H+-ATPase during growth in media supplemented with CuSO4 concentrations equal to or below 1 mM than did cells cultivated in the absence of copper stress. Maximal specific activities were found with 0.5 mM CuSO4. ATPase activity declined when cells were grown with higher concentrations up to 1.5 mM (the maximal concentration that allowed growth), probably due to severe disorganization of plasma membrane. Cu2+-induced maximal activation was reflected in an increase of Vmax (approximately threefold) and in the slight decrease of the Km for MgATP (from 0.93 +/- 0.13 to 0.65 +/- 0.16 mM). The expression of the gene encoding the essential plasma membrane ATPase (PMA1) was reduced with a dose-dependent pattern in cells grown with Inhibitory concentrations of copper, while the weakly expressed PMA2 gene promoter was moderately more efficient in cells cultivated under mild copper stress (1.5-fold maximal activation). ATPase was activated by copper despite the slightly lower content of ATPase protein in the plasma membrane of Cu2+-grown cells and the powerful inhibitory effect of Cu2+ in vitro.


[Method remarks and observations on the use of the respiratory function tests in occupational medicine].
FVC test represents a preliminary test used to approach the 2nd diagnostic level of non invasive screening in occupational pneumopathy (DLCO, N2 wash out, closure volume). Quality, validity and ability to be replicated of the test in spirometry have been evaluated. Results have been examined by Fisher exact test and by linear regression analysis. It was possible to demonstrate the validity and reproducyibility of this simple, diagnostic and non invasive screening in Occupational Health.


Retrospective analysis of SARS-CoV-2 omicron invasion over delta in French regions in 2021-22: a status-based multi-variant model.
SARS-CoV-2 is a rapidly spreading disease affecting human life and the economy on a global scale. The disease has caused so far more then 5.5 million deaths. The omicron outbreak that emerged in Botswana in the south of Africa spread around the globe at further increased rates, and caused unprecedented SARS-CoV-2 infection incidences in several countries. At the start of December 2021 the first omicron cases were reported in France. In this paper we investigate the spreading potential of this novel variant relatively to the delta variant that was also in circulation in France at that time. Using a dynamic multi-variant model accounting for cross-immunity through a status-based approach, we analyze screening data reported by Santé Publique France over 13 metropolitan French regions between 1st of December 2021 and the 30th of January 2022. During the investigated period, the delta variant was replaced by omicron in all metropolitan regions in approximately three weeks. The analysis conducted retrospectively allows us to consider the whole replacement time window and compare regions with different times of omicron introduction and baseline levels of variants' transmission potential. As large uncertainties regarding cross-immunity among variants persist, uncertainty analyses were carried out to assess its impact on our estimations. Assuming that 80% of the population was immunized against delta, a cross delta/omicron cross-immunity of 25% and an omicron generation time of 3.5 days, the relative strength of omicron to delta, expressed as the ratio of their respective reproduction rates, [Formula: see text], was found to range between 1.51 and 1.86 across regions. Uncertainty analysis on epidemiological parameters led to [Formula: see text] ranging from 1.57 to 2.34 on average over the metropolitan French regions, weighted by population size. Upon introduction, omicron spread rapidly through the French territory and showed a high fitness relative to delta. We documented considerable geographical heterogeneities on the spreading dynamics. The historical reconstruction of variant emergence dynamics provide valuable ground knowledge to face future variant emergence events.


Insulin- and insulin-like growth-factor-I receptor tyrosine-kinase activities in human renal carcinoma.
We studied expression and functional characteristics of the insulin- and insulin-like-growth-factor-I (IGF-I) receptors in human renal carcinoma. Ligand-binding properties and tyrosine-kinase activity of both receptors, as well as the expression of the 2 isoforms of the human insulin receptor (HIR-A and -B) were analyzed in renal carcinoma and normal adjacent kidney tissue of 8 adult patients. Partially purified insulin- and IGF-I receptors from normal and renal cell carcinoma tissue possessed identical affinities for their ligands. Renal cell carcinoma, however, contained 3- to 4-fold more specific insulin-binding sites and 2-fold more IGF-I binding sites than adjacent normal kidney tissue. In addition, we determined the relative content of insulin/IGF-I receptor hybrids in both tissues. Renal cell carcinoma and adjacent normal tissue revealed similar amounts of insulin/IGF-I receptor hybrids, i.e., 44 +/- 8.2% of tracer IGF-I binding in normal tissue and 46 +/- 12.0% in renal cell carcinoma. When equal amounts of insulin- and IGF-I receptor protein were studied, we found significantly increased receptor autophosphorylation and elevated substrate phosphorylation in carcinoma tissue. To assess whether the differences in insulin-receptor tyrosine-kinase activity were caused by an altered pattern of insulin receptor isoform expression, we determined mRNA levels for HIR-A and -B. The 2 insulin receptor isoforms were, however, expressed in highly variable ratios in both normal and tumor tissue. Our experiments show that renal carcinoma expresses an elevated amount of insulin- and IGF-I receptor protein with increased specific autophosphorylation and tyrosine-kinase activity each. The increase of insulin-receptor tyrosine-kinase activity in renal carcinoma cannot be explained by an altered expression pattern of insulin receptor isoforms.


A rare case of multiple port site incisional hernias repaired by laparoscopy-assisted intraperitoneal onlay mesh: A case report.
Port site herniation is a frequent complication of abdominal surgery, yet treatment strategies for multiple port site hernias are often difficult and case reports are rare. A 72-year-old woman, with a history of multiple abdominal surgeries, underwent laparoscopic surgery for rectal prolapse four years prior. Three 12 mm ports were inserted into the umbilical region, right upper quadrant and right lower abdomen, subsequently, incisional hernias developed at all three sites. In addition, an incisional hernia developed in the lower abdomen, for a total of four incisional hernias. She was taking apixaban for atrial fibrillation, and since the standard surgical method of placing the mesh in the extraperitoneal space was judged to be high risk for postoperative bleeding and hematoma formation, we performed a laparoscopy-assisted intraperitoneal onlay mesh repair (IPOM). The key points of the surgery performed are: Laparoscopic surgery was initiated with a small incision in the umbilical region, using two 5 mm ports because we reasoned that using a 12 mm port could cause a new hernia. In the lateral hernia repair, a mesh was placed in the preperitoneal space on the dorsal side of the hernia, the mesh was sutured to the peritoneum because tucking cannot be performed if nerves are present on the dorsal aspect. The medial hernia was repaired by IPOM via a small laparotomy incision. For multiple incisional hernias, it is necessary to consider appropriate repair methods for each site.


Differential myocardial strain in the early postoperative period in patients receiving arterial vs venous bypass grafts: A hypothesis-generating study.
Revascularization via coronary artery bypass grafting (CABG) remains a common therapy for coronary artery disease. CABG-based revascularization is most commonly performed via either single arterial graft (SAG) or multiple arterial grafting (MAG) strategies. Echo-derived global and regional longitudinal strain was used to test where SAG or MAG results in immediate differences in left ventricular (LV) function after CABG. Pre- and postprocedural intraoperative transesophageal echos were prospectively collected. Two-dimensional LV images were analyzed for global and regional longitudinal strain (GLS), LV ejection fraction, end-diastolic volume, end-systolic volume, and stroke volume (SV). Twenty patients underwent open, on-pump CABG (63.9 ± 10 years old, 85% male; 10 with SAG and 10 with MAG. Preprocedural GLS significantly differed between patients with SAG and MAG, with patients with MAG having greater GLS (mean [standard deviation, SD], 20.41 [5.54]) than patients with SAG (16.28 [3.48]). After CABG, in patients with MAG, LV strain decreased both globally (-1.13 [3.15]) and regionally in the anterior-lateral (-1.22 [3.84]) and inferior-lateral regions (-1.32 [5.69]), along with LVEF. In patients with SAG, LV strain increased after CABG globally (1.34 [2.73]) and regionally in the anterior-lateral (1.20 [6.49]) and inferior-lateral regions (0.39 [7.26]), as did LVEF and SV. Postprocedure, more patients with MAG were given vasopressor (100% vs 60%) and inotrope infusions (70% vs 40%) than patients with SAG. After CABG, LV function quantified through GLS changes both globally and regionally increased after SAG and decreased after MAG. This finding may have important clinical implications in terms of optimizing intraoperative management for patients with CABG and have the potential to guide the improvement of clinical outcomes.


Are there plastic particles in my sugar? A pioneering study on the characterization of microplastics in commercial sugars and risk assessment.
Although several studies are confirming the ubiquity of microplastics (MPs) in environments, our knowledge about their effects on human health is still very limited. Therefore, while we have not gathered definitive information on their consequences, studies that aim to identify the MPs sources constitute subsidies to better understand the various exposure pathways to these pollutants. Thus, we investigated the possible presence of MP-like particles in five brands of commercial sugars and two unpacked, unbranded, and unlabeled sugars (hereinafter referred to as "non-branded"), obtained from different supermarkets in Dhaka (Bangladesh). Surprisingly, MPs-like particles were identified in all analyzed samples and taken together, our data demonstrated similar variations (between branded and non-branded samples) in terms of number, size, shape, color, and polymer composition. The number of plastic particles/kg sugar was, on average, 343.7 ± 32.08 (mean ± SEM), having been observed a tendency for a higher frequency of MPs < 300 μm. Overall, microfibers and spherules were the most and the predominant colors of MPs (in general) were black, pink, blue, and brown. The FT-IR analysis confirmed the chemical nature of MPs (in branded and non-branded), having identified nine polymeric types (ABS, PCV, PET, EVA, CA, PTFE, HDPE, PC, and nylon), being ABS and PVC the most frequent. Furthermore, we estimate that sugar consumption in Dhaka City can cause the ingestion of millions of tons of MPs annually (2.4 to 25.6 tons) (with an average of 10.2 tons). Our study is the most comprehensive report on the MP's occurrence in sugar, confirming that the ingestion of this food constitutes an important route of human exposure to these micropollutants and, therefore, serves as a baseline for future assessments and useful for generating efficient strategies to control MPs.


Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids.
Adverse events of opioids may restrict their use in non-cancer pain. Analysis of the incidence of common adverse events in trials conducted in non-cancer pain has usually been limited to opioids used to treat severe pain according to the WHO three-step ladder. To examine the incidence of common adverse events of opioids in non-cancer pain, a systematic review and meta-analysis of information from randomised trials of all opioids in non-cancer pain was undertaken. Studies used were published randomised trials of oral opioid in non-cancer pain, with placebo or active comparator. Thirty-four trials with 5,546 patients were included with 4,212 patients contributing some information on opioid adverse events. Most opioids used (accounting for 90% of patients) were for treating moderate rather than severe pain. Including trials without a placebo increased the amount of information available by 1.4 times. Because of clinical heterogeneity in condition, opioid, opioid dose, duration, and use of titration, only broad results could be calculated. Use of any oral opioid produced higher rates of adverse events than did placebo. Dry mouth (affecting 25% of patients), nausea (21%), and constipation (15%) were the most common adverse events. A substantial proportion of patients on opioids (22%) withdrew because of adverse events. Because most trials were short, less than four weeks, and because few titrated the dose, these results have limited applicability to longer-term use of opioids in clinical practice. Suggestions for improved studies are made.


Improved Understanding of Acute Incisional Hernia Incarceration: Implications for Addressing the Excess Mortality of Emergent Repair.
Incisional hernia develops in up to 20% of patients undergoing abdominal operations. We sought to identify characteristics associated with poor outcomes after acute incisional hernia incarceration. We performed a retrospective cohort study of adult patients with incisional hernias undergoing elective repair or with acute incarceration between 2010 and 2017. The primary end point was 30-day mortality. Logistic regression was used to determine adjusted odds associated with 30-day mortality. The American College of Surgeons Surgical Risk Calculator was used to estimate outcomes had these patients undergone elective repair. A total of 483 patients experienced acute incarceration; 30-day mortality was 9.52%. Increasing age (adjusted odds ratio 1.05; 95% CI, 1.02 to 1.08) and bowel resection (adjusted odds ratio 3.18; 95% CI, 1.45 to 6.95) were associated with mortality. Among those with acute incarceration, 231 patients (47.9%) had no documentation of an earlier surgical evaluation and 252 (52.2%) had been evaluated but had not undergone elective repair. Among patients 80 years and older, 30-day mortality after emergent repair was high (22.9%) compared with estimated 30-day mortality for elective repair (0.73%), based on the American College of Surgeons Surgical Risk Calculator. Estimated mortality was comparable with observed elective repair mortality (0.82%) in an age-matched cohort. Similar mortality trends were noted for patients younger than 60 years and aged 60 to 79 years. Comparison of predicted elective repair and observed emergent repair mortality in patients with acute incarceration suggests that acceptable outcomes could have been achieved with elective repair. Almost one-half of acute incarceration patients had no earlier surgical evaluation, therefore, targeted interventions to address surgical referral can potentially result in fewer incarceration-related deaths.


Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.
Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4+ and CD8+ T cells. Co-culturing CD4+ with autologous CD8+ T cells from ART-suppressed HIV+ donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8+ T cells. This trispecific antibody mediates CD4+ and CD8+ T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection.


Toxoplasma Effectors that Affect Pregnancy Outcome.
As an immune-privileged organ, the placenta can tolerate the introduction of antigens without inducing a strong inflammatory response that would lead to abortion. However, for the control of intracellular pathogens, a strong Th1 response characterized by the production of interferon-γ is needed. Thus, invasion of the placenta by intracellular parasites puts the maternal immune system in a quandary: The proinflammatory response needed to eliminate the pathogen can also lead to abortion. Toxoplasma is a highly successful parasite that causes lifelong chronic infections and is a major cause of abortions in humans and livestock. Here, we discuss how Toxoplasma strain type and parasite effectors influence host cell signaling pathways, and we speculate about how this might affect the outcome of gestation.


Success factors for citizen science projects in water quality monitoring.
Attempts to monitor the quality of freshwater resources on a global scale unveil huge data lacks. Involving citizens in data collection has potential to resolve this lack of water quality data. However, it is widely unclear which factors drive the success of citizen science activities. Based on a systematic literature review of 56 peer-reviewed research articles, we identify three sets of factors for successful citizen science projects in water quality monitoring: (i) attributes of citizens (knowledge and experience in collecting data, awareness of environmental problems, motivation, and socio-economic background of citizens), (ii) attributes of institutions (motivation, type of organization, consistent and adequate funding), and (iii) the interactions between citizens and institutions (supporting structure, communication and feedback). These three sets of factors enable a systematic analysis and design of citizen science projects in the future.


Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats: the role of nitric oxide as a key mediator.
Atrial natriuretic peptide (ANP) is an important regulator of blood pressure (BP). One of the mechanisms whereby ANP impacts BP is by stimulation of nitric oxide (NO) production in different tissues involved in BP control. We hypothesized that ANP-stimulated NO is impaired in the kidneys of spontaneously hypertensive rats (SHR) and this contributes to the development and/or maintenance of high levels of BP. We investigated the effects of ANP on the NO system in SHR, studying the changes in renal nitric oxide synthase (NOS) activity and expression in response to peptide infusion, the signaling pathways implicated in the signaling cascade that activates NOS, and identifying the natriuretic peptide receptors (NPR), guanylyl cyclase receptors (NPR-A and NPR-B) and/or NPR-C, and NOS isoforms involved. In vivo, SHR and Wistar-Kyoto rats (WKY) were infused with saline (0.05 ml/min) or ANP (0.2 μg·kg(-1)·min(-1)). NOS activity and endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) NOS expression were measured in the renal cortex and medulla. In vitro, ANP-induced renal NOS activity was determined in the presence of iNOS and nNOS inhibitors, NPR-A/B blockers, guanine nucleotide-regulatory (G(i)) protein, and calmodulin inhibitors. Renal NOS activity was higher in SHR than in WKY. ANP increased NOS activity, but activation was lower in SHR than in WKY. ANP had no effect on expression of NOS isoforms. ANP-induced NOS activity was not modified by iNOS and nNOS inhibitors. NPR-A/B blockade blunted NOS stimulation via ANP in kidney. The renal NOS response to ANP was reduced by G(i) protein and calmodulin inhibitors. We conclude that ANP interacts with NPR-C, activating Ca-calmodulin eNOS through G(i) protein. NOS activation also involves NPR-A/B. The NOS response to ANP was diminished in kidneys of SHR. The impaired NO system response to ANP in SHR participates in the maintenance of high blood pressure.


Primary inferior oblique overaction in congenital esotropia, accommodative esotropia, and intermittent exotropia.
A statistical analysis of the onset and natural history of primary inferior oblique eye muscle overaction (IOOA) was conducted using the records of 456 strabismus patients. With 5 years or more of follow-up, IOOA developed in 72% of congenital esotropes (CETs), 34% of accommodative esotropes (AETs), and 32% of intermittent exotropes (X[T]s) at an average age of 3.6, 5.2, and 5.2 years, respectively. Incidence of IOOA was positively related to the number of horizontal surgeries in CETs but not in AETs or X(T)s. Incidence was not related to age of onset of strabismus, time from onset of strabismus to surgery, age at first surgery, or decompensation of ocular alignment. Mild IOOA did revert to normal in 12 patients after only horizontal surgery. The association of IOOA with dissociated vertical deviation, as well as symmetry, range of age of detection, and recurrence after surgery are also explored.


What information do parents need when facing end-of-life decisions for their child? A meta-synthesis of parental feedback.
The information needs of parents facing end-of-life decisions for their child are complex due to the wide-ranging dimensions within which such significant events unfold. While parents acknowledge that healthcare professionals are their main source of information, they also turn to a variety of additional sources of written information in an attempt to source facts, discover solutions, and find hope. Much has been written about the needs of parents faced with end-of-life decisions for their child but little is known about the written information needs such parents have. Research in the adult intensive care context has shown that written resources impact positively on the understanding of medical facts, including diagnoses and prognoses, communication between families and healthcare professionals, and the emotional wellbeing of families after their relative's death. A meta-synthesis of predominantly empirical research pertaining to features which assist or impede parental end-of-life decisions was undertaken to provide insight and guidance in our development of written resources (short print and online comprehensive version) for parents. The most prominently cited needs in the literature related to numerous aspects of information provision; the quantity, quality, delivery, and timing of information and its provision impacted not only on parents' ability to make end-of-life decisions but also on their emotional wellbeing. The meta-synthesis supports the value of written materials, as these provide guidance for both parents and healthcare professionals in pertinent content areas. Further research is required to determine the impact that written resources have on parental end-of-life decision-making and on parents' wellbeing during and after their experience and time in the hospital environment.


Glial cell component in retinoblastoma.
The right eye of a 4-month-old girl with a large, unilateral, sporadic retinoblastoma was enucleated. The tumor was unusual because it contained Flexner-Wintersteiner rosettes with extremely large lumina. Smaller rosettes and undifferentiated tumor cells were observed within the lumina. Also of importance were cells resembling glial cells which were intermixed with more typical cuboidal retinoblastoma cells. These cells had electron microscopic features typical of glial cells and stained positively for glial fibrillary acidic protein in immunohistochemical studies. Rosettes and glial cells continued to be observed in the tumor carried in tissue culture through two passages over a 7-month period. This tumor is presented because of its unusual rosette structures and because it confirms recent reports describing a glial cell component in retinoblastoma.