Environmental Impacts and Their Association With Performance and Excretion Traits in Growing Pigs.
The selection of pigs for improved production traits has been, for a long time, the major driver of pig breeding. More recently, because of the increasing concern with the environment, new selection criteria have been explored, such as nitrogen (N) excretion. However, many studies indicate that life cycle assessment (LCA) provides much better indicators of environmental impacts than excretion. Therefore, the objective of this study was to investigate, using a modeling approach, the relationships between production traits and LCA impacts of individual growing pigs calculated at the farm gate for 1 kg of body weight gain. Performances of pigs were simulated for 2-phase (2P) and precision feeding (PR), using the InraPorc population model (on 1,000 pigs). Nitrogen excretion was positively correlated with feed conversion ratio (FCR; r = +0.96), climate change (CC; r = +0.96), acidification potential (AC; r = +0.97), eutrophication potential (EU; r = +0.97), and land occupation (LO; r = +0.96), whatever the feeding program. However, FCR appeared to be a better indicator of LCA impacts, with very high and positive correlations (r > +0.99) with CC, AC, EU, and LO for both feeding programs. The CC, AC, and EU impacts of pig production for PR feeding were 1.3, 10, and 7.5% lower than for 2P, respectively, but the correlations within each outcome were very similar among feeding programs. It was concluded that the use of FCR as a selection criterion in pig breeding seems to be a promising approach to associate improved performance and low environmental impact of pig fattening.


Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses.
Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (TFH cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting TFH cell differentiation. In domestic pigs, immunization with a live bacterial vaccine induced robust TFH cell and antibody responses, but immunization with its heat-killed counterpart did not. Finally, a hypermorphic TLR8 polymorphism was associated with protective immunity elicited by vaccination with bacillus Calmette-Guérin (BCG) in a human cohort. We have thus identified TLR8 as an important driver of TFH cell differentiation and a promising target for TFH cell-skewing vaccine adjuvants.


Incidence of sclerotomy-related retinal breaks.
To estimate the incidence of sclerotomy-related retinal breaks (SRRBs) and identify possible associated risk factors. Medical records of patients who underwent pars plana vitrectomy (PPV) from January 1994 to January 1999 at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, were reviewed. The diagnosis, procedure, and possible associated risk factors were documented, in addition to the presence of SRRBs and time of discovery. Of the 441 eyes, 3.1% developed early SRRBs, while 2.9% of 350 eyes developed late SRRBs. Most of the eyes that developed SRRBs were phakic, and penetrating trauma was found statistically to increase the risk of SRRBs. SRRBs are an uncommon complication of PPV. Early detection and proper management can prevent serious sequelae of such complications.


Using the ADDIE model in designing library instruction.
Librarians are increasingly placed in the role of instructor and are required to design and deliver effective instruction. This article highlights ADDIE, an instructional design model that librarians at Weill Cornell Medical College used to redesign an evidence-based medicine course taken by first-year medical students. The ADDIE model incorporates the five phases of analysis, design, development, implementation, and evaluation. It was found that the application of ADDIE can result in instruction that focuses on learning outcomes relevant to students, meets students' needs, and facilitates active learning.


Safety and efficacy of atezolizumab with obinutuzumab and bendamustine in previously untreated follicular lymphoma.
Obinutuzumab (G) chemoimmunotherapy demonstrated improved progression-free survival (PFS) vs rituximab-based chemoimmunotherapy in patients with previously untreated follicular lymphoma (FL) in the GALLIUM trial. Atezolizumab (atezo) is a programmed death-ligand 1 inhibitor with a complementary mechanism of action to G by restoring cytotoxic T-cell function. We evaluated the safety and efficacy of atezo-G-bendamustine in patients with previously untreated FL in a phase Ib/II trial (#NCT02596971). A safety run-in phase was followed by an expansion phase with atezo-G-bendamustine induction and atezo-G maintenance for ≤24 months. Forty patients with previously untreated FL were enrolled and treated with atezo-G-bendamustine. The primary endpoint, complete response (CR) rate, assessed by an independent review committee (IRC; modified Lugano 2014 criteria) was 75.0% (95% confidence interval [CI], 61.3% to 85.8%). Three-year investigator-assessed PFS and overall survival rates were 80.9% (95% CI, 63.9% to 90.5%) and 89.3% (95% CI, 73.9% to 95.9%), respectively. At baseline, 21/40 patients had circulating lymphoma-specific clonotypes and underwent repeat testing at end of induction; all were minimal residual disease negative (10-5 sensitivity), with 16 (76.2%) CRs, 3 (14.3%) partial responses, and 2 (9.5%) with stable disease (IRC assessed). Grade 5 (fatal) adverse events (AEs) were reported in 5 patients. The efficacy of atezo-G-bendamustine in previously untreated FL did not appear superior to G-bendamustine efficacy as seen in the GALLIUM trial, and the addition of atezo to G-bendamustine was associated with an increased risk of AEs. Particularly due to the unfavorable safety profile, this regimen cannot be recommended in patients with previously untreated FL. This trial was registered at www.clinicaltrials.gov as #NCT02596971.


Response of white adipocyte of mouse and rabbit to catecholamines and ACTH. 1. Correlation of cyclic AMP levels and initial rates of lipolysis.
Hormone stimulated lipolysis of mouse and rabbit adipocytes as measured by both free fatty acid and glycerol release, is proportionally elevated with increase in the adipocyte cAMP level up to 1 nmol/g. The correlation coefficients are 0.94 and 0.97 for FFA/cAMP and glycerol/cAMP respectively. Increments in cAMP greater than 1 nmol/g show no correlation with increase in lipolysis. The release of lipolytic products, glycerol and free fatty acids, from white adipocytes in response to ACTH, epinephrine or norepinephrine was measured using radiochemical assays in short term incubation systems, with cAMP levels measured at the same time and from the same cell sample. Under the conditions studied, epinephrine is a more effective lipolytic hormone than ACTh in mouse adipocyte, and ACTH is more effective than epinephrine in rabbit adipocyte. The effect of catecholamines on the rabbit adipocyte is not modified by phentolamine (10 microM), but it is potentiated by 1-methyl-3-isobutyl xanthine (0.1 mM). The results suggest that cAMP mediates the action of these lipolytic hormones in white adipocytes of mouse and rabbit.


Macrophage Cytological Profiling and Anti-Inflammatory Drug Discovery.
Millions of people are affected by diseases and conditions related to the immune system. Unfortunately, our current supply of approved anti-inflammatory medicine is very limited and only treats a small fraction of inflammatory diseases. Nearly half of the drugs on the market today are natural products and natural product derivatives. The long-term objective of my research is to continue efforts toward the discovery of diverse chemical compounds and their mechanism of action (MOA) to inspire the next generation of novel therapeutics. This project approaches this objective by creating a robust platform for the in-depth phenotypic profiling of complex natural product samples with respect to their effect on pathways related to the innate immune response. This approach has the potential to elucidate the MOAs of novel natural products relevant to inflammation and accelerate the pace of drug discovery in this therapeutic area.


Meso- and Macroporous Polymer Gels for Efficient Adsorption of Block Copolymer Surfactants.
An understanding of surfactant adsorption at solid-liquid interfaces is important for solving many technological problems. This work evaluates surfactant adsorption abilities of high surface area (200-600 m2/g), high porosity (>90%), hierarchically structured open pore polymer gels. Specifically, the interactions of a nonionic block copolymer surfactant, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO), with three polymer gels, namely, syndiotactic polystyrene (sPS), polyimide (PI), and polyurea (PUA) offering different surface energy values, are evaluated at surfactant concentrations below and well above the critical micelle concentration (CMC). Two distinct surfactant adsorption behaviors are identified from the surface tension and nuclear magnetic resonance data. At concentrations below CMC, the surfactant molecules adsorb as a monolayer on polymer strands, inferred from the Langmuir-type adsorption isotherm, with the adsorbed amount increasing with the specific surface area of the polymer gel. The study reports for the first time that the gels show a strong surfactant adsorption above CMC, with the effective surfactant concentration in the gel reaching several folds of the CMC values. The effective surfactant concentration in the gel is analyzed using surfactant micelle size, polymer surface energy, and pore size of the gel. The findings of this study may have strong implications in liquid-liquid separation problems and in the removal of small dye molecules, heavy metal ions, and living organisms from aqueous streams.


Electronic cigarettes in mental health settings - solving a conundrum?
Electronic cigarettes (e-cigarettes), have recently been the focus of much attention and debate. This article attempts to highlight their relevance and potential importance for mental health settings, with a focus on in-patient units. To do so, the complexities involved in smoking among people with mental disorder, the debate surrounding e-cigarettes, and their potential to be utilised as a smoking cessation or temporary abstinence aid in the context of smoke-free policies and new National Institute for Health and Care Excellence guidance for smoking cessation in mental health settings, will be discussed and synthesised below.


Engineering Vero cells to secrete human insulin.
Cell therapy may have the potential for the treatment of Type I diabetes. To date, cells suitable for this purpose have not been developed. This study investigates the feasibility of modifying Vero, a cell line that may be considered safe to implant into humans, for this purpose. Stable Vero transfectants containing full-length human preproinsulin complementary deoxyribonucleic acid (cDNA) were generated using a liposomal transfection reagent. Reverse transcriptase-polymerase chain reaction, immunocytochemistry, Western blotting, and enzyme-linked immunosorbent assays were used to assess the resulting cells. Proinsulin was expressed but was not processed to insulin by these cells. Proinsulin cDNA was genetically modified, resulting in a form that is furin sensitive. The resulting stably transfected Vero clones constitutively release approximately 34%/h (32.68 +/- 2.21 to 35.62 +/- 3.14%) of the product formed, approximately 62% (59.99 +/- 6.45 to 64.64 +/- 4.57%) of which is mature insulin. These Vero transfectants did not exhibit glucose-stimulated insulin secretion. As GLUT2 and glucokinase (GCK) are not constitutively expressed by these cells, human GLUT2 cDNA and GCK cDNA were cotransfected with furin-sensitive preproinsulin cDNA into Vero cells. Insulin and GCK proteins were detected in the cytoplasmic region of the resulting cells, whereas GLUT2 was predominantly expressed in the nucleus. Coexpression of GLUT2 and GCK did not result in glucose-stimulated insulin secretion. The results from this study demonstrate the feasibility of engineering a relatively "safe" nonbeta cell line to produce human insulin. Coexpression of GLUT2 and GCK, at the levels achieved here, is not adequate enough to induce glucose-stimulated insulin secretion in such cells; the subcellular location of transfected components may be relevant.


In vitro cytotoxicity evaluation of a 50.8% NiTi single crystal.
To our knowledge, the biocompatibility of nickel-titanium (NiTi) single crystals has not been reported. Yet certain orientations of single crystals present several advantages over the polycrystalline form in terms of maximal strain, fatigue resistance, and temperature range of superelasticity. Therefore we tested the in vitro biocompatibility of 50.8% NiTi single crystals in the orientation <001> after four different heat treatments in a helium atmosphere followed by mechanical polishing. The study was performed on the material extracts after immersion of the specimens in cell culture medium (DMEM) for 7 days at 37 degrees C. Cytotoxicity studies were performed on L-929 mouse fibroblasts using the MTT assay. J-774 macrophages were used to assess the potential inflammatory effect of the extracts by IL1-beta and TNF-alpha dosages (sandwich ELISA method). Exposure of L-929 to material extracts did not affect cell viability. In addition, IL1-beta and TNF-alpha secretion was not stimulated after incubation with NiTi extracts compared to the negative controls. These results were predictable since atomic absorption spectroscopy did not detect nickel ions in the extracts with a resolution of 1 ppm. Within the limits of in vitro testing, our results demonstrate that the TiNi(50.8%) single crystals do not trigger a cytotoxic reaction.


ESIPT-exhibiting protein probes: a sensitive method for rice proteins detection during starch extraction.
The 2-(4'-isothiocyanate-2'-hydroxyphenyl)benzoxazole dye was successfully applied as label of rice proteins during the alkaline extraction of starch. Direct fluorescence measurements were used to observe the presence of proteins labelled in different steps of rice starch extraction. The results were compared to those obtained with the well-known biuret colorimetric test. Whereas the colorimetric test indicates the absence of protein after the third extraction step, the fluorescence emission of the conjugate could be observed in all extraction steps. The separation of different rice proteins could also be observed.


Child abuse in the irritable bowel syndrome.
Stress is considered a risk factor for the irritable bowel syndrome (IBS). One of the main stress sources is represented by the negative life events and trauma suffered in childhood. Several papers have endorsed the hypothesis that youth submitted to stress are prone to develop IBS. We have undertaken a review of the literature, searching all Pubmed papers pertinent to child abuse and IBS. The data suggest that indeed, children submitted to physical, psychological and sexual abuse are at risk to develop IBS as adults. However, cultural diffferences exist.


Neighborhood context and sexual behaviors among adolescents: findings from the national longitudinal study of adolescent health.
Adolescent sexual behaviors are a significant public health concern because of the risks of STDs and the negative social consequences of teenage pregnancies. Associations between neighborhood characteristics and adolescents' initiation of sex and contraceptive use are poorly understood. Multilevel logistic regression analyses of data from 14,151 adolescents in grades 7-12 in Wave 1 of the National Longitudinal Study of Adolescent Health examined the relationships between four neighborhood dimensions (socioeconomic characteristics, norms and opportunity structure, social disorganization, and racial and ethnic composition) and the initiation of sex and contraceptive use at first and most recent sex. Individual- and household-level covariates were family income, parental education, race and ethnicity, age and family structure. Multivariate analyses were stratified by gender. All four dimensions of neighborhood context were independently associated with sexual initiation. For females, living in a neighborhood with a greater concentration of youth who were idle or black residents was associated with increased odds of sexual initiation, whereas a greater concentration of married households or Hispanic residents was associated with decreased odds of initiation. Higher initiation among males was associated with a higher concentration of poverty or idle youth, while lower initiation was found with a higher concentration of affluent households or working women. The sole association with contraceptive use was that females in neighborhoods with more idle youth had a reduced likelihood of having used contraceptives at first sex. Neighborhood context appears to be modestly associated with the sexual initiation of adolescents. However, little support was found for neighborhood influence on contraceptive use, suggesting that other factors may play a more important role in shaping adolescents' contraceptive behaviors.


Functionalized graphene-based biomimetic microsensor interfacing with living cells to sensitively monitor nitric oxide release.
It is a great challenge to develop electrochemical sensors with superior sensitivity that concurrently possess high biocompatibility for monitoring at the single cell level. Herein we report a novel and reusable biomimetic micro-electrochemical sensor array with nitric oxide (NO) sensing-interface based on metalloporphyrin and 3-aminophenylboronic acid (APBA) co-functionalized reduced graphene oxide (rGO). The assembling of high specificity catalytic but semi-conductive metalloporphyrin with high electric conductive rGO confers the sensor with sub-nanomolar sensitivity. Further coupling with the small cell-adhesive molecule APBA obviously enhances the cytocompatibility of the microsensor without diminishing the sensitivity, while the reversible reactivity between APBA and cell membrane carbohydrates allows practical reusability. The microsensor was successfully used to sensitively monitor, in real-time, the release of NO molecules from human endothelial cells being cultured directly on the sensor. This demonstrates its potential application in the detection of NO with very low bioactive concentrations for the better understanding of its physiological function and for medical tracking of patient states.


The Kv1-associated molecules TAG-1 and Caspr2 are selectively targeted to the axon initial segment in hippocampal neurons.
Caspr2 and TAG-1 (also known as CNTNAP2 and CNTN2, respectively) are cell adhesion molecules (CAMs) associated with the voltage-gated potassium channels Kv1.1 and Kv1.2 (also known as KCNA1 and KCNA2, respectively) at regions controlling axonal excitability, namely, the axon initial segment (AIS) and juxtaparanodes of myelinated axons. The distribution of Kv1 at juxtaparanodes requires axo-glial contacts mediated by Caspr2 and TAG-1. In the present study, we found that TAG-1 strongly colocalizes with Kv1.2 at the AIS of cultured hippocampal neurons, whereas Caspr2 is uniformly expressed along the axolemma. Live-cell imaging revealed that Caspr2 and TAG-1 are sorted together in axonal transport vesicles. Therefore, their differential distribution may result from diffusion and trapping mechanisms induced by selective partnerships. By using deletion constructs, we identified two molecular determinants of Caspr2 that regulate its axonal positioning. First, the LNG2-EGF1 modules in the ectodomain of Caspr2, which are involved in its axonal distribution. Deletion of these modules promotes AIS localization and association with TAG-1. Second, the cytoplasmic PDZ-binding site of Caspr2, which could elicit AIS enrichment and recruitment of the membrane-associated guanylate kinase (MAGuK) protein MPP2. Hence, the selective distribution of Caspr2 and TAG-1 may be regulated, allowing them to modulate the strategic function of the Kv1 complex along axons.


Cross Talk in HEK293 Cells Between Nrf2, HIF, and NF-κB Activities upon Challenges with Redox Therapeutics Characterized with Single-Cell Resolution.
Many transcription factors with importance in health and disease are redox regulated. However, how their activities may be intertwined in responses to redox-perturbing stimuli is poorly understood. To enable in-depth characterization of this aspect, we here developed a methodology for simultaneous determination of nuclear factor E2-related factor 2 (Nrf2), hypoxia-inducible factor (HIF), and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation at single-cell resolution, using a new tool named pTRAF (plasmid for transcription factor reporter activation based upon fluorescence). The pTRAF allowed determination of Nrf2, HIF, and NF-κB activities in a high-resolution and high-throughput manner, and we here assessed how redox therapeutics affected the activities of these transcription factors in human embryonic kidney cells (HEK293). Cross talk was detected between the three signaling pathways upon some types of redox therapeutics, also by using inducers typically considered specific for Nrf2, such as sulforaphane or auranofin, hypoxia for HIF activation, or tumor necrosis factor alpha (TNFα) for NF-κB stimulation. Doxorubicin, at low nontoxic doses, potentiated TNFα-induced activation of NF-κB and HIF, without effects in stand-alone treatment. Stochastic activation patterns in cell cultures were also considerable upon challenges with several redox stimuli. A novel strategy was here used to study simultaneous activation of Nrf2, HIF, and NF-κB in single cells. The method can also be adapted for studies of other transcription factors. The pTRAF provides new opportunities for in-depth studies of transcription factor activities. In this study, we found that upon challenges of cells with several redox-perturbing conditions, Nrf2, HIF, and NF-κB are uniquely responsive to separate stimuli, but can also display marked cross talk to each other within single cells. Antioxid. Redox Signal. 26, 229-246.


miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy.
Chemotherapy is an important treatment modality for gastric cancer, and multidrug resistance (MDR) represents a major obstacle for successful cancer chemotherapy. There is a lack of research on whether microRNA (miR)-30a regulation affects the chemosensitivity of resistant gastric cancer cells, and mechanisms underlying the effects of miR-30a on drug resistance and cell autophagy require further investigation. In the present study, the expression of miR-30a and its effects in cisplatin (CDDP)-resistant human gastric cancer cells were investigated. A CDDP-resistant variant of the SGC-7901 cell line (SGC-7901/CDDP) was established by exposing the cells to gradually increasing drug concentrations, and miR-30a expression was detected by reverse transcription-semi quantitative polymerase chain reaction (RT-sqPCR). To examine the effect of miR-30a expression in the SGC-7901/CDDP cells, miR30a mimics or negative control miRNA were transfected into the cells, and a Cell Counting Kit-8 assay was performed to analyze the chemosensitivity of the different cell groups. RT-sqPCR and western blot analysis were also used to measure MDR1 mRNA and P-glycoprotein expression, and the light chain (LC)3-II/LC3-I ratio. Furthermore, apoptosis induced by the chemotherapeutic CDDP in the different groups was assessed using flow cytometry. The results demonstrated that low expression of miR-30a was associated with chemoresistance in gastric cancer cells, and in the chemoresistant cell line SGC7901/CDDP, CDDP-induced apoptosis was weakened. Additionally, it was demonstrated that the LC3-II/LC3-I ratio was elevated in SGC7901/CDDP cells compared with chemosensitive SGC7901 cells (P<0.001), which could be attenuated by upregulating miR-30a expression (P<0.001 vs. SGC7901/CDDP control cells). These results suggested that autophagy may contribute to drug resistance in gastric cancer cells, and that the reduction of LC3-II in response to miR-30a overexpression may inhibit chemoresistance-associated autophagy in gastric cancer cells.


Mobile Phone-Supported Physiotherapy for Frozen Shoulder: Feasibility Assessment Based on a Usability Study.
Patients with frozen shoulder show limited shoulder mobility often accompanied by pain. Common treatment methods include physiotherapy, pain medication, administration of corticosteroids, and surgical capsulotomy. Frozen shoulder often lasts from months to years and mostly affects persons in the age group of 40 to 70 years. It severely reduces the quality of life and the ability to work. The objective of this study was to evaluate the feasibility of a mobile health (mHealth) intervention that supports patients affected by "stage two" frozen shoulder. Patients were supported with app-based exercise instructions and tools to monitor their training compliance and progress. These training compliance and progress data supplement the patients' oral reports to the physiotherapists and physicians and can assist them in therapy adjustment. In order to assess the feasibility of the mHealth intervention, a pilot study of a newly developed app for frozen shoulder patients was conducted with 5 patients for 3 weeks. The main function of the app was the instruction for exercising at home. Standardized questionnaires on usability such as System Usability Scale (SUS) and USE (Usefulness, Satisfaction, and Ease of use), and Technology Acceptance Model-2 (TAM-2) were completed by the study participants at the end of the study. Additionally, a nonstandardized questionnaire was completed by all patients. The correctness of the exercises as conducted by the patients was assessed by a physiotherapist at the end of the study. The mobility of the shoulder and pain in shoulder movement was assessed by a physiotherapist at the start and the end of the study. The pilot study was successfully conducted, and the app was evaluated by the patients after 3 weeks. The results of the standardized questionnaires showed high acceptance (TAM-2) and high usability (SUS) of the developed app. The overall usability of the system as assessed by the SUS questionnaire was very good (an average score of 88 out of 100). The average score of the TAM-2 questionnaire on the intention to further use the app was 4.2 out of 5, which indicated that most patients would use the app if further available. The results of the USE questionnaires highlighted that the patients learned how to use the app easily (an average score of 4.2 out of 5) and were satisfied with the app (an average score of 4.7 out of 5). The frequency of app usage and training was very high based on patient reports and verified by analysis of the usage data. The patients conducted the exercises almost flawlessly. Our results indicate the feasibility of the mHealth intervention, as the app was easy to use and frequently used by the patients. The app supported the patients' physiotherapy by providing clear exercising instructions.


A Host Factor GPNMB Restricts Porcine Circovirus Type 2 (PCV2) Replication and Interacts With PCV2 ORF5 Protein.
Porcine circovirus type 2 (PCV2) is the infectious agent of postweaning multisystemic wasting syndrome (PMWS). The recently discovered open reading frame 5 (ORF5) in PCV2 genome encodes a non-structural protein. Previous study revealed that ORF5 protein inhibits cell proliferation and may interact with host transmembrane glycoprotein NMB (GPNMB). However, whether the GPNMB affects PCV2 replication and the underlying molecular mechanisms are still unknown. In this study, the transcriptome maps of PCV2-infected and ORF5-transfected porcine alveolar macrophages 3D4/2 (PAM) cells were profiled. The GPNMB gene was down-regulated in PCV2-infected and ORF5-transfected PAMs. By using glutathione S-transferase (GST) pull-down, co-immunoprecipitation (co-IP) and confocal microscopy approaches, we convincingly showed that PCV2 ORF5 protein interacts with GPNMB. Furthermore, by utilizing lentivirus mediated overexpression or knockdown approach, we showed that the cellular GPNMB significantly inhibits PCV2 replication and ORF5 expression. Moreover, GPNMB overexpressing leads to an increased Cyclin A expression and a reduced S phase, whereas GPNMB knockdown causes a decreased Cyclin A expression and a prolonged S phase. In conclusion, we identified a novel host factor GPNMB that interacts with PCV2 ORF5 protein and restricts PCV2 replication.


Interaction of human immunodeficiency virus with human sperm in vitro.
Transmission of human immunodeficiency virus (HIV) in semen by sexual intercourse is believed to be a major etiological factor in the spread of the disease. In order to explore the role of sperm in this transmission, cell-free HIV-1(IIIB) was coincubated with human sperm for 5 h. After incubation, unattached HIV-1 was extensively washed off the cells and the presence and location of HIV-1 in or on the sperm was determined by electron microscopic (EM) and immunofluorescence methods. Examination of sperm at the EM level showed that HIV-1 attaches to the sperm surface and enters the sperm through the intact cell membrane. Immunofluorescence studies, using polyvalent anti-HIV antibodies, demonstrated the presence of small round fluorescent particles in 5-10% of sperm heads after 5 h of incubation. A search for HIV-1 receptors (CD4 epitopes) revealed the presence of OKT4 epitopes, including OKT4A, B, D, and F on 5-10% of sperm by epifluorescence microscopy and on 10-20% of sperm by flow-cytometric analysis. These in vitro data suggest that human sperm may be the primary cellular element in the transmission of HIV by semen.


Inhibition of BCL11B expression leads to apoptosis of malignant but not normal mature T cells.
The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B gene (BCL11B) encodes a Krüppel-like zinc-finger protein, which plays a crucial role in thymopoiesis and has been associated with hematopoietic malignancies. It was hypothesized that BCL11B may act as a tumor-suppressor gene, but its precise function has not yet been elucidated. Here, we demonstrate that the survival of human T-cell leukemia and lymphoma cell lines is critically dependent on Bcl11b. Suppression of Bcl11b by RNA interference selectively induced apoptosis in transformed T cells whereas normal mature T cells remained unaffected. The apoptosis was effected by simultaneous activation of death receptor-mediated and intrinsic apoptotic pathways, most likely as a result of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) upregulation and suppression of the Bcl-xL antiapoptotic protein. Our data indicate an antiapoptotic function of Bcl11b. The resistance of normal mature T lymphocytes to Bcl11b suppression-induced apoptosis and restricted expression pattern make it an attractive therapeutic target in T-cell malignancies.


Hydrogel-microsphere-enhanced surface plasmon resonance for the detection of a K-ras point mutation employing peptide nucleic acid.
Highly-sensitive detection of a K-ras point mutation in codon 12, frequently found in pancreatic cancer, based on DNA-carrying hydrogel microspheres as a response enhancer for surface plasmon resonance (SPR), is described. Acrylamide-based microspheres with carboxyl groups were conjugated with DNA probes. Use of the DNA-carrying microsphere in the sandwich method, that is, binding of the microspheres with target DNAs at the sensor surface, enhanced the SPR response as a combined result of increased dielectric constant by the DNA-carrying microspheres. Microspheres lead to response enhancement, as shown by a 100-fold increase in sensitivity compared to that of non-amplified DNA target hybridization. In addition, the advantage of peptide nucleic acid (PNA) in the detection of a K-ras point mutation at the sensor surface by increasing temperature and flow rate is discussed. Results illustrate that the sandwich method through DNA-carrying microspheres for a SPR sensor is a promising approach for ultrasensitive DNA detection.


Differential regulation of brain and pituitary corticotropin-releasing factor receptors by corticosterone.
The regulatory actions of CRF during the neuroendocrine response to stress are mediated by specific receptors within the nervous system and the anterior pituitary gland. Glucocorticoids exert negative feedback inhibition on ACTH secretion by interacting at the pituitary corticotrophs and the central nervous system. To determine whether glucocorticoids influence ACTH secretion by regulating the concentration of CRF receptor sites, binding of [125I]Tyr-oCRF to pituitary and brain membrane-rich particles was studied after glucocorticoid treatment. Corticosterone administration (0.5-150 mg/day) for 1-4 days in adult male rats caused a dose-dependent decrease in the number of CRF receptors in the anterior pituitary in parallel with the reduction in ACTH secretion. In the brain, binding studies in membrane-rich fractions or by autoradiography in slide-mounted frozen sections revealed no changes in CRF receptors in the cortex, hippocampus, amygdala, septal area, and olfactory bulb, although circulating corticosterone levels were higher than during stress. The selective down-regulation of anterior pituitary CRF receptors after corticosterone administration, without alterations in brain CRF receptors, is similar to the change in CRF receptors previously reported after adrenalectomy and indicates that receptor regulatory mechanisms in secretory cells differ from those in neural tissue. Furthermore, the decrease in pituitary CRF receptors after physiological increases in circulating glucocorticoids may contribute to the inhibitory effects of adrenal steroids on ACTH secretion.


Rabies virus-specific T cell hybridomas: identification of class II MHC-restricted T-cell epitopes using synthetic peptides.
Rabies virus-specific T-cell hybridomas were produced from immune mice by somatic cell fusion. Cloned T-cell hybridomas were studied for antigen specificity using purified virus, a recombinant vaccinia virus expressing rabies glycoprotein and synthetic peptides containing amino acid sequences of rabies viral antigens. Two closely situated T-cell epitopes of rabies glycoprotein, and one of rabies nucleoprotein were identified using synthetic peptides corresponding to amino acid sequences of these proteins. The major histocompatibility gene complex elements that determine the recognition of antigen by these T-cell hybrids were determined using mouse fibroblasts (L cells) transfected with and expressing the I-Ad and I-Ed genes. Some of the T cell hybridomas exhibited significant cytotoxic activity against target cells expressing surface rabies antigens. This T cell mediated cytotoxicity requires cell-to-cell contact between target and effector cells since no by-stander cytotoxicity was observed. The results are discussed in the context of their significance for the design of newer subunit vaccines to prevent rabies infection.


Oil coating affects internal quality and sensory acceptance of selected attributes of raw eggs during storage.
Four (coconut, palm, rice bran, and soybean) edible oils and glycerol were applied on eggshell. All noncoated and coated eggs were stored for 5 wk at 25 ± 2 °C and drawn weekly for quality evaluation. All oil coatings were more effective in preserving internal quality of eggs than was glycerol coating. As storage time increased, the preservative effects of edible oil coating on weight loss, and albumen and yolk quality were significantly noticed. Oil-coated eggs had significantly lower weight loss (<0.43%) than did noncoated (3.87%) and glycerol-coated (3.73%) eggs after 5 wk of storage. Based on the Haugh unit, oil-coated eggs maintained AA grade up to 3 wk. After 5 wk of storage, noncoated, glycerol-coated, and oil-coated eggs changed from AA grade to below B, below B and A grade, respectively. The albumen pH of noncoated and glycerol-coated eggs considerably increased from 8.23 to 9.51 and 9.42, respectively, while those of oil-coated eggs either maintained or slightly increased to 8.32. The albumen viscosity of all eggs decreased with increased storage time. Consumers (N = 120) could differentiate surface glossiness of oil-coated eggs from uncoated eggs (R-index of 81.42% to 86.99%). All oil-coated eggs were acceptable for surface glossiness (liking scores of 6.22 to 6.77) and surface odor (liking scores of 6.20 to 6.55) with overall liking scores of 6.34 to 7.03. Overall, this study demonstrated that edible oil (coconut, palm, rice bran, and soybean) coating could preserve internal quality of eggs (maintaining grade A) at least 4 wk longer than noncoated eggs. Freshness is a major contribution to the egg quality. The internal quality of eggs begins to deteriorate after they have been laid due to loss of moisture and carbon dioxide via the eggshell pores. Refrigeration is very effective in preserving egg quality. Surface coating is an alternative method to preserve egg quality, although it is much less effective than refrigeration. This study demonstrated that coconut, rice bran, soybean, and palm oils, which are abundant and commonly consumed in many parts of the world, could preserve the internal quality and reduce weight loss of oil-coated eggs during room temperature storage.


Core-level electronic structure of solid-phase glycine, glycyl-glycine, diglycyl-glycine, and polyglycine: X-ray photoemission analysis and Hartree-Fock calculations of their zwitterions.
X-ray photoelectron spectroscopy (XPS) has been used to investigate the core-level electronic structures of glycine (G) and its peptides, including glycyl-glycine (GG), diglycyl-glycine (GGG), and polyglycine (poly-G), in their powder forms. Increasing the number of G units in the peptides does not change the locations of the respective C 1s, N 1s, and O 1s features corresponding to different functional groups: -COO(-), -NH(3)(+), >CH(2), and -CONH-. The electronic structures of the zwitterions of these molecules have been calculated as isolated molecules and as molecules in an aqueous environment under the periodic boundary conditions by quantum-mechanical and molecular mechanics methods. In the case of glycine zwitterion, the binding energies of the C 1s, N 1s, and O 1s XPS features are found to be in reasonable accord with the respective orbital energies obtained by Hartree-Fock self-consistent-field calculations, within the context of Koopmans' approximation. However, considerably worse agreement in the binding energies is found for the larger zwitterions (with the specific conformations considered in this work), indicating the need for higher-level calculations. The present work shows that optimizing the zwitterion in an aqueous environment under the periodic boundary conditions by molecular mechanics could be a very cost-effective approach for calculating the electronic structures of large, complex biomolecular systems.


Research Use of Nurses Working in the Critical Care Units: Barriers and Facilitators.
There is a distinct gap between theory and practice with respect to research use in clinical practice, particularly in critical care units, that could be related to the presence of a number of barriers that hinder the use of research findings. The aims of the study were to identify barriers and facilitators to research use as perceived by Jordanian nurses in critical care units and to examine the predictors of research use among those nurses. The study used a cross-sectional, correlational design. The self-administered "Barriers Scale" was introduced to 200 registered critical care nurses, using the drop-and-collect technique, between October and November 2015. The results revealed that "nurse does not have time to read research at work" was the top ranked barrier that hinders research use (mean [SD], 3.45 [0.79]). The first 7 ranked barriers were related to the organizational subscale. Managerial support was the top perceived facilitator for research use. Only "attending special training courses in nursing research" was the significant predictor of research use and explained 59.1% of the variance in research use, t(190) = -3.93, P = .003. The most identified barriers toward research use revealed by the qualitative data include dominant routine nursing tasks, existence of gap between theory and practice, shortage of nursing staff, and public negative image about nursing profession. Participants suggested the importance of increasing organizational support and creating an organizational research culture to further promote research use in clinical nursing practice. Research use has not been widely implemented yet in Jordan because of various barriers. The organization-related barriers were the most influential. Factors hindering research use are multidimensional, and optimizing them should be a shared responsibility of nurse managers, researchers, clinicians, and academicians. Further initiatives are required to raise awareness of the importance of using evidence-based practice.


Commercialization conditions and practices influence the microbiological quality of mineral waters.
The objective of the present study was to determine the microbiological quality of bottled mineral water marketed in commercial establishments and by street vendors and to evaluate the influence of the storage and maintenance conditions on the microbiological quality of the product. Ten samples from the same batches of five different brands of water were analyzed, for a total of 50 samples. Of the five brands analyzed, only one (brand A), when collected in a commercial establishment, complied with the legal Brazilian standards for mineral water with respect to the presence of total coliforms, fecal coliforms, and Pseudomonas aeruginosa. The remaining samples failed to comply with these microbiological standards for at least one of the parameters evaluated. The water samples obtained from street vendors were inferior in microbiological quality to samples from the same batch that were obtained from commercial establishments.


From somatic pain to psychic pain: The body in the psychoanalytic field.
The integration of psyche and soma begins with a baby's earliest contact with his or her parents. With the help of maternal empathy and reverie, β-elements are transformed into α-elements. While we understand this to be the case, we would like to enquire what actually happens to those parts of the affect which have not been transformed? For the most part they may be dealt with by evacuation, but they can also remain within the body, subsequently contributing to psychosomatic symptoms.This paper describes how the body serves as an intermediate store between the psychic (inner) and outer reality. The authors focuses on the unconscious communicative process between the analyst and the analysand, and in particular on how psychosomatic symptoms can spread to the analyst's body. The latter may become sensitive to the analysand's psychosomatic symptoms in order to better understand the psychoanalytical process. Sensory processes (visual and auditory) and psychic mechanisms such as projective identification can serve as a means for this communication.


Selenium supplementation modulates apoptotic processes in thyroid follicular cells.
Selenium (Se) is an essential micronutrient modulating several physiopathological processes in the human body. The aim of the study is to characterize the molecular effects determined by Se-supplementation in thyroid follicular cells, using as model the well-differentiated rat thyroid follicular cell line FRTL5. Experiments have been performed to evaluate the effects of Se on cell growth, mortality and proliferation and on modulation of pro- and antiapoptotic pathways. The results indicate that Se-supplementation improves FRTL5 growth rate. Furthermore, Se reduces the proportion of cell death and modulates both proapoptotic (p53 and Bim) and antiapoptotic (NF-kB and Bcl2) mRNA levels. In addition, incubation with high doses of Na-Se might prevent the ER-stress apoptosis induced by tunicamycin, as assessed by membrane integrity maintenance, reduction in caspase 3/7 activities, and reduction in Casp-3 and PARP cleavage. Taken together, these results provide molecular evidences indicating the role of Se supplementation on cell death and apoptosis modulation in thyroid follicular cells. These observations may be useful to understand the effects of this micronutrient on the physiopathology of the thyroid gland. © 2016 BioFactors, 43(3):415-423, 2017.


Phosphatidylcholine-associated aspirin accelerates healing of gastric ulcers in rats.
Based on our previous studies that aspirin (ASA) -induced gastric ulceration in rats can be significantly reduced if the drug is chemically associated with phosphatidylcholine (PC), we undertook the present study to compare gastric ulcer healing rates in rats administered either unmodified or PC-complexed ASA. Gastric ulcers were induced in anesthetized rats by briefly exposing the mucosal surface to 0.2 ml 60% acetic acid followed by randomization of the rats to study groups; daily intragastrically administered saline (control), ASA (36, 54 mg/kg), or ASA-PC complex. In contrast to the 65-70% reduction in ulcer size recorded in controls, ulcer healing was significantly retarded in rats administered unmodified ASA. Conversely, the size of the experimentally induced ulcers was less than control values in rats daily administered the PC-associated ASA, suggesting an acceleration in the rate of ulcer healing. Daily intragastric administration of ASA to rats over the study period also resulted in a significant decrease in surface hydrophobicity from control values as measured by contact angle analysis. However, surface hydrophobicity was partially restored in rats administered the PC-complexed ASA. Consistent with these findings, it was determined that ASA-treated rats had a lower hematocrit than control values, as an index of gastrointestinal bleeding, whereas this parameter remained at control levels in rats administered the PC-complexed ASA. We conclude that PC-associated ASA promotes ulcer healing above the values measured in rats treated with ASA or saline. This property may be attributable to the fact that in contrast to unmodified ASA, which aggravates ulcer healing by transforming the stomach to an acid-permeable state, the protective hydrophobic lining of the stomach is maintained in rats administered PC-associated ASA, thereby allowing ulcer healing of the tissue to proceed.


Is there a correlation between urological and cardiovascular dysfunction in Parkinson's disease?
It is well established that non-motor symptoms are a core feature of Parkinson's disease (PD). A dysregulation of the autonomic nervous system seems to be present in PD, supporting the coexistence of urological and cardiovascular non-motor features. We evaluated whether bladder dysfunctions in patients with PD are linked to blood pressure dysregulation. Twenty-eight mild PD patients, previously submitted to a urodynamic evaluation, underwent 24-hour ambulatory blood pressure and heart rate monitoring to allow assessment of their circadian blood pressure profile; the occurrence of postprandial hypotension and orthostatic hypotension was also investigated. No significant differences in blood pressure control were detected between bladder hyperreflexic and normoreflexic subjects. Our findings support different origins of urological and cardiovascular impairments in PD.


A metrics framework to get and keep management engaged.
Conferences and webinar presentations regularly extol the importance of executive support when building a successful, sustainable business continuity, IT disaster recovery, crisis or emergency management programme. When executives are engaged, it is a beautiful thing. One feels empowered and appreciated. Then one day, it is gone. Or worse, it was never there. Was it somebody's fault, or was it some other factor? Business continuity management (BCM) practitioners monitor the progression of their efforts and quality of results through metrics. However, which metrics or key performance indicators provide the greatest value, particularly in the context of gaining and keeping executive support? This paper reviews several traditional metrics models, assessing both the positive and negatives that each offer. This is followed by an in-depth overview of the Business Continuity Maturity Model (BCMM), a publicly-available organisation resilience programme assessment tool that, when applied effectively, provides a rigorous framework for programme assessment and ongoing metrics reporting. This is followed by an analysis of the models, and recommendations on the use of metrics to tell a resiliency story that demonstrates value.


Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques.
Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.


Interactions between toxic (As, Cd, Hg and Pb) and nutritional essential (Ca, Co, Cr, Cu, Fe, Mn, Mo, Ni, Se, Zn) elements in the tissues of cattle from NW Spain.
Since the toxicity of one metal or metalloid can be dramatically modulated by the interaction with other toxic or essential metals, studies addressing the chemical interactions between trace elements are increasingly important. In this study correlations between the main toxic (As, Cd, Hg and Pb) and nutritional essential (Ca, Co, Cr, Cu, Fe, Mn, Mo, Ni, Se, Zn) elements were evaluated in the tissues (liver, kidney and muscle) of 120 cattle from NW Spain, using Spearman rank correlation analysis based on analytical data obtained by ICP-AES. Although accumulation of toxic elements in cattle in this study is very low and trace essential metals are generally within the adequate ranges, there were significant associations between toxic and essential metals. Cd was positively correlated with most of the essential metals in the kidney, and with Ca, Co and Zn in the liver. Pb was significantly correlated with Co and Cu in the liver. A large number of significant associations between essential metals were found in the different tissues, these correlations being very strong between Ca, Cu, Fe, Mn, Mo and Zn in the kidney. Co was moderately correlated with most of the essential metals in the liver. In general, interactions between trace elements in this study were similar to those found in polluted areas or in experimental studies in animals receiving diets containing high levels of toxic metals or inadequate levels of nutritional essential elements. These interactions probably indicate that mineral balance in the body is regulated by important homeostatic mechanisms in which toxic elements compete with the essential metals, even at low levels of metal exposure. The knowledge of these correlations may be essential to understand the kinetic interactions of metals and their implications in the trace metal metabolism.


[Retroperitoneoscopic technologies in retroperitoneal procedures].
The active development of minimally invasive procedures on retroperitoneal organs using endoscopic technology raises the question of the most rational approach. The studies dedicated to the comparison of transperitoneal and retroperitoneoscopic approach are analyzed in the article. The advantages and the most common complications, as well as the factors limiting the widespread use of retroperitoneoscopic approach, are reviewed.


One-step Plasmodium falciparum cultivation--application to in-vitro drug testing.
P. falciparum was cultivated by a one-step method which requires medium renewal and addition of fresh RBC only every three days and allows high proliferation rates of the parasite. The method has been used for routine maintenance of strains and applied to the in-vitro evaluation of the effect of antimalarial compounds over 3 days periods as measured by 3H-Hypoxanthine incorporation.


Real-World Six-Year National Cost-Minimization Analysis of IncobotulinumtoxinA and OnabotulinumtoxinA in the VA/DoD Healthcare Systems.
This study sought to perform a real-world, long-term cost-minimization analysis for incobotulinumtoxinA (Xeomin®) versus onabotulinumtoxinA (Botox®), given the established non-inferiority when utilized at similar doses. The Department of Veterans Affairs (VA) and Department of Defense (DoD) national healthcare systems were included in this analysis. Real-world purchase data for incobotulinumtoxinA were used to estimate the direct drug costs between calendar years 2014 and 2019. Publicly available federal pharmaceutical prices (Federal Supply Schedule and Big 4) were used. The primary outcome was the difference in total direct costs nationally for incobotulinumtoxinA (real-world) versus having hypothetically utilized onabotulinumtoxinA (projected) for similar utilization. Sites utilizing ≥100 vials (of 100 Unit equivalents) of incobotulinumtoxinA annually were categorized as "major adopters". IncobotulinumtoxinA 50 Unit vials were assumed to be an alternative to a 100 Unit vial of onabotulinumtoxinA for 50% of such vial purchases in the base case scenario to account for differences in wastage. Over the six-year study time frame, 156 sites (76.8%) utilized incobotulinumtoxinA of the 203 total VA healthcare systems and DoD medical centers. Of these sites, 67 were major adopters for at least one year, with a mean of 3.4 years spent as a major adopter over the study period. Average annual savings per major adopter was $105,782. IncobotulinumtoxinA costs for all VA/DoD sites was $46.39 million for the six-year period versus a projected $71.92 million onabotulinumtoxinA cost-a total savings of $25.53 million (35.5% relative reduction). Approximately, 82.8% of savings stemmed from lower drug acquisition cost ($21.14 million) and 17.2% of savings ($4.39 million) was related to reduced wastage. It was estimated that a total of 9958 extra onabotulinumtoxinA 100 Unit vials would have been wasted during the six-year period, translating to the need for a 5.9% increase in vial purchases versus incobotulinumtoxinA. Meaningful cost savings were realized related to incobotulinumtoxinA adoption over a long-term time frame in the VA/DoD healthcare systems.


Immunosuppression in the surgical patient.
A review of both the healthy and altered immune response as it relates to the surgical patient is presented. An increasing number of immunosuppressive states have been defined in the surgical patient including trauma, burns, sepsis, malnutrition, cancer, and, more recently, acquired immunodeficiency syndrome (AIDS).Investigations of the healthy and altered immune response have led to the development of immunopharmacology, which involves the study of pharmacologic agents that modify host immune response to achieve desired therapeutic goals. Endogenous and exogenous immunomodulators are described that affect uniquely the host immune response as well as their therapeutic implications.


Transient lesions of the splenium of the corpus callosum following rapid withdrawal of levetiracetam.
Transient lesions of the splenium of the corpus callosum are characterized by MRI findings. The lesions are very rare, but significant from a clinical standpoint as differential diagnoses include serious conditions such as encephalitis, meningitis, and neuroleptic malignant syndrome. In addition, it is reported that some are attributed to the withdrawal of antiepileptic drugs. Here, we present a case of transient lesions of the splenium of the corpus callosum following rapid withdrawal of levetiracetam alone. To the best of our knowledge, this is the first report of such a case. Moreover, it is reported that cases of incidental transient lesions of the splenium of the corpus callosum are detected in Japan more often than in other countries, and as a result are prone to over-triage. Taking this into consideration, in the event of transient lesions of the splenium of the corpus callosum, the utmost attention must be paid to clinical symptoms and history relating to any of the aforementioned serious conditions.


Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus.
The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. Here we show that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock (clock-controlled). Receptor for PK2 (PKR2) is abundantly expressed in major target nuclei of the SCN output pathway. Inhibition of nocturnal locomotor activity in rats by intracerebroventricular delivery of recombinant PK2 during subjective night, when the endogenous PK2 mRNA level is low, further supports the hypothesis that PK2 is an output molecule that transmits behavioural circadian rhythm. The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output.


Effects of xylitol wipes on cariogenic bacteria and caries in young children.
The aim of the study was to investigate the efficacy of the use of xylitol-containing tooth-wipes in preventing dental caries in young children. In a double-blinded randomized controlled clinical trial, 44 mothers with active caries and their 6- to 35-month-old children were randomized to xylitol-wipe or placebo-wipe groups. The children's caries scores were recorded at baseline and 1 year. Salivary levels of mutans streptococci and lactobacilli were enumerated at baseline, 3, 6, and 12 months. Data were analyzed by intent-to-treat modeling with imputation for caries lesions and a linear mixed-effect model for bacterial levels. Significantly fewer children in the xylitol-wipe group had new caries lesions at 1 year compared with those in the placebo-wipe group (P < 0.05). No significant differences between the two groups were observed in levels of mutans streptococci and lactobacilli at all time-points. Daily xylitol-wipe application significantly reduced the caries incidence in young children as compared with wipes without xylitol, suggesting that the use of xylitol wipes may be a useful adjunct for caries control in infants (Clinicaltrials.gov registration number CT01468727).


Sex differences in neurology: a scoping review protocol.
Sex and gender are independently important in health and disease but have been incompletely explored in neurology. This is in part contributed to by the pre-existing male bias in scientific literature that results in fewer females being included in clinical research and the often interchangeable use of sex and gender in the literature. This scoping review intends to identify the advances as well as under-explored aspects of this field to provide a road map for future research. This paper outlines the methods for a scoping review of published, peer-reviewed literature on sex and gender differences in four subspecialty areas of neurology: demyelination, stroke, epilepsy and headache. A detailed search strategy will be used to search five databases pertaining only to sex differences. Specific inclusion and exclusion criteria will be applied to capture relevant literature published from 2014 to 2020. Data will be collected and synthesised to provide an overview of information retrieved, a narrative synthesis of each subspecialty area and map of results. Research ethics board approval was not required for this study. This study will aid in mapping recent trends in sex differences in four major neurological conditions and will help identify areas for further research. A manuscript will be compiled for publication and presentations of findings. The final protocol is registered with the Open Science Framework (https://osf.io/n937x/).


Mechanism of oxidative stress and Keap-1/Nrf2 signaling pathway in bronchopulmonary dysplasia.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in premature infants and is one of the leading causes of disability and death in newborns. The Keap-1/Nrf2 signaling pathway plays an important role in antioxidant and anti-inflammatory.Ten clean-grade, healthy pregnant Sprague-Dawley rats (purchased from Experimental Animal Center of Peking university, China) naturally gave birth to 55 neonatal rats from which 40 were selected and randomly divided into a hyperoxia group and a control group (N = 20, each). Thirty-two BPD patient samples are from Neonatal Department of the second Hospital of Jilin University from November 30, 2016 to May 1 2019.In present study, we observed that lung tissues of the control group did not undergo obvious pathological changes, whereas in the hyperoxia group, lung tissues had disordered structures. With increased time of hyperoxia exposure, the alveolar wall became attenuated. Under hypoxia conditions, the activity of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in lung samples was significantly lower than that before treatment. The expression level of Keap1 mRNA and protein in the hyperoxia group was slightly lower than that of control group. The expression of Nrf2 and HO-1 mRNA and protein in the hyperoxia group was significantly higher than that of control group. For the infants with BPD, we found that the activity of SOD, GSH-Px, and CAT was significantly different from those of control group.We constructed a premature BPD animal model and found the abnormal of oxidative stress in different groups and the expression levels of Keap1/Nrf2 signaling pathway-related molecules, and we validated the results in premature infants with BPD.


A study of morphometric and histopathological features of muscle biopsies from patients of myopathy.
The aim of this study is to analyse the morphological pattern of different types of myopathies including morphometric data. The cases were diagnosed as myopathy on the basis of clinical details, EMG findings, serum CK values. Muscle biopsies were performed and hematoxylin & eosin stain and Masson's trichrome stain were done. Muscle fiber diameters were measured using an eye piece micrometer of 100 fibers in each biopsy, these values were plotted and histograms were constructed. From this, mean fiber diameter (MFD), standard Deviation (SD), atrophy factor (AF), hypertrophy factor (HF) and variability coefficient (VC) were calculated. Degree of inflammation was scored semiquantitatively and presence of degenerating fibers, regenerating fibers, perifascicular atrophy, perivascular lymphocytic infiltration and vasculitis were noted. Out of 25 patients, 9 patients of inflammatory myopathy were adults, of the 16 patients of dystrophy 9 patients were adults. Along with weakness of limbs, skin rash was seen in 2 patients of dermatomyositis. Degree of inflammation was more in the patients of inflammatory myopathy than in the patients of dystrophy. Necrotic and regenerating fibers were seen in both groups. Perifascicular atrophy was seen in 1 case of dermatomyositis. Atrophy factor was higher in cases of dystrophy and so was hypertrophy factor. Variability coefficient >250 was found on 90% of dystrophy cases and it was <250 in the cases of inflammatory myopathy. Morphometry provides valuable data, which helps in distinguishing dystrophy from cases of myopathy with inflammation.


Effects of low-amplitude pulsed magnetic fields on cellular ion transport.
Pulsed magnetic fields (PMFs) are widely used to treat difficult fractures of bone and other disorders of connective tissue. It is not clear how they interact with tissue metabolism, although it has been proposed that induced currents or electric fields impinging on cell membranes may modify their ion transport function. This hypothesis was tested by treating in vitro models for ion transport processes with short-term exposure to PMFs. No change occurred in active transport of potassium or calcium in human red cells or in calcium transport through an epithelial membrane. We considered less direct action on red cell membranes, that their permeability might be modified after PMF treatment, and also that PMFs might alter the extracellular ionic activity within connective tissue by interacting with its Donnan potential. Each of these studies proved negative, and we conclude that the PMF waveforms used here do not exert a general short-term effect on cellular ion transport.


The TCF C-clamp DNA binding domain expands the Wnt transcriptome via alternative target recognition.
LEF/TCFs direct the final step in Wnt/β-catenin signalling by recruiting β-catenin to genes for activation of transcription. Ancient, non-vertebrate TCFs contain two DNA binding domains, a High Mobility Group box for recognition of the Wnt Response Element (WRE; 5'-CTTTGWWS-3') and the C-clamp domain for recognition of the GC-rich Helper motif (5'-RCCGCC-3'). Two vertebrate TCFs (TCF-1/TCF7 and TCF-4/TCF7L2) use the C-clamp as an alternatively spliced domain to regulate cell-cycle progression, but how the C-clamp influences TCF binding and activity genome-wide is not known. Here, we used a doxycycline inducible system with ChIP-seq to assess how the C-clamp influences human TCF1 binding genome-wide. Metabolic pulse-labeling of nascent RNA with 4'Thiouridine was used with RNA-seq to connect binding to the Wnt transcriptome. We find that the C-clamp enables targeting to a greater number of gene loci for stronger occupancy and transcription regulation. The C-clamp uses Helper sites concurrently with WREs for gene targeting, but it also targets TCF1 to sites that do not have readily identifiable canonical WREs. The coupled ChIP-seq/4'Thiouridine-seq analysis identified new Wnt target genes, including additional regulators of cell proliferation. Thus, C-clamp containing isoforms of TCFs are potent transcriptional regulators with an expanded transcriptome directed by C-clamp-Helper site interactions.


Matrix metalloproteinases 2 and 9 and their tissue inhibitors in low malignant potential ovarian tumors.
This study aimed to analyze the expression of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) and their tissue inhibitors TIMP-1 and TIMP-2 in low malignant potential (LMP) ovarian tumors and to compare these values with those recorded for benign and malignant ovarian neoplasms. A total of 53 ovarian tumors (16 benign, 15 LMP and 22 malignant) were evaluated by immunohistochemistry for the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2. MMP-2 expression was found in 56% of the benign, 40% of the LMP, and 90% of the malignant ovarian tumors (benign vs. malignant, p = 0.021; LMP vs. malignant, p = 0.002). The expression of MMP-9, TIMP-1 and TIMP-2 was lower in the benign and LMP tumors compared with the malignant ones. The data suggest that, in relation to the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2, LMP ovarian tumors are more similar to benign than to malignant ovarian tumors.


Communicating the Implementation of Open Notes to Health Care Professionals: Mixed Methods Study.
The literature on how to communicate reform in organizations has mainly focused on levels of hierarchy and has largely ignored the variety of professions that may be found within an organization. In this study, we focus on the relationship between media type and professional responses. The objective of this study was to investigate whether and how belonging to a profession influences the choice of communication media and the perception of information when a technical innovation is implemented in a health care setting. This study followed a mixed methods design based on observations and participant studies, as well as a survey of professionals in psychiatric health care in Sweden. The χ2 test was used to detect differences in perceptions between professional groups. The use of available communication media differed among professions. These differences seem to be related to the status attached to each profession. The sense-making of the information appears to be similar among the professions, but is based on their traditional professional norms rather than on reflection on the reform at hand. When communicating about the implementation of a new technology, the choice of media and the message need to be attuned to the employees in both hierarchical and professional terms. This also applies to situations where professional employees are only indirectly affected by the implementation. A differentiated communication strategy is preferred over a downward cascade of information.


Management of acquired von Willebrand's syndrome in a patient requiring major surgery.
We present the case of a patient with acquired von Willebrand's syndrome and a monoclonal gammopathy of undetermined significance who required cystectomy for relapsed transitional cell carcinoma (TCC) of the bladder. We demonstrated that infused von Willebrand factor (VWF) containing factor VIII concentrates had an unacceptably short half-life, but that this was significantly prolonged following combined therapy with plasma exchange and intravenous immunoglobulin (IVIgG). This approach was successfully utilized peri-operatively, with the total surgical blood loss less than would be expected even for a haemostatically normal patient. Trough VWF antigen and Ristocetin co-factor activity levels fell on the second postoperative day and we therefore administered further IVIgG. Levels again fell on the fifth postoperative day with the development of a Staphylococcus aureus septicaemia. At this point bleeding occurred from a surgical drain site requiring 'factor VIII inhibitor bypass activity' to secure haemostasis while further plasma exchange and IVIgG were administered. Now 5 years later, there is no evidence of recurrence of the TCC or progression of the monoclonal gammopathy.


Topotecan enhances immune clearance of gliomas.
Despite aggressive surgery, radiation therapy, and chemotherapy, glioblastoma multiforme (GBM) is refractory to therapy, recurs quickly, and results in a median survival time of only 14 months. The modulation of the apoptotic receptor Fas with cytotoxic agents could potentiate the response to therapy. However, Fas ligand (FasL) is not expressed in the brain and therefore this Fas-inducing cell death mechanism cannot be utilized. Vaccination of patients with gliomas has shown promising responses. In animal studies, brain tumors of vaccinated mice were infiltrated with activated T cells. Since activated immune cells express FasL, we hypothesized that combination of immunotherapy with chemotherapy can activate Fas signaling, which could be responsible for a synergistic or additive effect of the combination. When we treated the human glioma cell line U-87 and GBM tumor cells isolated from patients with TPT, Fas was up regulated. Subsequent administration of soluble Fas ligand (sFasL) to treated cells significantly increased their cell death indicating that these Fas receptors were functional. Similar effect was observed when CD3(+) T cells were used as a source of the FasL, indicating that the up regulated Fas expression on glioma cells increases their susceptibility to cytotoxic T cell killing. This additive effect was not observed when glioma cells were pre-treated with temozolomide, which was unable to increase Fas expression in tumor. Inhibition of FasL activity with the antagonistic antibody Nok-1 mitigated these effects confirming that these responses were specifically mediated by the Fas-FasL interaction. Furthermore, the CD3(+) T cells co-cultured with topotecan treated U-87 and autologous GBM tumor cells showed a significant increase in expression in IFN-gamma, a key cytokine produced by activated T cells, and accordingly enhanced tumor cytotoxicity. Based on our data we conclude that drugs, such as topotecan, which cause up regulation of Fas on glioma cells can be potentially exploited with immunotherapy to enhance immune clearance of tumors via Fas signaling.


Reversible Self-Assembled Monolayers (rSAMs) as Robust and Fluidic Lipid Bilayer Mimics.
Lipid bilayers, forming the outer barrier of cells, display a wide array of proteins and carbohydrates for modulating interfacial biological interactions. Formed by the spontaneous self-assembly of lipid molecules, these bilayers feature liquid crystalline order, while retaining a high degree of lateral mobility. Studies of these dynamic phenomena have been hampered by the fragility and instability of corresponding biomimetic cell membrane models. Here, we present the construct of a series of oligoethylene glycol-terminated reversible self-assembled monolayers (rSAMs) featuring lipid-bilayer-like fluidity, while retaining air and protein stability and resistance. These robust and ordered layers were prepared by simply immersing a carboxylic acid-terminated self-assembled monolayer into 5-50 μM aqueous ω-(4-ethylene glycol-phenoxy)-α-(4-amidinophenoxy)decane solutions. It is anticipated that this new class of robust and fluidic two-dimensional biomimetic surfaces will impact the design of rugged cell surface mimics and high-performance biosensors.


Development of a multiplexing fingerprint and high wavenumber Raman spectroscopy technique for real-time in vivo tissue Raman measurements at endoscopy.
We report on the development of a novel multiplexing Raman spectroscopy technique using a single laser light together with a volume phase holographic (VPH) grating that simultaneously acquires both fingerprint (FP) and high wavenumber (HW) tissue Raman spectra at endoscopy. We utilize a customized VPH dual-transmission grating, which disperses the incident Raman scattered light vertically onto two separate segments (i.e., -150 to 1950 cm⁻¹; 1750 to 3600 cm⁻¹) of a charge-coupled device camera. We demonstrate that the multiplexing Raman technique can acquire high quality in vivo tissue Raman spectra ranging from 800 to 3600 cm⁻¹ within 1.0 s with a spectral resolution of 3 to 6 cm⁻¹ during clinical endoscopy. The rapid multiplexing Raman spectroscopy technique covering both FP and HW ranges developed in this work has potential for improving in vivo tissue diagnosis and characterization at endoscopy.


New sulfate-reducing bacteria isolated from Buryatian alkaline brackish lakes: description of Desulfonatronum buryatense sp. nov.
New strains of sulfate-reducing bacteria were isolated from two alkaline brackish lakes located in the Siberian region of Russia, namely in the Southern Transbaikalia, Buriatia. The article presents data describing morphology, physiology, and biochemical characteristics of the isolated strains. These strains Ki4, Ki5, and Su2 were mesophilic and alkaliphilic with optimal growth at pH 8.9, 9.4, and 10.0, respectively. All isolated strains utilized lactate, formate, and ethanol in the presence of sulfate for growth and sulfidogenesis accompanied with formation of acetate and CO2. Strains Ki5 and Su2 were able to reduce Fe(III). The DNA G + C content in strains Ki4, Ki5 and Su2 was 56.3, 48.8 and 59.6 mol%, respectively. According to phylogenetic analysis of 16S rRNA sequences, the new strains were clustered within the genus Desulfonatronum, and the closest relative D. lacustre Z-7951(T) (=DSM 10312(T)) showed 99.3-99.6 % similarity. DNA-DNA relatedness values of the strains Ki4, Ki5, and Su2 with D. lacustre Z-7951(T) were 89, 53, and 79 %, respectively. Polyphasic taxonomy data suggest that strain Ki5(T) is representative of the proposed novel species Desulfonatronum buryatense sp. nov.


An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention.
The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18-1.92], p = 0.00096), peripheral artery disease (1.69 [1.01-2.82], p = 0.046), and coronary operations (1.78 [1.21-2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.


Neurological complications of prolonged hunger strike.
We investigated neurological findings in 41 prisoners (mean age: 28.6) who participated in a hunger strike between 2000 and 2002. All cases were evaluated using neuropsychological, neuroradiological, and electrophysiological methods. The total duration of fasting ranged from 130 to 324 days (mean 199 days). All cases had 200-600 mg/day thiamine orally for 60-294 days (mean 156) during the hunger strike, and had neurological findings consistent with Wernicke-Korsakoff syndrome. All 41 patients exhibited altered consciousness which lasted from 3 to 31 days. All patients also presented gaze-evoked horizontal nystagmus and truncal ataxia. Paralysis of lateral rectus muscles was found in 14. Amnesia was apparent in all cases. Abnormal nerve conduction study parameters were not found in the patient group, but the amplitude of compound muscle action potential of the median and fibular nerves and sensory nerve action potential amplitude of the sural nerve were lower than the control group, and distal motor latency of the posterior tibial nerve was significantly prolonged as compared with the control group. The latency of visual evoked potential was prolonged in 22 cases. Somatosensory evoked potential (P37) was prolonged but not statistically significant. Our most significant finding was that the effect of hunger was more prominent on the central nervous system than on the neuromuscular system, despite the fact that all patients were taking thiamine. In our opinion, partial recovery of neurological, and neurocognitive signs in prolonged hunger could be a result of permanent neurological injury.


High-risk behaviors among adult men and women in Botswana: implications for HIV/AIDS prevention efforts.
The government of Botswana has been spending a lot of money in the prevention, treatment, care and support for HIV/AIDS patient for decades. This paper uses data from the third Botswana AIDS Impact Survey (BAIS III) to explore high-risk behaviors of adults and how they affect government efforts to stop the spread of HIV/AIDS. The objective of this paper is to fill in the gap on the assessment of high-risk behaviors associated with HIV/AIDS and their implications on HIV/AIDS prevention efforts. A nationally representative sample of 10,159 men and women aged 20-64 years who had successfully completed the BAIS III individual questionnaire were used in the study. Both descriptive and binary logistic regression analyses were used for analysis. Crude odds ratios were obtained from gross effects model while adjusted odds ratios (AOR) were obtained from the net effects model. Statistically significant association was observed between multiple current partners and alcohol consumption (AOR = 1.5), drug abuse (AOR = 1.7), transactional sex (AOR = 2.6) and intergenerational sex (AOR = 1.07). Furthermore, statistically significant association was seen for inconsistent condom use and having tested for HIV (AOR = 1.5). These results show a worrying tendency that despite government's efforts to stop the spread of HIV/AIDS, adults in Botswana continue to indulge in high-risk behaviors. Therefore, any programs and policies on HIV/AIDS should first target these high-risk behaviors.


The impact of hyperthyroidism on sexual functions in men and women: a systematic review and meta-analysis.
This study aimed to review the current knowledge on sexual dysfunction in men and women with hyperthyroidism through a systematic review and meta-analysis. Available clinical trials from the MEDLINE database were searched using a prerecorded protocol (Protocol Prospero ID: CRD42022340587), and obtained data were analyzed and reported according to the PRISMA guidelines. Pooled effect estimates were computed using a random-effects model. Twenty eligible studies were identified, of which 15 were included in this meta-analysis. The prevalence of erectile dysfunction was significantly higher in participants with hyperthyroidism than that in controls [odds ratio = 9.16 (95% confidence interval [CI], 5.0-16.5)]. Treatment of hyperthyroidism alone improved erectile functions [effect size, ES = 0.36 (95% CI, -0.01-72)] and mean intra-vaginal ejaculation latency time [ES = 0.63 (95% CI, 0.27-98)] among men with erectile dysfunction and/or premature ejaculation. The prevalence of premature ejaculation also decreased with treatment of hyperthyroidism [odds ratio = 0.11 (95% CI, 0.04-28). Women with hyperthyroidism demonstrated higher odds in female sexual dysfunction than controls [odds ratio = 4.34 (95% CI, 2.63-7.18)]. Female sexual function index scores in women with hyperthyroidism were also significantly lower than those in the controls with moderate effect sizes. An evident and reversible disruption of sexual functions under hyperthyroidism conditions was observed in both sexes.


Detection of alternative splice and gene duplication by RNA sequencing in Japanese flounder, Paralichthys olivaceus.
Japanese flounder (Paralichthys olivaceus) is one of the economic important fish in China. Sexual dimorphism, especially the different growth rates and body sizes between two sexes, makes this fish a good model to investigate mechanisms responsible for such dimorphism for both fundamental questions in evolution and applied topics in aquaculture. However, the lack of "omics" data has hindered the process. The recent advent of RNA-sequencing technology provides a robust tool to further study characteristics of genomes of nonmodel species. Here, we performed de novo transcriptome sequencing for a double haploid Japanese flounder individual using Illumina sequencing. A single lane of paired-end sequencing produced more than 27 million reads. These reads were assembled into 107,318 nonredundant transcripts, half of which (51,563; 48.1%) were annotated by blastx to public protein database. A total of 1051 genes that had potential alternative splicings were detected by Chrysalis implemented in Trinity software. Four of 10 randomly picked genes were verified truly containing alternative splicing by cloning and Sanger sequencing. Notably, using a doubled haploid Japanese flounder individual allow us to analyze gene duplicates. In total, 3940 "single-nucleotide polymorphisms" were detected form 1859 genes, which may have happened gene duplicates. This study lays the foundation for structural and functional genomics studies in Japanese flounder.


MRC OX-2 defines a novel T cell costimulatory pathway.
T cell activation requires the engagement of the TCR as well as a second, costimulatory signal. In this study, we demonstrate that MRC OX-2 (OX-2) mediates a previously unrecognized T cell costimulatory signal leading to enhanced T cell proliferation. One extensively studied costimulatory pathway, the B7/CD28 pathway, delivers its signal when CD28 is engaged by either of two ligands, B7-1 or B7-2, expressed on APC. Recent data have suggested that an additional ligand may exist in this pathway. This possibility prompted us to search previously cloned genes with both structural and expression characteristics similar to B7-1 and B7-2. Our search yielded OX-2, a rat lymphocyte activation marker, as a promising candidate gene. We now report that Chinese hamster ovary cell transfectants expressing the OX-2 protein can costimulate murine CD4+ T cells to proliferate in an Ag-independent fashion using anti-CD3, as well as an Ag-dependent fashion using peptide. In contrast to B7-1-mediated costimulation, OX-2 does not result in detectable levels of IL-2, IL-4, or IFN-gamma. In addition, OX-2 transfectants do not bind the soluble receptor reagents of the B7/CD28 pathway (CD28-Ig and CTLA4Ig). Furthermore, OX-2 costimulation is not inhibited by CTLA4Ig, as is B7-1-mediated costimulation, but is readily inhibited with an anti-OX-2 mAb. Thus, OX-2 is a T cell costimulatory ligand that acts through a non-B7/CD28 pathway, which leads to functionally distinct consequences, as reflected by the resulting cytokine profile.


Protective effect of ethanol on X-ray-induced mitotic recombination in Drosophila melanogaster.
The effect of ethanol pretreatment on X-ray-induced mitotic recombination in D. melanogaster females was investigated by means of the white/white+ (w/w+) spot test. White females inseminated by yellow males were allowed to oviposit for 8 hr on medium containing 5%, 7.5% and 10% (v/v) ethanol and submitted to 10 Gy of X-rays 52 hr after the beginning of the egg laying period (chronic treatments). For acute treatments 56 +/- 4-hr-old larvae grown in regular medium were held in petri dishes containing filter paper soaked with 50% (v/v) ethanol for 30 min before being irradiated with 10 Gy. The emerging heterozygous w/w+ females were inspected for the presence of white spots (LS) in their eyes. Acute ethanol pretreatments lead to a significant reduction in the frequency of LS. This is suggested to be due to the scavenging by ethanol of free radicals originating during irradiation. If so, the contribution of the indirect action of radiation to mitotic recombination induced by X-rays must be significant. Chronic ethanol pretreatments also resulted in a decrease of LS, though impairment of larval development by ethanol may have partly contributed to the effect observed. At the concentrations tested, ethanol by itself did not modify the frequency of LS observed in the control.


Muckle-Wells syndrome: clinical perspectives.
Muckle-Wells syndrome (MWS) is a rare autoinflammatory disorder. It is due to NLRP3 gene mutations, responsible for excessive caspase-1 activation and interleukin 1β processing. MWS is the intermediate phenotype of severity of cryopyrin-associated periodic syndrome. Urticarial rash, conjunctivitis, recurrent fever, arthralgia, and fatigue are the main clinical manifestations of MWS. Yet, sensorineural hearing loss and renal amyloidosis can occur after long term evolution. Patients' quality of life has been drastically improved with the advent of IL-1 inhibitors. This review reports recent findings in MWS, particularly genotype/phenotype correlation, and discusses the clinical perspectives of this disease in a time of efficient treatment.


Using a school-based approach to deliver immunization—global update.
Vaccines, such as HPV vaccine, are increasingly administered to school-age children, and school-based immunization is an approach that can be used to reach these children. Limited information has thus far been published that provides an overview of the school-based approach worldwide. This article, based on self-reported data from countries, summarizes the extent to which a school-based immunization approach is used around the world, and what antigens are most frequently being administered. Of the 174 countries for which data on school-based immunization were available, ninety five countries reported using a school-based approach for immunization. Children in grades 1 and 6 (or at an age corresponding with these grades) are most often targeted, and tetanus and diphtheria toxoids are the most frequently administered antigens. The impact of the school-based approach may be reduced in areas with low school attendance, unless specific measures are taken to target out-of-school children. Methods to monitor coverage need to be standardized and data on coverage and on the reach of the approach need to be more systematically analyzed and reported.


Perceptions of Food Hypersensitivity Expertise on Social Media: Qualitative Study.
Seeking and sharing information are the primary uses of the internet and social media. It is therefore vital to understand the processes individuals go through when engaging with information on these diverse platforms, especially in areas such as health- and risk-related information. One important element of such engagement is evaluating and attributing expertise to others. This study aimed to explore how meanings around expertise in relation to food allergy and intolerance (food hypersensitivity) were constructed by 2 groups of social media users: (1) those who use platforms for reasons relating to food hypersensitivity and (2) those seen as experts by this community. Survey participants were asked open-ended questions to identify potential experts in food hypersensitivity issues on social media and to discuss their reasoning for their choices (n=143). Subsequently, 8 adult social media users with experience of managing food hypersensitivity and 5 participants designated as experts by those users took part in email interviews. Survey and interview data were analyzed thematically using Braun and Clarke's approach. Judging expertise on social media is a complex and multifaceted process. Users might be judged as experts through their professional background or their experience living with food hypersensitivities. How users behave on social media and the traces of their Web-based activity can influence how others will see them. Such considerations are both measured and moderated through the social media community itself. Findings highlighted how social media often act as a supportive information tool following a diagnosis, but this also raised concerns regarding the scenario of patients not being able to access suitable vetted information. This work has implications for understanding how users perceive expertise on social media in relation to a health concern and how information assessments are made during the management of risks. Findings provide practical insights to both medical and organizational stakeholders involved in the support of those living with life-changing conditions, such as food hypersensitivities.


Squamous cell carcinoma with clear cell differentiation in an equine eyelid.
A 15-y-old Miniature horse mare had a 6-mo history of an ulcerated mass on the right lower eyelid. An incisional biopsy and a subsequent excisional biopsy were submitted to the Michigan State University Veterinary Diagnostic Laboratory for microscopic evaluation. Histologically, the incisional biopsy was composed of sheets of large neoplastic vacuolated polygonal cells. A few regions contained poorly differentiated neoplastic round-to-basaloid cells that rimmed the sheets of highly vacuolated polygonal cells. Both vacuolated and basaloid cells exhibited strong perimembranous and cytoplasmic immunoreactivity for E-cadherin and cytokeratin 5/6, respectively. Vacuolated polygonal cells were histochemically negative for periodic acid-Schiff, mucicarmine, and oil red O, consistent with a diagnosis of poorly differentiated carcinoma. Within the excisional biopsy specimen, there were anastomosing cords and nests of neoplastic squamous epithelial cells that merged with sheets of similar vacuolated polygonal cells. These findings are consistent with a squamous cell carcinoma with clear cell differentiation. In addition, in the adjacent dermis, there was solar elastosis suggestive of ultraviolet (UV) damage. A clear cell variant of squamous cell carcinoma is a rare entity in humans that previously has not been described in animals, to our knowledge, and is often associated with chronic UV exposure.


Knowledge, attitudes and practices on malaria transmission in Mamfene, KwaZulu-Natal Province, South Africa 2015.
In South Africa malaria is endemic in Mpumalanga, Limpopo and the north-eastern areas of KwaZulu-Natal provinces. South Africa has set targets to eliminate malaria by 2018 and research into complementary vector control tools such as the Sterile Insect Technique (SIT) is ongoing. It is important to understand community perceptions regarding malaria transmission and control interventions to enable development of community awareness campaign messages appropriate to the needs of the community. We aimed to assess knowledge, attitudes, and practices regarding malaria transmission to inform a public awareness campaign for SIT in Jozini Local Municipality, Mamfene in KwaZulu-Natal province. We conducted a cross-sectional survey in three communities in Mamfene, KwaZulu-Natal during 2015. A structured field piloted questionnaire was administered to 400 randomly selected heads of households. Descriptive statistics were used to summarize data. Of the 400 participants interviewed, 99% had heard about malaria and correctly associated it with mosquito bites. The sources of malaria information were the local health facility (53%), radio (16%) and community meetings (7%). Approximately 63% of the participants were able to identify three or four symptoms of malaria. The majority (76%) were confident that indoor residual spraying (IRS) kills mosquitoes and prevents infection. Bed nets were used by 2% of the participants. SIT knowledge was poor (9%), however 63% of the participants were supportive of mosquito releases for research purposes. The remaining 37% raised concerns and fears, including fear of the unknown and lack of information on the SIT. Appropriate knowledge, positive attitude and acceptable treatment-seeking behaviour for malaria were demonstrated by members of the community. Community involvement will be crucial in achieving success of the SIT and future studies should further investigate concerns raised by the community. The existing communication channels used by the malaria control program can be used; however additional channels should be investigated.


[Pathogenesis of myeloproliferative neoplasms: insights from mouse models].
One of the main molecular features of myeloproliferative neoplasms (MPNs) is the high frequency of JAK2V617F or CALRexon 9 mutations. The mouse models driven by these mutations suggest that they are the direct cause of MPNs and that the expression levels of mutated genes define the disease phenotype. The function of MPN-initiating cells was also elucidated using these mouse models. Furthermore, these mouse models play important roles as disease models to investigate the effects and mechanisms of action of therapeutic drugs such as JAK2 inhibitors and interferon α against MPNs. The mutation landscape of hematological tumors has already been clarified using next-generation sequencing technology, and future research on the importance of the functional analysis of mutant genes in vivo should be emphasized. Thus, it is necessary to promote rapid genetic modification techniques such as genome editing.


The long road to schistosomiasis elimination in Zanzibar: A systematic review covering 100 years of research, interventions and control milestones.
Zanzibar is among the few places in sub-Saharan Africa where interruption of Schistosoma transmission seems an achievable goal. Our systematic review identifies and discusses milestones in schistosomiasis research, control and elimination efforts in Zanzibar over the past 100 years. The search in online databases, libraries, and the World Health Organization Archives revealed 153 records published between May 1928 and August 2022. The content of records was summarised to highlight the pivotal work leading towards urogenital schistosomiasis elimination and remaining research gaps. The greatest achievement following 100 years of schistosomiasis interventions and research is undoubtedly the improved health of Zanzibaris, exemplified by the reduction in Schistosoma haematobium prevalence from>50% historically down to<5% in 2020, and the absence of severe morbidities. Experiences from Zanzibar have contributed to global schistosomiasis guidelines, whilst also revealing challenges that impede progression towards elimination. Challenges include: transmission heterogeneity requiring micro-targeting of interventions, post-treatment recrudescence of infections in transmission hotspots, biological complexity of intermediate host snails, emergence of livestock Schistosoma species complicating surveillance whilst creating the risk for interspecies hybridisation, insufficient diagnostics performance for light intensity infections and female genital schistosomiasis, and a lack of acceptable sanitary alternatives to freshwater bodies. Our analysis of the past revealed that much can be achieved in the future with practical implementation of integrated interventions, alongside operational research. With continuing national and international commitments, interruption of S. haematobium transmission across both islands is within reach by 2030, signposting the future demise of urogenital schistosomiasis across other parts of sub-Saharan Africa.