Instantaneous exposure to nuclear medicine staff involved in PET-CT imaging in developing countries: experience from a tertiary care centre in India.
To assess the radiation exposure to nuclear medicine staff at a positron emission tomography-computed tomography (PET-CT) centre with high patient throughput. This prospective study included 70 adult patients who underwent 18F-fluorodeoxyglucose (FDG) PET-CT for their clinical indications. The patients' actual injected FDG activity was calculated by subtracting the syringe activity (post-injection) from the loaded syringe activity (pre-injection). The instantaneous exposure to nuclear medicine staff involved in PET-CT imaging was measured. The instantaneous dose rate of the physicians was recorded during FDG injection and that of the technologist was recorded during the patient's positioning, respectively, at 1.0-m distance from the anterior chest using a calibrated portable gamma-ray survey meter. The average FDG activity injected in adult patients was 308.5 MBq (range 173.1-438.8 MBq). The instantaneous exposure to the nuclear medicine (NM) physician during the injection time was 31 μSv/h (14-60 μSv/h). The instantaneous exposure to the NM technologist during positioning was 18 (10-34) μSv/h. With an average of 10 patients per day, the quarterly dose to physicians was 628 μSv and to technologists 182 μSv for 300 patients. The extrapolated annual dose was 2.5 mSv for physicians and 0.7 mSv for technologists, respectively. Instantaneous exposure of nuclear medicine staff involved in PET-CT imaging at a busy tertiary care centre is within permissible limits of the International Commission on Radiological Protection (ICRP-103) (total <100 mSv over 5 years and not >50 mSv in a single year) and atomic energy regulatory board (total <100 mSv over 5 years and not >30 mSv in a single year).


Seven new Y-STRs haplotypes of Chinese Han ethnic group.
Seven new Y-chromosome STRs loci (DYS456, DYS460, DYS461, DYS462, DYS459, DYS438 and DYS439) have been amplified in 105 healthy unrelated males of Chinese Han population, in order to investigate allele and haplotype frequencies of them, to evaluate their usefulness in forensic casework, and to compare with other groups.


Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17.
C57BL/6 mice infected with the helminth Schistosoma mansoni develop small hepatic granulomas around parasite eggs, but concomitant immunization with soluble schistosome egg Ags (SEA) in CFA (SEA/CFA) causes marked exacerbation of the lesions in a Th1-dominated environment characterized by high levels of IFN-gamma. We explored the cause of the severe immunopathology by using IL-12p40(-/-) and IL-12p35(-/-) mice. SEA/CFA-immunized IL-12p40(-/-) mice, incapable of making IL-12 or IL-23, were completely resistant to high pathology, and their SEA-stimulated lymphoid cells failed to secrete significant IFN-gamma or IL-17. In contrast, SEA/CFA-immunized IL-12p35(-/-) mice, able to make IL-23 but not IL-12, developed severe lesions that correlated with high levels of IL-17, low IFN-gamma, and an expansion of activated CD4 T cells with a CD44(high)/CD62L(low) memory phenotype. In vivo administration of neutralizing anti-IL-17 mAb markedly inhibited hepatic granulomatous inflammation. Importantly, CBA mice, a naturally high pathology strain, also displayed elevated IL-17 levels comparable to those seen in the SEA/CFA-immunized BL/6 mice, and their lesions were similarly reduced by in vivo treatment with anti-IL-17. Our findings indicate that an IL-17-producing T cell population, likely driven by IL-23, significantly contributes to severe immunopathology in schistosomiasis.


A proposed difficulty grading system for laparoscopic bile duct exploration: benefits to clinical practice, training and research.
A gap remains between the mounting evidence for single session management of bile duct stones and the adoption of this approach. Laparoscopic bile duct exploration (LBDE) is limited by the scarcity of training opportunities and adequate equipment and by the perception that the technique requires a high skill-set. The aim of this study was to create a new classification of difficulty based on operative characteristics and to stratify postoperative outcomes of easy vs. difficult LBDE irrespective of the surgeon's experience. A cohort of 1335 LBDEs was classified according to the location, number and size of ductal stones, the retrieval technique, utilisation of choledochoscopy and specific biliary pathologies encountered. A combination of features indicated easy (Grades I and II A & B) or difficult (Grades III A and B, IV and V) transcystic or transcholedochal explorations. 78.3% of patients with acute cholecystitis or pancreatitis, 37% with jaundice and 46% with cholangitis had easy explorations. Difficult explorations were more likely to present as emergencies, with obstructive jaundice, previous sphincterotomy and dilated bile ducts on ultrasound scans. 77.7% of easy explorations were transcystic and 62.3% of difficult explorations transductal. Choledochoscopy was utilised in 23.4% of easy vs. 98% of difficult explorations. The use of biliary drains, open conversions, median operative time, biliary-related complications, hospital stay, readmissions, and retained stones increased with the difficulty grade. Grades I and II patients had 2 or more hospital episodes in 26.5% vs. 41.2% for grades III to V. There were 2 deaths in difficulty Grade V and one in Grade IIB. Difficulty grading of LBDE is useful in predicting outcomes and facilitating comparison between studies. It ensures fair structuring and assessment of training and progress of the learning curve. LBDEs were easy in 72% with 77% completed transcystically. This may encourage more units to adopt this approach.


The CaMYB340 transcription factor induces chilling injury in post-harvest bell pepper by inhibiting fatty acid desaturation.
Bell pepper (Capsicum annuum L.) is a tradable and desirable crop; however, its perishable nature requires low-temperature handling. Paradoxically, cold causes chilling injury (CI) and post-harvest waste. Current knowledge about CI in pepper is limited. The mechanism of CI is multi-faceted; therefore, we focused on fatty acid (FA) desaturation. We identified an upstream nuclear transcription factor (TF), CaMYB340, belonging to the R2R3 MYB subfamily, that negatively regulates FA desaturation and CaCBF3 expression and whose gene and protein expression is induced by low temperature (4°C). Specifically, McrBC treatment and bisulfite sequencing PCR indicate that exposure to cold triggers DNA methylation on one of the CHH sites in the CaMYB340 promoter. This epigenetic event at least partly contributes to the upregulation of CaMYB340 transcript levels. Increased expression of CaMYB340 results in the formation of protein complexes with CabHLH93 and CaMYB1R1, which in turn downregulate the expression of downstream genes. For peppers held at low temperature, transient overexpression of CaMYB340 reduced unsaturated FA content and membrane fluidity, resulting in cold-induced poor peel texture. Transient CaMYB340 silencing increased FA desaturation and lowered electrolyte leakage, enhancing cold tolerance in CaMYB340 knockdown fruits. Overall, these results underscore the intricacy of transcriptional networks in plants and highlight the role of CaMYB340 in CI occurrence in pepper fruits.


Exploring allosteric coupling in the alpha-subunit of heterotrimeric G proteins using evolutionary and ensemble-based approaches.
Allosteric coupling, which can be defined as propagation of a perturbation at one region of the protein molecule (such as ligand binding) to distant sites in the same molecule, constitutes the most general mechanism of regulation of protein function. However, unlike molecular details of ligand binding, structural elements involved in allosteric effects are difficult to diagnose. Here, we identified allosteric linkages in the alpha-subunits of heterotrimeric G proteins, which were evolved to transmit membrane receptor signals by allosteric mechanisms, by using two different approaches that utilize fundamentally different and independent information. We analyzed: 1) correlated mutations in the family of G protein alpha-subunits, and 2) cooperativity of the native state ensemble of the Galphai1 or transducin. The combination of these approaches not only recovered already-known details such as the switch regions that change conformation upon nucleotide exchange, and those regions that are involved in receptor, effector or Gbetagamma interactions (indicating that the predictions of the analyses can be viewed with a measure of confidence), but also predicted new sites that are potentially involved in allosteric communication in the Galpha protein. A summary of the new sites found in the present analysis, which were not apparent in crystallographic data, is given along with known functional and structural information. Implications of the results are discussed. A set of residues and/or structural elements that are potentially involved in allosteric communication in Galpha is presented. This information can be used as a guide to structural, spectroscopic, mutational, and theoretical studies on the allosteric network in Galpha proteins, which will provide a better understanding of G protein-mediated signal transduction.


Mechanisms of network evolution: a focus on socioecological factors, intermediary mechanisms, and selection pressures.
Since group-living animals are embedded in a network of social interactions, socioecological factors may not only affect individual behavioral strategies but also the patterning of group-level social interactions, i.e., the network structure. These co-variations between socioecological factors, individual behavior, and group-level structure are important to study since ecological factors may strongly influence animal health outcomes and reproductive success. Besides factors such as social information and/or infectious agents, with far-reaching individual fitness consequences, seem independent of individuals' own social interactions but directly affected by the topology of the social network. This paper reviews how socio-ecological pressures, i.e., causal factors (food distribution, predation, and infectious agent risk), via intermediary mechanisms (stress, information sharing, and mating system), may affect individual social behavior and consequently, social network topology. We also discuss how evolutionary driving forces, genetic (i.e., genes) and cultural (i.e., learned behavior) selection, may result in a specific composition of individuals' social strategies that produce network topologies that might be optimized to specific socio-ecological conditions. We conclude that studies focusing on whether and how well networks resist changing conditions might provide a better understanding of the rules underlying individual behavior, which in turn influences network topology-a process we have called network evolution. Evolutionary processes may favor a group phenotypic composition, thus a network topology. This has been referred to as a "collective social niche construction".


Gender-inclusive practice in pregnancy determination for transgender, gender diverse and non-binary patients in medical imaging.
In recent years, there has been an increased awareness and understanding of the varying gender identities within our society. Consequently, there has also been a need for healthcare providers to be cognizant of the unique needs of a gender-diverse population. Determining the pregnancy status of transgender, gender-diverse and non-binary patients in medical imaging settings has been poorly handled, and there is a lack of standardisation in the Australian and Aotearoa New Zealand setting. The potential risk of exposing a gender-diverse pregnant patient to ionising radiation increases the need for guidance to ensure potentially pregnant persons are not missed during screening questionnaires. This review article explores various approaches to pregnancy status determination for gender-diverse patients, recognising the complexities involved and emphasising the need for future work to establish a widely accepted solution.


[Immunotherapy for metastatic prostate cancer: do we really need this?].
Following the approval of Sipuleucel-T, the development of new immunomodulatory approaches such as ipilimumab and tasquinimod, and the development of new antihormonal drugs (abiraterone acetate, MDV3100, TAK-700), treatment of castration-resistant prostate cancer is finally reaching a new era of management. Docetaxel based chemotherapy remains the standard treatment of choice for patients with a high tumour burden, rapidly progressiong castration resistant prostate cancer, and poorly differentiated prostate cancer. Sipuleucel-T might be an option in the pre-docetaxel management of castration-resistant prostate cancer resulting in a 4-months improvement of overall survival. However, as with all other modalities of immunotherapy patients with good prognostic factors such as minimal tumour burden, slow PSA doubling time, Gleason score ≤ 7, and a long survival probability of > 1 year might be the best candidates taking into account that immunomodulatory approaches demonstrate positive responses after 4-6 months of therapy. Ipilimumab and tasqunimod as inhibitors of the immune checkpoints are additional, promising therapeutic agents with high clinical potential. It is the aim of the current article to critically review the current options of immune therapy in men with castration resistant prostate cancer.


The hormonal and immunological status of vasectomised men.
The concentration of FSH, LH, testosterone and sperm agglutinating and cytotoxic antibodies have been determined in 87 men at varying time intervals after vasectomy. The results indicated that vasectomy is not associated with statistically significant changes in any of these parameters. Furthermore, no correlation existed between the development of sperm antibodies and the peripheral endocrine status of an individual.


Multivariate analysis of plasma hormones in patients with metastatic prostate cancer receiving combined LHRH-analog and antiandrogen therapy.
The following hormones, the plasma protein SHBG, and the tumor markers prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were assayed at 18 time-points over 1 month during a double-blind randomized study in 36 stage D2 cancer patients receiving either "buserelin+placebo" or "buserelin+nilutamide (Anandron)": LH, FSH, estradiol, testosterone, dihydrotestosterone, androstenedione, 5-androstene-3,17 beta-diol, dehydroepiandrosterone and its sulfate, cortisol, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolone, and 3 alpha-androstanediol glucuronide. Multivariate analysis of the treatment values (over 10,000 assays) by two complementary methods, correspondence factorial analysis (CFA) and the minimum spanning tree (MST) method, identified those variables within the pathways of androgen metabolism that were correlated over time and, in a comparison of the two treatment groups, identified the enzyme targets of nilutamide action in humans. Whereas nilutamide tended to decrease androstenedione slightly, it affected no other variables including cortisol, except for pregnenolone, 17 alpha-OH-pregnenolone, and 17 alpha-OH-progesterone, which were increased. These increases are indicative of weak inhibition of C17,20 lyase by nilutamide, but, according to the multivariate analysis, are insufficient to account for the more marked and rapid fall in PAP and PSA noted on addition of nilutamide to buserelin that must therefore be explained by another mechanism such as androgen receptor blockade by nilutamide.


[Comparative characteristics of bactericidal activity of various traditional and currently available antiseptics used in surgery].
Comparative study of the microbicidal activity of some traditional (hydrogen peroxide, boric acid, nitrofurazone) and currently available (Baliz-2, dioxidine, chlorhexidine bigluconate, pervomur) antiseptics against the most commonly encountered causative agents of purulent surgical infection showed 0.8%, 1.2%, and 2.4% pervomur solutions to possess the highest bactericidal and sporicidal activity. This circumstance allowed weak (0.8 and 1.2%) solutions of pervomur to be used in the clinic in 68 patients for the management of purulent postoperative complications and localized purulent infection, which improved the results of treatment significantly.


Effects of partial replacement of NaCl with KCl on bacterial communities and physicochemical characteristics of typical Chinese bacon.
This work aimed to determine the effects of partial substitution of NaCl with 0% (control), 30%, 50%, and 70% of KCl on the bacterial communities, proteolysis and lipid oxidation of Chinese bacon during processing. The proportion of genus Lactobacillus increased from 22.45% (fresh meat) to 72.78%, 81.64%, 76.53% and 85.63% at the end of processing for 0%, 30%, 50% and 70% KCl replacement samples, respectively. During the processing, Lactobacillus gradually became the dominant one, and higher the KCl ratio, more rapid was the process. After salting, the TBARS of control was markedly higher (P < 0.05) than that of the others, while a similar lipid oxidation level (P > 0.05) was observed at the end of processing for different groups. After salting, there was no difference in total free amino acids (TFAA) content among four treatments (P > 0.05), whereas KCl replacement samples shared significantly higher (P < 0.05) values than control at the end of processing. Redundancy analysis and Pearson correlation showed positive correlation between Lactobacillus versus TBARS and TFAA. Partial replacement of NaCl with KCl could, directly or subsequently by promoting the growth of Lactobacillus, influence proteolysis and lipid oxidation over the manufacturing process.


Mallotus philippinensis Muell. Arg fruit glandular hairs extract promotes wound healing on different wound model in rats.
Mallotus philippinensis Muell. Arg (MP, Euphorbiaceae) are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions. Since, Mallotus philippinensis have been shown to have a number of medicinal values. Hence our present study was to investigate the healing potential of fruit extract in rat wound models. The study includes acute toxicity and wound healing potential of 50% ethanol extract of MP fruit glandular hair (MPE). MPE (200 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound) and 22 days (excision wound). MPE was found safe when given to rats upto 10 times of optimal effective dose. Wound breaking strength (WBS) in Incision wound and rate of contraction, period of epithelization and scar area in Excision wound were evaluated. Granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology were studied in Dead space wound. MPE significantly increased WBS and enhanced wound contraction, and decreased both epithelization period and scar area compared with control group. MPE was found to decrease free radicals (50.8 to 55.2%, P<0.001) and myeloperoxidase (44.0%, P<0.001) but enhanced antioxidants (41.1 to 54.5%, P<0.05 to P<0.001) and connective tissue markers (39.5 to 67.3%, P<0.05 to P<0.01). Histopathological evaluation revealed more density of collagen formation with minimal inflammatory cells in deeper tissues. Thus, the study revealed Mallotus philippinensis fruit hair extract, safe and effective in wound healing and the healing effects seemed to be due to decrease in free radical generated tissue damage, promoting effects on antioxidant status and faster collagen deposition as evidenced biochemically and histology.


Distribution of progesterone receptors between the cytosol and nuclear fraction in normal and neoplastic human endometrium.
The progesterone receptor (PR) content was determined in the cytosol and in the nuclear fraction in 28 cases of endometrial adenocarcinoma after in vitro incubation of tissue slices in the presence of progesterone. In 17 instances besides the malignant, nontransformed tissue from the same uterus was taken for analysis. The level of PR was estimated by Scatchard plot analysis or by one-point assay, whenever not enough tissue was available. The distribution of PR between the cytosol and the nuclear fraction was studied. Positive correlation between the concentrations of total and of nuclear progesterone binding sites was found in all samples of nontransformed tissue whereas in cancerous tissue this was true only in about 40% of cases. In about 60% of neoplastic tissue samples the PR were namely found predominantly in the cytosol. Since we observe that in many malignant endometria the PR are poorly transferred from the cytoplasm to the nucleus even under optimal conditions for in vitro activation/translocation, we conclude that in these cases the action of progesterone is for some reason altered either at the level of receptor activation or at the level of translocation of the hormone-receptor complex from the cytoplasm to the nucleus.


Editors' introduction to the special issue on the sociology of digital technology.
An increasing number of sociologists today are examining the social production of digital technology. Although younger researchers may be digital natives and write from "within the algorithm," and older sociologists may begin by trying to define terms and concepts that have become commonplace in the tech "space," all share the goal of unpacking the "black box" of computer software by analyzing how, where, and by whom it is developed and asking who benefits most by its use. Some of the articles in this special issue of Theory and Society focus on questions of connectivity, privacy, and equity in light of classical sociology's concern with the state, the self, knowledge, and power; others look critically at forms of inequality in the operations of specific platforms, algorithms, urban tech ecosystems, and coworking spaces.


Potent inhibitors of human matriptase-1 based on the scaffold of sunflower trypsin inhibitor.
Sunflower trypsin inhibitor-1 (SFTI-1), a bicyclic tetradecapeptide, has become a versatile tool as a scaffold for the development of the inhibitors of therapeutically relevant serine proteases, among them matriptase and kallikreins. Herein, we report the rational design of potent monocyclic and bicyclic inhibitors of human matriptase-1. We found that the presence of positive charge and lack of bulky residues at the peptide N-terminus is required for the maintenance of inhibitory activity. Replacement of the N-terminal glycine residue by lysine allowed for the chemical conjugation with a fluorophor via the ε-amino group without significant loss of inhibitory activity. Head-to-tail and side-chain-to-tail cyclization resulted in potent inhibitors with comparable activities against matriptase-1. The most potent synthetic bicyclic inhibitor found in this study (Ki = 2.6 nM at pH 7.6) is a truncated version of SFTI-1 (cyclo-KRCTKSIPPRCH) lacking a C-terminal proline and aspartate residue. It combines an internal disulfide bond with a peptide macrocycle that is formed through side-chain-to-tail cyclization of the ε-amino group of an N-terminal lysine and a C-terminal proline.


Isolation and Genetic Characterization of Toxoplasma gondii from a Patas Monkey (Erythrocebus patas) in China.
Many cases of Toxoplasma gondii infection have been reported worldwide in non-human primates (NHPs), especially in captive New World monkeys. However, few studies on toxoplasmosis in Old World monkeys have been conducted. In this study, serological and molecular biological analyses were carried out to look for T. gondii antibodies and T. gondii infection in 13 NHPs from China. T. gondii infection was confirmed in 8 NHP cases. T. gondii antibodies were detected in 1/5 New World monkeys and in 4/7 Old World monkeys. T. gondii DNA was detected in 3/5 New World monkeys and 5/7 Old World monkeys. The one ring-tailed lemur was negative for both antibodies and DNA of T. gondii. The most common clinical manifestations of T. gondii infection were malaise, poor appetite, emaciation, and foamy nasal discharge. The most common histopathological findings were interstitial pneumonia, necrotic hepatitis, necrotizing myocarditis, lymphadenitis, and necrotic splenitis. One viable T. gondii strain was successfully isolated from the myocardium of a patas monkey (Erythrocebus patas) by bioassay in mice. T. gondii tachyzoites were obtained from cell cultures and were designated as TgMonkeyCHn2. The genotype of this strain belongs to ToxoDB genotype #9, and the allele of ROP18/ROP5 gene was 3/6. TgMonkeyCHn2 tachyzoites were avirulent in Swiss mice. To our knowledge, this is the first report of fatal toxoplasmosis in a patas monkey. T. gondii infection in patas monkeys may indicate environmental contamination by oocysts. The patas monkey is a new host record for T. gondii.


Difference in the thickness of mouthguards fabricated from ethylene-vinyl acetate co-polymer sheets with differently arranged v-shaped grooves.
To investigate the form of mouthguard sheets that best retains its thickness. Mouthguards were molded using ethylene-vinyl-acetate (EVA) sheets and a suction-type molding device. Five sheet conditions were compared. These were I-N (Incisal part of the cast positioned at the center - Normal sheet), I-H (Incisal part positioned at the center - Horizontal v-shaped groove 30 mm from the anterior end), I-C (Incisal part positioned at the center - Convexing v-shaped groove toward the back 10-40 mm from the anterior end), C-N (Center part positioned at the center - Normal sheet), and C-C (Center part positioned at the center - Convexing v-shaped groove toward the back 10-30 mm from the anterior end). Post-molding thickness was determined for the incisal (incisal edge and labial surface) and molar portion (cusp, central groove, and buccal surface). Sheets were heated until they sagged 15-mm below the clamp. Scheffé multivariate comparison was performed to compare changes in post-molding thickness among sheet conditions. Post-molding thickness of mouthguard material differed significantly between the two portions; rates of thickness reduction were smaller for I-C and C-C compared with other conditions. There were no significant differences between I-C and C-C at any measurement points. The present results suggested that thickness reduction of the EVA sheet material after vacuum-forming may be decreased at both incisal and molar portions if the v-shaped groove with a v-shaped cross section was given in the frontal teeth region of the sheet at the apparatus and materials for this study used.


Conformational mobility of small molecules in glass-forming solutions studied by FTIR spectroscopy.
Small molecules with two or more stable conformations when embedded in a glass-forming liquid (matrix) serve the role of "conformational probes", i.e., their conformational transitions are used to follow local mobility in the matrix. In the present study, conformational probes were embedded in low-molecular-weight glass-forming liquids, and the molecular mobility was studied in a broad temperature range including the glass transition temperature (T(g)). Paraffin oil, dibutylphthalate, bis(2-ethylhexyl)phthalate and isopropylbenzene were used as glass-forming liquids while 1,2-dichloroethane, 1,2-diphenylethane, chlorocyclohexane and bromocyclohexane were used as conformational probes. For some of the matrix/probe systems, the conformational mobility was found to freeze-in at T(g), while for the others it froze-in at certain temperatures T(f)<T(g). In the latter case, it was possible to evaluate the activation energies related to mobility of free volume entities in the glassy matrices. In addition, it was possible to estimate the volumes of sub-molecular groups of the matrix that freeze-in at T(f).


Nurses' use of the clinically aligned pain assessment tool: A mixed methods study.
Assessment of pain in the hospital has often relied on intensity rating alone. To address the gap in meeting patients' pain management expectations, a Midwestern medical center implemented the CAPA (Clinical Aligned Pain Assessment) tool for more comprehensive nursing pain assessments. This research described nurses' experience using CAPA on an adult general medicine unit and their documentation of the tool in the electronic health record (EHR) more than 5 years after CAPA implementation. Mixed methods exploratory sequential design. A convenience sample of nurses (N = 8) participated in 2 focus groups to describe how they used CAPA, how well it assessed pain, how it determined pain interventions, and the challenges and advantages of using CAPA. Patient EHR data (N = 373) for a 6-month period from the same unit were analyzed to evaluate CAPA documentation. Qualitative themes included: benefits of using CAPA, CAPA leads to a more comprehensive picture, variation in how CAPA is used, and challenges. Quantitative findings demonstrated most frequent documentation in the comfort domain and earlier, though still delayed, reassessment when a higher level of pain was noted. Mixed methods analysis revealed variation in knowledge and practice regarding which domains to document each shift and during reassessment. As patient advocates, nurses are integral to thorough assessment and treatment of pain. Findings identified the need for methodological research of CAPA. As with any assessment tool, when using CAPA, ongoing monitoring is needed to address how it is administered, coded, and used for decision-making about pain management.


Well-differentiated peripheral cholangiocarcinoma with an unusual clinical course.
A patient with an unresectable well-differentiated bile duct tumor who survived for 15 yr after biopsy diagnosis is presented. Histologic examination of the tumor revealed bland features of bile duct adenoma despite extensive spread within the liver. Over its subsequent course, the tumor progressively replaced the liver, achieving huge size, although there was no evidence of metastases until shortly before the patient's death. This clinical course was very unusual for either bile duct adenoma or cholangiocarcinoma, but would be more characteristic of another tumor of intrahepatic bile duct origin, the biliary cystadenoma. However, this latter diagnosis was excluded with both gross and microscopic pathologic criteria. Evidence is presented to support classification of this tumor as an unusual varient of peripheral cholangiocarcinoma which requires correlation of the clinical and pathologic findings for correst diagnosis.


Patterns of treatment and outcomes of patients with brain-only metastatic breast cancer.
We characterized the risk factors and survival of metastatic breast cancer (MBC) patients with brain metastases (BrM) as the first and only site of disease in a large, retrospective cohort. MBC patients treated for BrM with radiation at a quaternary institution between 2005 and 2019 were identified. MBC patients with BrM but without concurrent extracranial metastases (ECM) or leptomeningeal disease (LMD) were classified as brain-only. Factors associated with brain-only MBC, brain-specific progression free survival (bsPFS) and overall survival (OS) were investigated. A total of 691 patients with MBC and BrM were analyzed. Among them, 67 patients (9.7%, n = 67/691) presented with brain-only MBC without concurrent ECM/LMD. Within this subgroup, 40 patients (5.8%, n = 40/691) remained free of any ECM or LMD, while 17 patients (2.5%) developed LMD, and 10 patients (1.4%%) developed ECM with a median follow-up of 8 months (IQR 2-35). Patients with brain-only MBC were more likely to have a single BrM [OR 3.41 (1.62-7.19), p = 0.001] and either HER2+ [OR 3.3 (1.13-9.65), p = 0.03] or TNBC [OR 4.09 (1.42-11.74), p = 0.009] subtypes. Patients who presented with brain-only MBC also had significantly longer OS [HR 0.45, (0.22-0.86), p = 0.008] and a trend toward longer bsPFS [HR 0.67 (0.44-1.03), p = 0.05] compared to those with concurrent ECM/LMD. Patients with brain-only MBC had a longer bsPFS and OS than those with ECM. Patients with HER2+ and TNBC were more likely to have brain-only disease compared to those with HR+/HER2- MBC.


Multidisciplinary management of spinal lipoma.
Spinal lipomas (congenital lipomyelomeningoceles) can cause significant aesthetic deformity of the lower spine in addition to recognised neurological problems. Surgical management consists of untethering the cord in symptomatic cases, and debulking of the lipomatous component to improve the spinal contour. However, management remains controversial. Between May 1998 and November 2002, 23 cases of lumbosacral spinal lipoma were operated on by neurosurgeons at our hospital. Of these, eight (34%) patients were subsequently referred to plastic surgery for aesthetic revision, which was performed by a combined team of plastic surgeons and neurosurgeons. In addition, three new patients had their primary surgery as a planned procedure performed by the same combined team. The purpose of this paper is to present the method and results of combined plastic surgery and neurosurgery technique in these 11 cases of spinal lipoma. Follow up ranged between 12 months and 4 years (mean 20 months). One patient had wound break down and three patients developed seroma. Two patients had cerebrospinal fluid (CSF) leakage which required re-exploration and prolonged hospitalisation. The aesthetic results were very satisfactory in 10 out of the 11 patients. The frequency of secondary referral for aesthetic revision, together with the incidence of CSF leak, underlines the importance of managing spinal lipomas in a multidisciplinary team involving neurosurgeons and plastic surgeons. This series demonstrates that aesthetic results are encouraging but decreasing the CSF leakage rate remains a challenge. Further follow up will determine the role of early combined surgery in the management of spinal lipoma.


Cytomegalovirus prophylaxis with valganciclovir in cytomegalovirus-seropositive kidney-transplant patients.
The aims of this prospective, open-label, single-center pilot study were to assess the efficacy and safety of human cytomegalovirus (HCMV) prophylaxis using valganciclovir in HCMV- seropositive kidney-transplant patients to prevent HCMV infection and disease. Fifty-one HCMV seropositive kidney-transplant patients recipients who received transplants between 1 December 2005 and 30 November 2006 were included in the study. Valganciclovir was given from transplantation up to 114 (37-329) days, and was adapted to renal function, i.e., 900 mg/d if calculated creatinine clearance was >60 ml/min, or 450 mg/day if it was <60 ml/min. HCMV DNAemia was assessed every 2 weeks during prophylaxis, and on the same basis for 3 months post-prophylaxis. Immunosuppression was based on calcineurin inhibitors (ciclosporine A=22; tacrolimus=11), with mycophenolate mofetil (n=51), and low-dose steroids. Eighteen patients received no calcineurin-inhibitors, but Belatacept instead. During valganciclovir prophylaxis, asymptomatic HCMV DNAemia was observed in one patient, and no case of HCMV disease occurred. Within 252 days (45-425) post-valganciclovir prophylaxis, HCMV DNAemia was detected in 23.5% (n=12) of patients, of whom two had two or more consecutive HCMV DNAemias. Valganciclovir prophylaxis in HCMV-seropositive kidney-transplant patients is effective for preventing cytomegalovirus disease.


Modified integrated tumor burden, liver function, systemic inflammation, and tumor biology score to predict long-term outcomes after resection for hepatocellular carcinoma.
A preoperative predictive score for hepatocellular carcinoma (HCC) can help stratify patients who undergo resection relative to long-term outcomes and tailor treatment strategies. Patients who underwent curative-intent hepatectomy for HCC between 2000 and 2020 were identified from an international multi-institutional database. A risk score (mFIBA) was developed using an Eastern cohort and then validated using a Western cohort. Among 957 patients, 443 and 514 patients were included from the Eastern and Western cohorts, respectively. On multivariable analysis, alpha-feto protein (HR1.97, 95%CI 1.42-2.72), neutrophil-to-lymphocyte ratio (HR1.74, 95%CI 1.28-2.38), albumin-bilirubin grade (HR1.66, 95%CI 1.21-2.28), and imaging tumor burden score (HR1.25, 95%CI 1.12-1.40) were associated with OS. The c-index in the Eastern test and Western validation cohorts were 0.69 and 0.67, respectively. Notably, mFIBA score outperformed previous HCC staging systems. 5-year OS incrementally decreased with an increase in mFIBA. On multivariable Cox regression analysis, the mFIBA score was associated with worse OS (HR1.18, 95%CI 1.13-1.23) and higher risk of recurrence (HR1.16, 95%CI 1.11-1.20). An easy-to-use calculator of the mFIBA score was made available online (https://yutaka-endo.shinyapps.io/mFIBA_score/). The online mFIBA calculator may help surgeons with clinical decision-making to individualize perioperative treatment strategies for patients undergoing resection of HCC.


Thyroid hormone direct repeat 4 response element is a positive regulatory element for the human TR2 orphan receptor, a member of steroid receptor superfamily.
We demonstrate that TR2 orphan receptor (TR2) may induce transactivation activities via an AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE) system. TR2 showed a slightly greater binding affinity than thyroid hormone receptor alpha1 (TR alpha1)/retinoid X receptor alpha (RXR alpha) heterodimer with Kds 0.5 nM and 2.3 nM, respectively. These receptors, TR2 and TR alpha1/RXR alpha heterodimer, competed with each other on binding to limited amounts of DR4-TRE. TR2 canceled the suppression effect of unliganded-TR alpha1 on CAT reporter activity in a dose-dependent fashion. Estrogen receptor (ER) and 2P2 (a mutated TR2 with P box sequence of androgen receptor) failed not only to bind to DR4-TRE but also to recover this inhibitory effect of unliganded TRalpha1. However, when T3 was supplemented, estradiol-ER competed for a full CAT activity while TR2 showed an additive effect on the transcriptional activation. These results indicate that DNA binding is essential for TR2 to take action and fully functional liganded TR alpha1 may rely on common factors shared with ER but not TR2.


Prelymphoma, early lymphoma, and manifest lymphoma in immunosialadenitis (Sjögren's syndrome)--a model of lymphomagenesis.
The development of malignant lymphoma in myoepithelial sialadenitis with and without Sjögren's syndrome was investigated. At first, prelymphomatous proliferation areas showing a polytypic immunoglobulin (Ig) pattern were seen. These transformed into malignant lymphoma with a monotypic Ig pattern, at first in small, circumscribed proliferation areas ("early lymphoma") and later in large, confluent proliferation area ("manifest lymphoma"). The lymphomas were classified as LP immunocytoma. In some cases they transformed into high-grade malignant lymphomas of the same category, namely, B-immunoblastic lymphoma. The same types of lymphoma have been found in NZB mice and chronic graft-versus-host reactions. "Primary" malignant lymphomas of salivary glands that did not show myoepithelial sialadenitis were also studied. These lymphomas were mostly germinal center cell tumors and probably developed primarily in lymph nodes within parotid glands in most, if not all, cases.


A strategy for phage display selection of functional domain-exchanged immunoglobulin scaffolds with high affinity for glycan targets.
Monoclonal antibodies are essential reagents for deciphering gene or protein function and have been a fruitful source of therapeutic and diagnostic agents. However, the use of anticarbohydrate antibodies to target glycans for these purposes has been less successful. Glycans contain less hydrophobic functionality than do proteins or nucleic acids, thus individual glycan-antibody interactions are relatively weak. Information encoded by glycans often involves subtle variations of branched oligosaccharides that cannot be detected with conventional antibodies. Here we describe a new phage display selection strategy for identification of high-affinity and specific glycan antibodies. We designed and characterized a phage clone that functionally displays the unique architectural scaffold of 2G12, an antibody that targets oligomannoses on the HIV-1 glycoprotein gp120. The two heavy chain variable domains of 2G12 exchange positions to create an extended recognition surface containing four oligomannose binding sites per IgG molecule. We designed and characterized a phage clone in which this domain exchange architecture was recapitulated as an antigen binding fragment dimer [(Fab)(2)]on the phage surface by protein engineering. The functional display of the 2G12 (Fab)(2) fragment was validated by Western blot and phage enzyme-linked immunosorbent assay. Furthermore, we demonstrate that this 2G12 (Fab)(2) display system is amenable to selection of functional clones using a mock selection. These results provide proof-of-concept that the privileged 2G12 domain-exchanged scaffold can be used for design of novel antibody libraries that are biased toward glycan recognition.


[DTIC--one component of ABVD combination therapy in Hodgkin's disease (author's transl)].
11 pretreated patients with advanced Hodgkin's disease were treated according to the ABVD schedule. In 6 cases this treatment had to be prematurely terminated due to considerable side effects or due to progression of the disease. The other 6 cases responded favourably, but the improvement was only of short duration.


Outcomes of Percutaneous Atrial Septal Defect Closure With Mitral Transcatheter Edge-to-Edge Repair and Transseptal Mitral Valve Replacement (2015 to 2020).
Patients who underwent transcatheter edge-to-edge repair (TEER) or transcatheter mitral valve replacement (TMVR) have a transeptal access created by an iatrogenic atrial septal defect (ASD) which leads to significant complications requiring closure. Given limited data, we used the National Inpatient Sample between 2015 and 2020 to evaluate the clinical outcomes of percutaneous closure of ASD (PC-ASD) in TEER/TMVR hospitalizations. A total of 44,065 eligible weighted hospitalizations with either TEER (n = 39,625, 89.9%) or TMVR (n = 4,440, 10.1%) with a higher rate of PC-ASD in the TMVR group (10.7% vs 2.0%, p <0.01). The TEER with PC-ASD group were more likely to experience acute heart failure and right ventricular failure and had longer hospital stays but there was no difference in in-hospital mortality compared with the no PC-ASD group. In the TMVR group, there was no difference in the odds of acute heart failure, right ventricular failure, cardiogenic shock, or acute hypoxic respiratory failure, but the odds of mechanical circulatory support, in-hospital mortality, and length of stay were significantly higher in patients with PC-ASD in the TMVR group. In conclusion, rates of percutaneous closure of ASD after TEER were lower than after TMVR and associated with worse in-hospital mortality in TMVR but not in TEER. Further prospective clinical trials are needed to identify patients who would benefit from the closure of iatrogenic ASD.


Clinical aspects of systemic amyloid diseases.
Amyloidosis is a protein misfolding disorder in which soluble proteins aggregate as insoluble amyloid fibrils. Protein aggregates and amyloid fibrils cause functional and structural organ damage respectively. To date, at least 24 different proteins have been recognized as causative agents of amyloid diseases, localized or systemic. The two most common forms of systemic amyloidosis are light-chain (AL) amyloidosis and reactive AA amyloidosis due to chronic inflammatory diseases. beta(2)-microglobulin amyloidosis is a common complication associated with long-term hemodialysis. Hereditary systemic amyloidoses are a group of autosomal dominant disorders caused by mutations in the genes of several plasma proteins. Heterogeneity in clinical presentation, pattern of amyloid-related organ toxicity and rate of disease progression is observed among systemic amyloidoses. In particular, beta(2)-microglobulin presents unique clinical features compared to the other systemic forms. The phenotypic features of hereditary systemic amyloidoses may instead overlap those of the two more common forms of acquired amyloidoses mentioned above and therefore a correct diagnosis can not rely only on clinical grounds. Unequivocal identification of the deposited protein is essential in order to avoid misdiagnosis and inappropriate treatment. Amyloid deposits can be reabsorbed and organ dysfunction reversed if the concentration of the amyloidogenic protein is reduced or zeroed. At present, the most effective approach to treatment of the systemic amyloidoses involves shutting down, or substantially reducing the synthesis of the amyloid precursor, or, as in the case of beta(2)-microglobulin, promoting its clearance.


Synthesis, Biological Evaluation and Docking Study of Mono- and Di-Sulfonamide Derivatives as Antioxidant Agents and Acetylcholinesterase Inhibitors.
Mono(M1-M5)- and di(DM1-DM5)-sulfonamide derivatives were synthesized by the reaction of 4-iodobenzenesulfonyl chloride compound and aniline derivatives in basic medium. The structures of sulfonamide derivatives were characterized by spectroscopic and X-ray diffraction methods. All compounds were screened for acetylcholinesterase (AChE) inhibitory studies and 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging activities. Among the compounds tested, compound M1 showed the best activity against both AChE (IC50 =42.09 μg/mL for AChE) and DPPH (IC50 =9.94 μg/mL for DPPH). By placing compounds at the active site of AChE, their binding energies and modes were determined. Docking studies were performed in order to investigate binding interaction between the synthesized compounds and AChE. The most active M1 compound showed its low CDOCKER energy (-65,834 kcal/mol).


OLFM4 is associated with lymph node metastasis and poor prognosis in patients with gastric cancer.
The present study investigated the clinical significance of the relationship between olfactomedin 4 (OLFM4) expression and the clinicopathological features of patients with gastric cancer. Tumor tissue and adjacent normal tissue, lymph nodes, and peritoneal metastases were analyzed by the Affymetrix GeneChip(®) HG-U133A2.0 array. The expression of OLFM4 was detected by real-time quantitative RT-PCR in gastric tumor tissue and adjacent normal tissue. OLFM4 expression was analyzed by immunohistochemistry in 436 clinicopathologically characterized gastric cancer cases and in corresponding distant metastases from 61 patients. A total of 434 genes and 169 expressed sequence tags were upregulated, including OLFM4. The expression of OLFM4 mRNA or protein differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph node metastases. Further multivariate analysis suggested that lymph node metastases and distant metastases, TNM stage, and expression of OLFM4 were independent prognostic indicators for gastric cancer. Gene expression profiles were useful for simultaneously analyzing the expression levels of thousands of genes. Reduced expression of OLFM4 in gastric cancer is associated significantly with lymph node and distant metastases and with poor prognosis. OLFM4 may prove to be an important molecular marker for predicting the carcinogenesis, development, progression, and metastasis of gastric cancer.


Introduction to Telomeres and Telomerase.
Telomeres are ends of chromosomes that play an important part in the biology of eukaryotic cells. Continued optimization and development of technologies have enabled researchers to probe the mechanisms of telomere maintenance in ever expanding areas. A combination of molecular, genetic, proteomic, and biochemical approaches has revealed the complex and coordinated action of telomerase and telomere-associated proteins. The length and integrity of telomeres are maintained to prevent telomere dysfunction, which has been linked to senescence, aging, disease, and cancer. The tools and assays used to study telomeres today have helped assemble a more detailed, high-resolution picture of the various players and pathways at work at the telomeres.


Mutations in Spliceosomal Genes PPIL1 and PRP17 Cause Neurodegenerative Pontocerebellar Hypoplasia with Microcephaly.
Autosomal-recessive cerebellar hypoplasia and ataxia constitute a group of heterogeneous brain disorders caused by disruption of several fundamental cellular processes. Here, we identified 10 families showing a neurodegenerative condition involving pontocerebellar hypoplasia with microcephaly (PCHM). Patients harbored biallelic mutations in genes encoding the spliceosome components Peptidyl-Prolyl Isomerase Like-1 (PPIL1) or Pre-RNA Processing-17 (PRP17). Mouse knockouts of either gene were lethal in early embryogenesis, whereas PPIL1 patient mutation knockin mice showed neuron-specific apoptosis. Loss of either protein affected splicing integrity, predominantly affecting short and high GC-content introns and genes involved in brain disorders. PPIL1 and PRP17 form an active isomerase-substrate interaction, but we found that isomerase activity is not critical for function. Thus, we establish disrupted splicing integrity and "major spliceosome-opathies" as a new mechanism underlying PCHM and neurodegeneration and uncover a non-enzymatic function of a spliceosomal proline isomerase.


Clinico-Radiologic Outcomes After Stereotactic Radiosurgery for Patients with Complex High-Risk Multiple Arteriovenous Malformations.
The present study aims to define the outcome and risks of patients with multiple arteriovenous malformations (AVMs) treated by stereotactic radiosurgery (SRS). We retrospectively analyzed the records of 1232 patients with AVMs who underwent SRS at our center between 1987 and 2017. We identified 10 patients who had SRS for multiple AVMs (total of 25). Eight patients presented with intracranial hemorrhage before SRS. Four patients had hereditary hemorrhagic telangiectasia. A Spetzler-Martin grade I AVM was diagnosed in 11 AVMs, grade II in 7, grade III in 6, and grade IV in 1 AVM. The median maximum diameter was 12 mm, the median target volume was 1.1 cm3, and the median margin dose was 20 Gy. Twenty-four AVMs were treated with single-session SRS, and 1 AVM was treated with volume-staged SRS. The angiographic complete obliteration rate of each AVM was 18.2%, 58.0%, and 66.4% at 3, 5, and 7 years, respectively. The angiographic complete obliteration rate of all treated AVMs in each patient was 11.1%, 51.4%, and 51.4% at 3, 5, and 7 years, respectively. In multivariate analysis, higher marginal dose (≥18 Gy, P = 0.031) was significantly associated with complete obliteration of AVMs. After obliteration of all their AVMs was confirmed no patient bled. Patients with complex multiple AVMs often presented with a brain hemorrhage. Reduction in bleeding risk after SRS requires complete obliteration that is more likely if the initial AVM margin dose is ≥18 Gy for each AVM.


Mechanisms of collateral sensitivity to fluorouracil of a cis-diamminedichloroplatinum(II)-resistant human non-small lung cancer cell line.
A cisplatin(CDDP)-resistant subline of a human lung cancer cell line, PC-7/CDDP, was 4.7-fold more resistant to CDDP than the parent line in a colony-forming assay. The sensitivity of this cell line to anthracyclines, vinca-alkaloid, etoposide, mitomycin C, and bleomycin was similar to that of the parental line, PC-7. However, PC-7/CDDP exhibited 4-fold higher sensitivity to fluorouracil (FUra). Possible mechanisms associated with the collateral sensitivity to FUra were studied in PC-7/CDDP cells. The sensitivity of both cell lines to FUra did not correlate with the effect of FUra on RNA. On the other hand, FUra induced a greater reduction in dTTP pools and more single strand breaks in PC-7/CDDP than in PC-7 cells. These results suggest that the pathway for de novo deoxyribonucleotide synthesis may be a target for FUra in PC-7/CDDP cells. However, inhibition of thymidylate synthase after FUra treatment did not correlate with the DNA-directed activity of FUra. Based on the above findings, the decreased salvage synthesis of dTTP was considered a possible mechanism of the greater reduction of dTTP pools in PC-7/CDDP cells. However, the activity of dThd kinase was the same in both cell lines. In the presence of physiological concentrations of exogenous dThd in the serum, uptake of dThd was less in PC-7/CDDP cells than that in PC-7 cells. Our data suggest that FUra-induced cytotoxicity in PC-7/CDDP cells is associated with the inhibition of dTTP synthesis and that the decreased uptake of dThd is a possible mechanism of the collateral sensitivity to FUra in PC-7/CDDP cells.


Oxidative desulfurization of dibenzothiophene with hydrogen peroxide catalyzed by selenium(IV)-containing peroxotungstate.
With stoichiometric H(2)O(2) as oxidant, dibenzothiophene (DBT) is oxidized to its corresponding sulfone with high efficiency, catalyzed by a sub-valence heteronuclear peroxotungstate, [C(18)H(37)N(CH(3))(3)](4)[H(2)Se(IV)(3)W(6)O(34)], under mild biphase conditions and the catalyst shows remarkable selectivity of catalytic oxidation towards DBT, cinnamyl alcohol and quinoline.


Immunohistochemical features of lacrimal gland epithelial tumors.
To investigate the immunohistochemical features of ocular adnexal pleomorphic adenoma and adenoid cystic carcinoma. Retrospective clinicopathologic study. Clinical records and microscopic slides of 7 cases of each tumor type were reviewed. Immunohistochemical probes for Ki-67 and p53, and newer nuclear markers MYB for adenoid cystic carcinoma and PLAG1 for pleomorphic adenoma, were employed. Pleomorphic adenomas were asymptomatic, whereas adenoid cystic carcinomas were painful. No pleomorphic adenomas recurred; 4 adenoid cystic carcinomas recurred, resulting in 3 deaths. Unusual histopathologic variants for which immunohistochemistry proved useful included a myoepithelioma, an atypical pleomorphic adenoma, tubular and solid/basaloid variants of adenoid cystic carcinoma, and a morphologically heterogeneous adenoid cystic carcinoma of a Wolfring gland. For the pleomorphic adenomas, the average Ki-67 proliferation index was 3.8%; p53 was weakly staining, with an average positivity of 18.5%; PLAG1 was strongly positive in all cases; MYB was negative in 5 cases and weakly focally positive in 2 cases. For the adenoid cystic carcinomas, the average Ki-67 proliferation index was 29.1%; p53 stained positively and strongly with an average of 39%; none stained positively for PLAG1; and 6 out of 7 were MYB positive. Between pleomorphic adenoma and adenoid cystic carcinoma, there was no overlap in Ki-67 positivity. Positivity for p53 showed overlap in only one lesion of each type. PLAG1 and MYB positivity were highly discriminating between pleomorphic adenoma and adenoid cystic carcinoma. Immunohistochemical analysis should be investigated further for its role in the evaluation of pleomorphic adenoma and adenoid cystic carcinoma.


Worldwide rabies deaths prevention--A focus on the current inadequacies in postexposure prophylaxis of animal bite victims.
The World Health Organization reports that over 60,000 humans die of rabies annually, worldwide. Most occur in remote regions of developing countries. Almost all victims received no postexposure rabies prophylaxis (PEP). There are no facilities or health personnel able to provide it in many areas where the disease is prevalent. A first approach to correct this problem would be by extending provision of modern PEP to areas where human rabies is most prevalent.


Evaluation of neurotensin's thermolytic action by ICV infusion with receptor antagonists and a Ca++ chelator.
To investigate the mechanisms responsible for the thermolytic action of neurotensin (NT), cannulae for intracerebroventricular (ICV) injection were implanted stereotaxically in Sprague-Dawley rats. Postoperatively, body temperature in the unrestrained rat was monitored continuously by a colonic thermistor probe. NT in a dose of 1.5-4.5 micrograms or CSF carrier vehicle was infused bilaterally in the cerebral ventricle (ICV) in a volume of 7.5 microliters. With the rats kept at an ambient temperature of 22 degrees C, NT given ICV produced a dose-dependent fall in core temperature of greater than 0.8 degree C. Pre-treatment of the animal's cerebral ventricle with amine receptor antagonists, phentolamine (20.0 micrograms), butaclamol (10.0 micrograms), methysergide (20.0 micrograms) or atropine (25.0 micrograms), all similarly infused ICV, failed to alter the hypothermia induced by NT. However, the calcium chelating agent, EGTA, given ICV in a dose of 4.0-8.0 micrograms blocked the thermolytic effect of NT on body temperature in a concentration-dependent manner. These results suggest that the central thermolytic action of NT is not mediated by catecholamine or other aminergic pathways which are implicated in the central mechanisms of thermoregulation. Rather, the peptide may act on a cellular process involving calcium activity in the hypothalamus, presumably to impair the maintenance of the animal's "set-point" for body temperature.


The retina-lamina projection in the crab Leptograpsus variegatus.
In the crab, Leptograpsus variegatus, the projection of retinula cell axons to the lamina was investigated by tracing them through a series of semi-thin sections. Forty-four such axons were traced from a single group of ommatidia as far as the distal layers of the lamina. The eight receptor axons of one ommatidium project to a single lamina cartridge. Therefore, because the crab has a fused rhabdom, angular information is conserved in vision, and the outside world is projected literally onto the lamina, just as it is in the standard non-dipteran pattern of insects. The belief of previous workers that other decapod eyes show neural superposition was an inference based primarily on the patterns of penetration of the basement membrane by receptor axons, and on degeneration experiments. This evidence is reviewed, shown to be inadequate and discussed in the light of the projection now demonstrated for Leptograpsus.


Experimental tardive dyskinesia.
In this work, we have attempted to reproduce dyskinesia similar to tardive dyskinesia by two methods. In the first experiment, we have administered to 6 macaca mulatta, haloperidol 0.25 mg/kg daily for six months. During that period we observed in all monkeys, after each dose: restlessness, akinesia and tremor. One monkey developed choreoathetoid movements, which were seen each day after the first month. They disappeared however upon cessation of the drug administration. Only one animal developed a bucco lingual dyskinesia after two months which was still present when they were sacrificed six month after the drug administration was discontinued. At that time, harmaline 3 mg/kg induced a postural tremor in all monkeys suggesting a lesion of the rubro-olivo-cerebello rubral loop. Histological analysis of the brains revealed no gross abnormality. In a second experiment, a left midbrain electrolytic lesion was performed in twelve monkeys. One monkey, developed a contralateral tremor but five including the trembling one developed a buccolingual dyskinesia which has now lasted more than a year. This dyskinesia is present at rest but increased by dopaminergic agents and blocked by haloperidol. Histological analysis of the brain of one of the monkeys revealed a dorsal lesion involving the region of the nucleus parafascicularis thalami. The substantia nigra was spared.


A gold nanoparticles-based lateral flow assay utilizing baculovirus expressed recombinant nucleocapsid and receptor binding domain proteins for serodetection of IgG and IgM against SARS-CoV-2.
Serological assays for SARS-CoV-2 are being utilized at an exponential rate for surveillance programs. This enterprise was designed to develop and validate a qualitative immunochromatographic test, via the Lateral Flow Assay (LFA), for detection of immunoglobulins M and G (IgM and IgG) against both nucleocapsid (N) and the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Both targeted proteins were cloned and expressed in baculovirus expression system utilizing insect cells Sf9. The recombinant RBD and N proteins were purified and conjugated with gold nanoparticles (AuNPs) to set up the coating antigens pad. Both anti-human IgG and IgM were dispensed on nitrocellulose membrane to capture human antibodies in serum samples. A home-made dispensing system was developed to draw identical test and control lines. The validity of the developed LFA was verified by testing serum samples from 103 convalescent COVID-19 patients who were PCR positive for SARS-CoV-2 along with 28 control serum samples. The developed strips showed distinctive bands for IgM and IgG of both proteins (RBD and N) in positive samples. The sensitivity of RBD-based LFA was 70.9% and 39.8% for IgG and IgM, respectively, with a specificity of 100% for both. The N-based LFA exhibited a sensitivity of 73.8% and 35.9% for IgG and IgM, respectively, while its specificity was 75% and 100% for IgG and IgM, respectively. Our developed LFA could afford a tool for surveillance programs in low-resource countries. Moreover, it might be functional for rapid and inexpensive monitoring of the anti-SARS-CoV-2 antibodies in the sera of vaccinated individuals.


Trends in head and neck cancers in Peru between 1987 and 2008: Experience from a large public cancer hospital in Lima.
Few studies have evaluated the trends in head and neck cancer in developing countries. The purpose of this study was to estimate trends in incidence of human papillomavirus-related (HPV-R) and HPV-unrelated (HPV-U) head and neck cancer in Lima, Peru, from 1987 to 2008. Registry data from a single public cancer hospital were used to estimate age and sex-specific incidence rates. Annualized percent change was estimated using Poisson regression. The rate of total head and neck cancers, HPV-U, and HPV-R was 11.9, 10.9, and 0.8, respectively, per 100,000 person-years. Significant increases in HPV-U head and neck cancer were observed in men aged 30 to 44 (2.5%/year) and women 15 to 29 (4.2%/year), 30 to 44 (3.4%/year), and 60 to 74 (2.0%/year). Significant increases in HPV-R head and neck cancer were observed only among men aged 45 to 59 (9.6%/year). Although increased exposure to tobacco, occupational carcinogens, and changing sexual behaviors could be influencing these trends, additional analyses to assess generalizability of these findings to other regions of Peru are needed.


Neuronal nuclear calcium signaling suppression of microglial reactivity is mediated by osteoprotegerin after traumatic brain injury.
Traumatic brain injury (TBI) is characterized by massive changes in neuronal excitation, from acute excitotoxicity to chronic hyper- or hypoexcitability. Nuclear calcium signaling pathways are involved in translating changes in synaptic inputs and neuronal activity into discrete transcriptional programs which not only affect neuronal survival and synaptic integrity, but also the crosstalk between neurons and glial cells. Here, we report the effects of blunting neuronal nuclear calcium signals in the context of TBI. We used AAV vectors to express the genetically encoded and nuclear-targeted calcium buffer parvalbumin (PV.NLS.mCherry) or the calcium/calmodulin buffer CaMBP4.mCherry in neurons only. Upon TBI, the extent of neuroinflammation, neuronal death and synaptic loss were assessed by immunohistochemistry and targeted transcriptome analysis. Modulation of the overall level of neuronal activity was achieved by PSAM/PSEM chemogenetics targeted to parvalbumin interneurons. The functional impact of neuronal nuclear calcium buffering in TBI was assessed by quantification of spontaneous whisking. Buffering neuronal nuclear calcium unexpectedly resulted in a massive and long-lasting increase in the recruitment of reactive microglia to the injury site, which was characterized by a disease-associated and phagocytic phenotype. This effect was accompanied by a substantial surge in synaptic loss and significantly reduced whisking activity. Transcriptome analysis revealed a complex effect of TBI in the context of neuronal nuclear calcium buffering, with upregulation of complement factors, chemokines and interferon-response genes, as well as the downregulation of synaptic genes and epigenetic regulators compared to control conditions. Notably, nuclear calcium buffering led to a substantial loss in neuronal osteoprotegerin (OPG), whereas stimulation of neuronal firing induced OPG expression. Viral re-expression of OPG resulted in decreased microglial recruitment and synaptic loss. OPG upregulation was also observed in the CSF of human TBI patients, underscoring its translational value. Neuronal nuclear calcium signals regulate the degree of microglial recruitment and reactivity upon TBI via, among others, osteoprotegerin signals. Our findings support a model whereby neuronal activity altered after TBI exerts a powerful impact on the neuroinflammatory cascade, which in turn contributes to the overall loss of synapses and functional impairment.


We aren't especially fearful apes, and fearful apes aren't especially prosocial.
Grossmann posits that heightened fearfulness in humans evolved to facilitate cooperative caregiving. We argue that three of his claims - that children express more fear than other apes, that they are uniquely responsive to fearful expressions, and that expression and perception of fear are linked with prosocial behaviors - are inconsistent with existing literature or require additional supporting evidence.


Partitioning the Variability of Daily Emotion Dynamics in Dyadic Interactions with a Mixed-Effects Location Scale Model.
We examine the daily exchanges in affect and emotional experiences of individuals in dyads using a mixed-effects location scale model. We argue that this method is useful to characterize the daily fluctuations in emotions for each individual as well as their interrelations over time. Furthermore, we illustrate how to consider the potential effect of factors external to the dyads' emotion dynamics, an aspect often ignored in emotion research. In particular, we show how daily weather may influence within-person variability of affect toward one's relationship, beyond the influence of one's and the partner's affect. We interpret our findings in the context of emotion research and methodology for dyadic interactions.


Characterizing the role of Phlda3 in the development of acute toxicity and malignant transformation of hematopoietic cells induced by total-body irradiation in mice.
The tumor suppressor p53 is a transcriptional factor that plays a crucial role in controlling acute toxicity and long-term malignant transformation of hematopoietic cells induced by genotoxic stress such as ionizing radiation. Among all transcriptional targets of p53, one gene that is robustly induced by radiation is the pleckstrin homology domain-only protein Phlda3. However, the role that Phlda3 plays in regulating the response of hematopoietic cells to radiation is unknown. Here, using isogenic cell lines and genetically engineered mouse models, we showed that radiation induces Phlda3 in human leukemia cells and mouse normal hematopoietic cells in a p53-dependent manner. However, deletion of the Phlda3 gene did not ameliorate radiation-induced acute hematologic toxicity. In addition, distinct from mice that lose p53, loss of Phlda3 did not alter the latency and incidence of radiation-induced thymic lymphoma in mice. Remarkably, whole-exome sequencing data showed that lymphomas in irradiated Phlda3+/+ mice harbor a significantly higher number of single nucleotide variants (SNVs) and indels compared to lymphomas in irradiated Phlda3+/- and Phlda3-/- littermates. Together, our results indicate that although deletion of Phlda3 does not accelerate the development of radiation-induced thymic lymphoma, fewer SNVs and indels are necessary to initiate lymphomagenesis after radiation exposure when Phlda3 is silenced.


Correction: A Rare Case of Cord Compression From Extra-Medullary Hematopoiesis (EMH) in Beta Thalassemia.
[This corrects the article DOI: 10.7759/cureus.38520.].


Formation and stabilization mechanism of mesoscale clusters in solution.
To understand the existence of complex meso-sized solute-rich clusters, which challenge the understanding of phases and phase equilibria, the formation and stabilization mechanisms of clusters in solution during nucleation of crystals and the associated physico-chemical rules are studied in detail. An essential part of the mechanism is the formation of long-lived oligomers between solute molecules. By means of density functional theory simulation and nuclear magnetic resonance experiments, this work showed that the oligomers in solution tend to be π-π stacking dimers. Clusters are formed under the combined effect of diffusion and monomer-dimer reaction. The physically meaningful quantities such as the monomer-dimer reaction rate constants and the diffusion coefficients of both species were obtained by reaction-diffusion kinetics and diffusion-ordered spectroscopy results. The evolution of cluster radius as a function of time, and the qualitative spatial distributions of monomer and dimer densities under steady-state were plotted to better understand the formation process and the nature of the clusters.


Sleep disorders in patients with spinal cord injury.
Sleep disturbances are globally more frequent in patients with spinal cord injury (SCI) than in the able-bodied population, and could contribute to dysfunction and poor quality of life in these patients. Specific sleep disorders may also contribute to negative health outcomes enhancing cardiovascular risk in a condition that per se increases heart disease related mortality. This review focuses on prevalence, features and treatment of sleep disorders in SCI. Although data on these subjects have been produced, reports on pathophysiology, consequences and treatment of sleep disorders are scarce or contradictory and more studies are required.


Chinese female immigrants english-speaking ability and breast and cervical cancer early detection practices in the New York metropolitan area.
Breast and cervical cancers are significant causes of mortality and morbidity for Asian women, and poor English-speaking ability is a barrier to cancer prevention practices. This project tested relationships among English-speaking ability and early detection practices regarding to breast and cervical cancer among female Chinese immigrants. A descriptive cross-sectional survey was used. 175 female Chinese immigrants completed the survey in the breast cancer prevention section, and 35 of them also completed the cervical cancer prevention section. Some 63% of them had heard about the clinical breast exam (CBE), but only 54% had had a CBE. While 46% of the participants were aware of their need for a Pap smear, only 31% had heard about it and had undergone a pelvic exam. English-speaking ability was strongly associated with immigrant women's knowledge of female cancer early detection. Culturally and linguistic issues should be considered as the first step to access immigrant population in designing future education intervention.


A one-pot reaction to synthesize two types of fluorescent materials containing benzothiazolyl moiety.
Two different types of fluorescent materials containing benzothiazolyl moiety, 2-(benzothiazol-2-yl)phenol derivatives and 3-(benzothiazol-2-yl)coumarin derivatives, were synthesized synchronously using ethyl cyanoacetate, appropriate aromatic aldehyde and 2-aminothiophenol as the starting materials under the catalysis of benzoic acid by one-pot reaction. This method has the advantages of mild reaction conditions, easy processing and low waste. All synthesized compounds were characterized by elemental analysis, IR, (1)H NMR spectra. The structures of 2-(benzothiazol-2-yl)phenol derivatives, 2-(benzothiazol-2-yl)phenol (BTP) and 2-(benzothiazol-2-yl)naphthol (BTN), were determined by X-ray single crystal analysis. The UV-vis absorption and photoluminescence spectra of all synthesized compounds were investigated. The 2-(benzothiazol-2-yl)phenol derivatives exhibit bright green emissions and 3-(benzothiazol-2-yl)coumarin derivatives emit bright blue light in solutions.


Intradermal mast-cell secretion causing cutaneous mitogenesis.
This study demonstrated that mast-cell secretion elicited by intradermal injection of compound 48/80 initiated cell proliferation in rat skin. The mast-cell secretion was confirmed by microscopical demonstration of degranulation of mast cells, and by quantifying histamine release, whereas the proliferation was assessed by measuring DNA-synthesis and the frequency of mitosis. The results, which fully support our previous findings in the true mesentery, indicate that the common type of mast cell, when appropriately activated, is capable of playing a role in governing cell proliferation in diverse tissues.


[Increasing the efficacy of radiation damage to transplantable tumors using postradiation hypoxia].
It was shown that the duration of remission (by the criterion of the time of reaching an initial tumor size) of ascitic solid Ehrlich carcinoma of mice could be doubled by post-radiation tourniquet hypoxia both in single and fractionated irradiation. The effect of placing a tourniquet is equal to a 1.5-fold dose increase.


Respiratory rate as a determinant of optimal pacing rate.
Efforts have been made to utilize biologic parameters for determining optimal cardiac pacing rates. In this study of 67 patients, a significant relationship between heart rate and respiratory rate was observed during dynamic exercise. A system using a radiofrequency activator to modify pacing rate is described. Eleven patients have received VVI pacemakers with a similar implanted radio receiver coil. In two patients the fully automatic system has been successfully implanted. The experience with respiratory rate as a determinant of pacing rate is encouraging.


Portable and reversible smart labels for non-destructive detection of seafood freshness via amine-response fluorescent ionic liquids.
Herein, a functionalized ionic liquid (IL) 7-HDCP (7-hydroxycoumarin-quaternary phosphorus) was developed as NH3 trapping agents and fluorescent indicators to achieve in-time and on-site detection of seafood freshness. Interestingly, the IL displayed remarkable blue fluorescence "turn-on" enhancement to gaseous amine due to excellent amine solubility. By FTIR and 1H NMR spectrogram, this fluorescence "turn-on" phenomenon originated from the weak hydrogen bonding between the ester group of the coumarin functional group and the ammonia molecule. Moreover, the IL exhibited a rapid response (<11 s), prominent sensitivity (0.12 ppm), excellent selectivity (10 interfering substances) and outstanding reversibility (>22 cycles). Benefiting from ion characters, 7-HDCP obtained advantages of easy-to-fabricate and easy-to-use, which was fabricated by one-step simple immersion without aggregation-caused quenching phenomenon. This portable and sensitive smart label made of ion probes facilitates the timely and on-site NH3 detection in the early deterioration stages of aquatic products, enabling "early detection, early warning, and early treatment".


Blood transthyretin for predicting immunoglobulin A vasculitis nephritis outcome in children.
IgA vasculitis is characterized by inflammation of the blood vessels, which can result in microvascular destruction and consequently renal damage. Transthyretin is a newly discovered angiogenesis regulator in promoting microvascular regeneration. This indicates that transthyretin may act as a potential predictor of IgAV as well as IgAVN. This retrospective study included 125 patients newly diagnosed as IgAV with demographic and laboratory parameters. Of these, 78 patients had demonstrated internal organ damage and 47 patients with only skin and joint injury. Of 78 patients with organ impairment, 27 were diagnosed of renal involvement. Then we evaluated the relationship between NLR, total protein, albumin, globulin, transthyretin, B lymphocyte counts and the severity of IgAV. For patients with internal organ or renal involvement, the level of transthyretin were lower than non-internal organ damage group (p < 0.001 for both group). Remarkably, the NLR was only higher in patients with internal organ damage group (p = 0.019). Logistic regression analysis showed that NLR and transthyretin both were risk factors for internal organ involvement (OR = 1.768, 0.973 separately), and only transthyretin is the independent risk for renal involvement (OR = 0.981, p < 0.05). The ROC analysis showed an AUC of 0.626 for NLR, 0.815 for transthyretin in predicting organ damage, 0.755 for transthyretin in patients with renal involvement (p < 0.05, to all parameters). Transthyretin is a better predictor in predicting internal organ or renal involvement than NLR, and low plasma transthyretin concentration can increase the risk of renal involvement in IgAV patients.


Interleukin-1alpha expression in capillaries and major histocompatibility complex class I expression in type II muscle fibers from polymyositis and dermatomyositis patients: important pathogenic features independent of inflammatory cell clusters in muscle tissue.
To address the hypothesis that endothelial cells and/or muscle fibers are primary targets in the disease process by analysis of muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM). We included patients with laboratory signs and clinical symptoms typical of myositis, but without detectable infiltration of clusters of inflammatory cells in their muscle biopsy samples. An immunohistochemical technique was applied to identify CD3, CD68, lymphocyte function-associated antigen 1alpha, CD11b, very late activation antigen 4, endothelium 4, interleukin-1alpha (IL-1alpha), intercellular adhesion molecule 1, vascular cell adhesion molecule 1, IgG, IgM, IgA, and HLA-A/B/C in muscle tissue. Fiber type was defined by ATPase staining. IL-1alpha expression was detected in endothelial cells of capillaries to a greater extent in patients than in controls, and class I major histocompatibility complex (MHC) expression was significantly increased in muscle fibers. We also observed that class I MHC expression was mainly confined to type II muscle fibers. Our findings imply that defined molecular changes of blood vessels and muscle fibers are both independent of adjacent inflammatory infiltrates and could thus be primary events in the development of myositis. Moreover, both IL-1alpha and class I MHC molecules might be important for the development of clinical symptoms in PM and DM patients.


Nailing a key assessment. Learn the significance of certain nail anomalies.
Discover how a patient's fingernails can point out specific health problems.


What is the concordance rate of preoperative synovial fluid aspiration and intraoperative biopsy in detecting periprosthetic joint infection of the shoulder?
The accuracy of preoperative synovial fluid culture for microbe detection in shoulder periprosthetic joint infection (PJI) is poorly described. To evaluate the utility of preoperative culture data for early pathogen identification for shoulder PJI, we determined the concordance between preoperative synovial fluid culture results and intraoperative tissue culture results. Fifty patients who met the 2014 Musculoskeletal Infection Society criteria for shoulder PJI between January 2016 and December 2019 were retrospectively reviewed for clinical and demographic data. This cohort of patients was divided into 2 groups based on the concordance between preoperative and intraoperative culture results. The pathogens identified on preoperative and intraoperative cultures were classified as high-virulence or low-virulence. Student's t tests and Mann-Whitney U tests were used as appropriate for continuous variables, and χ2 and Fisher's exact tests were used as appropriate for categorical variables. Concordance between preoperative aspiration and intraoperative tissue culture was identified in 28 of 50 patients (56%). Preoperative cultures positive for Gram-positive species were more likely to be concordant than discordant (P = .015). Preoperative cultures positive for Cutibacterium acnes were more likely to be concordant with intraoperative cultures (P = .022). There were more patients with polymicrobial infection in the discordant group compared with the concordant group (P < .001). No statistically significant correlation between the preoperative serum C-reactive protein level and the intraoperative category of bacteria was reported. Staphylococcus aureus and coagulase-negative Staphylococci were associated with high specificity and negative predictive value. Preoperative cultures positive for C. acnes demonstrated sensitivity, specificity, positive predictive value, and negative predictive value lower than 0.8. Gram-negative pathogens demonstrated the highest sensitivity (1) and specificity (1), whereas polymicrobial infections exhibited the lowest sensitivity and positive predictive value. Preoperative synovial fluid aspiration for shoulder PJI poorly predicts intraoperative culture results, with a discordance of 44%. More favorable concordance was observed for monomicrobial preoperative cultures, particularly for Gram-negative organisms and methicillin-sensitive S. aureus. The overall high rate of discordance between preoperative and intraoperative culture may prompt surgeons to base medical and surgical management on patient history and other factors and avoid relying solely on preoperative synovial fluid culture data.


[Accumulation of acridine amino derivatives by electron-dense granules in thrombocytes].
The uptake and release of dense bodies' content were studied using fluorescent amines. Real-time measurements of fluorescence spectra by a device developed on the basis of a multichannel optical analyzer and computer technique of spectrum deconvolution made it possible to investigate the kinetics of monoamine uptake and release in intact cells.


Embryonic lesions of the substantia nigra prevent the patchy expression of opiate receptors, but not the segregation of patch and matrix compartment neurons, in the developing rat striatum.
Unilateral lesions of the substantia nigra on embryonic day 19 prevent the development of the normal patchy distribution of opiate receptors in the ipsilateral rat striatum. Independent, early and permanent labelling of patch compartment neurons in the same brains on embryonic day 14 with [3H]thymidine revealed that the substantia nigra lesions did not prevent the aggregation of early born neurons into patches, but rather blocked the normal expression of one phenotype (dense opiate receptor binding) of these patches. Thus, early nigrostriatal connections may not be critical for the fundamental patch/matrix compartmentation of the striatum, but may be important in the maturation of phenotypic markers of these compartments.


Etiology of late developing incisional hernias--the possible role of mechanical stress.
The etiology of incisional hernias that develop a year or more after laparotomy is not understood. This subset of incisional hernias is not associated with the etiologic factors usually implicated in incisional hernia formation. Mechanical stress is known to have a profound influence on the structure of both normal and wounded tissue. It is hypothesised that mechanical stress plays an important role in the development of late incisional hernias.


Radiological patterns of tumour progression in patients treated with a combination of immune checkpoint blockers and antiangiogenic drugs.
Immune checkpoint blockers (ICBs) in combination with antiangiogenic drugs showed synergistic efficacy in several tumour types. New patterns of progression have recently been defined upon treatment with ICB alone including atypical responses such as pseudoprogression (PsPD), dissociated response and hyperprogressive disease (HPD). This study aimed to describe the patterns of response observed in patients treated with combination ICB with antiangiogenic drugs. We conducted a monocentric retrospective analysis of patients (pts) enrolled in phase I trials at Gustave Roussy assessing the combination of ICB and antiangiogenic drugs. Radiological CT scans were centrally reviewed by a senior radiologist according to iRECIST criteria including progressive disease (PD), partial response (PR) and stable disease (SD). HPD was defined as a progression at the first evaluation with a delta tumour growth rate exceeding 50%. PsPD was defined as initial progression followed by stabilisation or decrease of tumour size, DisR as a concomitant size decrease in some tumour lesions and size increase in others. Both PsPD and DisR are defined as atypical responses. Overall response rate included PR and complete response (CR) and disease control rate included PR, CR and SD. Between December 2016 and June 2020, 111 pts were included. The median follow up was 12.8 months (11.3-15.1). The most common tumour types were lung and pleura (20%), kidney (18%) and bladder (17%). The overall response rate and disease control rate were 21.6% (n = 24) and 59% (n = 65), respectively. Twenty-one patients (19%) experienced PD as the best response. PsPD, DisR and HPD were observed in 4 (3.6%), 11 (9.9%) and 7 (6.3%) pts, respectively. DisR and PsPD were associated with longer iProgression Free Survival (median: 6.9 and 18.9 months, respectively) and iOverall Survival (median: 28.4 and 31.1 months, respectively) than a median of SD in immune progression-free survival (median: 4.2 months) and immune overall survival (median: 12.7 months). Patients treated with ICBs and antiangiogenic agents display atypical responses. Survival might be longer in patients with DisR responses and PsPD disease than patients with HPD, PD and SD.


Rat bite injury to the eyelids in a 3-month-old child.
A 3-month-old child received severe rat bit injuries to the face, including subtotal loss of upper and lower lids of one eye. The presentation and management are discussed.


Baseline survey of animal trypanosomosis in the region of the Boucle du Mouhoun, Burkina Faso.
In view of gathering baseline information about the prevalence of animal trypanosomosis, the Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) funded a cross sectional survey in the region of the Boucle du Mouhoun which constitutes the Northern limit of the tsetse distribution in Burkina. This cross sectional study was carried out in 53 villages located in the six provinces of the region. A total of 2002 cattle, 1466 small ruminants and 481 donkeys were sampled. This survey showed that about 25% of the cattle had been treated with trypanocidal drugs within 3 months before the survey compared to 3% and 0.42% for the small ruminants and donkeys, respectively. Parasitological prevalence in cattle was low: 0.77% (95% C.I. 0.30-1.95%). No goats and three donkeys were found infected with trypanosomes. Infections were mainly due to Trypanosoma vivax (75.0%) with cases of Trypanosoma congolense (25.0%). In cattle, the serological prevalence of trypanosomosis, for the entire region of the Boucle du Mouhoun, was 34.2% (95% C.I. 26.1-43.4%). For sheep, goats and donkeys, the prevalence were of 20.9% (95% C.I. 12.2-33.5%), 8.5% (95% C.I. 5.7-12.5%) and 5.8% (95% C.I. 3.9-8.6%), respectively. The age and distance to the river were the two main risk factors associated with seropositivity.


Cryopreservation of human spermatozoa. I. Effects of holding procedure and seeding on motility, fertilizability, and acrosome reaction.
Three experiments were conducted to evaluate effects of holding semen at +5.0 degrees C for 30 minutes or -5.0 degrees C for 10 minutes and ice crystal induction (seeding) on frozen-thawed human spermatozoa. In experiment 1, spermatozoa were frozen, and postthaw motility was evaluated immediately (0 hour) and 24 hours later. At both 0 and 24 hours, nonfrozen control samples had higher motility than all other treatment groups. At 0 hour postthaw, motility was higher in samples held at -5.0 degrees C for 10 minutes with no significant effect of seeding. At 24 hours, samples held at -5.0 degrees C for 10 minutes and seeded, but not samples held at -5.0 degrees C and not seeded, had higher motility than samples held at +5.0 degrees C. In experiment 2, semen samples were frozen, and fertilizability was evaluated in a zona-free hamster egg penetration assay. Seeded samples had a higher frequency of sperm penetration than either nonfrozen or nonseeded samples. In experiment 3, nonfrozen controls and frozen treatment groups were evaluated for the frequency of survival and acrosomal integrity. Seeded samples had higher frequencies of survival and loss of acrosomal integrity than nonseeded samples. All frozen-thawed samples had a lower frequency of survival and a higher frequency of loss of acrosomal integrity than nonfrozen controls. Although altered patterns of fertilizability and acrosomal integrity are induced, collectively these data suggest that incorporating a holding temperature of -5.0 degrees C for 10 minutes and seeding may result in a superior protocol for freezing human spermatozoa.


The effects of age on maintenance of intense neuromuscular block with rocuronium.
Increasing age is associated with a longer duration of action of neuromuscular block. The aim of this study was to determine the influence of ageing on the recovery of the post-tetanic count (PTC) from rocuronium-induced neuromuscular block. Twenty-two younger (20-60 years) and 22 older (> 70 years) patients were enrolled in this study. After induction of anaesthesia with fentanyl and propofol, all patients initially received 1 mg/kg rocuronium and neuromuscular block were evaluated by contractions of the adductor pollicis muscle to ulnar nerve train-of-four stimulation using an acceleromyograph. Subsequently, intense rocuronium-induced block was determined every 6 min using the PTC during 1.0-1.5% sevoflurane and remifentanil anaesthesia. When the first response to the PTC stimulus was detected, 0.2 mg/kg rocuronium was additionally administered, and again, spontaneous recovery of neuromuscular function was monitored until the first response to the PTC reappeared. Median values (range) of the times from the administration of 1 mg/kg and 0.2 mg/kg rocuronium until recovery of the first detectable PTC were significantly longer in the older [51.0 (27-100) min, P < 0.0001 and 30.0 (12-66) min, P = 0.0036, respectively] than the younger patients [31.5 (21-45) min and 18.0 (12-36) min, respectively]. The times from rocuronium injection to reappearance of the first response to PTC stimulation are approximately twofold longer and more variable in older than younger patients. Hence, the dosing interval of rocuronium should be adjusted using neuromuscular monitoring when maintaining intense neuromuscular block, especially in older patients.


Developing and using a smartphone-app to support the teaching of technical basics for 3D/4D obstetrical ultrasound applications in medical education.
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Nucleobase transport in opossum kidney epithelial cells and Xenopus laevis oocytes: the characterisation, structure-activity relationship of uracil analogues and oocyte expression studies of sodium-dependent and -independent hypoxanthine uptake.
The characteristics of hypoxanthine transport were examined in opossum kidney (OK) epithelial cells and Xenopus laevis oocytes. In both cell types hypoxanthine influx was mediated by two distinct transport systems: a high-affinity Na+-dependent system and a Na+-independent transporter. Na+-dependent hypoxanthine transport in OK cells was saturable (Km 0.78+/-0.29 microM) and was inhibited by guanine, uracil, thymine and 5-fluorouracil (Ki values 0.5-7 microM), whereas adenine had no effect. Substitutions at the 2- and 4-position had a marked effect on the ability of uracil to inhibit Na+/hypoxanthine influx by OK cells revealing that an oxo group at both the 2- and 4-positions of uracil is required for interacting with the transporter. The properties of Na+-dependent hypoxanthine influx in oocytes were similar to those observed in OK cells. In particular, xanthine and oxypurinol inhibited hypoxanthine influx, a characteristic not observed previously for the Na+/nucleobase carrier in pig LLC-PK1 renal cells. Na+-independent hypoxanthine influx in OK cells and oocytes was of a lower affinity (Km 90-180 microM). Adenine and guanine inhibited Na+-independent hypoxanthine flux in OK cells, but had no effect in oocytes. Injection of LLC-PK1 mRNA into oocytes resulted in a 1.5-fold stimulation of Na+/hypoxanthine flux over water-injected oocytes. These results reveal further heterogeneity in Na+/nucleobase cotransporters.


Pregnenolone biosynthesis in isolated cells of Snell rat adrenocortical carcinoma 494.
Adrenocorticotrophin (ACTH) produced an insignificant stimulation of pregnenolone biosynthesis from endogenous precursors in isolated cells prepared from the rat Snell adrenal carcinoma 494. On the addition of 25-hydroxycholesterol, the rate of pregnenolone synthesis increased 10-fold. These results, noting also the very low cholesterol content of the tumor cells, suggested that lack of cholesterol was responsible for the poor steroidogenic response of the cells to ACTH. Endogenous pregnenolone production was sensitive to cytochalasin B as well as cycloheximide. However, pregnenolone synthesis after the addition of 25-hydroxycholesterol was not affected by these inhibitors. Removal of cycloheximide from the cells resulted in the immediate restoration of the initial rate of pregnenolone synthesis from endogenous precursors. This suggested that cycloheximide was interfering with the action of a stable activated intracellular messenger.


Tissue Characterization in Cardiology: Moving Beyond Function.
Cardiovascular Magnetic Resonance (CMR) offers accurate and highly reproducible tissue characterization, beyond cardiac function. Late gadolinium enhancement (LGE), although represents a noninvasive biopsy for fibrosis quantification, it is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) are able to provide important information about processes involving both myocardial cells and interstitium that otherwise cannot be identified. Changes in myocardial native T1 mapping reflect cardiac diseases such as acute coronary syndromes, myocardial infarction, myocarditis, diffuse fibrosis, systemic disease such as cardiac amyloidosis, all presented with high T1 and Anderson-Fabry disease and siderosis, presented with low T1 mapping. The ECV, an index generated by native and postcontrast T1 mapping, introduces a new way to measure the cellular and extracellular interstitial matrix (ECM). ECV has a prognostic value equal to Left ventricular ejection fraction (LVEF); however, LVEF underscores the interstitial matrix. This myocyte-ECM dichotomy has important implications for identifying therapeutic targets that are of great value for heart failure (HF) treatment. Furthermore, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset HF. These indices will affect significantly the clinical decision making. However, there is still lack of multicenter studies and community-wide approach including MRI vendors, clinicians, fundings, softwares, and contrast agent manufacturers.


Prevalence of pressure ulcer and associated risk factors in middle- and older-aged medical inpatients in Norway.
To describe the prevalence of pressure ulcers among middle- and older-aged patients in a general medical hospital in Norway and to describe the associations between pressure ulcers and potential risk factors additional to the Braden risk score. Degrees of mobility, activity, perfusion and skin status are risk factors for development of pressure ulcer. Nurses' clinical judgements combined with risk assessment tools are effective to detect pressure ulcer risk. Cross-sectional study. The study was performed as part of a research project conducted between September 2012-May 2014 in a general hospital in the capital of Norway. Registered nurses and nursing students collected data from all eligible patients on 10 days during the students' clinical practice studies. The Braden scale was used to measure pressure ulcer risk, and skin examinations were performed to classify the skin area as normal or as indicative of pressure ulcer according to the definitions by the National Pressure Ulcer Advisory Panel. Comorbidities were collected by patient's self-report. This analysis focused on the 255 inpatients at the medical wards ≥52 years of age, most of whom had more than one comorbidity. The prevalence of pressure ulcers was 14.9% in this sample. Higher age, underweight, diabetes and worse Braden scores were factors associated with pressure ulcer, and pressure ulcer was most frequently sited at the sacrum or heel. Adding age, weight and diabetes status to pressure ulcer risk assessment scales may improve identification of patients at risk for pressure ulcers. Knowledge about strengths and limitations of risk assessment tools is important for clinical practice. Age, weight and diabetes status should be considered for inclusion in risk assessment tools for pressure ulcers in medical wards.


Template directed photodimerization of trans-1,2-bis(n-pyridyl)ethylenes and stilbazoles in water.
Template induced photodimerization of trans-1,2-bis(n-pyridyl)ethylene dihydrochlorides and trans-n-stilbazole hydrochlorides within cucurbit[8]uril in aqueous media leads to high yields of the syn dimer.